@article {pmid40082305,
year = {2025},
author = {Dratwa-Kuzmin, M and Lacina, P and Wysoczanska, B and Kilinska, D and Siemaszko, J and Sobczyk-Kruszelnicka, M and Fidyk, W and Solarska, I and Nasiłowska-Adamska, B and Skowronska, P and Bieniaszewska, M and Tomaszewska, A and Basak, G and Giebel, S and Bogunia-Kubik, K},
title = {Telomere length and telomerase reverse transcriptase gene polymorphism as potential markers of complete chimerism and GvHD development after allogeneic haematopoietic stem cell transplantation.},
journal = {Journal of cancer research and clinical oncology},
volume = {151},
number = {3},
pages = {109},
pmid = {40082305},
issn = {1432-1335},
support = {2018/31/B/NZ2/03065//Narodowym Centrum Nauki/ ; },
mesh = {Humans ; *Graft vs Host Disease/genetics/etiology ; *Telomerase/genetics ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; Male ; Female ; Adult ; *Polymorphism, Single Nucleotide ; Middle Aged ; *Transplantation, Homologous ; Young Adult ; Adolescent ; Telomere/genetics ; Transplantation Chimera/genetics ; Aged ; Telomere Homeostasis/genetics ; Child ; },
abstract = {INTRODUCTION: Telomerase reverse transcriptase (TERT) is a catalytic subunit of telomerase that maintains genome stability by maintaining telomere length (TL). The massive proliferation of donor cells in the recipient's body for engraftment results in accelerated telomere shortening. Genetic variability within the TERT gene affects telomerase activity, and was shown to influence of haematopoietic stem cell transplantation (HSCT) outcome. In the present study, we aimed to analyse the effect of recipient and donor TL and TERT single nucleotide polymorphism (SNP) on the occurrence of post-HSCT complications.<br><br>METHODS: Our study included 120 recipient-donor pairs. TERT promoter (TERTp) SNP (rs2853669) SNP variant was detected with the use of the LightSNiP typing assay employing real-time polymerase chain reaction (PCR) amplifications. Telomere length measurements were performed using qPCR test kits (ScienCell's Absolute Human Telomere Length Quantification qPCR Assay Kit [AHTLQ], Carlsbad, CA, USA).<br><br>RESULTS: The presence of TERTp rs2853669 T allele in the recipient was associated with a higher risk for acute graft-versus-host-disease (aGvHD) manifestation (p&#x2009;=&#x2009;0.046) and a significantly shorter aGvHD-free survival (p&#x2009;=&#x2009;0.041). The latter association was further confirmed in a Cox proportional hazards model (p&#x2009;=&#x2009;0.043). However, no statistically significant association between telomere length and post-transplant complications was observed. Furthermore, we found that shorter TL characterized donors of patients with late complete chimerism at 180&#xa0;day after HSCT (p&#x2009;=&#x2009;0.011).<br><br>CONCLUSION: Our results suggest that recipient allele TERTp rs2853669 T is a marker of unfavourable outcome in the context of aGvHD. Shorter TL in donors could be associated with later achievement of complete chimerism.},
}
@article {pmid40080344,
year = {2025},
author = {Alsurhi, TN and Shalaby, A and Al-Sinawi, S and Mabruk, M},
title = {Assessment of telomeres expression in melanoma and cutaneous squamous cell carcinoma: correlation with clinical parameters.},
journal = {Clinical &amp; translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico},
volume = {},
number = {},
pages = {},
pmid = {40080344},
issn = {1699-3055},
support = {IG/MED/ALIE/22/01//Sultan Qaboos University/ ; },
abstract = {BACKGROUND AND PURPOSE: The expression of the hTERT component of the human telomerase is elevated in different types of malignancies, including skin cancer. Early diagnosis of malignant melanoma is necessary to improve the prognosis of the disease. Although there are many diagnostic biomarkers for malignant melanoma, none is accurate, specific, and sensitive. The aim of the present study is to evaluate the expression rate and patterns of the hTERT component of human telomerase in melanoma and to compare this with squamous cell carcinoma as a common non melanoma skin cancer to investigate the potential of using telomerase as a molecular biomarker for the early diagnosis of this tumor. Additionally, the study compared the telomerase expression in these two tumor types with varying clinicopathological parameters.<br><br>METHODS: In this retrospective observational study, a total of 348 formalin-fixed paraffin-embedded tissue microarrays samples consisting of cutaneous melanoma (n = 189), squamous cell carcinoma (n = 115), and normal human skin samples (n = 44) were analyzed by immunohistochemistry for the expression of the hTERT component of human telomerase.<br><br>RESULTS: Out of 189 melanoma cases, 97 (51.3%) showed positive telomerase expression in contrast to detection of telomerase expression only in 3 out of 115 (2.6%) squamous cell carcinoma tissue samples. The telomerase was expressed only in 5 out of 44 normal human skins.<br><br>CONCLUSION: Our data indicate that telomerase expression is significantly more pronounced in melanoma compared to squamous cell carcinoma. These findings may support the potential utilization of telomerase as a biomarker for early diagnosis and monitoring of melanoma which can lead to timely treatment and enhances a better outcome.},
}
@article {pmid40079752,
year = {2025},
author = {Lee, SH and Song, DS and Kim, UC and Jee, SH and Lee, K},
title = {The causal relationship between telomere length and cancer risk: A two-sample Mendelian randomization.},
journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {},
number = {},
pages = {},
doi = {10.1158/1055-9965.EPI-24-1168},
pmid = {40079752},
issn = {1538-7755},
abstract = {BACKGROUND: Telomere length shortens with age and is associated with an increased risk of numerous chronic diseases. However, the causal direction between telomere length and cancer risk remains uncertain. This study aimed to assess the causal impact of telomere length on cancer risk using Mendelian randomization(MR) analysis.<br><br>METHODS: Genome-wide association studies(GWAS) from Singapore and China data, the Korean Cancer Prevention Study(KCPS)-II, the Korean Genome Epidemiologic Study(KoGES), and the Biobank of Japan(BBJ) were utilized. A two-sample MR study was performed using summary-level GWAS data from individuals of East Asian ancestry. Single nucleotide polymorphism(SNPs) associated with telomere length were used as instrumental variables.<br><br>RESULTS: Longer telomere length per 1SD increase due to germline genetic variants was associated with a higher risk of site-specific cancer. In the KCPS-II and KOGES, the strongest association was observed with thyroid cancer[OR 2.49(95%CI, 1.79-3.47), 2.27(1.49-3.46)], followed by lung cancer [OR 2.19(95%CI, 1.60-3.08) and 1.45(1.12-1.87)]. Similar results were observed in BBJ, with OR 2.92(95%CI, 1.75-4.88) for thyroid cancer and 2.04(1.41-2.94) for lung cancer. In histological subgroup analysis of KCPS-II, a significant relationship was found with lung adenocarcinoma [(OR 2.26(95%CI, 1.55-3.31)] but not with lung squamous cell carcinoma(1.21, 0.47-3.06). After removing outlier SNPs in the radial MR analysis, significant associations were identified for both lung adenocarcinoma [(OR 1.88(95%CI, 1.25-2.82)] and lung squamous cell carcinoma (2.29,1.05-4.98).<br><br>CONCLUSION: Our findings suggest that longer telomere length increases the risk of various cancers in East Asian populations.<br><br>IMPACT: Genetically determined longer telomere length may contribute to a risk of certain cancers.},
}
@article {pmid40075126,
year = {2025},
author = {Figueroa, D and Al Mamun, MM and Jung, DK and Li, G and Tan, ST and Jamshed, F and Butzin-Dozier, Z and Mertens, AN and Lin, J and Pitchik, HO and Parvin, K and Silvera, A and Fernald, LCH and Arnold, BF and Ali, S and Shoab, AK and Famida, SL and Akther, S and Rahman, MZ and Hossen, MS and Mutsuddi, P and Rahman, M and Unicomb, L and Kariger, P and Stewart, CP and Hubbard, AE and Benjamin-Chung, J and Dhabhar, FS and Luby, SP and Colford, JM and Naved, RT and Lin, A},
title = {Maternal experience of intimate partner violence, maternal depression, and parental stress are not associated with child telomere length in Bangladesh.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {8499},
pmid = {40075126},
issn = {2045-2322},
support = {OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; OPPGD759//Bill and Melinda Gates Foundation/ ; K01AI136885//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; Bangladesh/epidemiology ; Female ; Male ; *Stress, Psychological ; *Intimate Partner Violence/psychology ; *Depression/epidemiology/genetics ; Infant ; Adult ; Child, Preschool ; Mothers/psychology ; Pregnancy ; Telomere/genetics ; Telomere Shortening ; Rural Population ; },
abstract = {Shorter telomere length (TL) is associated with an increased risk for developing chronic or age-related diseases in adults. The process of telomere shortening is accelerated in response to stress and is well characterized in adult populations from high-income countries. Prior studies suggest the relationship between stress, shorter TL, and disease risk initiates in early life. Nested within the WASH Benefits Bangladesh trial, we examined associations between parental stressors, including maternal exposure to intimate partner violence (IPV), maternal depressive symptoms, and parental perceived stress, and child TL in rural Bangladesh. We measured whole blood relative TL in 660 children at median age 14 months and 702 children at median age 28 months. We estimated mean differences between the 25th and 75th percentile or absence and presence of each exposure using generalized additive models. IPV during pregnancy was associated with more TL attrition between 14 and 28 months (- 0.32 (95% CI - 0.64, - 0.01), p-value 0.05). This association was not significant after correction for multiple comparisons. Other parental psychosocial stressors were not associated with child TL outcomes at 14 or 28 months of age in rural Bangladesh. Telomere biology during early-life development may vary across settings.},
}
@article {pmid40072904,
year = {2025},
author = {Han, H and Salinas, N and Barbey, CR and Jang, YJ and Fan, Z and Verma, S and Whitaker, VM and Lee, S},
title = {A telomere-to-telomere phased genome of an octoploid strawberry reveals a receptor kinase conferring anthracnose resistance.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf005},
pmid = {40072904},
issn = {2047-217X},
support = {#2022-51181-38328//National Institute of Food and Agriculture/ ; //Rural Development Administration/ ; },
mesh = {*Fragaria/genetics/microbiology ; *Telomere/genetics ; *Genome, Plant ; *Disease Resistance/genetics ; *Plant Diseases/genetics/microbiology ; Plant Proteins/genetics ; Polyploidy ; Colletotrichum/pathogenicity/genetics ; Haplotypes ; },
abstract = {BACKGROUND: Cultivated strawberry (Fragaria xananassa Duch.), an allo-octoploid species arising from at least 3 diploid progenitors, poses a challenge for genomic analysis due to its high levels of heterozygosity and the complex nature of its polyploid genome.<br><br>RESULTS: This study developed the complete haplotype-phased genome sequence from a short-day strawberry, 'Florida Brilliance' without parental data, assembling 56 chromosomes from telomere to telomere. This assembly was achieved with high-fidelity long reads and high-throughput chromatic capture sequencing (Hi-C). The centromere core regions and 96,104 genes were annotated using long-read isoform RNA sequencing. Using the high quality of the haplotype-phased reference genome, FaFB1, we identified the causal mutation within the gene encoding Leaf Rust 10 Disease-Resistance Locus Receptor-like Protein Kinase (LRK10) that confers resistance to anthracnose fruit rot (AFR). This disease is caused by the Colletotrichum acutatum species complex and results in significant economic losses in strawberry production. Comparison of resistant and susceptible haplotype assemblies and full-length transcript data revealed a 29-bp insertion at the first exon of the susceptible allele, leading to a premature stop codon and loss of gene function. The functional role of LRK10 in resistance to AFR was validated using a simplified Agrobacterium-based transformation method for transient gene expression analysis in strawberry fruits. Transient knockdown and overexpression of LRK10 in fruit indicate a key role for LRK10 in AFR resistance in strawberry.<br><br>CONCLUSIONS: The FaFB1 assembly along with other resources will be valuable for the discovery of additional candidate genes associated with disease resistance and fruit quality, which will not only advance our understanding of genes and their functions but also facilitate advancements in genome editing in strawberry.},
}
@article {pmid40070565,
year = {2025},
author = {Song, Z and Yu, W and Yin, X},
title = {Identification of telomere-related gene subtypes and prognostic signatures in osteosarcoma.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1545913},
doi = {10.3389/fphar.2025.1545913},
pmid = {40070565},
issn = {1663-9812},
abstract = {BACKGROUND: Osteosarcoma (OS) is the prevalent primary bone cancer, with a high proclivity for local invasion and metastasis. Previous studies have indicated that telomeres are closely related to prognosis of cancer, but the significance of telomere-related features in OS remains uncertain. Thus, the goal of this work is to identified telomere-related subtypes based on the telomere-related genes (TRGs).<br><br>METHODS: The data of OS was collected from TARGET and Gene Expression Omnibus databases. Firstly, we identified the subtypes mediated by TRGs in OS. Subsequently, we analyzed the immune characteristics of telomeres-related subtypes in OS. Moreover, we built a telomere-related signature via univariate and LASSO Cox regression analyses, and analyzed the correlation of telomere-related signature with TME. Finally, we analyzed the expression of hub TRGs in OS.<br><br>RESULTS: We discovered that TRGs could distinguish OS patients into two telomeres-related subtypes (C1 and C2). The survival rate of OS patients in C2 was inferior to that of patients in C1. The scores of stromal, immune and ESTIMATES were observably increased, and tumor purity was decreased in C1 subtypes compared to C2 subtypes. Differentially expressed genes between C1 and C2 were highly enriched in immune-related pathways. Moreover, C1 and C2 subtypes had different immune characteristic. Furthermore, a telomere prognostic model including six genes (PDK2, PPARG, MORC4, SP110, TERT and MAP3K5) was established to predict the prognosis of OS patients. High-risk group was correlated with inferior prognosis of OS patients, and risk score model was correlated with TME. Finally, we discovered that expression of PDK2, PPARG, MORC4, SP110, TERT and MAP3K5 was significantly decreased in OS cells.<br><br>CONCLUSION: In conclusion, our study has uncovered the importance of TRGs in defining distinct subtypes of OS with different survival outcomes and immune contexts. The telomere-related signature we developed may serve as a valuable tool for prognosis prediction and could inform future therapeutic strategies targeting the TME in OS.},
}
@article {pmid40069335,
year = {2025},
author = {Rong, J and Liu, Q and Zhang, T and Lu, Y and Ye, Z and Teng, K and Luo, L and Wu, S and Zhao, L and Jin, W and Guan, Q and Li, Y and Qin, J and Cai, J and Zhang, Z},
title = {Associations of essential trace metals with telomere length in general population: a cross-sectional study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {8387},
pmid = {40069335},
issn = {2045-2322},
support = {AA22096026//The study was supported by the Major Science and Technology Projects in Guangxi/ ; 2019GXNSFGA245002//the Guangxi Natural Science Foundation for Innovation Research Team/ ; 82260629//the National Natural Science Foundation of China/ ; 81960583//he National Natural Science Foundation of China/ ; 20220120-2//Innovation Platform and Talent Plan in Guilin/ ; 2022-GKLEH-02//Xinghu Scholars Program of Guangxi Medical University&#xff0c;the Open Project Program of Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University/ ; KLLAD202304//Open Project of Key Laboratory of Longevity and Aging-related Diseases(Guangxi Medical University), Ministry of Education/ ; },
mesh = {Humans ; Middle Aged ; Male ; Female ; Cross-Sectional Studies ; Adult ; *Telomere ; *Trace Elements/blood ; Aged ; *Telomere Homeostasis ; Leukocytes/metabolism ; },
abstract = {This study investigated the relationship between essential plasma metals (Co, Cr, Cu, Mn, Mo, Se, Zn) and telomere length in 2,194 Chinese adults aged ≥ 30 years. Metal concentrations were measured using ICP-MS, and leukocyte relative telomere length (rTL) was assessed by qPCR. In the elderly, Cr and Mn were significantly positively correlated with rTL, while Mo, Zn, and Cu showed negative correlations. In the 30-59 age group, the overall metal mixture was significantly negatively associated with rTL (estimate = -0.069, P = 0.003), with Zn as the dominant contributor. In the elderly, the metal mixture was positively associated with rTL (estimate = 0.040, P = 0.031), with Cr and Mn as main contributors. The findings highlight the importance of maintaining adequate Cr and Mn levels in older adults, and the potential adverse impact of Cu, Mo, and Zn on telomere length.},
}
@article {pmid40068763,
year = {2025},
author = {Akopyan, K and Younis, M and Emtiazjoo, AM and Gries, C and Khamooshi, P and Rackauskas, M and Saha, BK},
title = {Short Telomere Syndrome in a patient with Primary Sjögren's Syndrome related Interstitial Lung Disease.},
journal = {The American journal of the medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.amjms.2025.03.003},
pmid = {40068763},
issn = {1538-2990},
abstract = {Interstitial lung disease (ILD) is a known complication of Primary Sjögren's syndrome (SS). We report the case of a 56-year-old man with a history of SS (SS-A positive) who was admitted with ILD exacerbation, causing respiratory failure requiring extracorporeal life support. Given the family history of rapidly progressive ILD and mixed connective tissue disease in his brother, the patient was tested for short telomere syndrome (STS) during hospitalization and found to have leukocyte telomere length (LTL) around the first percentile, suggesting the diagnosis of STS. The patient successfully underwent bilateral lung transplantation while being supported by venovenous extracorporeal membrane oxygenation (VV-ECMO). As STS has been associated with the development of ILD, the coexistence of STS and SS in our patient represents a unique scenario. This case also raises awareness of the connection between other connective tissue diseases (CTDs) and STS in patients diagnosed with ILD.},
}
@article {pmid40067965,
year = {2025},
author = {Thanaraj, TA and Abu-Farha, M and Albatineh, AN and Channanath, A and Melhem, M and Chandy, B and Anoop, E and Abubaker, J and Al-Mulla, F},
title = {Impact of Ethnicity on the Relationship Between Telomere Length and Metabolic Markers - a Multi-Ethnic Study from Kuwait.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1210/clinem/dgaf164},
pmid = {40067965},
issn = {1945-7197},
abstract = {OBJECTIVE: Telomere plays a critical role in maintaining genomic stability, and its length serves as a marker of cellular aging. Emerging evidence projects telomere length as a clinical risk factor for metabolic diseases. Our current study examines the associations between telomere length and demographic factors including metabolic health in a multi-ethnic cohort to provide insight into the impact of ethnicity on the potential use of telomere length as a biomarker for assessing diabetes risk.<br><br>METHODS: The cross-sectional study cohort comprised 2,083 individuals of Arab, South Asian, or Southeast Asian descent living in Kuwait. Telomere lengths were measured from peripheral venous blood DNA using qPCR-based techniques. Associations between telomere length and metabolic indicators (including BMI, being diabetic, HbA1c, FBG, and HOMA-IR) were analyzed using Spearman correlation and quantile regression, adjusting for covariates.<br><br>RESULTS: South Asian and Southeast Asian participants had significantly higher median telomere lengths than Arabs. Median telomere lengths varied significantly across sex, age tertiles, ethnicity, being diabetic, BMI, and HOMA-IR scores. Telomere length was negatively associated with being male (&#x3b2;=-0.49, 95% CI:[-0.85, -0.13]), diabetic (&#x3b2;=-0.77, 95% CI:[-1.25, -0.29]), age (&#x3b2;=-0.06, 95% CI:[-0.08, -0.04]), HOMA-IR (&#x3b2;=-1.01, 95% CI:[-1.43, -0.575]), BMI (&#x3b2;=-0.11, 95% CI:[-0.14, -0.083]), and HbA1c (&#x3b2;=-0.213, 95% CI:[-0.33, -0.096]). Negative correlations between telomere lengths and TG, HbA1c, FBG, insulin, and HOMA-IR levels were more highly significant in South Asians than in Arabs and Southeast Asians.<br><br>CONCLUSION: Our study underlines the significant influence of ethnicity on the the interplay between telomere length and metabolic health, and emphasizes the need to incorporate ethnic background when relating telomere biology to metabolic disorders. It further highlights the potential to incorporate telomere length into clinical risk factors for diabetes.},
}
@article {pmid40065531,
year = {2025},
author = {Chevalier, R and Murcia Pienkowski, V and Jullien, N and Caron, L and Pinard, PV and Magdinier, F and Robin, JD},
title = {Telomere Position Effect-Over Long Distances Acts as a Genome-Wide Epigenetic Regulator Through a Common Alu Element.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70027},
doi = {10.1111/acel.70027},
pmid = {40065531},
issn = {1474-9726},
support = {Inserm-First steps program UTelMe//Institut National de la Sant&#xe9; et de la Recherche M&#xe9;dicale/ ; A*Midex - p&#xe9;pini&#xe8;re d'excellence//Aix-Marseille Universit&#xe9;/ ; Institute MarMaRa AMX-19-IET007//Aix-Marseille Universit&#xe9;/ ; },
abstract = {Among epigenetic modifiers, telomeres represent attractive modulators of the genome in part through position effects. Telomere Position Effect-Over Long Distances (TPE-OLD) modulates gene expression by changes in telomere-dependent long-distance loops. To gain insights into the molecular mechanisms of TPE-OLD, we performed a genome-wide transcriptome and methylome analysis in proliferative fibroblasts and myoblasts or differentiated myotubes with controlled telomere lengths. By integrating omics data, we identified a common TPE-OLD dependent cis-acting motif that behaves as an insulator or enhancer. Next, we uncovered trans partners that regulate these activities and observed the consistent depletion of one candidate factor, RBPJ, at TPE-OLD associated loci upon telomere shortening. Importantly, we confirmed our findings by unbiased comparisons to recent Human transcriptomic studies, including those from the Genotype-Tissue Expression (GTEx) project. We concluded that TPE-OLD acts at the genome-wide level and can be relayed by RBPJ bridging Alu-like elements to telomeres. In response to physiological (i.e., aging) or pathological cues, TPE-OLD might coordinate the genome-wide impact of telomeres through recently evolved Alu elements acting as enhancers in association with RBPJ.},
}
@article {pmid40064353,
year = {2025},
author = {Solh, T and Cevher, &#x15e;C},
title = {The relationship between neuropsychiatric disorders and aging: A review on telomere length, oxidative stress, and inflammation.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {115528},
doi = {10.1016/j.bbr.2025.115528},
pmid = {40064353},
issn = {1872-7549},
abstract = {Aging is the group of time-independent changes that occur in an organism and that ultimately end in death. The relationship between aging and neuropsychiatric disorders is complex. Not only does the incidence of several neuropsychiatric disorders rise with age, but also these disorders are linked with premature mortality and are even thought to be syndromes of accelerated biological aging. Oxidative stress, inflammation and telomere length are factors commonly used to assess biological aging. The purpose of this review is to sum up the existing information about the state of those factors in schizophrenia, depression, bipolar disorder and anxiety disorders, and to summarize the effects of treatment on telomere length in patients with those neuropsychiatric disorders. The main focus, however, is on telomere length seeing the highly controversial study results on this biomarker in neuropsychiatric disorders. There is no scientific consensus on the state of those factors in the mentioned neuropsychiatric disorders or on the effects of treatment on telomere length, thus further research is needed where confounding variables are controlled. Regarding telomere length, it is highly important to explore whether short telomeres lead to the development of neuropsychiatric disorders or vice versa, as it carries huge clinical potential.},
}
@article {pmid40061812,
year = {2025},
author = {Jia, KH and Li, G and Wang, L and Liu, M and Wang, ZW and Li, RZ and Li, LL and Xie, K and Yang, YY and Tian, RM and Chen, X and Si, YJ and Zhang, XY and Song, FJ and Li, L and Li, NN},
title = {Telomere-to-telomere, gap-free genome of mung bean (Vigna radiata) provides insights into domestication under structural variation.},
journal = {Horticulture research},
volume = {12},
number = {3},
pages = {uhae337},
pmid = {40061812},
issn = {2662-6810},
abstract = {Mung bean (Vigna radiata), an essential annual legume, holds substantial value in global agriculture due to its short growth cycle, low input requirements, and nutritional benefits. Despite extensive domestication, the genetic mechanisms underlying its morphological and physiological evolution remain incompletely understood. In this study, we present a gap-free, telomere-to-telomere genome assembly of the mung bean cultivar 'Weilv-9', achieved through the integration of PacBio HiFi, Oxford Nanopore, and high-throughput chromosome conformation capture (Hi-C) sequencing technologies. The 500-Mb assembly, encompassing 11 chromosomes and containing 28 740 protein-coding genes, reveals that 49.17% of the genome comprises repetitive sequences. Within the genome, we found the recent amplification of transposable elements significantly impacts the expression of nearby genes. Furthermore, integrating structural variation and single-nucleotide polymorphism (SNP) data from resequencing, we identified that the fatty acid synthesis, suberin biosynthetic, and phenylpropanoid metabolic processes have undergone strong selection during domestication. These findings provide valuable insights into the genetic mechanisms driving domestication and offer a foundation for future genetic enhancement and breeding programs in mung beans and related species.},
}
@article {pmid40061142,
year = {2025},
author = {Sasmita, DMA and Permana, KG and Aryandono, T and Heriyanto, DS and Anwar, SL},
title = {Shorter telomere length as a prognostic marker for survival and recurrence in breast cancer: a systematic review and meta-analysis.},
journal = {Exploration of targeted anti-tumor therapy},
volume = {6},
number = {},
pages = {1002289},
pmid = {40061142},
issn = {2692-3114},
abstract = {BACKGROUND: Telomere length is a potential prognostic biomarker in breast cancer, but its clinical utility remains uncertain due to inconsistent findings across the literature. This systematic review and meta-analysis aims to evaluate the association between telomere length and breast cancer survival outcomes, including overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and recurrence-free survival (RFS).<br><br>METHODS: A systematic search of ten sources, including databases and publishers (JSTOR, Nature, ProQuest, PubMed, Sage Journals, ScienceDirect, Science, Scopus, Springer, and Wiley) was conducted to identify studies published up to December 31, 2023. Studies reporting associations between telomere length and survival outcomes in breast cancer patients were included. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) were extracted or calculated. Quality assessment was performed using the Newcastle-Ottawa Scale, and publication bias was evaluated using funnel plots, Egger's, and Begg's tests.<br><br>RESULTS: Nine studies involving 3,145 breast cancer patients were included. Shorter telomere length was significantly associated with increased recurrence risk (DFS/RFS) (pooled HR: 1.97; 95% CI: 1.04-3.74, P = 0.039), indicating a nearly twofold increase in risk. Trends toward worse OS (pooled HR: 1.60; 95% CI: 0.90-2.86, P = 0.110) and DSS (pooled HR: 1.09; 95% CI: 0.80-1.49, P = 0.565) were observed, but did not reach statistical significance. Additionally, shorter telomere length was significantly associated with premenopausal status (pooled OR: 1.34; 95% CI: 1.06-1.70, P = 0.01).<br><br>DISCUSSION: Shorter telomere length is associated with an increased risk of recurrence in breast cancer, highlighting its potential as a prognostic biomarker. However, further research is needed to standardize telomere length measurement methodologies and validate these findings across diverse populations and breast cancer subtypes.},
}
@article {pmid40058159,
year = {2025},
author = {Gadalla, SM and Katki, HA and Lai, TP and Auer, PL and Dagnall, CL and Bupp, C and Hutchinson, AA and Anderson, JJ and Mendez, KJW and Spellman, SR and Stewart, V and Savage, SA and Lee, SJ and Levine, JE and Saber, W and Aviv, A},
title = {Donor telomeres and their magnitude of shortening post-allogeneic haematopoietic cell transplant impact survival for patients with early-stage leukaemia or myelodysplastic syndrome.},
journal = {EBioMedicine},
volume = {114},
number = {},
pages = {105641},
doi = {10.1016/j.ebiom.2025.105641},
pmid = {40058159},
issn = {2352-3964},
abstract = {BACKGROUND: Donor selection is a key success factor in allogeneic haematopoietic cell transplant (HCT). We evaluated the potential impact of donor leucocyte telomere length (LTL) and LTL shortening in recipients at three-month post-HCT (LTL-3MS) on the two-year HCT outcomes.<br><br>METHODS: We identified a cohort of 384 HCT recipients for early-stage leukaemia or myelodysplastic syndrome in the Blood and Marrow Transplant Clinical Trial Network protocol#1202 with blood samples collected three-month post-HCT. Blood samples from respective donors were available at the Centre for International Blood and Marrow Transplant Research biorepository. We used Cox proportional hazards models for statistical analyses.<br><br>FINDINGS: A better two-year overall survival (OS) was associated with longer donor LTL (adjusted-hazard ratio [HR]&#xa0;=&#xa0;0.60, 95% confidence interval [CI]&#xa0;=&#xa0;0.37-0.96, for LTL &#x2265;6.7&#xa0;kb vs LTL< 6.7&#xa0;kb, p&#xa0;=&#xa0;0.03), and higher LTL-3MS (HR&#xa0;=&#xa0;0.52, 95% CI&#xa0;=&#xa0;0.34-0.80, for LTL-3MS&#xa0;&#x2265;&#xa0;230 vs&#xa0;<&#xa0;230 bp, p&#xa0;=&#xa0;0.003). Longer donor LTL was associated with a lower risk of non-relapse mortality (NRM; HR&#xa0;=&#xa0;0.48, p&#xa0;=&#xa0;0.05), while higher LTL-3MS was associated with lower relapse risk (HR for relapse risk&#xa0;=&#xa0;0.53, p&#xa0;=&#xa0;0.008). The adjusted 2-year cumulative risk of all-cause mortality was reduced by about half for patients with both donor LTL &#x2265;6.7&#xa0;kb and LTL-3MS&#xa0;&#x2265;&#xa0;230 bp vs patients with neither characteristic (21% vs 41%, respectively; p&#xa0;<&#xa0;0.0001).<br><br>INTERPRETATION: Selection of donors with longer LTL may improve HCT outcomes. Limited LTL shortening in recipients post-HCT may guide relapse prediction.<br><br>FUNDING: The NCI intramural research program and NIH grant U01AG066529.},
}
@article {pmid40057798,
year = {2025},
author = {Kasrineh, FA and Esmaeili, OS and Tavakoli, T and Khalili, P and Rajabi, Z and Vatankhah, H and Hajizadeh, MR and Mahmoodi, M and Hakimi, H and Jalali, Z},
title = {Prenatal irisin is inversely related to the term placental telomere length.},
journal = {BMC research notes},
volume = {18},
number = {1},
pages = {102},
pmid = {40057798},
issn = {1756-0500},
mesh = {Humans ; Female ; *Fibronectins/blood/metabolism ; Pregnancy ; Adult ; *Placenta/metabolism ; *Telomere/metabolism ; Young Adult ; Adolescent ; Infant, Newborn ; Biomarkers/blood ; Oxidative Stress ; Glutathione Peroxidase/blood/metabolism ; Superoxide Dismutase/blood/metabolism ; Telomere Homeostasis/physiology ; Cohort Studies ; },
abstract = {Irisin is a myokine mainly produced by skeletal muscle that impacts the body's systemic metabolism. It is connected to aging, telomere length, and oxidative stress markers in human adults and in vitro. The serum irisin concentration increases during pregnancy and has been linked to some birth outcomes like macrosomia. On the other hand, its inverse relation with the chance of pregnancy disorders like preeclampsia and gestational diabetes suggests a protective role for this myokine in pregnancy. It is suggested that irisin may exert its impact on pregnancy by affecting the placenta, which has not been studied yet. Here, we questioned whether prenatal serum irisin is related to placental markers, including telomere length and antioxidant activity. Research has shown that the status of these markers at birth can predict the predisposition to some chronic diseases later in life. We included 80 pregnant mothers (17-41 years old) and newborn dyads randomly selected from the enrolled participants of the Rafsanjan Birth Cohort Study (one of the five district areas of the PERSIAN birth cohort studies), who delivered at the Nik-Nafs Maternity Hospital in Rafsanjan in 2022. Irisin levels were measured in the mother's blood serum in pregnancy using ELISA. The relative telomere length and the GPX and SOD enzyme activities were measured in the term placenta using real-time PCR and colorimetric assays, respectively. We found an inverse relationship between the serum irisin levels during pregnancy and relative telomere length in the term placenta. Irisin level was not significantly associated with the activity of SOD and GPX enzymes. Therefore, our data does not support the protective role of prenatal irisin on the placental telomere shortening and oxidative stress. Future studies are warranted to assess more placental markers in relation to pregnancy irisin levels.},
}
@article {pmid40056294,
year = {2025},
author = {Chen, XB and Wang, L and Zhu, PY},
title = {Association between leukocyte telomere length and renal cell carcinoma: insight from Mendelian randomization study.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {285},
pmid = {40056294},
issn = {2730-6011},
abstract = {BACKGROUND: To investigate whether leukocyte telomere length (LTL) causally influences renal cell carcinoma (RCC) risk, this study applied Mendelian randomization (MR) analysis. Prior research examining LTL as a potential biomarker for RCC risk has yielded inconsistent findings.<br><br>METHODS: We obtained summary-level LTL data from the UK Biobank genome-wide association study (n&#x2009;=&#x2009;472,174) and gathered RCC data from both the FinnGen Consortium (n&#x2009;=&#x2009;289,360) and the International Agency for Research on Cancer (IARC) (n&#x2009;=&#x2009;13,230). To estimate odds ratios (OR) and 95% confidence intervals (CI), we primarily used the inverse-variance-weighted (IVW) method. We assessed potential heterogeneity and horizontal pleiotropy through Cochran's Q test, MR-PRESSO, and MR-Egger. We then integrated the estimates from these sources using random-effects meta-analysis techniques.<br><br>RESULTS: Within the FinnGen Consortium, an increase in the genetically predicted LTL corresponds to an elevated risk of RCC development (IVW OR&#x2009;=&#x2009;2.35; 95% CI 1.83-3.01; P&#x2009;=&#x2009;2.07&#x2009;&#xd7;&#x2009;10[-11]). This finding aligns with the outcomes observed in male patients within the IARC dataset (OR&#x2009;=&#x2009;1.69; 95% CI 1.21-2.37; P&#x2009;=&#x2009;0.002), although a consistent trend was not readily apparent among female patients. Sensitivity analyses validated the robustness of these findings. Upon pooling the results, a positive association between LTL and RCC risk was substantiated (OR&#x2009;=&#x2009;1.96; 95% CI 1.52-2.52, p&#x2009;=&#x2009;1.79&#x2009;&#xd7;&#x2009;10[-7]). Furthermore, the MR Steiger test demonstrated that LTL was causal for RCC, not vice-versa, with P&#x2009;<&#x2009;0.001.<br><br>CONCLUSION: Genetically determined longer LTL may increases RCC risk. Nevertheless, further research is essential to clarify the mechanisms driving this relationship.},
}
@article {pmid40057088,
year = {2025},
author = {Zhou, T and Huang, XJ and Cheng, YJ and Zhang, XY and Wang, XJ and Li, ZH},
title = {Telomere-to-telomere genome and multi-omics analysis of Prunus avium cv. Tieton provides insights into its genomic evolution and flavonoid biosynthesis.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {141809},
doi = {10.1016/j.ijbiomac.2025.141809},
pmid = {40057088},
issn = {1879-0003},
abstract = {The European sweet cherry (Prunus avium) is highly valued for its superior quality, delectable taste, and robust stress resistance, leading to its extensive cultivation in the world. However, the previous incomplete genome assemblies have impeded its evolution and genetic regulation studies. In this study, we generated a Telomere-to-Telomere gap-free genome assembly of P. avium cv. Tieton, using advanced sequencing technologies. The assembled genome comprises eight pseudochromosomes with a genome size of 342.23 Mb and a contig N50 of 40.66 Mb. Comparative genomic analysis identified several unique stress resistance-related genes, possibly associated with the species' environmental adaptation. The integrative analyses of genomics, transcriptomes and metabolomes identified some key structural genes and metabolites crucial to flavonoid biosynthesis of sweet cherry. Our analyses revealed that 85 flavonoid metabolites, which are highly differentially accumulated among five tissues (flesh, stem, leaf, bud, and seed) of cherry. Interestingly, eight abundant flavonoids (Narcissoside, Typhaneoside, Myricetin 3-0-galactoside, Diosmin, Neohesperidin, Liquiritin apioside, 5,6,7-Trimethoxyflavone and Oroxin B) were highly accumulated in cherry flesh tissues. The gene-metabolite correlation analysis revealed that seven genes (HTC8, HTC6, CYP75B1_9, CYP75B1_10, 4CL1, DFR1, and FLS1) significantly regulated flavonoid accumulation in cherry flesh. Additionally, some structural genes (4CL6, PAL3, CYP75A2, F3H1, CYP75B1_8, and CYP75B1_10) were identified in the flavonoid biosynthetic pathway and were highly expressed, aligning with high flavonoid metabolite content in cherry flesh. These identified genes and metabolites are likely pivotal in conferring sweet cherry's stress resistance and high-quality traits. These findings offer deep insights into the mechanisms of genomic evolution and flavonoid biosynthesis, which also lay a solid foundation for further function genomics studies and breeding improvement in cherry.},
}
@article {pmid40048909,
year = {2025},
author = {Qin, N and Sheng, Y and Shao, Y and Liao, Q and Huang, D and Li, J and Li, J and Liu, H and Peng, Y and Qiu, X and Li, H},
title = {Associations between prenatal phthalate exposure and newborn telomere length: Effect modification by infant sex.},
journal = {Ecotoxicology and environmental safety},
volume = {292},
number = {},
pages = {117977},
doi = {10.1016/j.ecoenv.2025.117977},
pmid = {40048909},
issn = {1090-2414},
abstract = {BACKGROUND: Phthalates are endocrine-disrupting chemicals (EDCs) ubiquitously present in the environment. There are limited studies on the impact of phthalate exposure during the gestational period on neonatal telomere length.<br><br>OBJECTIVES: The aim of this study is to investigate the correlation between maternal serum phthalate concentrations in early pregnancy and neonatal telomere length and whether this correlation exhibits sex-specificity.<br><br>METHODS: Between September 2015 and April 2018, 474 pregnant women were selected from the Guangxi Zhuang Birth Cohort (GZBC). Maternal serum samples from early pregnancy were measured for levels of five phthalates and four phthalate metabolites. Umbilical cord blood samples were collected to measure telomere length. The correlations between prenatal phthalate exposure and infant telomere length were assessed using multiple linear regression, Bayesian kernel machine regression (BKMR), quantile g-computation (qg-comp), and restricted cubic spline (RCS) models.<br><br>RESULTS: Multiple linear regression analyses revealed that per 2.7-fold increase in the concentration of butyl benzyl phthalate (BBP) and mono-ethyl phthalate (MEP), neonatal telomere length decreased by 2.66&#x202f;% (95&#x202f;% CI: -5.20&#x202f;%, -0.05&#x202f;%) and 3.43&#x202f;% (95&#x202f;% CI: -6.46&#x202f;%, -0.30&#x202f;%), respectively. Conversely, per 2.7-fold increase in di-butyl phthalate (DBP) concentration corresponded to a 3.01&#x202f;% (95&#x202f;% CI: 0.19&#x202f;%, 5.91&#x202f;%) increase in neonatal telomere length. Sex-stratified analyses demonstrated that BBP (percent change: -3.60&#x202f;%; 95&#x202f;% CI: -6.91&#x202f;%, -0.18&#x202f;%); mono-butyl phthalate (MBP) (percent change: -4.13&#x202f;%; 95&#x202f;% CI: -7.14&#x202f;%, -1.01&#x202f;%) and MEP (percent change: -7.66&#x202f;%, 95&#x202f;% CI: -11.53&#x202f;%, -3.62&#x202f;%) were inversely associated with neonatal telomere length in female infants only. Neonatal sex significantly modified the association between MEP exposure and neonatal telomere length (P-value for interaction = 0.018). Phthalate mixture was inversely associated with neonatal telomere length in female infants but not in male infants in qg-comp and BKMR models.<br><br>CONCLUSION: Our study suggests that maternal exposure to phthalates is linked to shorter telomere length in neonates, especially in female infants.},
}
@article {pmid40044947,
year = {2025},
author = {Huang, X and Huang, L and Lu, J and Cheng, L and Wu, D and Li, L and Zhang, S and Lai, X and Xu, L},
title = {The relationship between telomere length and aging-related diseases.},
journal = {Clinical and experimental medicine},
volume = {25},
number = {1},
pages = {72},
pmid = {40044947},
issn = {1591-9528},
support = {2023C03166//the Department of Science and Technology of Zhejiang Province/ ; 2023C03166//the Department of Science and Technology of Zhejiang Province/ ; 2023C03166//the Department of Science and Technology of Zhejiang Province/ ; 4285C50223204005//Hangzhou Normal University/ ; 4285C50223204005//Hangzhou Normal University/ ; },
mesh = {Humans ; *Aging/genetics ; *Telomere Shortening ; *Telomere ; Cellular Senescence/genetics ; Telomere Homeostasis ; },
abstract = {The intensifying global phenomenon of an aging population has spurred a heightened emphasis on studies on aging and disorders associated with aging. Cellular senescence and aging are known to be caused by telomere shortening. Telomere length (TL) has emerged as a biomarker under intense scrutiny, and its widespread use in investigations of diseases tied to advancing age. This review summarizes the current knowledge of the association between telomeres and aging-related diseases, explores the important contribution of dysfunctional telomeres to the development and progression of these diseases, and aims to provide valuable insights for the development of novel therapeutic strategies.},
}
@article {pmid40043570,
year = {2025},
author = {Gonçalves, JPB and Chile, T and de Paula, VJR and Teixeira, MZ and Ribeiz, SR and Schalling, M and Busatto Filho, G and Lucchetti, G and Vallada, H},
title = {Exploring the relationship between religiosity and telomere length in older individuals.},
journal = {Journal of psychosomatic research},
volume = {191},
number = {},
pages = {112085},
doi = {10.1016/j.jpsychores.2025.112085},
pmid = {40043570},
issn = {1879-1360},
abstract = {OBJECTIVES: Although telomere length is an established marker of biological aging, the impact of religious beliefs on telomere length remains uncertain.<br><br>METHODS: This cross-sectional study investigated the relationship between religiosity and telomere length among senior Brazilians, aged 60 and older. The study examined the association between organizational, non-organizational, and intrinsic religiosity with telomere length, adjusting for sociodemographic, mental, physical health, and medication. Hierarchical linear regression models were used.<br><br>RESULTS: 821 participants (62.2&#xa0;% female, mean age 68.9&#xa0;years, SD&#xa0;=&#xa0;6.48) were studied. Female gender and younger age were linked to longer telomeres, but no significant associations were found between religious beliefs and telomere length in adjusted or unadjusted models.<br><br>CONCLUSIONS: This study found no evidence of an association between religiosity and telomere length among older Brazilian adults. While prior research highlights religiosity's positive health effects, its direct influence on telomere length remains unclear, warranting further exploration.},
}
@article {pmid40038488,
year = {2025},
author = {Le Bras, A},
title = {A new mouse model with human-like telomeres.},
journal = {Lab animal},
volume = {54},
number = {3},
pages = {63},
doi = {10.1038/s41684-025-01530-7},
pmid = {40038488},
issn = {1548-4475},
}
@article {pmid40035723,
year = {2025},
author = {De Benedittis, G and Latini, A and Morgante, C and Bonini, C and Cela, E and Kroegler, B and Luciano, A and Chiocchi, M and Cavalli, F and Ora, J and Rogliani, P and Novelli, G and Ciccacci, C and Chimenti, MS and Conigliaro, P and Borgiani, P},
title = {Alteration of telomere length and mtDNA copy number in interstitial lung disease associated with rheumatoid arthritis.},
journal = {Autoimmunity},
volume = {58},
number = {1},
pages = {2473741},
doi = {10.1080/08916934.2025.2473741},
pmid = {40035723},
issn = {1607-842X},
mesh = {Humans ; *Arthritis, Rheumatoid/genetics/complications ; *DNA, Mitochondrial/genetics ; Female ; Male ; *Lung Diseases, Interstitial/genetics ; Middle Aged ; *DNA Copy Number Variations ; Aged ; *Telomere/genetics ; Adult ; DNA-Binding Proteins/genetics ; Telomere Shortening ; Telomere Homeostasis/genetics ; Case-Control Studies ; Gene Dosage ; },
abstract = {Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA). The inflammatory response in lung disease is characterized by severe oxidative stress, which enhances cellular senescence. Telomeric shortening and mitochondria dysregulation represent two hallmarks of cellular senescence. The maintenance of telomere length (TL) and mitochondrial DNA (mtDNA) copy number is preserved by many proteins, such as TERF1 and TFAM, respectively. Our aim was to evaluate the TL, the mtDNA copy number and the expression of two regulator gene factors in RA patients with (RA-ILD) and without lung involvement (RA-NILD). Eighty-five RA patients and 21 healthy subjects were enrolled. Relative TL, mtDNA copy number, and expression analysis of TERF1 and TFAM genes were measured using qPCR assay. All RA patients present a statistically significant telomere shortening; in particular, RA-ILD patients show shorter TL compared to both controls and RA-NILD. Patients with Usual Interstitial Pneumonia pattern show a more evident shortening of TL. Lastly, both RA-ILD and RA-NILD patients present a significant decrease in mtDNA copy number compared to controls. The analysis of regulatory genes showed an increase in TERF1 expression in RA patients compared to controls, also after stratification in the two subgroups, and a decrease in TFAM expression in RA patients compared to controls. These results show that the alteration of TL and mtDNA copy number in RA patients is more evident in the presence of ILD. The hypothesis is that, in these patients, oxidative stress could accelerate the shortening of telomeres and the decrease of mtDNA copy number.},
}
@article {pmid40029527,
year = {2025},
author = {Jebaraj, BMC},
title = {Quantification of Telomere Length in Peripheral Blood Mononuclear Cells Using Quantitative Polymerase Chain Reaction.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2909},
number = {},
pages = {257-267},
pmid = {40029527},
issn = {1940-6029},
mesh = {*Leukocytes, Mononuclear/metabolism ; Humans ; *Telomere/genetics ; *Real-Time Polymerase Chain Reaction/methods ; Telomere Homeostasis ; },
abstract = {Telomeres are crucial biomarkers of cellular aging and health, providing insights into various physiological and pathological processes. Large variety of methods are described for telomere length measurements, each with their own advantages and disadvantages. This chapter explains a quantitative polymerase chain reaction (qPCR)-based method for measuring telomere length in peripheral blood mononuclear cells (PBMCs), with special focus on ways to limit variability between qPCR run and improve comparability of telomere length values. With methodology of relative and absolute quantification, troubleshooting tips, and other guidelines, this chapter serves as a resource for researchers to benefit from this cost-effective and high-throughput assay.},
}
@article {pmid40028272,
year = {2025},
author = {Huang, W and Wang, W and Dong, TZ},
title = {Telomere Maintenance-Related Genes are Essential for Prognosis in Breast Cancer.},
journal = {Breast cancer (Dove Medical Press)},
volume = {17},
number = {},
pages = {225-239},
pmid = {40028272},
issn = {1179-1314},
abstract = {OBJECTIVE: Telomere maintenance mechanism significantly impacts the metastasis, progression, and survival of breast cancer (BC) patients. This study aimed to investigate the role of telomere maintenance-related genes (TMRGs) in BC prognosis and to construct a related prognostic model.<br><br>METHODS: Differentially expressed genes were identified from the TCGA-BC cohort, and functional enrichment analysis was conducted. TMRGs were sourced from the literature and intersected with DEGs. Candidate genes were selected using machine learning algorithms, including Lasso Cox, Random Forest, and XGBoost. Multivariate Cox regression analysis was conducted to construct a prognostic model and identify hub genes. Subsequent analyses included survival analysis, gene set enrichment analysis (GSEA), immune infiltration analysis, and drug sensitivity analysis of the hub genes. Finally, in vitro experiments were conducted to validate the expression of the hub genes.<br><br>RESULTS: A total of 1329 differentially expressed TMRGs were analyzed, with 128 significantly associated with overall survival. Machine learning identified 7 prognosis-related TMRGs: MECP2, PCMT1, PFKL, PTMA, TAGLN2, TRMT5, and XRCC4. These genes were used to construct a prognostic model, with MECP2, PCMT1, PFKL, TAGLN2, and XRCC4 as harmful factors, while PTMA and TRMT5 were protective. The model demonstrated a significant prognostic value (AUC: 0.81, 0.72, 0.69 for 1-, 3-, and 5-year, respectively). Survival analysis confirmed the prognostic relevance of these genes, and GSEA highlighted their roles in oxidative phosphorylation, glycolysis, and PI3K/AKT/mTOR signaling.<br><br>CONCLUSION: The study identified 7 key TMRGs with significant prognostic value in BC. The constructed model effectively stratifies patient risk, providing a foundation for targeted therapies and personalized treatment strategies.},
}
@article {pmid40027133,
year = {2025},
author = {Zheng, JH and Shi, D and Chen, YJ and Liu, JP and Zhou, Z},
title = {Develop a prognostic and drug therapy efficacy prediction model for hepatocellular carcinoma based on telomere maintenance-associated genes.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1544173},
pmid = {40027133},
issn = {2234-943X},
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) poses a substantial global health challenge because of its grim prognosis and limited therapeutic options. Telomere maintenance mechanisms (TMM) significantly influence cancer progression, yet their prognostic value in HCC remains largely unexamined. This research aims to establish a telomere maintenance-associated genes(TMGs)-based prognostic model using transcriptomic and clinical data to evaluate its effectiveness in predicting patient outcomes in HCC.<br><br>METHODS: The identified differentially expressed genes (DEGs) were derived from the analysis of transcriptomic and clinical information sourced from the database of the Cancer Genome Atlas (TCGA) and were cross-referenced with TMGs. Candidate risk factors were initially assessed using univariate Cox regression, subsequently followed by LASSO, and then refined through multivariate Cox regression to establish a risk prediction model. This model's predictive accuracy was validated through Kaplan-Meier(K-M) survival analysis, with external validation in the Gene Expression Omnibus (GEO) dataset. Additionally, a nomogram incorporating age and tumor stage was developed. Tumor mutation burden (TMB), immune profile, and drug sensitivity in HCC were also analyzed. Furthermore, we employed RT-PCR to confirm the expression levels of the genes related to TMGs in HepG2 cell lines.<br><br>RESULTS: A prognostic model comprising 3 core genes was constructed, with high-risk individuals showing significantly lower overall survival (OS). The association between elevated TMB and diminished survival in high-risk patients was uncovered through TMB analysis. Immune profiling indicated notable disparities in immune infiltration among these groups, with high-risk patients displaying elevated Tumor Immune Dysfunction and Exclusion (TIDE) scores, suggesting potential immune evasion.<br><br>CONCLUSION: In short, our prognosis model based on TMGs effectively categorized HCC patients using risk scores, enabling dependable prognostic forecasts and identification of potential therapeutic targets for personalized treatment in HCC management. Future studies should explore integrating this model into clinical practice to improve patient outcomes.},
}
@article {pmid40022541,
year = {2025},
author = {Aviv, A and Verhulst, S},
title = {Telomeres in Space.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70030},
doi = {10.1111/acel.70030},
pmid = {40022541},
issn = {1474-9726},
support = {1U24AG066528/NH/NIH HHS/United States ; R01ES035760/NH/NIH HHS/United States ; U01AG066529/NH/NIH HHS/United States ; #262700//Research Council of Norway/ ; },
abstract = {Recent studies have reported that the spaceflight environment lengthens leukocyte telomeres. We propose that this baffling finding reflects changes in the composition of leukocyte subsets rather than an actual increase in telomere length within individual leukocytes. Since leukocyte telomere length is associated with aging-related diseases and longevity in humans, it is crucial to understand the underlying factors driving telomere length changes in space.},
}
@article {pmid40016654,
year = {2025},
author = {Kang, K and Nie, H and Kuang, W and Li, X and Zhou, Y},
title = {A novel telomere-associated genes signature for the prediction of prognosis and treatment responsiveness of hepatocellular carcinoma.},
journal = {Biological procedures online},
volume = {27},
number = {1},
pages = {8},
pmid = {40016654},
issn = {1480-9222},
support = {1053320221933//the Graduate Student Innovation Fund of Central South University/ ; 82203353//National Natural Science Foundation of China/ ; 2022M723565//Fellowship of China Postdoctoral Science Foundation/ ; 2022JJ40851//Natural Science Foundation of Hunan Province for Youth Foundation/ ; 2021Q16//Youth Research Foundation of Xiangya Hospital, Central South University/ ; },
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent malignancy worldwide, characterized by its high malignancy and poor prognosis. Telomeres, crucial components of eukaryotic chromosomes, have been increasingly recognized for their involvement in tumorigenesis, development, and impact on the prognosis of cancer patients. However, the precise role of telomere-associated genes in HCC remains incompletely elucidated.<br><br>METHODS: The Cancer Genome Atlas (TCGA) database was utilized to download data from 374 HCC and 50 normal liver tissue samples. Differential genes were screened and intersected with 2093 telomere-related genes (TRGs) in GeneCards, resulting in the identification of 704 TRGs exhibiting survival differences. Through univariate Cox regression analysis, multivariate Cox regression analysis, and LASSO regression, a prognostic model consisting of 18 TRGs for HCC risk assessment was developed. The single-cell and spatial transcriptomics were utilized to analyze the expression and distribution of 18 TRGs in HCC. Subsequently, Mendelian randomization (MR) analysis confirmed a causal relationship between ASF1A and alcoholic HCC among the identified 18 TRGs. The expression and functional significance of ASF1A in HCC cell lines were investigated through colony formation assays, Transwell migration assays, and wound healing experiments.<br><br>RESULTS: We developed a prognostic risk model for HCC incorporating 18 TRGs. Kaplan-Meier analysis demonstrated that the overall survival (OS) rate of the high-risk group was significantly inferior to that of the low-risk group. Cox regression analysis identified age (HR&#x2009;=&#x2009;1.017, 95% CI: 1.002-1.032, P&#x2009;=&#x2009;0.03), stage (HR&#x2009;=&#x2009;1.389, 95% CI: 1.111-1.737, P&#x2009;=&#x2009;0.004), and risk score (HR&#x2009;=&#x2009;5.097, 95% CI: 3.273-7.936, P&#x2009;<&#x2009;0.001) as three independent risk factors for HCC patients. The five-year receiver operating characteristic curve (ROC) and multivariate Cox regression analysis further validated the accuracy of our model. Time-dependent ROC results revealed that the 1-year, 3-year, and 5-year AUC values were AUC&#x2009;=&#x2009;0.801, AUC&#x2009;=&#x2009;0.734, and AUC&#x2009;=&#x2009;0.690, respectively. The expression and distribution of 18 TRGs in HCC were further validated through single-cell and spatial transcriptomics data. Additionally, immune subtype analysis indicated a significantly lower proportion of C3 and C4 subtypes in the high-risk TRG group compared to the low-risk group. Meanwhile, tumor immune dysfunction and exclusion (TIDE) were significantly higher in the high-risk group than in the low-risk group. Furthermore, we observed differences in IC50 values among nine chemotherapeutic drugs across different TRG risk subtypes which partially confirmed our model's predictive efficacy for immunotherapy. Amongst these eighteen TRGs analyzed by MR analysis, ASF1A was found to be associated with alcoholic HCC pathogenesis. We further confirmed ASF1A was significant overexpression in HCC by Western blotting. We also explored it's the carcinogenic role of ASF1A in HCC via the transwell, wound healing, and clone formation experiments.<br><br>CONCLUSION: In this study, we developed a novel prognostic model comprising 18 TRGs for HCC, which exhibited remarkable accuracy in predicting HCC patients' prognosis. Additionally, through MR analysis, we have successfully established a causal relationship between ASF1A and alcoholic HCC for the first time, which also provided a new theoretical foundation for the management of alcoholic HCC.},
}
@article {pmid40016428,
year = {2025},
author = {Salgado, S and Abreu, PL and Moleirinho, B and Guedes, DS and Larcombe, L and Azzalin, CM},
title = {Author Correction: Human PC4 supports telomere stability and viability in cells utilizing the alternative lengthening of telomeres mechanism.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s44319-025-00408-6},
pmid = {40016428},
issn = {1469-3178},
}
@article {pmid40016269,
year = {2025},
author = {Zhang, K and Guo, S and Yang, S and Zhou, W and Wu, J and Zhang, X and Shi, Q and Deng, L},
title = {A telomere-to-telomere genome assembly of the protandrous hermaphrodite blackhead seabream, Acanthopagrus schlegelii.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {350},
pmid = {40016269},
issn = {2052-4463},
mesh = {Animals ; *Sea Bream/genetics ; *Genome ; *Telomere/genetics ; Male ; Female ; },
abstract = {A remarkable life cycle of the protandrous blackhead seabream (Acanthopagrus schlegelii), initiating as a male during the first two years and then naturally transforming to a female since the third year, makes this fish a valuable model for studying molecular mechanisms of sex change. Here, we constructed a gap-free telomere-to-telomere (T2T) genome assembly for a male blackhead seabream, by integration of PacBio HiFi, Ultra-long ONT and Hi-C sequencing techniques. With 97.87% of the entire sequences anchored into 24 chromosomes, this haplotypic genome assembly spans 714.98 Mb. In terms of correctness (quality value QV: 52.95) and completeness (BUSCO score: 99.9%), this chromosome-scale assembly is indeed of high quality. It has been annotated with 24,581 protein-coding genes, and predicted with low percentage (30.95%) of repetitive sequences. As the first reference T2T-level genome assembly of various protandrous fishes, it provides a valuable genetic resource for expansion of fish genomics database. It will also allow for in-depth genomic comparisons among diverse hermaphrodite vertebrates, as well as offer fundamental genome data to support extensive research on blackhead seabream.},
}
@article {pmid40015989,
year = {2025},
author = {Martin, A and Schabort, J and Bartke-Croughan, R and Tran, S and Preetham, A and Lu, R and Ho, R and Gao, J and Jenkins, S and Boyle, J and Ghanim, GE and Jagota, M and Song, YS and Li, H and Hockemeyer, D},
title = {Active telomere elongation by a subclass of cancer-associated POT1 mutations.},
journal = {Genes &amp; development},
volume = {},
number = {},
pages = {},
doi = {10.1101/gad.352492.124},
pmid = {40015989},
issn = {1549-5477},
abstract = {Mutations in the shelterin protein POT1 are associated with diverse cancers and thought to drive carcinogenesis by impairing POT1's suppression of aberrant telomere elongation. To classify clinical variants of uncertain significance (VUSs) and identify cancer-driving loss-of-function mutations, we developed a locally haploid human stem cell system to evaluate >1900 POT1 mutations, including >600 VUSs. Unexpectedly, many validated familial cancer-associated POT1 (caPOT1) mutations are haplosufficient for cellular viability, indicating that some pathogenic alleles do not act through a loss-of-function mechanism. Instead, POT1's DNA damage response suppression and telomere length control are genetically separable. ATR inhibition enables isolation of frameshift mutants, demonstrating that the only essential function of POT1 is to repress ATR. Furthermore, comparison of caPOT1 and frameshift alleles reveals a class of caPOT1 mutations that elongate telomeres more rapidly than full loss-of-function alleles. This telomere length-promoting activity is independent from POT1's role in overhang sequestration and fill-in synthesis.},
}
@article {pmid40011224,
year = {2025},
author = {Yi, J and Jiang, C and Xia, L},
title = {Mediated roles of oxidative stress and kidney function to leukocyte telomere length and prognosis in chronic kidney disease.},
journal = {Renal failure},
volume = {47},
number = {1},
pages = {2464828},
doi = {10.1080/0886022X.2025.2464828},
pmid = {40011224},
issn = {1525-6049},
mesh = {Humans ; *Oxidative Stress ; Male ; Female ; Middle Aged ; *Renal Insufficiency, Chronic/physiopathology/mortality ; *Leukocytes/metabolism ; Prognosis ; Aged ; *Glomerular Filtration Rate ; *Telomere ; *Nutrition Surveys ; Cardiovascular Diseases ; Neoplasms/mortality/genetics ; Risk Factors ; Adult ; Proportional Hazards Models ; Hypertension ; },
abstract = {BACKGROUND: Few studies have focused on the correlation between leukocyte telomere length (LTL) and cancer-related mortality or identified potential factors that mediate the relationship between LTL and mortality among chronic kidney disease (CKD) patients. Our study aimed to explore the associations between LTL and all-cause and cause-specific mortality and to identify the underlying mediators.<br><br>METHODS: CKD patients were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Cox regression analysis and restricted cubic spline analysis were used to explore the associations between LTL and all-cause or specific-cause mortality and their nonlinear connections. Stratified analyses were executed to assess the relationships among the different subgroups. The latent mediated factors were confirmed using mediation analysis. Sensitivity analyses were used to evaluate the robustness of our findings.<br><br>RESULTS: Longer LTL associated with the lower risk of all-cause mortality, cardiovascular disease (CVD) and cancer-related mortality, and U-shaped relationships were detected. Patients younger than 65&#xa0;years with greater LTL or who had hypertension had better prognoses. Age and history of hypertension were associated with LTL and overall mortality. In addition, estimated glomerular filtration rate (eGFR), albumin, and total bilirubin mediated the association, and the proportions of indirect effects were 7.81%, 3.77%, and 2.50%, respectively. Six sensitivity analyses confirmed the robustness of our findings.<br><br>CONCLUSIONS: This study revealed that LTL was a protective factor for survival among patients with CKD and emphasized the mediating roles of oxidative stress and kidney function.},
}
@article {pmid40011083,
year = {2025},
author = {Zeng, Y and Yuan, X and Zi, J and Hu, Y and Wang, X and Cheng, G and Xiong, J},
title = {Telomere length mediates the causal effects of excess adiposity on cardiovascular risk: A two-step Mendelian randomization study.},
journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD},
volume = {},
number = {},
pages = {103904},
doi = {10.1016/j.numecd.2025.103904},
pmid = {40011083},
issn = {1590-3729},
abstract = {BACKGROUND AND AIMS: Excess adiposity correlate to cardiovascular diseases, inflammation, and telomere shortening, while the latter two are associated with cardiovascular risks. Whether inflammation and telomere length mediate the excess adiposity-cardiovascular relationship is unclear.<br><br>METHODS AND RESULTS: We performed a two-step Mendelian randomization analysis utilizing data from the latest genome-wide association studies: body mass index (BMI, n&#xa0;=&#xa0;681,275), waist-to-hip ratio (WHR, n&#xa0;=&#xa0;697,734) and BMI adjusted WHR (WHRadjBMI, n&#xa0;=&#xa0;694,649), telomere length (n&#xa0;=&#xa0;472,174), C-reactive protein (n&#xa0;=&#xa0;204,402), interleukin-6 and interleukin-1 receptor antagonist (n&#xa0;=&#xa0;21,758), tumor necrosis factor-&#x3b1; (n&#xa0;=&#xa0;3454), hypertension (n&#xa0;=&#xa0;463,010), coronary artery disease (n&#xa0;=&#xa0;547,261), heart failure (n&#xa0;=&#xa0;977,323), stroke (n&#xa0;=&#xa0;446,696), ischemic stroke (n&#xa0;=&#xa0;440,328), intracerebral hemorrhage (n&#xa0;=&#xa0;343,663), aortic aneurysm (n&#xa0;=&#xa0;356,934), transient ischemic attack (n&#xa0;=&#xa0;360,692), peripheral vascular disease (n&#xa0;=&#xa0;463,010), systolic and diastolic blood pressure changes (n&#xa0;=&#xa0;757,601). We observed casual effects of excess adiposity on eight cardiovascular diseases, hypertension and blood pressure changes. Telomere length is causally associated with hypertension, blood pressure, coronary artery disease, aortic aneurysm, and intracerebral hemorrhage, mediates BMI's effect on coronary artery disease (2.41&#xa0;%) and aortic aneurysm (4.97&#xa0;%), and plays a suppressive role between WHR and systolic blood pressure changes (2.39&#xa0;%).<br><br>CONCLUSION: Telomere length mediates the causal effects of excess adiposity on the risks of coronary artery disease, aortic aneurysm, and systolic blood pressure changes.},
}
@article {pmid40008862,
year = {2025},
author = {Wąsowicz, W and Janasik, B and Reszka, E and Kasperczyk, E and Chrzanowski, J and Fendler, W},
title = {Metals (Cr, Mn, Co, Ni) concentration in the blood plasma and urine od Polish welders and telomere length as an potential indicator of toxicity of metals welding fumes exposure.},
journal = {International journal of occupational medicine and environmental health},
volume = {},
number = {},
pages = {},
doi = {10.13075/ijomeh.1896.02493},
pmid = {40008862},
issn = {1896-494X},
abstract = {OBJECTIVES: The study investigated the concentrations of metals (chromium [Cr], manganese [Mn], cobalt [Co], nickel [Ni]) in the blood plasma and urine of Polish welders exposed to these elements contained in welding dust/fumes based on the results of biological monitoring, analyze the interrelationships between these elements, and attempt to correlate these data with telomere length. It is believed that telomere length can be considered a marker of exposure, including occupational. Analysis of questionnaire surveys was also taken into consideration.<br><br>MATERIAL AND METHODS: The study included 118 male welders and 51 age-matched male controls. Metals analysis in plasma and urine were determined by ICP-MS technique. Telomere length was measured in blood genomic DNA using the qRT-PCR method.<br><br>RESULTS: Welders had significantly higher plasma levels of Cr, Ni, and Mn (p < 0.0001, respectively). Total concentrations of Cr, Ni, and Mn in the urine of pre-shift subjects were significantly higher compared to controls. Cobalt concentration in urine of exposed welders was significantly higher (p < 0.02) than in control group. Telomere length was exactly the same in the welder group compared to the control (mean &#xb1; standard deviation 0.99&#xb1;0.41 vs. 0.99&#xb1;0.52, respectively). Plasma and urine metal concentrations and telomere length were also studied in groups of welders in relation to personal protection equipment. Differences were found in plasma and urine metal concentrations according to the aspirators used. Statistically significant linear correlations were found between plasma and urine concentrations of the determined elements both before and after the work shift.<br><br>CONCLUSIONS: The findings suggest a positive relationship between Ni and Mn (end-shift) concentrations and telomere length, the effect which remained statistically significant even after adjusting for age and metabolic status. This indicates a complex interplay between metal exposure and biological aging markers. However, the relationship between exposure to welding fumes and changes in telomere length in welders requires further in-depth research. Int J Occup Med Environ Health. 2025;38(1).},
}
@article {pmid40004056,
year = {2025},
author = {Yan, B and Suen, MC and Xu, N and Lu, C and Liu, C and Zhu, G},
title = {G-Quadruplex Structures Formed by Human Telomere and C9orf72 GGGGCC Repeats.},
journal = {International journal of molecular sciences},
volume = {26},
number = {4},
pages = {},
doi = {10.3390/ijms26041591},
pmid = {40004056},
issn = {1422-0067},
support = {32071188//National Scientific Foundation of China/ ; 16101120, 161011121, AoE/M-403-16, AoE/M-401/20//Research Grants Council of the Hong Kong Special Administrative Region, China/ ; BGF.2023.019//Hong Kong University of Science and Technology, China/ ; 2021A1515220104//Guangdong Basic and Applied Basic Research Foundation, China/ ; 32301012//Young Scientists Fund of the National Natural Science Foundation of China/ ; },
mesh = {*G-Quadruplexes ; Humans ; *Telomere/genetics ; *C9orf72 Protein/genetics ; *DNA Repeat Expansion/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Frontotemporal Dementia/genetics/pathology ; },
abstract = {G-quadruplexes (G4s) are unique nucleic acid structures composed of guanine-rich (G-rich) sequences that can form diverse topologies based on the arrangement of their four strands. G4s have attracted attention for their potential roles in various biological processes and human diseases. In this review, we focus on the G4 structures formed by human telomeric sequences, (GGGTTA)n, and the hexanucleotide repeat expansion, (GGGGCC)n, in the first intron region of the chromosome 9 open reading frame 72 (C9orf72) gene, highlighting their structural diversity and biological significance. Human telomeric G4s play crucial roles in telomere retention and gene regulation. In particular, we provide an in-depth summary of known telomeric G4s and focus on our recently discovered chair-type conformation, which exhibits distinct folding patterns. The chair-type G4s represent a novel folding pattern with unique characteristics, expanding our knowledge of telomeric G4 structural diversity and potential biological functions. Specifically, we emphasize the G4s formed by the (GGGGCC)n sequence of the C9orf72 gene, which represents the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The thorough structural analysis in this review advances our comprehension of the disease mechanism and provides valuable insights into developing targeted therapeutic strategies in ALS/FTD.},
}
@article {pmid40004050,
year = {2025},
author = {Anatskaya, OV and Ponomartsev, SV and Elmuratov, AU and Vinogradov, AE},
title = {Transcriptome-Wide Insights: Neonatal Lactose Intolerance Promotes Telomere Damage, Senescence, and Cardiomyopathy in Adult Rat Heart.},
journal = {International journal of molecular sciences},
volume = {26},
number = {4},
pages = {},
doi = {10.3390/ijms26041584},
pmid = {40004050},
issn = {1422-0067},
support = {Agreement No. 075-15-2021-1075//Ministry of Science and Higher Education of the Russian Federation/ ; },
mesh = {Animals ; Rats ; *Cardiomyopathies/genetics/metabolism/pathology/etiology ; *Transcriptome ; *Myocytes, Cardiac/metabolism/pathology ; *Animals, Newborn ; Telomere/genetics/metabolism ; Oxidative Stress/genetics ; Cellular Senescence/genetics ; Gene Expression Profiling ; DNA Damage ; Male ; Lactose/metabolism ; },
abstract = {Cardiovascular diseases (CVD) are the primary cause of mortality globally. A significant aspect of CVD involves their association with aging and susceptibility to neonatal programming. These factors suggest that adverse conditions during neonatal development can disrupt cardiomyocyte differentiation, thereby leading to heart dysfunction. This study focuses on the long-term effects of inflammatory and oxidative stress due to neonatal lactose intolerance (NLI) on cardiomyocyte transcriptome and phenotype. Our recent bioinformatic study focused on toggle genes indicated that NLI correlates with the switch off of some genes in thyroid hormone, calcium, and antioxidant signaling pathways, alongside the switch-on/off genes involved in DNA damage response and inflammation. In the presented study, we evaluated cardiomyocyte ploidy in different regions of the left ventricle (LV), complemented by a transcriptomic analysis of genes with quantitative (gradual) difference in expression. Cytophotometric and morphologic analyses of LV cardiomyocytes identified hyperpolyploidy and bridges between nuclei suggesting telomere fusion. Transcriptomic profiling highlighted telomere damage, aging, and chromatin decompaction, along with the suppression of pathways governing muscle contraction and energy metabolism. Echocardiography revealed statistically significant LV dilation and a decrease in ejection fraction. The estimation of survival rates indicated that NLI shortened the median lifespan by approximately 18% (p < 0.0001) compared with the control. Altogether, these findings suggest that NLI may increase susceptibility to cardiovascular diseases by accelerating aging due to oxidative stress and increased telomere DNA damage, leading to hyperpolyploidization and reduced cardiac contractile function. Collectively, our data emphasize the importance of the early identification and management of neonatal inflammatory and metabolic stressors, such as NLI, to mitigate long-term cardiovascular risks.},
}
@article {pmid40003720,
year = {2025},
author = {Chaithanya, V and Kumar, J and Vajravelu Leela, K and Baig, HA and Soliman, M and Alenezy, A and Shalaby, NM},
title = {Multistrain Probiotics and Telomere Length in Type 2 Diabetes: A 24-Week Randomized Controlled Trial.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {2},
pages = {},
doi = {10.3390/life15020311},
pmid = {40003720},
issn = {2075-1729},
support = {SRMIST/R/AR(A)/SERI2023/174/21-3866.//SRM Institute of Science and Technology/ ; },
abstract = {BACKGROUND: This 24-week randomized controlled trial aimed to evaluate the impact of multistrain probiotic supplementation on telomere length in patients with type 2 diabetes (T2DM). The study also assessed secondary outcomes including high-sensitivity C-reactive protein (hs-CRP) and glycated hemoglobin (HbA1c).<br><br>METHODS: A total of 124 participants with T2DM were randomly assigned to either a probiotic group (n = 62) or a placebo group (n = 62). Participants in the probiotic group consumed a supplement containing fourteen live microbial strains, including Lactobacillus plantarum, L. fermentum, L. acidophilus, L. casei, L. rhamnosus, L. reuteri, L. salivarius, L. paracasei, L. gasseri, Bifidobacterium bifidum, B. lactis, B. breve, Streptococcus thermophilus, and Saccharomyces boulardii, with each strain providing 2.148 billion CFUs per capsule, totaling 30 billion CFUs. The placebo group received vitamin B12 capsules without probiotics. The primary outcome was telomere length, and secondary outcomes included hs-CRP and HbA1c levels. Data were analyzed using intention-to-treat (ITT) and per-protocol (PP) methods.<br><br>RESULTS: The probiotic group exhibited a statistically significant decrease in telomere shortening compared to the placebo group (p < 0.001). The hs-CRP levels decreased more significantly in the probiotic group (p < 0.001), suggesting potential anti-inflammatory effects. The HbA1c levels improved in the probiotic group, with a reduction of 0.44% (p = 0.004). An age-stratified analysis revealed more substantial improvements in the 30-49 years cohort, which showed greater reductions in telomere shortening, inflammatory markers, and metabolic indicators compared to the 50-69 years group.<br><br>CONCLUSIONS: Multistrain probiotic supplementation shows potential benefits in reducing telomere shortening and improving glycemic control. However, further long-term studies are needed to understand the underlying mechanisms and therapeutic implications of probiotics in T2DM.<br><br>TRIAL REGISTRATION: This trial was registered at the Clinical Trials Registry-India (CTRI/2023/07/055647).},
}
@article {pmid40002919,
year = {2025},
author = {Rajkumar, RP},
title = {Telomere Dynamics in Post-Traumatic Stress Disorder: A Critical Synthesis.},
journal = {Biomedicines},
volume = {13},
number = {2},
pages = {},
doi = {10.3390/biomedicines13020507},
pmid = {40002919},
issn = {2227-9059},
abstract = {Post-traumatic stress disorder (PTSD), a mental disorder caused by exposure to traumatic stress, affects 5-10% of the world's population. There is some evidence that PTSD is associated with accelerated cellular aging, leading to an increased risk of medical and neurodegenerative comorbidities. Alterations in telomere length (TL) and telomerase enzyme activity have been proposed as biomarkers of this process. This hypothesis was seemingly confirmed in preliminary research, but more recent studies have yielded mixed results. The current narrative review was conducted to provide a critical synthesis of existing research on telomere length and telomerase in PTSD. Data from 26 clinical studies suggest that TL in PTSD is highly variable and may be influenced by methodological, demographic, trauma-related, and psychosocial factors. There is no evidence for altered telomerase activity in PTSD. In contrast, animal research suggests that exposure to traumatic stress does lead to TL shortening. Overall, it is likely that TL is not, by itself, a reliable biomarker of cellular aging in PTSD. Other markers of cellular senescence, such as epigenetic changes, may prove to be more specific in measuring this process in patients with PTSD.},
}
@article {pmid40002695,
year = {2025},
author = {Lee, J and Choi, E and Kim, H and Kim, YJ and Kim, SH},
title = {NELL2-PAX7 Transcriptional Cascade Suggests Activation Mechanism for RAD52-Dependent Alternative Lengthening of Telomeres During Malignant Transformation of Malignant Peripheral Nerve Sheath Tumors: Elongation of Telomeres and Poor Survival.},
journal = {Biomedicines},
volume = {13},
number = {2},
pages = {},
doi = {10.3390/biomedicines13020281},
pmid = {40002695},
issn = {2227-9059},
support = {2017M3A9A7050614//National Research Foundation of Korea/ ; 2017R1D1A1B03031717//National Research Foundation of Korea/ ; 6-2016-0101//Yonsei University College of Medicine/ ; 2019-32-0024//Yonsei University College of Medicine/ ; },
abstract = {Background: In eukaryotes with a double-stranded linear DNA genome, the loss of terminal DNA during replication is inevitable due to an end-replication problem; here, telomeres serve as a buffer against DNA loss. Thus, the activation of the telomere maintenance mechanism (TMM) is a prerequisite for malignant transformation. Methods: We compared neurofibroma (NF, benign) and malignant peripheral nerve sheath tumors (MPNSTs) occurring in the same patient with type 1 neurofibromatosis, where each NF-MPNST pair shared the same genetic background and differentiation lineage; this minimizes the genetic bias and contrasts only those changes that are related to malignant transformation. A total of 20 NF-MPNST pairs from 20 NF1 patients were analyzed. Whole-transcriptome sequencing (WTS) was conducted to profile the transcriptional relationship, and whole-genome sequencing (WGS) was performed to measure the telomere length. Results: We identified 22 differentially expressed genes (DEGs) during the malignant transformation of MPNSTs. Among them, NELL2 activated PAX7, which sequentially activated RAD52, the recombinase of RAD52-dependent alternative lengthening of telomeres (ALT). RAD52 elongated MPNSTs-telomeres (p = 0.017). Otherwise, neither NELL2 nor PAX7 affected telomere length (p = 0.647 and p = 0.354, respectively). RAD52 increased MPNSTs-telomeres length, independently of NELL2 and PAX7 in multiple analyses (p = 0.021). The group with increased telomere length during the malignant transformation showed inferior overall survival (OS) (HR = 3.809, p = 0.038) to the group without increased telomere length. Accordingly, the group with increased PAX7 showed inferior OS (HR = 4.896, p = 0.046) and metastasis-free survival (MFS) (HR = 9.129, p = 0.007) in comparison to the group without increased PAX7; the group with increased RAD52 showed inferior MFS (HR = 8.669, p = 0.011) in comparison to the group without increased RAD52. Conclusions: We suggest that the NELL2-PAX7 transcriptional cascade activates RAD52-dependent ALT to increase telomere length during the malignant transformation of MPNSTs, resulting in a poor prognosis.},
}
@article {pmid39999893,
year = {2025},
author = {Burraco, P and Metcalfe, NB and Monaghan, P},
title = {Telomere dynamics in maturing frogs vary among organs.},
journal = {Biology letters},
volume = {21},
number = {2},
pages = {20240626},
doi = {10.1098/rsbl.2024.0626},
pmid = {39999893},
issn = {1744-957X},
support = {//ERC/ ; //Ram&#xf3;n y Cajal Fellowship/ ; //Spanish Ministry of Science and Innovation/ ; //European Union/ ; },
mesh = {Animals ; *Telomere ; *Xenopus laevis/genetics/physiology ; Male ; Female ; Liver/metabolism ; Temperature ; Aging ; Larva/growth &amp; development/physiology/genetics ; Telomere Shortening ; Muscle, Skeletal/growth &amp; development/metabolism/physiology ; Myocardium/metabolism ; Metamorphosis, Biological ; },
abstract = {It is important to know whether organs age at the same rate and are equally affected by developmental conditions as this provides insights into causes of ageing. However, data on organ-specific telomere dynamics remain scant. In a previous study of the early life of the amphibian Xenopus laevis, we detected changes in telomere lengths in gut cells, while liver, heart and muscle telomeres were unchanged; larval rearing temperature had minimal effects. Here, we extend that study to examine telomere dynamics in the same four organs and larval temperature treatments from 70-day post-metamorphic juvenile Xenopus through to sexually mature (2-year-old) adults. Telomeres shortened from juvenile to adult in the gut, heart and hindlimb muscle. In contrast, liver telomere lengths did not change with age but were shorter if the early life temperature was warm. Organ telomere lengths were influenced by sex only in adults. Warmer larval temperatures were also associated with longer gut telomeres in juveniles. Hence, pre-metamorphic conditions can influence post-metamorphic telomere dynamics, and telomere loss between juvenile and adult life stages occurs in different organs from those affected earlier in life. These findings indicate the existence of organ-dependent ageing rates across lifetimes, potentially related to developmental and environmental history.},
}
@article {pmid39998303,
year = {2025},
author = {Myers, KC and Davies, SM and Lutzko, C and Wahle, R and Grier, DD and Aubert, G and Norris, K and Baird, DM and Koga, M and Ko, AC and Amano, T and Amano, M and Yu, H and Ko, MSH},
title = {Clinical Use of ZSCAN4 for Telomere Elongation in Hematopoietic Stem Cells.},
journal = {NEJM evidence},
volume = {4},
number = {3},
pages = {EVIDoa2400252},
doi = {10.1056/EVIDoa2400252},
pmid = {39998303},
issn = {2766-5526},
mesh = {Humans ; Male ; Female ; *Hematopoietic Stem Cells/metabolism ; *Telomere/metabolism ; Adult ; Dyskeratosis Congenita/genetics/pathology/therapy ; Transcription Factors/genetics/metabolism ; Hematopoietic Stem Cell Transplantation/methods ; Hematopoietic Stem Cell Mobilization ; Adolescent ; Young Adult ; Antigens, CD34/metabolism ; },
abstract = {BACKGROUND: Extremely short telomeres in patients with dyskeratosis congenita and related telomere biology disorders (TBDs) lead to premature cellular senescence and bone marrow failure. Zinc finger and SCAN domain-containing 4 (ZSCAN4) elongates telomeres by recombination.<br><br>METHODS: We report a clinical study in which EXG34217, the term given for autologous CD34+ hematopoietic stem cells from patients with TBD exposed to a temperature-sensitive Sendai virus vector encoding human ZSCAN4 at 33&#xb0;C for 24 hours, was infused into patients without preconditioning.<br><br>RESULTS: Four patients were enrolled; two experienced successful CD34+ mobilization during the second mobilization attempt and underwent apheresis and EXG34217 infusion, with follow-up of 5 and 24 months (both ongoing). We observed telomere elongation (1.06- to 1.34-fold) in CD34+ cells ex vivo. In one patient, the treatment was associated with a change in the mean absolute neutrophil count (ANC) from 1.78&#xd7;10[3] to 3.18&#xd7;10[3] cells/&#x3bc;l; the lymphocyte subpopulation telomere length changed from 3.6 to 6.7 kb (50th percentile for age). In the other patient, the treatment was associated with a change in the lowest ANC from 0.6&#xd7;10[3]/&#x3bc;l to 1.2&#xd7;10[3]/&#x3bc;l; this has occurred in 5 months without the patient receiving prior intermittent low-dose granulocyte-colony-stimulating factor injections. During mobilization, all patients experienced mild to moderate bone pain or pain after line replacement, and one patient had a blood infection associated with fever and hypoxemia. After EXG34217 infusion, no acute safety issues were noted; in one patient mild to moderate long-term cardiac and pulmonary adverse events were noted; these were similar to symptoms of the patient's underlying conditions.<br><br>CONCLUSIONS: Although definitive conclusions cannot be drawn from the two EXG34217-treated patients, these results warrant further investigation of CD34+ cells exposed to ZSCAN4 for treating TBDs. (Funded by Elixirgen Therapeutics; ClinicalTrials.gov number, NCT04211714.).},
}
@article {pmid39992010,
year = {2025},
author = {},
title = {Expression of Concern: Mitogen Stimulation Cooperates with Telomere Shortening To Activate DNA Damage Responses and Senescence Signaling.},
journal = {Molecular and cellular biology},
volume = {},
number = {},
pages = {1},
doi = {10.1080/10985549.2025.2462481},
pmid = {39992010},
issn = {1098-5549},
}
@article {pmid39990381,
year = {2025},
author = {Quintanilla, I and Azeroglu, B and Sagar, MAK and Stracker, TH and Lazzerini Denchi, E and Pegoraro, G},
title = {Optical Pooled Screening for the Discovery of Regulators of the Alternative Lengthening of Telomeres Pathway.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.02.15.638448},
pmid = {39990381},
issn = {2692-8205},
abstract = {Telomere elongation is essential for the proliferation of cancer cells. Telomere length control is achieved by either the activation of the telomerase enzyme or the recombination-based Alternative Lengthening of Telomeres (ALT) pathway. ALT is active in about 10-15% of human cancers, but its molecular underpinnings remain poorly understood, preventing the discovery of potential novel therapeutic targets. Pooled CRISPR-based functional genomic screens enable the unbiased discovery of molecular factors involved in cancer biology. Recently, Optical Pooled Screens (OPS) have significantly extended the capabilities of pooled functional genomics screens to enable sensitive imaging-based readouts at the single cell level and large scale. To gain a better understanding of the ALT pathway, we developed a novel OPS assay that employs telomeric native DNA FISH (nFISH) as an optical quantitative readout to measure ALT activity. The assay uses standard OPS protocols for library preparation and sequencing. As a critical element, an optimized nFISH protocol is performed before in situ sequencing to maximize the assay performance. We show that the modified nFISH protocol faithfully detects changes in ALT activity upon CRISPR knock-out (KO) of the FANCM and BLM genes which were previously implicated in ALT. Overall, the OPS-nFISH assay is a reliable method that can provide deep insights into the ALT pathway in a high-throughput format.},
}
@article {pmid39986429,
year = {2025},
author = {Erickson, PA and Chang, VC and He, S and Dagnall, C and Teshome, K and Machiela, MJ and Barry, KH and Pereira, EFR and Gadalla, SM and Parks, CG and Berndt, SI and Beane Freeman, LE and Andreotti, G and Hofmann, JN},
title = {Occupational Pesticide Use and Relative Leukocyte Telomere Length in the Biomarkers of Exposure and Effect in Agriculture Study.},
journal = {Environmental research},
volume = {},
number = {},
pages = {121174},
doi = {10.1016/j.envres.2025.121174},
pmid = {39986429},
issn = {1096-0953},
abstract = {Previous epidemiological studies have reported increased risks of certain cancers in relation to pesticide exposures. Although the biologic mechanisms underlying these associations are not well understood, altered telomere length has been hypothesized to play a role. We examined associations between occupational use of specific pesticides and leukocyte telomere length in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiological investigation of pesticide applicators in Iowa and North Carolina. Relative telomere length (RTL) was measured using quantitative polymerase chain reaction in leukocytes from 1,539 male pesticide applicators ≥50 years of age. We evaluated lifetime use of 47 pesticides in terms of self-reported ever use and intensity-weighted lifetime days (IWLDs), a metric integrating lifetime days of use and other factors influencing exposure. Multivariable linear regression was used to estimate percent difference in geometric mean RTL in relation to ever (vs. never) use, IWLDs of use, and timing of use [recent (last 12 months) and former vs. never use]. Mean RTL was significantly longer among ever users of the insecticides lindane (percent difference=2.20%, 95%CI: 0.45%, 3.99%) and aldicarb (percent difference=3.27%, 95%CI: 0.23%, 6.40%). Longer RTL was also associated with increasing IWLDs of lindane (highest quartile vs. never use: percent difference=4.51%, 95%CI: -0.22%, 9.46%; p-trend=0.048) and the insecticide diazinon (4.77%, 95%CI: 0.17%, 9.58%; p-trend=0.055), and with recent use of the insecticide dichlorvos (vs. never use: 8.15%, 95%CI: 1.31%, 15.46%). Increasing IWLDs of the insecticide heptachlor and the herbicide 2,4,5-TP and recent use of the herbicide metolachlor were significantly associated with shorter RTL. Our findings provide novel evidence suggesting that use of certain pesticides is associated with altered leukocyte telomere length. Notably, diazinon and lindane have previously been associated with increased risks of lung and lymphoid malignancies, respectively, and longer leukocyte telomere length has been implicated in the development of these cancers.},
}
@article {pmid39983997,
year = {2025},
author = {Page, J and Stephens, C and Richard, M and Lyons, E and Baumler, E and Verklan, MT and Lorenzo, E},
title = {The relationship between physical activity and telomere length in women: A systematic review.},
journal = {Mechanisms of ageing and development},
volume = {},
number = {},
pages = {112042},
doi = {10.1016/j.mad.2025.112042},
pmid = {39983997},
issn = {1872-6216},
abstract = {Telomere length (TL) is a biomarker of cellular aging with variations observed by sex, age, race, and ethnicity. Prior studies have suggested that physical activity (PA) may positively impact TL by potentially elongating telomeres and slowing cellular aging. However, research examining the optimal type and intensity of PA needed to elicit these changes specific to women remains limited. This systematic review aimed to investigate variations in TL in response to PA among women, exploring how these effects differ by age, race, or ethnicity. Following PRISMA guidelines, searches across five databases identified 17 relevant studies published from 2008 to 2022. A narrative synthesis of study findings indicated PA did not have a significant relationship with TL in women. However, a possible positive relationship was noted between specific types of PA and TL, specific to combined aerobic and strength-training PA and high intensity interval training interventions. The impact of PA on TL appeared to be age-dependent as well, showing significant positive relationships between PA and TL in early and later adulthood but not in middle adulthood. Findings related to race or ethnicity were inconclusive due to limited analyses from the included studies. The studies varied greatly by PA type, intensity, duration, and frequency, which, along with the reliance on self-reported PA measures in the observational studies, impacted the ability to draw firm conclusions. This review underscores the necessity for future research in large cohort studies using objectively measured PA interventions to further clarify the complex associations between PA and TL in women.},
}
@article {pmid39983416,
year = {2025},
author = {Liu, Z and Liu, X},
title = {Prognostic model of osteosarcoma based on telomere-related genes and analysis of immune characteristics.},
journal = {International immunopharmacology},
volume = {151},
number = {},
pages = {114198},
doi = {10.1016/j.intimp.2025.114198},
pmid = {39983416},
issn = {1878-1705},
abstract = {OBJECTIVE: Osteosarcoma is a malignant tumor with significant challenges in treatment and prognosis. Telomeres play a crucial role in genetic stability and tumor development, and telomere-related genes (TRGs) have shown considerable prognostic potential in various cancers. However, the prognostic significance of TRGs in osteosarcoma and their involvement in the tumor immune microenvironment (TIME) remain poorly understood.<br><br>METHOD: This study initially identified 2086 TRGs from the TelNet database as candidate genes. Using RNA sequencing and clinical data from osteosarcoma patients available in the TARGET and GEO public databases, we developed a TRG-based prognostic scoring model through univariate, LASSO regression, and multivariate Cox regression analyses, with its predictive performance subsequently validated. Unsupervised clustering was performed on TRGs associated with prognosis. To investigate the TIME, we utilized several algorithms including ESTIMATE, CIBERSORT, xCELL, and ssGSEA to analyze the immune landscape associated with TRG patterns. Additionally, functional enrichment analysis of different subtypes was conducted using KEGG, GO, and GSVA approaches. We also performed single-cell localization and drug sensitivity analysis on the prognostic model genes. Finally, the predictive results were preliminarily validated through a series of in vitro experiments.<br><br>RESULT: Differential expression analysis revealed 841 TRGs with significant changes in osteosarcoma, where P-value&#xa0;<&#xa0;0.05 and |logFC|&#xa0;&#x2265;&#xa0;1. Based on the prognostic relevance of these TRGs, we successfully identified two subtypes with distinct clinical and immune characteristics. Immune infiltration levels between Cluster 1 and Cluster 2 were significantly different, as assessed by multiple algorithms. Furthermore, we constructed a prognostic scoring model based on TRGs, which demonstrated excellent predictive performance, with AUC values for 1-year, 3-year, and 5-year ROC curves being 92.43&#xa0;%, 87.08&#xa0;%, and 84.34&#xa0;% in the training cohort, respectively, and 74.49&#xa0;%, 87.77&#xa0;%, and 94.52&#xa0;% in the validation cohort, indicating good stability of the model. Notably, functional enrichment analysis highlighted a strong association between immune dysfunction and poor prognosis, while drug sensitivity analysis offered personalized chemotherapy recommendations for osteosarcoma patients with different subtypes. We observed that Fludarabine had a higher IC50 value in the high-risk group compared to the low-risk group, and it showed a strong correlation with the prognostic model genes, with all P-values less than 0.05.<br><br>CONCLUSION: This study successfully constructed a prognostic risk prediction model for osteosarcoma by systematically analyzing the expression patterns of TRGs. Fludarabine may represent a promising therapeutic option for patients with osteosarcoma.},
}
@article {pmid39982908,
year = {2025},
author = {Armendáriz-Castillo, I and García-Cárdenas, J and Espinosa, P and Hidalgo-Fernández, K and Peña-Zúñiga, L and Martínez, R and Moromenacho, J and Herrera-Yela, A and Cruz-Varela, J and Saucedo-Sariñana, A and Cerdán, ME and López-Cortés, A and Guerrero, S},
title = {Metabolic pathways of Alternative Lengthening of Telomeres in pan-carcinoma.},
journal = {PloS one},
volume = {20},
number = {2},
pages = {e0314012},
doi = {10.1371/journal.pone.0314012},
pmid = {39982908},
issn = {1932-6203},
mesh = {Humans ; *Telomere Homeostasis ; *Metabolic Networks and Pathways ; Neoplasms/metabolism/pathology/genetics ; Telomere/metabolism/genetics ; Purines/metabolism ; Metabolomics/methods ; },
abstract = {Alternative Lengthening of Telomeres (ALT) is a telomerase-independent mechanism deployed by several aggressive cancers to maintain telomere length. This contributes to their malignancy and resistance to conventional therapies. In prior studies, we have identified key proteins linked to the ALT process using multi-omic data integration strategies. In this work, we combined metabolomic datasets with our earlier results to identify targetable metabolic pathways for ALT-positive tumors. 39 ALT-related proteins were found to interact with 42 different metabolites in our analysis. Additional networking analysis revealed a complex interaction between metabolites and ALT-related proteins, suggesting that pan-cancer oncogenes may have an impact on these pathways. Three metabolic pathways have been primarily related with the ALT mechanism: purine metabolism, cysteine and methionine metabolism, and nicotinate and nicotinamide metabolism. Lastly, we prioritized FDA-approved drugs (azathioprine, thioguanine, and mercaptopurine) that could target ALT-positive tumors through purine metabolism. This work provides a wide perspective of the metabolomic pathways associated with ALT and reveals potential therapeutic targets that require further experimental validation.},
}
@article {pmid39982852,
year = {2025},
author = {Jiang, D and Li, Y and Zhuge, F and Zhou, Q and Zong, W and Liu, X and Shen, X},
title = {The telomere-to-telomere genome of flowering cherry (Prunus campanulata) reveals genomic evolution of the subgenus Cerasus.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf009},
pmid = {39982852},
issn = {2047-217X},
support = {2021C02071-4//Zhejiang Science and Technology Major Program on Agricultural New Variety Breeding/ ; 2023F1068-2//Special Support Funds of Zhejiang for Scientific Research Institutes/ ; 32101585//National Natural Science Foundation of China/ ; },
mesh = {*Genome, Plant ; *Telomere/genetics ; *Evolution, Molecular ; *Prunus/genetics ; Genomics/methods ; Phylogeny ; Molecular Sequence Annotation ; High-Throughput Nucleotide Sequencing ; },
abstract = {BACKGROUND: Prunus campanulata, a species of ornamental cherry, holds significant genetic and horticultural value. Despite the availability of various cherry genomes, a fully resolved telomere-to-telomere (T2T) assembly for this species has been lacking. Recent advancements in long-read sequencing technologies have made it possible to generate gap-free genome assemblies, providing comprehensive insights into genomic structures that were previously inaccessible.<br><br>FINDINGS: We present the first T2T genome assembly for P. campanulata "Lianmeiren" (v2.0), achieved through the integration of PacBio HiFi, ultra-long Oxford Nanopore Technologies, Illumina, and Hi-C sequencing. The assembly resulted in a highly contiguous genome with a total size of 266.23 Mb and a contig N50 of 31.6 Mb. The genome exhibits remarkable completeness (98.9% BUSCO) and high accuracy (quality value of 48.75). Additionally, 13 telomeres and putative centromere regions were successfully identified across the 8 pseudochromosomes. Comparative analysis with the previous v1.0 assembly revealed 336,943 single nucleotide polymorphisms, 107,521 indels, and 1,413 structural variations, along with the annotation of 1,402 new genes.<br><br>CONCLUSIONS: This T2T genome assembly of P. campanulata "Lianmeiren" provides a critical reference for understanding the genetic architecture of the species. It enhances our ability to study structural variations, gene function, and evolutionary biology within the Prunus genus.},
}
@article {pmid39981889,
year = {2025},
author = {Andreikos, D and Spandidos, DA and Georgakopoulou, VE},
title = {Telomeres and telomerase in mesothelioma: Pathophysiology, biomarkers and emerging therapeutic strategies (Review).},
journal = {International journal of oncology},
volume = {66},
number = {3},
pages = {},
doi = {10.3892/ijo.2025.5729},
pmid = {39981889},
issn = {1791-2423},
mesh = {Humans ; *Telomerase/genetics/metabolism ; *Biomarkers, Tumor/genetics/metabolism ; *Telomere/genetics/metabolism ; *Mesothelioma, Malignant/genetics/pathology/drug therapy ; Mesothelioma/genetics/pathology ; Lung Neoplasms/genetics/pathology ; Prognosis ; Polymorphism, Single Nucleotide ; Mutation ; Promoter Regions, Genetic ; },
abstract = {Malignant mesothelioma (MM) is a rare but aggressive cancer linked to asbestos exposure and characterized by advanced‑stage disease at presentation. Despite advances in treatment, prognosis remains abysmal, highlighting the imperative for the development of novel biomarkers and treatment approaches. Telomere biology plays a pivotal role in the tumorigenic process and has emerged as a key area in oncology research. Short telomeres have been associated with genomic instability, and substantially shorter telomere length (TL) has been identified in MM, showcasing the potential of TL in risk assessment, early detection, and disease progression monitoring. MM predominantly maintains TL through telomerase activity (TA), which in research has been identified in >90% of MM cases, underscoring the potential of TA as a biomarker in MM. Telomerase reverse transcriptase (TERT) polymorphisms may serve as valuable biomarkers, with research identifying associations between single nucleotide polymorphisms (SNPs) and the risk and prognosis of MM. Additionally, TERT promoter mutations have been associated with poor prognosis and advanced‑stage disease, with the non‑canonical functions of TERT hypothesized to contribute to the development of MM. TERT promoter mutations occur in ~12% of MM cases; C228T, C250T and A161C are the most common, while the distribution and frequency differ depending on histological subtype. Research reveals the promise of the various approaches therapeutically targeting telomerase, with favorable results in pre‑clinical models and inconclusive findings in clinical trials. The present review examines the role of telomere biology in MM and its implications in diagnosis, prognosis, and therapy.},
}
@article {pmid39980969,
year = {2024},
author = {Li, S and Zhang, L and Zhang, H},
title = {A telomere-related signature for predicting prognosis and assessing immune microenvironment in osteosarcoma.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1532610},
pmid = {39980969},
issn = {1663-9812},
abstract = {OBJECTIVE: Osteosarcoma is the most common primary bone cancer with a high propensity for local invasion and metastasis. An increasing number of research studies show that telomeres play an important role in the occurrence and development of cancer. Thus, we established a telomere-related signature in osteosarcoma to comprehensively evaluate the pathogenic roles of telomeres in this disease.<br><br>METHODS: The data on osteosarcoma were collected from the TARGET and Gene Expression Omnibus databases. First, we constructed a telomere-related signature using univariate and LASSO Cox regression analyses. Subsequently, we analyzed the prognostic value, functional annotation, immune microenvironment, and cell communication patterns of the telomere-related signature in osteosarcoma via comprehensive bioinformatics analyses. Cell proliferation was analyzed using the CCK-8 assay, and cell migration and invasion capabilities were evaluated using the Transwell assay.<br><br>RESULTS: Based on the SP110, HHAT, TUBB, MORC4, TERT, PPARG, MAP3K5, PAGE5, MAP7, and CAMK1G, a telomere-related signature was built in osteosarcoma patients. The telomere-related signature could effectively predict the prognosis of osteosarcoma patients. The osteosarcoma patients in the high TELscore group exhibited poor prognosis. In addition, the telomere-related signature demonstrated predictive value for the immune microenvironment and drug sensitivity in osteosarcoma. Finally, we discovered significant reduction in MAP7 expression in osteosarcoma cells, and patients with low MAP7 expression had poor prognosis. Moreover, the overexpression of MAP7 significantly reduced cell proliferation, the ability of cell migration, and invasion in osteosarcoma cells.<br><br>CONCLUSION: A telomere-related signature was constructed in osteosarcoma patients, offering predictive values into prognosis, the immune microenvironment, and drug sensitivity. Moreover, MAP7 might serve as a prognostic marker for osteosarcoma patients.},
}
@article {pmid39979386,
year = {2025},
author = {Oraon, PK and Ambreen, H and Yadav, P and Ramarao, S and Goel, S},
title = {A chromosome-scale reference assembly of Vigna radiata enables delineation of centromeres and telomeres.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {305},
pmid = {39979386},
issn = {2052-4463},
support = {IOE/FRP/LS/2020/27//University of Delhi (Delhi University)/ ; BT/190/NE/TBP/2011//Department of Biotechnology, Ministry of Science and Technology (DBT)/ ; BT/PR24637/NER/95/787/2017//Department of Biotechnology, Ministry of Science and Technology (DBT)/ ; 09/0045(1617)/2019-EMR-I//Council of Scientific and Industrial Research (CSIR)/ ; 09/0045(1624)/2019-EMR-I//Council of Scientific and Industrial Research (CSIR)/ ; },
mesh = {*Centromere/genetics ; *Vigna/genetics ; *Telomere/genetics ; *Genome, Plant ; *Chromosomes, Plant/genetics ; },
abstract = {Vigna radiata (L.) R. Wilczek var. radiata (mungbean) is a pulse crop important for both the global protein security and sustainable crop production. Here, to facilitate genomics-assisted breeding programs in mungbean, we present a high-quality reference genome originating from the crop's centre of origin, India. In this study, we present a significantly continuous genome assembly of V. radiata Indian cultivar, achieved through a combination of long-read PacBio HiFi sequencing and Hi-C sequencing. The total assembled genome size is ~596 Mb equating to ~98% of the predicted genome size complemented by a contig N50 value of 10.35 Mb and a BUSCO score of 98.5%. Around 502 Mb of the assembled genome is anchored on 11 pseudochromosomes conforming to the chromosome count in the crop with distinctly identified telomeres and centromeres. We predicted a total of 43,147 gene models of which 39,144 protein coding genes were functionally annotated. The present assembly was able to resolve several gaps in the genome and provides a high-quality genomic resource for accelerating mungbean breeding programs.},
}
@article {pmid39978211,
year = {2025},
author = {Brown, RA and Koss, KJ},
title = {The role of optimism, connectedness, and neighborhood collective efficacy as moderators of harsh parenting on telomere length.},
journal = {Psychoneuroendocrinology},
volume = {174},
number = {},
pages = {107373},
doi = {10.1016/j.psyneuen.2025.107373},
pmid = {39978211},
issn = {1873-3360},
abstract = {Research to date has examined telomere length in relation to adverse childhood events but few studies have examined whether protective factors act as a buffer to offset this effect. Further, research is lacking examining whether protective factors vary among minoritized youth. Data were from the Future Families and Child Wellbeing Study, a stratified, multistage sample of 4898 children born in large U.S. cities between 1998 and 2000. Births to unmarried mothers were oversampled by a 3-1 ratio, which resulted in the inclusion of a multi-ethnic and economically diverse sample (48 % Black; 27 % Hispanic; 21 % White; 4 % other racial and ethnic minorities). The current study examined optimism, social connectedness, and neighborhood collective efficacy at age 15 as potential protective factors against the effects of harsh parenting on telomere length in adolescence (analytic N = 1168 youth). This study examines cumulative exposure to harsh parenting across childhood (ages 3, 5, and 9 years). Results from analyses stratified by race/ethnicity show optimism, connectedness, and neighborhood collective efficacy serve as protective factors; however, unique protective factors emerged among different racial and ethnic youth suggesting the need to examine context-specific protective factors. Implications of these findings provide evidence for considering intersectionality in terms of protective factors for biomarkers among minoritized youth.},
}
@article {pmid39977333,
year = {2025},
author = {},
title = {Correction for Qian et al., Chemoptogenetic damage to mitochondria causes rapid telomere dysfunction.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {10},
pages = {e2501913122},
doi = {10.1073/pnas.2501913122},
pmid = {39977333},
issn = {1091-6490},
}
@article {pmid39975089,
year = {2025},
author = {Jeon, HJ and Levine, MT and Lampson, MA},
title = {A parent-of-origin effect on embryonic telomere elongation determines telomere length inheritance.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.01.28.635226},
pmid = {39975089},
issn = {2692-8205},
abstract = {Telomere length is inherited directly as a DNA sequence and as a classic quantitative trait controlled by many genes across the genome. Here, we show that neither paradigm fully accounts for telomere length inheritance, which also depends on a parent-of-origin effect on telomere elongation in the early embryo. By reciprocally crossing mouse strains with different telomere lengths, we find that telomeres elongate in hybrid embryos only when maternal telomeres are short and paternal telomeres are long. In the reciprocal cross, telomeres shorten. These differences in embryonic telomere elongation, which emerge before zygotic genome activation, predict adult telomere length. Moreover, when telomeres do elongate, we find molecular signatures of a recombination-based mechanism of telomere elongation, called the Alternative Lengthening of Telomeres (ALT) pathway, previously suggested to elongate telomeres in the pre-implantation embryo. We propose that ALT is triggered by a combination of genetic asymmetry in telomere length and epigenetic asymmetry between maternal and paternal chromosomes in the zygote. Our findings offer new insight into the complex interaction of genetic and epigenetic determinants of telomere length inheritance.},
}
@article {pmid39975053,
year = {2025},
author = {Sanford, SL and Badstübner, M and Gerber, M and Mannherz, W and Lampl, N and Dannenberg, R and Hinchie, A and Schaich, MA and Myong, S and Hedglin, M and Agarwal, S and Alder, J and Stone, MD and Opresko, PL},
title = {6-thio-2'-deoxyguanosine inhibits telomere elongation by inducing a non-productive stalled telomerase complex.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.02.05.636339},
pmid = {39975053},
issn = {2692-8205},
abstract = {Most cancers upregulate the telomere lengthening enzyme telomerase for unlimited cell division. The therapeutic nucleoside 6-thio-2'-deoxyguanosine (6-thio-dG) inhibits telomere maintenance in telomerase- expressing cancer cells and tumors by an unknown mechanism. Here, we demonstrate that telomerase insertion of 6-thio-dGTP prevents synthesis of additional telomeric repeats but does not disrupt telomerase binding to telomeres. Specifically, 6-thio-dG inhibits telomere extension after telomerase translocates along its product DNA to reposition the template, thereby inducing a non-productive complex rather than enzyme dissociation upon movement. We provide direct evidence that 6-thio-dG treatment inhibits telomere synthesis by telomerase in cancer cells. Furthermore, telomerase-expressing cancer cells harboring critically short telomeres are more sensitive to 6-thio-dG and show a greater induction of telomere losses, compared to cancer cells with long telomere reserves. Collectively, our studies reveal the molecular mechanism of 6-thio-dG inhibition of telomere maintenance in cancer cells is by producing a bound non-productive telomerase complex after 6-thio-dGTP insertion.},
}
@article {pmid39974130,
year = {2025},
author = {Toor, AA and Horton, M and Khalid, H and Krieger, E and Lai, TP and Spellman, SR and Levine, JE and Saber, W and Aviv, A and Stewart, V and Gadalla, SM},
title = {Understanding Telomere Biology in Hematopoietic Cell Transplantation: A Dynamical Systems Perspective.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.01.20.24319630},
pmid = {39974130},
abstract = {BACKGROUND: T cell proliferation and repertoire reconstitution is a hallmark of successful hematopoietic cell transplantation (HCT). This process may be modeled as a dynamical system and in such a system, precise telomere length (TL) measurement may reflect the proliferative capacity of donor T cells. TL for different chromosomes span a few orders of magnitude, and different T cell clones will display variable TL; these differences across the population are not represented when examining average TL. This study aims to develop a method that integrates the entire spectrum of TL observed within a sample to better understand the influence on clinical outcomes following HCT.<br><br>METHODS: To better reflect the entire span of TL , we used data generated using the TeLSA PCR technique that provided discrete measurments of individual telomeres for each DNA sample for 72 stem cell transplant (SCT) donor-recipient pairs. Donor and recipient TeSLA TL measurements was performed on samples taken before and 90 days post HCT, respectively. Set correspondence mathematical techniques and area under the curve (AUC) calculations were used to measured donor-recipient TL differences (delta-TL) incorporating the full distribution of measured TL from each sample.<br><br>RESULTS: Telomere band lengths ranged from 350 basepairs (BP) to 16.7 kilobases with a logarithmically declining distribution in all samples when arrayed in a descending order. Set correspondence methods yielded TL averages which were highly correlated with AUC calculations (r >0.9, p<0.001 for all) The AUC delta-TL method predicted patient overall survival (P-log rank <0.0001). HCT recipients with intermediate degrees of telomere attrition (25 [th] -75 [th] percentile) post-HCT experienced the best outcomes (2 years overall survival; OS=92%), whilst donors with the least (<25 [th] percentile; 2 years OS=33%; adjusted HR vs. intermediate shortening=9.3, p=0.001) and the greatest (>75 [th] percentile; 2 years OS=59%; adjusted HR=6.0, p=0.01) shortening had worse outcomes. By contrast, using the traditional method based on donor-recipient difference in TeSLA mean telomere length did not demonstrate survival association in this small sample set (p log-rank=0.95).<br><br>CONCLUSION: The findings described herein suggest that the degree of donor telomere attrition may reflect T cell proliferation and alloreactivity following transplant. Accounting for the entire span of telomere lengths, could better identify post-transplant risk groups.},
}
@article {pmid39972993,
year = {2025},
author = {Jin, T and Yang, R and Cheng, Y and Cao, Z and He, Z and Guo, S},
title = {Causality between Autism Spectrum Disorder and Telomere Length.},
journal = {Brain and behavior},
volume = {15},
number = {2},
pages = {e70362},
doi = {10.1002/brb3.70362},
pmid = {39972993},
issn = {2162-3279},
support = {2020KY443,2022KY506,2023KY044and2024KY025//the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission/ ; GZY-ZJ-KJ-23055//Zhejiang Provincial TCM Science and Technology Plan Project/ ; },
mesh = {*Autism Spectrum Disorder/genetics ; Humans ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; Telomere ; Telomere Shortening ; Causality ; },
abstract = {BACKGROUND: The association between telomere length (TL) and autism spectrum disorder (ASD) has received much attention. However, previous observational studies have yielded inconclusive evidence regarding this relationship. Our study aims to elucidate the causal relationship between TL and ASD using bidirectional Mendelian randomization (MR).<br><br>METHODS: We employed the largest genome-wide association studies (GWAS) summary statistics for TL (sample size = 472,174) and ASD (sample size = 46,351). The primary MR analysis method was the inverse-variance weighted (IVW) method, complemented by the MR-Egger method, weighted median (WM) method, and MR-PRESSO. Additionally, sensitivity analyses including Cochran's Q test, the intercept of MR-Egger regression, the global test of MR-PRESSO, and the leave-one-out analysis were conducted in our study.<br><br>RESULTS: The primary MR analysis indicated a significant association between ASD and shorter TL (IVW: OR = 0.98, 95% CI: 0.96-0.99, p = 0.03). However, no significant association was found in the reverse direction MR analysis (IVW: OR = 1.06, 95% CI: 0.94-1.23, p = 0.35). Raw and outlier-corrected MR estimates from MR-PRESSO were consistent with the IVW results. Sensitivity analyses confirmed the robustness of these findings.<br><br>CONCLUSIONS: Our study indicated that individuals with ASD have shorter TL, however, shorter TL does not appear to increase the risk of ASD.},
}
@article {pmid39971959,
year = {2025},
author = {Guerrero-López, R and Manguán-García, C and Carrascoso-Rubio, C and Lozano, ML and Toldos-Torres, M and García-Castro, L and Sánchez-Dominguez, R and Alberquilla, O and Sánchez-Pérez, I and Molina-Molina, M and Bueren, JA and Guenechea, G and Perona, R and Sastre, L},
title = {Premature ageing of lung alveoli and bone marrow cells from Terc deficient mice with different telomere lengths.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {6102},
pmid = {39971959},
issn = {2045-2322},
mesh = {Animals ; *Telomerase/genetics ; Mice ; *Telomere/genetics/metabolism ; *Aging, Premature/genetics/pathology ; *Mice, Inbred C57BL ; *RNA/genetics/metabolism ; *Bone Marrow Cells/metabolism ; Pulmonary Alveoli/pathology/metabolism ; Disease Models, Animal ; Telomere Homeostasis ; Mutation ; Male ; Telomere Shortening ; },
abstract = {Telomeres are terminal protective chromosome structures. Genetic variants in genes coding for proteins required for telomere maintenance cause rare, life-threatening Telomere Biology Disorders (TBDs) such as dyskeratosis congenita, aplastic anemia or pulmonary fibrosis. The more frequently used mice strains have telomeres much longer than the human ones which question their use as in vivo models for TBDs. One mice model with shorter telomeres based on the CAST/EiJ mouse strain carrying a mutation in the Terc gene, coding for the telomerase RNA component, has been studied in comparison with C57BL/6J mice, carrying the same mutation and long telomeres. The possible alterations produced in lungs and the haematopoietic system, frequently affected in TBD patients, were determined at different ages of the mice. Homozygous mutant mice presented a very shortened life span, more notorious in the short-telomeres CAST/EiJ strain. The lungs of mutant mice presented a transitory increase in fibrosis and a significant decrease in the relative amount of the alveolar epithelial type 2 cells from six months of age. This decrease was larger in mutant homozygous animals but was also observed in heterozygous animals. On the contrary the expression of the senescence-related protein P21 increased from six months of age in mutant mice of both strains. The analysis of the haematopoietic system indicated a decrease in the number of megakaryocyte-erythroid progenitors in homozygous mutants and an increase in the clonogenic potential of bone marrow and LSK cells. Bone marrow cells from homozygous mutant animals presented decreasing in vitro expansion capacity. The alterations observed are compatible with precocious ageing of lung alveolar cells and the bone marrow cells that correlate with the alterations observed in TBD patients. The alterations seem to be more related to the genotype of the animals that to the basal telomere length of the strains although they are more pronounced in the short-telomere CAST/EiJ-derived strain than in C57BL/6J animals. Therefore, both animal models, at ages over 6-8 months, could represent valuable and convenient models for the study of TBDs and for the assay of new therapeutic products.},
}
@article {pmid39970292,
year = {2025},
author = {Goncalves, T and Cunniffe, S and Ma, TS and Mattis, N and Rose, AW and Kent, T and Mole, DR and Geiller, HEB and van Bijsterveldt, L and Humphrey, TC and Hammond, EM and Gibbons, RJ and Clynes, D and Rose, AM},
title = {Elevated reactive oxygen species can drive the alternative lengthening of telomeres pathway in ATRX-null cancers.},
journal = {Nucleic acids research},
volume = {53},
number = {4},
pages = {},
doi = {10.1093/nar/gkaf061},
pmid = {39970292},
issn = {1362-4962},
support = {CL-2018-13-005//National Institute of Health and Care Research Clinical Lectureship/ ; SGL023\1055//Academy of Medical Sciences Starter/ ; 0&#xa0;011&#xa0;483//University of Oxford Medical Sciences/ ; 15-202//Children with Cancer UK/ ; 101&#xa0;136&#xa0;835//EU Horizon Europe Research and Innovation program Cancer Mission 'HIT-GLIO'/ ; C6078/A28736/CRUK_/Cancer Research UK/United Kingdom ; //MRC DPhil Studentship/ ; },
mesh = {*X-linked Nuclear Protein/genetics/metabolism ; *Reactive Oxygen Species/metabolism ; Humans ; *Telomere Homeostasis/genetics ; Cell Line, Tumor ; *Telomere/metabolism/genetics ; Glioma/genetics/metabolism/pathology ; R-Loop Structures ; Ribonuclease H/metabolism/genetics ; Tumor Microenvironment/genetics ; Osteosarcoma/genetics/pathology/metabolism ; Mutation ; },
abstract = {The alternative lengthening of telomeres (ALT) pathway is a telomerase-independent mechanism for immortalization in cancer cells and is commonly activated in low-grade and high-grade glioma, as well as osteosarcoma. The ALT pathway can be activated under various conditions and has often been shown to include mutational loss of ATRX. However, this is insufficient in isolation and so other cellular event must also be implicated. It has been shown that excessive accumulation of DNA:RNA hybrid structures (R-loops) and/or formation of DNA-protein crosslinks (DPCs) can be other important driving factors. The underlying cellular events leading to R-loop and DPC formation in ALT cancer cells to date remain unclear. Here, we demonstrate that excessive cellular reactive oxygen species (ROS) is an important causative factor in the evolution of ALT-telomere maintenance in ATRX-deficient glioma. We identified three sources of elevated ROS in ALT-positive gliomas: co-mutation of SETD2, downregulation of DRG2, and hypoxic tumour microenvironment. We demonstrate that elevated ROS leads to accumulation of R-loops and, crucially, resolution of R-loops by the enzyme RNase H1 prevents ALT pathway activity in cells exposed to elevated ROS. Further, we found a possible causal link between the formation of R-loops and the accumulation of DPCs, in particular, formation of TOP1 complexes covalently linked to DNA (Top1cc). We also demonstrate that elevation of ROS can trigger over-activity of the ALT pathway in osteosarcoma and glioma cell lines, resulting in excessive DNA damage and cell death. This work presents important mechanistic insights into the endogenous origin of excessive R-loops and DPCs in ALT-positive cancers, as well as highlighting potential novel therapeutic approaches in these difficult-to-treat cancer types.},
}
@article {pmid39969640,
year = {2025},
author = {Dutson, U and Lin, J and Jelliffe-Pawlowski, LL and Coleman-Phox, K and Rand, L and Wojcicki, JM},
title = {The Association Between Longer Maternal Leukocyte Telomere Length in the Immediate Postpartum Period and Preterm Birth in a Predominately Latina Cohort of Mothers.},
journal = {Maternal and child health journal},
volume = {},
number = {},
pages = {},
pmid = {39969640},
issn = {1573-6628},
support = {Wojcicki//UCSF Preterm Birth Initiative/ ; },
abstract = {OBJECTIVES: We investigated the association between maternal leukocyte telomere length (LTL) in the immediate postpartum period and moderate to late preterm birth (32- < 37 weeks) among Latinas, a population at high risk for preterm birth.<br><br>METHODS: Maternal LTL was measured using quantitative polymerase chain reaction at delivery in a prospective San Francisco primarily Latina birth cohort. Logistic regression models were used to investigate the association between postpartum maternal LTL and preterm birth. Maternal LTL was analyzed as a continuous predictor.<br><br>RESULTS: Out of 194 participants, 23 (11.9%) had preterm delivery. Longer postnatal maternal LTL was associated with preterm birth (crude OR 4.68; 95% confidence interval (CI) 1.07, 20.6, p&#x2009;=&#x2009;0.039; adjusted OR 12.8, 95% CI 1.83, 99.9, p&#x2009;=&#x2009;0.010). Age-stratified analysis showed that being under 35&#xa0;years increased the effect size of the association between maternal LTL and preterm birth (adjusted OR 32.5, 95% CI 2.58, 597, p&#x2009;<&#x2009;0.01).<br><br>CONCLUSIONS FOR PRACTICE: Latina mothers with moderate to late preterm infants had longer LTL in the immediate postpartum period compared to those with term infants. This association was stronger for mothers under the age of 35&#xa0;years. LTL may serve as a biomarker to better understand the pathophysiology and risk of preterm birth and could inform targeted interventions for prevention and early detection. Future studies&#xa0;are needed to understand physiological changes in maternal LTL from the prenatal to postnatal period in relation to birth outcomes.},
}
@article {pmid39967905,
year = {2025},
author = {Darvishi, FZ and Saadat, M},
title = {Association between leukocytes telomere length and parental consanguineous marriage.},
journal = {EXCLI journal},
volume = {24},
number = {},
pages = {177-178},
pmid = {39967905},
issn = {1611-2156},
}
@article {pmid39964637,
year = {2025},
author = {Mishra, A and Patel, TN},
title = {Locking the gates of immortality: targeting alternative lengthening of telomeres (ALT) pathways.},
journal = {Medical oncology (Northwood, London, England)},
volume = {42},
number = {3},
pages = {78},
pmid = {39964637},
issn = {1559-131X},
mesh = {Humans ; *Telomere Homeostasis/physiology ; *Neoplasms/genetics/pathology/metabolism ; Telomere ; Animals ; X-linked Nuclear Protein/genetics/metabolism ; Telomerase/metabolism/genetics ; },
abstract = {Telomere maintenance is essential for the unlimited proliferation of cancer cells. While most cancers reactivate telomerase to preserve telomeres, approximately 10-15% utilize the alternative lengthening of telomeres (ALT), a telomerase-independent mechanism driven by homologous recombination. ALT is primarily observed in sarcomas and neuroepithelial tumors and it is characterized by hallmarks such as heterogeneous telomere lengths, the presence of ALT-associated PML bodies (APBs), extrachromosomal telomeric repeats (ECTRs), and elevated replication stress. This review has a threefold aim: (1) to examine the mechanisms of ALT activation, (2) to highlight existing therapeutic interventions targeting ALT components and telosomic complexes, and, (3) to pinpoint potential molecular targets for novel anticancer treatments. Therapeutic strategies focus on disrupting APBs, stabilizing G-quadruplex structures, and inhibiting replication stress proteins such as FANCM and SMARCAL1. Emerging evidence highlights the role of shelterin proteins like TRF1 and TRF2, chromatin remodeling factors such as ATRX and DAXX, and the dysregulated cGAS-STING pathway in facilitating ALT activity. Moreover, the inhibitory role of RAP1-SUN1 protein interactions in telomere recombination provides a novel therapeutic avenue. Recent advances have elucidated the intricate balance of replication stress, DNA damage response, and recombination in ALT regulation. These insights can help overcome challenges posed by ALT + cancers, including their ability to transition from telomerase-dependent states. Targeting ALT-specific vulnerabilities offers a promising direction for developing innovative therapies that exploit the unique biology of ALT-driven tumors.},
}
@article {pmid39964064,
year = {2025},
author = {Shi, Y and Huang, H and Zhang, R and Yin, L},
title = {Causal association between telomere length and female cancers: a two-sample Mendelian randomization study.},
journal = {Postgraduate medical journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/postmj/qgaf028},
pmid = {39964064},
issn = {1469-0756},
abstract = {PURPOSE: To explore the causal associations between genetically predicted telomere length and gynecologic and breast cancers.<br><br>METHODS: This Mendelian randomization study used data from genome-wide association studies on telomere length and breast (BC), cervical cancer, endometrial (EC), and ovarian (OC) cancers. The primary analysis was performed using the inverse variance weighted (IVW) method, with confirmation using the weighted median, weighted mode, and MR-Egger methods. Heterogeneity was detected using Cochran's Q-test, horizontal pleiotropy using MR-Egger regression, outliers using MR-PRESSO, and discordant single-nucleotide polymorphisms using the leave-one-out method.<br><br>RESULTS: The genetic prediction results indicated causal associations between the risk of telomere length and EC [IVW; OR&#x2009;=&#x2009;1.29, 95% confidence interval (95%CI): 1.05-1.59, P&#xa0;=&#x2009;.02], leukocyte telomere length and EC (IVW; OR&#x2009;=&#x2009;1.23, 95%CI: 1.01-1.51, P&#x2009;=&#x2009;.04), telomere length and OC (IVW; OR&#x2009;=&#x2009;1.27, 95%CI: 1.01-1.60, P&#x2009;=&#x2009;.04), telomere length and BC (IVW; OR&#x2009;=&#x2009;1.12, 95%CI: 1.01-1.23, P&#x2009;=&#x2009;.03), and leukocyte telomere length and BC (IVW; OR&#x2009;=&#x2009;1.12, 95%CI: 1.02-1.24, P&#x2009;=&#x2009;.02). Cochran's Q-test revealed heterogeneity for telomere length and BC (P&#x2009;<&#x2009;.001), leukocyte telomere length and BC (P&#x2009;<&#x2009;.001), and B-cell telomere length and BC (P&#x2009;=&#x2009;.012). The MR-Egger regression results suggest that the analyses of telomere length and BC (P&#x2009;=&#x2009;.014) and leukocyte telomere length and BC (P&#x2009;=&#x2009;.044) were influenced by horizontal pleiotropy. The MR-PRESSO analysis indicated the presence of outliers in the analyses of telomere length and BC and leukocyte telomere length and breast cancer. After removing the outliers, the statistical significance remained.<br><br>CONCLUSION: This MR study suggests a causal association between telomere length and BC, EC, and OC, warranting additional study. Key message What is already known on this topic?&#xa0; Previous research has indicated an association between telomere length and the risk of various cancers, including breast and gynecologic cancers. However, the causal relationship remained unclear, necessitating further exploration to establish whether telomere length could be a modifiable risk factor for these cancers. What this study adds?&#xa0; This study provides robust evidence of a causal relationship between genetically predicted telomere length and an increased risk of breast cancer, endometrial cancer, and ovarian cancer, with specific odds ratios indicating a significant association. It highlights that both leukocyte and overall telomere length are important factors in cancer risk. How this study might affect research, practice, or policy?&#xa0; The findings could inform future research into telomere length as a biomarker for cancer risk, promote investigations into telomere-targeting interventions, and influence guidelines on screening and preventive strategies for at-risk populations based on genetic predispositions.},
}
@article {pmid39963020,
year = {2025},
author = {Chan, RNC and Huang, C and Ng, NYH and Tam, HCH and Tam, CHT and Cheng, F and Wong, KK and Shi, M and Ng, ACW and Tsang, AYT and Wang, CC and Cheung, LP and Tam, WH and Joglekar, MV and Hardikar, AA and Jenkins, AJ and Chan, JCN and Lim, CKP and Ma, RCW},
title = {Shortened Relative Leukocyte Telomere Length Is Associated With Polycystic Ovary Syndrome and Metabolic Traits.},
journal = {Endocrinology, diabetes &amp; metabolism},
volume = {8},
number = {2},
pages = {e70030},
doi = {10.1002/edm2.70030},
pmid = {39963020},
issn = {2398-9238},
support = {//University Grants Committee Research Grants Matching Scheme/ ; //Chinese University of Hong Kong Direct Grant/ ; 14102719//RGC General Research Fund/ ; 14110415//RGC General Research Fund/ ; CUHK471713//RGC General Research Fund/ ; CUHK473408//RGC General Research Fund/ ; //Croucher Foundation Senior Medical Research Fellowship/ ; R4012-18//Research Grants Council Research Impact Fund/ ; },
mesh = {Humans ; *Polycystic Ovary Syndrome/genetics ; Female ; Adult ; *Leukocytes/metabolism ; *Mendelian Randomization Analysis ; *Telomere ; Telomere Shortening ; Case-Control Studies ; },
abstract = {BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the commonest gyneco-endocrine disorders amongst women of reproductive age. Whether PCOS and cardiometabolic traits in PCOS patients are associated with shortened telomere length (TL) or relative leukocyte telomere length (rLTL) remains unclear.<br><br>METHODS: 214 women with PCOS and 214 age-matched women were recruited. rLTL was measured with an updated quantitative real-time PCR protocol and reported as &#x394;&#x394;Ct between telomere and a single-copy gene encoding &#x3b2;-globin relative to a normalisation control. A two-way Mendelian randomization analysis using the UK Biobank Resource was performed to assess the causal relationship between rLTL and PCOS.<br><br>RESULTS: Women with PCOS had significantly shortened rLTL (PCOS: 0.5&#x2009;&#xb1;&#x2009;0.7; control: 0.8&#x2009;&#xb1;&#x2009;0.6; p&#x2009;<&#x2009;0.001). Longer rLTL was associated with a lower risk of PCOS after adjusting for age, history of smoking and other cardiometabolic traits (OR: 0.503; 95% CI: 0.342-0.730; p&#x2009;<&#x2009;0.001). Longer rLTL was associated with reduced risk of dyslidpidemia (OR: 0.563; 95% CI: 0.450-0.968; p&#x2009;=&#x2009;0.042) in PCOS patients. PCOS subjects with rLTL shorter than mean of the rLTL of control subjects had an elevated risk of dysglycemia (OR: 2.09; 95% CI: 1.04-4.29; p&#x2009;=&#x2009;0.040). No causal relationships were found between rLTL and PCOS in the Mendelian randomization study.<br><br>CONCLUSIONS: Women with PCOS have significantly reduced rLTL and shorter LTL may be associated with cardiometabolic risk factors in PCOS subjects. There are no causal relationship between genetically determined PCOS and TL or vice versa.},
}
@article {pmid39962352,
year = {2025},
author = {Helia, O and Matúšová, B and Havlová, K and Hýsková, A and Lyčka, M and Beying, N and Puchta, H and Fajkus, J and Fojtová, M},
title = {Chromosome engineering points to the cis-acting mechanism of chromosome arm-specific telomere length setting and robustness of plant phenotype, chromatin structure and gene expression.},
journal = {The Plant journal : for cell and molecular biology},
volume = {121},
number = {4},
pages = {e70024},
doi = {10.1111/tpj.70024},
pmid = {39962352},
issn = {1365-313X},
support = {CZ.02.01.01/00/22_008/0004581//European Regional Development Fund/ ; 22-04364S//Grantov&#xe1; Agentura &#x10c;esk&#xe9; Republiky/ ; },
mesh = {*Arabidopsis/genetics ; *Telomere/genetics/metabolism ; *Phenotype ; *Chromatin/genetics/metabolism ; *Chromosomes, Plant/genetics ; Gene Expression Regulation, Plant ; Translocation, Genetic ; CRISPR-Cas Systems ; Telomere Homeostasis/genetics ; Genetic Engineering/methods ; Genome, Plant/genetics ; },
abstract = {The study investigates the impact of targeted chromosome engineering on telomere dynamics, chromatin structure, gene expression, and phenotypic stability in Arabidopsis thaliana. Using precise CRISPR/Cas-based engineering, reciprocal translocations of chromosome arms were introduced between non-homologous chromosomes. The subsequent homozygous generations of plants were assessed for phenotype, transcriptomic changes and chromatin modifications near translocation breakpoints, and telomere length maintenance. Phenotypically, translocated lines were indistinguishable from wild-type plants, as confirmed through morphological assessments and principal component analysis. Gene expression profiling detected minimal differential expression, with affected genes dispersed across the genome, indicating negligible transcriptional impact. Similarly, ChIPseq analysis showed no substantial alterations in the enrichment of key histone marks (H3K27me3, H3K4me1, H3K56ac) near junction sites or across the genome. Finally, bulk and arm-specific telomere lengths remained stable across multiple generations, except for minor variations in one translocation line. These findings highlight the remarkable genomic and phenotypic robustness of A. thaliana despite large-scale chromosomal rearrangements. The study offers insights into the cis-acting mechanisms underlying chromosome arm-specific telomere length setting and establishes the feasibility of chromosome engineering for studies of plant genome evolution and crop improvement strategies.},
}
@article {pmid39958913,
year = {2025},
author = {Lukhtanov, VA},
title = {Telomere DNA in the insect order Dermaptera and the first evidence for the non-canonical telomeric motif TTCGG in Arthropoda.},
journal = {Comparative cytogenetics},
volume = {19},
number = {},
pages = {13-18},
pmid = {39958913},
issn = {1993-0771},
abstract = {Despite recent advances in telomere research, the telomere DNA organization remains unknown for representatives of several insect orders. In this study, analysis of the chromosome-level genome assembly shows that the telomeric DNA of the earwig Labiaminor (Linnaeus, 1758) (Polyneoptera, Dermaptera, Spongiphoridae) consists of repeats of the 5 bp motif TTCGG/CCGAA. This is the first record describing the structure of telomeric DNA in the order Dermaptera. This record expands the spectrum of the known telomeric sequences, since the TTCGG motif has not been reported for insects previously.},
}
@article {pmid39955882,
year = {2025},
author = {Martino, P and Perez-Alarcón, M and Deconinck, L and De Raedt, R and Vanderhasselt, MA and Kozusznik, MW and Kooy, F and Hidalgo, V and Venero, C and Salvador, A and Baeken, C and Pulopulos, MM},
title = {Corrigendum to "Stress and telomere length in leukocytes: Investigating the role of GABRA6 gene polymorphism and cortisol" [Psychoneuroendocrinology (2025) 107358].},
journal = {Psychoneuroendocrinology},
volume = {174},
number = {},
pages = {107404},
doi = {10.1016/j.psyneuen.2025.107404},
pmid = {39955882},
issn = {1873-3360},
}
@article {pmid39955535,
year = {2025},
author = {Shen, J and Sun, J and Lin, S and Du, J},
title = {Association of leukocyte telomere length with periodontal attachment loss based on a cross-sectional study.},
journal = {BMC oral health},
volume = {25},
number = {1},
pages = {241},
pmid = {39955535},
issn = {1472-6831},
mesh = {Humans ; Cross-Sectional Studies ; Male ; *Leukocytes ; *Periodontal Attachment Loss ; Female ; Middle Aged ; *Telomere ; Aged ; Aged, 80 and over ; Nutrition Surveys ; United States ; },
abstract = {BACKGROUND: Leukocyte telomere length (LTL) has been implicated in various health outcomes, but its association with attachment loss in periodontal health remains underexplored.<br><br>METHODS: A total of 2521 US adults (Age: 61-85; Men: 50.5%) from the National Health and Nutrition Examination Survey (1999-2002) were included in this cross-sectional study. Baseline demographics were obtained from the questionaries, and LTL was determined using a polymerase chain reaction, and periodontal attachment loss was defined according to a professional physical examination. Multivariable regression analyses were conducted to assess the association between LTL, treated as a categorical and continuous variable, and periodontal attachment loss. The sensitivity analysis was verified by subgroup analyse, where interaction terms were used to examine the heterogeneity in associations across different subgroups.<br><br>RESULTS: Compared to the lowest quartile, the highest LTL quartile exhibited a significant positive association with periodontal attachment loss in the fully-adjusted model (&#x3b2;: 1.54 to 1.71, P&#x2009;<&#x2009;0.05). When LTL was treated as a continuous variable, a positive association persisted in the fully-adjusted model (&#x3b2;: 2.22 to 3.24, P&#x2009;<&#x2009;0.05). Subgroup analyses revealed a consistent positive association between LTL and periodontal attachment loss.<br><br>CONCLUSIONS: This study provides evidence of a positive association between leukocyte telomere length and attachment loss in periodontal health. Our results suggested that LTL may serve as a potential biomarker for periodontal health, emphasizing the importance of considering telomere length in understanding and managing periodontal conditions.},
}
@article {pmid39955533,
year = {2025},
author = {Wang, Q and Gao, Y and Taiwaikuli, D and Ding, H and Song, J and Yang, X and Tang, B and Zhou, X},
title = {DNA methylation-based telomere length is more strongly associated with long-term all-cause mortality than quantitative polymerase chain reaction-based telomere length among middle-aged and older hypertensive adults.},
journal = {Clinical epigenetics},
volume = {17},
number = {1},
pages = {22},
pmid = {39955533},
issn = {1868-7083},
support = {82260064//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Male ; Female ; *DNA Methylation/genetics ; Middle Aged ; *Hypertension/genetics/mortality ; Aged ; *Telomere/genetics ; Nutrition Surveys ; Cohort Studies ; Proportional Hazards Models ; Polymerase Chain Reaction/methods ; Telomere Homeostasis/genetics ; Cardiovascular Diseases/genetics/mortality ; },
abstract = {BACKGROUND: Telomere length (TL) has been linked to mortality risk across various populations. However, its predictive value for mortality risk specifically in hypertensive adults remains unclear.<br><br>METHODS: This cohort study utilized data from the 1999-2000 and 2001-2002 cycles of the National Health and Nutrition Examination Survey (NHANES). TL was assessed using DNA methylation (DNAmTL) and quantitative polymerase chain reaction (qPCRTL). Cox proportional hazards models were employed to examine the relationship between TL and mortality risk.<br><br>RESULTS: This study included 1601 participants, with 988 deaths occurring during a median follow-up of 184&#xa0;months, including 279 from cardiovascular disease (CVD). Deceased participants exhibited significantly lower levels of DNAmTL (6.45&#x2009;&#xb1;&#x2009;0.30 vs. 6.70&#x2009;&#xb1;&#x2009;0.28, P&#x2009;<&#x2009;0.001) and qPCRTL (0.89&#x2009;&#xb1;&#x2009;0.22 vs. 0.99&#x2009;&#xb1;&#x2009;0.24, P&#x2009;<&#x2009;0.001) compared to survivors. After full adjustment, each 1-kb decrement in DNAmTL and qPCRTL was associated with a 52% and 38% reduction in all-cause mortality risk, respectively. Participants in the highest TL quartile (Q4) for DNAmTL and qPCRTL had a 36% and 25% reduced risk of all-cause mortality&#xa0;than those in the lowest quartile (Q1), respectively. Receiver operating characteristic (ROC) curves demonstrated that DNAmTL had superior predictive value compared to qPCRTL (area under curve [AUC] 0.73 vs. 0.63, P&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: TL is inversely associated with all-cause mortality risk in middle-aged and older hypertensive adults, with DNAmTL showing greater predictive accuracy for long-term mortality than qPCRTL.},
}
@article {pmid39954068,
year = {2025},
author = {Ozcan, M and Burus, A and Mender, I and Dikmen, ZG and Gryaznov, SM and Bastug, T and Bayazit, Y},
title = {Investigation of the inhibitory effects of the telomere-targeted compounds on glutathione S-transferase P1.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {39954068},
issn = {1432-1912},
abstract = {Glutathione S-transferase P1 (GSTP1) plays a significant role in cancer progression and chemotherapy resistance, with its overexpression diminishing chemotherapeutic efficacy across various tumor types. This study evaluates the inhibitory effects of 6-thio-2'-deoxyguanosine (6-thio-dG) and its dimeric form (6-thio-2'-dG-Dimer) on GSTP1. Enzyme inhibition assays with recombinant human GSTP1, kinetic analysis, molecular docking, and molecular dynamic simulations were employed. Enzymatic assays were performed in 0.1 M phosphate buffer (pH 6.5) at 30 °C, containing 1 mM EDTA, 1 mM GSH, and 1 mM CDNB. The compounds 6-thio-dG and its dimer were dissolved in 2.5% DMSO for the experiments. The IC50 values indicated that the dimer exhibited a higher potency (IC50: 0.339 μM) than the monomer (IC50: 15.14 μM). Kinetic analysis revealed noncompetitive inhibition with glutathione (Ki: 12.26 μM) and mixed inhibition with CDNB (Ki: 11.41 μM) for the monomer, whereas the dimer showed mixed inhibition with glutathione (Ki: 0.972 μM) and competitive inhibition with CDNB (Ki: 0.723 μM). Molecular docking confirmed the higher binding affinity of the dimer (binding energy: - 7.9 kcal/mol, Ki: 1.595 μM) compared to the monomer (binding energy: - 6.2 kcal/mol, Ki: 28.21 μM). The dimer form of 6-thio-dG shows strong potential to enhance chemotherapeutic efficacy by effectively inhibiting GSTP1 and overcoming drug resistance. Its superior inhibitory properties make it a valuable candidate for targeted cancer therapies.},
}
@article {pmid39952372,
year = {2025},
author = {Lanna, A},
title = {Unexpected links between cancer and telomere state.},
journal = {Seminars in cancer biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.semcancer.2025.01.006},
pmid = {39952372},
issn = {1096-3650},
abstract = {Eukaryotes possess chromosome ends known as telomeres. As telomeres shorten, organisms age, a process defined as senescence. Although uncontrolled telomere lengthening has been naturally connected with cancer developments and immortalized state, many cancers are instead characterized by extremely short, genomically unstable telomeres that may hide cancer cells from immune attack. By contrast, other malignancies feature extremely long telomeres due to absence of 'shelterin' end cap protecting factors. The reason for rampant telomere extension in these cancers had remained elusive. Hence, while telomerase supports tumor progression and escape in cancers with very short telomeres, it is possible that different - transfer based or alternative - lengthening pathways be involved in the early stage of tumorigenesis, when telomere length is intact. In this Review, I hereby discuss recent discoveries in the field of telomeres and highlight unexpected links connecting cancer and telomere state. We hope these parallelisms may inform new therapies to eradicate cancers.},
}
@article {pmid39945220,
year = {2025},
author = {Gudmundsdottir, H and Graham, RP and Greipp, PT and Habermann, EB and Knudson, RA and Brandt, CA and Starlinger, P and Thiels, CA and Warner, SG and Smoot, RL and Truty, MJ and Kendrick, ML and Nagorney, DM and Cleary, SP and Halfdanarson, TR},
title = {Alternative lengthening of telomeres and Ki-67 proliferation index provide complementary information on recurrence risk after resection of pancreatic neuroendocrine tumors.},
journal = {Journal of neuroendocrinology},
volume = {},
number = {},
pages = {e70003},
doi = {10.1111/jne.70003},
pmid = {39945220},
issn = {1365-2826},
support = {//Robert D. and Patricia E Kern Center for the Science of Health Care Delivery/ ; //Department of Surgery at Mayo Clinic/ ; },
abstract = {Given the heterogeneous clinical behavior of pancreatic neuroendocrine tumors (pNETs), improved prognostic markers are needed to guide management and post-resection surveillance. Patients who underwent resection of large (≥3 cm) sporadic well-differentiated pNETs from 2000 to 2019 were identified. The Ki-67 proliferation index was determined using immunohistochemistry, and alternative lengthening of telomeres (ALT) status was assessed using fluorescence in situ hybridization. Recurrence-free and overall survival were estimated using Kaplan-Meier analysis. Multivariable Cox regression analysis evaluated factors associated with recurrence-free survival. A total of 106 patients were identified. ALT was positive in 57 (54%) and negative in 49 (46%). Ki-67 was ≥3% in 74 (70%) and <3% in 32 (30%). Tumors with Ki-67 ≥3% were more likely to be ALT positive (61% vs. 38%, p = .046). Stratifying by ALT status and Ki-67 proliferation index, median recurrence-free survival was 4.6 years for patients with ALT-positive/Ki-67 ≥3% tumors, 3.1 years for patients with ALT-positive/Ki-67 <3% tumors, 12.4 years for patients with ALT-negative/Ki-67 ≥3% tumors, and 20.2 years for patients with ALT-negative/Ki-67 <3% tumors (p < .001). Initial recurrence was distant in 82% and locoregional in 18%. Across all groups, overall survival was similar (p = .19). In multivariable analysis, advanced age, ALT positivity, perineural invasion, and lymph node metastases were associated with increased recurrence risk (all p < .05). ALT and Ki-67 provide complementary information on post-resection recurrence risk, which can guide subsequent surveillance and management strategies. These data support the incorporation of ALT testing into routine clinical practice.},
}
@article {pmid39943745,
year = {2025},
author = {Edwards, RJ and Chen, SH and Halliday, B and Bragg, JG},
title = {Small but mitey: a gapless telomere-to-telomere assembly of an unidentified mite with a streamlined genome.},
journal = {Genome biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/gbe/evaf023},
pmid = {39943745},
issn = {1759-6653},
abstract = {A draft assembly of the rainforest tree Rhodamnia argentea Benth. (malletwood, Myrtaceae) revealed contaminating DNA sequences that most closely matched those from mites in the family Eriophyidae. Eriophyoid mites are plant parasites that often induce galls or other deformities on their host plants. They are notable for their small size (averaging 200 μm), distinctive four-legged body structure, and heavily streamlined genomes, which are among the smallest known of all arthropods. Contaminating mite sequences were assembled into a high-quality gapless telomere-to-telomere nuclear genome. The entire genome was assembled on two fully contiguous chromosomes, capped with a novel TTTGG or TTTGGTGTTGG telomere sequence, and exhibited clear signs of genome reduction (34.5 Mbp total length, 68.6% arachnid BUSCO completeness). Phylogenomic analysis confirmed that this genome is that of a previously unsequenced eriophyoid mite. Despite its unknown identity, this complete nuclear genome provides a valuable resource to investigate invertebrate genome reduction.},
}
@article {pmid39943216,
year = {2025},
author = {Vernick, J and Martin, C and Montelpare, W and Dunham, AE and Overall, KL},
title = {Understanding the Influence of Early-Life Stressors on Social Interaction, Telomere Length, and Hair Cortisol Concentration in Homeless Kittens.},
journal = {Animals : an open access journal from MDPI},
volume = {15},
number = {3},
pages = {},
doi = {10.3390/ani15030446},
pmid = {39943216},
issn = {2076-2615},
support = {22-004//VetSRA/ ; W21-15//EveryCat/ ; 21-015//Winn Foundation/ ; 6010435//Sir James Dunn Animal Welfare Center/ ; 6010567//Companion Animal Trust Fund/ ; 6010567//AVC Internal Research Fund/ ; },
abstract = {The early postnatal period is a critical neurodevelopmental stage characterized by rapid neural maturation and is adversely affected by early-life stressors. This study explored the behavioural, physiological, and epigenetic consequences of early-life stress in a population of homeless rescue kittens. This longitudinal study included 50 kittens rescued and placed into foster care by the Prince Edward Island Humane Society. They underwent behavioural testing at 8, 10, and 12 weeks of age. Hair cortisol concentration was measured at 8 weeks and served as a physiological marker of the previous 3 months' cumulative stress response, which, for these kittens, included the late gestation period. A blood sample for relative telomere length measurement was taken at 10-12 weeks to estimate epigenetic changes as young kittens. Data were analyzed with respect to age and performance in all repeated measures tests, status as a stray or a surrender, and the presence of the dam in their foster homes. As expected, the performance of kittens in all tests changed over the 5 weeks of testing. Kittens separated from their mothers exhibited significantly higher hair cortisol concentrations (p = 0.02) and elongated relative telomere lengths (p = 0.04). No correlation was found between hair cortisol concentration and relative telomere lengths (p = 0.99). These results support the need for further study on the effects of epigenetics and early-life stress, both in kittens and across species.},
}
@article {pmid39940930,
year = {2025},
author = {Baldazzi, C and Bandini, L and Robustelli, V and Patuelli, A and Venturi, C and Grassi, A and Marzocchi, G and Ielpo, A and Solli, V and Bochicchio, MT and Paolini, S and Sartor, C and Zingarelli, F and Curti, A and Ottaviani, E and Testoni, N},
title = {Emergence and Cytogenetic Clonal Evolution of Chromosome 7 Abnormalities in Myeloid Malignancies: Investigating the Role of Telomere Dysfunction.},
journal = {International journal of molecular sciences},
volume = {26},
number = {3},
pages = {},
doi = {10.3390/ijms26031162},
pmid = {39940930},
issn = {1422-0067},
support = {GR-2018-12365278//Italian Ministry of Health/ ; },
mesh = {Humans ; *Chromosomes, Human, Pair 7/genetics ; *Clonal Evolution/genetics ; *Telomere/genetics ; Male ; Female ; *Chromosome Deletion ; Aged ; Middle Aged ; Chromosome Aberrations ; Adult ; Chromosomal Instability/genetics ; Aged, 80 and over ; Mutation ; Myeloproliferative Disorders/genetics/pathology ; },
abstract = {Monosomy 7 and deletion 7q are common chromosomal abnormalities in myeloid malignancies, and they are associated with a poor prognosis. The mechanism underlying their acquisition remains elusive. We identified a cohort of 24 patients exhibiting clones with different chromosome 7 abnormalities, such as deletion 7q, unstable derivatives (ring chromosomes or 'naked' centromeres), and monosomy 7. We designated this group as having cytogenetic clonal evolution of chromosome 7 abnormalities (CCE7). In some cases, CCE7 correlated with disease progression, suggesting that deletions or other derivatives involving the q-arm of chromosome 7 may arise early in the disease course. These abnormalities may be transient but can potentially evolve into monosomy 7. Within the CCE7 group, telomere loss or shortening may contribute to chromosomal instability and the emergence of unstable derivatives, as the chromosome 7 derivatives displayed loss or rearrangement of subtelomeric regions. Moreover, we identified variants in genes implicated in telomere biology disorders and observed specific genetic mutation profiles associated with different chromosome 7 abnormalities. These findings shed light on a potential mechanism leading to monosomy 7 through the evolution of chromosome 7q abnormalities. Identifying patients at risk of developing monosomy 7, based on the presence of unstable derivatives with telomere loss or a specific mutation profile, could potentially enhance patient management and guide the development of novel therapeutic strategies.},
}
@article {pmid39940762,
year = {2025},
author = {Assalve, G and Lunetti, P and Rocca, MS and Cosci, I and Di Nisio, A and Ferlin, A and Zara, V and Ferramosca, A},
title = {Exploring the Link Between Telomeres and Mitochondria: Mechanisms and Implications in Different Cell Types.},
journal = {International journal of molecular sciences},
volume = {26},
number = {3},
pages = {},
doi = {10.3390/ijms26030993},
pmid = {39940762},
issn = {1422-0067},
support = {2022KREEEF and P2022AXRW7//Ministero dell'universit&#xe0; e della ricerca/ ; },
mesh = {Humans ; *Mitochondria/metabolism ; *Telomere/metabolism/genetics ; Animals ; *Reactive Oxygen Species/metabolism ; Oxidative Stress ; DNA Damage ; Telomere Shortening ; Aging/metabolism/genetics ; Telomerase/metabolism ; Telomere Homeostasis ; },
abstract = {Telomeres protect chromosome ends from damage, but they shorten with each cell division due to the limitations of DNA replication and are further affected by oxidative stress. This shortening is a key feature of aging, and telomerase, an enzyme that extends telomeres, helps mitigate this process. Aging is also associated with mitochondrial dysfunction, leading to increased reactive oxygen species (ROS) that exacerbate cellular damage and promote apoptosis. Elevated ROS levels can damage telomeres by oxidizing guanine and disrupting their regulation. Conversely, telomere damage impacts mitochondrial function, and activation of telomerase has been shown to reverse this decline. A critical link between telomere shortening and mitochondrial dysfunction is the DNA damage response, which activates the tumor suppressor protein p53, resulting in reduced mitochondrial biogenesis and metabolic disruptions. This highlights the bidirectional relationship between telomere maintenance and mitochondrial function. This review explores the complex interactions between telomeres and mitochondria across various cell types, from fibroblasts to sperm cells, shedding light on the interconnected mechanisms underlying aging and cellular function.},
}
@article {pmid39938003,
year = {2025},
author = {Tometten, M and Beier, F and Kirschner, M and Schumacher, Y and Walter, J and Vieri, M and Kricheldorf, K and Röth, A and Platzbecker, U and Radsak, MP and Schafhausen, P and Corbacioglu, S and Höchsmann, B and Balabanov, S and Hinze, CH and Chromik, J and Heuser, M and Kreuter, M and Wlodarski, MW and Elbracht, M and Kurth, I and Koschmieder, S and Panse, JP and Meyer, R and Brümmendorf, TH},
title = {Late-Onset Telomere Biology Disorders: Clinical Insights and Treatment Outcomes from a Retrospective Registry Cohort.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024014632},
pmid = {39938003},
issn = {2473-9537},
abstract = {Pathogenic germline variants affecting proper telomere maintenance result in premature telomere shortening and cause telomere biology disorders (TBDs). While classical dyskeratosis congenita in children is rather well defined, late-onset ("cryptic") TBDs remain underrecognized, resulting in underdiagnosis and inadequate treatment in affected adults. Here, we present a series of adult TBD cases collected through the German TBD reference center between 2014 and 2024. Patients ≥18 years with an age-matched telomere length (TL) < 10th percentile in lymphocytes and detection of either a variant of uncertain significance, a pathogenic or a likely pathogenic variant in TBD-associated genes, and available clinical data were included in this analysis. On this basis, a novel point-based algorithm for categorization into proven, probable and suspected-only TBD cases, respectively, was developed. Out of a total of 1,537 TL analyses, 42 patients with proven (n=29) or probable (n=13) TBD were identified. Median age at first clinical manifestation and at diagnosis was 20.0 years and 34.1 years, respectively. Bone marrow failure (BMF) was the most frequent manifestation observed in our cohort (73.8%), followed by liver or interstitial lung diseases (50.0% and 41.5%, respectively). Immunosuppressive therapy was carried out in six patients with BMF, none of them responded. In comparison, eight of eight evaluable patients treated with androgen derivatives showed hematologic response. Our data provide novel real-world insight into the clinical manifestation spectrum, diagnosis as well as clinical course and treatment of TBD in adult, late-onset cases of this hereditary disease.},
}
@article {pmid39937009,
year = {2025},
author = {Levstek, T and Bahčič, E and Vujkovac, B and Cokan Vujkovac, A and Tesovnik, T and Remec, &#x17d;I and Čuk, V and Trebušak Podkrajšek, K},
title = {Telomere Length, Oxidative Stress, and Kidney Damage Biomarkers in Fabry Nephropathy.},
journal = {Cells},
volume = {14},
number = {3},
pages = {},
doi = {10.3390/cells14030218},
pmid = {39937009},
issn = {2073-4409},
support = {P1-0170//The Slovenian Research and Innovation Agency/ ; J3-50113//The Slovenian Research and Innovation Agency/ ; NA//Takeda Pharmaceuticals/ ; },
mesh = {Humans ; *Oxidative Stress ; *Fabry Disease/urine/genetics/pathology/metabolism ; Male ; *Biomarkers/urine/blood/metabolism ; Female ; Adult ; *Telomere/metabolism ; *Kidney Diseases/urine/pathology/genetics ; Middle Aged ; Kidney/pathology/metabolism ; Case-Control Studies ; Telomere Homeostasis ; Glomerular Filtration Rate ; },
abstract = {Fabry nephropathy is a life-threatening complication of Fabry disease characterized by complex and incompletely understood pathophysiological processes possibly linked to premature aging. We aimed to investigate leukocyte telomere length (LTL), oxidative stress, and kidney damage biomarkers in relation to kidney function. The study included 35 Fabry patients and 35 age and sex-matched control subjects. Based on the estimated slope of the glomerular filtration rate, the patients were divided into two groups. Relative LTL was quantified by qPCR, urinary biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) by UHPLC-MS/MS, and kidney damage biomarkers by flow cytometry. There was no statistically significant difference in LTL between Fabry patients and controls. However, a significant difference was observed in male patients compared to their matched control subjects (p = 0.013). Oxidative stress biomarkers showed no differences between patients and controls, while significant differences were observed in urinary IGFBP7, EGF, and OPN levels between Fabry patients with stable kidney function and those with progressive nephropathy (FDR = 0.021, 0.002, and 0.013, respectively). Significant differences were also observed in plasma levels of cystatin C, TFF3, and uromodulin between patients with progressive nephropathy and controls (all FDR = 0.039). Along with these biomarkers (FDR = 0.007, 0.017, and 0.010, respectively), NGAL also exhibited a significant difference between the two patient groups (FDR = 0.017). This study indicates accelerated telomere attrition, which may be related to disease burden in males. Furthermore, analyses of urinary oxidative stress markers revealed no notable disparities between the different kidney function groups, indicating their limited utility. However, promising differences were found in some biomarkers of kidney damage in urine and plasma.},
}
@article {pmid39934464,
year = {2025},
author = {Soares, MR and de Carvalho, RM and Dos Santos Cirino, H and Martins, R and Miranda Furtado, CL and Santana, BAA and Calado, RT and Ferriani, RA and Dos Reis, RM},
title = {Effect of SARS-CoV-2 infection on sperm telomere length.},
journal = {Journal of assisted reproduction and genetics},
volume = {},
number = {},
pages = {},
pmid = {39934464},
issn = {1573-7330},
support = {465482/2014-7//INCT - Institutos Nacionais de Ci&#xea;ncia e Tecnologia/ ; 465482/2014-7//INCT - Institutos Nacionais de Ci&#xea;ncia e Tecnologia/ ; 176841/2022-9//INCT - Institutos Nacionais de Ci&#xea;ncia e Tecnologia/ ; 13012/2023-7//CNPq - Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 306289/2022-9//CNPq - Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; },
abstract = {PURPOSE: The repercussions and outcomes of the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has raised concerns about potential adverse effects on the male reproductive system. Telomeres are crucial in maintaining the integrity and stability of genomic DNA, and viral infections can induce changes in telomere biology. In this study, the repercussions of SARS-CoV-2 infection in male reproductive health were analyzed.<br><br>METHODS: This case-control study enrolled subjects who donated blood and semen samples. Fifty-six men with and 56 without prior COVID-19 infection, ages 18-45&#xa0;years, were included. Semen analysis and hormonal levels were evaluated. The presence of SARS-CoV-2 RNA in semen and the sperm telomere length were assessed by quantitative polymerase chain reaction and associated with clinical and laboratory data. To reduce interference factors, known variables that influence telomere length were analyzed independently.<br><br>RESULTS: Sperm telomere length was significantly diminished in the COVID-19 positive group with a mean difference of 0.635 compared to the negative group (p&#x2009;=&#x2009;0.041). Most individuals in the COVID-19 positive group were clinically classified as asymptomatic/mild illness, and all samples were collected more than 90&#xa0;days after recovery. No statistically significant differences were observed between the groups in terms of clinical data, semen parameters, and serum levels of follicle-stimulation hormone, estradiol, and testosterone. Persistent or subgenomic SARS-CoV-2 RNA was not detected in the semen samples.<br><br>CONCLUSION: This study revealed that SARS-CoV-2 infection reduced sperm telomere length without alterations in semen parameters or hormonal levels. These results provide further evidence that SARS-CoV-2 infection can induce genomic alterations in human sperm.},
}
@article {pmid39933571,
year = {2025},
author = {Blanco, MB and Smith, DL and Greene, LK and Lin, J and Klopfer, PH},
title = {Food deprivation is associated with telomere elongation during hibernation in a primate.},
journal = {Biology letters},
volume = {21},
number = {2},
pages = {20240531},
doi = {10.1098/rsbl.2024.0531},
pmid = {39933571},
issn = {1744-957X},
support = {//Duke Lemur Center/ ; },
mesh = {Animals ; *Hibernation/physiology ; *Cheirogaleidae/physiology/genetics ; *Telomere/physiology ; *Food Deprivation ; Male ; Female ; Telomere Homeostasis ; },
abstract = {Telomeres, the protective ends of chromosomes, progressively shorten due to incomplete mitotic replication and oxidative stress. In some organisms, transient telomere elongation may occur, for example, when individuals have an energy surplus to counter stress-induced life events or when elongating telomeres is a last chance to increase fitness. Mammalian hibernators are good models to test telomere dynamics, as they cycle between prolonged bouts of metabolic depression (torpor) punctuated by short surges to euthermia (arousals). We studied captive fat-tailed dwarf lemurs (Cheirogaleus medius), strepsirrhine primate hibernators, that were food-deprived (n = 8) or fed daily (n = 7) during hibernation (4.5 months). We compared telomere lengths, assayed via qPCR from oral swabs, at five strategic time points that span a full year. Food-deprived subjects underwent multi-day torpor/arousal cycles, lost considerable body mass and elongated telomeres during hibernation but shortened them upon emergence. In contrast, food-provisioned subjects ate daily, lost body mass more slowly, underwent shallower and shorter torpor bouts and experienced little change in telomere lengths during the same periods. Our results highlight a complex relationship between telomere dynamics, energy balance and torpor expression. Further investigation is warranted to elucidate the regulation of protective mechanisms in these primate hibernators.},
}
@article {pmid39933569,
year = {2025},
author = {Shephard, AM and Ledón-Rettig, CC},
title = {A novel carnivorous diet reduces brain telomere length.},
journal = {Biology letters},
volume = {21},
number = {2},
pages = {20240593},
doi = {10.1098/rsbl.2024.0593},
pmid = {39933569},
issn = {1744-957X},
mesh = {Animals ; *Brain/metabolism ; *Diet ; *Telomere ; Larva/growth &amp; development/physiology/genetics ; Anura/physiology/genetics ; Carnivory ; Telomere Shortening ; },
abstract = {Developmental conditions can profoundly influence adult survival or longevity. One established correlate of longevity is the length of telomeres-non-coding DNA regions that protect chromosomal ends. Telomere length in adulthood can be influenced by environmental conditions during development, such as nutrient restriction. Yet, we lack experimental studies of how adult telomere length is affected by a different form of nutritional variation: diet type. Here, we asked how diet-type variation during larval development affects telomere length in multiple post-metamorphic somatic tissues of the Mexican spadefoot (Spea multiplicata), an anuran species whose larvae develop on two qualitatively distinct diets: an ancestral omnivorous diet of detritus or a more novel carnivorous diet of live shrimp. We found that larvae developing on the novel shrimp diet developed into post-metamorphic frogs with shorter telomeres in the brain-a structure that is particularly vulnerable to harmful effects of nutritional adversity, such as oxidative stress. Given known links between telomere length and neurological health outcomes, our study suggests that a dietary transition to carnivory might carry costs in terms of compromised neural integrity later in life. This work highlights the lasting impact of a developmental diet on somatic maintenance and health.},
}
@article {pmid39932851,
year = {2025},
author = {Gao, Z and Yu, Y and Eckel-Mahan, K and Kolonin, MG},
title = {Caloric Restriction and Telomere Preservation in TERT Knockout Adipocyte Progenitors Does Not Rescue Mice From Metabolic Dysfunction due to a TERT Function in Adipocyte Mitochondria.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e14499},
doi = {10.1111/acel.14499},
pmid = {39932851},
issn = {1474-9726},
support = {R01DK125922/NH/NIH HHS/United States ; },
abstract = {Inactivation of telomerase (TERT) in adipocyte progenitor cells (APC) expedites telomere attrition, and the onset of diabetes in mice fed high-fat diet (HFD), which promotes APC over-proliferation and replicative senescence. Here, we show that time-restricted feeding or caloric restriction in the postnatal development of mice subsequently subjected to HFD prevents telomere attrition but not glucose intolerance. This metabolic effect of dietary intervention was not observed for mice with TERT KO in endothelial or myeloid cells. To characterize the telomere-independent effects of TERT in the APC lineage, we analyzed mice with TERT knockout in mature adipocytes (AD-TERT-KO), which do not proliferate and avoid telomere attrition. Analysis of adipocytes from AD-TERT-KO mice indicated reliance on glycolysis and decreased mitochondrial oxidative metabolism. We show that AD-TERT-KO mice have reduced cold tolerance and metabolism abnormality indicating a defect in adaptive thermogenesis, characteristic of aging. Conversely, ectopic TERT expression in brown adipocytes-induced mitochondrial oxidation and thermogenic gene expression. We conclude that TERT plays an important non-canonical function in the mitochondria of adipocytes.},
}
@article {pmid39929725,
year = {2025},
author = {Opresko, PL and Sanford, SL and De Rosa, M},
title = {Oxidative Stress and DNA Damage at Telomeres.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041707},
pmid = {39929725},
issn = {1943-0264},
abstract = {Oxidative stress is associated with increasing telomere shortening and telomere dysfunction, as well as with numerous pathologies in humans, including inflammatory diseases and cancer. Critically short and dysfunctional telomeres lose their ability to protect chromosome ends, which triggers irreversible growth arrest, termed senescence, or genomic instability. Telomeres are highly sensitive to damage from reactive oxygen species, which increase under conditions of oxidative stress. This work covers the evidence that oxidative damage to telomeric DNA alters telomere maintenance by various mechanisms and describes the DNA repair pathways important for preserving telomere function under oxidative stress conditions.},
}
@article {pmid39928198,
year = {2025},
author = {Zhao, J and Ye, L and Yan, W and Huang, W and Wang, G},
title = {Exploration of telomere-related biomarkers for lung adenocarcinoma and targeted drug prediction.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {148},
pmid = {39928198},
issn = {2730-6011},
abstract = {AIM: Bioinformatics analyses were performed to identify telomere biomarkers to develop a diagnostic model for lung adenocarcinoma (LUAD) and to predict potential target drugs for patients with LUAD.<br><br>BACKGROUND: Telomeres function crucially in maintaining genome stability and chromosome integrity, and telomere-related genes (TRGs) serve as potential prognostic markers in a variety of cancers. However, studies focusing on TRGs in LUAD are limited.<br><br>OBJECTIVE: To screen key telomere-related markers for LUAD and to evaluate their potential impact on the occurrence and development of LUAD.<br><br>METHODS: LUAD samples were collected from University of California Santa Cruz (UCSC) Xena and 2093 telomere-related genes (TRGs) were obtained from TelNet database. Hub genes were screened using "WGCNA" package. Differentially expressed genes (DEGs) between tumor and control samples were filtered using "DESeq" package. Protein-protein interaction (PPI) network analysis was performed to select candidate genes, from which telomere-related biomarkers were identified by machine learning and used to develop a nomogram. Functional enrichment pathways of the biomarkers were analyzed using "clusterProfiler" package. Correlation between immune cell infiltration and the biomarkers was examined by Spearman method. Targeted drugs were predicted and molecular docking models were developed using AutoDockTools. Finally, the screened biomarkers were validated by performing in vitro cellular assays.<br><br>RESULTS: A total of 259 hub genes, 2848 DEGs, and 48 differentially expressed TRGs in LUAD were screened. Subsequently, 13 candidate genes were obtained by PPI network analysis. LASSO and support vector machine-recursive feature elimination (SVM-RFE) algorithms further reduced the number of telomere-related biomarkers to four (CCNB1, CDC20, PLK1, and TOP2A). A nomogram with a strong predictive performance was created. These four biomarkers were mainly enriched in the mitogenic pathways and exhibited a strong correlation with immune cell infiltration. Three drugs (Lucanthone, Fulvestrant, and Myricetin) targeting the four biomarkers were predicted to be able to treat LUAD. Finally, in vitro cellular experiments demonstrated that CCNB1 and PLK1 have potential effects on proliferation, migration, invasion and AKT/mTOR signaling pathway in LUAD cells.<br><br>CONCLUSION: This study provided novel diagnostic biomarkers, therapeutic targets, and potential drugs for LUAD.},
}
@article {pmid39925560,
year = {2025},
author = {Shakeri, F and Nabi, A and Farashahi, E and Erfanian, S and Agha-Rahimi, A},
title = {Selected Spermatozoa at Conventional Magnification Cannot Guarantee in Obtaining Spermatozoa With Long Telomere Length in Severe Teratozoospermia Patients.},
journal = {Cureus},
volume = {17},
number = {1},
pages = {e77240},
pmid = {39925560},
issn = {2168-8184},
abstract = {Background Sperm selection from the population of processed spermatozoa cells after density gradient centrifugation (DGC) can assist embryologists in selecting high-quality sperm. Sperm selection of low-quality and chromatin-damaged spermatozoa is inevitable in severe teratozoospermia semen specimens. This study was conducted to evaluate whether sperm selection at ×400 magnification enables embryologists to select a population of spermatozoa with low DNA fragmentation and high sperm telomere length (STL) in semen samples with severe teratozoospermia. Methods A total of 23 infertile men characterized by severe teratozoospermia were selected. Sperm DNA fragmentation (SDF) and relative STL (r-STL) were evaluated at three stages: specimen collection, after DGC, and during the single selection of spermatozoa at ×400 magnification (single selection). The 23 patients were divided into two groups, including 14 with normal morphology ≤1% and nine with normal morphology of 2%. SDF and r-STL were compared between the two groups at three stages. Results The results of this study showed that although SDF decreased remarkably after DGC and single selection (F=64.327, P-value=0.000), the DNA fragmentation index obtained for each semen sample was more than the cutoff point of 18% based on the Halo sperm test. No statistically significant differences were observed in r-STL after DGC and single selection (F=1.978, P-value=0.163). Meanwhile, the pairwise comparison of r-STL showed that in the 2% normal morphology group, the mean relative telomere length was significantly higher in the selected spermatozoa compared to the semen specimen (P=0.014). This increase can be attributed to DGC and single selection by the embryologist. Also, there was no correlation between SDF and r-STL in the semen samples with severe teratozoospermia (r=0.01, P-value=0.964). Conclusions This study suggests that investing more time in sperm selection can decrease SDF, but r-STL of spermatozoa selected by the embryologist does not increase in severe teratozoospermia semen samples with morphology ≤1%.},
}
@article {pmid39921881,
year = {2025},
author = {Hernández-Silva, D and López-Abellán, MD and Martínez-Navarro, FJ and García-Castillo, J and Cayuela, ML and Alcaraz-Pérez, F},
title = {Development of a Short Telomere Zebrafish Model for Accelerated Aging Research and Antiaging Drug Screening.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70007},
doi = {10.1111/acel.70007},
pmid = {39921881},
issn = {1474-9726},
support = {PI22/00861//Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union/ ; },
abstract = {Increased life expectancy is associated with a higher risk of age-related diseases, which represent a major public health challenge. Animal models play a crucial role in aging research, enabling the study of diseases at the organism level and facilitating drug development and repurposing. Among these models, zebrafish stands out as an excellent in vivo system due to its unique characteristics. However, the longevity of zebrafish is a limitation for research, as it often takes too long to obtain results within a reasonable timeframe. To address this, we have developed a short telomere zebrafish line (ST2) with a premature aging phenotype during the larval stage. Although less extreme than the tert-deficient G2 larvae, ST2 larvae exhibit reduced telomerase expression and activity, along with shortened telomeres. they also exhibit increased cellular senescence, apoptosis, and premature death. As a proof of concept, we evaluated the antiaging effects of two compounds: resveratrol (a polyphenol) and navitoclax (a senolytic). Our results confirm the antiaging properties of resveratrol, which improves telomere maintenance. However, navitoclax does not attenuate the ST2 phenotype. Taking advantage of the zebrafish larval model, this premature aging system provides a valuable platform for in vivo testing of rejuvenating molecules through drug screening, using telomere length or survival as a readout.},
}
@article {pmid39921567,
year = {2025},
author = {Goncalves, T and Cunniffe, S and Ma, TS and Mattis, N and Rose, AW and Kent, T and Mole, DR and Geiller, HEB and van Bijsterveldt, L and Humphrey, TC and Hammond, EM and Gibbons, RJ and Clynes, D and Rose, AM},
title = {Elevated reactive oxygen species can drive the alternative lengthening of telomeres pathway in ATRX-null cancers.},
journal = {Nucleic acids research},
volume = {53},
number = {4},
pages = {},
pmid = {39921567},
issn = {1362-4962},
support = {CL-2018-13-005//National Institute of Health and Care Research Clinical Lectureship/ ; SGL023\1055//Academy of Medical Sciences Starter/ ; 0&#xa0;011&#xa0;483//University of Oxford Medical Sciences/ ; 15-202//Children with Cancer UK/ ; 101&#xa0;136&#xa0;835//EU Horizon Europe Research and Innovation program Cancer Mission 'HIT-GLIO'/ ; C6078/A28736/CRUK_/Cancer Research UK/United Kingdom ; //MRC DPhil Studentship/ ; },
mesh = {*X-linked Nuclear Protein/genetics/metabolism ; *Reactive Oxygen Species/metabolism ; Humans ; *Telomere Homeostasis/genetics ; Cell Line, Tumor ; *Telomere/metabolism/genetics ; Glioma/genetics/metabolism/pathology ; R-Loop Structures ; Ribonuclease H/metabolism/genetics ; Tumor Microenvironment/genetics ; Osteosarcoma/genetics/pathology/metabolism ; Mutation ; },
abstract = {The alternative lengthening of telomeres (ALT) pathway is a telomerase-independent mechanism for immortalization in cancer cells and is commonly activated in low-grade and high-grade glioma, as well as osteosarcoma. The ALT pathway can be activated under various conditions and has often been shown to include mutational loss of ATRX. However, this is insufficient in isolation and so other cellular event must also be implicated. It has been shown that excessive accumulation of DNA:RNA hybrid structures (R-loops) and/or formation of DNA-protein crosslinks (DPCs) can be other important driving factors. The underlying cellular events leading to R-loop and DPC formation in ALT cancer cells to date remain unclear. Here, we demonstrate that excessive cellular reactive oxygen species (ROS) is an important causative factor in the evolution of ALT-telomere maintenance in ATRX-deficient glioma. We identified three sources of elevated ROS in ALT-positive gliomas: co-mutation of SETD2, downregulation of DRG2, and hypoxic tumour microenvironment. We demonstrate that elevated ROS leads to accumulation of R-loops and, crucially, resolution of R-loops by the enzyme RNase H1 prevents ALT pathway activity in cells exposed to elevated ROS. Further, we found a possible causal link between the formation of R-loops and the accumulation of DPCs, in particular, formation of TOP1 complexes covalently linked to DNA (Top1cc). We also demonstrate that elevation of ROS can trigger over-activity of the ALT pathway in osteosarcoma and glioma cell lines, resulting in excessive DNA damage and cell death. This work presents important mechanistic insights into the endogenous origin of excessive R-loops and DPCs in ALT-positive cancers, as well as highlighting potential novel therapeutic approaches in these difficult-to-treat cancer types.},
}
@article {pmid39918489,
year = {2025},
author = {Nagao, K and Watanuki, M and Hayashi, H and Kawamata, N and Kuroiwa, K and Narita, H and Okamura, R and Shimada, S and Arai, N and Kawaguchi, Y and Yanagisawa, K and Hattori, N},
title = {Clinical impact of donor telomere length after umbilical cord blood transplantation.},
journal = {Cytotherapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcyt.2025.01.011},
pmid = {39918489},
issn = {1477-2566},
abstract = {BACKGROUND AND AIMS: Several studies have shown that the telomere length of engrafted donor cells affects the clinical outcomes in patients with hematologic diseases after allogeneic stem-cell transplantation (allo-SCT). However, the relationship between donor telomere length and clinical outcomes after umbilical-cord blood transplantation (UCBT) remains unknown. The study aim was to assess the relationship between donor telomere length and transplantation outcomes.<br><br>METHODS: We measured donor-derived relative telomere length (RTL) in 75 patients after single-unit UCBT and evaluated the association between telomere length and transplantation outcomes.<br><br>RESULTS: Compared with patients with shorter RTL, patients with longer RTL had a higher risk of bacterial and bloodstream infections [hazard ratio (HR), 4.79; 95% confidence interval (CI), 1.70-13.46; P = 0.003 and HR, 3.43; 95% CI, 1.19-9.82; P = 0.022, respectively] and was possibly associated with reduced relapse (HR 0.44, 95% CI 0.15-1.27, P = 0.13) by multivariate analysis.<br><br>CONCLUSIONS: Patients after UCBT who received engrafted donor cells with longer RTL had a higher risk of bacterial and bloodstream infections. The measured donor-derived RTL at engraftment after UCBT may predict clinical outcomes.},
}
@article {pmid39911301,
year = {2025},
author = {Light, J and Schratz, KE and Nanegrungsunk, O and Rudnick, N and Armanios, M and Bressler, NM},
title = {Adult-Onset Presentations of Retinopathy Associated With Short Telomere Syndromes.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251316324},
pmid = {39911301},
issn = {2474-1272},
abstract = {Purpose: To describe the association between short telomere syndrome and exudative retinopathies in adults. Methods: This case series compared the presentation, course of treatment, and visual outcomes of 2 patients with adult-onset retinopathy associated with short telomere syndrome. Results: In Case 1, a 53-year-old man initially presented with bilateral retinal telangiectasias and preretinal hemorrhage in the left eye, which was followed by multiple vitreous hemorrhages. In the subsequent 15 years, the patient was diagnosed with pulmonary fibrosis, liver cirrhosis, and a RTEL1 gene mutation, consistent with short telomere syndrome. In Case 2, a previously asymptomatic 26-year-old man with paternally inherited short telomere syndrome (TERC gene mutation) presented with floaters, bilateral peripheral retinal capillary nonperfusion, and an aneurysmal lesion with surrounding exudation. Conclusions: Short telomere syndromes, with systemic features that can be life-threatening, can manifest initially in adulthood with retinal telangiectasia, aneurysmal lesions, exudation, or peripheral retinal capillary nonperfusion, preceding systemic manifestations. Because the systemic manifestations of retinal telangiectasia and peripheral retinal capillary nonperfusion are progressive and can be life-threatening, recognizing these findings in adults with retinal telangiectasia is crucial.},
}
@article {pmid39911233,
year = {2024},
author = {Zhu, S and Hao, Z and Chen, Q and Liu, X and Wu, W and Zhang, F},
title = {A two-sample bidirectional Mendelian randomization analysis between telomere length and hyperthyroidism.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1369800},
pmid = {39911233},
issn = {1664-2392},
mesh = {Humans ; *Mendelian Randomization Analysis ; *Hyperthyroidism/genetics ; *Genome-Wide Association Study ; *Polymorphism, Single Nucleotide ; Telomere/genetics ; Telomere Homeostasis/genetics ; Female ; Genetic Predisposition to Disease ; },
abstract = {BACKGROUND: hyperthyroidism characterized by low thyrotropin, highlighting complications and risks, including cardiac issues, osteoporosis, adverse pregnancy outcomes, unintentional weight loss, and increased mortality associated with untreated hyperthyroidism. However, the casual association between telomere length (TL) and hyperthyroidism remains unclear.<br><br>OBJECTIVE: We aim to explore the casual relationship between TL and hyperthyroidism.<br><br>METHODS: A two-sample bidirectional Mendelian randomization (MR) analysis employed the inverse variance weighted (IVW) method, supplemented by additional approaches such as Weighted Median (WM), and MR Egger.<br><br>RESULTS: The summary statistics for TL were derived from the UK Biobank, comprising 472,174 individuals, while the data for hyperthyroidism were sourced from the GWAS Catalog and the FinnGen database, encompassing cohorts of 460,499 and 173,938 individuals, respectively. Utilizing 139 genome-wide significant single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for TL, forward MR analyses indicated a negative causal effect of TL on hyperthyroidism. The risk of hyperthyroidism decreased as genetically predicted TL increased by one standard deviation, as determined by the IVW form GWAS Catalog (OR:0.659,95%CI: 0.541-0.802, p <0.001) and IVW from FinnGen(OR:0.634, 95%CI: 0.479-0.840, p = 0.001). Other MR methods exhibited a consistent trend in the impact of TL on hyperthyroidism. Reverse MR analysis suggested no causal association between TL and hyperthyroidism (p > 0.05). Sensitivity analyses confirmed the robustness of these results, suggesting minimal susceptibility to confounding factors and bias.<br><br>CONCLUSION: The finding that longer telomeres reduce hyperthyroidism risk highlights the need to validate hyperthyroidism's impact on telomere length, offering valuable insights for prevention and treatment.},
}
@article {pmid39908316,
year = {2025},
author = {Weixlbraun, J and Chapagain, D and Cornils, JS and Smith, S and Schwarzenberger, F and Hoelzl, F},
title = {Impact of trainability on telomere dynamics of pet dogs (Canis lupus familiaris): An explorative study in aging dogs.},
journal = {PloS one},
volume = {20},
number = {2},
pages = {e0317332},
pmid = {39908316},
issn = {1932-6203},
mesh = {Animals ; Dogs ; *Aging/physiology/genetics ; *Telomere/genetics/metabolism ; Male ; Female ; Pets ; Cognition/physiology ; Behavior, Animal/physiology ; Telomere Homeostasis ; Telomere Shortening ; },
abstract = {This research studied the impact of various factors (including social and physiological parameters) on telomere dynamics in pet dogs. Telomeres, essential for maintaining genomic integrity, undergo shortening with each cell division, leading to cellular senescence. Previous studies in humans have linked cognitive and social factors with telomere dynamics but in animals, such associations remain understudied. This study is based on a previous study, where behavioral and cognitive changes in aging pet dogs were investigated. Together with standard variables (sex, age, body weight, diet), behavioral predictors that were assessed in the "Modified Vienna Canine Cognitive Battery" were used. This study aimed to investigate the influence of these factors on telomere dynamics in aging pet dogs. The relative telomere length of 63 dogs was measured, using a qPCR method and a model selection approach was applied to assess which variables can explain the found telomere patterns. Results revealed a strong association of the behavioral factor called trainability and telomere change. Trainability was the best predictor for telomere change over time and was the only predictor having a relative variable importance (RVI) above 0.7. This finding suggests that higher trainability positively affects telomere dynamics in aging dogs and factors like age, sex, diet, and other cognitive parameters are less important. The study sheds light on the potential role of cognitive factors in canine aging and offers insights into improving the quality of life for aging dogs, but further research is needed to comprehensively understand the interplay between behavior, cognition, and telomere dynamics in dogs.},
}
@article {pmid39905075,
year = {2025},
author = {Zhang, F and Cheng, D and Porter, KI and Heck, EA and Wang, S and Zhang, H and Davis, CJ and Robertson, GP and Zhu, J},
title = {Modification of the telomerase gene with human regulatory sequences resets mouse telomeres to human length.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {1211},
pmid = {39905075},
issn = {2041-1723},
support = {R01AG073423//U.S. Department of Health &amp; Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R35GM149529//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; ME220261//United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP)/ ; ME220261//United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP)/ ; },
mesh = {Animals ; *Telomerase/genetics/metabolism ; Humans ; *Telomere/metabolism/genetics ; Mice ; *Mice, Knockout ; Male ; Telomere Homeostasis/genetics ; Female ; Telomere Shortening/genetics ; Regulatory Sequences, Nucleic Acid/genetics ; Aging/genetics ; Mice, Inbred C57BL ; },
abstract = {Telomeres shorten with each cell division, serving as biomarkers of aging, with human tissues exhibiting short telomeres and restricted telomerase expression. In contrast, mice have longer telomeres and widespread telomerase activity, limiting their relevance as models for human telomere biology. To address this, we engineer a mouse strain with a humanized mTert gene (hmTert), replacing specific non-coding sequences with human counterparts. The hmTert gene, which is repressed in adult tissues except the gonads and thymus, closely mimics human TERT regulation. This modification rescues telomere dysfunction in mTert-knockout mice. Successive intercrosses of Tert[h/-] mice stabilized telomere length below 10 kb, while Tert[h/h] mice achieve a human-like average length of 10-12 kb, compared to 50 kb in wildtype mice. Despite shortened telomeres, Tert[h/h] mice maintain normal body weight and cell homeostasis. These mice, with humanized telomere regulation, represent a valuable model to study human aging and cancer.},
}
@article {pmid39904253,
year = {2025},
author = {Yu, J and Liu, Y and Zhang, H and Ping, F and Li, W and Xu, L and Li, Y},
title = {Serum Growth Differentiation Factor 15 is Negatively Associated with Leukocyte Telomere Length.},
journal = {The journal of nutrition, health &amp; aging},
volume = {29},
number = {4},
pages = {100493},
doi = {10.1016/j.jnha.2025.100493},
pmid = {39904253},
issn = {1760-4788},
abstract = {BACKGROUND: Telomere length(TL)and mitochondrial DNA copy number(mtDNAcn) are classic biomarker of aging. Recently, growth differentiation factor 15(GDF15) has attracted considerable attention as a vital component in the aging process.<br><br>METHODS: The present study aimed to study the relationship between GDF15 and telomere length and mtDNAcn.This was a cross-sectional analysis nested in a longitudinal cohort study conducted in Changping District, Beijing, from 2014 to 2021. Serum GDF15,leukocyte lelomere length(LTL) and mtDNAcn were determined in 802 subjects.LTL and mtDNAcn was quantified by real-time PCR assay. Multivariate linear regression and restricted cubic spline diagram were used for statistical analysis.<br><br>RESULTS: Subjects with higher GDF15 were older,had larger waist circumference, higher systolic blood pressure and glycated hemoglobin A1c (HbA1c),shorter LTL and tended to had less mtDNAcn. In correlation analysis, GDF15 was positively correlated with age, while LTL and mtDNAcn were negatively correlated with age.After adjusting for confounding factors,GDF15 was negatively associated with LTL (&#x3b2;&#x2009;=&#x2009;-0.120, 95%CI [-0.197, -0.042], p&#x2009;=&#x2009;0.003) and the association was linear(p for nonlinear&#x2009;=&#x2009;0.645), while the negative association between GDF15 and mtDNAcn did not reach significance.In the stratified analyses,the negative associations between GDF15 and LTL were more prominent in women, overweight individuals, or subjects with abnormal glucose tolerance (AGT), but similar results were observed in younger and older subjects.<br><br>CONCLUSIONS: This study found a linear negative association between GDF 15 and LTL,which was more prominent in women, overweight or AGT subjects.These results supported that GDF15 might be a reliable biomarker of aging.},
}
@article {pmid39903555,
year = {2025},
author = {Stajnko, A and Pineda, D and Klus, JK and Love, TM and Thurston, SW and Mulhern, MS and Strain, JJ and McSorley, EM and Myers, GJ and Watson, GE and Shroff, E and Shamlaye, CF and Yeates, AJ and van Wijngaarden, E and Broberg, K},
title = {Associations of Prenatal Mercury Exposure and PUFA with Telomere Length and mtDNA Copy Number in 7-Year-Old Children in the Seychelles Child Development Nutrition Cohort 2.},
journal = {Environmental health perspectives},
volume = {133},
number = {2},
pages = {27002},
doi = {10.1289/EHP14776},
pmid = {39903555},
issn = {1552-9924},
mesh = {Humans ; Female ; Seychelles ; Child ; Pregnancy ; *Mercury/blood ; *Telomere/drug effects ; *Prenatal Exposure Delayed Effects ; Fatty Acids, Unsaturated ; Male ; DNA, Mitochondrial ; DNA Copy Number Variations ; Hair/chemistry ; Cohort Studies ; Fetal Blood/chemistry ; Environmental Pollutants/blood ; Environmental Exposure/statistics &amp; numerical data ; },
abstract = {BACKGROUND: Telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) variations are linked to age-related diseases and are associated with environmental exposure and nutritional status. Limited data, however, exist on the associations with mercury exposure, particularly early in life.<br><br>OBJECTIVE: We examined the association between prenatal mercury (Hg) exposure and TL and mtDNAcn in 1,145 Seychelles children, characterized by a fish-rich diet.<br><br>METHODS: Total mercury (THg) was determined in maternal hair at delivery and cord blood. TL and mtDNAcn were determined relative to a single-copy hemoglobin beta gene in the saliva of 7-y-old children. Linear regression models assessed associations between THg and relative TL (rTL) and relative mtDNAcn (rmtDNAcn) while controlling for maternal and cord serum polyunsaturated fatty acid (PUFA) status and sociodemographic factors. Interactions between THg and child sex, PUFA, and telomerase genotypes were evaluated for rTL and rmtDNAcn.<br><br>RESULTS: Higher THg concentrations in maternal hair and cord blood were associated with longer rTL [&#x3b2;=0.009; 95% confidence interval (CI): 0.002, 0.016 and &#x3b2;=0.002; 95% CI: 0.001, 0.003, respectively], irrespective of sex, PUFA, or telomerase genotypes. Maternal serum n-6 PUFA and n-6/n-3 ratio were associated with shorter [&#x3b2;=-0.24; 95% CI: -0.33, -0.15 and &#x3b2;=-0.032; 95% CI: -0.048, -0.016, respectively] and n-3 PUFA with longer (&#x3b2;=0.34; 95% CI: 0.032, 0.65) rTL. Cord blood n-6 PUFA was associated with longer (&#x3b2;=0.15; 95% CI: 0.050, 0.26) rTL. Further analyses revealed linoleic acid in maternal blood and arachidonic acid in cord blood as the main drivers of the n-6 PUFA associations. No associations were observed for THg and PUFA with rmtDNAcn.<br><br>DISCUSSION: Our results indicate that prenatal THg exposure and PUFA status are associated with rTL later in childhood, although not consistently aligned with our initial hypothesis. Subsequent research is needed to confirm this finding, further evaluate the potential confounding of fish intake, and investigate the underlying molecular mechanisms to verify the use of rTL as a true biomarker of THg exposure. https://doi.org/10.1289/EHP14776.},
}
@article {pmid39901177,
year = {2025},
author = {Polli, A and Godderis, L and Martens, DS and Patil, MS and Hendrix, J and Wyns, A and Van Campenhout, J and Richter, E and Fanning, L and Vandekerckhove, O and Claeys, E and Janssens, W and Lorent, N},
title = {Exploring DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVID.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {60},
pmid = {39901177},
issn = {1741-7015},
mesh = {Humans ; Male ; Female ; *COVID-19/immunology/epidemiology ; Middle Aged ; Prospective Studies ; Longitudinal Studies ; *DNA, Mitochondrial/genetics ; *DNA Methylation ; *SARS-CoV-2/genetics ; Aged ; Adult ; Telomere ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long-COVID is defined as the persistency or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. Common persistent symptoms are fatigue, sleep disturbances, post-exertional malaise (PEM), pain, and cognitive problems. Long-COVID is estimated to be present in about 65 million people. We aimed to explore clinical and biological factors that might contribute to Long-COVID.<br><br>METHODS: Prospective longitudinal cohort study including patients infected with SARS-CoV-2 between March 2020 and March 2022. Patients were assessed between 4 and 12&#xa0;months after infection at the COVID follow-up clinic at UZ Leuven. We performed a comprehensive clinical assessment (including questionnaires and the 6-min walking test) and biological measures (global DNA methylation, telomere length, mitochondrial DNA copy number, inflammatory cytokines, and serological markers such as C-reactive protein, D-dimer, troponin T).<br><br>RESULTS: Of the 358 participants, 328 were hospitalised, of which 130 had severe symptoms requiring intensive care admission; 30 patients were ambulatory referrals. Based on their clinical presentation, we could identify 6 main clusters. One-hundred and twenty-seven patients (35.4%) belonged to at least one cluster. The bigger cluster included PEM, fatigue, sleep disturbances, and pain (n&#x2009;=&#x2009;57). Troponin T and telomere shortening were the two main markers predicting Long-COVID and PEM-fatigue symptoms.<br><br>CONCLUSIONS: Long-COVID is not just one entity. Different clinical presentations can be identified. Cardiac involvement (as measured by troponin T levels) and telomere shortening might be a relevant risk factor for developing PEM-fatigue symptoms and deserve further exploring.},
}
@article {pmid39900600,
year = {2025},
author = {Ashraf, R and Polasek-Sedlackova, H and Marini, V and Prochazkova, J and Hasanova, Z and Zacpalova, M and Boudova, M and Krejci, L},
title = {RECQ4-MUS81 interaction contributes to telomere maintenance with implications to Rothmund-Thomson syndrome.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {1302},
pmid = {39900600},
issn = {2041-1723},
support = {21-22593X//Grantov&#xe1; Agentura &#x10c;esk&#xe9; Republiky (Grant Agency of the Czech Republic)/ ; },
mesh = {Humans ; *RecQ Helicases/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *Telomere/metabolism/genetics ; *DNA Replication ; *Rothmund-Thomson Syndrome/genetics/metabolism ; *Endonucleases/metabolism/genetics ; Telomere Homeostasis ; Chromosome Segregation ; Mutation ; Chromosomal Instability ; Protein Binding ; },
abstract = {Replication stress, particularly in hard-to-replicate regions such as telomeres and centromeres, leads to the accumulation of replication intermediates that must be processed to ensure proper chromosome segregation. In this study, we identify a critical role for the interaction between RECQ4 and MUS81 in managing such stress. We show that RECQ4 physically interacts with MUS81, targeting it to specific DNA substrates and enhancing its endonuclease activity. Loss of this interaction, results in significant chromosomal segregation defects, including the accumulation of micronuclei, anaphase bridges, and ultrafine bridges (UFBs). Our data further demonstrate that the RECQ4-MUS81 interaction plays an important role in ALT-positive cells, where MUS81 foci primarily colocalise with telomeres, highlighting its role in telomere maintenance. We also observe that a mutation associated with Rothmund-Thomson syndrome, which produces a truncated RECQ4 unable to interact with MUS81, recapitulates these chromosome instability phenotypes. This underscores the importance of RECQ4-MUS81 in safeguarding genome integrity and suggests potential implications for human disease. Our findings demonstrate the RECQ4-MUS81 interaction as a key mechanism in alleviating replication stress at hard-to-replicate regions and highlight its relevance in pathological conditions such as RTS.},
}
@article {pmid39895528,
year = {2025},
author = {Pradhan, K and Neupane, B and Niehues, P and Kirschner, M and Beier, F and Kuo, CC and Hilbold, EA and Bär, C and Thoma, OM and Waldner, M and Vieri, M and Brümmendorf, TH and Tharmapalan, V and Wagner, W and Kleines, M and Emrani, M and Zink, MD and Napp, A and Marx, N and Gramlich, M},
title = {Telomere Length Is Associated With Adverse Atrial Remodeling in Patients With Atrial Fibrillation.},
journal = {Journal of the American Heart Association},
volume = {},
number = {},
pages = {e037512},
doi = {10.1161/JAHA.124.037512},
pmid = {39895528},
issn = {2047-9980},
abstract = {BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia with a massive burden on global health. The prevalence of AF increases dramatically with age and can be up to 18% in patients older than 80 years. Telomeres, which are short, repeated DNA sequences at the end of chromosomes, are known to act as a biological aging marker. In this study, we investigated the relation of telomere shortening and AF in the context of atrial remodeling. Furthermore, we assessed changes in the gene expression profiles of patients with AF according to telomere length (TL) and left atrial fibrosis.<br><br>METHODS: We included 72 patients undergoing catheter ablation for AF. Bipolar voltage maps were obtained to determine left atrial low voltage areas as a surrogate for atrial fibrosis. TL was quantified and correlated to low voltage areas. 3' mRNA sequencing was performed for gene expression profiling. Clonal hematopoiesis of indeterminate potential was assessed by next generation sequencing. Telomerase reverse transcriptase knockout (Tert[-/-]) and telomerase RNA component knockout (Terc[-/-]) mice were used to investigate the mechanistic impact of telomere shortening on atrial remodeling.<br><br>RESULTS: Patients with advanced left atrial fibrosis had shorter telomeres compared with patients with healthy left atria. Furthermore, there was a strong correlation between the extent of left atrial low voltage areas, TL, and outcome after catheter ablation of AF. 24&#x2009;months after ablation, only 26.5% of patients with advanced fibrosis and short TL were in sinus rhythm compared with 62.5% of patients with no/low fibrosis and long TL. Gene expression profiles and clonal hematopoiesis of indeterminate potential frequency differed in patients with AF with short and long telomeres. Finally, atrial tissue of mouse models with shortened telomeres showed marked left atrial fibrosis and over-expression of fibrosis-related genes.<br><br>CONCLUSIONS: Telomere shortening is correlated with left atrial remodeling. Shorter telomeres are associated with a series of molecular events which could eventually lead to cardiac fibrosis and perpetuate AF.},
}
@article {pmid39891610,
year = {2025},
author = {Horwath, O and Montiel-Rojas, D and Ponsot, E and Féasson, L and Kadi, F},
title = {Increased muscle satellite cell content and preserved telomere length in response to combined exercise training in patients with FSHD.},
journal = {The Journal of physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/JP287033},
pmid = {39891610},
issn = {1469-7793},
support = {16122-15383//Association Francaise contre les myopathies (AFM)/ ; },
abstract = {Facioscapulohumeral muscular dystrophy (FSHD) is an inherited muscle disease characterized by weakness and muscle wasting. In the absence of available treatments, exercise training has emerged as a potential strategy to attenuate muscle tissue deterioration. However, little is known about the impact of chronic exercise on degenerative events and regenerative capacity in FSHD muscle. Muscle biopsies were obtained from 16 FSHD patients before and after a 24 week training program combining aerobic-, strength- and high-intensity exercise (Control; n = 8, Training; n = 8). Histochemical and immunohistochemical approaches were applied to assess histopathological signs, markers of regeneration, inflammatory infiltrates and satellite cell content. Muscle telomere length was measured as an indicator of the remaining regenerative capacity. The proportion of muscle fibres expressing developmental myosins and centralized myonuclei was not exacerbated after the intervention. Similarly, no alterations were observed in the number of inflammatory infiltrates (CD68[+] cells). Alongside muscle hypertrophy in slow (P = 0.022) and fast fibres (P = 0.022 and P = 0.008), satellite cell content increased specifically in fast fibres (+75 %, P = 0.015), indicating a functional satellite cell pool in FSHD muscle. Importantly, exercise training was not associated with a shortening of muscle telomere length, suggesting that muscle cell turnover was not accelerated despite an expansion of the satellite cell pool. Our findings suggest that combined exercise training elicits beneficial muscular adaptations without impairing important indicators of skeletal muscle regenerative capacity in patients with FSHD. KEY POINTS: A 24 week combined exercise training program is a safe and well-tolerated strategy to attenuate skeletal muscle deterioration in facioscapulohumeral muscular dystrophy (FSHD) patients. Markers of histopathology, muscle fibre regeneration and inflammatory infiltrates were not exacerbated following exercise training in FSHD muscle. Here, we show novel data that exercise training in FSHD patients induced muscle fibre hypertrophy and triggered an expansion of the satellite cell pool specifically in fast fibres. Exercise training in these patients is not associated with a shortening of muscle telomere length thereby indicating a preserved capacity for muscle regeneration.},
}
@article {pmid39889303,
year = {2025},
author = {Fajkus, P and Fajkus, J},
title = {Telomerase RNA evolution: a journey from plant telomeres to broader eukaryotic diversity.},
journal = {The Biochemical journal},
volume = {482},
number = {3},
pages = {},
doi = {10.1042/BCJ20240501},
pmid = {39889303},
issn = {1470-8728},
mesh = {*Telomerase/genetics/metabolism ; *Telomere/metabolism/genetics ; *RNA/genetics/metabolism ; *Evolution, Molecular ; Animals ; Phylogeny ; Plants/genetics ; Viridiplantae/genetics/metabolism ; },
abstract = {Telomeres, essential for maintaining genomic stability, are typically preserved through the action of telomerase, a ribonucleoprotein complex that synthesizes telomeric DNA. One of its two core components, telomerase RNA (TR), serves as the template for this synthesis, and its evolution across different species is both complex and diverse. This review discusses recent advancements in understanding TR evolution, with a focus on plants (Viridiplantae). Utilizing novel bioinformatic tools and accumulating genomic and transcriptomic data, combined with corresponding experimental validation, researchers have begun to unravel the intricate pathways of TR evolution and telomere maintenance mechanisms. Contrary to previous beliefs, a monophyletic origin of TR has been demonstrated first in land plants and subsequently across the broader phylogenetic megagroup Diaphoretickes. Conversely, the discovery of plant-type TRs in insects challenges assumptions about the monophyletic origin of TRs in animals, suggesting evolutionary innovations coinciding with arthropod divergence. The review also highlights key challenges in TR identification and provides examples of how these have been addressed. Overall, this work underscores the importance of expanding beyond model organisms to comprehend the full complexity of telomerase evolution, with potential applications in agriculture and biotechnology.},
}
@article {pmid39884801,
year = {2025},
author = {Murillo Ortiz, BO and Ramírez Emiliano, J and Romero Vázquez, MJ and Amador Medina, LF and Martínez Garza, S and Ramos Rodríguez, EM},
title = {Impact of iron chelation with deferasirox on telomere length and oxidative stress in hemodialysis patients: A randomized study.},
journal = {Nefrologia},
volume = {45},
number = {1},
pages = {68-76},
doi = {10.1016/j.nefroe.2025.01.003},
pmid = {39884801},
issn = {2013-2514},
mesh = {Humans ; *Deferasirox/therapeutic use ; *Oxidative Stress/drug effects ; *Renal Dialysis ; *Iron Chelating Agents/therapeutic use ; Male ; Female ; Middle Aged ; *Benzoates/therapeutic use/pharmacokinetics ; *Telomere/drug effects ; *Triazoles/therapeutic use ; *Ferritins/blood ; Aged ; Adult ; Kidney Failure, Chronic/therapy/blood ; },
abstract = {BACKGROUND: Recent studies have demonstrated the effectiveness, safety, and tolerability of deferasirox in patients in peritoneal dialysis, however, its effect has not been studied in patients undergoing hemodialysis.<br><br>OBJECTIVE: To investigate the impact of iron chelation on telomere length, oxidative stress, and ferritin levels in patients undergoing hemodialysis.<br><br>METHODS: This is an open-label study, with a control group of patients undergoing hemodialysis, who will receive treatment with deferasirox 15mg/kg/day for 6 months for iron chelation. Telomere length was measured using real-time PCR. Serum ferritin levels and oxidation markers were evaluated. To evaluate the pharmacokinetics and safety of deferasirox, plasma concentrations were analyzed by HPLC.<br><br>RESULTS: Fifty-four patients were included to receive deferasirox, and a control group of 50 patients. Significant differences were observed in serum ferritin levels (p<0.0001), TBARS (thiobarbituric acid reactive substances) (p<0.01). Telomere length had a significant increase after chelation (p<0.001). The serum deferasirox concentration at zero time at 48h was maintained within a range of 2.67-23.78mmol/L.<br><br>CONCLUSIONS: Our results demonstrate that iron chelation in hemodialysis patients significantly reduces ferritin and TBARS, resulting in an increase in telomere length. Deferasirox proves to be beneficial for patients with iron overload undergoing hemodialysis.},
}
@article {pmid39884762,
year = {2025},
author = {Shah, PD and Armanios, M},
title = {Pre- and post-lung transplant considerations for patients with ultra-short telomere length.},
journal = {The European respiratory journal},
volume = {},
number = {},
pages = {},
doi = {10.1183/13993003.01545-2024},
pmid = {39884762},
issn = {1399-3003},
}
@article {pmid39884423,
year = {2025},
author = {Marciau, C and Bestley, S and Costantini, D and Hicks, O and Hindell, M and Kato, A and Raclot, T and Ribout, C and Ropert-Coudert, Y and Angelier, F},
title = {Sibling similarity in telomere length in Adélie penguin chicks.},
journal = {Comparative biochemistry and physiology. Part A, Molecular &amp; integrative physiology},
volume = {},
number = {},
pages = {111818},
doi = {10.1016/j.cbpa.2025.111818},
pmid = {39884423},
issn = {1531-4332},
abstract = {Early life telomere length is thought to influence and predict an individual's fitness. It has been shown to vary significantly in early life compared to adulthood. Investigating the factors influencing telomere length in young individuals is therefore of particular interest, especially as the relative importance of heredity compared to post-natal conditions remains largely uncertain. Adélie penguins are eco-indicators of the Antarctic ecosystem and their population are currently undergoing variable trajectories due to climate change. Here, we conducted a correlative study to investigate how telomere length was influenced by external and internal factors in Adélie penguin chicks. We found that most of the parameters we tested, including sex, body mass, brood size and hatching order as well as parental foraging trip duration, did not significantly influence chick telomere length at 32 days. However, siblings had similar telomere length, suggesting that hereditary factors play a stronger role in determining telomere length at this stage compared to the post-natal environment. In addition, telomere length and oxidative damage did not directly correlate but did interact in a complex way mediated by chick mass. High levels of oxidative damage were associated with longer telomeres in heavy chicks, whereas they were associated with shorter telomeres in light chicks. Although this mass-dependent relationship between telomere length and oxidative damage needs to be confirmed in future studies, it could reflect two different scenarios: (1) short telomeres may mimic the cost of poor nutritional conditions and oxidative damage in light chicks; (2) long telomeres may be maintained despite high oxidative damage in heavy chicks thanks to optimal nutritional conditions.},
}
@article {pmid39883078,
year = {2025},
author = {Tedaldi, AM and Behrouzi, P and Grootswagers, P},
title = {Diet, lifestyle and telomere length: using Copula Graphical Models on NHANES data.},
journal = {Aging},
volume = {17},
number = {},
pages = {},
doi = {10.18632/aging.206194},
pmid = {39883078},
issn = {1945-4589},
abstract = {Telomere length has been related to human health and ageing in multiple studies. However, these studies have analyzed a small set of variables, according to pre-formulated hypotheses. We used data from NHANES 1999-2002 to perform a preregistered cross-sectional analysis. From these four years we selected the participants with available leukocyte telomere length measure and with plausible daily energy intake, leading to a total study population of 7096 participants. Then, we divided the participants in three groups according to age: Young 20-39 (n = 2623), Middle 40-59 (n = 2210), Old 60-84 (n = 2263). On each group we performed Copula Graphical Modelling (CGM) to capture the links between the variables of interest, and we conducted certainty and sensitivity analyses to understand the robustness of the results. Blood levels of C-reactive protein and γ-tocopherol, and intake of caffeine and fibers are inversely related to telomere length across the age strata. Sex, race, smoking, physical activity and indicators of socioeconomic status have almost no direct connection with telomeres; however, they are directly linked to C-reactive protein, which in turn is connected to leukocyte telomere length. C-reactive protein is therefore a possible central mediator of the effect of these factors on telomeres.},
}
@article {pmid39878307,
year = {2025},
author = {Campos-Sánchez, I and Navarrete-Muñoz, EM and Martens, DS and Riaño-Galán, I and Lertxundi, A and Llop, S and Guxens, M and Rodríguez-Dehli, C and Lertxundi, N and Soler-Blasco, R and Vrijheid, M and Nawrot, TS and Wright, J and Yang, TC and McEachan, R and Gützkow, KB and Chatzi, VL and Vafeiadi, M and Kampouri, M and Grazuleviciene, R and Andrusaityte, S and Lepeule, J and Valera-Gran, D},
title = {Telomere Length and Symptoms of Attention Deficit and Hyperactivity Disorder in Children at 6-12 Years.},
journal = {Journal of attention disorders},
volume = {},
number = {},
pages = {10870547251314923},
doi = {10.1177/10870547251314923},
pmid = {39878307},
issn = {1557-1246},
abstract = {OBJECTIVE: To explore the association between telomere length (TL) and attention deficit hyperactivity disorder (ADHD) symptoms in children at 6-12 years.<br><br>METHOD: Data from 1,759 children belonging to the HELIX project cohorts and the Asturias, Gipuzkoa and Valencia cohorts of INMA project were included. TL was determined by blood sample using a PCR protocol. ADHD symptoms were described by parents using the Conners' Parent Rating Scale-Revised: Short Form. Multiple negative binomial regression models adjusted for potential confounders were used to estimate associations.<br><br>RESULTS: Overall estimates showed no associations between TL and ADHD symptoms. However, we observed that a longer TL was significantly associated with a lower risk of presenting hyperactivity symptoms in children belonging to the HELIX project (IRR&#x2009;=&#x2009;0.93, 95% CI [0.87, 0.99]; p&#x2009;=&#x2009;.022).<br><br>CONCLUSION: While our study did not find a consistent association between TL and ADHD symptoms across all cohorts, the significant association found within the HELIX cohort suggests that longer TL may be linked to a lower risk of hyperactivity symptoms. Further research is needed to explore this association in more detail.},
}
@article {pmid39874713,
year = {2025},
author = {Li, X and Yu, X and Lian, X and Kang, L and Yang, L and Ba, F},
title = {Maternal urinary levels of PAH metabolites, umbilical cord blood telomere length and anthropometric indices in newborns.},
journal = {Ecotoxicology and environmental safety},
volume = {291},
number = {},
pages = {117767},
doi = {10.1016/j.ecoenv.2025.117767},
pmid = {39874713},
issn = {1090-2414},
abstract = {The existing evidence indicating that prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with a range of adverse outcomes, including alterations in anthropometric indices, underscores the need for further investigation into the underlying mechanisms. This study aims to examine the effects of prenatal PAH exposure on anthropometric indices and telomere length (TL), as well as to explore whether changes in TL can serve as a predictor of alterations in anthropometric measures. The study was conducted in Shenyang, China, with 2460 pregnant women participating between 2022 and 2023. Maternal urine samples were analyzed for eleven PAH metabolites, and neonatal outcomes, such as birth weight (BW), birth length (BL), and head circumference (HC), were extracted from medical records as anthropometric indices. We employed multiple linear regression (MLR), generalized quantile g-computation (g-comp), Bayesian Kernel Machine Regression (BKMR), and mediation analysis to comprehensively assess the associations between PAH exposure and umbilical TL and neonatal outcomes. Notably, significant negative associations were found between several PAH metabolites and umbilical telomere length (TL). These metabolites included 2-hydroxy naphthalene (2-OH Nap), 1-hydroxy pyrene (1-OH Pyr), 6-hydroxy chrysene (6-OH Chr), 9-hydroxy benzo(a)pyrene (9-OH Bap), and the sum of hydroxylated PAHs (Σ-OH PAHs). Additionally, negative correlations were identified between specific PAH metabolites and HC, although no significant associations were found for BW. Birth weight showed a significant inverse relationship with metabolites such as 1-hydroxy phenanthrene (1-OH Phe), 9-hydroxy phenanthrene (9-OH Phe), and 1-hydroxy naphthalene(1-OH Nap). Results from g-comp analysis and BKMR indicated significant mixture effects of PAHs on umbilical TL and HC, with more heterogeneous effects on BW and BL. Mediation analysis indicated that alterations in umbilical TL partially mediated the associations between PAH exposure and BW and HC. Notably, metabolites such as 2-OH Nap and the Σ-OH PAHs demonstrated substantial mediation effects. Overall, our findings suggest that changes in umbilical TL partially mediate the associations between prenatal PAH exposure and HC and BW, highlighting the complex pathways through which PAH metabolites may influence neonatal development.},
}
@article {pmid39871386,
year = {2025},
author = {Shou, S and Maolan, A and Zhang, D and Jiang, X and Liu, F and Li, Y and Zhang, X and Geer, E and Pu, Z and Hua, B and Guo, Q and Zhang, X and Pang, B},
title = {Telomeres, telomerase, and cancer: mechanisms, biomarkers, and therapeutics.},
journal = {Experimental hematology &amp; oncology},
volume = {14},
number = {1},
pages = {8},
pmid = {39871386},
issn = {2162-3619},
support = {ZYYCXTD-C-202205//the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine/ ; CI2021B009//the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences/ ; HLCMHPP2023085//the High Level Chinese Medical Hospital Promotion Project/ ; HLCMHPP202308506//the High Level Chinese Medical Hospital Promotion Project/ ; HLCMHPP2023005//the High Level Chinese Medical Hospital Promotion Project/ ; 81774294//the National Natural Science Foundation of China/ ; 82104961//the National Natural Science Foundation of China/ ; ZZ14-YQ-016//the Fundamental Research Funds for the Central public welfare research institutes/ ; ZZ13-YQ-028//the Fundamental Research Funds for the Central public welfare research institutes/ ; CI2021A01816//CACMS Innovation Fund/ ; CI2021A01814//CACMS Innovation Fund/ ; CI2021A01805//CACMS Innovation Fund/ ; },
abstract = {Telomeres and telomerase play crucial roles in the initiation and progression of cancer. As biomarkers, they aid in distinguishing benign from malignant tissues. Despite the promising therapeutic potential of targeting telomeres and telomerase for therapy, translating this concept from the laboratory to the clinic remains challenging. Many candidate drugs remain in the experimental stage, with only a few advancing to clinical trials. This review explores the relationship between telomeres, telomerase, and cancer, synthesizing their roles as biomarkers and reviewing the outcomes of completed trials. We propose that changes in telomere length and telomerase activity can be used to stratify cancer stages. Furthermore, we suggest that differential expression of telomere and telomerase components at the subcellular level holds promise as a biomarker. From a therapeutic standpoint, combining telomerase-targeted therapies with drugs that mitigate the adverse effects of telomerase inhibition may offer a viable strategy.},
}
@article {pmid39871190,
year = {2025},
author = {Wang, C and Martens, DS and Bustamante, M and Alfano, R and Plusquin, M and Maitre, L and Wright, J and McEachan, RRC and Lepeule, J and Slama, R and Vafeiadi, M and Chatzi, L and Grazuleviciene, R and Gutzkow, KB and Keun, H and Borràs, E and Sabidó, E and Carracedo, A and Escarami, G and Anguita-Ruiz, A and Pelegrí-Sisó, D and Gonzalez, JR and Vrijheid, M and Nawrot, TS},
title = {The multi-omics signatures of telomere length in childhood.},
journal = {BMC genomics},
volume = {26},
number = {1},
pages = {75},
pmid = {39871190},
issn = {1471-2164},
support = {IJC2018-035394-I//Spanish Ministerio de Econom&#xed;a, Industria y Competitividad/ ; },
mesh = {Humans ; Child ; Female ; Male ; *Telomere/genetics/metabolism ; *DNA Methylation ; Telomere Homeostasis/genetics ; Body Mass Index ; CpG Islands ; Genomics/methods ; MicroRNAs/genetics ; Multiomics ; },
abstract = {BACKGROUND: Telomere length is an important indicator of biological age and a complex multi-factor trait. To date, the telomere interactome for comprehending the high-dimensional biological aspects linked to telomere regulation during childhood remains unexplored. Here we describe the multi-omics signatures associated with childhood telomere length.<br><br>METHODS: This study included 1001 children aged 6 to 11 years from the Human Early-life Exposome (HELIX) project. Telomere length was quantified via qPCR in peripheral blood of the children. Blood DNA methylation, gene expression, miRNA expression, plasma proteins and serum and urinary metabolites were measured through microarrays or (semi-) targeted assays. The association between each individual omics feature and telomere length was assessed in omics-wide association analyses. In addition, a literature-guided, sparse supervised integration method was applied to multiple omics, and latent components were extracted as predictors of child telomere length. The association of these latent components with early-life aging risk factors (child lifestyle, body mass index (BMI), exposure to smoking, etc.), were interrogated.<br><br>RESULTS: After multiple-testing correction, only two CpGs (cg23686403 and cg16238918 at PARD6G gene) out of all the omics features were significantly associated with child telomere length. The supervised multi-omics integration approach revealed robust associations between latent components and child BMI, with metabolites and proteins emerging as the primary contributing features. In these latent components, the contributing molecular features were known as involved in metabolism and immune regulation-related pathways.<br><br>CONCLUSIONS: Findings of this multi-omics study suggested an intricate interplay between telomere length, metabolism and immune responses, providing valuable insights into the molecular underpinnings of the early-life biological aging.},
}
@article {pmid39866942,
year = {2025},
author = {Pazhakh, V and Fox, LC and Elzen, ND and Emerson, MR and Cohen, SB and Bryan, TM and Norris, K and Baird, DM and Cochrane, T and Mackintosh, J and Scott, A and Blombery, P},
title = {A novel TERT variant associated with a telomere biology disorder and challenges in variant classification.},
journal = {EJHaem},
volume = {6},
number = {1},
pages = {e1066},
pmid = {39866942},
issn = {2688-6146},
abstract = {Telomere biology disorders (TBDs) are inherited conditions associated with multisystem manifestations. We describe clinical and functional characterisation of a novel TERT variant. Whole-genome sequencing was performed along with single telomere length analysis (STELA). Telomerase activity and processivity were assessed. A novel TERT variant (K710R) was detected in a patient with classic TBD features showing reduced telomerase activity and processivity. Despite clinical and functional evidence, the variant was classified as a variant of uncertain significance. We have described a novel TERT variant and highlighted the need for further refinement of variant classification specific for TBDs.},
}
@article {pmid39864119,
year = {2025},
author = {Martino, P and Perez-Alarcón, M and Deconinck, L and De Raedt, R and Vanderhasselt, MA and Kozusznik, MW and Kooy, F and Hidalgo, V and Venero, C and Salvador, A and Baeken, C and Pulopulos, MM},
title = {Stress and telomere length in leukocytes: Investigating the role of GABRA6 gene polymorphism and cortisol.},
journal = {Psychoneuroendocrinology},
volume = {173},
number = {},
pages = {107358},
doi = {10.1016/j.psyneuen.2025.107358},
pmid = {39864119},
issn = {1873-3360},
abstract = {Telomere length (TL) is considered a biomarker of aging, and short TL in leukocytes is related to age and stress-related health problems. Cumulative lifetime stress exposure has also been associated with shorter TL and age-related health problems, but the mechanisms are not well understood. We tested in 108 individuals whether shorter TL in leukocytes is observed in individuals with the GABRA6 TT genotype, which has been associated with dysregulation of hypothalamic-pituitary-adrenal axis activity (the main biological stress system) compared to the CC genotype. We also investigated if individuals carrying the TT genotype show higher stress-induced and diurnal cortisol secretion and if cortisol explains the interindividual variability in TL. The analysis pipeline of this study was pre-registered, and the results showed that GABRA6 TT carriers had shorter TL in CD8+CD28+ cells (Bonferroni corrected). In contrast to previous studies, no differences between groups in cortisol secretion were observed, and TL and cortisol did not show significant associations. This study shows, for the first time, shorter TL in CD8+CD28+ cells in TT carriers for GABRA6 compared to CC carriers, suggesting accelerated cellular aging. Although this difference could be linked to an increased susceptibility to stress in the TT carriers, this could not be attributed to the direct influence of cortisol, suggesting the involvement of other mechanisms.},
}
@article {pmid39864023,
year = {2025},
author = {Benetos, A and Coudray, O and Gégout-Petit, A and Lenôtre, L and Toupance, S and Villemonais, D},
title = {A branching model for intergenerational telomere length dynamics.},
journal = {Journal of mathematical biology},
volume = {90},
number = {2},
pages = {21},
pmid = {39864023},
issn = {1432-1416},
support = {ANR-15-IDEX-04-LUE//Lorraine Universit&#xe9; d'Excellence/ ; },
mesh = {Humans ; *Mathematical Concepts ; *Telomere Homeostasis ; *Telomere/genetics ; *Models, Genetic ; *Computer Simulation ; Male ; Female ; Animals ; },
abstract = {We build and study an individual based model of the telomere length's evolution in a population across multiple generations. This model is a continuous time typed branching process, where the type of an individual includes its gamete mean telomere length and its age. We study its Malthusian's behaviour and provide numerical simulations to understand the influence of biologically relevant parameters.},
}
@article {pmid39863614,
year = {2025},
author = {Rat, A and Martinez Fernandez, V and Doumic, M and Teixeira, MT and Xu, Z},
title = {Mathematical model linking telomeres to senescence in Saccharomyces cerevisiae reveals cell lineage versus population dynamics.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {1024},
pmid = {39863614},
issn = {2041-1723},
support = {ANR-16-CE12-0026//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-11-LABX-0011-01//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-16-CE12-0026//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-16-CE12-0026//Agence Nationale de la Recherche (French National Research Agency)/ ; PLBIO20-312 INCa_15192//Institut National Du Cancer (French National Cancer Institute)/ ; PLBIO20-312 INCa_15192//Institut National Du Cancer (French National Cancer Institute)/ ; PLBIO20-312 INCa_15192//Institut National Du Cancer (French National Cancer Institute)/ ; Equipe Labellis&#xe9;e//Fondation pour la Recherche M&#xe9;dicale (Foundation for Medical Research in France)/ ; SKIPPERAD 306321//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; },
mesh = {*Saccharomyces cerevisiae/genetics/metabolism ; *Telomere/metabolism/genetics ; *Cell Lineage/genetics ; Telomere Shortening ; Cellular Senescence/genetics ; Telomerase/metabolism/genetics ; Models, Theoretical ; Genomic Instability ; Models, Biological ; },
abstract = {Telomere shortening ultimately causes replicative senescence. However, identifying the mechanisms driving replicative senescence in cell populations is challenging due to the heterogeneity of telomere lengths and the asynchrony of senescence onset. Here, we present a mathematical model of telomere shortening and replicative senescence in Saccharomyces cerevisiae which is quantitatively calibrated and validated using data of telomerase-deficient single cells. Simulations of yeast populations, where cells with varying proliferation capacities compete against each other, show that the distribution of telomere lengths of the initial population shapes population growth, especially through the distribution of cells' shortest telomere lengths. We also quantified how factors influencing cell viability independently of telomeres can impact senescence rates. Overall, we demonstrate a temporal evolution in the composition of senescent cell populations-from a state directly linked to critically short telomeres to a state where senescence onset becomes stochastic. This population structure may promote genome instability and facilitate senescence escape.},
}
@article {pmid39862003,
year = {2025},
author = {Ma, L and Liu, C and Song, R and Qian, Y and Zhang, F},
title = {Telomere Length and Oxidative Damage in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.},
journal = {Journal of integrative neuroscience},
volume = {24},
number = {1},
pages = {24948},
doi = {10.31083/JIN24948},
pmid = {39862003},
issn = {0219-6352},
mesh = {Humans ; *Autism Spectrum Disorder/metabolism ; *Oxidative Stress/physiology ; Adolescent ; Child ; Telomere/metabolism ; },
abstract = {BACKGROUND: Autism spectrum disorder (ASD) has been reported to confer an increased risk of natural premature death. Telomere erosion caused by oxidative stress is a common consequence in age-related diseases. However, whether telomere length (TL) and oxidative indicators are significantly changed in ASD patients compared with controls remains controversial. The aim of this study was to determine the associations of ASD with TL and oxidative indicators by performing a meta-analysis of all published evidence.<br><br>METHODS: The PubMed and Embase databases were searched for articles published up to April, 2024. The effect size was expressed as standardized mean difference (SMD) and 95% confidence interval (CI) via Stata 15.0 software.<br><br>RESULTS: Thirty-nine studies were included. Pooled results showed that compared with controls, children and adolescents with ASD were associated with significantly shorter TL (SMD = -0.48; 95% CI = -0.66- -0.29; p < 0.001; particularly in males), lower total antioxidant capacity (TAC: SMD = -1.15; 95% CI = -2.01- -0.30; p = 0.008), and higher oxidative DNA (8-hydroxy-2[']-deoxyguanosine, 8-OHdG: SMD = 0.63; 95% CI = 0.03-1.23; p = 0.039), lipid (hexanolyl-lysine, HEL: SMD = 0.37; 95% CI = 0.13-0.62; p = 0.003), and protein (3-nitrotyrosine, 3-NT: SMD = 0.86; 95% CI = 0.21-1.51; p = 0.01; dityrosine, DT: SMD = 0.66; 95% CI = 0.521-0.80; p < 0.01) damage. There were no significant differences between ASD and controls in 8-isoprostane and oxidative stress index after publication bias correction, and in N-formylkynurenine during overall meta-analysis.<br><br>CONCLUSIONS: TL, 8-OHdG, TAC, HEL, 3-NT, and DT represent potential biomarkers for prediction of ASD in children and adolescents.},
}
@article {pmid39861449,
year = {2025},
author = {De la Fuente, B and Milagro, FI and Cuervo, M and Martínez, JA and Riezu-Boj, JI and Zalba, G and Marti Del Moral, A and García-Calzón, S},
title = {Beneficial Effects of a Moderately High-Protein Diet on Telomere Length in Subjects with Overweight or Obesity.},
journal = {Nutrients},
volume = {17},
number = {2},
pages = {},
doi = {10.3390/nu17020319},
pmid = {39861449},
issn = {2072-6643},
support = {PT024//Gobierno de Navarra/ ; CB12/03/30002//Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition/ ; IJC2019-040796-I//Ministerio de Ciencia, Innovaci&#xf3;n y Universidades/ ; },
mesh = {Humans ; Male ; Female ; Adult ; Middle Aged ; *Obesity/diet therapy/genetics ; *Diet, High-Protein ; *Overweight/diet therapy ; Young Adult ; Aged ; Adolescent ; Telomere ; Diet, Fat-Restricted/methods ; Telomere Shortening ; Weight Loss ; Diet, Reducing/methods ; Dietary Proteins/administration &amp; dosage ; },
abstract = {BACKGROUND AND AIM: Telomere length (TL) is a key biomarker of cellular aging, with shorter telomeres associated with age-related diseases. Lifestyle interventions mitigating telomere shortening are essential for preventing such conditions. This study aimed to examine the effects of two weight loss dietary strategies, based on a moderately high-protein (MHP) diet and a low-fat (LF) diet on TL in individuals with overweight or obesity.<br><br>METHODS AND RESULTS: A total of 164 participants, aged 18-65 years from the OBEKIT trial received the MHP (n = 83) or the LF diet (n = 81) for 4 months and had TL data for analyses. TL was measured at baseline and after 4 months of the intervention using monochrome multiplex quantitative polymerase chain reaction (MMqPCR). Both groups experienced significant improvements in anthropometric and biochemical parameters after the dietary intervention (p < 0.001). The MHP group showed an increase in TL (+0.16 &#xb1; 0.13) compared to the LF group (-0.05 &#xb1; 0.13) in multiple-adjusted models (p = 0.016). An interaction was observed between the sex and dietary group, where women in the MHP group had increased TL (+0.23 &#xb1; 0.16) after 4 months compared to women in the LF group (-0.13 &#xb1; 0.15; p = 0.001); no differences between dietary groups were found in men. This increase in TL for women was associated with an increase in protein intake (p = 0.006), measured through dietary questionnaires.<br><br>CONCLUSION: This study shows that a MHP diet may have a protective effect on TL during weight loss, particularly in women, potentially contributing to healthier aging. These results highlight the importance of considering macronutrient composition in dietary interventions aimed at preserving TL.},
}
@article {pmid39858038,
year = {2025},
author = {Iskandar, M and Xiao Barbero, M and Jaber, M and Chen, R and Gomez-Guevara, R and Cruz, E and Westerheide, S},
title = {A Review of Telomere Attrition in Cancer and Aging: Current Molecular Insights and Future Therapeutic Approaches.},
journal = {Cancers},
volume = {17},
number = {2},
pages = {},
doi = {10.3390/cancers17020257},
pmid = {39858038},
issn = {2072-6694},
abstract = {BACKGROUND/OBJECTIVES: As cells divide, telomeres shorten through a phenomenon known as telomere attrition, which leads to unavoidable senescence of cells. Unprotected DNA exponentially increases the odds of mutations, which can evolve into premature aging disorders and tumorigenesis. There has been growing academic and clinical interest in exploring this duality and developing optimal therapeutic strategies to combat telomere attrition in aging and cellular immortality in cancer. The purpose of this review is to provide an updated overview of telomere biology and therapeutic tactics to address aging and cancer.<br><br>METHODS: We used the Rayyan platform to review the PubMed database and examined the ClinicalTrial.gov registry to gain insight into clinical trials and their results.<br><br>RESULTS: Cancer cells activate telomerase or utilize alternative lengthening of telomeres to escape telomere shortening, leading to near immortality. Contrarily, normal cells experience telomeric erosion, contributing to premature aging disorders, such as Werner syndrome and Hutchinson-Gilford Progeria, and (2) aging-related diseases, such as neurodegenerative and cardiovascular diseases.<br><br>CONCLUSIONS: The literature presents several promising therapeutic approaches to potentially balance telomere maintenance in aging and shortening in cancer. This review highlights gaps in knowledge and points to the potential of these optimal interventions in preclinical and clinical studies to inform future research in cancer and aging.},
}
@article {pmid39857599,
year = {2024},
author = {Vostatek, R and Ay, C},
title = {Biological Aging and Venous Thromboembolism: A Review of Telomeres and Beyond.},
journal = {Biomedicines},
volume = {13},
number = {1},
pages = {},
doi = {10.3390/biomedicines13010015},
pmid = {39857599},
issn = {2227-9059},
abstract = {Although venous thromboembolism (VTE) is the third most common cardiovascular disease, and the risk of VTE increases sharply with advancing age, approximately 40% of VTE cases are currently classified as unprovoked, highlighting the importance of risk factor research. While chronological aging is associated with the risk of VTE, the association with biological aging remains unclear. Biological aging is highly complex, influenced by several dysregulated cellular and biochemical mechanisms. In the last decade, advancements in omics methodologies provided insights into the molecular complexity of biological aging. Techniques such as high-throughput genomics, epigenomics, transcriptomics, proteomics, and metabolomics analyses identified and quantified numerous epigenetic markers, transcripts, proteins, and metabolites. These methods have also revealed the molecular alterations organisms undergo as they age. Despite the progress, there is still a lack of consensus regarding the methods for assessing and validating these biomarkers, and their application lacks standardization. This review gives an overview of biomarkers of biological aging, including telomere length, and their potential role for VTE. Furthermore, we critically examine the advantages and disadvantages of the proposed methods and discuss possible future directions for investigating biological aging in VTE.},
}
@article {pmid39857597,
year = {2024},
author = {Liu, S and Fu, Z and Liu, H and Wang, Y and Zhou, M and Ding, Z and Feng, Z},
title = {Lipid Profiles, Telomere Length, and the Risk of Malignant Tumors: A Mendelian Randomization and Mediation Analysis.},
journal = {Biomedicines},
volume = {13},
number = {1},
pages = {},
doi = {10.3390/biomedicines13010013},
pmid = {39857597},
issn = {2227-9059},
support = {82103785 and 82273582//This research was funded by the National Natural Science Foundation of China/ ; },
abstract = {Background/Objectives: The relationship between lipid profiles, telomere length (TL), and cancer risk remains unclear. Methods: This study employed two-sample Mendelian randomization (MR) with mediation analysis to investigate their causal relationships, examining lipid profiles as exposure, TL as mediator, and nine cancer types as outcomes. We conducted our analysis using two-stage least squares (2SLS) regression integrated with inverse variance weighted (IVW) methods to address potential endogeneity and strengthen our causal inference. Results: we found that unfavorable lipid profiles were causally linked to increased TL (p < 0.05). TL showed positive causal associations with lung and hematologic cancers (OR > 1, p < 0.05). Direct associations were observed between total and low-density lipoprotein (LDL) cholesterol and gastric cancer (OR < 1, p < 0.05), and between remnant cholesterol and colorectal cancer (OR > 1, p < 0.05). Mediation analysis revealed TL as a significant mediator in the pathway from lipid profiles to cancer development (p < 0.05). No horizontal pleiotropy was detected. Conclusions: Our findings suggest that lipid metabolism disorders may influence cancer development through telomere regulation, particularly in lung and hematologic cancers. This emphasizes the importance of lipid management in cancer prevention and treatment, especially for these cancer types.},
}
@article {pmid39849018,
year = {2025},
author = {Wong, KK and Maser, RS and Bachoo, RM and Menon, J and Carrasco, DR and Gu, Y and Alt, FW and DePinho, RA},
title = {Editorial Expression of Concern: Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing.},
journal = {Nature},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41586-025-08654-3},
pmid = {39849018},
issn = {1476-4687},
}
@article {pmid39846264,
year = {2025},
author = {Sánchez-González, JL and Sánchez-Rodríguez, JL and González-Sarmiento, R and Navarro-López, V and Juárez-Vela, R and Pérez, J and Martín-Vallejo, J},
title = {Effect of Physical Exercise on Telomere Length: Umbrella Review and Meta-Analysis.},
journal = {JMIR aging},
volume = {8},
number = {},
pages = {e64539},
doi = {10.2196/64539},
pmid = {39846264},
issn = {2561-7605},
mesh = {Humans ; *Exercise/physiology ; Telomere/metabolism ; Telomere Homeostasis/physiology ; Persons with Disabilities/rehabilitation ; },
abstract = {BACKGROUND: Telomere length (TL) is a marker of cellular health and aging. Physical exercise has been associated with longer telomeres and, therefore, healthier aging. However, results supporting such effects vary across studies. Our aim was to synthesize existing evidence on the effect of different modalities and durations of physical exercise on TL.<br><br>OBJECTIVE: The aim of this study was to explore the needs and expectations of individuals with physical disabilities and their interventionists for the use of a virtual reality physical activity platform in a community organization.<br><br>METHODS: We performed an umbrella review and meta-analysis. Data sources included PubMed, Embase, Web of Science, Cochrane Library, and Scopus. We selected systematic reviews and meta-analyses of randomized and nonrandomized controlled clinical trials evaluating the effect of physical exercise on TL.<br><br>RESULTS: Our literature search retrieved 12 eligible systematic reviews, 5 of which included meta-analyses. We identified 22 distinct primary studies to estimate the overall effect size of physical exercise on TL. The overall effect size was 0.28 (95% CI 0.118-0.439), with a heterogeneity test value Q of 43.08 (P=.003) and I&#xb2; coefficient of 51%. The number of weeks of intervention explained part of this heterogeneity (Q_B=8.25; P=.004), with higher effect sizes found in studies with an intervention of less than 30 weeks. Exercise modality explained additional heterogeneity within this subgroup (Q_B=10.28, P=.02). The effect sizes were small for aerobic exercise and endurance training, and moderate for high-intensity interval training.<br><br>CONCLUSIONS: Our umbrella review and meta-analysis detected a small-moderate positive effect of physical exercise on TL, which seems to be influenced by the duration and type of physical exercise. High quality studies looking into the impact of standardized, evidence-based physical exercise programs on TL are still warranted.},
}
@article {pmid39844515,
year = {2025},
author = {Gao, B and Zhao, J and Li, X and Zhang, J and Oliver, MJ and Zhang, D},
title = {Telomere-to-telomere genome of the desiccation-tolerant desert moss Syntrichia caninervis illuminates Copia-dominant centromeric architecture.},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.14549},
pmid = {39844515},
issn = {1467-7652},
support = {32100256//National Natural Science Foundation of China/ ; },
}
@article {pmid39844366,
year = {2025},
author = {Ormerod, MBEG and Ueland, T and Aas, M and Hjell, G and Rødevand, L and Sæther, LS and Lunding, SH and Johansen, IT and Mlakar, V and Andreou, D and Ueland, T and Lagerberg, TV and Melle, I and Djurovic, S and Andreassen, OA and Steen, NE},
title = {Limited evidence of association between dysregulated immune marker levels and telomere length in severe mental disorders.},
journal = {Acta neuropsychiatrica},
volume = {37},
number = {},
pages = {e4},
doi = {10.1017/neu.2024.62},
pmid = {39844366},
issn = {1601-5215},
mesh = {Humans ; Male ; *Bipolar Disorder/genetics/immunology/blood ; Female ; *Schizophrenia/genetics/blood/immunology ; Adult ; *Biomarkers/blood ; Middle Aged ; *Telomere ; *Leukocytes/metabolism ; Telomere Shortening ; Receptors, Tumor Necrosis Factor, Type I/blood/genetics ; Case-Control Studies ; Young Adult ; },
abstract = {OBJECTIVE: Accelerated ageing indexed by telomere attrition is suggested in schizophrenia spectrum- (SCZ) and bipolar disorders (BD). While inflammation may promote telomere shortening, few studies have investigated the association between telomere length (TL) and markers of immune activation and inflammation in severe mental disorders.<br><br>METHODS: Leucocyte TL defined as telomere template/amount of single-copy gene template (T/S ratio), was determined in participants with SCZ (N = 301) or BD (N = 211) and a healthy control group (HC, N = 378). TL was analysed with linear regressions for associations with levels of 12 immune markers linked to SCZ or BD. Adjustments were made for a broad range of potential confounding variables. TL was measured by quantitative polymerase chain reaction (qPCR) and the immune markers were measured by enzyme immunoassays.<br><br>RESULTS: A positive association between levels of soluble tumour necrosis factor receptor 1A (sTNF-R1) and TL in SCZ (&#x3b2; = 0.191, p = 0.012) was observed. Plasma levels of the other immune markers were not significantly associated with TL in the BD, SCZ or HC groups.<br><br>CONCLUSION: There was limited evidence of association between immune markers and TL in SCZ and BD. The results provide little support for involvement of immune dysregulation, as reflected by current systemic markers, in telomere attrition-related accelerated ageing in severe mental disorders.},
}
@article {pmid39842387,
year = {2025},
author = {Sabaie, H and Taghavi Rad, A and Shabestari, M and Seddiq, S and Saadattalab, T and Habibi, D and Saeidian, AH and Abbasi, M and Mirtavoos-Mahyari, H},
title = {Deciphering the bidirectional impact of leukocyte telomere length on multiple sclerosis progression: A Mendelian randomization study.},
journal = {Multiple sclerosis and related disorders},
volume = {94},
number = {},
pages = {106277},
doi = {10.1016/j.msard.2025.106277},
pmid = {39842387},
issn = {2211-0356},
abstract = {Observational studies have suggested a link between leukocyte telomere length (LTL) and multiple sclerosis (MS) progression, but the causal relationship remains uncertain. This study investigates the causal association between LTL and MS progression using a bidirectional two-sample Mendelian randomization (MR) approach. We analyzed genome-wide association summary statistics data from 472,174 individuals for LTL and 12,584 MS patients for disease progression. The primary method was the inverse variance weighted (IVW) approach, supported by sensitivity analyses to ensure robustness. The forward analysis revealed a significant positive causal relationship between LTL and MS progression (β = 0.107, 95 % CI = 0.006 to 0.209, P = 0.037). Conversely, the reverse analysis indicated a negative causal relationship (β = -0.010, 95 % CI = -0.020 to -0.001, P = 0.037). No heterogeneity or horizontal pleiotropy was found, and the sensitivity analyses confirmed consistent results. These findings suggest that telomere dynamics play a complex role in MS progression and highlight their potential as therapeutic targets. Further research is essential to uncover the biological mechanisms underlying the influence of telomeres on MS progression.},
}
@article {pmid39841197,
year = {2025},
author = {Masuda, Y and Sadato, D and Toya, T and Hirama, C and Shimizu, H and Najima, Y and Harada, H and Harada, Y and Doki, N},
title = {Telomere shortening in donor cell-derived acute promyelocytic leukemia after allogeneic hematopoietic stem cell transplantation: a case report.},
journal = {Annals of hematology},
volume = {},
number = {},
pages = {},
pmid = {39841197},
issn = {1432-0584},
abstract = {Donor cell leukemia (DCL), in which malignancy evolves from donor's stem cells, is an infrequent complication of allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) derived from donor cell is extremely rare and only four cases have been reported to date. Herein we report a case of donor cell-derived APL developing 32 months after haploidentical peripheral blood stem cell transplantation using posttransplant cyclophosphamide for myelodysplastic syndromes. Donor origin of APL cells was validated by conventional karyotyping, florescence in situ hybridization, and single-nucleotide polymorphisms-based chimerism analysis. Targeted sequencing of both the donor and the recipient demonstrated newly-acquired PML::RARA fusion only in the recipient's cells after transplantation, without additional genetic abnormalities. The telomere length was measured at multiple timepoints before and after transplantation. The analysis revealed markedly shortened telomere length at APL onset, which reflect both stem cell expansion following transplantation and expansion of APL cells. Our first-ever report of telomere dynamics in DCL cases provides evidence for the involvement of telomere attrition in DCL pathogenesis.},
}
@article {pmid39837488,
year = {2025},
author = {Schiavinato, M and Ronanki, S and Estruch, IM and van den Brink, N},
title = {Immune response accelerated telomere shortening during early life stage of a passerine bird, the blue tit (Cyanistes caeruleus).},
journal = {Biology letters},
volume = {21},
number = {1},
pages = {20240618},
doi = {10.1098/rsbl.2024.0618},
pmid = {39837488},
issn = {1744-957X},
support = {//HORIZON EUROPE Marie Sklodowska-Curie Actions/ ; },
mesh = {Animals ; *Telomere Shortening ; *Poly I-C/pharmacology ; Passeriformes/immunology/physiology ; Brain/metabolism ; Lipid Peroxidation ; Leukocyte Count ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Aging ; Erythrocytes ; },
abstract = {Dealing with infections is a daily challenge for wild animals. Empirical data show an increase in reactive oxygen species (ROS) production during immune response. This could have consequences on telomere length, the end parts of linear chromosomes, commonly used as proxy for good health and ageing. Telomere length dynamics may reflect the costs associated with physiological responses. In this study, immune system of blue tit (Cyanistes caeruleus) nestlings was experimentally challenged through a polyinosinic:polycytidylic acid (poly I:C) injection, a synthetic double-stranded RNA that mimics a virus, activating the pathway of immune response triggered via the toll-like receptors 3. This path is known to form ROS downstream. Immune response was quantified by white cell counts in blood, while brain lipoperoxidation has been evaluated as an indicator of oxidative damage. Finally, individuals' telomere length shortening between days 8 and 15 after hatching was measured in erythrocytes. Challenged nestlings showed increased leukocyte number when compared with control (treated with a saline solution), lower brain lipid peroxidation (likely as a result of a compensatory mechanism after oxidative stress burst) and accelerated telomere shortening. These findings support the 'ageing cost of infections pathway' hypothesis, which supposes a role for infections in quick biological ageing.},
}
@article {pmid39835465,
year = {2025},
author = {Paldino, G and Tedeschi, V and Proganò, V and Salvati, E and Licursi, V and Vertecchi, E and Bivolaru, AL and Molteni, E and Scrivo, R and Congia, M and Cauli, A and Caccavale, R and Paroli, M and Kunkl, M and Tuosto, L and Sorrentino, R and Fiorillo, MT},
title = {An immunosenescent CD8+ T cell subset in patients with axial Spondyloarthritis and Psoriatic Arthritis links spontaneous motility to telomere shortening and dysfunction.},
journal = {Arthritis &amp; rheumatology (Hoboken, N.J.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/art.43109},
pmid = {39835465},
issn = {2326-5205},
abstract = {OBJECTIVE: A pathogenetic role of CD8+ T lymphocytes in radiographic axial spondyloarthritis (r-axSpA) and other spondyloarthritis (SpA) is sustained by genome-wide association studies (GWAS) and by the expansion of public T cell clonotypes in the target tissues. This study investigates the migration of CD8+ T cells, along with their phenotype and functions in patients with r-axSpA and psoriatic arthritis (PsA).<br><br>METHODS: Peripheral blood CD8+ and CD4+ T cells were isolated from r-axSpA (n= 128), PsA (n= 60) and rheumatoid arthritis (RA, n= 74) patients and healthy donors (HD, n= 79). Transwell migration assay was performed in the presence of different chemokines. CD8+ T cell immunoprofiling and effector functions were assessed by multiparametric flow cytometry. Transcriptome signature was evaluated by RNA-seq analysis whereas telomere length and dysfunction were measured by RT-PCR and IF-fluorescence in situ hybridization (FISH), respectively.<br><br>RESULTS: A significantly higher number of CD8+ T cells migrating in the absence of chemokine stimuli was found in patients with SpA compared to HD and RA patients. This subset, producing cytotoxic (granzyme B, perforin, granulysin) and proinflammatory molecules (TNF&#x3b1;), was significantly enriched in terminally differentiated (CCR7-CD45RA+) and senescent (CD28-CD57+) cells having a gene expression profile characterized by cytolytic signature and natural killer (NK) markers. Remarkably, these spontaneously migrating CD8+ T cells showed DNA damage response (DDR) activation, telomere shortening and dysfunction.<br><br>CONCLUSION: These data describe a terminally differentiated CD8+ T cell subset with a senescent and cytotoxic/proinflammatory profile and an intrinsic invasive potential enriched in SpA patients that represents a possible player in disease pathogenesis.},
}
@article {pmid39834735,
year = {2024},
author = {Liu, M and Wang, C and Wei, B},
title = {Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and telomere length: the NHANES 1999-2002.},
journal = {Frontiers in cardiovascular medicine},
volume = {11},
number = {},
pages = {1407452},
doi = {10.3389/fcvm.2024.1407452},
pmid = {39834735},
issn = {2297-055X},
abstract = {BACKGROUND: The relationship between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and telomere length (TL) remains unclear. This study aims to investigate their association in a nationally representative US population.<br><br>METHODS: Data from 6,342 adults aged &#x2265;20 were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. The NHHR was calculated and categorized into tertiles. TL was measured as the telomere-to-standard reference DNA ratio. Multivariate linear regression and smooth curve fitting were employed to assess the association between NHHR and TL.<br><br>RESULTS: The study population (mean age 45.1&#x2009;&#xb1;&#x2009;0.4&#x2005;years, 48.9% male) was stratified into NHHR tertiles. Compared with the lowest NHHR tertile, the highest NHHR tertile was associated with adverse inflammatory and cardiometabolic profiles, including elevated white blood cell counts (6.88&#x2009;&#xb1;&#x2009;0.07-7.54&#x2009;&#xb1;&#x2009;0.08&#x2009;&#xd7;&#x2009;10[9]/L) and increased prevalence of hypertension (18.81%-25.71%) and diabetes (3.38%-7.17%). An elevated NHHR was significantly associated with a shorter TL (T/S ratio: 1.09&#x2009;&#xb1;&#x2009;0.02-1.03&#x2009;&#xb1;&#x2009;0.02; P&#x2009;=&#x2009;0.0005). This association remained significant in partially adjusted models but was attenuated in a fully adjusted model. Significant interactions were observed for age and hypertension status.<br><br>CONCLUSION: This study revealed a linear inverse association between NHHR and TL, suggesting the utility of the NHHR as a novel biomarker for biological aging. Further prospective studies are warranted to validate these findings.},
}
@article {pmid39833200,
year = {2025},
author = {Jiménez-Martín, A and Pineda-Santaella, A and Martín-García, R and Esteban-Villafañe, R and Matarrese, A and Pinto-Cruz, J and Camacho-Cabañas, S and León-Periñán, D and Terrizzano, A and Daga, RR and Braun, S and Fernández-Álvarez, A},
title = {Centromere positioning orchestrates telomere bouquet formation and the initiation of meiotic differentiation.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {837},
pmid = {39833200},
issn = {2041-1723},
mesh = {*Schizosaccharomyces/genetics/cytology/metabolism ; *Telomere/metabolism/genetics ; *Centromere/metabolism/genetics ; *Meiosis ; *Schizosaccharomyces pombe Proteins/metabolism/genetics ; Chromosomes, Fungal/genetics/metabolism ; },
abstract = {Accurate gametogenesis requires the establishment of the telomere bouquet, an evolutionarily conserved, 3D chromosomal arrangement. In this spatial configuration, telomeres temporarily aggregate at the nuclear envelope during meiotic prophase, which facilitates chromosome pairing and recombination. The mechanisms governing the assembly of the telomere bouquet remain largely unexplored, primarily due to the challenges in visualizing and manipulating the bouquet. Here, using Schizosaccharomyces pombe as a model system to elucidate telomere bouquet function, we reveal that centromeres, traditionally perceived as playing a passive role in the chromosomal reorganization necessary for bouquet assembly, play a key role in the initiation of telomere bouquet formation. We demonstrate that centromeres are capable to induce telomere mobilization, which is sufficient to trigger the first stages of bouquet assembly and the meiotic transcription program in mitotic cells. This discovery highlights the finely tuned control exerted over long-distance heterochromatic regions and underscores a pivotal step in the mechanism of eukaryotic telomere bouquet formation and meiotic transcriptional rewiring.},
}
@article {pmid39828703,
year = {2025},
author = {Zhao, Q and Yin, Z and Hou, Z},
title = {Near telomere-to-telomere genome assemblies of Silkie Gallus gallus and Mallard Anas platyrhynchos restored the structure of chromosomes and "missing" genes in birds.},
journal = {Journal of animal science and biotechnology},
volume = {16},
number = {1},
pages = {9},
pmid = {39828703},
issn = {1674-9782},
abstract = {BACKGROUND: Chickens and ducks are vital sources of animal protein for humans. Recent pangenome studies suggest that a single genome is insufficient to represent the genetic information of a species, highlighting the need for more comprehensive genomes. The bird genome has more than tens of microchromosomes, but comparative genomics, annotations, and the discovery of variations are hindered by inadequate telomere-to-telomere level assemblies. We aim to complete the chicken and duck genomes, recover missing genes, and reveal common and unique chromosomal features between birds.<br><br>RESULTS: The near telomere-to-telomere genomes of Silkie Gallus gallus and Mallard Anas platyrhynchos were successfully assembled via multiple high-coverage complementary technologies, with quality values of 36.65 and 44.17 for Silkie and Mallard, respectively; and BUSCO scores of 96.55% and 96.97% for Silkie and Mallard, respectively; the mapping rates reached over 99.52% for both assembled genomes, these evaluation results ensured high completeness and accuracy. We successfully annotated 20,253 and 19,621 protein-coding genes for Silkie and Mallard, respectively, and assembled gap-free sex chromosomes in Mallard for the first time. Comparative analysis revealed that microchromosomes differ from macrochromosomes in terms of GC content, repetitive sequence abundance, gene density, and levels of 5mC methylation. Different types of arrangements of centromeric repeat sequence centromeres exist in both Silkie and the Mallard genomes, with Mallard centromeres being invaded by CR1. The highly heterochromatic W chromosome, which serves as a refuge for ERVs, contains disproportionately long ERVs. Both Silkie and the Mallard genomes presented relatively high 5mC methylation levels on sex chromosomes and microchromosomes, and the telomeres and centromeres presented significantly higher 5mC methylation levels than the whole genome. Finally, we recovered 325 missing genes via our new genomes and annotated TNFA in Mallard for the first time, revealing conserved protein structures and tissue-specific expression.<br><br>CONCLUSIONS: The near telomere-to-telomere assemblies in Mallard and Silkie, with the first gap-free sex chromosomes in ducks, significantly enhanced our understanding of genetic structures in birds, specifically highlighting the distinctive chromosome features between the chicken and duck genomes. This foundational work also provides a series of newly identified missing genes for further investigation.},
}
@article {pmid39827100,
year = {2025},
author = {Domínguez-de-Barros, A and Pérez-Rubio, G and Fricke-Galindo, I and Ramírez-Venegas, A and Gajate-Arenas, M and Hernández-Zenteno, R and García-Carmona, S and Robles-Hernández, R and Ramírez-Díaz, ME and Cruz-Vicente, F and Martínez-Gómez, ML and Lorenzo-Morales, J and Falfán-Valencia, R and Córdoba-Lanús, E},
title = {Shorter telomere length in COPD cases secondary to biomass-burning smoke exposure.},
journal = {Respiratory research},
volume = {26},
number = {1},
pages = {23},
pmid = {39827100},
issn = {1465-993X},
support = {2023-2028, PI-CC20232222, Cabildo.23//Cabildo Insular de Tenerife/ ; 2023-2028, PI-CC20232222, Cabildo.23//Cabildo Insular de Tenerife/ ; 2023-2028, PI-CC20232222, Cabildo.23//Cabildo Insular de Tenerife/ ; ACIISI 2024//Agencia Canaria de Investigaci&#xf3;n, Innovaci&#xf3;n y Sociedad de la Informaci&#xf3;n/ ; (CB21/13/00100)//Consorcio Centro de Investigaci&#xf3;n Biom&#xe9;dica (CIBER) de Enfermedades Infecciosas (CIBERINFEC) , Instituto de Salud Carlos III, 28006 Madrid, Spain/ ; (CB21/13/00100)//Consorcio Centro de Investigaci&#xf3;n Biom&#xe9;dica (CIBER) de Enfermedades Infecciosas (CIBERINFEC) , Instituto de Salud Carlos III, 28006 Madrid, Spain/ ; },
mesh = {Humans ; *Pulmonary Disease, Chronic Obstructive/genetics/epidemiology/diagnosis ; Male ; Female ; Middle Aged ; *Smoke/adverse effects ; *Biomass ; Aged ; Telomere Shortening ; Telomere ; Adult ; Mexico/epidemiology ; Telomere Homeostasis/physiology ; },
abstract = {BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction and destruction of lung tissue, primarily attributed to tobacco smoking. However, other factors like biomass-burning smoke (BS) exposure are also implicated. COPD has been described as an accelerated aging disease, and telomere length is a biomarker of aging.<br><br>METHODS: This study examined telomere length in 189 Mexican individuals, from which 93 developed COPD secondary to BS exposure (BE-COPD); the rest of the participants were exposed to BS but did not develop the disease. Lung function parameters were measured by spirometry, and relative telomere length (rTL) from peripheral blood DNA was determined using multiplex qPCR.<br><br>RESULTS: Results showed rTL to inversely correlate with age (R[2]=-0.207, p&#x2009;=&#x2009;0.006) and with the hours-a-day of BS exposure (R[2]=-0.297, p&#x2009;<&#x2009;0.001). Within BE-COPD cases, rTL was associated with daily BS exposure, and BE-COPD individuals exhibited a reduced rTL compared to controls (1.39&#x2009;&#xb1;&#x2009;0.45 vs. 0.89&#x2009;&#xb1;&#x2009;0.50; p&#x2009;<&#x2009;0.001). When compared by rTL length in BE-COPD cases, longer telomeres were associated with decreased COPD risk (&#x3b2;&#x2009;=&#x2009;0.134, 95% CI&#x2009;=&#x2009;0.053-0.339; p&#x2009;<&#x2009;0.001). However, no significant relationship was found between rTL and clinical or lung function parameters in the BE-COPD group.<br><br>CONCLUSIONS: This is the first study to document that individuals with COPD secondary to biomass smoke exposure present shorter telomeres than BS-exposed subjects who did not develop the disease.},
}
@article {pmid39826692,
year = {2025},
author = {Comstock, W and Bhattarai, S and Sanford, E and Navarro, M and Smolka, MB},
title = {Profiling Tel1 Signaling Reveals a Non-Canonical Motif Targeting DNA Repair and Telomere Control Machineries.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {108194},
doi = {10.1016/j.jbc.2025.108194},
pmid = {39826692},
issn = {1083-351X},
abstract = {The stability of the genome relies on Phosphatidyl Inositol 3-Kinase-related Kinases (PIKKs) that sense DNA damage and trigger elaborate downstream signaling responses. In S. cerevisiae, the Tel1 kinase (ortholog of human ATM) is activated at DNA double strand breaks (DSBs) and short telomeres. Despite the well-established roles of Tel1 in the control of telomere maintenance, suppression of chromosomal rearrangements, activation of cell cycle checkpoints, and repair of DSBs, the substrates through which Tel1 controls these processes remain incompletely understood. Here we performed an in depth phosphoproteomic screen for Tel1-dependent phosphorylation events. To achieve maximal coverage of the phosphoproteome, we developed a scaled-up approach that accommodates large amounts of protein extracts and chromatographic fractions. Compared to previous reports, we expanded the number of detected Tel1-dependent phosphorylation events by over 10-fold. Surprisingly, in addition to the identification of phosphorylation sites featuring the canonical motif for Tel1 phosphorylation (S/T-Q), the results revealed a novel motif (D/E-S/T) highly prevalent and enriched in the set of Tel1-dependent events. This motif is unique to Tel1 signaling and not shared with the Mec1 kinase, providing clues to how Tel1 plays specialized roles in DNA repair and telomere length control. Overall, these findings define a Tel1-signaling network targeting numerous proteins involved in DNA repair, chromatin regulation, and telomere maintenance that represents a framework for dissecting the molecular mechanisms of Tel1 action.},
}
@article {pmid39826712,
year = {2025},
author = {Yu, X and Zhang, H},
title = {Biomolecular Condensates in Telomere Maintenance of ALT Cancer Cells.},
journal = {Journal of molecular biology},
volume = {},
number = {},
pages = {168951},
doi = {10.1016/j.jmb.2025.168951},
pmid = {39826712},
issn = {1089-8638},
abstract = {Alternative Lengthening of Telomeres (ALT) pathway is a telomerase-independent mechanism that utilizes homology-directed repair (HDR) to sustain telomere length in specific cancers. Biomolecular condensates, such as ALT-associated promyelocytic leukemia nuclear bodies (APBs), have emerged as critical players in the ALT pathway, supporting telomere maintenance in ALT-positive cells. These condensates bring together DNA repair proteins, telomeric repeats, and other regulatory elements. By regulating replication stress and promoting DNA synthesis, ALT condensates create an environment conducive to HDR-based telomere extension. This review explores recent advancements in ALT, focusing on understanding the role of biomolecular condensates in ALT and how they impact telomere dynamics and stability.},
}
@article {pmid39825185,
year = {2025},
author = {Cui, J and Wang, R and Gu, R and Chen, M and Wang, Z and Li, L and Hong, J and Cui, S},
title = {Telomere-to-telomere Phragmites australis reference genome assembly with a B chromosome provides insights into its evolution and polysaccharide biosynthesis.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {73},
pmid = {39825185},
issn = {2399-3642},
support = {31972934, 31170784//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {*Poaceae/genetics/metabolism ; *Genome, Plant ; *Evolution, Molecular ; *Polysaccharides/biosynthesis/metabolism/genetics ; *Chromosomes, Plant/genetics ; Telomere/genetics/metabolism ; Phylogeny ; Gene Duplication ; },
abstract = {Phragmites australis is a globally distributed grass species (Poaceae) recognized for its vast biomass and exceptional environmental adaptability, making it an ideal model for studying wetland ecosystems and plant stress resilience. However, genomic resources for this species have been limited. In this study, we assembled a chromosome-level reference genome of P. australis containing one B chromosome. An explosion of LTR-RTs, centered on the Copia family, occurred during the late Pleistocene, driving the expansion of P. australis genome size and subgenomic differentiation. Comparative genomic analysis showed that P. australis underwent two whole gene duplication events, was segregated from Cleistogenes songorica at 34.6 Mya, and that 41.26% of the gene families underwent expansion. Based on multi-tissue transcriptomic data, we identified structural genes in the biosynthetic pathway of pharmacologically active Phragmitis rhizoma polysaccharides with essential roles in rhizome development. This study deepens our understanding of Arundinoideae evolution, genome dynamics, and the genetic basis of key traits, providing essential data and a genetic foundation for wetland restoration, bioenergy development, and plant stress.},
}
@article {pmid39817136,
year = {2025},
author = {Wang, Q and Li, QR and Xu, L and Yuan, ZC and Liu, X and Tang, MJ and Luo, M and Zhong, XW and Ma, Q and Guo, XL},
title = {BIBR1532 inhibits proliferation and metastasis of esophageal squamous cancer cells by inducing telomere dysregulation.},
journal = {World journal of gastrointestinal oncology},
volume = {17},
number = {1},
pages = {99376},
pmid = {39817136},
issn = {1948-5204},
abstract = {BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high morbidity and mortality, and easy to develop resistance to chemotherapeutic agents. Telomeres are DNA-protein complexes located at the termini of chromosomes in eukaryotic cells, which are unreplaceable in maintaining the stability and integrity of genome. Telomerase, an RNA-dependent DNA polymerase, play vital role in telomere length maintain, targeting telomerase is a promising therapeutic strategy for cancer.<br><br>AIM: To investigate the efficacy and underlying mechanisms of BIBR1532, a telomerase inhibitor, in ESCC.<br><br>METHODS: KYSE150 and KYSE410 cells were cultured and exposed to various concentrations of BIBR1532. Cell viability was assessed at 48 hours and 72 hours to determine the IC50 values. The effects of BIBR1532 on ESCC cell proliferation, migration, and cellular senescence were evaluated using the cell counting kit-8 assay, plate colony formation assay, scratch assay, transwell assay, and &#x3b2;-galactosidase staining, respectively. Western blotting was performed to detect the expression of proteins in BIBR1532-treated ESCC cells, such as human telomerase reverse transcriptase (hTERT), key molecules involved in DNA damage response (DDR) or cellular senescence, as well as telomere-binding proteins. Additionally, a tumor-bearing nude mouse model was established to evaluate the anti-cancer effect of BIBR1532 in vivo.<br><br>RESULTS: The IC50 values for KYSE150 and KYSE410 cells after 48 hours of BIBR1532 exposure were 48.53 &#x3bc;M and 39.59 &#x3bc;M, respectively. These values decreased to 37.22 &#x3bc;M and 22.71 &#x3bc;M, respectively, following a longer exposure of 72 hours. BIBR1532 exhibited dose-dependent effects on KYSE150 and KYSE410 cells, including decreased hTERT expression, inhibition of proliferation and metastasis, and induction of cellular senescence. Mechanistically, BIBR1532 upregulated the expression of the DDR protein, &#x3b3;-H2AX, and activated the ataxia telangiectasia and Rad3-related protein (ATR)/ check point kinase 1 (CHK-1) and ataxia-telangiectasia mutated gene (ATM)/CHK2 pathways. BIBR1532 downregulated the expression of telomere-binding proteins, including telomeric-repeat binding factor 1 (TRF1), TRF2, protection of telomeres 1, and TIN2-interacting protein 1. In a nude mouse xenograft model, BIBR1532 significantly suppressed tumor growth, reduced hTERT expression, and increased &#x3b3;-H2AX protein levels. Hematoxylin and eosin staining of various organs, including the heart, liver, spleen, lungs, and kidneys, revealed no apparent adverse effects.<br><br>CONCLUSION: BIBR1532 exerts anti-cancer effects on ESCC by inducing DDR through the ATR/CHK1 and ATM/CHK2 pathways and downregulating the expression of telomere-binding proteins.},
}
@article {pmid39814758,
year = {2025},
author = {Krawczyk, K and Szablińska-Piernik, J and Paukszto, &#x141; and Maździarz, M and Sulima, P and Przyborowski, JA and Szczecińska, M and Sawicki, J},
title = {Chromosome-scale telomere to telomere genome assembly of common crystalwort (Riccia sorocarpa Bisch.).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {77},
pmid = {39814758},
issn = {2052-4463},
support = {2020/39/B/NZ8/02504//Narodowe Centrum Nauki (National Science Centre)/ ; },
mesh = {*Telomere/genetics ; *Genome, Plant ; Chromosomes, Plant ; Hepatophyta/genetics ; DNA Methylation ; },
abstract = {Riccia sorocarpa Bisch., commonly known as common crystalwort, is a plant belonging to the Marchantiales order with a cosmopolitan distribution among a wide range of habitats: fields, gardens, waste ground, on paths, cliff tops, and thin soil over rocks or by water bodies. However, research into the genetic aspects of this species is limited. In this study, the chromosome-scale telomere-to-telomere genome of R. sorocarpa was assembled exclusively by Oxford Nanopore long-read sequencing and Pore-C technology. A high-quality chromosomal-scale assembly was obtained with a final genome size of 376.690 Mbp, contig N50 of 49.132 Mbp and 97.02% of the assembled contigs associated with the eight chromosomes. Genome assembly completeness was confirmed by BUSCO analysis accounting 91.8%. Among 27,626 total genes, 23,562 (85.29%) were functionally annotated. Moreover, collinearity of Marchantiales was analyzed as well as gene family evolution and DNA methylation profile. The availability of this genome, which is the second telomere-to-telomere liverwort assembly, opens up new avenues for in-depth analysis of R. sorocarpa genetic diversity and genomic characteristics.},
}
@article {pmid39813504,
year = {2025},
author = {Castro, MCS and Costa, LC and Salum, KCR and Castro, HA and Ribeiro, PC and Costa, W and Nani, ASF and Kohlrausch, FB},
title = {Silica-exposed patients with silicosis show shorter telomeres than do unexposed individuals: a pilot study in a population in southeastern Brazil.},
journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia},
volume = {50},
number = {6},
pages = {e20240318},
doi = {10.36416/1806-3756/e20240318},
pmid = {39813504},
issn = {1806-3756},
mesh = {Humans ; *Silicosis/genetics ; Male ; Brazil/epidemiology ; Pilot Projects ; *Occupational Exposure/adverse effects ; *Silicon Dioxide/adverse effects/toxicity ; Middle Aged ; Case-Control Studies ; *Telomere Shortening/drug effects ; Adult ; Oxidative Stress ; Telomere/drug effects ; Severity of Illness Index ; Smoking/adverse effects ; },
abstract = {OBJECTIVE: Silicosis is a pneumoconiosis characterized by fibrosis of the lung parenchyma caused by the inhalation of silica particles. Silica dust inhalation is associated with inflammation and induction of oxidative stress in the lungs. This oxidative stress affects telomeres, which are short tandem DNA repeats that cap the end of linear chromosomes. We aimed to determine whether telomere length (TL) correlates with silicosis or severity of silicosis in silica-exposed workers in Brazil.<br><br>METHODS: We included 200 men in southeastern Brazil: 100 with silicosis and 100 who had not been exposed to silica. We extracted DNA from buccal cells and assessed TL by multiplex quantitative polymerase chain reaction.<br><br>RESULTS: The median TL was significantly shorter in the patients with silicosis than in the unexposed controls (p < 0.0001), although it did not differ between the patients with simple silicosis and those with complicated silicosis (p = 0.961). We also found that, in patients with silicosis, TL was influenced by smoking (p = 0.034) and by a history of personal protective equipment use in the workplace (p = 0.002).<br><br>CONCLUSIONS: Silica exposure appears to have an impact on TL, which was found to be shorter in patients with silicosis than in unexposed controls. Further studies are needed in order to confirm the impact that oxidative stress caused by silica inhalation has on telomeres.},
}
@article {pmid39809206,
year = {2024},
author = {Lyu, TT and Wang, JY and Tan, JS and Yang, YM and Wang, YM and Zhao, J and Qing, P and Wu, LM and Wang, XJ},
title = {Causal associations between telomere length and pulmonary arterial hypertension: A two-sample Mendelian randomization study.},
journal = {Medicine},
volume = {103},
number = {47},
pages = {e40407},
doi = {10.1097/MD.0000000000040407},
pmid = {39809206},
issn = {1536-5964},
support = {2022&#xe2;&#x20ac; GSP&#xe2;&#x20ac;GG&#xe2;&#x20ac;26//the High&#xe2;&#x20ac;Level Hospital Clinical Research Funding/ ; 2023-GSP-GG-41//the High&#xe2;&#x20ac;Level Hospital Clinical Research Funding/ ; 2023-GSP-GG-24//the High&#xe2;&#x20ac;Level Hospital Clinical Research Funding/ ; NCRC2020015//National Clinical Medical Research Center for Cardiovascular Diseases/ ; 7222142//the Beijing Natural Science Foundation/ ; 82170408//National Natural Science Foundation/ ; 82070353//National Natural Science Foundation/ ; 81800300//National Natural Science Foundation/ ; },
mesh = {*Mendelian Randomization Analysis ; Humans ; *Polymorphism, Single Nucleotide ; *Genome-Wide Association Study ; *Telomere/genetics ; Pulmonary Arterial Hypertension/genetics ; Hypertension, Pulmonary/genetics ; Telomere Homeostasis/genetics ; },
abstract = {Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by elevated pulmonary artery pressure, leading to right heart failure, and mortality. The role of telomere length, a marker of biological aging, in PAH remains unclear. We utilized summary-level data from genome-wide association studies for various measures of telomere length and PAH. Single nucleotide polymorphisms associated with telomere length at a genome-wide significance level were used as instrumental variables. The inverse variance weighted method was the primary analysis, with sensitivity analyses including the weighted median and Mendelian randomization-Egger regression. The odds ratios and 95% confidence intervals (CI) were calculated to estimate the causal effect of telomere length on PAH risk. The Mendelian randomization analyses revealed no significant causal association between overall telomere length and PAH (odds ratios per standard deviation increase = 1.229, 95% CI: 0.469-3.222, P = .676). Similar null findings were observed for granulocyte, lymphocyte, naive T-cell, memory T-cell, B-cell, and natural killer-cell telomere lengths. Sensitivity analyses confirmed the robustness of the results, with no evidence of horizontal pleiotropy or significant influence of individual single nucleotide polymorphisms on the overall estimates. This Mendelian randomization study didn't support a causal association between telomere length and PAH.},
}
@article {pmid39805504,
year = {2025},
author = {Boccardi, V and Marano, L},
title = {The telomere connection between aging and cancer: The burden of replication stress and dysfunction.},
journal = {Mechanisms of ageing and development},
volume = {},
number = {},
pages = {112026},
doi = {10.1016/j.mad.2025.112026},
pmid = {39805504},
issn = {1872-6216},
abstract = {Aging is a complex process that affects individuals at the molecular, cellular, tissue, and systemic levels, arising from the cumulative effects of damage and diminished repair mechanisms. This process leads to the onset of age-related diseases, including cancer, which exhibits increased incidence with age. Telomeres, the protective caps at chromosome ends, play a crucial role in genome stability and are closely connected with aging and age-related disorders. Both excessively short and long telomere lengths may contribute to cancer development when their balance is disrupted. Fragile telomeres, characterized by abnormalities and replication stress, may provide novel insights into the connection between aging and cancer. The accumulation of fragile telomeres, possibly due to intense replicative stress, may represent a key factor. Given the dynamic nature of telomeres, large longitudinal studies are essential for understanding their role in aging and cancer susceptibility, which is crucial for developing effective strategies to promote healthy aging and mitigate cancer risk.},
}
@article {pmid39803571,
year = {2024},
author = {Khandagale, P and Sun, Y and Saha, S and Saha, LK and Pommier, Y},
title = {Topoisomerase 3α (TOP3A) Dependent Alternative Lengthening of Telomeres (ALT).},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.11.18.624152},
pmid = {39803571},
issn = {2692-8205},
abstract = {Alternative Lengthening of Telomeres (ALT) is a homologous recombination-dependent telomere elongation mechanism utilized by at least 10-15% of all cancers. Here we identified that the DNA topoisomerase, TOP3A is enriched at the telomeres of ALT cells but not at the telomeres of telomerase-positive (Tel) cancer cells. We demonstrate that TOP3A stabilizes the shelterin protein TERF2 in ALT cancer cell lines but not in Tel cells and that long non-coding telomere transcribed RNA (TERRA) enrichment at telomeres depends upon TOP3A. TOP3A also promotes the generation of single-stranded telomeric C-strand (ssTeloC) DNA, which is a recently discovered marker for ALT. Additionally, we found that inducing TOP3A-DNA-protein crosslinks in ALT cells suppresses TERRA enrichment as well as destabilizes TERF2. Taken together these observations uncover the unexplored functions of TOP3A at ALT telomeres and suggest the potential of developing an ALT-specific cancer therapeutic strategy targeting TOP3A.},
}
@article {pmid39803201,
year = {2025},
author = {Krams, R and Cīrule, D and Munkevics, M and Popovs, S and Jõers, P and Contreras Garduño, J and Krams, IA and Krama, T},
title = {Great Tit (Parus major) Nestlings Have Longer Telomeres in Old-Growth Forests Than in Young Forests.},
journal = {Ecology and evolution},
volume = {15},
number = {1},
pages = {e70823},
pmid = {39803201},
issn = {2045-7758},
abstract = {Modification and deterioration of old-growth forests by industrial forestry have seriously threatened species diversity worldwide. The loss of natural habitats increases the concentration of circulating glucocorticoids and incurs chronic stress in animals, influencing the immune system, growth, survival, and lifespan of animals inhabiting such areas. In this study, we tested whether great tit (Parus major) nestlings grown in old-growth unmanaged coniferous forests have longer telomeres than great tit nestlings developing in young managed coniferous forests. This study showed that the patches of young managed coniferous forests had lower larval biomass than old-growth forests. Since insect larvae are the preferred food for great tit nestlings, the shortage of food may divert energy resources away from growth, which can show up as physiological stress, often raising the heterophil/lymphocyte (H/L) ratio. The H/L ratio revealed a significant difference in stress levels, being the highest in great tit nestlings developing in young-managed pine forests. We also found that the development of great tit nestlings in young managed forests had significantly shorter telomeres than in old-growth forests. Although nestling survival did not differ between the habitats, nestlings growing up in old-growth forests had greater telomere lengths, which can positively affect their lifespan. Our results suggest that the forest habitats affected by industrial forestry may represent ecological traps, as the development of young birds in deteriorated environments can affect the age structure of populations.},
}
@article {pmid39800618,
year = {2024},
author = {Su, Y and Yin, L and Zhao, Y and Zhao, Y and Zhang, W and Ke, Y and Wang, M and He, X and Liu, M and Liu, G and Qin, P and Hu, F and Zhang, M and Hu, D},
title = {The association of telomere length and coronary heart disease: A systematic review and dose-response meta-analysis.},
journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD},
volume = {},
number = {},
pages = {103830},
doi = {10.1016/j.numecd.2024.103830},
pmid = {39800618},
issn = {1590-3729},
abstract = {AIMS: The association of telomere length (TL) and coronary heart disease (CHD) is still debated, and there is a lack of dose-response meta-analyses on this issue. The aim is therefore to integrate existing evidence on the association between TL and CHD risk and explore the dose-response relationship between them.<br><br>DATA SYNTHESIS: PubMed, EMBASE, and Web of Science were searched for relevant studies up to September 2024. Meta-analysis was performed using a random-effects model, with data presented as RRs and 95&#xa0;% CIs. Restricted cubic splines were used to assess linear and nonlinear associations. Subgroup analysis and meta-regression were performed to explore sources of heterogeneity. Fourteen articles (8 prospective cohort studies, 2 case-cohort studies, 2 case-control studies, and 2 cross-sectional studies) were finally included in the meta-analysis, with a total sample size of 199,562 participants and 25,752 cases. For CHD, the total RR for the highest TL group compared to the lowest TL group was 0.69 (95&#xa0;% CI: 0.61, 0.78, I[2]&#xa0;=&#xa0;64.5&#xa0;%). For every 1 kilobase pair (kbp) increase in TL, the CHD risk decreased by 23&#xa0;% (RR&#xa0;=&#xa0;0.77, 95&#xa0;% CI: 0.69, 0.87, I[2]&#xa0;=&#xa0;89.0&#xa0;%). The nonlinearity test indicated a linear association between TL and CHD risk (Pnon-linearity&#xa0;=&#xa0;0.930). Sensitivity analyses indicated that the results were robust.<br><br>CONCLUSIONS: The meta-analysis showed a linear relationship between TL and CHD. People with low TL may be more likely to develop CHD than those with high TL. The association between the two did not change in a wide range of populations.},
}
@article {pmid39797337,
year = {2025},
author = {Sánchez-Badajos, S and Ortega-Vázquez, A and López-López, M and Monroy-Jaramillo, N},
title = {Valproic Acid and Lamotrigine Differentially Modulate the Telomere Length in Epilepsy Patients.},
journal = {Journal of clinical medicine},
volume = {14},
number = {1},
pages = {},
pmid = {39797337},
issn = {2077-0383},
support = {34605034//Universidad Aut&#xf3;noma Metropolitana Unidad Xochimilco/ ; },
abstract = {Background/Objectives: Antiseizure drugs (ASDs) are the primary therapy for epilepsy, and the choice varies according to seizure type. Epilepsy patients experience chronic mitochondrial oxidative stress and increased levels of pro-inflammatory mediators, recognizable hallmarks of biological aging; however, few studies have explored aging markers in epilepsy. Herein, we addressed for the first time the impact of ASDs on molecular aging by measuring the telomere length (TL) and mtDNA copy number (mtDNA-CN). Methods: We used real-time quantitative PCR (QPCR) in epilepsy patients compared to matched healthy controls (CTs) and assessed the association with plasma levels of ASDs and other clinical variables. The sample comprised 64 epilepsy patients and 64 CTs. Patients were grouped based on monotherapy with lamotrigine (LTG) or valproic acid (VPA), and those treated with a combination therapy (LTG + VPA). Multivariable logistic regression was applied to analyze the obtained data. Results: mtDNA-CN was similar between patients and controls, and none of the comparisons were significant for this marker. TL was shorter in not seizure-free patients than in CTs (1.50 ± 0.35 vs. 1.68 ± 0.34; p < 0.05), regardless of the ASD therapy. These patients exhibited the highest proportion of adverse drug reactions. TL was longer in patients on VPA monotherapy, followed by patients on LTG monotherapy and patients on an LTG + VPA combined scheme (1.77 ± 0.24; 1.50 ± 0.32; 1.36 ± 0.37, respectively; p < 0.05), suggesting that ASD treatment differentially modulates TL. Conclusions: Our findings suggest that clinicians could consider TL measurements to decide the best ASD treatment option (VPA and/or LTG) to help predict ASD responses in epilepsy patients.},
}
@article {pmid39796144,
year = {2024},
author = {Sawicki, K and Matysiak-Kucharek, M and Gorczyca-Siudak, D and Kruszewski, M and Kurzepa, J and Kapka-Skrzypczak, L and Dziemidok, P},
title = {Leukocyte Telomere Length as a Marker of Chronic Complications in Type 2 Diabetes Patients: A Risk Assessment Study.},
journal = {International journal of molecular sciences},
volume = {26},
number = {1},
pages = {},
doi = {10.3390/ijms26010290},
pmid = {39796144},
issn = {1422-0067},
support = {No. 21060//Instytut Medycyny Wsi im. Witolda Chod&#x17a;ki/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 2/complications/blood ; Male ; Female ; *Leukocytes/metabolism ; Middle Aged ; *Biomarkers/blood ; *Telomere/metabolism/genetics ; Aged ; Risk Assessment/methods ; Telomere Shortening ; Diabetic Nephropathies/blood/etiology/genetics ; Diabetic Retinopathy/etiology/blood ; Telomere Homeostasis ; },
abstract = {Telomere shortening has been linked to type 2 diabetes (T2D) and its complications. This study aims to determine whether leukocyte telomere length (LTL) could be a useful marker in predicting the onset of complications in patients suffering from T2D. Enrolled study subjects were 147 T2D patients. LTL was measured using a quantitative PCR method. Key subject's demographics and other clinical characteristics were also included. T2D patients with the shortest LTL had higher TC and non-HDL levels, compared to subjects with the longest LTL (p = 0.013). Also, T2D patients suffering from diabetic nephropathy showed significant differences in LDL levels (p = 0.023). While in the group of T2D patients with diabetic retinopathy, significant differences were observed for parameters, such as duration of diabetes (p = 0.043), HbA1c (p = 0.041), TC (p = 0.003), LDL (p = 0.015), Non-HDL (p = 0.004) and TG (p = 0.045). Logistic regression analysis confirmed a significant risk of association of TC and Non-HDL levels with LTL in the 3rd tertile LTL for the crude model adjusted for sex and age, with respective odds ratios of 0.71 (95% CI 0.56-0.91) and 0.73 (95% CI 0.58-0.91). No significant associations were found between LTL in T2D patients and the prevalence of common T2D complications. Nevertheless, a significant association was demonstrated between LTL and some markers of dyslipidemia, including in T2D patients with either diabetic nephropathy or retinopathy. Therefore, analysis of LTL in T2D patients' leukocytes demonstrates a promising potential as a marker in predicting the onset of complications in T2D. This could also help in establishing an effective treatment strategy or even prevent and delay the onset of these severe complications.},
}
@article {pmid39795052,
year = {2025},
author = {Dewulf, M and Duchateau, L and Meesters, M and Martens, DS and Nawrot, TS and Van Eetvelde, M and Opsomer, G},
title = {Telomere Length in Neonatal Dairy Calves in Relation to Lifetime Parameters.},
journal = {Animals : an open access journal from MDPI},
volume = {15},
number = {1},
pages = {},
doi = {10.3390/ani15010109},
pmid = {39795052},
issn = {2076-2615},
support = {1SH5N24N//Research Foundation - Flanders/ ; 12X9623N//Research Foundation - Flanders/ ; },
abstract = {Telomere length (TL) has gained attention as a biomarker for longevity and productivity in dairy cattle. This study explored the association between neonatal TL in Holstein calves and lifetime parameters (lifespan, milk production, and reproduction). Blood samples were collected from 210 calves (≤10d old) across four dairy farms in Flanders, Belgium. Telomere length was measured using qPCR and analyzed as a continuous variable and across three groups: the 10% shortest, the 10% longest, and the remaining 80%. Survival analyses showed no association between TL and lifespan (p = 0.1) or TL groups (p = 0.8). Similarly, TL showed no significant association with production traits. However, categorical analyses revealed that calves with the longest TL had lower lifetime fat (p = 0.01) and protein yields (p = 0.01) than those with the shortest TL. Reproductive analyses showed cows in the long TL group required fewer inseminations per lactation (p = 0.02) and exhibited longer calving intervals (p = 0.05). These findings suggest that while neonatal TL may not predict productive lifespan, it may provide insight into reproductive efficiency. Future studies should prioritize longitudinal assessments of TL dynamics to better understand their interactions with management practices and application in herd improvement.},
}
@article {pmid39791491,
year = {2025},
author = {Gan, D and Baylin, A and Peterson, KE and Rosero-Bixby, L and Ruiz-Narváez, EA},
title = {Social Connections, Leukocyte Telomere Length, and All-Cause Mortality in Older Adults From Costa Rica: The Costa Rican Longevity and Healthy Aging Study (CRELES).},
journal = {Journal of aging and health},
volume = {},
number = {},
pages = {8982643251313923},
doi = {10.1177/08982643251313923},
pmid = {39791491},
issn = {1552-6887},
abstract = {OBJECTIVES: To examine the association of social connections with blood leukocyte telomere length (LTL) and all-cause mortality in older Costa Ricans.<br><br>METHODS: Utilizing data from the Costa Rican Longevity and Healthy Aging Study (CRELES), a prospective cohort of 2827 individuals aged 60 and above followed since 2004, we constructed a Social Network Index (SNI) based on marital status, household size, interaction with non-cohabitating adult children, and church attendance. We used linear regression to assess SNI's association with baseline LTL (N = 1113), and Cox proportional-hazard models to examine SNI's relationship with all-cause mortality (N = 2735).<br><br>RESULTS: Higher SNI levels were associated with longer telomeres and decreased all-cause mortality during follow-up. Being married and regular church attendance were associated with 23% and 24% reductions of the all-cause mortality, respectively.<br><br>DISCUSSION: These findings underscore the importance of social engagement in promoting longevity among older Costa Ricans, suggesting broader implications for aging populations globally.},
}
@article {pmid39780848,
year = {2025},
author = {Medina-Neira, D and Alvarado-Gamarra, G and Huamaní-Condori, B and Purizaca-Rosillo, N and Atamari-Anahui, N and Matos-Villena, E and Garces-Ghilardi, R and Estupiñan-Vigil, M},
title = {Hemophagocytic lymphohistiocytosis as the initial manifestation of bone marrow failure in a child with a TERC variant telomere biology disorder.},
journal = {Therapeutic advances in rare disease},
volume = {6},
number = {},
pages = {26330040241311621},
pmid = {39780848},
issn = {2633-0040},
abstract = {Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome, rarely associated with bone marrow failure (BMF). Telomere biology disorders (TBD) are caused by inherited defects in telomerase processes and can have heterogeneous presentations including idiopathic pulmonary fibrosis, cirrhosis, and BMF. We report a case of a 10-year-old male from Lima, Peru, who presented with HLH as the initial manifestation of a TBD. He experienced fever, gastrointestinal symptoms, and mucocutaneous involvement. Initial laboratory analyses revealed pancytopenia and elevated inflammatory markers. Despite symptomatic and antibiotic treatment, his clinical condition persisted leading to a suspicion of Kawasaki disease and, subsequently, HLH. Immunomodulatory treatment was initiated with a good clinical response. Bone marrow aspiration revealed severe hypocellular bone marrow and cytophagocytosis. Genetic studies identified a pathogenic variant in the TERC gene (n.110_113del), which was also found in the patient's mother and brother. HLH as the initial manifestation of BMF is rare. This case highlights the importance of considering TBD in children with BMF of unclear etiology and the value of genetic testing in such cases.},
}
@article {pmid39779954,
year = {2025},
author = {Luo, LY and Wu, H and Zhao, LM and Zhang, YH and Huang, JH and Liu, QY and Wang, HT and Mo, DX and EEr, HH and Zhang, LQ and Chen, HL and Jia, SG and Wang, WM and Li, MH},
title = {Telomere-to-telomere sheep genome assembly identifies variants associated with wool fineness.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {39779954},
issn = {1546-1718},
support = {32320103006//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Ongoing efforts to improve sheep reference genome assemblies still leave many gaps and incomplete regions, resulting in a few common failures and errors in genomic studies. Here, we report a 2.85-Gb gap-free telomere-to-telomere genome of a ram (T2T-sheep1.0), including all autosomes and the X and Y chromosomes. This genome adds 220.05 Mb of previously unresolved regions and 754 new genes to the most updated reference assembly ARS-UI_Ramb_v3.0; it contains four types of repeat units (SatI, SatII, SatIII and CenY) in centromeric regions. T2T-sheep1.0 has a base accuracy of more than 99.999%, corrects several structural errors in previous reference assemblies and improves structural variant detection in repetitive sequences. Alignment of whole-genome short-read sequences of global domestic and wild sheep against T2T-sheep1.0 identifies 2,664,979 new single-nucleotide polymorphisms in previously unresolved regions, which improves the population genetic analyses and detection of selective signals for domestication (for example, ABCC4) and wool fineness (for example, FOXQ1).},
}
@article {pmid39778865,
year = {2025},
author = {Kim, J and Park, JL and Yang, JO and Kim, S and Joe, S and Park, G and Hwang, T and Cho, MJ and Lee, S and Lee, JE and Park, JH and Yeo, MK and Kim, SY},
title = {Highly accurate Korean draft genomes reveal structural variation highlighting human telomere evolution.},
journal = {Nucleic acids research},
volume = {53},
number = {1},
pages = {},
doi = {10.1093/nar/gkae1294},
pmid = {39778865},
issn = {1362-4962},
support = {2020M3E5D708517212//Ministry of Science and ICT/ ; RS-2024-00438566//Ministry of Health and Welfare/ ; P0009796//Ministry of Trade, Industry and Energy/ ; KGM5192221//KRIBB Research Initiative Program/ ; },
mesh = {Humans ; *Telomere/genetics ; *Genome, Human/genetics ; *Evolution, Molecular ; Republic of Korea ; Genomic Structural Variation ; DNA Repair/genetics ; Asian People/genetics ; Genomics/methods ; },
abstract = {Given the presence of highly repetitive genomic regions such as subtelomeric regions, understanding human genomic evolution remains challenging. Recently, long-read sequencing technology has facilitated the identification of complex genetic variants, including structural variants (SVs), at the single-nucleotide level. Here, we resolved SVs and their underlying DNA damage-repair mechanisms in subtelomeric regions, which are among the most uncharted genomic regions. We generated ∼20 × high-fidelity long-read sequencing data from three Korean individuals and their partially phased high-quality de novo genome assemblies (contig N50: 6.3-58.2 Mb). We identified 131 138 deletion and 121 461 insertion SVs, 41.6% of which were prevalent in the East Asian population. The commonality of the SVs identified among the Korean population was examined by short-read sequencing data from 103 Korean individuals, providing the first comprehensive SV set representing the population based on the long-read assemblies. Manual investigation of 19 large subtelomeric SVs (≥5 kb) and their associated repair signatures revealed the potential repair mechanisms leading to the formation of these SVs. Our study provides mechanistic insight into human telomere evolution and can facilitate our understanding of human SV formation.},
}
@article {pmid39775841,
year = {2025},
author = {Zhou, Y and Wang, C and Wang, B and Xu, D and Zhang, X and Ge, Y and Jiang, S and Tang, F and Chen, C and Li, X and Jian, J and You, Y},
title = {Telomere-to-telomere genome and resequencing of 254 individuals reveal evolution, genomic footprints in Asian icefish, Protosalanx chinensis.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giae115},
pmid = {39775841},
issn = {2047-217X},
support = {2023YFD2400900//National Key Research and Development Program of China/ ; },
mesh = {*Telomere/genetics ; *Evolution, Molecular ; *Genomics/methods ; Animals ; *Genome ; Genetic Variation ; Genetics, Population ; China ; },
abstract = {The Asian icefish, Protosalanx chinensis, has undergone extensive colonization in various waters across China for decades due to its ecological and physiological significance as well as its economic importance in the fishery resource. Here, we decoded a telomere-to-telomere (T2T) genome for P. chinensis combining PacBio HiFi long reads and ultra-long ONT (nanopore) reads and Hi-C data. The telomere was identified in both ends of the contig/chromosome. The expanded gene associated with circadian entrainment suggests that P. chinensis may exhibit a high sensitivity to photoperiod. The contracted genes' immune-related families and DNA repair associated with positive selection in P. chinensis suggested the selection pressure during adaptive evolution. The population genetic analysis reported the genetic diversity and genomic footprints in 254 individuals from 8 different locations. The natural seawater samples can be the highest diversity and different from other freshwater and introduced populations. The divergent regions' associated genes were found to be related to the osmotic pressure system, suggesting adaptations to alkalinity and salinity. Thus, the T2T genome and genetic variation can be valuable resources for genomic footprints in P. chinensis, shedding light on its evolution, comparative genomics, and the genetic differences between natural and introduced populations.},
}
@article {pmid39772744,
year = {2025},
author = {Dubois, JC and Bonnell, E and Filion, A and Frion, J and Zimmer, S and Riaz Khan, M and Teplitz, GM and Casimir, L and Méthot, &#xc9; and Marois, I and Idrissou, M and Jacques, P&#xc9; and Wellinger, RJ and Maréchal, A},
title = {The single-stranded DNA-binding factor SUB1/PC4 alleviates replication stress at telomeres and is a vulnerability of ALT cancer cells.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {2},
pages = {e2419712122},
doi = {10.1073/pnas.2419712122},
pmid = {39772744},
issn = {1091-6490},
support = {506663//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; FDN154315//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; },
mesh = {Humans ; *Telomere/metabolism ; *Telomere Homeostasis ; *DNA Replication ; Cell Line, Tumor ; DNA-Binding Proteins/metabolism/genetics ; Neoplasms/genetics/metabolism/pathology ; DNA, Single-Stranded/metabolism/genetics ; },
abstract = {To achieve replicative immortality, cancer cells must activate telomere maintenance mechanisms. In 10 to 15% of cancers, this is enabled by recombination-based alternative lengthening of telomeres pathways (ALT). ALT cells display several hallmarks including heterogeneous telomere length, extrachromosomal telomeric repeats, and ALT-associated PML bodies. ALT cells also have high telomeric replication stress (RS) enhanced by fork-stalling structures (R-loops and G4s) and altered chromatin states. In ALT cells, telomeric RS promotes telomere elongation but above a certain threshold becomes detrimental to cell survival. Manipulating RS at telomeres has thus been proposed as a therapeutic strategy against ALT cancers. Through analysis of genome-wide CRISPR fitness screens, we identified ALT-specific vulnerabilities and describe here our characterization of the roles of SUB1, a ssDNA-binding protein, in telomere stability. SUB1 depletion increases RS at ALT telomeres, profoundly impairing ALT cell growth without impacting telomerase-positive cells. During RS, SUB1 is recruited to stalled forks and ALT telomeres via its ssDNA-binding domain. This recruitment is potentiated by RPA depletion, suggesting that these factors may compete for ssDNA. The viability of ALT cells and their resilience toward RS also requires ssDNA binding by SUB1. SUB1 depletion accelerates cell death induced by FANCM depletion, triggering unsustainable levels of telomeric damage in ALT cells. Finally, combining SUB1 depletion with RS-inducing drugs rapidly induces replication catastrophe in ALT cells. Altogether, our work identifies SUB1 as an ALT susceptibility with roles in the mitigation of RS at ALT telomeres and suggests advanced therapeutic strategies for a host of still poorly managed cancers.},
}
@article {pmid39767532,
year = {2024},
author = {Han, CJ and Ning, X and Burd, CE and Tounkara, F and Kalady, MF and Noonan, AM and Von Ah, D},
title = {A Machine Learning Classification Model for Gastrointestinal Health in Cancer Survivors: Roles of Telomere Length and Social Determinants of Health.},
journal = {International journal of environmental research and public health},
volume = {21},
number = {12},
pages = {},
doi = {10.3390/ijerph21121694},
pmid = {39767532},
issn = {1660-4601},
support = {no grant number//The Ohio State University Cancer Center, ONF RE03/ ; },
mesh = {Humans ; *Machine Learning ; Male ; Middle Aged ; Female ; *Social Determinants of Health ; *Cancer Survivors/statistics &amp; numerical data ; Aged ; Adult ; Telomere ; Gastrointestinal Diseases ; Nutrition Surveys ; Health Status ; },
abstract = {BACKGROUND: Gastrointestinal (GI) distress is prevalent and often persistent among cancer survivors, impacting their quality of life, nutrition, daily function, and mortality. GI health screening is crucial for preventing and managing this distress. However, accurate classification methods for GI health remain unexplored. We aimed to develop machine learning (ML) models to classify GI health status (better vs. worse) by incorporating biological aging and social determinants of health (SDOH) indicators in cancer survivors.<br><br>METHODS: We included 645 adult cancer survivors from the 1999-2002 NHANES survey. Using training and test datasets, we employed six ML models to classify GI health conditions (better vs. worse). These models incorporated leukocyte telomere length (TL), SDOH, and demographic/clinical data.<br><br>RESULTS: Among the ML models, the random forest (RF) performed the best, achieving a high area under the curve (AUC = 0.98) in the training dataset. The gradient boosting machine (GBM) demonstrated excellent classification performance with a high AUC (0.80) in the test dataset. TL, several socio-economic factors, cancer risk behaviors (including lifestyle choices), and inflammatory markers were associated with GI health. The most significant input features for better GI health in our ML models were longer TL and an annual household income above the poverty level, followed by routine physical activity, low white blood cell counts, and food security.<br><br>CONCLUSIONS: Our findings provide valuable insights into classifying and identifying risk factors related to GI health, including biological aging and SDOH indicators. To enhance model predictability, further longitudinal studies and external clinical validations are necessary.},
}
@article {pmid39766323,
year = {2024},
author = {Yilmaz, M and Goksen, S and Mender, I and Esendagli, G and Erdener, SE and Ahmed, A and Tenekeci, AK and Birichevskaya, LL and Gryaznov, SM and Shay, JW and Dikmen, ZG},
title = {A Phosphatidyl Conjugated Telomerase-Dependent Telomere-Targeting Nucleoside Demonstrates Colorectal Cancer Direct Killing and Immune Signaling.},
journal = {Biomolecules},
volume = {14},
number = {12},
pages = {},
doi = {10.3390/biom14121616},
pmid = {39766323},
issn = {2218-273X},
support = {CA142543,CA070907/GF/NIH HHS/United States ; },
mesh = {Animals ; Humans ; Mice ; Antineoplastic Agents/pharmacology/chemistry ; Cell Line, Tumor ; *Colorectal Neoplasms/drug therapy/pathology/metabolism/genetics ; Nucleosides/pharmacology/chemistry ; Signal Transduction/drug effects ; *Telomerase/antagonists &amp; inhibitors/metabolism ; *Telomere/drug effects/metabolism ; },
abstract = {Telomerase and telomeres are crucial in cancer cell immortalization, making them key targets for anticancer therapies. Currently, 6-thio-dG (THIO) combined with the anti-PD-1 inhibitor Cemiplimab is under phase II clinical investigation (NCT05208944) in NSCLC patients resistant to prior immunotherapies. This study presents the design, synthesis, and evaluation of novel bimodular conjugate molecules combining telomere-targeting nucleoside analogs and phosphatidyl diglyceride groups. Among them, dihexanoyl-phosphatidyl-THIO (diC6-THIO) showed high anticancer activity with sub-µM EC50 values in vitro across various cancer cell lines. In mouse colorectal cancer models, diC6-THIO demonstrated strong anticancer effects alone and in combination with PD1/PD-L1 inhibitors. Administration of this compound resulted in the efficient formation of Telomere dysfunction Induced Foci (TIFs) in vitro, indicating an on-target, telomerase-mediated telomere-modifying mechanism of action for the molecule. Systemic treatment also activated CD4[+] and CD8[+] T cells while reducing regulatory T cells, indicating immune system enhancement. Notably, diC6-THIO exhibits an improved solubility profile while maintaining comparable anticancer properties, further supporting its potential as a promising therapeutic candidate. These findings highlight diC6-THIO as a promising telomere-targeting prodrug with dual effects on telomere modification and immune activation.},
}
@article {pmid39763972,
year = {2024},
author = {Janovič, T and Perez, GI and Schmidt, JC},
title = {TRF1 and TRF2 form distinct shelterin subcomplexes at telomeres.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.12.23.630076},
pmid = {39763972},
issn = {2692-8205},
abstract = {The shelterin complex protects chromosome ends from the DNA damage repair machinery and regulates telomerase access to telomeres. Shelterin is composed of six proteins (TRF1, TRF2, TIN2, TPP1, POT1 and RAP1) that can assemble into various subcomplexes in vitro . However, the stoichiometry of the shelterin complex and its dynamic association with telomeres in cells is poorly defined. To quantitatively analyze the shelterin function in living cells we generated a panel of cancer cell lines expressing HaloTagged shelterin proteins from their endogenous loci. We systematically determined the total cellular abundance and telomeric copy number of each shelterin subunit, demonstrating that the shelterin proteins are present at telomeres in equal numbers. In addition, we used single-molecule live-cell imaging to analyze the dynamics of shelterin protein association with telomeres. Our results demonstrate that TRF1-TIN2-TPP1-POT1 and TRF2-RAP1 form distinct subcomplexes that occupy non-overlapping binding sites on telomeric chromatin. TRF1-TIN2-TPP1-POT1 tightly associates with chromatin, while TRF2-RAP1 binding to telomeres is more dynamic, allowing it to recruit a variety of co-factors to chromatin to protect chromosome ends from DNA repair factors. In total, our work provides critical mechanistic insight into how the shelterin proteins carry out multiple essential functions in telomere maintenance and significantly advances our understanding of macromolecular structure of telomeric chromatin.},
}
@article {pmid39762386,
year = {2025},
author = {Bi, G and Zhao, S and Yao, J and Wang, H and Zhao, M and Sun, Y and Hou, X and Haas, FB and Varshney, D and Prigge, M and Rensing, SA and Jiao, Y and Ma, Y and Yan, J and Dai, J},
title = {Author Correction: Near telomere-to-telomere genome of the model plant Physcomitrium patens.},
journal = {Nature plants},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41477-024-01903-9},
pmid = {39762386},
issn = {2055-0278},
}
@article {pmid39760184,
year = {2025},
author = {Doolittle, BR and Britt, KC and Lekwauwa, R and Sebu, J and Boateng, A},
title = {The association of telomere length and religiosity: A systematic review.},
journal = {Biodemography and social biology},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/19485565.2024.2448946},
pmid = {39760184},
issn = {1948-5573},
abstract = {OBJECTIVE: Religiosity is a complex construct comprised observance, intrinsic beliefs, meditative practice, and communal elements. Religiosity has been associated with reduced mortality and improved overall health, but understanding the underlying biological associations is evolving. As increased telomere length has been associated with increased longevity, this project presents a systematic review of studies investigating the relationship between religiosity and telomere length.<br><br>DESIGN: The study protocol was registered prior to the search. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was followed. Seven databases were employed using relevant criteria: PubMed, PSYCHinfo, CINAHL, ATLA, Scopus, Sociological Abstracts, and the Cochrane Central Register of Controlled Clinical.<br><br>RESULTS: A total of 381 studies were identified and 46 studies met full screening. Eight studies met the final inclusion criteria. Of these eight studies, two showed no relationship between religiosity and telomere length, three showed a positive relationship, and three showed an equivocal or ambivalent relationship. Meta-analysis was not possible due to the heterogeneity of the studies.<br><br>CONCLUSION: Religiosity may be associated with telomere length, but results vary widely across the diverse studies included. Longitudinal studies with adequate sample size are needed to determine this association more rigorously.},
}
@article {pmid39759351,
year = {2024},
author = {Molina-Pinelo, S and Ferrer Sánchez, I and Najarro, P and Paz-Ares, L and Fernández, L and Castelló, N and Richart López, LA and Rodríguez Gambarte, JD and Sanz García, M and Salinas, A and Suárez, R and Romero-Romero, B and Martín-Juan, J and Viñuela, ME and Butler, RG and de Pedro, N},
title = {Telomere-based risk models for the early diagnosis of lung cancer.},
journal = {Heliyon},
volume = {10},
number = {24},
pages = {e41040},
pmid = {39759351},
issn = {2405-8440},
abstract = {BACKGROUND: The objective of this study was to evaluate the use of telomere length measurements as diagnostic biomarkers during early screening for lung cancer in high-risk patients.<br><br>METHODS: This was a prospective study of patients undergoing lung cancer diagnosis at two Spanish hospitals between April 2017 and January 2020. Telomeres from peripheral blood lymphocytes were analysed by Telomere Analysis Technology, which is based in high-throughput quantitative fluorescent in situ hybridization. Analytical predictive models were developed using Random Forest from the dataset of telomere-associated variables (TAV). Receiver Operating Characteristic curves were used to characterize model performance.<br><br>FINDINGS: From 233 patients undergoing lung cancer diagnosis, 106 patients aged 55-75 with lung cancer or lung cancer and COPD were selected. A control group (N&#xa0;=&#xa0;453) included individuals of similar age with COPD or healthy. Telomere analysis showed that patients in the cancer cohort had a higher proportion of short telomeres compared to the control cohort. A TAV-based predictive model assuming a prevalence of 5&#xa0;% of lung cancer among screened subjects showed an AUC of 0.98&#xa0;%, a positive predictive value of 0.60 (95&#xa0;% CI, 0.49-0.70) and a negative predictive value of 0.99 (95&#xa0;% CI, 0.98-0.99) for prediction of lung cancer.<br><br>INTERPRETATION: The results of this study suggest that TAV analysis in peripheral lymphocytes can be considered a useful diagnostic tool during screening for lung cancer in high-risk patients. TAV-based models could improve the predictive power of current initial diagnostic pathways, but further work is needed to integrate them into routine clinical evaluation.<br><br>FUNDING: Life Length SL.},
}
@article {pmid39757226,
year = {2025},
author = {Ye, Z and Huang, Y and Chen, T and Wu, Y},
title = {Comprehensive analysis of telomere and aging-related signature for predicting prognosis and immunotherapy response in lung adenocarcinoma.},
journal = {Journal of cardiothoracic surgery},
volume = {20},
number = {1},
pages = {31},
pmid = {39757226},
issn = {1749-8090},
mesh = {Humans ; *Adenocarcinoma of Lung/genetics/immunology/drug therapy ; *Lung Neoplasms/genetics/drug therapy/immunology ; Prognosis ; *Immunotherapy/methods ; *Telomere/genetics ; Male ; Female ; Aging/genetics/immunology ; Middle Aged ; Nomograms ; Aged ; Biomarkers, Tumor/genetics ; },
abstract = {BACKGROUND: Lung adenocarcinoma (LUAD) is a high-risk malignancy. Telomeres- (TRGs) and aging-related genes (ARGs) play an important role in cancer progression and prognosis. This study aimed to develop a novel prognostic model combined TRGs and ARGs signatures to predict the prognosis of patients with LUAD.<br><br>METHODS: LUAD patient's sample data and clinical data were obtained from public databases. The prognostic model was constructed and evaluated using the least absolute shrinkage and selection operator (LASSO), multivariate Cox analysis, time-dependent receiver operating characteristic (ROC), and Kaplan-Meier (K-M) analysis. Immune cell infiltration levels were assessed using single-sample gene set enrichment analysis (ssGSEA). Antitumor drugs with significant correlations between drug sensitivity and the expression of prognostic genes were identified using the CellMiner database. The distribution and expression levels of prognostic genes in immune cells were subsequently analyzed based on the TISCH database.<br><br>RESULTS: This study identified eight characteristic genes that are significantly associated with LUAD prognosis and could serve as independent prognostic factors, with the low-risk group demonstrating a more favorable outcome. Additionally, a comprehensive nomogram was developed, showing a high degree of prognostic predictive value. The results from ssGSEA indicated that the low-risk group had higher immune cell infiltration. Ultimately, our findings revealed that the high-risk group exhibited heightened sensitivity to the Linsitinib, whereas the low-risk group demonstrated enhanced sensitivity to the OSI-027 drug.<br><br>CONCLUSION: The risk score exhibited robust prognostic capabilities, offering novel insights for assessing immunotherapy. This will provide a new direction to achieve personalized and precise treatment of LUAD in the future.},
}
@article {pmid39755520,
year = {2025},
author = {Catalinas-Muñoz, E and Jiménez-Gómez, M and Díaz-Miravalls, J and Quezada-Loaiza, CA and Pérez-González, VL and De-Pablo-Gafas, A and Alonso-Moralejo, R},
title = {Impact of Telomere Shortening on Post-transplant Outcomes in Interstitial Lung Disease.},
journal = {Transplantation proceedings},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.transproceed.2024.12.004},
pmid = {39755520},
issn = {1873-2623},
abstract = {Shortened telomere length (STL) is associated with increased rates of interstitial lung diseases, malignancy, hematological disorders, and immunosuppressive treatment toxicities. In this single-center retrospective study, we aim to determine whether patients with interstitial lung diseases who have STL, as determined by quantitative PCR of buccal epithelial cells, exhibit worse post-transplant outcomes compared to recipients with normal telomere length. In our series of 26 patients, STL was associated with a higher incidence of chronic kidney disease following lung transplantation (100% vs 55%, P = .042). However, STL was not associated with an increased incidence of acute cellular rejection, infections, cytomegalovirus viremia, cytopenias, elevated liver enzymes, cancer diagnosis, venous thromboembolism, or mortality. Thus, lung transplant recipients with STL are at an increased risk of developing chronic kidney disease during the post-transplant period compared to those with normal telomere length.},
}
@article {pmid39754352,
year = {2025},
author = {Rodriguez, MD and Bay, RA and Ruegg, KC},
title = {Telomere Length Differences Indicate Climate Change-Induced Stress and Population Decline in a Migratory Bird.},
journal = {Molecular ecology},
volume = {},
number = {},
pages = {e17642},
doi = {10.1111/mec.17642},
pmid = {39754352},
issn = {1365-294X},
support = {006784//National Science Foundation Graduate Research Fellowship Program/ ; 62591-443863//National Geographic Society/ ; 1942313//National Science Foundation/ ; },
abstract = {Genomic projections of (mal)adaptation under future climate change, known as genomic offset, faces limited application due to challenges in validating model predictions. Individuals inhabiting regions with high genomic offset are expected to experience increased levels of physiological stress as a result of climate change, but documenting such stress can be challenging in systems where experimental manipulations are not possible. One increasingly common method for documenting physiological costs associated with stress in individuals is to measure the relative length of telomeres-the repetitive regions on the caps of chromosomes that are known to shorten at faster rates in more adverse conditions. Here we combine models of genomic offsets with measures of telomere shortening in a migratory bird, the yellow warbler (Setophaga petechia), and find a strong correlation between genomic offset, telomere length and population decline. While further research is needed to fully understand these links, our results support the idea that birds in regions where climate change is happening faster are experiencing more stress and that such negative effects may help explain the observed population declines.},
}
@article {pmid39750135,
year = {2024},
author = {Crous-Bou, M and Lázaro, I and Nadal-Zaragoza, N and Sala-Vila, A},
title = {Fatty acids and telomere length.},
journal = {Current opinion in clinical nutrition and metabolic care},
volume = {},
number = {},
pages = {},
doi = {10.1097/MCO.0000000000001093},
pmid = {39750135},
issn = {1473-6519},
abstract = {PURPOSE OF REVIEW: This narrative review includes the latest clinical and preclinical evidence on fatty acid exposure and telomere length, a widely accepted hallmark of aging.<br><br>RECENT FINDINGS: A large body of literature focused on n-3 (omega-3) polyunsaturated fatty acids (PUFAs). Observational studies reported beneficial associations with telomere length for self-reported consumption of n-3 PUFA-rich foods; for estimated intake of n-3 PUFAs; and for n-3 PUFAs blood-based biomarkers in most (but not all) studies involving lipidomics, a promising tool in the field. Benefits were also observed in preclinical studies using different mouse models. Regarding other lipids, inconsistent findings were observed for circulating linoleic acid, whereas inverse associations with telomere length were reported for the n-6/n-3 PUFA ratio. Finally, a study using Mendelian randomization reported that monounsaturated fatty acids and PUFAs have a positive effect on telomere length, whereas the opposite was observed for saturated fatty acids.<br><br>SUMMARY: Evidence supporting that n-3 PUFAs might have beneficial effects on maintaining telomere length reinforce the salutary effects of these dietary fats. Approach considering the n-6/n-3 PUFA ratio is discouraged because it is sustained in the incorrect assumption that all species from the n-6 and n-3 families are functionally equivalent.},
}
@article {pmid39747616,
year = {2025},
author = {Djelmis, J and Ivanisevic, M},
title = {Influence of subclinical hypothyroidism and brain-derived neurotropic factor on telomere length dynamics in type 1 diabetic pregnancies and their newborns.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {194},
pmid = {39747616},
issn = {2045-2322},
support = {IP2018-01-1284.//Hrvatska Zaklada za Znanost/ ; },
mesh = {Humans ; Female ; Pregnancy ; *Diabetes Mellitus, Type 1/metabolism/genetics/blood ; *Hypothyroidism/metabolism ; Infant, Newborn ; *Brain-Derived Neurotrophic Factor/genetics/blood ; Adult ; *Telomere/metabolism/genetics ; Prospective Studies ; Fetal Blood/metabolism ; Pregnancy in Diabetics/metabolism ; Thyrotropin/blood ; Male ; Telomere Homeostasis ; Pregnancy Trimester, First ; Telomere Shortening ; },
abstract = {Thyroid dysfunctions are common in type 1 diabetes mellitus (T1DM) pregnancies, impacting embryogenesis and fetal neurodevelopment. This study investigates the effects of subclinical hypothyroidism and BDNF (Brain-derived neurotrophic factor) telomere length in T1DM mothers and their newborns. In a recent study, researchers found an inverse relationship between TSH (thyroid-stimulating hormone) levels and telomere length in the cord blood of newborns. This was prospective cohort analysis of 70 mothers and their newborns with T1DM. The study measured leukocyte telomere length (LTL) in maternal and neonatal samples. Subclinical hypothyroidism during the first trimester was characterized by TSH levels ranging from 2.5 to 5.0 mIU/L alongside normal free thyroxine (FT4) concentrations. In this study, we proved that maternal telomere length predicts telomere length in the newborn. Furthermore, we investigated the influence of maternal hypothyroidism on telomere length in the newborn. Maternal hypothyroidism in the first trimester of pregnancy has a strong influence on the shortening of newborn telomeres. BDNF has a positive effect on maternal and newborn telomere length. These results can have an important impact on the subsequent development of a child born to a diabetic mother. Health and disease associated with telomere length later in life may be programmed at birth.},
}
@article {pmid39747057,
year = {2025},
author = {Theulot, B and Tourancheau, A and Simonin Chavignier, E and Jean, E and Arbona, JM and Audit, B and Hyrien, O and Lacroix, L and Le Tallec, B},
title = {Telomere-to-telomere DNA replication timing profiling using single-molecule sequencing with Nanotiming.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {242},
pmid = {39747057},
issn = {2041-1723},
support = {Allocation doctorale//Minist&#xe8;re de l'Education Nationale, de l'Enseignement Sup&#xe9;rieur et de la Recherche (MENESR)/ ; Allocation doctorale//Minist&#xe8;re de l'Education Nationale, de l'Enseignement Sup&#xe9;rieur et de la Recherche (MENESR)/ ; FRM FDT202106013030//Fondation pour la Recherche M&#xe9;dicale (Foundation for Medical Research in France)/ ; FRM EQU202203014910//Fondation pour la Recherche M&#xe9;dicale (Foundation for Medical Research in France)/ ; NanoPoRep ANR-18-CE45-0002//Agence Nationale de la Recherche (French National Research Agency)/ ; HUDROR ANR-19-CE12-0028//Agence Nationale de la Recherche (French National Research Agency)/ ; NanoPoRep ANR-18-CE45-0002//Agence Nationale de la Recherche (French National Research Agency)/ ; HUDROR ANR-19-CE12-0028//Agence Nationale de la Recherche (French National Research Agency)/ ; },
mesh = {*Telomere/genetics/metabolism ; *Saccharomyces cerevisiae/genetics ; *DNA Replication Timing ; *Telomere-Binding Proteins/metabolism/genetics ; Saccharomyces cerevisiae Proteins/metabolism/genetics ; DNA Replication ; DNA, Fungal/genetics/metabolism ; S Phase/genetics ; Single Molecule Imaging/methods ; Bromodeoxyuridine/metabolism ; Nanopore Sequencing/methods ; Repressor Proteins ; },
abstract = {Current temporal studies of DNA replication are either low-resolution or require complex cell synchronisation and/or sorting procedures. Here we introduce Nanotiming, a single-molecule, nanopore sequencing-based method producing high-resolution, telomere-to-telomere replication timing (RT) profiles of eukaryotic genomes by interrogating changes in intracellular dTTP concentration during S phase through competition with its analogue bromodeoxyuridine triphosphate (BrdUTP) for incorporation into replicating DNA. This solely demands the labelling of asynchronously growing cells with an innocuous dose of BrdU during one doubling time followed by BrdU quantification along nanopore reads. We demonstrate in S. cerevisiae model eukaryote that Nanotiming reproduces RT profiles generated by reference methods both in wild-type and mutant cells inactivated for known RT determinants. Nanotiming is simple, accurate, inexpensive, amenable to large-scale analyses, and has the unique ability to access RT of individual telomeres, revealing that Rif1 iconic telomere regulator selectively delays replication of telomeres associated with specific subtelomeric elements.},
}
@article {pmid39741705,
year = {2024},
author = {Yang, F and Cai, H and Ren, Y and Huang, K and Gao, H and Qin, L and Wang, R and Chen, Y and Zhou, L and Zhou, D and Chen, Q},
title = {Association between telomere length and idiopathic normal pressure hydrocephalus: a Mendelian randomization study.},
journal = {Frontiers in neurology},
volume = {15},
number = {},
pages = {1393825},
pmid = {39741705},
issn = {1664-2295},
abstract = {OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) is highly prevalent among elderly individuals, and there is a strong correlation between telomere length and biological aging. However, there is limited evidence to elucidate the relationship between telomere length and iNPH. This study aimed to investigate the associations between telomere length and iNPH using the Mendelian randomization (MR) method.<br><br>METHODS: The genetic variants of telomere length were obtained from 472,174 UK Biobank individuals. Summary level data of iNPH were acquired from 218,365 individuals of the FinnGen consortium. Five MR estimation methods, including inverse-variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple mode, were used for causal inference. Comprehensive sensitivity analyses were conducted to test the robustness of the results. In addition, multivariable MR was further implemented to identify potential mechanisms in the causal pathway from telomere length to iNPH.<br><br>RESULTS: Genetically determined longer telomere length was significantly associated with decreased risk of iNPH (OR&#x202f;=&#x202f;0.44, 95% CI 0.24-0.80; p&#x202f;=&#x202f;0.008). No evident heterogeneity (Cochran Q&#x202f;=&#x202f;138.11, p&#x202f;=&#x202f;0.386) and pleiotropy (MR Egger intercept&#x202f;=&#x202f;0.01, p&#x202f;=&#x202f;0.514) were observed in the sensitivity analysis. In addition, multivariable MR indicated that the observed association was attenuated after adjustment for several vascular risk factors, including essential hypertension (IVW OR&#x202f;=&#x202f;0.55, 95% CI 0.30-1.03; p&#x202f;=&#x202f;0.061), type 2 diabetes (IVW OR&#x202f;=&#x202f;0.71, 95% CI 0.09-5.39; p&#x202f;=&#x202f;0.740) and coronary artery disease (IVW OR&#x202f;=&#x202f;0.58, 95% CI 0.31-1.07; p&#x202f;=&#x202f;0.082).<br><br>CONCLUSION: Our MR study revealed a strong negative correlation of telomere length with iNPH. The causal relationship might be driven by several vascular risk factors.},
}
@article {pmid39741153,
year = {2024},
author = {Yang, W and Zhou, H and Huang, J and Zhu, W and Hou, H and Li, H and Zhao, L and Zhang, J and Liu, J and Qin, C and Wang, L and Luo, H and Zhu, J and Xiao, F and Yao, J and Yang, C and Meng, H},
title = {Near telomere-to-telomere assembly of the Tarim pigeon (Columba livia) genome.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {1455},
pmid = {39741153},
issn = {2052-4463},
mesh = {*Columbidae/genetics ; Animals ; *Genome ; *Telomere/genetics ; },
abstract = {Pigeons serve as important model animals and commercial poultry. The Tarim pigeon, as a breed of Columba livia, is a locally indigenous breed unique to China. While the genome of C. livia was published in 2013, its assembly was fragmented and incomplete. In this study, we generated a near telomere-to-telomere assembly of the pigeon genome using the sequencing platform of PacBio HiFi, Nanopore long reads and Hi-C. The assembled genome spans 1295.8 Mb, with a contig N50 size of 49 Mb and a scaffold N50 size of 85 Mb. Approximately 98.4% of the assembly is anchored onto 41 chromosomes, with a BUSCO assessment indicating a completeness of 97.2%. And telomeres were identified at both ends of the four chromosomes. A total of 21,450 genes were annotated. The genome assembly of C. livia lays the foundation for understanding their genetic composition and evolutionary history and contributes to the pigeon breeding industry. Additionally, it will provide a basis for further management and conservation of pigeon breed diversity.},
}
@article {pmid39738483,
year = {2024},
author = {Dewulf, M and Pascottini, OB and Heirbaut, S and Meesters, M and Martens, DS and Nawrot, TS and Zhang, M and Jing, XP and Vandaele, L and Fievez, V and Van Eetvelde, M and Opsomer, G},
title = {Shortening of the telomere length during the transition period of dairy cows in relation to biological stress.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {31756},
pmid = {39738483},
issn = {2045-2322},
support = {1SH5N24N//Fonds Wetenschappelijk Onderzoek/ ; 12X9623N//Fonds Wetenschappelijk Onderzoek/ ; LA170830//Agentschap Innoveren en Ondernemen/ ; },
mesh = {Animals ; Cattle ; Female ; *Telomere Shortening ; *Stress, Physiological ; Oxidative Stress ; Milk/metabolism ; Biomarkers/blood ; Telomere/metabolism ; Lactation ; Dairying ; },
abstract = {Telomere length (TL) is a recognized biomarker for ageing in multiple species. In dairy cattle, the transition period is considered a very stressful period. We hypothesized that TL shortens during this period. Holstein cows (n = 61) were followed during the transition period. Blood and milk samples were collected at - 7, 3, 6, 9, 21d relative to calving to determine concentrations of oxidative, energetic metabolic, and inflammatory markers. Average relative leukocyte TL was measured by a modified qPCR protocol 7d before and 21d after parturition. We confirmed TL attrition during the transition period (P = 0.02), as TL was 1.05 ± 0.229 (mean ± SD) before, and 0.97 ± 0.191 (mean ± SD) after parturition. Univariable analyses assessed associations between blood markers and TL shortening. Greater plasma oxidative parameters, including oxidized glutathione and glutathione peroxidase, were positively and negatively (respectively) associated with TL attrition. Higher blood α- and β-globulin were all positively associated, while IGF-1, albumin-globulin ratio and albumin were negatively associated with TL attrition. Greater serum amyloid A and haptoglobin were linked with greater TL shortening. This study reveals significant TL shortening during the transition period in dairy cows and identifies significant associations with oxidative stress, metabolic stress, and inflammation. While these associations are observed, no causality can be established. Our findings suggest the need for further research to explore the effects of transition-related stress on TL dynamics.},
}
@article {pmid39738205,
year = {2024},
author = {Guillen-Parra, M and Lin, J and Prather, AA and Wolkowitz, OM and Picard, M and Epel, ES},
title = {The relationship between mitochondrial health, telomerase activity and longitudinal telomere attrition, considering the role of chronic stress.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {31589},
pmid = {39738205},
issn = {2045-2322},
support = {1R01AG030424-01A2/NH/NIH HHS/United States ; 1R01AG030424-01A2/NH/NIH HHS/United States ; },
mesh = {Humans ; *Telomerase/metabolism ; Female ; *Mitochondria/metabolism ; Longitudinal Studies ; *Leukocytes, Mononuclear/metabolism ; Male ; *Telomere/metabolism ; Adult ; Stress, Psychological/metabolism ; Telomere Shortening ; Child ; Autism Spectrum Disorder/metabolism/genetics ; Telomere Homeostasis ; Middle Aged ; },
abstract = {Telomere attrition is a hallmark of biological aging, contributing to cellular replicative senescence. However, few studies have examined the determinants of telomere attrition in vivo in humans. Mitochondrial Health Index (MHI), a composite marker integrating mitochondrial energy-transformation capacity and content, may be one important mediator of telomere attrition, as it could impact telomerase activity, a direct regulator of telomere maintenance. In this observational longitudinal study, we examined in peripheral blood mononuclear cells (PBMCs), whether MHI predicted changes in telomerase activity over a 9-month period, thus impacting telomere maintenance over this same period of time. We secondarily examined the role of chronic stress, by comparing these relationships in mothers of children with an autism spectrum disorder (caregivers) vs. mothers of a neurotypical child (controls). Here we show that both chronic stress exposure and lower MHI independently predicted decreases in telomerase activity over the subsequent 9 months. Finally, changes in telomere length were directly related with changes in telomerase activity, and indirectly with MHI and chronic stress, as revealed by a path analysis. These results highlight the potential role of chronic stress and MHI as drivers of telomere attrition in human PBMCs, through an impairment of both energy-transformation capacity and telomerase production.},
}
@article {pmid39737735,
year = {2025},
author = {Marasco, V and Boner, W and Griffiths, K and Raveh, S and Monaghan, P},
title = {Hidden Causes of Variation in Offspring Reproductive Value: Negative Effects of Maternal Breeding Age on Offspring Telomere Length Persist Undiminished Across Multiple Generations.},
journal = {Ecology letters},
volume = {28},
number = {1},
pages = {e70043},
doi = {10.1111/ele.70043},
pmid = {39737735},
issn = {1461-0248},
support = {I 6634//Austrian Science Fund/ ; M2520-B29//Austrian Science Fund/ ; 101020037//H2020 European Research Council/ ; 268926//H2020 European Research Council/ ; BB/P009174/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {Animals ; Female ; *Finches/physiology/genetics ; *Reproduction ; *Longevity ; Telomere ; Male ; Telomere Shortening ; Aging ; },
abstract = {Offspring of older breeders frequently show reduced longevity, which has been linked to shorter offspring telomere length. It is currently unknown whether such telomere reduction persists beyond a single generation, as would be the case if germline transmission is involved. In a within-grandmother, multi-generational study using zebra finches, we show that the shorter telomeres observed in F1 offspring of older mothers are still present in the F2 generation even when the breeding age of their F1 mothers is young. The effect was substantial: 43% shorter telomeres in grandoffspring from the 'grandmother old at breeding' line compared with those from the 'grandmother young at breeding' line. Shorter telomeres at fledging in this species are associated with a reduction in lifespan. Our data demonstrate the need to look beyond a single generation to explain inter-individual variation in ageing rates and thereby variation in optimal allocation of age-specific reproductive effort.},
}
@article {pmid39736866,
year = {2024},
author = {Liu, S and Xu, L and Cheng, Y and Liu, D and Zhang, B and Chen, X and Zheng, M},
title = {Decreased telomerase activity and shortened telomere length in infants whose mothers have gestational diabetes mellitus and increased severity of telomere shortening in male infants.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1490336},
pmid = {39736866},
issn = {1664-2392},
mesh = {Humans ; *Diabetes, Gestational/metabolism ; Female ; Pregnancy ; Male ; *Telomerase/metabolism/genetics ; *Telomere Shortening ; Adult ; Infant, Newborn ; *Fetal Blood/metabolism ; *Oxidative Stress ; Telomere/metabolism ; Case-Control Studies ; Blood Glucose/metabolism ; Telomere Homeostasis/physiology ; },
abstract = {OBJECTIVE: Gestational diabetes mellitus (GDM) is a common complication during pregnancy and increases the risk of metabolic diseases in offspring. We hypothesize that the poor intrauterine environment in pregnant women with GDM may lead to chromosomal DNA damage and telomere damage in umbilical cord blood cells, providing evidence of an association between intrauterine programming and increased long-term metabolic disease risk in offspring.<br><br>METHODS: We measured telomere length (TL), serum telomerase (TE) activity, and oxidative stress markers in umbilical cord blood mononuclear cells (CBMCs) from pregnant women with GDM (N=200) and healthy controls (Ctrls) (N=200) and analysed the associations of TL with demographic characteristics, biochemical indicators, and blood glucose levels.<br><br>RESULTS: The length of telomeres in umbilical CBMCs in the GDM group was significantly shorter than that in the Ctrl group (P<0.001), and the shortening of telomeres in male infants in the GDM group was more significant than that in the Ctrl group (P<0.001) after adjustment for Pre-pregnancy body mass index (PBMI), Pregnancy weight gain (PGW), and Triglyceride (TG) as confounding factors. In addition, the TE expression level in the GDM group was lower after adjustment. There was no statistically significant difference in oxidative stress hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA) and superoxide dismutase (SOD) between the two groups. TL was positively correlated with TE activity, and both were negatively correlated with blood glucose levels. There was no correlation between TL and Gestational age (GA), PBMI, PGW, or TG levels.<br><br>CONCLUSION: The poor intrauterine environment in pregnant women with GDM increases telomere attrition and reduces TE activity, which may be potential genetic risk factors for an increased risk of metabolic diseases in offspring later in life due to intrauterine reprogramming.},
}
@article {pmid39735642,
year = {2024},
author = {Yi, J and Guo, H and Jiang, C and Duan, J and Xue, J and Zhao, Y and He, W and Xia, L},
title = {Leukocyte telomere length decreased the risk of mortality in patients with alcohol-associated liver disease.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1462591},
pmid = {39735642},
issn = {1664-2392},
mesh = {Humans ; Male ; Female ; Middle Aged ; *Leukocytes/metabolism/pathology ; *Liver Diseases, Alcoholic/mortality ; *Telomere ; Adult ; Nutrition Surveys ; Prognosis ; Telomere Homeostasis ; Aged ; Risk Factors ; Cardiovascular Diseases/mortality ; },
abstract = {BACKGROUND: It is necessary to find latent indicators to predict the survival of alcohol-associated liver disease (ALD) patients. Leukocyte telomere length (LTL) was regarded as an indicator of prognosis in several diseases. However, the relationships between LTL and survival as well as cause-specific mortality in ALD patients were still unknown.<br><br>OBJECTIVE: This study aimed at exploring the underlying link between LTL and the risk of mortality in patients with ALD.<br><br>METHODS: The LTL and survival data were gathered from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. The connection between LTL and mortality was assessed by Cox regression models and stratified analyses. The non-linear relationship was explored by restricted cubic spline (RCS) analysis. Sensitivity analyses were used to evaluate the robustness of our findings.<br><br>RESULTS: LTL was a negative factor for all-cause mortality (all p-value < 0.05). The risk of cardiovascular disease (CVD)-related death was decreased in Q3 (p < 0.001) and Q4 levels of LTL (p < 0.001) compared with the Q1 group. Shorter LTL resulted in higher cancer-caused mortality (p = 0.03) in the Q2 group. Longer LTL improved survival especially for elder patients (p for trend < 0.001) or men (p for trend = 0.001). Moreover, there were L-shaped correlations between LTL and all-cause mortality (p for non-linearity = 0.02), as well as cancer-related mortality (p for non-linearity < 0.001). Four sensitivity analyses proved the robustness of our findings.<br><br>CONCLUSION: Our research found that longer LTL improved survival in patients with ALD and decreased CVD and cancer-related mortality. LTL decreased all-cause mortality especially for patients older than 65 years or men. LTL might be a useful biomarker for prognosis among patients with ALD. More prospective studies are needed to assess the relevance between LTL and mortality and explore the underlying mechanisms between them.},
}
@article {pmid39735175,
year = {2025},
author = {Fernández Alonso, AM and Varikasuvu, SR and Pérez-López, FR},
title = {Telomere length and telomerase activity in men and non-pregnant women with and without metabolic syndrome: a systematic review and bootstrapped meta-analysis.},
journal = {Journal of diabetes and metabolic disorders},
volume = {24},
number = {1},
pages = {24},
pmid = {39735175},
issn = {2251-6581},
abstract = {PURPOSE: We performed a systematic review and meta-analysis to examine the associations between telomere length and telomerase activity in subjects with and without metabolic syndrome (MetS).<br><br>METHODS: The meta-analysis protocol was registered in the PROSPERO database. The PubMed, Embase, Cochrane Library, and LILACS databases were searched for studies reporting telomere length or telomerase activity in adult men and non-pregnant women with and without MetS. The risk of bias was assessed with the Newcastle-Ottawa Scale. Random effects and inverse variance methods were used to meta-analyze associations. We conducted a bootstrapped analysis to test the accuracy of clinical results.<br><br>RESULTS: Five studies reported telomere length and two studies telomerase activity. There was no significant difference in telomere length (standardized mean difference [SMD]: 0.10, 95% confidence interval [CI]: -0.07, 0.28, I [2]: 54%), between subjects of similar age (mean difference: 2.68, 95%CI: -0.04, 5.40 years) with and without the MetS. Subjects with MetS displayed significantly higher body mass index, triglycerides, and blood pressure, and lower HDL-cholesterol values than subjects without the syndrome. A bootstrapping mediation analysis of telomere length confirmed the clinical results. There was no significant difference in telomerase activity (SMD: 1.19, 95% CI -0.17, 2.55, I [2]: 93%) between subjects with and without the MetS.<br><br>CONCLUSION: There were no significant differences of telomere length and telomerase activity in patients with MetS and subjects of similar age without the syndrome.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-024-01513-4.},
}
@article {pmid39735156,
year = {2024},
author = {Giridharan, S},
title = {Yoga and Telomeres: A Path to Cellular Longevity?.},
journal = {Cureus},
volume = {16},
number = {11},
pages = {e74552},
pmid = {39735156},
issn = {2168-8184},
abstract = {Telomeres, which protect the chromosomal ends, are vital for cellular senescence and health. Telomere shortening, often due to stress, inflammation, and oxidative damage, is linked to age-related diseases such as cancer, cardiovascular issues, and neurodegeneration. Evidence suggests that meditation may affect telomere dynamics by reducing stress and inflammation and improving emotional regulation. Clinical trials have demonstrated that the effectiveness of these practices in increasing telomerase activity and maintaining telomere length varies by type, intensity, and duration of the practice. Yoga and meditation boost cellular resilience by lowering stress, inflammation, and oxidative damage and enhancing neuroendocrine regulation. Despite promising results, study design variability and limited long-term data require further research. Future studies should identify the most effective components, dose-response relationships, and long-term effects across populations. Increasing evidence suggests that yoga and meditation could be key preventive and therapeutic strategies to improve cellular health and longevity.},
}
@article {pmid39730524,
year = {2024},
author = {Inui, T and Kawamura, N and Yamamura, M and Kubo, K and Yamakage, H and Satoh-Asahara, N and Ogawa, Y and Katsuura, G},
title = {Oral intake of degalactosylated whey protein increases peripheral blood telomere length in young and aged mice.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {30859},
pmid = {39730524},
issn = {2045-2322},
mesh = {Animals ; *Whey Proteins/administration &amp; dosage ; *Telomerase/genetics/metabolism ; Mice ; *Telomere/metabolism/genetics ; Administration, Oral ; *Aging ; Male ; Telomere Homeostasis/drug effects ; RNA, Messenger/genetics/metabolism ; RNA/metabolism/genetics ; },
abstract = {In order to elucidate novel actions of degalactosylated whey protein (D-WP) in comparison with intact whey protein (WP), the effects of oral intake of D-WP on peripheral blood telomere length and telomerase were examined in young and aged mice. In young mice, peripheral blood telomere length was significantly elongated following oral intake of D-WP for 4 weeks. mRNA expression of both telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) was significantly increased in the peripheral blood following oral intake of D-WP for 4 weeks. In aged mice, peripheral blood telomere length was significantly decreased as compared with that of young mice, and significantly restored to the level of young mice drinking water by the oral intake of D-WP for 4 weeks. The mRNA expression of peripheral blood TERT and TERC mRNA in aged mice significantly decreased as compared with the level in young mice drinking water, and was significantly restored to the level of expression of young mice drinking water by oral intake of D-WP for 4 weeks. These results suggest that D-WP, but not WP, potently increases peripheral blood telomere length accompanied by increased mRNA expression of TERT and TERC in both young and aged mice.},
}
@article {pmid39728924,
year = {2024},
author = {Mukherjee, AK and Dutta, S and Singh, A and Sharma, S and Roy, SS and Sengupta, A and Chatterjee, M and Vinayagamurthy, S and Bagri, S and Khanna, D and Verma, M and Soni, D and Budharaja, A and Bhisade, SK and Anand, V and Perwez, A and George, N and Faruq, M and Gupta, I and Sabarinathan, R and Chowdhury, S},
title = {Telomere length sensitive regulation of interleukin receptor 1 type 1 (IL1R1) by the shelterin protein TRF2 modulates immune signalling in the tumour microenvironment.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
pmid = {39728924},
issn = {2050-084X},
support = {IA/S/18/2/504021//Wellcome Trust DBt India Alliance/ ; },
mesh = {Humans ; *Tumor Microenvironment ; *Signal Transduction ; *Telomeric Repeat Binding Protein 2/metabolism/genetics ; Animals ; *Telomere/metabolism ; Cell Line, Tumor ; Mice ; Female ; Triple Negative Breast Neoplasms/genetics/immunology/metabolism/pathology ; Gene Expression Regulation, Neoplastic ; Promoter Regions, Genetic ; Receptors, Interleukin-1 Type I ; },
abstract = {Telomeres are crucial for cancer progression. Immune signalling in the tumour microenvironment has been shown to be very important in cancer prognosis. However, the mechanisms by which telomeres might affect tumour immune response remain poorly understood. Here, we observed that interleukin-1 signalling is telomere-length dependent in cancer cells. Mechanistically, non-telomeric TRF2 (telomeric repeat binding factor 2) binding at the IL-1-receptor type-1 (IL1R1) promoter was found to be affected by telomere length. Enhanced TRF2 binding at the IL1R1 promoter in cells with short telomeres directly recruited the histone-acetyl-transferase (HAT) p300, and consequent H3K27 acetylation activated IL1R1. This altered NF-kappa B signalling and affected downstream cytokines like IL6, IL8, and TNF. Further, IL1R1 expression was telomere-sensitive in triple-negative breast cancer (TNBC) clinical samples. Infiltration of tumour-associated macrophages (TAM) was also sensitive to the length of tumour cell telomeres and highly correlated with IL1R1 expression. The use of both IL1 Receptor antagonist (IL1RA) and IL1R1 targeting ligands could abrogate M2 macrophage infiltration in TNBC tumour organoids. In summary, using TNBC cancer tissue (>90 patients), tumour-derived organoids, cancer cells, and xenograft tumours with either long or short telomeres, we uncovered a heretofore undeciphered function of telomeres in modulating IL1 signalling and tumour immunity.},
}
@article {pmid39726249,
year = {2024},
author = {Li, X and Hu, D and Zhang, M and Wang, W},
title = {Human telomere length detected by quantitative fluorescent in situ hybridization: overlooked importance and application.},
journal = {Critical reviews in clinical laboratory sciences},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/10408363.2024.2441733},
pmid = {39726249},
issn = {1549-781X},
abstract = {The technique of Quantitative Fluorescence in Situ Hybridization (Q-FISH) plays a crucial role in determining the length of telomeres for studies in molecular biology and cytogenetics. Throughout the years, the use of Q-FISH for measuring telomere length has made substantial contributions to research in aging, cancer, and stem cells. The objective of this analysis is to delineate the categorization, fundamental concepts, pros and cons, and safety measures of Q-FISH in telomere length analysis, encapsulate, and anticipate its principal uses across diverse human biomedical research fields.},
}
@article {pmid39724986,
year = {2024},
author = {Wang, X and Gao, Z and Liu, Y and Wang, P and Fang, X and Sun, M and Ma, K and Wang, B and Han, W},
title = {Design and synthesis of novel structures with anti-tumor effects: Targeting telomere G-quadruplex and hTERT.},
journal = {Bioorganic &amp; medicinal chemistry letters},
volume = {},
number = {},
pages = {130083},
doi = {10.1016/j.bmcl.2024.130083},
pmid = {39724986},
issn = {1464-3405},
abstract = {The telomeric G-quadruplex (G4) along with the telomerase catalytic subunit hTERT are crucial in the extension of telomeres. Tumor cells can establish replicative immortality by activating the telomere-maintenance mechanism (TMM).Small molecule ligands can limit cancer telomere lengthening by by targeting at G4 and hTERT. The 144 structures were designed by summarising the common structure-activity relationship of G4 stabilisers and hTERT inhibitors.Molecular docking and mtQSAR activity prediction experiments finally identified a16 and a35 as the optimal structures. Subsequently their derivative compounds b1-b6 were synthesised,with b4 exhibiting the most pronounced inhibitory effect on tumour cells. The ability of b4 to distinguish single-stranded DNA, double-stranded DNA and telomere G4 was verified by fluorescence experiment, and the stable combination of b4 and hTERT was verified by molecular dynamics simulation. This suggests that the structural design of targeting G4 and hTERT is reasonable and has anti-tumor potential.},
}
@article {pmid39719503,
year = {2024},
author = {Xue, CC and Nusinovici, S and Yu, M and Chee, ML and Teo, K and Su, X and Cheung, CMG and Sabanayagam, C and Cheng, CY and Tham, YC},
title = {Associations between shorter leucocyte telomere length and increased risk of age-related macular degeneration in women: insights from the United Kingdom Biobank study.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {39719503},
issn = {1476-5454},
support = {NMRC/LCG/004/2018; NMRC/MOH/ HCSAINV21nov-0001//Ministry of Health -Singapore (MOH)/ ; },
abstract = {OBJECTIVES: To determine the association between telomere length (TL) and age-related macular degeneration (AMD) and examine the potential variations with sex and ethnicity.<br><br>METHODS: Population-based, cross-sectional study. A total of 52,083 participants from the UK Biobank were included. Leucocyte TL, measured using quantitative polymerase chain reaction assay, was presented as the ratio of telomere repeat copy number relative to that of a single copy gene, and then log-transformed and Z-standardised. AMD cases were identified based on a combination of in-patient, self-reported and primary care data, and furtherly classified as early, intermediate and late AMD using the Beckmann classification system (based on more severe eye).<br><br>RESULTS: Among the 52,083 participants aged 60.2&#x2009;&#xb1;&#x2009;5.4 years, 725 were any-AMD cases. AMD patients had shorter TL than those without AMD (-0.22&#x2009;&#xb1;&#x2009;0.95 vs. -0.10&#x2009;&#xb1;&#x2009;0.99, P&#x2009;=&#x2009;0.001). In multivariable model, shorter TL (per standard deviation) was significantly associated with higher odds of AMD in Whites (OR:1.09; 95% CI: 1.01-1.18; P&#x2009;=&#x2009;0.036). When stratified by sex and ethnicity, this association was only significant in White women (OR:1.14; 95%CI: 1.02, 1.27; P&#x2009;=&#x2009;0.018), but not in men and nonwhite populations (all P&#x2009;&#x2265;&#x2009;0.335). Among white women, the association was more pronounced (OR:1.47; 95%CI:1.23-1.77; P&#x2009;<&#x2009;0.001) for intermediate/late AMD but not for early AMD (P&#x2009;=&#x2009;0.789).<br><br>CONCLUSIONS: Shorter TL was associated with any AMD in white women but not in men and other ethnicities. Our findings highlight the potential role of telomere length in the pathogenesis of AMD and the importance of considering sex and ethnicity variation in this research area.},
}
@article {pmid39719362,
year = {2024},
author = {Mohamed, HABE and Agus, HH and Palabiyik, B},
title = {A novel method for telomere length detection in fission yeast.},
journal = {FEMS yeast research},
volume = {},
number = {},
pages = {},
doi = {10.1093/femsyr/foae040},
pmid = {39719362},
issn = {1567-1364},
abstract = {Fission yeast is the ideal model organism for studying telomere maintenance in higher eukaryotes. Telomere length has been directly correlated with life expectancy and the onset of aging-related diseases in mammals. In this study, we developed a novel simple, and reproducible method to measure the telomere length, by investigating the effect of Caffeine and Cisplatin on the telomere length in fission yeast. Hydroxyurea synchronized fission yeast cells were exposed to 62 μM Cisplatin and 8.67 mM Caffeine treatments for 2 hours then their telomere lengths were evaluated with two different methods. first: the quantitative PCR assay was used as a confirmative method where telomere length was determined relative to a single copy gene in the genome. Second: the newly developed method standard PCR/ImageJ assay assessed the telomere length based on the amplified PCR band intensity using a set of telomere primers, reflecting telomeric sequence availability in the genome. Both methods show a significant decrease and a notable telomere lengthening in response to Cisplatin and Caffeine treatments respectively. The finding supports the accuracy and productivity of the standard PCR/ImageJ assay as it can serve as a quick screening tool to study the effect of suspected chemotherapeutic and anti-aging drugs on telomere length in fission yeast.},
}
@article {pmid39718587,
year = {2024},
author = {Spinou, M and Naska, A and Nelson, CP and Codd, V and Samani, NJ and Bountziouka, V},
title = {Correction: Micronutrient intake and telomere length: findings from the UK Biobank.},
journal = {European journal of nutrition},
volume = {64},
number = {1},
pages = {53},
doi = {10.1007/s00394-024-03543-3},
pmid = {39718587},
issn = {1436-6215},
}
@article {pmid39715566,
year = {2024},
author = {Mony, V and Subramanian, S and Kanchibhotla, D},
title = {Sudarshan Kriya Yoga Promotes Telomere Elongation: A Pilot Study.},
journal = {Alternative therapies in health and medicine},
volume = {},
number = {},
pages = {},
pmid = {39715566},
issn = {1078-6791},
abstract = {BACKGROUND: Telomere length has been identified as a marker for biological aging and stressful body states. Mind-body interventions for stress reduction such as meditation, yoga, and pranayama have been previously tested to evaluate their efficacy in restricting telomere shortening.<br><br>PRIMARY STUDY OBJECTIVE: In this study, the effect of Sudarshan Kriya Yoga (SKY) is investigated for its influence on telomere length.<br><br>METHODS: Isolating the genomic DNA from the blood, relative telomere length was found using a quantitative PCR method for the SKY intervention group and a control group. Telomere maintenance gene expression was assessed from a microarray gene expression dataset.<br><br>SETTING: Sri Sri Institute for Advanced Research, Bangalore.<br><br>PARTICIPANTS: Employees, working at a corporate organization were the participants of this study. 11 individuals were enrolled in the intervention group while 5 were enrolled in the control group.<br><br>INTERVENTION: The integrated yoga-meditation practice, Sudarshan Kriya Yoga (SKY).<br><br>PRIMARY OUTCOME MEASURES: The relative telomere length and the expression of telomere maintenance genes from the genomic DNA isolated from the participants' blood samples.<br><br>RESULTS: Telomere length after SKY increased significantly compared to the baseline. However, in the controls, the corresponding change was insignificant. The telomere maintenance gene expression analysis reveals an intervention response conducive to telomere length extension at the molecular level.<br><br>CONCLUSION: The extension of telomere length after SKY underscores its efficacy in stress reduction and improved health-span.},
}
@article {pmid39713403,
year = {2024},
author = {Smeds, L and Kamali, K and Kejnovská, I and Kejnovský, E and Chiaromonte, F and Makova, KD},
title = {Non-canonical DNA in human and other ape telomere-to-telomere genomes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.09.02.610891},
pmid = {39713403},
issn = {2692-8205},
abstract = {Non-canonical (non-B) DNA structures-e.g., bent DNA, hairpins, G-quadruplexes, Z-DNA, etc.-which form at certain sequence motifs (e.g., A-phased repeats, inverted repeats, etc.), have emerged as important regulators of cellular processes and drivers of genome evolution. Yet, they have been understudied due to their repetitive nature and potentially inaccurate sequences generated with short-read technologies. Here we comprehensively characterize such motifs in the long-read telomere-to-telomere (T2T) genomes of human, bonobo, chimpanzee, gorilla, Bornean orangutan, Sumatran orangutan, and siamang. Non-B DNA motifs are enriched at the genomic regions added to T2T assemblies, and occupy 9-15%, 9-11%, and 12-38% of autosomes, and chromosomes X and Y, respectively. Functional regions (e.g., promoters and enhancers) and repetitive sequences are enriched in non-B DNA motifs. Non-B DNA motifs concentrate at short arms of acrocentric chromosomes in a pattern reflecting their satellite repeat content and might contribute to satellite dynamics in these regions. Most centromeres and/or their flanking regions are enriched in at least one non-B DNA motif type, consistent with a potential role of non-B structures in determining centromeres. Our results highlight the uneven distribution of predicted non-B DNA structures across ape genomes and suggest their novel functions in previously inaccessible genomic regions.},
}
@article {pmid39709617,
year = {2024},
author = {Helmstetter, N and Harrison, K and Gregory, J and Harrison, J and Ballou, E and Farrer, RA},
title = {A near-complete telomere-to-telomere genome assembly for Batrachochytrium dendrobatidis GPL JEL423 reveals a larger CBM18 gene family and a smaller M36 metalloprotease gene family than previously recognised.},
journal = {G3 (Bethesda, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1093/g3journal/jkae304},
pmid = {39709617},
issn = {2160-1836},
abstract = {Batrachochytrium dendrobatidis (Bd) is responsible for mass extinctions and extirpations of amphibians, mainly driven by the Global Panzootic Lineage (BdGPL). BdGPL isolate JEL423 is a commonly used reference strain in studies exploring the evolution, epidemiology and pathogenicity of chytrid pathogens. These studies have been hampered by the fragmented, erroneous and incomplete B. dendrobatidis JEL423 genome assembly, which includes long stretches of ambiguous positions, and poorly resolved telomeric regions. Here we present and describe a substantially improved, near telomere-to-telomere genome assembly and gene annotation for B. dendrobatidis JEL423. Our new assembly is 24.5 Mb in length, ∼800 kb longer than the previously published assembly for this organism, comprising 18 nuclear scaffolds and 2 mitochondrial scaffolds and including an extra 839 kb of repetitive sequence. We discovered that the patterns of aneuploidy in B. dendrobatidis JEL423 have remained stable over approximately 5 years. We found that our updated assembly encodes fewer than half the number of M36 metalloprotease genes predicted in the previous assembly. In contrast, members of the crinkling and necrosis gene family were found in similar numbers to the previous assembly. We also identified a more extensive carbohydrate binding module 18 gene family than previously observed. We anticipate our findings, and the updated genome assembly will be a useful tool for further investigation of the genome evolution of the pathogenic chytrids.},
}
@article {pmid39707531,
year = {2024},
author = {Lehodey, A and Kaliman, P and Palix, C and de Florès, R and Touron, E and Turpin, AL and Fauvel, S and Mézenge, F and Landeau, B and Chocat, A and Vrillon, A and Paquet, C and Vivien, D and de La Sayette, V and Chételat, G and Poisnel, G and , },
title = {Association of critically short telomeres with brain and blood markers of ageing and Alzheimer's disease in older adults.},
journal = {Alzheimer's research &amp; therapy},
volume = {16},
number = {1},
pages = {269},
pmid = {39707531},
issn = {1758-9193},
mesh = {Humans ; Male ; Aged ; Female ; *Alzheimer Disease/blood/genetics/diagnostic imaging ; Cross-Sectional Studies ; *Aging/genetics/blood ; *Brain/diagnostic imaging/pathology/metabolism ; *Biomarkers/blood ; *Telomere Shortening/physiology ; Aged, 80 and over ; Apolipoprotein E4/genetics ; Neurofilament Proteins/blood ; },
abstract = {BACKGROUND: Accumulation of critically short telomeres (CST) is implicated in decreased tissular regenerative capacity and increased susceptibility to degenerative diseases such as Alzheimer's disease (AD). Telomere shortening has also been associated with age-related brain changes. However, it remains unclear whether CST accumulation is directly associated with AD markers or instead amplifies age-related effects, potentially increasing susceptibility of developing AD in cognitively healthy older adults.<br><br>METHODS: This cross-sectional study used baseline data of 129 community-dwelling cognitively healthy older adults from the Age-Well trial (NCT02977819), aged 65&#xa0;years and older enrolled between 2016 and 2018, in France. Using linear regressions, we analyzed the relationship between an innovative marker of telomere shortening, the percentage of CST (%CST), structural, functional and molecular neuroimaging outcomes, and multiple blood-based biomarkers related to AD pathophysiology. The effect of apolipoprotein E &#x3b5;4 genotype (APOE4) was assessed on these relationships using interaction analysis.<br><br>RESULTS: A higher %CST was associated with lower global kurtosis fractional anisotropy (&#x3b2;&#x2009;=&#x2009;-.230; P&#x2009;=&#x2009;.010), particularly in frontal and temporal regions. A higher %CST was also related to higher plasma levels of Neurofilament light chain (&#x3b2;&#x2009;=&#x2009;.195; P&#x2009;=&#x2009;.020) and a lower subiculum volume (&#x3b2;&#x2009;=&#x2009;-.206; P&#x2009;=&#x2009;.020), although these associations did not meet the threshold for multiple comparisons. %CST was not associated with AD-related neuroimaging markers, including the AD-sensitive gray matter pattern (&#x3b2;&#x2009;=&#x2009;-.060; P&#x2009;=&#x2009;.441), glucose metabolism pattern (&#x3b2;&#x2009;=&#x2009;-.099; P&#x2009;=&#x2009;.372), brain perfusion pattern (&#x3b2;&#x2009;=&#x2009;-.106; P&#x2009;=&#x2009;.694) or hippocampus volume (&#x3b2;&#x2009;=&#x2009;-.106; P&#x2009;=&#x2009;.194). In APOE4 carriers, higher %CST was associated with lower subiculum (&#x3b2;&#x2009;=&#x2009;-.423; P&#x2009;=&#x2009;0.003), DG (&#x3b2;&#x2009;=&#x2009;-.410; P&#x2009;=&#x2009;0.018) and CA1 volumes (&#x3b2;&#x2009;=&#x2009;-.373; P&#x2009;=&#x2009;0.024), even though associations with DG and CA1 volumes did not survive multiple comparison.<br><br>CONCLUSIONS: Although an increase in %CST does not appear to be directly linked to the pathophysiology of AD in cognitively healthy older adults, it could heighten the susceptibility of APOE4 carriers to develop AD plausibly due to greater vulnerability to age-related effects. However, longitudinal studies would be necessary to determine whether %CST influences the development and progression of AD later in life.},
}
@article {pmid39704849,
year = {2024},
author = {Alwehaidah, MS and Al-Awadhi, R and AlRoomy, M and Baqer, TA},
title = {Impact of telomere length for risk assessment and prognosis in papillary thyroid cancer depending on the clinicopathological features.},
journal = {Molecular genetics and genomics : MGG},
volume = {300},
number = {1},
pages = {2},
pmid = {39704849},
issn = {1617-4623},
mesh = {Humans ; Female ; Male ; *Thyroid Cancer, Papillary/genetics/pathology/mortality ; Middle Aged ; Prognosis ; *Thyroid Neoplasms/genetics/pathology ; *Telomere/genetics ; Adult ; Risk Assessment/methods ; Aged ; Case-Control Studies ; Kaplan-Meier Estimate ; Telomere Homeostasis/genetics ; },
abstract = {OBJECTIVE: . Despite the establishment of a link between telomere status and carcinogenesis, lack of a consensus in the cancer specific pattern of telomere length has a severe impact on the use of relative telomere length (RTL) in cancer diagnosis. The disparity in assessing the relationship between telomere length and cancer risk is complex and may vary as it is influenced by other factors. The objective of this study is to thoroughly examine the intricate relationship between telomere length and cancer incidence in Papillary Thyroid Cancer (PTC) depending on the tumor type, stage, patients' sex and age. Therefore, the current study is focused on the association of RTL in PTC patients with different clinicopathological characteristics and compared with controls to determine the risk of PTC and expected survival time after surgery.<br><br>METHOD: . This study included 126 patients with PTC and 80 controls. RTL in thyroid tissues was measured using quantitative (q) PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. Kaplan-Meier and Cox regression were used to analyze postsurgical outcomes.<br><br>RESULT: . The RTL of patients was significantly shorter than that of controls. A short RTL was significantly correlated with an elevated risk of PTC in patients aged&#x2009;&#x2265;&#x2009;55 years, female sex, classic subtype, and tumor size&#x2009;>&#x2009;2&#xa0;cm. A short RTL did not affect the overall survival of patients with PTC; however, it was associated with poor survival in patients with tumor size&#x2009;>&#x2009;2&#xa0;cm and tumor invasion.<br><br>CONCLUSION: . This unique study combines the use of RTL with various clinicopathological features of patients with PTC. In conclusion, RTL is a promising tumor marker that correlates with the clinical characteristics of patients with PTC. Specifically, RTL&#x2009;<&#x2009;0.6 could be used with age, sex, tumor size&#x2009;>&#x2009;2&#xa0;cm and tumor invasion to predict the risk of PTC development and prognosis of the disease. This study will open new horizon in the use of molecular marker such as RTL for understanding its association with increased cancer risk in patients with different clinicopathological features.},
}
@article {pmid39701464,
year = {2024},
author = {Zhang, B and Yuan, F and Zhang, L and Xia, L and Zhu, X and Lu, S and Wang, L and He, Z},
title = {From potential biomarker to clinical predictive models: Integrating socioeconomic status and sleep into leukocyte telomere length of depression and anxiety research.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jad.2024.12.063},
pmid = {39701464},
issn = {1573-2517},
}
@article {pmid39697975,
year = {2024},
author = {Guillen-Parra, M and Barcenas-Flores, R and Velando, A and Wiley, A and Montoya, B and Torres, R},
title = {Sex-Specific Variation in Foraging Behavior is Related to Telomere Length in a Long-Lived Seabird.},
journal = {Ecology and evolution},
volume = {14},
number = {12},
pages = {e70732},
pmid = {39697975},
issn = {2045-7758},
abstract = {Foraging during breeding is a demanding activity linked to breeding investment and possibly constrained by individual quality. Telomere length, the protective nucleoproteins located at the ends of the chromosomes, is considered a trait reflecting somatic maintenance and individual quality. Therefore, foraging effort and parental investment may be positively related to telomere length, if individuals with longer telomeres are of better quality and thus able to maintain better body condition and allocate more resources to parental activities. In the brown booby (Sula leucogaster), we investigated if telomere length is related to body mass (a proxy of condition) and whether variation in foraging behavior and provisioning effort is related to telomere length or body mass. Then, we explored whether variation in foraging and provisioning influences the chick mass growth rate. In 34 pairs nesting in Isla de San Jorge, in the Gulf of California, México, we sampled their blood to estimate telomere length, measured their body mass, and for 10 days, recorded their foraging behavior via global positioning system (GPS) loggers and their chick provisioning rate and chicks' mass growth rate. We found a positive relationship between parents' body mass and telomere length. Body mass did not affect foraging behavior. Females with longer telomeres were more prone to travel longer distances toward offshore and deeper waters than females with shorter telomeres. In contrast, males with longer telomere lengths performed more nearshore foraging trips than males with shorter telomeres. The chick provisioning rate was unrelated to telomere length or body mass, but females fed the chick at a rate 2.4 times greater than males. Females' offshore foraging, but not males', was positively related to chick mass growth rate. Our results suggest that individual quality, indicated by telomere length, is an important driver of sex-specific, between-individual variation in foraging behavior, indirectly affecting offspring condition.},
}
@article {pmid39695676,
year = {2024},
author = {Skåra, KH and Lee, Y and Jugessur, A and Gjessing, HK and Aviv, A and Brumpton, B and Næss, &#xd8; and Hernáez, &#xc1; and Hanevik, HI and Magnus, P and Magnus, MC},
title = {Telomere length in relation to fecundability and use of assisted reproductive technologies: the Norwegian Mother, Father, and Child Cohort Study.},
journal = {BMC medicine},
volume = {22},
number = {1},
pages = {580},
pmid = {39695676},
issn = {1741-7015},
support = {947684//HORIZON EUROPE European Research Council/ ; 947684//HORIZON EUROPE European Research Council/ ; 947684//HORIZON EUROPE European Research Council/ ; 320656//Norges Forskningsr&#xe5;d/ ; 320656//Norges Forskningsr&#xe5;d/ ; 320656//Norges Forskningsr&#xe5;d/ ; 320656//Norges Forskningsr&#xe5;d/ ; 320656//Norges Forskningsr&#xe5;d/ ; 320656//Norges Forskningsr&#xe5;d/ ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; 101071773/ERC_/European Research Council/International ; R01 1HL134840-01/NH/NIH HHS/United States ; },
mesh = {Humans ; Female ; Norway ; Male ; *Reproductive Techniques, Assisted ; *Fertility/genetics ; Adult ; Cohort Studies ; *Telomere/genetics ; Infertility/genetics ; },
abstract = {BACKGROUND: Telomere length (TL) has been reported to be associated with conditions such as endometriosis and polycystic ovary syndrome, with some studies finding associations with shorter TL and others with longer TL. In men, studies mostly report associations between shorter TL and sperm quality. To our knowledge, no studies have thus far investigated associations between TL and fecundability or the use of assisted reproductive technologies (ART).<br><br>METHODS: This study is based on the Norwegian Mother, Father, and Child Cohort (MoBa) Study and uses data from the Medical Birth Registry of Norway (MBRN). We included women (24,645 with genotype data and 1054 with TL measurements) and men (18,339 with genotype data and 965 with TL measurements) participating between 1998 and 2008. We investigated associations between leukocyte TL (LTL) and fecundability (defined as the probability to conceive within a given menstrual cycle), infertility (defined has having spent 12 months or more trying to conceive without success), and ART use. We also repeated the analyses using instrumental variables for LTL consisting of genetic risk scores for LTL and genetically predicted LTL.<br><br>RESULTS: Approximately 11% of couples had experienced infertility and 4% had used ART. LTL was not associated with fecundability in women (fecundability ratio [FR], 0.98; 95% confidence interval [CI], 0.92-1.04) or men (FR, 0.99; CI, 0.93-1.06), nor with infertility in women (odds ratio [OR], 1.03; CI, 0.85-1.24) or men (OR, 1.05; CI, 0.87-1.28). We observed an increased likelihood of using ART with increasing LTL in men (OR, 1.22; CI, 1.03-1.46), but not in women (OR, 1.10; CI, 0.92-1.31). No significant associations were observed using the instrumental variables for LTL.<br><br>CONCLUSIONS: We found no indication that LTL is a suitable biomarker for assessing fecundability, infertility, or ART use. Additional studies are required to replicate the association observed between LTL and ART use in men.},
}
@article {pmid39695460,
year = {2024},
author = {Eren Ozdemir, A},
title = {Evaluation of the effect of melatonin treatment on telomere length of the retinal pigment epithelium in streptozotocin-induced diabetic rat model.},
journal = {BMC ophthalmology},
volume = {24},
number = {1},
pages = {532},
pmid = {39695460},
issn = {1471-2415},
mesh = {Animals ; *Melatonin/pharmacology/therapeutic use ; *Diabetes Mellitus, Experimental/drug therapy ; *Rats, Sprague-Dawley ; Male ; *Retinal Pigment Epithelium/drug effects/pathology ; *Diabetic Retinopathy/drug therapy ; Rats ; Telomere/drug effects ; Antioxidants/pharmacology ; Streptozocin ; },
abstract = {OBJECTIVES: We aimed to investigate the effect of diabetic retinopathy and melatonin treatment on the relative telomer lengths (RTL) in retinal pigment epithelium (RPE) cells in a streptozotocin-induced diabetic rat model.<br><br>BACKGROUND: TL can be used to evaluate diabetes mellitus, its complications, and the effectiveness of its treatment. However, TL assessment has not been performed in retinal cells in a diabetic retinopathy model until now.<br><br>METHODS: Forty Sprague-Dawley male rats were randomly divided into four groups. The experimental groups were: Control Group (C): non- diabetic rats; Diabetes Mellitus Group (DM): rats induced to diabetes without treatment; Melatonin and Diabetes Mellitus Group (Mel&#x2009;+&#x2009;DM): rats induced to diabetes and after confirmation, treated with melatonin; Melatonin Group (Mel): rats were not induced to diabetes, treated with melatonin. Diabetes was induced by intraperitoneal administration of streptozotocin solution after 12&#xa0;h food fasting. For eight weeks after the diabetes was induced, melatonin was administered via subcutaneous injection at a dose of 10&#xa0;mg / kg. RTLs were measured by qPCR method with modifications. The comparison of averaged data among groups was performed using least significant difference (LSD) and Kruskal - Wallis Test and One way ANOVA test.<br><br>RESULTS: RTL was significantly similar in control and melatonin group. RTL was thinnest in DM group, in addition melatonin treatment significantly prevented the RTL shortening in DM&#x2009;+&#x2009;Mel group (p&#x2009;=&#x2009;0.031).<br><br>CONCLUSION: We demonstrated that diabetic retinopathy led to the shortening of RTL in RPE cells in rats and melatonin treatment prevents this shortening.},
}
@article {pmid39695221,
year = {2024},
author = {Wang, B and Zhang, R and Sun, W and Yang, J},
title = {A nearly telomere-to-telomere diploid genome assembly of Firmiana kwangsiensis, a threatened species in China.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {1394},
pmid = {39695221},
issn = {2052-4463},
mesh = {*Endangered Species ; *Telomere/genetics ; China ; *Haplotypes ; *Genome, Plant ; Diploidy ; },
abstract = {Firmiana kwangsiensis is a tree species of high ornamental value. The species is critically endangered in the wild, and is listed as a first-class national protected wild plant in China, and a Plant Species with Extremely Small Populations in need of urgent protection. We have assembled a chromosome-scale, haplotype-resolved genome for F. kwangsiensis using a combination of PacBio HiFi sequencing, ONT sequencing, and Hi-C sequencing. The final assembled genome is 2.3 G in size and comprises 2n = 40 chromosomes. All chromosomal ends contain telomeric characteristic motifs (TTTAGGG), and there are only 2 gaps within the rDNA regions, both close to a T2T genome assembly. Two complete sets of haplotypes are present, Haplotype A (1169.19 Mb) and Haplotype B (1157.87 Mb), with contig N50 lengths of 58.37 Mb and 57.27 Mb, respectively. The genome contains a total of 67,527 coding genes, with 62,351 genes functionally annotated here. This is the first report of the genome of F. kwangsiensis, and lays the foundation for future conservation genomics research into this species.},
}
@article {pmid39694814,
year = {2024},
author = {Cacchione, S and Cenci, G and Dion-Côté, AM and Barbash, DA and Raffa, GD},
title = {Maintaining Telomeres without Telomerase in Drosophila: Novel Mechanisms and Rapid Evolution to Save a Genus.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041708},
pmid = {39694814},
issn = {1943-0264},
abstract = {Telomere maintenance is crucial for preventing the linear eukaryotic chromosome ends from being mistaken for DNA double-strand breaks, thereby avoiding chromosome fusions and the loss of genetic material. Unlike most eukaryotes that use telomerase for telomere maintenance, Drosophila relies on retrotransposable elements-specifically HeT-A, TAHRE, and TART (collectively referred to as HTT)-which are regulated and precisely targeted to chromosome ends. Drosophila telomere protection is mediated by a set of fast-evolving proteins, termed terminin, which bind to chromosome termini without sequence specificity, balancing DNA damage response factors to avoid erroneous repair mechanisms. This unique telomere capping mechanism highlights an alternative evolutionary strategy to compensate for telomerase loss. The modulation of recombination and transcription at Drosophila telomeres offers insights into the diverse mechanisms of telomere maintenance. Recent studies at the population level have begun to reveal the architecture of telomere arrays, the diversity among the HTT subfamilies, and their relative frequencies, aiming to understand whether and how these elements have evolved to reach an equilibrium with the host and to resolve genetic conflicts. Further studies may shed light on the complex relationships between telomere transcription, recombination, and maintenance, underscoring the adaptive plasticity of telomeric complexes across eukaryotes.},
}
@article {pmid39694812,
year = {2024},
author = {Markiewicz-Potoczny, M and Denchi, EL},
title = {Telomere Protection in Stem Cells.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041686},
pmid = {39694812},
issn = {1943-0264},
abstract = {The natural ends of chromosomes resemble double-strand breaks (DSBs), which would activate the DNA damage response (DDR) pathway without the protection provided by a specialized protein complex called shelterin. Over the past decades, extensive research has uncovered the mechanism of action and the high degree of specialization provided by the shelterin complex to prevent aberrant activation of DNA repair machinery at chromosome ends in somatic cells. However, recent findings have revealed striking differences in the mechanisms of end protection in stem cells compared to somatic cells. In this review, we discuss what is known about the differences between stem cells and somatic cells regarding chromosome end protection.},
}
@article {pmid39695150,
year = {2024},
author = {Zhou, Q and Liu, X and Song, Y and Li, M and Fan, G and Chen, S},
title = {Telomere-to-telomere gapless genome assembly of the giant grouper (Epinephelus lanceolatus).},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {1342},
pmid = {39695150},
issn = {2052-4463},
mesh = {Animals ; *Genome ; *Telomere/genetics ; Bass/genetics ; Chromosomes ; },
abstract = {The giant grouper (Epinephelus lanceolatus) is a large coral reef fish distributed in the Indian Ocean and the Pacific Ocean. With a high market value, this species can grow up to approximately 2.7 meters in length and weigh 440 kilograms. With the rapid development of bioinformatics, higher standards of genome analysis are now required compared to previous reference genomes. This study presents a gapless assembly of the giant grouper genome, which has a length of 1.03 Gb. The sequences were assembled onto 24 chromosomes with a coverage of over 99% (1.02 Gb), and telomeres were detected on 24 chromosomes. Analysis using Merqury indicated a high level of accuracy, with an average consensus quality value of 59.24. The ONT ultralong and PacBio HiFi data were aligned with the assembly using minimap2, resulting in a mapping rate of 99.9%. The study inferred 25,815 protein-coding genes. These results lay a foundation for exploring the evolution and biology of the giant grouper, and advancing molecular breeding techniques.},
}
@article {pmid39694813,
year = {2024},
author = {Ferreira, MG},
title = {Telomere Dynamics in Zebrafish Aging and Disease.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041696},
pmid = {39694813},
issn = {1943-0264},
abstract = {Fish telomere lengths vary significantly across the numerous species, implicating diverse life strategies and environmental adaptations. Zebrafish have telomere dynamics that are comparable to humans and are emerging as a key model in which to unravel the systemic effects of telomere shortening on aging and interorgan communication. Here, we discuss zebrafish telomere biology, focusing on the organismal impact of telomere attrition beyond cellular senescence, with particular emphasis on how telomeric shortening in specific tissues can unleash widespread organ dysfunction and disease. This highlights a novel aspect of tissue communication, whereby telomere shortening in one organ can propagate through biological networks, influencing the aging process systemically. These discoveries position zebrafish as a valuable model for studying the complex interactions between telomeres, aging, and tissue cross talk, providing important insights with direct relevance to human health and longevity.},
}
@article {pmid39693631,
year = {2024},
author = {Su, R and Zhou, H and Yang, W and Moqir, S and Ritu, X and Liu, L and Shi, Y and Dong, A and Bayier, M and Letu, Y and Manxi, X and Chulu, H and Nasenochir, N and Meng, H and Herrid, M},
title = {Near telomere-to-telomere genome assembly of Mongolian cattle: implications for population genetic variation and beef quality.},
journal = {GigaScience},
volume = {13},
number = {},
pages = {},
doi = {10.1093/gigascience/giae099},
pmid = {39693631},
issn = {2047-217X},
support = {//Department of Science and Technology/ ; 2022JBGS0023//Inner Mongolia Autonomous Region/ ; },
mesh = {Animals ; Cattle/genetics ; *Telomere/genetics ; *Genetic Variation ; *Genome ; Molecular Sequence Annotation ; Red Meat/standards ; Genetics, Population ; Whole Genome Sequencing/methods ; Male ; Genomics/methods ; },
abstract = {BACKGROUND: Mongolian cattle, a unique breed indigenous to China, represent valuable genetic resources and serve as important sources of meat and milk. However, there is a lack of high-quality genomes in cattle, which limits biological research and breeding improvement.<br><br>FINDINGS: In this study, we conducted whole-genome sequencing on a Mongolian bull. This effort yielded a 3.1 Gb Mongolian cattle genome sequence, with a BUSCO integrity assessment of 95.9%. The assembly achieved both contig N50 and scaffold N50 values of 110.9 Mb, with only 3 gaps identified across the entire genome. Additionally, we successfully assembled the Y chromosome among the 31 chromosomes. Notably, 3 chromosomes were identified as having telomeres at both ends. The annotation data include 54.31% repetitive sequences and 29,794 coding genes. Furthermore, a population genetic variation analysis was conducted on 332 individuals from 56 breeds, through which we identified variant loci and potentially discovered genes associated with the formation of marbling patterns in beef, predominantly located on chromosome 12.<br><br>CONCLUSIONS: This study produced a genome with high continuity, completeness, and accuracy, marking the first assembly and annotation of a near telomere-to-telomere genome in cattle. Based on this, we generated a variant database comprising 332 individuals. The assembly of the genome and the analysis of population variants provide significant insights into cattle evolution and enhance our understanding of breeding selection.},
}
@article {pmid39693366,
year = {2024},
author = {Sato, MP and Arafa, RA and Rakha, M and Emeran, AA and Isobe, S and Shirasawa, K},
title = {Near-complete telomere-to-telomere de novo genome assembly in Egyptian clover (Trifolium alexandrinum).},
journal = {DNA research : an international journal for rapid publication of reports on genes and genomes},
volume = {},
number = {},
pages = {},
doi = {10.1093/dnares/dsae036},
pmid = {39693366},
issn = {1756-1663},
abstract = {Egyptian clover (Trifolium alexandrinum L.), also known as berseem clover, is an important forage crop to Semi-arid conditions that was domesticated in ancient Egypt since 6,000 years BC and introduced and well adapted to numerous countries including India, Pakistan, Turkey, and Mediterranean region. Despite its agricultural importance, genomic research on Egyptian clover has been limited to developing efficient modern breeding programs. In the present study, we constructed near-complete telomere-to-telomere-level genome assemblies for two Egyptian clover cultivars, Helaly and Fahl. Initial assemblies were established by using highly-fidelity long-read technology. To extend sequence contiguity, we developed a gap-targeted sequencing (GAP-Seq) method, in which contig ends are targeted for sequencing to obtain long reads bridging two contigs. The total length of the resultant chromosome-level assemblies was 547.7 Mb for Helaly and 536.3 Mb for Fahl. These differences in sequence length can be attributed to the expansion of DNA transposons. Population genomic analysis using single-nucleotide polymorphisms revealed genomic regions highly differentiated between two cultivars and increased genetic uniformity within each cultivar. Gene ontologies associated with metabolic and biosynthetic processes and developmental processes were enriched in these genomic regions, indicating that these genes may determine the unique characteristics of each cultivar. Comprehensive genomic resources can provide valuable insights into genetic improvements in Egyptian clover and legume genomics.},
}
@article {pmid39692822,
year = {2024},
author = {Zhou, K and Liu, X and Wang, M and Duan, J and Zhao, X and Yin, H},
title = {The landscape in telomere related gene prognostic signature for survival and medication treatment effectiveness prediction in hepatocellular carcinoma.},
journal = {Discover oncology},
volume = {15},
number = {1},
pages = {765},
pmid = {39692822},
issn = {2730-6011},
abstract = {OBJECTIVE: Telomeres, made of repetitive DNA sequences and shelterin complexes, which were found at the ends of chromosomes and had been extensively studied in cancer research. However, in hepatocellular carcinoma (HCC) was still relatively scarce. In this study, we investigated the correlation between telomerase-related genes (TRGs) and the prognosis and immunotherapy of HCC patients to enhance clinical outcomes.<br><br>METHODS: In this work, TRGs were gathered using TelNet, while clinical information and gene expression data for HCC patients were retrieved from the Cancer Genome Atlas (TCGA) database. A risk prediction model based on TRGs was created using COX and Lasso regression analyses, with ROC curves used to assess prognostic efficacy. Univariate and multifactorial COX regression analyses were used to determine if the risk model had an independent impact on prognosis. Nomograms were created to enhance clinical usability, and calibration curves were used to assess predictive ability at various time points. The Tumor Immune Dysfunction and Exclusion (TIDE) score was used to analyze differences in immune infiltrating cells between risk groups. The study analyzed the relationship between risk ratings and drug treatment effectiveness using data from the CellMiner database. The hub gene was identified and its relationship to prognostic markers of HCC patients was examined. The expression of hub genes in immune cell subpopulations was also investigated by single-cell data.<br><br>RESULTS: 2093 TRGs were identified, with 949 showing significant differences in expression between HCC and paracancerous tissues. Seven risk genes were overexpressed in tumor tissues, leading to lower survival rates in high-risk patients. Risk model could independently predict the prognosis of HCC patients. Analysis of tumor immune infiltrating cells revealed significant differences in cell abundance between risk groups, with notable variations in immune subset enrichment between subgroups. Higher risk scores correlated with increased sensitivity to sorafenib, mitoxantrone, oxaliplatin, gemcitabine, and entinostat, while sensitivity decreased for vincristine, etc. CDCA8 was identified as a key gene in the Protein Interaction Network, while high expression associated with poorer overall survival, tumor proliferation and metastasis. The results of single-cell data analysis suggest that CDCA8 may promote the development of HCC by affecting T lymphocytes.<br><br>CONCLUSION: The TRG-based risk model could predict HCC patient prognosis and closely linked to tumor immune environment, which could offer new possibilities for clinical treatment.},
}
@article {pmid39689933,
year = {2024},
author = {van Duijvenboden, S and Nelson, CP and Raisi-Estabragh, Z and Ramirez, J and Orini, M and Wang, Q and Aung, N and Codd, V and Stoma, S and Allara, E and Wood, AM and Di Angelantonio, E and Danesh, J and Harvey, NC and Petersen, SE and Munroe, PB and Samani, NJ},
title = {Leucocyte telomere length and conduction system ageing.},
journal = {Heart (British Cardiac Society)},
volume = {},
number = {},
pages = {},
doi = {10.1136/heartjnl-2024-324875},
pmid = {39689933},
issn = {1468-201X},
abstract = {BACKGROUND: Deterioration of the cardiac conduction system is an important manifestation of cardiac ageing. Cellular ageing is accompanied by telomere shortening and telomere length (TL) is often regarded as a marker of biological ageing, potentially adding information regarding conduction disease over and above chronological age. We therefore sought to evaluate the association between leucocyte telomere length (LTL) on two related, but distinct aspects of the cardiac conduction system: ECG measures of conduction (PR interval and QRS duration) and incident pacemaker implantation in a large population-based cohort.<br><br>METHODS: In the UK Biobank, we measured PR interval and QRS duration from signal-averaged ECG waveforms in 59&#x2009;868 and 62&#x2009;266 participants, respectively. Incident pacemaker implantation was ascertained using hospital episode data from 420&#x2009;071 participants. Associations with LTL were evaluated in (Cox) multivariable regression analyses adjusted for potential confounders. Putative causal effects of LTL were investigated by mendelian randomisation (MR).<br><br>RESULTS: Mean PR interval and QRS duration were 144.2 ms (&#xb1; 20.4) and 92.3 ms (&#xb1; 7.8), respectively, and there were 7169 (1.7%) incident pacemaker implantations, during a median follow-up period of 13.6 (IQR 1.5) years. LTL was significantly associated with PR interval (0.19 ms (95%&#x2009;CI: 0.03 to 0.35), per 1 SD shorter LTL, p=0.021), but not QRS duration. After adjusting for age, sex and cardiovascular risk factors, shorter LTL remained associated with an increased risk for incident pacemaker implantation (HR per SD decrease in LTL: 1.03 (95% CI: 1.01 to 1.06), p=0.012). MR analysis showed a trend towards an association of shorter LTL with longer PR interval and higher risk of pacemaker implantation but was likely to be underpowered.<br><br>CONCLUSIONS: Shorter LTL was significantly, and possibly causally, associated with prolongation of atrioventricular conduction and pacemaker implantation, independent of traditional cardiovascular risk factors. Our findings support further research to explore the role of ageing on cardiac conduction beyond chronological age.},
}
@article {pmid39689244,
year = {2024},
author = {Pickler, RH and Ford, JL and Tan, A and Browning, C and Tarrence, J and Kertes, DA},
title = {Childhood Adversity and Telomere Length.},
journal = {Biological research for nursing},
volume = {},
number = {},
pages = {10998004241309368},
doi = {10.1177/10998004241309368},
pmid = {39689244},
issn = {1552-4175},
abstract = {Purpose: Exposure to adversity during childhood and adolescence is associated with numerous health conditions in adulthood; telomere shortening may be a mechanism through which adversity contributes to poor outcomes. We studied three areas of adversity (parent relational instability, child household instability, and financial instability) occurring during three epochs across childhood and adolescence and their associations with telomere length during adolescence. Methods: Data were obtained from the first wave of a longitudinal cohort study of youth aged 11-17 and their primary caregiver. Caregivers completed demographic and adversity questionnaires; youth provided a saliva sample for DNA extraction for telomere analysis. Results: Of 879 youth, over half experienced some adversity. More than one third experienced parent relational instability in each age epoch, with nearly a quarter experiencing parent relational instability in all age epochs. Youth experienced a similar pattern of financial instability but lower rates of child household instability. Youth experiencing parent relational instability at two or three epochs had shorter telomeres compared to those without any parent relational instability (p < .004). Youth who experienced child household instability in two age epochs had shorter telomeres (p = .003) and youth who experienced financial instability across all three epochs had shorter telomeres (p = .013) compared to youth without these adversities. Conclusion: Continuing exposure to adversity in early childhood may be more likely to affect telomere length. Research is needed to further determine adversities exerting the most effect and to understand if early telomere shortening has long term health effects.},
}
@article {pmid39688874,
year = {2024},
author = {Olsson, M and Miller, E and Rollings, N and Lillie, M and Hufton, J and Hansson, A and Wapstra, E},
title = {The effects of costly telomere maintenance on lifespan - reproductive tradeoffs in sand lizards.},
journal = {Evolution; international journal of organic evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/evolut/qpae181},
pmid = {39688874},
issn = {1558-5646},
abstract = {Telomeres are DNA-protein structures that primarily protect chromosomes and serve multiple functions of gene regulation. When cells divide, telomeres shorten and their main repair system in ectotherms - telomerase - replaces lost nucleotide complexes ((T2AG3)n in vertebrates). It remains a challenge to experimentally investigate resource requirements for telomere maintenance and its effects on lifespan-reproductive tradeoffs in the wild. In sand lizards (Lacerta agilis), we show that higher female investments into reproduction results in corresponding shortening of telomeres and that males have less frequent and less profound telomere shortening than females; a contributing factor to this may be males' higher telomerase levels. To manipulate resource access for telomere maintenance, we exploit a pseudo-experimental opportunity to analyze 'onboard' resources long-term using lizards that drop their tails with fat and nutrient deposits when attacked by predators. Females with less resources due to regrown tails less often and less profoundly elongate telomeres. Adult lizards with the most TL elongation live the longest, females with the highest lifetime reproductive success shorten telomeres the most, whereas males with the most telomere elongation have the highest lifetime reproductive success. This suggests ongoing evolution of resource-constrained telomere maintenance.},
}
@article {pmid39681615,
year = {2024},
author = {Weisert, N and Majewski, V and Hartleb, L and Luko, K and Lototska, L and Krapoth, NC and Ulrich, HD and Janzen, CJ and Butter, F},
title = {TelAP2 links TelAP1 to the telomere complex in Trypanosoma brucei.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {30493},
pmid = {39681615},
issn = {2045-2322},
mesh = {*Trypanosoma brucei brucei/genetics/metabolism ; *Telomere/metabolism/genetics ; *Protozoan Proteins/metabolism/genetics ; Telomere-Binding Proteins/metabolism/genetics ; Variant Surface Glycoproteins, Trypanosoma/genetics/metabolism ; Protein Binding ; Proteomics/methods ; },
abstract = {The extracellular parasite Trypanosoma brucei evades the immune system of the mammalian host by periodically exchanging its variant surface glycoprotein (VSG) coat. Hereby, only one VSG gene is transcribed from one of 15 subtelomeric so-called bloodstream form expression sites (BES) at any given timepoint, while all other BESs are silenced. VSG gene expression is altered by homologous recombination using a large VSG gene repertoire or by a so-called in situ switch, which activates a previously silent BES. Transcriptional activation, VSG switching and VSG silencing during developmental differentiation from the bloodstream form to the procyclic form present in the tsetse fly vector are tightly regulated. Due to their subtelomeric position, telomere-associated proteins are involved in the regulation of VSG expression. Three functional homologs of mammalian telomere complex proteins have been characterized thus far, and novel telomere-interacting proteins, such as telomere-associated protein 1 (TelAP1), have recently been identified. Here, we used mass spectrometry-based proteomics and interactomics approaches, telomere pull-down assays with recombinant material and immunofluorescence analysis to elucidate the interactions of 21 other putative TelAPs. We investigated the influence on VSG expression and showed that depletion of TelAPs does not ultimately lead to changes in VSG expression. Additionally, we examined the interaction patterns of four TelAPs with the TbTRF/TbTIF2/TbRAP1 telomere complex by reciprocal affinity purification. We further propose that TelAP1 interacts with Tb927.6.4330, now called TelAP2, and that TelAP1 depends on this interaction to form a complex with the telomeric proteins TbTRF, TbTIF2 and TbRAP1.},
}
@article {pmid39680438,
year = {2024},
author = {Pearce, EE and Majid, A and Brown, T and Shepherd, RF and Rising, C and Wilsnack, C and Thompson, AS and Gilkey, MB and Ribisl, KM and Lazard, AJ and Han, PK and Werner-Lin, A and Hutson, SP and Savage, SA},
title = {"Crying in the Wilderness"-The Use of Web-Based Support in Telomere Biology Disorders: Thematic Analysis.},
journal = {JMIR formative research},
volume = {8},
number = {},
pages = {e64343},
doi = {10.2196/64343},
pmid = {39680438},
issn = {2561-326X},
mesh = {Humans ; Female ; Male ; Middle Aged ; Adult ; Aged ; *Qualitative Research ; *Internet ; *Social Support ; Information Seeking Behavior ; Telomere/genetics ; Caregivers/psychology ; },
abstract = {BACKGROUND: Web-based information and social support are commonly used in rare disease communities where geographic dispersion and limited provider expertise complicate in-person support. We examined web-based resource use among caregivers of individuals with telomere biology disorders (TBDs), which are rare genetic conditions with long diagnostic odysseys and uncertain prognoses including multiorgan system cancer risk.<br><br>OBJECTIVE: This study explored internet-based information-seeking and social support practices and perspectives of patients with TBDs and their caregivers.<br><br>METHODS: Our qualitative descriptive study used semistructured interviews of patients with TBDs and caregivers. Data were transcribed verbatim and thematically analyzed by an interdisciplinary team.<br><br>RESULTS: A total of 32 adults completed interviews. Participant ages ranged from 27 to 74 years. The majority (n=28, 88%) were female, occupied multiple TBD roles (eg, patient and parent), and had undergone genetic testing. Most engaged in web-based information-seeking (n=29, 91%) and TBD-specific social media (n=26, 81%). Participants found web-based resources useful for information-seeking but reported privacy concerns and frustration with forming supportive relationships. Most participants described ambivalence toward web-based resource use, citing tensions between hunger for information versus distrust, empowerment versus overwhelm, disclosure versus privacy, and accessibility versus connection. Fluctuations in web-based support use arose from perceived harms, information saturation, or decreased relevance over the course of TBD illness experience.<br><br>CONCLUSIONS: Individuals with TBDs and their caregivers reported frequent use of web-based informational and emotional support. However, ambivalence about the benefits and liabilities of web-based resources and persistent medical uncertainty may impact the adoption of and adherence to web-based support among patients with TBD and caregivers. Our findings suggest web-based psychosocial support should target long-term and multifaceted informational and emotional needs, be user-initiated, be offered alongside in-person formats, provide expert-informed information, and be attentive to personal privacy and evolving support needs of the TBD community. This study suggests web-based resources will be most effective in the TBD context when they achieve the following features: (1) offer a variety of ways to engage (eg, active and passive), (2) provide privacy protections in moderated "safe spaces" designed for personal disclosure, (3) offer separate venues for informational versus emotional support, (4) combine web-based relationship formation with opportunities for in-person gathering, (5) provide information that is reliable, easy to access, and informed by medical professionals, (6) remain mindful of user distress, and (7) are responsive to variations in levels and types of engagement. Additionally, advocacy organizations may wish to avoid traditional social media platforms when designing safe spaces for web-based emotional support, instead pivoting to internet-based tools that minimize privacy threats and limit the perpetual public availability of shared information.},
}
@article {pmid39675625,
year = {2024},
author = {Xie, JW and Wang, HL and Lin, LQ and Guo, YF and Wang, M and Zhu, XZ and Niu, JJ and Lin, LR},
title = {Telomere-Methylation Genes: Novel Prognostic Biomarkers for Hepatocellular Carcinoma.},
journal = {Clinics and research in hepatology and gastroenterology},
volume = {},
number = {},
pages = {102516},
doi = {10.1016/j.clinre.2024.102516},
pmid = {39675625},
issn = {2210-741X},
abstract = {BACKGROUND: Since telomere length and DNA methylation both correlate with hepatocellular carcinoma (HCC) prognosis, telomere-methylation genes could be novel prognostic markers for HCC.<br><br>METHOD: This study first investigated the interaction between telomere length and DNA methylation in HCC through Mendelian randomization analysis. Then, this study identified telomere-methylation genes in HCC by employing the TCGA-LIHC cohort, and explored the expression patterns of these genes in the tumor microenvironment of HCC and potential underlying mechanisms. Finally, the HCC risk-scoring model and prognostic model based on these genes were established, and the performance of the model was assessed.<br><br>RESULT: The findings revealed a bidirectional relationship between telomere length and DNA methylation in HCC. Fifty telomere-methylation genes were identified, and the prognosis-related telomere-methylation genes were closely associated with Treg and Tprolif cell subsets within the HCC tumor microenvironment. Telomere-methylation genes could potentially impact the prognosis of HCC patients by modulating chromosome stability and regulating the cell cycle. Additionally, the constructed risk scoring model and prognostic prediction model showcased compelling clinical applicability, as evidenced by the receiver operating characteristic curve, the decision curve analysis, and the calibration curves.<br><br>CONCLUSION: This study elucidated the potential of telomere-methylation genes as prognostic biomarkers for HCC and paves the way for novel approaches in prognostication and treatment management for HCC patients.},
}
@article {pmid39667908,
year = {2024},
author = {Jung, JH and Byun, MS and Yi, D and Ahn, H and Lee, JH and Lee, JS and Lee, HS and Lee, JY and Kim, YK and Lee, YS and Kang, KM and Sohn, CH and Lee, DY and , },
title = {Telomere length, in vivo Alzheimer's disease pathologies and cognitive decline in older adults.},
journal = {Journal of neurology, neurosurgery, and psychiatry},
volume = {},
number = {},
pages = {},
doi = {10.1136/jnnp-2024-334314},
pmid = {39667908},
issn = {1468-330X},
abstract = {BACKGROUND: Whether telomere length (TL), an indicator of biological ageing, reflects Alzheimer's disease (AD)-related neuropathological change remains unclear. We investigated the relationships between TL, in vivo AD pathologies, including cerebral beta-amyloid and tau deposition, and cognitive outcomes in older adults.<br><br>METHODS: A total of 458 older adults were included, encompassing both cognitively normal (CN) individuals and those cognitively impaired (CI), with the CI group consisting of individuals with mild cognitive impairment or AD dementia. All participants underwent clinical and neuropsychological assessments, amyloid positron emission tomography (PET) scan and DNA extraction for measuring TL at baseline. A subset of participants (n=140) underwent tau PET scan. At follow-up, the participants underwent neuropsychological assessments annually for up to 4 years.<br><br>RESULTS: Overall, longer TL was associated with greater brain tau deposition (B=0.139, 95% CI 0.040, 0.238) and a faster decline in global cognition (B = - 0.371, 95% CI - 0.720, -0.023). In the subgroup analysis, the association between longer TL and greater in vivo AD pathologies, as well as faster cognitive decline, was observed particularly in the CI group. Mediation analysis suggested that longer TL was associated with cognitive decline through increased tau deposition in the CI group.<br><br>CONCLUSION: Our finding suggests that older adults with relatively longer TL, particularly in the CI group, may have greater in vivo AD pathologies and experience more rapid cognitive decline, potentially mediated by brain tau deposition. Further studies are necessary to elucidate the biological links underlying these associations.},
}
@article {pmid39665795,
year = {2024},
author = {Ying, C and Han, C and Li, Y and Zhang, M and Xiao, S and Zhao, L and Zhang, H and Yu, Q and An, J and Mao, W and Cai, Y},
title = {Plasma circulating cell-free DNA integrity and relative telomere length as diagnostic biomarkers for Parkinson's disease and multiple system atrophy: a cross-sectional study.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-24-00599},
pmid = {39665795},
issn = {1673-5374},
abstract = {In clinical specialties focusing on neurological disorders, there is a need for comprehensive and integrated non-invasive, sensitive, and specific testing methods. Both Parkinson's disease and multiple system atrophy are classified as α-synucleinopathies, characterized by abnormal accumulation of α-synuclein protein, which provides a shared pathological background for their comparative study. In addition, both Parkinson's disease and multiple system atrophy involve neuronal death, a process that may release circulating cell-free DNA (cfDNA) into the bloodstream, leading to specific alterations. This premise formed the basis for investigating cell-free DNA as a potential biomarker. Cell-free DNA has garnered attention for its potential pathological significance, yet its characteristics in the context of Parkinson's disease and multiple system atrophy are not fully understood. This study investigated the total concentration, nonapoptotic level, integrity, and cell-free DNA relative telomere length of cell-free DNA in the peripheral blood of 171 participants, comprising 76 normal controls, 62 patients with Parkinson's disease, and 33 patients with multiple system atrophy. In our cohort, 75.8% of patients with Parkinson's disease (stage 1-2 of Hoehn &amp; Yahr) and 60.6% of patients with multiple system atrophy (disease duration less than 3 years) were in the early stages. The diagnostic potential of the cell-free DNA parameters was evaluated using receiver operating characteristic (ROC) analysis, and their association with disease prevalence was examined through logistic regression models, adjusting for confounders such as age, sex, body mass index, and education level. The results showed that cell-free DNA integrity was significantly elevated in both Parkinson's disease and multiple system atrophy patients compared with normal controls (P < 0.001 for both groups), whereas cell-free DNA relative telomere length was markedly shorter (P = 0.003 for Parkinson's disease and P = 0.010 for multiple system atrophy). Receiver operating characteristic analysis indicated that both cell-free DNA integrity and cell-free DNA relative telomere length possessed good diagnostic accuracy for differentiating Parkinson's disease and multiple system atrophy from normal controls. Specifically, higher cell-free DNA integrity was associated with increased risk of Parkinson's disease (odds ratio [OR]: 5.72; 95% confidence interval [CI]: 1.54-24.19) and multiple system atrophy (OR: 10.10; 95% CI: 1.55-122.98). Conversely, longer cell-free DNA relative telomere length was linked to reduced risk of Parkinson's disease (OR: 0.16; 95% CI: 0.04-0.54) and multiple system atrophy (OR: 0.10; 95% CI: 0.01-0.57). These findings suggest that cell-free DNA integrity and cell-free DNA relative telomere length may serve as promising biomarkers for the early diagnosis of Parkinson's disease and multiple system atrophy, potentially reflecting specific underlying pathophysiological processes of these neurodegenerative disorders.},
}
@article {pmid39664691,
year = {2024},
author = {Wang, J and Xu, D and Sang, YL and Sun, M and Liu, C and Niu, M and Li, Y and Liu, L and Han, X and Li, J},
title = {A telomere-to-telomere gap-free reference genome of Chionanthus retusus provides insights into the molecular mechanism underlying petal shape changes.},
journal = {Horticulture research},
volume = {11},
number = {12},
pages = {uhae249},
pmid = {39664691},
issn = {2662-6810},
abstract = {Chionanthus retusus, an arbor tree of the Oleaceae family, is an ecologically and economically valuable ornamental plant for its remarkable adaptability in landscaping. During C. retusus breeding, we observed diverse floral shapes; however, no available genome for C. retusus has hindered the widespread identification of genes related to flower morphology. Thus, a de novo telomere-to-telomere (T2T) gap-free genome was generated. The assembly, incorporating high-coverage and long-read sequencing data, successfully yielded two complete haplotypes (687 and 683 Mb). The genome encompasses 42 864 predicted protein-coding genes, with all 46 telomeres and 23 centromeres in one haplotype. Whole-genome duplication analysis revealed that C. retusus underwent one fewer event of whole-genome duplication after differentiation compared to other species in the Oleaceae family. Furthermore, flower vein diversity was the main reason for the differences in floral shapes. Auxin-related genes were responsible for petal shape formation on genome-based transcriptome analysis. Specifically, the removal and retention of the first intron in CrAUX/IAA20 resulted in the production of two transcripts, and the differences in the expression levels of CrAUX/IAA20 resulted in the variations of flower veins. Compared to transcripts lacking the first intron, transcripts with intron retention caused more severe decreases in the number and length of flower veins in transgenic Arabidopsis thaliana. Our findings will deepen our understanding of flower morphology development and provide important theoretical support for the cultivation of Oleaceae.},
}
@article {pmid39662066,
year = {2024},
author = {Fragkiadaki, P and Apetroaei, MM and Kouvidi, E and Vakonaki, E and Renieri, E and Fragkiadoulaki, I and Spanakis, M and Baliou, S and Alegakis, A and Tsatsakis, A},
title = {The association between short telomere length and cardiovascular disease.},
journal = {Cytogenetic and genome research},
volume = {},
number = {},
pages = {1-18},
doi = {10.1159/000542795},
pmid = {39662066},
issn = {1424-859X},
abstract = {INTRODUCTION: Telomeres, repetitive DNA sequences at chromosome ends, shorten with cell division, countered by telomerase. Short telomeres are linked to cardiovascular disease (CVD), alongside its risk factors like aging, hypertension, diabetes, obesity, inactivity, and smoking. Many studies have claimed the implication of TL in cardiac diseases. This study examines telomere length's (TL) impact on heart conditions using quantitative fluorescence in situ hybridization (Q-FISH) technology.<br><br>METHODS: Thirteen CVD patients (nine men and four women) aged 30 to 70 years and aged-matched healthy participants from BIOTEL population TL database, were included in the study. Each chromosome's TL from peripheral blood cells (PBCs) was measured using metaphase Q-FISH. An independent samples t-test was used to compare participants' mean or median TL with various medical factors and habits Results: The mean TL of whole and short telomeres in cardiac disease patients was lower compared to aged-matched healthy controls; however, there was no statistical significance due to the limited patient sample. The mean TL of short telomeres in cardiac disease patients showed a remarkable decline with advanced age. Accordingly, the mean TL of whole and short telomeres in patients with cardiac diseases showed a similar reduced trend.<br><br>CONCLUSION: In our study, shorter TL was observed in cardiac disease patients compared to those of healthy controls by using metaphase Q-FISH. However, more cases need to be studied to elucidate the use of TL as a potential biomarker for the diagnosis of patients with CVD.},
}
@article {pmid39661724,
year = {2024},
author = {Peng, D and Hong, Z and Kan, S and Wu, Z and Liao, X},
title = {The telomere-to-telomere (T2T) genome provides insights into the evolution of specialized centromere sequences in sandalwood.},
journal = {GigaScience},
volume = {13},
number = {},
pages = {},
doi = {10.1093/gigascience/giae096},
pmid = {39661724},
issn = {2047-217X},
support = {2021QN02N792//Guangdong Provincial Pearl River Talents Program/ ; 110243160001007//Chinese Academy of Agricultural Sciences/ ; JCYJ20220818103212025//Shenzhen Fundamental Research Program/ ; },
mesh = {*Centromere/genetics ; *Telomere/genetics ; *Genome, Plant ; *Evolution, Molecular ; Chromosomes, Plant ; Genomics/methods ; },
abstract = {BACKGROUND: Sandalwood, a prized hemiparasitic plant, is highly sought in the commercial market because of its aromatic core materia. The structure and stability of the genome are instrumental in the rapid adaptation of parasitic plants to their surroundings. However, there is a conspicuous lack of research on the genomic-level adaptive evolution of sandalwood.<br><br>RESULTS: In this study, we assembled a gap-free telomere-to-telomere (T2T) reference genome for Santalum album using PacBio HiFi, Hi-C, and ultra-long ONT data. The T2T reference genome (Sal_t2t) encompassed annotations of 24,171 genes and 25.34% repetitive sequences, in addition to all 10 centromeres and 20 telomeres across the 10 chromosomes. The results revealed that the 3 distinct parasitic species of Santalales had diverse centromeric compositions. The Copia-type long terminal repeat transposon emerged as the most significant in the S. album genome, constituting the primary sequence of the centromere and influencing gene expression. Third, in sandalwood, the presence of Copia affected the size of the centromeres and, consequently, the genome size. Identification of the sandalwood T2T genome in this study also enabled the identification of more precise organelle transfer fragments.<br><br>CONCLUSIONS: Our research provides a sandalwood T2T genome, laying the groundwork for future investigations on the evolution of energy organs in parasitic plants. Moreover, it offers novel insights into the function and evolution of centromeres, as well as the mechanisms of adaptation and parasitism.},
}
@article {pmid39661387,
year = {2024},
author = {Niewisch, MR and Kim, J and Giri, N and Lunger, JC and McReynolds, LJ and Savage, SA},
title = {Genotype and Associated Cancer Risk in Individuals With Telomere Biology Disorders.},
journal = {JAMA network open},
volume = {7},
number = {12},
pages = {e2450111},
doi = {10.1001/jamanetworkopen.2024.50111},
pmid = {39661387},
issn = {2574-3805},
mesh = {Humans ; Male ; Female ; Adult ; *Neoplasms/genetics/epidemiology ; Longitudinal Studies ; Middle Aged ; Genotype ; Telomere/genetics ; Aged ; Risk Factors ; Genetic Predisposition to Disease ; Bone Marrow Failure Disorders/genetics ; Incidence ; Young Adult ; Adolescent ; },
abstract = {IMPORTANCE: Telomere biology disorders (TBDs) are inherited cancer-prone bone marrow failure syndromes with differences in morbidity and mortality based on mode of inheritance.<br><br>OBJECTIVE: To quantify cancer risks in TBDs by genetic subgroups.<br><br>This longitudinal cohort study of TBDs assessed cancer occurrences from 2002 through 2022. Participants were individuals with a TBD-associated pathogenic germline variant recruited across institutions by self-referral. Data were collected and analyzed through June 30, 2022.<br><br>EXPOSURES: The exposure was TBD genotypes, with subgroups defined by inheritance pattern (autosomal-dominant [AD-non-TINF2] vs autosomal-recessive/X-linked [AR/XLR] vs AD-TINF2).<br><br>MAIN OUTCOMES AND MEASURES: The main outcome was cancer; secondary outcomes included death, or organ transplant. Cumulative cancer incidence was determined considering death or transplant as competing events. Observed:expected (O:E) ratios of cancer before and after any organ transplant were calculated using the National Cancer Institute's Surveillance, Epidemiology, and End Results Program.<br><br>RESULTS: Among 230 individuals with TBD (135 [58.7%] male; median [range] age at last follow-up, 34.6 [1.4-82.2] years) included, the risk of cancer was 3-fold higher than the general population (O:E, 3.35 [95% CI, 2.32-4.68]). The highest risk was observed in individuals with AR/XLR (O:E, 19.16 [95% CI, 9.19-35.24]) with a significantly younger cancer onset than in individuals with AD-non-TINF2 (median [range] age, 36.7 [25.2-53.6] years vs 44.5 [32.2-67.5] years; P&#x2009;=&#x2009;.01). The risk of solid tumors was highest in individuals with AR/XLR (O:E&#x2009;=&#x2009;23.97 [95% CI, 10.96-45.50]), predominantly head and neck squamous cell carcinomas (O:E, 276.00 [95% CI, 75.20-706.67]). Hematologic malignant neoplasm risk was highest in individuals with AD-non-TINF2 (O:E, 9.41 [95% CI, 4.30-17.86]). Solid tumor cumulative incidence increased to 12% for individuals with AR/XLR by age 45 years and to 13% for individuals with AD-non-TINF2 by age 70 years. The cumulative incidence of hematologic malignant neoplasms leveled off at 2% by age 30 years and 19% by age 70 years in individuals with AR/XLR and AD-non-TINF2, respectively. Individuals with AD-TINF2 showed the highest cumulative incidence for transplant or death (49% by age 15 years). Following transplant, individuals with AR/XLR (O:E, 136.11 [95% CI, 54.72-280.44) or AD-TINF2 (O:E, 81.07 [95% CI, 16.72-236.92]) had the highest cancer risk, predominantly young-onset head and neck squamous cell carcinomas (median [range] age, 32.2 [10.5-35.5] years).<br><br>CONCLUSIONS AND RELEVANCE: This cohort study of individuals with TBDs found an increased cancer risk compared with the general population, with the earliest age at onset for individuals with AR/XLR inheritance. Cancer risks increased after organ transplant across all subgroups. These differences in TBD-associated cancer risks by mode of inheritance suggest cancer screening could be tailored by genotype, but additional research is warranted.},
}
@article {pmid39658339,
year = {2024},
author = {Lame-Jouybari, AH and Fahami, MS and Hosseini, MS and Moradpour, M and Hojati, A and Abbasalizad-Farhangi, M},
title = {Association Between Maternal Prepregnancy and Pregnancy Body Mass Index and Children's Telomere Length: A Systematic Review and Meta-analysis.},
journal = {Nutrition reviews},
volume = {},
number = {},
pages = {},
doi = {10.1093/nutrit/nuae187},
pmid = {39658339},
issn = {1753-4887},
support = {75731//Tabriz University of Medical Sciences/ ; },
abstract = {CONTEXT: Telomeres maintain chromosome stability and mark cellular aging, and their shortening with age compromises genomic stability.<br><br>OBJECTIVE: The purpose of this study was to conduct a meta-analysis of existing evidence to evaluate the relationship between the maternal pregnancy body mass index (BMI) and children's telomere length (TL).<br><br>DATA SOURCE: Web of Science, Scopus, and PubMed databases were systematically searched from their inception to August 27, 2023, for pertinent observational studies.<br><br>DATA EXTRACTION: The random-effects meta-analysis was conducted on eligible studies that investigated the linear relationship between exposure and the outcomes of interest, utilizing the reported &#x3b2;-coefficient. Cochran's Q test and I2 statistics were used to assess heterogeneity.<br><br>DATA ANALYSIS: A significant association was observed between maternal pregnancy BMI and children's TL (32 studies, pooled effect size [ES]: -0.04; 95% CI: -0.06 to -0.01; I2 = 47.51%, P&#x2009;<&#x2009;.001) and maternal prepregnancy BMI and children's TL at birth (16 studies; pooled ES: -0.05; 95% CI: -0.08 to -0.02; I2 = 53.49%, P&#x2009;<&#x2009;.001).<br><br>CONCLUSION: The findings indicate an inverse association between maternal prepregnancy BMI and TL in infants, which is evident within the normal to obese BMI range. This underscores the significance of maternal weight status before pregnancy as a determinant of offspring TL.<br><br>PROSPERO registration no. CRD42023466425.},
}
@article {pmid39653745,
year = {2024},
author = {Banu, S and Mk, K and George, JK and Siby, E and Bhagat, R and Ms, S and Patil, SJ and Phadke, SR and Sowpati, DT and Tallapaka, KB},
title = {Enhanced resolution of optical genome mapping utilizing telomere-to-telomere reference in genetic disorders.},
journal = {European journal of human genetics : EJHG},
volume = {},
number = {},
pages = {},
pmid = {39653745},
issn = {1476-5438},
abstract = {Reference genomes serve as a baseline criterion for comparison of personal genomes to deduce clinical variants. The widely used reference genome, GRCh38, contains stretches of gaps and unresolved bases particularly in complex regions which could obscure variant discovery. In contrast, the gapless telomere-to-telomere CHM13 (T2T-CHM13) reference genome can be used to assess difficult regions of the genome. Optical genome mapping (OGM), an imaging technique for structural variation identification has improved resolution compared to traditional cytogenetic methods. Our study showcases the utility of the T2T-CHM13 reference genome for enhanced structural variant (SV) detection in complex regions. We illustrate this through two clinical cases, where improved alignment with T2T-CHM13 led to significantly higher confidence scores for critical SVs. We demonstrate improved clinical diagnostic outcomes with the updated T2T-CHM13 reference and advocate its adoption.},
}
@article {pmid39652599,
year = {2024},
author = {Syed, S and Aloe, S and Sutherland, JH and Holloman, WK and Lue, NF},
title = {Ustilago maydis Trf2 ensures genome stability by antagonizing Blm-mediated telomere recombination: Fine-tuning DNA repair factor activity at telomeres through opposing regulations.},
journal = {PLoS genetics},
volume = {20},
number = {12},
pages = {e1011515},
doi = {10.1371/journal.pgen.1011515},
pmid = {39652599},
issn = {1553-7404},
abstract = {TRF2 is an essential and conserved double-strand telomere binding protein that stabilizes chromosome ends by suppressing DNA damage response and aberrant DNA repair. Herein we investigated the mechanisms and functions of the Trf2 ortholog in the basidiomycete fungus Ustilago maydis, which manifests strong resemblances to metazoans with regards to the telomere and DNA repair machinery. We showed that UmTrf2 binds to Blm in vitro and inhibits Blm-mediated unwinding of telomeric DNA substrates. Consistent with a similar inhibitory activity in vivo, over-expression of Trf2 induces telomere shortening, just like deletion of blm, which is required for efficient telomere replication. While the loss of Trf2 engenders growth arrest and multiple telomere aberrations, these defects are fully suppressed by the concurrent deletion of blm or mre11 (but not other DNA repair factors). Over-expression of Blm alone triggers aberrant telomere recombination and the accumulation of aberrant telomere structures, which are blocked by concurrent Trf2 over-expression. Together, these findings highlight the suppression of Blm as a key protective mechanism of Trf2. Notably, U. maydis harbors another double-strand telomere-binding protein (Tay1), which promotes Blm activity to ensure efficient replication. We found that deletion of tay1 partially suppresses the telomere aberration of Trf2-depleted cells. Our results thus point to opposing regulation of Blm helicase by telomere proteins as a strategy for optimizing both telomere maintenance and protection. We also show that aberrant transcription of both telomere G- and C-strand is a recurrent phenotype of telomere mutants, underscoring another potential similarity between double strand breaks and de-protected telomeres.},
}
@article {pmid39650708,
year = {2024},
author = {Wang, J and Xie, F and Zhu, W and Ye, D and Xiao, Y and Shi, M and Zeng, R and Bian, J and Xu, X and Chen, L and Zhu, A and Zhu, K and Fan, T and Liu, B and Xiao, L and Zhang, X},
title = {Relationship between serum carotenoids and telomere length in overweight or obese individuals.},
journal = {Frontiers in nutrition},
volume = {11},
number = {},
pages = {1479994},
doi = {10.3389/fnut.2024.1479994},
pmid = {39650708},
issn = {2296-861X},
abstract = {BACKGROUND: Previous researches have demonstrated an association between carotenoids and elongated telomeres. Nonetheless, there is scant scientific evidence examining this relationship in individuals who are overweight or obese, a demographic more predisposed to accelerated aging. This study aims to elucidate the correlation between serum carotenoid concentrations and telomere length within this population group.<br><br>METHODS: Data were sourced from the 2001-2002 National Health and Nutrition Examination Survey, encompassing 2,353 overweight or obese participants. The levels of &#x3b1;-carotene, &#x3b2;-carotene (both trans and cis isomers), &#x3b2;-cryptoxanthin, lutein/zeaxanthin, and trans-lycopene were quantified via high-performance liquid chromatography. Telomere length was assessed using quantitative polymerase chain reaction.<br><br>RESULTS: Following adjustment for potential confounders, telomere length exhibited an increase of 1.83 base pairs (bp) per unit elevation in &#x3b2;-carotene levels (&#x3b2;&#x2009;=&#x2009;1.83; 95% CI: 0.48, 3.18). Within the fully adjusted model, telomere length incremented by 1.7&#x2009;bp per unit increase in serum &#x3b2;-carotene among overweight individuals (&#x3b2;&#x2009;=&#x2009;1.7; 95% CI: 0.1, 3.3), and by 2.6&#x2009;bp per unit increase among obese individuals (&#x3b2;&#x2009;=&#x2009;2.6; 95% CI: 0.1, 5.0). Furthermore, restricted cubic spline analysis revealed a linear relationship between &#x3b2;-carotene levels and telomere length, whereas a non-linear association was observed between &#x3b2;-cryptoxanthin levels and telomere length.<br><br>CONCLUSION: This investigation indicates that higher serum &#x3b2;-carotene concentrations are linked with extended telomere length in overweight and obese populations in the United States. These findings warrant further validation through prospective studies.},
}
@article {pmid39647990,
year = {2024},
author = {Yang, H and Chen, L and Liu, Y},
title = {Association of leukocyte telomere length with the risk of digestive diseases: A large-scale cohort study.},
journal = {Chinese medical journal},
volume = {},
number = {},
pages = {},
pmid = {39647990},
issn = {2542-5641},
abstract = {BACKGROUND: Leukocyte telomere length (LTL) shortening, a biomarker of telomere attrition, has been linked to multiple diseases. However, the relationship between LTL and digestive diseases remains uncertain. This study aimed to investigate the association between LTL and the risk of digestive diseases.<br><br>METHODS: A cohort analysis of over 500,000 participants from the UK Biobank (UKB) between 2006 and 2021 was conducted to estimate the associations of LTL with more than 90 common digestive diseases. LTL was quantified using multiplex quantitative polymerase chain reaction, and cases of each disease were determined according to inpatient and primary care data. Multivariable Cox proportional hazards regression analysis was used to evaluate the associations of LTL with the risk of digestive diseases. Furthermore, such associations were also evaluated after stratification by sex and ethnicity.<br><br>RESULTS: After a mean follow-up time of 11.8&#xa0;years, over 20 the International Classification of Diseases 10th Revision (ICD-10) codes were observed to be associated with telomere attrition. LTL shortening is associated with an increased risk of several digestive diseases, including gastroesophageal reflux disease (K21: hazard ratio [HR]&#xa0;= 1.30, 95% confidence interval [95% CI]: 1.19-1.42), esophageal ulcer (K221: HR&#xa0;= 1.81, 95% CI: 1.22-2.71), Barrett's esophagus (K227: HR&#xa0;= 1.58 95% CI: 1.14-2.17), gastritis (K29: HR&#xa0;= 1.39, 95% CI: 1.26-1.52), duodenal ulcer (K26: HR&#xa0;= 1.55, 95% CI: 1.14-2.12), functional dyspepsia (K30X: HR&#xa0;= 1.36, 95% CI: 1.06-1.69), non-alcoholic fatty liver disease (NAFLD) (K760: HR&#xa0;= 1.39, 95% CI: 1.09-1.78), liver cirrhosis (K74: HR&#xa0;= 4.73, 95% CI: 3.27-6.85), cholangitis (K830: HR&#xa0;= 2.55, 95% CI: 1.30-5.00), and hernia (K43: HR&#xa0;= 1.50, 95% CI: 1.17-1.94; K44: HR&#xa0;= 1.29, 95% CI: 1.17-1.42). The risk of rectal polyps (K621: HR&#xa0;= 0.77, 95% CI: 0.63-0.92) decreased per unit shortening of LTL.<br><br>CONCLUSIONS: This study suggests that LTL shortening is associated with an increased risk of most digestive diseases except for rectal polyps. These findings may provide some clues for understanding the pathogenesis of digestive diseases.},
}
@article {pmid39647324,
year = {2024},
author = {Li, X and Wang, X and Yu, F and Li, Z and Chen, D and Qi, Y and Lu, Z and Liu, Y and Chen, D and Wu, Y},
title = {Development and validation of a prognostic and drug sensitivity model for gastric cancer utilizing telomere-related genes.},
journal = {Translational oncology},
volume = {52},
number = {},
pages = {102232},
doi = {10.1016/j.tranon.2024.102232},
pmid = {39647324},
issn = {1936-5233},
abstract = {BACKGROUND: Gastric cancer (GC) poses a major global health challenge because of its unfavorable prognosis. Elevated telomerase activity has been linked to the rapid growth and invasiveness of GC tumors. Investigating the expression profiles of telomerase could improve our understanding of the mechanisms underlying telomere-related GC advancement and its applicability as potential targets for diverse therapeutic strategies for GC.<br><br>METHODS: The TCGA and GEO databases were utilized to access transcriptome and clinical data related to GC. After assessing differentially expressed genes (DEGs), a prognostic risk model was developed through Cox univariate regression, LASSO-Cox regression. The prognostic risk model was validated using data from the GSE62254 cohort. The significant influence of the risk model on the tumor immune microenvironment (TIME) and its sensitivity to various drugs was assessed.<br><br>RESULTS: Differential expression analysis identified 328 significantly telomere-related DEGs in GC, with 35 of them showing a significant association with GC prognosis. A predictive risk model composed of four telomere-related genes (TRGs) was established, enabling the accurate stratification of GC patients into two distinct prognostic groups. The LASSO risk model demonstrated notable variations in immune-cell infiltration and drug sensitivity patterns between high- and low-risk groups.<br><br>CONCLUSIONS: The study establishes suggestive relationships between four TRGs (LRRN1, SNCG, GAMT, and PDE1B) and the prognosis of GC. The comprehensive characterization of the TRG model reveals their possible roles in the prognosis, TIME, and drug sensitivity in GC.},
}
@article {pmid39642730,
year = {2024},
author = {Li, R and Chen, G and Liao, W and Yuchi, Y and Yang, X and Zhang, Z and Liu, X and Mao, Z and Li, L and Zhao, J and Li, H and Huo, W and Guo, Y and Li, S and Wu, W and Wang, C and Hou, J},
title = {The role of telomere shortening in ambient ozone exposure-related insulin resistance.},
journal = {Journal of hazardous materials},
volume = {484},
number = {},
pages = {136768},
doi = {10.1016/j.jhazmat.2024.136768},
pmid = {39642730},
issn = {1873-3336},
abstract = {BACKGROUND: Ozone (O3) exposure and telomere shortening are associated with insulin resistance (IR). However, the role of telomere shortening in ambient O3 exposure-related IR is largely unclear.<br><br>METHODS: The Henan Rural Cohort recruited participants and performed a random forest method to estimate residential O3 concentration. IR was reflected by homeostasis model assessment-IR, quantitative insulin sensitivity check index, triglyceride and glucose index, etc. Generalized linear model, quantile regression model, and mediation effects analysis were utilized to assess the associations of O3 exposure and relative telomere length (RTL) with longitudinal IR markers and their change rates. Furthermore, the role of telomere homeostasis in O3-exposure-induced IR in vivo and in vitro experiments was verified.<br><br>RESULTS: O3 exposure was positively associated with longitudinal IR. The proportions of RTL mediated associations between O3 exposure and longitudinal IR markers ranged from 11.92&#xa0;% to 60.36&#xa0;%. O3-exposed mice exhibited a higher glucose load, upregulation of GSK-3&#x3b2; and G-6-Pase expression at mRNA levels, glycogen accumulation reduction, telomere shortening, and decreased telomerase reverse transcriptase activity relative to air-exposed mice. In vitro experiments reveal that overexpression of TERT in HepG2 cells up-regulated G-6-Pase mRNA expression level.<br><br>CONCLUSIONS: Impaired telomere homeostasis may be involved in O3 exposure-related IR via inhibition of glycogen synthesis and acceleration of gluconeogenesis and the specific mechanisms are still further elucidated.},
}
@article {pmid39639361,
year = {2024},
author = {Tan, L and Zhong, MM and Zhao, YQ and Feng, Y and Ye, Q and Hu, J and Ou-Yang, ZY and Chen, NX and Su, XL and Zhang, Q and Liu, Q and Yuan, H and Wang, MY and Feng, YZ and Guo, Y},
title = {The role of circulating polyunsaturated fatty acids in mediating the effect of BMI on leukocyte telomere length: analysis using Mendelian randomization.},
journal = {Nutrition &amp; metabolism},
volume = {21},
number = {1},
pages = {104},
pmid = {39639361},
issn = {1743-7075},
support = {202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; 202208043514//The Hunan Provincial Health Commission/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (81800788 and 81773339)//the National Natural Science Foundation of China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (2017WK2041 and 2018SK52511)//the Science and Technology Department of Hunan Province, China/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; (kq2202403 and kq2202412)//the Natural Science Foundation of Changsha City/ ; },
abstract = {BACKGROUND: polyunsaturated fatty acids (PUFAs) are a category of fatty acids that contain omega-3 and omega-6 fatty acids, which constitute a substantial portion of the Western diet and are vital for maintaining human wellness. The extent to which circulating PUFAs influence the effects of BMI on leukocyte telomere length (LTL) is unknown. Additionally, the impact of circulating PUFA on LTL remains controversial in observational studies.<br><br>METHODS: Using publicly accessible datasets, a genome-wide association study (GWAS) was carried out to determine genetic association estimates for BMI, circulating PUFAs, and LTL. The circulating PUFAs considered were omega-3 PUFAs (i.e., docosahexaenoic acid (DHA) and total omega-3 PUFAs) and omega-6 PUFAs (i.e., linoleic acid (LA) and total omega-6 PUFAs). Two-sample Mendelian randomization (MR) was used to investigate the causal relationships between BMI and PUFA with LTL. Additionally, we examined whether certain PUFA mediate the impact of BMI on LTL.<br><br>RESULTS: None of the evidence supported a causal effect of genetically predicted DHA and total omega-3 PUFA on LTL (DHA: &#x3b2;&#x2009;=&#x2009;0.001, 95% CI: -0.023 to 0.026, p&#x2009;=&#x2009;0.926; total omega-3 PUFA: &#x3b2;&#x2009;=&#x2009;0.008, 95% CI: -0.013 to 0.029, p&#x2009;=&#x2009;0.466). After conducting sensitivity analyses to account for various models of horizontal pleiotropy, the causal association between higher levels of LA and longer LTL persisted (&#x3b2;&#x2009;=&#x2009;0.034, 95% CI 0.016 to 0.052, p&#x2009;<&#x2009;0.001). Adjusting for LA in genetics reduced the effect of BMI on LTL from &#x3b2; = -0.039 (95% CI: -0.058 to -0.020, p&#x2009;<&#x2009;0.001) to -0.034 (95% CI: -0.054 to -0.014, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: This MR study indicates that an increase in genetically predicted circulating LA levels is associated with longer LTL. Additionally, it appears that circulating LA levels play a role in mediating some of the impact that BMI has on LTL.},
}
@article {pmid39639031,
year = {2024},
author = {Dai, M and Li, K and Sacirovic, M and Zemmrich, C and Ritter, O and Bramlage, P and Persson, AB and Buschmann, E and Buschmann, I and Hillmeister, P},
title = {Cell-free plasma telomere length correlated with the risk of cardiovascular events using machine learning classifiers.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {30390},
pmid = {39639031},
issn = {2045-2322},
mesh = {Humans ; *Machine Learning ; Male ; Female ; Middle Aged ; *Coronary Artery Disease/blood/diagnosis ; Retrospective Studies ; Aged ; *Heart Failure/blood/diagnosis ; Telomere ; Biomarkers/blood ; Telomere Homeostasis ; Risk Factors ; },
abstract = {This retrospective study explored the association between circulating cell-free plasma telomere length (cf-TL) and coronary artery disease (CAD) and heart failure (HF). Data from 518 participants were collected, including clinical and laboratory data. cf-TL was measured in plasma samples and machine learning (ML) classification models were developed to differentiate between CAD, HF and control conditions. Our results showed that cf-TL was significantly prolonged in HF patients compared to controls, but no significant difference was observed between CAD patients and controls. Additionally, cf-TL was significantly correlated with nitric oxide metabolites (NOx) and flow-mediated dilation (FMD), suggesting a potential link with endothelial function. To avoid data leakage and ensure the model captured only relationships relevant to the research question, we utilized a temporal data split, holding out the last year's data for testing (n = 81) and using the remaining data for training (n = 324) and validation (n = 109). The ML models using four variables achieved an area under the curve (AUC) of 0.795 in the validation dataset and 0.717 in the test dataset for CAD classification, and 0.829 in the validation dataset and 0.806 in the test dataset for HF classification. SHAP analysis revealed that cf-TL had minimal impact on the predictions of the CAD model, as indicated by consistently low SHAP values, whereas in the HF model, cf-TL exhibited a broader range of SHAP values, indicating a greater contribution to the model's classification. These findings suggest that cf-TL may play a more prominent role in HF pathophysiology and could serve as a valuable biomarker for predicting HF risk. Further studies are warranted to explore cf-TL's diagnostic and prognostic potential across different cardiovascular diseases.},
}
@article {pmid39638969,
year = {2024},
author = {Sadr, Z and Ghasemi, M and Jafarpour, S and Seyfi, R and Ghasemi, A and Boustanipour, E and Khorshid, HRK and Ehtesham, N},
title = {Beginning at the ends: telomere and telomere-based cancer therapeutics.},
journal = {Molecular genetics and genomics : MGG},
volume = {300},
number = {1},
pages = {1},
pmid = {39638969},
issn = {1617-4623},
mesh = {Humans ; *Neoplasms/genetics/therapy/drug therapy ; *Telomere/genetics/metabolism ; *Telomerase/genetics/metabolism ; *Telomere Homeostasis ; Animals ; },
abstract = {Telomeres, which are situated at the terminal ends of chromosomes, undergo a reduction in length with each cellular division, ultimately reaching a critical threshold that triggers cellular senescence. Cancer cells circumvent this senescence by utilizing telomere maintenance mechanisms (TMMs) that grant them a form of immortality. These mechanisms can be categorized into two primary processes: the reactivation of telomerase reverse transcriptase and the alternative lengthening of telomeres (ALT) pathway, which is dependent on homologous recombination (HR). Various strategies have been developed to inhibit telomerase activation in 85-95% of cancers, including the use of antisense oligonucleotides such as small interfering RNAs and endogenous microRNAs, agents that simulate telomere uncapping, expression modulators, immunotherapeutic vaccines targeting telomerase, reverse transcriptase inhibitors, stabilization of G-quadruplex structures, and gene therapy approaches. Conversely, in the remaining 5-15% of human cancers that rely on ALT, mechanisms involve modifications in the chromatin environment surrounding telomeres, upregulation of TERRA long non-coding RNA, enhanced activation of the ataxia telangiectasia and Rad-3-related protein kinase signaling pathway, increased interactions with nuclear receptors, telomere repositioning driven by HR, and recombination events between non-sister chromatids, all of which present potential targets for therapeutic intervention. Additionally, combinatorial therapy has emerged as a strategy that employs selective agents to simultaneously target both telomerase and ALT, aiming for optimal clinical outcomes. Given the critical role of anti-TMM strategies in cancer treatment, this review provides an overview of the latest insights into the structure and function of telomeres, their involvement in tumorigenesis, and the advancements in TMM-based cancer therapies.},
}
@article {pmid39638831,
year = {2024},
author = {Zhu, N and Wang, X and Zhu, H and Zheng, Y},
title = {Exploring the role of alternative lengthening of telomere-related genes in diagnostic modeling for non-alcoholic fatty liver disease.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {30309},
pmid = {39638831},
issn = {2045-2322},
mesh = {*Non-alcoholic Fatty Liver Disease/genetics/pathology/diagnosis/metabolism ; Animals ; Mice ; Humans ; Telomere Homeostasis/genetics ; Disease Models, Animal ; Gene Regulatory Networks ; Gene Expression Profiling ; Telomere/genetics/metabolism ; Prognosis ; },
abstract = {Previous studies have reported an association between telomere length and non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the involvement of alternative lengthening of telomere-related genes (ALTRGs) in the pathology of NAFLD, construct a risk signature, and evaluate both treatment and prognosis. Three NAFLD datasets (GSE48452, GSE89632, and GSE63067) were collected from the GEO database and merged into combined GEO datasets. ALTRGs were collected from GeneCards and PubMed databases. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. This study employed a support vector machine algorithm and least absolute shrinkage and selection operator regression analysis to identify key genes for constructing a diagnostic model. High- and low-risk groups were identified from the combined GEO datasets using the diagnostic model. Gene set enrichment analysis, regulatory network analysis, and intergroup immune infiltration analysis were performed. This study identified the key genes using receiver operating characteristic and Friends analysis. Expression of these genes was validated in a mouse model of NAFLD. Twenty-five genes were differentially expressed, with a positive correlation between FOS and EGR1 and a negative correlation between MYC and CEBPA. A diagnostic model was constructed using 12 genes, and high- and low-risk groups were identified. CAMK2G, ERBB2, FOSB, WT1, and CEBPA showed certain accuracy, and their expression levels were significantly different in the model. Immune infiltration analysis between the risk groups revealed that six immune cells were statistically significant. This includes a strong negative interaction between type 2 T helper cells and SPHK2 in the high-risk group. These findings suggest that ALTRDEGs are potential therapeutic targets and prognostic indicators for NAFLD. However, further investigations are required to elucidate the specific underlying mechanisms.},
}
@article {pmid39636971,
year = {2024},
author = {Liu, J and Li, Q and Hu, Y and Yu, Y and Zheng, K and Li, D and Qin, L and Yu, X},
title = {The complete telomere-to-telomere sequence of a mouse genome.},
journal = {Science (New York, N.Y.)},
volume = {386},
number = {6726},
pages = {1141-1146},
doi = {10.1126/science.adq8191},
pmid = {39636971},
issn = {1095-9203},
mesh = {Animals ; Mice ; *Telomere/genetics ; *Genome ; Repetitive Sequences, Nucleic Acid ; Sequence Analysis, DNA ; Mouse Embryonic Stem Cells ; Haploidy ; },
abstract = {The current reference genome of Mus musculus, GRCm39, has major gaps in both euchromatic and heterochromatic regions associated with repetitive sequences. In this work, we have sequenced and assembled the telomere-to-telomere genome of mouse haploid embryonic stem cells. The results reveal more than 7.7% of previously uncovered sequences of the mouse genome, including ribosomal DNA arrays and pericentromeric and subtelomeric regions, as well as an additional 140 genes predicted to be protein-coding. This study helps to address knowledge gaps in the mouse genome.},
}
@article {pmid39636650,
year = {2024},
author = {Myllymäki, M and Reilly, CR},
title = {Somatic symphony: telomeres and CH.},
journal = {Blood},
volume = {144},
number = {23},
pages = {2369-2371},
doi = {10.1182/blood.2024026841},
pmid = {39636650},
issn = {1528-0020},
}
@article {pmid39635126,
year = {2024},
author = {Burkert, M and Blanc, E and Thiessen, N and Weber, C and Toedling, J and Monti, R and Dombrowe, VM and Stella de Biase, M and Kaufmann, TL and Haase, K and Waszak, SM and Eggert, A and Beule, D and Schulte, JH and Ohler, U and Schwarz, RF},
title = {Copy-number dosage regulates telomere maintenance and disease-associated pathways in neuroblastoma.},
journal = {iScience},
volume = {27},
number = {10},
pages = {110918},
pmid = {39635126},
issn = {2589-0042},
abstract = {Telomere maintenance in neuroblastoma is linked to poor outcome and caused by either telomerase reverse transcriptase (TERT) activation or through alternative lengthening of telomeres (ALT). In contrast to TERT activation, commonly caused by genomic rearrangements or MYCN amplification, ALT is less well understood. Alterations at the ATRX locus are key drivers of ALT but only present in ∼50% of ALT tumors. To identify potential new pathways to telomere maintenance, we investigate allele-specific gene dosage effects from whole genomes and transcriptomes in 115 primary neuroblastomas. We show that copy-number dosage deregulates telomere maintenance, genomic stability, and neuronal pathways and identify upregulation of variants of histone H3 and H2A as a potential alternative pathway to ALT. We investigate the interplay between TERT activation, overexpression and copy-number dosage and reveal loss of imprinting at the RTL1 gene associated with poor clinical outcome. These results highlight the importance of gene dosage in key oncogenic mechanisms in neuroblastoma.},
}
@article {pmid39633874,
year = {2024},
author = {Almuraikhy, S and Naja, K and Anwardeen, N and Sellami, M and Al-Amri, HS and Al-Sulaiti, H and Bashraheel, SS and Aden, AA and Elrayess, MA},
title = {Metabolic signatures of combined exercise and fasting: an expanded perspective on previous telomere length findings.},
journal = {Frontiers in aging},
volume = {5},
number = {},
pages = {1494095},
pmid = {39633874},
issn = {2673-6217},
abstract = {INTRODUCTION: Aging is a complex process marked by a gradual decline in physiological function and increased susceptibility to diseases. Telomere length is frequently regarded as one of the primary biomarkers of aging. Metabolic profiles are key features in longevity and have been associated with both age and age-related diseases. We previously reported an increase in the telomere length in healthy female subjects when Ramadan fasting was combined with physical training. This study aims to characterize the metabolic signature differentiating the combined effects of exercise and fasting from exercise alone and explore the correlations with the previously reported telomere length changes.<br><br>METHODS: Twenty-nine young, non-obese, and healthy female subjects were previously randomized into two groups: one group followed a 4-week exercise program, while the other group followed the same 4-week exercise program but also fasted during Ramadan. Metabolic profiles were assessed pre- and post-intervention using untargeted metabolomics.<br><br>RESULTS AND DISCUSSION: Our results showed a significant decrease in many lipid metabolites in the exercise-while-fasting group, particularly ceramides. Our study sheds light on the dynamic changes in lipid metabolism and its potential role in inflammation and age-related diseases, and contributes to the broader understanding of how lifestyle factors can influence cellular aging and metabolic health.},
}
@article {pmid39633416,
year = {2024},
author = {Wang, Q and Gao, Y and Song, J and Taiwaikuli, D and Ding, H and Yang, X and Tang, B and Zhou, X},
title = {DNA methylation-based telomere length is more strongly associated with cardiovascular disease and long-term mortality than quantitative polymerase chain reaction-based telomere length: evidence from the NHANES 1999-2002.},
journal = {Clinical epigenetics},
volume = {16},
number = {1},
pages = {177},
pmid = {39633416},
issn = {1868-7083},
support = {82260064//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Cardiovascular Diseases/genetics/mortality ; Female ; Male ; Middle Aged ; Aged ; *DNA Methylation/genetics ; *Nutrition Surveys ; *Telomere/genetics ; Telomere Homeostasis/genetics ; Polymerase Chain Reaction/methods ; Proportional Hazards Models ; Cohort Studies ; },
abstract = {BACKGROUND: Telomere length (TL) serves as a pivotal gauge of cellular aging, with shorter TL linked to various age-related ailments. Recently, a DNA methylation-based TL estimator, known as DNAmTL, has emerged as a novel TL measurement tool. Our current investigation scrutinized the correlation between DNAmTL and the risks of cardiovascular disease (CVD) and enduring mortality among middle-aged and elderly individuals.<br><br>METHODS: We enrolled a nationwide, population-based cohort of subjects from the National Health and Nutrition Examination Survey spanning 1999 to 2002, possessing data on both DNAmTL and quantitative polymerase chain reaction-based TL (qPCRTL). Logistic regression models and Cox proportional hazards models were employed to evaluate the associations of DNAmTL with CVD risk and mortality, respectively.<br><br>RESULTS: The cohort comprised 2532 participants, with a weighted CVD prevalence of 19.06%. Notably, each one-kilobase increase in DNAmTL was linked to a 53% diminished CVD risk [odds ratio (OR): 0.47, 95% confidence interval (CI): 0.23-0.95, P&#x2009;=&#x2009;0.035]. Over a median follow-up period of 206&#xa0;months, 1361 deaths were recorded (53.75%), with 590 (23.30%) ascribable to CVD. Individuals with the lengthiest DNAmTL exhibited a 36% lower risk of all-cause mortality (hazard ratio (HR): 0.64, 95% CI: 0.49-0.85, P&#x2009;=&#x2009;0.002) and a 35% decrease in CVD mortality (HR: 0.65, 95% CI: 0.43-0.98, P&#x2009;=&#x2009;0.044) compared to those with shortest DNAmTL. Notably, a stronger association with age was observed for DNAmTL compared to qPCRTL (r&#x2009;=&#x2009;-0.58 vs. r&#x2009;=&#x2009;-&#x2009;0.25). Analysis of receiver operating characteristic (ROC) curves suggested superior predictive performance of DNAmTL over qPCRTL for CVD (area under curve (AUC): 0.63 vs. 0.55, P&#x2009;<&#x2009;0.001), all-cause (AUC: 0.74 vs. 0.62, P&#x2009;<&#x2009;0.001), and CVD mortality (AUC: 0.75 vs. 0.64, P&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Longer DNAmTL was positively correlated with reduced CVD risk and long-term mortality in middle-aged and elderly cohorts. Notably, DNAmTL outperformed qPCRTL as an aging biomarker in the stratification of CVD risks and mortality.},
}
@article {pmid39633034,
year = {2024},
author = {Saraswati, S and Martínez, P and Serrano, R and Mejías, D and Graña-Castro, O and Álvarez Díaz, R and Blasco, MA},
title = {Author Correction: Renal fibroblasts are involved in fibrogenic changes in kidney fibrosis associated with dysfunctional telomeres.},
journal = {Experimental &amp; molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s12276-024-01370-4},
pmid = {39633034},
issn = {2092-6413},
}
@article {pmid39628055,
year = {2024},
author = {Wang, X and Sun, Z and Qi, F and Zhou, Z and Du, P and Shi, L and Dong, W and Huang, B and Han, S and Pavan, S and Zhang, M and Cui, M and Xu, J and Liu, H and Qin, L and Zhang, Z and Dai, X and Gao, W and Miao, L and Zhao, R and Wang, J and Wang, M and Zhi, C and Hu, Y and Zhao, H and Chen, L and Jin, X and Sun, Y and Zheng, Z and Zhang, X},
title = {A telomere-to-telomere genome assembly of the cultivated peanut.},
journal = {Molecular plant},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molp.2024.12.001},
pmid = {39628055},
issn = {1752-9867},
}
@article {pmid39624822,
year = {2024},
author = {Saretzki, G},
title = {Editorial: Chronic stress, telomeres and aging.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1504405},
pmid = {39624822},
issn = {1664-2392},
}
@article {pmid39623492,
year = {2024},
author = {Sumesh, D and Lin, J and Wojcicki, JM},
title = {High school diploma is associated with longer postpartum leukocyte telomere length in a cohort of primarily Latina women.},
journal = {Maternal health, neonatology and perinatology},
volume = {10},
number = {1},
pages = {25},
pmid = {39623492},
issn = {2054-958X},
abstract = {OBJECTIVE: This study investigates correlates of maternal leukocyte telomere length (LTL) in the immediate postpartum period using a cross-sectional study design from an existing prospective longitudinal birth cohort of primarily Latina women. The study focuses on the role of maternal health and dietary habits in pregnancy and maternal education level and LTL at delivery.<br><br>STUDY DESIGN: Latina mothers were recruited during the immediate postpartum period prior to 24&#xa0;h at two San Francisco hospitals and dried blood spots were collected for LTL analysis via quantitative polymerase chain reaction (qPCR). We used multivariable linear regression models to determine independent predictors of maternal LTL during the postpartum period.<br><br>RESULTS: In multivariable regression models, increasing maternal age was associated with shorter LTL during the immediate postpartum period (Coeff -&#x2009;0.015; p&#x2009;<&#x2009;0.01) whereas having a high school diploma was associated with longer LTL versus not having graduated from high school (Coeff 0.12; p&#x2009;<&#x2009;0.01).<br><br>CONCLUSION: Maternal education level as a potential marker of exposure to life stressors and socioeconomic status was associated with maternal LTL after adjusting for age and other potential confounders in women of reproductive age.},
}
@article {pmid39618119,
year = {2024},
author = {Chen, J and Liu, H and Pang, Y and Wang, Y and Ren, Z and Liu, J and Nan, Y and Liu, D},
title = {Genetic Association of Chronic Pains and Analgesics With Telomere Length: A Mendelian Randomization Study.},
journal = {Biological research for nursing},
volume = {},
number = {},
pages = {10998004241303536},
doi = {10.1177/10998004241303536},
pmid = {39618119},
issn = {1552-4175},
abstract = {Objective: The aim of this study was to explore the causal relationships between chronic pains (back pain, facial pain, general pain, headaches, knee pain, hip pain, neck/shoulder pain, stomach/abdominal pain) and analgesics (codeine, diclofenac, ibuprofen, morphine, paracetamol, tramadol) with telomere length using Mendelian randomization methods. Methods: In the study, various statistical methods including inverse variance weighted (IVW), Mendelian Randomization-Egger, weighted median, simple mode, and weighted mode were used to investigate the relationships between chronic pains, analgesics, and telomere length. Heterogeneity and pleiotropy tests were conducted to ensure the accuracy of the results. Results: The results of the IVW analysis revealed positive causal relationships between hip pain (odds ratio (OR): 1.145; 95% confidence interval (CI): 1.021-1.285; p = .020), and stomach/abdominal pain (OR: 1.100; 95% CI: 1.008-1.200; p = 0.033) with telomere length. Use of tramadol (OR: 0.074; 95% CI: 0.009-0.605; p = 0.015) had a negative causal relationships with telomere length. Conclusion: This study found positive associations between hip pain and stomach/abdominal pain with telomere length, and a negative association between tramadol and telomere length. However, no significant causal relationships were found with other types of chronic pains and analgesics. This could help develop healthier chronic pain treatments, avoiding the abuse of analgesics.},
}
@article {pmid39616267,
year = {2024},
author = {Kvarnung, M and Pettersson, M and Chun-On, P and Rafati, M and McReynolds, LJ and Norberg, A and Moura, PL and Pesonen, I and Chaireti, R and Grönros Söderholm, B and Burlin, J and Rydén, J and Lindberg, EH and Giri, N and Savage, SA and Agarwal, S and Nordgren, A and Tesi, B},
title = {Identification of biallelic POLA2 variants in two families with an autosomal recessive telomere biology disorder.},
journal = {European journal of human genetics : EJHG},
volume = {},
number = {},
pages = {},
pmid = {39616267},
issn = {1476-5438},
support = {SLS-973171//Svenska L&#xe4;kares&#xe4;llskapet (Swedish Society of Medicine)/ ; FoUI-985957//Stockholms L&#xe4;ns Landsting (Stockholm County Council)/ ; FoUI-972766//Stockholms L&#xe4;ns Landsting (Stockholm County Council)/ ; },
abstract = {POLA2 encodes the accessory subunit of DNA polymerase α (polα)/primase, which is crucial for telomere C-strand fill-in. Incomplete fill-in of the C-rich telomeric strand after DNA replication has been proposed as a mechanism for Coats plus syndrome, a phenotype within the broader spectrum of telomere biology disorders (TBD). Coats plus syndrome has so far been associated with pathogenic variants in POT1, CTC1, and STN1. Here we report the findings of biallelic deleterious rare variants in POLA2 gene detected by whole genome sequencing and segregation analysis in five young adults from two unrelated families. All five individuals displayed abnormally short telomeres and a clinical phenotype suggesting a TBD disorder with Coats plus features including retinal and gastrointestinal telangiectasias. Our results suggest POLA2 as a novel autosomal recessive gene for a TBD with Coats plus features.},
}
@article {pmid39616073,
year = {2024},
author = {Modi, P and Pennington, K and Shah, S and Mangaonkar, A and Goswami, U},
title = {Clinical Outcomes of Lung Transplant Recipients with Myelodysplastic Syndrome and Short Telomere Syndrome-Case Series.},
journal = {Transplantation proceedings},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.transproceed.2024.10.038},
pmid = {39616073},
issn = {1873-2623},
abstract = {Limited data exists concerning the postlung transplantation outcomes of patients diagnosed with myelodysplastic syndrome (MDS). We delineate the clinical trajectories and outcomes for 3 patients with MDS and Short Telomere Syndrome (STS) who underwent lung transplantation. Our findings suggest that patients with STS and low-risk MDS, especially those harboring the SF3B1 mutation, tolerated standard immunosuppression and antimicrobial prophylaxis well without significant deviation from a typical post-transplant course. Therefore, individuals with low-risk MDS should not be automatically excluded from lung transplantation consideration. Post-transplant monitoring is crucial to promptly detect and manage cytopenias. Conversely, our patient, diagnosed with high-risk MDS post-transplantation faced a poor prognosis, with severe cytopenias limiting immunosuppression treatment and resulting in rejection. Thus, abundance of caution is warranted when contemplating lung transplantation for individuals with high-risk MDS and STS. Further research is necessary to validate these findings.},
}
@article {pmid39615158,
year = {2024},
author = {Tilekli, MM and Yılmaz, AK and Yasul, Y and Çon, N and Mercan, S and Tek, N},
title = {Influence of diet and exercise on leukocyte telomere length, markers of oxidative stress and inflammation in rats.},
journal = {Experimental and molecular pathology},
volume = {140},
number = {},
pages = {104947},
doi = {10.1016/j.yexmp.2024.104947},
pmid = {39615158},
issn = {1096-0945},
abstract = {Telomere length is an important biomarker of biological aging and is affected by nutrition and physical activity. This study investigated the effects of diets with different fat contents and increased physical activity on certain pro/anti-inflammatory and oxidative stress markers and aging. The study is performed in a randomized, experimental, and controlled design with 48 rats, 8 weeks old, divided into 6 different groups (Control (C), exercise (E), unsaturated fat diet (USF), saturated fat diet (SF), unsaturated fat diet + exercise (USF + E), and saturated fat diet + exercise (SF + E)). The rats performed aerobic swimming exercise for 50 days and were fed a diet with different fat content. TAS, TOS, and MDA levels were determined by colorimetric analysis while 8-OHdG, IL-10, and TNF-α were determined by ELISA. Additionally, leukocyte telomere length is determined by the PCR method. Weight changes were also recorded. Plasma TOS, OSI, and TNF-α were lowest in the USF group and highest in the SF and SF + E groups. MDA, 8-OHdG and TG levels were highest in the SF group. The lowest IL-10 level was detected in group C. TL level was the highest in the USF group. There was also a moderate, negative, and significant correlation between telomeres and TOS, OSI, and TNF-α. The groups with the highest body weight gain were C, SF, and SF + E. Diets low in saturated fat or high in unsaturated fat, and physical activity were associated with leukocyte telomere length and alteration of oxidative and pro/anti-inflammatory markers.},
}
@article {pmid39614920,
year = {2024},
author = {Taseva, T and Koycheva, Y and Racheva, R and Raycheva, T and Hodzhev, Y and Nikolova, E and Ilieva, M and Krasteva, M},
title = {Altered Mitochondrial DNA Copy Number and Telomere Length in Patients with Substance Use Disorder: Correlation with Age, Sex, and Chronic Diseases.},
journal = {Biochemical genetics},
volume = {},
number = {},
pages = {},
pmid = {39614920},
issn = {1573-4927},
support = {Grant number KP-06-H25/5//Bulgarian National Science Fund (BNSF), Ministry of Education and Science, Bulgaria/ ; Grant number KP-06-H25/5//Bulgarian National Science Fund (BNSF), Ministry of Education and Science, Bulgaria/ ; Grant number KP-06-H25/5//Bulgarian National Science Fund (BNSF), Ministry of Education and Science, Bulgaria/ ; Grant number KP-06-H25/5//Bulgarian National Science Fund (BNSF), Ministry of Education and Science, Bulgaria/ ; Grant number KP-06-H25/5//Bulgarian National Science Fund (BNSF), Ministry of Education and Science, Bulgaria/ ; Grant number KP-06-H25/5//Bulgarian National Science Fund (BNSF), Ministry of Education and Science, Bulgaria/ ; },
abstract = {Substance use disorder (SUD) is a complex condition involving psychological, sociocultural, and genetic factors. In this study, we examined the alternations in mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) and their relationship to demographic, medical, heredity, and substance use characteristics in patients with SUD and healthy controls. We investigated a total cohort of 54 participants: 21 healthy individuals, 17 patients with alcohol dependence (AD), and 16 patients with drug dependence (DD). TL and mtDNAcn were measured using quantitative real-time PCR, with statistical methods used to assess the association between variables. We observed a significant decrease in mtDNAcn in both SUD groups, particularly associated with chronic diseases in the AD group. No significant differences in TL were found among the three groups. Sex-associated analysis revealed a significant mtDNAcn reduction in the DD males and elevated TL in AD males compared to control males. Correlation analyses showed associations between the two biomarkers and age, sex, and chronic diseases. Our findings suggest that leukocyte mtDNAcn is a more sensitive marker than TL in patients with SUD, indicating sex-specific patterns of alterations. These findings require confirmation through larger cohort recruitment.},
}
@article {pmid39614014,
year = {2024},
author = {Jones-Weinert, C and Mainz, L and Karlseder, J},
title = {Telomere function and regulation from mouse models to human ageing and disease.},
journal = {Nature reviews. Molecular cell biology},
volume = {},
number = {},
pages = {},
pmid = {39614014},
issn = {1471-0080},
abstract = {Telomeres protect the ends of chromosomes but shorten following cell division in the absence of telomerase activity. When telomeres become critically short or damaged, a DNA damage response is activated. Telomeres then become dysfunctional and trigger cellular senescence or death. Telomere shortening occurs with ageing and may contribute to associated maladies such as infertility, neurodegeneration, cancer, lung dysfunction and haematopoiesis disorders. Telomere dysfunction (sometimes without shortening) is associated with various diseases, known as telomere biology disorders (also known as telomeropathies). Telomere biology disorders include dyskeratosis congenita, Høyeraal-Hreidarsson syndrome, Coats plus syndrome and Revesz syndrome. Although mouse models have been invaluable in advancing telomere research, full recapitulation of human telomere-related diseases in mice has been challenging, owing to key differences between the species. In this Review, we discuss telomere protection, maintenance and damage. We highlight the differences between human and mouse telomere biology that may contribute to discrepancies between human diseases and mouse models. Finally, we discuss recent efforts to generate new 'humanized' mouse models to better model human telomere biology. A better understanding of the limitations of mouse telomere models will pave the road for more human-like models and further our understanding of telomere biology disorders, which will contribute towards the development of new therapies.},
}
@article {pmid39613012,
year = {2024},
author = {Liu, Q and Fan, G and Bi, J and Fang, Q and Luo, F and Huang, X and Li, H and Liu, B and Yan, L and Guo, W and Hu, L and Mei, S and Wang, Y and Song, L},
title = {Exposure to multiple metals and leukocyte telomere length in children and adolescents: The mediating effect of thyroid hormones.},
journal = {Environmental research},
volume = {},
number = {},
pages = {120483},
doi = {10.1016/j.envres.2024.120483},
pmid = {39613012},
issn = {1096-0953},
abstract = {Exposure to metals has been related to alterations in leukocyte telomere length (LTL), an aging marker. However, the evidence regarding this relationship in children and adolescents, as well as the underlying mechanisms, remains unclear. Therefore, we aimed to explore the individual and mixture effects of metals on LTL in children and adolescents and to assess the mediating role of thyroid hormones and the modifying effect of a healthy lifestyle. In a cross-sectional study performed in Liuzhou, China, we assessed 5 serum thyroid hormones, 18 urinary metals, and LTL among 1050 children and adolescents aged 6-18 years. We employed multivariate linear regression and weighted quantile sum (WQS) regression to assess the associations of urinary metals with LTL in children and adolescents. Mediation analyses were conducted to explore the effects of thyroid hormones on these relationships. Urinary cobalt (Co), nickel (Ni), strontium (Sr), mercury (Hg), cadmium (Cd), and thallium (Tl) were related to a shorter LTL in children and adolescents. The WQS regression showed a 6.31% (95% CI: -8.76%, -3.79%) decrease in LTL per quartile increase in the WQS index, and identified Ni (23.3%), Sr (21.7%), and Tl (18.0%) as the major contributors. Mediation analyses showed that triiodothyronine (T3) mediated 14.8% and 8.1% of the associations of urinary Sr and Hg with LTL, respectively, and suppressed 9.3% of the association with urinary Co. Furthermore, the inverse associations of Sr, Cd, and Tl with LTL were attenuated among participants who adopted a healthy lifestyle. Our findings suggested that exposure to Co, Ni, Sr, Cd, Hg, Tl, and their mixture were related to a shorter LTL in children and adolescents, potentially mediated by thyroid hormones. Additionally, adopting a healthy lifestyle may alleviate these adverse effects.},
}
@article {pmid39608550,
year = {2024},
author = {Fang, H and Wu, J and Xie, L and Li, Y and Huang, J and Yan, X and He, X and Deng, W and Chen, J and Ji, Y and Li, R and Wen, C and Yu, W and Wang, P},
title = {Telomere-to-telomere genome assembly of eggplant (Solanum melongena L.) promotes gene fine localization of the green stripe (GS) in pericarp.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {138094},
doi = {10.1016/j.ijbiomac.2024.138094},
pmid = {39608550},
issn = {1879-0003},
abstract = {Fruit appearance of eggplant is a key commercial trait, and the precise selection of new varieties with diverse aesthetics aligns with current breeding objectives. However, functional genomics research in eggplant remains underdeveloped. Here, we assembled the first telomere-to-telomere (T2T) eggplant genome, as well as chloroplast and mitochondrial genomes for the inbred line 'NO211'. The 1.06-Gb SmT2T genome is anchored to 12 chromosomes, nine of which are gap-free, totaling three gaps. This assembly harbors 36,505 genes and 64.08 % repetitive sequences, identifying 12 centromeres and 22 telomeres. Utilizing the SmT2T genome for bulked segregant analysis (BSA) and forward genetic approach with green-striped 'NO211' and pure green 'P13' as parents, the green stripe (GS) locus was finely mapped to a 9-Kb region on Chr4, containing a single gene, eggplant.04G07850 (GLK protein). Sequence analysis and qRT-PCR revealed that a single-base deletion in the exon of SmGLK in 'P13' led to premature stop codon, and SmGLK expression was significantly higher in the pericarp of 'NO211' compared to 'P13'. A marker was developed and validated in 36 germplasms, demonstrating co-segregation with green-striped rind trait. This study provides an ideal reference genome for eggplant functional genomics studies, facilitating mechanistic research on peel stripe formation and molecular-assisted selection for fruit appearance.},
}
@article {pmid39608081,
year = {2024},
author = {Tan, MY and Zhang, P and Gao, M},
title = {Letter to the editor - "Association of healthy and unhealthy plant-based diets with telomere length".},
journal = {Clinical nutrition (Edinburgh, Scotland)},
volume = {44},
number = {},
pages = {12-13},
doi = {10.1016/j.clnu.2024.11.030},
pmid = {39608081},
issn = {1532-1983},
}
@article {pmid39605578,
year = {2024},
author = {Lin, SY and Futeran, H and Levine, MT},
title = {Adaptive protein coevolution preserves telomere integrity.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.11.11.623029},
pmid = {39605578},
issn = {2692-8205},
abstract = {Many essential conserved functions depend, paradoxically, on proteins that evolve rapidly under positive selection. How such adaptively evolving proteins promote biological innovation while preserving conserved, essential functions remains unclear. Here, we experimentally test the hypothesis that adaptive protein-protein coevolution within an essential multi-protein complex mitigates the deleterious incidental byproducts of innovation under pressure from selfish genetic elements. We swapped a single, adaptively evolving subunit of a telomere protection complex from Drosophila yakuba into its close relative, D. melanogaster . The heterologous subunit uncovered a catastrophic interspecies incompatibility that caused lethal telomere fusions. Restoring six adaptively evolving sites on the protein-protein interaction surface, or introducing the D. yakuba interaction partner, rescued telomere integrity and viability. Our in vivo , evolution-guided manipulations illuminate how adaptive protein-protein coevolution preserves essential functions threatened by an evolutionary pressure to innovate.},
}
@article {pmid39603404,
year = {2024},
author = {Teng, Y and Gao, Y and Liu, L and Zhang, W and Li, C and Lian, B and Sun, H and Sun, L},
title = {Sex differential effects of early maternal separation on PTSD susceptibility in adult rats accompanied by telomere shortening in the hippocampus.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2024.11.058},
pmid = {39603404},
issn = {1873-7544},
abstract = {Early life stress (ELS) is thought to be a leading cause of mental disorders in adulthood, including PTSD. Recent studies have found that such stress has a gender and resilient specific effect on adult PTSD. This study aimed to assess emotion, and cognitive behavior, and to examine the sex differences and resilience of ELS on adult PTSD. At the same time, the expression of hippocampal telomere length and telomere repeat binding factors (TRF1 and TRF2) were detected to explore the mechanism of telomere length change. Rat offspring were separated from their dams (3 h/day or 6 h/day from PND2 ∼ PND14). Then, pups were treated with a single prolonged stress (SPS) procedure when they reached adulthood (PND80). Rats exposed early to MS and SPS showed anxiety-like and depression-like behaviors as well as impaired learning and memory. The rats exposed to MS3h showed reduced anxiety-like and depression-like behavior upon re-experiencing "secondary stress" compared to the SPS and MS6h groups. Behavioral results showed no significant gender difference. However, gender and SPS factors significantly affected telomere length and TRF1 and TRF2 gene expression in hippocampus. The SPS effect and MS*SPS interaction significantly impacted TRF1 and TRF2 protein expression. In conclusion, this study shows that MS has different effects on anxiety, depression, and cognitive memory deficits in rats experiencing "secondary stress" in adulthood and is accompanied by telomere shortening in the hippocampus. This reveals the potential impact of early MS on PTSD and provides a new perspective for further research in the field of psychological stress.},
}
@article {pmid39603108,
year = {2024},
author = {Li, X and Li, M and Cheng, J and Guan, S and Hou, L and Zu, S and Yang, L and Wu, H and Li, H and Fan, Y and Zhang, B},
title = {"Reply - Letter to the editor" - "Association of healthy and unhealthy plant-based diets with telomere length".},
journal = {Clinical nutrition (Edinburgh, Scotland)},
volume = {44},
number = {},
pages = {9-11},
doi = {10.1016/j.clnu.2024.11.032},
pmid = {39603108},
issn = {1532-1983},
}
@article {pmid39596838,
year = {2024},
author = {Tucker, LA and Bates, CJ},
title = {Telomere Length and Biological Aging: The Role of Strength Training in 4814 US Men and Women.},
journal = {Biology},
volume = {13},
number = {11},
pages = {},
doi = {10.3390/biology13110883},
pmid = {39596838},
issn = {2079-7737},
abstract = {Telomere length is an index of cellular aging. Healthy lifestyles are associated with reduced oxidative stress and longer telomeres, whereas unhealthy behaviors are related to shorter telomeres and greater biological aging. This investigation was designed to determine if strength training accounted for differences in telomere length in a random sample of 4814 US adults. Data from the National Health and Nutrition Examination Survey (NHANES) were employed to answer the research questions using a cross-sectional design. Time spent strength training was calculated by multiplying days of strength training per week by minutes per session. Participation in other forms of physical activity was also calculated based on reported involvement in 47 other activities. Weighted multiple regression and partial correlation were used to calculate the mean differences in telomere length across levels of strength training, adjusting for differences in potential confounders. With the demographic covariates controlled, strength training and telomere length were linearly related (F = 14.7, p = 0.0006). Likewise, after adjusting for all the covariates, the linear association remained strong and significant (F = 14.7, p = 0.0006). In this national sample, 90 min per week of strength training was associated with 3.9 years less biological aging, on average. Regular strength training was strongly related to longer telomeres and less biological aging in 4814 US adults.},
}
@article {pmid39596019,
year = {2024},
author = {Zhao, L and Li, Z and Jiang, S and Xia, C and Deng, K and Liu, B and Wang, Z and Liu, Q and He, M and Zou, M and Xia, Z},
title = {The Telomere-to-Telomere Genome of Jaboticaba Reveals the Genetic Basis of Fruit Color and Citric Acid Content.},
journal = {International journal of molecular sciences},
volume = {25},
number = {22},
pages = {},
doi = {10.3390/ijms252211951},
pmid = {39596019},
issn = {1422-0067},
support = {ZDYF2022XDNY149//Hainan Province Science and Technology Special Fund/ ; },
mesh = {*Fruit/genetics/metabolism ; *Citric Acid/metabolism ; *Genome, Plant ; Telomere/genetics/metabolism ; Myrtaceae/genetics/metabolism ; Gene Expression Regulation, Plant ; Pigmentation/genetics ; Phylogeny ; },
abstract = {Jaboticaba is a typical tropical plant that blossoms and bears fruit on the tree trunks and branches. The fruits resemble grapes in appearance and texture and are also known as "treegrapes". Currently, research on the genomics of jaboticaba is lacking. In this study, we constructed an integrated, telomere-to-telomere (T2T) gap-free reference genome and two nearly complete haploid genomes, thereby providing a high-quality genomic resource. Furthermore, we unveiled the evolutionary history of several species within the Myrtaceae family, highlighting significant expansions in metabolic pathways such as the citric acid cycle, glycolysis/gluconeogenesis, and phenylpropanoid biosynthesis throughout their evolutionary process. Transcriptome analysis of jaboticaba fruits of different colors revealed that the development of fruit skin color in jaboticaba is associated with the phenylpropanoid and flavonoid biosynthesis pathways, with the flavanone 3-hydroxylase (F3H) gene potentially regulating fruit skin color. Additionally, by constructing the regulatory pathway of the citric acid cycle, we found that low citric acid content is correlated with high expression levels of genes such as thiamin diphosphate (ThDP) and low expression of phosphoenolpyruvate carboxykinase (PEPCK), indicating that PEPCK positively regulates citric acid content. These T2T genomic resources will accelerate jaboticaba pepper genetic improvement and help to understand jaboticaba genome evolution.},
}
@article {pmid39595175,
year = {2024},
author = {Lv, J and Zhao, X and Zhao, L and Gong, C and Zheng, W and Guo, L and Wang, J and Liang, T},
title = {The Notable Role of Telomere Length Maintenance in Complex Diseases.},
journal = {Biomedicines},
volume = {12},
number = {11},
pages = {},
pmid = {39595175},
issn = {2227-9059},
support = {62171236//National Natural Science Foundation of China/ ; BE2022799//the Key Project of Social Development in Jiangsu Province, China/ ; 22KJA180006//the Key Projects of Natural Science Research in Universities of Jiangsu Province, China/ ; NA//the Priority Academic Program Development of Jiangsu Higher Education Institution (PAPD)/ ; },
abstract = {Telomere length function serves as a critical biomarker for biological aging and overall health. Its maintenance is linked to cancer, neurodegenerative conditions, and reproductive health. This review mainly examines genetic variations and environmental influences on telomere dynamics, highlighting key regulatory genes and mechanisms. Advances in telomere measurement methodologies are also reviewed, underscoring the importance of precise telomere assessment for disease prevention and treatment. Telomerase activation offers potential for cellular lifespan extension and anti-aging effects, whereas its inhibition emerges as a promising therapeutic approach for cancer. Regulatory mechanisms of tumor suppressor genes on telomerase activity are analyzed, with a comprehensive overview of the current state and future potential of telomerase inhibitors. In addition, the association between telomeres and neurodegenerative diseases is discussed, detailing how telomere attrition heightens disease risk and outlining multiple pathways by which telomerase protects neurons from damage and apoptosis.},
}
@article {pmid39590949,
year = {2024},
author = {Jiang, Y and Xu, Z and Wang, M and Liu, H and Li, Y and Xu, S},
title = {Association Between Prenatal Exposure to Organochlorine Pesticides and Telomere Length in Neonatal Cord Blood.},
journal = {Toxics},
volume = {12},
number = {11},
pages = {},
doi = {10.3390/toxics12110769},
pmid = {39590949},
issn = {2305-6304},
support = {(91643207, 81273083)//National Natural Science Foundation of China/ ; (2017YFC0212003)//National Key R&amp;D Program of China/ ; (JCYJ20210324131213037)//Shenzhen Science and Technology Innovation Committee/ ; (SZSM202103008)//High-Level Project of Medicine in Nanshan, Shenzhen; Sanming Project of Medicine in Shenzhen/ ; },
abstract = {Objectives: Environmental exposure may affect the telomere length (TL) of newborns, which is considered as an early biomarker indicating susceptibility for later life diseases. However, the effects of prenatal organochlorine pesticide (OCP) exposure on newborn TL remain unclear. This study aimed to investigate the association between prenatal exposure levels of OCPs during pregnancy and TL in neonatal cord blood. Methods: A total of 168 mother-infant pairs from a birth cohort in Wuhan, China, were included this study. The concentrations of hexachlorocyclohexanes (HCHs, including β-HCH, α-HCH, and γ-HCH), p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) and its metabolites (p,p'-dichlorodiphenyldichloroethane, p,p'-DDD; p,p'-dichlorodiphenyldichloroethylene, p,p'-DDE) were measured in cord blood. The associations between the OCPs and the TL in newborns were analyzed by a generalized linear regression model. Stratified analyses by newborn sex, maternal gestational weight gain, and pregnancy body mass index (BMI) were performed to evaluate if the associations were modified by these factors. Results: The detection rates of various OCPs ranged from 50.9% to 100.0%. The median concentration of p,p'-DDE was the highest (33.90 ng/g lipid), followed by β-HCH (8.67 ng/g lipid), and the median concentrations of the other OCPs were between 0.12 and 0.33 ng/g lipid. Among the all newborns, a two-fold increase in the γ-HCH concentration in the cord blood was significantly associated with a 0.024 (95% CI: -0.041, -0.007) decrease in the TL. After stratification by newborn sex, the inverse association between γ-HCH and the TL was only statistically significant in boys, but not in girls (P for interaction <0.05). In addition, after stratification by pre-pregnancy BMI, β-HCH and p,p'-DDT concentrations were significantly associated with a decreased TL in the overweight pre-pregnancy BMI group [-0.111 (95% CI: -0.203, -0.018) and -0.036 (95% CI: -0.049, -0.023), respectively]. Conclusions: Prenatal exposure to OCPs during pregnancy was associated with a decreased neonatal telomere length, which may be affected by the newborn sex and pre-pregnancy BMI. These findings may provide new insights into the mechanisms underlying OCP-induced adverse health effects.},
}
@article {pmid39589440,
year = {2024},
author = {Hong, L and Xu, XD and Yang, L and Wang, M and Li, S and Yang, H and Ye, SY and Chen, LL and Song, JM},
title = {Construction and analysis of telomere-to-telomere genomes for 2 sweet oranges: Longhuihong and Newhall (Citrus sinensis).},
journal = {GigaScience},
volume = {13},
number = {},
pages = {},
doi = {10.1093/gigascience/giae084},
pmid = {39589440},
issn = {2047-217X},
support = {KYLX20240900007//Chongqing Municipal Financial Science and Technology Innovation Project/ ; NKY-2022AB005//Ministry of Agriculture/ ; },
mesh = {*Citrus sinensis/genetics ; *Genome, Plant ; *Telomere/genetics ; Genomics/methods ; },
abstract = {BACKGROUND: Sweet orange (Citrus sinensis Osbeck) is a fruit crop of high nutritional value that is widely consumed around the world. However, its susceptibility to low-temperature stress limits its cultivation and production in regions prone to frost damage, severely impacting the sustainable development of the sweet orange industry. Therefore, developing cold-resistant sweet orange varieties is of great necessity. Traditional hybrid breeding methods are not feasible due to the polyembryonic phenomenon in sweet oranges, necessitating the enhancement of its germplasm through molecular breeding. High-quality reference genomes are valuable for studying crop resistance to biotic and abiotic stresses. However, the lack of genomic resources for cold-resistant sweet orange varieties has hindered the progress in developing such varieties and researching their molecular mechanisms of cold resistance.<br><br>FINDINGS: This study integrated PacBio HiFi, ONT, Hi-C, and Illumina sequencing data to assemble telomere-to-telomere (T2T) reference genomes for the cold-resistant sweet orange mutant "Longhuihong" (Citrus sinensis [L.] Osb. cv. LHH) and its wild-type counterpart "Newhall" (C. sinensis [L.] Osb. cv. Newhall). Comprehensive evaluations based on multiple criteria revealed that both genomes exhibit high continuity, completeness, and accuracy. The genome sizes were 340.28 Mb and 346.33 Mb, with contig N50 of 39.31 Mb and 36.77 Mb, respectively. In total, 31,456 and 30,021 gene models were annotated in the respective genomes. Leveraging these assembled genomes, comparative genomics analyses were performed, elucidating the evolutionary history of the sweet orange genome. Moreover, the study identified 2,886 structural variants between the 2 genomes, with several SVs located in the upstream, downstream, or intronic regions of homologous genes known to be associated with cold resistance.<br><br>CONCLUSIONS: The study de novo assembled 2 T2T reference genomes of sweet orange varieties exhibiting different levels of cold tolerance. These genomes serve as valuable foundational resources for genomic research and molecular breeding aimed at enhancing cold tolerance in sweet oranges. Additionally, they expand the existing repository of reference genomes and sequencing data resources for C. sinensis. Moreover, these genomes provide a critical data foundation for comparative genomics analyses across different plant species.},
}
@article {pmid39587573,
year = {2024},
author = {Hassan, R and Bhat, GR and Mir, FA and Ganie, HA and Mushtaq, I and Bhat, MA and Asimi, RP and Afroze, D},
title = {Concomitant telomere attrition is associated with spinal muscular atrophy in highly inbred region of North India: unraveling the thread in Kashmir region.},
journal = {BMC medical genomics},
volume = {17},
number = {1},
pages = {275},
pmid = {39587573},
issn = {1755-8794},
mesh = {Humans ; *Muscular Atrophy, Spinal/genetics ; India ; Male ; Female ; *Telomere Shortening ; *Telomere/genetics ; Child, Preschool ; Child ; Case-Control Studies ; Adolescent ; Infant ; Survival of Motor Neuron 1 Protein/genetics ; Adult ; },
abstract = {Spinal muscular atrophy (SMA) is a rare genetic disorder that unequivocally results in the degeneration of motor neurons, leading to muscle weakness and atrophy. This condition is caused by a mutation in the survival motor neuron 1 (SMN1) gene, which inevitably results in a deficiency of the SMN protein. In present study, we investigated the potential role of telomere attrition in SMA patients. Relative telomere length in peripheral blood lymphocytes was measured by Monochrome Multiplex Quantitative Polymerase Chain Reaction (MMQPCR) in 98 subjects and we conclusively found that SMA cases exhibit telomere attrition compared to healthy controls (P = 4 × 10[- 2]). Moreover, significant attrition was also observed in severe form of SMA, i.e. SMA type 0 (P = 0.04) as well.Although, the exact mechanism through which telomere shortening contributes to the pathogenesis of SMA is not fully understood and is yet to be delineated. However, one possibility is that telomere shortening leads to genomic instability and DNA damage, which can contribute to motor neuron degeneration. Another possibility is that telomere shortening leads to cellular senescence, which can impair the ability of motor neurons to regenerate and repair themselves. Recent studies have suggested that telomere shortening may be a potential therapeutic target in SMA. Thus, understanding the role of SMN1 gene in disease pathogenesis &amp; its effect on telomere length will aid in estimating the risk &amp; prognosis of SMA in genetically less explored &amp; highly inbred region of Kashmir, Northern India.},
}
@article {pmid39586626,
year = {2024},
author = {Baird, DM},
title = {Telomere Dynamics in Human Health and Disease.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041701},
pmid = {39586626},
issn = {1943-0264},
abstract = {Telomere function is critical for genomic stability; in the context of a functional TP53 response, telomere erosion leads to a G1/S cell-cycle arrest and the induction of replicative senescence, a process that is considered to underpin the ageing process in long-lived species. Abrogation of the TP53 pathway allows for continued cell division, telomere erosion, and the complete loss of telomere function; the ensuing genomic instability facilitates clonal evolution and malignant progression. Telomeres display extensive length heterogeneity in the population that is established at birth, and this affects the individual risk of a broad range of diseases, including cardiovascular disease and cancer. In this perspective, I discuss telomere length heterogeneity at the levels of the population, individual, and cell, and consider how the dynamics of these essential chromosomal structures contribute to human disease.},
}
@article {pmid39582797,
year = {2025},
author = {Kaliman, P and Álvarez-López, MJ and Lehodey, A and Fernández, D and Chocat, A and Schlosser, M and de La Sayette, V and Vivien, D and Marchant, NL and Chételat, G and Lutz, A and Poisnel, G and , },
title = {Effect of an 18-Month Meditation Training on Telomeres in Older Adults: A Secondary Analysis of the Age-Well Randomized Controlled Trial.},
journal = {Biological psychiatry global open science},
volume = {5},
number = {1},
pages = {100398},
pmid = {39582797},
issn = {2667-1743},
abstract = {BACKGROUND: Shorter telomeres are associated with increased risk of cognitive decline and age-related diseases. Developing interventions to promote healthy aging by preserving telomere integrity is of paramount importance. Here, we investigated the effect of an 18-month meditation intervention on telomere length (TL) measures in older people without cognitive impairment.<br><br>METHODS: A total of 137 adults age &#x2265;65 years were randomized to one of the 3 groups (meditation training, non-native language training, or passive control). We evaluated the 50th and 20th percentile TL and the percentage of critically short telomeres (<3 kbp) in peripheral blood mononuclear cells.<br><br>RESULTS: Mixed model analysis showed a time effect indicating a general decrease on the 50th percentile TL (F&#xa0;=&#xa0;80.72, p adjusted < .001), without a significant group effect or time&#xa0;&#xd7; group interaction. No significant effect was detected in the 20th percentile TL or the percentage of critically short telomeres. Secondary analysis showed that only in the meditation training group 1) the 50th percentile TL positively correlated with class attendance time (r&#xa0;= 0.45, p adjusted < .011), 2) the 50th and 20th percentile TL positively correlated with responsiveness to the intervention, evaluated through a composite score (r&#xa0;= 0.46, p adjusted < .010 and r&#xa0;= 0.41, p adjusted&#xa0;= .029, respectively), and 3) lower scores on a measure of the personality trait "openness to experience" correlated with a lower percentage of critically short telomeres after the intervention (r&#xa0;= 0.44, p adjusted&#xa0;= .015).<br><br>CONCLUSIONS: In older adults, we found no evidence for a main effect of an 18-month meditation training program on TL compared with the control groups. Our findings highlight the importance of considering the impact of moderating factors when measuring the effectiveness of meditation-based trainings.},
}
@article {pmid39580387,
year = {2024},
author = {Li, P and Meng, L and Tu, H and Luo, S and Gong, X},
title = {The impact of Radioresistant-Related Telomere Genes in the prognosis and immune infiltration in lung adenocarcinoma.},
journal = {Cancer cell international},
volume = {24},
number = {1},
pages = {387},
pmid = {39580387},
issn = {1475-2867},
support = {82473378//National Natural Science Foundation of China/ ; 2021071//Shanghai Talents Development Fund Project/ ; SKPY2021006//Clinical Research fundation of Shanghai Pulmonary Hospital/ ; fkzr2436//National Natural Science Foundation Cultivation Project of Shanghai Pulmonary Hospital/ ; },
abstract = {INTRODUCTION: Lung adenocarcinoma (LUAD), a common subtype of NSCLC, has a high mortality rate. Telomere genes are influenced by radiation therapy, affecting treatment response. Additionally, immune cell presence in the tumor microenvironment plays a crucial role in cancer prognosis. However, the role of Radioresistant-Related Telomere Genes (RRTGs) in LUAD prognosis and immune infiltration remains unclear.<br><br>METHODS: In this research, we utilized diverse bioinformatics techniques to examine our personally tested information along with publicly accessible datasets. We conducted a comprehensive study on the genetic and transcriptional differences, predictive significance, and expression profiles of RRTGs. Afterwards, a RRTGs score was developed to forecast the overall survival (OS) and ascertain its reliable predictive capacity for patients with LUAD. Following this, dependable nomograms were developed to enhance the practicality of RRTGs scoring in a clinical setting. Furthermore, the investigation delved into the associations among RRTGs, infiltration of immune cells, prognosis, and clinical treatments of patients. Gene Set Enrichment Analysis (GSEA) was conducted to explore the potential mechanisms by which RRTGs influence the regulation of LUAD. Then, Western blot, qRT-PCR and Immunohistochemistry were used to detect the expression levels of RRTGs in cell lines and LUAD tumor tissues.<br><br>RESULTS: Our research indicates that certain genes related to telomeres have a notable correlation with the prognosis of patients diagnosed with LUAD. The RRTGs score, which includes three key genes (ARRB1, PLK1, and DSG2), was developed to forecast the OS and its dependable predictive capability for individuals diagnosed with LUAD was ascertained. Afterwards, extremely reliable nomograms were developed to improve the practicality of the RRTGs score. Moreover, as illustrated, genetic characteristics can be utilized to assess the infiltration of immune cells in tumors, as well as clinical attributes and prognosis. RRTGs score characterizes tumor mutational burden, immune activity, and notable survival probabilities in addition. Furthermore, GSEA results revealed that RRTGs may influence LUAD by modulating immune-related pathways in high-risk groups and regulating cell cycle and DNA repair processes in low-risk groups. The RRTGs (ARRB1 and PLK1) were upregulated in A549 cells and radiosensitive NSCLC tissues compared to radioresistant A549 cells and NSCLC tissues.<br><br>CONCLUSION: In conclusion, this research emphasizes the significance of RRTGs in the outlook of LUAD. The findings contributed to a better understanding of the link between radiotherapy, telomere-related genes, and prognosis in LUAD, and identified potential therapeutic targets for patients with LUAD.},
}
@article {pmid39578472,
year = {2024},
author = {Lu, S and Liu, Y and Li, M and Ge, Q and Wang, C and Song, Y and Zhou, B and Chen, S},
title = {Gap-free telomere-to-telomere haplotype assembly of the tomato hind (Cephalopholis sonnerati).},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {1268},
pmid = {39578472},
issn = {2052-4463},
mesh = {*Haplotypes ; *Telomere/genetics ; *Solanum lycopersicum/genetics ; Animals ; High-Throughput Nucleotide Sequencing ; Genome, Plant ; Bees/genetics ; },
abstract = {The tomato hind (Cephalopholis sonnerati) is an emerging economically important grouper in recent years. With the increasing maturity of sequencing technologies and assembly methodologies, a higher quality reference genome has become both accessible and necessary. In this study, we present two telomere-to-telomere (T2T) gap-free haplotype assemblies of the tomato hind with lengths of 1039.53 Mb (YSFRI_Csonn_HA_1.0, N50 43.83 Mb) and 1039.91 Mb (YSFRI_Csonn_HB_1.0, N50 44.09 Mb). Reads from next-generation sequencing, ONT ultra-long sequencing, and PacBio HiFi sequencing exhibited mapping rates exceeding 99.8% when aligned to these two assemblies. Evaluation using Merqury indicated high accuracy for both assemblies, with average quality values of 51.80 and 51.83, respectively. Percentages of 97.9% and 97.8% of complete BUSCOs were achieved, and a total of 23,270 and 23,184 protein-code genes were inferred in each assembly. Moreover, telomere identification, centromere prediction, and repetitive sequence annotation were also successfully performed. These two assemblies provide robust foundation for the genetic analysis and development of molecular genetic breeding technologies in C. sonnerati.},
}
@article {pmid39574740,
year = {2024},
author = {Mohanty, SK and Chiaromonte, F and Makova, KD},
title = {Evolutionary Dynamics of G-Quadruplexes in Human and Other Great Ape Telomere-to-Telomere Genomes.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.11.05.621973},
pmid = {39574740},
issn = {2692-8205},
abstract = {G-quadruplexes (G4s) are non-canonical DNA structures that can form at approximately 1% of the human genome. G4s contribute to point mutations and structural variation and thus facilitate genomic instability. They play important roles in regulating replication, transcription, and telomere maintenance, and some of them evolve under purifying selection. Nevertheless, the evolutionary dynamics of G4s has remained underexplored. Here we conducted a comprehensive analysis of predicted G4s (pG4s) in the recently released, telomere-to-telomere (T2T) genomes of human and other great apes-bonobo, chimpanzee, gorilla, Bornean orangutan, and Sumatran orangutan. We annotated tens of thousands of new pG4s in T2T compared to previous ape genome assemblies, including 41,236 in the human genome. Analyzing species alignments, we found approximately one-third of pG4s shared by all apes studied and identified thousands of species- and genus-specific pG4s. pG4s accumulated and diverged at rates consistent with divergence times between the studied species. We observed a significant enrichment and hypomethylation of pG4 shared across species at regulatory regions, including promoters, 5' and 3'UTRs, and origins of replication, strongly suggesting their formation and functional role in these regions. pG4s shared among great apes displayed lower methylation levels compared to species-specific pG4s, suggesting evolutionary conservation of functional roles of the former. Many species-specific pG4s were located in the repetitive and satellite regions deciphered in the T2T genomes. Our findings illuminate the evolutionary dynamics of G4s, their role in gene regulation, and their potential contribution to species-specific adaptations in great apes, emphasizing the utility of high-resolution T2T genomes in uncovering previously elusive genomic features.},
}
@article {pmid39574517,
year = {2024},
author = {Peker Eyüboğlu, &#x130; and Koca, S and Çelik, B and Güllü Amuran, G and Uğurlu, M&#xdc; and Alan, &#xd6; and Akın Telli, T and Yumuk, PF and Akkiprik, M},
title = {Neoadjuvant Chemotherapy Shortens the cfDNA Telomere Length in Breast Cancer Patients.},
journal = {International journal of breast cancer},
volume = {2024},
number = {},
pages = {6117394},
pmid = {39574517},
issn = {2090-3170},
abstract = {Introduction: Cancer is a genetic disease that affects people worldwide, and breast cancer is the most common cancer in women. Studies have been conducted on molecular parameters to predict tumor behavior and develop therapeutic strategies. Telomeres, which are at the end of chromosomes, have been studied for their relationship with breast cancer, but more research is needed to understand their role in the disease. Circulating-free DNA (cfDNA) is DNA that is free in the bloodstream and is considered a promising target for early cancer detection, treatment response monitoring, and prognosis assessment. This study is aimed at comparing cfDNA telomere length of breast cancer patients and healthy individuals and analyzing the impact of neoadjuvant chemotherapy on telomere length in cfDNA. Materials and Methods: Blood samples were collected from 33 breast cancer patients undergoing neoadjuvant chemotherapy before and after treatment. The quantitative PCR method is used to measure the average telomere lengths. Results: This study found that the telomere length of cfDNA in breast cancer patients before and after treatment is significantly shorter than in the control group. Neoadjuvant chemotherapy is found to shorten the cfDNA telomere length, especially in the treatment-responsive group. Conclusion: Our study suggests that telomere length in cfDNA may be a useful biomarker for predicting therapy response and possible reoccurrence of the disease in breast cancer patients.},
}
@article {pmid39574146,
year = {2024},
author = {Wang, L and Zhang, J and Liu, F and Shi, Q and Gao, F and Li, J and Liu, Y and Kong, F and Xu, D},
title = {Maternal infection of SARS-CoV-2 during the first and second trimesters leads to newborn telomere shortening.},
journal = {Journal of translational medicine},
volume = {22},
number = {1},
pages = {1049},
pmid = {39574146},
issn = {1479-5876},
mesh = {Humans ; Female ; Infant, Newborn ; *COVID-19/virology ; Pregnancy ; *Telomere Shortening ; Adult ; *Pregnancy Complications, Infectious/virology ; *SARS-CoV-2/physiology ; Pregnancy Trimester, Second ; Placenta/virology/metabolism ; Fetal Blood/virology ; Telomere/metabolism ; Cytokines/metabolism/blood ; Male ; },
abstract = {BACKGROUND: Initial telomere length (TL) in newborns is the major determinant for TL in later life while TL in newborn/early-life predicts long-term health and lifespan. It is important to identify key factors that affect telomere homeostasis throughout embryonic development for precision interventions to maintain optimal TL in fetus/prenatal infants. SARS-CoV-2 has caused a widespread global pandemic of COVID-19, but it remains unclear whether maternal SARS-CoV-2 infection impairs prenatal telomere homeostasis.<br><br>METHODS: We recruited 413 normally delivered newborns whose mothers were either non-infected or infected with SARS-CoV-2 during different trimesters of pregnancy (otherwise healthy). Telomere length (TL) in cord blood (CB) was assessed using qPCR. CB and maternal blood were analyzed for cytokine levels. Placental senescence was determined using senescence-associated &#x3b2;-galactosidase staining.<br><br>RESULTS: Control (non-infected maternal) newborn TL was significantly longer than that from maternal infection (1.568&#x2009;&#xb1;&#x2009;0.340 vs 1.390&#x2009;&#xb1;&#x2009;0.350, P&#x2009;=&#x2009;0.005). Such shorter TL was observed only if maternal infection of SARS-CoV-2 occurred in the first and second trimesters of pregnancy (1.261&#x2009;&#xb1;&#x2009;0.340 and 1.346&#x2009;&#xb1;&#x2009;0.353, P&#x2009;<&#x2009;0.0001 and 0.001, respectively). There were no differences in TL between controls and infection at the third trimester (1.568&#x2009;&#xb1;&#x2009;0.340 vs 1.565&#x2009;&#xb1;&#x2009;0.329, P&#x2009;>&#x2009;0.05). Across the first trimester, there was a positive correlation between newborn TL and gestational weeks with maternal infection, suggesting that the earlier maternal infection occurs, the worse effect is taken on fetal telomere homeostasis. Placental senescence coupled with the downregulated expression of telomerase reverse transcriptase was significantly more frequent from the maternal infection at the first trimester. There were no differences in IL-6, C reactive protein and other cytokine levels in CB and maternal serum or placentas.<br><br>CONCLUSIONS: Maternal SARS-CoV-2 infection at the first and second trimesters leads to significantly shorter TL and earlier infection causes much more severe TL damage. The infection-mediated cell senescence and other histopathological abnormalities result in defective placental function through which fetal telomere homeostasis is impaired. Thus, vaccination against COVID-19 should be done in advance for women who plan pregnancy.},
}
@article {pmid39568075,
year = {2024},
author = {Di Pietro, E and Burla, R and La Torre, M and González-García, MP and Dello Ioio, R and Saggio, I},
title = {Telomeres: an organized string linking plants and mammals.},
journal = {Biology direct},
volume = {19},
number = {1},
pages = {119},
pmid = {39568075},
issn = {1745-6150},
support = {A0375E0189-2020-36640//POR FESR Lazio 2014-2020/ ; 20229LHY5L//Ministero dell'Universit&#xe0; e della Ricerca/ ; IG-24614//Fondazione AIRC per la ricerca sul cancro ETS/ ; },
abstract = {Telomeres are pivotal determinants of cell stemness, organismal aging, and lifespan. Herein, we examined similarities in telomeres of Arabidopsis thaliana, mice, and humans. We report the common traits, which include their composition in multimers of TTAGGG sequences and their protection by specialized proteins. Moreover, given the link between telomeres, on the one hand, and cell proliferation and stemness on the other, we discuss the counterintuitive convergence between plants and mammals in this regard, focusing on the impact of niches on cell stemness. Finally, we suggest that tackling the study of telomere function and cell stemness by taking into consideration both plants and mammals can aid in the understanding of interconnections and contribute to research focusing on aging and organismal lifespan determinants.},
}
@article {pmid39567477,
year = {2024},
author = {Wu, H and Luo, LY and Zhang, YH and Zhang, CY and Huang, JH and Mo, DX and Zhao, LM and Wang, ZX and Wang, YC and He-Hua, E and Bai, WL and Han, D and Dou, XT and Ren, YL and Dingkao, R and Chen, HL and Ye, Y and Du, HD and Zhao, ZQ and Wang, XJ and Jia, SG and Liu, ZH and Li, MH},
title = {Telomere-to-telomere genome assembly of a male goat reveals variants associated with cashmere traits.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {10041},
pmid = {39567477},
issn = {2041-1723},
support = {2021YFD1200900//Ministry of Science and Technology of the People&apos;s Republic of China (Chinese Ministry of Science and Technology)/ ; },
mesh = {Animals ; *Goats/genetics ; *Telomere/genetics ; Male ; *Polymorphism, Single Nucleotide ; *Genome/genetics ; Breeding ; Genetic Variation ; Y Chromosome/genetics ; Genomic Structural Variation ; },
abstract = {A complete goat (Capra hircus) reference genome enhances analyses of genetic variation, thus providing insights into domestication and selection in goats and related species. Here, we assemble a telomere-to-telomere (T2T) gap-free genome (2.86 Gb) from a cashmere goat (T2T-goat1.0), including a Y chromosome of 20.96 Mb. With a base accuracy of >99.999%, T2T-goat1.0 corrects numerous genome-wide structural and base errors in previous assemblies and adds 288.5 Mb of previously unresolved regions and 446 newly assembled genes to the reference genome. We sequence the genomes of five representative goat breeds for PacBio reads, and use T2T-goat1.0 as a reference to identify a total of 63,417 structural variations (SVs) with up to 4711 (7.42%) in the previously unresolved regions. T2T-goat1.0 was applied in population analyses of global wild and domestic goats, which revealed 32,419 SVs and 25,397,794 SNPs, including 870 SVs and 545,026 SNPs in the previously unresolved regions. Also, our analyses reveal a set of selective variants and genes associated with domestication (e.g., NKG2D and ABCC4) and cashmere traits (e.g., ABCC4 and ASIP).},
}
@article {pmid39563242,
year = {2024},
author = {Ferguson, S and Bar-Ness, YD and Borevitz, J and Jones, A},
title = {Correction: A telomere-to-telomere Eucalyptus regnans genome: unveiling haplotype variance in structure and genes within one of the world's tallest trees.},
journal = {BMC genomics},
volume = {25},
number = {1},
pages = {1107},
doi = {10.1186/s12864-024-10952-5},
pmid = {39563242},
issn = {1471-2164},
}
@article {pmid39561615,
year = {2024},
author = {Panelli, DM and Mayo, JA and Wong, RJ and Becker, M and Feyaerts, D and Marić, I and Wu, E and Gotlib, IH and Gaudillière, B and Aghaeepour, N and Druzin, ML and Stevenson, DK and Shaw, GM and Bianco, K},
title = {Corrigendum to "Mode of delivery predicts postpartum maternal leukocyte telomere length" [Eur. J. Obstetr. Gynecol. Reprod. Biol. 300 (2024) 224-229].},
journal = {European journal of obstetrics, gynecology, and reproductive biology},
volume = {304},
number = {},
pages = {35},
doi = {10.1016/j.ejogrb.2024.11.017},
pmid = {39561615},
issn = {1872-7654},
}
@article {pmid39561502,
year = {2024},
author = {Pedklang, N and Navasumrit, P and Chompoobut, C and Promvijit, J and Hunsonti, P and Ruchirawat, M},
title = {Effects of particulate air pollution on BPDE-DNA adducts, telomere length, and mitochondrial DNA copy number in human exhaled breath condensate and BEAS-2B cells.},
journal = {International journal of hygiene and environmental health},
volume = {263},
number = {},
pages = {114488},
doi = {10.1016/j.ijheh.2024.114488},
pmid = {39561502},
issn = {1618-131X},
abstract = {Traffic-related particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) have been linked to respiratory diseases and cancer risk in humans. Genomic damage, including benzo[a]pyrene diolepoxide (BPDE)-DNA adducts as well as alterations in telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) are associated with respiratory diseases. This study aimed to investigate the association between exposure to traffic-related particulate pollutants and genomic damage in exhaled breath condensate (EBC) in human subjects and a bronchial epithelial cell line (BEAS-2B). Among the 60 healthy recruited subjects, residents living in high-traffic-congested areas were exposed to higher concentrations of PM2.5 (1.66-fold, p < 0.01), UFPs (1.79-fold, p < 0.01), PM2.5-PAHs (1.50-fold, p < 0.01), and UFPs-PAHs (1.35-fold, p < 0.05), than those in low-traffic-congested areas. In line with increased exposure to particulate air pollution, the high-traffic-exposed group had significantly increased BPDE-DNA adducts (1.40-fold, p < 0.05), TL shortening (1.24-fold, p < 0.05), and lower mtDNA-CN (1.38-fold, p < 0.05) in EBC. The observations in the human study linking exposure to PM2.5, UFPs, PM2.5-PAHs, and UFPs-PAHs with the aforementioned biological effects were confirmed by an in vitro cell-based study, in which BEAS-2B cells were treated with diesel exhaust particulate matter (DEP) containing fine and ultrafine PM and PAHs. Increased BPDE-DNA adducts levels, shortened TL, and decreased mtDNA-CN were also found in treated BEAS-2B cells. The shortened TL and decreased mtDNA-CN were in part mediated by decreased transcript levels of hTERT, and SIRT1, which are involved in telomerase activity and mitochondrial biogenesis, respectively. These results suggest that exposure to traffic-related particulate pollutants can cause genomic instability in respiratory cells, which may increase the health risk of respiratory diseases and the development of cancer.},
}
@article {pmid39556024,
year = {2024},
author = {Laemmerer, A and Lehmann, C and Mayr, L and Bruckner, K and Gabler, L and Senfter, D and Meyer, P and Balber, T and Pirker, C and Jaunecker, CN and Kirchhofer, D and Vician, P and Griesser, M and Spiegl-Kreinecker, S and Schmook, MT and Traub-Weidinger, T and Kuess, P and Eckert, F and Federico, A and Madlener, S and Stepien, N and Robl, B and Baumgartner, A and Hainfellner, JA and Dieckmann, K and Dorfer, C and Roessler, K and Corsini, NS and Holzmann, K and Schmidt, WM and Peyrl, A and Azizi, AA and Haberler, C and Beck, A and Pfister, SM and Schueler, J and Loetsch-Gojo, D and Knoblich, JA and Berger, W and Gojo, J},
title = {Alternative lengthening of telomere-based immortalization renders H3G34R -mutant diffuse hemispheric glioma hypersensitive to PARP inhibitor combination regimens.},
journal = {Neuro-oncology},
volume = {},
number = {},
pages = {},
doi = {10.1093/neuonc/noae228},
pmid = {39556024},
issn = {1523-5866},
abstract = {BACKGROUND: Diffuse hemispheric glioma, H3G34R/V-mutant (DHG-H3G34) is characterized by poor prognosis and lack of effective treatment options. DHG-H3G34R further harbor deactivation of Alpha-Thalassemia/Mental Retardation Syndrome X-linked protein (ATRX; DHG-H3G34R_ATRX) suggesting a unique interaction of these two oncogenic alterations. In this study, we dissect their cell biological interplay, investigate the impact on telomere stabilization and, consequently, validate a targeted therapy approach.<br><br>METHODS: We characterized patient-derived primary pediatric high-grade glioma (pHGG) models for telomere-maintenance mechanisms, DNA damage stress (including protein expression, pH2AX/Rad51 foci, cell-cycle arrest) and their sensitivity towards poly-ADP polymerase inhibitor (PARPi) combinations. Human induced pluripotent stem cells (iPSCs) were used for modelling the disease. The anticancer activity of PARPi combinations in vivo was studied in Chorioallantoic Membrane (CAM) and orthotopic in vivo experiments. Finally, we treated a DHG-H3G34R_ATRX patient with a PARPi combination therapy.<br><br>RESULTS: We elaborate that alternative lengthening of telomeres (ALT) is a key characteristic of DHG-H3G34R_ATRX. A dominant cooperative effect between H3G34R and ATRX loss in ALT activation also became apparent in iPSCs, which endogenously exert telomerase activity. In both, patient-derived DHG-H3G34R_ATRX models and H3G34R+/ATRX- iPSCs, the ALT phenotype was associated with increased basal DNA damage stress, mediating synergistic susceptibility towards PARPi (talazoparib, niraparib) combinations with topoisomerase-I inhibitors (topotecan, irinotecan). In a first-of-its-kind case, treatment of a DHG-H3G34R_ATRX patient with the brain-penetrant PARP inhibitor niraparib and topotecan resulted in a significant tumor reduction.<br><br>CONCLUSION: Our preclinical and clinical data strongly support the further development of PARPis together with DNA damage stress-inducing treatment regimens for DHG-H3G34R_ATRX.},
}
@article {pmid39554689,
year = {2024},
author = {Pearce, E and Majid, A and Brown, T and Wilsnack, C and Rising, C and Thompson, AS and Shepherd, RF and Niknafs, A and Werner-Lin, A and Gilkey, MB and Ribisl, KM and Hutson, SP and Han, PKJ and Savage, SA},
title = {A "rotating menu" of medical uncertainty for families affected by telomere biology disorders: A qualitative interview study.},
journal = {SSM. Qualitative research in health},
volume = {6},
number = {},
pages = {},
pmid = {39554689},
issn = {2667-3215},
abstract = {BACKGROUND: Medical uncertainty may cause distress and challenge medical decision-making for patients with rare diseases and their caregivers. Few studies have examined the experience and management of medical uncertainty in rare disease and the dynamics of multiple medical uncertainty sources, issues, and management strategies.<br><br>OBJECTIVE: We explored the experience and management of uncertainty in individuals with telomere biology disorders (TBDs), a set of rare cancer-prone bone marrow failure syndromes, and their caregivers.<br><br>DESIGN: Participants (N=32) in this qualitative-descriptive study were individuals with a TBD (n=17) and/or their caregivers (n=15). We thematically analyzed transcripts to describe the presence and dynamics of medical uncertainty in TBDs using categories from a previously published taxonomy.<br><br>RESULTS: Individuals with TBDs and caregivers described medical uncertainty as a chronic burden embodied amidst a range of interrelated sources and issues. Scientific uncertainty included diagnostic and prognostic ambiguity. Practical uncertainty focused on logistical challenges of building and maintaining medical care teams. Personal uncertainty included difficulty realigning self-identity, goals, and relationship expectations post-diagnosis. Scientific, practical, and personal uncertainty issues were entangled. The rarity of TBDs resulted in limited scientific knowledge, which gave rise to practical and personal uncertainties affecting medical decision-making and relationship formation (e.g., creating trusted care teams where patient knowledge of TBDs may exceed that of clinicians). Participants used multiple strategies for uncertainty management, particularly information-seeking and community-building. However, these management strategies could intensify, rather than resolve, participants' medical uncertainty.<br><br>CONCLUSION: In TBDs, medical uncertainty manifests as a network of multiple, interrelated, sources and issues, which require evolving management strategies. Researchers must be mindful that complex, synergistic uncertainty networks contribute to psychosocial challenges in TBDs. Additional research is warranted to address scientific uncertainty in TBDs, including clinical manifestations and underlying biology, and to develop psychosocial interventions that recognize and anticipate evolving uncertainty.},
}
@article {pmid39554068,
year = {2024},
author = {Chung, G and Piano, F and Gunsalus, KC},
title = {TeloSearchLR: an algorithm to detect novel telomere repeat motifs using long sequencing reads.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.10.29.617943},
pmid = {39554068},
issn = {2692-8205},
abstract = {Telomeres are eukaryotic chromosome end structures that guard against sequence loss and aberrant chromosome fusions. Telomeric repeat motifs (TRMs), the minimal repeating unit of a telomere, vary from species to species, with some evolutionary clades experiencing a rapid sequence divergence. To explore the full scope of this evolutionary divergence, many bioinformatic tools have been developed to infer novel TRMs using repetitive sequence search on short sequencing reads. However, novel telomeric motifs remain unidentified in up to half of the sequencing libraries assayed with these tools. A possible reason may be that short reads, derived from extensively sheared DNA, preserve little to no positional context of the repetitive sequences assayed. On the other hand, if a sequencing read is sufficiently long, telomeric sequences must appear at either end rather than in the middle. The TeloSearchLR algorithm relies on this to help identify novel TRMs on long reads, in many cases where short-read search tools have failed. In addition, we demonstrate that TeloSearchLR can reveal unusually long telomeric motifs not maintained by telomerase, and it can also be used to anchor terminal scaffolds in new genome assemblies.},
}
@article {pmid39553389,
year = {2024},
author = {Packer, A and Habiballa, L and Tato-Barcia, E and Breen, G and Brooker, H and Corbett, A and Arathimos, R and Ballard, C and Hampshire, A and Palmer, A and Dima, D and Aarsland, D and Creese, B and Malanchini, M and Powell, TR},
title = {Telomere length and cognitive changes in 7,877 older UK adults of European ancestry.},
journal = {Frontiers in aging},
volume = {5},
number = {},
pages = {1480326},
pmid = {39553389},
issn = {2673-6217},
abstract = {BACKGROUND: Telomere length (TL) has been linked to cognitive function, decline and dementia. This study aimed to explore whether both measured TL and genetic disposition for TL predict dimensions of cognitive performance in a longitudinal sample of older UK adults.<br><br>METHODS: We analysed data from PROTECT study participants aged &#x2265;50&#xa0;years without a dementia diagnosis, who had completed longitudinal cognitive testing. We calculated polygenic scores for telomere length (PGS-TL) for 7,877 participants and measured relative telomere length (RTL) in a subgroup of 846 participants using DNA extracted from saliva samples collected within 6&#xa0;months either side of their baseline cognitive testing. Latent growth models were used to examine whether RTL and PGS-TL predict both baseline and longitudinal changes in cognitive performance (4 time-points, annually).<br><br>RESULTS: In the whole sample, we did not observe significant associations between either measure of telomere length and initial or longitudinal changes in cognitive performance. Stratifying by median age, in older adults (&#x2265; &#x223c;62&#xa0;years), longer baseline RTL showed a nominal association with poorer baseline verbal reasoning performance (n = 423, M intercept = 47.58, B = -1.05, p = .011) and PGS-TL was associated with performance over time (n = 3,939; slope factor, M slope = 3.23, B = -0.45, p = .001; slope [2] factor, M slope [2] = 0.21, B = 0.13, p = .002).<br><br>CONCLUSION: Our findings suggest either the absence of a significant relationship between telomere length (RTL and PGS-TL) and cognitive performance (baseline and change over time), or possibly a weak age-dependent and domain-specific relationship, in older adults of European ancestry. More research is needed in representative and ancestrally diverse samples over a longer assessment period. Alternative biological ageing indicators may still provide utility in the early detection of individuals at risk for cognitive decline (e.g., pace-of ageing epigenetic clocks).},
}
@article {pmid39553152,
year = {2024},
author = {Xie, S and Xiao, H and Zhang, F and Lan, Y and Luo, M},
title = {Identification and Validation of Telomere-Related Gene Signature in Intervertebral Disc Degeneration.},
journal = {Cureus},
volume = {16},
number = {10},
pages = {e71735},
pmid = {39553152},
issn = {2168-8184},
abstract = {This study investigates the role of telomere-related differentially expressed genes (TRDEGs) in intervertebral disc degeneration (IVDD) through comprehensive bioinformatics analyses. Data were sourced from the Gene Expression Omnibus (GEO) with datasets GSE245147 and GSE124272 used for initial identification and validation, respectively. The GSE245147 dataset comprised transcriptional profiles from nucleus pulposus cells of both degenerated and non-degenerated human nucleus pulposus (NP) tissues. Using the limma package, 198TRDEGs were identified by intersecting differentially expressed genes (DEGs) with telomere-related genes (TRGs) from the TelNet database. Functional enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID) revealed that TRDEGs are significantly involved in cell division, chromosome segregation, and other mitotic processes. Protein-protein interaction (PPI) networks constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized with Cytoscape (Cytoscape Consortium, San Diego, CA, USA) identified key hub genes such as CDK1, CCNA2, and AURKB. Pearson correlation and receiver operating characteristic (ROC) analyses highlighted five hub genes (ASPM, BUB1B, CDC20, KIF2C, TTK) with significant predictive value for IVDD. Additionally, mRNA-microRNA (miRNA) interaction analysis using NetworkAnalyst identified key miRNAs interacting with these hub genes. This study provides insights into the molecular mechanisms of IVDD and identifies potential targets for therapeutic intervention.},
}
@article {pmid39548087,
year = {2024},
author = {Piras, M and Lin, J and Sadler, MC and Ranjbar, S and Grosu, C and Laaboub, N and Preisig, M and Gamma, F and Plessen, KJ and von Gunten, A and Conus, P and Kutalik, Z and Eap, CB},
title = {Psychotropic-induced weight gain and telomere length: results from a one-year longitudinal study and a large population-based cohort.},
journal = {Translational psychiatry},
volume = {14},
number = {1},
pages = {471},
pmid = {39548087},
issn = {2158-3188},
mesh = {Humans ; *Weight Gain/drug effects/genetics ; Male ; Female ; Longitudinal Studies ; *Psychotropic Drugs/adverse effects ; Middle Aged ; *Telomere Shortening/drug effects ; Adult ; *C-Reactive Protein ; Body Mass Index ; Telomere/drug effects/genetics ; Aged ; },
abstract = {Weight-inducing psychotropic treatments are risk factors for age-related diseases such as cardiovascular disorders, which are associated with both inflammation and telomere length shortening. With a longitudinal design, the present study evaluates telomere length trajectories after 1 year of weight-inducing psychotropic medication, accounting for weight changes and the inflammatory biomarker high-sensitivity C-Reactive Protein (CRP). Among 200 patients, an overall median telomere shortening of -41.2 bp was observed (p = 0.014), which is comparable with the general population's yearly telomere attrition. Linear regression showed on average -93.1 and -58.9 bp of further telomere shortening per five units of BMI for BMI values < or ≥30 kg/m[2], respectively (p = 0.003 and p = 0.009, respectively). Importantly, the overall telomere shortening was predicted to be increased four-fold among patients with low baseline weight (i.e., 50 kg) and with clinically relevant weight gain (≥ 7%) after 1 year of treatment (interaction term between relevant weight gain and baseline weight: +6.3 bp, p = 0.016). Patients with relevant weight gain showed greater CRP levels (+ 49%; p = 0.016), and a telomere shortening of -36.2 bp (p = 0.010) was estimated whenever CRP level doubled. Mendelian randomization using UKBiobank data showed a causal effect of BMI on telomere shortening, notably stronger among patients receiving weight-inducing psychotropic treatments (n = 9798) than among psychiatric patients without such drugs (n = 16228) and non-psychiatric controls (n = 252932) (beta: -0.37, -0.12, -0.06, respectively; p = 0.004, p < 0.001, p < 0.001, respectively). Ultimately, telomere trajectories were associated with 1 year weight gain and increases in CRP levels, with telomere shortening strongly enhanced by BMI increments among patients receiving weight-inducing psychotropic treatments.},
}
@article {pmid39543404,
year = {2024},
author = {Muñoz-Pardeza, J and López-Gil, JF and Huerta-Uribe, N and Hormazábal-Aguayo, I and Ojeda-Rodríguez, A and Del Moral, AM and Izquierdo, M and García-Hermoso, A},
title = {Is physical fitness associated with leucocyte telomere length in youth with type 1 diabetes?.},
journal = {Pediatric research},
volume = {},
number = {},
pages = {},
pmid = {39543404},
issn = {1530-0447},
abstract = {BACKGROUND: In type 1 diabetes, telomere length (TL) may predict complications and could be influenced by glycaemic control and physical activity, but its relationship with physical fitness in youths remains unexplored. The aim of the study was to assess the association between physical fitness and TL in youth with type 1 diabetes, both at baseline and one year later.<br><br>METHODS: Eighty-three children and adolescents (aged 6-18 years; 44.6% girls) with type 1 diabetes from the Diactive-1 Cohort Study were involved in this study. Physical fitness was assessed using spirometry on a cycloergometer (i.e., peak oxygen consumption), dynamometry, and maximal isometric strength (one-repetition maximum [1RM]), and muscle power. Leucocyte TL was assessed using multiplex monochrome real-time quantitative polymerase chain reaction.<br><br>RESULTS: Positive cross-sectional associations were identified between 1RM (unstandardized beta coefficient [B]&#xa0;=&#x2009;0.042, 95% bias corrected and accelerated [BCa] confidence interval [CI] 0.012-0.069), muscle power (B&#x2009;=&#x2009;0.056, 95% BCa CI 0.02-0.250), and overall physical fitness (B&#x2009;=&#x2009;0.043, 95% BCa CI 0.015-0.071) with TL independent of maturation, glycated haemoglobin, and diabetes duration. However, no associations were observed one year later.<br><br>CONCLUSION: Higher levels of fitness, particularly muscle&#xa0;strength, may play a role in telomere dynamics in youth with type 1 diabetes, suggesting that strength training exercise could be beneficial.<br><br>IMPACT: This is the first study to examine cross-sectional and longitudinal perspectives on the correlation among muscle strength, peak oxygen consumption [VO2peak] and telomere length in youths with type 1 diabetes. Higher physical&#xa0;fitness levels, as assessed by measures such as one-repetition maximum, muscle power, and overall physical fitness, are positively associated with telomere length in youths with type 1 diabetes. Understanding this link could improve management strategies, prioritizing muscle strength training for better long-term health in type 1 diabetes.},
}
@article {pmid39538053,
year = {2024},
author = {da Cunha Agostini, L and da Silva, GN},
title = {Telomere length as a biomarker for cerebrovascular diseases: current evidence.},
journal = {Molecular biology reports},
volume = {51},
number = {1},
pages = {1150},
pmid = {39538053},
issn = {1573-4978},
support = {001//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 314486/2023-2//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico , Brasil/ ; APQ-03555-22//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de Minas Gerais , Brasil/ ; 23109.016819/2023-81//Pr&#xf3;-Reitoria de Pesquisa e P&#xf3;s-Gradua&#xe7;&#xe3;o, Universidade Federal de Ouro Preto/ ; 23109.009436/2023-56//Pr&#xf3;-Reitoria de Pesquisa e P&#xf3;s-Gradua&#xe7;&#xe3;o, Universidade Federal de Ouro Preto/ ; },
mesh = {Humans ; *Cerebrovascular Disorders/genetics/diagnosis ; *Biomarkers ; *Telomere/genetics/metabolism ; Risk Factors ; Telomere Homeostasis ; Telomere Shortening/genetics ; Stroke/genetics ; },
abstract = {Cerebrovascular disease (CVD) includes a range of conditions affecting the brain's blood vessels, which can result in reduced blood flow to brain tissue. The most common manifestation of CVD is stroke, the second leading cause of death and the third leading cause of disability worldwide. Major risk factors for CVD encompass gender, age, smoking, hypertension, diabetes, physical inactivity, obesity, alcohol consumption, and metabolic syndrome. Research suggests a link between telomere length and an increased risk of CVD, particularly in ischemic stroke cases. This review highlights key findings on the relationship between telomere length and CVD, underscoring its clinical importance. The analysis utilizes scientific literature from PubMed, Scopus, and SciELO up to 2024. Results show that shorter telomere length is associated with various types of CVD, including stroke, ischemic stroke, hemorrhagic stroke, and cardioembolic stroke. Some studies propose that telomere length measurement could be a valuable biomarker for CVD, potentially improving prevention, diagnosis, and management strategies.},
}
@article {pmid39537670,
year = {2024},
author = {Katneni, VK and Krishnan, K and Prabhudas, SK and Jayaraman, R and Quraishi, N and Vasagam, K and Jangam, AK and Angel, JRJ and Kaikkolante, N and Jayaraman, K and Mudagandur, SS},
title = {Genome assembly at chromosome scale with telomere ends for Pearlspot, Etroplus suratensis.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {1226},
pmid = {39537670},
issn = {2052-4463},
support = {BT/PR34518/AAQ/3/965/2019//Department of Biotechnology, Ministry of Science and Technology (DBT)/ ; },
mesh = {Animals ; *Cichlids/genetics ; *Genome ; *Telomere/genetics ; Chromosomes ; Salinity ; },
abstract = {The pearlspot, Etroplus suratensis is a climate resilient cichlid fish that exhibits unusual adaptation to salinity. The fish is able to complete full life cycle in diverse salinity habitats ranging from fresh water to marine environments. High-quality primary and phased genome assemblies were generated for pearlspot fish using PacBio HiFi and Arima HiC sequencing technologies, for the first time. The primary assembly is highly contiguous with contig N50 length of 36 Mb. The final assembly is of 1.247 Gb with N50 length of 51.57 Mb and 98% of the genome length anchored to 24 chromosomes. The genome was assessed to be 99.9% complete based on BUSCO evaluation and was predicted to contain 52.96% repeat elements. We have predicted 27,192 protein encoding genes, of which 21,580 were functionally annotated. The genome offers an invaluable resource to understand adaptation of pearlspot fish to diverse salinity habitats.},
}
@article {pmid39533571,
year = {2024},
author = {Li, J and Hu, L and Huang, X},
title = {Causal relationship between leukocyte telomere length and two cardiomyopathies based on a bidirectional Mendelian randomization approach.},
journal = {Medicine},
volume = {103},
number = {45},
pages = {e40308},
doi = {10.1097/MD.0000000000040308},
pmid = {39533571},
issn = {1536-5964},
support = {No. 2022YFC3500102//National Key Research and Development Program of China/ ; },
mesh = {Humans ; *Mendelian Randomization Analysis ; *Leukocytes ; Telomere/genetics ; Cardiomyopathy, Dilated/genetics ; Cardiomyopathies/genetics ; Cardiomyopathy, Hypertrophic/genetics ; Genetic Predisposition to Disease ; },
abstract = {This study aims to employ the Mendelian randomization (MR) approach to investigate the relationship between leukocyte telomere length (TL) and 2 prevalent forms of cardiomyopathies. Using R software (4.3.1) for MR study, independent genetic variants associated with leukocyte TL were extracted from the Integrative Epidemiology Unit database, while cardiomyopathies data were pooled from FinnGen and European Bioinformatics Institute databases. Analytical methodologies included inverse-variance weighting, MR-Egger regression, and weighted median methods. Further analyses involved MR-Egger intercept and MR-PRESSO for handling horizontal pleiotropy and Cochran Q test for study heterogeneity. Our forward Mendelian randomization study indicates a positive correlation between longer leukocyte TL and the risk of 2 forms of cardiomyopathies: the longer the leukocyte telomere, the higher is the risk of cardiomyopathies. Specifically, for hypertrophic obstructive cardiomyopathy the OR is 2.23 (95% CI: 1.19-4.14, P = .01), for hypertrophic cardiomyopathy the OR is 1.80 (95% CI: 1.14-2.85, P = .01), and for dilated cardiomyopathy the OR is 1.32 (95% CI: 1.01-1.71, P = .04). In contrast, our reverse Mendelian randomization showed that cardiomyopathies were not directly associated with TL, and the inverse-variance-weighted test was not statistically significant for any of the 3 (P > .05). The reliability tests for the forward Mendelian randomization, including both MR-Egger intercept and MR-PRESSO tests, show no evidence of horizontal pleiotropy, and Cochran Q test indicates no heterogeneity. The "leave-one-out" sensitivity analysis revealed no outlier genes. The reliability tests for the reverse Mendelian randomization, including both MR-Egger intercept and MR-PRESSO tests, also indicate no genetic pleiotropy. Despite the heterogeneity shown in our study between hypertrophic cardiomyopathy and leukocyte TL, the sensitivity analysis did not identify any anomalies. Our Mendelian randomization study suggests that longer leukocyte TL is associated with an increased risk of hypertrophic obstructive cardiomyopathy, hypertrophic cardiomyopathy, and dilated cardiomyopathy. However, the onset of these 2 kinds of disease does not directly lead to changes in leukocyte TL.},
}
@article {pmid39531590,
year = {2024},
author = {Zhang, B and Zhao, Y},
title = {Association Analysis of Telomere Length and Vision in a Large Community-Based Survey.},
journal = {Ophthalmic epidemiology},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/09286586.2024.2422349},
pmid = {39531590},
issn = {1744-5086},
abstract = {PURPOSE: To investigate whether there is a direct, age-independent association between telomere length and visual acuity decline in a large community-based cohort study.<br><br>METHODS: Participants older than 40 with linked leukocyte telomere length (LTL) were enrolled in NHANES. LTL was assayed using qPCR from the participants' blood samples. Best corrected visual acuity (BCVA) of the better-seeing eye was analyzed, with visual impairment (VI) defined as BCVA&#x2009;&#x2265;&#x2009;20/40. LTL was grouped into quartiles, and its association with BCVA and VI was evaluated after adjusting for covariates.<br><br>RESULTS: Among the 4,480 enrolled participants, the weighted means of age, BCVA, and telomere length were 56.1&#x2009;&#xb1;&#x2009;11.9&#x2009;years, 0.05&#x2009;&#xb1;&#x2009;0.08 logMAR, and 5,662&#x2009;&#xb1;&#x2009;36 base pairs, respectively. The proportion of VI was 2.6%. After adjusting for covariates including sex, ethnicity, education, family poverty income ratio, general health status, hypertension, diabetes, smoking, and body mass index, BCVA was significantly worse in participants with shorter LTL, with a significant trend (p&#x2009;=&#x2009;0.002). However, after further adjusting for age, the association between LTL and BCVA was no longer significant, without a trend (p&#x2009;=&#x2009;0.640). No significant association or trend between LTL and VI was found in the stepwise logistic model.<br><br>CONCLUSIONS: No age-independent association between LTL and BCVA was found. Our study indicates LTL may not serve as a biomarker for age-related visual acuity decline.},
}
@article {pmid39529015,
year = {2024},
author = {Zeng, F and Chen, Y and Lin, J},
title = {Identification of alternative lengthening of telomeres-related genes prognosis model in hepatocellular carcinoma.},
journal = {BMC cancer},
volume = {24},
number = {1},
pages = {1386},
pmid = {39529015},
issn = {1471-2407},
mesh = {Humans ; *Carcinoma, Hepatocellular/genetics/pathology/mortality ; *Liver Neoplasms/genetics/pathology/mortality ; Prognosis ; *Biomarkers, Tumor/genetics ; *Gene Expression Regulation, Neoplastic ; Telomere Homeostasis/genetics ; Cell Proliferation/genetics ; Nomograms ; Cell Line, Tumor ; Female ; Male ; Gene Expression Profiling ; Kaplan-Meier Estimate ; },
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide, characterized by high mortality. This study aimed to explore the prognostic value and function of alternative lengthening of telomeres (ALT)-related genes in HCC.<br><br>METHODS: Differentially expressed genes (DEGs) were identified based on The Cancer Genome Atlas (TCGA) and then intersected with ALT-related genes to obtain ALTDEGs. Risk score model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression and validated with Gene Expression Omnibus (GEO) datasets. The predictive efficacy of the risk score and ALTs-score was evaluated by Kaplan-Meier curves, time-ROC curves, and the nomogram analyses. The impacts of SMG5 silencing on the HCC cell behaviors were assessed by CCK-8, wound healing, and Transwell assays.<br><br>RESULTS: A total of 500 ALTDEGs were screened and 13 genes (CDCA8, SMG5, RAD54B, FOXD2, NOL10, RRP12, CCT5, CCT4, HDAC1, DDX1, HRG, HDAC2, and PPP1CB) were identified for constructing a prognostic model. The overall survival (OS) curves, time-ROC curves, and nomograms based on the risk score or ALTs-score were developed to optimally predict the survival of HCC patients. ALTs-score was correlated with immune infiltration and confirmed its value in predicting immunotherapy outcomes. Furthermore, RT-qPCR demonstrated that eight risk signature genes were up-regulated in HCC cells. SMG5 silencing suppressed the proliferation, migration, and invasion of HCC cells. It was also found that SMG5 silencing reduced C-circle level in SNU-387 cells.<br><br>CONCLUSION: We identified new ALT-related prognostic biomarkers for HCC. SMG5 knockdown inhibited the HCC progression, which might be a promising target for HCC therapy.},
}
@article {pmid39528945,
year = {2024},
author = {Kezer, CA and Kusztos, V and Kassmeyer, B and Lennon, R and Rattan, P and Kamath, PS and Shah, VH and Simonetto, DA},
title = {Impact of sociodemographic disparities on sarcopenia, telomere length, and mortality in patients with liver disease in the US population.},
journal = {BMC gastroenterology},
volume = {24},
number = {1},
pages = {404},
pmid = {39528945},
issn = {1471-230X},
mesh = {Humans ; *Sarcopenia/mortality ; Male ; Female ; Middle Aged ; *Liver Diseases/mortality ; United States/epidemiology ; Aged ; Adult ; *Nutrition Surveys ; Age Factors ; Telomere/genetics ; Proportional Hazards Models ; Telomere Shortening ; Sociodemographic Factors ; Socioeconomic Factors ; Comorbidity ; },
abstract = {BACKGROUND &amp; AIMS: Sarcopenia is common in patients with liver disease and both sarcopenia and short telomeres are associated with mortality, however their relationship in patients with liver disease remains unknown.<br><br>METHODS: A cohort of 16,072 adults from the National Health and Nutrition Examination Survey from 1999 to 2006 was analyzed. Liver disease was defined by aminotransferases and classified into etiology-based categories. Sarcopenia was defined by dual-energy x-ray absorptiometry. All analyses were conducted separately on each multiple imputation data set and combined via Rubin's rules. P-values for group comparisons were calculated by testing logistic regression parameter estimates. Cox proportional hazards regression was used for mortality analysis with mortality data available until 2015.<br><br>RESULTS: Sarcopenia was present in 9.5% of patients with liver disease. Age, race, income, education, physical inactivity, and certain medical comorbidities were associated with sarcopenia. Patients with liver disease and sarcopenia had significantly shorter telomeres than patients with liver disease without sarcopenia when unadjusted for age. The interaction between telomere length and sarcopenia was significantly associated with all-cause mortality.<br><br>CONCLUSIONS: The implications of telomere length on all-cause mortality in patients with liver disease varied by age and sarcopenia status. Shorter telomeres appear to be more highly associated with increased mortality in older patients without sarcopenia.},
}
@article {pmid39528488,
year = {2024},
author = {Giaccherini, M and Clay-Gilmour, AI and Liotti, R and Macauda, A and Gentiluomo, M and Brown, EE and Machiela, MJ and Chanock, SJ and Hildebrandt, MAT and Norman, AD and Manasanch, E and Rajkumar, SV and Hofmann, JN and Berndt, SI and Bhatti, P and Giles, GG and Ziv, E and Kumar, SK and Camp, NJ and Cozen, W and Slager, SL and Canzian, F and Gemignani, F and Vachon, CM and Campa, D},
title = {Genetically determined telomere length in monoclonal gammopathy of undetermined significance, multiple myeloma risk and outcome.},
journal = {Blood cancer journal},
volume = {14},
number = {1},
pages = {200},
pmid = {39528488},
issn = {2044-5385},
}
@article {pmid39527203,
year = {2025},
author = {Zhang, H and Kerr, C and Audry, J and Runge, KW},
title = {A Rapidly Inducible DNA Double-Strand Break to Monitor Telomere Formation, DNA Repair, and Checkpoint Activation.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2862},
number = {},
pages = {209-221},
pmid = {39527203},
issn = {1940-6029},
mesh = {*DNA Breaks, Double-Stranded ; *Schizosaccharomyces/genetics/metabolism ; *DNA Repair ; *Telomere/metabolism/genetics ; Cell Cycle Checkpoints ; Deoxyribonucleases, Type II Site-Specific/metabolism ; DNA, Fungal/genetics/metabolism ; Schizosaccharomyces pombe Proteins/metabolism/genetics ; },
abstract = {The study of processes that govern genome integrity has been augmented by the ability to create a precise DNA double-strand break (DSB) in a short period of time that allows the kinetics of DNA metabolism and protein recruitment to be followed. Defined DSBs are made by expressing endonucleases with long recognition sites that are rare or absent in the genome, and require that the endonuclease is only active when induced. Research in this area in Schizosaccharomyces pombe was limited because rapidly inducible promoters were not available until around 2005, and several rapidly inducible DSB systems are now available. Here, we describe a system to rapidly induce a modified I-SceI endonuclease that can generate a DSB 20 min after induction. I-SceI has no recognition sites in the S. pombe genome, allowing the introduction of complex substrates to monitor the effects of a new DSB in real time. This chapter describes how I-SceI can be most efficiently induced and a simple cell length measurement assay to monitor cell cycle checkpoint activation from a single DSB.},
}
@article {pmid39526375,
year = {2024},
author = {Blanchard, M and Lin, J and Hurley, S and Goldberg, D and Von Behren, J and Wang, SS and Reynolds, P and Clague DeHart, J},
title = {Telomere length and chronotype among women in the California Teachers Study (CTS).},
journal = {Chronobiology international},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/07420528.2024.2422865},
pmid = {39526375},
issn = {1525-6073},
abstract = {While links between certain chronotypes and poorer health outcomes have been well established in previous studies, few studies have examined the relationship between chronotype and cellular aging. Using data from the California Teachers Study (CTS), the present study evaluates the relationship between cellular aging and chronobiology through an analysis of leukocyte telomere length (LTL) and chronotype among 817 predominantly postmenopausal women with no history of cancer and occupations not associated with night-shift work. Unconditional logistic regression models were run to estimate odds ratios (ORs) for each chronotype category, adjusted for age, ethnicity, and smoking status. Analyses were then stratified by potential modifiers to assess whether results varied among specific subgroups within the sample. Women who reported being current evening types and evening types from teen years to now were significantly less likely to have short LTL compared to women who reported being current morning types or morning types from teen years to now (OR = 0.72; 95% CI = 0.53-0.98; OR = 0.57; 95% CI = 0.39-0.84). Our results suggest that women with no history of cancer who identify as evening chronotypes may undergo decreased cellular aging compared to women in the same population who identify as morning types. Further studies on populations of postmenopausal women are warranted.},
}
@article {pmid39525171,
year = {2024},
author = {Mazumdar, J and Chowdhury, P and Mondal, BC and Das, AK and Ghosh, U},
title = {Elevated Telomeric Repeat-Containing RNA (TERRA) Levels Linked to Telomere Dysfunction and Telomerase Inactivity in Blood Cells of Children With Aplastic Anemia.},
journal = {Cureus},
volume = {16},
number = {10},
pages = {e71241},
doi = {10.7759/cureus.71241},
pmid = {39525171},
issn = {2168-8184},
abstract = {Background Aplastic anemia (AA) is characterized by pancytopenia and hypocellularity of the bone marrow. Certain inherited or genetic forms of AA have also been associated with telomere dysfunction. Here, we report the clinical manifestations of eleven AA patients aged between one and 12 years, along with the expression of a few candidate genes involved in the telomere length (TL) maintenance pathway. Methods The clinical manifestations were recorded for all the patients. The average telomere length of peripheral blood mononuclear cells (PBMC), the expression of telomerase subunits, telomere-associated proteins, and chromosome-specific telomeric repeat-containing RNA (TERRA) in whole blood cells of each patient was compared with an age-matched control group consisting of five clinically confirmed normal individuals. Results Out of 11 AA patients, four were found to have upper limb anomalies, and two showed short stature along with other defects. All the patients showed significantly shorter telomere length compared with the age-matched control group. The essential subunits of telomerase (hTERT and hTERC) were significantly low, and the shelterin protein is abnormally expressed in all patients implicating a compromised TL maintenance pathway. Notably, AA with combined androgen and prednisolone treatment showed a marked reduction of TERRA level than that of AA without androgen/prednisolone therapy. Conclusion Based on the findings and observations made, it appears that there might be an association between telomere dysfunction and elevated levels of TERRA in patients diagnosed with aplastic anemia who are 12 years of age or younger.},
}
@article {pmid39523870,
year = {2024},
author = {Qi, X and Gao, L and Qi, L},
title = {Genetic Determinants of Telomere Length and Risk of Aneurysmal Subarachnoid Hemorrhage: A Bidirectional Two-Sample Mendelian Randomization Study.},
journal = {The International journal of neuroscience},
volume = {},
number = {},
pages = {1-22},
doi = {10.1080/00207454.2024.2414285},
pmid = {39523870},
issn = {1563-5279},
abstract = {BACKGROUND: Our objective is to investigate the potential causal relationship between telomere length (TL) and aneurysmal subarachnoid hemorrhage (aSAH) and intracranial aneurysms (IAs) by conducting a bidirectional two-sample Mendelian Randomization (MR) study.<br><br>METHODS: We utilized publicly available summary data from genome-wide association studies (GWAS) for comprehensive analysis. Telomere length-associated data were sourced from the Epidemiology Unit (IEU) GWAS database (n&#x2009;=&#x2009;472,174), while data pertaining to intracranial aneurysms were derived from a GWAS meta-analysis conducted by Bakker et al, encompassing aneurysmal subtypes including aSAH (n&#x2009;=&#x2009;77,074), IAs (n&#x2009;=&#x2009;79,429), and unruptured intracranial aneurysms (uIA) (n&#x2009;=&#x2009;74,004), all sampled from European populations. The primary method for MR analysis employed was the Inverse Variance Weighted (IVW) method. Additionally, we conducted various sensitivity analyses to assess the heterogeneity and pleiotropy of study findings. Reverse MR analysis was employed to explore potential reverse causality.<br><br>RESULTS: In the forward MR analysis, the IVW method indicated a negative association between TL and aSAH (OR = 0.636, 95% CI: 0.459-0.883, p&#x2009;=&#x2009;0.006) as well as IAs (OR = 0.670, 95% CI: 0.499-0.900, p&#x2009;=&#x2009;0.0079). There was no evidence of heterogeneity or horizontal pleiotropy in the forward MR analysis. Reverse MR analysis did not reveal any causal relationship between aSAH, IAs, uIA and TL.<br><br>CONCLUSIONS: In European populations, there exists a causal relationship between longer TL and reduced risks of aSAH and IAs Further research is warranted to elucidate the underlying mechanisms and the potential of TL as an intervention target for lowering the incidence of aSAH and IAs.},
}
@article {pmid39522643,
year = {2024},
author = {Heaphy, CM and Patel, S and Smith, K and Wondisford, AR and Lynskey, ML and O'Sullivan, RJ and Fuhrer, K and Han, X and Seethala, RR and Liu, TC and Cao, D and Ertunc, O and Zheng, Q and Stojanova, M and Zureikat, AH and Paniccia, A and Lee, K and Ongchin, MC and Pingpank, JF and Zeh, HJ and Hogg, ME and Geller, D and Marsh, JW and Brand, RE and Chennat, JS and Das, R and Fasanella, KE and Gabbert, C and Khalid, A and McGrath, K and Lennon, AM and Sarkaria, S and Singh, H and Slivka, A and Hsu, D and Zhang, JY and Nacev, BA and Nikiforova, MN and Wald, AI and Vaddi, N and De Marzo, AM and Singhi, AH and Bell, PD and Singhi, AD},
title = {Detection of Alternative Lengthening of Telomeres via Chromogenic in situ Hybridization (ALT-CISH) for the Prognostication of PanNETs and Other Neoplasms.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {},
number = {},
pages = {100651},
doi = {10.1016/j.modpat.2024.100651},
pmid = {39522643},
issn = {1530-0285},
abstract = {Molecular studies have shown ALT to be an important prognostic biomarker of shorter relapse-free survival (RFS) for patients with pancreatic neuroendocrine tumors (PanNETs) and other neoplasms. However, the preferred method of detecting ALT in tissue is by fluorescence in situ hybridization (FISH), which has several clinical limitations. These issues necessitate the creation of a chromogenic ALT assay that can be easily implemented into routine practice. A CISH assay was developed using genetically modified osteosarcoma cell lines, 20 normal pancreata, 20 ALT-positive PanNETs, and 20 ALT-negative PanNETs. Thereafter, it was validated on a multi-institutional cohort of 360 surgically resected PanNETs and correlated with multiple clinicopathologic features, RFS, and FISH results. Separately, 109 leiomyosarcomas (LMS) were evaluated by both CISH and FISH, and, similarly, the prognostic significance of ALT status was assessed. Upon optimization, ALT-CISH was identified in 112 of 360 (31%) primary PanNETs and was 100% concordant with FISH testing. ALT correlated with several adverse prognostic findings and distant metastasis (all p<0.004). The 5-year RFS for patients with ALT-positive PanNETs was 35% as compared to 94% for ALT-negative PanNETs. By multivariate analysis, ALT was an independent prognostic factor for shorter RFS. Similarly, ALT was associated with shorter RFS in LMS patients and, analogous to PanNETs, a negative, independent prognostic factor. ALT-CISH was developed and validated in not only PanNETs, but also sarcomas, specifically LMS. CISH testing has multiple advantages over FISH that facilitate its widespread clinical use in the detection of ALT and prognostication of patients with diverse neoplasms.},
}
@article {pmid39520989,
year = {2024},
author = {Mostovoy, Y and Boone, PM and Huang, Y and Garimella, KV and Tan, KT and Russell, BE and Salani, M and de Esch, CEF and Lemanski, J and Curall, B and Hauenstein, J and Lucente, D and Bowers, T and DeSmet, T and Gabriel, S and Morton, CC and Meyerson, M and Hastie, AR and Gusella, J and Quintero-Rivera, F and Brand, H and Talkowski, ME},
title = {Resolution of ring chromosomes, Robertsonian translocations, and complex structural variants from long-read sequencing and telomere-to-telomere assembly.},
journal = {American journal of human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajhg.2024.10.006},
pmid = {39520989},
issn = {1537-6605},
abstract = {Delineation of structural variants (SVs) at sequence resolution in highly repetitive genomic regions has long been intractable. The sequence properties, origins, and functional effects of classes of genomic rearrangements such as ring chromosomes and Robertsonian translocations thus remain unknown. To resolve these complex structures, we leveraged several recent milestones in the field, including (1) the emergence of long-read sequencing, (2) the gapless telomere-to-telomere (T2T) assembly, and (3) a tool (BigClipper) to discover chromosomal rearrangements from long reads. We applied these technologies across 13 cases with ring chromosomes, Robertsonian translocations, and complex SVs that were unresolved by short reads, followed by validation using optical genome mapping (OGM). Our analyses resolved 10 of 13 cases, including a Robertsonian translocation and all ring chromosomes. Multiple breakpoints were localized to genomic regions previously recalcitrant to sequencing such as acrocentric p-arms, ribosomal DNA arrays, and telomeric repeats, and involved complex structures such as a deletion-inversion and interchromosomal dispersed duplications. We further performed methylation profiling from long-read data to discover phased differential methylation in a gene promoter proximal to a ring fusion, suggesting a long-range position effect (LRPE) with heterochromatin spreading. Breakpoint sequences suggested mechanisms of SV formation such as microhomology-mediated and non-homologous end-joining, as well as non-allelic homologous recombination. These methods provide some of the first glimpses into the sequence resolution of Robertsonian translocations and illuminate the structural diversity of ring chromosomes and complex chromosomal rearrangements with implications for genome biology, prediction of LRPEs from integrated multi-omics technologies, and molecular diagnostics in rare disease cases.},
}
@article {pmid39514990,
year = {2024},
author = {Amatya, S and Bhatia, P and Raina, S and Sreedharanunni, S and Singh, M and Rahman, E and Archana, MV and Trehan, A},
title = {Corrigendum to "Clinical utility of relative telomere length analysis in pediatric bone marrow failure" [Blood Cells Mol. Dis. 109 (2024) 102882].},
journal = {Blood cells, molecules &amp; diseases},
volume = {110},
number = {},
pages = {102899},
doi = {10.1016/j.bcmd.2024.102899},
pmid = {39514990},
issn = {1096-0961},
}
@article {pmid39513855,
year = {2024},
author = {Knecht, H and Petrogiannis-Haliotis, T and Louis, S and Mai, S},
title = {3D-Q-FISH/Telomere/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma.},
journal = {Cells},
volume = {13},
number = {21},
pages = {},
doi = {10.3390/cells13211748},
pmid = {39513855},
issn = {2073-4409},
mesh = {*Hodgkin Disease/genetics/pathology/virology/metabolism/diagnosis ; Humans ; *Telomere/metabolism ; Cell Line, Tumor ; In Situ Hybridization, Fluorescence ; Nanotechnology/methods ; Reed-Sternberg Cells/metabolism/pathology ; Shelterin Complex/metabolism ; },
abstract = {The bi- or multinucleated Reed-Sternberg cell (RS) is the diagnostic cornerstone of Epstein-Barr Virus (EBV)-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL is a germinal center (GC)-derived B-cell disease. Hodgkin cells (H) are the mononuclear precursors of RS. An experimental model has to fulfill three conditions to qualify as common pathogenic denominator: (i) to be of GC-derived B-cell origin, (ii) to be EBV-negative to avoid EBV latency III expression and (iii) to support permanent EBV-encoded oncogenic latent membrane protein (LMP1) expression upon induction. These conditions are unified in the EBV-, diffuse large B-Cell lymphoma (DLBCL) cell line BJAB-tTA-LMP1. 3D reconstructive nanotechnology revealed spatial, quantitative and qualitative disturbance of telomere/shelterin interactions in mononuclear H-like cells, with further progression during transition to RS-like cells, including progressive complexity of the karyotype with every mitotic cycle, due to BBF (breakage/bridge/fusion) events. The findings of this model were confirmed in diagnostic patient samples and correlate with clinical outcomes. Moreover, in vitro, significant disturbance of the lamin AC/telomere interaction progressively occurred. In summary, our research over the past three decades identified cHL as the first lymphoid malignancy driven by a disturbed telomere/shelterin/lamin AC interaction, generating the diagnostic RS. Our findings may act as trailblazer for tailored therapies in refractory cHL.},
}
@article {pmid39512472,
year = {2024},
author = {Zhu, S and Zheng, W and Rao, D and Tang, Z and Liao, X},
title = {Leukocyte telomere length and lung function: a mendelian randomization study in European population.},
journal = {Frontiers in physiology},
volume = {15},
number = {},
pages = {1373064},
doi = {10.3389/fphys.2024.1373064},
pmid = {39512472},
issn = {1664-042X},
abstract = {BACKGROUND: The telomere has long been regarded as a dependable biomarker for cellular senescence. The lung function can reflect the function and status of the lungs. As individuals age beyond adulthood, there is a gradual decline in lung function. However, the existence of a associated between leukocyte telomere length (LTL) and lung function remains uncertain.<br><br>METHODS: A two-sample Mendelian randomization (MR) analysis was used. The Single-nucleotide polymorphisms (SNPs) of LTL from the genome-wide association (GWAS) study were used as exposure instruments variable, and the lung function indicator including Forced expiratory volume in 1-s (FEV1), FEV1 Best measure, FEV1 predicted and Forced vital capacity (FVC) from the Neale Lab and MRC-IEU were used as outcomes. The associated between the exposures and outcomes was assessed using inverse-variance weighted (IVW), MR-Egger, and weighted median methods. Sensitivity analysis was conducted using Cochran's Q-test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and Steriger test.<br><br>RESULTS: Using the IVW method, a significant association was identified between genetically determined telomere length extension and enhanced lung function in FEV1, with ukb-a-336 (P = 0.127, OR = 1.028,95CI% = 1.003-1.042) and ukb-b-19657 (P = 7.26E-05, OR = 1.051,95CI% = 1.025-1.077),in FEV1 predicted, ukb-a-234 (P = 0.013, OR = 1.029,95CI% = 1.003-1.042), ukb-b-8428 (P = 0.001, OR = 1.032,95CI% = 1.012-1.052), in FEV1 best measure, ukb-a-231 (P = 7.24E-05, OR = 1.050,95CI% = 1.025-1.075), ukb-b-11141 (P = 1.40E-09, OR = 1.067,95CI% = 1.045-1.090).The sensitivity analysis did not reveal heterogeneity or horizontal pleiotropy.Meanwhile, the Steriger test results also indicate that the directionality between exposure and outcome is correct. Therefore, the results indicated robustness.<br><br>CONCLUSION: There is a correlation between longer LTL and better lung function in the European dataset.},
}
@article {pmid39511975,
year = {2024},
author = {Hu, T and Duan, L and Shangguan, L and Zhao, Q and Hang, Y and Wang, X and Li, X and Yang, N and Yan, F and Lv, Q and Tang, L and Liu, M and Qiang, W and Wang, X and Wang, X and Zhang, M},
title = {Haploid-Phased Chromosomal Telomere-to-Telomere Genome Assembly of Medicinal Plant Uncaria rhynchophylla Dissects Genetic Controls on the Biosynthesis of Bioactive Alkaloids.},
journal = {Plant, cell &amp; environment},
volume = {},
number = {},
pages = {},
doi = {10.1111/pce.15257},
pmid = {39511975},
issn = {1365-3040},
support = {//This work was supported by the Key Core Technology Research Project for Mountainous Agriculture in Guizhou (GZNYGJHX-2023011); the Major Special Project of Science and Technology Programme in Guizhou (2017-5411-06); the Construction Project of State Engineering Technology Institute for Karst Desertification Control of China (2012FU125X13); the Construction Project of Modern Industry Technology system of traditional Chinese Medicinal Materials in Guizhou (GZCYTX-02); Guizhou Provincial Basic Research Programme (Natural Science) (Qian Ke He Ji Chu-ZK [2022] General 096) and the Scientific Research Project of Ordinary Undergraduate Colleges and Universities of Guizhou Provincial Department of Education (Qian Jiao Ji [2022] No. 145)./ ; },
abstract = {Natural indole alkaloids provide important medicinal resources and defences to environmental stresses. The Uncaria genus is a recorded traditional medicinal woody plant with high alkaloids. Genomic insights into alkaloid variation remain elusive. Here, we have dissected the haploid-resolved chromosomal T2T genome assembly of Uncaria rhynchophylla with a size of ~634 Mb and contig N50 of 27 Mb using PacBio HiFi long-reads plus Hi-C reads and anchored the contigs on 22 pairs of confirmed chromosomes. This genome contains 56% repeat sequences and ~29 000 protein-encoding genes. U. rhynchophylla diverged from a common ancestor shared with Coffea around 20 million years ago and contains expanded and contracted gene families associated with secondary metabolites and defences/resistance to stresses. We constructed the pathway and mined genes for rhynchophylline alkaloid biosynthesis. Fifty-three alkaloids in this pathway and eight differentially expressed genes are the keys to alkaloid accumulation. Elevated alkaloid levels are driven by high copy numbers of critical genes STRs and SGRs involved in strictosidine synthesis and hydrolysis as evidenced by phylogenetic, expression and RNA interference analyses. These results advance our genetic understanding and guide further breeding improvements, stress adaptation studies and pharmaceutical development.},
}
@article {pmid39509271,
year = {2024},
author = {Lynskey, ML and Brown, EE and Bhargava, R and Wondisford, AR and Ouriou, JB and Freund, O and Bowman, RW and Smith, BA and Lardo, SM and Schamus-Hayes, S and Hainer, SJ and O'Sullivan, RJ},
title = {HIRA protects telomeres against R-loop-induced instability in ALT cancer cells.},
journal = {Cell reports},
volume = {43},
number = {11},
pages = {114964},
doi = {10.1016/j.celrep.2024.114964},
pmid = {39509271},
issn = {2211-1247},
abstract = {Inactivating mutations in chromatin modifiers, like the α-thalassemia/mental retardation, X-linked (ATRX)-death domain-associated protein (DAXX) chromatin remodeling/histone H3.3 deposition complex, drive the cancer-specific alternative lengthening of telomeres (ALT) pathway. Prior studies revealed that HIRA, another histone H3.3 chaperone, compensates for ATRX-DAXX loss at telomeres to sustain ALT cancer cell survival. How HIRA rescues telomeres from the consequences of ATRX-DAXX deficiency remains unclear. Here, using an assay for transposase-accessible chromatin using sequencing (ATAC-seq) and cleavage under targets and release using nuclease (CUT&amp;RUN), we establish that HIRA-mediated deposition of new H3.3 maintains telomeric chromatin accessibility to prevent the detrimental accumulation of nucleosome-free single-stranded DNA (ssDNA) in ATRX-DAXX-deficient ALT cells. We show that the HIRA-UBN1/UBN2 complex deposits new H3.3 to prevent TERRA R-loop buildup and transcription-replication conflicts (TRCs) at telomeres. Furthermore, HIRA-mediated H3.3 incorporation into telomeric chromatin links productive ALT to the phosphorylation of serine 31, an H3.3-specific amino acid, by Chk1. Therefore, we identify a critical role for HIRA-mediated H3.3 deposition that ensures the survival of ATRX-DAXX-deficient ALT cancer cells.},
}
@article {pmid39506437,
year = {2024},
author = {Song, B and Lou, J and Mu, L and Lu, X and Sun, J and Tang, B},
title = {An Innovative Telomere-associated Prognosis Model in AML: Predicting Immune Infiltration and Treatment Responsiveness.},
journal = {Current medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298673334218241021044800},
pmid = {39506437},
issn = {1875-533X},
abstract = {AIMS: To build an innovative telomere-associated scoring model to predict prognosis and treatment responsiveness in acute myeloid leukemia (AML).<br><br>BACKGROUND: AML is a highly heterogeneous malignant hematologic disorder with a poor prognosis. While telomere maintenance is frequently observed in tumors, investigations into telomere-related genes (TRGs) in AML remain limited.<br><br>OBJECTIVES: This study aimed to identify prognostic TRGs using the least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression, evaluate their predictive value, explore the association between TRG scores and immune cell infiltration, and assess the sensitivity of high-scoring AML patients to chemotherapeutic agents.<br><br>METHOD: Univariate Cox regression analysis was conducted on the TCGA cohort to identify prognostic TRGs and to develop the TRG scoring model using LASSO-Cox and multivariate Cox regression. Validation was performed on the GSE37642 cohort. Immune cell infiltration patterns were assessed through computational analysis, and the sensitivity to chemotherapeutic agents was evaluated.<br><br>RESULTS: Thirteen prognostic TRGs were identified, and a seven-TRG scoring model (including NOP10, OBFC1, PINX1, RPA2, SMG5, MAPKAPK5, and SMN1) was developed. Higher TRG scores were associated with a poorer prognosis, as confirmed in the GSE37642 cohort, and remained an independent prognostic factor even after adjusting for other clinical characteristics. The high-score group was characterized by elevated infiltration of B cells, T helper cells, natural killer cells, tumor-infiltrating lymphocytes, regulatory T (Treg) cells, M2 macrophages, neutrophils, and monocytes, along with reduced infiltration of gamma delta T cells, CD4- T cells, and resting mast cells. Moreover, high infiltration of M2 macrophages and Tregs was associated with poor overall survival compared to low infiltration. Notably, high-risk AML patients were resistant to Erlotinib, Parthenolide, and Nutlin-3a, but sensitive to AC220, Midostaurin, and Tipifarnib. Additionally, using RT-qPCR, we observed significantly higher expression of two model genes, OBFC1 and SMN1, in AML tissues compared to control tissues.<br><br>CONCLUSION: This innovative TRG scoring model demonstrates considerable predictive value for AML patient prognosis, offering valuable insights for optimizing treatment strategies and personalized medicine approaches. The identified TRGs and associated scoring models could aid in risk stratification and guide tailored therapeutic interventions in AML patients.},
}
@article {pmid39506036,
year = {2024},
author = {Allsopp, RC and Hernández, LM and Taylor, MK},
title = {The Val66Met variant of brain-derived neurotrophic factor is linked to reduced telomere length in a military population: a pilot study.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {27013},
pmid = {39506036},
issn = {2045-2322},
abstract = {In military populations, gene-environment interactions can influence performance and health outcomes. Brain-derived neurotrophic factor (BDNF) is a central nervous system protein that is important for neuronal function and synaptic plasticity. A BDNF single nucleotide polymorphism, rs6265, leads to an amino acid substitution of valine (Val) with methionine (Met) at codon 66 (Val66Met), which may influence an individual's response to occupational stress, and predispose military members to psychological disorders. Telomere length (TL), a novel measure of biological aging, can be used as a biomarker of stress. Accordingly, telomere shortening may be a surrogate indicator of physiological weathering due to chronic disease and stressful life events. To increase our understanding about the potential effect of the Val66Met mutation on the human stress response, we evaluated the relationships between Val66Met, TL, and mental health symptoms in a military population. In this pilot study (N = 164), we observed an association between Val66Met and reduced TL (p = 0.048). There was no relationship between Val66Met and mental health symptoms. These results support the investigation of gene-environment interactions, and their potential influence on TL due to occupational stress such as military service.},
}
@article {pmid39503976,
year = {2024},
author = {Yılmaz, &#x15e;G and Bozkurt, H},
title = {The expression of shelterin genes and telomere repeat analysis and their effect on Alzheimer's disease.},
journal = {Molecular biology reports},
volume = {51},
number = {1},
pages = {1124},
pmid = {39503976},
issn = {1573-4978},
support = {RM.21.01, RM.19.01, RM.16.01, SBF.14.01//Gaziantep &#xdc;niversitesi/ ; },
mesh = {Humans ; *Alzheimer Disease/genetics ; *Telomere-Binding Proteins/genetics/metabolism ; Male ; Female ; *Shelterin Complex/metabolism ; *Telomere/genetics/metabolism ; Middle Aged ; Telomeric Repeat Binding Protein 2/genetics/metabolism ; Telomere Shortening/genetics ; Adult ; Case-Control Studies ; Telomere Homeostasis/genetics ; Gene Expression Regulation ; Tripeptidyl-Peptidase 1 ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is an age-related dementia disorder characterized by memory loss and behavioral changes. Maintaining the integrity of telomere shortening in AD is important for cellular survival and homeostasis in all cells, especially glial cells. The shelterin protein complex provides telomere integrity. Measuring the expression levels of shelterin genes and determining the telomere lengths regulated by this complex will reveal their effects on AD progression and adult neurogenesis and will allow the detection of the disease or the determination of the progression process from an accessible tissue.<br><br>METHODS AND RESULTS: The study population included 111 patients and 91 healthy controls (male and female, <&#x2009;50 age). The clinical histories (age, gender, hypertension, diabetes mellitus, obesity, cardiovascular disease, MMSE, medication use, family history, sleep disorders, seizure), covariates (HGB, ESR, Na, P, Cl, BUN, CRP, B12, TSH, Glucose, and MRI findings) and the expressional changes of shelterin genes (TERF1, TERF2, TINF2, POT1, TPP1, and RAP1) between the patient and control groups were evaluated relatively. ROC analyses determined the diagnostic power of telomere repeats and gene expressions.<br><br>CONCLUSIONS: In conclusion, upregulation of expression of shleterin complex genes was detected in AD, where telomeres are significantly shorter than in controls (P&#x2009;<&#x2009;0.05). However, only TERF2 and RAP1 were significant (P&#x2009;<&#x2009;0.05). A positive relationship was detected between telomere repeats and these genes (P&#x2009;<&#x2009;0.05). Telomere repeats may be a strong diagnostic criterion to distinguish AD individuals from healthy individuals (AUC&#x2009;=&#x2009;1.000). The upregulation of TERF2 and RAP1 core genes required for telomere integrity results in the instability of excessively shortened telomeres. Expression silencing of these genes may increase telomerase activity and maintain cellular survival. Also, the detection of telomere repeats has potential in the early diagnosis of AD patients.},
}
@article {pmid39501561,
year = {2024},
author = {Gao, B and Sun, PC and Song, YC and Chen, MX and Zhang, DY and Liu, YG and Dai, T and Zhu, FY},
title = {A telomere-to-telomere genome assembly of Salix cheilophila reveals its evolutionary signatures for environmental adaptation.},
journal = {Plant communications},
volume = {},
number = {},
pages = {101182},
doi = {10.1016/j.xplc.2024.101182},
pmid = {39501561},
issn = {2590-3462},
}
@article {pmid39500624,
year = {2024},
author = {Billing, D and Sfeir, A},
title = {The Role of Microhomology-Mediated End Joining (MMEJ) at Dysfunctional Telomeres.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041687},
pmid = {39500624},
issn = {1943-0264},
abstract = {DNA double-strand break (DSB) repair pathways are crucial for maintaining genome stability and cell viability. However, these pathways can mistakenly recognize chromosome ends as DNA breaks, leading to adverse outcomes such as telomere fusions and malignant transformation. The shelterin complex protects telomeres from activation of DNA repair pathways by inhibiting nonhomologous end joining (NHEJ), homologous recombination (HR), and microhomology-mediated end joining (MMEJ). The focus of this paper is on MMEJ, an error-prone DSB repair pathway characterized by short insertions and deletions flanked by sequence homology. MMEJ is critical in mediating telomere fusions in cells lacking the shelterin complex and at critically short telomeres. Furthermore, studies suggest that MMEJ is the preferred pathway for repairing intratelomeric DSBs and facilitates escape from telomere crisis. Targeting MMEJ to prevent telomere fusions in hematologic malignancies is of potential therapeutic value.},
}
@article {pmid39500623,
year = {2024},
author = {O'Sullivan, RJ and Greenberg, RA},
title = {Mechanisms of Alternative Lengthening of Telomeres.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041690},
pmid = {39500623},
issn = {1943-0264},
abstract = {In recent years, significant advances have been made in understanding the intricate details of the mechanisms underlying alternative lengthening of telomeres (ALT). Studies of a specialized DNA strand break repair mechanism, known as break-induced replication, and the advent of telomere-specific DNA damaging strategies and proteomic methodologies to profile the ribonucleoprotein composition of telomeres enabled the discovery of networks of proteins that coordinate the stepwise homology-directed DNA repair and DNA synthesis processes of ALT. These networks couple mediators of homologous recombination, DNA template-switching, long-range template-directed DNA synthesis, and DNA strand resolution with SUMO-dependent liquid condensate formation to create discrete nuclear bodies where telomere extension occurs. This review will discuss the recent findings of how these networks may cooperate to mediate telomere extension by the ALT mechanism and their impact on telomere function and integrity in ALT cancer cells.},
}
@article {pmid39500371,
year = {2024},
author = {Burraco, P and Gabor, C and Bryant, A and Gardette, V and Lengagne, T and Bonzom, JM and Orizaola, G},
title = {Ionizing radiation has negligible effects on the age, telomere length and corticosterone levels of Chornobyl tree frogs.},
journal = {Biology letters},
volume = {20},
number = {11},
pages = {20240287},
doi = {10.1098/rsbl.2024.0287},
pmid = {39500371},
issn = {1744-957X},
support = {//Carl Tryggers Foundation/ ; //Helga Ax:son Johnsons Stiftelse/ ; //Ministerio de Ciencia e Innovaci&#xf3;n/ ; //Uppsala University Zoological Foundation/ ; //French Institute for Radiological Protection and Nuclear Safety-IRSN/ ; //Spanish Association of Terrestrial Ecology-AEET/ ; //Swedish Radiation Protection Agency-SSM/ ; //Spanish Ministry of Science, Innovation and Universities/ ; },
mesh = {Animals ; *Corticosterone/blood ; *Chernobyl Nuclear Accident ; *Anura/genetics ; Ukraine ; Telomere/radiation effects ; Radiation, Ionizing ; Aging/radiation effects ; Male ; },
abstract = {The accident that occurred at the Chornobyl nuclear power plant (Ukraine, 1986) contaminated a large extension of territory after the deposition of radioactive material. It is still under debate whether the chronic exposure to the radiation levels currently present in the area has long-term effects on organisms, such as decreases in longevity. Here, we investigate whether current levels of radiation in Chornobyl negatively impact the age of the Eastern tree frog Hyla orientalis. We also explore whether radiation induces changes in an ageing marker, telomere length or the stress hormone corticosterone. We found no effect of total individual absorbed radiation (including both external and internal exposure) on frog age (n = 197 individuals sampled in 3 consecutive years). We also did not find any relationship between individual absorbed radiation and telomere length, nor between individual absorbed radiation and corticosterone levels. Our results suggest that radiation levels currently experienced by Chornobyl tree frogs may not be high enough to cause severe chronic damage to semi-aquatic vertebrates such as this species. This is the first study addressing age and stress hormones in Chornobyl wildlife, and thus future research will confirm if these results can be extended to other taxa.},
}
@article {pmid39499700,
year = {2024},
author = {Rodrigues, P and Furtado, G and Martins, M and Vieira, R and Orlandi, A and Brito-Costa, S and Moisão, A and Corona, L and Lima, D and Brito, T},
title = {Exposing telomere length's impact on malnutrition risk among older adults residing in the community: Insights from cross-sectional data analysis.},
journal = {PloS one},
volume = {19},
number = {11},
pages = {e0308612},
doi = {10.1371/journal.pone.0308612},
pmid = {39499700},
issn = {1932-6203},
mesh = {Humans ; *Malnutrition/epidemiology ; Aged ; Female ; Male ; Cross-Sectional Studies ; Middle Aged ; Risk Factors ; *Telomere/genetics ; Aged, 80 and over ; Brazil/epidemiology ; Independent Living ; Nutritional Status ; Telomere Shortening ; Nutrition Assessment ; Geriatric Assessment/methods ; },
abstract = {BACKGROUND: Successful aging is associated with an increase in life expectancy. For a better understanding of the aging process, recognize the relationship between telomere length and nutritional status is a novel approach in geriatric science. Telomers shortening coincides with a decrease in life expectancy, and an increased risk of malnutrition-related diseases.<br><br>GOALS: The goal of this study was to investigate whether a shorter telomere length is associated with a greater likelihood of malnutrition in community-dwelling older adults.<br><br>METHODS: A cross-sectional study with a probabilistic sample of 448 older people aged 60 years old or over, and living in the urban area of an inland Brazilian municipality was conducted. The information was gathered in two stages: a) a personal interview was conducted to obtain sociodemographic, cognitive, and functional autonomy data. The Mini Nutritional Assessment was used to assess the risk of malnutrition. b) a blood sample was taken to proceed with the relative quantitative study of telomere length using real-time qPCR method. The differences between the groups were estimated using Pearson's v2 and Fisher's exact tests. In the data analysis, descriptive statistics and multiple logistic regression were applied.<br><br>RESULTS: In 34.15% of the total sample, malnutrition was recognized as a risk factor. Older people with the shortest telomere length had more chances of getting malnutrition (OR = 1.63; IC:95% = 1.04-2.55) compared to those with longer telomeres, independent of age groups, family income, multimorbidity, cognitive decline, and depressive symptoms.<br><br>CONCLUSION: The creation of clinical trials and the implementation of therapies to reduce the risk of malnutrition will be aided using the telomere length as an aging innovative biomarker, connected with nutritional status.},
}
@article {pmid39497037,
year = {2024},
author = {Mao, H and Lin, T and Huang, S and Xie, Z and Chen, J and Shen, X and Ding, Y and Xu, G and Chen, Z},
title = {Association between monocyte to high-density lipoprotein cholesterol ratio and telomere length: based on NHANES 1999-2002.},
journal = {BMC cardiovascular disorders},
volume = {24},
number = {1},
pages = {616},
pmid = {39497037},
issn = {1471-2261},
support = {2023KY244//Medical Science and Technology Project of Zhejiang Province/ ; },
abstract = {BACKGROUND: Telomere length is closely associated with the occurrence and development of cardiovascular and other diseases. Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel indicator of inflammation, oxidative stress, and metabolic syndrome, with some predictive ability for related disease risks in clinical practice. However, there is no research on the correlation between these two factors.<br><br>METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002, we conducted analysis and research on the correlation between MHR and telomere length using the Kruskal-Wallis H test, Spearman rank correlation analysis, and partial correlation analysis. Weighted linear regression analysis assessed the strength of the association between the two variables, while restricted cubic spline regression (RCS) explored potential nonlinear relationships between them.<br><br>RESULTS: The results of correlation analysis showed that MHR levels were negatively correlated with telomere length (&#x3c1;=-0.083, P&#x2009;<&#x2009;0.001), and this relationship remained statistically significant after controlling for other covariates (P all <&#x2009;0.001). Weighted linear regression analysis showed that after adjusting for all covariates, MHR remained negatively associated with telomere length (&#x3b2; = -0.020; 95% CI: -0.039 to -0.002; P&#x2009;=&#x2009;0.037). Subgroup analysis shows that the negative association between MHR and telomere length appeared more striking among females (&#x1d6fd; = -0.024; 95%CI: -0.050 to 0.001; P&#x2009;=&#x2009;0.058), the Non-Hispanic White (&#x1d6fd; = -0.022; 95%CI: -0.045 to 0.002; P&#x2009;=&#x2009;0.066), and other race (&#x1d6fd; = -0.067; 95%CI: -0.134 to -0.000; P&#x2009;=&#x2009;0.049). Using RCS explored potential nonlinear relationships between MHR and telomere length, revealing no nonlinear relationship between the two (P&#x2009;=&#x2009;0.102).<br><br>CONCLUSIONS: This study suggests a negative correlation between MHR levels and telomere length in American adults. More comprehensive research is needed to confirm these findings in the future.},
}
@article {pmid39493885,
year = {2024},
author = {Herrera-Moyano, E and Porreca, RM and Ranjha, L and Skourti, E and Gonzalez-Franco, R and Stylianakis, E and Sun, Y and Li, R and Saleh, A and Montoya, A and Kramer, H and Vannier, JB},
title = {Human SKI component SKIV2L regulates telomeric DNA-RNA hybrids and prevents telomere fragility.},
journal = {iScience},
volume = {27},
number = {11},
pages = {111096},
pmid = {39493885},
issn = {2589-0042},
abstract = {Super killer (SKI) complex is a well-known cytoplasmic 3'-5' mRNA decay complex that functions with the exosome to degrade excessive and aberrant mRNAs, is implicated with the extraction of mRNA at stalled ribosomes, tackling aberrant translation. Here, we show that SKIV2L and TTC37 of the hSKI complex are present within the nucleus, localize on chromatin and at some telomeres during the G2 cell cycle phase. In cells, SKIV2L prevents telomere replication stress, independently of its helicase domain, and increases the stability of telomere DNA-RNA hybrids in G2. We further demonstrate that purified hSKI complex binds telomeric DNA and RNA substrates in vitro and SKIV2L association with telomeres is dependent on DNA-RNA hybrids. Taken together, our results provide a nuclear function for SKIV2L of the hSKI complex in overcoming replication stress at telomeres mediated by its recruitment to DNA-RNA hybrid structures in G2 and thus maintaining telomere stability.},
}
@article {pmid39493361,
year = {2024},
author = {Zhao, W and Wu, J and Tian, M and Xu, S and Hu, S and Wei, Z and Lin, G and Tang, L and Wang, R and Feng, B and Wang, B and Lyu, H and Paetz, C and Feng, X and Xue, JY and Li, P and Chen, Y},
title = {Characterization of O-methyltransferases in the biosynthesis of phenylphenalenone phytoalexins based on the telomere-to-telomere gapless genome of Musella lasiocarpa.},
journal = {Horticulture research},
volume = {11},
number = {4},
pages = {uhae042},
pmid = {39493361},
issn = {2662-6810},
abstract = {Phenylphenalenones (PhPNs), phytoalexins in wild bananas (Musaceae), are known to act against various pathogens. However, the abundance of PhPNs in many Musaceae plants of economic importance is low. Knowledge of the biosynthesis of PhPNs and the application of biosynthetic approaches to improve their yield is vital for fighting banana diseases. However, the processes of PhPN biosynthesis, especially those involved in methylation modification, remain unclear. Musella lasiocarpa is a herbaceous plant belonging to Musaceae, and due to the abundant PhPNs, their biosynthesis in M. lasiocarpa has been the subject of much attention. In this study, we assembled a telomere-to-telomere gapless genome of M. lasiocarpa as the reference, and further integrated transcriptomic and metabolomic data to mine the candidate genes involved in PhPN biosynthesis. To elucidate the diversity of PhPNs in M. lasiocarpa, three screened O-methyltransferases (Ml01G0494, Ml04G2958, and Ml08G0855) by phylogenetic and expressional clues were subjected to in vitro enzymatic assays. The results show that the three were all novel O-methyltransferases involved in the biosynthesis of PhPN phytoalexins, among which Ml08G0855 was proved to function as a multifunctional enzyme targeting multiple hydroxyl groups in PhPN structure. Moreover, we tested the antifungal activity of PhPNs against Fusarium oxysporum and found that the methylated modification of PhPNs enhanced their antifungal activity. These findings provide valuable genetic resources in banana breeding and lay a foundation for improving disease resistance through molecular breeding.},
}
@article {pmid39491652,
year = {2024},
author = {Zhou, F and Sun, Z and Cheng, L and Dong, Y},
title = {Leptin modulates ovarian granulosa cell apoptosis by regulating telomerase activity and telomere length in polycystic ovary syndrome.},
journal = {Laboratory investigation; a journal of technical methods and pathology},
volume = {},
number = {},
pages = {102169},
doi = {10.1016/j.labinv.2024.102169},
pmid = {39491652},
issn = {1530-0307},
abstract = {Leptin (LEP) is implicated in the pathogenesis of polycystic ovary syndrome (PCOS). This study investigates the mechanism of LEP in PCOS. The baseline information of 80 PCOS patients and matched controls was analyzed, with serum and follicular fluid (FF) LEP and LEP receptor (LEPR) levels, telomerase activity, and relative telomere length (TL) measured. The correlation of FF LEP with telomerase activity and TL was analyzed. The viability and apoptosis of KGN cells (the ovarian granulosa cells) treated with gradient LEP were assessed. LEP-LEPR interaction was examined. LEPR, c-MYC, and TERT levels and c-MYC protein expression in the TERT promoter region were determined. Nuclear c-MYC translocation was detected. LEP was upregulated in sera and FF of PCOS patients. FF LEP positively-correlated with telomerase activity and TL. Low-concentration LEP facilitated KGN cell proliferation and high-concentration LEP dose-dependently suppressed cell proliferation, promoted apoptosis, upregulated LEPR and increased telomerase activity and relative TL. LEP-LEPR interaction upregulated c-MYC and facilitated its nuclear accumulation. c-MYC enrichment in the TERT promoter region upregulated TERT, altering telomerase activity and TL and inducing cell apoptosis. Briefly, LEP/LEPR activate c-MYC, modulate TERT expression, and increase telomerase activity and TL, thus inducing ovarian granulosa cell apoptosis and participating in PCOS.},
}
@article {pmid39489788,
year = {2024},
author = {Trachu, N and Reungwetwattana, T and Meanwatthana, J and Sukasem, C and Majam, T and Saengsiwaritt, W and Jittikoon, J and Udomsinprasert, W},
title = {Leukocytes telomere length as a biomarker of adverse drug reactions induced by Osimertinib in advanced non-small cell lung cancer.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {26543},
pmid = {39489788},
issn = {2045-2322},
mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics ; Female ; *Acrylamides/adverse effects ; Male ; *Leukocytes/drug effects/metabolism ; *Lung Neoplasms/drug therapy/genetics ; *Aniline Compounds/adverse effects ; Middle Aged ; Aged ; *Telomere/drug effects ; Antineoplastic Agents/adverse effects/therapeutic use ; Telomere Homeostasis/drug effects ; Biomarkers/blood ; Drug-Related Side Effects and Adverse Reactions/diagnosis ; Biomarkers, Tumor/blood/genetics ; Case-Control Studies ; Indoles ; Pyrimidines ; },
abstract = {This study aimed to measure relative telomere length (RTL) in blood leukocytes of advanced-stage NSCLC patients either with or without Osimertinib-induced ADRs and determine whether RTL could serve as a biomarker of Osimertinib-induced ADRs. Blood leukocytes RTL were measured in 63 advanced-stage NSCLC patients and 62 age-matched healthy controls using real-time polymerase chain reaction. In patients with advanced-stage NSCLC, RTL was significantly shorter than that in healthy controls (P < 0.001). Compared to patients without ADRs and those with mild/moderate ADRs, patients with severe ADRs exhibited significantly decreased RTL (P < 0.001, P < 0.001, respectively). ROC curve analysis uncovered a diagnostic value of RTL as a biomarker of Osimertinib-induced ADRs (AUC = 1.000, P < 0.001). Kaplan-Meier analysis revealed a significant association between shorter RTL and increased cumulative incidence of Osimertinib-induced ADRs in patients with advanced-stage NSCLC (P < 0.001). Shorter RTL in blood leukocytes would reflect the occurrence of Osimertinib-induced ADRs and might emerge as a promising biomarker for identifying advanced-stage NSCLC patients who are at risk of experiencing Osimertinib-induced ADRs, particularly those with severe ADRs.},
}
@article {pmid39482583,
year = {2024},
author = {Hu, J and Zhang, J and Liu, Y and Qin, J and Bai, H and Qin, X},
title = {Causal linkage of Graves' disease with aging: Mendelian randomization analysis of telomere length and age-related phenotypes.},
journal = {BMC geriatrics},
volume = {24},
number = {1},
pages = {901},
pmid = {39482583},
issn = {1471-2318},
support = {2018YFE0207300//National Key Research and Development Program of China/ ; 345 Talent Project//Shengjing Hospital of China Medical University/ ; },
mesh = {Humans ; *Mendelian Randomization Analysis/methods ; *Graves Disease/genetics/epidemiology ; *Aging/genetics ; *Genome-Wide Association Study/methods ; *Phenotype ; Telomere ; Telomere Homeostasis/physiology ; Female ; Male ; Aged ; Polymorphism, Single Nucleotide ; },
abstract = {BACKGROUND: Aging is an irreversible progressive decline in physical function. Graves' disease (GD) is a common cause of hyperthyroidism and is characterized by elevated levels of the thyroid hormone (TH). High TH levels are associated with aging and a shortened lifespan. The causal relationship between GD and aging has yet to be investigated.<br><br>METHODS: We used genome-wide association study (GWAS) datasets and Mendelian randomization (MR) analysis to explore the causal link between GD and aging. To assess the statistical power of instrumental variables (IVs), F-statistics and R[2] were used. MR analysis was conducted using inverse-variance weighting (IVW), MR-Egger, weighted median, and weighted mode. The odds ratio (OR) and 95% CI were calculated to estimate the relative risk of GD to the outcomes. The Cochran Q test, I[2], MR-PRESSO test, and MR-Egger regression intercept were calculated using statistical and leave-one-out analyses to test the heterogeneity, horizontal pleiotropy, and stability of the IVs on the outcomes.<br><br>RESULTS: F-statistics of the five IVs were greater than 10, and the R[2] values ranged from 0.033 to 0.156 (R[2]&#x2009;>&#x2009;0.01). According to the results of the IVW analysis, GD had no causal effect on facial aging (p&#x2009;=&#x2009;0.189), age-related macular degeneration (p&#x2009;=&#x2009;0.346), and Alzheimer's disease (p&#x2009;=&#x2009;0.479). There was a causal effect of GD on the remaining outcomes: telomere length (TL) (OR&#x2009;=&#x2009;0.982; 95%CI:0.969-0.994; p&#x2009;=&#x2009;0.004), senile cataract (OR&#x2009;=&#x2009;1.031; 95%CI:1.002-1.060; p&#x2009;=&#x2009;0.033), age-related hearing impairment (OR&#x2009;=&#x2009;1.009; 95%CI:1.004-1.014; p&#x2009;=&#x2009;0.001), chronic obstructive pulmonary disease (COPD) (OR&#x2009;=&#x2009;1.055; 95%CI:1.008-1.103; p&#x2009;=&#x2009;0.020), and sarcopenia (OR&#x2009;=&#x2009;1.027; 95%CI:1.009-1.046; p&#x2009;=&#x2009;0.004).<br><br>CONCLUSIONS: GD accelerates the occurrence of age-related phenotypes including TL, senile cataracts, age-related hearing impairment, COPD, and sarcopenia. In contrast, there are no causal linkages between GD and facial aging, age-related macular degeneration, or Alzheimer's disease. Further experimental studies could be conducted to elucidate the mechanisms by which GD facilitates aging, which could help slow down the progress of aging.},
}
@article {pmid39483338,
year = {2024},
author = {Harman, A and Bryan, TM},
title = {Telomere maintenance and the DNA damage response: a paradoxical alliance.},
journal = {Frontiers in cell and developmental biology},
volume = {12},
number = {},
pages = {1472906},
pmid = {39483338},
issn = {2296-634X},
abstract = {Telomeres are the protective caps at the ends of linear chromosomes of eukaryotic organisms. Telomere binding proteins, including the six components of the complex known as shelterin, mediate the protective function of telomeres. They do this by suppressing many arms of the canonical DNA damage response, thereby preventing inappropriate fusion, resection and recombination of telomeres. One way this is achieved is by facilitation of DNA replication through telomeres, thus protecting against a "replication stress" response and activation of the master kinase ATR. On the other hand, DNA damage responses, including replication stress and ATR, serve a positive role at telomeres, acting as a trigger for recruitment of the telomere-elongating enzyme telomerase to counteract telomere loss. We postulate that repression of telomeric replication stress is a shared mechanism of control of telomerase recruitment and telomere length, common to several core telomere binding proteins including TRF1, POT1 and CTC1. The mechanisms by which replication stress and ATR cause recruitment of telomerase are not fully elucidated, but involve formation of nuclear actin filaments that serve as anchors for stressed telomeres. Perturbed control of telomeric replication stress by mutations in core telomere binding proteins can therefore cause the deregulation of telomere length control characteristic of diseases such as cancer and telomere biology disorders.},
}
@article {pmid39484296,
year = {2023},
author = {Themoteo, RM and De Paula, VJR and Rocha, NKR and Brentani, H and Forlenza, OV},
title = {Lithium Prevents Telomere Shortening in Cortical Neurons in Amyloid-Beta Induced Toxicity.},
journal = {NeuroSci},
volume = {4},
number = {1},
pages = {1-8},
pmid = {39484296},
issn = {2673-4087},
abstract = {BACKGROUND: There is consistent evidence of the potential benefits of lithium attenuating mechanisms of neurodegeneration, including those related to the pathophysiology of Alzheimer's disease (AD), and facilitating neurotrophic and protective responses, including maintenance of telomere length. The aim was to investigate the protective effect of the pre-treatment with lithium on amyloid-beta (Aβ)-induced toxicity and telomere length in neurons.<br><br>METHODS: Cortical neurons were treated with lithium chloride at therapeutic and subtherapeutic concentrations (2 mM, 0.2 mM and 0.02 mM) for seven days. Amyloid toxicity was induced 24 h before the end of lithium treatment.<br><br>RESULTS: Lithium resulted in 120% (2 mM), 180% (0.2 mM) and 140% (0.02 mM) increments in telomere length as compared to untreated controls. Incubation with A&#x3b2;1-42 was associated with significant reductions in MTT uptake (33%) and telomere length (83%) as compared to controls.<br><br>CONCLUSIONS: Lithium prevented loss of culture viability and telomere shortening in neuronal cultures challenged with A&#x3b2; fibrils.},
}
@article {pmid39482017,
year = {2024},
author = {Chuang, LC},
title = {Which one occurs first?Telomere length (TL) shortening or PCOS?.},
journal = {Taiwanese journal of obstetrics &amp; gynecology},
volume = {63},
number = {6},
pages = {967},
doi = {10.1016/j.tjog.2024.05.028},
pmid = {39482017},
issn = {1875-6263},
}
@article {pmid39474987,
year = {2024},
author = {Ye, Q and Apsley, AT and Hastings, WJ and Etzel, L and Newschaffer, C and Shalev, I},
title = {Parental age at birth, telomere length, and autism spectrum disorders in the UK Biobank cohort.},
journal = {Autism research : official journal of the International Society for Autism Research},
volume = {},
number = {},
pages = {},
doi = {10.1002/aur.3258},
pmid = {39474987},
issn = {1939-3806},
abstract = {Older parental age at birth is associated with increased risk of autism spectrum disorders (ASD) in offspring. Independently, shorter telomere length (TL) has also been shown to be associated with ASD in children. However, older paternal age at birth, with or without controlling for maternal age, has been associated with longer TL, a seemingly contradictory finding. Here, we conducted a retrospective cohort study among participants in the UK Biobank to disentangle associations between leukocyte TL and ASD status in adults, and the potential moderation by parental age on adult offspring's TL. Participants with ASD diagnosis (N = 87) with a mean age of 46.0 (SD 4.4) years were matched to participants without ASD diagnosis (N = 870) based on age, sex, ethnicity, education, household income, and assessment center. No statistically significant differences were seen in TL between participants with and without ASD when parental age at birth was not considered. However, there was a significant interaction between ASD diagnostic status and parental age on participants' TL, such that older paternal or maternal age at birth was more strongly associated with longer TL in participants with ASD. This study suggests that the shortened TL observed in children with ASD in previous research may partially depend on parental age at birth. Future studies tracking TL attrition before ASD diagnosis are warranted to depict temporal associations and the interacting effects of parental age at birth and ASD status on TL across the lifespan.},
}
@article {pmid39474905,
year = {2024},
author = {Bianco-Miotto, T and Phillips, AL and Heinze, DR and Pennell, CE and Maganga, RK and Beilin, LJ and Mori, TA and Grieger, JA},
title = {Adverse pregnancy outcomes are associated with shorter telomere length in the 17-year-old child.},
journal = {Journal of developmental origins of health and disease},
volume = {15},
number = {},
pages = {e26},
doi = {10.1017/S2040174424000291},
pmid = {39474905},
issn = {2040-1752},
mesh = {Humans ; Female ; Pregnancy ; Adolescent ; Male ; *Pregnancy Outcome/epidemiology ; *Telomere ; Prospective Studies ; Adult ; Pregnancy Complications/genetics/epidemiology ; Infant, Newborn ; Telomere Shortening ; Western Australia/epidemiology ; },
abstract = {This study examined associations between pregnancy and infant birth outcomes with child telomere length at age 17 years; and investigated if there are sex differences between pregnancy complications and telomere length. We utilised the population-based prospective Raine cohort study in Western Australia, Australia. 2900 pregnant women were recruited at 16-20 weeks' gestation (Gen 1), and their children (Gen 2) were followed up over several years. Generalised linear models were used to examine relationships between pregnancy or birth outcomes (gestational diabetes, pre-eclampsia, preterm birth, low birth weight, macrosomia), and as a composite, with telomere length, measured via a DNA sample from blood at 17 years of age. Analyses were adjusted for a range of confounders. Among the 1202 included children, there were no differences in child telomere length for any of the individual maternal or birth weight pregnancy outcomes nor were there any significant interactions between each of the complications (individual or composite) and the sex of the child. However, females born from any of the 5 adverse outcomes had shorter telomeres (estimated mean (SE) = -0.159 (0.061), p = 0.010) than females born in the absence of these complications. Specifically, females born from a pre-eclamptic pregnancy had shorter telomeres than females not born from a pre-eclamptic pregnancy (estimated mean (SE) = -0.166 (0.072), p = 0.022). No relationships were observed in males. Further longitudinal studies are needed to understand mediating factors that are important in predicting offspring telomere length and the necessity to investigate females and males independently.},
}
@article {pmid39474122,
year = {2024},
author = {Fernández de la Puente, M and Valle-Hita, C and Salas-Huetos, A and Martínez, M&#xc1; and Sánchez-Resino, E and Canudas, S and Torres-Oteros, D and Relat, J and Babio, N and Salas-Salvadó, J},
title = {Sperm and leukocyte telomere length are related to sperm quality parameters in healthy men from the Led-Fertyl study.},
journal = {Human reproduction open},
volume = {2024},
number = {4},
pages = {hoae062},
pmid = {39474122},
issn = {2399-3529},
abstract = {STUDY QUESTION: Could sperm and leukocyte telomere length (TL) be associated with sperm quality parameters and reproductive health in men from the general population?<br><br>SUMMARY ANSWER: A positive association between sperm and leukocyte TL with sperm concentration and total count has been demonstrated.<br><br>WHAT IS KNOWN ALREADY: Male factors account for almost half of cases of couple infertility, and shorter TLs have been observed in sperm from men with impaired sperm parameters. However, evidence in men from the general population is limited.<br><br>STUDY DESIGN SIZE DURATION: A total of 200 volunteers of reproductive age were recruited between February 2021 and April 2023 to participate in the Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters (Led-Fertyl) cross-sectional study.<br><br>TLs in sperm and leukocytes were measured using quantitative polymerase chain reaction (qPCR) in 168 and 194 participants, respectively. Sperm parameters, including concentration, total count, motility, vitality, and morphology, were analyzed using a computer-assisted sperm analysis (CASA) SCA[&#xae;] system according to the World Health Organization (WHO) 2010&#xa0;guidelines. Multivariable regression models were performed to assess the associations between sperm and leukocyte TL, either in tertiles or as continuous variables, and sperm quality parameters while adjusting for potential confounders.<br><br>Participants in tertiles 2 (T2) and 3 (T3) of sperm TL showed a higher sperm concentration (&#x3b2;: 1.09; 95% CI: 0.09-2.09 and &#x3b2;: 2.06; 95% CI: 1.04-3.09 for T2 and T3, respectively; P-trend&#x2009;<&#x2009;0.001), compared to those in the reference tertile (T1). Participants in the highest tertile of sperm TL showed higher total sperm count (&#x3b2;: 3.83; 95% CI: 2.08-5.58 for T3 vs T1; P-trend&#x2009;<&#x2009;0.001). Participants in the top tertile of leukocyte TL showed higher sperm concentration (&#x3b2;: 1.49; 95% CI: 0.44-2.54 for T3 vs T1; P-trend&#x2009;=&#x2009;0.004), and total count (&#x3b2;: 3.49; 95% CI: 1.62-5.35 for T3 vs T1; P-trend&#x2009;<&#x2009;0.001) compared with participants in T1. These results remained consistent when sperm and leukocyte TL were modelled as continuous variables.<br><br>One limitation is the impossibility of establishing a cause-effect relationship due to the cross-sectional study design. Additionally, the sample size of the study cannot be considered large.<br><br>Sperm and leukocyte TLs are associated with sperm quality parameters in the general population. Additional determinations and further studies with larger sample sizes are needed to clarify the mechanisms underlying these associations and to investigate the further implications.<br><br>The Led-Fertyl study was supported by the Spanish government's official funding agency for biomedical research, Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigaci&#xf3;n para la Salud (FIS) and co-funded by the European Union ERDF/ESF, 'A way to make Europe'/'Investing in your future' (PI21/01447), and the Diputaci&#xf3; de Tarragona (2021/11-No.Exp. 8004330008-2021-0022642). J.S.-S., senior author of the present study, is partially supported by ICREA under the ICREA Academia program. M.F.d.l.P. was supported by a predoctoral grant from the Rovira i Virgili University and Diputaci&#xf3; de Tarragona (2020-PMF-PIPF-8). C.V.-H. received a predoctoral grant from the Generalitat de Catalunya (2022 FI_B100108). M.&#xc1;.M. was supported by the Sara Borrell postdoctoral fellowship (CD21/00045-Instituto de Salud Carlos III (ISCIII)). All authors declare that they have no conflicts of interest.<br><br>TRIAL REGISTRATION NUMBER: N/A.},
}
@article {pmid39468654,
year = {2024},
author = {Lyu, Y and Zhao, H and Zeng, G and Yang, J and Shao, Q and Wu, H},
title = {Mapping the evolving trend of research on leukocyte telomere length: a text-mining study.},
journal = {Human genomics},
volume = {18},
number = {1},
pages = {117},
pmid = {39468654},
issn = {1479-7364},
support = {LHGJ20210294//2021 joint construction project of Henan Medical Science and Technology Breakthrough Plan/ ; },
mesh = {Humans ; *Leukocytes ; *Telomere/genetics ; *Data Mining ; *Bibliometrics ; *Telomere Homeostasis/genetics ; Aging/genetics ; },
abstract = {BACKGROUND: Substantial evidence indicates that measuring leukocyte telomere length (LTL) is a useful tool that may be considered as a valuable biomarker of individual biological age, correlating with numerous chronic disorders. However, to date, there has been a lack of in-depth understanding regarding the current landscape and forthcoming developments in the LTL field. Therefore, this study aimed to utilize bibliometric methods to summarize the knowledge structure, current focus, and emerging directions in this field.<br><br>METHOD: Scientific publications on LTL spanning the period from 2000 to 2022 were acquired from the Web of Science Core Collection database. Several bibliometric tools including CiteSpace, VOSviewer, and an online website were utilized for bibliometric analysis. The primary evaluations encompassed investigating the major contributors and their collaborative relationships among countries/regions, institutions, and authors, conducting co-citation analyses of authors, journals, as well as reference, examining reference bursts, as well as performing co-occurrence analyses of keywords.<br><br>RESULTS: There are 1818 papers with 66,668 citations identified. Both the annual publication and citation counts on LTL exhibited significant upward trends. The United States emerged as the most prominent contributor, as evidenced by the greatest volume of papers and the highest H-index value. University of California San Francisco and Aviv A were identified as the most productive institution and author in this domain, respectively. Reference analysis revealed that longitudinal study and mendelian randomization study are the most concerned research method in this field recently. Keywords analysis showed that the most concerned diseases in LTL fields were aging, inflammation, cardiovascular diseases, endocrine diseases, neurological and psychiatric diseases, and cancers. In addition, the following research directions such as "COPD", "mendelian randomization", "adiposity", "colorectal cancer", "National Health and Nutrition Examination Survey (NHNES)", "telomerase reverse transcriptase", "pregnancy" have garnered increasing attention in recent times and hold the potential to evolve into research foci in the foreseeable future.<br><br>CONCLUSION: This is the first bibliometric study that provides comprehensive overview of LTL research. The findings of this study could become valuable references for investigators to explore and address the current and emerging challenges in LTL research.},
}
@article {pmid39468351,
year = {2024},
author = {Salgado, S and Abreu, PL and Moleirinho, B and Guedes, DS and Larcombe, L and Azzalin, CM},
title = {Human PC4 supports telomere stability and viability in cells utilizing the alternative lengthening of telomeres mechanism.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
pmid = {39468351},
issn = {1469-3178},
support = {2021.00143.CEECIND//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia (FCT)/ ; PTDC/MED-ONC/7864/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia (FCT)/ ; 2022.11369.BD//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia (FCT)/ ; LCF/PR/HP21/52310016//LaCaixa Foundation/ ; LCF/PR/HP21/52310016//TessellateBio/ ; },
abstract = {Cancer cells with an activated Alternative Lengthening of Telomeres (ALT) mechanism elongate telomeres via homology-directed repair. Sustained telomeric replication stress is an essential trigger of ALT activity; however, it can lead to cell death if not properly restricted. By analyzing publicly available data from genome-wide CRISPR KO screenings, we have identified the multifunctional protein PC4 as a novel factor essential for ALT cell viability. Depletion of PC4 results in rapid ALT cell death, while telomerase-positive cells show minimal effects. PC4 depletion induces replication stress and telomere fragility primarily in ALT cells, and increases ALT activity. PC4 binds to telomeric DNA in cells, and its binding can be enhanced by telomeric replication stress. Finally, a mutant PC4 with partly impaired single stranded DNA binding activity is capable to localize to telomeres and suppress ALT activity and telomeric replication stress. We propose that PC4 supports ALT cell viability, at least partly, by averting telomere dysfunction. Further studies of PC4 interactions at ALT telomeres may hold promise for innovative therapies to eradicate ALT cancers.},
}
@article {pmid39467523,
year = {2024},
author = {Alwehaidah, MS and Bakhiet, M},
title = {Association of leukocyte telomere length and the risk of disease severity and metabolic comorbidities in Arab patients with psoriasis.},
journal = {Cytogenetic and genome research},
volume = {},
number = {},
pages = {1-13},
doi = {10.1159/000542323},
pmid = {39467523},
issn = {1424-859X},
abstract = {INTRODUCTION: Several studies have related shortened leukocyte telomere length (LTL) with age-related diseases and worse prognosis. Telomere length attrition has recently been associated with inflammatory diseases, including psoriasis. However, no study has demonstrated an association between LTL and the risk of disease severity and metabolic comorbidities in Arab patients with psoriasis (Ps).<br><br>METHODS: 68 Ps and 42 normal controls (NC) were included. LTL and oxidative damage were determined by quantitative (q) PCR. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression. Statistical differences between the groups were determined using &#xf063;2 and t-tests.<br><br>RESULTS: Patients with psoriasis had significantly shorter LTL (P= 0.032) and higher oxidative damage (P= 0.015) than those without psoriasis. Patients with moderate-to-severe index (P= 0.03) and metabolic comorbidity showed significantly shorter LTL (P= 0.003) compared to patients with mild index and without metabolic comorbidity, respectively. Patients with short LTL (&#x2264; 0.9) were correlated with higher risk of moderate-to-severe conditions (OR= 6.98, 95% CI= 2.3-20.8, P= 0.001) and metabolic comorbidities (OR= 2.89, 95% CI= 1.02- 8.2, P= 0.04).<br><br>CONCLUSION: LTL shortening may be a consequence of increased oxidative damage, and is related to the risk of severe psoriasis and metabolic comorbidities. Therefore, LTL may be a good candidate biomarker for predicting the risk of poor prognosis in patients with psoriasis.},
}
@article {pmid39464117,
year = {2024},
author = {McLester-Davis, LWY and Norton, D and Papale, LA and James, TT and Salazar, H and Asthana, S and Johnson, SC and Gooding, DC and Roy, TR and Alisch, RS and Drury, SS and Gleason, CE and Zuelsdorff, M},
title = {Telomere length and cognitive function among middle-aged and older participants from communities underrepresented in aging research: A preliminary study.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.10.14.618331},
pmid = {39464117},
issn = {2692-8205},
abstract = {OBJECTIVE: Accelerated biological aging is a plausible and modifiable determinant of dementia burden facing minoritized communities, but is not well-studied in these historically underrepresented populations. Our objective was to preliminarily characterize relationships between telomere length and cognitive health among American Indian/Alaska Native (AI/AN) and Black/African American (B/AA) middle-aged and older adults.<br><br>METHODS: This study included data on telomere length and cognitive test performance from 187 participants, enrolled in one of two community-based cognitive aging cohorts and who identified their primary race as AI/AN or B/AA.<br><br>RESULTS: Nested multivariable regression models revealed preliminary evidence for associations between telomere length and cognitive performance, and these associations were partially independent of chronological age.<br><br>DISCUSSION: Small sample size limited estimate precision, however, findings suggest future work on telomere length and cognitive health in underrepresented populations at high risk for dementia is feasible and valuable as a foundation for social and behavioral intervention research.},
}
@article {pmid39463989,
year = {2024},
author = {Kim, D and Bhargava, R and Wang, SC and Lee, D and Patel, R and Oh, S and Bowman, RW and Na, CH and O'Sullivan, RJ and Miller, KM},
title = {TRIM24 directs replicative stress responses to maintain ALT telomeres via chromatin signaling.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.10.18.618947},
pmid = {39463989},
issn = {2692-8205},
abstract = {An inability to replicate the genome can cause replication stress and genome instability. Here, we develop BLOCK-ID, a proteomic method to identify and visualize proteins at stressed replication forks. This approach successfully identified novel mediators of the replication stress response, including the chromatin acetylation reader protein TRIM24. In validating TRIM24 function, we uncovered its crucial role in coordinating Alternative Lengthening of Telomeres (ALT), a cancer-specific telomere extension pathway involving replication stress. Our data reveal that TRIM24 is directed to telomeres via a p300/CBP-dependent acetylation chromatin signaling cascade, where it organizes ALT-associated PML bodies (APBs) to promote telomere DNA synthesis. Strikingly, we demonstrate that when artificially tethered at telomeres, TRIM24 can stimulate new telomere DNA synthesis in a SUMO-dependent manner, independently of p300/CBP or PML-dependent APBs. Thus, this study identifies a TRIM24 chromatin signaling pathway required for ALT telomere maintenance.},
}
@article {pmid39463735,
year = {2024},
author = {Rodriguez, MD and Bailey, SM and Doherty, PF and Huyvaert, KP},
title = {Increased Reproductive Output and Telomere Shortening Following Calcium Supplementation in a Wild Songbird.},
journal = {Ecology and evolution},
volume = {14},
number = {10},
pages = {e70483},
pmid = {39463735},
issn = {2045-7758},
abstract = {Life history theory predicts increased parental investment comes with fitness costs, often expressed as negative effects on survival and future reproduction. To better understand the costs of reproduction and life history trade-offs, we evaluated calcium supplementation at a high-elevation site in Colorado as a novel approach to experimentally alter reproductive investment in nesting female Tachycineta bicolor (tree swallow). Calcium is a nutrient critical to avian reproduction as the intake of natural calcium is essential for egg production, embryo development, and nestling growth. Altering calcium availability exclusively during the breeding season allowed examination of individual biological responses to experimental modification of reproduction, as well as the reproductive costs associated with egg production and laying an entire clutch. As a functional endpoint and proxy for fitness and longevity, telomere length was measured at the beginning and end of each breeding season. Telomeres-protective "caps" at the ends of chromosomes-have been shown to shorten with aging and a variety of stressors, including higher reproductive output. Results demonstrate that tree swallow mothers supplemented with calcium during the breeding season experience higher reproductive output and produce offspring with longer telomeres, which came at the cost of relatively shorter telomeres during the reproductive season. These findings provide additional support for reproductive trade-offs, and also challenge previous calcium supplementation studies that suggest excess calcium reduces the cost of reproduction.},
}
@article {pmid39462986,
year = {2024},
author = {Savage, SA and Bertuch, AA and , },
title = {Different phenotypes with different endings-Telomere biology disorders and cancer predisposition with long telomeres.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.19851},
pmid = {39462986},
issn = {1365-2141},
support = {/CP/NCI NIH HHS/United States ; R01&#xa0;HL131744/GF/NIH HHS/United States ; },
abstract = {Rare germline pathogenic variants (GPVs) in genes essential in telomere length maintenance and function have been implicated in two broad classes of human disease. The telomere biology disorders (TBDs) are a spectrum of life-threatening conditions, including bone marrow failure, liver and lung disease, cancer and other complications caused by GPVs in telomere maintenance genes that result in short and/or dysfunctional telomeres and reduced cellular replicative capacity. In contrast, cancer predisposition with long telomeres (CPLT) is a disorder associated with elevated risk of a variety of cancers, primarily melanoma, thyroid cancer, sarcoma, glioma and lymphoproliferative neoplasms caused by GPVs in shelterin complex genes that lead to excessive telomere elongation and increased cellular replicative capacity. While telomeres are at the root of both disorders, the term TBD is used to convey the clinical phenotypes driven by critically short or otherwise dysfunctional telomeres and their biological consequences.},
}
@article {pmid39461942,
year = {2024},
author = {Qi, Y and Shan, D and Cao, Y and Ma, N and Lu, L and Tian, L and Feng, Z and Ke, F and Jian, J and Gao, Z and Xu, Y},
title = {Telomere-to-telomere Genome Assembly of two representative Asian and European pear cultivars.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {1170},
pmid = {39461942},
issn = {2052-4463},
support = {CARS-28//Earmarked Fund for China Agriculture Research System/ ; CARS-28//Earmarked Fund for China Agriculture Research System/ ; },
mesh = {*Pyrus/genetics ; *Genome, Plant ; *Telomere/genetics ; Genetic Variation ; Chromosomes, Plant ; },
abstract = {As the third most important temperate fruit, Pear (Pyrus spp.) exhibits a remarkable genetic diversity and is classified into two mainly categories known as Asian pear and European pear. Although several pear genomes are available, most of the released versions are fragmented and not chromosome-level high-quality. In this study, we report two high-quality genomes for Pyrus bretschneideri Rhed. cv. 'Danshansuli' (DS) and Pyrus communis L. cv. 'Conference' (KFL), which represent the predominant Asian and European cultivars, respectively, with nearly telomere-to-telomere (T2T) gap-free level. The finally assembled genome sizes for DS and KFL were 510.98 Mb and 510.71 Mb, respectively, with Contig N50 of 29.47 Mb and 30.47 Mb, where each chromosome was represented by a single contig. The DS and KFL genomes yielded a total of 46,394 and 44,702 protein-coding genes, respectively. Among these genes, the functional annotation accounted for 96.47% and 96.46% in the DS and KFL genomes. The two novels nearly T2T genomic information offers an invaluable resource for comparative genomics, genetic diversity analysis, molecular breeding strategies, and functional exploration.},
}
@article {pmid39461596,
year = {2024},
author = {Rattan, P and Nguyen, K and Penrice, DD and Povero, D and Simonetto, DA},
title = {Underrecognized Association of Porto-Sinusoidal Vascular Disorder and Telomere Biology Disorders.},
journal = {Journal of hepatology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jhep.2024.10.029},
pmid = {39461596},
issn = {1600-0641},
}
@article {pmid39459444,
year = {2024},
author = {Lee, SH and Kim, TK and Yoo, JH and Park, HJ and Kim, JH and Lee, JH},
title = {Analysis of the Association between Telomere Length and Neurological Disability in Stroke Types.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {60},
number = {10},
pages = {},
doi = {10.3390/medicina60101657},
pmid = {39459444},
issn = {1648-9144},
support = {2022R1G1A100745513//National Research Foundation of Korea/ ; },
mesh = {Humans ; Female ; Male ; Prospective Studies ; Aged ; Middle Aged ; *Stroke/complications/physiopathology/genetics ; Telomere ; Ischemic Stroke/complications/genetics/physiopathology ; Disability Evaluation ; Prognosis ; Disabled Persons/statistics &amp; numerical data ; Aged, 80 and over ; },
abstract = {Background and Objectives: The association between neurological disability, prognosis, and telomere length (TL) in patients with stroke has been investigated in various ways. However, analysis of the type of stroke and ischemic stroke subgroups is limited. In this study, we aimed to determine the association between TL and neurological disability according to stroke type. Materials and Methods: This prospective study included patients with stroke who visited a single-center emergency department (ED) between January 2022 and December 2023. The association between TL and neurological disabilities, using the Modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS), was evaluated according to the patient's stroke type and subgroup of ischemic stroke. Multivariate analysis was performed to determine the association between neurological disabilities in patients with ischemic stroke and the subgroups. Results: A total of 271 patients with stroke were enrolled. The NIHSS score was found to be higher at the time of ED visit (adjusted odds ratio [OR], 5.23; 95% confidence interval [CI], 1.59-17.2, p < 0.01) and 1 day later (adjusted OR, 7.78; 95% CI, 1.97-30.70, p < 0.01) in the ischemic stroke group with a short TL. In the other determined etiology (OD) or undetermined etiology (UD) group, the NIHSS was higher in the short TL group at the ED visit (adjusted OR, 7.89; 95% CI, 1.32-47.25, p = 0.02) and 1 day after (adjusted OR, 7.02; 95% CI, 1.14-43.47, p = 0.04). Conclusions: TL is associated with neurological disability in early ischemic stroke and is prominent in the UD and OD subgroups.},
}
@article {pmid39457663,
year = {2024},
author = {Zole, E and Baumanis, E and Freimane, L and Dāle, R and Leiše, A and Lietuvietis, V and Ranka, R},
title = {Changes in TP53 Gene, Telomere Length, and Mitochondrial DNA in Benign Prostatic Hyperplasia Patients.},
journal = {Biomedicines},
volume = {12},
number = {10},
pages = {},
doi = {10.3390/biomedicines12102349},
pmid = {39457663},
issn = {2227-9059},
abstract = {BACKGROUND: Benign prostatic hyperplasia (BPH) is a growing issue due to an ageing population. Our study investigated the possible associations between BPH and ageing hallmarks, including the telomere length (TL) and mitochondrial genome copy number (mtDNA CN), along with genetic variations in the TP53 gene and mtDNA.<br><br>METHODS: Prostate tissue samples were obtained from 32 patients with BPH, together with 30 blood samples. As a healthy control group, age-matching blood DNA samples were used. For the comparison of mtDNA sequence data, 50 DNA samples of the general Latvian population were used. The full mtDNA genome was analyzed by using Next-Generation Sequencing (NGS), the TP53 gene by Sanger sequencing, and the mtDNA copy number (mtDNA CN) and telomere length (TL) byqPCR assay.<br><br>RESULTS: The results showed that in BPH patients, telomeres in the prostate tissue were significantly longer than in blood cells, while the TL in blood cells of the healthy controls was the shortest. Also, the mtDNA amount in the prostate tissue of BPH patients was significantly greater in comparison with blood cells, and controls had the smallest mtDNA CN. We did not find any mutations in the TP53 gene that could be linked to BPH; however, in mtDNA, we found several unique mutations and heteroplasmic changes, as well as genetic changes that have been previously associated with prostate cancer.<br><br>CONCLUSIONS: In conclusion, prolonged telomeres and changes in the mtDNA amount might be involved in the molecular mechanisms of BPH. Some of the heteroplasmic or homoplasmic mtDNA variants might also contribute to the development of BPH. Additional studies are needed to substantiate these findings.},
}
@article {pmid39457609,
year = {2024},
author = {Villar-Juárez, GE and Genis-Mendoza, AD and Martínez-López, JNI and Fresan, A and Tovilla-Zaráte, CA and Nolasco-Rosales, GA and Juárez-De la Cruz, GI and Ramos, DR and Villar-Soto, M and Mejía-Ortiz, P and Gómez Mendiola, M and Juárez-Rojop, IE and Nicolini, H},
title = {Exploring the Relationship between Telomere Length and Cognitive Changes in Post-COVID-19 Subjects.},
journal = {Biomedicines},
volume = {12},
number = {10},
pages = {},
doi = {10.3390/biomedicines12102296},
pmid = {39457609},
issn = {2227-9059},
abstract = {BACKGROUND/OBJECTIVES: Emerging evidence suggests that patients suffering from COVID-19 may experience neurocognitive symptoms. Furthermore, other studies indicate a probable association between leukocyte telomere length (LTL) and neurocognitive changes in subjects with post-COVID-19 condition. Our study was designed to determine the correlation between telomere length and cognitive changes in post-COVID-19 subjects.<br><br>METHODS: This study included 256 subjects, categorized based on SARS-CoV-2 infection from 2020 to 2023. In addition, subjects with a psychiatric diagnosis were considered. Moreover, the MoCA and MMSE scales were applied. Telomere length was determined using a polymerase chain reaction, and statistical analysis was employed using ANOVA and X[2] tests.<br><br>RESULTS: We identified a decrease in LTL in individuals with post-COVID-19 conditions compared to those without SARS-CoV-2 infection (p &#x2264; 0.05). However, no association was found between LTL and cognitive impairment in the subjects post-COVID-19.<br><br>CONCLUSIONS: The findings suggest that LTL is affected by SARS-CoV-2 infection. Nonetheless, this important finding requires further research by monitoring neurological changes in subjects with post-COVID condition.},
}
@article {pmid39456511,
year = {2024},
author = {Kapetanou, M and Athanasopoulou, S and Goutas, A and Makatsori, D and Trachana, V and Gonos, E},
title = {α-Terpineol Induces Shelterin Components TRF1 and TRF2 to Mitigate Senescence and Telomere Integrity Loss via A Telomerase-Independent Pathway.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {13},
number = {10},
pages = {},
doi = {10.3390/antiox13101258},
pmid = {39456511},
issn = {2076-3921},
support = {Biomage project//Private/ ; Postdoctoral Fellowship//Hellenic Pasteur Institute/ ; },
abstract = {Cellular senescence is a hallmark of aging characterized by irreversible growth arrest and functional decline. Progressive telomeric DNA shortening in dividing somatic cells, programmed during development, leads to critically short telomeres that trigger replicative senescence and thereby contribute to aging. Therefore, protecting telomeres from DNA damage is essential in order to avoid entry into senescence and organismal aging. In several organisms, including mammals, telomeres are protected by a protein complex named shelterin that prevents DNA damage at the chromosome ends through the specific function of its subunits. Here, we reveal that the nuclear protein levels of shelterin components TRF1 and TRF2 decline in fibroblasts reaching senescence. Notably, we identify α-terpineol as an activator that effectively enhances TRF1 and TRF2 levels in a telomerase-independent manner, counteracting the senescence-associated decline in these crucial proteins. Moreover, α-terpineol ameliorates the cells' response to oxidative DNA damage, particularly at the telomeric regions, thus preserving telomere length and delaying senescence. More importantly, our findings reveal the significance of the PI3K/AKT pathway in the regulation of shelterin components responsible for preserving telomere integrity. In conclusion, this study deepens our understanding of the molecular pathways involved in senescence-associated telomere dysfunction and highlights the potential of shelterin components to serve as targets of therapeutic interventions, aimed at promoting healthy aging and combating age-related diseases.},
}
@article {pmid39456194,
year = {2024},
author = {Han, F and Riaz, F and Pu, J and Gao, R and Yang, L and Wang, Y and Song, J and Liang, Y and Wu, Z and Li, C and Tang, J and Xu, X and Wang, X},
title = {Connecting the Dots: Telomere Shortening and Rheumatic Diseases.},
journal = {Biomolecules},
volume = {14},
number = {10},
pages = {},
doi = {10.3390/biom14101261},
pmid = {39456194},
issn = {2218-273X},
mesh = {Humans ; *Rheumatic Diseases/genetics/metabolism ; *Telomere Shortening/genetics ; *Telomerase/metabolism/genetics ; *Telomere/metabolism/genetics ; Oxidative Stress/genetics ; Animals ; },
abstract = {Telomeres, repetitive sequences located at the extremities of chromosomes, play a pivotal role in sustaining chromosomal stability. Telomerase is a complex enzyme that can elongate telomeres by appending telomeric repeats to chromosome ends and acts as a critical factor in telomere dynamics. The gradual shortening of telomeres over time is a hallmark of cellular senescence and cellular death. Notably, telomere shortening appears to result from the complex interplay of two primary mechanisms: telomere shelterin complexes and telomerase activity. The intricate interplay of genetic, environmental, and lifestyle influences can perturb telomere replication, incite oxidative stress damage, and modulate telomerase activity, collectively resulting in shifts in telomere length. This age-related process of telomere shortening plays a considerable role in various chronic inflammatory and oxidative stress conditions, including cancer, cardiovascular disease, and rheumatic disease. Existing evidence has shown that abnormal telomere shortening or telomerase activity abnormalities are present in the pathophysiological processes of most rheumatic diseases, including different disease stages and cell types. The impact of telomere shortening on rheumatic diseases is multifaceted. This review summarizes the current understanding of the link between telomere length and rheumatic diseases in clinical patients and examines probable telomere shortening in peripheral blood mononuclear cells and histiocytes. Therefore, understanding the intricate interaction between telomere shortening and various rheumatic diseases will help in designing personalized treatment and control measures for rheumatic disease.},
}
@article {pmid39448973,
year = {2024},
author = {Hassanpour, H and Javdani, M and Changaniyan-Khorasgani, Z and Rezazadeh, E and Jalali, R and Mojtahed, M},
title = {Is castration leading to biological aging in dogs? Assessment of lipid peroxidation, inflammation, telomere length, mitochondrial DNA copy number, and expression of telomerase and age-related genes.},
journal = {BMC veterinary research},
volume = {20},
number = {1},
pages = {485},
pmid = {39448973},
issn = {1746-6148},
mesh = {Animals ; Dogs ; Male ; *Lipid Peroxidation ; *Aging ; *Telomerase/genetics/metabolism ; *Inflammation/veterinary/genetics/metabolism ; *DNA, Mitochondrial/genetics ; Telomere ; Orchiectomy/veterinary ; Malondialdehyde/blood/metabolism ; C-Reactive Protein/metabolism/genetics/analysis ; DNA Copy Number Variations ; },
abstract = {BACKGROUND: Biological aging is a complex process influenced by various factors, including reproductive status and castration. This study aimed to evaluate the impact of castration on biological aging in dogs.<br><br>METHOD: Fifteen male crossbred dogs were randomly divided into a sham-operation control group (n&#x2009;=&#x2009;5) and a castrated group (n&#x2009;=&#x2009;10). Blood samples were collected at weeks 0, 4, 8, 12, 16, and 18 post-surgery. Malondialdehyde (MDA as indicator of Lipid peroxidation), C-reactive protein (as an indicator of inflammation), telomere length, mitochondrial DNA (mtDNA) copy number, and the expression of age-related (P16, P21, TBX2) and telomerase-related (TERT) genes were assessed in blood samples.<br><br>RESULTS: Plasma MDA levels were higher in the control group at weeks 16 and 18, while CRP levels were higher only at week 18. Telomere length and mtDNA copy number were lower in the control group at week 18. Gene expression analysis showed that P16 was lower in the control group at weeks 8 and 12, P21 and TERT were lower at weeks 16 and 18, and TBX2 was lower at weeks 16 and 18. The TBX2/P16 ratio was lower in the control group at weeks 16 and 18 but higher at week 12, while the TBX2/P21 ratio did not differ between groups.<br><br>CONCLUSION: Castration appears to have a protective effect against biological aging in dogs, as evidenced by lower lipid peroxidation, inflammation, and age-related changes in telomere length, mtDNA copy number, and gene expression.},
}
@article {pmid39448517,
year = {2024},
author = {Domínguez-de-Barros, A and Sifaoui, I and Dorta-Guerra, R and Lorenzo-Morales, J and Castro-Fuentes, R and Córdoba-Lanús, E},
title = {Telomere- and oxidative stress dynamics in Psittacidae species with different longevity trajectories.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {39448517},
issn = {2509-2723},
support = {PP-167-2019-19//Loro Parque Fundaci&#xf3;n/ ; CB21/13/00100//Instituto de Salud Carlos III/ ; 2023-2028 - PI-CC202302222//Cabildo de Tenerife/ ; Cabildo.23//Cabildo de Tenerife/ ; },
abstract = {Telomeres, conserved DNA sequences at chromosome ends, naturally shorten with age, exacerbated by external factors like environmental challenges and reproduction. Birds, particularly psittacine, are gaining prominence as new aging models over the years because of their unique characteristics. This study explores erythrocyte telomere length (TL) and oxidative stress markers in plasma of long- and short-lived captive birds of the order Psittaciformes over four years. Long-lived birds consistently exhibited longer TL than short-lived ones (p = 0.012) but experienced a more pronounced TL shortening rate (p < 0.001) than short-lived ones. Breeding individuals experienced increased TL shortening compared to non-reproductive counterparts in long-lived birds (p = 0.008). Interestingly, long-lived birds showed a higher total antioxidant capacity than short-lived ones (p < 0.001), which was also increased during breeding (p = 0.026). A significant correlation was found between the telomere length shortening rate within the 4 years of study and the accumulated oxidative stress (r = 0.426, p = 0.069) in short-lived birds. These findings shed light on TL and oxidative stress dynamics over time, revealing distinct patterns influenced by life-traits among longevity groups.},
}
@article {pmid39443618,
year = {2024},
author = {Kandemir, I and Sahin, AY and Oyaci, Y and Khudiyeva, S and Sahin, M and Aksakal, MT and Pehlivan, M and Bas, F and Pehlivan, S},
title = {Effect of obesity and NAFLD on leukocyte telomere length and hTERT gene MNS16A VNTR variant.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {25055},
pmid = {39443618},
issn = {2045-2322},
mesh = {Humans ; Adolescent ; *Telomerase/genetics ; Female ; Male ; *Non-alcoholic Fatty Liver Disease/genetics/pathology ; *Obesity/genetics/complications ; Child ; *Minisatellite Repeats/genetics ; *Telomere/genetics ; Young Adult ; Leukocytes/metabolism ; Case-Control Studies ; },
abstract = {It is known that telomere length (TL) (evaluated with T/S ratio) is shortened in the presence of obesity. In this study, we aimed to investigate how obesity in adolescents and non-alcoholic liver disease (NAFLD) within the obese group affect TL and the clinical significance of the human telomerase reverse transcriptase (hTERT) gene MNS16A VNTR variant in terms of NAFLD. Adolescents with exogenous obesity and healthy controls (aged 10-19 years) who applied to our adolescent outpatient clinic between May-October 2023 were included in this study. We performed upper abdominal ultrasonography to investigate the presence of NAFLD in adolescents with obesity and divided into two groups: those without hepatosteatosis (obese NAFLD (-)) and those with hepatosteatosis (obese NAFLD (+)). We recorded body weight, height, waist circumference, and blood pressure measurements and measured the T/S ratio (telomere sequence copy number/gene single copy number) by the Quantitative Polymerase Chain Reaction method. The groups were compared using frequentist and Bayesian methods. Eighty-three obese adolescents [63 NAFLD(+) 20 NAFLD(-)] and 69 lean controls were included in the study. Pairwise comparisons revealed that T/S ratio was significantly lower in the obese NAFLD (-) group than the obese NAFLD (+) and the control group (p = 0.025, p = 0.007, respectively). T/S ratio was lower in the LL allele group than in the other alleles (p = 0.022) and slightly higher in the obese group with metabolic syndrome compared to the obese group without metabolic syndrome (p = 0.072). hTERT-MNS16A-VNTR gene variant LL allele had a negative correlation with T/S ratio among the obese adolescent group. Patients with LL alleles had higher ALT, GGT, HOMA-IR, and ALT/AST. Diastolic blood pressure had a significant correlation with the T/S ratio. The T/S ratio was shorter in the obese adolescent group compared to healthy ones but was higher in the NAFLD (+) obese compared to the NAFLD (-) obese. ALT level and ALT/AST ratio were higher, T/S ratio was lower in the hTERT MNS16A VNTR variant LL allele group among obese adolescents. In addition, there was a significant correlation between the T/S ratio and diastolic blood pressure in obese adolescents.},
}
@article {pmid39441032,
year = {2024},
author = {Gao, Q and Yu, J and Liu, Y and Xing, B and Ping, F and Xu, L and Li, W and Zhang, H and Li, Y},
title = {Elevated 1-Hour Post Load Glucose as a Predictor for Telomere Attrition: a study based on a Chinese Community population.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1210/clinem/dgae748},
pmid = {39441032},
issn = {1945-7197},
abstract = {CONTEXT: 1-hour post-load glucose (1h-PG) detects dysglycemia-related disorders more effectively than traditional glycemic parameters. Hyperglycemia accelerates aging, whether 1h-PG outperforms in predicting aging remains unclear.<br><br>OBJECTIVE: To Compare the effectiveness of 1h-PG with other glycemic parameters in identifying and predicting telomere attrition.<br><br>METHODS: We conducted a cross-sectional and longitudinal study based on a Chinese community cohort. Multivariate linear regression and logistic regression were used to analyze the associations between glycemic parameters and telomere length. The area under the receiver operating characteristic (AUROC) curve were used to compare the differentiating and predictive ability. Populations were regrouped by glucose tolerance status and 1h-PG to compare telomere length. Analyses were separately conducted in non-diabetic and diabetic populations.<br><br>RESULTS: The cross-sectional study included 715 participants. Only 1h-PG was significantly negatively associated with RTL in both non-diabetic (&#x3b2; = -0.106, 95%CI -0.068 to -0.007, P = 0.017) (odds ratio [OR] = 1.151, 95% CI 1.069 to 1.239, P = 0.005) and diabetic (&#x3b2; = -0.222, 95%CI -0.032 to -0.007, P = 0.002) (OR = 1.144, 95% CI 1.041 to 1.258, P = 0.035) populations. The longitudinal study recruited 437 populations and 112 remained in 7-years follow-up. 1h-PG was associated with telomere shortening in the non-diabetic group (&#x3b2; = -0.314, 95%CI -0.276 to -0.032, P = 0.016) (OR = 2.659, 95% CI 1.158 to 6.274, P = 0.021). AUROC analysis showed that 1h-PG outperformed other glycemic parameters in identifying and predicting telomere attrition. Reclassification revealed that normal glucose tolerance and prediabetic individuals with elevated 1h-PG had telomere lengths comparable to prediabetic and diabetic populations, respectively.<br><br>CONCLUSIONS: 1h-PG outperforms other glycemic parameters in predicting telomere attrition and can be a valuable marker for early aging detection.},
}
@article {pmid39438947,
year = {2024},
author = {Coulter, T and Hill, C and McKnight, AJ},
title = {Insights into the length and breadth of methodologies harnessed to study human telomeres.},
journal = {Biomarker research},
volume = {12},
number = {1},
pages = {127},
pmid = {39438947},
issn = {2050-7771},
abstract = {Telomeres are protective structures at the end of eukaryotic chromosomes that are strongly implicated in ageing and ill health. They attrition upon every cellular reproductive cycle. Evidence suggests that short telomeres trigger DNA damage responses that lead to cellular senescence. Accurate methods for measuring telomeres are required to fully investigate the roles that shortening telomeres play in the biology of disease and human ageing. The last two decades have brought forth several techniques that are used for measuring telomeres. This editorial highlights strengths and limitations of traditional and emerging techniques, guiding researchers to choose the most appropriate methodology for their research needs. These methods include Quantitative Polymerase Chain Reaction (qPCR), Omega qPCR (Ω-qPCR), Terminal Restriction Fragment analysis (TRF), Single Telomere Absolute-length Rapid (STAR) assays, Single TElomere Length Analysis (STELA), TElomere Shortest Length Assays (TESLA), Telomere Combing Assays (TCA), and Long-Read Telomere Sequencing. Challenges include replicating telomere measurement within and across cohorts, measuring the length of telomeres on individual chromosomes, and standardised reporting for publications. Areas of current and future focus have been highlighted, with recent methodical advancements, such as long-read sequencing, providing significant scope to study telomeres at an individual chromosome level.},
}
@article {pmid39438690,
year = {2024},
author = {Tyer, C},
title = {High-resolution measurement of individual telomere lengths with Telo-seq.},
journal = {Nature reviews. Cancer},
volume = {},
number = {},
pages = {},
pmid = {39438690},
issn = {1474-1768},
}
@article {pmid39435041,
year = {2024},
author = {},
title = {Erratum: Targeting Telomere Dynamics as an Effective Approach for the Development of Cancer Therapeutics [Corrigendum].},
journal = {International journal of nanomedicine},
volume = {19},
number = {},
pages = {10367-10368},
doi = {10.2147/IJN.S500182},
pmid = {39435041},
issn = {1178-2013},
abstract = {[This corrects the article DOI: 10.2147/IJN.S448556.].},
}
@article {pmid39432594,
year = {2024},
author = {Dai, H and Chen, Z},
title = {Association between dietary vitamin K and telomere length: Based on NHANES 2001 to 2002.},
journal = {Medicine},
volume = {103},
number = {42},
pages = {e40157},
doi = {10.1097/MD.0000000000040157},
pmid = {39432594},
issn = {1536-5964},
mesh = {Humans ; Male ; Female ; *Nutrition Surveys ; Middle Aged ; *Telomere/drug effects ; *Vitamin K/administration &amp; dosage ; *Diet/statistics &amp; numerical data ; Adult ; Aged ; Cross-Sectional Studies ; Body Mass Index ; },
abstract = {As an anti-inflammatory and antioxidant, vitamin K has the potential to reduce telomere attrition. However, the correlation between dietary vitamin K and telomere length (TL) has not been reported. We aimed to investigate the association between these 2 variables. This study included 3754 participants from the National Health and Nutrition Examination Survey 2001-2002 database. We used multivariate linear regression and restricted cubic splines to assess the relationship between dietary vitamin K intake and TL. Subgroup analyses and interaction tests were utilized to examine the stability of the results. After adjusting for all variables, each unit increase in daily dietary intake of vitamin K lengthened telomeres by 0.22 base pairs (β = 0.22, 95% CI: 0.09-0.36, P = .001). Individuals with the highest dietary vitamin K intake had significantly longer TL (β = 80.27, 95% CI: 20.83-139.71, P = .008). Subgroup analyses suggested that this association persisted in populations stratified by gender, age, diabetes, cardiovascular disease (CVD), body mass index and total energy intake (P for interaction > .05). A linear relationship between dietary vitamin K intake and TL was observed in restricted cubic splines (P for nonlinear = .554). In conclusion, our findings suggest that dietary vitamin K intake is positively associated with TL, providing recent evidence to guide the management of healthy diets.},
}
@article {pmid39430825,
year = {2024},
author = {Ding, X and Zhang, Y and You, S},
title = {A novel prognostic model based on telomere-related lncRNAs in gastric cancer.},
journal = {Translational cancer research},
volume = {13},
number = {9},
pages = {4608-4624},
pmid = {39430825},
issn = {2219-6803},
abstract = {BACKGROUND: Telomeres are specialized structures at the ends of chromosomes that are important for their protection. Over time, long non-coding RNAs (lncRNAs) have gradually come into the spotlight as essential biomarkers of proliferation, migration, and invasion of human malignant tumors. Nevertheless, the impact of telomere-related lncRNAs (TRLs) in gastric cancer is currently unknown. In the present study, we screen the TRLs and identify a prognostic TRLs signature in gastric cancer.<br><br>METHODS: First, telomere-related genes (TRGs) were retrieved from the website, and RNA sequencing (RNA-seq) data and clinical data of stomach adenocarcinoma (STAD) patients were gathered from The Cancer Genome Atlas (TCGA) database. Gastric cancer patients' lncRNAs and overall survival (OS) were found to be related using univariate Cox regression analysis. Next, least absolute shrinkage and selection operator (LASSO) regression analysis and multifactorial Cox regression analysis were used to further screen telomere-related differentially expressed lncRNAs (TRDELs), and finally six lncRNAs were obtained, including LINC01537, CFAP61-AS1, DIRC1, RABGAP1L-IT1, DBH-AS1, and REPIN1-AS1. According to these six TRDELs, a prognostic model for gastric cancer was constructed. The samples were divided into the training group and the testing group at random, and the reliability of prognostic model was validated in both groups and overall samples. In addition, we performed Kaplan-Meier (K-M) survival curve analysis, independent prognostic analysis, and functional enrichment analysis to validate the predictive value and independence of the model, as well as immune cell correlation analysis, clustering analysis, and principal component analysis (PCA) to further explore the relationship between this model and the tumor cells. Finally, we performed the drug sensitivity analysis to identify a few small molecules that may have a therapeutic effect on gastric cancer.<br><br>RESULTS: Finally, we constructed a prognostic model for gastric cancer consisting of six TRDELs. According to the K-M curve, the prognosis of the low-risk group was noticeably superior than that of the high-risk group. Multivariate Cox regression analysis suggested that risk score was an independent prognostic element. Receiver operating characteristic (ROC) curves, nomogram, and calibration curve indicated that the prognostic model had good predictive ability. Functional enrichment analysis demonstrated major pathways with high- and low-risk groups. Next, both tumor microenvironment (TME) and immune correlation analysis showed discrepancy in the high- and low-risk groups. Through drug sensitivity analysis, we screened four small molecules that might be beneficial for gastric cancer treatment.<br><br>CONCLUSIONS: A prognostic model consisting of these six TRDELs was capable to predict the prognosis of gastric cancer patients.},
}
@article {pmid39430816,
year = {2024},
author = {Lin, H and Yin, W},
title = {Telomere-related prognostic signature for survival assessments in lung adenocarcinoma.},
journal = {Translational cancer research},
volume = {13},
number = {9},
pages = {4520-4533},
pmid = {39430816},
issn = {2219-6803},
abstract = {BACKGROUND: Telomere-related genes (TRGs) are important in many different types of cancers. However, there is a lack of research on the relationship between their expression and prognosis in lung adenocarcinoma (LUAD) patients. This study is to investigate the prognostic value of TRGs in LUAD and to develop a TRG signature that can predict patient survival.<br><br>METHODS: A total of 2,086 TRGs were obtained from a database of genes involved in telomere maintenance (TelNet), while the clinical information and tumor RNA expression profiles of 513 LUAD patients were acquired from The Cancer Genome Atlas (TCGA) database. Statistical methodologies, such as least absolute shrinkage and selection operator (LASSO)-Cox, were employed to construct a prognostic model with predictive capabilities.<br><br>RESULTS: We analyzed 1,339 telomere-associated differentially expressed genes and identified a ten-gene predictive signature for LUAD. This signature exhibited effective prognostic classification capabilities across multiple datasets, including GSE3141 (58 samples), GSE8894 (63 samples), GSE50081 (127 samples), and GSE72094 (398 samples). Furthermore, we screened tumor-sensitive drugs targeting this signature. High telomere levels were associated with reduced survival in lung cancer patients who underwent surgery. Compared to the traditional TNM (tumor node metastasis classification) grading method, our telomere-associated gene panel demonstrated superior prediction accuracy. Notably, patients in the high-risk group, defined by the telomere-associated signature, exhibited improved responses to immunotherapy, suggesting potential benefits for this subgroup of patients.<br><br>CONCLUSIONS: This study presents a comprehensive molecular signature comprising TRGs, which holds potential for functional and therapeutic investigations. Additionally, it serves as an integrated tool to identify crucial molecules for immunotherapy in lung cancer.},
}
@article {pmid39429092,
year = {2024},
author = {Rubio-Carrasco, K and de la Torre, PG and Martínez-Ezquerro, JD and Sánchez-García, S and García-Vences, E and Camacho-Arroyo, I and Rodríguez-Dorantes, M and González-Covarrubias, V},
title = {Hypertension Control Is Associated with Telomere Length in Older Adults.},
journal = {DNA and cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1089/dna.2024.0173},
pmid = {39429092},
issn = {1557-7430},
abstract = {Hypertension is the leading risk for cardiovascular disease and worldwide mortality. Uncontrolled blood pressure worsens with age and its control is part of public health strategies especially for older adults. Telomere length (TL) has been associated with hypertension, with age and sex as relevant confounding factors, but it is not clear whether hypertension control in older adults impacts on TL and if this relationship is consistently age and sex dependent. TL was assessed in leukocytes of 369 hypertensive patients. Individuals were >60 years male (169) and female (200) and have been diagnosed and treated for hypertension for at least four years. TL was measured by RT-PCR using a commercial probe. Regression models were developed considering systolic and diastolic blood pressure control as dependent variables and age, sex, glucose, and lipid levels as confounding factors. TL showed a mean of 7.5 ± 5.1 Kb, and no difference between males and females was observed. We identified a significant association between systolic blood pressure control and TL (p value = 0.039) and a trend for diastolic blood pressure (p value = 0.061). These observations confirm and expand previous reports showing that hypertension control can have an impact on TL and consequently on other factors of healthy aging.},
}
@article {pmid39426946,
year = {2024},
author = {Wang, B and Kou, H and Wang, Y and Zhang, Q and Jiang, D and Wang, J and Zhao, Z and Zhou, Y and Zhang, M and Sui, L and Zhao, M and Liu, Y and Liu, Y and Shi, L and Wang, F},
title = {LAP2α orchestrates alternative lengthening of telomeres suppression through telomeric heterochromatin regulation with HDAC1: unveiling a potential therapeutic target.},
journal = {Cell death &amp; disease},
volume = {15},
number = {10},
pages = {761},
pmid = {39426946},
issn = {2041-4889},
support = {32170762//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Humans ; Animals ; *Telomere Homeostasis/drug effects ; *Telomere/metabolism ; *Heterochromatin/metabolism ; Mice ; Cell Line, Tumor ; Osteosarcoma/genetics/pathology/metabolism/drug therapy ; Sister Chromatid Exchange ; DNA-Binding Proteins/metabolism/genetics ; Methotrexate/pharmacology/therapeutic use ; Cell Proliferation/drug effects ; Membrane Proteins ; },
abstract = {In response to the challenge of telomere attrition during DNA replication, cancer cells predominantly employ telomerase or, in 10-15% of cases, the alternative lengthening of telomeres (ALT). The intricate details of ALT, however, remain elusive. In this study, we unveil that the knockdown of lamina-associated polypeptide 2 alpha (LAP2α) in ALT cells results in telomere dysfunction, triggering a notable increase in ALT-associated hallmarks, including high frequencies of PML bodies (APBs), C-rich extrachromosomal circles (C-circles), and telomere sister chromatid exchange (T-SCE). Furthermore, LAP2α emerges as a crucial player in break-induced telomere replication for telomerase-positive cells following telomeric double-strand breaks. Mechanistically, our investigation suggests that LAP2α may influence the regulation of the heterochromatic state of telomeres, thereby affecting telomeric accessibility. In line with our findings, LAP2α expression is markedly reduced in ALT-positive osteosarcoma. And the use of methotrexate (MTX) can restore the heterochromatin state altered by LAP2α depletion. This is evidenced by a significant inhibition of tumor proliferation in ALT-positive patient-derived xenograft (PDX) mouse models. These results indicate the important role of LAP2α in regulating ALT activity and offer insights into the interplay between lamina-associated proteins and telomeres in maintaining telomere length. Importantly, our findings may help identify a more appropriate target population for the osteosarcoma therapeutic drug, MTX.},
}
@article {pmid39426311,
year = {2024},
author = {Douglas, ME},
title = {How to write an ending: Telomere replication as a multistep process.},
journal = {DNA repair},
volume = {144},
number = {},
pages = {103774},
doi = {10.1016/j.dnarep.2024.103774},
pmid = {39426311},
issn = {1568-7856},
abstract = {Telomeres are protective nucleoprotein caps found at the natural ends of eukaryotic chromosomes and are crucial for the preservation of stable chromosomal structure. In cycling cells, telomeres are maintained by a multi-step process called telomere replication, which involves the eukaryotic replisome navigating a complex repetitive template tightly bound by specific proteins, before terminating at the chromosome end prior to a 5' resection step that generates a protective 3' overhang. In this review, we examine mechanistic aspects of the telomere replication process and consider how individual parts of this multistep event are integrated and coordinated with one-another.},
}
@article {pmid39422841,
year = {2024},
author = {Fu, H and Zhu, Y and Lin, L and Jiang, P and Cai, G and Zeng, L and Li, X and Zhang, Y and Li, C and Zhan, H and Zhang, B and Yang, Z},
title = {Shorter Leukocyte Telomere Length Is Associated with Increased Major Adverse Cardiovascular Events or Mortality in Patients with Essential Hypertension.},
journal = {Journal of cardiovascular translational research},
volume = {},
number = {},
pages = {},
pmid = {39422841},
issn = {1937-5395},
support = {82171578//National Natural Science Foundation of China/ ; 2023B03J0121//Science and Technology Project of Guangzhou City/ ; 20221800906192//Dongguan Science and Technology of Social Development Program/ ; },
abstract = {The association between leukocyte telomere length (LTL) alteration and major adverse cardiovascular events (MACE) or mortality in patients with hypertension is still unclear. 20,034 patients with essential hypertension were enrolled from UK biobank. Multivariable COX regression models were performed to assess the association. LTL was shorter in hypertensive patients with MACE compared to those without MACE. Hypertensive patients in the lowest LTL quartile were at higher risk to develop MACE (adjusted HR 1.15 [95% CI 1.02-1.29], vs top LTL quartile, p-trend = 0.03). Similarly, shorter LTL was related with increased mortality (adjusted HR 1.18[95% CI 1.06-1.3], lowest vs top LTL quartile, p-trend < 0.001). This investigation demonstrated that shorter LTL is associated with increased risk of MACE or mortality in patients with essential hypertension, which indicates that LTL may be a potential predictor of prognosis or underlying therapeutic target for hypertension.},
}
@article {pmid39420560,
year = {2024},
author = {Lu, D and Liu, C and Ji, W and Xia, R and Li, S and Liu, Y and Liu, N and Liu, Y and Deng, XW and Li, B},
title = {Nanopore Ultra-long Sequencing and Adaptive Sampling Spur Plant Complete Telomere-to-Telomere Genome Assembly.},
journal = {Molecular plant},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molp.2024.10.008},
pmid = {39420560},
issn = {1752-9867},
abstract = {The pursuit of complete telomere-to-telomere (T2T) genome assembly in plants, challenged by genomic complexity, has been advanced by Oxford Nanopore Technologies (ONT), which offers ultra-long, real-time sequencing. Despite its promise, sequencing length and gap filling remain significant challenges. This study optimized DNA extraction and library preparation, achieving DNA lengths exceeding 485 Kb, average N50 read lengths of 80.57 Kb, with reaching up to 440 Kb, and maximum reads of 5.83 Mb. Importantly, it demonstrated that combining ultra-long sequencing and adaptive sampling can effectively fill gaps during assembly, evidenced by successfully achieving the Arabidopsis genome remaining gaps and an unknown telomeric region in watermelon. Our methodologies improve the feasibility of complete T2T genomic assemblies across plants, enhancing genome-based research in diverse fields.},
}
@article {pmid39420004,
year = {2024},
author = {Lam, SY and van der Lugt, R and Cerutti, A and Yalçin, Z and Thouin, AM and Simonetta, M and Jacobs, JJL},
title = {OTUD5 promotes end-joining of deprotected telomeres by promoting ATM-dependent phosphorylation of KAP1[S824].},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {8960},
pmid = {39420004},
issn = {2041-1723},
support = {812829//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 Marie Sk&#x142;odowska-Curie Actions (H2020 Excellent Science - Marie Sk&#x142;odowska-Curie Actions)/ ; 2019-2/12826//KWF Kankerbestrijding (Dutch Cancer Society)/ ; institutional grant to the Netherlands Cancer Institute//KWF Kankerbestrijding (Dutch Cancer Society)/ ; Institutional grant to the Netherlands Cancer Institute//Dutch Ministry of Health, Welfare and Sport | Rijksinstituut voor Volksgezondheid en Milieu (Netherlands National Institute for Public Health and the Environment)/ ; },
mesh = {Phosphorylation ; *Tripartite Motif-Containing Protein 28/metabolism/genetics ; *Ataxia Telangiectasia Mutated Proteins/metabolism/genetics ; *Telomere/metabolism ; Humans ; *DNA End-Joining Repair ; DNA Damage ; Ubiquitin-Protein Ligases/metabolism/genetics ; Heterochromatin/metabolism ; Endopeptidases/metabolism/genetics ; HEK293 Cells ; Ubiquitination ; },
abstract = {Appropriate repair of damaged DNA and the suppression of DNA damage responses at telomeres are essential to preserve genome stability. DNA damage response (DDR) signaling consists of cascades of kinase-driven phosphorylation events, fine-tuned by proteolytic and regulatory ubiquitination. It is not fully understood how crosstalk between these two major classes of post-translational modifications impact DNA repair at deprotected telomeres. Hence, we performed a functional genetic screen to search for ubiquitin system factors that promote KAP1[S824] phosphorylation, a robust DDR marker at deprotected telomeres. We identified that the OTU family deubiquitinase (DUB) OTUD5 promotes KAP1[S824] phosphorylation by facilitating ATM activation, through stabilization of the ubiquitin ligase UBR5 that is required for DNA damage-induced ATM activity. Loss of OTUD5 impairs KAP1[S824] phosphorylation, which suppresses end-joining mediated DNA repair at deprotected telomeres and at DNA breaks in heterochromatin. Moreover, we identified an unexpected role for the heterochromatin factor KAP1 in suppressing DNA repair at telomeres. Altogether our work reveals an important role for OTUD5 and KAP1 in relaying DDR-dependent kinase signaling to the control of DNA repair at telomeres and heterochromatin.},
}
@article {pmid39416992,
year = {2024},
author = {Cadiñanos, J and Rodríguez-Centeno, J and Montejano, R and Esteban-Cantos, A and Mena-Garay, B and Jiménez-González, M and Saiz-Medrano, G and de Miguel, R and Rodríguez-Artalejo, F and Bernardino, JI and Marcelo-Calvo, C and Gutierrez-García, L and Martínez-Martín, P and Díez Vidal, A and de Gea Grela, A and Ortolá, R and Rodés, B and Arribas, JR},
title = {Partial Recovery of Telomere Length After Long-term Virologic Suppression in Persons With HIV-1.},
journal = {Open forum infectious diseases},
volume = {11},
number = {10},
pages = {ofae550},
pmid = {39416992},
issn = {2328-8957},
abstract = {BACKGROUND: People with HIV-1 (PWH) age differently than the general population. Blood telomere length (BTL) attrition is a surrogate biomarker of immunosenescence and aging in PWH. BTL is reduced immediately after HIV-1 infection and recovers in PWH with long-term virologic suppression, but the extent of this recovery is unknown.<br><br>METHODS: This prospective 6-year observational study assessed the evolution of BTL in PWH who were virologically suppressed. A cross-sectional analysis additionally compared BTL with age- and sex-matched blood donors and sex-matched persons older than 60 years from a general population cohort. DNA from whole blood was isolated, and relative BTL was determined by monochrome quantitative multiplex polymerase chain reaction assay and expressed as the ratio of telomere to single-copy gene (T/S).<br><br>RESULTS: A total of 128 PWH were included in the prospective 6-year observational study. These same 128 PWH (median age, 55 years; 27.3% women) were compared cross-sectionally at 6-year follow-up with 128 age- and gender-matched blood donors (median age, 55 years) and 128 gender-matched individuals older than 60 years from a general population cohort (median age, 70 years). An inverse correlation between age and BTL was observed. The median BTL of PWH was shorter than their matched blood donors (T/S, 1.07 [IQR, 0.95-1.17] vs 1.28 [IQR, 1.12-1.48]; P < .001) but longer than the elderly population (T/S, 0.89 [IQR, 0.77-0.98], P < .001). PWH experienced a BTL increase at 6 years of 2.9% (T/S, 1.04 vs 1.07; P = .002). In PWH, age was associated with a shorter BTL (coefficient, -0.007 45, SE = 0.002 04, P = .002) and baseline lower CD4 count with a gain in BTL (coefficient, -0.000 06, SE = 0.000 02, P = .004). Shorter baseline BTL (odds ratio, 0.91 [95% CI, .87-.94]; P < .001) and higher glucose levels (odds ratio, 1.04 [95% CI, 1.02-1.07]; P = .003) were associated with a greater similarity of BTL to the elderly population.<br><br>CONCLUSIONS: PWH with long-term virologic suppression experience a trend toward an increased BTL after 6 years of follow-up. Middle-aged people with long-term controlled HIV-1 have a shorter BTL than expected for their chronologic age but longer than that of people 15 years older in the general population.},
}
@article {pmid39413125,
year = {2024},
author = {Zhang, Y and Ma, Z and Kang, L and Yang, L},
title = {Effect of telomere shortening on disease progression in patients with inflammatory bowel disease: A systematic review and meta-analysis protocol.},
journal = {PloS one},
volume = {19},
number = {10},
pages = {e0311662},
doi = {10.1371/journal.pone.0311662},
pmid = {39413125},
issn = {1932-6203},
mesh = {Humans ; *Inflammatory Bowel Diseases/genetics/pathology ; *Systematic Reviews as Topic ; *Disease Progression ; *Telomere Shortening ; *Meta-Analysis as Topic ; Telomere/genetics ; },
abstract = {INTRODUCTION: Inflammatory bowel disease (IBD) remains a major public health challenge worldwide. In recent years, it has been discovered that a link between telomere shortening and disease progression in IBD patients has been present. However, there is controversy as to whether telomere shortening precipitates disease progression or disease progression causes telomere shortening. There is also a shortage of systematic reviews and data synthesis to explain the association between telomere shortening and disease progression in individuals with IBD. We aimed to systematically review the association between telomere shortening and disease advancement in individuals with IBD to inform future studies.<br><br>METHODS AND ANALYSIS: We will undertake a thorough search of the electronic database from the beginning until December 31, 2023. We will search the databases: MEDLINE/PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), VIP, Wanfang Database (Wanfang), CMB, Cochrane Library, Cochran Clinical Trials Registry, and the World Health Organization International Clinical Trials Registry Platform. Two reviewers will assess the discovered citations for eligibility based on the title and abstract before proceeding to the full-text and data extraction phases. These reviewers will debate and settle any conflicts that arise during the inclusion process; a third reviewer will settle any issues that remain. The validated data extraction form will be used to collect data for eligible research. The included studies will undergo a quality and bias check and will proceed meta-analysis.<br><br>DISCUSSION: This systematic review and meta-analysis will reveal a positive correlation between illness progression and telomere shortening in individuals with IBD, perhaps demonstrating three causal links between them. This study will conduct the first systematic review and meta-analysis examining the correlation between telomere shortening and illness advancement in individuals with IBD. Exploring the connection between these two situations can enhance the comprehension of the development and advancement of IBD.<br><br>PROSPERO registration number: CRD42024501171.},
}
@article {pmid39410901,
year = {2024},
author = {Polo, CM and Pereira de Brito, TR and Roberto Silva, W and Lima, DB and Nunes, DP and Colombo, FA and Orlandi, AADS and Corona, LP},
title = {Shorter Telomere Length is Associated with Food Insecurity in Older People: A Cross-Sectional Study.},
journal = {Current aging science},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118746098320942240924074044},
pmid = {39410901},
issn = {1874-6128},
abstract = {BACKGROUND: Telomere length has been investigated as a biomarker of biological aging and is associated with several diseases, lifestyle, and socioeconomic factors.<br><br>OBJECTIVE: This study aimed to verify whether food insecurity is associated with shorter telomere length in older people.<br><br>METHODS: This is a cross-sectional study carried out in a municipality in the interior of Brazil, with a sample of 440 older people from the community. For telomere length analysis, a blood sample was obtained from each participant, followed by real-time qPCR, and sociodemographic and health information was collected through interviews. Food security/insecurity was measured using the reduced version of the Brazilian Food Insecurity Scale. Descriptive analysis and multiple logistic regression were performed to analyze the factors associated with shorter telomere length, adopting a significance level of 5%.<br><br>RESULTS: We found that food insecurity was significantly associated with shorter telomere length, regardless of age group, skin color, tabagism, physical activity, milk and dairy consumption, living arrangement, and basic activities of daily life.<br><br>CONCLUSION: The findings show the importance of ensuring full access to adequate nutrition for the older population, who are physiologically and socially vulnerable.},
}
@article {pmid39409990,
year = {2024},
author = {Loukopoulou, C and Nikolouzakis, T and Koliarakis, I and Vakonaki, E and Tsiaoussis, J},
title = {Telomere Length and Telomerase Activity as Potential Biomarkers for Gastrointestinal Cancer.},
journal = {Cancers},
volume = {16},
number = {19},
pages = {},
doi = {10.3390/cancers16193370},
pmid = {39409990},
issn = {2072-6694},
abstract = {Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromosome ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering insights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers.},
}
@article {pmid39408829,
year = {2024},
author = {Rubtsova, MP and Nikishin, DA and Vyssokikh, MY and Koriagina, MS and Vasiliev, AV and Dontsova, OA},
title = {Telomere Reprogramming and Cellular Metabolism: Is There a Link?.},
journal = {International journal of molecular sciences},
volume = {25},
number = {19},
pages = {},
doi = {10.3390/ijms251910500},
pmid = {39408829},
issn = {1422-0067},
support = {23-SH04-20//Development Program of the MSU Interdisciplinary Scientific and Educational School "Molecular technologies of living systems and synthetic biology" at the Lomonosov Moscow State University/ ; },
mesh = {Humans ; *Telomere/metabolism/genetics ; Animals ; *Telomere Homeostasis ; Cell Proliferation ; Cellular Reprogramming/genetics ; Germ Cells/metabolism ; },
abstract = {Telomeres-special DNA-protein structures at the ends of linear eukaryotic chromosomes-define the proliferation potential of cells. Extremely short telomeres promote a DNA damage response and cell death to eliminate cells that may have accumulated mutations after multiple divisions. However, telomere elongation is associated with the increased proliferative potential of specific cell types, such as stem and germ cells. This elongation can be permanent in these cells and is activated temporally during immune response activation and regeneration processes. The activation of telomere lengthening mechanisms is coupled with increased proliferation and the cells' need for energy and building resources. To obtain the necessary nutrients, cells are capable of finely regulating energy production and consumption, switching between catabolic and anabolic processes. In this review, we focused on the interconnection between metabolism programs and telomere lengthening mechanisms during programmed activation of proliferation, such as in germ cell maturation, early embryonic development, neoplastic lesion growth, and immune response activation. It is generally accepted that telomere disturbance influences biological processes and promotes dysfunctionality. Here, we propose that metabolic conditions within proliferating cells should be involved in regulating telomere lengthening mechanisms, and telomere length may serve as a marker of defects in cellular functionality. We propose that it is possible to reprogram metabolism in order to regulate the telomere length and proliferative activity of cells, which may be important for the development of approaches to regeneration, immune response modulation, and cancer therapy. However, further investigations in this area are necessary to improve the understanding and manipulation of the molecular mechanisms involved in the regulation of proliferation, metabolism, and aging.},
}
@article {pmid39408588,
year = {2024},
author = {Kim, M and Kang, D and Kim, HS and Lee, JM and Park, S and Kwag, D and Lee, C and Hong, Y and Na, D and Koh, Y and Sun, CH and An, H and Kim, YJ and Kim, Y},
title = {Influence of the Bone Marrow Microenvironment on Hematopoietic Stem Cell Behavior Post-Allogeneic Transplantation: Development of Clonal Hematopoiesis and Telomere Dynamics.},
journal = {International journal of molecular sciences},
volume = {25},
number = {19},
pages = {},
doi = {10.3390/ijms251910258},
pmid = {39408588},
issn = {1422-0067},
support = {NRF-2022R1A2C2006746//National Research Foundation of Korea/ ; },
mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/methods ; Male ; Middle Aged ; Female ; *Clonal Hematopoiesis/genetics ; Adult ; *Hematopoietic Stem Cells/metabolism ; *Telomere/genetics ; Aged ; Transplantation, Homologous ; Mutation ; Myelodysplastic Syndromes/genetics/therapy/etiology ; Bone Marrow/metabolism ; },
abstract = {Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential cure for myelodysplastic neoplasms (MDSs) and other hematologic malignancies. This study investigates post-transplantation genetic evolution and telomere dynamics in hematopoietic cells, with a focus on clonal hematopoiesis (CH). We conducted a longitudinal analysis of 21 MDS patients who underwent allo-HSCT between September 2009 and February 2015. Genetic profiles of hematopoietic cells from both recipients and donors were compared at equivalent pre- and post-transplantation time points. Targeted sequencing identified CH-associated mutations, and real-time quantitative PCR measured telomere length. Furthermore, we compared CH incidence between recipients and age-matched controls from the GENIE cohort from routine health checkups. Post-allo-HSCT, 38% of recipients developed somatic mutations not detected before transplantation, indicating de novo CH originating from donor cells. Compared to age-matched healthy controls, recipients showed a significantly higher incidence of CH, suggesting increased susceptibility to genetic changes post-transplant. Telomere length analysis also revealed accelerated shortening in transplanted cells, highlighting the heightened stress and proliferation demands in the new microenvironment. Our findings reveal a notable incidence of donor-derived CH in allo-HSCT recipients, alongside significant telomere attrition. This suggests the potential influence of the marrow microenvironment on genetic and molecular changes in hematopoietic cells.},
}
@article {pmid39406502,
year = {2024},
author = {Kamath, SS and Bindra, M and Pal, D and Jain, C},
title = {Telomere-to-telomere assembly by preserving contained reads.},
journal = {Genome research},
volume = {},
number = {},
pages = {},
doi = {10.1101/gr.279311.124},
pmid = {39406502},
issn = {1549-5469},
abstract = {Automated telomere-to-telomere (T2T) de novo assembly of diploid and polyploid genomes remains a formidable task. A string graph is a commonly used assembly graph representation in the assembly algorithms. The string graph formulation employs graph simplification heuristics, which drastically reduce the count of vertices and edges. One of these heuristics involves removing the reads contained in longer reads. In practice, this heuristic occasionally introduces gaps in the assembly by removing all reads that cover one or more genome intervals. The factors contributing to such gaps remain poorly understood. In this work, we mathematically derived the frequency of observing a gap near a germline and a somatic heterozygous variant locus. Our analysis shows that (i) an assembly gap due to contained read deletion is an order of magnitude more frequent in Oxford Nanopore reads than PacBio HiFi reads due to differences in their read-length distributions, and (ii) this frequency decreases with an increase in the sequencing depth. Drawing cues from these observations, we addressed the weakness of the string graph formulation by developing the RAFT assembly algorithm. RAFT addresses the issue of contained reads by fragmenting reads and producing a more uniform read-length distribution. The algorithm retains spanned repeats in the reads during the fragmentation. We empirically demonstrate that RAFT significantly reduces the number of gaps using simulated datasets. Using real Oxford Nanopore and PacBio HiFi datasets of the HG002 human genome, we achieved a twofold increase in the contig NG50 and the number of haplotype-resolved T2T contigs compared to Hifiasm.},
}
@article {pmid39401753,
year = {2023},
author = {Baser, E and Inandiklioglu, N and Aydogan Kırmızı, D and Ercan, F and Caniklioğlu, A and Kara, M and Onat, T and Yalvac, ES},
title = {Correction: Placental and Umbilical Cord Blood Oxidative Stress Level and Telomere Homeostasis in Early Onset Severe Preeclampsia.},
journal = {Zeitschrift fur Geburtshilfe und Neonatologie},
volume = {227},
number = {2},
pages = {e267},
doi = {10.1055/a-2416-9430},
pmid = {39401753},
issn = {1439-1651},
}
@article {pmid39400911,
year = {2024},
author = {Machelová, A and Dadejová, MN and Franek, M and Mougeot, G and Simon, L and Le Goff, S and Duc, C and Bassler, J and Demko, M and Schwarzerová, J and Desset, S and Probst, AV and Dvořáčková, M},
title = {The histone chaperones ASF1 and HIRA are required for telomere length and 45S rDNA copy number homeostasis.},
journal = {The Plant journal : for cell and molecular biology},
volume = {},
number = {},
pages = {},
doi = {10.1111/tpj.17041},
pmid = {39400911},
issn = {1365-313X},
support = {23-06643S//Grantov&#xe1; Agentura &#x10c;esk&#xe9; Republiky/ ; MUNI/R/1364/2023//Grant Agency of Masaryk University/ ; ANR-11 JSV2 009 01//French National Research Agency/ ; ANR-12 ISV6 0001//French National Research Agency/ ; CZ.02.01.01/00/22_008/0004581//European Regional Development Fund Programme Johannes Amos Comenius/ ; },
abstract = {Genome stability is significantly influenced by the precise coordination of chromatin complexes that facilitate the loading and eviction of histones from chromatin during replication, transcription, and DNA repair processes. In this study, we investigate the role of the Arabidopsis H3 histone chaperones ANTI-SILENCING FUNCTION 1 (ASF1) and HISTONE REGULATOR A (HIRA) in the maintenance of telomeres and 45S rDNA loci, genomic sites that are particularly susceptible to changes in the chromatin structure. We find that both ASF1 and HIRA are essential for telomere length regulation, as telomeres are significantly shorter in asf1a1b and hira mutants. However, these shorter telomeres remain localized around the nucleolus and exhibit a comparable relative H3 occupancy to the wild type. In addition to regulating telomere length, ASF1 and HIRA contribute to silencing 45S rRNA genes and affect their copy number. Besides, ASF1 supports global heterochromatin maintenance. Our findings also indicate that ASF1 transiently binds to the TELOMERE REPEAT BINDING 1 protein and the N terminus of telomerase in vivo, suggesting a physical link between the ASF1 histone chaperone and the telomere maintenance machinery.},
}
@article {pmid39399813,
year = {2024},
author = {Yerukala Sathipati, S and Jeong, S and Sharma, P and Mayer, J and Sharma, R and Ho, SY and Hebbring, S},
title = {Exploring prognostic implications of miRNA signatures and telomere maintenance genes in kidney cancer.},
journal = {Molecular therapy. Oncology},
volume = {32},
number = {4},
pages = {200874},
pmid = {39399813},
issn = {2950-3299},
abstract = {Kidney cancer, particularly clear cell renal cell carcinoma (KIRC), presents significant challenges in disease-specific survival. This study investigates the prognostic potential of microRNAs (miRNAs) in kidney cancers, including KIRC and kidney papillary cell carcinoma (KIRP), focusing on their interplay with telomere maintenance genes. Utilizing data from The Cancer Genome Atlas, miRNA expression profiles of 166 KIRC and 168 KIRP patients were analyzed. An evolutionary learning-based kidney survival estimator identified robust miRNA signatures predictive of 5-year survival for both cancer types. For KIRC, a 37-miRNA signature showed a correlation coefficient (R) of 0.82 and mean absolute error (MAE) of 0.65 years. Similarly, for KIRP, a 23-miRNA signature exhibited an R of 0.82 and MAE of 0.64 years, demonstrating comparable predictive accuracy. These signatures also displayed diagnostic potential with receiver operating characteristic curve values between 0.70 and 0.94. Bioinformatics analysis revealed targeting of key telomere-associated genes such as TERT, DKC1, CTC1, and RTEL1 by these miRNAs, implicating crucial pathways such as cellular senescence and proteoglycans in cancer. This study highlights the significant link between miRNAs and telomere genes in kidney cancer survival, offering insights for therapeutic targets and improved prognostic markers.},
}
@article {pmid39388510,
year = {2024},
author = {Song, X and Lin, D and Wang, D and Weng, S and Qiu, S and Zhou, W and Xiao, A and Zhang, N},
title = {Association of lymphocyte count and serum albumin concentration with telomere length in Chinese sanitation workers.},
journal = {PloS one},
volume = {19},
number = {10},
pages = {e0311736},
doi = {10.1371/journal.pone.0311736},
pmid = {39388510},
issn = {1932-6203},
mesh = {Humans ; Male ; Lymphocyte Count ; Adult ; China ; Female ; Case-Control Studies ; Middle Aged ; *Sanitation ; *Serum Albumin/analysis ; Telomere/metabolism ; Lymphocytes/metabolism ; Inflammation/blood ; Telomere Homeostasis ; East Asian People ; },
abstract = {OBJECTIVE: This study aimed to examine the association between inflammation-related indicators (IRIs) and telomere length (TL) in Chinese sanitation workers.<br><br>METHODS: This study adopted a case-control design, conducted from January to December 2022 in Shenzhen, a city in eastern China. A total of 80 sanitation workers, as well as 80 matched controls, were randomly recruited from the Luohu district of Shenzhen city in China. Their blood samples were collected and analyzed for the IRIs and TL in the Medical Laboratory of Shenzhen Prevention and Treatment Center for Occupational Diseases. The relationship between IRIs and TL was analyzed using multivariate linear regression, and their dose-response relationship was explored using restricted cubic spline analysis.<br><br>RESULTS: The systemic inflammatory index (SII), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were significantly elevated in the sanitation workers in comparison to the controls. Moreover, the lymphocyte count (LYM), serum albumin concentration (ALB), and TL were found to be lower in the sanitation workers compared to the controls (P < 0.05). After adjusting for potential confounding variables, LYM was negatively correlated with TL in the sanitation workers (&#x3b2; = -0.31, 95% CI: -0.57, -0.05), whereas no correlation was observed in the controls. Furthermore, ALB demonstrated a non-linear relationship with TL in sanitation workers.<br><br>CONCLUSION: We found higher novel inflammatory markers (SII, PLR, and NLR) in the sanitation workers, and identified a correlation between LYM and ALB with shortened TL in them, providing new evidence for the effect of elevated inflammation on accelerated aging in Chinese sanitation workers.},
}
@article {pmid39385582,
year = {2024},
author = {Fernández de la Puente, M and Marti, A and Canudas, S and Zalba, G and Razquin, C and Boccardi, V and Mecocci, P and Babio, N and Castañer-Niño, O and Toledo, E and Buil-Cosiales, P and Salas-Salvadó, J and García-Calzón, S},
title = {Telomere length and 4-year changes in cognitive function in an older Mediterranean population at high risk of cardiovascular disease.},
journal = {Age and ageing},
volume = {53},
number = {10},
pages = {},
doi = {10.1093/ageing/afae216},
pmid = {39385582},
issn = {1468-2834},
support = {021/CB07/03/2004//CIBEROBN/ ; //Instituto de Salud Carlos III/ ; //Fondo de Investigaci&#xf3;n para la Salud/ ; PI13/00462//European Regional Development Fund/ ; //Instituci&#xf3;n Catalana de Investigaci&#xf3;n y Estudios Avanzados/ ; IJC2019-040796-I//Juan de la Cierva-Incorporaci&#xf3;n/ ; 2020-PMF-PIPF-8//Rovira i Virgili University and Diputaci&#xf3; de Tarragona/ ; },
mesh = {Humans ; Male ; Aged ; Female ; *Cognition ; *Cardiovascular Diseases/epidemiology/prevention &amp; control ; *Cognitive Dysfunction/epidemiology/diagnosis/psychology/prevention &amp; control ; Middle Aged ; Spain/epidemiology ; Time Factors ; Telomere ; Cognitive Aging/psychology ; Age Factors ; Risk Factors ; Telomere Homeostasis ; Diet, Mediterranean ; Risk Assessment ; Executive Function ; Aging/psychology ; Heart Disease Risk Factors ; Telomere Shortening ; },
abstract = {BACKGROUND: Cognitive decline, a common process of brain ageing, has been associated with telomere length (TL). Delving into the identification of reliable biomarkers of brain ageing is essential to prevent accelerated cognitive impairment.<br><br>METHODS: We selected 317 non-smoking 'Prevenci&#xf3;n con Dieta Mediterr&#xe1;nea-Plus' (PREDIMED-Plus) participants (mean age, 65.8&#x2009;&#xb1;&#x2009;5.0&#xa0;years) with metabolic syndrome from two trial centres who were following a lifestyle intervention. We measured TL and cognitive function at baseline and after 3 and 4&#xa0;years of follow-up, respectively. Associations between baseline or 3-year changes in TL and baseline or 4-year changes in cognitive function were analysed using multivariable regression models.<br><br>RESULTS: Baseline TL was not associated with baseline cognitive performance. Nevertheless, longer baseline TL was associated with improved 4-year changes in the Executive Function domain (&#x3b2;: 0.29; 95%CI: 0.12 to 0.44; P < 0.001) and the Global Cognitive Function domain (&#x3b2;: 0.19; 95%CI: 0.05 to 0.34; P =&#xa0;0.010). Besides, a positive association was found between longer baseline TL and improved 4-year changes in the animal version of the Verbal Fluency Test (&#x3b2;: 0.33; 95%CI: 0.12 to 0.52; P =&#xa0;0.002). By contrast, 3-year changes in TL were not associated with changes in cognitive function after 4&#xa0;years.<br><br>CONCLUSIONS: Longer baseline TL could protect from cognitive decline and be used as a useful biomarker of brain ageing function in an older Mediterranean population at risk of cardiovascular disease and cognitive impairment.},
}
@article {pmid39379870,
year = {2024},
author = {Vrettou, M and Lager, S and Toffoletto, S and Iliadis, SI and Kallak, TK and Agnafors, S and Nieratschker, V and Skalkidou, A and Comasco, E},
title = {Peripartum depression symptom trajectories, telomere length and genotype, and adverse childhood experiences.},
journal = {BMC psychiatry},
volume = {24},
number = {1},
pages = {661},
pmid = {39379870},
issn = {1471-244X},
abstract = {BACKGROUND: As a biological marker for cellular senescence, telomere length (TL) has been linked to a variety of psychiatric disorders and adverse childhood experiences (ACE), though only preliminarily to peripartum depression (PPD). The present study sought to examine the association between TL and PPD, assessing the moderating role of ACE and genetic polymorphic variations related with the telomere machinery.<br><br>METHODS: Adversity was self-reported, likewise were depressive symptoms evaluated at pregnancy week 17 and 32, as well as six-weeks and six-months postpartum. TL was assessed by use of qPCR in blood samples collected during delivery from females with antenatal depression resolving postpartum, females with depression persisting to postpartum, and healthy controls. Twenty haplotype-tagging Single Nucleotide Polymorphisms in the Telomerase Reverse Transcriptase (TERT) and three in the Telomerase RNA Component (TERC) genes were genotyped.<br><br>RESULTS: TL was negatively correlated with severity of PPD symptoms at pregnancy week 32 and postpartum week 6. PPD was associated with shorter TL. Lastly, ACE, but not the TERT/TERC genotype, moderated the TL-trajectory association; with increasing ACE, individuals with persistent PPD symptoms had shorter TL, whereas the opposite pattern (longer TL) was observed in the controls.<br><br>CONCLUSIONS: The findings contribute to further understanding of PPD underpinnings, suggesting a negative relationship with TL.},
}
@article {pmid39379607,
year = {2024},
author = {Barchitta, M and Maugeri, A and La Mastra, C and Favara, G and La Rosa, MC and Magnano San Lio, R and Gholizade Atani, Y and Gallo, G and Agodi, A},
title = {Pre-pregnancy BMI, gestational weight gain, and telomere length in amniotic fluid: a causal graph analysis.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {23396},
pmid = {39379607},
issn = {2045-2322},
support = {"La coorte Mamma and Bambino: un approccio Multisettoriale Alla salute Materno-Infantile Mediante valutazione dell'Esposoma nelle Donne, MAMI-MED"//University of Catania, Italy, Department of Medical and Surgical Science and Advanced Technologies "GF Ingrassia" Programma ricerca di ateneo UNICT 2020-22 linea 2, PIAno di inCEntivi per la RIcerca di Ateneo 2020/2022/ ; },
mesh = {Humans ; Female ; Pregnancy ; *Body Mass Index ; *Amniotic Fluid/metabolism ; *Gestational Weight Gain ; Adult ; Telomere/genetics ; Telomere Homeostasis ; Overweight/genetics ; Infant, Newborn ; },
abstract = {Previous investigations have suggested a potential association between pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with telomere length (TL) in various tissues of pregnant women and newborns. Nonetheless, as association does not imply causation, our objective was to investigate the causal connections among pre-pregnancy BMI, GWG, and TL in amniotic fluid. The analysis included 136 mother-child pairs from the Mamma &amp; Bambino cohort, and three causal graph models were developed to depict the interconnections between pre-pregnancy BMI, GWG, and TL. Causal graph analysis was conducted utilizing the do-operator to estimate the causal effect of GWG and the controlled direct effect of pregestational BMI. We revealed that transitioning from non-adequate to adequate GWG had a positive impact on the probability of having "long" TL (i.e., a value greater than the population median) in all three models. When considering the effect of pre-pregnancy BMI, the highest probability of "long" TL was observed in normal weight women with adequate GWG. In contrast, the effect of adequate GWG became minimal among overweight women. These results shed light on the potential causality between pre-pregnancy BMI, GWG, and TL in amniotic fluid, emphasizing the importance of appropriate weight management before and during pregnancy for optimal TL outcomes.},
}
@article {pmid39377032,
year = {2024},
author = {Assari, S and Dezfuli, M and Peyrovinasab, A and Zare, H},
title = {Does Adulthood Socioeconomic Status Predict Subsequent Telomere Length in Racially and Ethnically Diverse Women?.},
journal = {Journal of biomedical and life sciences},
volume = {4},
number = {1},
pages = {47-59},
pmid = {39377032},
issn = {2771-2303},
abstract = {BACKGROUND: Telomere length is a critical biomarker of cellular aging and overall health. While childhood socioeconomic status (SES) indicators such as education and poverty can have long-lasting effects on biological aging, research has shown contradictory results regarding the impact of adulthood SES on future telomere length, particularly in racially and ethnically diverse individuals. This study investigates the effects of baseline adulthood SES indicators such as education and poverty on telomere length nine years later in women, using data from the Future of Families and Child Wellbeing Study (FFCWS).<br><br>METHODS: We analyzed data from the FFCWS, a longitudinal cohort study. The sample included baseline adulthood SES and follow-up telomere length measure of women (n = 2,421) with varying socioeconomic conditions. Telomere length was measured from saliva samples nine years after the baseline measure of adulthood SES. Education, poverty, and marital status at baseline were assessed. Multivariate linear regression models were used to examine the association between adulthood SES indicators at baseline and future telomere length, controlling for potential confounders.<br><br>RESULTS: From the total 2,421 women, 675 were Latino White, 1,158 were non-Latino Black, and 588 were non-Latino White. Our findings indicate that for non-Latino White women poverty at certain level, and childbirth weight, and for non-Latino Black maternal age were predictors of telomere lengths nine years later.<br><br>CONCLUSION: Poverty at a specific level, maternal age and childbirth weight serve as predictors of telomere lengths nine years later in some women. These findings underscore the importance of socioeconomic factors and early-life influences in understanding telomere dynamics and aging processes among women from varied racial and ethnic backgrounds.},
}
@article {pmid39373625,
year = {2024},
author = {Jiang, G and Cao, L and Wang, Y and Li, L and Wang, Z and Zhao, H and Qiu, Y and Feng, B},
title = {Causality between telomere length and the risk of hematologic malignancies: A bidirectional Mendelian randomization study.},
journal = {Cancer research communications},
volume = {},
number = {},
pages = {},
doi = {10.1158/2767-9764.CRC-24-0402},
pmid = {39373625},
issn = {2767-9764},
abstract = {Growing evidence indicates a relationship between telomere length (TL) and the stage, prognosis, and treatment responsiveness of hematopoietic malignancies. However, the relationship between TL and the risk of hematologic malignancies remains unclear, considering the vulnerability of observational studies to potential confounding and reverse causation. Two-sample bidirectional mendelian randomization (MR) analysis was conducted utilizing publicly available genome-wide association study data to assess whether TL was causally associated with the risk of hematologic malignancies. The inverse variance-weighted approach was used as the primary assessment approach to evaluate the effects of the causes, augmented by the weighted median and MR-Egger methods. Cochran's Q test, MR Egger intercept test, MR-PRESSO, and leave-one-out analysis were performed to evaluate sensitivity, heterogeneity, and pleiotropy. According to forward MR estimations, longer TL was related to an increased risk of acute lymphocytic leukemia (OR=2.690, p=0.041), chronic lymphocytic leukemia (OR=2.155, p=0.005), multiple myeloma (OR=1.845, p=0.024), Hodgkin lymphoma (OR=1.697, p=0.014), and non-Hodgkin lymphoma (OR=1.737, p=0.009). Specific types of non-Hodgkin lymphoma were also associated with TL. The reverse MR results revealed that hematological malignancies had no effect on TL. This MR analysis revealed an association between longer TL and an increased risk of specific hematologic malignancies, indicating a potential role of TL in the risk evaluation and management in hematologic malignancies.},
}
@article {pmid39371255,
year = {2024},
author = {Rolles, B and Tometten, M and Meyer, R and Kirschner, M and Beier, F and Brümmendorf, TH},
title = {Inherited Telomere Biology Disorders: Pathophysiology, Clinical Presentation, Diagnostics, and Treatment.},
journal = {Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie},
volume = {51},
number = {5},
pages = {292-309},
pmid = {39371255},
issn = {1660-3796},
abstract = {BACKGROUND: Telomeres are the end-capping structures of all eukaryotic chromosomes thereby protecting the genome from damage and degradation. During the aging process, telomeres shorten continuously with each cell division until critically short telomeres prevent further proliferation whereby cells undergo terminal differentiation, senescence, or apoptosis. Premature aging due to critically short telomere length (TL) can also result from pathogenic germline variants in the telomerase complex or related genes that typically counteract replicative telomere shortening in germline and certain somatic cell populations, e.g., hematopoetic stem cells. Inherited diseases that result in altered telomere maintenance are summarized under the term telomere biology disorder (TBD).<br><br>SUMMARY: Since TL both reflects but more importantly restricts the replicative capacity of various human tissues, a sufficient telomere reserve is particularly important in cells with high proliferative activity (e.g., hematopoiesis, immune cells, intestinal cells, liver, lung, and skin). Consequently, altered telomere maintenance as observed in TBDs typically results in premature replicative cellular exhaustion in the respective organ systems eventually leading to life-threatening complications such as bone marrow failure (BMF), pulmonary fibrosis, and liver cirrhosis.<br><br>KEY MESSAGES: The recognition of a potential congenital origin in approximately 10% of adult patients with clinical BMF is of utmost importance for the proper diagnosis, appropriate patient and family counseling, to prevent the use of inefficient treatment and to avoid therapy-related toxicities including appropriate donor selection when patients have to undergo stem cell transplantation from related donors. This review summarizes the current state of knowledge about TBDs with particular focus on the clinical manifestation patterns in children (termed early onset TBD) compared to adults (late-onset TBD) including typical treatment- and disease course-related complications as well as their prognosis and adequate therapy. Thereby, it aims to raise awareness for a disease group that is currently still highly underdiagnosed particularly when it first manifests itself in adulthood.},
}
@article {pmid39370492,
year = {2024},
author = {Farias, TG and Santos, MSD and Mencalha, AL and da Fonseca, AS},
title = {Low-power red laser and blue LED modulate telomere maintenance and length in human breast cancer cells.},
journal = {Lasers in medical science},
volume = {39},
number = {1},
pages = {248},
pmid = {39370492},
issn = {1435-604X},
support = {88887.636295/2021-00//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; E26/019.001958/2019//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado do Rio de Janeiro/ ; },
mesh = {Humans ; *Breast Neoplasms/radiotherapy/genetics/pathology ; Female ; *Telomeric Repeat Binding Protein 2/metabolism/genetics ; *Telomere/radiation effects ; *Low-Level Light Therapy/methods ; *Telomeric Repeat Binding Protein 1/metabolism/genetics ; Cell Line, Tumor ; RNA, Messenger/metabolism/genetics ; MCF-7 Cells ; Telomere Homeostasis/radiation effects ; Shelterin Complex ; Telomere-Binding Proteins ; },
abstract = {Cancer cells have the ability to undergo an unlimited number of cell divisions, which gives them immortality. Thus, the cancer cell can extend the length of its telomeres, allowing these cells to divide unlimitedly and avoid entering the state of senescence or cellular apoptosis. One of the main effects of photobiomodulation (PBM) is the increase in the production of adenosine triphosphate (ATP) and free radicals, mainly reactive oxygen species (ROS). Existent data indicates that high levels of ROS can cause shortening and dysfunctional telomeres. Therefore, a better understanding of the effects induced by PBM on cancer cell telomere maintenance is needed. This work aimed to evaluate the effects of low-power red laser (658 nm) and blue LED (470 nm) on the TRF1 and TRF2 mRNA levels and telomere length in human breast cancer cells. MCF-7 and MDA-MB-231 cells were irradiated with a low-power red laser (69 J cm[-2], 0.77 W/cm[-2]) and blue LED (482 J cm[-2], 5.35 W/cm[-2]), alone or in combination, and the relative mRNA levels of the genes and telomere length were assessed by quantitative reverse transcription polymerase chain reaction. The results suggested that exposure to certain red laser and blue LED fluences decreased the TRF1 and TRF2 mRNA levels in both human breast cancer cells. Telomere length was increased in MCF-7 cells after exposure to red laser and blue LED. However, telomere length in MDA-MB-231 was shortened after exposure to red laser and blue LED at fluences evaluated. Our research suggests that photobiomodulation induced by red laser and low-power blue LED could alter telomere maintenance and length.},
}
@article {pmid39368029,
year = {2024},
author = {Xing, B and Yu, J and Liu, Y and He, S and Gao, Q and Chen, X and Ping, F and Xu, L and Li, W and Zhang, H and Li, Y},
title = {The negative association between sodium-driven nutrient pattern and telomere length: the chain mediating role of diastolic pressure and waist circumference.},
journal = {Aging clinical and experimental research},
volume = {36},
number = {1},
pages = {201},
pmid = {39368029},
issn = {1720-8319},
support = {2022YFC2010102//National Key R&amp;D Program of China/ ; CIFMS,2021-I2M-1-002//the CAMS Innovation Fund for Medical Sciences/ ; },
mesh = {Humans ; Male ; Female ; Middle Aged ; *Waist Circumference ; Cross-Sectional Studies ; *Blood Pressure/physiology ; *Telomere ; Adult ; China ; Sodium, Dietary ; Diet ; Aged ; Leukocytes/metabolism/physiology ; Telomere Homeostasis/physiology ; },
abstract = {BACKGROUND: Numerous single nutrients have been suggested to be linked with leukocyte telomere length (LTL). However, data on nutrient patterns (NPs), particularly in Chinese population, are scarce. This study aimed to examine the relationship between nutrient-based dietary patterns and LTL, and the potential role of metabolic factors.<br><br>METHODS: Dietary data was obtained via 24-hour food recalls, and principal component analysis (PCA) was used to identify NPs. LTL was assessed using a real-time PCR assay. Multiple linear regression was conducted to determine the association between NPs and LTL. The potential role of metabolism among them was analyzed using mediation models.<br><br>RESULTS: A total of 779 individuals from northern China were included in this cross-sectional analysis. Five main nutrient patterns were identified. Adjusted linear regression showed that the "high sodium" pattern was inversely associated with LTL (B=-0.481(-0.549, -0.413), P&#x2009;<&#x2009;0.05). The "high vitamin E-fat" pattern exhibited a positive correlation (B&#x2009;=&#x2009;0.099(0.029, 0.170), P&#x2009;<&#x2009;0.05), whereas the "high vitamin A-vitamin B2" pattern was negatively correlated with LTL (B=-0.120(-0.183, -0.057), P&#x2009;<&#x2009;0.05), respectively. No significant associations were observed for the remaining nutrient patterns. The mediation model demonstrated that diastolic blood pressure and waist circumference could individually and collectively mediate the negative impact of the "high sodium" pattern on LTL (BDBP=-0.0173(-0.0333, -0.0041), BWC=-0.0075(-0.0186, -0.0004), Bjoint=-0.0033 (-0.0072, -0.0006), all P&#x2009;<&#x2009;0.05). Moreover, glycosylated hemoglobin and non-high-density lipoprotein cholesterol mediate the relationship between the "high vitamin E-fat" pattern and LTL (BHbA1c=0.0170(0.0010,0.0347), Bnon-HDL-C= 0.0335 (0.0067, 0.0626), all P&#x2009;<&#x2009;0.05), respectively.<br><br>CONCLUSIONS: The "high sodium" and "high vitamin E-fat" nutrient patterns demonstrated negative and positive associations with LTL and metabolic indicators may play complex mediating roles in these relationships.},
}
@article {pmid39367328,
year = {2024},
author = {Félix, NQ and Tornquist, L and Sehn, AP and D'avila, HF and Todendi, PF and de Moura Valim, AR and Reuter, CP},
title = {The association of telomere length with body mass index and immunological factors differs according to physical activity practice among children and adolescents.},
journal = {BMC pediatrics},
volume = {24},
number = {1},
pages = {633},
pmid = {39367328},
issn = {1471-2431},
support = {001//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior , Brasil/ ; 001//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior , Brasil/ ; 001//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior , Brasil/ ; },
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; *Body Mass Index ; Child ; Adolescent ; *Exercise ; *Sleep ; *Telomere ; Brazil ; Screen Time ; Leisure Activities ; Immunologic Factors ; Linear Models ; },
abstract = {BACKGROUND: This study aims to verify the relationship between screen and sleep time, body mass index (BMI) and immunological factors with telomere length according to leisure-time physical activity (PA) in children and adolescents.<br><br>METHODS: A cross-sectional study involving a sample of 476 schoolchildren of both sexes, aged seven to 17 years, from a community in southern Brazil. Behavioral variables (PA, sleep time, and screen time) were self-reported using a questionnaire. PA was classified as inactive and any PA (doing some physical activity). The associations of screen time, sleep time, BMI, and immunologic factors with telomere length were tested using multiple linear regression models, with the sample divided according to the schoolchildren's leisure-time physical activity practices.<br><br>RESULTS: An inverse association between BMI and telomere length (&#x3b2;: -0.239; 95% CI: -0.468; -0.010) and a direct association of leukocytes (&#x3b2;: 0.151; 95% CI: 0.029; 0.278) and neutrophils (&#x3b2;: 0.131; 95% CI: 0.008; 0.254) with telomeres were found in the inactive students. No association was found between screen time and sleep time and telomeres. No association was found among students who engaged in any PA.<br><br>CONCLUSION: The associations between telomeres, BMI, and immunologic factors were found only in inactive students. These results suggest that the association between BMI and immunological factors and telomere length may be influenced by physical activity.},
}
@article {pmid39353511,
year = {2024},
author = {Wu, Y and Huang, C and Fan, B and Wu, H and Mei, Y and Cheng, F},
title = {The relationship between leukocyte telomere length and risk of depression and anxiety: Evidence from UK Biobank.},
journal = {Journal of affective disorders},
volume = {369},
number = {},
pages = {195-201},
doi = {10.1016/j.jad.2024.09.138},
pmid = {39353511},
issn = {1573-2517},
abstract = {BACKGROUND: Telomere length is a cellular aging marker implicated in various health outcomes. A growing body of evidence suggests a link between leukocyte telomere length (LTL) and mental health outcomes. However, there have been no studies focused on the relationship between LTL and the future risk of depression and anxiety. This study aimed to investigate the associations between LTL and depression/anxiety, examining both cross-sectional prevalence and prospective incidence.<br><br>METHODS: Data from 364,331 UK Biobank participants were analyzed. LTL was measured at baseline, and mental health status was assessed through hospital records and online surveys. Logistic regression and Cox proportional hazards models were employed for cross-sectional and prospective analyses with appropriate adjustment, respectively.<br><br>RESULTS: The mean (SD) age of the subjects was 57.03 (13.34) years and follow-up duration was 8.80 (5.39) years. Cross-sectionally, shorter LTL was associated with increased odds of depression (OR: 1.401, 95&#xa0;% CI: 1.291-1.521) and anxiety (1.347 (1.198-1.515)) at baseline, which remained significant after adjustment. Among those free of depression/anxiety at baseline, baseline shorter LTL was associated with a higher risk of incident depression (HR: 1.615, 95&#xa0;% CI: 1.447-1.803) and anxiety (1.430 (1.293-1.581)) during follow-up period. These associations remained robust after adjusting for various covariates.<br><br>CONCLUSIONS: Our findings indicated an association between shorter telomeres and an increased risk of prevalent depression/anxiety and shorter telomeres precede the onset of these mental health conditions. Considering the potential clinical implications, our study underscores the relevance of LTL as a predictive tool for identifying individuals at risk of developing depression and anxiety.},
}
@article {pmid39356569,
year = {2024},
author = {Premužić, V and Toupance, S and Hollander, A and Stipančić, &#x17d; and Bukal, N and Jelaković, A and Brzić, I and Čulig, B and Slade, N and Benetos, A and Jelaković, B},
title = {Longer Telomere Length in Balkan Endemic Nephropathy Patients Undergoing Chronic Hemodialysis is Associated with Lower Cardiovascular Mortality.},
journal = {Kidney360},
volume = {},
number = {},
pages = {},
doi = {10.34067/KID.0000000603},
pmid = {39356569},
issn = {2641-7650},
abstract = {BACKGROUND: Balkan endemic nephropathy (BEN) is characterized with later onset and milder forms of hypertension, and with lower pulse wave velocity (PWV) than other end-stage kidney disease (ESKD). Longer telomeres are associated with better cardiovascular (CV) prognosis. Therefore, we hypothesized that telomere length (TL) could be longer in BEN patients compared to other ESKD patients.<br><br>METHODS: A total of 124 patients undergoing hemodialysis (HD) (68 BEN, 56 non-BEN) were enrolled and followed-up for 72 months. TL was measured in leukocytes by Southern blot at inclusion.<br><br>RESULTS: Age and sex-adjusted TL was significantly longer in the BEN group (p<0.001). TL was negatively associated with carotid-femoral PWV in BEN patients. BEN patients had significantly lower CV mortality than non-BEN ESKD patients (p<0.001). In the BEN group shorter TL (1kb change) was the only determinant of shorter survival (HR 0.11). Using the TL threshold defined by ROC analysis (TL < 6.21 kb), we showed in both groups significantly higher CV mortality in the presence of short telomeres (Log-rank (Mantel-p<0.001).<br><br>CONCLUSIONS: Longer telomeres are associated with less CV mortality in patients undergoing chronic HD. BEN patients had longer TL and longer survival than other ESKD patients. In BEN patients, TL was negatively associated with arterial stiffness and positively associated with survival. This study confirmed our hypothesis that BEN is associated with slower vascular aging and that longer TL may partially explain this phenomenon.},
}
@article {pmid39355591,
year = {2024},
author = {Sun, JY and Xu, Q and Shen, H and Huang, W and Qu, Q and Sun, W and Kong, XQ},
title = {The Association between Leucocyte Telomere Length and Survival Outcomes in Patients with Cardiovascular Disease.},
journal = {Reviews in cardiovascular medicine},
volume = {25},
number = {9},
pages = {333},
pmid = {39355591},
issn = {2153-8174},
abstract = {BACKGROUND: We explore the association between leucocyte telomere length (LTL) and all-cause and cardiovascular disease (CVD)-specific death in CVD patients.<br><br>METHODS: We acquired 1599 CVD patients from a nationally representative US population survey for this study. We applied Kaplan-Meier curves, adjusted weighted Cox regression models, and restricted cubic spline to investigate the association between LTL and all-cause death. Additionally, we employed competing risk regression to assess the impact of LTL on cardiovascular-specific death, setting non-cardiovascular death as a competing event.<br><br>RESULTS: The overall mortality rate was 31.0% after a median follow-up of 13.9 years. Patients with shorter LTL exhibited a higher risk of all-cause death, with an adjusted hazard ratio (HR) of 1.25 (95% confidence interval (CI): 1.05-1.48). Restricted cubic spline illustrated a linear dose-response relationship. In gender-specific analyses, female patients with shorter LTL showed a higher risk of death (weighted HR, 1.79; 95% CI, 1.29-2.48), whereas this association was not observed in males (weighted HR, 0.90; 95% CI, 0.61-1.32). The Fine-Gray competing risk model revealed no significant relationship between LTL and cardiovascular-specific mortality but a significant association with non-cardiovascular death (adjusted HR, 1.24; 95% CI, 1.02-1.51).<br><br>CONCLUSIONS: LTL is inversely associated with all-cause death in female CVD patients. The significant correlation between reduced LTL and increased all-cause mortality emphasizes LTL as a potential marker for tertiary prevention against cardiovascular disease.},
}
@article {pmid39355254,
year = {2024},
author = {Xu, W and Sang, S and Wang, J and Guo, S and Zhang, X and Zhou, H and Chen, Y},
title = {Identification of telomere-related lncRNAs and immunological analysis in ovarian cancer.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1452946},
pmid = {39355254},
issn = {1664-3224},
mesh = {Humans ; *RNA, Long Noncoding/genetics ; Female ; *Ovarian Neoplasms/genetics/immunology/mortality ; Prognosis ; *Biomarkers, Tumor/genetics ; *Gene Expression Regulation, Neoplastic ; *Telomere/genetics ; Cell Line, Tumor ; Nomograms ; Middle Aged ; Lymphocytes, Tumor-Infiltrating/immunology/metabolism ; },
abstract = {BACKGROUND: Ovarian cancer (OC) is a global malignancy characterized by metastatic invasiveness and recurrence. Long non-coding RNAs (lncRNAs) and Telomeres are closely connected with several cancers, but their potential as practical prognostic markers in OC is less well-defined.<br><br>METHODS: Relevant mRNA and clinical data for OC were sourced from The Cancer Genome Atlas (TCGA) database. The telomere-related lncRNAs (TRLs) prognostic model was established by univariate/LASSO/multivariate regression analyses. The effectiveness of the TRLs model was evaluated and measured via the nomogram. Additionally, immune infiltration, tumor mutational load (TMB), and drug sensitivity were evaluated. We validated the expression levels of prognostic genes. Subsequently, PTPRD-AS1 knockdown was utilized to perform the CCK8 assay, colony formation assay, transwell assay, and wound healing assay of CAOV3 cells.<br><br>RESULTS: A six-TRLs prognostic model (PTPRD-AS1, SPAG5-AS1, CHRM3-AS2, AC074286.1, FAM27E3, and AC018647.3) was established, which can effectively predict patient survival rates and was successfully validated using external datasets. According to the nomogram, the model could effectively predict prognosis. Furthermore, we detected the levels of regulatory T cells and M2 macrophages were comparatively higher in the high-risk TRLs group, but the levels of activated CD8 T cells and monocytes were the opposite. Finally, the low-risk group was more sensitive to anti-cancer drugs. The mRNA levels of PTPRD-AS1, SPAG5-AS1, FAM27E3, and AC018647.3 were significantly over-expressed in OC cell lines (SKOV3, A2780, CAOV3) in comparison to normal IOSE-80 cells. AC074286.1 were over-expressed in A2780 and CAOV3 cells and CHRM3-AS2 only in A2780 cells. PTPRD-AS1 knockdown decreased the proliferation, cloning, and migration of CAOV3 cells.<br><br>CONCLUSION: Our study identified potential biomarkers for the six-TRLs model related to the prognosis of OC.},
}
@article {pmid39354183,
year = {2024},
author = {Wilsnack, C and Rising, CJ and Pearce, EE and Forbes Shepherd, R and Thompson, AS and Majid, A and Werner-Lin, A and Savage, SA and Hutson, SP},
title = {Defining the complex needs of families with rare diseases-the example of telomere biology disorders.},
journal = {European journal of human genetics : EJHG},
volume = {},
number = {},
pages = {},
pmid = {39354183},
issn = {1476-5438},
abstract = {Families with rare diseases, such as telomere biology disorders (TBDs), may have extensive unmet needs given the heterogeneity, chronicity, and potential severity of illness. TBDs are rare inherited syndromes associated with high risk of bone marrow failure, cancer, pulmonary fibrosis, and other severe, chronic complications. To identify gaps in clinical care, we aimed to ascertain the perceived unmet needs of adults and family caregivers, current or bereaved, of individuals with TBDs. Participants were aged ≥18 years with a self-reported TBD diagnosis and/or ever caregivers to one or more family members with a TBD. Participants completed an online survey (N = 35) and/or an audio-recorded telephone interview (N = 32). We calculated descriptive statistics in SPSS and thematically analyzed interview transcripts. Quantitative and qualitative data were analyzed concurrently. Most participants were aged ≥35 years, female, highly educated, and medically insured. Survey respondents reported numerous unmet needs in psychosocial, medical, financial, and daily activity domains. In interviews, participant descriptions validated and contextualized the salience of these unmet needs. Both qualitative and quantitative data identified critical shortfalls in addressing chronic family distress and specialty care coordination. Adults and caregivers of individuals with TBDs have a high risk of adverse psychosocial sequelae given extensive unmet needs. These findings provide a foundation for understanding the range and extent of gaps in care for families with rare diseases, especially TBDs but that are likely applicable to others. Tailored multi-disciplinary interventions involving patients, families, clinicians, researchers, and patient advocacy communities are required to appropriately address care needs for all rare diseases.},
}
@article {pmid39351882,
year = {2024},
author = {Lee, H and Niida, H and Sung, S and Lee, J},
title = {Haplotype-resolved de novo assembly revealed unique characteristics of alternative lengthening of telomeres in mouse embryonic stem cells.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae842},
pmid = {39351882},
issn = {1362-4962},
support = {NRF-2020R1A2C3003352//National Research Foundation of Korea/ ; SSTF-BA1501-52//Samsung Science and Technology Foundation/ ; },
abstract = {Telomeres protect chromosome ends from DNA damage responses, and their dysfunction triggers genomic alterations like chromosome fusion and rearrangement, which can lead to cellular death. Certain cells, including specific cancer cells, adopt alternative lengthening of telomere (ALT) to counteract dysfunctional telomeres and proliferate indefinitely. While telomere instability and ALT activity are likely major sources of genomic alteration, the patterns and consequences of such changes at the nucleotide level in ALT cells remain unexplored. Here we generated haplotype-resolved genome assemblies for type I ALT mouse embryonic stem cells, facilitated by highly accurate or ultra-long reads and Hi-C reads. High-quality genome revealed ALT-specific complex chromosome end structures and various genomic alterations including over 1000 structural variants (SVs). The unique sequence (mTALT) used as a template for type I ALT telomeres showed traces of being recruited into the genome, with mTALT being replicated with remarkably high accuracy. Subtelomeric regions exhibited distinct characteristics: resistance to the accumulation of SVs and small variants. We genotyped SVs at allele resolution, identifying genes (Rgs6, Dpf3 and Tacc2) crucial for maintaining ALT telomere stability. Our genome assembly-based approach elucidated the unique characteristics of ALT genome, offering insights into the genome evolution of cells surviving telomere-derived crisis.},
}
@article {pmid39350941,
year = {2024},
author = {Lin, F and Luo, J and Zhu, Y and Liang, H and Li, D and Han, D and Chang, Q and Pan, P and Zhang, Y},
title = {Association Between Adverse Early Life Factors and Telomere Length in Middle and Late Life.},
journal = {Innovation in aging},
volume = {8},
number = {9},
pages = {igae070},
pmid = {39350941},
issn = {2399-5300},
abstract = {BACKGROUND AND OBJECTIVES: Telomere length (TL) has been acknowledged as biomarker of biological aging. Numerous investigations have examined associations between individual early life factors and leukocyte TL; however, the findings were far from consistent.<br><br>RESEARCH DESIGN AND METHODS: We evaluated the relationship between individual and combined early life factors and leukocytes TL in middle and late life using data from the UK Biobank. The early life factors (eg, maternal smoking, breastfeeding, birth weight, and comparative body size and height to peers at age 10) were measured. The regression coefficients (&#x3b2;) and 95% confidence interval (CI) were applied to assess the link of the early life factors and TL in adulthood. Flexible parametric survival models incorporated age to calculate the relationship between early life factors and life expectancy.<br><br>RESULTS: Exposure to maternal smoking, lack of breastfeeding, low birth weight, and shorter height compared to peers at age 10 were identified to be associated with shorter TL in middle and older age according to the large population-based study with 197&#x2005;504 participants. Individuals who experienced more than 3 adverse early life factors had the shortest TL in middle and late life (&#x3b2; = -0.053; 95% CI = -0.069 to -0.038; p&#x2005;<&#x2005;.0001), as well as an average of 0.54 years of life loss at the age of 45 and 0.49 years of life loss at the age of 60, compared to those who were not exposed to any early life risk factors.<br><br>DISCUSSION AND IMPLICATIONS: Early life factors including maternal smoking, non-breastfed, low birth weight, and shorter height compared to peers at age 10 were associated with shorter TL in later life. In addition, an increased number of the aforementioned factors was associated with a greater likelihood of shorter TL in adulthood, as well as a reduced life expectancy.},
}
@article {pmid39350032,
year = {2024},
author = {Ferguson, S and Bar-Ness, YD and Borevitz, J and Jones, A},
title = {A telomere-to-telomere Eucalyptus regnans genome: unveiling haplotype variance in structure and genes within one of the world's tallest trees.},
journal = {BMC genomics},
volume = {25},
number = {1},
pages = {913},
pmid = {39350032},
issn = {1471-2164},
abstract = {BACKGROUND: Eucalyptus regnans (Mountain Ash) is an Australian native giant tree species which form forests that are among the highest known carbon-dense biomasses in the world. To enhance genomic studies in this ecologically important species, we assembled a high-quality, mostly telomere-to-telomere complete, chromosome-level, haplotype-resolved reference genome. We sampled a single tree, the Centurion, which is currently a contender for the world's tallest flowering plant.<br><br>RESULTS: Using long-read sequencing data (PacBio HiFi, Oxford Nanopore ultra-long reads) and chromosome conformation capture data (Hi-C), we assembled the most contiguous and complete Eucalyptus reference genome to date. For each haplotype, we observed contig N50s exceeding 36 Mbp, scaffold N50s exceeding 43 Mbp, and genome BUSCO completeness exceeding 99%. The assembled genome revealed extensive structural variations between the two haplotypes, consisting mostly of insertions, deletions, duplications and translocations. Analysis of gene content revealed haplotype-specific genes, which were enriched in functional categories related to transcription, energy production and conservation. Additionally, many genes reside within structurally rearranged regions, particularly duplications, suggesting that haplotype-specific variation may contribute to environmental adaptation in the species.<br><br>CONCLUSIONS: Our study provides a foundation for future research into E. regnans environmental adaptation, and the high-quality genome will be a powerful resource for conservation of carbon-dense giant tree forests.},
}
@article {pmid39349834,
year = {2024},
author = {Saraswati, S and Martínez, P and Serrano, R and Mejías, D and Graña-Castro, O and Álvarez Díaz, R and Blasco, MA},
title = {Renal fibroblasts are involved in fibrogenic changes in kidney fibrosis associated with dysfunctional telomeres.},
journal = {Experimental &amp; molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {39349834},
issn = {2092-6413},
abstract = {Tubulointerstitial fibrosis associated with chronic kidney disease (CKD) represents a global health care problem. We previously reported that short and dysfunctional telomeres lead to interstitial renal fibrosis; however, the cell-of-origin of kidney fibrosis associated with telomere dysfunction is currently unknown. We induced telomere dysfunction by deleting the Trf1 gene encoding a telomere-binding factor specifically in renal fibroblasts in both short-term and long-term life-long experiments in mice to identify the role of fibroblasts in renal fibrosis. Short-term Trf1 deletion in renal fibroblasts was not sufficient to trigger kidney fibrosis but was sufficient to induce inflammatory responses, ECM deposition, cell cycle arrest, fibrogenesis, and vascular rarefaction. However, long-term persistent deletion of Trf1 in fibroblasts resulted in kidney fibrosis accompanied by an elevated urinary albumin-to-creatinine ratio (uACR) and a decrease in mouse survival. These cellular responses lead to the macrophage-to-myofibroblast transition (MMT), endothelial-to-mesenchymal transition (EndMT), and partial epithelial-to-mesenchymal transition (EMT), ultimately causing kidney fibrosis at the humane endpoint (HEP) when the deletion of Trf1 in fibroblasts is maintained throughout the lifespan of mice. Our findings contribute to a better understanding of the role of dysfunctional telomeres in the onset of the profibrotic alterations that lead to kidney fibrosis.},
}
@article {pmid39349547,
year = {2024},
author = {Geng, D and Liu, H and Wang, H and Wang, H},
title = {Telomere length exhibits inverse association with migraine among Americans aged 20-50 years, without implications beyond age 50: a cross-sectional study.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {22597},
pmid = {39349547},
issn = {2045-2322},
support = {H2020307041//the Natural Science Foundation of Hebei Province/ ; 236Z7745G//the Central Government Guides Local Funds for Science and Technology Development/ ; },
mesh = {Humans ; *Migraine Disorders/genetics ; Middle Aged ; Adult ; Cross-Sectional Studies ; Male ; Female ; Young Adult ; *Telomere/genetics ; United States/epidemiology ; Nutrition Surveys ; Telomere Shortening ; Age Factors ; Telomere Homeostasis ; Aged ; Leukocytes/metabolism ; },
abstract = {Migraine, common in individuals under 50 years, is linked to oxidative stress. The association between telomere length shortening and migraine, along with potential age-related influences, has not been comprehensively studied. This cross-sectional study included data from 6169 participants in the National Health and Nutrition Survey (NHANES) from 1999 to 2002, encompassing information on peripheral blood leukocyte telomere length, severe headache or migraine, and potential confounders. Stratifying by age (20-50 years, > 50 years), we employed multivariable logistic regression, restricted cubic splines and interaction test to investigate age-influenced telomere length in relation to migraine. In participants aged 20-50 years, the odds ratio (OR) for migraine in the shortest telomere length group T1 (0.39-0.89) was 1.35 (95% confidence interval [95% CI] 1.01, 1.79) compared to the longest group T3 (1.10-9.42), whereas in those aged > 50 years, the OR of T1 was 0.93 (95% CI 0.60, 1.43). Additionally, telomere length and age interacted in the development of migraine (p for interaction: 0.010). In individuals aged 20-50, an L-shaped relationship was found between telomere length and migraine, with an inflection point at 1.02T/S ratio. The OR was 9.34 (95% CI 1.56, 55.99) for telomere lengths < 1.02T/S ratio. These findings suggest age influences the association between telomere length and migraine in U.S. adults.},
}
@article {pmid39348051,
year = {2025},
author = {Nonaka, K and Aida, J and Hasegawa, Y and Arai, T and Ishiwata, T and Takubo, K},
title = {Telomere Length Measurement in Human Tissue Sections by Quantitative Fluorescence In Situ Hybridization (Q-FISH).},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2857},
number = {},
pages = {9-14},
pmid = {39348051},
issn = {1940-6029},
mesh = {Humans ; *In Situ Hybridization, Fluorescence/methods ; *Telomere/genetics/metabolism ; *Peptide Nucleic Acids/metabolism/genetics ; *Paraffin Embedding/methods ; Tissue Fixation/methods ; Telomere Homeostasis ; Centromere/metabolism/genetics ; },
abstract = {Telomeres in most somatic cells shorten with each cell division, and critically short telomeres lead to cellular dysfunction, cell cycle arrest, and senescence. Thus, telomere shortening is an important hallmark of human cellular senescence. Quantitative fluorescence in situ hybridization (Q-FISH) using formalin-fixed paraffin-embedded (FFPE) tissue sections allows the estimation of telomere lengths in individual cells in histological sections. In our Q-FISH method, fluorescently labelled peptide nucleic acid (PNA) probes are hybridized to telomeric and centromeric sequences in FFPE human tissue sections, and relative telomere lengths (telomere signal intensities relative to centromere signal intensities) are measured. This chapter describes our Q-FISH protocols for assessing relative telomere lengths in FFPE human tissue sections.},
}
@article {pmid39346776,
year = {2024},
author = {Fu, C and Tian, X and Wu, S and Chu, X and Cheng, Y and Wu, X and Yang, W},
title = {Role of telomere dysfunction and immune infiltration in idiopathic pulmonary fibrosis: new insights from bioinformatics analysis.},
journal = {Frontiers in genetics},
volume = {15},
number = {},
pages = {1447296},
pmid = {39346776},
issn = {1664-8021},
abstract = {BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by unexplained irreversible pulmonary fibrosis. Although the etiology of IPF is unclear, studies have shown that it is related to telomere length shortening. However, the prognostic value of telomere-related genes in IPF has not been investigated.<br><br>METHODS: We utilized the GSE10667 and GSE110147 datasets as the training set, employing differential expression analysis and weighted gene co-expression network analysis (WGCNA) to screen for disease candidate genes. Then, we used consensus clustering analysis to identify different telomere patterns. Next, we used summary data-based mendelian randomization (SMR) analysis to screen core genes. We further evaluated the relationship between core genes and overall survival and lung function in IPF patients. Finally, we performed immune infiltration analysis to reveal the changes in the immune microenvironment of IPF.<br><br>RESULTS: Through differential expression analysis and WGCNA, we identified 35 significant telomere regulatory factors. Consensus clustering analysis revealed two distinct telomere patterns, consisting of cluster A (n = 26) and cluster B (n = 19). Immune infiltration analysis revealed that cluster B had a more active immune microenvironment, suggesting its potential association with IPF. Using GTEx eQTL data, our SMR analysis identified two genes with potential causal associations with IPF, including GPA33 (PSMR = 0.0013; PHEIDI = 0.0741) and MICA (PSMR = 0.0112; PHEIDI = 0.9712). We further revealed that the expression of core genes is associated with survival time and lung function in IPF patients. Finally, immune infiltration analysis revealed that NK cells were downregulated and plasma cells and memory B cells were upregulated in IPF. Further correlation analysis showed that GPA33 expression was positively correlated with NK cells and negatively correlated with plasma cells and memory B cells.<br><br>CONCLUSION: Our study provides a new perspective for the role of telomere dysfunction and immune infiltration in IPF and identifies potential therapeutic targets. Further research may reveal how core genes affect cell function and disease progression, providing new insights into the complex mechanisms of IPF.},
}
@article {pmid39344239,
year = {2024},
author = {Li, J and Liu, PP and Wang, Y and Ren, CY and Zhang, M},
title = {Lectin YKL-40 Level and Telomere Length are Indicators of Insomnia Disorder.},
journal = {Journal of integrative neuroscience},
volume = {23},
number = {9},
pages = {180},
doi = {10.31083/j.jin2309180},
pmid = {39344239},
issn = {0219-6352},
support = {QN2019124//Anhui University of Science and Technology university-level project/ ; YZ2023H1A002//Anhui University of Science and Technology medical special cultivation project/ ; },
mesh = {Humans ; *Chitinase-3-Like Protein 1/blood ; Male ; Female ; *Sleep Initiation and Maintenance Disorders/blood/metabolism ; Adult ; Middle Aged ; *Telomere/metabolism ; Biomarkers/blood ; Leukocytes/metabolism ; },
abstract = {OBJECTIVE: To explore the relationship between YKL-40 level, telomere length, and different subtypes of insomnia disorder.<br><br>METHODS: A total of 145 individuals suffering from insomnia were enrolled and divided into four groups according to the insomniac subtypes: difficulty initiating sleep, early morning awakening, difficulty maintaining sleep, and mixed symptoms. Eighty healthy controls were also collected at the same time. Peripheral leukocyte genomic DNA was extracted, relative telomere lengths were measured using the real-time quantitative polymerase chain reaction method, and YKL-40 levels were determined using enzyme-linked immunoassay. Logistic regression modeling was used to analyze the correlation between different insomnia subtypes, YKL-40 level, and telomere length.<br><br>RESULTS: People with telomere lengths in the lowest tertile were more likely to have trouble falling asleep (odds ratio (OR) 2.13, 95% confidence interval (CI) 1.22-3.63; p = 0.03) and had a higher frequency of mixed symptoms (OR 1.49, 95% CI 1.30-2.81; p = 0.04). People in the highest tertile of YKL-40 level had an increased chance of waking up early (OR 2.98, 95% CI 1.54-5.33; p = 0.01) and more mixed symptoms (OR 1.47, 95% CI 1.22-2.79; p = 0.02). Furthermore, using receiver operating characteristic curve analysis, the area under the curve of YKL-40 level and telomere length was 0.806 and 0.746, respectively.<br><br>CONCLUSIONS: Telomere length in patients with difficulty initiating sleep and mixed symptoms was significantly shortened and the level of YKL-40 in people who have early morning awakening and mixed symptoms was significantly increased. Our findings provide the first evidence that leukocyte telomere length and YKL-40 level are individually linked to mixed symptoms.},
}
@article {pmid39344121,
year = {2024},
author = {Li, Z and Wang, M and Zeng, S and Wang, Z and Ying, Y and Chen, Q and Zhang, C and He, W and Sheng, C and Wang, Y and Zhang, Z and Xu, C and Wang, H},
title = {Investigating the Shared Genetic Architecture Between Leukocyte Telomere Length and Prostate Cancer.},
journal = {The world journal of men's health},
volume = {},
number = {},
pages = {},
doi = {10.5534/wjmh.240062},
pmid = {39344121},
issn = {2287-4208},
support = {81772720/NNSFC/National Natural Science Foundation of China/China ; 81972391/NNSFC/National Natural Science Foundation of China/China ; 82172871/NNSFC/National Natural Science Foundation of China/China ; 2021008149//Naval Medical University/China ; 2020YXK019//Naval Medical University/China ; },
abstract = {PURPOSE: Evidence of an association between leukocyte telomere length (LTL) and prostate cancer (PCa) is accumulating; however, their shared genetic basis remains unclear.<br><br>MATERIALS AND METHODS: Using summary statistics obtained from the genome-wide association study (GWAS), we quantified the global and local genetic correlations between two traits. Subsequently, we identified potential pleiotropic loci, common tissue-enriched regions, and risk gene loci while inferring assumed causal relationships.<br><br>RESULTS: Our study demonstrated a global genetic correlation between LTL and PCa (genetic correlation=0.066, p=0.017), which was further confirmed in local genomic regions. Cross-trait GWAS meta-analysis revealed 44 shared loci, including 10 novel pleiotropic single nucleotide polymorphisms appearing concurrently in significant local genetic correlation regions. Notably, two new loci (rs9419958; rs3730668) were additionally validated to co-localize. For the first time, we identified a significant shared genetic enrichment of both traits in the small intestine tissue at the terminal ileum, with functional genes in this region affecting both LTL and PCa. Concurrently, Mendelian randomization analysis indicated a positive causal relationship between LTL and PCa.<br><br>CONCLUSIONS: In conclusion, our study makes a significant contribution to the ongoing debate concerning the potential association between longer LTL and a higher risk of PCa. Additionally, we provide new evidence for the development of therapeutic targets for PCa and propose new directions for future risk prediction in this regard.},
}
@article {pmid39342869,
year = {2024},
author = {Kyriacou, E and Lingner, J},
title = {TERRA long noncoding RNA: At the interphase of telomere damage, rescue and signaling.},
journal = {Current opinion in cell biology},
volume = {91},
number = {},
pages = {102437},
doi = {10.1016/j.ceb.2024.102437},
pmid = {39342869},
issn = {1879-0410},
abstract = {TERRA long noncoding RNAs play key roles in telomere function and maintenance. They can orchestrate telomeric chromatin remodeling, regulate telomere maintenance by telomerase and homology-directed repair, and they participate in the telomeric DNA damage response. TERRA associates with chromosome ends through base-pairing forming R-loops, which are mediated by the RAD51 DNA recombinase and its partner RAD51AP1. Telomeric R-loops interfere with replication fork progression, stimulating a switch of telomere maintenance from semiconservative DNA replication to homology-directed repair (HDR). The latter mechanism is exploited by a subset of cancer cells that lack telomerase, referred to as ALT. In addition, TERRA stimulates HDR at short telomeres during aging, delaying cellular senescence. During carcinogenesis, when cells with eroded telomeres enter replicative crisis, TERRA acts as a signaling molecule to mediate autophagic cell death.},
}
@article {pmid39339711,
year = {2024},
author = {Boccardi, V and Polom, J},
title = {Searching for Beauty and Health: Aging in Women, Nutrition, and the Secret in Telomeres.},
journal = {Nutrients},
volume = {16},
number = {18},
pages = {},
doi = {10.3390/nu16183111},
pmid = {39339711},
issn = {2072-6643},
mesh = {Humans ; Female ; *Telomere ; *Aging/physiology ; *Nutritional Status ; *Beauty ; Women's Health ; Quality of Life ; Longevity ; Healthy Aging ; Life Style ; Diet ; },
abstract = {Women typically outlive men, yet they often experience greater frailty and a higher incidence of chronic diseases as they age. By exploring the biological foundations of aging, with a particular focus on telomere dynamics, this manuscript aims to describe how dietary and lifestyle choices can significantly influence the aging process. The review comprehensively examines current research, underscoring the power of nutrition to counteract age-related changes, support healthy aging, and maintain vitality and beauty in women. The exploration of telomeres-the protective caps at the ends of chromosomes-reveals how they serve as markers of cellular aging and are potential targets for interventions aimed at enhancing women's longevity and quality of life. This study also emphasizes the importance of sex-specific approaches and precision medicine in understanding the unique health challenges women face as they age. By proposing targeted strategies, the review seeks to address these challenges, offering insights into preventive measures that can foster resilience, promote well-being, and extend healthy life expectancy in women. Ultimately, this work provides a sophisticated understanding of the aging process in women, highlighting the pivotal role of tailored interventions in preserving both health and beauty.},
}
@article {pmid39338301,
year = {2024},
author = {Mantadaki, AE and Baliou, S and Linardakis, M and Vakonaki, E and Tzatzarakis, MN and Tsatsakis, A and Symvoulakis, EK},
title = {Quercetin Intake and Absolute Telomere Length in Patients with Type 2 Diabetes Mellitus: Novel Findings from a Randomized Controlled Before-and-After Study.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {9},
pages = {},
doi = {10.3390/ph17091136},
pmid = {39338301},
issn = {1424-8247},
abstract = {Telomeres, the protective chromosomal ends, progressively shorten and potentially are implicated in the pathogenesis of age-related diseases. In type 2 diabetes (T2DM), telomere shortening may play an important role, but the whole 'picture' remains limited. From a therapeutic perspective, the phytonutrient quercetin appears to be clinically effective and safe for patients with T2DM. Considering the above, we aimed to examine whether quercetin could interfere with telomere length (TL) dynamics. One hundred patients with T2DM on non-insulin medications registered within a primary healthcare facility were stratified by age and sex and randomly assigned to either standard care or standard care plus quercetin (500 mg/day) for 12 weeks, succeeded by an 8-week washout period and another 12 weeks of supplementation. Of the 88 patients completing the trial, 82 consented to blood sampling for TL measurements. Health assessments and whole blood absolute TL measurements using quantitative polymerase chain reaction (qPCR) were conducted at baseline and study end, and the findings of this subcohort are presented. Quercetin supplementation was associated with a significant increase in mean TL (odds ratio ≥ 2.44; p < 0.05) with a strengthened association after full adjustment for potential confounders through multiple logistic regression analysis (odds ratio = 3.48; p = 0.026), suggesting it as a potentially promising supplementation option. Further studies are needed to confirm this finding, elucidating the underlying molecular mechanisms of quercetin.},
}
@article {pmid39335189,
year = {2024},
author = {Fabiani, R and Chiavarini, M and Rosignoli, P and Giacchetta, I},
title = {Leucocyte Telomere Length and Lung Cancer Risk: A Systematic Review and Meta-Analysis of Prospective Studies.},
journal = {Cancers},
volume = {16},
number = {18},
pages = {},
doi = {10.3390/cancers16183218},
pmid = {39335189},
issn = {2072-6694},
abstract = {Although numerous epidemiological studies are available, the relationship between leukocyte telomere length (LTL) and lung cancer risk is still controversial. This systematic review and meta-analysis, performed according to the PRISMA statement and MOOSE guidelines, aims to summarize the evidence and calculate the risk of lung cancer associated with LTL. The literature search was performed on PubMed, Web of Science, and Scopus databases through May 2024. A random-effects model was used to calculate the pooled risk. Heterogeneity was assessed using I[2] and Cochran's Q statistic. Begg's and Egger's tests were used to detect publication bias. Based on 8055 lung cancer cases and 854,653 controls (nine prospective studies), longer LTL was associated with a significant 42% increment in all types of lung cancer risk (OR 1.42, 95% CI 1.24-1.63). The effect was even more evident for adenocarcinomas (OR 1.98, 95% CI 1.69-2.31), while no association was observed for squamous cell carcinoma (OR 0.87, 95% CI 0.72-1.06). Significantly, no association was found for current smokers (OR 1.08, 95% CI 0.90-1.30), while it remained high for both never-smokers (OR 1.92, 95% CI 1.62-2.28) and former smokers (OR 1.34, 95% CI 1.11-1.62). No significant publication bias was evidenced. Longer LTL is associated with an increment in lung cancer risk particularly in never-smoker subjects.},
}
@article {pmid39333471,
year = {2024},
author = {Olagunju, TA and Rosen, BD and Neibergs, HL and Becker, GM and Davenport, KM and Elsik, CG and Hadfield, TS and Koren, S and Kuhn, KL and Rhie, A and Shira, KA and Skibiel, AL and Stegemiller, MR and Thorne, JW and Villamediana, P and Cockett, NE and Murdoch, BM and Smith, TPL},
title = {Telomere-to-telomere assemblies of cattle and sheep Y-chromosomes uncover divergent structure and gene content.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {8277},
pmid = {39333471},
issn = {2041-1723},
support = {USDA-NIFA-2021-67016-33416//United States Department of Agriculture | National Institute of Food and Agriculture (NIFA)/ ; IDA01566//United States Department of Agriculture | National Institute of Food and Agriculture (NIFA)/ ; 3040-31000-104-000-D//United States Department of Agriculture | Agricultural Research Service (USDA Agricultural Research Service)/ ; 8042-31000-112-000-D//United States Department of Agriculture | Agricultural Research Service (USDA Agricultural Research Service)/ ; },
mesh = {Animals ; *Telomere/genetics ; Cattle/genetics ; Sheep/genetics ; *Y Chromosome/genetics ; Male ; Centromere/genetics ; Evolution, Molecular ; Genome/genetics ; Female ; },
abstract = {Reference genomes of cattle and sheep have lacked contiguous assemblies of the sex-determining Y chromosome. Here, we assemble complete and gapless telomere to telomere (T2T) Y chromosomes for these species. We find that the pseudo-autosomal regions are similar in length, but the total chromosome size is substantially different, with the cattle Y more than twice the length of the sheep Y. The length disparity is accounted for by expanded ampliconic region in cattle. The genic amplification in cattle contrasts with pseudogenization in sheep suggesting opposite evolutionary mechanisms since their divergence 19MYA. The centromeres also differ dramatically despite the close relationship between these species at the overall genome sequence level. These Y chromosomes have been added to the current reference assemblies in GenBank opening new opportunities for the study of evolution and variation while supporting efforts to improve sustainability in these important livestock species that generally use sire-driven genetic improvement strategies.},
}
@article {pmid39332705,
year = {2024},
author = {da Cruz, NFS and Sengillo, JD and Shah, SM and López-Font, FJ and Negron, CI and Berrocal, AM},
title = {Telomere Biology Disorders: Report on Clinical and Angiographic Findings.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2024.09.011},
pmid = {39332705},
issn = {2468-6530},
abstract = {PURPOSE: To evaluate the retinal vasculature in pediatric patients with telomere biology disorders (TBD).<br><br>DESIGN: Retrospective consecutive case series.<br><br>SUBJECTS: Pediatric patients with a diagnosis of TBD who underwent widefield fluorescein angiography (FA).<br><br>METHODS: Electronic medical records of pediatric patients with TBD at a tertiary referral eye center were reviewed from January 2019 to July 2023. Vascular phenotype was assessed by reviewing FA images.<br><br>MAIN OUTCOMES MEASURES: Incomplete peripheral vascularization, aneurysmal dilatation, terminal arborization, anastomotic loops, capillary dropout, neovascularization, tortuosity, leakage from tractional membranes, and blockage from hemorrhage.<br><br>RESULTS: Fourteen eyes from 7 patients were included. All patients were genetically confirmed for TBD. The most common genetic variants were in CTC1 (5 patients; 71.4%), ACD (1 patient; 14.3%), and RTEL1 (1 patient; 14.3%). On FA, the most common findings were incomplete peripheral vascularization (14 eyes, 100%), aneurysmal dilatation (12 eyes, 85.7%), terminal arborization (12 eyes, 85.7%), anastomotic loops (12 eyes, 85.7%), capillary dropout (10 eyes, 71.4%), and neovascularization (9 eyes, 64.3%). Regarding treatment, laser photocoagulation (14 eyes, 100%), intravitreal bevacizumab injection (13 eyes, 92.6%), and sub-tenon's Kenalog (11 eyes, 78.6%) were utilized. All patients managed with laser photocoagulation and/or bevacizumab required multiple treatments.<br><br>CONCLUSION: Our study describes a spectrum of vascular changes evidenced by widefield FA in pediatric patients with genetically confirmed TBD. Although further research is warranted to fully understand the etiology of these subtle vascular anomalies, widefield FA should be conducted in patients with genetically confirmed or suspected TBD.},
}
@article {pmid39331358,
year = {2024},
author = {Mattiolo, P and Bevere, M and Mafficini, A and Verschuur, AVD and Calicchia, M and Hackeng, WM and Simbolo, M and Paiella, S and Dreijerink, KMA and Landoni, L and Pedron, S and Cingarlini, S and Salvia, R and Milella, M and Lawlor, RT and Valk, GD and Vriens, MR and Scarpa, A and Brosens, LA and Luchini, C},
title = {Glucagon-Producing Pancreatic Neuroendocrine Tumors (Glucagonomas) are Enriched in Aggressive Neoplasms with ARX and PDX1 Co-expression, DAXX/ATRX Mutations, and ALT (Alternative Lengthening of Telomeres).},
journal = {Endocrine pathology},
volume = {},
number = {},
pages = {},
pmid = {39331358},
issn = {1559-0097},
support = {26343, 28054, 29829//Associazione Italiana per la Ricerca sul Cancro/ ; 26343, 28054, 29829//Associazione Italiana per la Ricerca sul Cancro/ ; 2020-1 12978//KWF Kankerbestrijding/ ; 2020-1 12978//KWF Kankerbestrijding/ ; J38D19000690001//Fondazione Italiana per la ricerca sulle Malattie del Pancreas/ ; J38D19000690001//Fondazione Italiana per la ricerca sulle Malattie del Pancreas/ ; (RF CO-2019-12369662: CUP: B39C21000370001//Ministero della Salute/ ; },
abstract = {Glucagonomas are functioning pancreatic neuroendocrine tumors (PanNETs) responsible for glucagonoma syndrome. This study aims to shed light on the clinicopathological and molecular features of these neoplasms. Six patients with glucagonomas were identified. All neoplasms were investigated with immunohistochemistry for neuroendocrine markers (Synaptophysin, Chromogranin-A), ATRX, DAXX, ARX, and PDX1 transcription factors. Fluorescent in situ hybridization (FISH) for assessing alternative lengthening of telomeres (ALT), and next-generation sequencing (NGS) for molecular profiling were performed. All cases were large single masses (mean size of 8.2 cm), with necrolytic migratory erythema as the most common symptom (6/6 cases, 100%). All neoplasms were well-differentiated G1 tumors, except one case that was G2. The tumors consistently showed classic/conventional histomorphology, with solid-trabecular and nested architecture. Lymphatic and vascular invasion (6/6, 100%), perineural infiltration (4/6, 66.6%), and nodal metastasis (4/6, 66.6%) were frequently observed. Transcription factors expression showed strong ARX expression in all tumors, and PDX1 expression in 5/6 cases (83.3%), indicating co-occurring alpha- and beta-cell differentiation. NGS showed recurrent somatic MEN1 and ATRX/DAXX biallelic inactivation. Cases with ATRX or DAXX mutations also showed matched loss of ATRX or DAXX protein expression and ALT. One case harbored somatic MUTYH inactivation and showed a high tumor mutational burden (TMB, 41.0 mut/Mb). During follow-up, one patient died of the disease, and four patients developed distant metastasis. Pancreatic glucagonomas are distinct PanNETs with specific clinicopathological and molecular features, including histological aspects of biological aggressiveness, co-occurring alpha- and beta-cell differentiation, MEN1 and DAXX/ATRX mutations enrichment, and the possible presence of high-TMB as an actionable marker.},
}
@article {pmid39330362,
year = {2024},
author = {Chen, X and Wei, Y and Meng, G and Wang, M and Peng, X and Dai, J and Dong, C and Huo, G},
title = {Telomere-to-Telomere Haplotype-Resolved Genomes of Agrocybe chaxingu Reveals Unique Genetic Features and Developmental Insights.},
journal = {Journal of fungi (Basel, Switzerland)},
volume = {10},
number = {9},
pages = {},
doi = {10.3390/jof10090602},
pmid = {39330362},
issn = {2309-608X},
support = {JXXTCX202409//Collaborative Innovation Project of Modern Agricultural Research of Jiangxi Province/ ; 20212BBF61002, 20212BBF63013//Project of Science and Technology Department of Jiangxi Province/ ; JXXTCXBSJJ202213//Collaborative Innovation Project of Modern Agricultural Research of Jiangxi Province/ ; none//Crop Seeds Joint Research of Jiangxi Province/ ; CARS20//China Agriculture Research System/ ; },
abstract = {Agrocybe chaxingu is a widely cultivated edible fungus in China, which is rich in nutrients and medicinal compounds. However, the lack of a high-quality genome hinders further research. In this study, we assembled the telomere-to-telomere genomes of two sexually compatible monokaryons (CchA and CchB) derived from a primarily cultivated strain AS-5. The genomes of CchA and CchB were 50.60 Mb and 51.66 Mb with contig N50 values of 3.95 Mb and 3.97 Mb, respectively. Each contained 13 complete chromosomes with telomeres at both ends. The high mapping rate, uniform genome coverage, high LAI score, all BUSCOs with 98.5%, and all base accuracy exceeding 99.999% indicated the high level of integrity and quality of these two assembled genomes. Comparison of the two genomes revealed that approximately 30% of the nucleotide sequences between homologous chromosomes were non-syntenic, including 19 translocations, 36 inversions, and 15 duplications. An additional gene CchA_000467 was identified at the Mat A locus of CchA, which was observed exclusively in the Cyclocybe cylindracea species complex. A total of 613 (4.26%) and 483 (3.4%) unique genes were identified in CchA and CchB, respectively, with over 80% of these being hypothetical proteins. Transcriptomic analysis revealed that the expression levels of unique genes in CchB were significantly higher than those in CchA, and both CchA and CchB had unique genes specifically expressed at stages of mycelium and fruiting body. It was indicated that the growth and development of the A. chaxingu strain AS-5 required the coordinated action of two different nuclei, with CchB potentially playing a more significant role. These findings contributed to a more profound comprehension of the growth and developmental processes of basidiomycetes.},
}
@article {pmid39329317,
year = {2024},
author = {Naish, M},
title = {Bridging the gap: unravelling plant centromeres in the telomere-to-telomere era.},
journal = {The New phytologist},
volume = {},
number = {},
pages = {},
doi = {10.1111/nph.20149},
pmid = {39329317},
issn = {1469-8137},
support = {//School of the Biological Sciences, University of Cambridge/ ; },
abstract = {Centromeres are specific regions of the chromosomes that play a pivotal role in the segregation of chromosomes, by facilitating the loading of the kinetochore, which forms the link between the chromosomes to the spindle fibres during cell division. In plants and animals, these regions often form megabase-scale loci of tandemly repeated DNA sequences, which have presented a challenge to genomic studies even in model species. The functional designation of centromeres is determined epigenetically by the incorporation of a centromere-specific variant of histone H3. Recent developments in long-read sequencing technology have allowed the assembly of these regions for the first time and have prompted a reassessment of fidelity of centromere function and the evolutionary dynamics of these regions.},
}
@article {pmid39329264,
year = {2024},
author = {Granger, SL and Sharma, R and Kaushik, V and Razzaghi, M and Honda, M and Gaur, P and Bhat, DS and Labenz, SM and Heinen, JE and Williams, BA and Tabei, SMA and Wlodarski, MW and Antony, E and Spies, M},
title = {Human hnRNPA1 reorganizes telomere-bound replication protein A.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae834},
pmid = {39329264},
issn = {1362-4962},
support = {R35GM131704/NH/NIH HHS/United States ; K08 DK134873/DK/NIDDK NIH HHS/United States ; CA078586/BC/NCI NIH HHS/United States ; },
abstract = {Human replication protein A (RPA) is a heterotrimeric ssDNA binding protein responsible for many aspects of cellular DNA metabolism. Dynamic interactions of the four RPA DNA binding domains (DBDs) with DNA control replacement of RPA by downstream proteins in various cellular metabolic pathways. RPA plays several important functions at telomeres where it binds to and melts telomeric G-quadruplexes, non-canonical DNA structures formed at the G-rich telomeric ssDNA overhangs. Here, we combine single-molecule total internal reflection fluorescence microscopy (smTIRFM) and mass photometry (MP) with biophysical and biochemical analyses to demonstrate that heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) specifically remodels RPA bound to telomeric ssDNA by dampening the RPA configurational dynamics and forming a ternary complex. Uniquely, among hnRNPA1 target RNAs, telomeric repeat-containing RNA (TERRA) is selectively capable of releasing hnRNPA1 from the RPA-telomeric DNA complex. We speculate that this telomere specific RPA-DNA-hnRNPA1 complex is an important structure in telomere protection.},
}
@article {pmid39324245,
year = {2024},
author = {Sánchez-González, JL and Juárez-Vela, R and Dutil Muñoz de la Torre, V and Andrés-Olivera, MDP and Martín-Vallejo, J and Morán-Bayón, &#xc1; and Gonçalves-Cerejeira, JI and Gestoso-Uzal, N and González-Sarmiento, R and Pérez, J},
title = {Effect of strength-based physical exercise on telomere length as a marker of premature ageing in patients with schizophrenia: study protocol for a pilot randomised controlled trial.},
journal = {BJPsych open},
volume = {10},
number = {5},
pages = {e162},
doi = {10.1192/bjo.2024.753},
pmid = {39324245},
issn = {2056-4724},
abstract = {BACKGROUND: Patients with schizophrenia die decades earlier than the general population. Among the factors involved in this mortality gap, evidence suggests a telomere length shortening in this clinical population, which is associated with premature ageing. Recent studies support the use of strength-based training exercise programmes to maintain, or even elongate, telomere length in healthy elderly populations. However, studies aiming at modifying telomere length in severe mental illnesses, such as schizophrenia, are still very scarce.<br><br>AIMS: To investigate the effect of a strength-based physical exercise programme on the telomere length of individuals with schizophrenia.<br><br>METHOD: We propose a pragmatic, randomised controlled trial including 40 patients aged &#x2265;18 years, with a stable diagnosis of schizophrenia, attending the Complejo de Rehabilitaci&#xf3;n Psicosocial (CRPS, Psychosocial Rehabilitation Centre) in Salamanca, Spain. These patients will be randomly assigned (1:1) to either receive the usual treatment and rehabilitation programmes offered by CRPS (treatment-as-usual group) or these plus twice weekly sessions of an evidence-based, strength-based training exercise programme for 12 weeks (intervention group). The primary outcome will be effect on telomere length. Secondary outcomes will include impact on cognitive function, frailty and quality of life.<br><br>RESULTS: We expect to show the importance of implementing strength-based physical exercise programmes for patients with schizophrenia. We could find that such programmes induce biological and genetic changes that may lengthen life expectancy and decrease physical fragility.<br><br>CONCLUSIONS: We anticipate that our trial findings could contribute to parity of esteem for mental health, reducing premature ageing in patients with severe mental illnesses, such as schizophrenia.},
}
@article {pmid39317127,
year = {2024},
author = {Katerina, S},
title = {Telomeres and immunodeficiencies.},
journal = {Human immunology},
volume = {85},
number = {6},
pages = {111146},
doi = {10.1016/j.humimm.2024.111146},
pmid = {39317127},
issn = {1879-1166},
abstract = {The function of the immune system is highly dependent on cellular differentiation and clonal expansion of antigen-specific lymphocytes. Telomeres are conserved DNA-protein structures of linear chromosome termini. Telomere length has been investigated to be different in various lymphocyte subpopulations depending on their function and to change with aging. Association of accelerated telomere loss compared to matched controls has already been confirmed in many syndromes with immune dysregulation. Immunodeficiencies connected with dysfunction of telomere termini are dyskeratosis congenita, ICF syndrome (Immunodeficiency, centromeric instability and facial anomalies syndrome) genetic disorders involving DNA repair and disorders involving the VDJ recombination.},
}
@article {pmid39316766,
year = {2024},
author = {Gutierrez-Rodrigues, F and Groarke, EM and Thongon, N and Rodriguez-Sevilla, JJ and Bazzo Catto, LF and Niewisch, MR and Shalhoub, RN and McReynolds, LJ and Clé, DV and Patel, BA and Ma, X and Hironaka, D and Donaires, FS and Spitofsky, NR and Santana, BA and Lai, TP and Alemu, L and Kajigaya, S and Darden, I and Zhou, W and Browne, PV and Paul, S and Lack, J and Young, DJ and DiNardo, CD and Aviv, A and Ma, F and Michels de Oliveira, M and Azambuja, AP and Dunbar, CE and Olszewska, M and Olivier, E and Papapetrou, EP and Giri, N and Alter, BP and Bonfim, CMS and Wu, CO and Garcia-Manero, G and Savage, SA and Young, NS and Colla, S and Calado, RT},
title = {Clonal landscape and clinical outcomes of telomere biology disorders: somatic rescuing and cancer mutations.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024025023},
pmid = {39316766},
issn = {1528-0020},
abstract = {Telomere biology disorders (TBD), caused by pathogenic germline variants in telomere-related genes, present with multi-organ disease and a predisposition to cancer. Clonal hematopoiesis (CH) as a marker of cancer development and survival in TBD is poorly understood. Here, we characterized the clonal landscape of a large cohort of 207 TBD patients with a broad range of age and phenotype. CH occurred predominantly in symptomatic patients and in signature genes typically associated with cancers: PPM1D, POT1, TERT promoter (TERTp), U2AF1S34, and/or TP53. Chromosome 1q gain (Chr1q+) was the commonest karyotypic abnormality. Clinically, multiorgan involvement and CH in TERTp, TP53, and splicing factor genes associated with poorer overall survival. Chr1q+, and splicing factor or TP53 mutations significantly increased the risk of hematologic malignancies, regardless of the clonal burden. Chr1q+ and U2AF1S34 mutated clones were pre-malignant events associated with the secondary acquisition of mutations in genes related to hematologic malignancies. Like known effects of Chr1q+ and TP53-CH, functional studies demonstrated that U2AF1S34 mutations primarily compensated for aberrant upregulation of TP53 and interferon pathways in telomere-dysfunctional hematopoietic stem cells, highlighting the TP53 pathway as a canonical route of malignancy in TBD. In contrast, somatic POT1/PPM1D/TERTp-CH had distinct trajectories unrelated to cancer development. With implications beyond TBD, our data show that telomere dysfunction is a strong selective pressure for CH. In TBD, CH is a poor prognostic marker associated with worse overall survival. The identification of key regulatory pathways that drive clonal transformation in TBD allows the identification of patients at a higher risk of cancer development.},
}
@article {pmid39312382,
year = {2024},
author = {Song, T and Liu, J and Zhao, K and Li, S and Qiu, M and Zhang, M and Wang, H},
title = {The causal effect of telomere length on the risk of malignant lymphoma: A Mendelian randomization study.},
journal = {Medicine},
volume = {103},
number = {38},
pages = {e39584},
doi = {10.1097/MD.0000000000039584},
pmid = {39312382},
issn = {1536-5964},
mesh = {*Mendelian Randomization Analysis/methods ; Humans ; *Genome-Wide Association Study ; Lymphoma/genetics/epidemiology ; Hodgkin Disease/genetics/epidemiology ; Telomere/genetics ; Risk Factors ; Lymphoma, Follicular/genetics/epidemiology ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; },
abstract = {Telomere length (TL) has been implicated in the risk assessment of numerous cancers in observational studies. Nevertheless, the relationship between TL and malignant lymphoma remains unclear, displaying inconsistent patterns across different studies. A summary dataset for genome-wide association study of TL and malignant lymphoma was acquired from the OpenGWAS website. An extensive 2-sample Mendelian randomization (MR) analysis was performed, encompassing various methodologies such as MR-Egger, weighted median, weighted mode, simple mode, and the primary method of inverse-variance weighting (IVW). Sensitivity evaluations were performed using the Cochran Q test, MR-Egger regression, and leave-one-out analysis. The main method IVW revealed that TL substantially increased the risk of Hodgkin lymphoma (HL; odds ratio [OR] = 2.135; 95% confidence interval [CI] = 1.181-3.859; P = .012). Both the IVW and weighted median methods indicated statistical associations between genetically predicted TL and other types of non-HL (OR = 1.671, 95% CI = 1.009-2.768, P = .045; OR = 2.310, 95% CI = 1.033-5.169, P = .042). However, there was no association between TL and diffuse large B-cell lymphoma, follicular lymphoma, or mature T/natural Killer-cell lymphoma, and sensitivity analysis revealed no heterogeneity or horizontal pleiotropy, indicating that the causal effect was robust. Our study shows that TL plays different roles in different types of lymphomas. A longer TL significantly increases the risk of HL and other types of non-HL.},
}
@article {pmid39307671,
year = {2024},
author = {Lan, L and Zhang, R and Liang, Y and Chen, H and Zhao, H and Zhuo, X},
title = {Evaluating the Effect of Telomere Length on Oral and Oropharyngeal Cancer Risk Using Mendelian Randomization.},
journal = {International dental journal},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.identj.2024.07.1218},
pmid = {39307671},
issn = {1875-595X},
abstract = {INTRODUCTION: The aim of this study was to explore the causal relationship between telomere length and Oral and oropharyngeal cancers by using Mendelian randomization (MR) analysis.<br><br>METHODS: We carried out a 2-sample MR to examine the causal association between telomere length and Oral and oropharyngeal cancers. Two large genome-wide association studies (GWAS) were employed to identify single nucleotide polymorphisms (SNPs) as instrumental variables through statistical and biological approaches. The data on SNP-oral and oropharyngeal cancer risk factor associations were sourced from various consortia/UK Biobank. The inverse variance weighted (IVW) method was employed as the primary approach for overall causal estimation in MR, with sensitivity analyses conducted to assess potential confounding by pleiotropy, heterogeneity, and the leave-one-out analysis.<br><br>RESULTS: The statistically driven approach indicates limited evidence of a genetically causal effect of telomere length on the risk of oral cavity cancer (OR = 0.999, 95% CI 0.998-1.000, P = .100), oropharyngeal cancer (OR = 0.999, 95% CI 0.998-1.001, P = .650), combined oral and oropharyngeal cancer (OR = 0.999, 95% CI 0.998-1.000, P = .119) in Europeans. The biologically driven approach demonstrated consistent causal effects across all MR methods, thereby further strengthening the reliability of the results. Moreover, the MR-Egger (Q [df] 170.816 [130], P = .009) and inverse variance weighted methods (Q [df] 171.656 [131], P = .010) identified considerable heterogeneity among instrumental variable estimates in Oral cavity cancer, and no evidence of horizontal pleiotropy was detected.<br><br>CONCLUSIONS: No significant causal associations between telomere length and Oral and oropharyngeal cancers were found in this study.},
}
@article {pmid39297884,
year = {2024},
author = {Chen, Z and Vallega, KA and Wang, D and Quan, Z and Fan, S and Wang, Q and Leal, T and Ramalingam, SS and Sun, SY},
title = {Inhibition of hTERT/telomerase/telomere mediates therapeutic efficacy of osimertinib in EGFR mutant lung cancer.},
journal = {The Journal of experimental medicine},
volume = {221},
number = {11},
pages = {},
doi = {10.1084/jem.20240435},
pmid = {39297884},
issn = {1540-9538},
support = {UG1 CA233259/NH/NIH HHS/United States ; /CA/NCI NIH HHS/United States ; },
mesh = {*Acrylamides/pharmacology/therapeutic use ; *Telomerase/genetics/metabolism/antagonists &amp; inhibitors ; *Aniline Compounds/pharmacology/therapeutic use ; Humans ; *ErbB Receptors/genetics/antagonists &amp; inhibitors/metabolism ; *Lung Neoplasms/drug therapy/genetics/pathology ; Animals ; *Telomere/metabolism/drug effects ; *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology ; *Mutation ; Cell Line, Tumor ; *Drug Resistance, Neoplasm/genetics/drug effects ; Mice ; Xenograft Model Antitumor Assays ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Antineoplastic Agents/pharmacology/therapeutic use ; Indoles ; Pyrimidines ; },
abstract = {The inevitable acquired resistance to osimertinib (AZD9291), an FDA-approved third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) for the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR activating or T790M resistant mutations, limits its long-term clinical benefit. Telomere maintenance via telomerase reactivation is linked to uncontrolled cell growth and is a cancer hallmark and an attractive cancer therapeutic target. Our effort toward understanding the action mechanisms, including resistance mechanisms, of osimertinib has led to the identification of a novel and critical role in maintaining c-Myc-dependent downregulation of hTERT, a catalytic subunit of telomerase, and subsequent inhibition of telomerase/telomere and induction of telomere dysfunction in mediating therapeutic efficacy of osimertinib. Consequently, osimertinib combined with the telomere inhibitor, 6-Thio-dG, which is currently tested in a phase II trial, effectively inhibited the growth of osimertinib-resistant tumors, regressed EGFRm NSCLC patient-derived xenografts, and delayed the emergence of acquired resistance to osimertinib, warranting clinical validation of this strategy to manage osimertinib acquired resistance.},
}
@article {pmid39303890,
year = {2024},
author = {Ma, K and Zhu, M and Zhang, A and Zuo, M and Huang, Y and Wan, Y and Tao, F and Sun, Y},
title = {Intergenerational continuation of parent-child separation and 1-year telomere length attrition among mother-offspring dyads in rural China: The moderating effects of resilience.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jad.2024.09.098},
pmid = {39303890},
issn = {1573-2517},
abstract = {BACKGROUND: Although stressor exposure early in life was known risk factor for telomere length (TL) attrition, limited literature explored it across generations. Furthermore, the effects of resilience have rarely been examined. Here, we examined whether the effects of intergenerational parent-child separation on offspring 1-year TL attrition vary by the levels of resilience.<br><br>METHOD: In a sample of 342 mother-child dyads living in rural China, the intergenerational continuation of parent-child separation was defined as the two generations both experiencing parent-child separation from both parents for >6&#x202f;months a year early in life assessed by the parent-reported questionnaire, whereas intergenerational discontinuity refers to parent-child separation exposed in one generation only. TL was measured at baseline (from June to November 2021) and 1-year later with children's buccal mucosa swabs, with resilience polygenic risk scores (PRS) evaluated based on 4 single-nucleotide variations in 4 resilience-related genes (OXTR, FKBP5, NPY, and TNF-&#x3b1;).<br><br>RESULTS: Among 342 mother-offspring dyads, 35 (10.2&#x202f;%) experienced intergenerational continuation of parent-child separation, and 139 (40.6&#x202f;%) were identified as discontinuous. Remarkably, a 0.12-point reduction in TL attrition was only associated with intergenerational continuation of parent-child separation (95&#x202f;% CI: 0.04, 0.21, P&#x202f;<&#x202f;0.01) but not discontinuity. Importantly, the association between intergenerational continuation of parent-child separation with accelerated TL attrition disappeared in offspring with high resilience PRS (&#x3b2;&#x202f;=&#x202f;0.07, 95%CI: -0.06, 0.21).<br><br>CONCLUSION: Our findings highlight the importance of breaking the intergenerational cycle of parent-child separation and the moderating effects of resilience on TL attrition for children exposed to adversity.},
}
@article {pmid39303531,
year = {2024},
author = {Hailu, EM and Gao, X and Needham, BL and Seeman, T and Lewis, TT and Mujahid, MS},
title = {Associations between historical and contemporary measures of structural racism and leukocyte telomere length: The Multi-Ethnic Study of Atherosclerosis (MESA).},
journal = {Social science &amp; medicine (1982)},
volume = {360},
number = {},
pages = {117229},
doi = {10.1016/j.socscimed.2024.117229},
pmid = {39303531},
issn = {1873-5347},
abstract = {BACKGROUND: We assessed the link between two manifestations of structural racism-historical redlining and contemporary racial residential segregation-and baseline and 10-year changes in leukocyte telomere length (LTL).<br><br>METHODS: We used data on Black and Hispanic/Latinx participants from Exams I and V of the Multi-Ethnic Study of Atherosclerosis Stress Ancillary Study (N&#xa0;=&#xa0;741, age range&#xa0;=&#xa0;45-84 years). LTL was defined as the ratio of telomeric DNA to a single copy gene (T/S), and 10-year changes were adjusted for regression to the mean. We used 1930s Home Owners' Loan Corporation maps to assign three historical redlining grades (A&amp;B: best/still desirable, C: declining, D: hazardous/redlined) to participants' neighborhoods (census-tracts) at baseline. The Getis-Ord Gi&#x2217; statistic was used to evaluate census-tract level baseline residential segregation (low/moderate/high).<br><br>RESULTS: In mixed-effects regression models accounting for neighborhood clustering, individual characteristics, and current neighborhood environments, those living in highly segregated Black neighborhoods had 0.08 shorter baseline LTL (95% CI: -0.13, -0.04), than those residing in the least segregated neighborhoods. We did not find a relationship between residing in segregated neighborhoods and 10-year LTL changes, and associations between residing in historically redlined neighborhoods and both baseline LTL and 10-year changes in LTL were null. Across discriminatory disinvestment trajectories examined, individuals residing in highly segregated but non-redlined neighborhoods had 0.6 shorter baseline LTL than individuals residing in non-redlined neighborhoods with low/moderate segregation (95% CI: -0.12, -0.01).<br><br>CONCLUSIONS: Our results highlight the impact of racial segregation on cellular aging and underscore the need to ameliorate structural inequities within segregated neighborhoods.},
}
@article {pmid39303078,
year = {2024},
author = {Zhang, J and Liu, S and Zhao, S and Nie, Y and Zhang, Z},
title = {A telomere-to-telomere haplotype-resolved genome of white-fruited strawberry reveals the complexity of fruit colour formation of cultivated strawberry.},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.14479},
pmid = {39303078},
issn = {1467-7652},
support = {RC220306//Shenyang Young and Middle-aged Science and Technology Innovation Talents Support Plan/ ; 2023020525-JH1/102-02//sub-project of Liaoning Province Germplasm Innovation Grain Storage and Technology Special Program/ ; 32130092//National Natural Science Foundation of China/ ; 32272681//National Natural Science Foundation of China/ ; },
}
@article {pmid39296266,
year = {2024},
author = {Froney, MM and Cook, CR and Cadiz, AM and Flinter, KA and Ledeboer, ST and Chan, B and Burris, LE and Hardy, BP and Pearce, KH and Wardell, AC and Golitz, BT and Jarstfer, MB and Pattenden, SG},
title = {A First-in-Class High-Throughput Screen to Discover Modulators of the Alternative Lengthening of Telomeres (ALT) Pathway.},
journal = {ACS pharmacology &amp; translational science},
volume = {7},
number = {9},
pages = {2799-2819},
pmid = {39296266},
issn = {2575-9108},
abstract = {Telomeres are a protective cap that prevents chromosome ends from being recognized as double-stranded breaks. In somatic cells, telomeres shorten with each cell division due to the end replication problem, which eventually leads to senescence, a checkpoint proposed to prevent uncontrolled cell growth. Tumor cells avoid telomere shortening by activating one of two telomere maintenance mechanisms (TMMs): telomerase reactivation or alternative lengthening of telomeres (ALT). TMMs are a viable target for cancer treatment as they are not active in normal, differentiated cells. Whereas there is a telomerase inhibitor currently undergoing clinical trials, there are no known ALT inhibitors in development, partially because the complex ALT pathway is still poorly understood. For cancers such as neuroblastoma and osteosarcoma, the ALT-positive status is associated with an aggressive phenotype and few therapeutic options. Thus, methods that characterize the key biological pathways driving ALT will provide important mechanistic insight. We have developed a first-in-class phenotypic high-throughput screen to identify small-molecule inhibitors of ALT. Our screen measures relative C-circle level, an ALT-specific biomarker, to detect changes in ALT activity induced by compound treatment. To investigate epigenetic mechanisms that contribute to ALT, we screened osteosarcoma and neuroblastoma cells against an epigenetic-targeted compound library. Hits included compounds that target chromatin-regulating proteins and DNA damage repair pathways. Overall, the high-throughput C-circle assay will help expand the repertoire of potential ALT-specific therapeutic targets and increase our understanding of ALT biology.},
}
@article {pmid39292074,
year = {2024},
author = {Pérez-López, FR and Fernández-Alonso, AM and Ulloque-Badaracco, JR and Benites-Zapata, VA and Varikasuvu, SR},
title = {Telomere length in subjects with and without SARS-CoV-2 infection: a systematic review and meta-analysis.},
journal = {Revista da Associacao Medica Brasileira (1992)},
volume = {70},
number = {9},
pages = {e20240387},
doi = {10.1590/1806-9282.20240387},
pmid = {39292074},
issn = {1806-9282},
mesh = {Humans ; *COVID-19 ; *SARS-CoV-2 ; Telomere/genetics ; Telomere Shortening ; },
}
@article {pmid39291738,
year = {2024},
author = {Zheng, YL and Wu, X and Williams, M and Verhulst, S and Lin, J and Takahashi, Y and Ma, JX and Wang, Y},
title = {High-throughput single telomere analysis using DNA microarray and fluorescent in situ hybridization.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae812},
pmid = {39291738},
issn = {1362-4962},
support = {U01ES011786//National Institute of Health/ ; //Georgetown University/ ; },
abstract = {The human telomere system is highly dynamic. Both short and long leucocyte average telomere lengths (aTL) are associated with an increased risk of cancer and early death, illustrating the complex relationship between TL and human health and the importance of assessing TL distributions with single TL analysis. A DNA microarray and telomere fluorescent in situ hybridization (DNA-array-FISH) approach was developed to measure the base-pair (bp) lengths of single telomeres. On average 32000 telomeres were measured per DNA sample with one microarray chip assaying 96 test DNA samples. Various telomere parameters, i.e. aTL and the frequency of short/long telomeres, were computed to delineate TL distribution. The intra-assay and inter-assay coefficient of variations of aTL ranged from 1.37% to 3.98%. The correlation coefficient (r) of aTL in repeated measurements ranged from 0.91 to 1.00, demonstrating high measurement precision. aTLs measured by DNA-array-FISH predicted aTLs measured by terminal restriction fragment (TRF) analysis with r ranging 0.87-0.99. A new accurate and high-throughput method has been developed to measure the bp lengths of single telomeres. The large number of single TL data provides an opportunity for an in-depth analysis of telomere dynamics and the complex relationship between telomere and age-related diseases.},
}
@article {pmid39291733,
year = {2024},
author = {Kim, S and Park, SH and Kang, N and Ra, JS and Myung, K and Lee, KY},
title = {Polyubiquitinated PCNA triggers SLX4-mediated break-induced replication in alternative lengthening of telomeres (ALT) cancer cells.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae785},
pmid = {39291733},
issn = {1362-4962},
support = {IBS-R022-D1//Institute for Basic Science/ ; //National Research Foundation of Korea/ ; RS-2023-00251939//MSIT/ ; //National Research Foundation of Korea/ ; },
abstract = {Replication stresses are the major source of break-induced replication (BIR). Here, we show that in alternative lengthening of telomeres (ALT) cells, replication stress-induced polyubiquitinated proliferating cell nuclear antigen (PCNA) (polyUb-PCNA) triggers BIR at telomeres and the common fragile site (CFS). Consistently, depleting RAD18, a PCNA ubiquitinating enzyme, reduces the occurrence of ALT-associated promyelocytic leukemia (PML) bodies (APBs) and mitotic DNA synthesis at telomeres and CFS, both of which are mediated by BIR. In contrast, inhibiting ubiquitin-specific protease 1 (USP1), an Ub-PCNA deubiquitinating enzyme, results in an increase in the above phenotypes in a RAD18- and UBE2N (the PCNA polyubiquitinating enzyme)-dependent manner. Furthermore, deficiency of ATAD5, which facilitates USP1 activity and unloads PCNAs, augments recombination-associated phenotypes. Mechanistically, telomeric polyUb-PCNA accumulates SLX4, a nuclease scaffold, at telomeres through its ubiquitin-binding domain and increases telomere damage. Consistently, APB increase induced by Ub-PCNA depends on SLX4 and structure-specific endonucleases. Taken together, our results identified the polyUb-PCNA-SLX4 axis as a trigger for directing BIR.},
}
@article {pmid39287993,
year = {2024},
author = {Li, W and Chen, H and Yuan, X and Yao, Q and Zhang, M},
title = {Study of the role of leukocyte telomere length-related lncRNA NBR2 in Alzheimer's disease.},
journal = {Aging},
volume = {16},
number = {},
pages = {},
doi = {10.18632/aging.206107},
pmid = {39287993},
issn = {1945-4589},
abstract = {Alzheimer's Syndrome (AD) is a neurodegenerative disease that is prevalent in middle-aged and elderly people. As the disease progresses, patients gradually lose the ability to take care of themselves, which brings a heavy burden to the family. There is a link between leukocyte telomere length (LTL) and cognitive ability. To search for possible pathogenic mechanisms and potential therapeutic agents, we demonstrated a causal link between LTL and AD using Mendelian randomization analysis (MR). The expression of the target gene NBR2 and the downstream mRNA GJA1 and GJA1-related genes, pathway enrichment, and association with immune cells were further explored. Using the gene cluster-drug target interaction network, we obtained potential therapeutic drugs. Our study provides evidence for a causal link between AD and LTL, suggesting medicines that may treat and alleviate AD symptoms.},
}
@article {pmid39284832,
year = {2024},
author = {Zhao, J and Yang, K and Lu, Y and Zhou, L and Fu, H and Feng, J and Wu, J},
title = {Proteomic Mendelian randomization to identify protein biomarkers of telomere length.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {21594},
pmid = {39284832},
issn = {2045-2322},
mesh = {Humans ; *Mendelian Randomization Analysis ; *Biomarkers/blood ; *Genome-Wide Association Study ; *Quantitative Trait Loci ; *Proteomics/methods ; Telomere Homeostasis ; Telomere/metabolism/genetics ; Proteome/metabolism ; Blood Proteins/genetics/metabolism ; Telomere Shortening ; },
abstract = {Shortening of telomere length (TL) is correlated with many age-related disorders and is a hallmark of biological aging. This study used proteome-wide Mendelian randomization to identify the protein biomarkers associated with telomere length. Protein quantitative trait loci (pQTL) were derived from two studies, the deCODE Health study (4907 plasma proteins) and the UK Biobank Pharma Proteomics Project (2923 plasma proteins). Summary data from genome-wide association studies (GWAS) for TL were obtained from the UK Biobank (472,174 cases) and GWAS Catalog (418,401 cases). The association between proteins and TL was further assessed using colocalization and summary data-based Mendelian randomization (SMR) analyses. The protein-protein network, druggability assessment, and phenome-wide MR were used to further evaluate the potential biological effects, druggability, and safety of the target proteins. Proteome-wide MR analysis identified 22 plasma proteins that were causally associated with telomere length. Five of these proteins (APOE, SPRED2, MAX, RALY, and PSMB1) had the highest evidence of association with TL and should be prioritized. This study revealed telomere length-related protein biomarkers, providing new insights into the development of new treatment targets for chronic diseases and anti-aging intervention strategies.},
}
@article {pmid39283687,
year = {2024},
author = {Yin, D and Chen, C and Lin, D and Hua, Z and Ying, C and Zhang, J and Zhao, C and Liu, Y and Cao, Z and Zhang, H and Wang, C and Liang, L and Xu, P and Jian, J and Liu, K},
title = {Telomere-to-telomere gap-free genome assembly of the endangered Yangtze finless porpoise and East Asian finless porpoise.},
journal = {GigaScience},
volume = {13},
number = {},
pages = {},
doi = {10.1093/gigascience/giae067},
pmid = {39283687},
issn = {2047-217X},
support = {2021YFD1200304//National Key Research and Development of China/ ; },
mesh = {*Porpoises/genetics ; *Telomere/genetics ; Animals ; *Genome ; Endangered Species ; Phylogeny ; Genomics/methods ; East Asian People ; },
abstract = {BACKGROUND: The Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis, YFP) and the East Asian finless porpoise (Neophocaena asiaeorientalis sunameri, EFP) are 2 subspecies of the narrow-ridged finless porpoise that live in freshwater and saltwater, respectively. The main objective of this study was to provide contiguous chromosome-level genome assemblies for YFP and EFP.<br><br>RESULTS: Here, we generated and upgraded the genomes of YFP and EFP at the telomere-to-telomere level through the integration of PacBio HiFi long reads, ultra-long ONT reads, and Hi-C sequencing data with a total size of 2.48 Gb and 2.50 Gb, respectively. The scaffold N50 of 2 genomes was 125.12&#x2009;Mb (YFP) and 128&#x2009;Mb (EFP) with 1 contig for 1 chromosome. The telomere repeat and centromere position were clearly identified in both YFP and EFP genomes. In total, 5,480 newfound genes were detected in the YFP genome, including 56 genes located in the newly identified centromere regions. Additionally, synteny blocks, structural similarities, phylogenetic relationships, gene family expansion, and inference of selection were studied in connection with the genomes of other related mammals.<br><br>CONCLUSIONS: Our research findings provide evidence for the gradual adaptation of EFP in a marine environment and the potential sensitivity of YFP to genetic damage. Compared to the 34 cetacean genomes sourced from public databases, the 2 new assemblies demonstrate superior continuity with the longest contig N50 and scaffold N50 values, as well as the lowest number of contigs. The improvement of telomere-to-telomere gap-free reference genome resources supports conservation genetics and population management for finless porpoises.},
}
@article {pmid39279436,
year = {2024},
author = {Thompson, AS and Niewisch, MR and Giri, N and McReynolds, LJ and Savage, SA},
title = {Germline RTEL1 Variants in Telomere Biology Disorders.},
journal = {American journal of medical genetics. Part A},
volume = {},
number = {},
pages = {e63882},
doi = {10.1002/ajmg.a.63882},
pmid = {39279436},
issn = {1552-4833},
support = {//Division of Cancer Epidemiology and Genetics, National Cancer Institute/ ; },
abstract = {Rare germline variation in regulator of telomere elongation helicase 1 (RTEL1) is associated with telomere biology disorders (TBDs). Biallelic RTEL1 variants result in childhood onset dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome whereas heterozygous individuals usually present later in life with pulmonary fibrosis or bone marrow failure. We compiled all TBD-associated RTEL1 variants in the literature and assessed phenotypes and outcomes of 44 individuals from 14 families with mono- or biallelic RTEL1 variants enrolled in clinical trial NCT00027274. Variants were classified by adapting ACMG-AMP guidelines using clinical information, telomere length, and variant allele frequency data. Compared with heterozygotes, individuals with biallelic RTEL1 variants had an earlier age at diagnosis (median age 35.5 vs. 5.1 years, p < 0.01) and worse overall survival (median age 66.5 vs. 22.9 years, p < 0.001). There were 257 unique RTEL1 variants reported in 47 publications, and 209 had a gnomAD minor allele frequency <1%. Only 38.3% (80/209) met pathogenic/likely pathogenic criteria. Notably, 8 of 209 reported disease-associated variants were benign or likely benign and the rest were variants of uncertain significance. Given the considerable differences in outcomes of TBDs associated with RTEL1 germline variants and the extent of variation in the gene, systematic functional studies and standardization of variant curation are urgently needed to inform clinical management.},
}
@article {pmid39279213,
year = {2024},
author = {Maillet, F and Galimard, JE and Borie, R and Lainey, E and Larcher, L and Passet, M and Plessier, A and Leblanc, T and Terriou, L and Lebon, D and Alcazer, V and Cathebras, P and Loschi, M and Wadih, AC and Marcais, A and Marceau-Renaut, A and Couque, N and Lioure, B and Soulier, J and Ba, I and Socié, G and Peffault de Latour, R and Kannengiesser, C and Sicre de Fontbrune, F},
title = {Haematological features of telomere biology disorders diagnosed in adulthood: A French nationwide study of 127 patients.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.19767},
pmid = {39279213},
issn = {1365-2141},
abstract = {Data on haematological features of telomere biology disorders (TBD) remain scarce. We describe haematological, extra-haematological characteristics and prognosis of 127 genetically confirmed TBD patients diagnosed after the age of 15. Ninety-three index cases and 34 affected relatives were included. At diagnosis of TBD, 76.3% of index cases had haematological features, half pulmonary features and a third liver features. At diagnosis, bone marrow failure (BMF) was present in 59 (46.5%), myelodysplastic syndrome (MDS) in 22 (17.3%) and acute myeloid leukaemia (AML) in 2 (1.6%) while 13 (10.2%) developed or worsened bone marrow involvement during follow-up. At diagnosis, compared to MDS/AML patients, BMF patients were younger (median 23.1 years vs. 43.8, p = 0.007), and had a better outcome (4-year overall survival 76.3% vs. 31.8%, p < 0.001). While frequencies and burden of cytogenetical and somatic mutations increased significantly in myeloid malignancies, some abnormalities were also observed in patients with normal blood counts and BMF, notably somatic spliceosome variants. Solid cancers developed in 8.7% patients, mainly human papillomavirus-related cancers and hepatocellular carcinomas. TBD is a multiorgan progressive disease. While BMF is the main haematological disorder, high-risk myeloid malignancies are common, and are, together with age, the only factors associated with a worse outcome.},
}
@article {pmid39267212,
year = {2024},
author = {Rivera, AS and Chao, CR and Hechter, RC},
title = {Disparities in Telomere length by Sexual Orientation in Adults from the Genetic Epidemiology Research on Aging Cohort.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwae352},
pmid = {39267212},
issn = {1476-6256},
abstract = {The weathering hypothesis proposes that marginalized people experience faster biologic aging due to cumulative stress which translates to chronic disease disparities. We assessed telomere length (TL) differences, an aging biomarker, by sexual orientation (bisexual, gay/lesbian, straight) among 102,258 individuals enrolled in the Resource for Genetic Epidemiology Research on Aging Cohort during 2008 through 2011 (mean age of 60.6 years, 58% female, and 7.6% bisexual/gay/lesbian). We used linear models to estimate differences in telomere length, stratified by sex/gender and adjusted for age (at salivary sample) and socio-demographic variables and Kitagawa-Blinder-Oaxaca decomposition to quantify contributions of participant factors on TL differences. Among females, there was no significant difference in age-adjusted telomere length by sexual orientation after adjustment for socio-demographics (ref: straight; bisexual 0.007, 95%CI: -0.03 to 0.04; lesbian: 0.005, 95%CI: -0.02 to 0.03). Among males, only gay (-0.04, 95%CI: -0.06 to -0.02) but not bisexual (-0.02, 95%CI: -0.06 to 0.02) men had significantly shorter age-adjusted telomere length compared to straight men after adjusting for socio-demographic variables. Decomposition analysis identified ever smoking and marital status as significant drivers of the gay-straight disparity. Studies confirming our findings are needed and the implications of shorter telomeres on gay men's health requires further investigation.},
}
@article {pmid39275278,
year = {2024},
author = {de Jaeger, C and Kruiskamp, S and Voronska, E and Lamberti, C and Baramki, H and Beaudeux, JL and Cherin, P},
title = {A Natural Astragalus-Based Nutritional Supplement Lengthens Telomeres in a Middle-Aged Population: A Randomized, Double-Blind, Placebo-Controlled Study.},
journal = {Nutrients},
volume = {16},
number = {17},
pages = {},
doi = {10.3390/nu16172963},
pmid = {39275278},
issn = {2072-6643},
mesh = {Humans ; Double-Blind Method ; Middle Aged ; *Dietary Supplements ; Male ; Female ; *Astragalus Plant/chemistry ; *Telomere/drug effects ; *Telomerase/metabolism ; Telomere Homeostasis/drug effects ; Telomere Shortening/drug effects ; },
abstract = {Telomeres are ribonucleoprotein structures that form a protective buffer at the ends of chromosomes, maintaining genomic integrity during the cell cycle. A decrease in average telomere length is associated with with age and with aging-related diseases such as cancer and cardiovascular disease. In this study, we conducted a randomized, double-blind, placebo-controlled trial over six months to compare the effects of the Astragalus-based supplement versus a placebo on telomere length (TL) in 40 healthy volunteers (mean age 56.1 ± 6.0 years). Twenty subjects received the supplement, and 20 received placebo capsules. All participants completed the study, and no adverse side effects were reported at six months. Subjects taking the Astragalus-based supplement exhibited significantly longer median TL (p = 0.01) and short TL (p = 0.004), along with a lower percentage of short telomeres, over the six-month period, while the placebo group showed no change in TL. This trial confirmed that the supplement significantly lengthens both median and short telomeres by increasing telomerase activity and reducing the percentage of short telomeres (<3 Kbp) in a statistically and possibly clinically significant manner. These results align with a previous open prospective trial, which found no toxicity associated with the supplement's intake. These findings suggest that this Astragalus-based supplement warrants further investigation for its potential benefits in promoting health, extending life expectancy, and supporting healthy aging.},
}
@article {pmid39273401,
year = {2024},
author = {Dratwa-Kuzmin, M and Hadra, BA and Oguz, F and Ogret, Y and Constantinescu, I and Apostol, D and Talangescu, A and Constantinescu, AE and Maruntelu, I and Kościńska, K and Lukanov, T and Naumova, E and Bogunia-Kubik, K},
title = {Telomere Length, HLA, and Longevity-Results from a Multicenter Study.},
journal = {International journal of molecular sciences},
volume = {25},
number = {17},
pages = {},
doi = {10.3390/ijms25179457},
pmid = {39273401},
issn = {1422-0067},
mesh = {Humans ; *Longevity/genetics ; Aged ; Middle Aged ; Male ; Adult ; Female ; Aged, 80 and over ; Adolescent ; *HLA Antigens/genetics ; Young Adult ; Telomere/genetics ; Alleles ; Telomere Homeostasis ; Aging/genetics/immunology ; Haplotypes ; },
abstract = {Aging is an exceptionally complex process that depends on genetic, environmental, and lifestyle factors. Previous studies within the International HLA and Immunogenetics Workshop (IHIWS) component "Immunogenetics of Ageing" showed that longevity is associated with positive selection of HLA-DRB1*11- and DRB1*16-associated haplotypes, shown to be protective against diseases. Within the 18th IHIWS, we aimed to investigate the relevance of telomere length for successful aging and its association with classical HLAs. In total 957 individuals from Bulgaria, Turkey, Romania, and Poland in two age groups, elderly individuals (age 65-99 years) and ethnically matched young group (age 18-64 years), were investigated. The obtained results confirmed interpopulation differences in the distribution of HLA alleles, documented the lengths of telomeres in analyzed populations, and demonstrated significant associations of telomere length with aging as well as with the presence of some HLA class I or class II alleles. They suggest that telomere length assessment combined with HLA genotyping may help identify immunogenetic profiles associated with longevity. The associations between HLA and telomeres support the theory that HLA genes influence the aging process. However, further research is needed to clarify the biological basis of the observed relationships.},
}
@article {pmid39265426,
year = {2024},
author = {Edzie, J and Alcala, C and Bloomquist, TR and Gutierrez-Avila, I and Just, AC and Midya, V and Téllez Rojo, MM and Estrada-Gutierrez, G and Wright, RJ and Wright, RO and Baccarelli, AA and Rosa, MJ},
title = {Prenatal and early life exposure to fine particulate matter and telomere length in early childhood.},
journal = {International journal of hygiene and environmental health},
volume = {263},
number = {},
pages = {114447},
doi = {10.1016/j.ijheh.2024.114447},
pmid = {39265426},
issn = {1618-131X},
abstract = {BACKGROUND: Telomere length is a biomarker of molecular aging that may be impacted by air pollution exposure starting in utero. We aimed to examine the association between prenatal and early life exposure to fine particulate matter (PM2.5) and leukocyte telomere length (LTL) in children and explore sex differences.<br><br>METHODS: Analyses included 384 mother-child pairs enrolled in the Programming Research in Obesity, Growth, and Environmental Stressors (PROGRESS) birth cohort in Mexico City. Exposure to PM2.5 was estimated at the residential level using a satellite based spatio-temporally resolved prediction model. Average relative LTL was measured in DNA isolated from blood collected at age 4-6 years using quantitative real-time polymerase chain reaction. Linear regression models were used to examine the association between average PM2.5 across pregnancy, individual trimesters, first postnatal year, and LTL. Models were adjusted for maternal age and education at enrollment, prenatal environmental tobacco smoke exposure, child sex, age, and body mass index z-score at LTL measurement. Effect modification by sex was investigated with interaction terms and stratification.<br><br>RESULTS: In trimester specific models, we found an association between 2nd trimester PM2.5 and elongated LTL (&#x3b2;: 4.34, 95%CI [0.42, 8.42], per 5&#xa0;&#x3bc;g/m[3] increase). There was suggestive effect modification by sex on average 2nd trimester PM2.5 with stronger associations seen in females compared to males (&#x3b2;: 7.12, [95%CI: 0.98, 13.6] and &#x3b2;: 1.43 [95%CI: -3.46, 6.57]) per 5&#xa0;&#x3bc;g/m[3] increase respectively.<br><br>CONCLUSION: Second trimester PM2.5 levels were associated with changes in LTL in early childhood. Understanding temporal and sex differences in PM2.5 exposure may provide insights into telomere dynamics over early life.},
}
@article {pmid39261898,
year = {2024},
author = {Zhao, W and Li, B and Zhang, M and Zhou, P and Zhu, Y},
title = {As a novel prognostic model for breast cancer, the identification and validation of telomere-related long noncoding RNA signatures.},
journal = {World journal of surgical oncology},
volume = {22},
number = {1},
pages = {245},
pmid = {39261898},
issn = {1477-7819},
support = {PW2023A-18//Pudong New Area Health Research General Project/ ; PWRd2023-10//Pudong New District Health Committee Discipline Leader Program/ ; },
abstract = {BACKGROUND: Telomeres are a critical component of chromosome integrity and are essential to the development of cancer and cellular senescence. The regulation of breast cancer by telomere-associated lncRNAs is not fully known, though. The goals of this study were to describe predictive telomere-related LncRNAs (TRL) in breast cancer and look into any possible biological roles for these RNAs.<br><br>METHODS: We obtained RNA-seq data, pertinent clinical data, and a list of telomere-associated genes from the cancer genome atlas and telomere gene database, respectively. We subjected differentially expressed TRLs to co-expression analysis and univariate Cox analysis to identify a prognostic TRL. Using LASSO regression analysis, we built a prognostic model with 14 TRLs. The accuracy of the model's prognostic predictions was evaluated through the utilization of Kaplan-Meier (K-M) analysis as well as receiver operating characteristic (ROC) curve analysis. Additionally, immunological infiltration and immune drug prediction were done using this model. Patients with breast cancer were divided into two subgroups using cluster analysis, with the latter analyzed further for variations in response to immunotherapy, immune infiltration, and overall survival, and finally, the expression of 14-LncRNAs was validated by RT-PCR.<br><br>RESULTS: We developed a risk model for the 14-TRL, and we used ROC curves to demonstrate how accurate the model is. The model may be a standalone prognostic predictor for patients with breast cancer, according to COX regression analysis. The immune infiltration and immunotherapy results indicated that the high-risk group had a low level of PD-1 sensitivity and a high number of macrophages infiltrating. In addition, we've discovered a number of small-molecule medicines with considerable for use in treating high-risk groups. The cluster 2 subtype showed the highest immune infiltration, the highest immune checkpoint expression, and the worst prognosis among the two subtypes defined by cluster analysis, which requires more attention and treatment.<br><br>CONCLUSION: As a possible biomarker, the proposed 14-TRL signature could be utilized to evaluate clinical outcomes and treatment efficacy in breast cancer patients.},
}
@article {pmid39256983,
year = {2024},
author = {Musa, I and Yang, N and Breslin, J and Paulden, O and Geliebter, J and Tiwari, R and Li, XM},
title = {Inhibition of Myeloma Cell Function by Cannabinoid-Enriched Product Associated With Regulation of Telomere and TP53.},
journal = {Integrative cancer therapies},
volume = {23},
number = {},
pages = {15347354241267979},
doi = {10.1177/15347354241267979},
pmid = {39256983},
issn = {1552-695X},
mesh = {Humans ; *Multiple Myeloma/drug therapy ; Cell Line, Tumor ; *Telomere/drug effects/metabolism ; *Tumor Suppressor Protein p53/metabolism ; *Cannabinoids/pharmacology ; *Telomerase/metabolism ; Cell Survival/drug effects ; NF-kappa B/metabolism ; Immunoglobulin E ; Immunoglobulin G ; Cell Proliferation/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; },
abstract = {Multiple myeloma is a hematological cancer caused by the uncontrolled proliferation of abnormal plasma cells in the bone marrow, leading to excessive immunoglobulin production. Our study aimed to examine the anticancer properties of BRF1A, a cannabinoid (CBD)-enriched product, on 2 myeloma cell lines: U266 and ARH-7. We treated U266 and ARH-77 myeloma cells with varying doses of BRF1A and measured the production of IgE and IgG antibodies using ELISA. Cell viability was assessed using trypan blue and CCK-8 assays. We measured the expression of genes related to the production of IgE and IgG antibodies, IgEH, and IgGH. We determined its effect on the expression of telomerase and its phosphorylated form as an indicator of telomere stabilization. Furthermore, we determined its effect on other cancer-related targets such as NF-ĸB, c-Myc, and TP53 in U266 cells using reverse transcription polymerase chain reaction (RT-PCR) and western blotting. BRF1A reduced myeloma cell IgE and IgG production in a time and dose-dependent manner. It also suppressed the expression of p-IκBα, p-NFκB (p65), and total NFκB protein, as well as XBP1u and XBP1s. It increased the gene and protein expression of telomere and hTERT and significantly increased cancer suppressor TP53 gene and p53 protein expression. Additionally, BRF1A decreased the c-Myc gene and protein expression. Our study has shown that a CBD-enriched product can reduce the growth of myeloma cells by suppressing the critical functions of IgE- and IgG-producing cells. This study could help bridge the gap in understanding how cannabinoid-containing products affect cancer, aging, telomere, and cancer-suppressor gene activity.},
}
@article {pmid39256139,
year = {2024},
author = {Pepke, ML and Hansen, SB and Limborg, MT},
title = {Telomere dynamics as mediators of gut microbiota-host interactions.},
journal = {Trends in cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tcb.2024.08.003},
pmid = {39256139},
issn = {1879-3088},
abstract = {The highly proliferative gut tissue exhibits rapid telomere shortening with systemic effects on the host organism. Recent studies have demonstrated a bidirectionality in interactions between intestinal telomere length dynamics and the composition and activity of the gut microbiome thus linking processes of inflammation, dysbiosis and aging across different vertebrate species.},
}
@article {pmid39253978,
year = {2024},
author = {Carr, L and Norris, K and Parker, H and Nilsson-Takeuchi, A and Bryant, D and Amarasinghe, H and Kadalayil, L and Else, M and Pettitt, A and Hillmen, P and Schuh, A and Walewska, R and Baird, DM and Oscier, DG and Oakes, CC and Gibson, J and Pepper, C and Strefford, JC},
title = {Telomere length and DNA methylation epitype both provide independent prognostic information in CLL patients; data from the UK CLL4, ARCTIC and ADMIRE clinical trials.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.19765},
pmid = {39253978},
issn = {1365-2141},
support = {Cancer Research UK Southampton Centre grant C34999/CRUK_/Cancer Research UK/United Kingdom ; ECRIN-M3 accelerator award C42023/A29370/CRUK_/Cancer Research UK/United Kingdom ; programme C2750/A23669/CRUK_/Cancer Research UK/United Kingdom ; },
}
@article {pmid39253325,
year = {2024},
author = {Liu, J and Pan, R},
title = {Genetic liability to human serum metabolites is causally linked to telomere length: insights from genome-wide Mendelian randomization and metabolic pathways analysis.},
journal = {Frontiers in nutrition},
volume = {11},
number = {},
pages = {1458442},
doi = {10.3389/fnut.2024.1458442},
pmid = {39253325},
issn = {2296-861X},
abstract = {BACKGROUND: Telomere has been recognized as a biomarker of accelerating aging, and telomere length (TL) shortening is closely related to diverse chronic illnesses. Human serum metabolites have demonstrated close correlations with TL maintenance or shortening in observational studies. Nevertheless, little is known about the underlying pathological mechanisms, and Mendelian randomization (MR) analysis of serum metabolites may provide a more comprehensive understanding of the potential biological process.<br><br>METHODS: We employed a two-sample MR analysis method to assess the causal links between 486 serum metabolites and TL. We applied the inverse-variance weighted (IVW) approach as our primary analysis, and to assure the stability and robustness of our results, additional analysis methods including the weighted median, MR-Egger, and weighted mode were conducted. MR-Egger intercept test was utilized to detect the pleiotropy. Cochran's Q test was implemented to quantify the extent of heterogeneity. Furthermore, the pathway analysis was conducted to identify potential metabolic pathways.<br><br>RESULTS: We identified 11 known blood metabolites associated with TL. Among these metabolites, four were lipid (taurocholate, dodecanedioate, 5,8-tetradecadienoate, and 15-methylpalmitate), one amino acid (levulinate (4-oxovaleate)), one carbohydrate (lactate), one nucleotide (pseudouridine), one energy (phosphate), and three xenobiotics (2-hydroxyacetaminophen sulfate, paraxanthine, and ergothioneine). The known protective metabolites included levulinate (4-oxovaleate), dodecanedioate, 5,8-tetradecadienoate, lactate, phosphate, paraxanthine, and ergothioneine. Multiple metabolic pathways have been identified as being implicated in the maintenance of telomere length.<br><br>CONCLUSION: Our MR analysis provided suggestive evidence supporting the causal relationships between 11 identified blood metabolites and TL, necessitating further exploration to clarify the mechanisms by which these serum metabolites and metabolic pathways may affect the progression of telomeres.},
}
@article {pmid39252519,
year = {2024},
author = {Furui, Y and Saito, S and Maruyama, Y and Okura, E and Hirabayashi, K and Tanaka, M and Nakazawa, Y},
title = {Successful ibrutinib treatment for pulmonary involvement in a post-transplant patient with inherited bone marrow failure syndrome and very short telomeres.},
journal = {Pediatric blood &amp; cancer},
volume = {},
number = {},
pages = {e31314},
doi = {10.1002/pbc.31314},
pmid = {39252519},
issn = {1545-5017},
}
@article {pmid39250995,
year = {2024},
author = {Feng, Y and Guo, X and Luo, M and Sun, Y and Sun, L and Zhang, H and Zou, Y and Liu, D and Lu, H},
title = {GbHSP90 act as a dual functional role regulated in telomere stability in Ginkgo biloba.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {135240},
doi = {10.1016/j.ijbiomac.2024.135240},
pmid = {39250995},
issn = {1879-0003},
abstract = {The heat shock protein 90 (HSP90) family members are not only widely involved in animal cellular immune response and signal transduction pathway regulation, but also play an important role in plant development and environmental stress response. Here,we identified a HSP90 family member in Ginkgo biloba, designated as GbHSP90, which performs a dual functional role to regulate telomere stability. GbHSP90 was screened by a yeast one-hybrid library using the Ginkgo biloba telomeric DNA (TTTAGGG)5. Fluorescence polarization, surface plasmon resonance(SPR) and EMSA technologyies revealed a specific interaction between GbHSP90 and the double-stranded telomeric DNA via its N-CR region, with no affinity for the single-stranded telomeric DNA or human double-stranded telomeric DNA. Furthermore, yeast two-hybrid system and Split-LUC assay demonstrated that GbHSP90 can interacts with two telomere end-binding proteins:the ginkgo telomerase reverse transcriptase (GbTERT) and the ginkgo Structural Maintenance of Chromosomes protein 1 (GbSMC1). Overexpression of GbHSP90 in human 293 T and HeLa cells increased cell growth rate, the content of telomerase reverse transcriptase (TERT), and promote cell division and inhibit cell apoptosis. Our results indicated GbHSP90 have dually functions: as a telomere-binding protein that binds specifically to double-stranded telomeric DNA and as a molecular chaperone that modulates cell differentiation and apoptosis by binding to telomere protein complexes in Ginkgo biloba. This study contributes to a significantly understanding of the unique telomere complex structure and regulatory mechanisms in Ginkgo biloba, a long-lived tree species.},
}
@article {pmid39250900,
year = {2024},
author = {Vostatek, R and Hohensinner, P and Schmaldienst, S and Lorenz, M and Klauser-Braun, R and Pabinger, I and Säemann, M and Ay, C and Königsbrügge, O},
title = {Telomere length is associated with increased risk of cardiovascular events in patients with end-stage kidney disease on hemodialysis.},
journal = {Cardiorenal medicine},
volume = {},
number = {},
pages = {1-16},
doi = {10.1159/000541112},
pmid = {39250900},
issn = {1664-5502},
abstract = {INTRODUCTION: Patients with chronic kidney disease (CKD), especially those with end-stage kidney disease (ESKD) on hemodialysis (HD), are at increased risk for cardiovascular disease (CVD), including myocardial infarction and ischemic stroke. A shortening in telomere length, as a parameter for accelerated vascular aging, is an established biomarker for CVD in the general population. We aimed to elucidate the role of telomere length in ESKD patient on HD and its association with cardiovascular outcomes.<br><br>METHODS: Telomere length was measured in a prospective population-based cohort study of prevalent HD patients. DNA was isolated from whole blood, sampled at baseline, and analyzed for telomere length via a qPCR-based approach. The risk for the occurrence of the independently adjudicated 3P-MACE outcome (myocardial infarction, ischemic stroke, and cardiovascular death) was statistically analyzed considering the competing risk of non-cardiovascular death.<br><br>RESULTS: In the cohort of 308 patients with ESKD (115 (37.3%) women, median (25th-75th percentile) age: 67.0 (56.8 - 76.0), the median telomere length was 1.51 kb (25th-75th percentile 0.6-3.2 kb). The 3P-MACE outcome occurred with an incidence rate of 9.4 per 100 patient-years. Patients with longer telomere length more frequently had vascular nephropathy compared to patients with shorter telomere length. Interestingly, patients in the highest quartile of telomere length had a 1.8-fold increased risk for 3P-MACE (95%CI 1.051-3.201, p=0.033), after multivariable adjustment for age, history of stroke, myocardial infarction, venous thromboembolism, presence of heart valve replacement, atrial fibrillation, smoking, anticoagulation, or immunosuppressive use.<br><br>CONCLUSION: Surprisingly, in this high-risk cohort of patients with ESKD on HD, longer telomere lengths were associated with increased risk of cardiovascular events.},
}
@article {pmid39248546,
year = {2024},
author = {Nayır Büyükşahin, H and Emiralioğlu, N and Yalçın, E and Ozcan, HN and Oğuz, B and Utine, GE and Kiper, P&#xd6; and Karaosmanoğlu, B and Orhan, D and Unal, S and Güzelkaş, &#x130; and Alboğa, D and Doğru, D and Özçelik, U and Kiper, N},
title = {Two cases with undefined childhood interstitial lung disease: Can it be related to telomere variants?.},
journal = {Journal of paediatrics and child health},
volume = {},
number = {},
pages = {},
doi = {10.1111/jpc.16666},
pmid = {39248546},
issn = {1440-1754},
}
@article {pmid39246285,
year = {2024},
author = {Piedrabuena, MA and Correale, J and Farez, MF and Rodríguez Murúa, S and Martínez Canyazo, C and Fiol, M and Marrodan, M and Ysrraelit, MC},
title = {Telomere length as a biomarker in multiple sclerosis.},
journal = {Multiple sclerosis (Houndmills, Basingstoke, England)},
volume = {},
number = {},
pages = {13524585241273054},
doi = {10.1177/13524585241273054},
pmid = {39246285},
issn = {1477-0970},
abstract = {BACKGROUND: Leukocyte telomere length (LTL) shortens with age and may be related to multiple sclerosis (MS).<br><br>OBJECTIVE: We hypothesize that chronologically young people with MS (pwMS) with short LTL behave similarly to older MS subjects.<br><br>METHODS: Prospective 2-year study including two cohorts of young (18-35 years) and elderly (&#x2a7e;50 years) pwMS with similar disease duration. Physical and cognitive evaluation, 3 T brain magnetic resonance imaging (MRI) and retinal nerve fiber layer (RNFL) measurement by optical coherence tomography were performed. LTL was measured by quantitative polymerase chain reaction assay.<br><br>RESULTS: Around 105 patients were included, 57 young and 48 elderly. LTL was shorter in older patients (0.61 versus 0.57, p = 0.0081) and in males (female, 0.60; male, 0.59; p = 0.01335). For every 10-year increase in age, LTL was 0.02 U shorter. In elderly, LTL correlated with disease duration (p = 0.05), smoking (p = 0.03), Expanded Disability Status Scale (EDSS; p = 0.004), 9HPT (p = 0.00007), high-efficacy therapies (p = 0.001), brain lesion volume (BLV) (p = 0.011), and number of T2 lesions (p = 0.01). In young patients, LTL did not correlate with clinical or radiological variables. For every 0.1 U shorter LTL, gray matter volume decreased 1.75 cm[3] and white matter volume 1.78 cm[3].<br><br>CONCLUSION: LTL correlated with disability and BLV in elderly. Besides LTL shortening, other variables should be considered as mechanisms of neurodegeneration that might be involved in aging pwMS.},
}
@article {pmid39239547,
year = {2024},
author = {Huang, J and Feng, Y and Shi, Y and Shao, W and Li, G and Chen, G and Li, Y and Yang, Z and Yao, Z},
title = {Telomeres and telomerase in Sarcoma disease and therapy.},
journal = {International journal of medical sciences},
volume = {21},
number = {11},
pages = {2065-2080},
pmid = {39239547},
issn = {1449-1907},
mesh = {Humans ; *Telomerase/genetics/metabolism ; *Sarcoma/genetics/therapy/pathology ; *Telomere/genetics/metabolism ; *Telomere Homeostasis/genetics ; Prognosis ; Mutation ; },
abstract = {Sarcoma is a rare tumor derived from the mesenchymal tissue and mainly found in children and adolescents. The outcome for patients with sarcoma is relatively poor compared with that for many other solid malignant tumors. Sarcomas have a highly heterogeneous pathogenesis, histopathology and biological behavior. Dysregulated signaling pathways and various gene mutations are frequently observed in sarcomas. The telomere maintenance mechanism (TMM) has recently been considered as a prognostic factor for patients with sarcomas, and alternative lengthening of telomeres (ALT) positivity has been correlated with poor outcomes in patients with several types of sarcomas. Therefore, telomeres and telomerases may be useful targets for treating sarcomas. This review aims to provide an overview of telomere and telomerase biology in sarcomas.},
}
@article {pmid39237122,
year = {2024},
author = {Cao, Z and Li, Y and Wu, J},
title = {Causal linkage of psoriasis with ageing: Mendelian randomization and enrichment analysis towards telomere length and psoriasis.},
journal = {Postgraduate medical journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/postmj/qgae115},
pmid = {39237122},
issn = {1469-0756},
support = {2019YFA0112100//National Key Research and Development Program of China/ ; },
abstract = {OBJECTIVE: Several studies demonstrated potential associations between the telomere length (TL) in leukocytes and psoriasis or psoriatic arthritis (PsA). This study aimed to investigate whether there was the causal genetic relationship between TL and psoriatic diseases bidirectionally.<br><br>METHODS: Two-sample univariable MR (UVMR) analysis was applied to explore the bidirectional causal association of TL with overall psoriasis, psoriasis vulgaris (PV) and PsA. Multivariable MR (MVMR) and the mediation effects analysis were applied to test whether the bidirectional associations between TLs and psoriasis were mediated by body mass index (BMI), alcohol, and smoking status.<br><br>RESULTS: According to the UVMR results, a negative causal impact of TL on the risk of overall psoriasis was found (OR&#x2009;=&#x2009;0.775; 95% CI: 0.646-0.931; P&#x2009;=&#x2009;6.36&#x2009;&#xd7;&#x2009;10-3), and a similar trend was observed in the reversed direction for psoriasis-TL (IVW-&#x3b2;&#x2009;=&#x2009;-0.0097; 95% CI: -0.0170 to -0.0024; P&#x2009;=&#x2009;9.12&#x2009;&#xd7;&#x2009;10-3). There were also negative genetic associations between TL and PV bidirectionally. The independent association of genetically predicted TL and overall psoriasis persisted in the MVMR results controlled for BMI, smoking, and alcohol consumption (ORMVMR&#x2009;=&#x2009;0.736; 95% CI: 0.597 to 0.907; P&#x2009;=&#x2009;0.004). An independent significant association of genetic predisposition to PsA with TL was also found (&#x3b2;MVMR&#x2009;=&#x2009;0.006; 95% CI: 0.001 to 0.012; P&#x2009;=&#x2009;0.033). The mediation analysis showed that BMI partially mediated the reverse association between PSO and TL.<br><br>CONCLUSION: This MR study revealed an association between genetic indicators of shortened TL and risk of overall psoriasis and PV, and genetic predisposition to PsA was associated with longer TL. Key message What is already known on this topic?&#xa0; Telomere length (TL) is acknowledged to reflect an individual's biological age but is also associated with dysregulated immune function and immunosenescence. The impact of aging on psoriasis is controversial. Existing evidence suggests that aging may influence pathological changes and clinical course but whether aging is an independent risk factor remains unclear. What this study adds?&#xa0; The current study found an association between genetic indicators of shortened TL and the risk of overall psoriasis and psoriasis vulgaris (PV). There was a bidirectional link between genetically indicated overall psoriasis and shortened TL. A possible positive genetic association between PsA and TL was also found. How this study might affect research, practice, or policy?&#xa0; Our study may provide evidence for TL as new diagnostic and therapeutic strategies in clinical practices for psoriasis. Greater efforts to psoriasis management may substantially reduce the aging attributable to TL shortening. Future large-scale GWAS and experimental studies are warranted to examine the mechanistic basis for links between TL and psoriasis to improve understanding and illuminate possible therapeutic targets for psoriatic disease.},
}
@article {pmid39235665,
year = {2024},
author = {Scarabino, D and Veneziano, L and Nethisinghe, S and Mantuano, E and Fiore, A and Granata, G and Solanky, N and Zanni, G and Cavalcanti, F and Corbo, RM and Giunti, P},
title = {Unusual Age-Dependent Behavior of Leukocytes Telomere Length in Friedreich's Ataxia.},
journal = {Movement disorders : official journal of the Movement Disorder Society},
volume = {},
number = {},
pages = {},
doi = {10.1002/mds.29976},
pmid = {39235665},
issn = {1531-8257},
support = {//Department of Health's National Institute for Health Research Biomedical Research Centre's/ ; //National Institute for Health Research University College London/ ; project 739510//European Reference Network for Rare Neurological Diseases/ ; MR/N028767/1//Medical Research Council Centre for Neurodevelopmental Disorders/ ; 2018/2019 grants//Sapienza University of Rome/ ; },
abstract = {BACKGROUND: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by an expanded GAA repeat in the first intron of the FXN gene.<br><br>OBJECTIVE: The aim of this study was to analyze leukocyte telomeres length (LTL) in FRDA to verify the possible relationships between LTL and disease progression. We investigated LTL in a cohort of FRDA biallelic patients (n&#x2009;=&#x2009;61), heterozygous (n&#x2009;=&#x2009;29), and age-matched healthy subjects (n&#x2009;=&#x2009;87).<br><br>METHODS: LTL was measured by real-time polymerase chain reaction quantitative analysis (qPCR).<br><br>RESULTS: The results showed that before 35&#x2009;years of age, leukocyte telomeres were longer in patients than in controls, whereas the reverse applies in patients above 36&#x2009;years of age. Interestingly, LTL was greater than controls at any age in heterozygous subjects. This picture mirrors what has been previously observed in vitro in FRDA cultured fibroblasts, showing significantly longer telomeres at early passages because of activation of an alternative lengthening of telomeres (ALT)-like mechanism, but showing accelerated telomere shortening as population doubling increases. GAA1 repeat length is positively correlated with the LTL and negatively correlated with the age at blood sampling. The relationship of LTL with clinical parameters (cardiomyopathy, diabetes, dependence on a wheelchair) was also analyzed. Significantly shorter leukocyte telomeres were associated with the presence of cardiomyopathy, but not with diabetes and the dependence on a wheelchair.<br><br>CONCLUSIONS: Overall, the present study indicates that telomere length analysis in FRDA may be a relevant biomarker for following the stages of the disease. &#xa9; 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.},
}
@article {pmid39234237,
year = {2024},
author = {Zhang, J and Xia, X and He, S},
title = {Deciphering the causal association and underlying transcriptional mechanisms between telomere length and abdominal aortic aneurysm.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1438838},
pmid = {39234237},
issn = {1664-3224},
mesh = {*Aortic Aneurysm, Abdominal/genetics/immunology ; Animals ; Mice ; Humans ; *Genome-Wide Association Study ; *Telomere Homeostasis ; *Telomere/genetics ; Mendelian Randomization Analysis ; Biomarkers ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Transcriptome ; Genetic Predisposition to Disease ; },
abstract = {BACKGROUND: The purpose of this study is to investigate the causal effect and potential mechanisms between telomere length and abdominal aortic aneurysm (AAA).<br><br>METHODS: Summary statistics of telomere length and AAA were derived from IEU open genome-wide association studies and FinnGen R9, respectively. Bi-directional Mendelian randomization (MR) analysis was conducted to reveal the causal relationship between AAA and telomere length. Three transcriptome datasets were retrieved from the Gene Expression Omnibus database and telomere related genes was down-loaded from TelNet. The overlapping genes of AAA related differentially expressed genes (DEGs), module genes, and telomere related genes were used for further investigation. Telomere related diagnostic biomarkers of AAA were selected with machine learning algorisms and validated in datasets and murine AAA model. The correlation between biomarkers and immune infiltration landscape was established.<br><br>RESULTS: Telomere length was found to have a suggestive negative associations with AAA [IVW, OR 95%CI = 0.558 (0.317-0.701), P < 0.0001], while AAA showed no suggestive effect on telomere length [IVW, OR 95%CI = 0.997 (0.990-1.004), P = 0.4061]. A total of 40 genes was considered as telomere related DEGs of AAA. PLCH2, PRKCQ, and SMG1 were selected as biomarkers after multiple algorithms and validation. Immune infiltration analysis and single cell mRNA analysis revealed that PLCH2 and PRKCQ were mainly expressed on T cells, while SMG1 predominantly expressed on T cells, B cells, and monocytes. Murine AAA model experiments further validated the elevated expression of biomarkers.<br><br>CONCLUSION: We found a suggestive effect of telomere length on AAA and revealed the potential biomarkers and immune mechanism of telomere length on AAA. This may shed new light for diagnosis and therapeutics on AAA.},
}
@article {pmid39231615,
year = {2024},
author = {Kochman, R and Ba, I and Yates, M and Pirabakaran, V and Gourmelon, F and Churikov, D and Lafaille, M and Kermasson, L and Hamelin, C and Marois, I and Jourquin, F and Braud, L and Bechara, M and Lainey, E and Nunes, H and Breton, P and Penhouet, M and David, P and Géli, V and Lachaud, C and Maréchal, A and Revy, P and Kannengiesser, C and Saintomé, C and Coulon, S},
title = {Heterozygous RPA2 variant as a novel genetic cause of telomere biology disorders.},
journal = {Genes &amp; development},
volume = {},
number = {},
pages = {},
doi = {10.1101/gad.352032.124},
pmid = {39231615},
issn = {1549-5477},
abstract = {Premature telomere shortening or telomere instability is associated with a group of rare and heterogeneous diseases collectively known as telomere biology disorders (TBDs). Here we identified two unrelated individuals with clinical manifestations of TBDs and short telomeres associated with the identical monoallelic variant c.767A>G; Y256C in RPA2 Although the replication protein A2 (RPA2) mutant did not affect ssDNA binding and G-quadruplex-unfolding properties of RPA, the mutation reduced the affinity of RPA2 with the ubiquitin ligase RFWD3 and reduced RPA ubiquitination. Using engineered knock-in cell lines, we found an accumulation of RPA at telomeres that did not trigger ATR activation but caused short and dysfunctional telomeres. Finally, both patients acquired, in a subset of blood cells, somatic genetic rescue events in either POT1 genes or TERT promoters known to counteract the accelerated telomere shortening. Collectively, our study indicates that variants in RPA2 represent a novel genetic cause of TBDs. Our results further support the fundamental role of the RPA complex in regulating telomere length and stability in humans.},
}
@article {pmid39232410,
year = {2024},
author = {Konishi, K and Jacobs, EG and Aroner, S and De Vivo, I and Smith, B and Scribner-Weiss, B and Makris, N and Seitz-Holland, J and Remington, A and Aizley, H and Kubicki, M and Goldstein, JM},
title = {Leukocyte telomere length and memory circuitry and cognition in early aging: Impact of sex and menopausal status.},
journal = {Hormones and behavior},
volume = {165},
number = {},
pages = {105631},
doi = {10.1016/j.yhbeh.2024.105631},
pmid = {39232410},
issn = {1095-6867},
abstract = {Telomere length (TL) is an important cellular marker of biological aging impacting the brain and heart. However, how it is related to the brain (e.g., cognitive function and neuroanatomic architecture), and how these relationships may vary by sex and reproductive status, is not well established. Here we assessed the association between leukocyte TL and memory circuitry regional brain volumes and memory performance in early midlife, in relation to sex and reproductive status. Participants (N = 198; 95 females, 103 males; ages 45-55) underwent structural MRI and neuropsychological assessments of verbal, associative, and working memory. Overall, shorter TL was associated with smaller white matter volume in the parahippocampal gyrus and dorsolateral prefrontal cortex. In males, shorter TL was associated with worse working memory performance and corresponding smaller white matter volumes in the parahippocampal gyrus, anterior cingulate cortex, and dorsolateral prefrontal cortex. In females, the impact of cellular aging was revealed over the menopausal transition. In postmenopausal females, shorter TL was associated with poor associative memory performance and smaller grey matter volume in the right hippocampus. In contrast, TL was not related to memory performance or grey and white matter volumes in any memory circuitry region in pre/perimenopausal females. Results demonstrated that shorter TL is associated with worse memory function and smaller volume in memory circuitry regions in early midlife, an association that differs by sex and reproductive status. Taken together, TL may serve as an early indicator of sex-dependent brain abnormalities in early midlife.},
}
@article {pmid39231146,
year = {2024},
author = {Rönne-Petersén, L and Niemi, M and Walach, H and Lavebratt, C and Yang, LL and Gerdle, B and Ghafouri, B and Falkenberg, T},
title = {Exploring emotional well-being, spiritual, religious and personal beliefs and telomere length in chronic pain patients-A pilot study with cross-sectional design.},
journal = {PloS one},
volume = {19},
number = {9},
pages = {e0308924},
doi = {10.1371/journal.pone.0308924},
pmid = {39231146},
issn = {1932-6203},
mesh = {Humans ; Male ; Female ; Pilot Projects ; Cross-Sectional Studies ; Middle Aged ; *Chronic Pain/psychology ; Aged ; *Quality of Life ; *Spirituality ; Adult ; Emotions ; Telomere/genetics ; Surveys and Questionnaires ; Sweden ; Patient Reported Outcome Measures ; Depression/psychology ; Telomerase/metabolism/genetics ; Religion ; },
abstract = {Living with chronic pain is associated with substantial suffering and high societal costs. Patient reported outcomes (PROM's) and cellular ageing should be considered in pain management. The aim of this study was to explore correlations of PROM's and cellular ageing (telomere length [TL] and telomerase activity [TA]) amongst patients with chronic non-malignant pain. This was an explorative pilot study with cross-sectional design and recruitment was done at two pain rehabilitation facilities in Sweden, with inpatient setting/integrative care and outpatient setting/multimodal care, respectively. Eighty-four patients were enrolled by referral to pain rehabilitation in Sweden. The main outcome measures collected after admission in addition to TL and TA were the following PROMs: Numerical Rating Scale (NRS), Chronic Pain Acceptance Questionnaire (CPAQ), Hospital Anxiety and Depression Scale (HADS), Five Facets Mindfulness Questionnaire (FFMQ), WHO Quality of Life-Spiritual, Religious and Personal Beliefs (WHOQoL-SRPB) and EuroQol 5 Dimensions (EQ-5D). All the PROM's showed evidence of poor overall health status among the participants. TL correlated negatively with HADS score (r = -.219, p = .047) and positively with WHOQoL-SRPB (r = .224, p = .052). TL did not correlate with any of the pain measures. TA correlated positively with pain spread (r = .222, p = .049). A mediation of the direct effect of spiritual well-being on TL by anxiety and depression could be shown (b = 0.008; p = .045). The correlations between TL and SRPB and anxiety and depression suggest some importance of emotional and SRPB dimensions in pain management, with implications for cellular aging, which may warrant further study. Trial registration: ClinicalTrials.gov Identifier: NCT02459639.},
}
@article {pmid39225247,
year = {2024},
author = {Noveir, SD and Galamgam, J and Pithadia, D and Truong, A and Hogeling, M and Cheng, CE},
title = {Reticulated pigmentary changes and Terry's nails in a patient with a TERT variant-associated telomere biology disorder.},
journal = {Pediatric dermatology},
volume = {},
number = {},
pages = {},
doi = {10.1111/pde.15735},
pmid = {39225247},
issn = {1525-1470},
abstract = {Telomere biology disorders (TBD) are a complex set of inherited illnesses characterized by short telomeres. Dyskeratosis congenita (DC), which is now considered a severe TBD phenotype, is characterized by reticulated pigmentary changes, nail dystrophy, premalignant oral leukoplakia, and systemic involvement. This case describes a 2-year-old female with reticulated pigmentary changes and Terry's nails who was found to have a TERT variant and short telomeres; she lacked other mucocutaneous and systemic features of TBD. This report describes a unique clinical presentation of TBD and highlights the importance of upholding suspicion for TBD in individuals with limited or subtle features of classic DC.},
}
@article {pmid39224814,
year = {2024},
author = {Burrow, TA and Koneru, B and Macha, SJ and Sun, W and Barr, FG and Triche, TJ and Reynolds, CP},
title = {Prevalence of alternative lengthening of telomeres in pediatric sarcomas determined by the telomeric DNA C-circle assay.},
journal = {Frontiers in oncology},
volume = {14},
number = {},
pages = {1399442},
pmid = {39224814},
issn = {2234-943X},
abstract = {INTRODUCTION: Alternative lengthening of telomeres (ALT) occurs in sarcomas and ALT cancers share common mechanisms of therapy resistance or sensitivity. Telomeric DNA C-circles are self-primed circular telomeric repeats detected with a PCR assay that provide a sensitive and specific biomarker exclusive to ALT cancers. We have previously shown that 23% of high-risk neuroblastomas are of the ALT phenotype. Here, we investigate the frequency of ALT in Ewing's family sarcoma (EFS), rhabdomyosarcoma (RMS), and osteosarcoma (OS) by analyzing DNA from fresh frozen primary tumor samples utilizing the real-time PCR C-circle Assay (CCA).<br><br>METHODS: We reviewed prior publications on ALT detection in pediatric sarcomas. DNA was extracted from fresh frozen primary tumors, fluorometrically quantified, C-circles were selectively enriched by isothermal rolling cycle amplification and detected by real-time PCR.<br><br>RESULTS: The sample cohort consisted of DNA from 95 EFS, 191 RMS, and 87 OS primary tumors. One EFS and 4 RMS samples were inevaluable. Using C-circle positive (CC+) cutoffs previously defined for high-risk neuroblastoma, we observed 0 of 94 EFS, 5 of 187 RMS, and 62 of 87 OS CC+ tumors.<br><br>CONCLUSIONS: Utilizing the ALT-specific CCA we observed ALT in 0% of EFS, 2.7% of RMS, and 71% of OS. These data are comparable to prior studies in EFS and OS using less specific ALT markers. The CCA can provide a robust and sensitive means of identifying ALT in sarcomas and has potential as a companion diagnostic for ALT targeted therapeutics.},
}
@article {pmid39223261,
year = {2024},
author = {Sung, JY and Kim, SG and Park, SY and Kim, JR and Choi, HC},
title = {Telomere stabilization by metformin mitigates the progression of atherosclerosis via the AMPK-dependent p-PGC-1α pathway.},
journal = {Experimental &amp; molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {39223261},
issn = {2092-6413},
support = {2022R1A5A2018865//National Research Foundation of Korea (NRF)/ ; 2022R1I1A1A01055818//National Research Foundation of Korea (NRF)/ ; },
abstract = {Telomere dysfunction is a well-known molecular trigger of senescence and has been associated with various age-related diseases, including atherosclerosis. However, the mechanisms involved have not yet been elucidated, and the extent to which telomeres contribute to atherosclerosis is unknown. Therefore, we investigated the mechanism of metformin-induced telomere stabilization and the ability of metformin to inhibit vascular smooth muscle cell (VSMC) senescence caused by advanced atherosclerosis. The present study revealed that metformin inhibited the phenotypes of atherosclerosis and senescence in VSMCs. Metformin increased the phosphorylation of AMPK-dependent PGC-1α and thus increased telomerase activity and the protein level of TERT in OA-treated VSMCs. Mechanistically, the phosphorylation of AMPK and PGC-1α by metformin not only enhanced telomere function but also increased the protein level of TERT, whereas TERT knockdown accelerated the development of atherosclerosis and senescent phenotypes in OA-treated VSMCs regardless of metformin treatment. Furthermore, the in vivo results showed that metformin attenuated the formation of atherosclerotic plaque markers in the aortas of HFD-fed ApoE KO mice. Although metformin did not reduce plaque size, it inhibited the phosphorylation of the AMPK/PGC-1α/TERT signaling cascade, which is associated with the maintenance and progression of plaque formation, in HFD-fed ApoE KO mice. Accordingly, metformin inhibited atherosclerosis-associated phenotypes in vitro and in vivo. These observations show that the enhancement of telomere function by metformin is involved in specific signaling pathways during the progression of atherosclerosis. These findings suggest that telomere stabilization by metformin via the AMPK/p-PGC-1α pathway might provide a strategy for developing therapeutics against vascular diseases such as atherosclerosis.},
}
@article {pmid39222545,
year = {2024},
author = {Cao, X and Fang, L and Jiang, Y and Zeng, T and Bai, S and Li, S and Liu, Y and Zhong, W and Lu, C and Yang, H},
title = {Nanoscale octopus guiding telomere entanglement: An innovative strategy for inducing apoptosis in cancer cells.},
journal = {Biomaterials},
volume = {313},
number = {},
pages = {122777},
doi = {10.1016/j.biomaterials.2024.122777},
pmid = {39222545},
issn = {1878-5905},
abstract = {Telomere length plays a crucial role in cellular aging and the risk of diseases. Unlike normal cells, cancer cells can extend their own survival by maintaining telomere stability through telomere maintenance mechanism. Therefore, regulating the lengths of telomeres have emerged as a promising approach for anti-cancer treatment. In this study, we introduce a nanoscale octopus-like structure designed to induce physical entangling of telomere, thereby efficiently triggering telomere dysfunction. The nanoscale octopus, composed of eight-armed PEG (8-arm-PEG), are functionalized with cell penetrating peptide (TAT) to facilitate nuclear entry and are covalently bound to N-Methyl Mesoporphyrin IX (NMM) to target G-quadruplexes (G4s) present in telomeres. The multi-armed configuration of the nanoscale octopus enables targeted binding to multiple G4s, physically disrupting and entangling numerous telomeres, thereby triggering telomere dysfunction. Both in vitro and in vivo experiments indicate that the nanoscale octopus significantly inhibits cancer cell proliferation, induces apoptosis through telomere entanglement, and ultimately suppresses tumor growth. This research offers a novel perspective for the development of innovative anti-cancer interventions and provides potential therapeutic options for targeting telomeres.},
}
@article {pmid39222177,
year = {2024},
author = {Kienzl, P and Deloria, AJ and Hunjadi, M and Hadolt, JM and Haering, MF and Bothien, A and Mejri, D and Korkut-Demirbaş, M and Sampl, S and Weber, G and Pirker, C and Laengle, S and Braunschmid, T and Dragona, E and Marian, B and Gagos, S and Lu, L and Henson, JD and Lau, LMS and Reddel, RR and Mikulits, W and Stättner, S and Holzmann, K},
title = {Telomere transcripts act as tumor suppressor and are associated with favorable prognosis in colorectal cancer with low proliferating cell nuclear antigen expression.},
journal = {Cellular oncology (Dordrecht, Netherlands)},
volume = {},
number = {},
pages = {},
doi = {10.1007/s13402-024-00986-y},
pmid = {39222177},
issn = {2211-3436},
abstract = {Telomeric repeat-containing RNAs (TERRA) and telomerase RNA component (TERC) regulate telomerase activity (TA) and thereby contribute to telomere homeostasis by influencing telomere length (TL) and the cell immortality hallmark of cancer cells. Additionally, the non-canonical functions of telomerase reverse transcriptase (TERT) and TERRA appear to be involved in the epithelial-mesenchymal transition (EMT), which is important for cancer progression. However, the relationship between TERRA and patient prognosis has not been fully characterized. In this small-scale study, 68 patients with colorectal cancer (CRC) were evaluated for correlations between telomere biology, proliferation, and EMT gene transcripts and disease outcome. The proliferating cell nuclear antigen (PCNA) and the epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) showed a positive correlation with TERRA, while TA and TERRA exhibited an inverse correlation. Consistent with previous findings, the present study revealed higher expression levels of TERT and TERC, and increased TA and TL in CRC tumor tissue compared to adjacent non-tumor tissue. In contrast, lower expression levels of TERRA were observed in tumor tissue. Patients with high TERRA expression and low PCNA levels exhibited favorable overall survival rates compared to individuals with the inverse pattern. Furthermore, TERRA suppressed CRC tumor growth in severe combined immunodeficiency disease (SCID) mice. In conclusion, our study extends previously published research on TERRA suggesting its potential therapeutic role in telomerase-positive CRC.},
}
@article {pmid39216403,
year = {2024},
author = {Yun, Z and Liu, Z and Shen, Y and Sun, Z and Zhao, H and Du, X and Lv, L and Zhang, Y and Hou, L},
title = {Genetic analysis from multiple cohorts implies causality between 2200 druggable genes, telomere length, and leukemia.},
journal = {Computers in biology and medicine},
volume = {181},
number = {},
pages = {109064},
doi = {10.1016/j.compbiomed.2024.109064},
pmid = {39216403},
issn = {1879-0534},
abstract = {BACKGROUND: Clinical therapeutic targets for leukemia remain to be identified and the causality between leukemia and telomere length is unclear.<br><br>METHODS: This work employed cis expression quantitative trait locus (eQTL) for 2,200 druggable genes from the eQTLGen Consortium and genome-wide association studies (GWAS) summary data for telomere length in seven blood cell types from the UK Biobank, Netherlands Cohort as exposures. GWAS data for lymphoid leukemia (LL) and myeloid leukemia (ML) from FinnGen and Lee Lab were used as outcomes for discovery and replication cohorts, respectively. Robust Mendelian randomization (MR) findings were generated from seven MR models and a series of sensitivity analyses. Summary-data-based MR (SMR) analysis and transcriptome-wide association studies (TWAS) were further implemented to verify the association between identified druggable genes and leukemia. Single-cell type expression analysis was employed to identify the specific expression of leukemia casual genes on human bone marrow and peripheral blood immune cells. Multivariable MR analysis, linkage disequilibrium score regression (LDSC), and Bayesian colocalization analysis were performed to further validate the relationship between telomere length and leukemia. Mediation analysis was used to assess the effects of identified druggable genes affecting leukemia via telomere length. Phenome-wide MR (Phe-MR) analysis for assessing the effect of leukemia causal genes and telomere length on 1,403 disease phenotypes.<br><br>RESULTS: Combining the results of the meta-analysis for MR estimates from two cohorts, SMR and TWAS analysis, we identified five LL causal genes (TYMP, DSTYK, PPIF, GDF15, FAM20A) and three ML causal genes (LY75, ADA, ABCA2) as promising drug targets for leukemia. Univariable MR analysis showed genetically predicted higher leukocyte telomere length increased the risk of LL (odds ratio [OR]&#xa0;=&#xa0;2.33, 95&#xa0;% confidence interval [95&#xa0;% CI] 1.70-3.18; P&#xa0;=&#xa0;1.33E-07), and there was no heterogeneity and horizontal pleiotropy. Evidence from the meta-analysis of two cohorts strengthened this finding (OR&#xa0;=&#xa0;1.88, 95&#xa0;% CI 1.06-3.05; P&#xa0;=&#xa0;0.01). Multivariable MR analysis showed the causality between leukocyte telomere length and LL without interference from the other six blood cell telomere length (OR&#xa0;=&#xa0;2.72, 95&#xa0;% CI 1.88-3.93; P&#xa0;=&#xa0;1.23E-07). Evidence from LDSC supported the positive genetic correlation between leukocyte telomere length and LL (rg&#xa0;=&#xa0;0.309, P&#xa0;=&#xa0;0.0001). Colocalization analysis revealed that the causality from leukocyte telomere length on LL was driven by the genetic variant rs770526 in the TERT region. The mediation analysis via two-step MR showed that the causal effect from TYMP on LL was partly mediated by leukocyte telomere length, with a mediated proportion of 12&#xa0;%.<br><br>CONCLUSION: Our study identified several druggable genes associated with leukemia risk and provided new insights into the etiology and drug development of leukemia. We also found that genetically predicted higher leukocyte telomere length increased LL risk and its potential mechanism of action.},
}
@article {pmid39214240,
year = {2024},
author = {Sung, YN and Stojanova, M and Shin, S and Cho, H and Heaphy, CM and Hong, SM},
title = {Gradual Telomere Shortening in the Tumorigenesis of Pancreatic and Hepatic Mucinous Cystic Neoplasms.},
journal = {Human pathology},
volume = {},
number = {},
pages = {105653},
doi = {10.1016/j.humpath.2024.105653},
pmid = {39214240},
issn = {1532-8392},
abstract = {Mucinous cystic neoplasm (MCN) is one of the precursor lesions of pancreatic ductal adenocarcinoma and intrahepatic cholangiocarcinoma. The aim of this study is to examine the presence of short telomeres in promoting the tumorigenesis of MCN by measuring telomere lengths in distinct components of MCN, including the mucinous lining epithelium, non-mucinous lining epithelium, and ovarian-type stroma. A total of 45 patients with MCN (30 pancreatic and 15 hepatic cases) were obtained. Quantitative telomere-specific fluorescent in situ hybridization was performed to measure the telomere length of specific cell types within MCNs, including mucinous lining epithelium, non-mucinous lining epithelium, and ovarian-type stroma, as well as normal ductal epithelium and adenocarcinoma. Relative telomere lengths tended to decrease between normal ductal epithelium, ovarian-type stroma, non-mucinous lining epithelium, mucinous lining epithelium, and adenocarcinoma regardless of the involved organs. Among the analyzed cell types, relative telomere lengths were significantly different between normal ductal epithelium (3.31 ± 0.78), ovarian-type stroma (2.90 ± 0.93), non-mucinous lining epithelium (2.84 ± 0.79), mucinous lining epithelium (2.49 ± 0.93), and adenocarcinoma (1.19 ± 0.59), respectively (P < 0.001, mixed-effects model). As expected, no difference in relative telomere lengths was observed between normal ductal epithelium and ovarian-type stroma; however, significant differences were observed in pair-wise comparisons between ovarian-type stroma vs. non-mucinous lining epithelium (P = 0.001), non-mucinous lining epithelium vs. mucinous lining epithelium (P = 0.005), and mucinous lining epithelium vs. adenocarcinoma (P < 0.001). These findings suggest gradual telomere shortening occurs in the tumorigenesis of MCN, which may have important implications for the progression of this disease.},
}
@article {pmid39213174,
year = {2024},
author = {Martens, DS and Lammertyn, EJ and Goeminne, PC and Colpaert, K and Proesmans, M and Vanaudenaerde, BM and Nawrot, TS and Dupont, LJ},
title = {Leukocyte telomere length and attrition in association with disease severity in cystic fibrosis patients.},
journal = {Aging},
volume = {16},
number = {},
pages = {},
doi = {10.18632/aging.206093},
pmid = {39213174},
issn = {1945-4589},
abstract = {Cystic fibrosis (CF) is characterized by chronic airway inflammation and premature aging. The link with leukocyte telomere length (LTL) as a marker of biological aging is unclear. We studied disease severity and LTL in 168 CF patients of which 85 patients had a second retrospective LTL assessment. A higher FEV1 was associated with longer LTL, with a stronger effect in men (5.08% longer LTL) compared to women (0.41% longer LTL). A higher FEV1/FVC ratio was associated with 7.05% (P=0.017) longer LTL in men. CF asthma, as defined by the treatment with inhaled corticosteroids, was associated with -6.65% shorter LTL (P=0.028). Men homozygous for the ΔF508 genotype showed a -10.48% (P=0.026) shorter LTL compared to heterozygotes. A genotype-specific non-linear association between LTL shortening and chronological age was observed. Stronger age-related LTL shortening was observed in patients homozygous for the ΔF508 genotype (P-interaction= 0.044). This work showed that disease severity in CF patients negatively influences LTL, with slightly more pronounced effects in men. The homozygous genotype for ΔF508 may play a role in LTL attrition in CF patients. Understanding factors in CF patients that accelerate biological aging provides insights into mechanisms that can extend the overall life quality in CF-diseased.},
}
@article {pmid39208769,
year = {2024},
author = {Mlakar, V and Akkouh, I and Halff, EF and Srivastava, DP and Birkenæs, V and Ueland, T and Quintana, DS and Ormerod, MBEG and Steen, NE and Djurovic, S and Andreassen, OA and Aas, M},
title = {Telomere biology and its maintenance in schizophrenia spectrum disorders: Exploring links to cognition.},
journal = {Schizophrenia research},
volume = {272},
number = {},
pages = {89-95},
doi = {10.1016/j.schres.2024.08.011},
pmid = {39208769},
issn = {1573-2509},
abstract = {OBJECTIVE: Contemporary research suggests reduced telomere length in schizophrenia spectrum disorders (SZ) compared to age-adjusted non-affected individuals. However, the role of telomere maintenance and telomere repair in SZ is poorly understood as well as the involvement of telomere biology in cognitive abnormalities in SZ.<br><br>METHODS: The study consisted of 758 participants (SZ [n&#xa0;=&#xa0;357] and healthy controls, HC [n&#xa0;=&#xa0;401]) collected as part of the Norwegian TOP study. Participants were assessed with standardized neuropsychological tests measuring five cognitive domains. Leucocyte telomere length (TL) was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio), used to estimate the mean telomere length. Telomerase activity was assessed by the expression levels of the Telomerase Reverse Transcriptase (TERT) and Telomerase RNA Component (TERC) genes. To assess telomere maintenance and telomere repair we calculated the telomerase expression to TL ratio (TERT/TL and TERC/TL respectively).<br><br>RESULTS: Patients had reduced TERT (F&#xa0;=&#xa0;5.03, p&#xa0;=&#xa0;0.03), but not TERC expression (F&#xa0;=&#xa0;1.04, p&#xa0;=&#xa0;0.31), and higher TERT/TL (F&#xa0;=&#xa0;6.68, p&#xa0;=&#xa0;0.01) and TERC/TL (F&#xa0;=&#xa0;6.71, p&#xa0;=&#xa0;0.01), adjusted for age, sex, and ethnicity. No statistically significant association was observed between any of the telomere biology markers and the cognitive domains (p&#xa0;>&#xa0;0.05).<br><br>CONCLUSION: Our study shows changes in TERT expression and telomere maintenance and telomere repair in SZ compared HC. However, the role of telomere biology in the mechanism underlying cognitive impairment in psychosis seems limited.},
}
@article {pmid39201686,
year = {2024},
author = {Andreikos, D and Kyrodimos, E and Kotsinas, A and Chrysovergis, A and Papacharalampous, GX},
title = {The Association between Telomere Length and Head and Neck Cancer Risk: A Systematic Review and Meta-Analysis.},
journal = {International journal of molecular sciences},
volume = {25},
number = {16},
pages = {},
doi = {10.3390/ijms25169000},
pmid = {39201686},
issn = {1422-0067},
mesh = {Humans ; *Head and Neck Neoplasms/genetics/pathology ; *Telomere Homeostasis ; *Telomere/genetics/metabolism ; Risk Factors ; Odds Ratio ; },
abstract = {Telomeres play a crucial role in maintaining chromosomal integrity and regulating the number of cell divisions and have been associated with cellular aging. Telomere length (TL) has been widely studied in manifold cancer types; however, the results have been inconsistent. This systematic review and meta-analysis aims to analyze the evidence on the association between TL and head and neck cancer (HNC) risk. We comprehensively searched the literature in PubMed, Cochrane Library, and Scopus and identified nine eligible studies, which yielded 11 datasets. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to ascertain the strength of the association. On the basis of the median TL, we defined two groups, short TL and long TL, with the latter being the reference group. Our analysis found a significant relationship between short TL and increased HNC risk (OR 1.38, 95% CI: 1.10-1.73, p = 0.005), while significant heterogeneity among the studies was noted. The subgroup analysis on HNC subtypes revealed a significant association between short TL and oral cancers (OR 2.08, 95% CI: 1.23-3.53, p = 0.007). Additionally, subgroup analysis indicates that adjustments for age, sex, and smoking did not affect the significance of our findings. In conclusion, our meta-analysis found evidence for an association between short TL and HNC risk, which could indicate that TL might act as a potential biomarker for HNC risk, but high-quality prospective studies are imperative to validate our findings.},
}
@article {pmid39201341,
year = {2024},
author = {Pańczyszyn, A and Boniewska-Bernacka, E and Wertel, I and Sadakierska-Chudy, A and Goc, A},
title = {Telomeres and SIRT1 as Biomarkers of Gamete Oxidative Stress, Fertility, and Potential IVF Outcome.},
journal = {International journal of molecular sciences},
volume = {25},
number = {16},
pages = {},
doi = {10.3390/ijms25168652},
pmid = {39201341},
issn = {1422-0067},
mesh = {Humans ; *Oxidative Stress ; *Biomarkers ; *Fertilization in Vitro/methods ; *Telomere/metabolism/genetics ; *Sirtuin 1/metabolism/genetics ; Germ Cells/metabolism ; Fertility/genetics ; Female ; Male ; },
abstract = {The number of infertile couples undergoing in vitro fertilisation (IVF) has increased significantly. The efficacy of this procedure is contingent upon a multitude of factors, including gamete quality. One factor influencing gamete quality is oxidative stress, which leads to telomere damage and accelerates cellular ageing. Identifying new biomarkers that can predict the success of assisted reproduction techniques is a current relevant area of research. In this review, we discuss the potential role of SIRT1, a protein known to protect against oxidative stress and telomeres, which are responsible for genome stability, as biomarkers of gamete quality and assisted reproduction technique outcomes.},
}
@article {pmid39200358,
year = {2024},
author = {Khalatyan, AS and Shishparenok, AN and Avetisov, KS and Gladilina, YA and Blinova, VG and Zhdanov, DD},
title = {Association of Telomere Length in T Lymphocytes, B Lymphocytes, NK Cells and Monocytes with Different Forms of Age-Related Macular Degeneration.},
journal = {Biomedicines},
volume = {12},
number = {8},
pages = {},
doi = {10.3390/biomedicines12081893},
pmid = {39200358},
issn = {2227-9059},
abstract = {BACKGROUND: Age plays a primary role in the development of age-related macular degeneration (AMD). Telomere length (TL) is one of the most relevant biomarkers of aging. In our study, we aimed to determine the association of TL with T lymphocytes, B lymphocytes, NK cells or monocytes with different forms of AMD.<br><br>METHODS: Our study included 62 patients with AMD: geographic atrophy (GA), neovascular AMD (NVAMD) with and without macular atrophy and 22 healthy controls. Each leukocyte subtype was isolated from peripheral blood by immunomagnetic separation, and the DNA was purified. The TL in the genomic DNA was determined using qPCR by amplifying the telomere region with specific oligonucleotide primers and normalizing to the control gene. Statistical analysis was performed using R version 4.5.1.<br><br>RESULTS: We observed a statistically significant increase in TL in the T cells between the control and NVAMD groups but not for the GA group. The B cells and monocytes showed a significant decrease in TL in all AMD groups. The TL in the NK cells did not decrease in any of the AMD groups.<br><br>CONCLUSIONS: The TL in the monocytes had the strongest association with AMD. It reflects a person's "telomeric status" and may become a diagnostic hallmark of these degenerative processes.},
}
@article {pmid39200189,
year = {2024},
author = {Levstek, T and Breznik, N and Vujkovac, B and Nowak, A and Trebušak Podkrajšek, K},
title = {Dynamics of Leukocyte Telomere Length in Patients with Fabry Disease.},
journal = {Biomedicines},
volume = {12},
number = {8},
pages = {},
doi = {10.3390/biomedicines12081724},
pmid = {39200189},
issn = {2227-9059},
support = {P1-0170//Slovenian Research Agency/ ; NA//Takeda Pharmaceuticals/ ; },
abstract = {Fabry disease (FD) leads to significant morbidity and mortality, which may indicate accelerated ageing. However, it is still unclear whether there is a relationship between telomere length (TL), a marker of biological ageing, and disease outcome. We aimed to examine the relationship between leukocyte TL (LTL) dynamics and the presence of advanced disease stages and/or late complications of FD, including hypertrophic cardiomyopathy, nephropathy and stroke, both cross-sectionally and longitudinally. DNA was extracted from peripheral blood leukocytes and quantitative PCR was utilized to determine relative LTL in 99 Fabry patients. In the longitudinal analysis, we included 50 patients in whom at least three measurements were performed over a period of 5-10 years. The results showed a significant inverse correlation between LTL and age (ρ = -0.20, p = 0.05). No significant differences in LTL were found between females and males (p = 0.79) or between patients receiving disease-specific therapy and those without (p = 0.34). In a cross-sectional analysis, no association was found between the presence (p = 0.15) or number (p = 0.28) of advanced stages of the disease and/or late complications and LTL. Similarly, in a longitudinal analysis, no difference in LTL dynamics was found regarding the presence (p = 0.16) of advanced stage organ involvement and/or late complications or their number. These findings indicate that LTL dynamics in adulthood may not be a reliable indicator of disease outcomes in Fabry patients. Therefore, LTL may more accurately reflect the disease burden in early life, when TL is primarily determined.},
}
@article {pmid39198715,
year = {2024},
author = {Tummala, H and Walne, AJ and Badat, M and Patel, M and Walne, AM and Alnajar, J and Chow, CC and Albursan, I and Frost, JM and Ballard, D and Killick, S and Szitányi, P and Kelly, AM and Raghavan, M and Powell, C and Raymakers, R and Todd, T and Mantadakis, E and Polychronopoulou, S and Pontikos, N and Liao, T and Madapura, P and Hossain, U and Vulliamy, T and Dokal, I},
title = {The evolving genetic landscape of telomere biology disorder dyskeratosis congenita.},
journal = {EMBO molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {39198715},
issn = {1757-4684},
support = {MR/P018440/1//UKRI | Medical Research Council (MRC)/ ; MR/P018440/1//UKRI | Medical Research Council (MRC)/ ; MR/P018440/1//UKRI | Medical Research Council (MRC)/ ; 14032/LLR_/Blood Cancer UK/United Kingdom ; 14032/LLR_/Blood Cancer UK/United Kingdom ; },
abstract = {Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome, caused by genetic mutations that principally affect telomere biology. Approximately 35% of cases remain uncharacterised at the genetic level. To explore the genetic landscape, we conducted genetic studies on a large collection of clinically diagnosed cases of DC as well as cases exhibiting features resembling DC, referred to as 'DC-like' (DCL). This led us to identify several novel pathogenic variants within known genetic loci and in the novel X-linked gene, POLA1. In addition, we have also identified several novel variants in POT1 and ZCCHC8 in multiple cases from different families expanding the allelic series of DC and DCL phenotypes. Functional characterisation of novel POLA1 and POT1 variants, revealed pathogenic effects on protein-protein interactions with primase, CTC1-STN1-TEN1 (CST) and shelterin subunit complexes, that are critical for telomere maintenance. ZCCHC8 variants demonstrated ZCCHC8 deficiency and signs of pervasive transcription, triggering inflammation in patients' blood. In conclusion, our studies expand the current genetic architecture and broaden our understanding of disease mechanisms underlying DC and DCL disorders.},
}
@article {pmid39198664,
year = {2024},
author = {Qiu, YD and Yan, Q and Wang, Y and Ye, YF and Wang, Y and Wang, MY and Wang, PP and Zhang, SY and Wang, DL and Yan, H and Ruan, J and Zhao, YJ and Huang, LH and Cho, N and Wang, K and Zheng, XH and Liu, ZG},
title = {Author Correction: Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells.},
journal = {Acta pharmacologica Sinica},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41401-024-01370-0},
pmid = {39198664},
issn = {1745-7254},
}
@article {pmid39197728,
year = {2024},
author = {Neto, IVS and Pinto, AP and de Andrade, RV and de Souza, FHV and de Souza, PEN and Assis, V and Tibana, RA and Neves, RVP and Rosa, TDS and Prestes, J and da Silva, ASR and Marqueti, RC},
title = {Paternal exercise induces antioxidant defenses by α-Klotho/Keap1 pathways in the skeletal muscle of offspring exposed to a high fat-diet without changing telomere length.},
journal = {The Journal of nutritional biochemistry},
volume = {},
number = {},
pages = {109747},
doi = {10.1016/j.jnutbio.2024.109747},
pmid = {39197728},
issn = {1873-4847},
abstract = {Although previous studies demonstrated that the ancestral lifestyle can enhance the metabolic health of offspring exposed to an obesogenic diet, the specific connections between these positive effects in redox state and telomere length are unknown. We investigated the impact of paternal resistance training (RT) on stress-responsive signaling and the pathways involved in telomere homeostasis in skeletal muscle. This investigation encompassed both the fathers and first-generation litter exposed to a long-term standard diet (24 weeks) and high fat diet (HFD). Wistar rats were randomized into sedentary or trained fathers (8 weeks of resistance training). The offspring were obtained by mating with sedentary females. Upon weaning, male offspring were divided into four groups: offspring of sedentary or trained fathers exposed to either a control diet or HFD. The gastrocnemius was prepared for reverse transcription-quantitative polymerase chain reaction, immunoblotting, ELISA, and electron paramagnetic resonance spectroscopy. RT upregulated shelterin mRNA levels and antioxidant protein, preserving muscle telomere in fathers. Conversely, HFD induced a disturbance in the redox balance, which may have contributed to the offspring telomere shortening from sedentary fathers. Pre-conceptional paternal RT downregulates Kelch-like ECH-associated protein 1 (Keap1) mRNA levels in the skeletal muscle of progeny exposed to HFD, driving an increase in Glutathione reductase mRNA levels, Sod1 and Catalase protein levels to mitigate ROS production. Also, paternal exercise upregulates α-Klotho protein levels, mediating antioxidative responses without altering shelterin mRNA levels and telomere length. We provide the first in-depth analysis that the offspring's redox state seems to be directly associated with the beneficial effects of paternal exercise.},
}
@article {pmid39197110,
year = {2024},
author = {Roka, K and Solomou, E and Kattamis, A and Stiakaki, E},
title = {Telomere biology disorders: from dyskeratosis congenita and beyond.},
journal = {Postgraduate medical journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/postmj/qgae102},
pmid = {39197110},
issn = {1469-0756},
abstract = {Defective telomerase function or telomere maintenance causes genomic instability. Alterations in telomere length and/or attrition are the primary features of rare diseases known as telomere biology disorders or telomeropathies. Recent advances in the molecular basis of these disorders and cutting-edge methods assessing telomere length have increased our understanding of this topic. Multiorgan manifestations and different phenotypes have been reported even in carriers within the same family. In this context, apart from dyskeratosis congenita, disorders formerly considered idiopathic (i.e. pulmonary fibrosis, liver cirrhosis) frequently correlate with underlying defective telomere maintenance mechanisms. Moreover, these patients are prone to developing specific cancer types and exhibit exceptional sensitivity and toxicity in standard chemotherapy regimens. The current review describes the diverse spectrum of clinical manifestations of telomere biology disorders in pediatric and adult patients, their correlation with pathogenic variants, and considerations during their management to increase awareness and improve a multidisciplinary approach.},
}
@article {pmid39195250,
year = {2024},
author = {Ghilain, C and Vidal-Cruchez, O and Joly, A and Debatisse, M and Gilson, E and Giraud-Panis, MJ},
title = {Innovative Tools for DNA Topology Probing in Human Cells Reveal a Build-Up of Positive Supercoils Following Replication Stress at Telomeres and at the FRA3B Fragile Site.},
journal = {Cells},
volume = {13},
number = {16},
pages = {},
doi = {10.3390/cells13161361},
pmid = {39195250},
issn = {2073-4409},
support = {TELOCHROM//Agence Nationale de la Recherche/ ; REPLITOP//French National Cancer Institute/ ; Equipe labellis&#xe9;e//Fondation ARC pour la Recherche sur le Cancer/ ; },
mesh = {Humans ; *Telomere/metabolism ; *DNA, Superhelical/metabolism ; *DNA Replication ; Chromosome Fragile Sites ; Telomeric Repeat Binding Protein 2/metabolism/genetics ; Nucleic Acid Conformation ; DNA/metabolism ; DNA Topoisomerases, Type II/metabolism ; },
abstract = {Linear unconstrained DNA cannot harbor supercoils since these supercoils can diffuse and be eliminated by free rotation of the DNA strands at the end of the molecule. Mammalian telomeres, despite constituting the ends of linear chromosomes, can hold supercoils and be subjected to topological stress. While negative supercoiling was previously observed, thus proving the existence of telomeric topological constraints, positive supercoils were never probed due to the lack of an appropriate tool. Indeed, the few tools available currently could only investigate unwound (Trioxsalen) or overwound (GapR) DNA topology (variations in twist) but not the variations in writhe (supercoils and plectonemes). To address this question, we have designed innovative tools aimed at analyzing both positive and negative DNA writhe in cells. Using them, we could observe the build-up of positive supercoils following replication stress and inhibition of Topoisomerase 2 on telomeres. TRF2 depletion caused both telomere relaxation and an increase in positive supercoils while the inhibition of Histone Deacetylase I and II by TSA only caused telomere relaxation. Moving outside telomeres, we also observed a build-up of positive supercoils on the FRA3B fragile site following replication stress, suggesting a topological model of DNA fragility for this site.},
}
@article {pmid39192622,
year = {2024},
author = {Aali, R and Asli Gharehbagh, H and Gholampour, A and Sorooshian, A and Panahi, Y},
title = {Children exposed to salt-dust emission from Urmia Lake have short telomere length: a case-control pilot study.},
journal = {International journal of environmental health research},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/09603123.2024.2394136},
pmid = {39192622},
issn = {1369-1619},
abstract = {This study aimed to measure telomere length in healthy children living next to Urmia Lake, Iran, which is exposed to salt dust from a drying lakebed. In this case-control pilot study, we recruited 39 sex- and age-matched healthy children from two different geographic regions to study the relative telomere lengths using qPCR. We categorized the study samples into high-impact and low-impact areas based on wind direction, aerosol particle level, and distance from the lake. Our main results revealed that children living in high-impact areas have shorter telomeres than those living in low-impact areas. Furthermore, according to our statistical model, parental age significantly affected telomere length in children, but inversely. When the father's age impact was positive, the mother had a negative effect. Based on our results, to prevent Urmia Lake from dying out completely, national and international organizations should implement comprehensive visions and strategies for its restoration.},
}
@article {pmid39192284,
year = {2024},
author = {Zhuang, X and Chen, P and Yang, R and Man, X and Wang, R and Shi, Y},
title = {Mendelian randomization analysis reveals the combined effects of epigenetics and telomere biology in hematologic cancers.},
journal = {Clinical epigenetics},
volume = {16},
number = {1},
pages = {120},
pmid = {39192284},
issn = {1868-7083},
support = {Y20240077//the Public Welfare Science and Technology Project of Wenzhou/ ; Y20240077//the Public Welfare Science and Technology Project of Wenzhou/ ; Y20240077//the Public Welfare Science and Technology Project of Wenzhou/ ; Y20240077//the Public Welfare Science and Technology Project of Wenzhou/ ; Y20240077//the Public Welfare Science and Technology Project of Wenzhou/ ; Y20240077//the Public Welfare Science and Technology Project of Wenzhou/ ; No. LQ19H080002//Natural Science Foundation of Zhejiang Province/ ; },
abstract = {BACKGROUND: Telomere shortening and epigenetic modifications are key factors in aging and hematologic diseases. This study investigates the relationship of telomere length and epigenetic age acceleration (EAA) with hematologic cancers, blood cells, and biochemical markers through the epigenetic clocks.<br><br>METHODS: This study primarily utilizes genome-wide association studies of populations of European descent as instrumental variables, exploring the causal relationships between exposures and outcomes through a bidirectional two-sample Mendelian randomization (MR) approach. MR techniques include inverse variance weighted (IVW), MR Egger, and weighted median modes. Heterogeneity and pleiotropy in MR are assessed using Cochran's Q test and the MR Egger intercept, with the robustness of the conclusions further validated by multivariable MR (MVMR).<br><br>RESULTS: Our research shows that longer telomere lengths significantly increase the risk of multiple myeloma, leukemia, and lymphoma (OR&#x2009;>&#x2009;1, P&#x2009;<&#x2009;0.05) and establish a causal relationship between telomere length and red blood cell indices such as RBC (OR&#x2009;=&#x2009;1.121, PIVW&#x2009;=&#x2009;0.034), MCH (OR&#x2009;=&#x2009;0.801, PIVW&#x2009;=&#x2009;2.046e-06), MCV (OR&#x2009;=&#x2009;0.801, PIVW&#x2009;=&#x2009;0.001), and MCHC (OR&#x2009;=&#x2009;0.813, PIVW&#x2009;=&#x2009;0.002). Additionally, MVMR analysis revealed an association between DNA methylation PhenoAge acceleration and alkaline phosphatase (OR&#x2009;=&#x2009;1.026, PIVW&#x2009;=&#x2009;0.007).<br><br>CONCLUSION: The study clarifies the relationships between telomere length, EAA, and hematological malignancies, further emphasizing the prognostic significance of telomere length and EAA. This deepens our understanding of the pathogenesis of hematological diseases, which can inform risk assessment and therapeutic strategies.},
}
@article {pmid39192095,
year = {2024},
author = {Burren, OS and Dhindsa, RS and Deevi, SVV and Wen, S and Nag, A and Mitchell, J and Hu, F and Loesch, DP and Smith, KR and Razdan, N and Olsson, H and Platt, A and Vitsios, D and Wu, Q and , and Codd, V and Nelson, CP and Samani, NJ and March, RE and Wasilewski, S and Carss, K and Fabre, M and Wang, Q and Pangalos, MN and Petrovski, S},
title = {Genetic architecture of telomere length in 462,666 UK Biobank whole-genome sequences.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {39192095},
issn = {1546-1718},
support = {MR/M012816/1//RCUK | Medical Research Council (MRC)/ ; MR/M012816/1//RCUK | Medical Research Council (MRC)/ ; MR/M012816/1//RCUK | Medical Research Council (MRC)/ ; BRC-1215-20010//DH | National Institute for Health Research (NIHR)/ ; BRC-1215-20010//DH | National Institute for Health Research (NIHR)/ ; BRC-1215-20010//DH | National Institute for Health Research (NIHR)/ ; MR/M012816/1//British Heart Foundation (BHF)/ ; },
abstract = {Telomeres protect chromosome ends from damage and their length is linked with human disease and aging. We developed a joint telomere length metric, combining quantitative PCR and whole-genome sequencing measurements from 462,666 UK Biobank participants. This metric increased SNP heritability, suggesting that it better captures genetic regulation of telomere length. Exome-wide rare-variant and gene-level collapsing association studies identified 64 variants and 30 genes significantly associated with telomere length, including allelic series in ACD and RTEL1. Notably, 16% of these genes are known drivers of clonal hematopoiesis-an age-related somatic mosaicism associated with myeloid cancers and several nonmalignant diseases. Somatic variant analyses revealed gene-specific associations with telomere length, including lengthened telomeres in individuals with large SRSF2-mutant clones, compared with shortened telomeres in individuals with clonal expansions driven by other genes. Collectively, our findings demonstrate the impact of rare variants on telomere length, with larger effects observed among genes also associated with clonal hematopoiesis.},
}
@article {pmid39190187,
year = {2024},
author = {Milosevic, T and Naumovic, R and Sopic, M and Vekic, J and Guzonjic, A and Pesic, S and Miljkovic-Trailovic, M and Kotur-Stevuljevic, J},
title = {COVID-19 increases mortality in hemodialysis patients: exploring links with inflammation and telomere attrition.},
journal = {Molecular biology reports},
volume = {51},
number = {1},
pages = {938},
pmid = {39190187},
issn = {1573-4978},
support = {451-03-47/2023 01/ 200161//Ministry of Education, Science, and Technological Development, Republic of Serbia, through Grant Agreement with the University of Belgrade-Faculty of Pharmacy/ ; 451-03-47/2023 01/ 200161//Ministry of Education, Science, and Technological Development, Republic of Serbia, through Grant Agreement with the University of Belgrade-Faculty of Pharmacy/ ; 451-03-47/2023 01/ 200161//Ministry of Education, Science, and Technological Development, Republic of Serbia, through Grant Agreement with the University of Belgrade-Faculty of Pharmacy/ ; 451-03-47/2023 01/ 200161//Ministry of Education, Science, and Technological Development, Republic of Serbia, through Grant Agreement with the University of Belgrade-Faculty of Pharmacy/ ; 451-03-47/2023 01/ 200161//Ministry of Education, Science, and Technological Development, Republic of Serbia, through Grant Agreement with the University of Belgrade-Faculty of Pharmacy/ ; },
mesh = {Humans ; *COVID-19/mortality/virology ; Male ; Female ; *Renal Dialysis ; Middle Aged ; Aged ; *C-Reactive Protein/metabolism ; *Inflammation ; Lymphocytes/metabolism ; Neutrophils/metabolism ; Telomere/genetics/metabolism ; SARS-CoV-2 ; L-Lactate Dehydrogenase/blood ; Kaplan-Meier Estimate ; Kidney Failure, Chronic/therapy/mortality/blood ; },
abstract = {BACKGROUND AND OBJECTIVE: An increased risk of mortality and hospitalization was consistently demonstrated in hemodialysis (HD) patients affected by pandemic coronavirus infection (COVID-19). In this study, we analyzed parameters that may impact mortality in COVID-19 HD patients, including neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP), COVID-19 disease status and telomere length in peripheral blood cells (TL).<br><br>MATERIALS AND METHODS: A total of 130 chronic hemodialysis patients were enrolled and followed up for 18 months. Patients were categorized into groups based on their COVID-19 disease history and subsequent data about their survival status at the end of the study. Routine laboratory parameters were assessed using standard automated methods and TL was determined using the modified Cawthon method. Survival predictors were analyzed using Kaplan-Meier analysis.<br><br>RESULTS: Deceased patients (30%) were older with higher body mass index (BMI), higher levels of LDH, NLR index, CRP and lower TL and lymphocytes count compared to survivors. Kaplan-Meier survival analysis showed six parameters were significant mortality predictors in the following order of significance: COVID-19 history, 2-years cardiovascular mortality risk score, NLR, TL, CRP, LDH. Using binary logistic regression analysis Summary risk score, a combination of these six parameters revealed as the best predictor of patient's survival in this group of parameters (log rank 25.4, p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Compared to the general population, the mortality rate among HD patients persists at a higher level despite advancements in HD technology and patient care. The situation has been exacerbated by COVID-19, by significant increase in mortality rate among these patients.},
}
@article {pmid39189448,
year = {2024},
author = {Wondimagegnhu, B and Ma, W and Paul, T and Liao, TW and Lee, CY and Sanford, S and Opresko, PL and Myong, S},
title = {The molecular mechanism for TERRA recruitment and annealing to telomeres.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae732},
pmid = {39189448},
issn = {1362-4962},
support = {F31CA268939/GF/NIH HHS/United States ; },
abstract = {Telomeric repeat containing RNA (TERRA) is a noncoding RNA that is transcribed from telomeres. Previous study showed that TERRA trans anneals by invading into the telomeric duplex to form an R-loop in mammalian cells. Here, we elucidate the molecular mechanism underlying TERRA recruitment and invasion into telomeres in the context of shelterin proteins, RAD51 and RNase H using single molecule (sm) assays. We demonstrate that TERRA trans annealing into telomeric DNA exhibits dynamic movement that is stabilized by TRF2. TERRA annealing to the telomeric duplex results in the formation of a stable triplex structure which differs from a conventional R-loop. We identified that the presence of a sub-telomeric DNA and a telomeric overhang in the form of a G-quadruplex significantly enhances TERRA annealing to telomeric duplex. We also demonstrate that RAD51-TERRA complex invades telomere duplex more efficiently than TERRA alone. Additionally, TRF2 increases TERRA affinity to telomeric duplex and protects it from RNase H digestion. In contrast, TRF1 represses TERRA annealing to telomeric duplex and fails to provide protection against RNase H digestion. Our findings provide an in-depth molecular mechanism underpinning TERRA recruitment and annealing to the telomere.},
}
@article {pmid39188883,
year = {2024},
author = {Murillo-Ortiz, BO and García-Corrales, K and Martínez-Garza, S and Romero-Vázquez, MJ and Agustín-Godínez, E and Escareño-Gómez, A and Silva-Guerrero, DG and Mendoza-Ramírez, S and Murguia-Perez, M},
title = {Association of hTERT expression, Her2Neu, estrogen receptors, progesterone receptors, with telomere length before and at the end of treatment in breast cancer patients.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1450147},
pmid = {39188883},
issn = {2296-858X},
abstract = {BACKGROUND: Breast cancer shows significant clinical, morphologic, and molecular variation. Telomeres are nucleoprotein complexes composed of hexanucleotide repeat DNA sequence, TTAGGG, and numerous telomere-associated proteins. The maintenance of telomere length is carried out by a ribonucleoprotein called telomerase, which consists of two main components: a catalytic subunit called hTERT (human telomerase reverse transcriptase) and an RNA template called hTR (human telomerase RNA). The importance of evaluating hTERT expression lies in its potential therapeutic application, being an attractive target due to its almost non-existent expression in normal somatic cells. It is also expected that the anti-neoplastic effect would appear earlier in neoplastic cells with shorter telomeres. Additionally, a significant relationship has been observed between Her2-Neu overexpression and Her2-Neu positivity, which could suggest new combined therapies.The aim of this study was to detect the expression of hTERT, estrogen receptor (ER), progesterone receptor (PR), and HER2-Neu in neoplastic breast tissue embedded in paraffin before treatment and to investigate the relationship between them and with baseline and post-treatment telomere length, as well as with various clinicopathological parameters.<br><br>MATERIALS AND METHODS: A cross-sectional-correlational, 21 women diagnosed with breast cancer at the Oncology Service of the High Specialty Medical Unit No. 1 of Bajio of the Mexican Institute of Social Security. The study complies with the Helsinki Declaration and was approved by the Institutional Ethical Committee of the Mexican Institute of Social Security (R-2019-1001-127). A peripheral blood sample was obtained before oncological treatment and at the end of oncological treatment for the measurement of telomere length by extracting DNA from leukocytes, was performed by the quantitative polymerase chain reaction (PCR) method described by Cawthon. Tumor samples were collected from each patient at the oncology department for immunohistochemical determination of biomarker expression (ER, PR, Her2/neu) and hTERT.<br><br>RESULTS: Of the 21 cases included in the study, the median age was 57.57&#x2009;years. Eighteen cases were classified as invasive ductal carcinoma NOS (85.71%), 10 were histologic grade 2 (47.61%), 16 cases were hormone receptor positive (76.19%), 7 were Her2Neu positive (33.33%), and only 2 cases were triple negative (9.52%). Positive hTERT expression was detected in 11 cases (52.38%) and was negative in the remaining cases. A significant association was identified between hTERT-positive cases and Her2-Neu positive cases (p&#x2009;=&#x2009;0.04). Baseline and post-treatment telomere lengths showed a significant difference using the non-parametric Wilcoxon t-test (p&#x2009;=&#x2009;0.002). In hTERT-positive cases, there was significant telomere shortening at the end of oncological treatment (6.14&#x2009;&#xb1;&#x2009;1.54 vs. 4.75&#x2009;&#xb1;&#x2009;1.96 Kb, p&#x2009;=&#x2009;0.007).<br><br>CONCLUSION: Positive hTERT immunostaining cases were associated with poor prognostic factors, such as Her2-Neu overexpression and post-treatment telomere shortening. In the future, hTERT immunostaining could be used to select patients for therapies with antagonistic effects on hTERT, as well as in the selection of more appropriate chemotherapy regimens for patients who express it.},
}
@article {pmid39188229,
year = {2024},
author = {Kim, D and Danpanichkul, P and Wijarnpreecha, K and Cholankeril, G and Ahmed, A},
title = {Leukocyte Telomere Shortening in MASLD and All-cause/Cause-specific Mortality.},
journal = {Clinical and molecular hepatology},
volume = {},
number = {},
pages = {},
doi = {10.3350/cmh.2024.0691},
pmid = {39188229},
issn = {2287-285X},
}
@article {pmid39180127,
year = {2024},
author = {Song, Y and Xu, J and Geng, W and Yin, L and Wang, J and Zhao, J},
title = {Association and causal impact of TERT genetic variants on peripheral blood leukocyte telomere length and cerebral small vessel disease risk in a Chinese Han population: a mendelian randomization analysis.},
journal = {Orphanet journal of rare diseases},
volume = {19},
number = {1},
pages = {309},
pmid = {39180127},
issn = {1750-1172},
support = {no. 19-1124-038//Shenyang Science and Technology Bureau, China/ ; },
mesh = {Humans ; *Telomerase/genetics ; *Mendelian Randomization Analysis ; *Cerebral Small Vessel Diseases/genetics ; *Polymorphism, Single Nucleotide/genetics ; Female ; *Leukocytes/metabolism ; Male ; Middle Aged ; Asian People/genetics ; Aged ; Telomere/genetics ; Genetic Predisposition to Disease ; Genotype ; China ; Risk Factors ; East Asian People ; },
abstract = {BACKGROUND: Previous observational studies have highlighted potential relationships between the telomerase reverse transcriptase (TERT) gene, short leukocyte telomere length (LTL), and cerebrovascular disease. However, it remains to be established as to whether TERT gene variants are associated with an elevated risk of cerebral small vessel disease (CSVD), and whether there is a causal relationship between LTL and CSVD.<br><br>METHODS: Five TERT single nucleotide polymorphisms (SNPs) were analyzed in 307 CSVD patients and 320 healthy controls in whom LTL values were quantified. Allele models and four genetic models were used to explore the relationship between these SNP genotypes and CSVD risk. A Mendelian randomization analysis of CSVD risk was then performed using LTL-related SNPs and the polygenic risk score (PRS) constructed from these SNPs as genetic instrumental variables to predict the causal relationship between LTL and CSVD risk.<br><br>RESULTS: Model association analyses identified two SNPs that were significantly associated with CSVD risk. LTL was significantly correlated with age (P&#x2009;<&#x2009;0.001), and the MR analysis revealed an association between short LTL and an elevated risk of CSVD. PRS-based genetic prediction of short LTLs was also significantly related to an elevated CSVD risk.<br><br>CONCLUSION: Multiple genetic models and MR results indicate that TERT gene SNPs may be related to an elevated risk of CSVD, and that shorter LTL may be causally linked to such CSVD risk.},
}
@article {pmid39179728,
year = {2024},
author = {Jin, Z and Liu, X and Guo, H and Chen, S and Zhu, X and Pan, S and Wu, Y},
title = {Sex-specific modulating role of social support in the associations between oxidative stress, inflammation, and telomere length in older adults.},
journal = {Journal of behavioral medicine},
volume = {},
number = {},
pages = {},
pmid = {39179728},
issn = {1573-3521},
support = {81971019//National Natural Science Foundation of China/ ; 82271482//National Natural Science Foundation of China/ ; },
abstract = {Telomere length, a biomarker of human aging, is related to adverse health outcomes. Growing evidence indicates that oxidative stress and inflammation contributes to telomere shortening, whereas social support may protect from telomere shortening. Despite sex differences in telomere length and social support, little is known about whether there are sex differences in the relationship between oxidative stress/inflammation and telomere length, and sex-specific moderating roles of social support in older adults. Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002, this study assessed whether the associations between oxidative stress/inflammation and telomere length vary with sex and explored social support as a moderator in these associations among 2289 older adults. Oxidative stress was measured based on serum Gamma-glutamyl transferase (GGT), and inflammation was measured based on C-reactive protein (CRP). After adjusting for the covariates, GGT was significantly associated with telomere length in females only (β = - 0.037, 95% CI = - 0.070, - 0.005), while CRP was associated with telomere length in males only (β = - 0.019, 95% CI = - 0.035, - 0.002). Moreover, high social support mitigated the negative association between GGT and telomere length, which was more evident in females. Furthermore, social support moderated the association between CRP and telomere length in males aged 70 and above. Our findings indicated that biological mechanisms related to telomere length may vary with sex, while social support plays a sex-specific moderating role.},
}
@article {pmid39178054,
year = {2024},
author = {Squassina, A and Pisanu, C and Menesello, V and Meloni, A and Congiu, D and Manchia, M and Paribello, P and Abate, M and Bortolomasi, M and Baune, BT and Gennarelli, M and Minelli, A},
title = {Leukocyte Telomere Length and Mitochondrial DNA Copy Number in Treatment-Resistant Depression and Response to Electroconvulsive Therapy: A Pilot Longitudinal Study.},
journal = {The journal of ECT},
volume = {},
number = {},
pages = {},
doi = {10.1097/YCT.0000000000001060},
pmid = {39178054},
issn = {1533-4112},
abstract = {OBJECTIVES: In this study, we investigated if changes in leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-cn), 2 markers of cellular aging, are associated with treatment-resistant depression (TRD) and with response to electroconvulsive therapy (ECT).<br><br>METHODS: LTL and mtDNA-cn were measured in 31 TRD patients before (T0), 1 week (T1), and 4 weeks (T2) after the ECT course, as well as in a sample of 65 healthy controls.<br><br>RESULTS: TRD patients had significantly shorter LTL and higher mtDNA-cn compared with healthy controls at baseline. In the TRD sample, LTL was inversely correlated with Montgomery-&#xc5;sberg Depression Rating Scale scores at baseline. Baseline levels of LTL or mtDNA-cn were not correlated with response to ECT. Similarly, changes in LTL or mtDNA-cn were not associated with response to ECT either when considered as a dichotomous trait (responders vs nonresponders) or as a percentage change in symptoms improvements.<br><br>CONCLUSIONS: Ours is the first longitudinal study exploring the role of LTL and mtDNA-cn in response to ECT. Findings of this pilot investigation suggest that LTL and mtDNA-cn may constitute disease biomarkers for TRD but are not involved in response to ECT.},
}
@article {pmid39177475,
year = {2024},
author = {He, Z and Wu, J and Li, W and Du, Y and Lu, L},
title = {Investigation of G-Quadruplex DNA-Mediated Charge Transport for Exploring DNA Oxidative Damage in Telomeres.},
journal = {Langmuir : the ACS journal of surfaces and colloids},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.langmuir.4c01604},
pmid = {39177475},
issn = {1520-5827},
abstract = {The human telomeric DNA 3' single-stranded overhang comprises tandem repeats of the sequence d(TTAGGG), which can fold into the stable secondary structure G-quadruplex (G4) and is susceptible to oxidative damage due to the enrichment of G bases. 8-Oxoguanine (8-oxoG) formed in telomeric DNA destabilizes G4 secondary structures and then inhibits telomere functions such as the binding of G4 proteins and the regulation of the length of telomeres. In this work, we developed a G4-DNA self-assembled monolayer electrochemical sensing interface using copper-free click chemistry based on the reaction of dibenzocyclooctyl with azide, resulting in a high yield of DNA tethers with order and homogeneity surfaces, that is more suitable for G-quadruplex DNA charge transport (CT) research. At high DNA coverage density surfaces, G-quadruplex DNA is 4 times more conductive than double-stranded DNA owing to the well-stacked aromatic rings of G-quartets acting as good charge transfer channels. The effect of telomeric oxidative damage on G-quadruplex-mediated CT is investigated. The accommodation of 8-oxoG at G sites originally in the syn or anti conformation around the glycosyl bond in the nonsubstituted hTel G-quadruplex causes structural perturbation and a conformational shift, which disrupts the π-stack, affecting the charge transfer and attenuating the electrochemical signal. The current intensity was found to correlate with the amount of 8-oxodG, and the detection limit was estimated to be approximately one lesion in 286 DNA bases, which can be converted into 64.7 fmol on the basis of the total surface DNA coverage. The improved G4-DNA order and homogeneity sensing interface represent a major step forward in this regard, providing a reliable and controlled electrochemical platform for the accurate measurement and diagnosis of G4-DNA oxidative damage.},
}
@article {pmid39173315,
year = {2024},
author = {Vaz, D and Vasconcelos, S and Caniçais, C and Costa, B and Ramalho, C and Marques, J and Dória, S},
title = {X-chromosome inactivation pattern and telomere length in recurrent pregnancy loss.},
journal = {Reproductive biology},
volume = {24},
number = {4},
pages = {100933},
doi = {10.1016/j.repbio.2024.100933},
pmid = {39173315},
issn = {2300-732X},
abstract = {Recurrent pregnancy loss is a reproductive disorder affecting about 1 to 5 % of pregnant women worldwide that requires our attention, especially considering that about 50 % of cases are idiopathic. The present study is focused on testing a possible association between extreme skewed X-chromosome inactivation patterns and/or shortened telomeres with idiopathic cases since both are considered non-consensual potential causes underlying recurrent pregnancy loss in the scientific community. For this purpose, two groups of women were analyzed and compared: a group of women with idiopathic recurrent pregnancy loss and a second group of age-matched women with proven fertility, and both X-chromosome inactivation patterns and telomere length were measured and compared from maternal DNA extracted from peripheral blood. Our data showed no statistically significant differences between groups, suggesting no association between extreme skewed X-chromosome inactivation or shortened telomeres with recurrent pregnancy losses. Additionally, the effect of maternal age on both X-chromosome inactivation pattern and telomere length was tested, but no significant correlation was observed between advanced maternal age and extreme skewed X-chromosome inactivation or telomere shortening. This study represents one more valid contribution to the investigation of causes underlying recurrent pregnancy loss suggesting that, new variables may be considered since the pattern of X-chromosome inactivation and telomere length do not seem to be related to this reproductive disorder. Briefly, considering its clinical relevance, it is mandatory a continuous effort in the scientific community to cover new potential recurrent pregnancy loss-related causes.},
}
@article {pmid39174689,
year = {2024},
author = {Spinou, M and Naska, A and Nelson, CP and Codd, V and Samani, NJ and Bountziouka, V},
title = {Micronutrient intake and telomere length: findings from the UK Biobank.},
journal = {European journal of nutrition},
volume = {},
number = {},
pages = {},
pmid = {39174689},
issn = {1436-6215},
support = {MR/M012816/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {PURPOSE: To investigate whether micronutrient intake from food as well as the regular uptake of specific vitamins and/or minerals are associated with leucocyte telomere length (LTL).<br><br>METHODS: This is a cross-sectional study using data from 422,693 UK Biobank participants aged from 40 to 69 years old, during 2006-2010. LTL was measured as the ratio of telomere repeat number to a single-copy gene and was loge-transformed and z-standardized (z-LTL). Information concerning supplement use was collected at baseline through the touchscreen assessment, while micronutrient intake from food were self-reported through multiple web-based 24&#xa0;h recall diaries. The association between micronutrient intake or supplement use and z-LTL was assessed using multivariable linear regression models adjusting for demographic, lifestyle and clinical characteristics.<br><br>RESULTS: About 50% (n&#x2009;=&#x2009;131,810) of the participants, with complete data on all covariates, self-reported regular supplement intake. Whilst overall supplement intake was not associated with z-LTL, trends toward shorter z-LTL with regular vitamin B (-0.019 (95% CI: -0.041; 0.002)) and vitamin B9 (-0.027 (-0.054; 0.000)) supplement intake were observed. z-LTL was associated with food intake of pantothenic acid (-0.020 (-0.033; -0.007)), vitamin B6 (-0.015 (-0.027; -0.003)), biotin (0.010 (0.002; 0.018)) and folate (0.016 (0.003; 0.030)). Associations of z-LTL with these micronutrients were differentiated according to supplement intake.<br><br>CONCLUSION: Negative associations equivalent to a year or less of age-related change in LTL between micronutrient intake and LTL were observed. Due to this small effect, the clinical importance of the associations and any relevance to the effects of vitamin and micronutrient intake toward chronic disease prevention remains uncertain.},
}
@article {pmid39170634,
year = {2024},
author = {Domínguez-de-Barros, A and Sifaoui, I and Dorta-Guerra, R and Lorenzo-Morales, J and Castro-Fuentes, R and Córdoba-Lanús, E},
title = {DNA damage (8-OHdG) and telomere length in captive Psittacidae birds with different longevity.},
journal = {Frontiers in veterinary science},
volume = {11},
number = {},
pages = {1430861},
pmid = {39170634},
issn = {2297-1769},
abstract = {Aging is a complex process influenced by internal and external factors. Oxidative stress damages DNA, leading to 8-hydroxy-2' deoxyguanosine formation (8-OHdG). Telomere shortening is considered a biomarker of aging and oxidative stress may enhance its attrition. The ability to manage and repair oxidative stress varies among species and life histories. Avian species, such as Psittacidae birds, exhibit exceptional lifespans despite their physiological characteristics that might suggest otherwise. This study investigates 8-OHdG levels in serum samples from long- and short-lived birds of the order Psittaciformes, examining their relationship with telomere length and antioxidant capacity based on lifespan strategies. Among 43 individuals analyzed 26 belonged to the "long-lived species" group and 17 belonged to the "short-lived species" one. Relative telomere length (rTL) was measured in DNA isolated from whole blood by qPCR, and oxidative stress markers, such as Total Antioxidant Capacity (TAC) and 8-OHdG, were determined by spectrophotometry in serum samples. Long-lived birds had longer rTL than short-lived ones [1.308 ± 0.11 vs. 0.565 ± 0.13, (p < 0.001)]. On the contrary, short-lived birds showed more DNA damage than their counterparts [3.847 ± 0.351 vs. 2.012 ± 0.308, respectively, (p < 0.001)]. Old birds had shorter rTL than young ones, for both longevity groups (p < 0.001). Although no correlation was found between 8-OHdG levels and age, nor 8-OHdG and telomere length, long-lived birds exhibited 75.42-unit increased TAC levels when increased 8-OHdG concentrations (p = 0.046). These findings highlight distinct patterns of telomere length and oxidative stress influenced by lifespan strategies among avian longevity groups.},
}
@article {pmid39164231,
year = {2024},
author = {Ghosh, S and Nguyen, MT and Choi, HE and Stahl, M and Kühn, AL and Van der Auwera, S and Grabe, HJ and Völzke, H and Homuth, G and Myers, SA and Hogaboam, CM and Noth, I and Martinez, FJ and Petsko, GA and Glimcher, LH},
title = {RIOK2 transcriptionally regulates TRiC and dyskerin complexes to prevent telomere shortening.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {7138},
pmid = {39164231},
issn = {2041-1723},
mesh = {Humans ; *Idiopathic Pulmonary Fibrosis/genetics/metabolism/pathology ; *Telomere Shortening ; *Telomerase/metabolism/genetics ; *Nuclear Proteins/metabolism/genetics ; *Cell Cycle Proteins/metabolism/genetics ; Fibroblasts/metabolism ; Myelodysplastic Syndromes/genetics/metabolism ; Telomere/metabolism/genetics ; Gene Expression Regulation ; Lung/metabolism/pathology ; },
abstract = {Telomere shortening is a prominent hallmark of aging and is emerging as a characteristic feature of Myelodysplastic Syndromes (MDS) and Idiopathic Pulmonary Fibrosis (IPF). Optimal telomerase activity prevents progressive shortening of telomeres that triggers DNA damage responses. However, the upstream regulation of telomerase holoenzyme components remains poorly defined. Here, we identify RIOK2, a master regulator of human blood cell development, as a critical transcription factor for telomere maintenance. Mechanistically, loss of RIOK2 or its DNA-binding/transactivation properties downregulates mRNA expression of both TRiC and dyskerin complex subunits that impairs telomerase activity, thereby causing telomere shortening. We further show that RIOK2 expression is diminished in aged individuals and IPF patients, and it strongly correlates with shortened telomeres in MDS patient-derived bone marrow cells. Importantly, ectopic expression of RIOK2 alleviates telomere shortening in IPF patient-derived primary lung fibroblasts. Hence, increasing RIOK2 levels prevents telomere shortening, thus offering therapeutic strategies for telomere biology disorders.},
}
@article {pmid39159130,
year = {2024},
author = {Maimaiti, A and Ma, J and Hao, C and Han, D and Wang, Y and Wang, Z and Abudusalamu, R},
title = {DNA methylation-estimated phenotypes, telomere length and risk of ischemic stroke: epigenetic age acceleration of screening and a Mendelian randomization study.},
journal = {Aging},
volume = {16},
number = {},
pages = {},
doi = {10.18632/aging.206072},
pmid = {39159130},
issn = {1945-4589},
abstract = {BACKGROUND: Aging is a complex biological process that may be accelerated in certain pathological conditions. DNA methylation age (DNAmAge) has emerged as a biomarker for biological age, which can differ from chronological age. This research peels back the layers of the relationship between fast-forward aging and ischemic stroke, poking and prodding the potential two-way causal influences between stroke and biological aging indicators.<br><br>METHODS: We analyzed a cohort of ischemic stroke patients, comparing DNAmAge with chronological age to measure age acceleration. We assessed variations in age acceleration among stroke subtypes and between sexes. Using Mendelian randomization, we examined the causal links between stroke, aging biomarkers like telomere length, and age acceleration's effect on stroke risk.<br><br>RESULTS: Our investigation reveals a pronounced association between ischemic stroke and age acceleration, most notably in patients with cardioembolic strokes, who exhibited a striking median difference of 9 years between DNAmAge and chronological age. Furthermore, age acceleration differed significantly across stroke subtypes and was higher in women than in men. In terms of causality, MR analysis indicated a modest negative effect of stroke on telomere length, but no causal effect of age phenotypes on stroke or its subtypes. However, some indication of a potential causal effect of ischemic stroke on PhenoAge acceleration was observed.<br><br>CONCLUSION: The study provides insight into the relationship between DNAmAge and ischemic stroke, particularly cardioembolic stroke, and suggests possible gender differences. These insights carry profound clinical significance and set stage for future investigations into the entwined pathways of stroke and accelerated aging.},
}
@article {pmid39153550,
year = {2024},
author = {Wang, SM and Chang, HH and Chang, YH and Tsai, TY and Chen, PS and Lu, RB and Wang, TY},
title = {Shortening of telomere length may be associated with inflammatory cytokine levels in patients with bipolar disorder.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jad.2024.08.084},
pmid = {39153550},
issn = {1573-2517},
abstract = {BACKGROUND: Bipolar disorder (BD) is hypothesized to be associated with accelerated biological aging. Telomere length (TL) is a biomarker of aging, and although TL decreases with each cell division, the rate of telomere shortening may be affected by inflammation. We aimed to investigate whether TL is decreased in BD patients and to determine the association between TL and inflammatory markers in such patients.<br><br>METHODS: 137 BD patients and 118 healthy controls (HCs) were recruited. Leukocyte TL and plasma levels of cytokines [tumor necrosis factor (TNF)-&#x3b1;, interleukin (IL)-8, IL-6, IL-10, transforming growth factor (TGF)-&#x3b2;1], C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were assessed.<br><br>RESULTS: TL did not differ significantly between the BD patients and HCs after adjustment for potential confounding factors (P&#x202f;=&#x202f;0.79). TL was significantly negatively associated with age (&#x3b2;&#x202f;=&#x202f;-0.006, P&#x202f;<&#x202f;0.001). In addition, log TNF-&#x3b1; levels were significantly negatively associated with TL (P&#x202f;=&#x202f;0.009), in both the BD patients (P&#x202f;=&#x202f;0.02) and HCs (P&#x202f;=&#x202f;0.05).<br><br>CONCLUSION: We found a significant association between TNF-&#x3b1; levels and TL shortening in both BD patients and HCs. However, BD patients did not display increased TL shortening relative to HCs. Studies that involve larger sample sizes and control for the heterogeneity of BD participants will be needed.},
}
@article {pmid39151532,
year = {2024},
author = {Liu, H and Yan, W and Li, J and Luo, D and Yan, D},
title = {Causal relationship between telomere length and osteonecrosis: Bidirectional two-sample Mendelian randomization analysis.},
journal = {Medicine},
volume = {103},
number = {33},
pages = {e39324},
doi = {10.1097/MD.0000000000039324},
pmid = {39151532},
issn = {1536-5964},
mesh = {*Mendelian Randomization Analysis ; Humans ; *Genome-Wide Association Study ; *Osteonecrosis/genetics ; Telomere Shortening/genetics ; Telomere/genetics ; Genetic Predisposition to Disease ; },
abstract = {Recent mounting evidence suggests that shortening of telomere length (TL) is associated with impaired bone health; yet, a genetic causal relationship between TL and osteonecrosis remains uncertain. This study aimed to investigate the potential causal relationship between TL and osteonecrosis using bidirectional two-sample Mendelian randomization (MR). Genome-wide association study summary statistics for TL were sourced from the IEU Open genome-wide association study project, while osteonecrosis data were obtained from the FinnGen Biobank database. A range of MR methodologies-including inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode-were utilized for analysis, along with the MR-Egger intercept method for horizontal pleiotropy assessment, and Cochran Q and leave-one-out methods for heterogeneity testing. The forward MR analysis indicated a significant causal relationship between TL and osteonecrosis, suggesting that genetically predicted shorter TL is associated with an elevated risk of developing osteonecrosis (OR = 0.611, 95% confidence interval 0.394-0.948, P = .028). The reverse MR analysis revealed no significant influence of osteonecrosis on TL (OR = 0.999, 95% confidence interval 0.994-1.005, P = .802). Analyses for heterogeneity and horizontal pleiotropy yielded robust results. Our study demonstrates that individuals with shorter TL have an increased risk of developing osteonecrosis, whereas osteonecrosis has no effect on TL.},
}
@article {pmid39149261,
year = {2024},
author = {Porubsky, D and Dashnow, H and Sasani, TA and Logsdon, GA and Hallast, P and Noyes, MD and Kronenberg, ZN and Mokveld, T and Koundinya, N and Nolan, C and Steely, CJ and Guarracino, A and Dolzhenko, E and Harvey, WT and Rowell, WJ and Grigorev, K and Nicholas, TJ and Oshima, KK and Lin, J and Ebert, P and Watkins, WS and Leung, TY and Hanlon, VCT and McGee, S and Pedersen, BS and Goldberg, ME and Happ, HC and Jeong, H and Munson, KM and Hoekzema, K and Chan, DD and Wang, Y and Knuth, J and Garcia, GH and Fanslow, C and Lambert, C and Lee, C and Smith, JD and Levy, S and Mason, CE and Garrison, E and Lansdorp, PM and Neklason, DW and Jorde, LB and Quinlan, AR and Eberle, MA and Eichler, EE},
title = {A familial, telomere-to-telomere reference for human de novo mutation and recombination from a four-generation pedigree.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.08.05.606142},
pmid = {39149261},
issn = {2692-8205},
abstract = {Using five complementary short- and long-read sequencing technologies, we phased and assembled >95% of each diploid human genome in a four-generation, 28-member family (CEPH 1463) allowing us to systematically assess de novo mutations (DNMs) and recombination. From this family, we estimate an average of 192 DNMs per generation, including 75.5 de novo single-nucleotide variants (SNVs), 7.4 non-tandem repeat indels, 79.6 de novo indels or structural variants (SVs) originating from tandem repeats, 7.7 centromeric de novo SVs and SNVs, and 12.4 de novo Y chromosome events per generation. STRs and VNTRs are the most mutable with 32 loci exhibiting recurrent mutation through the generations. We accurately assemble 288 centromeres and six Y chromosomes across the generations, documenting de novo SVs, and demonstrate that the DNM rate varies by an order of magnitude depending on repeat content, length, and sequence identity. We show a strong paternal bias (75-81%) for all forms of germline DNM, yet we estimate that 17% of de novo SNVs are postzygotic in origin with no paternal bias. We place all this variation in the context of a high-resolution recombination map (∼3.5 kbp breakpoint resolution). We observe a strong maternal recombination bias (1.36 maternal:paternal ratio) with a consistent reduction in the number of crossovers with increasing paternal (r=0.85) and maternal (r=0.65) age. However, we observe no correlation between meiotic crossover locations and de novo SVs, arguing against non-allelic homologous recombination as a predominant mechanism. The use of multiple orthogonal technologies, near-telomere-to-telomere phased genome assemblies, and a multi-generation family to assess transmission has created the most comprehensive, publicly available "truth set" of all classes of genomic variants. The resource can be used to test and benchmark new algorithms and technologies to understand the most fundamental processes underlying human genetic variation.},
}
@article {pmid39147445,
year = {2024},
author = {Souza, MR and Garcia, ALH and Dalberto, D and Picinini, J and Touguinha, LBA and Salvador, M and da Silva, J},
title = {Multiple factors influence telomere length and DNA damage in individuals environmentally exposed to a coal-burning power plant.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {898},
number = {},
pages = {503793},
doi = {10.1016/j.mrgentox.2024.503793},
pmid = {39147445},
issn = {1879-3592},
mesh = {Humans ; Male ; *DNA Damage ; *Coal/adverse effects ; *Power Plants ; Middle Aged ; Adult ; *Environmental Exposure/adverse effects ; *Telomere/drug effects/genetics ; *Oxidative Stress/drug effects ; Telomere Shortening/drug effects ; Comet Assay ; Micronucleus Tests ; Coal Mining ; Occupational Exposure/adverse effects ; Aged ; Telomere Homeostasis/drug effects ; },
abstract = {Coal is a mixture of several chemicals, many of which have mutagenic and carcinogenic effects and are a key contributor to the global burden of mortality and disease. Previous studies suggest that coal is related to telomeric shortening in individuals occupationally exposed, however little is known about the effects of mining and burning coal on the telomeres of individuals living nearby. Therefore, the primary objective of this investigation was to assess the impact of proximity to coal power plants and coal mines on the genomic instability of individuals environmentally exposed, while also exploring potential associations with individual characteristics, oxidative stress, inflammatory responses, and the presence of inorganic elements. This study involved 80 men participants from three cities around a thermoelectric power plant and one city unexposed to coal and byproducts. DNA was extracted from peripheral blood samples obtained from each participant, and the telomeres length (TL) was assessed using quantitative real-time polymerase chain reaction (qPCR) methodology. No significant difference was observed between exposed individuals (6227 ± 2884 bp) when compared to the unexposed group (5638 ± 2452 bp). Nevertheless, TL decrease was associated with age and risk for cardiovascular disease; and longer TL was found to be linked with increased concentrations of silicon and phosphorus in blood samples. No correlations were observed between TL with comet assay (visual score), micronucleus test, oxidative stress, and inflammatory results. Additional research is required to ascertain the potential correlation between these changes and the onset of diseases and premature mortality.},
}
@article {pmid39147922,
year = {2024},
author = {Huang, G and Bao, Z and Feng, L and Zhai, J and Wendel, JF and Cao, X and Zhu, Y},
title = {A telomere-to-telomere cotton genome assembly reveals centromere evolution and a Mutator transposon-linked module regulating embryo development.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {39147922},
issn = {1546-1718},
support = {32388101//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32201747//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Assembly of complete genomes can reveal functional genetic elements missing from draft sequences. Here we present the near-complete telomere-to-telomere and contiguous genome of the cotton species Gossypium raimondii. Our assembly identified gaps and misoriented or misassembled regions in previous assemblies and produced 13 centromeres, with 25 chromosomal ends having telomeres. In contrast to satellite-rich Arabidopsis and rice centromeres, cotton centromeres lack phased CENH3 nucleosome positioning patterns and probably evolved by invasion from long terminal repeat retrotransposons. In-depth expression profiling of transposable elements revealed a previously unannotated DNA transposon (MuTC01) that interacts with miR2947 to produce trans-acting small interfering RNAs (siRNAs), one of which targets the newly evolved LEC2 (LEC2b) to produce phased siRNAs. Systematic genome editing experiments revealed that this tripartite module, miR2947-MuTC01-LEC2b, controls the morphogenesis of complex folded embryos characteristic of Gossypium and its close relatives in the cotton tribe. Our study reveals a trans-acting siRNA-based tripartite regulatory pathway for embryo development in higher plants.},
}
@article {pmid39145950,
year = {2024},
author = {da Cruz, NFS and Berrocal, AM},
title = {Genetic Testing for Rare Retinal Diseases in Telomere Biology Disorders.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2024.2947},
pmid = {39145950},
issn = {2168-6173},
}
@article {pmid39145097,
year = {2024},
author = {Liu, X and Wang, J and Su, D and Wang, Q and Li, M and Zuo, Z and Han, Q and Li, X and Zhen, F and Fan, M and Chen, T},
title = {Development and validation of a glioma prognostic model based on telomere-related genes and immune infiltration analysis.},
journal = {Translational cancer research},
volume = {13},
number = {7},
pages = {3182-3199},
pmid = {39145097},
issn = {2219-6803},
abstract = {BACKGROUND: Gliomas are the most prevalent primary brain tumors, and patients typically exhibit poor prognoses. Increasing evidence suggests that telomere maintenance mechanisms play a crucial role in glioma development. However, the prognostic value of telomere-related genes in glioma remains uncertain. This study aimed to construct a prognostic model of telomere-related genes and further elucidate the potential association between the two.<br><br>METHODS: We acquired RNA-seq data for low-grade glioma (LGG) and glioblastoma (GBM), along with corresponding clinical information from The Cancer Genome Atlas (TCGA) database, and normal brain tissue data from the Genotype-Tissue Expression (GTEX) database for differential analysis. Telomere-related genes were obtained from TelNet. Initially, we conducted a differential analysis on TCGA and GTEX data to identify differentially expressed telomere-related genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on these genes. Subsequently, univariate Cox analysis and log-rank tests were employed to obtain prognosis-related genes. Least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox regression analysis were sequentially utilized to construct prognostic models. The model's robustness was demonstrated using receiver operating characteristic (ROC) curve analysis, and multivariate Cox regression of risk scores for clinical characteristics and prognostic models were calculated to assess independent prognostic factors. The aforementioned results were validated using the Chinese Glioma Genome Atlas (CGGA) dataset. Finally, the CIBERSORT algorithm analyzed differences in immune cell infiltration levels between high- and low-risk groups, and candidate genes were validated in the Human Protein Atlas (HPA) database.<br><br>RESULTS: Differential analysis yielded 496 differentially expressed telomere-related genes. GO and KEGG pathway analyses indicated that these genes were primarily involved in telomere-related biological processes and pathways. Subsequently, a prognostic model comprising ten telomere-related genes was constructed through univariate Cox regression analysis, log-rank test, LASSO regression analysis, and multivariate Cox regression analysis. Patients were stratified into high-risk and low-risk groups based on risk scores. Kaplan-Meier (K-M) survival analysis revealed worse outcomes in the high-risk group compared to the low-risk group, and establishing that this prognostic model was a significant independent prognostic factor for glioma patients. Lastly, immune infiltration analysis was conducted, uncovering notable differences in the proportion of multiple immune cell infiltrations between high- and low-risk groups, and eight candidate genes were verified in the HPA database.<br><br>CONCLUSIONS: This study successfully constructed a prognostic model of telomere-related genes, which can more accurately predict glioma patient prognosis, offer potential targets and a theoretical basis for glioma treatment, and serve as a reference for immunotherapy through immune infiltration analysis.},
}
@article {pmid39145075,
year = {2024},
author = {Chen, H and Pan, Y and Lv, C and He, W and Wu, D and Xuan, Q},
title = {Telomere-related gene risk model for prognosis prediction in colorectal cancer.},
journal = {Translational cancer research},
volume = {13},
number = {7},
pages = {3495-3521},
pmid = {39145075},
issn = {2219-6803},
abstract = {BACKGROUND: Colorectal cancer (CRC) is the third-most prevalent cancer globally. The biological significance of telomeres in CRC carcinogenesis and progression is underscored by accumulating data. Nevertheless, not much is known about how telomere-related genes (TRGs) affect CRC prognosis. Therefore, the aim of this study was to investigate the role of TRGs in CRC prognosis.<br><br>METHODS: We retrospectively obtained the expression profiles and clinical data of CRC patients from public databases. Utilizing least absolute shrinkage and selection operator (LASSO) regression analysis, we created a telomere-related risk model to predict survival outcomes, identifying ten telomere-related differentially expressed genes (TRDEGs). Based on TRDEGs, we stratified patients from The Cancer Genome Atlas (TCGA) into low- and high-risk subsets. Subsequently, we conducted comprehensive analyses, including survival assessment, immune cell infiltration, drug sensitivity, and prediction of molecular interactions using Kaplan-Meier curves, ESTIMATE, CIBERSORT, OncoPredict, and other approaches.<br><br>RESULTS: The model showed exceptional predictive accuracy for survival. Significant differences in survival were observed between the two groups of participants grouped according to the model (P<0.001), and this difference was further confirmed in the external validation set (GSE39582) (P=0.004). Additionally, compared to the low-risk group, the high-risk group exhibited significantly advanced tumor node metastasis (TNM) stages, lower proportions of activated CD4[+] T cells, effector memory CD4[+] T cells, and memory B cells, but increased ratios of M2 macrophages and regulatory T cells (Tregs), elevated tumor immune dysfunction and exclusion (TIDE) scores, and diminished sensitivity to dabrafenib, lapatinib, camptothecin, docetaxel, and telomerase inhibitor IX, reflecting the signature's capacity to distinguish clinical pathological characteristics, immune environment, and drug efficacy. Finally, we validated the expression of the ten TRDEGs (ACACB, TPX2, SRPX, PPARGC1A, CD36, MMP3, NAT2, MMP10, HIGD1A, and MMP1) through quantitative real-time polymerase chain reaction (qRT-PCR) and found that compared to normal cells, the expression levels of ACACB, HIGD1A, NAT2, PPARGC1A, and TPX2 in CRC cells were elevated, whereas those of CD36, SRPX, MMP1, MMP3, and MMP10 were reduced.<br><br>CONCLUSIONS: Overall, we constructed a telomere-related biomarker capable of predicting prognosis and treatment response in CRC individuals, offering potential guidance for drug therapy selection and prognosis prediction.},
}
@article {pmid39141123,
year = {2024},
author = {Huang, W and Han, G and Taylor, BD and Neal, G and Kochan, K and Page, RL},
title = {Maternal peripheral blood telomere length and preterm birth in African American women: a pilot study.},
journal = {Archives of gynecology and obstetrics},
volume = {},
number = {},
pages = {},
pmid = {39141123},
issn = {1432-0711},
abstract = {PURPOSE: This study aimed to explore the association between preterm birth and telomere length of maternal peripheral blood in African American women.<br><br>METHODS: 78 African American women were recruited for this study between 2018 and 2023 from 2 prenatal clinics in central and east Texas. Participants provided blood samples and completed clinic questionnaires, with clinical data collected from their post-delivery medical records. Telomere length was measured using monochrome multiplex quantitative real-time polymerase chain reaction. Linear regression and multinomial logistic regression were used to analyze the association between telomere length and gestational length. Kruskal-Wallis's test and Fisher's exact test were used to compare preterm birth, early-term birth and full-term birth by telomere length, social-demographic characteristics, stress and discrimination.<br><br>RESULTS: The rates of preterm birth was higher in pregnant women with shorter telomeres. After adjusting for confounders, for every 10-units increase in the relative telomere-to-single-copy gene (T/S) ratio, gestational days increased by 1.090 days (90% CI 0.182, 1.997), and for every 10-units decrease in the T/S ratio, the odds of preterm birth was 2.664 (90% CI 1.064, 6.673) times greater than the odds of full-term birth. No statistically significant associations were observed between stress, discrimination, and either preterm birth or telomere length.<br><br>CONCLUSIONS: Maternal peripheral blood telomere shortening is associated with preterm birth, providing support to further explore the clinical utility of maternal telomere testing for prediction and early intervention of preterm birth and the study of biological mechanisms of spontaneous preterm birth.},
}
@article {pmid39137932,
year = {2024},
author = {Xerfan, EMS and Tempaku, PF and Tufik, S and Andersen, ML},
title = {The effects of the space environment on circadian rhythm and sleep in astronauts: An emphasis on the telomere length dynamics associated with sleep.},
journal = {Journal of sleep research},
volume = {},
number = {},
pages = {e14312},
doi = {10.1111/jsr.14312},
pmid = {39137932},
issn = {1365-2869},
support = {//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; //Associa&#xe7;&#xe3;o Fundo de Incentivo &#xe0; Pesquisa/ ; #2020/13467-8//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; },
}
@article {pmid39127691,
year = {2024},
author = {Chen, Y and Zhang, X and Wang, L and Fang, M and Lu, R and Ma, Y and Huang, Y and Chen, X and Sheng, W and Shi, L and Zheng, Z and Qiu, Y},
title = {Telomere-to-telomere genome assembly of Eleocharis dulcis and expression profiles during corm development.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {869},
pmid = {39127691},
issn = {2052-4463},
mesh = {*Telomere/genetics ; *Genome, Plant ; *Eleocharis/genetics/growth &amp; development ; Transcriptome ; },
abstract = {Eleocharis dulcis (Burm. f.) Trin. ex Hensch., commonly known as Chinese water chestnut, is a traditional aquatic vegetable in China, and now is widely cultivated throughout the world because of its high nutritional value and unique tastes. Here, we report the assembly of a 493.24 Mb telomere-to-telomere (T2T) genome of E. dulcis accomplished by integrating ONT ultra-long reads, PacBio long reads and Hi-C data. The reference genome was anchored onto 111 gap-free chromosomes, containing 48.31% repeat elements and 33,493 predicted protein-coding genes. Whole genome duplication (WGD) and inter-genomic synteny analyses indicated that chromosome breakage and genome duplication in E. dulcis possibly occurred multiple times during genome evolution after its divergence from a common ancestor with Rhynchospora breviuscula at ca. 35.6 Mya. A comparative time-course transcriptome analysis of corm development revealed different patterns of gene expression between cultivated and wild accessions with the highest number of differentially expressed genes (DEGs, 15,870) at the middle swelling stage and some of the DEGs were significantly enriched for starch metabolic process.},
}
@article {pmid39125728,
year = {2024},
author = {Boniewska-Bernacka, E and Pańczyszyn, A and Głąb, G and Goc, A},
title = {Telomere Length, Telomerase Activity, and Vaginal Microbiome in Patients with HPV-Related Precancerous Lesions.},
journal = {International journal of molecular sciences},
volume = {25},
number = {15},
pages = {},
doi = {10.3390/ijms25158158},
pmid = {39125728},
issn = {1422-0067},
support = {P-2023-007//Institute of Medical Sciences, University of Opole, Opole, Poland./ ; },
mesh = {Humans ; Female ; *Telomerase/metabolism/genetics ; *Vagina/microbiology/virology ; *Microbiota/genetics ; *Papillomavirus Infections/virology/complications/genetics ; Adult ; *Telomere/metabolism/genetics ; Middle Aged ; *Precancerous Conditions/virology/microbiology/genetics/pathology ; *Uterine Cervical Neoplasms/virology/microbiology/genetics/pathology ; Telomere Homeostasis ; Papillomaviridae/genetics ; },
abstract = {Persistent high-risk human papillomaviruses (HR HPVs) infection leads to the development of squamous intraepithelial lesions in cervical cells that may lead to cancer. The telomere length, telomerase activity, and species composition of the vaginal microbiome may influence the dynamic of changes and the process of carcinogenesis. In the present study, we analyze relative telomere length (RTL), relative hTERT expression (gene for the telomerase component-reverse transcriptase) in cervical smear cells and vaginal microbiomes. Total RNA and DNA were isolated from tissue samples of 109 patients from the following groups: control, carrier, low-grade or high-grade squamous intraepithelial lesion (L SIL and H SIL, respectively), and cancer. The quantitative PCR method was used to measure telomere length and telomerase expression. Vaginal microbiome bacteria were divided into community state types using morphotype criteria. Significant differences between histopathology groups were confirmed for both relative telomere length and relative hTERT expression (p < 0.001 and p = 0.001, respectively). A significant difference in RTL was identified between carriers and H SIL (p adj < 0.001) groups, as well as between carriers and L SIL groups (p adj = 0.048). In both cases, RTL was lower among carriers. The highest relative hTERT expression level was recorded in the H SIL group, and the highest relative hTERT expression level was recorded between carriers and the H SIL group (p adj < 0.001). A correlation between genotype and biocenosis was identified for genotype 16+A (p < 0.001). The results suggest that identification of HPV infection, telomere length assessment, and hTERT expression measurement together may be more predictive than each of these analyses performed separately.},
}
@article {pmid39125404,
year = {2024},
author = {Baliou, S and Ioannou, P and Apetroaei, MM and Vakonaki, E and Fragkiadaki, P and Kirithras, E and Tzatzarakis, MN and Arsene, AL and Docea, AO and Tsatsakis, A},
title = {The Impact of the Mediterranean Diet on Telomere Biology: Implications for Disease Management-A Narrative Review.},
journal = {Nutrients},
volume = {16},
number = {15},
pages = {},
doi = {10.3390/nu16152525},
pmid = {39125404},
issn = {2072-6643},
mesh = {Humans ; *Diet, Mediterranean ; *Telomere ; Telomere Homeostasis ; Telomere Shortening ; Aging ; Telomerase/metabolism ; Disease Management ; Oxidative Stress ; Polyphenols ; Autoimmune Diseases ; },
abstract = {INTRODUCTION: Telomeres are nucleoprotein complexes at the ends of chromosomes that are under the control of genetic and environmental triggers. Accelerated telomere shortening is causally implicated in the increasing incidence of diseases. The Mediterranean diet has recently been identified as one that confers protection against diseases. This review aimed to identify the effect of each component of the Mediterranean diet on telomere length dynamics, highlighting the underlying molecular mechanisms.<br><br>METHODS: PubMed was searched to identify relevant studies to extract data for conducting a narrative review.<br><br>RESULTS: The Mediterranean diet alleviates clinical manifestations in many diseases. Focusing on autoimmune diseases, the Mediterranean diet can be protective by preventing inflammation, mitochondrial malfunction, and abnormal telomerase activity. Also, each Mediterranean diet constituent seems to attenuate aging through the sustenance or elongation of telomere length, providing insights into the underlying molecular mechanisms. Polyphenols, vitamins, minerals, and fatty acids seem to be essential in telomere homeostasis, since they inhibit inflammatory responses, DNA damage, oxidative stress, mitochondrial malfunction, and cell death and induce telomerase activation.<br><br>CONCLUSIONS: The Mediterranean diet is beneficial for maintaining telomere dynamics and alleviating age-related illnesses. This review provides a comprehensive overview of cross-sectional, observational, and randomized controlled trials regarding the beneficial impact of every constituent in the Mediterranean diet on telomere length and chronic disease management.},
}
@article {pmid39118803,
year = {2024},
author = {Samadi, FM and Suhail, S and Sonam, M and Ahmad, MK and Kumar, V and Chandra, S and Mohammad, S},
title = {Comparing Length and Telomere Expression at Oral Precancerous and Cancerous Stages.},
journal = {Iranian journal of pathology},
volume = {19},
number = {2},
pages = {146-151},
doi = {10.30699/IJP.2024.1996330.3081},
pmid = {39118803},
issn = {1735-5303},
abstract = {BACKGROUND &amp; OBJECTIVE: Telomeres consist of repetitive G-rich nucleotides located at the end of each chromosome, acting as protein binding sites. The aim of this study was to examine the differences in telomere length in blood, saliva, and tissue samples at various stages of oral precancerous and cancerous lesions.<br><br>METHODS: Samples of blood, tissue, and saliva were collected from patients with oral precancerous and cancerous lesions. DNA extraction was performed. Then, a TRAP assay was conducted to assess and compare the telomere length and telomerase expression.<br><br>RESULTS: The levels of telomerase activity (TA) in the DNA samples ranged from 0.19 to 6.91 (2.05+1.37) among oral squamous cell carcinoma (OSCC) patients and from 0.17 to 4.5 (0.28+4.25) among precancerous patients. A significant difference was observed in TA levels between OSCC and precancerous samples (t=3.9691, P= 0.0000).<br><br>CONCLUSION: Assessing the telomerase activity is crucial for studying the behavior of carcinoma in the clinical setting. The augmented telomerase expression and the length of telomere contribute to OSCC progression. Hence, this study adds a diagnostic tool that can serve as a biomarker for the early detection and prognosis of OSCC.},
}
@article {pmid39116978,
year = {2024},
author = {Sun, S and Ma, W and Mi, C and Mao, P},
title = {Telomerase reverse transcriptase, a telomere length maintenance protein in alfalfa (Medicago sativa), confers Arabidopsis thaliana seeds aging tolerance via modulation of telomere length.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {134388},
doi = {10.1016/j.ijbiomac.2024.134388},
pmid = {39116978},
issn = {1879-0003},
abstract = {Numerous studies have investigated seed aging, with a particular emphasis on the involvement of reactive oxygen species. Reactive oxygen species diffuse into the nucleus and damage telomeres, resulting in loss of genetic integrity. Telomerase reverse transcriptase (TERT) plays an essential role in maintaining plant genomic stability. Genome-wide analyses of TERT genes in alfalfa (Medicago sativa) have not yet been conducted, leaving a gap in our understanding of the mechanisms underlying seed aging associated with TERT genes. In this study, four MsTERT genes were identified in the alfalfa genome. The expression profiles of the four MsTERT genes during seed germination indicated that MS. gene79077 was significantly upregulated by seed aging. Transgenic seeds overexpressing MS. gene79077 in Arabidopsis exhibited enhanced tolerance to seed aging by reducing the levels of H2O2 and increasing telomere length and telomerase activity. Furthermore, transcript profiling of aging-treated Arabidopsis wild-type and overexpressing seeds showed an aging response in genes related to glutathione-dependent detoxification and antioxidant defense pathways. These results revealed that MS. gene79077 conferred Arabidopsis seed-aging tolerance via modulation of antioxidant defense and telomere homeostasis. This study provides a new way to understand stress-responsive MsTERT genes for the potential genetic improvement of seed vigor.},
}
@article {pmid39113664,
year = {2024},
author = {Li, Y and Sági-Kiss, V and James, ELN and Dokal, I and Parkinson, KE and Bundy, JG},
title = {Nucleotide sugars correlate with leukocyte telomere length as part of a dyskeratosis congenita metabolomic plasma signature.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2023.284721},
pmid = {39113664},
issn = {1592-8721},
abstract = {Not available.},
}
@article {pmid39113075,
year = {2024},
author = {Virseda-Berdices, A and Behar-Lagares, R and Martínez-González, O and Blancas, R and Bueno-Bustos, S and Brochado-Kith, O and Manteiga, E and Mallol Poyato, MJ and López Matamala, B and Martín Parra, C and Resino, S and Jiménez-Sousa, M&#xc1; and Fernández-Rodríguez, A},
title = {Longer ICU stay and invasive mechanical ventilation accelerate telomere shortening in COVID-19 patients 1 year after recovery.},
journal = {Critical care (London, England)},
volume = {28},
number = {1},
pages = {267},
pmid = {39113075},
issn = {1466-609X},
support = {1.013.005//Fundaci&#xf3;n Universidad Alfonso X el Sabio/ ; CB21/13/00044//CIBER - Consorcio Centro de Investigaci&#xf3;n Biom&#xe9;dica en Red-(CB 2021), Instituo de Salud Carlos III, Ministerio de Ciencia e Innovaci&#xf3;n and Uni&#xf3;n Europea - NextGenerationEU/ ; COV20/1144//Instituto de Salud Carlos III/ ; },
abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed.},
}
@article {pmid39110381,
year = {2024},
author = {Vazquez-Moreno, M and Perales-Herrera, A and Ramírez-Silva, I and Martínez-Gómez, LE and García-Cerón, A and Paredes-Barrientos, JC and Hernández-Mendoza, H and Martinez-Garza, S and Murillo-Ortiz, B and Cruz, M},
title = {Dietary Zinc Intake and the Association of Insulin Level and HOMA-IR with Telomere Shortening in Mexican Children.},
journal = {Biological trace element research},
volume = {},
number = {},
pages = {},
pmid = {39110381},
issn = {1559-0720},
support = {FIS/IMSS/PROT/PRIO/ 18/079//Instituto Mexicano del Seguro Social/ ; },
abstract = {PURPOSE: The relationship between dietary zinc (Zn) intake, metabolic diseases, and telomere length has been little explored in the children population. This observational cross-sectional study assesses the association between obesity (OB), cardiometabolic traits, telomere length, and dietary Zn intake in children with normal weight (NW) and OB from Mexico City.<br><br>METHODS: Anthropometric data, blood pressure, biochemical measurements, the homeostatic model assessment of insulin resistance (HOMA-IR) and leucocyte telomere length (determined by quantitative-PCR) were analyzed in 171 children with NW and 172 with OB. Furthermore, dietary Zn intake was evaluated in 117 children NW and 120 with OB.<br><br>RESULTS: Telomere shortening was associated with fasting plasma insulin (FPI) and HOMA-IR in NW (beta coefficient [&#x3b2;]FPI&#x2009;=&#x2009;-0.022&#x2009;&#xb1;&#x2009;0.008, p&#x2009;=&#x2009;0.009; &#x3b2;HOMA-IR&#x2009;=&#x2009;-0.096&#x2009;&#xb1;&#x2009;0.040, p&#x2009;=&#x2009;0.020) and OB (&#x3b2;FPI&#x2009;=&#x2009;-0.007&#x2009;&#xb1;&#x2009;0.002,&#xa0;p&#x2009;=&#x2009;0.003; &#x3b2;HOMA-IR&#x2009;=&#x2009;-0.034&#x2009;&#xb1;&#x2009;0.012,&#xa0;p&#x2009;=&#x2009;0.005) children. Dietary Zn intake resulted negatively associated with FPI (&#x3b2;&#x2009;=&#x2009;-2.418&#x2009;&#xb1;&#x2009;0.764, p&#x2009;=&#x2009;0.002) and HOMA-IR (&#x3b2;&#x2009;=&#x2009;-0.399&#x2009;&#xb1;&#x2009;0.014, p&#x2009;=&#x2009;0.009) in children with OB. Then, in children with OB, the association between FPI, HOMA-IR, and telomere shortening was evaluated separately in groups of low, medium, and high dietary Zn intake (according to tertiles). The association between FPI, HOMA-IR, and telomere shortening was not significant in the high Zn intake group (PFPI&#x2009;=&#x2009;0.633; PHOMA-IR&#x2009;=&#x2009;0.567).<br><br>CONCLUSION: Our results suggest that a high Zn intake may ameliorate the telomere shortening related to high FPI and HOMA-IR.},
}
@article {pmid39109967,
year = {2024},
author = {Feng, J and Zhang, W and Chen, C and Liang, Y and Li, T and Wu, Y and Liu, H and Wu, J and Lin, W and Li, J and He, Y and He, J and Luan, A},
title = {The pineapple reference genome: Telomere-to-telomere assembly, manually curated annotation, and comparative analysis.},
journal = {Journal of integrative plant biology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jipb.13748},
pmid = {39109967},
issn = {1744-7909},
support = {32272677//National Natural Science Foundation of China/ ; 2019YFD1001104//National Key R&amp;D Program of China/ ; 1630032024026//Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences/ ; 1630032024001//Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences/ ; 1630052023011//Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences/ ; 323QN279//Hainan Provincial Natural Science Foundation of China/ ; },
abstract = {Pineapple is the third most crucial tropical fruit worldwide and available in five varieties. Genomes of different pineapple varieties have been released to date; however, none of them are complete, with all exhibiting substantial gaps and representing only two of the five pineapple varieties. This significantly hinders the advancement of pineapple breeding efforts. In this study, we sequenced the genomes of three varieties: a wild pineapple variety, a fiber pineapple variety, and a globally cultivated edible pineapple variety. We constructed the first gap-free reference genome (Ref) for pineapple. By consolidating multiple sources of evidence and manually revising each gene structure annotation, we identified 26,656 protein-coding genes. The BUSCO evaluation indicated a completeness of 99.2%, demonstrating the high quality of the gene structure annotations in this genome. Utilizing these resources, we identified 7,209 structural variations across the three varieties. Approximately 30.8% of pineapple genes were located within ±5 kb of structural variations, including 30 genes associated with anthocyanin synthesis. Further analysis and functional experiments demonstrated that the high expression of AcMYB528 aligns with the accumulation of anthocyanins in the leaves, both of which may be affected by a 1.9-kb insertion fragment. In addition, we developed the Ananas Genome Database, which offers data browsing, retrieval, analysis, and download functions. The construction of this database addresses the lack of pineapple genome resource databases. In summary, we acquired a seamless pineapple reference genome with high-quality gene structure annotations, providing a solid foundation for pineapple genomics and a valuable reference for pineapple breeding.},
}
@article {pmid39108072,
year = {2024},
author = {Biswas, A and Bhattacharya, M and Ghosh, P and Dey, SK},
title = {Role of Telomere Length in Radiation Response of Hematopoietic Stem &amp; Progenitor Cells in Newborns.},
journal = {Fetal and pediatric pathology},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/15513815.2024.2381752},
pmid = {39108072},
issn = {1551-3823},
abstract = {OBJECTIVE: Wide inter-individual variations in ionizing radiation (IR) responses of neonatal hematopoietic system calls for identifying reliable biomarkers to effectively estimate radiation exposure damages in neonates.<br><br>METHODS: Association between telomere length (TL) at birth and radiation sensitivity of cord blood hematopoietic stem cells (HSC) from 166 healthy newborns were investigated by assessing their clonogenic differentiation. TL was determined as terminal restriction fragment (TRF) by Southern blot method.<br><br>RESULTS: TL correlated with surviving fractions of total progenitor colony forming cell (CFC) content at 0.75&#x2009;Gy (p&#x2009;<&#x2009;0.05), granulo-macrophagic lineage colony forming units (CFU-GM) at 0.75&#x2009;Gy (p&#x2009;<&#x2009;0.05) and erythroid burst forming unit (BFU-E) at 0.75&#x2009;Gy (p&#x2009;<&#x2009;0.05) &amp; at 3&#x2009;Gy (p&#x2009;<&#x2009;0.05) of newborns.<br><br>CONCLUSION: Our results indicate risks for HSC clonogenic survival in neonates with shorter telomeres after IR exposure. These observations might aid in considering TL at birth as an assessment factor for radiation related hematopoietic challenges in children.},
}
@article {pmid39107495,
year = {2024},
author = {Nai, S and Wang, M and Yang, J and Ling, B and Dong, Q and Yang, X and Du, X and Lu, M and Liu, L and Yu, Z and Chen, L},
title = {Novel role for Ddx39 in differentiation and telomere length regulation of embryonic stem cells.},
journal = {Cell death and differentiation},
volume = {},
number = {},
pages = {},
pmid = {39107495},
issn = {1476-5403},
abstract = {Erk signaling is indispensable for the self-renewal and differentiation of mouse embryonic stem cells (ESCs), as well as telomere homeostasis. But how Erk regulates these biological processes remains unclear. We identified 132 Erk2 interacting proteins by co-immunoprecipitation and mass spectrometric analysis, and focused on Ddx39 as a potential Erk2 substrate. We demonstrated that Erk2 phosphorylates Ddx39 on Y132 and Y138. Ddx39 knockout (KO) ESCs are defective in differentiation, due to reduced H3K27ac level upon differentiation. Phosphorylation of Ddx39 promotes the recruitment of Hat1 to acetylate H3K27 and activate differentiation genes. In addition, Ddx39 KO leads to telomere elongation in ESCs. Ddx39 is recruited to telomeres by the telomere-binding protein Trf1, consequently disrupting the DNA loop formed by Trf1 and suppressing the alternative lengthening of telomeres (ALT). Phosphorylation of Ddx39 weakens its interaction with Trf1, releasing it from telomeres. Thus, ALT activity is enhanced, and telomeres are elongated. Altogether, our studies reveal an essential role of Ddx39 in the differentiation and telomere homeostasis of ESCs.},
}
@article {pmid39103182,
year = {2024},
author = {Strauss, JD and Brown, DW and Zhou, W and Dagnall, C and Yuan, JM and Im, A and Savage, SA and Wang, Y and Rafati, M and Spellman, SR and Gadalla, SM},
title = {Telomere length and clonal chromosomal alterations in peripheral blood of patients with severe aplastic anaemia.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.19681},
pmid = {39103182},
issn = {1365-2141},
support = {75N910D00024/CA/NCI NIH HHS/United States ; U24CA076518/CA/NCI NIH HHS/United States ; N00014-21-1-2954//Office of Naval Research/ ; N00014-23-1-2057//Office of Naval Research/ ; HHSH250201700006C/HRSA/HRSA HHS/United States ; //National Marrow Donor Program/ ; },
abstract = {Severe aplastic anaemia (SAA) is a rare and life-threatening bone marrow failure disorder. We used data from the transplant outcomes in aplastic anaemia study to characterize mosaic chromosomal alterations (mCAs) in the peripheral blood of 738 patients with acquired SAA and evaluate their associations with telomere length (TL) and survival post-haematopoietic cell transplant (HCT). The median age at HCT was 20.4 years (range = 0.2-77.4). Patients with SAA had shorter TL than expected for their age (median TL percentile for age: 35.7th; range <1-99.99). mCAs were detected in 211 patients (28.6%), with chr6p copy-neutral loss of heterozygosity (6p-CNLOH) in 15.9% and chr7 loss in 3.0% of the patients; chrX loss was detected in 4.1% of female patients. Negative correlations between mCA cell fraction and measured TL (r = -0.14, p = 0.0002), and possibly genetically predicted TL (r = -0.07, p = 0.06) were noted. The post-HCT 3-year survival probability was low in patients with chr7 loss (39% vs. 72% in patients with chr6-CNLOH, 60% in patients with other mCAs and 70% in patients with no mCAs; p-log rank = 0.001). In multivariable analysis, short TL (p = 0.01), but not chr7 loss (p = 0.29), was associated with worse post-HCT survival. TL may guide clinical decisions in patients with SAA.},
}
@article {pmid39103649,
year = {2024},
author = {Kalbfleisch, TS and McKay, SD and Murdoch, BM and Adelson, DL and Almansa-Villa, D and Becker, G and Beckett, LM and Benítez-Galeano, MJ and Biase, F and Casey, T and Chuong, E and Clark, E and Clarke, S and Cockett, N and Couldrey, C and Davis, BW and Elsik, CG and Faraut, T and Gao, Y and Genet, C and Grady, P and Green, J and Green, R and Guan, D and Hagen, D and Hartley, GA and Heaton, M and Hoyt, SJ and Huang, W and Jarvis, E and Kalleberg, J and Khatib, H and Koepfi, KP and Koltes, J and Koren, S and Kuehn, C and Leeb, T and Leonard, A and Liu, GE and Low, WY and McConnell, H and McRae, K and Miga, K and Mousel, M and Neibergs, H and Olagunju, T and Pennell, M and Petry, B and Pewsner, M and Phillippy, AM and Pickett, BD and Pineda, P and Potapova, T and Rachagani, S and Rhie, A and Rijnkels, M and Robic, A and Rodriguez Osorio, N and Safonova, Y and Schettini, G and Schnabel, RD and Sirpu Natesh, N and Stegemiller, M and Storer, J and Stothard, P and Stull, C and Tosser-Klopp, G and Traglia, GM and Tuggle, CK and Van Tassell, CP and Watson, C and Weikard, R and Wimmers, K and Xie, S and Yang, L and Smith, TPL and O'Neill, RJ and Rosen, BD},
title = {The Ruminant Telomere-to-Telomere (RT2T) Consortium.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {39103649},
issn = {1546-1718},
support = {Grant Number 2023-67015-39000//United States Department of Agriculture | Agricultural Research Service (USDA Agricultural Research Service)/ ; },
abstract = {Telomere-to-telomere (T2T) assemblies reveal new insights into the structure and function of the previously 'invisible' parts of the genome and allow comparative analyses of complete genomes across entire clades. We present here an open collaborative effort, termed the 'Ruminant T2T Consortium' (RT2T), that aims to generate complete diploid assemblies for numerous species of the Artiodactyla suborder Ruminantia to examine chromosomal evolution in the context of natural selection and domestication of species used as livestock.},
}
@article {pmid39100478,
year = {2024},
author = {Wang, Y and Sun, F and Yue, C and Man, Q},
title = {Peripheral blood leukocyte Telomere length and endometriosis: A Mendelian randomization study.},
journal = {Heliyon},
volume = {10},
number = {14},
pages = {e33854},
pmid = {39100478},
issn = {2405-8440},
abstract = {BACKGROUND: The link between peripheral blood leukocyte telomere length (LTL) and endometriosis has remained uncertain. In order to investigate this association, a two-sample Mendelian randomization(MR) analysis was performed.<br><br>METHODS: We extracted Single-nucleotide polymorphisms (SNPs) associated with LTL from a published genome-wide association study (GWAS) comprising 472,174 individuals. Data on endometriosis, including its seven subtypes, were sourced from the iue open gwas project. Four methods were employed for MR: Inverse-variance weighted analysis (IVW), Mendelian randomization-Egger regression (MR Egger), weighted-median analysis, and Weighted Mode.<br><br>RESULTS: Genetically determined LTL was identified as a factor that can promote the occurrence of endometriosis. With every 1-SD increase in LTL, the risk of endometriosis increased by 26&#xa0;% (OR&#xa0;=&#xa0;1.260, 95&#xa0;% CI&#xa0;=&#xa0;1.073 to 1.479; P&#xa0;=&#xa0;0.005). Genetically determined LTL also contributed to endometriosis subtypes: intestine (OR&#xa0;=&#xa0;3.584, 95&#xa0;% CI&#xa0;=&#xa0;1.597 to 8.041; P&#xa0;=&#xa0;0.002), ovary (OR&#xa0;=&#xa0;1.308, 95&#xa0;% CI&#xa0;=&#xa0;1.033 to 1.655; P&#xa0;=&#xa0;0.026), rectovaginal septum and vagina (OR&#xa0;=&#xa0;1.360, 95&#xa0;% CI&#xa0;=&#xa0;1.000 to 1.851; P&#xa0;=&#xa0;0.049). There was no observed causal relationship between LTL and the other four subtypes.<br><br>CONCLUSION: This study, utilizing genetic data, offers evidence that longer LTL may cause increased risks of endometriosis, specifically endometriosis of the intestine, ovary, rectovaginal septum and vagina. These findings not only suggest that LTL may serve as a predictive factor for assessing the prevalence of three endometriosis subtypes but also provide new insights into the study of endometriosis pathogenesis.},
}
@article {pmid39097069,
year = {2024},
author = {Sun, S and Ma, W and Mao, P},
title = {Overexpression of protection of telomeres 1 (POT1), a single-stranded DNA-binding proteins in alfalfa (Medicago sativa), enhances seed vigor.},
journal = {International journal of biological macromolecules},
volume = {277},
number = {Pt 3},
pages = {134300},
doi = {10.1016/j.ijbiomac.2024.134300},
pmid = {39097069},
issn = {1879-0003},
abstract = {Extensive bodies of research are dedicated to the study of seed aging with a particular focus on the roles of reactive oxygen species (ROS), and the ensuing oxidative damage during storage, as a primary cause of seed vigor decreasing. ROS diffuse to the nucleus and damage the telomeres, resulting in a loss of genetic integrity. Protection of telomeres 1 (POT1) is a telomeric protein that binds to the telomere region, and plays an essential role in maintaining genomic stability in plants. In this study, there were totally four MsPOT1 genes obtained from alfalfa genome. Expression analysis of four MsPOT1 genes in germinated seed presented the different expressions. Four MsPOT1 genes displayed high expression levels at the early stage of seed germination, Among the four POT1 genes, it was found that MS. gene040108 was significantly up-regulated in the early germination stage of CK seeds, but down-regulated in aged seeds. RT-qPCR assays and RNA-seq data revealed that MsPOT1-X gene was significantly induced by seed aging treatment. Transgenic seeds overexpressing MsPOT1-X gene in Arabidopsis thaliana and Medicago trunctula exhibited enhanced seed vigor, telomere length, telomerase activity associated with reduced H2O2 content. These results would provide a new way to understand aging stress-responsive MsPOT1 genes for genetic improvement of seed vigor. Although a key gene regulating seed vigor was identified in this study, the specific mechanism of MsPOT1-X gene regulating seed vigor needs to be further explored.},
}
@article {pmid39096784,
year = {2024},
author = {Amatya, S and Bhatia, P and Raina, S and Sreedharanunni, S and Singh, M and Rahman, E and Archana, MV and Trehan, A},
title = {Clinical utility of relative telomere length analysis in pediatric bone marrow failure.},
journal = {Blood cells, molecules &amp; diseases},
volume = {109},
number = {},
pages = {102882},
doi = {10.1016/j.bcmd.2024.102882},
pmid = {39096784},
issn = {1096-0961},
abstract = {INTRODUCTION: Telomere length related studies are limited in pediatric marrow failure cases due to difficulty in establishing population specific age related normograms. Moreover, there is paucity of data related to clinical relevance of telomere length in idiopathic aplastic anemia (IAA) and non telomere biology inherited bone marrow failure syndrome (IBMFS) cases.<br><br>METHODOLOGY: Hence, in current study we investigated Relative telomere length (RTL) by RQ-PCR in 83 samples as: healthy controls (n&#xa0;=&#xa0;44), IAA (n&#xa0;=&#xa0;15) and IBMFS (n&#xa0;=&#xa0;24). In addition, we performed chromosomal breakage studies and targeted NGS to screen for pathogenic variants.<br><br>RESULTS &amp; CONCLUSION: Median RTL was significantly different between control vs. IBMFS (p-0.002), IAA vs. IBMFS (p-0.0075) and DC vs. non-DC IBMFS (p-0.011) but not between control vs. IAA (p-0.46). RTL analysis had clinical utility in differentiating BMF cases as 75&#xa0;% (9/12) of DC had short/very short telomeres compared to only 17&#xa0;% (2/12) of non-DC IBMFS, 7&#xa0;% (1/15) of IAA and 7&#xa0;% (3/44) of controls (p&#xa0;<&#xa0;0.001).},
}
@article {pmid39095379,
year = {2024},
author = {Li, M and Chen, C and Wang, H and Qin, H and Hou, S and Yang, X and Jian, J and Gao, P and Liu, M and Mu, Z},
title = {Telomere-to-telomere genome assembly of sorghum.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {835},
pmid = {39095379},
issn = {2052-4463},
mesh = {*Sorghum/genetics ; *Genome, Plant ; *Telomere/genetics ; },
abstract = {"Cuohu Bazi" (CHBZ) is an ancient sorghum variety collected from the fields of China, known for its agronomic traits like dwarf stature, early maturation. In this study, we present the first telomere-to-telomere (T2T) and gap-free genome assembly of CHBZ using PacBio HiFi reads, Oxford Nanopore Technologies, and Hi-C data. The assembled genome comprises 724.85 Mb, effectively resolving all 3,913 gaps that were present in the previous sorghum BTx623 reference genome. Notably, the T2T assembly captures 10 centromeres and all 20 telomeres, providing strong support for their integrity. This assembly is of high quality in terms of contiguity (contig N50: 71.1 Mb), completeness (BUSCO score: 99.01%, k-mer completeness: 98.88%), and correctness (QV: 61.60). Repetitive sequences accounted for 70.41% of the genome and a total of 32,855 protein-coding genes have been annotated. Furthermore, 161 CHBZ-specific presence/absence variants genes have been identified when comparing to BTx623 genome. This study provides valuable insights for future research on sorghum genetics, genomics, and evolutionary history.},
}
@article {pmid39093267,
year = {2024},
author = {McCullough, KB and Vege, SS and Mangaonkar, AA and Ferrer, A and Patnaik, MM},
title = {Pancreatitis as a Potential Consequence of Danazol Therapy for Telomere Biology Disorders.},
journal = {Mayo Clinic proceedings},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.mayocp.2024.03.019},
pmid = {39093267},
issn = {1942-5546},
}
@article {pmid39087945,
year = {2024},
author = {He, X and Cao, L and Fu, X and Wu, Y and Wen, H and Gao, Y and Huo, W and Wang, M and Liu, M and Su, Y and Liu, G and Zhang, M and Hu, F and Hu, D and Zhao, Y},
title = {The association between telomere length and diabetes mellitus: accumulated evidence from observational studies.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1210/clinem/dgae536},
pmid = {39087945},
issn = {1945-7197},
abstract = {OBJECTIVE: In order to assess the associations between telomere length (TL) and diabetes mellitus (DM), especially type 2 diabetes (T2DM), we performed this systematic review and meta-analysis.<br><br>METHODS: PubMed, Embase, and Web of Science were thoroughly searched up to July 11, 2023. The pooled standardized mean difference (SMD) and the 95% confidence interval (CI) were evaluated using the random-effects model. Age, sex, study design, duration of diabetes, region, sample size, and body mass index (BMI) were used to stratify subgroup analyses.<br><br>RESULTS: A total of 37 observational studies involving 18,181 participants from 14 countries were included in the quantitative meta-analysis. In this study, patients with diabetes had shorter TL than the non-diabetic, whether those patients had T1DM (-2.70; 95% CI: -4.47, -0.93; P<0.001), T2DM (-3.70; 95% CI: -4.20, -3.20; P<0.001), or other types of diabetes (-0.71; 95% CI: -1.10, -0.31; P<0.001). Additionally, subgroup analysis of T2DM showed that TL was significantly correlated with age, sex, study design, diabetes duration, sample size, detection method, region, and BMI.<br><br>CONCLUSION: A negative correlation was observed between TL and DM. To validate this association in the interim, more extensive, superior prospective investigations and clinical trials are required.},
}
@article {pmid39086950,
year = {2024},
author = {Zhu, S and Hao, Z and Chen, Q and Liu, X and Wu, W and Luo, Y and Zhang, F},
title = {Casual effects of telomere length on sarcoidosis: a bidirectional Mendelian randomization analysis.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1408980},
pmid = {39086950},
issn = {2296-858X},
abstract = {BACKGROUND: Telomere length, crucial for genomic stability, have been implicated in various inflamm-aging diseases, but their role in sarcoidosis remains unexplored.<br><br>OBJECTIVE: This study aims to explore the casual effects between TL and sarcoidosis via a bidirectional Mendelian Randomization (MR) study.<br><br>METHODS: We examined single nucleotide polymorphisms (SNPs) associated with TL and sarcoidosis, utilizing available open-access genome-wide association study (GWAS) databases from the UK Biobank and FinnGen. We employed five MR techniques, including Inverse Variance Weighted (IVW), MR Egger, weighted median (WM), Robust adjusted profile score (RAPS), and Maximum likelihood, to assess causal relationships and explore pleiotropy.<br><br>RESULTS: Summary data extracted from GWAS datasets of TL (n&#x2009;=&#x2009;472,174) and (n&#x2009;=&#x2009;217,758) of European ancestry. Employing 130 SNPs with genome-wide significance as instrumental factors for TL, we detect a significant negative correlation between TL and sarcoidosis (OR: 0.682, 95% confidence interval: 0.524-0.888, p : 0.0045). Similarly, utilizing 6 SNPs with genome-wide significance as instrumental factors for sarcoidosis, we fail to identify a noteworthy association between sarcoidosis and TL (OR: 0.992, 95% confidence interval: 0.979-1.005, p : 0.2424).<br><br>CONCLUSION: Our results suggest that longer telomeres may reduce the risk of sarcoidosis, highlighting TL as a potential biomarker for diagnosis and long-term monitoring. Understanding the critical role of telomere shortening enables more effective focus on diagnosing, treating, and curing sarcoidosis linked to telomeres. Clinical investigations into treatments that enhance TL are warranted.},
}
@article {pmid39086030,
year = {2024},
author = {Liu, Q and Fan, G and Bi, J and Fang, Q and Luo, F and Huang, X and Li, H and Liu, B and Yan, L and Guo, W and Wang, Y and Song, L},
title = {Associations of childhood and adulthood body size, and child-to-adult body size change with adult telomere length.},
journal = {Diabetes, obesity &amp; metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1111/dom.15825},
pmid = {39086030},
issn = {1463-1326},
support = {2023AFB663//Hubei Provincial Natural Science Foundation of China/ ; 82003479//National Natural Science Foundation of China/ ; 82073660//National Natural Science Foundation of China/ ; 2019M662646//China Postdoctoral Science Foundation/ ; 2020T130220//China Postdoctoral Science Foundation/ ; },
abstract = {AIM: To comprehensively examine the associations of childhood and adulthood body size, and child-to-adult body size change with adult leucocyte telomere length (LTL).<br><br>METHODS: We included 453&#x2009;602 participants from the UK Biobank. Childhood body size at the age of 10&#x2009;years was collected through a questionnaire. Adulthood body size was assessed using body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fat mass index (FMI), and fat-free mass index (FFMI).<br><br>RESULTS: Individuals with plumper body size in childhood exhibited shorter LTL in adulthood (-0.0086 [-0.0017, -0.0004]). Adulthood BMI (-0.0286 [-0.0315, -0.0258]), WC (-0.0271 [-0.0303, -0.0238]), WHR (-0.0269 [-0.0308, -0.0230]) and FMI (-0.0396 [-0.0438, -0.0351]) were negatively associated with LTL, whereas FFMI (0.0095 [0.0039, 0.0152]) was positively associated with LTL. Compared to individuals consistently having an average/normal weight in both childhood and adulthood, those who maintained or developed overweight/obesity from childhood to adulthood had a shorter adult LTL, regardless of childhood body size. Notably, the LTL shortening effect was not observed in individuals with plumper body size in childhood but normal weight in adulthood.<br><br>CONCLUSIONS: Childhood and adulthood obesity are both associated with LTL shortening in adulthood. Transitioning to or maintaining overweight/obese status from childhood to adulthood is associated with shorter adult LTL, whereas this effect can be reversed if plumper children become normal weight.},
}
@article {pmid39082280,
year = {2024},
author = {Prince, S and Maguemoun, K and Ferdebouh, M and Querido, E and Derumier, A and Tremblay, S and Chartrand, P},
title = {CoPixie, a novel algorithm for single-particle track colocalization, enables efficient quantification of telomerase dynamics at telomeres.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae669},
pmid = {39082280},
issn = {1362-4962},
support = {PJT-162156/CAPMC/CIHR/Canada ; //Natural Sciences and Engineering Research Council of Canada/ ; //Fonds de recherche du Qu&#xe9;bec-Nature et technologies/ ; },
abstract = {Single-particle imaging and tracking can be combined with colocalization analysis to study the dynamic interactions between macromolecules in living cells. Indeed, single-particle tracking has been extensively used to study protein-DNA interactions and dynamics. Still, unbiased identification and quantification of binding events at specific genomic loci remains challenging. Herein, we describe CoPixie, a new software that identifies colocalization events between a theoretically unlimited number of imaging channels, including single-particle movies. CoPixie is an object-based colocalization algorithm that relies on both pixel and trajectory overlap to determine colocalization between molecules. We employed CoPixie with live-cell single-molecule imaging of telomerase and telomeres, to test the model that cancer-associated POT1 mutations facilitate telomere accessibility. We show that POT1 mutants Y223C, D224N or K90E increase telomere accessibility for telomerase interaction. However, unlike the POT1-D224N mutant, the POT1-Y223C and POT1-K90E mutations also increase the duration of long-lasting telomerase interactions at telomeres. Our data reveal that telomere elongation in cells expressing cancer-associated POT1 mutants arises from the dual impact of these mutations on telomere accessibility and telomerase retention at telomeres. CoPixie can be used to explore a variety of questions involving macromolecular interactions in living cells, including between proteins and nucleic acids, from multicolor single-particle tracks.},
}
@article {pmid39082275,
year = {2024},
author = {Liang, F and Rai, R and Sodeinde, T and Chang, S},
title = {TRF2-RAP1 represses RAD51-dependent homology-directed telomere repair by promoting BLM-mediated D-loop unwinding and inhibiting BLM-DNA2-dependent 5'-end resection.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae642},
pmid = {39082275},
issn = {1362-4962},
support = {W81XWH-22-1-0099//Department of Defense/ ; RO1GM141350/NH/NIH HHS/United States ; },
abstract = {Inappropriate homology-directed repair (HDR) of telomeres results in catastrophic telomere loss and aberrant chromosome fusions, leading to genome instability. We have previously shown that the TRF2-RAP1 heterodimer protects telomeres from engaging in aberrant telomere HDR. Cells lacking the basic domain of TRF2 and functional RAP1 display HDR-mediated telomere clustering, resulting in the formation of ultrabright telomeres (UTs) and massive chromosome fusions. Using purified proteins, we uncover three distinct molecular pathways that the TRF2-RAP1 heterodimer utilizes to protect telomeres from engaging in aberrant HDR. We show mechanistically that TRF2-RAP1 inhibits RAD51-initiated telomeric D-loop formation. Both the TRF2 basic domain and RAP1-binding to TRF2 are required to block RAD51-mediated homology search. TRF2 recruits the BLM helicase to telomeres through its TRFH domain to promote BLM-mediated unwinding of telomere D-loops. In addition, TRF2-RAP1 inhibits BLM-DNA2-mediated 5' telomere end resection, preventing the generation of 3' single-stranded telomere overhangs necessary for RAD51-dependent HDR. Importantly, cells expressing BLM mutants unable to interact with TRF2 accumulate telomere D-loops and UTs. Our findings uncover distinct molecular mechanisms coordinated by TRF2-RAP1 to protect telomeres from engaging in aberrant HDR.},
}
@article {pmid39081620,
year = {2024},
author = {Obeagu, EI and Obeagu, GU},
title = {Telomere Dynamics in Sickle Cell Anemia: Unraveling Molecular Aging and Disease Progression.},
journal = {Journal of blood medicine},
volume = {15},
number = {},
pages = {313-323},
doi = {10.2147/JBM.S462758},
pmid = {39081620},
issn = {1179-2736},
abstract = {Sickle Cell Anemia (SCA) is a hereditary blood disorder characterized by the presence of abnormal hemoglobin, leading to the formation of sickle-shaped red blood cells. While extensive research has unraveled many aspects of the genetic and molecular basis of SCA, the role of telomere dynamics in disease progression remains a relatively unexplored frontier. This review seeks to provide a comprehensive examination of telomere biology within the context of SCA, aiming to elucidate its potential impact on molecular aging and the progression of the disease. The impact of oxidative stress on telomere dynamics in SCA is explored, with a particular focus on how increased reactive oxygen species (ROS) may contribute to accelerated telomere shortening and genomic instability. Furthermore, the potential relationship between telomere dysfunction and cellular senescence in SCA is investigated, shedding light on how telomere dynamics may contribute to the premature aging of cells in this population. The review concludes by summarizing key findings and proposing potential therapeutic strategies targeting telomere dynamics to mitigate disease progression in SCA. It also identifies gaps in current understanding and suggests avenues for future research, emphasizing the importance of further investigating telomere biology to advance our understanding of molecular aging and disease progression in Sickle Cell Anemia. This comprehensive exploration of telomere dynamics in SCA offers insights into potential mechanisms of molecular aging and disease progression, paving the way for targeted therapeutic interventions and improved disease management.},
}
@article {pmid39080469,
year = {2024},
author = {Hussein-Agha, R and Kannengiesser, C and Lainey, E and Marcais, A and Srour, M and Sterin, A and Buchbinder, N and Borie, R and Plessier, A and Socié, G and Peffault de Latour, R and Sicre de Fontbrune, F},
title = {Alemtuzumab-based conditioning regimen before hematopoietic stem cell transplantation in patients with short telomere syndromes: a retrospective study of the SFGM-TC.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {39080469},
issn = {1476-5365},
abstract = {While HSCT is the only curative option for patients with short telomere syndromes (STSs) and severe bone marrow failure (BMF) or myeloid malignancies (MM), their increase sensitivity to conditioning regimen strongly affect outcomes. To minimize HSCT related mortality, alemtuzumab-based conditioning regimens have been proposed, but the number of patients transplanted with those regimens reported in the literature remains very low. We retrospectively analyzed outcome of adults and adolescents with STSs transplanted after an alemtuzumab, fludarabine and cyclophosphamide based regimen registered by the SFGM-TC. Seven patients were transplanted for a BMF and 5 for a MM (median age 34 years, (IQR [22-45])). The 2-year GRFS for patients with MM was 20% (95% CI [3;100]), and 57% (95% CI [30;100]) in others. In univariate (hazard ratio, HR = 6, 95% CI [1;31]) and multivariate analysis (HR = 26, 95% CI [2;414]) stem cell source was a predictive factor for GRFS. Three of the 5 patients with pre-transplant MM relapsed and 2 of them died at last follow up. The 2-year OS was 66% (95% CI [43;99]) in the whole cohort with a median follow up of 32 months (IQR [13-56]). In conclusion, Alemtuzumab-based conditioning regimen with bone marrow is an option for patients with STSs and BMF, but others modalities have to be explored for patients with MM.},
}
@article {pmid39074257,
year = {2024},
author = {Han, MH and Kwon, HS and Hwang, M and Park, HH and Jeong, JH and Park, KW and Kim, EJ and Yoon, SJ and Yoon, B and Jang, JW and Hong, JY and Choi, SH and Koh, SH},
title = {Association between osteoporosis and the rate of telomere shortening.},
journal = {Aging},
volume = {16},
number = {},
pages = {},
doi = {10.18632/aging.206034},
pmid = {39074257},
issn = {1945-4589},
abstract = {A shorter leukocyte telomere length (LTL) is reported to be associated with age-related diseases, including osteoporosis. Many studies have tried identifying the association between LTL and osteoporosis, although it remains controversial. This study aimed to determine whether osteoporosis is independently associated with LTL shortening in a prospective longitudinal cohort. The KBASE study is an independent multicenter prospective cohort in South Korea, which began in 2014. We compared the LTL values for each participant at baseline and over a 2-year follow-up period. Boxplots were used to demonstrate the differences in the change in LTL over a 2-year follow-up according to osteoporosis. Multivariable linear regression was conducted to identify whether osteoporosis is independently associated with the rate of telomere shortening. A total of 233 subjects (from 55 to 88 years) from the KBASE cohort were finally enrolled in the study. We observed that the LTL decreased by approximately 1.2 kbp over 2 years. While the LTL decreased as age increased, the rate of LTL shortening did not increase with age. Multivariable linear regression analysis indicated that only osteoporosis was independently associated with rapid LTL shortening over 2 years (B, -8.08; p = 0.038). We sought to identify an association between osteoporosis and LTL shortening in an independent prospective cohort. We found that participants with osteoporosis had significantly faster LTL shortening over 2 years than those without osteoporosis. We hope this study will help elucidate the underlying mechanisms in the relationship between LTL and osteoporosis in the future.},
}
@article {pmid39068742,
year = {2024},
author = {Chen, X and Ren, Q and Wu, F and Zhu, K and Tao, J and Zhang, A},
title = {Exposure to four typical heavy metals induced telomere shortening of peripheral blood mononuclear cells in relevant with declined urinary aMT6s in rats.},
journal = {Ecotoxicology and environmental safety},
volume = {283},
number = {},
pages = {116791},
doi = {10.1016/j.ecoenv.2024.116791},
pmid = {39068742},
issn = {1090-2414},
abstract = {Environmental heavy metals pollution have seriously threatened the health of human beings. An increasing number of researches have demonstrated that environmental heavy metals can influence the telomere length of Peripheral Blood Mononuclear Cells (PBMCs), which implicate biological aging as well as predicts diseases. Our previous study has shown that methylmercury (MeHg)-induced telomere shortening in rat brain tissue was associated with urinary melatonin metabolite 6-sulfatoxymelatonin (aMT6s) levels. Here, we aimed to further elucidate the impact of 4 typical heavy metals (As, Hg, Cd and Pb) on telomere length of PBMCs and their association with urinary aMT6s in rats. In this study, eighty-eight male Sprague-Dawley rats were randomized grouped into eleven groups. Among them, forty 3-month-old (young) and forty 12-month-old (middle-aged) rats were divided into young or middle-aged control groups as well as typical heavy metals exposed groups, respectively. Eight 24-month-old rats (old) was divided into aging control group. The results showed that MeHg exposure in young rats while sodium arsenite (iAs), MeHg, cadmium chloride (CdCl2), lead acetate (PbAc) exposure in middle-aged rats for 3 months significantly reduced the levels of and urinary aMT6s, as well as telomere length of PBMCs. In addition, they also induced abnormalities in serum oxidative stress (SOD, MDA and GPx) and inflammatory (IL-1β, IL-6 and TNF-α) indicators. Notably, there was a significant positive correlation between declined level of urinary aMT6s and the shortening of telomere length in PBMCs in rats exposed to 4 typical heavy metals. These results suggested that 4 typical heavy metals exposure could accelerate the reduction of telomere length of PBMCs partially by inducing oxidative stress and inflammatory in rats, while ageing may be an important synergistic factor. Urinary aMT6s detection may be a alternative method to reflect telomere toxic effects induced by heavy metal exposure.},
}
@article {pmid39062937,
year = {2024},
author = {Apetroaei, MM and Fragkiadaki, P and Velescu, B&#x218; and Baliou, S and Renieri, E and Dinu-Pirvu, CE and Drăgănescu, D and Vlăsceanu, AM and Nedea, MII and Udeanu, DI and Docea, AO and Tsatsakis, A and Arsene, AL},
title = {Pharmacotherapeutic Considerations on Telomere Biology: The Positive Effect of Pharmacologically Active Substances on Telomere Length.},
journal = {International journal of molecular sciences},
volume = {25},
number = {14},
pages = {},
doi = {10.3390/ijms25147694},
pmid = {39062937},
issn = {1422-0067},
abstract = {Telomeres are part of chromatin structures containing repeated DNA sequences, which function as protective caps at the ends of chromosomes and prevent DNA degradation and recombination, thus ensuring the integrity of the genome. While telomere length (TL) can be genetically inherited, TL shortening has been associated with ageing and multiple xenobiotics and bioactive substances. TL has been characterised as a reliable biomarker for the predisposition to developing chronic pathologies and their progression. This narrative review aims to provide arguments in favour of including TL measurements in a complex prognostic and diagnostic panel of chronic pathologies and the importance of assessing the effect of different pharmacologically active molecules on the biology of telomeres. Medicines used in the management of cardiovascular diseases, diabetes, schizophrenia, hormone replacement therapy at menopause, danazol, melatonin, and probiotics have been studied for their positive protective effects against TL shortening. All these classes of drugs are analysed in the present review, with a particular focus on the molecular mechanisms involved.},
}
@article {pmid39059352,
year = {2024},
author = {Al-Dulaimi, S and Matta, S and Slijepcevic, P and Roberts, T},
title = {5-aza-2'-deoxycytidine induces telomere dysfunction in breast cancer cells.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {178},
number = {},
pages = {117173},
doi = {10.1016/j.biopha.2024.117173},
pmid = {39059352},
issn = {1950-6007},
abstract = {AIMS: Azacitidine, a drug that epigenetically modifies DNA, is widely used to treat haematological malignancies. However, at low doses, it demethylates DNA, and as a result, can alter gene expression. In our previous publication, we showed that low doses of azacitidine induce telomere length elongation in breast cancer cells. In this study, we aim to identify the mechanisms which lead to telomere length increases.<br><br>METHODS: Breast cancer cell lines representing different molecular sub-types were exposed to 5-aza-2'-deoxycytidine (5-aza) in 2 and 3D cultures, followed by DNA, RNA, and protein extractions. Samples were then analysed for telomere length, DNA damage, telomerase, and ALT activity.<br><br>RESULTS: We show that treatment of the cell lines with 5-aza for 72&#x202f;h induced DNA damage at the telomeres and increased ALT activity 3-fold. We also identified a gene, POLD3, which may be involved in the ALT activity seen after treatment.<br><br>CONCLUSION: Our results indicate that while 5-aza is a useful drug for treating haematological cancers, surviving cancer cells that have been exposed to lower doses of the drug may activate mechanisms such as ALT. This could lead to cancer cell survival and possible resistance to 5-aza clinically.},
}
@article {pmid39057072,
year = {2024},
author = {Macamo, ED and Mkhize-Kwitshana, ZL and Mthombeni, J and Naidoo, P},
title = {The Impact of HIV and Parasite Single Infection and Coinfection on Telomere Length: A Systematic Review.},
journal = {Current issues in molecular biology},
volume = {46},
number = {7},
pages = {7258-7290},
doi = {10.3390/cimb46070431},
pmid = {39057072},
issn = {1467-3045},
support = {HDID5149/KR/2021//SAMRC/ ; },
abstract = {HIV and parasite infections accelerate biological aging, resulting in immune senescence, apoptosis and cellular damage. Telomere length is considered to be one of the most effective biomarkers of biological aging. HIV and parasite infection have been reported to shorten telomere length in the host. This systematic review aimed to highlight work that explored the influence of HIV and parasite single infections and coinfection on telomere length. Using specific keywords related to the topic of interest, an electronic search of several online databases (Google Scholar, Web of Science, Scopus, Science Direct and PubMed) was conducted to extract eligible articles. The association between HIV infection or parasite infection and telomere length and the association between HIV and parasite coinfection and telomere length were assessed independently. The studies reported were mostly conducted in the European countries. Of the 42 eligible research articles reviewed, HIV and parasite single infections were independently associated with telomere length shortening. Some studies found no association between antiretroviral therapy (ART) and telomere length shortening, while others found an association between ART and telomere length shortening. No studies reported on the association between HIV and parasite coinfection and telomere length. HIV and parasite infections independently accelerate telomere length shortening and biological aging. It is possible that coinfection with HIV and parasites may further accelerate telomere length shortening; however, this is a neglected field of research with no reported studies to date.},
}
@article {pmid39057051,
year = {2024},
author = {Macamo, ED and Mkhize-Kwitshana, ZL and Duma, Z and Mthombeni, J and Naidoo, P},
title = {Telomere Length in a South African Population Co-Infected with HIV and Helminths.},
journal = {Current issues in molecular biology},
volume = {46},
number = {7},
pages = {6853-6867},
doi = {10.3390/cimb46070409},
pmid = {39057051},
issn = {1467-3045},
support = {HDID5149/KR/202//SAMRC/ ; },
abstract = {Biological ageing refers to the gradual decrease in physiological functions, resulting in immune senescence, cellular damage and apoptosis. Telomere length is a biomarker of biological ageing. Limited studies have associated shorter telomere length with HIV and parasite single infections, with no studies reporting the association of HIV and parasite co-infection with telomere length. The study aimed to investigate whether telomere length shortening is accelerated in a South African population co-infected with HIV and helminths compared to participants singly infected with either HIV or helminths. Additionally, telomere length data were compared with participants' biochemical and full blood count parameters. A total of 200 participants were in groups of uninfected control, HIV single infection, helminth single infection and HIV and helminth co-infection groups. Relative telomere length (RTL) was determined using Real-Time PCR and associated with biochemical and full blood count parameters using multivariate regression analysis models that were adjusted for confounders. The uninfected control group was used as a reference group. The uninfected control group had the highest mean RTL (1.21 ± 0.53) while the HIV-infected (0.96 ± 0.42) and co-infected (0.93 ± 0.41) groups had similar RTLs, and lastly, the helminth-infected group (0.83 ± 0.33) had the lowest RTL (p = 0.0002). When compared to the uninfected control group, a significant association between RTL and biochemical parameters, including blood iron (β = -0.48), ferritin (β = -0.48), transferrin saturation (β = -0.57), transferrin (β = -0.57), phosphate (β = -0.47), vitamin A (β = -0.49) and C-reactive protein (β = -0.52) were noted in the co-infected group (p < 0.05). In addition, a significant association between RTL and full blood count, including (β = -0.47), haematocrit (β = -0.46), mean corpuscular volume (β = -0.47), lymphocytes (β = -0.45), mean corpuscular haemoglobin concentration (β = -0.45), red cell distribution width (β = -0.47), monocytes (β = -0.45), eosinophils (β = -0.45), basophils (β = -0.44) and transferrin saturation (β = -0.57) were also noted in the co-infected group (p < 0.05). Accelerated biological ageing, as indicated by telomere length shortening, is associated with HIV and helminth co-infections.},
}
@article {pmid39055058,
year = {2024},
author = {Chen, X and Liu, B and Zhou, J and Lin, J and Jiang, W and Xie, R},
title = {Association between telomere length and erectile dysfunction: a cross-sectional study.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1391013},
doi = {10.3389/fendo.2024.1391013},
pmid = {39055058},
issn = {1664-2392},
mesh = {Humans ; Male ; *Erectile Dysfunction ; Cross-Sectional Studies ; Middle Aged ; *Telomere ; Leukocytes/metabolism/pathology ; Aged ; Adult ; Nutrition Surveys ; Telomere Homeostasis ; Telomere Shortening ; Risk Factors ; },
abstract = {BACKGROUND: Leukocyte telomere length (LTL) serves as a significant biomarker of aging. Erectile dysfunction (ED) is a commonly observed condition among middle-aged and older men. The objective of this study is to explore the potential association between LTL and ED.<br><br>METHODS: We utilized data from the National Health and Nutrition Examination Survey (NHANES) to examine the association between LTL and ED. Weighted multivariate regression analyses were performed as the primary statistical method. Subgroup analyses were conducted to investigate specific population subsets, and restricted cubic spline (RCS) analyses were employed to assess the non-linear relationship between LTL and ED.<br><br>RESULTS: The results of weighted multivariate regression analyses revealed a negative correlation between LTL and the risk of ED. Individuals with ED exhibited shorter LTL compared to those without ED. For each unit increase in LTL, there was a 54% reduction in the risk of ED (odds ratios[OR] 0.46, 95% confidence intervals[CI] 0.25-0.85). When LTL was considered as a categorical variable, the group with the longest LTL (Q5) had a 44% lower risk of ED compared to the group with the shortest LTL(Q1) (OR 0.56, 95% CI 0.39-0.81). A non-linear relationship was observed between TL and ED. Various sensitivity analyses were conducted to validate the stability of the results, and consistent findings were obtained.<br><br>CONCLUSION: The negative association between leukocyte LTL and ED suggests that delaying the shortening of LTL may decrease the risk of ED.},
}
@article {pmid39054789,
year = {2024},
author = {Tempaku, PF and D'Almeida, V and Andersen, ML and Tufik, S},
title = {Sleep is associated with telomere shortening: A population-based longitudinal study.},
journal = {Journal of sleep research},
volume = {},
number = {},
pages = {e14274},
doi = {10.1111/jsr.14274},
pmid = {39054789},
issn = {1365-2869},
support = {#23/08657-0 to VDA//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; #20/13467-8 to MLA//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; },
abstract = {As the chronological age increases, there is a decrease in the telomere length (TL). Associations between TL and age-related diseases have been described. Since the major pathophysiological factors related to inadequate sleep (including sleep complaints and sleep disorders) contribute to the exacerbation of inflammation and oxidative stress, an association of sleep and TL has been proposed. The aim of this study was to evaluate the association between sleep-related variables with TL in a longitudinal framework. We used data derived from the EPISONO cohort, which was followed over 8 years. All individuals answered sleep-related questionnaires, underwent a full-night polysomnography (PSG), and had their blood collected for DNA extraction. The TL was measured through a quantitative real time polymerase chain reaction. Age, sex, body mass index (BMI), smoking, physical activity status, and the 10 principal components (ancestry estimate) were considered covariables. Of the 1042 individuals in the EPISONO cohort, 68.3% agreed to participate in the follow-up study (n = 712). Baseline SpO2 (ß = 0.008, p = 0.007), medium SpO2 (ß = 0.013, p = 0.013), and total sleep time <90% (ß = -0.122, p = 0.012) had an effect on TL from the follow-up. The 8 year TL attrition was inversely associated with total sleep time, sleep efficiency, sleep architecture variables, wake after sleep onset, arousal index, oxygen-related variables baseline, and the presence of obstructive sleep apnea (OSA). We conclude that individuals with worse sleep quality, alterations in sleep architecture, and OSA had greater TL attrition over the 8 years. Using a longitudinal approach, these findings confirm previous cross-sectional evidence linking sleep with accelerated biological ageing.},
}
@article {pmid39054004,
year = {2024},
author = {Ng, GYQ and Hande, MP},
title = {Use of peptide nucleic acid probe to determine telomere dynamics in improving chromosome analysis in genetic toxicology studies.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {897},
number = {},
pages = {503773},
doi = {10.1016/j.mrgentox.2024.503773},
pmid = {39054004},
issn = {1879-3592},
mesh = {*Peptide Nucleic Acids ; *Telomere/drug effects/genetics ; Humans ; *In Situ Hybridization, Fluorescence/methods ; Animals ; Mutagens/toxicity ; Karyotyping/methods ; },
abstract = {Genetic toxicology, strategically located at the intersection of genetics and toxicology, aims to demystify the complex interplay between exogenous agents and our genetic blueprint. Telomeres, the protective termini of chromosomes, play instrumental roles in cellular longevity and genetic stability. Traditionally karyotyping and fluorescence in situ hybridisation (FISH), have been indispensable tools for chromosomal analysis following exposure to genotoxic agents. However, their scope in discerning nuanced molecular dynamics is limited. Peptide Nucleic Acids (PNAs) are synthetic entities that embody characteristics of both proteins and nucleic acids and have emerged as potential game-changers. This perspective report comprehensively examines the vast potential of PNAs in genetic toxicology, with a specific emphasis on telomere research. PNAs' superior resolution and precision make them a favourable choice for genetic toxicological assessments. The integration of PNAs in contemporary analytical workflows heralds a promising evolution in genetic toxicology, potentially revolutionizing diagnostics, prognostics, and therapeutic avenues. In this timely review, we attempted to assess the limitations of current PNA-FISH methodology and recommend refinements.},
}
@article {pmid39052566,
year = {2024},
author = {Huang, SH and Abrametz, K and McGrath, SL and Kobryn, K},
title = {Design and characterization of hyperactive mutants of the Agrobacterium tumefaciens telomere resolvase, TelA.},
journal = {PloS one},
volume = {19},
number = {7},
pages = {e0307590},
doi = {10.1371/journal.pone.0307590},
pmid = {39052566},
issn = {1932-6203},
mesh = {*Agrobacterium tumefaciens/genetics/enzymology ; *Telomere/metabolism/genetics ; *Bacterial Proteins/genetics/metabolism/chemistry ; Mutation ; Models, Molecular ; },
abstract = {Telomere resolvases are a family of DNA cleavage and rejoining enzymes that produce linear DNAs terminated by hairpin telomeres from replicated intermediates in bacteria that possess linear replicons. The telomere resolvase of Agrobacterium tumefaciens, TelA, has been examined at the structural and biochemical level. The N-terminal domain of TelA, while not required for telomere resolution, has been demonstrated to play an autoinhibitory role in telomere resolution, conferring divalent metal responsiveness on the reaction. The N-terminal domain also inhibits the competing reactions of hp telomere fusion and recombination between replicated telomere junctions. Due to the absence of the N-terminal domain from TelA/DNA co-crystal structures we produced an AlphaFold model of a TelA monomer. The AlphaFold model suggested the presence of two inhibitory interfaces; one between the N-terminal domain and the catalytic domain and a second interface between the C-terminal helix and the N-core domain of the protein. We produced mutant TelA's designed to weaken these putative interfaces to test the validity of the modeled interfaces. While our analysis did not bear out the details of the predicted interfaces the model was, nonetheless, extremely useful in guiding design of mutations that, when combined, demonstrated an additive activation of TelA exceeding 250-fold. For some of these hyperactive mutants stimulation of telomere resolution has also been accompanied by activation of competing reactions. However, we have also characterized hyperactive TelA mutants that retain enough autoinhibition to suppress the competing reactions.},
}
@article {pmid39050459,
year = {2024},
author = {Tomasova, K and Seborova, K and Kroupa, M and Horak, J and Kavec, M and Vodickova, L and Rob, L and Hruda, M and Mrhalova, M and Bartakova, A and Bouda, J and Fleischer, T and Kristensen, VN and Vodicka, P and Vaclavikova, R},
title = {Telomere length as a predictor of therapy response and survival in patients diagnosed with ovarian carcinoma.},
journal = {Heliyon},
volume = {10},
number = {13},
pages = {e33525},
pmid = {39050459},
issn = {2405-8440},
abstract = {Impaired telomere length (TL) maintenance in ovarian tissue may play a pivotal role in the onset of epithelial ovarian cancer (OvC). TL in either target or surrogate tissue (blood) is currently being investigated for use as a predictor in anti-OvC therapy or as a biomarker of the disease progression, respectively. There is currently an urgent need for an appropriate approach to chemotherapy response prediction. We performed a monochrome multiplex qPCR measurement of TL in peripheral blood leukocytes (PBL) and tumor tissues of 209 OvC patients. The methylation status and gene expression of the shelterin complex and telomerase catalytic subunit (hTERT) were determined within tumor tissues by High-Throughput DNA methylation profiling and RNA sequencing (RNA-Seq) analysis, respectively. The patients sensitive to cancer treatment (n = 46) had shorter telomeres in PBL compared to treatment-resistant patients (n = 93; P = 0.037). In the patients with a different therapy response, transcriptomic analysis showed alterations in the peroxisome proliferator-activated receptor (PPAR) signaling pathway (q = 0.001). Moreover, tumor TL shorter than the median corresponded to better overall survival (OS) (P = 0.006). TPP1 gene expression was positively associated with TL in tumor tissue (P = 0.026). TL measured in PBL could serve as a marker of platinum therapy response in OvC patients. Additionally, TL determined in tumor tissue provides information on OvC patients' OS.},
}
@article {pmid39048791,
year = {2024},
author = {Garg, V and Bohra, A and Mascher, M and Spannagl, M and Xu, X and Bevan, MW and Bennetzen, JL and Varshney, RK},
title = {Unlocking plant genetics with telomere-to-telomere genome assemblies.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {39048791},
issn = {1546-1718},
abstract = {Contiguous genome sequence assemblies will help us to realize the full potential of crop translational genomics. Recent advances in sequencing technologies, especially long-read sequencing strategies, have made it possible to construct gapless telomere-to-telomere (T2T) assemblies, thus offering novel insights into genome organization and function. Plant genomes pose unique challenges, such as a continuum of ancient to recent polyploidy and abundant highly similar and long repetitive elements. Owing to progress in sequencing approaches, for most crop plants, chromosome-scale reference genome assemblies are available, but T2T assembly construction remains challenging. Here we describe methods for haplotype-resolved, gapless T2T assembly construction in plants, including various crop species. We outline the impact of T2T assemblies in elucidating the roles of repetitive elements in gene regulation, as well as in pangenomics, functional genomics, genome-assisted breeding and targeted genome manipulation. In conjunction with sequence-enriched germplasm repositories, T2T assemblies thus hold great promise for basic and applied plant sciences.},
}
@article {pmid39045889,
year = {2024},
author = {Yang, C and Zhang, Y and Li, J and Liu, X and Qiu, J and Zhang, J and Liu, X and Zhang, Y and Zhao, Y},
title = {Short leukocyte telomere length and high plasma phospholipid fatty acids increase the risk of type 2 diabetes.},
journal = {Endocrine connections},
volume = {},
number = {},
pages = {},
doi = {10.1530/EC-24-0033},
pmid = {39045889},
issn = {2049-3614},
abstract = {In the last forty years, there has been a notable rise in the occurrence of diabetes within China, leading to the country now having the highest number of individuals affected by this condition globally. This prospective observational study examined the effect of different baseline relative leukocyte telomere length (RTL) and the combined effect of baseline RTL and plasma phospholipid fatty acid (PPFA) on the risk of developing diabetes. Adults from Ningxia Province who underwent baseline and follow-up surveys were included in the study. The correlation between the baseline RTL and PPFA was investigated using a multiple linear regression model. The combined effect of baseline RTL and PPFA levels on the risk of developing type 2 diabetes mellitus (T2DM) were investigated using a cox regression model with time as the covariate. A total of 1461 study subjects were included in this study. 141 subjects developed T2DM during the follow-up period. The baseline age was negatively correlated with RTL.Multiple linear regression analysis showed that C16:0 and MUFA concentrations influenced RTL. Subjects with shorter RTL at baseline had a higher risk of developing diabetes than those with longer RTL. Subjects with shorter RTL and higher C16:0 and MUFA concentrations at baseline had a higher risk of developing T2DM than those with longer RTL and lower C16:0 and MUFA concentrations. Our findings indicated that PPFA affects changes in RTL. In addition, RTL and PPFA are associated with the occurrence of T2DM.},
}
@article {pmid39045323,
year = {2024},
author = {Ibraheem Shelash Al-Hawary, S and Ali Alzahrani, A and Ghaleb Maabreh, H and Abed Jawad, M and Alsaadi, SB and Kareem Jabber, N and Alawadi, A and Alsalamy, A and Alizadeh, F},
title = {The association of metabolic syndrome with telomere length as a marker of cellular aging: a systematic review and meta-analysis.},
journal = {Frontiers in genetics},
volume = {15},
number = {},
pages = {1390198},
pmid = {39045323},
issn = {1664-8021},
abstract = {BACKGROUND: It has been suggested that metabolic syndrome (MetS) accelerates the aging process, potentially contributing to the development of age-related complications. Available studies examining the relation of MetS to telomere length (TL), a putative biological marker of aging, have yielded inconclusive findings. This meta-analysis was performed to investigate the association between MetS and TL.<br><br>METHODS: A comprehensive systematic search was conducted in PubMed and Scopus databases to identify relevant literature published up to February 2024. Standard mean difference (SMD) and standardized beta coefficient (&#x3b2;) with their 95% confidence intervals (CI) were used as effect sizes to measure the associations using the random effects model.<br><br>RESULTS: A total of nine studies, comprising a total sample size of 8,606 participants, were eligible for the meta-analysis. No significant difference in mean TL was found between patients with and without MetS (SMD = -0.03, 95%CI = -0.17 to 0.10), with a significant heterogeneity across the studies (I [2] = 89.7.0%, p &#x2264; 0.001). In contrast, it was revealed that MetS is negatively related to TL (&#x3b2; = -0.08, 95%CI = -0.15 to -0.004). In the subgroup analysis, this finding was supported by the International Diabetes Federation (IDF) definition of MetS.<br><br>CONCLUSION: This meta-analysis highlighted that MetS may be linked to a shorter TL. Additional studies are required to confirm this finding.},
}
@article {pmid39045115,
year = {2022},
author = {Zakharova, N and Bravve, L and Mamedova, G and Kaydan, M and Ershova, E and Martynov, A and Veiko, N and Kostyuk, S},
title = {Telomere Length as a Marker of Suicidal Risk in Schizophrenia.},
journal = {Consortium psychiatricum},
volume = {3},
number = {2},
pages = {37-47},
pmid = {39045115},
issn = {2713-2919},
abstract = {BACKGROUND: Schizophrenia and suicidal behavior are associated with shortening in the length of telomeres. The aim of the study was to compare the content (pg/mcg) of telomeric repeat in DNA isolated from peripheral blood cells in three groups of subjects: patients with schizophrenia and a history of suicide attempts, patients with schizophrenia without suicidal tendencies, and healthy control volunteers.<br><br>METHODS: Relapses according to gender and age were examined in 47 patients with schizophrenia with suicidal behavior, 47 patients without self-destructive conditions, and 47 volunteers with healthy control and maintenance for the content of telomeric and the number of copies of mitochondrial DNA (mtDNA) in peripheral blood leukocytes.<br><br>RESULTS: Analysis of determining the content of telomeric repeat (TR) in the DNA of massive weight gain in the series: patients with schizophrenia and suicidal attempts - patients with schizophrenia without suicidal observations - healthy controls (225&#xb1;28.4 (227 [190; 250]) vs. 243&#xb1;21 (245 [228; 260]) vs. 255&#xb1;17.9 (255 [242; 266]), p <0.005. The same trend is observed for the number of mtDNA copies (257&#xb1;101.5 (250 [194; 297])) vs. 262.3&#xb1;59.3 (254 [217; 312]) vs. 272&#xb1;79.9 (274 [213; 304]); p=0.012), but no significant differences were recorded.<br><br>CONCLUSIONS: For the first time, the phenomenon of telomere shortening was discovered in schizophrenics with suicidal risk. The length of the telomere corresponds to the parameter of a biological marker - an objectively measured indicator of normal or pathological processes, but gaining an idea of its reliability is still necessary for verification with an assessment of its sensitivity, specificity, and positive and negative predictive value. The telomere may be considered a putative predictive indicator of suicidal risk.},
}
@article {pmid39042999,
year = {2024},
author = {L Rocha, J and Lou, RN and Sudmant, PH},
title = {Structural variation in humans and our primate kin in the era of telomere-to-telomere genomes and pangenomics.},
journal = {Current opinion in genetics &amp; development},
volume = {87},
number = {},
pages = {102233},
doi = {10.1016/j.gde.2024.102233},
pmid = {39042999},
issn = {1879-0380},
abstract = {Structural variants (SVs) account for the majority of base pair differences both within and between primate species. However, our understanding of inter- and intra-species SV has been historically hampered by the quality of draft primate genomes and the absence of genome resources for key taxa. Recently, advances in long-read sequencing and genome assembly have begun to radically reshape our understanding of SVs. Two landmark achievements include the publication of a human telomere-to-telomere (T2T) genome as well as the development of the first human pangenome reference. In this review, we first look back to the major works laying the foundation for these projects. We then examine the ways in which T2T genome assemblies and pangenomes are transforming our understanding of and approach to primate SV. Finally, we discuss what the future of primate SV research may look like in the era of T2T genomes and pangenomics.},
}
@article {pmid39043540,
year = {2024},
author = {Goncalves da Silva, D and Graciano da Silva, N and Amato, AA},
title = {Leukocyte telomere length in subjects with metabolic dysfunction-associated steatotic liver disease.},
journal = {Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajg.2024.06.005},
pmid = {39043540},
issn = {2090-2387},
abstract = {BACKGROUND AND STUDY AIMS: This study aimed to examine the association between peripheral leukocyte telomere length and indicators of metabolic abnormalities in subjects with metabolic dysfunction-associated steatotic liver disease (MASLD) assessed by magnetic resonance imaging (MRI).<br><br>PATIENTS AND METHODS: This cross-sectional study included adults over 20&#xa0;years with body mass index (BMI) of over >25&#xa0;kg/m[2] and sonographic evidence of hepatic steatosis. The subjects were evaluated by clinical and biochemical variables, determination of hepatic fat fraction by MRI and relative peripheral leukocyte telomere length by quantitative real-time polymerase chain reaction.<br><br>RESULTS: Thirty-two subjects (22 men and 10 women) with MASLD were included, with a median age of 40&#xa0;years, median BMI of 33.75&#xa0;kg/m[2], median HFF 19&#xa0;%, and median relative T/S ratio of 0.64. Subjects with relative T/S ratio below the median had significantly higher age, lower BMI, higher AST serum levels, higher GGT serum levels, lower serum ferritin levels, and higher FIB4 score. In a multivariable logistic regression model considering relative T/S ratio below or above the median only age was significantly associated with relative T/S ratio. Our findings suggest that age is the most important factor associated with telomere length among subjects with MASLD.<br><br>CONCLUSION: Our findings suggest that age is the most important factor associated with telomere length among subjects with MASLD.},
}
@article {pmid39042290,
year = {2024},
author = {Bortoletto, S and Nunes-Souza, E and Marchi, R and Ruthes, MO and Okano, LM and Tofolo, MV and Centa, A and Fonseca, AS and Rosolen, D and Cavalli, LR},
title = {MicroRNAs role in telomere length maintenance and telomerase activity in tumor cells.},
journal = {Journal of molecular medicine (Berlin, Germany)},
volume = {},
number = {},
pages = {},
pmid = {39042290},
issn = {1432-1440},
abstract = {MiRNAs, a class of non-coding RNA molecules, have emerged as critical modulators of telomere length and telomerase activity by finely tuning the expression of target genes (and not gene targets) within signaling pathways involved in telomere homeostasis. The primary objective of this systematic review was to compile and synthesize the existing body of knowledge on the role, association, and involvement of miRNAs in telomere length. Additionally, the review explored the regulation, function, and activation mechanism of the human telomerase reverse transcriptase (hTERT) gene and telomerase activity in tumor cells. A comprehensive analysis of 47 selected articles revealed 40 distinct miRNAs involved in these processes. These miRNAs were shown to exert their function, in both clinical cases and cell line models, either directly or indirectly, regulating hTERT and telomerase activity through distinct molecular mechanisms. The regulatory roles of these miRNAs significantly affected major cancer phenotypes, with outcomes largely dependent on the tissue type and the cellular actions within the tumor cells, whereby they functioned as oncogenes or tumor suppressors. These findings strongly support the pivotal role of miRNAs in modulating telomere length and telomerase activity, thereby contributing to the intricate and complex regulation of telomere homeostasis in tumor cells. Moreover, they emphasize the potential of targeting miRNAs and key regulatory genes as therapeutic strategies to disrupt cancer cell growth and promote senescence, offering promising avenues for novel cancer treatments.},
}
@article {pmid39038850,
year = {2024},
author = {Zhao, R and Xu, M and Yu, X and Wondisford, AR and Lackner, RM and Salsman, J and Dellaire, G and Chenoweth, DM and O'Sullivan, RJ and Zhao, X and Zhang, H},
title = {SUMO promotes DNA repair protein collaboration to support alternative telomere lengthening in the absence of PML.},
journal = {Genes &amp; development},
volume = {},
number = {},
pages = {},
doi = {10.1101/gad.351667.124},
pmid = {39038850},
issn = {1549-5477},
abstract = {The alternative lengthening of telomeres (ALT) pathway maintains telomere length in a significant fraction of cancers that are associated with poor clinical outcomes. A better understanding of ALT mechanisms is therefore necessary for developing new treatment strategies for ALT cancers. SUMO modification of telomere proteins contributes to the formation of ALT telomere-associated PML bodies (APBs), in which telomeres are clustered and DNA repair proteins are enriched to promote homology-directed telomere DNA synthesis in ALT. However, it is still unknown whether-and if so, how-SUMO supports ALT beyond APB formation. Here, we show that SUMO condensates that contain DNA repair proteins enable telomere maintenance in the absence of APBs. In PML knockout ALT cell lines that lack APBs, we found that SUMOylation is required for manifesting ALT features independent of PML and APBs. Chemically induced telomere targeting of SUMO produces condensate formation and ALT features in PML-null cells. This effect requires both SUMOylation and interactions between SUMO and SUMO interaction motifs (SIMs). Mechanistically, SUMO-induced effects are associated with the accumulation of DNA repair proteins, including Rad52, Rad51AP1, RPA, and BLM, at telomeres. Furthermore, Rad52 can undergo phase separation, enrich SUMO at telomeres, and promote telomere DNA synthesis in collaboration with the BLM helicase in a SUMO-dependent manner. Collectively, our findings suggest that SUMO condensate formation promotes collaboration among DNA repair factors to support ALT telomere maintenance without PML. Given the promising effects of SUMOylation inhibitors in cancer treatment, our findings suggest their potential use in perturbing telomere maintenance in ALT cancer cells.},
}
@article {pmid39037376,
year = {2024},
author = {Coukos, A and Saglietti, C and Sempoux, C and Haubitz, M and Greuter, T and Mittaz-Crettol, L and Maurer, F and Mdawar-Bailly, E and Moradpour, D and Alberio, L and Good, JM and Baerlocher, GM and Fraga, M},
title = {High prevalence of short telomeres in idiopathic porto-sinusoidal vascular disorder.},
journal = {Hepatology communications},
volume = {8},
number = {8},
pages = {},
doi = {10.1097/HC9.0000000000000500},
pmid = {39037376},
issn = {2471-254X},
mesh = {Humans ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; *Telomere Shortening/genetics ; Aged ; Adult ; Prevalence ; Telomere/genetics ; Hypertension, Portal/genetics ; In Situ Hybridization, Fluorescence ; Telomere-Binding Proteins/genetics ; Telomerase/genetics ; },
abstract = {BACKGROUND: Telomeres prevent damage to coding DNA as end-nucleotides are lost during mitosis. Mutations in telomere maintenance genes cause excessive telomere shortening, a condition known as short telomere syndrome (STS). One hepatic manifestation documented in STS is porto-sinusoidal vascular disorder (PSVD).<br><br>METHODS: As the etiology of many cases of PSVD remains unknown, this study explored the extent to which short telomeres are present in patients with idiopathic PSVD.<br><br>RESULTS: This monocentric cross-sectional study included patients with histologically defined idiopathic PSVD. Telomere length in 6 peripheral blood leukocyte subpopulations was assessed using fluorescent in situ hybridization and flow cytometry. Variants of telomere-related genes were identified using high-throughput exome sequencing. In total, 22 patients were included, of whom 16 (73%) had short (9/22) or very short (7/22) telomeres according to age-adjusted reference ranges. Fourteen patients (64%) had clinically significant portal hypertension. Shorter telomeres were more frequent in males (p = 0.005) and patients with concomitant interstitial lung disease (p < 0.001), chronic kidney disease (p < 0.001), and erythrocyte macrocytosis (p = 0.007). Portal hypertension (p = 0.021), low serum albumin level (p < 0.001), low platelet count (p = 0.007), and hyperbilirubinemia (p = 0.053) were also associated with shorter telomeres. Variants in known STS-related genes were identified in 4 patients with VSTel and 1 with STel.<br><br>CONCLUSIONS: Short and very short telomeres were highly prevalent in patients with idiopathic PSVD, with 31% presenting with variants in telomere-related genes. Telomere biology may play an important role in vascular liver disease development. Clinicians should consider measuring telomeres in any patient presenting with PSVD.},
}
@article {pmid39033276,
year = {2024},
author = {Panelli, DM and Wang, X and Mayo, J and Wong, RJ and Hong, X and Becker, M and Aghaeepour, N and Druzin, ML and Zuckerman, BS and Stevenson, DK and Shaw DrPH, GM and Bianco, K},
title = {Association of pregnancy complications and postpartum maternal leukocyte telomeres in two diverse cohorts: a nested case-control study.},
journal = {BMC pregnancy and childbirth},
volume = {24},
number = {1},
pages = {490},
pmid = {39033276},
issn = {1471-2393},
support = {NIH K12HD103084/NH/NIH HHS/United States ; R35GM138353/GF/NIH HHS/United States ; },
mesh = {Humans ; Female ; Pregnancy ; Case-Control Studies ; Adult ; *Leukocytes ; *Postpartum Period ; *Pre-Eclampsia/blood ; *Premature Birth/epidemiology ; Pilot Projects ; Pregnancy Complications/blood ; Telomere ; Cohort Studies ; Urban Population/statistics &amp; numerical data ; Telomere Shortening ; Young Adult ; },
abstract = {BACKGROUND: Biologic strain such as oxidative stress has been associated with short leukocyte telomere length (LTL), as well as with preeclampsia and spontaneous preterm birth, yet little is known about their relationships with each other. We investigated associations of postpartum maternal LTL with preeclampsia and spontaneous preterm birth.<br><br>METHODS: This pilot nested case control study included independent cohorts of pregnant people with singleton gestations from two academic institutions: Cohort 1 (hereafter referred to as Suburban) were enrolled prior to 20 weeks' gestation between 2012 and 2018; and Cohort 2 (hereafter referred to as Urban) were enrolled at delivery between 2000 and 2012. Spontaneous preterm birth or preeclampsia were the selected pregnancy complications and served as cases. Cases were compared with controls from each study cohort of uncomplicated term births. Blood was collected between postpartum day 1 and up to 6 months postpartum and samples were frozen, then simultaneously thawed for analysis. Postpartum LTL was the primary outcome, measured using quantitative polymerase chain reaction (PCR) and compared using linear multivariable regression models adjusting for maternal age. Secondary analyses were done stratified by mode of delivery and self-reported level of stress during pregnancy.<br><br>RESULTS: 156 people were included; 66 from the Suburban Cohort and 90 from the Urban Cohort. The Suburban Cohort was predominantly White, Hispanic, higher income and the Urban Cohort was predominantly Black, Haitian, and lower income. We found a trend towards shorter LTLs among people with preeclampsia in the Urban Cohort (6517 versus 6913&#xa0;bp, p&#x2009;=&#x2009;0.07), but not in the Suburban Cohort. There were no significant differences in LTLs among people with spontaneous preterm birth compared to term controls in the Suburban Cohort (6044 versus 6144&#xa0;bp, p&#x2009;=&#x2009;0.64) or in the Urban Cohort (6717 versus 6913, p&#x2009;=&#x2009;0.37). No differences were noted by mode of delivery. When stratifying by stress levels in the Urban Cohort, preeclampsia was associated with shorter postpartum LTLs in people with moderate stress levels (p&#x2009;=&#x2009;0.02).<br><br>CONCLUSION: Our exploratory results compare postpartum maternal LTLs between cases with preeclampsia or spontaneous preterm birth and controls in two distinct cohorts. These pilot data contribute to emerging literature on LTLs in pregnancy.},
}
@article {pmid39032311,
year = {2024},
author = {Panelli, DM and Mayo, JA and Wong, RJ and Becker, M and Feyaerts, D and Marić, I and Wu, E and Gotlib, IH and Gaudillière, B and Aghaeepour, N and Druzin, ML and Stevenson, DK and Shaw, GM and Bianco, K},
title = {Mode of delivery predicts postpartum maternal leukocyte telomere length.},
journal = {European journal of obstetrics, gynecology, and reproductive biology},
volume = {300},
number = {},
pages = {224-229},
doi = {10.1016/j.ejogrb.2024.07.026},
pmid = {39032311},
issn = {1872-7654},
abstract = {BACKGROUND: Recent studies have suggested that pregnancy accelerates biologic aging, yet little is known about how biomarkers of aging are affected by events during the peripartum period. Given that immune shifts are known to occur following surgery, we explored the relation between mode of delivery and postpartum maternal leukocyte telomere length (LTL), a marker of biologic aging.<br><br>STUDY DESIGN: Postpartum maternal blood samples were obtained from a prospective cohort of term, singleton livebirths without hypertensive disorders or peripartum infections between 2012 and 2018. The primary outcome was postpartum LTLs from one blood sample drawn between postpartum week 1 and up to 6&#xa0;months postpartum, measured from thawed frozen peripheral blood mononuclear cells using quantitative PCR in basepairs (bp). Multivariable linear regression models compared LTLs between vaginal versus cesarean births, adjusting for age, body mass index, and nulliparity as potential confounders. Analyses were conducted in two mutually exclusive groups: those with LTL measured postpartum week 1 and those measured up to 6&#xa0;months postpartum. Secondarily, we compared multiomics by mode of delivery using machine-learning methods to evaluate whether other biologic changes occurred following cesarean. These included transcriptomics, metabolomics, microbiomics, immunomics, and proteomics (serum and plasma).<br><br>RESULTS: Of 67 included people, 50 (74.6&#xa0;%) had vaginal and 17 (25.4&#xa0;%) had cesarean births. LTLs were significantly shorter after cesarean in postpartum week 1 (5755.2&#xa0;bp cesarean versus 6267.8&#xa0;bp vaginal, p&#xa0;=&#xa0;0.01) as well as in the later draws (5586.6 versus 5945.6&#xa0;bp, p&#xa0;=&#xa0;0.04). After adjusting for confounders, these differences persisted in both week 1 (adjusted beta -496.1, 95&#xa0;% confidence interval [CI] -891.1, -101.1, p&#xa0;=&#xa0;0.01) and beyond (adjusted beta -396.8; 95&#xa0;% CI -727.2, -66.4. p&#xa0;=&#xa0;0.02). Among the 15 participants who also had complete postpartum multiomics data available, there were predictive signatures of vaginal versus cesarean births in transcriptomics (cell-free [cf]RNA), metabolomics, microbiomics, and proteomics that did not persist after false discovery correction.<br><br>CONCLUSION: Maternal LTLs in postpartum week 1 were nearly 500&#xa0;bp shorter following cesarean. This difference persisted several weeks postpartum, even though other markers of inflammation had normalized. Mode of delivery should be considered in any analyses of postpartum LTLs and further investigation into this phenomenon is warranted.},
}
@article {pmid39031441,
year = {2024},
author = {Djos, A and Svensson, J and Gaarder, J and Umapathy, G and Nilsson, S and Ek, T and Vogt, H and Georgantzi, K and Öra, I and Träger, C and Kogner, P and Martinsson, T and Fransson, S},
title = {Loss of Chromosome Y in Neuroblastoma Is Associated With High-Risk Disease, 11q-Deletion, and Telomere Maintenance.},
journal = {Genes, chromosomes &amp; cancer},
volume = {63},
number = {7},
pages = {e23260},
doi = {10.1002/gcc.23260},
pmid = {39031441},
issn = {1098-2264},
support = {TM 22-156; SF 18-99 18-099//Swedish Childhood Cancer Foundation/ ; PK PR2023-007//Swedish Childhood Cancer Foundation/ ; KP2020-0021//Swedish Childhood Cancer Foundation/ ; PROF2019-0001//Swedish Childhood Cancer Foundation/ ; TM 22-2359//Swedish Cancer Foundation/ ; PK 22-2492 Pj//Swedish Cancer Foundation/ ; ALFGBG-447171//Swedish state under the LUA/ALF agreement/ ; TM 521-2014-3031//Swedish Research Council/ ; TM/PK-RB13-0204//Swedish Foundation for Strategic Research/ ; },
mesh = {Humans ; *Neuroblastoma/genetics/pathology ; Male ; *Chromosomes, Human, Y/genetics ; *Chromosome Deletion ; *Chromosomes, Human, Pair 11/genetics ; Infant ; Child, Preschool ; Female ; Telomere Homeostasis/genetics ; Child ; Histone Demethylases/genetics ; Telomere/genetics ; N-Myc Proto-Oncogene Protein/genetics ; Sweden/epidemiology ; },
abstract = {Neuroblastoma (NB) is a heterogeneous childhood cancer with a slightly higher incidence in boys than girls, with the reason for this gender disparity unknown. Given the growing evidence for the involvement of loss of the Y chromosome (LoY) in male diseases including cancer, we investigated Y chromosome status in NB. Male NB tumor samples from a Swedish cohort, analyzed using Cytoscan HD SNP-microarray, were selected. Seventy NB tumors were analyzed for aneuploidy of the Y chromosome, and these data were correlated with other genetic, biological, and clinical parameters. LoY was found in 21% of the male NB tumors and it was almost exclusively found in those with high-risk genomic profiles. Furthermore, LoY was associated with increased age at diagnosis and enriched in tumors with 11q-deletion and activated telomere maintenance mechanisms. In contrast, tumors with an MYCN-amplified genomic profile retained their Y chromosome. The understanding of LoY in cancer is limited, making it difficult to conclude whether LoY is a driving event in NB or function of increased genomic instability. Gene expression analysis of Y chromosome genes in male NB tumors showed low expression of certain genes correlating with worse overall survival. KDM5D, encoding a histone demethylase stands out as an interesting candidate for further studies. LoY has been shown to impact the epigenomic layer of autosomal loci in nonreproductive tissues, and KDM5D has been reported as downregulated and/or associated with poor survival in different malignancies. Further studies are needed to explore the mechanisms and functional consequences of LoY in NB.},
}
@article {pmid39030357,
year = {2024},
author = {Jeon, HJ and Levine, MT and Lampson, MA},
title = {Telomere Elongation During Pre-Implantation Embryo Development.},
journal = {Advances in anatomy, embryology, and cell biology},
volume = {238},
number = {},
pages = {121-129},
pmid = {39030357},
issn = {0301-5556},
mesh = {Animals ; *Embryonic Development/genetics ; *Telomere/metabolism ; Humans ; Telomere Homeostasis ; Telomerase/metabolism/genetics ; },
abstract = {The primary mechanism of telomere elongation in mammals is reverse transcription by telomerase. An alternative (ALT) pathway elongates telomeres by homologous recombination in some cancer cells and during pre-implantation embryo development, when telomere length increases rapidly within a few cell cycles. The maternal and paternal telomeres in the zygote are genetically and epigenetically distinct, with differences in telomere length and in chromatin packaging. We discuss models for how these asymmetries may contribute to telomere regulation during the earliest embryonic cell cycles and suggest directions for future research.},
}
@article {pmid39023108,
year = {2024},
author = {Bem, MMS and Paraizo-Horvath, CMS and Freitas, PS and Brito, TRP},
title = {Is it possible that menopause is associated with telomere length? Findings of an integrative review.},
journal = {Climacteric : the journal of the International Menopause Society},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/13697137.2024.2376193},
pmid = {39023108},
issn = {1473-0804},
abstract = {OBJECTIVE: Knowing the important repercussions of menopause for women's health and that female longevity can be better understood through studies based on aging biomarkers, studies on the relationship between menopause and telomere shortening may help to better understand this stage of life. This study aimed to analyze what research has been produced regarding the relationship between menopause and telomere length.<br><br>METHODS: This integrative literature review included searches in PubMed, CINAHL, LILACS, Web of Science and Scopus databases. Four studies were selected for the final sample.<br><br>RESULTS: The findings of these studies indicate that older age for menopause and longer reproductive life (difference between age at menopause and menarche) are associated with longer telomeres, that is, with longevity.<br><br>CONCLUSION: The relationship between menopause and telomere length is uncertain. The small number of studies included in this review, and the fact that the results indicate that the relationship between menopause and telomere length may be dependent on the stage of the menopause and race/ethnicity, suggest that additional research focusing on these variables should be carried out.},
}
@article {pmid39021990,
year = {2024},
author = {Nila, NN and Mahmud, Z and Paul, A and Rahman, T and Hossain Howlader, MZ and Hosen, MI},
title = {Investigating the structural and functional consequences of germline single nucleotide polymorphisms located in the genes of the alternative lengthening of telomere (ALT) pathway.},
journal = {Heliyon},
volume = {10},
number = {12},
pages = {e33110},
pmid = {39021990},
issn = {2405-8440},
abstract = {BACKGROUND: The Alternative Lengthening of Telomeres (ALT) pathway represents a non-canonical mechanism of telomere maintenance that operates independently of the conventional telomerase activity. The three biologically significant proteins, designated as SMARCAL1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1), DAXX (Death domain-associated protein 6) and ATRX (alpha-thalassemia/mental retardation, X-linked) are associated with ALT in certain cancer types. The purpose of this study was to identify the most high-risk nsSNPs (non-synonymous Single Nucleotide Polymorphisms) within these three genes and assess their impacts on the structure and function of the proteins they encode.<br><br>METHODS: The reported genetic polymorphisms of SMARCAL1, DAXX and ATRX genes were retrieved from the Ensembl database. Later, various computational tools like PROVEAN, PolyPhen2, SNPs and GO, SNAP2, Predict-SNP, Panther and PMut were used to predict the most deleterious nsSNPs. MutPred was used to understand the underlying molecular reasons of those nsSNPs being deleterious, followed by prediction of Post Translational Modification Sites (PTMs) using ModPred. I-Mutant and MUpro were used to predict the effect of SNP on energy stability. Later, 3D clustering analysis was done using Mutation 3D server. Moreover, ConSurf was utilized to identify the conservation scores of wild-type amino acids. Additionally, the NCBI conserved domain search tool was employed to pinpoint conserved domains within these three proteins. Project-Hope helped for biophysical validation, followed by prediction of these genes' interaction and function by using GeneMANIA.<br><br>RESULT: Analysis on SMARCAL1 protein revealed that among 665 nsSNPs, four were identified as the most deleterious: L578S, T581S, P582A, and P582S. Similarly, within the DAXX protein, among a pool of 480 nsSNPs, P284S, R230C, and R230S were found out to be the most deleterious variants. In case of ATRX protein, V178D, R246C, and V277G, from the total of 1009 nsSNPs, were predicted to be the most deleterious. All these nsSNPs were found to occur at residue positions that are 100&#xa0;% conserved within protein domains and were predicted to be most damaging from both structural and functional perspectives and highly destabilizing to their corresponding proteins.<br><br>CONCLUSION: Computational investigation on the 3 proteins-SMARCAL1, DAXX and ATRX through different bioinformatics analysis tools concludes that the identified high risk nsSNPs of these proteins are pathogenic SNPs. These variants potentially exert functional and structural influences, thus making them valuable candidates for future genetic studies.},
}
@article {pmid39019487,
year = {2024},
author = {Salberg, S and Smith, MJ and Lamont, R and Chen, Z and Beauchamp, MH and Craig, W and Doan, Q and Gravel, J and Zemek, R and Lannin, NA and Yeates, KO and Mychasiuk, R},
title = {Shorter Telomere Length Is Associated With Older Age, Poor Sleep Hygiene, and Orthopedic Injury, but Not Mild Traumatic Brain Injury, in a Cohort of Canadian Children.},
journal = {The Journal of head trauma rehabilitation},
volume = {},
number = {},
pages = {},
pmid = {39019487},
issn = {1550-509X},
abstract = {BACKGROUND: Predicting recovery following pediatric mild traumatic brain injury (mTBI) remains challenging. The identification of objective biomarkers for prognostic purposes could improve clinical outcomes. Telomere length (TL) has previously been used as a prognostic marker of cellular health in the context of mTBI and other neurobiological conditions. While psychosocial and environmental factors are associated with recovery outcomes following pediatric mTBI, the relationship between these factors and TL has not been investigated. This study sought to examine the relationships between TL and psychosocial and environmental factors, in a cohort of Canadian children with mTBI or orthopedic injury (OI).<br><br>METHODS: Saliva was collected at a postacute (median 7&#xa0;days) timepoint following injury to assess TL from a prospective longitudinal cohort of children aged 8 to 17&#xa0;years with either mTBI (n&#xa0;=&#xa0;202) or OI (n&#xa0;=&#xa0;90), recruited from 3 Canadian sites. Questionnaires regarding psychosocial and environmental factors were obtained at a postacute follow-up visit and injury outcomes were assessed at a 3-month visit. Univariable associations between TL and psychosocial, environmental, and outcome variables were assessed using Spearman's correlation. Further adjusted analyses of these associations were performed by including injury group, age, sex, and site as covariates in multivariable generalized linear models with a Poisson family, log link function, and robust variance estimates.<br><br>RESULTS: After adjusting for age, sex, and site, TL in participants with OI was 7% shorter than those with mTBI (adjusted mean ratio&#xa0;=&#xa0;0.93; 95% confidence interval, 0.89-0.98; P =&#xa0;.003). As expected, increasing age was negatively associated with TL (Spearman's r =&#xa0;-0.14, P =&#xa0;.016). Sleep hygiene at 3&#xa0;months was positively associated with TL (adjusted mean ratio&#xa0;=&#xa0;1.010; 95% confidence interval, 1.001-1.020; P =&#xa0;.039).<br><br>CONCLUSION: The relationships between TL and psychosocial and environmental factors in pediatric mTBI and OI are complex. TL may provide information regarding sleep quality in children recovering from mTBI or OI; however, further investigation into TL biomarker validity should employ a noninjured comparison group.},
}
@article {pmid39013263,
year = {2024},
author = {Martínez-Ezquerro, JD and Ortiz-Ramírez, M and García-delaTorre, P and González-Covarrubias, V and Sánchez-García, S},
title = {Physical Performance and Telomere Length in Older Adults.},
journal = {Archives of medical research},
volume = {55},
number = {6},
pages = {103046},
doi = {10.1016/j.arcmed.2024.103046},
pmid = {39013263},
issn = {1873-5487},
abstract = {BACKGROUND: The aging population prompts studying risk factors and markers to predict healthy aging. Telomere length is a promising candidate for assessing various age-related traits.<br><br>AIM OF THE STUDY: To investigate the association between physical performance and telomere length.<br><br>METHODS: We enrolled 323 older Mexican adults from the "Cohort of Obesity, Sarcopenia, and Frailty of Older Mexican Adults" affiliated with the Instituto Mexicano del Seguro Social and assessed their physical performance using the Short Physical Performance Battery, dividing participants into low (&#x2264;7) and high (>7) groups. Absolute telomere length was determined by qPCR, and individuals were classified into short (&#x2264;4.22 kb) and long (>4.22 kb) groups. We calculated the mean and adjusted mean, considering sex and age, among others, with 95% CI. We estimated the effect size between physical performance and telomere length using Cohen's d for unequal group sizes and calculated the odds ratio for physical performance based on telomere length.<br><br>RESULTS: Participants with low physical performance had significantly shorter telomeres (mean 4.14.44.7 kb, adjusted mean 3.54.04.5 kb, p <0.001), while those with high physical performance exhibited longer telomeres (mean 5.55.75.9 kb, adjusted mean 4.75.35.8 kb, p <0.001), with a medium-to-high telomere length effect size (d = 0.762). The odds of low physical activity increased 2.13.66.1-fold per kb of telomere attrition (adjOR 1.73.36.3, p <0.001).<br><br>CONCLUSION: Decreased physical function is associated with shorter telomere length. Absolute telomere length presents a promising biomarker for distinguishing between healthy and unhealthy aging, warranting further investigation.},
}
@article {pmid39013662,
year = {2024},
author = {Band, G and Leffler, EM},
title = {Malaria endemicity linked to shorter telomeres in leukocytes.},
journal = {Trends in parasitology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.pt.2024.06.017},
pmid = {39013662},
issn = {1471-5007},
abstract = {Leukocyte telomere length is a highly polygenic trait that has been associated with a complex range of lifestyle factors and disease risk. McQuillan et al.'s results comparing telomere length to malaria incidence rates suggest that infections may be another important factor, possibly through permanent shortening of telomeres in hematopoietic progenitor cells.},
}
@article {pmid39012375,
year = {2024},
author = {Kallingal, A and Krzemieniecki, R and Maciejewska, N and Brankiewicz-Kopcińska, W and Baginski, M},
title = {TRF1 and TRF2: pioneering targets in telomere-based cancer therapy.},
journal = {Journal of cancer research and clinical oncology},
volume = {150},
number = {7},
pages = {353},
pmid = {39012375},
issn = {1432-1335},
mesh = {Humans ; *Neoplasms/genetics/drug therapy/metabolism/therapy ; *Telomeric Repeat Binding Protein 2/metabolism/genetics ; *Telomeric Repeat Binding Protein 1/metabolism/genetics ; *Telomere/metabolism ; Molecular Targeted Therapy/methods ; Antineoplastic Agents/therapeutic use/pharmacology ; Shelterin Complex ; Telomere-Binding Proteins ; },
abstract = {This article presents an in-depth exploration of the roles of Telomere Repeat-binding Factors 1 and 2 (TRF1 and TRF2), and the shelterin complex, in the context of cancer biology. It emphasizes their emerging significance as potential biomarkers and targets for therapeutic intervention. Central to the shelterin complex, TRF1 and TRF2 are crucial in maintaining telomere integrity and genomic stability, their dysregulation often being a hallmark of cancerous cells. The article delves into the diagnostic and prognostic capabilities of TRF1 and TRF2 across various cancer types, highlighting their sensitivity and specificity. Furthermore, it reviews current strides in drug discovery targeting the shelterin complex, detailing specific compounds and their modes of action. The review candidly addresses the challenges in developing therapies aimed at the shelterin complex, including drug resistance, off-target effects, and issues in drug delivery. By synthesizing recent research findings, the article sheds light on the intricate relationship between telomere biology and cancer development. It underscores the urgency for continued research to navigate the existing challenges and fully leverage the therapeutic potential of TRF1, TRF2, and the shelterin complex in the realm of cancer treatment.},
}
@article {pmid39010148,
year = {2024},
author = {Yang, Q and Zhang, J and Fan, Z},
title = {Causal association between telomere length and female reproductive endocrine diseases: a univariable and multivariable Mendelian randomization analysis.},
journal = {Journal of ovarian research},
volume = {17},
number = {1},
pages = {146},
pmid = {39010148},
issn = {1757-2215},
abstract = {BACKGROUND: The relationship between leukocyte telomere length (LTL) and female reproductive endocrine diseases has gained significant attention and research interest in recent years. However, there is still limited understanding of the exact impacts of LTL on these diseases. Therefore, the primary objective of this study was to investigate the genetic causal association between LTL and female reproductive endocrine diseases by employing Mendelian randomization (MR) analysis.<br><br>METHODS: Instruments for assessing genetic variation associated with exposure and outcome were derived from summary data of published genome-wide association studies (GWAS). Inverse-variance weighted (IVW) was utilized as the main analysis method to investigate the causal relationship between LTL and female reproductive endocrine diseases. The exposure data were obtained from the UK Biobanks GWAS dataset, comprising 472,174 participants of European ancestry. The outcome data were acquired from the FinnGen consortium, including abnormal uterine bleeding (menorrhagia and oligomenorrhea), endometriosis (ovarian endometrioma and adenomyosis), infertility, polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI) and premenstrual syndrome (PMS). Furthermore, to account for potential confounding factors such as smoking, alcohol consumption, insomnia, body mass index (BMI) and a history of pelvic inflammatory disease (PID), multivariable MR (MVMR) analysis was also conducted. Lastly, a series of pleiotropy tests and sensitivity analyses were performed to ensure the reliability and robustness of our findings. P&#x2009;<&#x2009;0.0063 was considered to indicate statistically significant causality following Bonferroni correction.<br><br>RESULTS: Our univariable MR analysis demonstrated that longer LTL was causally associated with an increased risk of menorrhagia (IVW: odds ratio [OR]: 1.1803; 95% confidence interval [CI]: 1.0880-1.2804; P&#x2009;=&#x2009;0.0001) and ovarian endometrioma (IVW: OR: 1.2946; 95%CI: 1.0970-1.5278; P&#x2009;=&#x2009;0.0022) at the Bonferroni significance level. However, no significant correlation was observed between LTL and oligomenorrhea (IVW: OR: 1.0124; 95%CI: 0.7350-1.3946; P&#x2009;=&#x2009;0.9398), adenomyosis (IVW: OR: 1.1978; 95%CI: 0.9983-1.4372; P&#x2009;=&#x2009;0.0522), infertility (IVW: OR: 1.0735; 95%CI: 0.9671-1.1915; P&#x2009;=&#x2009;0.1828), PCOS (IVW: OR: 1.0633; 95%CI: 0.7919-1.4278; P&#x2009;=&#x2009;0.6829), POI (IVW: OR: 0.8971; 95%CI: 0.5644-1.4257; P&#x2009;=&#x2009;0.6459) or PMS (IVW: OR: 0.7749; 95%CI: 0.4137-1.4513; P&#x2009;=&#x2009;0.4256). Reverse MR analysis indicated that female reproductive endocrine diseases have no causal effect on LTL. MVMR analysis suggested that the causal effect of LTL on menorrhagia and ovarian endometrioma remained significant after accounting for smoking, alcohol consumption, insomnia, BMI and a history of PID. Pleiotropic and sensitivity analyses also showed robustness of our results.<br><br>CONCLUSION: The results of our bidirectional two-sample MR analysis revealed that genetically predicted longer LTL significantly increased the risk of menorrhagia and ovarian endometrioma, which is consistent with the findings from MVMR studies. However, we did not notice any significant effects of LTL on oligomenorrhea, adenomyosis, infertility, PCOS, POI or PMS. Additionally, reproductive endocrine disorders were found to have no impact on LTL. To enhance our understanding of the effect and underlying mechanism of LTL on female reproductive endocrine diseases, further large-scale studies are warranted in the future.},
}
@article {pmid39005478,
year = {2024},
author = {Comstock, W and Sanford, E and Navarro, M and Smolka, MB},
title = {Profiling Tel1 Signaling Reveals a Non-Canonical Motif Targeting DNA Repair and Telomere Control Machineries.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.07.03.601872},
pmid = {39005478},
issn = {2692-8205},
abstract = {The stability of the genome relies on Phosphatidyl Inositol 3-Kinase-related Kinases (PIKKs) that sense DNA damage and trigger elaborate downstream signaling responses. In S. cerevisiae , the Tel1 kinase (ortholog of human ATM) is activated at DNA double strand breaks (DSBs) and short telomeres. Despite the well-established roles of Tel1 in the control of telomere maintenance, suppression of chromosomal rearrangements, activation of cell cycle checkpoints, and repair of DSBs, the substrates through which Tel1 controls these processes remain incompletely understood. Here we performed an in depth phosphoproteomic screen for Tel1-dependent phosphorylation events. To achieve maximal coverage of the phosphoproteome, we developed a scaled-up approach that accommodates large amounts of protein extracts and chromatographic fractions. Compared to previous reports, we expanded the number of detected Tel1-dependent phosphorylation events by over 10-fold. Surprisingly, in addition to the identification of phosphorylation sites featuring the canonical motif for Tel1 phosphorylation (S/T-Q), the results revealed a novel motif (D/E-S/T) highly prevalent and enriched in the set of Tel1-dependent events. This motif is unique to Tel1 signaling and not shared with the Mec1 kinase, providing clues to how Tel1 plays specialized roles in DNA repair and telomere length control. Overall, these findings define a Tel1-signaling network targeting numerous proteins involved in DNA repair, chromatin regulation, and telomere maintenance that represents a framework for dissecting the molecular mechanisms of Tel1 action.},
}
@article {pmid39002862,
year = {2024},
author = {Dimitrov, M and Merkle, S and Cao, Q and Tryon, RK and Vercellotti, GM and Holtan, SG and Kao, RL and Srikanthan, M and Terezakis, SA and Tolar, J and Ebens, CL},
title = {Allogeneic hematopoietic cell transplant for bone marrow failure or myelodysplastic syndrome in dyskeratosis congenita/telomere biology disorders: Single-center single-arm open-label trial of reduced intensity conditioning without radiation.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2024.07.007},
pmid = {39002862},
issn = {2666-6367},
abstract = {BACKGROUND: Dyskeratosis congenita/Telomere biology disorders (DC/TBD) often manifest as bone marrow failure (BMF) or myelodysplastic syndrome (MDS). Allogeneic hematopoietic cell transplant (alloHCT) rescues hematologic complications, but radiation and alkylator-based conditioning regimens cause diffuse whole-body toxicity and may expedite DC/TBD-specific non-hematopoietic complications. Optimization of conditioning intensity in DC/TBD to allow for donor hematopoietic cell engraftment with the least amount of toxicity remains a critical goal of the alloHCT field.<br><br>OBJECTIVES/STUDY DESIGN: We report prospectively collected standard alloHCT outcomes from a single-center single-arm open-label clinical trial of bone marrow or peripheral blood stem cell alloHCT for DC/TBD-associated BMF or MDS. Conditioning was reduced intensity (RIC) including alemtuzumab 1mg/kg, fludarabine 200 mg/m[2], and cyclophosphamide 50 mg/kg. A previous single-arm open-label phase II clinical trial for the same patient population conducted at the same center, differing only by inclusion of 200 centigray of total body irradiation (TBI), served as a control cohort.<br><br>RESULTS: The Non-TBI cohort included 10 patients (ages 1.7-65.9 years, median follow-up of 3.9 years) compared to the control TBI cohort which included 12 patients (ages 2.2-52.2 years, median follow-up of 10.5 years). Baseline characteristics differed only in total CD34+ cells received, with a median of 5.6 (Non-TBI) compared to 2.6 (TBI) x 10[6]/kg (p=0.02; no difference in total nucleated cells). The cumulative incidence of day +100 grade II-IV acute and 4-year chronic graft-versus-host disease (GvHD) were low at 0 and 10% (Non-TBI) and 8 and 17% (TBI), respectively (acute, p=0.36; chronic, p=0.72). Primary graft failure was absent. Secondary non-neutropenic graft failure occurred in one (Non-TBI cohort). The Non-TBI cohort demonstrated delayed achievement of full donor chimerism but superior lymphocyte recovery. There was no difference in 4-year overall survival at 80% (Non-TBI) and 75% (TBI; p=0.78). MDS as an indication for alloHCT was uncommon, but overall associated with poor outcomes. There were 3 MDS patients in the Non-TBI cohort: 1 relapsed and died at day+387; 1 relapsed at day+500 and is alive 5.5 years later following salvage with a 2[nd] alloHCT; 1 relapsed at day+1093 and is alive at day +100 after a 2[nd] alloHCT. There was 1 MDS patient in the TBI cohort who achieved 100% donor myeloid engraftment without relapse but died at day+827 from a bacterial infection in the setting of immune mediated cytopenia.<br><br>CONCLUSION: Elimination of TBI from the RIC regimen for DC/TBD was not associated with significant changes in rates of graft failure, GvHD, and overall survival, but was associated with delayed achievement of full donor chimerism and improved lymphocyte reconstitution. For DC/TBD-associated BMF, TBI appears to be dispensable. Optimal approaches to DC/TBD-associated MDS remain unclear. Larger cohorts are needed to better assess the unique contribution of TBI and donor CD34+ cell dose. Longer follow-up is required to assess differences in DC/TBD complications and late effects.},
}
@article {pmid39002254,
year = {2024},
author = {Redon, L and Constant, T and Smith, S and Habold, C and Giroud, S},
title = {Understanding seasonal telomere length dynamics in hibernating species.},
journal = {Journal of thermal biology},
volume = {123},
number = {},
pages = {103913},
doi = {10.1016/j.jtherbio.2024.103913},
pmid = {39002254},
issn = {0306-4565},
abstract = {Oxidative stress is thought to be one of the main causes of ageing as it progressively damages cell components throughout life, eventually causing cellular failure and apoptosis. In many organisms, telomeres shorten throughout life under the effect of, amongst other factors, oxidative stress, and are therefore commonly used as marker of biological ageing. However, hibernators, which are regularly exposed to acute oxidative stress when rewarming from torpor, are unexpectedly long-lived. In this review, we explore the causes of oxidative stress associated with hibernation and its impact on telomere dynamics in different taxa, focussing on hibernating rodents. We then speculate on the adaptive mechanisms of hibernators to compensate for the effects of oxidative stress, which may explain their increased longevity. Because winter hibernation appears to be associated with high oxidative stress, hibernators, particularly rodents, may periodically invest in repair mechanisms and antioxidant defences, resulting in seasonal variations in telomere lengths. This research shows how species with a slow life-history strategy deal with large changes in oxidative stress, unifying evolutionary and physiological theories of ageing. Because of the marked seasonal variation in telomere length, we also draw attention when using telomeres as markers for biological aging in seasonal heterotherms and possibly in other highly seasonal species.},
}
@article {pmid39001954,
year = {2024},
author = {Boccardi, V and Cari, L and Bastiani, P and Scamosci, M and Cecchetti, R and Nocentini, G and Mecocci, P},
title = {Aberrant telomeric structures and serum markers of telomere dysfunction in healthy aging: a preliminary study.},
journal = {Biogerontology},
volume = {},
number = {},
pages = {},
pmid = {39001954},
issn = {1573-6768},
abstract = {Telomeres undergo a progressive shortening process as individuals age, and it has been proposed that severely shortened and dysfunctional telomeres play a role in the aging process and the onset of age-related diseases in human beings. An emerging body of evidence indicates that the shortening of telomeres in cultured human cells is also influenced by other replication defects occurring within telomeric repeats. These abnormalities can be detected on metaphase chromosomes. Recent studies have also identified a set of serological markers for telomere dysfunction and DNA damage (elongation factor 1α [EF-1α], stathmin, and N-acetyl-glucosaminidase). With this study, the correlation between telomere abnormalities (by FISH) and these biomarkers as measured in blood serum (by ELISA) from a cohort of 22 healthy subjects at different ages (range 26-101 years) was analyzed. A strong positive correlation between aging and the presence of aberrant telomere structures, sister telomere loss (STL), and sister telomere chromatid fusions (STCF) was detected. When serum markers of telomere dysfunction were correlated with telomere abnormalities, we found that stathmin correlated with total aberrant telomeres structures (r = 0.431, p = 0.0453) and STCF (r = 0.533, p = 0.0107). These findings suggest that serum stathmin can be considered an easy-to-get marker of telomere dysfunction and may serve as valuable indicators of aging.},
}
@article {pmid39001406,
year = {2024},
author = {Park, M and Lee, DE and Hong, Y and Suh, JK and Lee, JA and Kim, M and Park, HJ},
title = {Telomere Length in Adolescent and Young Adult Survivors of Childhood Cancer.},
journal = {Cancers},
volume = {16},
number = {13},
pages = {},
doi = {10.3390/cancers16132344},
pmid = {39001406},
issn = {2072-6694},
support = {2022-0195//National Cancer Center/Republic of Korea ; },
abstract = {We examined the leukocyte relative telomere length (RTL) in Korean adolescent and young adult (AYA) survivors of childhood cancer and evaluated the association of leukocyte RTL with multiple factors, including malignancy type, cancer treatment, age, and chronic health conditions (CHCs). Eighty-eight AYA survivors of childhood cancer with a median follow-up period of 73 months were recruited. RTL in pediatric cancer survivors was not significantly shorter than the predicted value for age-matched references. Neither age at diagnosis nor duration of therapy influenced the RTL. Among the 43 patients with hematologic malignancies, those who underwent allogeneic hematopoietic stem cell transplantation (HSCT) showed a significant shortening of the RTL compared with those who did not (p = 0.039). Among the 15 patients who underwent allogeneic HSCT, those who developed acute graft-versus-host disease (GVHD) of grade II or higher had significantly shorter RTL than those who did not (p = 0.012). Patients with grade II CHCs had significantly shorter RTL than those without CHCs or with grade I CHCs (p = 0.001). Survivors with ≥2 CHCs also exhibited shorter RTL (p = 0.027). Overall, pediatric cancer survivors had similar telomere lengths compared to age-matched references. HSCT recipients and patients with severe or multiple CHCs had shorter telomeres. GVHD augmented telomere attrition in HSCT recipients.},
}
@article {pmid38993011,
year = {2024},
author = {Chik, HYJ and Mannarelli, ME and Dos Remedios, N and Simons, MJP and Burke, T and Schroeder, J and Dugdale, HL},
title = {Adult telomere length is positively correlated with survival and lifetime reproductive success in a wild passerine.},
journal = {Molecular ecology},
volume = {},
number = {},
pages = {e17455},
doi = {10.1111/mec.17455},
pmid = {38993011},
issn = {1365-294X},
support = {PCIG12-GA-2012-333096/ERC_/European Research Council/International ; NE/J024567/1//Natural Environment Research Council/ ; },
abstract = {Explaining variation in individual fitness is a key goal in evolutionary biology. Recently, telomeres, repeating DNA sequences capping chromosome ends, have gained attention as a biomarker for body state, physiological costs, and senescence. Existing research has provided mixed evidence for whether telomere length correlates with fitness, including survival and reproductive output. Moreover, few studies have examined how the rate of change in telomere length correlates with fitness in wild populations. Here, we intensively monitored an insular population of house sparrows, and collected longitudinal telomere and life history data (16 years, 1225 individuals). We tested whether telomere length and its rate of change predict fitness measures, namely survival, lifespan and annual and lifetime reproductive effort and success. Telomere length positively predicted short-term survival, independent of age, but did not predict lifespan, suggesting either a diminishing telomere length-survival correlation with age or other extrinsic factors of mortality. The positive association of telomere length with survival translated into reproductive benefits, as birds with longer telomeres produced more genetic recruits, hatchlings and reared more fledglings over their lifetime. In contrast, there was no association between telomere dynamics and annual reproductive output, suggesting telomere dynamics might not reflect the costs of reproduction in this population, potentially masked by variation in individual quality. The rate of change of telomere length did not correlate with neither lifespan nor lifetime reproductive success. Our results provide further evidence that telomere length correlates with fitness, and contribute to our understanding of the selection on, and evolution of, telomere dynamics.},
}
@article {pmid38987851,
year = {2024},
author = {Yin, Q and Tang, TT and Lu, XY and Ni, WJ and Yin, D and Zhang, YL and Jiang, W and Zhang, Y and Li, ZL and Wen, Y and Gan, WH and Zhang, AQ and Lv, LL and Wang, B and Liu, BC},
title = {Macrophage-derived exosomes promote telomere fragility and senescence in tubular epithelial cells by delivering miR-155.},
journal = {Cell communication and signaling : CCS},
volume = {22},
number = {1},
pages = {357},
pmid = {38987851},
issn = {1478-811X},
support = {82070735;82030024;81720108007//National Natural Science Foundation of China/ ; 82070735;82030024;81720108007//National Natural Science Foundation of China/ ; 2018YFC130046, 2018YFC1314000//National Key Research Programme of Ministry of Science and Technology/ ; },
abstract = {BACKGROUND: Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence.<br><br>METHODS: Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155[-/-] mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization.<br><br>RESULTS: Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16[INK4A] expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16[INK4A]/p21expression and senescence-associated &#x3b2;-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs.<br><br>CONCLUSIONS: Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.},
}
@article {pmid38979576,
year = {2024},
author = {Semper, C and Watanabe, N and Karimullina, E and Patel, DT and Di Leo, R and Castellanos, M and Patel, DH and Chaconas, G and Savchenko, A},
title = {Structure analysis of the telomere resolvase from the Lyme disease spirochete Borrelia garinii reveals functional divergence of its C-terminal domain.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae580},
pmid = {38979576},
issn = {1362-4962},
support = {//National Institute of Allergy and Infectious Diseases/ ; HHSN272201700060C/NH/NIH HHS/United States ; /HH/HHS/United States ; PJT-153336/CAPMC/CIHR/Canada ; },
abstract = {Borrelia spirochetes are the causative agents of Lyme disease and relapsing fever, two of the most common tick-borne illnesses. A characteristic feature of these spirochetes is their highly segmented genomes which consists of a linear chromosome and a mixture of up to approximately 24 linear and circular extrachromosomal plasmids. The complexity of this genomic arrangement requires multiple strategies for efficient replication and partitioning during cell division, including the generation of hairpin ends found on linear replicons mediated by the essential enzyme ResT, a telomere resolvase. Using an integrative structural biology approach employing advanced modelling, circular dichroism, X-ray crystallography and small-angle X-ray scattering, we have generated high resolution structural data on ResT from B. garinii. Our data provides the first high-resolution structures of ResT from Borrelia spirochetes and revealed active site positioning in the catalytic domain. We also demonstrate that the C-terminal domain of ResT is required for both transesterification steps of telomere resolution, and is a requirement for DNA binding, distinguishing ResT from other telomere resolvases from phage and bacteria. These results advance our understanding of the molecular function of this essential enzyme involved in genome maintenance in Borrelia pathogens.},
}
@article {pmid38977857,
year = {2024},
author = {Zhang, Y and Zhao, M and Tan, J and Huang, M and Chu, X and Li, Y and Han, X and Fang, T and Tian, Y and Jarret, R and Lu, D and Chen, Y and Xue, L and Li, X and Qin, G and Li, B and Sun, Y and Deng, XW and Deng, Y and Zhang, X and He, H},
title = {Telomere-to-telomere Citrullus super-pangenome provides direction for watermelon breeding.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {38977857},
issn = {1546-1718},
abstract = {To decipher the genetic diversity within the cucurbit genus Citrullus, we generated telomere-to-telomere (T2T) assemblies of 27 distinct genotypes, encompassing all seven Citrullus species. This T2T super-pangenome has expanded the previously published reference genome, T2T-G42, by adding 399.2 Mb and 11,225 genes. Comparative analysis has unveiled gene variants and structural variations (SVs), shedding light on watermelon evolution and domestication processes that enhanced attributes such as bitterness and sugar content while compromising disease resistance. Multidisease-resistant loci from Citrullus amarus and Citrullus mucosospermus were successfully introduced into cultivated Citrullus lanatus. The SVs identified in C. lanatus have not only been inherited from cordophanus but also from C. mucosospermus, suggesting additional ancestors beyond cordophanus in the lineage of cultivated watermelon. Our investigation substantially improves the comprehension of watermelon genome diversity, furnishing comprehensive reference genomes for all Citrullus species. This advancement aids in the exploration and genetic enhancement of watermelon using its wild relatives.},
}
@article {pmid38974386,
year = {2024},
author = {Zhang, Z and Zhang, J and Zhang, K and Ge, X and Zhai, X},
title = {Robust evidence supports a causal link between higher birthweight and longer telomere length: a mendelian randomization study.},
journal = {Frontiers in genetics},
volume = {15},
number = {},
pages = {1264028},
pmid = {38974386},
issn = {1664-8021},
abstract = {BACKGROUND: Observational studies have suggested a potential relationship between birthweight and telomere length. However, the causal link between these two parameters remains undefined. In this study, we use Mendelian Randomization (MR). This method employs genetic variants as instrumental variables, to explore the existence of causal associations and elucidate the causal relationship between birth weight and telomere length.<br><br>METHODS: We used 35 single nucleotide polymorphisms (SNPs) as instrumental variables for birth weight. These SNPs were identified from a meta-analysis involving 153,781 individuals. Furthermore, we obtained summary statistics for telomere length from a study conducted on 472,174 United Kingdom Biobank participants. To evaluate the causal estimates, we applied the random effect inverse variance weighted method (IVW) and several other MR methods, such as MR-Egger, weighted median, and MR-PRESSO, to verify the reliability of our findings.<br><br>RESULTS: Our analysis supports a significant causal relationship between genetically predicted birth weight and telomer3e length. The inverse variance weighted analysis results for birth weight (Beta = 0.048; 95%CI = 0.023 to 0.073; p < 0.001) corroborate this association.<br><br>CONCLUSION: Our study provides robust evidence supporting a causal link between higher birth weight and longer telomere length.},
}
@article {pmid38973734,
year = {2024},
author = {Farzan, SF and Niu, Z and Guo, F and Shahriar, M and Kibriya, MG and Jasmine, F and Sarwar, G and Jackson, BP and Ahsan, H and Argos, M},
title = {Exposure to metal mixtures and telomere length in Bangladeshi children.},
journal = {American journal of epidemiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/aje/kwae181},
pmid = {38973734},
issn = {1476-6256},
abstract = {Telomere length is associated with chronic diseases and in younger populations, may represent a biomarker of disease susceptibility. As growing evidence suggests that environmental factors, including metals, may impact telomere length, we investigated the association between 17 metals measured in toenail samples and leukocyte relative telomere length (RTL), among 472 five- to seven-year-old children enrolled in the Bangladesh Environmental Research in Children's Health (BiRCH) cohort. In single exposure linear regression models, a doubling of arsenic (As) and mercury (Hg) (μg/g) were associated with a -0.21 (95%CI: -0.032, -0.010; p=0.0005) and -0.017 (95%CI: -0.029, -0.004; p=0.006) difference in RTL, respectively. In Bayesian Kernel Machine Regression (BKMR) mixture models, the overall metal mixture was inversely associated with RTL (P-for-trend <0.001). Negative associations with RTL were observed with both log2-As and log2-Hg, while an inverted U-shaped association was observed for log2-zinc (Zn) with RTL. We found little evidence of interaction among metals. Sex-stratification identified stronger associations of the overall mixture and log2-As with RTL among females, compared to males. Our study suggests that As and Hg may independently influence RTL in mid-childhood. Further studies are needed to investigate potential long-term impacts of metal-associated telomere shortening in childhood on health outcomes in adult life.},
}
@article {pmid38972874,
year = {2024},
author = {Zhao, H and Zhou, H and Sun, G and Dong, B and Zhu, W and Mu, X and Li, X and Wang, J and Zhao, M and Yang, W and Zhang, G and Ji, R and Geng, T and Gong, D and Meng, H and Wang, J},
title = {Telomere-to-telomere genome assembly of the goose Anser cygnoides.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {741},
pmid = {38972874},
issn = {2052-4463},
mesh = {Animals ; *Geese/genetics ; *Telomere/genetics ; *Genome ; Molecular Sequence Annotation ; },
abstract = {Our study presents the assembly of a high-quality Taihu goose genome at the Telomere-to-Telomere (T2T) level. By employing advanced sequencing technologies, including Pacific Biosciences HiFi reads, Oxford Nanopore long reads, Illumina short reads, and chromatin conformation capture (Hi-C), we achieved an exceptional assembly. The T2T assembly encompasses a total length of 1,197,991,206 bp, with contigs N50 reaching 33,928,929 bp and scaffold N50 attaining 81,007,908 bp. It consists of 73 scaffolds, including 38 autosomes and one pair of Z/W sex chromosomes. Importantly, 33 autosomes were assembled without any gap, resulting in a contiguous representation. Furthermore, gene annotation efforts identified 34,898 genes, including 436,162 RNA transcripts, encompassing 806,158 exons, 743,910 introns, 651,148 coding sequences (CDS), and 135,622 untranslated regions (UTR). The T2T-level chromosome-scale goose genome assembly provides a vital foundation for future genetic improvement and understanding the genetic mechanisms underlying important traits in geese.},
}
@article {pmid38967394,
year = {2024},
author = {Liang, C and Zhao, R and Du, J and Zhao, G and Zhang, Y},
title = {The association between dietary selenium intake and telomere length in hypertension.},
journal = {Journal of clinical hypertension (Greenwich, Conn.)},
volume = {},
number = {},
pages = {},
doi = {10.1111/jch.14861},
pmid = {38967394},
issn = {1751-7176},
support = {82100283//National Natural Science Foundation of China/ ; 82270407//National Natural Science Foundation of China/ ; 232102310181//The Scientific and Technological Project of Henan Province/ ; },
abstract = {Telomere length is closely linked to biological aging, oxidative stress, and the development of cardiovascular diseases. This study aimed to assess the association between dietary selenium intake and telomere length in individuals with hypertension. Data on dietary selenium intake were captured through the National Health and Nutrition Examination Survey (NHANES) computer-assisted dietary interview system (CADI). Telomere length determination entailed selecting blood samples from all participants in the NHANES database. The analysis was performed using Analysis System software, with Empower stats utilized for data analysis. Results showed that there was a significant association between dietary selenium intake and telomere length in hypertension, particularly within the female group. In female hypertension cases, a 1 mcg increase in dietary selenium intake corresponded to a telomere length increase of 1.19 bp, even after adjusting for age, race, BMI, marital status, physical activity, energy intake, and stroke history. The relationship between dietary selenium intake and telomere length exhibited a linear pattern in female hypertension patients. This study identified a positive association between dietary selenium intake and telomere length in hypertension, particularly within the female group.},
}
@article {pmid38966866,
year = {2024},
author = {Yang, T and Cai, Y and Huang, T and Yang, D and Yang, X and Yin, X and Zhang, C and Yang, Y and Yang, Y},
title = {A telomere-to-telomere gap-free reference genome assembly of avocado provides useful resources for identifying genes related to fatty acid biosynthesis and disease resistance.},
journal = {Horticulture research},
volume = {11},
number = {7},
pages = {uhae119},
doi = {10.1093/hr/uhae119},
pmid = {38966866},
issn = {2662-6810},
abstract = {Avocado (Persea americana Mill.) is an economically valuable plant because of the high fatty acid content and unique flavor of its fruits. Its fatty acid content, especially the relatively high unsaturated fatty acid content, provides significant health benefits. We herein present a telomere-to-telomere gapless genome assembly (841.6 Mb) of West Indian avocado. The genome contains 40 629 predicted protein-coding genes. Repeat sequences account for 57.9% of the genome. Notably, all telomeres, centromeres, and a nucleolar organizing region are included in this genome. Fragments from these three regions were observed via fluorescence in situ hybridization. We identified 376 potential disease resistance-related nucleotide-binding leucine-rich repeat genes. These genes, which are typically clustered on chromosomes, may be derived from gene duplication events. Five NLR genes (Pa11g0262, Pa02g4855, Pa07g3139, Pa07g0383, and Pa02g3196) were highly expressed in leaves, stems, and fruits, indicating they may be involved in avocado disease responses in multiple tissues. We also identified 128 genes associated with fatty acid biosynthesis and analyzed their expression patterns in leaves, stems, and fruits. Pa02g0113, which encodes one of 11 stearoyl-acyl carrier protein desaturases mediating C18 unsaturated fatty acid synthesis, was more highly expressed in the leaves than in the stems and fruits. These findings provide valuable insights that enhance our understanding of fatty acid biosynthesis in avocado.},
}
@article {pmid38964064,
year = {2024},
author = {Chang-Chien, J and Kuo, ML and Tseng, YL and Huang, HY and Tsai, HJ and Yao, TC},
title = {Differential effects of long- and short-term exposure to PM2.5 on accelerating telomere shortening: from in vitro to epidemiological studies.},
journal = {Ecotoxicology and environmental safety},
volume = {281},
number = {},
pages = {116650},
doi = {10.1016/j.ecoenv.2024.116650},
pmid = {38964064},
issn = {1090-2414},
abstract = {Exposure to air pollutants has been associated with DNA damage and increases the risks of respiratory diseases, such as asthma and COPD; however short- and long-term effects of air pollutants on telomere dysfunction remain unclear. We investigated the impact of short- and long-term exposure to fine particulate matter with an aerodynamic diameter below 2.5 μm (PM2.5) on telomere length in human bronchial epithelial BEAS-2B cells, and assessed the potential correlation between PM2.5 exposure and telomere length in the LIGHTS childhood cohort study. We observed that long-term, but not short-term, PM2.5 exposure was significantly associated with telomere shortening, along with the downregulation of human telomerase reverse transcriptase (hTERT) mRNA and protein levels. Moreover, long-term exposure to PM2.5 induced proinflammatory cytokine secretion, notably interleukin 6 (IL-6) and IL-8, triggered subG1 cell cycle arrest, and ultimately caused cell death. Long-term exposure to PM2.5 upregulated the LC3-II/ LC3-I ratio but led to p62 protein accumulation in BEAS-2B cells, suggesting a blockade of autophagic flux. Moreover, consistent with our in vitro findings, our epidemiological study found significant association between annual average exposure to higher PM2.5 and shortening of leukocyte telomere length in children. However, no significant association between 7-day short-term exposure to PM2.5 and leukocyte telomere length was observed in children. By combining in vitro experimental and epidemiological studies, our findings provide supportive evidence linking potential regulatory mechanisms to population level with respect to long-term PM2.5 exposure to telomere shortening in humans.},
}
@article {pmid38963484,
year = {2024},
author = {Lim, CJ},
title = {Telomere C-Strand Fill-In Machinery: New Insights into the Human CST-DNA Polymerase Alpha-Primase Structures and Functions.},
journal = {Sub-cellular biochemistry},
volume = {104},
number = {},
pages = {73-100},
pmid = {38963484},
issn = {0306-0225},
mesh = {Humans ; *Telomere/metabolism/genetics ; *DNA Polymerase I/metabolism/genetics/chemistry ; *DNA Primase/metabolism/genetics/chemistry ; *Telomere-Binding Proteins/metabolism/genetics ; *DNA Replication ; Telomerase/metabolism/genetics ; },
abstract = {Telomeres at the end of eukaryotic chromosomes are extended by a specialized set of enzymes and telomere-associated proteins, collectively termed here the telomere "replisome." The telomere replisome acts on a unique replicon at each chromosomal end of the telomeres, the 3' DNA overhang. This telomere replication process is distinct from the replisome mechanism deployed to duplicate the human genome. The G-rich overhang is first extended before the complementary C-strand is filled in. This overhang is extended by telomerase, a specialized ribonucleoprotein and reverse transcriptase. The overhang extension process is terminated when telomerase is displaced by CTC1-STN1-TEN1 (CST), a single-stranded DNA-binding protein complex. CST then recruits DNA polymerase α-primase to complete the telomere replication process by filling in the complementary C-strand. In this chapter, the recent structure-function insights into the human telomere C-strand fill-in machinery (DNA polymerase α-primase and CST) will be discussed.},
}
@article {pmid38960007,
year = {2024},
author = {Alehagen, U and Aaseth, J and Schomburg, L and Larsson, A and Opstad, T and Alexander, J},
title = {Selenoprotein P increases upon Selenium and Coenzyme Q10 Supplementation and is Associated with Telomere Length, Quality of Life and Reduced Inflammation and Mortality.},
journal = {Free radical biology &amp; medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2024.06.027},
pmid = {38960007},
issn = {1873-4596},
abstract = {BACKGROUND: Selenoprotein P (SELENOP) transports selenium to extrahepatic tissues and is a biomarker of selenium status. Low soil selenium leads to low dietary selenium intake. A consequence is an increased risk of cardiovascular disease.<br><br>OBJECTIVE: To investigate clinical aspects associated with SELENOP deficiency, including biomarkers of inflammation, quality of life, and mortality within 12 years, and the effect of dietary selenium and coenzyme Q10 supplementation on SELENOP.<br><br>METHODS: SELENOP was determined at inclusion and after four years of supplementation in 403 elderly community-living participants low in selenium receiving selenium yeast (200 &#x3bc;g/day) and coenzyme Q10 (200 mg/ day), or placebo. Pre-intervention, the average serum selenium level was 67&#x3bc;g/L. T-tests, repeated measures of variance, Cox proportional regressions analyses, Kaplan-Meier graphs and ANCOVA analyses were applied. Associations with biomarkers of inflammation, telomere length, quality of life and mortality were investigated. Benchmark modelling was used to determine the serum selenium concentration at which the saturation levels of SELENOP and GPx3 was achieved. Comparison with GPx3 and serum selenium to identify increased mortality risk was performed, and the effect of supplementation on SELENOP levels were evaluated.<br><br>RESULTS: Inverse associations were observed between the level of SELENOP at inclusion and biomarkers for inflammation. At follow-up, shorter telomere lengths were seen in those with low levels of SELENOP at inclusion, whereas high levels of SELENOP were associated with better quality of life and decreased mortality. SELENOP had increased prognostic power compared to GPx3 and selenium. Saturation of SELENOP was achieved at a serum selenium level of 146 &#x3bc;g/L, and for GPx3 at 99 &#x3bc;g/L. Supplementation induced higher levels of SELENOP.<br><br>CONCLUSION: Significant associations between SELENOP and inflammation, length of telomeres, quality of life, and mortality were observed. Thus, selenium supplementation improved SELENOP expression, thereby facilitating systemic selenium bioavailability and resulting in the observed positive health effects.},
}
@article {pmid38959478,
year = {2024},
author = {Panda, S and Roychowdhury, T and Dutta, A and Chakraborty, S and Das, T and Chatterjee, S},
title = {ALTering Cancer by Triggering Telomere Replication Stress through the Stabilization of Promoter G-Quadruplex in SMARCAL1.},
journal = {ACS chemical biology},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschembio.4c00285},
pmid = {38959478},
issn = {1554-8937},
abstract = {Most of the human cancers are dependent on telomerase to extend the telomeres. But ∼10% of all cancers use a telomerase-independent, homologous recombination mediated pathway called alternative lengthening of telomeres (ALT). Due to the poor prognosis, ALT status is not being considered yet in the diagnosis of cancer. No such specific treatment is available to date for ALT positive cancers. ALT positive cancers are dependent on replication stress to deploy DNA repair pathways to the telomeres to execute homologous recombination mediated telomere extension. SMARCAL1 (SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily A-like 1) is associated with the ALT telomeres to resolve replication stress thus providing telomere stability. Thus, the dependency on replication stress regulatory factors like SMARCAL1 made it a suitable therapeutic target for the treatment of ALT positive cancers. In this study, we found a significant downregulation of SMARCAL1 expression by stabilizing the G-quadruplex (G4) motif found in the promoter of SMARCAL1 by potent G4 stabilizers, like TMPyP4 and BRACO-19. SMARCAL1 downregulation led toward the increased localization of PML (promyelocytic leukemia) bodies in ALT telomeres and triggered the formation of APBs (ALT-associated promyelocytic leukemia bodies) in ALT positive cell lines, increasing telomere replication stress and DNA damage at a genomic level. Induction of replication stress and hyper-recombinogenic phenotype in ALT positive cells mediated by G4 stabilizing molecules already highlighted their possible application as a new therapeutic window to target ALT positive tumors. In accordance with this, our study will also provide a valuable insight toward the development of G4-based ALT therapeutics targeting SMARCAL1.},
}
@article {pmid38953168,
year = {2024},
author = {Estrem, B and Davis, RE and Wang, J},
title = {End resection and telomere healing of DNA double-strand breaks during nematode programmed DNA elimination.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae579},
pmid = {38953168},
issn = {1362-4962},
support = {AI155588/NH/NIH HHS/United States ; //University of Tennessee, Knoxville/ ; },
abstract = {Most DNA double-strand breaks (DSBs) are harmful to genome integrity. However, some forms of DSBs are essential to biological processes, such as meiotic recombination and V(D)J recombination. DSBs are also required for programmed DNA elimination (PDE) in ciliates and nematodes. In nematodes, the DSBs are healed with telomere addition. While telomere addition sites have been well characterized, little is known regarding the DSBs that fragment nematode chromosomes. Here, we used embryos from the human and pig parasitic nematode Ascaris to characterize the DSBs. Using END-seq, we demonstrate that DSBs are introduced before mitosis, followed by extensive end resection. The resection profile is unique for each break site, and the resection generates 3'-overhangs before the addition of neotelomeres. Interestingly, telomere healing occurs much more frequently on retained DSB ends than on eliminated ends. This biased repair of the DSB ends may be due to the sequestration of the eliminated DNA into micronuclei, preventing neotelomere formation at their ends. Additional DNA breaks occur within the eliminated DNA in both Ascaris and Parascaris, ensuring chromosomal breakage and providing a fail-safe mechanism for PDE. Overall, our data indicate that telomere healing of DSBs is specific to the break sites responsible for nematode PDE.},
}
@article {pmid38950694,
year = {2024},
author = {Zhang, D and Eckhardt, CM and McGroder, C and Benesh, S and Porcelli, J and Depender, C and Bogyo, K and Westrich, J and Thomas-Wilson, A and Jobanputra, V and Garcia, CK},
title = {Clinical Impact of Telomere Length Testing for Interstitial Lung Disease.},
journal = {Chest},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chest.2024.06.006},
pmid = {38950694},
issn = {1931-3543},
abstract = {BACKGROUND: Shortened telomere length (TL) is a genomic risk factor for fibrotic interstitial lung disease (ILD), but its role in clinical management is unknown.<br><br>RESEARCH QUESTION: What is the clinical impact of TL testing on the management of ILD?<br><br>STUDY DESIGN AND METHODS: Patients were evaluated in the Columbia University ILD clinic and underwent CLIA-certified TL testing by flow cytometry and fluorescence in-situ hybridization (FlowFISH) as part of clinical management. Short TL was defined as below the 10[th] age-adjusted percentile for either granulocytes or lymphocytes by FlowFISH. Patients were offered genetic counseling and testing if they had short TL or a family history of ILD. FlowFISH TL was compared against research qPCR TL measurement.<br><br>RESULTS: A total of 108 patients underwent TL testing, including those with clinical features of short telomere syndrome such as familial pulmonary fibrosis (50%) or extrapulmonary manifestations in the patient (25%) or a relative (41%). The overall prevalence of short TL was 46% and was similar across clinical ILD diagnoses. The number of short telomere clinical features was independently associated with detecting short TL (OR 2.00, 95% CI [1.27, 3.32]). TL testing led to clinical management changes for 35 (32%) patients, most commonly resulting in reduction or avoidance of immunosuppression. Of the patients who underwent genetic testing (n=34), a positive or candidate diagnostic finding in telomere-related genes was identified in 10 (29%) patients. Inclusion of TL testing below the 1[st] percentile helped reclassify 8 of 9 variants of uncertain significance (VUS) into actionable findings. The qPCR test correlated with FlowFISH, but age-adjusted percentile cutoffs may not be equivalent between the two assays.<br><br>INTERPRETATION: Incorporating TL testing in ILD impacted clinical management and led to the discovery of new actionable genetic variants.},
}
@article {pmid38951712,
year = {2024},
author = {Lechel, A and Ande, S and Ju, Z and Plentz, RR and Schaetzlein, S and Rudolph, C and Wilkens, L and Wiemann, SU and Saretzki, G and Malek, NP and Manns, MP and Buer, J and Rudolph, KL},
title = {Author Correction: The cellular level of telomere dysfunction determines induction of senescence or apoptosis in vivo.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s44319-024-00192-9},
pmid = {38951712},
issn = {1469-3178},
}
@article {pmid38946430,
year = {2024},
author = {Longo, M and Greco, E and Listorti, I and Varricchio, MT and Litwicka, K and Arrivi, C and Mencacci, C and Greco, P},
title = {Telomerase activity, telomere length, and the euploidy rate of human embryos.},
journal = {Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology},
volume = {40},
number = {1},
pages = {2373742},
doi = {10.1080/09513590.2024.2373742},
pmid = {38946430},
issn = {1473-0766},
mesh = {Humans ; Female ; Adult ; *Telomerase/genetics/metabolism ; *Telomere ; Prospective Studies ; Pregnancy ; Aneuploidy ; Fertilization in Vitro ; Granulosa Cells/metabolism ; Infertility, Female/genetics/therapy ; Ovulation Induction ; Blastocyst ; Telomere Homeostasis/physiology ; Sperm Injections, Intracytoplasmic ; },
abstract = {BACKGROUND: Telomeres maintain chromosome stability, while telomerase counteracts their progressive shortening. Telomere length varies between cell types, with leukocyte telomere length (LTL) decreasing with age. Reduced telomerase activity has been linked to reproductive issues in females, such as low pregnancy rates and premature ovarian failure, with recent studies indicating correlations between telomere length in granulosa cells and IVF outcomes.<br><br>OBJECTIVES: The study aims to explore the relationship between telomere length, telomerase activity, and euploid blastocyst rate in infertile women undergoing IVF/ICSI PGT-A cycles.<br><br>METHODS: This prospective study involves 108 patients undergoing controlled ovarian stimulation and PGT-A. Telomere length and telomerase activity were measured in peripheral mononuclear cells and granulosa cells (GC), respectively.<br><br>RESULTS: The telomere repeat copy number to single gene copy number ratio (T/S) results respectively 0.6&#x2009;&#xb1;&#x2009;0.8 in leukocytes and 0.7&#x2009;&#xb1;&#x2009;0.9 in GC. An inverse relationship was found between LTL and the patient's age (p&#x2009;<&#x2009;.01). A higher aneuploid rate was noticed in patients with short LTL, with no differences in ovarian reserve markers (p&#x2009;=&#x2009;.15), number of oocytes retrieved (p&#x2009;=&#x2009;.33), and number of MII (p&#x2009;=&#x2009;0.42). No significant association was noticed between telomere length in GC and patients' age (p&#x2009;=&#x2009;0.95), in ovarian reserve markers (p&#x2009;=&#x2009;0.32), number of oocytes retrieved (p&#x2009;=&#x2009;.58), number of MII (p&#x2009;=&#x2009;.74) and aneuploidy rate (p&#x2009;=&#x2009;.65).<br><br>CONCLUSION: LTL shows a significant inverse correlation with patient age and higher aneuploidy rates. Telomere length in GCs does not correlate with patient age or reproductive outcomes, indicating differential telomere dynamics between leukocytes and granulosa cells.},
}
@article {pmid38945863,
year = {2024},
author = {Teramoto, N and Okada, Y and Aburada, N and Hayashi, M and Ito, J and Shirasuna, K and Iwata, H},
title = {Resveratrol intake by males increased the mitochondrial DNA copy number and telomere length of blastocysts derived from aged mice.},
journal = {The Journal of reproduction and development},
volume = {},
number = {},
pages = {},
doi = {10.1262/jrd.2024-043},
pmid = {38945863},
issn = {1348-4400},
abstract = {The present study examined whether male resveratrol intake affected mitochondrial DNA copy number (mt-cn) and telomere length (TL) in blastocysts fathered by young and aged male mice. C57BL/6N male mice supplied with water or water containing 0.1 mM resveratrol were used for embryo production at 14-23 and 48-58 weeks of age. Two-cell-stage embryos were collected from the oviducts of superovulated female mice (8-15 weeks old) and cultured for 3 days until the blastocyst stage. Mt-cn and TL levels were measured by real-time polymerase chain reaction. Resveratrol intake did not affect body weight or water consumption. Resveratrol intake increased the expression levels of SIRT1 in the liver, the antioxidative ability of serum, and extended TL in the heart, whereas there was no significant difference in mt-cn in the heart or TL in sperm. The rate of blastocyst development was significantly lower in aged male mice than in younger mice, and resveratrol intake increased the total number of blastocysts derived from both young and aged males. Resveratrol intake did not affect mt-cn or TL in blastomeres of blastocyst-stage embryos derived from young mice, but significantly increased both mt-cn and TL in blastomeres of blastocysts derived from aged fathers. In conclusion, resveratrol intake increased mt-cn and TL levels in blastocysts derived from aged male mice.},
}
@article {pmid38943658,
year = {2024},
author = {Moeckel, C and Gaydosh, L and Schneper, L and Mitchell, C and Notterman, DA},
title = {Material hardship and telomere length in children.},
journal = {Child development},
volume = {},
number = {},
pages = {},
doi = {10.1111/cdev.14126},
pmid = {38943658},
issn = {1467-8624},
support = {P2CHD047879//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R01HD036916//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R01HD076592//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R01HD36916//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R01HD39135//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R01HD40421//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; },
abstract = {Telomere length (TL) serves as a biomarker of exposure to stressors, including material hardship. Data from the Future of Families and Child Wellbeing Study (1998-2015) were utilized to determine whether prior material hardship was associated with shorter salivary TL at years 9 and 15. 49% of the year 9 study population were female, 49% were Black, and 25% were Hispanic. At year 9 (N = 1990), regression analyses found a significant association between prior material hardship and shorter TL (β = -.005, p < .01). Additionally, at year 15 (N = 1874), material hardship experienced during infancy and toddlerhood was associated with shorter TL (β = -.009, p < .01), pointing toward infancy and toddlerhood as a sensitive period.},
}
@article {pmid38943263,
year = {2024},
author = {Lee, Y and Jugessur, A and Gjessing, HK and Harris, JR and Susser, E and Magnus, P and Aviv, A},
title = {Effect of polygenic scores of telomere length alleles on telomere length in newborns and parents.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e14241},
doi = {10.1111/acel.14241},
pmid = {38943263},
issn = {1474-9726},
support = {R01 HL134840/NH/NIH HHS/United States ; 223273//Norges Forskningsr&#xe5;d/ ; 229624//Norges Forskningsr&#xe5;d/ ; 262043//Norges Forskningsr&#xe5;d/ ; 262700//Norges Forskningsr&#xe5;d/ ; },
abstract = {In adults, polygenic scores (PGSs) of telomere length (TL) alleles explain about 4.5% of the variance in TL, as measured by quantitative polymerase chain reaction (qPCR). Yet, these PGSs strongly infer a causal role of telomeres in aging-related diseases. To better understand the determinants of TL through the lifespan, it is essential to examine to what extent these PGSs explain TL in newborns. This study investigates the effect of PGSs on TL in both newborns and their parents, with TL measured by Southern blotting and expressed in base-pairs (bp). Additionally, the study explores the impact of PGSs related to transmitted or non-transmitted alleles on TL in newborns. For parents and newborns, the PGS effects on TL were 172 bp (p = 2.03 × 10[-15]) and 161 bp (p = 3.06 × 10[-8]), explaining 6.6% and 5.2% of the TL variance, respectively. The strongest PGS effect was shown for maternally transmitted alleles in newborn girls, amounting to 214 bp (p = 3.77 × 10[-6]) and explaining 7.8% of the TL variance. The PGS effect of non-transmitted alleles was 56 bp (p = 0.0593) and explained 0.6% of the TL variance. Our findings highlight the importance of TL genetics in understanding early-life determinants of TL. They point to the potential utility of PGSs composed of TL alleles in identifying susceptibility to aging-related diseases from birth and reveal the presence of sexual dimorphism in the effect of TL alleles on TL in newborns. Finally, we attribute the higher TL variance explained by PGSs in our study to TL measurement by Southern blotting.},
}
@article {pmid38937972,
year = {2024},
author = {Wang, K and Jin, J and Wang, J and Wang, X and Sun, J and Meng, D and Wang, X and Guo, L},
title = {The complete telomere-to-telomere genome assembly of lettuce.},
journal = {Plant communications},
volume = {},
number = {},
pages = {101011},
doi = {10.1016/j.xplc.2024.101011},
pmid = {38937972},
issn = {2590-3462},
}
@article {pmid38936230,
year = {2024},
author = {Rodríguez-Fernández, B and Sánchez-Benavides, G and Genius, P and Minguillon, C and Fauria, K and De Vivo, I and Navarro, A and Molinuevo, JL and Gispert, JD and Sala-Vila, A and Vilor-Tejedor, N and Crous-Bou, M and , },
title = {Association between telomere length and cognitive function among cognitively unimpaired individuals at risk of Alzheimer's disease.},
journal = {Neurobiology of aging},
volume = {141},
number = {},
pages = {140-150},
doi = {10.1016/j.neurobiolaging.2024.05.015},
pmid = {38936230},
issn = {1558-1497},
abstract = {INTRODUCTION: Leukocyte telomere length (LTL) is an objective biomarker of biological aging, and it is proposed to play a crucial role in Alzheimer's disease (AD) risk. We aimed at evaluating the cross-sectional association between LTL and cognitive performance in middle-aged cognitively unimpaired individuals at increased risk of AD.<br><br>METHODS: A total of 1520 participants from the ALFA cohort were included. Relative telomere length was measured in leukocytes through qPCR. LTL was residualized against age and sex, and associations with cognitive performance were assessed in short and long groups based on residualized LTL (rLTL). Interactions with sex and genetic risk of AD were tested.<br><br>RESULTS: Non-linear associations were found between LTL and episodic memory (EM). Better EM was associated with longer rLTL among women in the short rLTL group.<br><br>DISCUSSION: Results suggest a potential role of telomeres in the cognitive aging process with sex-specific patterns.},
}
@article {pmid38935034,
year = {2024},
author = {Vaghefi, E and An, S and Corbett, R and Squirrell, D},
title = {Association of retinal image-based, deep learning cardiac BioAge with telomere length and cardiovascular biomarkers.},
journal = {Optometry and vision science : official publication of the American Academy of Optometry},
volume = {},
number = {},
pages = {},
doi = {10.1097/OPX.0000000000002158},
pmid = {38935034},
issn = {1538-9235},
abstract = {SIGNIFICANCE: Our retinal image-based deep learning (DL) cardiac biological age (BioAge) model could facilitate fast, accurate, noninvasive screening for cardiovascular disease (CVD) in novel community settings and thus improve outcome with those with limited access to health care services.<br><br>PURPOSE: This study aimed to determine whether the results issued by our DL cardiac BioAge model are consistent with the known trends of CVD risk and the biomarker leukocyte telomere length (LTL), in a cohort of individuals from the UK Biobank.<br><br>METHODS: A cross-sectional cohort study was conducted using those individuals in the UK Biobank who had LTL data. These individuals were divided by sex, ranked by LTL, and then grouped into deciles. The retinal images were then presented to the DL model, and individual's cardiac BioAge was determined. Individuals within each LTL decile were then ranked by cardiac BioAge, and the mean of the CVD risk biomarkers in the top and bottom quartiles was compared. The relationship between an individual's cardiac BioAge, the CVD biomarkers, and LTL was determined using traditional correlation statistics.<br><br>RESULTS: The DL cardiac BioAge model was able to accurately stratify individuals by the traditional CVD risk biomarkers, and for both males and females, those issued with a cardiac BioAge in the top quartile of their chronological peer group had a significantly higher mean systolic blood pressure, hemoglobin A1c, and 10-year Pooled Cohort Equation CVD risk scores compared with those individuals in the bottom quartile (p<0.001). Cardiac BioAge was associated with LTL shortening for both males and females (males: -0.22, r2 = 0.04; females: -0.18, r2 = 0.03).<br><br>CONCLUSIONS: In this cross-sectional cohort study, increasing CVD risk whether assessed by traditional biomarkers, CVD risk scoring, or our DL cardiac BioAge, CVD risk model, was inversely related to LTL. At a population level, our data support the growing body of evidence that suggests LTL shortening is a surrogate marker for increasing CVD risk and that this risk can be captured by our novel DL cardiac BioAge model.},
}
@article {pmid38929154,
year = {2024},
author = {Shan, J and Mo, J and An, C and Xiang, L and Qi, J},
title = {β-Cyclocitral from Lavandula angustifolia Mill. Exerts Anti-Aging Effects on Yeasts and Mammalian Cells via Telomere Protection, Antioxidative Stress, and Autophagy Activation.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {13},
number = {6},
pages = {},
doi = {10.3390/antiox13060715},
pmid = {38929154},
issn = {2076-3921},
support = {2022YFE0104000//the National Key R&amp;D Program of China/ ; 22177102//NSFC/ ; },
abstract = {We used a replicative lifespan (RLS) experiment of K6001 yeast to screen for anti-aging compounds within lavender extract (Lavandula angustifolia Mill.), leading to the discovery of β-cyclocitral (CYC) as a potential anti-aging compound. Concurrently, the chronological lifespan (CLS) of YOM36 yeast and mammalian cells confirmed the anti-aging effect of CYC. This molecule extended the yeast lifespan and inhibited etoposide (ETO)-induced cell senescence. To understand the mechanism of CYC, we analyzed its effects on telomeres, oxidative stress, and autophagy. CYC administration resulted in notable increases in the telomerase content, telomere length, and the expression of the telomeric shelterin protein components telomeric-repeat binding factor 2 (TRF2) and repressor activator protein 1 (RAP1). More interestingly, CYC reversed H2O2-induced telomere damage and exhibited strong antioxidant capacity. Moreover, CYC improved the survival rate of BY4741 yeast under oxidative stress induced by 6.2 mM H2O2, increasing the antioxidant enzyme activity while reducing the reactive oxygen species (ROS), reactive nitrogen species (RNS), and malondialdehyde (MDA) levels. Additionally, CYC enhanced autophagic flux and free green fluorescent protein (GFP) expression in the YOM38-GFP-ATG8 yeast strain. However, CYC did not extend the RLS of K6001 yeast mutants, such as Δsod1, Δsod2, Δcat, Δgpx, Δatg2, and Δatg32, which lack antioxidant enzymes or autophagy-related genes. These findings reveal that CYC acts as an anti-aging agent by modifying telomeres, oxidative stress, and autophagy. It is a promising compound with potential anti-aging effects and warrants further study.},
}
@article {pmid38928414,
year = {2024},
author = {Harutyunyan, T and Sargsyan, A and Kalashyan, L and Igityan, H and Grigoryan, B and Davtyan, H and Aroutiounian, R and Liehr, T and Hovhannisyan, G},
title = {Changes in Telomere Length in Leukocytes and Leukemic Cells after Ultrashort Electron Beam Radiation.},
journal = {International journal of molecular sciences},
volume = {25},
number = {12},
pages = {},
doi = {10.3390/ijms25126709},
pmid = {38928414},
issn = {1422-0067},
support = {22SC-BMBF-1C001//RA MESCS Science Committee and German Federal Ministry of Education and Research/ ; 21AG-1F068//RA MESCS Science Committee/ ; 01DK24003//German Aerospace Center (= Deutsches Forschungszentrum f&#xfc;r Luft- und Raumfahrt, DLR)/ ; },
mesh = {Humans ; K562 Cells ; *Leukocytes/radiation effects/metabolism ; *Electrons ; *Telomere/radiation effects/genetics/metabolism ; Leukemia/genetics/pathology/radiotherapy ; Telomere Homeostasis/radiation effects ; In Situ Hybridization, Fluorescence ; Telomere Shortening/radiation effects ; DNA Damage/radiation effects ; Dose-Response Relationship, Radiation ; },
abstract = {Application of laser-generated electron beams in radiotherapy is a recent development. Accordingly, mechanisms of biological response to radiation damage need to be investigated. In this study, telomere length (TL) as endpoint of genetic damage was analyzed in human blood cells (leukocytes) and K562 leukemic cells irradiated with laser-generated ultrashort electron beam. Metaphases and interphases were analyzed in quantitative fluorescence in situ hybridization (Q-FISH) to assess TL. TLs were shortened compared to non-irradiated controls in both settings (metaphase and interphase) after irradiation with 0.5, 1.5, and 3.0 Gy in blood leukocytes. Radiation also caused a significant TL shortening detectable in the interphase of K562 cells. Overall, a negative correlation between TL and radiation doses was observed in normal and leukemic cells in a dose-dependent manner. K562 cells were more sensitive than normal blood cells to increasing doses of ultrashort electron beam radiation. As telomere shortening leads to genome instability and cell death, the results obtained confirm the suitability of this biomarker for assessing genotoxic effects of accelerated electrons for their further use in radiation therapy. Observed differences in TL shortening between normal and K562 cells provide an opportunity for further development of optimal radiation parameters to reduce side effects in normal cells during radiotherapy.},
}
@article {pmid38927760,
year = {2024},
author = {Arellano, MYG and VanHeest, M and Emmadi, S and Abdul-Hafez, A and Ibrahim, SA and Thiruvenkataramani, RP and Teleb, RS and Omar, H and Kesaraju, T and Mohamed, T and Madhukar, BV and Omar, SA},
title = {Role of Mesenchymal Stem/Stromal Cells (MSCs) and MSC-Derived Extracellular Vesicles (EVs) in Prevention of Telomere Length Shortening, Cellular Senescence, and Accelerated Biological Aging.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {11},
number = {6},
pages = {},
doi = {10.3390/bioengineering11060524},
pmid = {38927760},
issn = {2306-5354},
abstract = {Biological aging is defined as a progressive decline in tissue function that eventually results in cell death. Accelerated biologic aging results when the telomere length is shortened prematurely secondary to damage from biological or environmental stressors, leading to a defective reparative mechanism. Stem cells therapy may have a potential role in influencing (counteract/ameliorate) biological aging and maintaining the function of the organism. Mesenchymal stem cells, also called mesenchymal stromal cells (MSCs) are multipotent stem cells of mesodermal origin that can differentiate into other types of cells, such as adipocytes, chondrocytes, and osteocytes. MSCs influence resident cells through the secretion of paracrine bioactive components such as cytokines and extracellular vesicles (EVs). This review examines the changes in telomere length, cellular senescence, and normal biological age, as well as the factors contributing to telomere shortening and accelerated biological aging. The role of MSCs-especially those derived from gestational tissues-in prevention of telomere shortening (TS) and accelerated biological aging is explored. In addition, the strategies to prevent MSC senescence and improve the antiaging therapeutic application of MSCs and MSC-derived EVs in influencing telomere length and cellular senescence are reviewed.},
}
@article {pmid38927389,
year = {2024},
author = {Almuraikhy, S and Sellami, M and Naja, K and Al-Amri, HS and Anwardeen, N and Aden, A and Dömling, A and Elrayess, MA},
title = {Joint Effects of Exercise and Ramadan Fasting on Telomere Length: Implications for Cellular Aging.},
journal = {Biomedicines},
volume = {12},
number = {6},
pages = {},
doi = {10.3390/biomedicines12061182},
pmid = {38927389},
issn = {2227-9059},
support = {IRCC-2022-467//Qatar University/ ; },
abstract = {Aging is a fundamental biological process that progressively impairs the functionality of the bodily systems, leading to an increased risk of diseases. Telomere length is one of the most often used biomarkers of aging. Recent research has focused on developing interventions to mitigate the effects of aging and improve the quality of life. The objective of this study was to investigate the combined effect of exercise and Ramadan fasting on telomere length. Twenty-nine young, non-obese, healthy females were randomized into two groups: the control group underwent a 4-week exercise training program, and the second group underwent a 4-week exercise training program while fasting during Ramadan. Blood samples were collected, and measurements of clinical traits, cytokines, oxidative stress, and telomere length were performed before and after intervention. Telomere length increased significantly from baseline in the exercise-while-fasting group, but showed no significant change in the exercise control group. This increase was accompanied by a reduction in TNF-α, among other cytokines. Additionally, a significant positive correlation was observed between the mean change in telomere length and HDL in the exercise-while-fasting group only. This study is the first to report an increase in telomere length after combining Ramadan fasting with training, suggesting that exercising while fasting may be an effective tool for slowing down the aging rate. Further studies using larger and more diverse cohorts are warranted.},
}
@article {pmid38926996,
year = {2024},
author = {Li, DN and Wen, XH},
title = {[Role of Telomere in Clonal Evolution of Acquired Aplastic Anemia--Review].},
journal = {Zhongguo shi yan xue ye xue za zhi},
volume = {32},
number = {3},
pages = {962-964},
doi = {10.19746/j.cnki.issn.1009-2137.2024.03.048},
pmid = {38926996},
issn = {1009-2137},
mesh = {*Anemia, Aplastic/genetics ; Humans ; *Telomere/genetics ; *Clonal Evolution ; *Telomerase/genetics ; Telomere Shortening ; },
abstract = {Studies have found that 1/3 patients with acquired aplastic anemia have shortened telomere length, and the shorter the telomere, the longer the disease course, the more prone to relapse, the lower the overall survival rate, and the higher the probability of clonal evolution. The regulation of telomere length is affected by many factors, including telomerase activity, telomerase-related genes, telomere regulatory proteins and other related factors. Telomere shortening can lead to genetic instability and increases the probability of clonal evolution in patients with acquired aplastic anemia. This article reviews the role of telomere in the clonal evolution of acquired aplastic anemia and factors affecting telomere length.},
}
@article {pmid38933758,
year = {2023},
author = {Zhang, Y and Pang, N and Huang, X and Meng, W and Meng, L and Zhang, B and Jiang, Z and Zhang, J and Yi, Z and Luo, Z and Wang, Z and Niu, L},
title = {Ultrasound deep brain stimulation decelerates telomere shortening in Alzheimer's disease and aging mice.},
journal = {Fundamental research},
volume = {3},
number = {3},
pages = {469-478},
doi = {10.1016/j.fmre.2022.02.010},
pmid = {38933758},
issn = {2667-3258},
abstract = {Telomere length is a reliable biomarker for health and longevity prediction in both humans and animals. The common neuromodulation techniques, including deep brain stimulation (DBS) and optogenetics, have excellent spatial resolution and depth penetration but require implementation of electrodes or optical fibers. Therefore, it is important to develop methods for noninvasive modulation of telomere length. Herein, we reported on a new method for decelerating telomere shortening using noninvasive ultrasound deep brain stimulation (UDBS). Firstly, we found that UDBS could activate the telomerase-associated proteins in normal mice. Then, in the Alzheimer's disease mice, UDBS was observed to decelerate telomere shortening of the cortex and myocardial tissue and to effectively improve spatial learning and memory abilities. Similarly, UDBS was found to significantly slow down telomere shortening of the cortex and peripheral blood, and improve motor and cognitive functions in aging mice. Finally, transcriptome analysis revealed that UDBS upregulated the neuroactive ligand-receptor interaction pathway. Overall, the present findings established the critical role of UDBS in delaying telomere shortening and indicated that ultrasound modulation of telomere length may constitute an effective therapeutic strategy for aging and aging-related diseases.},
}
@article {pmid38926610,
year = {2024},
author = {Wang, Z and Zuo, M and Li, W and Chen, S and Yuan, Y and He, Y and Yang, Y and Mao, Q and Liu, Y},
title = {The impact of telomere length on the risk of idiopathic normal pressure hydrocephalus: a bidirectional Mendelian randomization study.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {14713},
pmid = {38926610},
issn = {2045-2322},
support = {2023YFG0127//the Sichuan Science and Technology Program/ ; 2023YFQ0002//the Sichuan Science and Technology Program/ ; },
abstract = {Idiopathic normal pressure hydrocephalus (iNPH) affects mainly aged populations. The gradual shortening of telomere length (TL) is one of the hallmarks of aging. Whereas the genetic contribution of TL to the iNPH is incompletely understood. We aimed to investigate the causal relationship between TL and iNPH through the Mendelian randomization (MR) analysis. We respectively obtained 186 qualified single nucleotide polymorphisms (SNPs) of TL and 20 eligible SNPs of iNPH for MR analysis. The result of MR analysis showed that genetically predicted longer TL was significantly associated with a reduced odd of iNPH (odds ratio [OR] = 0.634 95% Confidence interval [CI] 0.447-0.899, p = 0.011). The causal association remained consistent in multivariable MR (OR = 0.530 95% CI 0.327-0.860, p = 0.010). However, there was no evidence that the iNPH was causally associated with the TL (OR = 1.000 95% CI 0.996-1.004, p = 0.955). Our study reveals a potential genetic contribution of TL to the etiology of iNPH, that is a genetically predicted increased TL might be associated with a reduced risk of iNPH.},
}
@article {pmid38922965,
year = {2024},
author = {Joo, SY and Sung, K and Lee, H},
title = {Balancing act: BRCA2's elaborate management of telomere replication through control of G-quadruplex dynamicity.},
journal = {BioEssays : news and reviews in molecular, cellular and developmental biology},
volume = {},
number = {},
pages = {e2300229},
doi = {10.1002/bies.202300229},
pmid = {38922965},
issn = {1521-1878},
support = {2020R1A5A1018081//National Research Foundation of Korea (NRF)/ ; 2021R1A2C1006191//National Research Foundation of Korea (NRF)/ ; },
abstract = {In billion years of evolution, eukaryotes preserved the chromosome ends with arrays of guanine repeats surrounded by thymines and adenines, which can form stacks of four-stranded planar structure known as G-quadruplex (G4). The rationale behind the evolutionary conservation of the G4 structure at the telomere remained elusive. Our recent study has shed light on this matter by revealing that telomere G4 undergoes oscillation between at least two distinct folded conformations. Additionally, tumor suppressor BRCA2 exhibits a unique mode of interaction with telomere G4. To elaborate, BRCA2 directly interacts with G-triplex (G3)-derived intermediates that form during the interconversion of the two different G4 states. In doing so, BRCA2 remodels the G4, facilitating the restart of stalled replication forks. In this review, we succinctly summarize the findings regarding the dynamicity of telomeric G4, emphasize its importance in maintaining telomere replication homeostasis, and the physiological consequences of losing G4 dynamicity at the telomere.},
}
@article {pmid38922089,
year = {2024},
author = {Ouyang, C and Yang, Y and Pan, J and Liu, H and Wang, X and Zhou, S and Shi, X and Zhang, Y and Wang, D and Hu, X},
title = {Leukocyte Telomere Length Mediates the Associations between Blood Lead and Cadmium with Hypertension among Adults in the United States: A Cross-Sectional Study.},
journal = {Toxics},
volume = {12},
number = {6},
pages = {},
doi = {10.3390/toxics12060409},
pmid = {38922089},
issn = {2305-6304},
support = {No. 23JRRA0969//Gansu Provincial Natural Science Foundation/ ; },
abstract = {There is evidence to support the links between lead and cadmium exposure with hypertension and also with leukocyte telomere length (LTL). The objective of this study is to investigate the role that LTL may play in the relationship between lead and cadmium exposure and hypertension. This study consisted of 3718 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Logistic regression was used to analyze the relationship between blood metals with hypertension, and the mediating model was used to evaluate the mediating effect of LTL. In the fully adjusted model, both blood lead and cadmium ln-transformed concentrations were significantly positively associated with hypertension risk, as were all quartiles of blood lead. Additionally, we observed positive linear dose-response relationships with hypertension by restricted cubic spline analysis (both p overall < 0.001, p non-linear = 0.3008 for lead and p non-linear = 0.7611 for cadmium). The ln-transformed blood lead and cadmium concentrations were associated with shorter LTL. LTL was inversely related to hypertension and the OR was 0.65 (95% CI: 0.47 to 0.89). Furthermore, LTL had mediating effects on the associations of blood lead and cadmium with hypertension risk, and the mediation proportions were 2.25% and 4.20%, respectively. Our findings suggested that exposure to lead and cadmium raised the risk of hypertension, while LTL played as a mediating factor.},
}
@article {pmid38919841,
year = {2024},
author = {Croons, H and Martens, DS and Vanderstukken, C and Sleurs, H and Rasking, L and Peusens, M and Renaers, E and Plusquin, M and Nawrot, TS},
title = {Telomere length in early childhood and its association with attention: a study in 4-6 year old children.},
journal = {Frontiers in pediatrics},
volume = {12},
number = {},
pages = {1358272},
pmid = {38919841},
issn = {2296-2360},
abstract = {Telomere length (TL), a marker of cellular aging, has been studied in adults with regard to its connection to cognitive function. However, little is known about the association between TL and cognitive development in children. This study investigated the interplay between TL and cognitive functioning in 283 Belgian children aged four to six years of the Environmental Influence on Aging in Early Life (ENVIRONAGE) birth cohort. Child leukocyte TL was measured using qPCR, while cognitive functioning, including attention and memory, was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Linear regression models were employed to examine the association between TL and cognitive outcomes, adjusting for potential confounders. We found an inverse association between TL and the spatial errors made during the Motor Screening task (p = 0.017), indicating a higher motor accuracy in children with longer telomeres. No significant associations were found between TL and other cognitive outcomes. Our results suggest a specific link between TL and motor accuracy but not with the other cognitive domains.},
}
@article {pmid38917803,
year = {2024},
author = {Tan, KT and Slevin, MK and Leibowitz, ML and Garrity-Janger, M and Shan, J and Li, H and Meyerson, M},
title = {Neotelomeres and telomere-spanning chromosomal arm fusions in cancer genomes revealed by long-read sequencing.},
journal = {Cell genomics},
volume = {},
number = {},
pages = {100588},
doi = {10.1016/j.xgen.2024.100588},
pmid = {38917803},
issn = {2666-979X},
abstract = {Alterations in the structure and location of telomeres are pivotal in cancer genome evolution. Here, we applied both long-read and short-read genome sequencing to assess telomere repeat-containing structures in cancers and cancer cell lines. Using long-read genome sequences that span telomeric repeats, we defined four types of telomere repeat variations in cancer cells: neotelomeres where telomere addition heals chromosome breaks, chromosomal arm fusions spanning telomere repeats, fusions of neotelomeres, and peri-centromeric fusions with adjoined telomere and centromere repeats. These results provide a framework for the systematic study of telomeric repeats in cancer genomes, which could serve as a model for understanding the somatic evolution of other repetitive genomic elements.},
}
@article {pmid38916238,
year = {2024},
author = {Zhang, J and Yang, XY and Chen, J and Zhou, Q and Pan, G and Wang, Y and Luo, W and Hou, J and Bao, H and Xu, G and Tang, G and Bai, H and Yu, R},
title = {A Poly(amino acid)-Based Nanomedicine Strategy: Telomere-Telomerase Axis Targeting and Magnetic Resonance Imaging in Hepatocellular Carcinoma Treatment.},
journal = {Nano letters},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.nanolett.4c01767},
pmid = {38916238},
issn = {1530-6992},
abstract = {Targeting telomere maintenance has emerged as a promising strategy for hepatocellular carcinoma (HCC) treatment. However, given the duality of the telomere-telomerase axis in telomere maintenance, a comprehensive strategy is urgently needed. Herein, we develop a poly(amino acid) (D-PAAs)-based strategy for spatiotemporal codelivery of telomerase inhibitor, BIBR1523, and AKT inhibitor, isobavachalcone. By leveraging D-PAAs' modifiability, we synthesize polymer-inhibitor conjugates (PB and PI) and a folic acid-decorated tumor-targeting vector (PF). These building blocks undergo micellization to fabricate a codelivery nanomedicine (P-BI@P-FA) by exploiting D-PAAs' noncovalent assembly. P-BI@P-FA improves the pharmacokinetics, tumor selectivity, and bioavailability of small molecule inhibitors and initiates a dual telomere-specific inhibition by combining telomerase deactivation with telomere disruption. Furthermore, a hybrid tumor-targeting magnetic nanosystem is designed using D-PAAs and manganese dioxide to showcase magnetic resonance imaging capacities. Our D-PAAs-based strategy addresses the pressing need for telomere-specific HCC treatment while allowing for diagnostic application, presenting a promising avenue for nanomedicine design.},
}
@article {pmid38915611,
year = {2024},
author = {Teplitz, GM and Pasquier, E and Bonnell, E and Laurentiis, E and Bartle, L and Lucier, JF and Sholes, S and Greider, CW and Wellinger, RJ},
title = {A mechanism for telomere-specific telomere length regulation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.06.12.598646},
pmid = {38915611},
abstract = {Telomeric DNA, composed of short, direct repeats, is of crucial importance for chromosome stability. Due to intrinsic problems with replicating this DNA, the repeat tracts shorten at each cell division. Once repeat tracts become critically short, a telomeric stress signal induces cellular senescence and division arrest, which eventually may lead to devastating age-related degenerative diseases associated with dysfunctional telomers. Conversely, maintenance of telomere length by telomerase upregulation is a hallmark of cancer. Therefore, telomere length is a critical determinant of telomere function. How telomere length is established and molecular mechanisms for telomere-specific length regulation remained unknown. Here we show that subtelomeric chromatin is a determinant for how telomere equilibrium set-length is established in cis . The results demonstrate that telomerase recruitment mediated by the telomere-associated Sir4 protein is modulated on chromosome 3L in a telomere-specific way. Increased Sir4 abundance on subtelomeric heterochromatin of this specific telomere leads to telomere lengthening of only that telomere in cis , but not at other telomeres. Therefore, this work describes a mechanism for a how telomere-specific repeat tract length can be established. Further, our results will force the evaluation of telomere length away from a generalized view to a more telomere-specific consideration.},
}
@article {pmid38914514,
year = {2024},
author = {Yang, SH and Liu, HT and Wang, TF and Liou, YS and Sun, DS and Wang, JH and Chen, LY},
title = {Shorter donor leukocyte telomere length is associated with poor peripheral blood stem cell mobilization induced by granulocyte colony-stimulating factor.},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2024.06.017},
pmid = {38914514},
issn = {0929-6646},
abstract = {BACKGROUND/PURPOSE: Insufficient numbers of peripheral blood stem cells (PBSC) after granulocyte colony-stimulating factor (G-CSF) mobilization occurs in a significant proportion of PBSC collections, often from older age donors. Telomere length (TL) is often used as an indicator of an individual's biological age. This study aimed to investigate the relationship between donors' leukocyte TL and the outcome of G-CSF-induced PBSC mobilization in healthy unrelated donors.<br><br>METHODS: Donors' leukocyte TLs and the outcome of G-CSF-induced PBSC mobilization, as assessed by pre-harvest CD34[+] cell counts, were analyzed in 39 healthy PBSC donors. TL in a non-mobilized general population (n&#xa0;=&#xa0;90) was included as a control group. G-CSF mobilization effect was categorized into three groups according to pre-harvest CD34[+] cell count: poor (&#x2264;25/&#x3bc;L, PMD), intermediate (between 25 and 180/&#x3bc;L), and good (&#x2265;180/&#x3bc;l, GMD).<br><br>RESULTS: Leukocyte TL of PBSC donors correlated well with pre-harvest CD34[+] cell counts (r&#xa0;=&#xa0;0.645, p&#xa0;<&#xa0;0.001). Leukocyte TLs of PMDs (n&#xa0;=&#xa0;8) were significantly shorter than those of GMDs (n&#xa0;=&#xa0;9) and non-mobilization controls (p&#xa0;<&#xa0;0.05). Moreover, all PMD TLs were below the 50th percentile, and 62.5% of PMDs had TLs below the 10th percentile of age-matched control participants. In contrast, no GMD TLs were below the 10th percentile; in fact, 33.3% (3/9) of them were above the 90th percentile.<br><br>CONCLUSION: Our results indicate that shorter donor leukocyte TL is associated with poor G-CSF-induced PBSC mobilization. TL, which represents a donor's biological age, could be a potential predictor for mobilization outcome.},
}
@article {pmid38910895,
year = {2024},
author = {Gu, L and Liu, M and Zhang, Y and Zhou, H and Wang, Y and Xu, ZX},
title = {Telomere-related DNA damage response pathways in cancer therapy: prospective targets.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1379166},
pmid = {38910895},
issn = {1663-9812},
abstract = {Maintaining the structural integrity of genomic chromosomal DNA is an essential role of cellular life and requires two important biological mechanisms: the DNA damage response (DDR) mechanism and telomere protection mechanism at chromosome ends. Because abnormalities in telomeres and cellular DDR regulation are strongly associated with human aging and cancer, there is a reciprocal regulation of telomeres and cellular DDR. Moreover, several drug treatments for DDR are currently available. This paper reviews the progress in research on the interaction between telomeres and cellular DNA damage repair pathways. The research on the crosstalk between telomere damage and DDR is important for improving the efficacy of tumor treatment. However, further studies are required to confirm this hypothesis.},
}
@article {pmid38902824,
year = {2024},
author = {Zhao, S and Li, J and Duan, S and Liu, C and Wang, H and Lu, J and Zhao, N and Sheng, X and Wu, Y and Li, Y and Sun, B and Liu, L},
title = {UBQLN1 links proteostasis and mitochondria function to telomere maintenance in human embryonic stem cells.},
journal = {Stem cell research &amp; therapy},
volume = {15},
number = {1},
pages = {180},
pmid = {38902824},
issn = {1757-6512},
support = {32030033//National Natural Science Foundation of China/ ; 82230052//National Natural Science Foundation of China/ ; 32261160571//National Natural Science Foundation of China/ ; 20JCZDJC00550//Tianjin Science and Technology Plan Key Project/ ; },
abstract = {BACKGROUND: Telomeres consist of repetitive DNA sequences at the chromosome ends to protect chromosomal stability, and primarily maintained by telomerase or occasionally by alternative telomere lengthening of telomeres (ALT) through recombination-based mechanisms. Additional mechanisms that may regulate telomere maintenance remain to be explored. Simultaneous measurement of telomere length and transcriptome in the same human embryonic stem cell (hESC) revealed that mRNA expression levels of UBQLN1 exhibit linear relationship with telomere length.<br><br>METHODS: In this study, we first generated UBQLN1-deficient hESCs and compared with the wild-type (WT) hESCs the telomere length and molecular change at RNA and protein level by RNA-seq and proteomics. Then we identified the potential interacting proteins with UBQLN1 using immunoprecipitation-mass spectrometry (IP-MS). Furthermore, the potential mechanisms underlying the shortened telomeres in UBQLN1-deficient hESCs were analyzed.<br><br>RESULTS: We show that Ubiquilin1 (UBQLN1) is critical for telomere maintenance in human embryonic stem cells (hESCs) via promoting mitochondrial function. UBQLN1 deficiency leads to oxidative stress, loss of proteostasis, mitochondria dysfunction, DNA damage, and telomere attrition. Reducing oxidative damage and promoting mitochondria function by culture under hypoxia condition or supplementation with N-acetylcysteine partly attenuate the telomere attrition induced by UBQLN1 deficiency. Moreover, UBQLN1 deficiency/telomere shortening downregulates genes for neuro-ectoderm lineage differentiation.<br><br>CONCLUSIONS: Altogether, UBQLN1 functions to scavenge ubiquitinated proteins, preventing their overloading mitochondria and elevated mitophagy. UBQLN1 maintains mitochondria and telomeres by regulating proteostasis and plays critical role in neuro-ectoderm differentiation.},
}
@article {pmid38900410,
year = {2024},
author = {Alarabi, M and Pan, Z and Romero-Gómez, M and George, J and Eslam, M},
title = {Telomere length and mortality in lean MAFLD: the other face of metabolic adaptation.},
journal = {Hepatology international},
volume = {},
number = {},
pages = {},
pmid = {38900410},
issn = {1936-0541},
support = {APP1053206//National Health and Medical Research Council/ ; APP2001692//National Health and Medical Research Council/ ; APP1107178//National Health and Medical Research Council/ ; APP1108422//National Health and Medical Research Council/ ; },
abstract = {BACKGROUND AND AIMS: Healthy weight (lean) patients with metabolic dysfunction-associated fatty liver disease (MAFLD) have a more favorable metabolic and histological profile in cross-sectional studies compared with their non-lean counterparts. Paradoxically, they also have higher overall mortality. The underpinning pathophysiology of this paradox is not understood. Telomere attrition is associated with increased mortality in various diseases.<br><br>METHODS: We investigated the role of telomere length in the pathogenesis of lean MAFLD in cohorts with biopsy-proven MAFLD (n&#x2009;=&#x2009;303). We measured serum malondialdehyde (MDA) levels and hepatic 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (4-HNE) expression (reactive oxygen species (ROS) markers), growth/differentiation factor-15 (GDF-15) and tested the effect of H2O2 on telomere length and activity in hepatocyte cell lines. The association between leukocyte telomere length and mortality was examined.<br><br>RESULTS: Telomere length was significantly lower in patients with lean MAFLD (p&#x2009;<&#x2009;0.001). They also demonstrated an increase in ROS levels and decreases in GDF-15. H2O2 induced telomere shortening and reducing telomere activity in hepatocyte cell lines. We subsequently confirmed that telomere length shortening at baseline is associated with increased hazards of all-cause mortality; the deleterious effect was more profound in lean people.<br><br>CONCLUSION: Differences in telomere length in part explain the increased mortality of lean compared to non-lean patients with MAFLD. The effect is in part mediated through ROS activation and provide opportunities for therapy.},
}
@article {pmid38899963,
year = {2024},
author = {Sheng, Y and Liang, S and Wu, S and Shao, Y and Qiu, X and Liu, S and Huang, D and Pan, D and Wang, L and Juan, JTH and Zeng, X},
title = {Sex-specific effects of maternal blood pressure on newborn telomere length: A prospective study.},
journal = {International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijgo.15721},
pmid = {38899963},
issn = {1879-3479},
support = {AB17195012//Guangxi&#x2002;Science and Technology Program/ ; 81860587//National Natural Science Foundation of China/ ; GXMUYSF202203//Youth Science Foundation of Guangxi Medical University/ ; },
abstract = {OBJECTIVE: To investigate the relationship between maternal blood pressure (BP) and neonatal cord blood telomere length (TL) during pregnancy, and to clarify the sensitive period.<br><br>METHODS: We conducted a prospective cohort study with 621 mother-newborn pairs from the Guangxi Zhuang Birth Cohort (GZBC) in China. Multiple informant models, restricted cubic spline regression (RCS) models, and quantile regression models were conducted to analyze the correlation between maternal BP and neonatal TL.<br><br>RESULTS: Maternal diastolic blood pressure (DBP) was inversely related to neonatal cord blood TL in the second trimester (P&#x2009;=&#x2009;0.015) and the third trimester (P&#x2009;=&#x2009;0.011). There was a male-specific relationship between maternal BP and neonatal TL. A 1&#x2009;mmHg increment in maternal systolic blood pressure (SBP) and DBP during the second trimester was related with 0.42% (95% CI: -0.80%, -0.04%) and 0.61% (95% CI: -1.13%, -0.09%) shorter TL in male newborns, respectively. Per unit increase of maternal DBP during the third trimester was related with 0.54% (95% CI: -1.03%, -0.05%) shorter TL in male newborns. Pregnant women with hypertensive disease of pregnancy (HDP) had male offspring with shorter TL (P&#x2009;=&#x2009;0.003). However, no significant relationships were found in female newborns (P&#x2009;=&#x2009;0.570).<br><br>CONCLUSION: Maternal BP during pregnancy is inversely correlated with male neonatal TL and the second and third trimesters are sensitive windows.},
}
@article {pmid38896081,
year = {2024},
author = {Wang, YM and Kaj-Carbaidwala, B and Lane, A and Agarwal, S and Beier, F and Bertuch, A and Borovsky, KA and Brennan, SK and Calado, RT and Catto, LFB and Dufour, C and Ebens, CL and Fioredda, F and Giri, N and Gloude, N and Goldman, F and Hertel, PM and Himes, R and Keel, SB and Koura, DT and Kratz, CP and Kulkarni, S and Liou, I and Nakano, TA and Nastasio, S and Niewisch, MR and Penrice, DD and Sasa, GS and Savage, SA and Simonetto, DA and Ziegler, DS and Miethke, AG and Myers, KC and , },
title = {Liver disease and transplantation in telomere biology disorders: An international multicenter cohort.},
journal = {Hepatology communications},
volume = {8},
number = {7},
pages = {},
doi = {10.1097/HC9.0000000000000462},
pmid = {38896081},
issn = {2471-254X},
mesh = {Humans ; *Liver Transplantation ; Female ; Male ; Retrospective Studies ; Adult ; Middle Aged ; Telomere ; Adolescent ; Liver Diseases/surgery/genetics ; Young Adult ; Child ; Treatment Outcome ; Child, Preschool ; },
abstract = {BACKGROUND: Patients with telomere biology disorders (TBD) develop hepatic disease, including hepatitis, cirrhosis, and hepatopulmonary syndrome. No specific treatment exists for TBD-related liver disease, and the role of liver transplantation (LT) remains controversial. Our study objectives were to describe the clinical characteristics, management, and outcomes in patients with TBD-related liver disease, and their LT outcomes.<br><br>METHODS: Data from 83 patients with TBD-associated liver disease were obtained from 17 participating centers in the Clinical Care Consortium of Telomere-Associated Ailments and by self-report for our retrospective, multicenter, international cohort study.<br><br>RESULTS: Group A ("Advanced") included 40 patients with advanced liver disease. Of these, 20 underwent LT (Group AT). Group M ("Mild") included 43 patients not warranting LT evaluation, none of whom were felt to be medically unfit for liver transplantation. Supplemental oxygen requirement, pulmonary arteriovenous malformation, hepatopulmonary syndrome, and higher bilirubin and international normalized ratio values were associated with Group A. Other demographics, clinical manifestations, and laboratory findings were similar between groups. Six group A patients were declined for LT; 3 died on the waitlist. Median follow-up post-LT was 2.9 years (range 0.6-13.2&#xa0;y). One-year survival post-LT was 73%. Median survival post-LT has not been reached. Group AT patients had improved survival by age compared to all nontransplant patients (log-rank test p = 0.02). Of 14 patients with pretransplant hypoxemia, 8 (57%) had improved oxygenation after transplant.<br><br>CONCLUSIONS: LT recipients with TBD do not exhibit excessive posttransplant mortality, and LT improved respiratory status in 57%. A TBD diagnosis should not exclude LT consideration.},
}
@article {pmid38896046,
year = {2024},
author = {Cianciosi, D and Forbes-Hernandez, T and Armas Diaz, Y and Elexpuru-Zabaleta, M and Quiles, JL and Battino, M and Giampieri, F},
title = {Manuka honey's anti-metastatic impact on colon cancer stem-like cells: unveiling its effects on epithelial-mesenchymal transition, angiogenesis and telomere length.},
journal = {Food &amp; function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d4fo00943f},
pmid = {38896046},
issn = {2042-650X},
abstract = {Colorectal cancer often leads to metastasis, with cancer stem cells (CSCs) playing a pivotal role in this process. Two closely linked mechanisms, epithelial-mesenchymal transition and angiogenesis, contribute to metastasis and recent research has also highlighted the impact of telomere replication on this harmful tumor progression. Standard chemotherapy alone can inadvertently promote drug-resistant CSCs, posing a challenge. Combining chemotherapy with other compounds, including natural ones, shows promise in enhancing effectiveness while minimizing side effects. This study investigated the anti-metastatic potential of Manuka honey, both alone and in combination with 5-fluorouracil, using a 3D model of colonospheres enriched with CSC-like cells. In summary, it was observed that the treatment reduced migration ability by downregulating the transcription factors Slug, Snail, and Twist, which are key players in epithelial-mesenchymal transition. Additionally, Manuka honey downregulated pro-angiogenic factors and shortened CSC telomeres by downregulating c-Myc - demonstrating an effective anti-metastatic potential. This study suggests new research opportunities for studying the impact of natural compounds when combined with pharmaceuticals, with the potential to enhance effectiveness and reduce side effects.},
}
@article {pmid38895181,
year = {2024},
author = {Mori, JO and Platz, EA and Lu, J and Brame, A and Han, M and Joshu, CE and De Marzo, AM and Meeker, AK and Heaphy, CM},
title = {Longer prostate stromal cell telomere length is associated with increased risk of death from other cancers.},
journal = {Frontiers in medicine},
volume = {11},
number = {},
pages = {1390769},
pmid = {38895181},
issn = {2296-858X},
abstract = {BACKGROUND: Telomeres are located at chromosomal termini and function to maintain genomic integrity. Telomere dysfunction is a well-recognized contributor to aging and age-related diseases, such as prostate cancer. Since telomere length is highly heritable, we postulate that stromal cell telomere length in the tissue of a particular solid organ may generally reflect constitutive stromal cell telomere length in other solid organs throughout the body. Even with telomere loss occurring with each round of cell replication, in general, telomere length in prostate stromal cells in mid-life would still be correlated with the telomere length in stromal cells in other organs. Thus, we hypothesize that prostate stromal cell telomere length and/or telomere length variability is a potential indicator of the likelihood of developing future solid cancers, beyond prostate cancer, and especially lethal cancer.<br><br>METHODS: To explore this hypothesis, we conducted a cohort study analysis of 1,175 men who were surgically treated for prostate cancer and were followed for death, including from causes other than their prostate cancer.<br><br>RESULTS: In this cohort study with a median follow-up of 19 years, we observed that longer prostate stromal cell telomere length measured in tissue microarray spots containing prostate cancer was associated with an increased risk of death from other solid cancers. Variability in telomere length among these prostate stromal cells was possibly positively associated with risk of death from other solid cancers.<br><br>CONCLUSION: Studying the link between stromal cell telomere length and cancer mortality may be important for guiding the development of cancer interception and prevention strategies.},
}
@article {pmid38892366,
year = {2024},
author = {Lohberger, B and Barna, S and Glänzer, D and Eck, N and Leithner, A and Georg, D},
title = {DNA-PKcs Inhibition Sensitizes Human Chondrosarcoma Cells to Carbon Ion Irradiation via Cell Cycle Arrest and Telomere Capping Disruption.},
journal = {International journal of molecular sciences},
volume = {25},
number = {11},
pages = {},
pmid = {38892366},
issn = {1422-0067},
support = {P32103-B//Austrian Science Foundation/ ; },
mesh = {Humans ; *DNA-Activated Protein Kinase/antagonists &amp; inhibitors/metabolism/genetics ; Cell Line, Tumor ; *Chondrosarcoma/metabolism/genetics/radiotherapy/drug therapy ; *Heavy Ion Radiotherapy ; *Telomere/drug effects/metabolism ; Cell Cycle Checkpoints/drug effects/radiation effects ; DNA Repair/drug effects ; Radiation Tolerance/drug effects ; Pyrazoles/pharmacology ; Cell Proliferation/drug effects ; Bone Neoplasms/metabolism/genetics/pathology/drug therapy ; G2 Phase Cell Cycle Checkpoints/drug effects/radiation effects ; },
abstract = {In order to overcome the resistance to radiotherapy in human chondrosarcoma cells, the prevention from efficient DNA repair with a combined treatment with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) inhibitor AZD7648 was explored for carbon ion (C-ion) as well as reference photon (X-ray) irradiation (IR) using gene expression analysis, flow cytometry, protein phosphorylation, and telomere length shortening. Proliferation markers and cell cycle distribution changed significantly after combined treatment, revealing a prominent G2/M arrest. The expression of the G2/M checkpoint genes cyclin B, CDK1, and WEE1 was significantly reduced by IR alone and the combined treatment. While IR alone showed no effects, additional AZD7648 treatment resulted in a dose-dependent reduction in AKT phosphorylation and an increase in Chk2 phosphorylation. Twenty-four hours after IR, the key genes of DNA repair mechanisms were reduced by the combined treatment, which led to impaired DNA repair and increased radiosensitivity. A time-dependent shortening of telomere length was observed in both cell lines after combined treatment with AZD7648 and 8 Gy X-ray/C-ion IR. Our data suggest that the inhibition of DNA-PKcs may increase sensitivity to X-rays and C-ion IR by impairing its functional role in DNA repair mechanisms and telomere end protection.},
}
@article {pmid38891017,
year = {2024},
author = {Deb, S and Berei, J and Miliavski, E and Khan, MJ and Broder, TJ and Akurugo, TA and Lund, C and Fleming, SE and Hillwig, R and Ross, J and Puri, N},
title = {The Effects of Smoking on Telomere Length, Induction of Oncogenic Stress, and Chronic Inflammatory Responses Leading to Aging.},
journal = {Cells},
volume = {13},
number = {11},
pages = {},
pmid = {38891017},
issn = {2073-4409},
support = {Bridge Grant//University of Illinois Chicago, Rockford campus/ ; },
mesh = {Humans ; *Inflammation/genetics/pathology ; *Aging/genetics ; *Telomeric Repeat Binding Protein 2/metabolism/genetics ; *Shelterin Complex ; *Cytokines/metabolism ; *Telomere/metabolism ; *Telomerase/metabolism/genetics ; *Smoking/adverse effects ; Ubiquitins/metabolism/genetics ; Telomere-Binding Proteins/metabolism/genetics ; Interferon-gamma/metabolism ; Telomere Homeostasis ; Male ; Telomere Shortening ; Female ; Middle Aged ; },
abstract = {Telomeres, potential biomarkers of aging, are known to shorten with continued cigarette smoke exposure. In order to further investigate this process and its impact on cellular stress and inflammation, we used an in vitro model with cigarette smoke extract (CSE) and observed the downregulation of telomere stabilizing TRF2 and POT1 genes after CSE treatment. hTERT is a subunit of telomerase and a well-known oncogenic marker, which is overexpressed in over 85% of cancers and may contribute to lung cancer development in smokers. We also observed an increase in hTERT and ISG15 expression levels after CSE treatment, as well as increased protein levels revealed by immunohistochemical staining in smokers' lung tissue samples compared to non-smokers. The effects of ISG15 overexpression were further studied by quantifying IFN-γ, an inflammatory protein induced by ISG15, which showed greater upregulation in smokers compared to non-smokers. Similar changes in gene expression patterns for TRF2, POT1, hTERT, and ISG15 were observed in blood and buccal swab samples from smokers compared to non-smokers. The results from this study provide insight into the mechanisms behind smoking causing telomere shortening and how this may contribute to the induction of inflammation and/or tumorigenesis, which may lead to comorbidities in smokers.},
}
@article {pmid38890299,
year = {2024},
author = {Schmidt, TT and Tyer, C and Rughani, P and Haggblom, C and Jones, JR and Dai, X and Frazer, KA and Gage, FH and Juul, S and Hickey, S and Karlseder, J},
title = {High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {5149},
pmid = {38890299},
issn = {2041-1723},
support = {CA227934//U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute (NCI)/ ; P30CA014195//U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute (NCI)/ ; CA234047//U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute (NCI)/ ; GM142173//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; AG0773424//U.S. Department of Health &amp; Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; 19PABH134610000//American Heart Association (American Heart Association, Inc.)/ ; ALTF 668-2019//European Molecular Biology Organization (EMBO)/ ; },
mesh = {Humans ; *Telomere/genetics/metabolism ; *Neoplasms/genetics/metabolism ; *Aging/genetics ; Telomerase/genetics/metabolism ; Cell Line, Tumor ; Telomere Shortening/genetics ; Sequence Analysis, DNA/methods ; High-Throughput Nucleotide Sequencing/methods ; Alleles ; },
abstract = {Telomeres are the protective nucleoprotein structures at the end of linear eukaryotic chromosomes. Telomeres' repetitive nature and length have traditionally challenged the precise assessment of the composition and length of individual human telomeres. Here, we present Telo-seq to resolve bulk, chromosome arm-specific and allele-specific human telomere lengths using Oxford Nanopore Technologies' native long-read sequencing. Telo-seq resolves telomere shortening in five population doubling increments and reveals intrasample, chromosome arm-specific, allele-specific telomere length heterogeneity. Telo-seq can reliably discriminate between telomerase- and ALT-positive cancer cell lines. Thus, Telo-seq is a tool to study telomere biology during development, aging, and cancer at unprecedented resolution.},
}
@article {pmid38890274,
year = {2024},
author = {Sanchez, SE and Gu, Y and Wang, Y and Golla, A and Martin, A and Shomali, W and Hockemeyer, D and Savage, SA and Artandi, SE},
title = {Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {5148},
pmid = {38890274},
issn = {2041-1723},
mesh = {Humans ; *Telomere/genetics/metabolism ; *Telomere Homeostasis/genetics ; *Machine Learning ; Adult ; Healthy Aging/genetics ; Middle Aged ; Male ; Aged ; Female ; Telomere Shortening/genetics ; Aging/genetics ; Nanopore Sequencing/methods ; Young Adult ; },
abstract = {Telomere length is an important biomarker of organismal aging and cellular replicative potential, but existing measurement methods are limited in resolution and accuracy. Here, we deploy digital telomere measurement (DTM) by nanopore sequencing to understand how distributions of human telomere length change with age and disease. We measure telomere attrition and de novo elongation with up to 30 bp resolution in genetically defined populations of human cells, in blood cells from healthy donors and in blood cells from patients with genetic defects in telomere maintenance. We find that human aging is accompanied by a progressive loss of long telomeres and an accumulation of shorter telomeres. In patients with defects in telomere maintenance, the accumulation of short telomeres is more pronounced and correlates with phenotypic severity. We apply machine learning to train a binary classification model that distinguishes healthy individuals from those with telomere biology disorders. This sequencing and bioinformatic pipeline will advance our understanding of telomere maintenance mechanisms and the use of telomere length as a clinical biomarker of aging and disease.},
}
@article {pmid38886039,
year = {2024},
author = {Alcock, LJ and Sudhakar, HK and Young, R and Lau, YH},
title = {Fluorescence polarization assay for screening FANCM-RMI inhibitors to target the alternative lengthening of telomeres.},
journal = {Methods in enzymology},
volume = {698},
number = {},
pages = {361-378},
doi = {10.1016/bs.mie.2024.04.014},
pmid = {38886039},
issn = {1557-7988},
mesh = {Humans ; *Fluorescence Polarization/methods ; *Telomere Homeostasis/drug effects ; Protein Binding ; Telomere/metabolism/genetics ; DNA Helicases ; },
abstract = {Alternative Lengthening of Telomeres (ALT) is a mechanism used by 10-15% of all cancers to achieve replicative immortality, bypassing the DNA damage checkpoint associated with short telomeres that leads to cellular senescence or apoptosis. ALT does not occur in non-cancerous cells, presenting a potential therapeutic window for cancers where this mechanism is active. Disrupting the FANCM-RMI interaction has emerged as a promising therapeutic strategy that induces synthetic ALT lethality in genetic studies on cancer cell lines. There are currently no chemical inhibitors reported in the literature, in part due to the lack of reliable biophysical or biochemical assays to screen for FANCM-RMI disruption. Here we describe the development of a robust competitive fluorescence polarization (FP) assay that quantifies target binding at the FANCM-RMI interface. The assay employs a labeled peptide tracer TMR-RaMM2 derived from the native MM2 binding motif, which binds to recombinant RMI1-RMI2 and can be displaced by competitive inhibitors. We report the methods for recombinant production of RMI1-RMI2, design and evaluation of the tracer TMR-RaMM2, along with unlabeled peptide inhibitor controls to enable ALT-targeted drug discovery.},
}
@article {pmid38886520,
year = {2024},
author = {Chung, HG and Yang, PS and Cho, S and Jang, E and Kim, D and Yu, HT and Kim, TH and Uhm, JS and Sung, JH and Pak, HN and Lee, MH and Joung, B},
title = {The associations of leukocyte telomere length and intermediary cardiovascular phenotype with adverse cardiovascular outcomes in the white population.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {13975},
pmid = {38886520},
issn = {2045-2322},
abstract = {The evidence about the associations of leukocyte telomere length (LTL) and intermediary cardiovascular phenotypes with adverse cardiovascular outcomes is inconclusive. This study assessed these relationships with cardiovascular imaging, electrocardiography, and the risks of sudden cardiac death (SCD), coronary events, and heart failure (HF) admission. We conducted a cross-sectional analysis of UK Biobank participants enrolled between 2006 and 2010. LTL was measured using quantitative polymerase chain reactions. Electronic health records were used to determine the incidence of SCD, coronary events, and HF admission. Cardiovascular measurements were made using cardiovascular magnetic resonance imaging and machine learning. The associations of LTL with SCD, coronary events, and HF admission and cardiac magnetic resonance imaging, electrocardiogram parameters of 33,043 and 19,554 participants were evaluated by multivariate regression. The median (interquartile range) follow-up period was 11.9 (11.2-12.6) years. Data was analyzed from January to May 2023. Among the 403,382 white participants without coronary artery disease or HF, 181,637 (45.0%) were male with a mean age of 57.1 years old. LTL was independently negatively associated with a risk of SCD (LTL third quartile vs first quartile: hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.72-0.92), coronary events (LTL third quartile vs first quartile: HR: 0.88, 95% CI: 0.84-0.92), and HF admission (LTL fourth quartile vs first quartile: HR: 0.84, 95% CI: 0.74-0.95). LTL was also independently positively associated with cardiac remodeling, specifically left ventricular mass index, left-ventricular-end systolic and diastolic volumes, mean left ventricular myocardial wall thickness, left ventricular stroke volume, and with electrocardiogram changes along the negative degree of T-axis. Cross-sectional study results showed that LTL was positively associated with heart size and cardiac function in middle age, but electrocardiography results did not show these associations, which could explain the negative association between LTL and risk of SCD, coronary events, and HF admission in UK Biobank participants.},
}
@article {pmid38884214,
year = {2024},
author = {Khayat, F and Alshmery, M and Pal, M and Oliver, AW and Bianchi, A},
title = {Binding of the TRF2 iDDR motif to RAD50 highlights a convergent evolutionary strategy to inactivate MRN at telomeres.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae509},
pmid = {38884214},
issn = {1362-4962},
support = {C302/A24386/CRUK_/Cancer Research UK/United Kingdom ; //University of Sussex/ ; },
abstract = {Telomeres protect chromosome ends from unscheduled DNA repair, including from the MRN (MRE11, RAD50, NBS1) complex, which processes double-stranded DNA breaks (DSBs) via activation of the ATM kinase, promotes DNA end-tethering aiding the non-homologous end-joining (NHEJ) pathway, and initiates DSB resection through the MRE11 nuclease. A protein motif (MIN, for MRN inhibitor) inhibits MRN at budding yeast telomeres by binding to RAD50 and evolved at least twice, in unrelated telomeric proteins Rif2 and Taz1. We identify the iDDR motif of human shelterin protein TRF2 as a third example of convergent evolution for this telomeric mechanism for binding MRN, despite the iDDR lacking sequence homology to the MIN motif. CtIP is required for activation of MRE11 nuclease action, and we provide evidence for binding of a short C-terminal region of CtIP to a RAD50 interface that partly overlaps with the iDDR binding site, indicating that the interaction is mutually exclusive. In addition, we show that the iDDR impairs the DNA binding activity of RAD50. These results highlight direct inhibition of MRN action as a crucial role of telomeric proteins across organisms and point to multiple mechanisms enforced by the iDDR to disable the many activities of the MRN complex.},
}
@article {pmid38883734,
year = {2024},
author = {Skåra, KH and Lee, Y and Jugessur, A and Gjessing, HK and Aviv, A and Brumpton, B and Naess, &#xd8; and Hernáez, &#xc1; and Hanevik, HI and Magnus, P and Magnus, MC},
title = {Telomere length in relation to fecundability and use of assisted reproductive technologies: the Norwegian Mother, Father, and Child Cohort Study.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-4430021/v1},
pmid = {38883734},
abstract = {In women, shorter telomeres have been reported to be associated with conditions such as endometriosis and polycystic ovary syndrome, whereas other studies have reported the opposite. In men, studies mostly report associations between shorter telomeres and sperm quality. To our knowledge, no studies have thus far investigated the associations between TL and fecundability or the use of ART. This study is based on the Norwegian Mother, Father, and Child Cohort (MoBa) Study and uses data from the Medical Birth Registry of Norway (MBRN). We included women (24,645 with genotype data and 1,054 with TL measurements) and men (18,339 with genotype data and 965 with TL measurements) participating between 1998 and 2008. We investigated the associations between leukocyte TL and fecundability, infertility, and the use of ART. We also repeated the analyses using instrumental variables for TL, including genetic risk scores for TL and genetically predicted TL. Approximately 11% of couples had experienced infertility and 4% had used ART. TL was not associated with fecundability among women (fecundability ratio [FR], 0.98; 95% confidence interval [CI], 0.92-1.04) or men (FR, 0.99; CI, 0.93-1.06), nor with infertility among women (odds ratio [OR], 1.03; CI, 0.85-1.24) or men (OR, 1.05; CI, 0.87-1.28). We observed an increased likelihood of using ART with increasing TL among men (OR, 1.22; CI, 1.03-1.46), but not among women (OR, 1.10; CI, 0.92-1.31). No significant associations were observed using the instrumental variables. Our results indicate that TL is a poor biomarker of fecundability, infertility and use of ART in MoBa. Additional studies are required to replicate the association observed between TL and ART in men.},
}
@article {pmid38883396,
year = {2024},
author = {Castro, A and Lardone, MC and Giraudo, F and López, P and Ortiz, E and Iñiguez, G and Cassorla, F and Codner, E},
title = {Differential Effect of 2 Hormonal Contraceptives on the Relative Telomere Length of Youth With Type 1 Diabetes.},
journal = {Journal of the Endocrine Society},
volume = {8},
number = {7},
pages = {bvae091},
pmid = {38883396},
issn = {2472-1972},
abstract = {CONTEXT: Adolescents and young women (AYA) with type 1 diabetes (T1D) may require hormonal contraception for an extended period. However, it is unclear what effect hormonal contraception has on telomere length, a marker of the risk for complications.<br><br>OBJECTIVE: To investigate the relative telomere length (RTL) in AYA with T1D (AYA-T1D) and healthy young women (AYA-C) after 18 months of combined oral contraception use (COC) with ethinyl estradiol/desogestrel, or a subdermal etonogestrel implant (IM).<br><br>METHODS: A nonrandomized prospective study was performed in which 39 AYA-T1D and 40 AYA-C chose the COC or the IM. RTL was measured by monochrome multiplex-quantitative PCR in DNA from peripheral blood mononuclear cells (PBMC). The impact of contraceptives and clinical variables on RTL was assessed using lineal regression analysis.<br><br>RESULTS: Longer RTL compared to baseline was observed in AYA-T1D (P < .05) and AYA-C (P &#xa0;< .01) after using the IM. However, the total of AYA and the AYA-C group treated with COC decreased RTL after 18 months of treatment compared to baseline (P < .05). The type of contraceptive used was determinant for the changes in RTL compared to baseline in all subjects and controls (P &#x2264; .006). For AYA-T1D, HbA1c levels were not associated with RTL, but the high-sensitivity C-reactive protein was negatively related with the changes in RTL at 18 months compared to baseline (standardized R[2] : 0.230, P &#xa0;= .003).<br><br>CONCLUSION: IM was associated with longer RTL in AYA-T1D and AYA-C. In contrast, a shortening of telomere length in PBMC was observed after using COC.},
}
@article {pmid38883331,
year = {2024},
author = {Song, Y and Zhang, Y and Wang, X and Yu, X and Liao, Y and Zhang, H and Li, L and Wang, Y and Liu, B and Li, W},
title = {Telomere-to-telomere reference genome for Panax ginseng highlights the evolution of saponin biosynthesis.},
journal = {Horticulture research},
volume = {11},
number = {6},
pages = {uhae107},
pmid = {38883331},
issn = {2662-6810},
abstract = {Ginseng (Panax ginseng) is a representative of Chinese traditional medicine, also used worldwide, while the triterpene saponin ginsenoside is the most important effective compound within it. Ginseng is an allotetraploid, with complex genetic background, making the study of its metabolic evolution challenging. In this study, we assembled a telomere-to-telomere ginseng reference genome, constructed of 3.45 Gb with 24 chromosomes and 77 266 protein-coding genes. Additionally, the reference genome was divided into two subgenomes, designated as subgenome A and B. Subgenome A contains a larger number of genes, whereas subgenome B has a general expression advantage, suggesting that ginseng subgenomes experienced asymmetric gene loss with biased gene expression. The two subgenomes separated approximately 6.07 million years ago, and subgenome B shows the closest relation to Panax vietnamensis var. fuscidiscus. Comparative genomics revealed an expansion of gene families associated with ginsenoside biosynthesis in both ginseng subgenomes. Furthermore, both tandem duplications and proximal duplications play crucial roles in ginsenoside biosynthesis. We also screened functional genes identified in previous research and found that some of these genes located in colinear regions between subgenomes have divergence functions, revealing an unbalanced evolution in both subgenomes and the saponin biosynthesis pathway in ginseng. Our work provides important resources for future genetic studies and breeding programs of ginseng, as well as the biosynthesis of ginsenosides.},
}
@article {pmid38882679,
year = {2024},
author = {Zhang, J and Wen, J and Dai, Z and Zhang, H and Zhang, N and Lei, R and Liu, Z and Peng, L and Cheng, Q},
title = {Causal association and shared genetics between telomere length and COVID-19 outcomes: New evidence from the latest large-scale summary statistics.},
journal = {Computational and structural biotechnology journal},
volume = {23},
number = {},
pages = {2429-2441},
pmid = {38882679},
issn = {2001-0370},
abstract = {BACKGROUND: Observational studies suggested that leukocyte telomere length (LTL) is shortened in COVID-19 patients. However, the genetic association and causality remained unknown.<br><br>METHODS: Based on the genome-wide association of LTL&#xa0;(N&#xa0;=&#xa0;472,174) and COVID-19 phenotypes (N&#xa0;=&#xa0;1086,211-2597,856), LDSC and SUPERGNOVA were used to estimate the genetic correlation. Cross-trait GWAS meta-analysis, colocalization, fine-mapping analysis, and transcriptome-wide association study were conducted to explore the shared genetic etiology. Mendelian randomization (MR) was utilized to infer the causality. Upstream and downstream two-step MR was performed to investigate the potential mediating effects.<br><br>RESULTS: LDSC identified a significant genetic association between LTL and all COVID-19 phenotypes (rG < 0, p&#xa0;<&#xa0;0.05). Six significant regions were observed for LTL and COVID-19 susceptibility and hospitalization, respectively. Colocalization analysis found rs144204502, rs34517439, and rs56255908 were shared causal variants between LTL and COVID-19 phenotypes. Numerous biological pathways associated with LTL and COVID-19 outcomes were identified, mainly involved in -immune-related pathways. MR showed that longer LTL was significantly associated with a lower risk of COVID-19 severity (OR [95% CI] = 0.81 [0.71-0.92], p&#xa0;=&#xa0;1.24&#xa0;&#xd7;10[-3]) and suggestively associated with lower risks of COVID-19 susceptibility (OR [95% CI] = 0.96 [0.92-1.00], p&#xa0;=&#xa0;3.44&#xa0;&#xd7;10[-2]) and COVID-19 hospitalization (OR [95% CI] = 0.89 [0.80-0.98], p&#xa0;=&#xa0;1.89&#xa0;&#xd7;10[-2]). LTL partially mediated the effects of BMI, smoking, and education on COVID-19 outcomes. Furthermore, six proteins partially mediated the causality of LTL on COVID-19 outcomes, including BNDF, QPCT, FAS, MPO, SFTPB, and APOF.<br><br>CONCLUSIONS: Our findings suggested that shorter LTL was genetically associated with a higher risk of COVID-19 phenotypes, with shared genetic etiology and potential causality.},
}
@article {pmid38882488,
year = {2024},
author = {Wei, C and Gao, L and Xiao, R and Wang, Y and Chen, B and Zou, W and Li, J and Mace, E and Jordan, D and Tao, Y},
title = {Complete telomere-to-telomere assemblies of two sorghum genomes to guide biological discovery.},
journal = {iMeta},
volume = {3},
number = {2},
pages = {e193},
pmid = {38882488},
issn = {2770-596X},
abstract = {The assembly of two sorghum T2T genomes corrected the assembly errors in the current reference, uncovered centromere variation, boosted functional genomics research, and accelerated sorghum improvement.},
}
@article {pmid38879916,
year = {2024},
author = {Li, X and Li, M and Cheng, J and Guan, S and Hou, L and Zu, S and Yang, L and Wu, H and Li, H and Fan, Y and Zhang, B},
title = {Association of healthy and unhealthy plant-based diets with telomere length.},
journal = {Clinical nutrition (Edinburgh, Scotland)},
volume = {43},
number = {8},
pages = {1694-1701},
doi = {10.1016/j.clnu.2024.06.004},
pmid = {38879916},
issn = {1532-1983},
abstract = {BACKGROUND &amp; AIMS: Previous studies have shown that plant-rich dietary patterns, such as the Mediterranean diet, are associated with longer telomeres. However, no association has been found between vegetarian diet and telomere length. We hypothesized that the quality of plant-based diets plays an important role in telomere length.<br><br>METHODS: Data were obtained from the National Health and Nutrition Examination Survey 1999-2002. Diet was assessed using a 24-h recall method. Plant-based diet quality was assessed using the overall plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI). Telomere length was measured using quantitative PCR. Linear and ordinal logistic regression models were used to assess the association of PDIs with log-transformed telomere length and ordinal quintiles of telomere length in descending order, respectively.<br><br>RESULTS: In both regression models, the overall PDI was not associated with telomere length. The hPDI was associated with longer telomere length [percentage change&#xa0;=&#xa0;2.34%, 95% confidence interval (CI): 0.42%, 4.31%, Ptrend&#xa0;=&#xa0;0.016; odds ratio (OR)&#xa0;=&#xa0;0.81, 95% CI: 0.69, 0.95, Ptrend&#xa0;=&#xa0;0.013]. However, uPDI was associated with shorter telomere length (percentage change&#xa0;=&#xa0;-3.17%, 95% CI:&#xa0;-5.65%,&#xa0;-0.62%, Ptrend&#xa0;=&#xa0;0.017; OR&#xa0;=&#xa0;1.25, 95% CI:1.03, 1.53, Ptrend&#xa0;=&#xa0;0.014) and this inverse association was stronger in the non-Hispanic white population (Pinteraction&#xa0;=&#xa0;0.001 in both regression models).<br><br>CONCLUSIONS: A plant-based dietary pattern rich in healthy plant foods is associated with longer telomeres. However, plant-based dietary patterns rich in unhealthy plant-based foods are associated with shorter telomere lengths, especially in non-Hispanic white populations.},
}
@article {pmid38875394,
year = {2024},
author = {Fu, Y and Lou, H and Chen, Q and Wu, S and Chen, H and Liang, K and Ge, Y and Zhao, C},
title = {Objective assessment of the association between telomere length, a biomarker of aging, and health screening indicators: A cross-sectional study.},
journal = {Medicine},
volume = {103},
number = {24},
pages = {e38533},
doi = {10.1097/MD.0000000000038533},
pmid = {38875394},
issn = {1536-5964},
mesh = {Humans ; Cross-Sectional Studies ; Male ; Female ; Middle Aged ; *Aging/genetics/physiology ; Adult ; Aged ; *Telomere ; *Biomarkers/blood ; Young Adult ; Physical Examination/methods ; Aged, 80 and over ; Health Status ; Health Status Indicators ; },
abstract = {Physical examination data are used to indicate individual health status and organ health, and understanding which physical examination data are indicative of physiological aging is critical for health management and early intervention. There is a lack of research on physical examination data and telomere length. Therefore, the present study analyzed the association between blood telomere length and physical examination indices in healthy people of different ages to investigate the role and association of various organs/systems with physiological aging in the human body. The present study was a cross-sectional study. Sixteen physical examination indicators of different tissue and organ health status were selected and analyzed for trends in relation to actual age and telomere length (TL). The study included 632 individuals with a total of 11,766 data for 16 physical examination indicators. Age was linearly correlated with 11 indicators. Interestingly, telomere length was strongly correlated only with the renal indicators eGFR (P < .001), CYS-C (P < .001), and SCR (P < .001). The study established that renal aging or injury is a risk factor for Physical aging of the human body. Early identification and management are essential to healthcare.},
}
@article {pmid38875139,
year = {2024},
author = {Gillooly, JF and Khazan, ES},
title = {Telomeres and the Rate of Living: Linking Biological Clocks of Senescence.},
journal = {Ecological and evolutionary physiology},
volume = {97},
number = {3},
pages = {157-163},
doi = {10.1086/730588},
pmid = {38875139},
issn = {2993-7973},
mesh = {Animals ; *Telomere/metabolism ; *Aging/genetics/physiology ; *Biological Clocks/physiology/genetics ; Telomere Shortening ; Longevity/genetics/physiology ; Energy Metabolism/physiology ; Vertebrates/genetics/physiology ; },
abstract = {AbstractTwo prominent theories of aging, one based on telomere dynamics and the other on mass-specific energy flux, propose biological time clocks of senescence. The relationship between these two theories, and the biological clocks proposed by each, remains unclear. Here, we examine the relationships between telomere shortening rate, mass-specific metabolic rate, and lifespan among vertebrates (mammals, birds, fishes). Results show that telomere shortening rate increases linearly with mass-specific metabolic rate and decreases nonlinearly with increasing body mass in the same way as mass-specific metabolic rate. Results also show that both telomere shortening rate and mass-specific metabolic rate are similarly related to lifespan and that both strongly predict differences in lifespan, although the slopes of the relationships are less than linear. On average, then, telomeres shorten a fixed amount per unit of mass-specific energy flux. So the mitotic clock of telomere shortening and the energetics-based clock described by metabolic rate can be viewed as alternative measures of the same biological clock. These two processes may be linked, we speculate, through the process of cell division.},
}
@article {pmid38869742,
year = {2024},
author = {Wang, Q and Xi, L and Yang, N and Song, J and Taiwaikul, D and Zhang, X and Bo, Y and Tang, B and Zhou, X},
title = {Association of leukocyte telomere length with risk of all-cause and cardiovascular mortality in middle-aged and older individuals without cardiovascular disease: a prospective cohort study of NHANES 1999-2002.},
journal = {Aging clinical and experimental research},
volume = {36},
number = {1},
pages = {131},
pmid = {38869742},
issn = {1720-8319},
support = {82060069//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Cardiovascular Diseases/mortality/genetics ; Male ; Middle Aged ; *Leukocytes/metabolism ; Female ; *Nutrition Surveys ; Prospective Studies ; *Telomere/genetics ; Aged ; Risk Factors ; },
abstract = {BACKGROUND: Leukocyte telomere length (LTL) shorting was significantly associated with mortality. This study aimed to investigate the potential association between LTL and all-cause mortality as well as cardiovascular disease (CVD) mortality in middle-aged or older individuals without a history of CVD.<br><br>METHODS: A total of 4174 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2002 were included in this analysis. Cox proportional hazards regression models were utilized to estimate the association between LTL and mortality outcomes. Restricted cubic spline (RCS) curves were employed to evaluate the potential non-linear association.<br><br>RESULTS: Over a median follow-up period of 217 months, the weighted rates of all-cause mortality and CVD mortality were 28.58% and 8.32% respectively. Participants in the highest LTL group exhibited a significantly decreased risk of both all-cause mortality (HR: 0.65, 95% CI: 0.54-0.78, P&#x2009;<&#x2009;0.001) and CVD mortality (HR: 0.64, 95% CI: 0.45-0.93, P&#x2009;<&#x2009;0.001) compared to those in the lowest group. Kaplan-Meier survival curves further supported a significant association between shorter telomere length and increased risks of both all-cause and CVD mortality (log-rank test P&#x2009;<&#x2009;0.001). RCS curves demonstrated a linear dose-response relationship between LTL and all-cause mortality as well as CVD mortality. Subgroup and sensitivity analyses confirmed the robustness of the results.<br><br>CONCLUSION: Shorter leukocyte telomere length could serve as a potential biomarker for risk stratification of all-cause and CVD mortality among middle-aged and older individuals without a history of CVD.},
}
@article {pmid38865824,
year = {2024},
author = {Du, B and Liu, B and Fang, YK and Zheng, JZ and Wu, J and Tao, FZ and Zhang, MY and Zhang, TJ},
title = {Shugan Tongluo Qiangjing recipe protects against varicocele of EVC rats through modulating sperm DNA damage, telomere expression and oxidative stress.},
journal = {Tissue &amp; cell},
volume = {89},
number = {},
pages = {102414},
doi = {10.1016/j.tice.2024.102414},
pmid = {38865824},
issn = {1532-3072},
abstract = {Varicocele (VC) refers to expansion and tortuosity of spreading venous plexus in spermatic cord due to poor blood flow. This study aimed to investigate effects of Shugan Tongluo Qiangjing recipe (SGTL) on sperm DNA damage and oxidative stress in experimental VC (EVC) rats. EVC model was established by partial ligation of left renal vein. Spermatic vein diameter, testicular weight, sperm DNA fragmentation index (DFI) were evaluated. Telomere reverse transcriptase (TERT) expression, telomere gene transcription, and testicular tissue morphology were determined·H2O2, catalase, SOD, T-AOC were measured with colorimetry. SGTL significantly decreased spermatic vein diameter (P=0.000) and increased testicular weight (P=0.013) of rats compared those of EVC rats. SGTL maintained testicular tissue morphology in EVC rats. SGTL markedly reduced sperm DFI value in sperm of rats compared to EVC rats (P=0.000). SGTL significantly enhanced TERT expression and telomere gene transcription (P=0.028) in testis of rats compared to EVC rats. SGTL reduced H2O2 levels (P=0.001) and promoted CAT activity (P=0.016), SOD activity (P=0.049), and T-AOC activity (P=0.047) of rats, compared to EVC rats. In conclusion, SGTL could reduce pathogenic process of EVC by reducing sperm DNA damage and regulating telomere length in EVC rats, which may be related to oxidative stress regulation.},
}
@article {pmid38865460,
year = {2024},
author = {Bettin, N and Querido, E and Gialdini, I and Grupelli, GP and Goretti, E and Cantarelli, M and Andolfato, M and Soror, E and Sontacchi, A and Jurikova, K and Chartrand, P and Cusanelli, E},
title = {TERRA transcripts localize at long telomeres to regulate telomerase access to chromosome ends.},
journal = {Science advances},
volume = {10},
number = {24},
pages = {eadk4387},
doi = {10.1126/sciadv.adk4387},
pmid = {38865460},
issn = {2375-2548},
mesh = {*Telomerase/metabolism/genetics ; Humans ; *Telomere/metabolism/genetics ; Telomere Homeostasis ; HeLa Cells ; RNA/metabolism/genetics ; Transcription, Genetic ; Telomere-Binding Proteins/metabolism/genetics ; Cell Cycle/genetics ; Chromosomes, Human/metabolism/genetics ; DNA-Binding Proteins ; Transcription Factors ; },
abstract = {The function of TERRA in the regulation of telomerase in human cells is still debated. While TERRA interacts with telomerase, how it regulates telomerase function remains unknown. Here, we show that TERRA colocalizes with the telomerase RNA subunit hTR in the nucleoplasm and at telomeres during different phases of the cell cycle. We report that TERRA transcripts relocate away from chromosome ends during telomere lengthening, leading to a reduced number of telomeric TERRA-hTR molecules and consequent increase in "TERRA-free" telomerase molecules at telomeres. Using live-cell imaging and super-resolution microscopy, we show that upon transcription, TERRA relocates from its telomere of origin to long chromosome ends. Furthermore, TERRA depletion by antisense oligonucleotides promoted hTR localization to telomeres, leading to increased residence time and extended half-life of hTR molecules at telomeres. Overall, our findings indicate that telomeric TERRA transcripts inhibit telomere elongation by telomerase acting in trans, impairing telomerase access to telomeres that are different from their chromosome end of origin.},
}
@article {pmid38863926,
year = {2024},
author = {Yang, S and Wang, X and Li, Y and Zhou, L and Guo, G and Wu, M},
title = {The association between telomere length and blood lipids: a bidirectional two-sample Mendelian randomization study.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1338698},
pmid = {38863926},
issn = {1664-2392},
mesh = {Humans ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; *Lipids/blood ; Cholesterol, LDL/blood ; Triglycerides/blood ; Telomere/genetics ; Cholesterol, HDL/blood ; Polymorphism, Single Nucleotide ; Telomere Homeostasis ; Apolipoprotein A-I/blood/genetics ; },
abstract = {BACKGROUND: Observational studies suggest an association between telomere length (TL) and blood lipid (BL) levels. Nevertheless, the causal connections between these two traits remain unclear. We aimed to elucidate whether genetically predicted TL is associated with BL levels via Mendelian randomization (MR) and vice versa.<br><br>METHODS: We obtained genetic instruments associated with TL, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) from large-scale genome-wide association studies (GWASs). The causal relationships between TL and BL were investigated via bidirectional MR, multivariable MR and mediation analysis methods. The inverse variance weighted (IVW) method was employed as the principal methodology, complemented by several other estimators to enhance the robustness of the analysis.<br><br>RESULTS: In the forward MR analyses, we identified significant positive correlation between genetically predicted TL and the levels of TG (&#x3b2;=0.04, 95% confidence interval [CI]: 0.01 to 0.06, p&#x2009;=&#x2009;0.003). In the reverse MR analysis, TG (&#x3b2;=0.02, 95% CI: 0.01 to 0.03, p&#x2009;=&#x2009;0.004), LDL-C (&#x3b2;=0.03, 95% CI: 0.01 to 0.04, p&#x2009;=&#x2009;0.001) and ApoB (&#x3b2;=0.03, 95% CI: 0.01 to 0.04, p&#x2009;=&#x2009;9.71&#xd7;10[-5]) were significantly positively associated with TL, although this relationship was not observed in the multivariate MR analysis. The mediation analysis via two-step MR showed no significant mediation effects acting through obesity-related phenotypes in analysis of TL with TG, while the effect of LDL-C on TL was partially mediated by body mass index (BMI) in the reverse direction, with mediated proportion of 12.83% (95% CI: 0.62% to 25.04%).<br><br>CONCLUSIONS: Our study indicated that longer TL were associated with higher TG levels, while conversely, higher TG, LDL-C, and ApoB levels predicted longer TL, with BMI partially mediating these effects. Our findings present valuable insights into the development of preventive strategies and interventions that specifically target TL-related aging and age-related diseases.},
}
@article {pmid38857178,
year = {2024},
author = {Asim Javed, M and Mukhopadhyay, S and Normandeau, E and Brochu, AS and Pérez-López, E},
title = {Telomere-to-telomere genome assembly of the clubroot pathogen Plasmodiophora brassicae.},
journal = {Genome biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/gbe/evae122},
pmid = {38857178},
issn = {1759-6653},
abstract = {Plasmodiophora brassicae (Woronin, 1877), a biotrophic, obligate parasite, is the causal agent of clubroot disease in brassicas. The clubroot pathogen has been reported in more than 80 countries worldwide, causing economic losses of hundreds of millions every year. Despite its widespread impact, very little is known about the molecular strategies it employs to induce the characteristic clubs in the roots of susceptible hosts during infection, nor about the mechanisms it uses to overcome genetic resistance. Here, we provide the first telomere-to-telomere complete genome of Plasmodiophora brassicae. We generated ∼ 27 Gb of Illumina, Oxford Nanopore, and PacBio HiFi data from resting spores of strain Pb3A and produced a 25.3 Mb assembly comprising 20 chromosomes, with an N50 of 1.37 Mb. The BUSCO score, the highest reported for any member of the group Rhizaria (Eukaryota: 88.2%), highlights the limitations within the Eukaryota database for members of this lineage. Using available transcriptomic data and protein evidence, we annotated the Pb3A genome, identifying 10,521 protein-coding gene models. This high-quality, complete genome of Plasmodiophora brassicae will serve as a crucial resource for the plant pathology community to advance the much-needed understanding of the evolution of the clubroot pathogen.},
}
@article {pmid38856709,
year = {2024},
author = {Vieira, RA and Nunes, DP and Lima, DB and Rocha, GDS and Corona, LP and Santos-Orlandi, AAD and Sampaio, ES and Rodrigues, PCOG and de Brito, TRP},
title = {Association between telomere length and anorexia of ageing: a cross-sectional study conducted with community-dwelling older people.},
journal = {Journal of human nutrition and dietetics : the official journal of the British Dietetic Association},
volume = {},
number = {},
pages = {},
doi = {10.1111/jhn.13338},
pmid = {38856709},
issn = {1365-277X},
support = {//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de Minas Gerais - FAPEMIG/ ; //Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; },
abstract = {BACKGROUND: To verify whether shorter telomere length is associated with anorexia of ageing in community-dwelling older people.<br><br>METHODS: Conducted as a cross-sectional investigation, the study enrolled 448 participants residing in an urban area of a municipality in Brazil. Relative telomere length in blood samples was measured using quantitative polymerase chain reaction (qPCR), whereas the presence of anorexia of ageing was determined using the Simplified Appetite Nutritional Questionnaire. Data analysis employed multiple logistic regression.<br><br>RESULTS: Among the 448 older individuals surveyed, 70.69% were female, and the predominant age bracket ranged from 60 to 69 years (45.08%). Approximately 25% exhibited the shortest telomeric length, with a corresponding anorexia of ageing prevalence of 41.16%. Older individuals with diminished telomere lengths displayed an increased likelihood of experiencing anorexia of ageing (odds ratio [OR]&#x2009;=&#x2009;1.92; 95% confidence interval [CI]&#x2009;=&#x2009;1.12-3.29), independent of factors such as gender, age group, depressive symptoms, pain and performance in basic daily life activities.<br><br>CONCLUSIONS: The observed association between anorexia of ageing and a telomeric biomarker underscores the imperative to meticulously evaluate the nutritional dimensions of older people, with a view to implementing interventions that may enhance their overall health status.},
}
@article {pmid38851349,
year = {2024},
author = {Colominas-Ciuró, R and Gray, FE and Arikan, K and Zahn, S and Meier, C and Criscuolo, F and Bize, P},
title = {Effects of persistent organic pollutants on telomere dynamics are sex and age-specific in a wild long-lived bird.},
journal = {The Science of the total environment},
volume = {},
number = {},
pages = {173785},
doi = {10.1016/j.scitotenv.2024.173785},
pmid = {38851349},
issn = {1879-1026},
abstract = {Chemical pollution is a major man-made environmental threat to ecosystems and natural animal populations. Of concern are persistent organic pollutants (POPs), which can persist in the environment for many years. While bioaccumulating throughout the lives of wild animals, POPs can affect their health, reproduction, and survival. However, measuring long-term effects of POPs in wild populations is challenging, and therefore appropriate biomarkers are required in wildlife ecotoxicology. One potential target is telomere length, since telomere preservation has been associated to survival and longevity, and stressors as chemical pollution can disrupt its maintenance. Here, we investigated the effects of different classes of POPs on relative telomere length (RTL) and its rate of change (TROC) in wild long-lived Alpine swifts (Tachymarptis melba). As both RTL and TROC are often reported to differ between sexes and with chronological age, we tested for sex- and age-specific (pre-senescent vs. senescent, ≥ 9 age of years, individuals) effects of POPs. Our results showed that senescent females presented longer RTL and elongated telomeres over time compared to pre-senescent females and males. These sex- and age-related differences in RTL and TROC were influenced by POPs, but differently depending on whether they were organochlorine pesticides (OCPs) or industrial polychlorinated biphenyls (PCBs). OCPs (particularly drins) were negatively associated with RTL, with the strongest negative effects being found in senescent females. Conversely, PCBs led to slower rates of telomere shortening, especially in females. Our study indicates diametrically opposed effects of OCPs on RTL and PCBs on TROC, and these effects were more pronounced in females and senescent individuals. The mechanisms behind these effects (e.g., increased oxidative stress by OCPs; upregulation of telomerase activity by PCBs) remain unknown. Our results highlight the importance in wildlife ecotoxicology to account for sex- and age-related effects when investigating the health effects of pollutants on biomarkers such as telomeres.},
}
@article {pmid38849401,
year = {2024},
author = {Sánchez-Ortí, JV and Correa-Ghisays, P and Balanzá-Martínez, V and Macías Saint-Gerons, D and Berenguer-Pascual, E and Romá-Mateo, C and Victor, VM and Forés-Martos, J and San-Martin, C and Selva-Vera, G and Tabarés-Seisdedos, R},
title = {Systemic inflammation, oxidative damage and neurocognition predict telomere length in a transdiagnostic sample stratified by global DNA methylation levels.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {13159},
pmid = {38849401},
issn = {2045-2322},
support = {UGP-14-184 Project//Fundaci&#xf3;n para el Fomento de la Investigaci&#xf3;n Sanitaria y Biom&#xe9;dica de la Comunitat Valenciana/ ; PI22/1009//Instituto de Salud Carlos III/ ; PI22/00424//Instituto de Salud Carlos III/ ; PROMETEO/2019/027//European Regional Development Fund/ ; CIPROM/2022/32//European Regional Development Fund/ ; CB06/04/0071//Ministerio de Ciencia e Innovaci&#xf3;n/ ; 0456-03-40//Grand Challenges Canada/ ; },
mesh = {Humans ; *DNA Methylation ; Male ; Female ; *Oxidative Stress ; *Inflammation/blood/genetics ; Adult ; Middle Aged ; *Telomere/genetics/metabolism ; *Schizophrenia/genetics/blood ; Diabetes Mellitus, Type 2/genetics ; Biomarkers/blood ; Bipolar Disorder/genetics/blood ; Depressive Disorder, Major/genetics/blood ; Leukocytes/metabolism ; Epigenesis, Genetic ; Telomere Homeostasis ; Cognition ; Case-Control Studies ; },
abstract = {Epigenetic mechanisms contribute to the maintenance of both type 2 diabetes mellitus (T2DM) and psychiatric disorders. Emerging evidence suggests that molecular pathways and neurocognitive performance regulate epigenetic dynamics in these disorders. The current combined and transdiagnostic study investigated whether inflammatory, oxidative stress, adhesion molecule, neurocognitive and functional performance are significant predictors of telomere dynamics in a sample stratified by global DNA methylation levels. Peripheral blood inflammation, oxidative stress and adhesion molecule biomarkers and neurocognitive function were assessed twice over a 1-year period in 80 individuals, including 16 with schizophrenia (SZ), 16 with bipolar disorder (BD), 16 with major depressive disorder (MDD), 15 with T2DM, and 17 healthy controls (HCs). Leukocyte telomere length (LTL) was measured by qRT-PCR using deoxyribonucleic acid (DNA) extracted from peripheral blood samples. A posteriori, individuals were classified based on their global methylation score (GMS) at baseline into two groups: the below-average methylation (BM) and above-average methylation (AM) groups. Hierarchical and k-means clustering methods, mixed one-way analysis of variance and linear regression analyses were performed. Overall, the BM group showed a significantly higher leukocyte telomere length (LTL) than the AM group at both time points (p = 0.02; η[2]p = 0.06). Moreover, the BM group had significantly lower levels of tumor necrosis factor alpha (TNF-α) (p = 0.03; η[2]p = 0.06) and C-reactive protein (CRP) (p = 0.03; η[2]p = 0.06) than the AM group at the 1-year follow-up. Across all participants, the regression models showed that oxidative stress (reactive oxygen species [ROS]) (p = 0.04) and global cognitive score [GCS] (p = 0.02) were significantly negatively associated with LTL, whereas inflammatory (TNF-α) (p = 0.04), adhesion molecule biomarkers (inter cellular adhesion molecule [ICAM]) (p = 0.009), and intelligence quotient [IQ] (p = 0.03) were significantly positively associated with LTL. Moreover, the model predictive power was increased when tested in both groups separately, explaining 15.8% and 28.1% of the LTL variance at the 1-year follow-up for the AM and BM groups, respectively. Heterogeneous DNA methylation in individuals with T2DM and severe mental disorders seems to support the hypothesis that epigenetic dysregulation occurs in a transdiagnostic manner. Our results may help to elucidate the interplay between epigenetics, molecular processes and neurocognitive function in these disorders. DNA methylation and LTL are potential therapeutic targets for transdiagnostic interventions to decrease the risk of comorbidities.},
}
@article {pmid38849156,
year = {2024},
author = {Murphy, WJ and Harris, AJ},
title = {Toward telomere-to-telomere cat genomes for precision medicine and conservation biology.},
journal = {Genome research},
volume = {},
number = {},
pages = {},
doi = {10.1101/gr.278546.123},
pmid = {38849156},
issn = {1549-5469},
abstract = {Genomic data from species of the cat family Felidae promise to stimulate veterinary and human medical advances, and clarify the coherence of genome organization. We describe how interspecies hybrids have been instrumental in the genetic analysis of cats, from the first genetic maps to propelling cat genomes toward the T2T standard set by the human genome project. Genotype-to-phenotype mapping in cat models has revealed dozens of health-related genetic variants, the molecular basis for mammalian pigmentation and patterning, and species-specific adaptations. Improved genomic surveillance of natural and captive populations across the cat family tree will increase our understanding of the genetic architecture of traits, population dynamics, and guide a future of genome-enabled biodiversity conservation.},
}
@article {pmid38845982,
year = {2024},
author = {Shi, HZ and Wang, MW and Huang, YS and Liu, Z and Li, L and Wan, LP},
title = {A telomere-related gene risk model for predicting prognosis and treatment response in acute myeloid leukemia.},
journal = {Heliyon},
volume = {10},
number = {11},
pages = {e31705},
doi = {10.1016/j.heliyon.2024.e31705},
pmid = {38845982},
issn = {2405-8440},
abstract = {Acute myeloid leukemia (AML) is a prevalent hematological malignancy among adults. Recent studies suggest that the length of telomeres could significantly affect both the risk of developing AML and the overall survival (OS). Despite the limited focus on the prognostic value of telomere-related genes (TRGs) in AML, our study aims at addressing this gap by compiling a list of TRGs from TelNet, as well as collecting clinical information and TRGs expression data through the Gene Expression Omnibus (GEO) database. The GSE37642 dataset, sourced from GEO and based on the GPL96 platform, was divided into training and validation sets at a 6:4 ratio. Additionally, the GSE71014 dataset (based on the GPL10558 platform), GSE12417 dataset (based on the GPL96 and GPL570 platforms), and another portion of the GSE37642 dataset (based on the GPL570 platform) were designated as external testing sets. Univariate Cox regression analysis identified 96 TRGs significantly associated with OS. Subsequent Lasso-Cox stepwise regression analysis pinpointed eight TRGs (MCPH1, SLC25A6, STK19, PSAT1, KCTD15, DNMT3B, PSMD5, and TAF2) exhibiting robust predictive potential for patient survival. Both univariate and multivariate survival analyses unveiled TRG risk scores and age as independent prognostic variables. To refine the accuracy of survival prognosis, we developed both a nomogram integrating clinical parameters and a predictive risk score model based on TRGs. In subsequent investigations, associations were emphasized not solely regarding the TRG risk score and immune infiltration patterns but also concerning the response to immune-checkpoint inhibitor (ICI) therapy. In summary, the establishment of a telomere-associated genetic risk model offers a valuable tool for prognosticating AML outcomes, thereby facilitating informed treatment decisions.},
}
@article {pmid38843356,
year = {2024},
author = {Yeo, D and Zars Fisher, EL and Khosla, S and Farr, JN and Westendorf, JJ},
title = {Hdac3-deficiency increases senescence-associated distention of satellite DNA and telomere-associated foci in osteoprogenitor cells.},
journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research},
volume = {},
number = {},
pages = {},
doi = {10.1093/jbmr/zjae085},
pmid = {38843356},
issn = {1523-4681},
abstract = {Histone deacetylase 3 (Hdac3) is an epigenetic regulator of gene expression and interacts with skeletal transcription factors such as Runx2. We previously reported that conditional deletion of Hdac3 in Osterix-Cre recombinase-expressing osteoprogenitor cells (Hdac3 CKOOsx) caused osteopenia and increased marrow adiposity, both hallmarks of skeletal aging. We also showed that Runx2+ cells within osteogenic cultures of Hdac3-depleted bone marrow stromal cells (BMSCs) contain lipid droplets (LDs). Cellular senescence, a non-proliferative metabolically active state, is associated with increased marrow adiposity, bone loss and aging. In this study, we sought to determine if Hdac3 depleted Runx2+ pre-osteoblasts from young mice exhibit chromatin changes associated with early cellular senescence and how these events correlate with the appearance of LDs. We first confirmed that BMSCs from Hdac3 CKOOsx mice have more Runx2 + LD+ cells compared to controls under osteogenic conditions. We then measured senescence-associated distention of satellite DNA (SADS) and telomere-associated foci (TAFs) in Hdac3 CKOOsx and control BMSCs. In situ, Runx2+ cells contained more SADs per nuclei in Hdac3 CKOOsx femora than in controls. Runx2+ BMSCs from Hdac3 CKOOsx mice also contained more SADS and TAFs per nuclei than Runx2+ cells from age-matched control mice in vitro. SADs and TAFs were present at similar levels in Runx2 + LD+ cells and Runx2 + LD- cells from Hdac3 CKOOsx mice. Hdac inhibitors also increased the number of SADS in Runx2 + LD+ and Runx2 + LD- wildtype BMSCs. Senolytics reduced viable cell numbers in Hdac3 CKOOsx BMSC cultures. These data demonstrate that depletion of Hdac3 in osteochondral progenitor cells triggers LD formation and early events in cellular senescence in Runx2+ BMSCs through mutually exclusive mechanisms.},
}
@article {pmid38838667,
year = {2024},
author = {Cai, SW and Takai, H and Zaug, AJ and Dilgen, TC and Cech, TR and Walz, T and de Lange, T},
title = {POT1 recruits and regulates CST-Polα/primase at human telomeres.},
journal = {Cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cell.2024.05.002},
pmid = {38838667},
issn = {1097-4172},
abstract = {Telomere maintenance requires the extension of the G-rich telomeric repeat strand by telomerase and the fill-in synthesis of the C-rich strand by Polα/primase. At telomeres, Polα/primase is bound to Ctc1/Stn1/Ten1 (CST), a single-stranded DNA-binding complex. Like mutations in telomerase, mutations affecting CST-Polα/primase result in pathological telomere shortening and cause a telomere biology disorder, Coats plus (CP). We determined cryogenic electron microscopy structures of human CST bound to the shelterin heterodimer POT1/TPP1 that reveal how CST is recruited to telomeres by POT1. Our findings suggest that POT1 hinge phosphorylation is required for CST recruitment, and the complex is formed through conserved interactions involving several residues mutated in CP. Our structural and biochemical data suggest that phosphorylated POT1 holds CST-Polα/primase in an inactive, autoinhibited state until telomerase has extended the telomere ends. We propose that dephosphorylation of POT1 releases CST-Polα/primase into an active state that completes telomere replication through fill-in synthesis.},
}
@article {pmid38837945,
year = {2024},
author = {Bai, M and Jiang, S and Chu, S and Yu, Y and Shan, D and Liu, C and Zong, L and Liu, Q and Liu, N and Xu, W and Mei, Z and Jian, J and Zhang, C and Zhao, S and Chiu, TY and Simonsen, HT},
title = {The telomere-to-telomere (T2T) genome of Peucedanum praeruptorum Dunn provides insights into the genome evolution and coumarin biosynthesis.},
journal = {GigaScience},
volume = {13},
number = {},
pages = {},
doi = {10.1093/gigascience/giae025},
pmid = {38837945},
issn = {2047-217X},
support = {2022YFD1201600//National Key Research and Development Program of China/ ; },
mesh = {*Coumarins/metabolism ; *Genome, Plant ; *Apiaceae/genetics/metabolism ; *Telomere/genetics/metabolism ; Evolution, Molecular ; Phylogeny ; Genomics/methods ; Biosynthetic Pathways/genetics ; },
abstract = {BACKGROUND: Traditional Chinese medicine has used Peucedanum praeruptorum Dunn (Apiaceae) for a long time. Various coumarins, including the significant constituents praeruptorin (A-E), are the active constituents in the dried roots of P. praeruptorum. Previous transcriptomic and metabolomic studies have attempted to elucidate the distribution and biosynthetic network of these medicinal-valuable compounds. However, the lack of a high-quality reference genome impedes an in-depth understanding of genetic traits and thus the development of better breeding strategies.<br><br>RESULTS: A telomere-to-telomere (T2T) genome was assembled for P. praeruptorum by combining PacBio HiFi, ONT ultra-long, and Hi-C data. The final genome assembly was approximately 1.798 Gb, assigned to 11 chromosomes with genome completeness >98%. Comparative genomic analysis suggested that P. praeruptorum experienced 2 whole-genome duplication events. By the transcriptomic and metabolomic analysis of the coumarin metabolic pathway, we presented coumarins' spatial and temporal distribution and the expression patterns of critical genes for its biosynthesis. Notably, the COSY and cytochrome P450 genes showed tandem duplications on several chromosomes, which may be responsible for the high accumulation of coumarins.<br><br>CONCLUSIONS: A T2T genome for P. praeruptorum was obtained, providing molecular insights into the chromosomal distribution of the coumarin biosynthetic genes. This high-quality genome is an essential resource for designing engineering strategies for improving the production of these valuable compounds.},
}
@article {pmid38837897,
year = {2024},
author = {Graham, MK and Xu, B and Davis, C and Meeker, AK and Heaphy, CM and Yegnasubramanian, S and Dyer, MA and Zeineldin, M},
title = {The TERT promoter is polycomb-repressed in neuroblastoma cells with long telomeres.},
journal = {Cancer research communications},
volume = {},
number = {},
pages = {},
doi = {10.1158/2767-9764.CRC-22-0287},
pmid = {38837897},
issn = {2767-9764},
abstract = {Acquiring a telomere maintenance mechanism is a hallmark of high-risk neuroblastoma and commonly occurs by expressing telomerase (TERT). Telomerase-negative neuroblastoma has long telomeres and utilize the telomerase-independent alternative lengthening of telomeres (ALT) mechanism. Conversely, no discernable telomere maintenance mechanism is detected in a fraction of neuroblastoma with long telomeres. Here, we show, unlike most cancers, DNA of the TERT promoter is broadly hypomethylated in neuroblastoma. In telomerase-positive neuroblastoma cells, the hypomethylated DNA promoter is approximately 1.5-kb. The TERT locus shows active chromatin marks with low enrichment for the repressive mark, H3K27me3. MYCN, a commonly amplified oncogene in neuroblstoma, binds to the promoter and induces TERT expression. Strikingly, in neuroblastoma with long telomeres, the hypomethylated region spans the entire TERT locus, including multiple nearby genes with enrichment for the repressive H3K27me3 chromatin mark. Furthermore, subtelomeric regions showed enrichment of repressive chromatin marks in neuroblastomas with long telomeres relative to those with short telomeres. These repressive marks were even more evident at the genic loci, suggesting a telomere position effect. Inhibiting H3K27 methylation by three different EZH2 inhibitors induced the expression of TERT in cell lines with long telomeres and H3K27me3 marks in the promoter region. EZH2 inhibition facilitated MYCN binding to the TERT promoter in neuroblastoma cells with long telomeres. Taken together, these data suggest that epigenetic regulation of TERT expression differs in neuroblastoma depending on the telomere maintenance status, and H3K27 methylation is important in repressing TERT expression in neuroblastoma with long telomeres.},
}
@article {pmid38837510,
year = {2024},
author = {Sun, P and Gu, KJ and Zheng, G and Sikora, AG and Li, C and Zafereo, M and Wei, P and Wu, J and Shete, S and Liu, J and Li, G},
title = {Genetic variations associated with telomere length predict the risk of recurrence of non-oropharyngeal head and neck squamous cell carcinoma.},
journal = {Molecular carcinogenesis},
volume = {},
number = {},
pages = {},
doi = {10.1002/mc.23768},
pmid = {38837510},
issn = {1098-2744},
abstract = {Genetic factors underlying lymphocyte telomere length (LTL) may provide insights into genomic stability and integrity, with direct links to susceptibility to cancer recurrence. Polymorphisms in telomere-associated genes are strongly associated with LTL and cancer risk, while few large studies have explored the associations between LTL-related polymorphisms and recurrence risk of non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC). Totally 1403 non-OPHNSCC patients were recruited and genotyped for 16 LTL-related polymorphisms identified by genome-wide association studies. Univariate and multivariate analyzes were performed to evaluate associations between the polymorphisms and non-OPHNSCC recurrence risk. Patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes exhibited shorter DFS than those with the rs755017 AA, rs2487999 CC, rs2736108 CC, or s6772228 TT genotypes, respectively (all log-rank p < 0.05). Multivariable analysis confirmed an increased risk of recurrence for patients carrying rs755017 GA/GG, rs2487999 TC/TT, rs2736108 TC/TT, or rs6772228 AT/AA genotypes (adjusted hazard ratio [aHR]: 1.66, 95% confidence interval [CI]: 1.32-2.07; aHR: 1.77, 95% CI: 1.41-2.23; aHR: 1.56, 95% CI: 1.22-1.99; aHR: 1.52, 95% CI: 1.20-1.93, respectively). Further stratified analysis revealed stronger associations between these genotypes and recurrence risk in ever-smokers and patients undergoing chemoradiotherapy. The similar but particularly pronounced results were observed for the combined risk genotypes of the four significant polymorphisms. This is the first large study on non-OPHNSCC patients showing that LTL-related polymorphisms may modify risk of non-OPHNSCC recurrence individually and jointly, particularly when analyzed in the context of smoking status and personized treatment. Larger studies are needed to validate these results.},
}
@article {pmid38837026,
year = {2024},
author = {Liu, WS and Wu, BS and Yang, L and Chen, SD and Zhang, YR and Deng, YT and Wu, XR and He, XY and Yang, J and Feng, JF and Cheng, W and Xu, YM and Yu, JT},
title = {Whole exome sequencing analyses reveal novel genes in telomere length and their biomedical implications.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {38837026},
issn = {2509-2723},
support = {2022ZD0211600//Science and Technology Innovation 2030 Major Projects/ ; 92249305//National Natural Science Foundation of China/ ; 82271471//National Natural Science Foundation of China/ ; 82071201//National Natural Science Foundation of China/ ; 2018SHZDZX01//Shanghai Municipal Science and Technology Major Project/ ; },
abstract = {Telomere length is a putative biomarker of aging and is associated with multiple age-related diseases. There are limited data on the landscape of rare genetic variations in telomere length. Here, we systematically characterize the rare variant associations with leukocyte telomere length (LTL) through exome-wide association study (ExWAS) among 390,231 individuals in the UK Biobank. We identified 18 robust rare-variant genes for LTL, most of which estimated effects on LTL were significant (> 0.2 standard deviation per allele). The biological functions of the rare-variant genes were associated with telomere maintenance and capping and several genes were specifically expressed in the testis. Three novel genes (ASXL1, CFAP58, and TET2) associated with LTL were identified. Phenotypic association analyses indicated significant associations of ASXL1 and TET2 with cancers, age-related diseases, blood assays, and cardiovascular traits. Survival analyses suggested that carriers of ASXL1 or TET2 variants were at increased risk for cancers; diseases of the circulatory, respiratory, and genitourinary systems; and all-cause and cause-specific deaths. The CFAP58 carriers were at elevated risk of deaths due to cancers. Collectively, the present whole exome sequencing study provides novel insights into the genetic landscape of LTL, identifying novel genes associated with LTL and their implications on human health and facilitating a better understanding of aging, thus pinpointing the genetic relevance of LTL with clonal hematopoiesis, biomedical traits, and health-related outcomes.},
}
@article {pmid38831447,
year = {2024},
author = {Wu, X and Hu, C and Wu, T and Du, X and Peng, Z and Xue, W and Chen, Y and Dong, L},
title = {Mendelian randomization evidence based on European ancestry for the causal effects of leukocyte telomere length on prostate cancer.},
journal = {Human genomics},
volume = {18},
number = {1},
pages = {56},
pmid = {38831447},
issn = {1479-7364},
support = {82103485//National Natural Science Foundation of China/ ; 2022YQ014//Shanghai Municipal Health Commission Talent Plan/ ; },
abstract = {BACKGROUND: Several lines of evidence suggest that leukocyte telomere length (LTL) can affect the development of prostate cancer (PC).<br><br>METHODS: Here, we employed single nucleoside polymorphisms (SNPs) as instrumental variables (IVs) for LTL (n&#x2009;=&#x2009;472,174) and conducted Mendelian randomization analysis to estimate their causal impact on PCs (79,148 patients/61,106 controls and 6311 patients/88,902 controls).<br><br>RESULTS: Every 1-s.d extension of LTL increased the risk of PCs by 34%. Additionally, the analysis of candidate mediators between LTL and PCs via two-step Mendelian randomization revealed that among the 23 candidates, Alzheimer's disease, liver iron content, sex hormone binding global levels, naive CD4-CD8-T cell% T cell, and circulating leptin levels played substantial mediating roles. There is no robust evidence to support the reverse causal relationship between LTL and the selected mediators of PCs. Adjusting for the former four mediators, rather than adjusting for circulating leptin levels, decreased the impact of LTL on PCs.<br><br>CONCLUSION: This study provides potential intervention measures for preventing LTL-induced PCs.},
}
@article {pmid38830842,
year = {2024},
author = {Nageshan, RK and Ortega, R and Krogan, N and Cooper, JP},
title = {Fate of telomere entanglements is dictated by the timing of anaphase midregion nuclear envelope breakdown.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {4707},
pmid = {38830842},
issn = {2041-1723},
support = {GM145820-01//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; },
mesh = {*Nuclear Envelope/metabolism ; *Schizosaccharomyces/genetics/metabolism ; *Telomere/metabolism ; *Schizosaccharomyces pombe Proteins/metabolism/genetics ; *Telomere-Binding Proteins/metabolism/genetics ; *Anaphase ; DNA Replication ; },
abstract = {Persisting replication intermediates can confer mitotic catastrophe. Loss of the fission yeast telomere protein Taz1 (ortholog of mammalian TRF1/TRF2) causes telomeric replication fork (RF) stalling and consequently, telomere entanglements that stretch between segregating mitotic chromosomes. At ≤20 °C, these entanglements fail to resolve, resulting in lethality. Rif1, a conserved DNA replication/repair protein, hinders the resolution of telomere entanglements without affecting their formation. At mitosis, local nuclear envelope (NE) breakdown occurs in the cell's midregion. Here we demonstrate that entanglement resolution occurs in the cytoplasm following this NE breakdown. However, in response to taz1Δ telomeric entanglements, Rif1 delays midregion NE breakdown at ≤20 °C, in turn disfavoring entanglement resolution. Moreover, Rif1 overexpression in an otherwise wild-type setting causes cold-specific NE defects and lethality, which are rescued by membrane fluidization. Hence, NE properties confer the cold-specificity of taz1Δ lethality, which stems from postponement of NE breakdown. We propose that such postponement promotes clearance of simple stalled RFs, but resolution of complex entanglements (involving strand invasion between nonsister telomeres) requires rapid exposure to the cytoplasm.},
}
@article {pmid38830229,
year = {2024},
author = {Koyuncu, H and Kara, N and Dabak, &#x15e;},
title = {Investigation of the possible effects of night shift on telomere length and mtDNA copy number in nurses.},
journal = {Nucleosides, nucleotides &amp; nucleic acids},
volume = {},
number = {},
pages = {1-14},
doi = {10.1080/15257770.2024.2348089},
pmid = {38830229},
issn = {1532-2335},
abstract = {In this study, we aimed to investigate the impacts of altered circadian rhythm on telomere length and mtDNA copy number (mtDNA-CN) in nurses working night shifts. In our study, 52 healthy nurses working in shifts at Ondokuz Mayıs University Hospital and 45 healthy control subjects working during the day were included. qRT-PCR technique was used for the determination of telomere length and mtDNA-CN. It was observed that the shift-work group had poor sleep quality (p = 0.004), feeling tired (p < 0.01) and stressed (p = 0.02) more than control group working during the day. Nurses working in shifts were found to have 1.18 times longer telomeres with respect to the control group working during the day (p = 0.005). When compared among shift workers, poor sleep quality and insufficient sleep duration shortened telomeres (r = 0.32; p = 0.02). There was no statistically significantdisparity regarding mtDNA-CN among the nurses working in shifts and the control group working during the day (p = 0.07). Insufficient sleep was associated with decreased mtDNA-CN when shift-working nurses were compared according to sleep quality (p = 0.006). Furthermore, mtDNA-CN of nurses with poor sleep quality was correlated with lower mtDNA-CN in comparison to nurses with good sleep quality (r = 0.284; p = 0.04). The mtDNA-CN of the nurses was positively associated with the sleep duration the night sleep before the night shift (r = 0.32; p = 0.02). Inadequate sleep duration and quality were observed to cause a reduction in mtDNA-CN of nurses. In conclusion, it has been observed that poor sleep quality and duration are related to shortened telomere length and decreased mtDNA-CN in night shift nurses.},
}
@article {pmid38825615,
year = {2024},
author = {Zheng, J and Chen, J and Li, H and Li, Y and Dong, W and Jiang, X},
title = {Predicting prostate adenocarcinoma patients' survival and immune signature: a novel risk model based on telomere-related genes.},
journal = {Discover oncology},
volume = {15},
number = {1},
pages = {203},
pmid = {38825615},
issn = {2730-6011},
support = {82072808//the National Natural Science Foundation of China/ ; 2023QNYXYB016//Youth Medical Innovation and Practice Research Program of Guangzhou/ ; },
abstract = {Alterations in telomeres constitute some of the earliest occurrences in the tumourigenesis of prostate adenocarcinoma (PRAD) and persist throughout the progression of the tumour. While the activity of telomerase and the length of telomeres have been demonstrated to correlate with the prognosis of PRAD, the prognostic potential of telomere-related genes (TRGs) in this disease remains unexplored. Utilising mRNA expression data from the Cancer Genome Atlas (TCGA), we devised a risk model and a nomogram to predict the survival outcomes of patients with PRAD. Subsequently, our investigations extended to the relationship between the risk model and immune cell infiltration, sensitivity to chemotherapeutic drugs, and specific signalling pathways. The risk model we developed is predicated on seven key TRGs, and immunohistochemistry results revealed significant differential expression of three TRGs in tumours and paracancerous tissues. Based on the risk scores, PRAD patients were stratified into high-risk and low-risk cohorts. The Receiver operating characteristics (ROC) and Kaplan-Meier survival analyses corroborated the exceptional predictive performance of our novel risk model. Multivariate Cox regression analysis indicated that the risk score was an independent risk factor associated with Overall Survival (OS) and was significantly associated with T and N stages of PRAD patients. Notably, the high-risk group exhibited a greater response to chemotherapy and immunosuppression compared to the low-risk group, offering potential guidance for treatment strategies for high-risk patients. In conclusion, our new risk model, based on TRGs, serves as a reliable prognostic indicator for PRAD. The model holds significant value in guiding the selection of immunotherapy and chemotherapy in the clinical management of PRAD patients.},
}
@article {pmid38824190,
year = {2024},
author = {Hinchie, AM and Sanford, SL and Loughridge, KE and Sutton, RM and Parikh, AH and Gil Silva, AA and Sullivan, DI and Chun-On, P and Morrell, MR and McDyer, JF and Opresko, PL and Alder, JK},
title = {A persistent variant telomere sequence in a human pedigree.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {4681},
pmid = {38824190},
issn = {2041-1723},
support = {R01HL135062//U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; },
mesh = {Humans ; *Telomere/metabolism/genetics ; *Telomere-Binding Proteins/metabolism/genetics ; *Shelterin Complex/metabolism ; *Pedigree ; *Telomerase/genetics/metabolism ; Male ; Female ; Telomere Homeostasis/genetics ; Base Sequence ; Adult ; },
abstract = {The telomere sequence, TTAGGG, is conserved across all vertebrates and plays an essential role in suppressing the DNA damage response by binding a set of proteins termed shelterin. Changes in the telomere sequence impair shelterin binding, initiate a DNA damage response, and are toxic to cells. Here we identify a family with a variant in the telomere template sequence of telomerase, the enzyme responsible for telomere elongation, that led to a non-canonical telomere sequence. The variant is inherited across at least one generation and one family member reports no significant medical concerns despite ~9% of their telomeres converting to the novel sequence. The variant template disrupts telomerase repeat addition processivity and decreased the binding of the telomere-binding protein POT1. Despite these disruptions, the sequence is readily incorporated into cellular chromosomes. Incorporation of a variant sequence prevents POT1-mediated inhibition of telomerase suggesting that incorporation of a variant sequence may influence telomere addition. These findings demonstrate that telomeres can tolerate substantial degeneracy while remaining functional and provide insights as to how incorporation of a non-canonical telomere sequence might alter telomere length dynamics.},
}
@article {pmid38816532,
year = {2024},
author = {Agabekian, IA and Abdulkina, LR and Lushnenko, AY and Young, PG and Valeeva, LR and Boskovic, O and Lilly, EG and Sharipova, MR and Shippen, DE and Juenger, TE and Shakirov, EV},
title = {Arabidopsis AN3 and OLIGOCELLULA genes link telomere maintenance mechanisms with cell division and expansion control.},
journal = {Plant molecular biology},
volume = {114},
number = {3},
pages = {65},
pmid = {38816532},
issn = {1573-5028},
support = {GM127402/GM/NIGMS NIH HHS/United States ; GM065383/GM/NIGMS NIH HHS/United States ; 21-14-00147//Russian Science Foundation/ ; },
mesh = {*Arabidopsis/genetics/metabolism ; *Arabidopsis Proteins/genetics/metabolism ; *Telomere/genetics/metabolism ; *Cell Division/genetics ; *Telomerase/genetics/metabolism ; Telomere Homeostasis/genetics ; Gene Expression Regulation, Plant ; Mutation ; Transcription Factors/metabolism/genetics ; Cell Proliferation/genetics ; Meristem/genetics/metabolism ; },
abstract = {Telomeres are conserved chromosomal structures necessary for continued cell division and proliferation. In addition to the classical telomerase pathway, multiple other genes including those involved in ribosome metabolism and chromatin modification contribute to telomere length maintenance. We previously reported that Arabidopsis thaliana ribosome biogenesis genes OLI2/NOP2A, OLI5/RPL5A and OLI7/RPL5B have critical roles in telomere length regulation. These three OLIGOCELLULA genes were also shown to function in cell proliferation and expansion control and to genetically interact with the transcriptional co-activator ANGUSTIFOLIA3 (AN3). Here we show that AN3-deficient plants progressively lose telomeric DNA in early homozygous mutant generations, but ultimately establish a new shorter telomere length setpoint by the fifth mutant generation with a telomere length similar to oli2/nop2a -deficient plants. Analysis of double an3 oli2 mutants indicates that the two genes are epistatic for telomere length control. Telomere shortening in an3 and oli mutants is not caused by telomerase inhibition; wild type levels of telomerase activity are detected in all analyzed mutants in vitro. Late generations of an3 and oli mutants are prone to stem cell damage in the root apical meristem, implying that genes regulating telomere length may have conserved functional roles in stem cell maintenance mechanisms. Multiple instances of anaphase fusions in late generations of oli5 and oli7 mutants were observed, highlighting an unexpected effect of ribosome biogenesis factors on chromosome integrity. Overall, our data implicate AN3 transcription coactivator and OLIGOCELLULA proteins in the establishment of telomere length set point in plants and further suggest that multiple regulators with pleiotropic functions can connect telomere biology with cell proliferation and cell expansion pathways.},
}
@article {pmid38816389,
year = {2024},
author = {Zhang, Z and Zhang, X and Tian, Y and Wang, L and Cao, J and Feng, H and Li, K and Wang, Y and Dong, S and Ye, W and Wang, Y},
title = {Complete telomere-to-telomere genomes uncover virulence evolution conferred by chromosome fusion in oomycete plant pathogens.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {4624},
pmid = {38816389},
issn = {2041-1723},
support = {32172374//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {*Telomere/genetics ; *Oomycetes/genetics/pathogenicity ; *Phylogeny ; Virulence/genetics ; *Evolution, Molecular ; Plant Diseases/microbiology/genetics ; Pythium/genetics/pathogenicity ; Phytophthora/genetics/pathogenicity ; Chromosomes/genetics ; Plants/microbiology/genetics ; Genome/genetics ; },
abstract = {Variations in chromosome number are occasionally observed among oomycetes, a group that includes many plant pathogens, but the emergence of such variations and their effects on genome and virulence evolution remain ambiguous. We generated complete telomere-to-telomere genome assemblies for Phytophthora sojae, Globisporangium ultimum, Pythium oligandrum, and G. spinosum. Reconstructing the karyotype of the most recent common ancestor in Peronosporales revealed that frequent chromosome fusion and fission drove changes in chromosome number. Centromeres enriched with Copia-like transposons may contribute to chromosome fusion and fission events. Chromosome fusion facilitated the emergence of pathogenicity genes and their adaptive evolution. Effectors tended to duplicate in the sub-telomere regions of fused chromosomes, which exhibited evolutionary features distinct to the non-fused chromosomes. By integrating ancestral genomic dynamics and structural predictions, we have identified secreted Ankyrin repeat-containing proteins (ANKs) as a novel class of effectors in P. sojae. Phylogenetic analysis and experiments further revealed that ANK is a specifically expanded effector family in oomycetes. These results revealed chromosome dynamics in oomycete plant pathogens, and provided novel insights into karyotype and effector evolution.},
}
@article {pmid38808110,
year = {2024},
author = {McCollum, SE and Canter, O and Fasanello, VJ and Gronsky, S and Haussmann, MF},
title = {Birds of a feather age together: telomere dynamics and social behavior predict life span in female Japanese quail (Coturnix japonica).},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1363468},
doi = {10.3389/fendo.2024.1363468},
pmid = {38808110},
issn = {1664-2392},
mesh = {Animals ; *Coturnix/physiology ; Female ; *Longevity ; *Telomere ; *Social Behavior ; *Aging/physiology ; Behavior, Animal ; Feathers ; Telomere Shortening ; Aggression/physiology ; Corticosterone/blood ; },
abstract = {Social support is vital for mental and physical health and is linked to lower rates of disease and early mortality. Conversely, anti-social behavior can increase mortality risks, both for the initiator and target of the behavior. Chronic stress, which also can increase mortality, may serve as an important link between social behavior and healthy lifespan. There is a growing body of literature in both humans, and model organisms, that chronic social stress can result in more rapid telomere shortening, a measure of biological aging. Here we examine the role of anti-social behavior and social support on physiological markers of stress and aging in the social Japanese quail, Coturnix Japonica. Birds were maintained in groups for their entire lifespan, and longitudinal measures of antisocial behavior (aggressive agonistic behavior), social support (affiliative behavior), baseline corticosterone, change in telomere length, and lifespan were measured. We found quail in affiliative relationships both committed less and were the targets of less aggression compared to birds who were not in these relationships. In addition, birds displaying affiliative behavior had longer telomeres, and longer lifespans. Our work suggests a novel pathway by which social support may buffer against damage at the cellular level resulting in telomere protection and subsequent longer lifespans.},
}
@article {pmid38805768,
year = {2024},
author = {Salinas-Rodriguez, A and Manrique-Espinoza, B and Rivera-Almaraz, A and Sánchez-López, JM and Rosas-Vargas, H},
title = {Telomere Length is Associated with the Prevalence, Persistence, and Incidence of Sarcopenia.},
journal = {Archives of medical research},
volume = {55},
number = {4},
pages = {103007},
doi = {10.1016/j.arcmed.2024.103007},
pmid = {38805768},
issn = {1873-5487},
abstract = {BACKGROUND: Telomere length (TL) shortening has been identified as a marker of aging and associated with adverse health outcomes, but evidence of its association with sarcopenia is inconclusive.<br><br>AIMS: Estimate the cross-sectional and prospective associations between TL and sarcopenia.<br><br>METHODS: We used data from Waves 3 and 4 (2017, 2021) of the Study on Global Aging and Adult Health in Mexico (SAGE-Mexico). The cross-sectional sample consisted of 1,738 adults aged 50 and older, and the longitudinal sample consisted of 1,437. Relative TL was determined by real-time quantitative polymerase chain reaction (qPCR) on DNA extracted from saliva samples and quantified as the telomere/single-copy gene (T/S) ratio. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People (EWGSOP2).<br><br>RESULTS: The mean salivary TL was 1.50 T/S units (95% CI: 1.49-1.52). The baseline prevalence of sarcopenia was 13.3% (95% CI: 9.8-16.8%). The incidence and persistence of sarcopenia were 6.8% (95% CI: 5.0-9.5%) and 7.0% (95% CI: 5.1-9.6%), respectively. The results showed that a one standard deviation decrease in TL was cross-sectionally associated with higher odds of sarcopenia (OR = 1.31; 95% CI: 1.03-1.67) and prospectively with a higher incidence (RRR = 1.55; 95% CI: 1.06-2.25) and persistence (RRR = 1.50; 95% CI: 1.01-2.24) of sarcopenia.<br><br>CONCLUSIONS: Older adults with shorter TL had higher rates of incident and persistent sarcopenia. Implementation of interventions to delay the decline of TL in older adults is warranted. Further translational studies are needed to elucidate the effects of exercise or diet on DNA repair in the telomeric region and their associations with sarcopenia.},
}
@article {pmid38802448,
year = {2024},
author = {Sadler, DE and Watts, PC and Uusi-Heikkilä, S},
title = {Directional selection, not the direction of selection, affects telomere length and copy number at ribosomal RNA loci.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {12162},
pmid = {38802448},
issn = {2045-2322},
support = {325107//Research Council of Finland/ ; 324602//Research Council of Finland/ ; 325107//Research Council of Finland/ ; },
mesh = {Animals ; *Telomere/genetics ; *Zebrafish/genetics ; *DNA Copy Number Variations ; *DNA, Mitochondrial/genetics ; *Selection, Genetic ; *RNA, Ribosomal/genetics ; Temperature ; Telomere Homeostasis ; Body Size/genetics ; },
abstract = {Many fisheries exert directional selection on traits such as body size and growth rate. Whether directional selection impacts regions of the genome associated with traits related to growth is unknown. To address this issue, we characterised copy number variation in three regions of the genome associated with cell division, (1) telomeric DNA, (2) loci transcribed as ribosomal RNA (rDNA), and (3) mitochondrial DNA (mtDNA), in three selection lines of zebrafish reared at three temperatures (22 °C, 28 °C, and 34 °C). Selection lines differed in (1) the direction of selection (two lines experienced directional selection for large or small body size) and (2) whether they experienced any directional selection itself. Lines that had experienced directional selection were smaller, had lower growth rate, shorter telomeres, and lower rDNA copy number than the line that experiencing no directional selection. Neither telomere length nor rDNA copy number were affected by temperature. In contrast, mtDNA content increased at elevated temperature but did not differ among selection lines. Though directional selection impacts rDNA and telomere length, direction of such selection did not matter, whereas mtDNA acts as a stress marker for temperature. Future work should examine the consequences of these genomic changes in natural fish stocks.},
}
@article {pmid38802042,
year = {2024},
author = {Bolzán, AD},
title = {CONSIDERATIONS ON THE SCORING OF TELOMERE ABERRATIONS IN VERTEBRATE CELLS DETECTED BY TELOMERE OR TELOMERE PLUS CENTROMERE PNA-FISH.},
journal = {Mutation research. Reviews in mutation research},
volume = {},
number = {},
pages = {108507},
doi = {10.1016/j.mrrev.2024.108507},
pmid = {38802042},
issn = {1388-2139},
abstract = {Given that telomeres play a fundamental role in maintaining genomic stability, the study of the chromosomal aberrations involving telomeric sequences is a topic of considerable research interest. In recent years, the scoring of these types of aberrations has been used in vertebrate cells, particularly human cells, to evaluate the effects of genotoxic agents on telomeres and the involvement of telomeric sequences on chromosomal aberrations. Currently, chromosomal aberrations involving telomeric sequences are evaluated in peripheral blood lymphocytes or immortalized cell lines, using telomere or telomere plus centromere fluorescence in situ hybridization (FISH) with Peptide Nucleic Acid (PNA) probes (PNA-FISH). The telomere PNA probe is more efficient in the detection of telomeric sequences than conventional FISH with a telomere DNA probe. In addition, the intensity of the telomeric PNA-FISH probe signal is directly correlated with the number of telomeric repeats. Therefore, use of this type of probe can identify chromosomal aberrations involving telomeres as well as determine the telomere length of the sample. There are several mistakes and inconsistencies in the literature regarding the identification of telomere aberrations, which prevent accurate scoring and data comparison between different publications concerning these types of aberrations. The aim of this review is to clarify these issues, and provide proper terminology and criteria for the identification, scoring, and analysis of telomere aberrations.},
}
@article {pmid38794655,
year = {2024},
author = {Feng, Z and Wang, Y and Fu, Z and Liao, J and Liu, H and Zhou, M},
title = {Exploring the Causal Effects of Mineral Metabolism Disorders on Telomere and Mitochondrial DNA: A Bidirectional Two-Sample Mendelian Randomization Analysis.},
journal = {Nutrients},
volume = {16},
number = {10},
pages = {},
doi = {10.3390/nu16101417},
pmid = {38794655},
issn = {2072-6643},
support = {2022A1515012593//Guangdong Basic and Applied Basic Research Foundation/ ; 82273582 and 82103785//National Natural Science Foundation of China/ ; },
mesh = {*Mendelian Randomization Analysis ; Humans ; *DNA, Mitochondrial/genetics ; *Telomere/metabolism ; Minerals/metabolism ; Aging/genetics ; DNA Copy Number Variations ; Trace Elements/blood ; Iron/metabolism/blood ; Biomarkers/blood ; },
abstract = {The aim of this study was to assess the causal relationships between mineral metabolism disorders, representative of trace elements, and key aging biomarkers: telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN). Utilizing bidirectional Mendelian randomization (MR) analysis in combination with the two-stage least squares (2SLS) method, we explored the causal relationships between mineral metabolism disorders and these aging indicators. Sensitivity analysis can be used to determine the reliability and robustness of the research results. The results confirmed that a positive causal relationship was observed between mineral metabolism disorders and TL (p < 0.05), while the causal relationship with mtDNA-CN was not significant (p > 0.05). Focusing on subgroup analyses of specific minerals, our findings indicated a distinct positive causal relationship between iron metabolism disorders and both TL and mtDNA-CN (p < 0.05). In contrast, disorders in magnesium and phosphorus metabolism did not exhibit significant causal effects on either aging biomarker (p > 0.05). Moreover, reverse MR analysis did not reveal any significant causal effects of TL and mtDNA-CN on mineral metabolism disorders (p > 0.05). The combination of 2SLS with MR analysis further reinforced the positive causal relationship between iron levels and both TL and mtDNA-CN (p < 0.05). Notably, the sensitivity analysis did not indicate significant pleiotropy or heterogeneity within these causal relationships (p > 0.05). These findings highlight the pivotal role of iron metabolism in cellular aging, particularly in regulating TL and sustaining mtDNA-CN, offering new insights into how mineral metabolism disorders influence aging biomarkers. Our research underscores the importance of trace element balance, especially regarding iron intake, in combating the aging process. This provides a potential strategy for slowing aging through the adjustment of trace element intake, laying the groundwork for future research into the relationship between trace elements and healthy aging.},
}
@article {pmid38793637,
year = {2024},
author = {Yang, NY and Hsieh, AYY and Chen, Z and Campbell, AR and Gadawska, I and Kakkar, F and Sauve, L and Bitnun, A and Brophy, J and Murray, MCM and Pick, N and Krajden, M and Côté, HCF and Cihr Team On Cellular Aging And Hiv Comorbidities In Women And Children Carma, },
title = {Chronic and Latent Viral Infections and Leukocyte Telomere Length across the Lifespan of Female and Male Individuals Living with or without HIV.},
journal = {Viruses},
volume = {16},
number = {5},
pages = {},
doi = {10.3390/v16050755},
pmid = {38793637},
issn = {1999-4915},
support = {HET-85515/CAPMC/CIHR/Canada ; TCO-125269//Canadian Institutes of Health Researc/ ; GER-163053/CAPMC/CIHR/Canada ; },
mesh = {Humans ; Female ; *HIV Infections/virology/immunology ; Male ; *Leukocytes/virology ; Middle Aged ; Adult ; Aged ; Young Adult ; Adolescent ; Child ; Telomere/genetics ; Infant ; Child, Preschool ; Latent Infection/virology ; Virus Diseases/virology/immunology ; Chronic Disease ; Cohort Studies ; Infant, Newborn ; },
abstract = {BACKGROUND: Chronic/latent viral infections may accelerate immunological aging, particularly among people living with HIV (PLWH). We characterized chronic/latent virus infections across their lifespan and investigated their associations with leukocyte telomere length (LTL).<br><br>METHODS: Participants enrolled in the CARMA cohort study were randomly selected to include n = 15 for each decade of age between 0 and >60 y, for each sex, and each HIV status. Cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), herpes simplex virus 1 (HSV-1), and HSV-2 infection were determined serologically; HIV, hepatitis C (HCV), and hepatitis B (HBV) were self-reported. LTLs were measured using monochrome multiplex qPCR. Associations between the number of viruses, LTL, and sociodemographic factors were assessed using ordinal logistic and linear regression modeling.<br><br>RESULTS: The study included 187 PLWH (105 female/82 male) and 190 HIV-negative participants (105 female/84 male), ranging in age from 0.7 to 76.1 years. Living with HIV, being older, and being female were associated with harbouring a greater number of chronic/latent non-HIV viruses. Having more infections was in turn bivariately associated with a shorter LTL. In multivariable analyses, older age, living with HIV, and the female sex remained independently associated with having more infections, while having 3-4 viruses (vs. 0-2) was associated with a shorter LTL.<br><br>CONCLUSIONS: Our results suggest that persistent viral infections are more prevalent in PLWH and females, and that these may contribute to immunological aging. Whether this is associated with comorbidities later in life remains an important question.},
}
@article {pmid38792881,
year = {2024},
author = {Tariq, JA and Mandokhail, K and Sajjad, N and Hussain, A and Javaid, H and Rasool, A and Sadaf, H and Javaid, S and Durrani, AR},
title = {Effects of Age and Biological Age-Determining Factors on Telomere Length in Type 2 Diabetes Mellitus Patients.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {60},
number = {5},
pages = {},
doi = {10.3390/medicina60050698},
pmid = {38792881},
issn = {1648-9144},
mesh = {Humans ; *Diabetes Mellitus, Type 2/genetics ; Male ; Female ; Middle Aged ; *Telomere ; Adult ; Aged ; *Aging/physiology ; Age Factors ; Pakistan/epidemiology ; Telomere Shortening ; Leukocytes/metabolism ; },
abstract = {Background and Objectives: Telomere length (TL) undergoes attrition over time, indicating the process of aging, and is linked to a higher risk of diabetes mellitus type 2 (DM-2). This molecular epidemiological study investigated the correlation between leukocyte TL variations and determinants of molecular aging in 121 Pakistani DM-2 patients. Materials and Methods: The ratio of telomere repeats to the SCG copy number was calculated to estimate the TL in each sample through qPCR assays. Results: In this study, smaller mean TLs were observed in 48.8% of males (6.35 ± 0.82 kb), 3.3% of underweight patients (5.77 ± 1.14 kb), 61.2% of patients on regular medication (6.50 ± 0.79 kb), 9.1% with very high stress levels (5.94 ± 0.99 kb), 31.4% of smokers (5.83 ± 0.73 kb), 40.5% of patients with low physical activity (6.47 ± 0.69 kb), 47.9% of hypertensive patients (5.93 ± 0.64 kb), 10.7% of patients with DM-2 for more than 15 years, and 3.3% of patients with a delayed onset of DM-2 (6.00 ± 0.93 kb). Conclusion: This research indicated a significant negative correlation (R[2] = 0.143) between TL and the age of DM-2 patients. This study demonstrated that the correlation of telomere length with age in DM-2 patients was also influenced by various age-determining factors, including hypertension and smoking habits, with significant strong (R[2] = 0.526) and moderate (R[2] = 0.299) correlations, respectively; sex, obesity, the stress level and age at the onset of diabetes with significant weak correlations (R[2] = 0.043, 0.041, 0.037, and 0.065, respectively), and no significant correlations of medication routine, rate of physical activity, and the durations of DM-2 with age-adjusted telomere length. These results challenge TL as the sole marker of aging, thus highlighting the need for further research to understand underlying factors and mitigate the effect of aging or premature aging on diabetic patients.},
}
@article {pmid38789417,
year = {2024},
author = {Keener, R and Chhetri, SB and Connelly, CJ and Taub, MA and Conomos, MP and Weinstock, J and Ni, B and Strober, B and Aslibekyan, S and Auer, PL and Barwick, L and Becker, LC and Blangero, J and Bleecker, ER and Brody, JA and Cade, BE and Celedon, JC and Chang, YC and Cupples, LA and Custer, B and Freedman, BI and Gladwin, MT and Heckbert, SR and Hou, L and Irvin, MR and Isasi, CR and Johnsen, JM and Kenny, EE and Kooperberg, C and Minster, RL and Naseri, T and Viali, S and Nekhai, S and Pankratz, N and Peyser, PA and Taylor, KD and Telen, MJ and Wu, B and Yanek, LR and Yang, IV and Albert, C and Arnett, DK and Ashley-Koch, AE and Barnes, KC and Bis, JC and Blackwell, TW and Boerwinkle, E and Burchard, EG and Carson, AP and Chen, Z and Chen, YI and Darbar, D and de Andrade, M and Ellinor, PT and Fornage, M and Gelb, BD and Gilliland, FD and He, J and Islam, T and Kaab, S and Kardia, SLR and Kelly, S and Konkle, BA and Kumar, R and Loos, RJF and Martinez, FD and McGarvey, ST and Meyers, DA and Mitchell, BD and Montgomery, CG and North, KE and Palmer, ND and Peralta, JM and Raby, BA and Redline, S and Rich, SS and Roden, D and Rotter, JI and Ruczinski, I and Schwartz, D and Sciurba, F and Shoemaker, MB and Silverman, EK and Sinner, MF and Smith, NL and Smith, AV and Tiwari, HK and Vasan, RS and Weiss, ST and Williams, LK and Zhang, Y and Ziv, E and Raffield, LM and Reiner, AP and , and , and , and Arvanitis, M and Greider, CW and Mathias, RA and Battle, A},
title = {Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {4417},
pmid = {38789417},
issn = {2041-1723},
support = {R35GM139580//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 5K12GM123914//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01HL-120393//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01HL153805//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01 DK071891/DK/NIDDK NIH HHS/United States ; R01AG081244//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01AG069120//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R35CA209974//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01HL68959//U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL68959//U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL87681//U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL079915//U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL105756//U.S. Department of Health &amp; Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; },
mesh = {Humans ; *Genome-Wide Association Study ; *Telomere/genetics/metabolism ; K562 Cells ; *Telomere Homeostasis/genetics ; Polymorphism, Single Nucleotide ; Gene Expression Regulation ; CRISPR-Cas Systems ; },
abstract = {Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.},
}
@article {pmid38781848,
year = {2024},
author = {Bao, L and Zhou, Y and Shu, J and Li, H and Xi, S and Xu, M and Cai, Q and Dai, X and Zeng, Y and Zeng, F},
title = {Impact of telomere length and mitochondrial DNA copy number variants on survival of newborn cloned calves.},
journal = {Theriogenology},
volume = {225},
number = {},
pages = {1-8},
doi = {10.1016/j.theriogenology.2024.05.019},
pmid = {38781848},
issn = {1879-3231},
abstract = {An established technology to create cloned animals is through the use of somatic cell nuclear transfer (SCNT), in which reprogramming the somatic cell nucleus to a totipotent state by enucleated oocyte cytoplasm is a necessary process, including telomere length reprogramming. The limitation of this technology; however, is that the live birth rate of offspring produced through SCNT is significantly lower than that of IVF. Whether and how telomere length play a role in the development of cloned animals is not well understood. Only a few studies have evaluated this association in cloned mice, and fewer still in cloned cows. In this study, we investigated the difference in telomere length as well as the abundance of some selected molecules between newborn deceased cloned calves and normal cows of different ages either produced by SCNT or via natural conception, in order to evaluate the association between telomere length and abnormal development of cloned cows. The absolute telomere length and relative mitochondrial DNA (mtDNA) copy number were determined by real-time quantitative PCR (qPCR), telomere related gene abundance by reverse-transcription quantitative PCR (RT-qPCR), and senescence-associated β-galactosidase (SA-β-gal) expression by SA-β-gal staining. The results demonstrate that the newborn deceased SCNT calves had significantly shortened telomere lengths compared to newborn naturally conceived calves and newborn normal SCNT calves. Significantly lower mtDNA copy number, and significantly lower relative abundance of LMNB1 and TERT, higher relative abundance of CDKN1A, and aberrant SA-β-gal expression were observed in the newborn deceased SCNT calves, consistent with the change in telomere length. These results demonstrate that abnormal telomere shortening, lower mtDNA copy number and abnormal abundance of related genes were specific to newborn deceased SCNT calves, suggesting that abnormally short telomere length may be associated with abnormal development in the cloned calves.},
}
@article {pmid38777848,
year = {2024},
author = {Dhawan, V and Malhotra, N and Singh, N and Dadhwal, V and Dada, R},
title = {Yoga and its effect on sperm genomic integrity, gene expression, telomere length and perceived quality of life in early pregnancy loss.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {11711},
pmid = {38777848},
issn = {2045-2322},
mesh = {*Yoga ; Humans ; *Quality of Life ; Male ; Female ; Pregnancy ; *Spermatozoa/metabolism ; Adult ; Abortion, Habitual/genetics/psychology/therapy ; Telomere/genetics/metabolism ; Prospective Studies ; Telomere Homeostasis ; Sperm Motility/genetics ; },
abstract = {Achieving successful pregnancy outcomes is a delicate interplay between the maternal and the fetal counterparts. Paternal factors play a critical role in health and disease of offspring. Early pregnancy loss (EPL) is a psychologically devastating condition affecting the quality of life (QOL). Thus, it needs to be managed by a mind body integrated approach like yoga.The prospective single arm exploratory studyincluded male partners of couples experiencing recurrent pregnancy loss (RPL, n = 30), and recurrent implantation failure (RIF, n = 30) and semen samples wereassessed at the beginning and completion of yoga (6 weeks) (WHO 2010).A significant increase in the sperm concentration, motility, decrease in seminal ROS, DFI and increase in relative sperm telomere length was found at the end of yoga. The relative expression of genes critical for early embryonic developmentnormalized towards the levels of controls. WHOQOL-BREF questionnaire scores to assess QOL also showed improvement.Integration of regular practice yoga into our lifestyle may help in improving seminal redox status, genomic integrity, telomere length, normalizing gene expression and QOL, highlighting the need to use an integrated, holistic approach in management of such cases. This is pertinent for decreasing the transmission of mutation and epimutation load to the developing embryo, improving pregnancy outcomes and decreasing genetic and epigenetic disease burden in the next generation.},
}
@article {pmid38775978,
year = {2024},
author = {Jeremian, R and Lytvyn, Y and Fotovati, R and Li, K and Sachdeva, M and Tarafdar, N and Georgakopoulos, JR and Piguet, V and Litvinov, IV and Yeung, J},
title = {Signatures of epigenetic, biological and mitotic age acceleration and telomere shortening are associated with arsenic-induced skin lesions.},
journal = {Archives of dermatological research},
volume = {316},
number = {5},
pages = {195},
pmid = {38775978},
issn = {1432-069X},
mesh = {Humans ; *Epigenesis, Genetic ; Adult ; *Arsenic/adverse effects/toxicity ; Female ; *DNA Methylation/drug effects ; *Telomere Shortening/drug effects ; Male ; Child ; Adolescent ; Young Adult ; Middle Aged ; Mitosis/drug effects/genetics ; Skin/pathology/drug effects ; Skin Diseases/chemically induced/genetics/pathology ; Skin Neoplasms/genetics/chemically induced/pathology ; },
abstract = {Chronic arsenic exposure is a global health hazard significantly associated with the development of deleterious cutaneous changes and increased keratinocyte cancer risk. Although arsenic exposure is associated with broad-scale cellular and molecular changes, gaps exist in understanding how these changes impact the skin and facilitate malignant transformation. Recently developed epigenetic "clocks" can accurately predict chronological, biological and mitotic age, as well as telomere length, on the basis of tissue DNA methylation state. Deviations of predicted from expected age (epigenetic age dysregulation) have been associated with numerous complex diseases, increased all-cause mortality and higher cancer risk. We investigated the ability of these algorithms to detect molecular changes associated with chronic arsenic exposure in the context of associated skin lesions. To accomplish this, we utilized a multi-algorithmic approach incorporating seven "clocks" (Horvath, Skin&amp;Blood, PhenoAge, PCPhenoAge, GrimAge, DNAmTL and epiTOC2) to analyze peripheral blood of pediatric and adult cohorts of arsenic-exposed (n = 84) and arsenic-naïve (n = 33) individuals, among whom n = 18 were affected by skin lesions. Arsenic-exposed adults with skin lesions exhibited accelerated epigenetic (Skin&amp;Blood: + 7.0 years [95% CI 3.7; 10.2], q = 6.8 × 10[-4]), biological (PhenoAge: + 5.8 years [95% CI 0.7; 11.0], q = 7.4 × 10[-2], p = 2.8 × 10[-2]) and mitotic age (epiTOC2: + 19.7 annual cell divisions [95% CI 1.8; 37.7], q = 7.4 × 10[-2], p = 3.2 × 10[-2]) compared to healthy arsenic-naïve individuals; and accelerated epigenetic age (Skin&amp;Blood: + 2.8 years [95% CI 0.2; 5.3], q = 2.4 × 10[-1], p = 3.4 × 10[-2]) compared to lesion-free arsenic-exposed individuals. Moreover, lesion-free exposed adults exhibited accelerated Skin&amp;Blood age (+ 4.2 [95% CI 1.3; 7.1], q = 3.8 × 10[-2]) compared to their arsenic-naïve counterparts. Compared to the pediatric group, arsenic-exposed adults exhibited accelerated epigenetic (+ 3.1 to 4.4 years (95% CI 1.2; 6.4], q = 2.4 × 10[-4]-3.1 × 10[-3]), biological (+ 7.4 to 7.8 years [95% CI 3.0; 12.1] q = 1.6 × 10[-3]-2.8 × 10[-3]) and mitotic age (+ 50.0 annual cell divisions [95% CI 15.6; 84.5], q = 7.8 × 10[-3]), as well as shortened telomere length (- 0.23 kilobases [95% CI - 0.13; - 0.33], q = 2.4 × 10[-4]), across all seven algorithms. We demonstrate that lifetime arsenic exposure and presence of arsenic-associated skin lesions are associated with accelerated epigenetic, biological and mitotic age, and shortened telomere length, reflecting altered immune signaling and genomic regulation. Our findings highlight the usefulness of DNA methylation-based algorithms in identifying deleterious molecular changes associated with chronic exposure to the heavy metal, serving as potential prognosticators of arsenic-induced cutaneous malignancy.},
}
@article {pmid38773655,
year = {2024},
author = {Carlund, O and Thörn, E and Osterman, P and Fors, M and Dernstedt, A and Forsell, MNE and Erlanson, M and Landfors, M and Degerman, S and Hultdin, M},
title = {Semimethylation is a feature of diffuse large B-cell lymphoma, and subgroups with poor prognosis are characterized by global hypomethylation and short telomere length.},
journal = {Clinical epigenetics},
volume = {16},
number = {1},
pages = {68},
pmid = {38773655},
issn = {1868-7083},
mesh = {Humans ; *Lymphoma, Large B-Cell, Diffuse/genetics/mortality ; *DNA Methylation/genetics ; Female ; Male ; Prognosis ; Middle Aged ; Aged ; Adult ; Rituximab/therapeutic use ; Aged, 80 and over ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Vincristine/therapeutic use ; Prednisone/therapeutic use ; Telomere/genetics ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Telomere Shortening/genetics ; Epigenesis, Genetic/genetics ; CpG Islands/genetics ; },
abstract = {BACKGROUND: Large B-cell lymphoma (LBCL) is the most common lymphoma and is known to be a biologically heterogeneous disease regarding genetic, phenotypic, and clinical features. Although the prognosis is good, one-third has a primary refractory or relapsing disease which underscores the importance of developing predictive biological markers capable of identifying high- and low-risk patients. DNA methylation (DNAm) and telomere maintenance alterations are hallmarks of cancer and aging. Both these alterations may contribute to the heterogeneity of the disease, and potentially influence the prognosis of LBCL.<br><br>RESULTS: We studied the DNAm profiles (Infinium MethylationEPIC BeadChip) and relative telomere lengths (RTL) with qPCR of 93 LBCL cases: Diffuse large B-cell lymphoma not otherwise specified (DLBCL, n&#x2009;=&#x2009;66), High-grade B-cell lymphoma (n&#x2009;=&#x2009;7), Primary CNS lymphoma (n&#x2009;=&#x2009;8), and transformation of indolent B-cell lymphoma (n&#x2009;=&#x2009;12). There was a substantial methylation heterogeneity in DLBCL and other LBCL entities compared to normal cells and other B-cell neoplasms. LBCL cases had a particularly aberrant semimethylated pattern (0.15&#x2009;&#x2264;&#x2009;&#x3b2;&#x2009;&#x2264;&#x2009;0.8) with large intertumor variation and overall low hypermethylation (&#x3b2;&#x2009;>&#x2009;0.8). DNAm patterns could not be used to distinguish between germinal center B-cell-like (GC) and non-GC DLBCL cases. In cases treated with R-CHOP-like regimens, a high percentage of global hypomethylation (&#x3b2;&#x2009;<&#x2009;0.15) was in multivariable analysis associated with worse disease-specific survival (DSS) (HR&#x2009;6.920, 95% CI&#x2009;1.499-31.943) and progression-free survival (PFS) (HR&#x2009;4.923, 95% CI&#x2009;1.286-18.849) in DLBCL and with worse DSS (HR&#x2009;5.147, 95% CI&#x2009;1.239-21.388) in LBCL. These cases with a high percentage of global hypomethylation also had a higher degree of CpG island methylation, including islands in promoter-associated regions, than the cases with less hypomethylation. Additionally, telomere length was heterogenous in LBCL, with a subset of the DLBCL-GC cases accounting for the longest RTL. Short RTL was independently associated with worse DSS (HR&#x2009;6.011, 95% CI&#x2009;1.319-27.397) and PFS (HR&#x2009;4.689, 95% CI&#x2009;1.102-19.963) in LBCL treated with R-CHOP-like regimens.<br><br>CONCLUSION: We hypothesize that subclones with high global hypomethylation and hypermethylated CpG islands could have advantages in tumor progression, e.g. by inactivating tumor suppressor genes or promoting treatment resistance. Our findings suggest that cases with high global hypomethylation and thus poor prognosis could be candidates for alternative treatment regimens including hypomethylating drugs.},
}
@article {pmid38771124,
year = {2024},
author = {Brown, LM and Elbon, MC and Bharadwaj, A and Damle, G and Lachance, J},
title = {Does effective population size govern evolutionary differences in telomere length?.},
journal = {Genome biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/gbe/evae111},
pmid = {38771124},
issn = {1759-6653},
abstract = {Lengths of telomeres vary by an order of magnitude across mammalian species. Similarly, age- and sex-standardized telomere lengths differ by up to 1 kb (14%) across human populations. How to explain these differences? Telomeres play a central role in senescence and aging, and genes that affect telomere length are likely under weak selection (i.e., telomere length is a trait that is subject to nearly neutral evolution). Importantly, natural selection is more effective in large populations than small populations. Here, we propose that observed differences in telomere length across species and populations are largely due to differences in effective population sizes. In this perspective, we present preliminary evolutionary genetic evidence supporting this hypothesis and highlight the need for more data.},
}
@article {pmid38769327,
year = {2024},
author = {Chen, W and Wang, X and Sun, J and Wang, X and Zhu, Z and Ayhan, DH and Yi, S and Yan, M and Zhang, L and Meng, T and Mu, Y and Li, J and Meng, D and Bian, J and Wang, K and Wang, L and Chen, S and Chen, R and Jin, J and Li, B and Zhang, X and Deng, XW and He, H and Guo, L},
title = {Two telomere-to-telomere gapless genomes reveal insights into Capsicum evolution and capsaicinoid biosynthesis.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {4295},
pmid = {38769327},
issn = {2041-1723},
mesh = {*Capsicum/genetics/metabolism ; *Capsaicin/metabolism ; *Genome, Plant ; *Telomere/genetics/metabolism ; *Phylogeny ; *Evolution, Molecular ; Fruit/genetics/metabolism ; Retroelements/genetics ; Gene Expression Regulation, Plant ; },
abstract = {Chili pepper (Capsicum) is known for its unique fruit pungency due to the presence of capsaicinoids. The evolutionary history of capsaicinoid biosynthesis and the mechanism of their tissue specificity remain obscure due to the lack of high-quality Capsicum genomes. Here, we report two telomere-to-telomere (T2T) gap-free genomes of C. annuum and its wild nonpungent relative C. rhomboideum to investigate the evolution of fruit pungency in chili peppers. We precisely delineate Capsicum centromeres, which lack high-copy tandem repeats but are extensively invaded by CRM retrotransposons. Through phylogenomic analyses, we estimate the evolutionary timing of capsaicinoid biosynthesis. We reveal disrupted coding and regulatory regions of key biosynthesis genes in nonpungent species. We also find conserved placenta-specific accessible chromatin regions, which likely allow for tissue-specific biosynthetic gene coregulation and capsaicinoid accumulation. These T2T genomic resources will accelerate chili pepper genetic improvement and help to understand Capsicum genome evolution.},
}
@article {pmid38763334,
year = {2024},
author = {Hakobyan, M and Binder, H and Arakelyan, A},
title = {Pan-cancer analysis of telomere maintenance mechanisms.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {107392},
doi = {10.1016/j.jbc.2024.107392},
pmid = {38763334},
issn = {1083-351X},
abstract = {Telomeres, protective caps at chromosome ends, maintain genomic stability and control cell lifespan. Dysregulated telomere maintenance mechanisms (TMM) are cancer hallmarks, enabling unchecked cell proliferation. We conducted a pan-cancer evaluation of TMM using RNA sequencing data from The Cancer Genome Atlas (TCGA) for 33 different cancer types and analyzed the activities of telomerase-dependent (TEL) and alternative lengthening of telomeres (ALT) TMM pathways in detail. To further characterize the TMM profiles, we categorized the tumors based on their ALT and TEL TMM pathway activities into five major phenotypes: ALT [high] TEL [low], ALT [low] TEL [low], ALT [middle] TEL [middle], ALT [high] TEL [high], and ALT [low] TEL [high]. These phenotypes refer to variations in telomere maintenance strategies, shedding light on the heterogeneous nature of telomere regulation in cancer. Moreover, we investigated the clinical implications of TMM phenotypes by examining their associations with clinical characteristics and patient outcomes. Specific TMM profiles were linked to specific survival patterns, emphasizing the potential of TMM profiling as a prognostic indicator and aiding in personalized cancer treatment strategies. Gene ontology analysis of the TMM phenotypes unveiled enriched biological processes associated with cell cycle regulation (both TEL and ALT), DNA replication (TEL), and chromosome dynamics (ALT) showing that telomere maintenance is tightly intertwined with cellular processes governing proliferation and genomic stability. Overall, our study provides an overview of the complexity of transcriptional regulation of telomere maintenance mechanisms in cancer.},
}
@article {pmid38760657,
year = {2024},
author = {Moix, S and Sadler, MC and Kutalik, Z and Auwerx, C},
title = {Breaking down causes, consequences, and mediating effects of telomere length variation on human health.},
journal = {Genome biology},
volume = {25},
number = {1},
pages = {125},
pmid = {38760657},
issn = {1474-760X},
support = {310030_189147//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung/ ; },
mesh = {Humans ; Male ; Female ; *Telomere/metabolism/genetics ; *Mendelian Randomization Analysis ; Telomere Shortening ; Middle Aged ; Leukocytes/metabolism ; Aged ; Telomere Homeostasis ; Life Style ; Adult ; Body Mass Index ; },
abstract = {BACKGROUND: Telomeres form repeated DNA sequences at the ends of chromosomes, which shorten with each cell division. Yet, factors modulating telomere attrition and the health consequences thereof are not fully understood. To address this, we leveraged data from 326,363 unrelated UK Biobank participants of European ancestry.<br><br>RESULTS: Using linear regression and bidirectional univariable and multivariable Mendelian randomization (MR), we elucidate the relationships between leukocyte telomere length (LTL) and 142 complex traits, including diseases, biomarkers, and lifestyle factors. We confirm that telomeres shorten with age and show a stronger decline in males than in females, with these factors contributing to the majority of the 5.4% of LTL variance explained by the phenome. MR reveals 23 traits modulating LTL. Smoking cessation and high educational attainment associate with longer LTL, while weekly alcohol intake, body mass index, urate levels, and female reproductive events, such as childbirth, associate with shorter LTL. We also identify 24 traits affected by LTL, with risk for cardiovascular, pulmonary, and some autoimmune diseases being increased by short LTL, while longer LTL increased risk for other autoimmune conditions and cancers. Through multivariable MR, we show that LTL may partially mediate the impact of educational attainment, body mass index, and female age at childbirth on proxied lifespan.<br><br>CONCLUSIONS: Our study sheds light on the modulators, consequences, and the mediatory role of telomeres, portraying an intricate relationship between LTL, diseases, lifestyle, and socio-economic factors.},
}
@article {pmid38757009,
year = {2024},
author = {Pańczyszyn, A and Boniewska-Bernacka, E and Włodarczyk, K and Wertel, I and Goc, A},
title = {Telomeres and telomerase in endometrial cancer and hyperplasia.},
journal = {Archives of medical science : AMS},
volume = {20},
number = {2},
pages = {682-685},
doi = {10.5114/aoms/186189},
pmid = {38757009},
issn = {1734-1922},
abstract = {INTRODUCTION: The study aimed to measure telomeres length (TL) and telomerase expression in normal endometrium and endometrial hyperplasia and cancer.<br><br>METHODS: Total RNA and DNA were isolated from endometrium samples of 117 patients. The RT-PCR method was used to determine telomerase expression and relative telomere length.<br><br>RESULTS: The control group had the longest telomeres in comparison to the hyperplasia and endometrial cancer groups. Only in the endometrial cancer group was telomerase expressed and positively correlated with telomere length.<br><br>CONCLUSIONS: Telomere extension in endometrial cancer is mediated by telomerase, but telomere length may not be an indicator of endometrioid cancer development.},
}
@article {pmid38755561,
year = {2024},
author = {Stephens, Z and Kocher, JP},
title = {Characterization of telomere variant repeats using long reads enables allele-specific telomere length estimation.},
journal = {BMC bioinformatics},
volume = {25},
number = {1},
pages = {194},
pmid = {38755561},
issn = {1471-2105},
abstract = {Telomeres are regions of repetitive DNA at the ends of linear chromosomes which protect chromosome ends from degradation. Telomere lengths have been extensively studied in the context of aging and disease, though most studies use average telomere lengths which are of limited utility. We present a method for identifying all 92 telomere alleles from long read sequencing data. Individual telomeres are identified using variant repeats proximal to telomere regions, which are unique across alleles. This high-throughput and high-resolution characterization of telomeres could be foundational to future studies investigating the roles of specific telomeres in aging and disease.},
}
@article {pmid38755232,
year = {2024},
author = {Grula, CC and Rinehart, JD and Anacleto, A and Kittilson, JD and Heidinger, BJ and Greenlee, KJ and Rinehart, JP and Bowsher, JH},
title = {Telomere length is longer following diapause in two solitary bee species.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {11208},
pmid = {38755232},
issn = {2045-2322},
support = {3060-21220-032-00D.//USDA-ARS/ ; 1557940//NSF-IOS/ ; FEC 1826834//NSF RII Track-2/ ; },
mesh = {Animals ; Bees/genetics/physiology ; *Telomere/genetics/metabolism ; Pupa/growth &amp; development/genetics ; Female ; Male ; Telomere Homeostasis ; Larva/genetics/growth &amp; development/physiology ; Diapause/genetics ; },
abstract = {The mechanisms that underlie senescence are not well understood in insects. Telomeres are conserved repetitive sequences at chromosome ends that protect DNA during replication. In many vertebrates, telomeres shorten during cell division and in response to stress and are often used as a cellular marker of senescence. However, little is known about telomere dynamics across the lifespan in invertebrates. We measured telomere length in larvae, prepupae, pupae, and adults of two species of solitary bees, Osmia lignaria and Megachile rotundata. Contrary to our predictions, telomere length was longer in later developmental stages in both O. lignaria and M. rotundata. Longer telomeres occurred after emergence from diapause, which is a physiological state with increased tolerance to stress. In O. lignaria, telomeres were longer in adults when they emerged following diapause. In M. rotundata, telomeres were longer in the pupal stage and subsequent adult stage, which occurs after prepupal diapause. In both species, telomere length did not change during the 8 months of diapause. Telomere length did not differ by mass similarly across species or sex. We also did not see a difference in telomere length after adult O. lignaria were exposed to a nutritional stress, nor did length change during their adult lifespan. Taken together, these results suggest that telomere dynamics in solitary bees differ from what is commonly reported in vertebrates and suggest that insect diapause may influence telomere dynamics.},
}
@article {pmid38755031,
year = {2024},
author = {Giri, P and Thakor, F and Dwivedi, M},
title = {Implication of regulatory T cells' telomere shortening in pathogenesis of generalized vitiligo.},
journal = {Human immunology},
volume = {},
number = {},
pages = {110812},
doi = {10.1016/j.humimm.2024.110812},
pmid = {38755031},
issn = {1879-1166},
abstract = {Generalized vitiligo(GV) is a skin depigmenting condition due to loss of melanocytes. Regulatory T cells(Tregs), responsible for peripheral tolerance, show altered numbers and functions in GV patients, likely influenced by the aging process. Therefore, the present study was focused on measuring the relative telomere length of Tregs in 96 GV patients and 90 controls by qPCR, along with correlation of relative telomere length with in vitro Treg suppressive capacity. Interestingly, we found significantly decreased relative telomere length in Tregs of GV patients as compared to controls(p = 0.0001). Additionally, age based-analysis suggested significant decrease in relative telomere length in elderly GV patients(>40 years) in comparison to young GV patients(0-20 years; p = 0.0027). Furthermore, age of onset analysis suggested for reduced relative telomere length in early onset GV patients (0-20 years) in comparison to late onset GV patients(>40 years; p = 0.0036). The correlation analysis suggested positive correlation for relative telomere length with in vitro Tregs suppressive capacity(r = 0.68 &amp; r = 0.45; p < 0.0001). Additionally, the in vitro Tregs suppressive capacity was significantly reduced in elderly GV patients(p = 0.003) and early onset GV patients(p = 0.0074). Overall, our study for the first time demonstrated that, the Tregs ageing due to telomere shortening may be responsible for altered Treg functions and number.},
}
@article {pmid38747543,
year = {2024},
author = {Kumar, S and Rajkumar, SV and Jevremovic, D and Kyle, RA and Shifrin, Y and Nguyen, M and Husain, Z and Alikhah, A and Jafari, A and Mai, S and Anderson, K and Louis, S},
title = {Three-dimensional telomere profiling predicts risk of progression in smoldering multiple myeloma.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.27364},
pmid = {38747543},
issn = {1096-8652},
support = {//Telo Genomics Corp./ ; },
abstract = {Smoldering multiple myeloma (SMM) is a precursor stage that precedes multiple myeloma (MM). SMM is heterogenous with nearly 40% of patients progressing to MM in the first 5 years. The high rate of progression of SMM patients highlights the need for early intervention, which underscores the importance of identifying SMM patients with the highest risk of progression. Several risk stratification models showed utility in identifying high-risk SMM patients; however, these systems showed limited sensitivity. To date, identifying high-risk SMM patients remains an important clinical need. In this study, we present the 3-dimensional telomere profiling as a structural biomarker capable of stratifying SMM patients as a function of genomic instability. Quantifying telomere dysfunction using the TeloView technology showed utility in risk stratification of cancer patients, particularly hematological malignancies. In this study, we analyzed 168 SMM patients. We report an AUC in ROC analysis of 0.8 using a subset of the patients as a training dataset. We then conducted a blind validation on a different cohort and demonstrated a positive predictive value of 85% and negative predictive value of 73%, with sensitivity and specificity of 83% and 76%, respectively. We examined the correlation between the TeloView prediction and the 20-2-20 scoring system, and cytogenetic abnormalities. We report a correlation of 53% with the 20-2-20 scores and over 60% correlation with cytogenetic abnormalities. The result of this study presents the telomere profiling as an effective biomarker able to stratify SMM patients to their respective risk groups with high sensitivity and specificity.},
}
@article {pmid38747360,
year = {2024},
author = {Nanda, A and Logan, A and Tennyson, RL},
title = {The influence of perceived stress and motivation on telomere length among NCAA swimmers.},
journal = {American journal of human biology : the official journal of the Human Biology Council},
volume = {},
number = {},
pages = {e24091},
doi = {10.1002/ajhb.24091},
pmid = {38747360},
issn = {1520-6300},
support = {//The Center for Leadership in Athletics at the University of Washington/ ; //Shanahan Endowment Fellowship/ ; T32 HD101442-01//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; //Center for Studies in Demography &amp; Ecology/ ; //University of Washington (UW)/ ; NIH/NIA5T32AG66574-2//Biological Mechanisms for Healthy Aging Training Grant/ ; //Mary Gates Endowment Fund for Research/ ; },
abstract = {INTRODUCTION: Telomere length (TL) shortening is associated with increased cellular senescence and functional decline with age. Regular physical activity is posited to safeguard against TL shortening, but there is disagreement on how concurrent psychosocial stress may influence this relationship. The current analysis explored whether psychosocial stress is associated with TL differences in highly physically active individuals.<br><br>METHODS: TL was measured from capillary dried blood spots collected from Division-I (D-1) and Division-III (D-3) National Collegiate Athletics Association (NCAA) swimmers (N&#x2009;=&#x2009;28) and non-athlete students from the same schools (N&#x2009;=&#x2009;15). All participants completed Cohen's Perceived Stress Scale (PSS) and student-athletes completed an additional questionnaire to assess psychosocial factors associated with their lifestyle; The Student Athletes' Motivation towards Sports and Academics Questionnaire (SAMSAQ). Semi-structured interviews further contextualized how student-athletes internalize their stress.<br><br>RESULTS: There was no significant difference in TL or PSS scores between swimmers and controls. D-1 swimmers reported significantly higher career and student-athlete motivation scores compared to D-3, but non-significantly higher PSS and similar academic motivation scores. Themes from interviews with collegiate swimmers included COVID-19 stress, fear of injury, pressure from academics, expectations to perform, and financial pressures.<br><br>CONCLUSIONS: These themes may have contributed to higher PSS scores in D-1 swimmers compared to D-3 but did not appear to impact their TL. Given differences in perceived stress, sources of stress, and SAMSAQ scores, further analyses with larger sample sizes are needed to better understand how these factors influence human biology and health while engaged in intense physical activity.},
}
@article {pmid38744897,
year = {2024},
author = {Siametis, A and Stratigi, K and Giamaki, D and Chatzinikolaou, G and Akalestou-Clocher, A and Goulielmaki, E and Luke, B and Schumacher, B and Garinis, GA},
title = {Transcription stress at telomeres leads to cytosolic DNA release and paracrine senescence.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {4061},
pmid = {38744897},
issn = {2041-1723},
support = {GA 64663//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; },
mesh = {*Cellular Senescence/genetics ; Animals ; *Telomere/metabolism/genetics ; Mice ; *Cytosol/metabolism ; *DNA Damage ; *Paracrine Communication ; DNA/metabolism ; Transcription, Genetic ; Mice, Knockout ; Humans ; Extracellular Vesicles/metabolism ; Genomic Instability ; Aging/genetics/metabolism ; Oxidative Stress ; Mice, Inbred C57BL ; },
abstract = {Transcription stress has been linked to DNA damage -driven aging, yet the underlying mechanism remains unclear. Here, we demonstrate that Tcea1[-/-] cells, which harbor a TFIIS defect in transcription elongation, exhibit RNAPII stalling at oxidative DNA damage sites, impaired transcription, accumulation of R-loops, telomere uncapping, chromatin bridges, and genome instability, ultimately resulting in cellular senescence. We found that R-loops at telomeres causally contribute to the release of telomeric DNA fragments in the cytoplasm of Tcea1[-/-] cells and primary cells derived from naturally aged animals triggering a viral-like immune response. TFIIS-defective cells release extracellular vesicles laden with telomeric DNA fragments that target neighboring cells, which consequently undergo cellular senescence. Thus, transcription stress elicits paracrine signals leading to cellular senescence, promoting aging.},
}
@article {pmid38743757,
year = {2024},
author = {Tannemann, N and Erbel, R and Nöthen, MM and Jöckel, KH and Pechlivanis, S},
title = {Genetic polymorphisms affecting telomere length and their association with cardiovascular disease in the Heinz-Nixdorf-Recall study.},
journal = {PloS one},
volume = {19},
number = {5},
pages = {e0303357},
doi = {10.1371/journal.pone.0303357},
pmid = {38743757},
issn = {1932-6203},
mesh = {Humans ; *Polymorphism, Single Nucleotide ; *Cardiovascular Diseases/genetics ; Male ; Female ; Middle Aged ; Aged ; *Telomere/genetics ; *Genetic Predisposition to Disease ; Risk Factors ; Telomere Homeostasis/genetics ; },
abstract = {Short telomeres are associated with cardiovascular disease (CVD). We aimed to investigate, if genetically determined telomere-length effects CVD-risk in the Heinz-Nixdorf-Recall study (HNRS) population. We selected 14 single-nucleotide polymorphisms (SNPs) associated with telomere-length (p<10-8) from the literature and after exclusion 9 SNPs were included in the analyses. Additionally, a genetic risk score (GRS) using these 9 SNPs was calculated. Incident CVD was defined as fatal and non-fatal myocardial infarction, stroke, and coronary death. We included 3874 HNRS participants with available genetic data and had no known history of CVD at baseline. Cox proportional-hazards regression was used to test the association between the SNPs/GRS and incident CVD-risk adjusting for common CVD risk-factors. The analyses were further stratified by CVD risk-factors. During follow-up (12.1±4.31 years), 466 participants experienced CVD-events. No association between SNPs/GRS and CVD was observed in the adjusted analyses. However, the GRS, rs10936599, rs2487999 and rs8105767 increase the CVD-risk in current smoker. Few SNPs (rs10936599, rs2487999, and rs7675998) showed an increased CVD-risk, whereas rs10936599, rs677228 and rs4387287 a decreased CVD-risk, in further strata. The results of our study suggest different effects of SNPs/GRS on CVD-risk depending on the CVD risk-factor strata, highlighting the importance of stratified analyses in CVD risk-factors.},
}
@article {pmid38743633,
year = {2024},
author = {Su, Y and Yang, X and Wang, Y and Li, J and Long, Q and Cao, S and Wang, X and Liu, Z and Huang, S and Chen, Z and Peng, Y and Zhang, F and Xue, H and Cao, X and Zhang, M and Yisilam, G and Chu, Z and Gao, Y and Zhou, Y and Liu, Z and Xiao, H and Tian, X},
title = {Phased Telomere-to-Telomere Reference Genome and Pangenome Reveal an Expansion of Resistance Genes during Apple Domestication.},
journal = {Plant physiology},
volume = {},
number = {},
pages = {},
doi = {10.1093/plphys/kiae258},
pmid = {38743633},
issn = {1532-2548},
abstract = {The cultivated apple (Malus domestica Borkh.) is a cross-pollinated perennial fruit tree of great economic importance. Previous versions of apple reference genomes were unphased, fragmented, and lacked comprehensive insights into the highly heterozygous genome, which impeded genetic studies and breeding programs in apple. In this study, we assembled a haplotype-resolved telomere-to-telomere reference genome for the diploid apple cultivar Golden Delicious. Subsequently, we constructed a pangenome based on twelve assemblies from wild and cultivated apples to investigate different types of resistance gene analogs (RGAs). Our results revealed the dynamics of the gene gain and loss events during apple domestication. Compared with cultivated species, more gene families in wild species were significantly enriched in oxidative phosphorylation, pentose metabolic process, responses to salt, and abscisic acid biosynthesis process. Interestingly, our analyses demonstrated a higher prevalence of RGAs in cultivated apples than their wild relatives, partially attributed to segmental and tandem duplication events in certain RGAs classes. Other types of structural variations, mainly deletions and insertions, have affected the presence and absence of TIR-NB-ARC-LRR (TNL), NB-ARC-LRR (NL), and CC-NB-ARC-LRR (CNL) genes. Additionally, hybridization/introgression from wild species has also contributed to the expansion of resistance genes in domesticated apples. Our haplotype-resolved T2T genome and pangenome provide important resources for genetic studies of apples, emphasizing the need to study the evolutionary mechanisms of resistance genes in apple breeding programs.},
}
@article {pmid38738582,
year = {2024},
author = {Rasouli, S and Dakic, A and Wang, QE and Mitchell, D and Blakaj, DM and Putluri, N and Li, J and Liu, X},
title = {Noncanonical functions of telomerase and telomeres in viruses-associated cancer.},
journal = {Journal of medical virology},
volume = {96},
number = {5},
pages = {e29665},
doi = {10.1002/jmv.29665},
pmid = {38738582},
issn = {1096-9071},
support = {R01CA222148/NH/NIH HHS/United States ; R33CA258016/NH/NIH HHS/United States ; R01CA276474/NH/NIH HHS/United States ; U01CA278927/NH/NIH HHS/United States ; R33CA258016/NH/NIH HHS/United States ; R01CA276474/NH/NIH HHS/United States ; U01CA278927/NH/NIH HHS/United States ; },
mesh = {*Telomerase/metabolism/genetics ; Humans ; *Neoplasms/virology/genetics ; *Telomere/metabolism ; Herpesvirus 4, Human/genetics/pathogenicity/physiology ; RNA/metabolism/genetics ; },
abstract = {The cause of cancer is attributed to the uncontrolled growth and proliferation of cells resulting from genetic changes and alterations in cell behavior, a phenomenon known as epigenetics. Telomeres, protective caps on the ends of chromosomes, regulate both cellular aging and cancer formation. In most cancers, telomerase is upregulated, with the telomerase reverse transcriptase (TERT) enzyme and telomerase RNA component (TERC) RNA element contributing to the maintenance of telomere length. Additionally, it is noteworthy that two viruses, human papillomavirus (HPV) and Epstein-Barr virus (EBV), utilize telomerase for their replication or persistence in infected cells. Also, TERT and TERC may play major roles in cancer not related to telomere biology. They are involved in the regulation of gene expression, signal transduction pathways, cellular metabolism, or even immune response modulation. Furthermore, the crosstalk between TERT, TERC, RNA-binding proteins, and microRNAs contributes to a greater extent to cancer biology. To understand the multifaceted roles played by TERT and TERC in cancer and viral life cycles, and then to develop effective therapeutic strategies against these diseases, are fundamental for this goal. By investigating deeply, the complicated mechanisms and relationships between TERT and TERC, scientists will open the doors to new therapies. In its analysis, the review emphasizes the significance of gaining insight into the multifaceted roles that TERT and TERC play in cancer pathogenesis, as well as their involvement in the viral life cycle for designing effective anticancer therapy approaches.},
}
@article {pmid38735573,
year = {2024},
author = {Li, C and Zhang, Y and Zhang, K and Fu, H and Lin, L and Cai, G and Zhang, X and Yang, X and Zhang, Z and Yang, Z and Zhang, B},
title = {Association Between Ultra-Processed Foods Consumption and Leucocyte Telomere Length: A cross-sectional study of UK Biobank.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tjnut.2024.05.001},
pmid = {38735573},
issn = {1541-6100},
abstract = {OBJECTIVE: This study investigates the association between consumption of ultra-processed foods and leucocyte telomere length.<br><br>METHODS: This cross-sectional study utilized data from the UK Biobank, including a total of 64,690 participants. LTL was measured using Q-PCR with natural logarithmic conversion and Z-score normalization. Dietary data were collected through a 24-hour recall questionnaire from 2009 to 2010. UPFs were identified using the Nova food classification as either a continuous or a categorical variable respectively. Multiple linear regression models were employed to analyze the association between UPF consumption and LTL.<br><br>RESULTS: The included participants had an average age of 56.26 years, of whom 55.2% were female. After adjusting for demographic and health-related variables, LTL exhibited a decrease of 0.005 (95% CI:-0.007,-0.002) with one UPF serving increase. Compared to participants consuming &#x2264;3.5 servings/day, those consuming 3.5 to <6 servings showed a shortening of LTL by 0.025 (95% CI: -0.046, -0.003). Participants consuming 6 to &#x2264;8 servings/day and >8 servings/day had LTL shortening of 0.032 (95% CI: -0.054, -0.011) and 0.037 (95% CI: -0.060, -0.014), respectively (P for trend=0.002). Subgroup analyses by UPF subclasses revealed that the consumption of ready-to-eat/heated food (&#x3b2;=-0.010, 95% CI:-0.016,-0.004), beans and potatoes (&#x3b2;=-0.027, 95% CI:-0.043,-0.012), animal-based products (&#x3b2;=-0.012, 95% CI:-0.020,-0.005), artificial sugar (&#x3b2;=-0.014, 95% CI:-0.025,-0.003), and beverages (&#x3b2;=-0.005, 95% CI:-0.009,-0.001) showed negative associations with LTL. Conversely, breakfast cereals (&#x3b2;=0.022, 95% CI:0.006,0.038) and vegetarian alternatives (&#x3b2;=0.056, 95% CI:0.026,0.085) showed positive correlations with LTL.<br><br>CONCLUSIONS: Our study found that a higher consumption of total UPF was associated with a shorter LTL. However, some UPFs may be associated with longer LTL, depending on their nutritional composition.},
}
@article {pmid38731223,
year = {2024},
author = {Duseikaite, M and Gedvilaite, G and Mikuzis, P and Andrulionyte, J and Kriauciuniene, L and Liutkeviciene, R},
title = {Investigating the Relationship between Telomere-Related Gene Variants and Leukocyte Telomere Length in Optic Neuritis Patients.},
journal = {Journal of clinical medicine},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/jcm13092694},
pmid = {38731223},
issn = {2077-0383},
abstract = {Optic neuritis (ON) is a condition marked by optic nerve inflammation due to various potential triggers. Research indicates a link between telomeres and inflammation, as studies demonstrate that inflammation can lead to increased telomere shortening. Aim: We aimed to determine the associations of telomere-related telomeric repeat binding factor 1 (TERF1) rs1545827, rs10107605, and telomeric repeat binding factor 2 (TERF2) rs251796 polymorphisms and relative leukocyte telomere length (LTL) with the occurrence of ON. Methods: In this research, a total of 73 individuals diagnosed with optic neuritis (ON) were studied and the control group included 170 individuals without any health issues. The DNA samples were obtained from peripheral blood leukocytes, which were purified using the DNA salting-out technique. Real-time polymerase chain reaction (RT-PCR) assessed single-nucleotide polymorphisms (SNPs) and relative leukocyte telomere lengths (LTL). The data obtained were processed and analyzed using the "IBM SPSS Statistics 29.0" program. Results: Our study revealed the following results: in the male group, TERF2 rs251796 (AA, AG, and TT) statistically significantly differed between the long and short telomere group, with frequencies of 65.7%, 22.9%, and 2.0% in long telomeres, compared to 35.1%, 56.8%, and 8.1% in the short telomere group (p = 0.013). The TERF2 rs251796 CT genotype, compared to CC, under the codominant genetic model, was associated with 4.7-fold decreased odds of telomere shortening (p = 0.005). Meanwhile, CT+TT genotypes, compared to CC under the dominant genetic model, were associated with 3.5-fold decreased odds of telomere shortening (p = 0.011). Also, the CT genotype, compared to CC+TT, under the overdominant genetic model, was associated with 4.4-fold decreased odds of telomere shortening (p = 0.004). Conclusions: The current evidence may suggest a protective role of TERF2 rs251796 in the occurrence of ON in men.},
}
@article {pmid38730258,
year = {2024},
author = {Cheng, H and Asri, M and Lucas, J and Koren, S and Li, H},
title = {Scalable telomere-to-telomere assembly for diploid and polyploid genomes with double graph.},
journal = {Nature methods},
volume = {},
number = {},
pages = {},
pmid = {38730258},
issn = {1548-7105},
support = {R01HG010040//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; U01HG010971//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; U41HG010972//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; K99HG012798//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; },
abstract = {Despite advances in long-read sequencing technologies, constructing a near telomere-to-telomere assembly is still computationally demanding. Here we present hifiasm (UL), an efficient de novo assembly algorithm combining multiple sequencing technologies to scale up population-wide near telomere-to-telomere assemblies. Applied to 22 human and two plant genomes, our algorithm produces better diploid assemblies at a cost of an order of magnitude lower than existing methods, and it also works with polyploid genomes.},
}
@article {pmid38729362,
year = {2024},
author = {Lozano, M and McEachan, RRC and Wright, J and Yang, TC and Dow, C and Kadawathagedara, M and Lepeule, J and Bustamante, M and Maitre, L and Vrijheid, M and Brantsæter, AL and Meltzer, HM and Bempi, V and Roumeliotaki, T and Thomsen, C and Nawrot, T and Broberg, K and Llop, S},
title = {Early life exposure to mercury and relationships with telomere length and mitochondrial DNA content in European children.},
journal = {The Science of the total environment},
volume = {},
number = {},
pages = {173014},
doi = {10.1016/j.scitotenv.2024.173014},
pmid = {38729362},
issn = {1879-1026},
abstract = {BACKGROUND: Telomere length (TL) and mitochondrial function expressed as mitochondrial DNA copy number (mtDNAcn) are biomarkers of aging and oxidative stress and inflammation, respectively. Methylmercury (MeHg), a common pollutant in fish, induces oxidative stress. We hypothesized that elevated oxidative stress from exposure to MeHg decreases mtDNAcn and shortens TL.<br><br>METHODS: Study participants are 6-11-year-old children from the HELIX multi-center birth cohort study, comprising six European countries. Prenatal and postnatal total mercury (THg) concentrations were measured in blood samples, TL and mtDNAcn were determined in child DNA. Covariates and confounders were obtained by questionnaires. Robust regression models were run, considering sociodemographic and lifestyle covariates, as well as fish consumption. Sex, ethnicity, and fish consumption interaction models were also run.<br><br>RESULTS: We found longer TL with higher pre- and postnatal THg blood concentrations, even at low-level THg exposure according to the RfD proposed by the US EPA. The prenatal association showed a significant linear relationship with a 3.46&#x202f;% increase in TL for each unit increased THg. The postnatal association followed an inverted U-shaped marginal non-linear relationship with 1.38&#x202f;% an increase in TL for each unit increased THg until reaching a cut-point at 0.96&#x202f;&#x3bc;g/L blood THg, from which TL attrition was observed. Higher pre- and postnatal blood THg concentrations were consistently related to longer TL among cohorts and no modification effect of fish consumption nor children's sex was observed. No association between THg exposure and mtDNAcn was found.<br><br>DISCUSSION: We found evidence that THg is associated with TL but the associations seem to be time- and concentration-dependent. Further studies are needed to clarify the mechanism behind the telomere changes of THg and related health effects.},
}
@article {pmid38718720,
year = {2024},
author = {Ogłuszka, M and Chen, CY and Poławska, E and Starzyński, RR and Liput, K and Siekierko, U and Pareek, CS and Pierzchała, M and Kang, JX},
title = {Elevated tissue status of omega-3 fatty acids protects against age-related telomere attrition in fat-1 transgenic mice.},
journal = {Clinical nutrition (Edinburgh, Scotland)},
volume = {43},
number = {6},
pages = {1488-1494},
doi = {10.1016/j.clnu.2024.05.001},
pmid = {38718720},
issn = {1532-1983},
abstract = {BACKGROUND &amp; AIMS: Leukocyte telomere length (LTL) is a biomarker of aging that may be influenced by dietary factors. Omega-3 fatty acids (n-3 FA) have been suggested to affect LTL. However, research on this effect has been inconclusive. The aim of the study was to test the hypothesis about the positive effect of n-3 FA on LTL.<br><br>METHODS: Fat-1 transgenic mice, which can convert omega-6 fatty acids (n-6 FA) to n-3 FA and have elevated levels of endogenous n-3 FA in their tissues, were used to study the effects of n-3 FA on LTL at different ages. Blood samples from 10-month-old wild-type (WT) mice (n&#xa0;=&#xa0;10) and fat-1 mice (n&#xa0;=&#xa0;10) and 3-month-old WT mice (n&#xa0;=&#xa0;5) and fat-1 mice (n&#xa0;=&#xa0;5) were used to measure relative and absolute LTL. The levels of proteins critical for telomere maintenance were examined by Western blot analysis.<br><br>RESULTS: Fat-1 transgenic mice had longer leukocyte telomeres than their WT siblings, suggesting a slower rate of age-related telomere shortening in fat-1 mice. In animals aged 10 months, the LTL was significantly longer in fat-1 than in WT mice (mean&#xa0;&#xb1;&#xa0;SEM; relative LTL: WT&#xa0;=&#xa0;1.00&#xa0;&#xb1;&#xa0;0.09 vs. fat-1: 1.25&#xa0;&#xb1;&#xa0;0.05, P&#xa0;=&#xa0;0.031; absolute LTL: WT&#xa0;=&#xa0;64.41&#xa0;&#xb1;&#xa0;6.50 vs. fat-1: 78.53&#xa0;&#xb1;&#xa0;3.86, P&#xa0;=&#xa0;0.048). The difference in LTL observed in three-month-old mice was insignificant, however the mean LTL was still longer in fat-1 mice than in the WT mice. Fat-1 mice also had abundant levels of two shelterin proteins: TRF1 (27%, P&#xa0;=&#xa0;0.028) and TRF2 (47%, P&#xa0;=&#xa0;0.040) (telomeric repeat binding factor 1 and 2) compared to WT animals.<br><br>CONCLUSION: This study, for the first time in a unique animal model free of dietary confounders, has demonstrated that increased levels of n-3 FA in tissues can reduce telomere attrition. The data presented indicate the possibility of using omega-3 fatty acids to reduce accelerated telomere attrition and, consequently, counteract premature aging and reduce the risk of age-related diseases.},
}
@article {pmid38714889,
year = {2024},
author = {Wondisford, AR and Lee, J and Lu, R and Schuller, M and Groslambert, J and Bhargava, R and Schamus-Haynes, S and Cespedes, LC and Opresko, PL and Pickett, HA and Min, J and Ahel, I and O'Sullivan, RJ},
title = {Deregulated DNA ADP-ribosylation impairs telomere replication.},
journal = {Nature structural &amp; molecular biology},
volume = {},
number = {},
pages = {},
pmid = {38714889},
issn = {1545-9985},
abstract = {The recognition that DNA can be ADP ribosylated provides an unexpected regulatory level of how ADP-ribosylation contributes to genome stability, epigenetics and immunity. Yet, it remains unknown whether DNA ADP-ribosylation (DNA-ADPr) promotes genome stability and how it is regulated. Here, we show that telomeres are subject to DNA-ADPr catalyzed by PARP1 and removed by TARG1. Mechanistically, we show that DNA-ADPr is coupled to lagging telomere DNA strand synthesis, forming at single-stranded DNA present at unligated Okazaki fragments and on the 3' single-stranded telomere overhang. Persistent DNA-linked ADPr, due to TARG1 deficiency, eventually leads to telomere shortening. Furthermore, using the bacterial DNA ADP-ribosyl-transferase toxin to modify DNA at telomeres directly, we demonstrate that unhydrolyzed DNA-linked ADP-ribose compromises telomere replication and telomere integrity. Thus, by identifying telomeres as chromosomal targets of PARP1 and TARG1-regulated DNA-ADPr, whose deregulation compromises telomere replication and integrity, our study highlights and establishes the critical importance of controlling DNA-ADPr turnover for sustained genome stability.},
}
@article {pmid38708177,
year = {2024},
author = {Tao, HY and Zhao, CY and Wang, Y and Sheng, WJ and Zhen, YS},
title = {Targeting Telomere Dynamics as an Effective Approach for the Development of Cancer Therapeutics.},
journal = {International journal of nanomedicine},
volume = {19},
number = {},
pages = {3805-3825},
pmid = {38708177},
issn = {1178-2013},
mesh = {Humans ; *Neoplasms/drug therapy/therapy ; *Telomere/drug effects ; *Antineoplastic Agents/pharmacology/chemistry ; *Telomerase/antagonists &amp; inhibitors ; Animals ; Drug Delivery Systems/methods ; Nanoparticles/chemistry ; Immunotherapy/methods ; Neoplastic Stem Cells/drug effects ; },
abstract = {Telomere is a protective structure located at the end of chromosomes of eukaryotes, involved in maintaining the integrity and stability of the genome. Telomeres play an essential role in cancer progression; accordingly, targeting telomere dynamics emerges as an effective approach for the development of cancer therapeutics. Targeting telomere dynamics may work through multifaceted molecular mechanisms; those include the activation of anti-telomerase immune responses, shortening of telomere lengths, induction of telomere dysfunction and constitution of telomerase-responsive drug release systems. In this review, we summarize a wide variety of telomere dynamics-targeted agents in preclinical studies and clinical trials, and reveal their promising therapeutic potential in cancer therapy. As shown, telomere dynamics-active agents are effective as anti-cancer chemotherapeutics and immunotherapeutics. Notably, these agents may display efficacy against cancer stem cells, reducing cancer stem levels. Furthermore, these agents can be integrated with the capability of tumor-specific drug delivery by the constitution of related nanoparticles, antibody drug conjugates and HSA-based drugs.},
}
@article {pmid38706908,
year = {2024},
author = {Yan, M and Zhang, Z and Wang, L and Huang, H and Wang, J and Zhu, C and Li, Z and Xu, Z},
title = {Cross-talk of Three Molecular Subtypes of Telomere Maintenance Defines Clinical Characteristics and Tumor Microenvironment in Gastric Cancer.},
journal = {Journal of Cancer},
volume = {15},
number = {10},
pages = {3227-3241},
pmid = {38706908},
issn = {1837-9664},
abstract = {Background: Telomere maintenance takes part in the regulation of gastric cancer (GC) pathogenesis and is essential for patients' clinical features. Though the correlation between a single telomere maintenance-related gene and GC has previously been published, comprehensive exploration and systematic analysis remain to be studied. Our study is aimed at determining telomere maintenance-related molecular subtypes and examining their role in GC. Methods: By analyzing the transcriptome data, we identified three telomere maintenance-associated clusters (TMCs) with heterogeneity in clinical features and tumor microenvironment (TME). Then, we screened five prognostic telomere maintenance-related genes and established corresponding TM scores. Additionally, the expression level and biological function of tubulin beta 6 class V (TUBB6) were validated in GC tissues and cells. Results: TMC1 was correlated with EMT and TGF-beta pathway and predicted low tumor mutation burden (TMB) as well as bad prognostic outcomes. TMC3 was associated with cell cycle and DNA repair. In terms of TMB and overall survival, TMC3 exhibited opposite results against TMC1. Significant heterogeneity was observed between TMCs. TUBB6 was upregulated and could promote GC proliferation, migration, and invasion. Conclusion: Altogether, combining bioinformatics and functional experiments, we identified three molecular subtypes based on telomere maintenance-associated genes in GC, which could bring new ideas and novel biomarkers to the clinic.},
}
@article {pmid38701745,
year = {2024},
author = {McQuillan, MA and Verhulst, S and Hansen, MEB and Beggs, W and Meskel, DW and Belay, G and Nyambo, T and Mpoloka, SW and Mokone, GG and Fokunang, C and Njamnshi, AK and Chanock, SJ and Aviv, A and Tishkoff, SA},
title = {Association between telomere length and Plasmodium falciparum malaria endemicity in sub-Saharan Africans.},
journal = {American journal of human genetics},
volume = {111},
number = {5},
pages = {927-938},
doi = {10.1016/j.ajhg.2024.04.003},
pmid = {38701745},
issn = {1537-6605},
mesh = {Humans ; *Malaria, Falciparum/genetics/epidemiology/parasitology ; Male ; Female ; Adult ; Africa South of the Sahara/epidemiology ; *Telomere/genetics ; Endemic Diseases ; Plasmodium falciparum/genetics/pathogenicity ; Black People/genetics ; Middle Aged ; Leukocytes/metabolism ; Telomere Homeostasis/genetics ; Young Adult ; Sub-Saharan African People ; },
abstract = {Leukocyte telomere length (LTL) varies significantly across human populations, with individuals of African ancestry having longer LTL than non-Africans. However, the genetic and environmental drivers of LTL variation in Africans remain largely unknown. We report here on the relationship between LTL, genetics, and a variety of environmental and climatic factors in ethnically diverse African adults (n = 1,818) originating from Botswana, Tanzania, Ethiopia, and Cameroon. We observe significant variation in LTL among populations, finding that the San hunter-gatherers from Botswana have the longest leukocyte telomeres and that the Fulani pastoralists from Cameroon have the shortest telomeres. Genetic factors explain ∼50% of LTL variation among individuals. Moreover, we observe a significant negative association between Plasmodium falciparum malaria endemicity and LTL while adjusting for age, sex, and genetics. Within Africa, adults from populations indigenous to areas with high malaria exposure have shorter LTL than those in populations indigenous to areas with low malaria exposure. Finally, we explore to what degree the genetic architecture underlying LTL in Africa covaries with malaria exposure.},
}
@article {pmid38696464,
year = {2024},
author = {Lee, J and Lee, J and Sohn, EJ and Taglialatela, A and O'Sullivan, RJ and Ciccia, A and Min, J},
title = {Extrachromosomal telomere DNA derived from excessive strand displacements.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {19},
pages = {e2318438121},
doi = {10.1073/pnas.2318438121},
pmid = {38696464},
issn = {1091-6490},
support = {CA207209//HHS | NIH | National Cancer Institute (NCI)/ ; CA262316//HHS | NIH | National Cancer Institute (NCI)/ ; CA197774//HHS | NIH | National Cancer Institute (NCI)/ ; CA245259//HHS | NIH | National Cancer Institute (NCI)/ ; },
mesh = {*Telomere/genetics/metabolism ; Humans ; *DNA, Single-Stranded/metabolism/genetics ; *Telomere Homeostasis ; DNA Replication ; DNA/genetics/metabolism ; DNA, Circular/genetics/metabolism ; Blotting, Southern ; DNA Polymerase III/metabolism/genetics ; },
abstract = {Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism mediated by break-induced replication, evident in approximately 15% of human cancers. A characteristic feature of ALT cancers is the presence of C-circles, circular single-stranded telomeric DNAs composed of C-rich sequences. Despite the fact that extrachromosomal C-rich single-stranded DNAs (ssDNAs), including C-circles, are unique to ALT cells, their generation process remains undefined. Here, we introduce a method to detect single-stranded telomeric DNA, called 4SET (Strand-Specific Southern-blot for Single-stranded Extrachromosomal Telomeres) assay. Utilizing 4SET, we are able to capture C-rich single-stranded DNAs that are near 200 to 1500 nucleotides in size. Both linear C-rich ssDNAs and C-circles are abundant in the fractions of cytoplasm and nucleoplasm, which supports the idea that linear and circular C-rich ssDNAs are generated concurrently. We also found that C-rich ssDNAs originate during Okazaki fragment processing during lagging strand DNA synthesis. The generation of C-rich ssDNA requires CST-PP (CTC1/STN1/TEN1-PRIMASE-Polymerase alpha) complex-mediated priming of the C-strand DNA synthesis and subsequent excessive strand displacement of the C-rich strand mediated by the DNA Polymerase delta and the BLM helicase. Our work proposes a model for the generation of C-rich ssDNAs and C-circles during ALT-mediated telomere elongation.},
}
@article {pmid38695985,
year = {2024},
author = {Fragkiadaki, P and Kouvidi, E and Angelaki, A and Nikolopoulou, D and Vakonaki, E and Tsatsakis, A},
title = {Evaluation of telomere length and telomerase activity on predicting in vitro fertilization treatment outcomes.},
journal = {Journal of assisted reproduction and genetics},
volume = {},
number = {},
pages = {},
pmid = {38695985},
issn = {1573-7330},
abstract = {The current article is a literature review aiming to provide an overview of the existing knowledge on the association between telomere length and telomerase activity and in vitro fertilization. Recently, telomeres have been used as an effective biomarker to determine biological age, which may differ from chronological age due to genetic, lifestyle, and environmental factors. Cellular senescence, along with other exogenous and mainly environmental factors, can enhance telomere wear, further shortening their ends and may also affect reproductive aging. IVF is a common fertility treatment caused by female reasons (age, ovulation disorders, damaged or blocked fallopian tubes, endometriosis), male reasons (low sperm quantity or quality), or unexplained infertility. A growing number of studies have proposed a relationship between telomere length and telomerase activity and IVF success and have suggested their use as candidate biomarkers for IVF outcome. Nevertheless, additional studies are necessary to be conducted, in order to clarify the possible implication of telomeres in IVF and to evaluate their possible role as valuable predictors of IVF result.},
}
@article {pmid38695626,
year = {2024},
author = {Wirtz, L and Casanova, F and Schaffrath, U and Wegner, A},
title = {Development of a telomere vector-based approach to overcome limitations caused by lethal phenotypes in the study of essential genes in Magnaporthe oryzae.},
journal = {Molecular plant pathology},
volume = {25},
number = {5},
pages = {e13460},
doi = {10.1111/mpp.13460},
pmid = {38695626},
issn = {1364-3703},
support = {//RWTH Aachen University scholarships for Doctoral Students/ ; SCHA 631/11-1//Deutsche Forschungsgemeinschaft/ ; },
mesh = {*Telomere/genetics ; *Phenotype ; *Genes, Essential ; *Genetic Vectors/genetics ; CRISPR-Cas Systems/genetics ; Genes, Fungal/genetics ; Gene Deletion ; Magnaporthe/genetics/pathogenicity ; *Ascomycota ; },
abstract = {Reverse genetic approaches are common tools in genomics for elucidating gene functions, involving techniques such as gene deletion followed by screening for aberrant phenotypes. If the generation of gene deletion mutants fails, the question arises whether the failure stems from technical issues or because the gene of interest (GOI) is essential, meaning that the deletion causes lethality. In this report, we introduce a novel method for assessing gene essentiality using the phytopathogenic ascomycete Magnaporthe oryzae. The method is based on the observation that telomere vectors are lost in transformants during cultivation without selection pressure. We tested the hypothesis that essential genes can be identified in deletion mutants co-transformed with a telomere vector. The M. oryzae gene MoPKC, described in literature as essential, was chosen as GOI. Using CRISPR/Cas9 technology transformants with deleted GOI were generated and backed up by a telomere vector carrying a copy of the GOI and conferring fenhexamid resistance. Transformants in which the GOI deletion in the genome was not successful lost the telomere vector on media without fenhexamid. In contrast, transformants with confirmed GOI deletion retained the telomere vector even in absence of fenhexamid selection. In the latter case, the maintenance of the telomere indicates that the GOI is essential for the surveillance of the fungi, as it would have been lost otherwise. The method presented here allows to test for essentiality of genes when no mutants can be obtained from gene deletion approaches, thereby expanding the toolbox for studying gene function in ascomycetes.},
}
@article {pmid38690161,
year = {2024},
author = {Khattar, E and Salvati, E},
title = {Editorial: Novel insights connecting telomere biology to cancer development and progression.},
journal = {Frontiers in oncology},
volume = {14},
number = {},
pages = {1405618},
doi = {10.3389/fonc.2024.1405618},
pmid = {38690161},
issn = {2234-943X},
}
@article {pmid38689496,
year = {2024},
author = {Yun, L and Zhang, C and Liang, T and Tian, Y and Ma, G and Courdavault, V and Sun, S and Ma, B and Li, Z and Li, R and Cao, F and Shen, X and Wei, J and Li, Y and Guo, B and Sun, C},
title = {Insights into the dammarane-type triterpenoid spaonin biosynthesis from the telomere-to-telomere genome of Gynostemma pentaphyllum.},
journal = {Plant communications},
volume = {},
number = {},
pages = {100932},
doi = {10.1016/j.xplc.2024.100932},
pmid = {38689496},
issn = {2590-3462},
}
@article {pmid38689492,
year = {2024},
author = {Bao, J and Zhang, H and Wang, F and Li, L and Zhu, X and Xu, J and Wang, Y and Liu, Z and Zhai, G and Xu, H and Lin, F and Zhu, Y},
title = {Telomere-to-telomere genome assemblies of two Chinese Baijiu-brewing sorghum landraces.},
journal = {Plant communications},
volume = {},
number = {},
pages = {100933},
doi = {10.1016/j.xplc.2024.100933},
pmid = {38689492},
issn = {2590-3462},
}
@article {pmid38688277,
year = {2024},
author = {DeBoy, EA and Nicosia, AM and Liyanarachchi, S and Iyer, SS and Shah, MH and Ringel, MD and Brock, P and Armanios, M},
title = {Telomere-lengthening germline variants predispose to a syndromic papillary thyroid cancer subtype.},
journal = {American journal of human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajhg.2024.04.006},
pmid = {38688277},
issn = {1537-6605},
abstract = {Papillary thyroid cancer (PTC) is the most common endocrine malignancy. 10% to 15% of individuals show familial clustering with three or more affected members, but the factors underlying this risk are unknown. In a group of recently studied individuals with POT1 pathogenic variants and ultra-long telomere length, PTC was the second most common solid tumor. We tested whether variants in POT1 and four other telomere-maintenance genes associated with familial cancer underlie PTC susceptibility. Among 470 individuals, we identified pathogenic or likely pathogenic variants in three genes encoding telomere-binding proteins: POT1, TINF2, and ACD. They were found in 4.5% and 1.5% of familial and unselected cases, respectively. Individuals harboring these variants had ultra-long telomere length, and 15 of 18 (83%) developed other cancers, of which melanoma, lymphoma, and sarcoma were most common. Among individuals with PTC and melanoma, 22% carried a deleterious germline variant, suggesting that a long-telomere syndrome might be clinically recognizable. Successive generations had longer telomere length than their parents and, at times, developed more cancers at younger ages. Tumor sequencing identified a single oncogenic driver, BRAF p.Val600Glu, in 10 of 10 tumors studied, but no telomere-maintenance mechanism, including at the TERT promoter. These data identify a syndromic subset of PTCs with locus heterogeneity and telomere lengthening as a convergent mechanism. They suggest these germline variants lower the threshold to cancer by obviating the need for an acquired telomere-maintenance mechanism in addition to sustaining the longevity of oncogenic mutations.},
}
@article {pmid38685189,
year = {2024},
author = {Walker, CG and Thayer, ZM and Marks, EJ and Ly, KN and Pillai, A and Waldie, K and Underwood, L and Snell, RG and Knowles, SD and Cha, JE and Morton, SMB},
title = {Association between maternal depression symptoms and child telomere length.},
journal = {Journal of psychiatric research},
volume = {174},
number = {},
pages = {319-325},
doi = {10.1016/j.jpsychires.2024.04.037},
pmid = {38685189},
issn = {1879-1379},
abstract = {The biological mechanisms that explain how adverse early life events influence adult disease risk are poorly understood. One proposed mechanism is via the induction of accelerated biological aging, for which telomere length is considered a biomarker. We aimed to determine if maternal depression pre- and post-partum was associated with telomere length in children at 4 years of age (n = 4299). Mothers completed structured questionnaires assessing depression during pregnancy (Edinburgh Depression Scale), at 9 months (Edinburgh Depression Scale), and at 54 months postpartum (Patient Health Questionnaire 9). Regression methods were used to investigate the relationship between telomere length (DNA from saliva) and maternal depression score recorded at each stage. Significant covariates included in the final model were: maternal age at pregnancy; child sex; child ethnicity; gestational age group, and rurality group. Child telomere length was found to be longer if their mother had a higher depression score at both postpartum time points tested (9 months of age; coefficient 0.003, SE = 0.001, P = 0.01, 54 months of age; coefficient 0.003, SE = 0.002, P = 0.02). Although these findings seem paradoxical, increased telomere length may be an adaptive response to early life stressors. We propose several testable hypotheses for these results and to determine if the positive association between depression and telomere length is a developmental adaptation or an indirect consequence of environmental factors.},
}
@article {pmid38680187,
year = {2024},
author = {Yudin, NS and Igoshin, AV and Romashov, GA and Martynov, AA and Larkin, DM},
title = {Influence of breed and environment on leukocyte telomere length in cattle.},
journal = {Vavilovskii zhurnal genetiki i selektsii},
volume = {28},
number = {2},
pages = {190-197},
doi = {10.18699/vjgb-24-23},
pmid = {38680187},
issn = {2500-0462},
abstract = {High milk yield is associated with reduced longevity in high-producing dairy cattle breeds. Pre-term culling leads to high replacement heifer demand and economic losses for the dairy industry. Selection for this trait is limited because of low heritability and difficulties in phenotype measurement. Telomeres are elements found at the ends of chromosomes, consisting of repetitive DNA sequences, several thousand base pairs in length, coupled with nucleoprotein complexes. Eventually, in humans and most other animals, telomere length reduces with age. When telomeric DNA is truncated to a critical length, cell ageing, cell cycle arrest, and apoptosis are induced. As a result, telomere length can be considered as a predictor of health risks and an individual's lifespan. The leukocyte telomere length may be used as a proxy phenotype of productive lifespan to improve cattle selection. Our objectives were to assess the effects of breed and breed group (dairy vs. beef) on the leukocyte telomere length and to estimate the effect of cold climate on this trait in Kalmyk cattle populations from the South (Rostov Oblast) and Far North (Republic of Sakha) regions of Russia. The leukocyte telomere lengths were estimated computationally from whole-genome resequencing data. We leveraged data on leukocyte telomere length, sex, and age of 239 animals from 17 cattle breeds. The breed factor had a significant effect on leukocyte telomere length across our sample. There was no difference in leukocyte telomere length between dairy and beef groups. The population factor had a significant effect on leukocyte telomere length in Kalmyk animals. In conclusion, we found that breed, but not breed group (dairy vs. beef), was significantly associated with leukocyte telomere length in cattle. Residence in colder climates was associated with longer leukocyte telomere length in Kalmyk breed cattle.},
}
@article {pmid38679744,
year = {2024},
author = {Limardi, PC and Panigoro, SS and Siregar, NC and Sutandyo, N and Witjaksono, F and Priliani, L and Oktavianthi, S and Malik, SG},
title = {Higher peripheral blood mitochondrial DNA copy number and relative telomere length in under 48 years Indonesian breast cancer patients.},
journal = {BMC research notes},
volume = {17},
number = {1},
pages = {120},
pmid = {38679744},
issn = {1756-0500},
mesh = {Humans ; *Breast Neoplasms/genetics/blood ; Female ; *DNA, Mitochondrial/blood/genetics ; Indonesia ; Middle Aged ; Case-Control Studies ; Adult ; *DNA Copy Number Variations/genetics ; *Telomere/genetics ; Telomere Homeostasis ; Biomarkers, Tumor/blood/genetics ; Aged ; },
abstract = {OBJECTIVE: Breast cancer is the leading cause of cancer incidence and mortality among Indonesian women. A comprehensive investigation is required to enhance the early detection of this disease. Mitochondrial DNA copy number (mtDNA-CN) and relative telomere length (RTL) have been proposed as potential biomarkers for several cancer risks, as they are linked through oxidative stress mechanisms. We conducted a case-control study to examine peripheral blood mtDNA-CN and RTL patterns in Indonesian breast cancer patients (n = 175) and healthy individuals (n = 181). The relative ratios of mtDNA-CN and RTL were determined using quantitative real-time PCR (qPCR).<br><br>RESULTS: Median values of mtDNA-CN and RTL were 1.62 and 0.70 in healthy subjects and 1.79 and 0.73 in breast cancer patients, respectively. We found a positive association between peripheral blood mtDNA-CN and RTL (p&#x2009;<&#x2009;0.001). In under 48&#xa0;years old breast cancer patients, higher peripheral blood mtDNA-CN (mtDNA-CN&#x2009;&#x2265;&#x2009;1.73 (median), p&#x2009;=&#x2009;0.009) and RTL (continuous variable, p&#x2009;=&#x2009;0.010) were observed, compared to the corresponding healthy subjects. We also found a significantly higher 'High-High' pattern of mtDNA-CN and RTL in breast cancer patients under 48&#xa0;years old (p&#x2009;=&#x2009;0.011). Our findings suggest that peripheral blood mtDNA-CN and RTL could serve as additional minimally invasive biomarkers for breast cancer risk evaluation.},
}
@article {pmid38676403,
year = {2024},
author = {Wong, JYY and Blechter, B and Liu, Z and Shi, J and Roger, VL},
title = {Genetic susceptibility to chronic diseases leads to heart failure among Europeans: the influence of leukocyte telomere length.},
journal = {Human molecular genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/hmg/ddae063},
pmid = {38676403},
issn = {1460-2083},
support = {1ZIACP010120-28/CA/NCI NIH HHS/United States ; 1ZIAHL006285-01/HL/NHLBI NIH HHS/United States ; },
abstract = {BACKGROUND: Genetic susceptibility to various chronic diseases has been shown to influence heart failure (HF) risk. However, the underlying biological pathways, particularly the role of leukocyte telomere length (LTL), are largely unknown. We investigated the impact of genetic susceptibility to chronic diseases and various traits on HF risk, and whether LTL mediates or modifies the pathways.<br><br>METHODS: We conducted prospective cohort analyses on 404&#x2009;883 European participants from the UK Biobank, including 9989 incident HF cases. Multivariable Cox regression was used to estimate associations between HF risk and 24 polygenic risk scores (PRSs) for various diseases or traits previously generated using a Bayesian approach. We assessed multiplicative interactions between the PRSs and LTL previously measured in the UK Biobank using quantitative PCR. Causal mediation analyses were conducted to estimate the proportion of the total effect of PRSs acting indirectly through LTL, an integrative marker of biological aging.<br><br>RESULTS: We identified 9 PRSs associated with HF risk, including those for various cardiovascular diseases or traits, rheumatoid arthritis (P&#x2009;=&#x2009;1.3E-04), and asthma (P&#x2009;=&#x2009;1.8E-08). Additionally, longer LTL was strongly associated with decreased HF risk (P-trend&#x2009;=&#x2009;1.7E-08). Notably, LTL strengthened the asthma-HF relationship significantly (P-interaction&#x2009;=&#x2009;2.8E-03). However, LTL mediated only 1.13% (P&#x2009;<&#x2009;0.001) of the total effect of the asthma PRS on HF risk.<br><br>CONCLUSIONS: Our findings shed light onto the shared genetic susceptibility between HF risk, asthma, rheumatoid arthritis, and other traits. Longer LTL strengthened the genetic effect of asthma in the pathway to HF. These results support consideration of LTL and PRSs in HF risk prediction.},
}
@article {pmid38669426,
year = {2024},
author = {Xia, J and Xu, L and Yu, Y and Wu, M and Wang, X and Wang, Y and Li, C and Sun, J and Lv, X and Zhao, J and Zhang, Y},
title = {Associations between weight-adjusted-waist index and telomere length: Results from NHANES: An observational study.},
journal = {Medicine},
volume = {103},
number = {17},
pages = {e37905},
doi = {10.1097/MD.0000000000037905},
pmid = {38669426},
issn = {1536-5964},
mesh = {Humans ; Male ; Female ; *Nutrition Surveys ; Cross-Sectional Studies ; Middle Aged ; Adult ; *Telomere/genetics ; Obesity/genetics ; Waist Circumference ; Aged ; Body Weight ; Body Mass Index ; },
abstract = {Previous studies have demonstrated the connection between obesity and telomere length. A recently devised metric for determining obesity, the weight-adjusted-waist index (WWI), offers a distinct advantage in predicting fat and lean mass by depicting weight-independent abdominal adiposity. This article presents the results of the inaugural study on the relationship between WWI and telomere length in adult populations. The cross-sectional investigation analyzed data from 3479 participants from the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2000. To inspect linear and nonlinear correlations, we adopted weighted multiple logistic regression analysis and smooth curve fit, respectively. In addition, threshold effects and subgroup analyses were accomplished. In the fully adapted model, a significant adverse association of WWI with telomere length was detected [β = -0.02, 95% CI: (-0.03, -0.00), P value = 0.01]. The adverse correlation remained consistent across all subcategories. We also discovered an inverted U-shaped curve linking WWI and telomere length, with a conspicuous inflection point of 10.07 cm/√kg. For the first time, our research demonstrated strong links between WWI and telomere length. The inflection point suggests that controlling WWI within an optimum range might be essential for aging and health.},
}
@article {pmid38663933,
year = {2024},
author = {Yan, X and Yang, P and Li, Y and Liu, T and Zha, Y and Wang, T and Zhang, J and Feng, Z and Li, M},
title = {New insights from bidirectional Mendelian randomization: causal relationships between telomere length and mitochondrial DNA copy number in aging biomarkers.},
journal = {Aging},
volume = {16},
number = {},
pages = {},
doi = {10.18632/aging.205765},
pmid = {38663933},
issn = {1945-4589},
abstract = {Mitochondrial DNA (mtDNA) copy number and telomere length (TL) are dynamic factors that have been linked to the aging process in organisms. However, the causal relationship between these variables remains uncertain. In this research, instrumental variables (IVs) related to mtDNA copy number and TL were obtained from publicly available genome-wide association studies (GWAS). Through bidirectional Mendelian randomization (MR) analysis, we examined the potential causal relationship between these factors. The forward analysis, with mtDNA copy number as the exposure and TL as the outcome, did not reveal a significant effect (B=-0.004, P>0.05). On the contrary, upon conducting a reverse analysis, it was found that there exists a positive causal relationship (B=0.054, P<0.05). Sensitivity analyses further confirmed the reliability of these results. The outcomes of this study indicate a one-way positive causal relationship, indicating that telomere shortening in the aging process may lead to a decrease in mtDNA copy number, providing new perspectives on their biological mechanisms.},
}
@article {pmid38663837,
year = {2024},
author = {Inoue, Y and Aoki, S and Ito, J and Hara, S and Shirasuna, K and Iwata, H},
title = {Telomere length determines the mitochondrial copy number in blastocyst-stage embryos.},
journal = {Mitochondrion},
volume = {},
number = {},
pages = {101887},
doi = {10.1016/j.mito.2024.101887},
pmid = {38663837},
issn = {1872-8278},
abstract = {Telomere length (TL) and mitochondrial DNA copy number (mt-cn) are associated with embryonic development. Here, we investigated the correlation between TL and mt-cn in bovine embryos to determine whether TL regulates mt-cn. TL and mt-cn were closely correlated in embryos derived from six bulls. Treatment of embryos with a telomerase inhibitor (TMPyP) and siTERT shortened the TL and reduced mt-cn in blastocysts. RNA-sequencing of blastocysts developed with TMPyP revealed differentially expressed genes associated with transforming growth factor-β1 signaling and inflammation. In conclusion, TL regulates mt-cn in embryos.},
}
@article {pmid38658004,
year = {2024},
author = {Tunnicliffe, L and Muzambi, R and Bartlett, JW and Howe, L and Abdul Basit, K and Warren-Gash, C},
title = {Infection and telomere length: a systematic review protocol.},
journal = {BMJ open},
volume = {14},
number = {4},
pages = {e081881},
doi = {10.1136/bmjopen-2023-081881},
pmid = {38658004},
issn = {2044-6055},
mesh = {Humans ; *Systematic Reviews as Topic ; *Research Design ; Telomere Shortening ; Telomere/genetics ; Infections ; },
abstract = {INTRODUCTION: Telomeres are a measure of cellular ageing with potential links to diseases such as cardiovascular diseases and cancer. Studies have shown that some infections may be associated with telomere shortening, but whether an association exists across all types and severities of infections and in which populations is unclear. Therefore we aim to collate available evidence to enable comparison and to inform future research in this field.<br><br>METHODS AND ANALYSIS: We will search for studies involving telomere length and infection in various databases including MEDLINE (Ovid interface), EMBASE (Ovid interface), Web of Science, Scopus, Global Health and the Cochrane Library. For grey literature, the British Library of electronic theses databases (ETHOS) will be explored. We will not limit by study type, geographical location, infection type or method of outcome measurement. Two researchers will independently carry out study selection, data extraction and risk of bias assessment using the ROB2 and ROBINS-E tools. The overall quality of the studies will be determined using the Grading of Recommendations Assessment, Development and Evaluation criteria. We will also evaluate study heterogeneity with respect to study design, exposure and outcome measurement and if there is sufficient homogeneity, a meta-analysis will be conducted. Otherwise, we will provide a narrative synthesis with results grouped by exposure category and study design.<br><br>ETHICS AND DISSEMINATION: The present study does not require ethical approval. Results will be disseminated via publishing in a peer-reviewed journal and conference presentations.<br><br>PROSPERO REGISTRATION NUMBER: CRD42023444854.},
}
@article {pmid38657142,
year = {2024},
author = {Nageshan, RK and Krogan, N and Cooper, JP},
title = {Parallel genetic screens identify nuclear envelope homeostasis as a key determinant of telomere entanglement resolution in fission yeast.},
journal = {G3 (Bethesda, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1093/g3journal/jkae078},
pmid = {38657142},
issn = {2160-1836},
abstract = {In fission yeast lacking the telomere binding protein, Taz1, replication forks stall at telomeres, triggering deleterious downstream events. Strand invasion from one taz1Δ telomeric stalled fork to another on a separate (non-sister) chromosome leads to telomere entanglements, which are resolved in mitosis at 32°C; however, entanglement resolution fails at ≤20°C, leading to cold-specific lethality. Previously, we found that loss of the mitotic function of Rif1, a conserved DNA replication and repair factor, suppresses cold sensitivity by promoting resolution of entanglements without affecting entanglement formation. To understand the underlying pathways of mitotic entanglement resolution, we performed a series of genomewide synthetic genetic array screens to generate a comprehensive list of genetic interactors of taz1Δ and rif1Δ. We modified a previously described screening method to ensure that the queried cells were kept in log phase growth. In addition to recapitulating previously identified genetic interactions, we find that loss of genes encoding components of the nuclear pore complex (NPC) promotes telomere disentanglement and suppresses taz1Δ cold sensitivity. We attribute this to more rapid anaphase midregion nuclear envelope (NE) breakdown in the absence of these NPC components. Loss of genes involved in lipid metabolism reverses the ability of rif1+ deletion to suppress taz1Δ cold sensitivity, again pinpointing NE modulation. A rif1+ separation-of-function mutant that specifically loses Rif1's mitotic functions yields similar genetic interactions. Genes promoting membrane fluidity were enriched in a parallel taz1+ synthetic lethal screen at permissive temperature, cementing the idea that the cold specificity of taz1Δ lethality stems from altered NE homeostasis.},
}
@article {pmid38656297,
year = {2024},
author = {Hu, C and Zhu, XT and He, MH and Shao, Y and Qin, Z and Wu, ZJ and Zhou, JQ},
title = {Elimination of subtelomeric repeat sequences exerts little effect on telomere essential functions in Saccharomyces cerevisiae.},
journal = {eLife},
volume = {12},
number = {},
pages = {},
doi = {10.7554/eLife.91223},
pmid = {38656297},
issn = {2050-084X},
support = {2023YFA0913400//National Key Research and Development Program of China/ ; 32150004//The National Natural Science Foundation of China/ ; },
mesh = {*Saccharomyces cerevisiae/genetics ; *Telomere/metabolism/genetics ; *Repetitive Sequences, Nucleic Acid/genetics ; *Telomerase/genetics/metabolism ; Telomere Homeostasis ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Sequence Deletion ; },
abstract = {Telomeres, which are chromosomal end structures, play a crucial role in maintaining genome stability and integrity in eukaryotes. In the baker's yeast Saccharomyces cerevisiae, the X- and Y'-elements are subtelomeric repetitive sequences found in all 32 and 17 telomeres, respectively. While the Y'-elements serve as a backup for telomere functions in cells lacking telomerase, the function of the X-elements remains unclear. This study utilized the S. cerevisiae strain SY12, which has three chromosomes and six telomeres, to investigate the role of X-elements (as well as Y'-elements) in telomere maintenance. Deletion of Y'-elements (SY12[YΔ]), X-elements (SY12[XYΔ+Y]), or both X- and Y'-elements (SY12[XYΔ]) did not impact the length of the terminal TG1-3 tracks or telomere silencing. However, inactivation of telomerase in SY12[YΔ], SY12[XYΔ+Y], and SY12[XYΔ] cells resulted in cellular senescence and the generation of survivors. These survivors either maintained their telomeres through homologous recombination-dependent TG1-3 track elongation or underwent microhomology-mediated intra-chromosomal end-to-end joining. Our findings indicate the non-essential role of subtelomeric X- and Y'-elements in telomere regulation in both telomerase-proficient and telomerase-null cells and suggest that these elements may represent remnants of S. cerevisiae genome evolution. Furthermore, strains with fewer or no subtelomeric elements exhibit more concise telomere structures and offer potential models for future studies in telomere biology.},
}
@article {pmid38649458,
year = {2024},
author = {Li, H and Durbin, R},
title = {Genome assembly in the telomere-to-telomere era.},
journal = {Nature reviews. Genetics},
volume = {},
number = {},
pages = {},
pmid = {38649458},
issn = {1471-0064},
abstract = {Genome sequences largely determine the biology and encode the history of an organism, and de novo assembly - the process of reconstructing the genome sequence of an organism from sequencing reads - has been a central problem in bioinformatics for four decades. Until recently, genomes were typically assembled into fragments of a few megabases at best, but now technological advances in long-read sequencing enable the near-complete assembly of each chromosome - also known as telomere-to-telomere assembly - for many organisms. Here, we review recent progress on assembly algorithms and protocols, with a focus on how to derive near-telomere-to-telomere assemblies. We also discuss the additional developments that will be required to resolve remaining assembly gaps and to assemble non-diploid genomes.},
}
@article {pmid38643009,
year = {2024},
author = {Dilixiati, D and Kadier, K and Laihaiti, D and Lu, JD and Azhati, B and Rexiati, M},
title = {Association between leucocyte telomere length and erectile dysfunction in US adults: a secondary study based on 2001-2002 NHANES data.},
journal = {BMJ open},
volume = {14},
number = {4},
pages = {e077808},
doi = {10.1136/bmjopen-2023-077808},
pmid = {38643009},
issn = {2044-6055},
abstract = {OBJECTIVE: We aimed to explore the association between the leucocyte telomere length (LTL) and erectile dysfunction (ED) among a nationally representative sample of US adults.<br><br>DESIGN: Secondary population-based study.<br><br>SETTING: The National Health and Nutrition Examination Survey (NHANES) (2001-2002).<br><br>PARTICIPANTS: A total of 1694 male participants were extracted from the NHANES database for 2001-2002.<br><br>The primary focus of the study was to determine the association between the LTL and ED, using multivariate logistic regression and restricted cubic spline models for examination. The secondary outcome measures involved conducting stratified subgroup analyses to exclude interactions of different variables with the LTL.<br><br>RESULTS: Participants with ED had shorter LTLs than those without ED (p<0.05). After adjusting for confounding factors, compared with the reference lowest LTL quartile, the ORs and 95% CIs for the second, third and fourth LTL quartiles were (OR 1.51; 95%&#x2009;CI 1.01 to 2.26), (OR 1.79; 95%&#x2009;CI 1.24 to 2.58) and (OR 1.25; 95%&#x2009;CI 0.74 to 2.11), respectively. In addition, restricted cubic splines showed an inverted J-curve relationship between the LTL and ED. At an LTL of 1.037, the curve showed an inflection point. The ORs (95%&#x2009;CI) of ED on the left and right sides of the inflection point were (OR 1.99; 95%&#x2009;CI 0.39 to 10.20; p=0.385) and (OR 0.17; 95%&#x2009;CI 0.03 to 0.90; p=0.039).<br><br>CONCLUSION: Our results demonstrated an inverted J-curve relationship between the LTL and ED. When the LTL was &#x2265;1.037, the incidence of ED decreased with increasing LTL.},
}
@article {pmid38641551,
year = {2024},
author = {Fernández-Varas, B and Manguan-García, C and Rodriguez-Centeno, J and Mendoza-Lupiáñez, L and Calatayud, J and Perona, R and Martín-Martínez, M and Gutierrez-Rodriguez, M and Benítez-Buelga, C and Sastre, L},
title = {Clinical mutations in the TERT and TERC genes coding for telomerase components induced oxidative stress, DNA damage at telomeres and cell apoptosis besides decreased telomerase activity.},
journal = {Human molecular genetics},
volume = {33},
number = {9},
pages = {818-834},
doi = {10.1093/hmg/ddae015},
pmid = {38641551},
issn = {1460-2083},
support = {//Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III/ ; PI20-00335//European Regional Development/ ; PIE-202180E073//Consejo Superior de Investigaciones Cientificas, Spain/ ; POSTD20042BENI//Fundaci&#xf3;n Cient&#xed;fica Asociaci&#xf3;n Espa&#xf1;ola Contra el Cancer/ ; },
abstract = {Telomeres are nucleoprotein structures at the end of chromosomes that maintain their integrity. Mutations in genes coding for proteins involved in telomere protection and elongation produce diseases such as dyskeratosis congenita or idiopathic pulmonary fibrosis known as telomeropathies. These diseases are characterized by premature telomere shortening, increased DNA damage and oxidative stress. Genetic diagnosis of telomeropathy patients has identified mutations in the genes TERT and TERC coding for telomerase components but the functional consequences of many of these mutations still have to be experimentally demonstrated. The activity of twelve TERT and five TERC mutants, five of them identified in Spanish patients, has been analyzed. TERT and TERC mutants were expressed in VA-13 human cells that express low telomerase levels and the activity induced was analyzed. The production of reactive oxygen species, DNA oxidation and TRF2 association at telomeres, DNA damage response and cell apoptosis were determined. Most mutations presented decreased telomerase activity, as compared to wild-type TERT and TERC. In addition, the expression of several TERT and TERC mutants induced oxidative stress, DNA oxidation, DNA damage, decreased recruitment of the shelterin component TRF2 to telomeres and increased apoptosis. These observations might indicate that the increase in DNA damage and oxidative stress observed in cells from telomeropathy patients is dependent on their TERT or TERC mutations. Therefore, analysis of the effect of TERT and TERC mutations of unknown function on DNA damage and oxidative stress could be of great utility to determine the possible pathogenicity of these variants.},
}
@article {pmid38634789,
year = {2024},
author = {Li, B and Xiong, W and Zuo, W and Shi, Y and Wang, T and Chang, L and Wu, Y and Ma, H and Bian, Q and Chang, ACY},
title = {Proximal telomeric decompaction due to telomere shortening drives FOXC1-dependent myocardial senescence.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae274},
pmid = {38634789},
issn = {1362-4962},
support = {82070248//National Natural Science Foundation of China/ ; 0900000024//Shanghai Institutions of Higher Learning/ ; },
abstract = {Telomeres, TTAGGGn DNA repeat sequences located at the ends of eukaryotic chromosomes, play a pivotal role in aging and are targets of DNA damage response. Although we and others have demonstrated presence of short telomeres in genetic cardiomyopathic and heart failure cardiomyocytes, little is known about the role of telomere lengths in cardiomyocyte. Here, we demonstrate that in heart failure patient cardiomyocytes, telomeres are shortened compared to healthy controls. We generated isogenic human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) with short telomeres (sTL-CMs) and normal telomeres (nTL-CMs) as model. Compared to nTL-CMs, short telomeres result in cardiac dysfunction and expression of senescent markers. Using Hi-C and RNASeq, we observe that short telomeres induced TAD insulation decrease near telomeric ends and this correlated with a transcription upregulation in sTL-CMs. FOXC1, a key transcription factor involved in early cardiogenesis, was upregulated in sTL-CMs and its protein levels were negatively correlated with telomere lengths in heart failure patients. Overexpression of FOXC1 induced hiPSC-CM aging, mitochondrial and contractile dysfunction; knockdown of FOXC1 rescued these phenotypes. Overall, the work presented demonstrate that increased chromatin accessibility due to telomere shortening resulted in the induction of FOXC1-dependent expression network responsible for contractile dysfunction and myocardial senescence.},
}
@article {pmid38634106,
year = {2024},
author = {Garcia-Medina, JS and Sienkiewicz, K and Narayanan, SA and Overbey, EG and Grigorev, K and Ryon, KA and Burke, M and Proszynski, J and Tierney, B and Schmidt, CM and Mencia-Trinchant, N and Klotz, R and Ortiz, V and Foox, J and Chin, C and Najjar, D and Matei, I and Chan, I and Cruchaga, C and Kleinman, A and Kim, J and Lucaci, A and Loy, C and Mzava, O and De Vlaminck, I and Singaraju, A and Taylor, LE and Schmidt, JC and Schmidt, MA and Blease, K and Moreno, J and Boddicker, A and Zhao, J and Lajoie, B and Altomare, A and Kruglyak, S and Levy, S and Yu, M and Hassane, DC and Bailey, SM and Bolton, K and Mateus, J and Mason, CE},
title = {Genome and clonal hematopoiesis stability contrasts with immune, cfDNA, mitochondrial, and telomere length changes during short duration spaceflight.},
journal = {Precision clinical medicine},
volume = {7},
number = {1},
pages = {pbae007},
pmid = {38634106},
issn = {2516-1571},
abstract = {BACKGROUND: The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure.<br><br>METHODS: To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction. Telomere length was measured by quantitative PCR, while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations. A robust bioinformatic pipeline was used for data analysis, including variant calling to assess mutational burden.<br><br>RESULT: Telomere elongation occurred during spaceflight and shortened after return to Earth. Cell-free DNA analysis revealed increased immune cell signatures post-flight. No significant clonal hematopoiesis of indeterminate potential (CHIP) or whole-genome instability was observed. The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight.<br><br>CONCLUSION: Our findings provide valuable insights into the physiological consequences of short-duration spaceflight, with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth. CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts, an understudied phenomenon as previous studies have focused on career astronauts. This study will serve as a reference point for future commercial and non-commercial spaceflight, low Earth orbit (LEO) missions, and deep-space exploration.},
}
@article {pmid38633384,
year = {2024},
author = {Yu, HJ and Byun, YH and Park, CK},
title = {Techniques for assessing telomere length: A methodological review.},
journal = {Computational and structural biotechnology journal},
volume = {23},
number = {},
pages = {1489-1498},
pmid = {38633384},
issn = {2001-0370},
abstract = {Telomeres are located at the ends of chromosomes and have specific sequences with a distinctive structure that safeguards genes. They possess capping structures that protect chromosome ends from fusion events and ensure chromosome stability. Telomeres shorten in length during each cycle of cell division. When this length reaches a certain threshold, it can lead to genomic instability, thus being implicated in various diseases, including cancer and neurodegenerative disorders. The possibility of telomeres serving as a biomarker for aging and age-related disease is being explored, and their significance is still under study. This is because post-mitotic cells, which are mature cells that do not undergo mitosis, do not experience telomere shortening due to age. Instead, other causes, for example, exposure to oxidative stress, can directly damage the telomeres, causing genomic instability. Nonetheless, a general agreement has been established that measuring telomere length offers valuable insights and forms a crucial foundation for analyzing gene expression and epigenetic data. Numerous approaches have been developed to accurately measure telomere lengths. In this review, we summarize various methods and their advantages and limitations for assessing telomere length.},
}
@article {pmid38631323,
year = {2024},
author = {de Punder, K and Salinas-Manrique, J and Dietrich, DE and Karabatsiakis, A},
title = {Serum levels of the steroid hormone dehydroepiandrosterone (DHEA) are associated with psychological trauma and lymphocyte telomere integrity in women suffering from depression.},
journal = {Neuroimmunomodulation},
volume = {},
number = {},
pages = {},
doi = {10.1159/000538893},
pmid = {38631323},
issn = {1423-0216},
abstract = {INTRODUCTION: Emerging studies highlight the telomere system as an aging mechanism underlying the association between exposure to psychological trauma and the development of a wide range of physical and mental disorders, including major depressive disorder (MDD). Here, we investigated associations of circulating levels of the steroid hormone dehydroepiandrosterone (DHEA) with immune cell telomere length (TL) in the context of lifetime trauma exposure and MDD.<br><br>METHODS: Lifetime traumatic events (trauma load) were assessed using the Essener Trauma Inventory (ETI) in n=22 postmenopausal female inpatients with MDD and n=22 non-depressed controls. All women completed the Beck's Depression Inventory-II to assess the severity of current depressive symptoms. DHEA concentration in serum was measured by immunoassay and TL was quantified in kilobase units using quantitative fluorescent in situ hybridization (qFISH) in total peripheral blood mononuclear cells (PBMC) and in selected T cell subpopulations isolated by FACS separation.<br><br>RESULTS: Higher trauma load was significantly associated with lower DHEA concentration, which in turn was linked to more depression-related fatigue. Furthermore, DHEA concentration was positively and significantly associated with TL in memory CD4+ T cells as well as in na&#xef;ve and memory CD8+ T cells, but not in na&#xef;ve CD4+ T cells and total PBMC. Mediational analysis suggested that DHEA concentration is a mediator in the relationship between trauma load and memory CD8+ T cell TL.<br><br>CONCLUSION: The current findings suggest a potential role of DHEA as a biological resilience factor that may exert beneficial effects on telomere integrity, especially in conditions related to distress.},
}
@article {pmid38631073,
year = {2024},
author = {Zhong, M and Salberg, S and Sampangi, S and van der Walt, A and Butzkueven, H and Mychasiuk, R and Jokubaitis, V},
title = {Leukocyte telomere length in multiple sclerosis: relationship between disability severity and pregnancy history.},
journal = {Multiple sclerosis and related disorders},
volume = {86},
number = {},
pages = {105607},
doi = {10.1016/j.msard.2024.105607},
pmid = {38631073},
issn = {2211-0356},
abstract = {BACKGROUND: Aging-related processes contribute to neurodegeneration and disability in multiple sclerosis (MS). Biomarkers of biological aging such as leukocyte telomere length (LTL) could help personalise prognosis. Pregnancy has been shown to be protective against disability accumulation in women with MS, though it is unclear if this effect relates to aging mechanisms or LTL.<br><br>OBJECTIVES: This study aimed to cross-sectionally characterise LTL in a cohort of individuals with MS, and to correlate LTL with disability severity and pregnancy history.<br><br>METHODS: We extracted DNA from the whole blood of 501 people with MS in Melbourne, Australia. Expanded Disability Status Scale (EDSS) score and demographic data, as well as pregnancy history for 197 females, were obtained at sample collection. Additional data were extracted from the MSBase Registry. LTL was determined in base pairs (bp) using real-time quantitative polymerase chain reaction.<br><br>RESULTS: A relationship between EDSS score and shorter LTL was robust to multivariable adjustment for demographic and clinical factors including chronological age, with an adjusted LTL reduction per 1.0 increase in EDSS of 97.1 bp (95 % CI = 9.7-184.5 bp, p = 0.030). Adjusted mediation analysis found chronological age accounted for 33.6 % of the relationship between LTL and EDSS score (p = 0.018). In females with pregnancy data, history of pregnancy was associated with older age (median 49.7 vs 33.0 years, p < 0.001). There were no significant relationships between adjusted LTL and any history of pregnancy (LTL increase of 65.3 bp, 95 % CI = -471.0-601.5 bp, p = 0.81) or number of completed pregnancies (LTL increase of 14.6 bp per pregnancy, 95 % CI = -170.3-199.6 bp, p = 0.87).<br><br>CONCLUSIONS: The correlation between LTL and disability independent of chronological age and other factors points to a link between neurological reserve in MS and biological aging, and a potential research target for pathophysiological and therapeutic mechanisms. Although LTL did not significantly differ by pregnancy history, longitudinal analyses could help identify interactions with prospectively captured pregnancy effects.},
}
@article {pmid38629454,
year = {2024},
author = {Liang, X and Aouizerat, BE and So-Armah, K and Cohen, MH and Marconi, VC and Xu, K and Justice, AC},
title = {DNA methylation-based telomere length is associated with HIV infection, physical frailty, cancer, and all-cause mortality.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e14174},
doi = {10.1111/acel.14174},
pmid = {38629454},
issn = {1474-9726},
support = {R01-DA035616/DA/NIDA NIH HHS/United States ; R01-DA038632/DA/NIDA NIH HHS/United States ; R01-DA047063/DA/NIDA NIH HHS/United States ; R01-DA047820/DA/NIDA NIH HHS/United States ; R03-DA039745/DA/NIDA NIH HHS/United States ; U01-AA020790/AA/NIAAA NIH HHS/United States ; U01-AA020795/AA/NIAAA NIH HHS/United States ; U01-AA020799/AA/NIAAA NIH HHS/United States ; U10-AA013566/AA/NIAAA NIH HHS/United States ; U24-AA020794/AA/NIAAA NIH HHS/United States ; },
abstract = {Telomere length (TL) is an important indicator of cellular aging. Shorter TL is associated with several age-related diseases including coronary heart disease, heart failure, diabetes, osteoporosis, and cancer. Recently, a DNA methylation-based TL (DNAmTL) estimator has been developed as an alternative method for directly measuring TL. In this study, we examined the association of DNAmTL with cancer prevalence and mortality risk among people with and without HIV in the Veterans Aging Cohort Study Biomarker Cohort (VACS, N = 1917) and Women's Interagency HIV Study Cohort (WIHS, N = 481). We profiled DNAm in whole blood (VACS) or in peripheral blood mononuclear cells (WIHS) using an array-based method. Cancer prevalence was estimated from electronic medical records and cancer registry data. The VACS Index was used as a measure of physiologic frailty. Models were adjusted for self-reported race and ethnicity, batch, smoking status, alcohol consumption, and five cell types (CD4, CD8, NK, B cell, and monocyte). We found that people with HIV had shorter average DNAmTL than those without HIV infection [beta = -0.25, 95% confidence interval (-0.32, -0.18), p = 1.48E-12]. Greater value of VACS Index [beta = -0.002 (-0.003, -0.001), p = 2.82E-05] and higher cancer prevalence [beta = -0.07 (-0.10, -0.03), p = 1.37E-04 without adjusting age] were associated with shortened DNAmTL. In addition, one kilobase decrease in DNAmTL was associated with a 40% increase in mortality risk [hazard ratio: 0.60 (0.44, 0.82), p = 1.42E-03]. In summary, HIV infection, physiologic frailty, and cancer are associated with shortening DNAmTL, contributing to an increased risk of all-cause mortality.},
}
@article {pmid38621495,
year = {2024},
author = {Moura, HF and Schuch, JB and Ornell, F and Bandeira, CE and Massuda, R and Dotto Bau, CH and Grevet, EH and Kessler, FHP and von Diemen, L},
title = {Association between telomere length with alcohol use disorder and internalizing/externalizing comorbidities in a Brazilian male sample.},
journal = {Alcohol (Fayetteville, N.Y.)},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.alcohol.2024.04.004},
pmid = {38621495},
issn = {1873-6823},
abstract = {BACKGROUND: Shortening telomere length (TL) is an important ageing marker associated with substance use disorder (SUD). However, the influence of psychiatric and clinical comorbidities and alcohol-related outcomes has not been much explored in the context of TL in individuals with alcohol use disorder (AUD) and may be a source of heterogeneity in AUD studies. Therefore, our aim was to investigate the influence of AUD, alcohol-related outcomes, and common psychiatric comorbidities on TL in men with AUD and healthy controls (HC).<br><br>METHODS: Men with AUD (n=108, mean age=52.4, SD=8.6) were recruited in a detoxification unit, and HC (n=80, mean age=50.04, SD=9.1) from the blood bank, both located in Brazil. HC had no current or lifetime diagnosis of any substance use disorder. Psychiatric comorbidities were assessed using SCID-I. TL ratio was measured in triplicates using quantitative multiplex PCR.<br><br>RESULTS: Telomere length did not differ between individuals with AUD and HC (p=0.073) or was associated with AUD-related outcomes, trauma, or clinical comorbidities. Individuals with externalizing disorders had longer TL when comparing with those with internalizing disorders (p=0.018) or without comorbidity (p=0.018).<br><br>CONCLUSION: Our findings indicate that TL was influenced by the presence of psychiatric comorbidity rather than case or control status. These results were adjusted for potential confounders, such as age.},
}
@article {pmid38617276,
year = {2024},
author = {Greshnova, A and Pál, K and Martinez, JFI and Canzar, S and Makova, KD},
title = {Transcript Isoform Diversity of Y Chromosome Ampliconic Genes of Great Apes Uncovered Using Long Reads and Telomere-to-Telomere Reference Genome Assemblies.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.04.02.587783},
pmid = {38617276},
abstract = {Y chromosomes of great apes harbor A mpliconic G enes (YAGs)-multi-copy gene families (BPY2 , CDY , DAZ , HSFY , PRY , RBMY , TSPY , VCY , and XKRY) that encode proteins important for spermatogenesis. Previous work assembled YAG transcripts based on their targeted sequencing but not using reference genome assemblies, potentially resulting in an incomplete transcript repertoire. Here we used the recently produced gapless telomere-to-telomere (T2T) Y chromosome assemblies of great ape species (bonobo, chimpanzee, human, gorilla, Bornean orangutan, and Sumatran orangutan) and analyzed RNA data from whole-testis samples for the same species. We generated hybrid transcriptome assemblies by combining targeted long reads (Pacific Biosciences), untargeted long reads (Pacific Biosciences) and untargeted short reads (Illumina)and mapping them to the T2T reference genomes. Compared to the results from the reference-free approach, average transcript length was more than two times higher, and the total number of transcripts decreased three times, improving the quality of the assembled transcriptome. The reference-based transcriptome assemblies allowed us to differentiate transcripts originating from different Y chromosome gene copies and from their non-Y chromosome homologs. We identified two sources of transcriptome diversity-alternative splicing and gene duplication with subsequent diversification of gene copies. For each gene family, we detected transcribed pseudogenes along with protein-coding gene copies. We revealed previously unannotated gene copies of YAGs as compared to currently available NCBI annotations, as well as novel isoforms for annotated gene copies. This analysis paves the way for better understanding Y chromosome gene functions, which is important given their role in spermatogenesis.},
}
@article {pmid38615081,
year = {2024},
author = {Li, Z and Yang, J and Ji, X and Liu, J and Yin, C and Bhadauria, V and Zhao, W and Peng, YL},
title = {First telomere-to-telomere gapless assembly of the rice blast fungus Pyricularia oryzae.},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {380},
pmid = {38615081},
issn = {2052-4463},
abstract = {Rice blast caused by Pyricularia oryzae (syn., Magnaporthe oryzae) was one of the most destructive diseases of rice throughout the world. Genome assembly was fundamental to genetic variation identification and critically impacted the understanding of its ability to overcome host resistance. Here, we report a gapless genome assembly of rice blast fungus P. oryzae strain P131 using PacBio, Illumina and high throughput chromatin conformation capture (Hi-C) sequencing data. This assembly contained seven complete chromosomes (43,237,743 bp) and a circular mitochondrial genome (34,866 bp). Approximately 14.31% of this assembly carried repeat sequences, significantly greater than its previous assembled version. This assembly had a 99.9% complement in BUSCO evaluation. A total of 14,982 genes protein-coding genes were predicted. In summary, we assembled the first telomere-to-telomere gapless genome of P. oryzae, which would be a valuable genome resource for future research on the genome evolution and host adaptation.},
}
@article {pmid38615017,
year = {2024},
author = {Li, J and Yang, C and Zhang, Y and Li, Q and Liu, X and Zhang, Y and Zhao, Y},
title = {Study of association of leptin with leukocyte telomere length in a Chinese rural population.},
journal = {Lipids in health and disease},
volume = {23},
number = {1},
pages = {103},
pmid = {38615017},
issn = {1476-511X},
support = {U22A20360//National Natural Science Foundation of China/ ; 82060592//National Natural Science Foundation of China/ ; 2021BEG02026//key R&amp;D projects in Ningxia Hui Autonomous Region/ ; },
abstract = {BACKGROUND: Previous studies have demonstrated the relationship between adipocyte factors, insulin resistance, and other indicators with telomere length. However, these studies did not consider the influence of changes in different indicators on telomere length over time. Therefore, the aim of this study is to elucidate the impact of changes in adipocyte factors, HOMA-IR, and other indicators on the dynamic variation of telomere length.<br><br>METHODS: The data were from a cohort study conducted in Ningxia, China. A total of 1624 subjects were analyzed. Adipokines and relative leukocyte telomere length (RLTL) were measured, and changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Homeostatic Model Assessment for &#x3b2;-Cell Function (HOMA-&#x3b2;), and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated. Generalized linear models evaluated associations between changes in adipokines and RLTL changes. Furthermore, univariate analyses examined the effects of changes in adipokines and insulin resistance indicators on &#x394;RLTL.<br><br>RESULTS: The research findings indicate that females generally have shorter telomeres compared to males. In comparison to the low-level group of &#x394;leptin (LEP), the high-level group of &#x394;LEP shows a negative correlation with &#x394;RLTL (B=-1.32, 95% CI (-2.38, -0.27)). Even after multivariable adjustments, this relationship persists (B=-1.31, 95% CI (-2.24, -0.23)). Further analysis reveals that after adjusting for &#x394;HOMA-IR, &#x394;HOMA-&#x3b2;, and &#x394;QUICKI, the high-level group of &#x394;LEP still exhibits a significant negative correlation with &#x394;RLTL (B=-1.37, 95% CI (-2.43, -0.31)). However, the interaction effects between &#x394;HOMA-IR, &#x394;HOMA-&#x3b2;, &#x394;QUICKI, and &#x394;LEP do not affect &#x394;RLTL.<br><br>CONCLUSIONS: Elevated levels of leptin were significantly correlated with shortened telomere length. This suggests that increased leptin levels may impact overall individual health by affecting telomere length, underscoring the importance of measures to reduce leptin levels to mitigate the onset and progression of related diseases.},
}
@article {pmid38611064,
year = {2024},
author = {Wakita, H and Lu, Y and Li, X and Kobayashi, T and Hachiya, T and Ide, H and Horie, S},
title = {Evaluating Leukocyte Telomere Length and Myeloid-Derived Suppressor Cells as Biomarkers for Prostate Cancer.},
journal = {Cancers},
volume = {16},
number = {7},
pages = {},
doi = {10.3390/cancers16071386},
pmid = {38611064},
issn = {2072-6694},
abstract = {BACKGROUND: Leukocyte telomere length (LTL) and myeloid-derived suppressor cells (MDSC) are associated with aging and the development and progression of cancer. However, the exact nature of this relationship remains unclear. Our study aimed to investigate the potential of LTL and MDSC as diagnostic biomarkers for prostate cancer while also seeking to deepen our understanding of the relationship of these potential biomarkers to each other.<br><br>METHODS: Our study involved patients undergoing a prostate biopsy. We analyzed the relative LTL in genomic DNA obtained from peripheral blood leukocytes as well as the percentage of MDSC and their subtypes in peripheral blood mononuclear cells (PBMC). Our evaluation focused on examining the relationship between LTL and MDSC and pathological diagnoses as well as investigating the correlation between LTL and MDSC levels.<br><br>RESULTS: In our study of 102 participants, 56 were pathologically diagnosed with localized prostate cancer (cancer group), while 46 tested negative (control group). The cancer group exhibited significantly shorter LTL in comparison to the control group (p = 0.024). Additionally, the cancer group showed a tendency towards a higher percentage of monocytic MDSC (M-MDSC), although this difference did not reach statistical significance (p = 0.056). Our multivariate logistic regression analysis revealed that patients with shorter LTL and higher percentages of M-MDSC had a 2.98-fold (95% CI = 1.001-8.869, p = 0.049) and 3.03-fold (95% CI = 1.152-7.977, p = 0.025) increased risk of prostate cancer diagnosis, respectively. There was also a significant negative correlation between LTL and M-MDSC. (r = -0.347, p < 0.001).<br><br>CONCLUSIONS: Our research has established a correlation between LTL and MDSC in patients undergoing biopsy for prostate cancer. Notably, we observed that individuals with localized prostate cancer tend to have shorter LTL and a higher percentage of M-MDSC prior to their diagnosis. These findings suggest that LTL and M-MDSC could potentially serve as adjunctive biomarkers for the early diagnosis of prostate cancer.},
}
@article {pmid38610915,
year = {2024},
author = {Moustakli, E and Zikopoulos, A and Skentou, C and Dafopoulos, S and Stavros, S and Dafopoulos, K and Drakakis, P and Georgiou, I and Zachariou, A},
title = {Association of Obesity with Telomere Length in Human Sperm.},
journal = {Journal of clinical medicine},
volume = {13},
number = {7},
pages = {},
doi = {10.3390/jcm13072150},
pmid = {38610915},
issn = {2077-0383},
abstract = {Background: Telomere attrition and mitochondrial dysfunction are two fundamental aspects of aging. Calorie restriction (CR) is the best strategy to postpone aging since it can enhance telomere attrition, boost antioxidant capacity, and lower the generation of reactive oxygen species (ROS). Since ROS is produced by mitochondria and can readily travel to cell nuclei, it is thought to be a crucial molecule for information transfer between mitochondria and cell nuclei. Important variables that affect the quality and functionality of sperm and may affect male reproductive health and fertility include telomere length, mitochondrial content, and the ratio of mitochondrial DNA (mtDNA) to nuclear DNA (nDNA). Telomere damage results from mitochondrial failure, whereas nuclear DNA remains unaffected. This research aims to investigate potential associations between these three variables and how they might relate to body mass index. Methods: Data were collected from 82 men who underwent IVF/ICSI at the University Hospital of Ioannina's IVF Unit in the Obstetrics and Gynecology Department. Evaluations included sperm morphology, sperm count, sperm motility, and participant history. To address this, male participants who were categorized into three body mass index (ΒΜΙ) groups-normal, overweight, and obese-had their sperm samples tested. Results: For both the normal and overweight groups, our results show a negative connection between relative telomere length and ΒΜI. As an illustration of a potential connection between mitochondrial health and telomere maintenance, a positive correlation was found for the obese group. Only the obese group's results were statistically significant (p < 0.05). More evidence that longer telomeres are associated with lower mitochondrial content can be found in the negative connection between telomere length and mitochondrial content in both the normal and overweight groups. However, the obese group showed a positive association. The data did not reach statistical significance for any of the three groups. These associations may affect sperm quality since telomere length and mitochondrial concentration are indicators of cellular integrity and health. Moreover, the ratio of mtDNA to nDNA was positively correlated with the relative telomere lengths of the obese group, but negatively correlated with the normal and overweight groups. In every group that was studied, the results were not statistically significant. According to this, male fertility may be negatively impacted by an imbalance in the copy number of the mitochondrial genome compared to the nuclear DNA in sperm. Conclusions: Essentially, the goal of our work is to determine whether mitochondria and telomere length in human sperm interact. Understanding these connections may aid in the explanation of some male infertility causes and possibly contribute to the creation of new treatment modalities for problems pertaining to reproductive health. The functional implications of these connections and their applications in therapeutic settings require further investigation.},
}
@article {pmid38607251,
year = {2024},
author = {Wang, B and Xiong, Y and Li, R and Zhang, J and Zhang, S},
title = {Shorter telomere length increases the risk of lymphocyte immunodeficiency: A Mendelian randomization study.},
journal = {Immunity, inflammation and disease},
volume = {12},
number = {4},
pages = {e1251},
doi = {10.1002/iid3.1251},
pmid = {38607251},
issn = {2050-4527},
support = {2020SF-072//Key project of Research and development program of Shaanxi Province/ ; YXJLRH2022062//Innovation project for medical Integration in Xi'an Jiaotong University/ ; 2020YJ(ZYTS)018//Free exploration project of the second affiliated hospital of Xi'an Jiaotong University/ ; },
abstract = {BACKGROUND: For a long time, the prevailing viewpoint suggests that shorter telomere contribute to chromosomal instability, which is a shared characteristic of both aging and cancer. The newest research presented that T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to some cancers. However, the relationship between genetically determined telomere length (TL) and immune cells remains unclear.<br><br>METHODS: The two-sample Mendelian randomization analysis was conducted to elucidate the potential causal relationship. The genetic data of TL and immune cells were obtained from the Genome-Wide Association Study. The inverse variance weighted (IVW) method was used to estimate the effects primarily and another four methods were as a supplement. Sensitivity analysis was used to test the results.<br><br>RESULTS: The IVW method showed a significant correlation between TL and the percentage of T cells in lymphocytes (odds ratio [OR]: 1.222, 95% confidence interval [CI]: 1.014-1.472, p&#x2009;=&#x2009;.035), indicating that shorter TL significantly increases the risk of low T cell percentage. Further analysis of T cell subsets indicated that shorter TL may primarily lead to a lower percentage of Natural Killer T cells (OR: 1.574, 95% CI: 1.281-1.935, p&#x2009;<&#x2009;.001). Analysis of B cell subsets revealed that shorter TL may be associated with a higher percentage of Naive-mature B cells, and a lower percentage of Memory B cells. And the sensitivity analysis indicated the validity and robustness of our findings.<br><br>CONCLUSION: In summary, our findings suggest that shorter TL may be associated with a decline in the percentage of T cell, as well as impediments in the differentiation of B cell, consequently leading to the onset of immunosenescence and immunodeficiency. The relevant mechanisms and potential therapeutic avenues still need further investigation.},
}
@article {pmid38606545,
year = {2024},
author = {Nitschke, NJ and Jelsig, AM and Lautrup, C and Lundsgaard, M and Severinsen, MT and Cowland, JB and Maroun, LL and Andersen, MK and Grønbæk, K},
title = {Expanding the understanding of telomere biology disorder with reports from two families harboring variants in ZCCHC8 and TERC.},
journal = {Clinical genetics},
volume = {},
number = {},
pages = {},
doi = {10.1111/cge.14534},
pmid = {38606545},
issn = {1399-0004},
support = {//Rigshospitalet/ ; R302-A17259//Kr&#xe6;ftens Bek&#xe6;mpelse/ ; R223-A13071//Kr&#xe6;ftens Bek&#xe6;mpelse/ ; },
abstract = {Telomere biology disorder (TBD) can present within a wide spectrum of symptoms ranging from severe congenital malformations to isolated organ dysfunction in adulthood. Diagnosing TBD can be challenging given the substantial variation in symptoms and age of onset across generations. In this report, we present two families, one with a pathogenic variant in ZCCHC8 and another with a novel variant in TERC. In the literature, only one family has previously been reported with a ZCCHC8 variant and TBD symptoms. This family had multiple occurrences of pulmonary fibrosis and one case of bone marrow failure. In this paper, we present a second family with the same ZCCHC8 variant (p.Pro186Leu) and symptoms of TBD including pulmonary fibrosis, hematological disease, and elevated liver enzymes. The suspicion of TBD was confirmed with the measurement of short telomeres in the proband. In another family, we report a novel likely pathogenic variant in TERC. Our comprehensive description encompasses hematological manifestations, as well as pulmonary and hepatic fibrosis. Notably, there are no other reports which associate this variant to disease. The families expand our understanding of the clinical implications and genetic causes of TBD.},
}
@article {pmid38605518,
year = {2024},
author = {Jia, KH and Zhang, X and Li, LL and Shi, TL and Liu, D and Yang, Y and Cong, Y and Li, R and Pu, Y and Gong, Y and Chen, X and Si, YJ and Tian, R and Qian, Z and Ding, H and Li, N},
title = {Telomere-to-telomere cultivated and wild soybean genome assembly provides insights into evolution and domestication under structural variation.},
journal = {Plant communications},
volume = {},
number = {},
pages = {100919},
doi = {10.1016/j.xplc.2024.100919},
pmid = {38605518},
issn = {2590-3462},
}
@article {pmid38603928,
year = {2024},
author = {Chang, CH and Hwang, PA},
title = {Low-molecular-weight fucoidan increases telomere length and immunostimulatory effects on NK-92 cells following inhaled anesthetic injury.},
journal = {Mutation research},
volume = {828},
number = {},
pages = {111857},
doi = {10.1016/j.mrfmmm.2024.111857},
pmid = {38603928},
issn = {1873-135X},
abstract = {Inhaled anesthetics, such as isoflurane, may cause side effects, including short-term immunosuppression and DNA damage. In contrast, low molecular weight fucoidan (LMF), derived from brown seaweed, exhibits promising immunomodulatory effects. In this study, we determined the effect of isoflurane on telomeres and examined the potential of LMF to ameliorate the harmful effects of isoflurane. Male Lewis rats, the mouse lymphoma cell line YAC-1, and the human nature killer cell line NK-92 MI were exposed to isoflurane. The relative telomere length (T/S) ratio and mRNA expression were determined by quantitative PCR. The viability assay was used to assess cell viability. In vivo, 2% isoflurane exposure, which is a clinically relevant concentration, reduced telomere length, and correlated with exposure frequency and duration. Isoflurane concentrations above 2% shortened YAC-1 telomeres, with minimal impact on cell viability. LMF pre-treatment enhanced NK-92 MI cell survival resulting from isoflurane exposure and exerted superior telomere protection compared with LMF post-treatment. Furthermore, adding LMF during isoflurane exposure resulted in a significant increase in IFN-γ, TNF-α, and IL-10 mRNA compared with the untreated group. LMF protected against isoflurane-induced telomere shortening, enhanced NK cell viability, and modulated cytokine expression, thus mitigating postoperative immune suppression and risk of tumor metastasis.},
}
@article {pmid38603523,
year = {2024},
author = {Karimian, K and Groot, A and Huso, V and Kahidi, R and Tan, KT and Sholes, S and Keener, R and McDyer, JF and Alder, JK and Li, H and Rechtsteiner, A and Greider, CW},
title = {Human telomere length is chromosome end-specific and conserved across individuals.},
journal = {Science (New York, N.Y.)},
volume = {},
number = {},
pages = {eado0431},
doi = {10.1126/science.ado0431},
pmid = {38603523},
issn = {1095-9203},
abstract = {Short telomeres cause age-related disease and long telomeres predispose to cancer; however, the mechanisms regulating telomere length are unclear. We developed a nanopore-based method, Telomere Profiling, to determine telomere length at nearly single nucleotide resolution. Mapping telomere reads to chromosome ends showed chromosome end-specific length distributions that could differ by more than six kilobases. Telomere lengths in 147 individuals showed certain chromosome ends were consistently longer or shorter. The same rank order was found in newborn cord blood, suggesting that telomere length is determined at birth and chromosome end-specific telomere length differences are maintained as telomeres shorten with age. Telomere Profiling makes precision investigation of telomere length widely accessible for laboratory, clinical, and drug discovery efforts and will allow deeper insights into telomere biology.},
}
@article {pmid38600880,
year = {2024},
author = {Gao, Y and Xu, DD and Hu, Z},
title = {Telomere-to-telomere genome assembly of Oldenlandia diffusa.},
journal = {DNA research : an international journal for rapid publication of reports on genes and genomes},
volume = {},
number = {},
pages = {},
doi = {10.1093/dnares/dsae012},
pmid = {38600880},
issn = {1756-1663},
abstract = {We report the complete telomere-to-telomere genome assembly of Oldenlandia diffusa which renowned in traditional Chinese medicine, comprising 16 chromosomes and spanning 499.7 Mb. The assembly showcases 28 telomeres and minimal gaps, with a total of only five. Repeat sequences constitute 46.41% of the genome, and 49,701 potential protein-coding genes have been predicted. Compared with O. corymbosa, O. diffusa exhibits chromosome duplication and fusion events, diverging 20.34 million years ago. Additionally, a total of 11 clusters of terpene synthase have been identified. The comprehensive genome sequence, gene catalog, and terpene synthase clusters of O. diffusa detailed in this study will significantly contribute to advancing research in this species' genetic, genomic, and pharmacological aspects.},
}
@article {pmid38600443,
year = {2024},
author = {Wang, B and Jia, Y and Dang, N and Yu, J and Bush, SJ and Gao, S and He, W and Wang, S and Guo, H and Yang, X and Ma, W and Ye, K},
title = {Near telomere-to-telomere genome assemblies of two Chlorella species unveil the composition and evolution of centromeres in green algae.},
journal = {BMC genomics},
volume = {25},
number = {1},
pages = {356},
pmid = {38600443},
issn = {1471-2164},
support = {32200510//National Natural Science Foundation of China/ ; 2022YFC3400300//National Key Research and Development Program of China/ ; },
abstract = {BACKGROUND: Centromeres play a crucial and conserved role in cell division, although their composition and evolutionary history in green algae, the evolutionary ancestors of land plants, remains largely unknown.<br><br>RESULTS: We constructed near telomere-to-telomere (T2T) assemblies for two Trebouxiophyceae species, Chlorella sorokiniana NS4-2 and Chlorella pyrenoidosa DBH, with chromosome numbers of 12 and 13, and genome sizes of 58.11 Mb and 53.41 Mb, respectively. We identified and validated their centromere sequences using CENH3 ChIP-seq and found that, similar to humans and higher plants, the centromeric CENH3 signals of green algae display a pattern of hypomethylation. Interestingly, the centromeres of both species largely comprised transposable elements, although they differed significantly in their composition. Species within the Chlorella genus display a more diverse centromere composition, with major constituents including members of the LTR/Copia, LINE/L1, and LINE/RTEX families. This is in contrast to green algae including Chlamydomonas reinhardtii, Coccomyxa subellipsoidea, and Chromochloris zofingiensis, in which centromere composition instead has a pronounced single-element composition. Moreover, we observed significant differences in the composition and structure of centromeres among chromosomes with strong collinearity within the Chlorella genus, suggesting that centromeric sequence evolves more rapidly than sequence in non-centromeric regions.<br><br>CONCLUSIONS: This study not only provides high-quality genome data for comparative genomics of green algae but gives insight into the composition and evolutionary history of centromeres in early plants, laying an important foundation for further research on their evolution.},
}
@article {pmid38593805,
year = {2024},
author = {Jiang, H and Zhang, T and Kaur, H and Shi, T and Krishnan, A and Kwon, Y and Sung, P and Greenberg, RA},
title = {BLM helicase unwinds lagging strand substrates to assemble the ALT telomere damage response.},
journal = {Molecular cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molcel.2024.03.011},
pmid = {38593805},
issn = {1097-4164},
abstract = {The Bloom syndrome (BLM) helicase is critical for alternative lengthening of telomeres (ALT), a homology-directed repair (HDR)-mediated telomere maintenance mechanism that is prevalent in cancers of mesenchymal origin. The DNA substrates that BLM engages to direct telomere recombination during ALT remain unknown. Here, we determine that BLM helicase acts on lagging strand telomere intermediates that occur specifically in ALT-positive cells to assemble a replication-associated DNA damage response. Loss of ATRX was permissive for BLM localization to ALT telomeres in S and G2, commensurate with the appearance of telomere C-strand-specific single-stranded DNA (ssDNA). DNA2 nuclease deficiency increased 5'-flap formation in a BLM-dependent manner, while telomere C-strand, but not G-strand, nicks promoted ALT. These findings define the seminal events in the ALT DNA damage response, linking aberrant telomeric lagging strand DNA replication with a BLM-directed HDR mechanism that sustains telomere length in a subset of human cancers.},
}
@article {pmid38594465,
year = {2024},
author = {Shou, S and Li, Y and Chen, J and Zhang, X and Zhang, C and Jiang, X and Liu, F and Yi, L and Zhang, X and Geer, E and Pu, Z and Pang, B},
title = {Understanding, diagnosing, and treating pancreatic cancer from the perspective of telomeres and telomerase.},
journal = {Cancer gene therapy},
volume = {},
number = {},
pages = {},
pmid = {38594465},
issn = {1476-5500},
abstract = {Telomerase is associated with cellular aging, and its presence limits cellular lifespan. Telomerase by preventing telomere shortening can extend the number of cell divisions for cancer cells. In adult pancreatic cells, telomeres gradually shorten, while in precancerous lesions of cancer, telomeres in cells are usually significantly shortened. At this time, telomerase is still in an inactive state, and it is not until before and after the onset of cancer that telomerase is reactivated, causing cancer cells to proliferate. Methylation of the telomerase reverse transcriptase (TERT) promoter and regulation of telomerase by lactate dehydrogenase B (LDHB) is the mechanism of telomerase reactivation in pancreatic cancer. Understanding the role of telomeres and telomerase in pancreatic cancer will help to diagnose and initiate targeted therapy as early as possible. This article reviews the role of telomeres and telomerase as biomarkers in the development of pancreatic cancer and the progress of research on telomeres and telomerase as targets for therapeutic intervention.},
}
@article {pmid38593475,
year = {2024},
author = {Teixeira, GA and Travenzoli, NM and Tavares, MG},
title = {Chromosomal organization of different repetitive sequences in four wasp species of the genus Trypoxylon Latreille (Hymenoptera: Crabronidae) and insights into the composition of wasp telomeres.},
journal = {Genome},
volume = {},
number = {},
pages = {},
doi = {10.1139/gen-2023-0132},
pmid = {38593475},
issn = {1480-3321},
abstract = {This study characterizes the chromosomal organization of DNA repetitive sequences and the karyotypic evolution in four representatives of the solitary wasp genus Trypoxylon using conventional and molecular cytogenetic techniques. Our findings present the first cytogenetic data for T. rogenhoferi (2n=30) and T. albonigrum (2n=32) while the karyotypes of T. nitidum (2n=30) and T. lactitarse (2n=30) were similar to those described previously. Fluorochrome staining and microsatellite distribution data revealed differences in the constitutive heterochromatin composition among species. Trypoxylon nitidum and T. albonigrum exhibited a single rRNA gene site, potentially representing an ancestral pattern for aculeate Hymenoptera, while T. rogenhoferi and T. lactitarse showed two pericentromeric rRNA gene sites, suggesting amplification events in their ancestral clade. The (TCAGG)n motif hybridized in the terminal regions of the chromosomes in all four Trypoxylon species, which may suggest that this sequence is part of their telomeres. Notably, the presence of this repetitive sequence in the centromeric regions of certain chromosome pairs in two species supports the hypothesis of chromosomal fusions or inversions in the ancestral karyotype of Trypoxylon. The study expands the chromosomal mapping data of repetitive sequences in wasps and offers insights into the dynamic evolutionary landscape of karyotypes in these insects.},
}
@article {pmid38593055,
year = {2024},
author = {Karadağ, A and Dirican, E and Özmerdiven, &#xc7;G and Özen, A and Ayan, S and Kabadere, S},
title = {Evaluation of miR-130b-3p and miR-375 levels and telomere length with telomerase activity in prostate cancer.},
journal = {Nucleosides, nucleotides &amp; nucleic acids},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/15257770.2024.2334896},
pmid = {38593055},
issn = {1532-2335},
abstract = {Prostate cancer (PC) is the most frequent cancer in males, as well as the second highest cause of cancer-related deaths in men. Differences in expression levels of miRNAs were linked with prostat cancer pathogenesis. qPCR was used to evaluate the expression of miR-130b-3p and miR-375 in Benign Prostate Hyperplasia (BPH (n = 20) and PC (n = 22, pre- and post-operative) patients plasma. Relative telomere lengths (RLTs) in genomic DNA isolated from plasma were measured with qPCR, and telomerase activity analyzed by the ELISA method. PSA levels of PC patients were greater than of BPH patients (p = 0.0473). miR-130b-3p and miR-375 levels were significantly lower in pre-operative specimens of PC patients according to BPH (p = 0,0362, p = 0.0168, respectively). Similarly, post-operative miR-375 levels were lower in PC patients than in BPH patients (p = 0.1866). BPH patients had shorter RTLs than PC patients in both pre- (p=0.0438) and post-operative (p=0.0297) specimens. Telomerase activity was higher in PC patients than BPH(p = 0.0129). Interestingly, telomerase activity was further increased after surgery (p = 0.0003). We aim to identify the levels of miR-130b-3p and miR-375 expression and their relationship with telomerase activity in PC patients. Our data suggest that miRNAs and telomere length (TL) with telomerase activity may play a role in regulating prostate tumorgenesis and may be used as biomarkers for PC diagnosis.},
}
@article {pmid38588482,
year = {2024},
author = {de la Rosa, R and Le, A and Holm, S and Ye, M and Bush, NR and Hessler, D and Koita, K and Bucci, M and Long, D and Thakur, N},
title = {Associations Between Early-Life Adversity, Ambient Air Pollution, and Telomere Length in Children.},
journal = {Psychosomatic medicine},
volume = {},
number = {},
pages = {},
doi = {10.1097/PSY.0000000000001276},
pmid = {38588482},
issn = {1534-7796},
abstract = {OBJECTIVE: Examine the independent associations and interaction between early-life adversity and residential ambient air pollution exposure on relative buccal telomere length (rBTL).<br><br>METHODS: Experiences of abuse, neglect, household challenges, and related life events were identified in a cross-sectional sample of children ages 1-11 years (n = 197) using the 17-item Pediatric ACEs and Related Life Event Screener (PEARLS) tool. The PEARLS tool was analyzed both as a total score and across established domains (Maltreatment, Household Challenges, and Social Context). Ground-level fine particulate matter (PM2.5) concentrations were matched to residential locations for the one and twelve months prior to biospecimen collection. We used multivariable linear regression models to examine for independent associations between continuous PM2.5 exposure and PEARLS score/domains with rBTL. Additionally, effect modification by PEARLS scores and domains on associations between PM2.5 exposure and rBTL was examined.<br><br>RESULTS: Study participants were 47% girls, with mean age = 5.9 years [standard deviation: 3.4] median reported PEARLS score of 2 [interquartile range (IQR): 4], median 12-month prior PM2.5 concentrations of 11.8 &#x3bc;g/m3 [IQR: 2.7], median 1-month prior PM2.5 concentrations of 10.9 &#x3bc;g/m3 [IQR: 5.8], and rBTL of 0.1 [IQR: 0.03]. Mean 12-month prior PM2.5 exposure was inversely associated with rBTL (&#xdf; = -0.02, 95% CI: -0.04, -0.01). While reported PEARLS scores and domains were not independently associated with rBTL, we observed a greater decrement in rBTL with increment of average annual PM2.5 as reported Social Context domain items increased (p-interaction<0.05).<br><br>CONCLUSION: Our results suggest that adverse Social Context factors may accelerate the association between chronic PM2.5 exposure on telomere shortening during childhood.},
}
@article {pmid38588418,
year = {2024},
author = {Padmanaban, S and Lambacher, NJ and Tesmer, VM and Zhang, J and Shibuya, H and Nandakumar, J},
title = {Caenorhabditis elegans telomere-binding proteins TEBP-1 and TEBP-2 adapt the Myb module to dimerize and bind telomeric DNA.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {121},
number = {16},
pages = {e2316651121},
doi = {10.1073/pnas.2316651121},
pmid = {38588418},
issn = {1091-6490},
support = {R01HD108809//HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/ ; R35GM148276//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; 211377Pj//Cancerfonden (Swedish Cancer Society)/ ; },
abstract = {Protecting chromosome ends from misrecognition as double-stranded (ds) DNA breaks is fundamental to eukaryotic viability. The protein complex shelterin prevents a DNA damage response at mammalian telomeres. Mammalian shelterin proteins TRF1 and TRF2 and their homologs in yeast and protozoa protect telomeric dsDNA. N-terminal homodimerization and C-terminal Myb-domain-mediated dsDNA binding are two structural hallmarks of end protection by TRF homologs. Yet our understanding of how Caenorhabditis elegans protects its telomeric dsDNA is limited. Recently identified C. elegans proteins TEBP-1 (also called DTN-1) and TEBP-2 (also called DTN-2) are functional homologs of TRF proteins, but how they bind DNA and whether or how they dimerize is not known. TEBP-1 and TEBP-2 harbor three Myb-containing domains (MCDs) and no obvious dimerization domain. We demonstrate biochemically that only the third MCD binds DNA. We solve the X-ray crystal structure of TEBP-2 MCD3 with telomeric dsDNA to reveal the structural mechanism of telomeric dsDNA protection in C. elegans. Mutagenesis of the DNA-binding site of TEBP-1 and TEBP-2 compromises DNA binding in vitro, and increases DNA damage signaling, lengthens telomeres, and decreases brood size in vivo. Via an X-ray crystal structure, biochemical validation of the dimerization interface, and SEC-MALS analysis, we demonstrate that MCD1 and MCD2 form a composite dimerization module that facilitates not only TEBP-1 and TEBP-2 homodimerization but also heterodimerization. These findings provide fundamental insights into C. elegans telomeric dsDNA protection and highlight how different eukaryotes have evolved distinct strategies to solve the chromosome end protection problem.},
}
@article {pmid38587381,
year = {2024},
author = {Martin, NA and McLester-Davis, LWY and Roy, TR and Magruder, MG and Hastings, WJ and Drury, SS},
title = {Monochrome Multiplex Quantitative PCR Telomere Length Measurement.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {205},
pages = {},
doi = {10.3791/66545},
pmid = {38587381},
issn = {1940-087X},
abstract = {Telomeres are ribonucleoprotein structures at the end of all eukaryotic chromosomes that protect DNA from damage and preserve chromosome stability. Telomere length (TL) has been associated with various exposures, biological processes, and health outcomes. This article describes the monochrome multiplex quantitative polymerase chain reaction (MMqPCR) assay protocol routinely conducted in our laboratory for measuring relative mean TL from human DNA. There are several different PCR-based TL measurement methods, but the specific protocol for the MMqPCR method presented in this publication is repeatable, efficient, cost-effective, and suitable for population-based studies. This detailed protocol outlines all information necessary for investigators to establish this assay in their laboratory. In addition, this protocol provides specific steps to increase the reproducibility of TL measurement by this assay, defined by the intraclass correlation coefficient (ICC) across repeated measurements of the same sample. The ICC is a critical factor in evaluating expected power for a specific study population; as such, reporting cohort-specific ICCs for any TL assay is a necessary step to enhance the overall rigor of population-based studies of TL. Example results utilizing DNA samples extracted from peripheral blood mononuclear cells demonstrate the feasibility of generating highly repeatable TL data using this MMqPCR protocol.},
}
@article {pmid38587189,
year = {2024},
author = {Lee, JJ and Kim, H and Park, H and Lee, U and Kim, C and Lee, M and Shin, Y and Jung, JJ and Lee, HB and Han, W and Lee, H},
title = {Disruption of G-quadruplex dynamicity by BRCA2 abrogation instigates phase separation and break-induced replication at telomeres.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae251},
pmid = {38587189},
issn = {1362-4962},
support = {2020R1A5A1018081//National Research Foundation of Korea/ ; //Hyundai Motor Chung Mong-Koo Foundation/ ; },
abstract = {Dynamic interaction between BRCA2 and telomeric G-quadruplexes (G4) is crucial for maintaining telomere replication homeostasis. Cells lacking BRCA2 display telomeric damage with a subset of these cells bypassing senescence to initiate break-induced replication (BIR) for telomere synthesis. Here we show that the abnormal stabilization of telomeric G4 following BRCA2 depletion leads to telomeric repeat-containing RNA (TERRA)-R-loop accumulation, triggering liquid-liquid phase separation (LLPS) and the assembly of Alternative Lengthening of Telomeres (ALT)-associated promyelocytic leukemia (PML) bodies (APBs). Disruption of R-loops abolishes LLPS and impairs telomere synthesis. Artificial engineering of telomeric LLPS restores telomere synthesis, underscoring the critical role of LLPS in ALT. TERRA-R-loops also recruit Polycomb Repressive Complex 2 (PRC2), leading to tri-methylation of Lys27 on histone H3 (H3K27me3) at telomeres. Half of paraffin-embedded tissue sections from human breast cancers exhibit APBs and telomere length heterogeneity, suggesting that BRCA2 mutations can predispose individuals to ALT-type tumorigenesis. Overall, BRCA2 abrogation disrupts the dynamicity of telomeric G4, producing TERRA-R-loops, finally leading to the assembly of telomeric liquid condensates crucial for ALT. We propose that modulating the dynamicity of telomeric G4 and targeting TERRA-R-loops in telomeric LLPS maintenance may represent effective therapeutic strategies for treating ALT-like cancers with APBs, including those with BRCA2 disruptions.},
}
@article {pmid38584235,
year = {2024},
author = {Lagunas-Rangel, FA},
title = {Giardia telomeres and telomerase.},
journal = {Parasitology research},
volume = {123},
number = {4},
pages = {179},
pmid = {38584235},
issn = {1432-1955},
abstract = {Giardia duodenalis, the protozoan responsible for giardiasis, is a significant contributor to millions of diarrheal diseases worldwide. Despite the availability of treatments for this parasitic infection, therapeutic failures are alarmingly frequent. Thus, there is a clear need to identify new therapeutic targets. Giardia telomeres were previously identified, but our understanding of these structures and the critical role played by Giardia telomerase in maintaining genomic stability and its influence on cellular processes remains limited. In this regard, it is known that all Giardia chromosomes are capped by small telomeres, organized and protected by specific proteins that regulate their functions. To counteract natural telomere shortening and maintain high proliferation, Giardia exhibits constant telomerase activity and employs additional mechanisms, such as the formation of G-quadruplex structures and the involvement of transposable elements linked to telomeric repeats. Thus, this study aims to address the existing knowledge gap by compiling the available information (until 2023) about Giardia telomeres and telomerase, focusing on highlighting the distinctive features within this parasite. Furthermore, the potential feasibility of targeting Giardia telomeres and/or telomerase as an innovative therapeutic strategy is discussed.},
}
@article {pmid38581556,
year = {2024},
author = {Mason, CE and Sierra, MA and Feng, HJ and Bailey, SM},
title = {Telomeres and aging: on and off the planet!.},
journal = {Biogerontology},
volume = {25},
number = {2},
pages = {313-327},
pmid = {38581556},
issn = {1573-6768},
abstract = {Improving human healthspan in our rapidly aging population has never been more imperative. Telomeres, protective "caps" at the ends of linear chromosomes, are essential for maintaining genome stability of eukaryotic genomes. Due to their physical location and the "end-replication problem" first envisioned by Dr. Alexey Olovnikov, telomeres shorten with cell division, the implications of which are remarkably profound. Telomeres are hallmarks and molecular drivers of aging, as well as fundamental integrating components of the cumulative effects of genetic, lifestyle, and environmental factors that erode telomere length over time. Ongoing telomere attrition and the resulting limit to replicative potential imposed by cellular senescence serves a powerful tumor suppressor function, and also underlies aging and a spectrum of age-related degenerative pathologies, including reduced fertility, dementias, cardiovascular disease and cancer. However, very little data exists regarding the extraordinary stressors and exposures associated with long-duration space exploration and eventual habitation of other planets, nor how such missions will influence telomeres, reproduction, health, disease risk, and aging. Here, we briefly review our current understanding, which has advanced significantly in recent years as a result of the NASA Twins Study, the most comprehensive evaluation of human health effects associated with spaceflight ever conducted. Thus, the Twins Study is at the forefront of personalized space medicine approaches for astronauts and sets the stage for subsequent missions. We also extrapolate from current understanding to future missions, highlighting potential biological and biochemical strategies that may enable human survival, and consider the prospect of longevity in the extreme environment of space.},
}
@article {pmid38580193,
year = {2024},
author = {Yun, JJ and Unai, S and Budev, MM and Anandamurthy, B and Almeida, F and Turowski, J and McCurry, KR and Pettersson, G},
title = {Salvage Lung Retransplantation: En-Bloc Double Lung with Bronchial Artery Revascularization For Bronchial Dehiscence Related to Short Telomeres.},
journal = {The Journal of thoracic and cardiovascular surgery},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtcvs.2024.03.026},
pmid = {38580193},
issn = {1097-685X},
}
@article {pmid38577209,
year = {2024},
author = {Rodseth, E and Sumasgutner, P and Tate, G and Nilsson, JF and Watson, H and Maritz, MF and Ingle, RA and Amar, A},
title = {Pleiotropic effects of melanin pigmentation: haemoparasite infection intensity but not telomere length is associated with plumage morph in black sparrowhawks.},
journal = {Royal Society open science},
volume = {11},
number = {4},
pages = {230370},
pmid = {38577209},
issn = {2054-5703},
abstract = {There is increasing recognition of the potential pleiotropic effects of melanin pigmentation, particularly on immunity, with reports of variation in haemoparasite infection intensity and immune responses between the morphs of colour-polymorphic bird species. In a population of the black sparrowhawk (Accipiter melanoleucus) in western South Africa, light morphs have a higher haemoparasite infection intensity, but no physiological effects of this are apparent. Here, we investigate the possible effects of haemoparasite infection on telomere length in this species and explore whether relative telomere length is associated with either plumage morph or sex. Using quantitative polymerase chain reaction analysis, we confirmed that dark morphs had a lower haemoparasite infection intensity than light morphs. However, we found no differences in telomere length associated with either the haemoparasite infection status or morph in adults, although males have longer telomeres than females. While differences in haemoparasite intensity between morphs are consistent with pleiotropic effects of melanin pigmentation in the black sparrowhawk, we found no evidence that telomere length was associated with haemoparasite infection. Further work is needed to investigate the implications of possible pleiotropic effects of plumage morph and their potential role in the maintenance of colour polymorphism in this species.},
}
@article {pmid38577142,
year = {2024},
author = {Prasad, R and Kaur, G},
title = {Recent Domains in Telomere and Telomerase Targeting for Accomplished Cancer Therapy.},
journal = {Indian journal of clinical biochemistry : IJCB},
volume = {39},
number = {2},
pages = {151-153},
pmid = {38577142},
issn = {0970-1915},
}
@article {pmid38574731,
year = {2024},
author = {LaBella, KA and Hsu, WH and Li, J and Qi, Y and Liu, Y and Liu, J and Wu, CC and Liu, Y and Song, Z and Lin, Y and Blecher, JM and Jiang, S and Shang, X and Han, J and Spring, DJ and Zhang, J and Xia, Y and DePinho, RA},
title = {Telomere dysfunction alters intestinal stem cell dynamics to promote cancer.},
journal = {Developmental cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.devcel.2024.03.020},
pmid = {38574731},
issn = {1878-1551},
abstract = {Telomere dynamics are linked to aging hallmarks, and age-associated telomere loss fuels the development of epithelial cancers. In Apc-mutant mice, the onset of DNA damage associated with telomere dysfunction has been shown to accelerate adenoma initiation via unknown mechanisms. Here, we observed that Apc-mutant mice engineered to experience telomere dysfunction show accelerated adenoma formation resulting from augmented cell competition and clonal expansion. Mechanistically, telomere dysfunction induces the repression of EZH2, resulting in the derepression of Wnt antagonists, which causes the differentiation of adjacent stem cells and a relative growth advantage to Apc-deficient telomere dysfunctional cells. Correspondingly, in this mouse model, GSK3β inhibition countered the actions of Wnt antagonists on intestinal stem cells, resulting in impaired adenoma formation of telomere dysfunctional Apc-mutant cells. Thus, telomere dysfunction contributes to cancer initiation through altered stem cell dynamics, identifying an interception strategy for human APC-mutant cancers with shortened telomeres.},
}
@article {pmid38566416,
year = {2024},
author = {Amiard, S and Feit, L and Vanrobays, E and Simon, L and Le Goff, S and Loizeau, L and Wolff, L and Butter, F and Bourbousse, C and Barneche, F and Tatout, C and Probst, AV},
title = {The TELOMERE REPEAT BINDING proteins TRB4 and TRB5 function as transcriptional activators of PRC2-controlled genes to regulate plant development.},
journal = {Plant communications},
volume = {},
number = {},
pages = {100890},
doi = {10.1016/j.xplc.2024.100890},
pmid = {38566416},
issn = {2590-3462},
abstract = {Plant-specific transcriptional regulators called TELOMERE REPEAT BINDING proteins (TRBs) combine two DNA-binding domains, the GH1 domain, which binds to linker DNA and is shared with H1 histones, and the Myb/SANT domain, which specifically recognizes the telobox DNA-binding site motif. TRB1, TRB2, and TRB3 proteins recruit Polycomb group complex 2 (PRC2) to deposit H3K27me3 and JMJ14 to remove H3K4me3 at gene promoters containing telobox motifs to repress transcription. Here, we demonstrate that TRB4 and TRB5, two related paralogs belonging to a separate TRB clade conserved in spermatophytes, regulate the transcription of several hundred genes involved in developmental responses to environmental cues. Indeed, TRB4 binds to several thousand sites in the genome, mainly at TSS and promoter regions of transcriptionally active and H3K4me3-marked genes, but unlike TRB1 it is not enriched at H3K27me3-marked gene bodies. Yet, TRB4 can physically interact with the catalytic components of PRC2, SWINGER and CURLY LEAF (CLF). Unexpectedly, we show that TRB4 and TRB5 are required for distinctive phenotypic traits observed in clf mutant plants and accordingly function as transcriptional activators of several hundred of CLF-controlled genes, including key flowering genes. We further demonstrate that TRB4 shares multiple target genes with TRB1 and physically and genetically interacts with members of both TRB clades. Collectively, this study uncovers that TRB proteins engage in both positive and negative interactions with other members of the family to regulate plant development through both PRC2-dependent and independent mechanisms.},
}
@article {pmid38565156,
year = {2024},
author = {Ravindran, S and Underwood, SL and Dorrens, J and Seeker, LA and Watt, K and Wilbourn, RV and Sparks, AM and Sinclair, R and Chen, Z and Pilkington, JG and McNeilly, TN and Harrington, L and Pemberton, JM and Nussey, DH and Froy, H},
title = {No correlative evidence of costs of infection or immunity on leucocyte telomere length in a wild population of Soay sheep.},
journal = {Proceedings. Biological sciences},
volume = {291},
number = {2020},
pages = {20232946},
doi = {10.1098/rspb.2023.2946},
pmid = {38565156},
issn = {1471-2954},
abstract = {Telomere length (TL) is a biomarker hypothesized to capture evolutionarily and ecologically important physiological costs of reproduction, infection and immunity. Few studies have estimated the relationships among infection status, immunity, TL and fitness in natural systems. The hypothesis that short telomeres predict reduced survival because they reflect costly consequences of infection and immune investment remains largely untested. Using longitudinal data from a free-living Soay sheep population, we tested whether leucocyte TL was predicted by infection with nematode parasites and antibody levels against those parasites. Helminth parasite burdens were positively associated with leucocyte TL in both lambs and adults, which is not consistent with TL reflecting infection costs. We found no association between TL and helminth-specific IgG levels in either young or old individuals which suggests TL does not reflect costs of an activated immune response or immunosenescence. Furthermore, we found no support for TL acting as a mediator of trade-offs between infection, immunity and subsequent survival in the wild. Our results suggest that while variation in TL could reflect short-term variation in resource investment or environmental conditions, it does not capture costs of infection and immunity, nor does it behave like a marker of an individual's helminth-specific antibody immune response.},
}
@article {pmid38565848,
year = {2024},
author = {Muoio, D and Laspata, N and Dannenberg, RL and Curry, C and Darkoa-Larbi, S and Hedglin, M and Uttam, S and Fouquerel, E},
title = {PARP2 promotes Break Induced Replication-mediated telomere fragility in response to replication stress.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {2857},
pmid = {38565848},
issn = {2041-1723},
support = {R35GM142982//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; },
abstract = {PARP2 is a DNA-dependent ADP-ribosyl transferase (ARTs) enzyme with Poly(ADP-ribosyl)ation activity that is triggered by DNA breaks. It plays a role in the Base Excision Repair pathway, where it has overlapping functions with PARP1. However, additional roles for PARP2 have emerged in the response of cells to replication stress. In this study, we demonstrate that PARP2 promotes replication stress-induced telomere fragility and prevents telomere loss following chronic induction of oxidative DNA lesions and BLM helicase depletion. Telomere fragility results from the activity of the break-induced replication pathway (BIR). During this process, PARP2 promotes DNA end resection, strand invasion and BIR-dependent mitotic DNA synthesis by orchestrating POLD3 recruitment and activity. Our study has identified a role for PARP2 in the response to replication stress. This finding may lead to the development of therapeutic approaches that target DNA-dependent ART enzymes, particularly in cancer cells with high levels of replication stress.},
}
@article {pmid38565642,
year = {2024},
author = {Huang, R and Bornman, MSR and Stricker, PD and Simoni Brum, I and Mutambirwa, SBA and Jaratlerdsiri, W and Hayes, VM},
title = {The impact of telomere length on prostate cancer aggressiveness, genomic instability and health disparities.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {7706},
pmid = {38565642},
issn = {2045-2322},
support = {International Research Training Program Scholarship//Australian Government/ ; APP2001098//National Health and Medical Research Council/ ; APP2001098//National Health and Medical Research Council/ ; PC210168//Congressionally Directed Medical Research Programs/ ; PC210168//Congressionally Directed Medical Research Programs/ ; Petre Chair//Petre Foundation/ ; },
abstract = {The telomere repetitive TTAGGG motif at the ends of chromosomes, serves to preserve genomic integrity and chromosomal stability. In turn, genomic instability is a hallmark of cancer-implicating telomere disturbance. Prostate cancer (PCa) shows significant ancestral disparities, with men of African ancestry at the greatest risk for aggressive disease and associated genomic instability. Yet, no study has explored the role of telomere length (TL) with respect to ancestrally driven PCa health disparities. Patient- and technically-matched tumour-blood whole genome sequencing data for 179 ancestrally defined treatment naïve PCa patients (117 African, 62 European), we assessed for TL (blood and tumour) associations. We found shortened tumour TL to be associated with aggressive PCa presentation and elevated genomic instabilities, including percentage of genome alteration and copy number gains, in men of African ancestry. For European patients, tumour TL showed significant associations with PCa driver genes PTEN, TP53, MSH2, SETBP1 and DDX11L1, while shorter blood TL (< 3200 base pairs) and tumour TL (< 2861 base pairs) were correlated with higher risk for biochemical recurrence. Concurring with previous studies linking TL to PCa diagnosis and/or prognosis, for the first time we correlated TL differences with patient ancestry with important implications for future treatments targeting telomere dysfunction.},
}
@article {pmid38559121,
year = {2024},
author = {Estrem, B and Davis, RE and Wang, J},
title = {End resection and telomere healing of DNA double-strand breaks during nematode programmed DNA elimination.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.03.15.585292},
pmid = {38559121},
abstract = {Most DNA double-strand breaks (DSBs) are harmful to genome integrity. However, some forms of DSBs are essential to biological processes, such as meiotic recombination and V(D)J recombination. DSBs are also required for programmed DNA elimination (PDE) in ciliates and nematodes. In nematodes, the DSBs are healed with telomere addition. While telomere addition sites have been well-characterized, little is known regarding the DSBs that fragment nematode chromosomes. Here, we used embryos from the nematode Ascaris to study the timing of PDE breaks and examine the DSBs and their end processing. Using END-seq, we characterize the DSB ends and demonstrate that DNA breaks are introduced before mitosis, followed by extensive end resection. The resection profile is unique for each break site, and the resection generates 3' overhangs before the addition of telomeres. Interestingly, telomere healing occurs much more frequently on retained DSB ends than on eliminated ends. This biased repair of the DSB ends in Ascaris may be due to the sequestration of the eliminated DNA into micronuclei, preventing their ends from telomere healing. Additional DNA breaks occur within the eliminated DNA in both Ascaris and Parascaris , ensuring chromosomal breakage and providing a fail-safe mechanism for nematode PDE.},
}
@article {pmid38553835,
year = {2024},
author = {Kirk, B and Kuo, CL and Liu, P and Xiang, M and Earp, JE and Kositsawat, J and Kuchel, GA and Duque, G},
title = {Leukocyte telomere length is associated with MRI-thigh fat-free muscle volume: data from 16 356 UK Biobank adults.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {},
number = {},
pages = {},
doi = {10.1002/jcsm.13461},
pmid = {38553835},
issn = {2190-6009},
support = {NR018963-01A1//National Institute of Nursing Research, National Institute of Health, USA/ ; P30AG067988//National Institute on Aging, National Institute of Health, USA./ ; //TSI Pharmaceuticals/ ; ICG001874//Australian Government (Department of Industry, Science and Resources)/ ; },
abstract = {BACKGROUND: Telomere attrition may share common biological mechanisms with bone and muscle loss with aging. Here, we investigated the association between these hallmarks of aging using data from UK Biobank, a large observational study.<br><br>METHODS: Leukocyte telomere length (LTL as T/S ratio) was measured using a multiplex qPCR assay at baseline (2006-2010). Bone mineral density (whole body and regional; via dual-energy X-ray absorptiometry), trabecular bone score (via lumbar-spine dual-energy X-ray absorptiometry images), fat-free muscle volume (thighs; via magnetic resonance imaging), and muscle fat infiltration (thighs; via magnetic resonance imaging) were measured during the imaging visit (2014-2018). Regression models were used to model LTL against a muscle or bone outcome, unadjusted and adjusted for covariates.<br><br>RESULTS: A total of 16&#xa0;356 adults (mean age: 62.8&#xa0;&#xb1;&#xa0;7.5&#xa0;years, 50.5% women) were included. In the fully adjusted model, thigh fat-free muscle volume was associated with LTL in the overall sample (adjusted standardized &#x3b2; (a&#x3b2;)&#xa0;=&#xa0;0.017, 95% CI 0.009 to 0.026, P&#xa0;<&#xa0;0.001, per SD increase in LTL), with stronger associations in men (a&#x3b2;&#xa0;=&#xa0;0.022, 95% CI 0.010 to 0.034, P&#xa0;<&#xa0;0.001) than in women (a&#x3b2;&#xa0;=&#xa0;0.013, 95% CI 0.000 to 0.025, P&#xa0;=&#xa0;0.041) (sex-LTL P&#xa0;=&#xa0;0.028). The adjusted odds ratio (aOR) for low thigh fat-free muscle volume (body mass index-adjusted, sex-specific bottom 20%) was 0.93 per SD increase in LTL (95% CI 0.89 to 0.96, P&#xa0;<&#xa0;0.001) in the overall sample, with stronger associations in men (aOR&#xa0;=&#xa0;0.92, 95% CI 0.87 to 0.99, P&#xa0;=&#xa0;0.008) than women (aOR&#xa0;=&#xa0;0.93, 95% CI 0.88 to 0.98, P&#xa0;=&#xa0;0.009), although the sex difference was not statistically significant in this model (sex-LTL P&#xa0;=&#xa0;0.37). LTL was not associated with bone mineral density, trabecular bone score, or muscle fat infiltration in the overall or subgroup analyses (P&#xa0;>&#xa0;0.05).<br><br>CONCLUSIONS: LTL was consistently associated with thigh fat-free muscle volume in men and women. Future research should investigate moderating effects of lifestyle factors (e.g., physical activity, nutrition, or chronic diseases) in the association between LTL and muscle volume.},
}
@article {pmid38552826,
year = {2024},
author = {Dehdashti, B and Miri, M and Khanahmad, H and Feizi, A and Mohammadi, F and Rouholamin, S and Amin, MM},
title = {In-Utero exposure to potential sources of indoor air pollution and umbilical cord blood leukocyte telomere length.},
journal = {Environmental research},
volume = {},
number = {},
pages = {118791},
doi = {10.1016/j.envres.2024.118791},
pmid = {38552826},
issn = {1096-0953},
abstract = {Indoor air pollution (IAP) has been associated with various adverse health effects. However, the evidence regarding such an association with leukocyte telomere length (LTL) in cord blood samples is still scarce. Therefore, the present study aimed to assess the relationship between exposure to indicators of IAP and LTL in umbilical cord blood samples. This cross-sectional study was based on 188 mother-newborn pairs who participated in our study between 2020 and 2022 in Isfahan, Iran. Umbilical LTL was measured by quantitative real-time polymerase chain reaction (qRT-PCR) technique. Linear mixed-effect models were used to assess the relationship between IAP indicators and umbilical LTL, adjusted for relevant covariates. The median (interquartile range (IQR)) of umbilical LTL was 0.92 (0.47). In fully adjusted models, frequency of using degreasing spray during pregnancy (times per month) (β = -0.047, 95% CI:0.09, -0.05, P-value = 0.02), using air freshener spray during pregnancy (β = -0.26, 95% CI: -0.5, -0.02, P-value = 0.03) and frequency of using insecticides during pregnancy (times per month) (β = -0.025, 95% CI: -0.047, -0.003, P-value = 0.02) were significantly associated with shorter umbilical LTL. There was a positive significant relationship between the frequency of using cleaning spray during pregnancy (times per month) with umbilical LTL (β = 0.019, 95% CI: 0.005, 0.033, P-value = 0.01). Furthermore, the direct connection of the parking with home and the frequency of using barbecue (times per week) were marginally associated with shorter umbilical LTL. For other indicators of IAP, we did not observe any statistically significant associations. Overall, this study suggested a negative association between prenatal exposure to IAP during pregnancy and umbilical LTL.},
}
@article {pmid38550590,
year = {2024},
author = {Kraft, BD and Verhulst, S and Lai, TP and Sullenger, BA and Wang, Y and Rountree, W and Chen, L and Woods, CW and Denny, TN and Aviv, A},
title = {T-cell count and T-cell telomere length in patients with severe COVID-19.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1356638},
doi = {10.3389/fimmu.2024.1356638},
pmid = {38550590},
issn = {1664-3224},
abstract = {Lymphocyte telomere length (TL) is highly variable and shortens with age. Short telomeres may impede TL-dependent T-cell clonal expansion with viral infection. As SARS-CoV-2 infection can induce prolonged and severe T-cell lymphopenia, infected adults, and particularly older adults with short telomeres, may display severe T-cell lymphopenia. To examine the relationship between T-cell TL parameters and T-cell counts, we studied 40 patients hospitalized with severe COVID-19. T-cells were isolated from lymphocytes, counted using flow cytometry, and their TL parameters were measured using the Telomere Shortest Length Assay. The cohort (median age = 62 years, 27% female) was racially and ethnically diverse (33% White, 35% Black, and 33% Other). On intensive care unit study day 1, T-cell count (mean=1.03 x10[9]/L) was inversely related to age (p=0.007) and higher in females than males (p=0.025). Mean TL was 3.88 kilobases (kb), and 45.3% of telomeres were shorter than 3 kb. Using multiple regression analysis and adjusting for age and sex, T-cell count decreased with increased proportion of T-cell telomeres shorter than 3 kb (p=0.033) and increased with mean TL (p=0.052). Our findings suggest an association between the buildup of short telomeres within T-cells and explain in part reduced peripheral blood T-cell counts in patients with severe COVID-19. Shortened T-cell telomeres may be a risk factor for COVID-19-associated T-cell lymphopenia.},
}
@article {pmid38542157,
year = {2024},
author = {Pochechueva, TV and Schwenzer, N and Kohl, T and Brandenburg, S and Kaltenecker, G and Wollnik, B and Lehnart, SE},
title = {3D Super-Resolution Nuclear Q-FISH Imaging Reveals Cell-Cycle-Related Telomere Changes.},
journal = {International journal of molecular sciences},
volume = {25},
number = {6},
pages = {},
doi = {10.3390/ijms25063183},
pmid = {38542157},
issn = {1422-0067},
support = {EXC 2067//Deutsche Forschungsgemeinschaft/ ; },
abstract = {We present novel workflows for Q-FISH nanoscopy with the potential for prognostic applications and resolving novel chromatin compaction changes. DNA-fluorescence in situ hybridization (DNA-FISH) is a routine application to visualize telomeres, repetitive terminal DNA sequences, in cells and tissues. Telomere attrition is associated with inherited and acquired diseases, including cancer and cardiomyopathies, and is frequently analyzed by quantitative (Q)-FISH microscopy. Recently, nanoscopic imaging techniques have resolved individual telomere dimensions and their compaction as a prognostic marker, in part leading to conflicting conclusions still unresolved to date. Here, we developed a comprehensive Q-FISH nanoscopy workflow to assess telomeres with PNA telomere probes and 3D-Stimulated Emission Depletion (STED) microscopy combined with Dynamic Intensity Minimum (DyMIN) scanning. We achieved single-telomere resolution at high, unprecedented telomere coverage. Importantly, our approach revealed a decrease in telomere signal density during mitotic cell division compared to interphase. Innovatively expanding FISH-STED applications, we conducted double FISH targeting of both telomere- and chromosome-specific sub-telomeric regions and accomplished FISH-STED in human cardiac biopsies. In summary, this work further advanced Q-FISH nanoscopy, detected a new aspect of telomere compaction related to the cell cycle, and laid the groundwork for future applications in complex cell types such as post-mitotic neurons and muscle cells.},
}
@article {pmid38540683,
year = {2024},
author = {Olson, CL and Wuttke, DS},
title = {Guardians of the Genome: How the Single-Stranded DNA-Binding Proteins RPA and CST Facilitate Telomere Replication.},
journal = {Biomolecules},
volume = {14},
number = {3},
pages = {},
doi = {10.3390/biom14030263},
pmid = {38540683},
issn = {2218-273X},
support = {R01 GM139274/NH/NIH HHS/United States ; },
abstract = {Telomeres act as the protective caps of eukaryotic linear chromosomes; thus, proper telomere maintenance is crucial for genome stability. Successful telomere replication is a cornerstone of telomere length regulation, but this process can be fraught due to the many intrinsic challenges telomeres pose to the replication machinery. In addition to the famous "end replication" problem due to the discontinuous nature of lagging strand synthesis, telomeres require various telomere-specific steps for maintaining the proper 3' overhang length. Bulk telomere replication also encounters its own difficulties as telomeres are prone to various forms of replication roadblocks. These roadblocks can result in an increase in replication stress that can cause replication forks to slow, stall, or become reversed. Ultimately, this leads to excess single-stranded DNA (ssDNA) that needs to be managed and protected for replication to continue and to prevent DNA damage and genome instability. RPA and CST are single-stranded DNA-binding protein complexes that play key roles in performing this task and help stabilize stalled forks for continued replication. The interplay between RPA and CST, their functions at telomeres during replication, and their specialized features for helping overcome replication stress at telomeres are the focus of this review.},
}
@article {pmid38540177,
year = {2024},
author = {Younoussa, H and Gadji, M and Soumboundou, M and Colicchio, B and Said, A and Ndoye, NA and Junker, S and Plesch, A and Heidingsfelder, L and Diagne, NR and Dieterlen, A and Voisin, P and Carde, P and Jeandidier, E and M'kacher, R},
title = {Telomere Dysfunction in Pediatric Patients with Differences/Disorders of Sexual Development.},
journal = {Biomedicines},
volume = {12},
number = {3},
pages = {},
doi = {10.3390/biomedicines12030565},
pmid = {38540177},
issn = {2227-9059},
abstract = {UNLABELLED: Differences/Disorders of sex development (DSDs) are conditions in which the development of chromosomal, gonadal, and anatomical sexes is atypical. DSDs are relatively rare, but their incidence is becoming alarmingly common in sub-Saharan Africa (SSA). Their etiologies and mechanisms are poorly understood. Therefore, we have investigated cytogenetic profiles, including telomere dysfunction, in a retrospective cohort of Senegalese DSD patients.<br><br>MATERIALS AND METHODS: Peripheral blood lymphocytes were sampled from 35 DSD patients (mean age: 3.3 years; range 0-18 years) admitted to two hospital centers in Dakar. Peripheral blood lymphocytes from 150 healthy donors were used as a control. Conventional cytogenetics, telomere, and centromere staining followed by multiplex FISH, as well as FISH with SRY-specific probes, were employed.<br><br>RESULTS: Cytogenetic analysis identified 19 male and 13 female patients with apparently normal karyotypes, two patients with Turner syndrome, and one patient with Klinefelter syndrome. Additional structural chromosome aberrations were detected in 22% of the patients (8/35). Telomere analysis revealed a reduction in mean telomere lengths of DSD patients compared to those of healthy donors of similar age. This reduction in telomere length was associated with an increased rate of telomere aberrations (telomere loss and the formation of telomere doublets) and the presence of additional chromosomal aberrations.<br><br>CONCLUSIONS: To the best of our knowledge, this study is the first to demonstrate a correlation between telomere dysfunction and DSDs. Further studies may reveal the link between telomere dysfunction and possible mechanisms involved in the disease itself, such as DNA repair deficiency or specific gene mutations. The present study demonstrates the relevance of implementing telomere analysis in prenatal tests as well as in diagnosed genetic DSD disorders.},
}
@article {pmid38540151,
year = {2024},
author = {Duseikaite, M and Vilkeviciute, A and Kunceviciene, E and Gedvilaite, G and Kriauciuniene, L and Liutkeviciene, R},
title = {Associations between ZNF676, CTC1 Gene Polymorphisms and Relative Leukocyte Telomere Length with Myopia and Its Degree.},
journal = {Biomedicines},
volume = {12},
number = {3},
pages = {},
doi = {10.3390/biomedicines12030538},
pmid = {38540151},
issn = {2227-9059},
abstract = {BACKGROUND: The interaction between environmental and genetic factors that influence eye growth, regulated by vision, contributes to the development and progression of myopia. This dynamic interaction significantly contributes to the multifaceted development and progression of myopia, a prevalent ocular condition. Our study delves into the associations between ZNF676 and CTC1 gene polymorphisms and their impact on the relative leukocyte telomere length (relative LTL) in myopia, as well as its degree. By unravelling these underpinnings in conjunction with environmental influences, we aim to enhance our understanding of the complex mechanisms that drive the onset and severity of myopia.<br><br>METHODS: This study included patients with myopia and ophthalmologically healthy subjects. DNA was extracted from peripheral venous blood by the salting out method. Genotyping of ZNF676 rs412658 and CTC1 rs3027234, as well as the measurement of relative LTL, were conducted using a real-time polymerase chain reaction method (RT-PCR). The data obtained were statistically analyzed using the "IBM SPSS Statistics 29.0" software program.<br><br>RESULTS: The results show that myopic patients who are homozygous for the rs3027234 rare allele genotype of the CTC1 gene have statistically significantly shorter relative LTL compared to patients with the CC and CT genotypes. Also, men with the CTC1 rs3027234 TT genotype have statistically significantly longer leukocyte telomeres than women with the same genotype. The respective median (IQR) of the relative LTL for women and men is 0.280 (0.463) vs. 0.696 (0.440), with a p-value of 0.027. The myopia group with the ZNF676 rs412658 CC genotype has statistically significantly shorter leukocyte telomeres than the control group with the same genotype (age &#x2264; 29), and the p-value is 0.011. Also, the myopia group with the ZNF676 rs412658 CT and CTC1 rs3027234 CT genotypes have statistically significantly longer leukocyte telomeres than the control group with the same genotypes (age > 29), with p-values that are, respectively, 0.016 and 0.012. The evaluation of the genotype distributions of the polymorphisms in the myopia patients showed that ZNF676 rs412658 CT genotype carriers have 4-fold decreased odds of high myopia occurrence (OR = 0.250; CI: 0.076-0.826; p = 0.023). Also, the evaluation of the allele distributions of the polymorphism under the additive genetic model in the myopia group showed that the ZNF676 rs412658 T allele was associated with similar odds of high myopia (OR = 0.269; 95% CI: 0.090-0.807; p = 0.019). The comprehensive p-value, assessing the relative LTL of subjects across the different levels of myopia, signifies a statistical difference in the relative LTL among individuals with varying degrees of myopia. There was a statistically significant difference in relative LTL between mild and moderate myopia degrees (0.819 (1.983) vs. 0.083 (0.930), p = 0.007).<br><br>CONCLUSIONS: CTC1 rs3027234 TT may be considered a protective genotype for telomere shortening in men, while the overall telomere shortening might be linked to the worse myopia degree. The ZNF676 rs412658 T allele may protect against a high myopia occurrence.},
}
@article {pmid38539016,
year = {2024},
author = {Mutz, J and Wong, WLE and Powell, TR and Young, AH and Dawe, GS and Lewis, CM},
title = {The duration of lithium use and biological ageing: telomere length, frailty, metabolomic age and all-cause mortality.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {38539016},
issn = {2509-2723},
abstract = {Lithium is an established first-line treatment for bipolar disorder. Beyond its therapeutic effect as a mood stabiliser, lithium exhibits potential anti-ageing effects. This study aimed to examine the relationship between the duration of lithium use, biological ageing and mortality. The UK Biobank is an observational study of middle-aged and older adults. We tested associations between the duration of lithium use (number of prescriptions, total duration of use and duration of the first prescription period) and telomere length, frailty, metabolomic age (MileAge) delta, pulse rate and all-cause mortality. Five hundred ninety-one individuals (mean age = 57.49 years; 55% females) had been prescribed lithium. There was no evidence that the number of prescriptions (β = - 0.022, 95% CI - 0.081 to 0.037, p = 0.47), the total duration of use (β = - 0.005, 95% CI - 0.023 to 0.013, p = 0.57) or the duration of the first prescription period (β = - 0.018, 95% CI - 0.051 to 0.015, p = 0.29) correlated with telomere length. There was also no evidence that the duration of lithium use correlated with frailty or MileAge delta. However, a higher prescription count and a longer duration of use was associated with a lower pulse rate. The duration of lithium use did not predict all-cause mortality. We observed no evidence of associations between the duration of lithium use and biological ageing markers, including telomere length. Our findings suggest that the potential anti-ageing effects of lithium do not differ by the duration of use.},
}
@article {pmid38533417,
year = {2024},
author = {Xu, B and Ren, J and Zhu, S and Ding, Y and Zhou, W and Guo, Q and Fang, Y and Zheng, J},
title = {Causal relationship between telomere length and risk of intracranial aneurysm: a bidirectional Mendelian randomization study.},
journal = {Frontiers in neurology},
volume = {15},
number = {},
pages = {1355895},
pmid = {38533417},
issn = {1664-2295},
abstract = {BACKGROUND: Telomere length is closely linked to the aging phenotype, where cellular aging results in the production of a cascade of cell factors and the senescence-associated secretory phenotype (SASP), leading to an inflammatory response. The presence of inflammation plays a crucial role in the formation of intracranial aneurysms. Nevertheless, the relationship between telomere length and intracranial aneurysms remains unclear. This study aims to explore the causal connection between telomere length and intracranial aneurysms through the utilization of Mendelian randomization (MR) analysis.<br><br>METHODS: Data on telomere length were obtained from the genome-wide association studies conducted on the UK Biobank, comprising a total of 472,174 participants. Data on intracranial aneurysms were obtained from the summary dataset of the Global Genome-wide Association Study (GWAS) conducted by the International Stroke Genetics Consortium. The dataset consisted of 7,495 cases and 71,934 controls, all of European descent. Initially, the linkage disequilibrium score was used to investigate the connection between telomere length and intracranial aneurysms. Subsequently, a bidirectional MR was conducted using two-sample analysis to assess whether there is a causal connection between telomere length and intracranial aneurysm risk. The results were analyzed utilizing five MR methods, with the inverse variance weighted method serving as the main methodology. In addition, we did various analyses to evaluate the presence of heterogeneity, pleiotropy, and sensitivity in the study results. A reverse MR analysis was conducted to investigate potential reverse causal links.<br><br>RESULTS: In the forward MR analysis, it was observed that both the inverse variance-weighted and weighted median analyses implied a potential causal relationship between longer telomere length and a decreased incidence of intracranial aneurysms (IVW: OR&#x2009;=&#x2009;0.66, 95% CI: 0.47-0.92, p&#x2009;=&#x2009;1.49&#x2009;&#xd7;&#x2009;10[-2]). There was no heterogeneity or horizontal pleiotropy. The findings were verified to be robust through the utilization of leave-one-out analysis. The use of reverse MR analysis did not establish a potential causal link between the occurrence of intracranial aneurysms and telomere length.<br><br>CONCLUSION: There may exist a potential correlation between longer telomere length and a decreased likelihood of intracranial aneurysms within the European population. The present study offers novel insights into the correlation between telomere length and intracranial aneurysms. Additional research is required to clarify the underlying mechanisms and validate our discoveries in diverse populations.},
}
@article {pmid38525449,
year = {2024},
author = {Chauhan, VS and Sibin, MK and Yadav, P and Sharma, M},
title = {To study childhood trauma in patients with bipolar affective disorder and its association with leucocyte telomere length.},
journal = {Medical journal, Armed Forces India},
volume = {80},
number = {2},
pages = {184-191},
pmid = {38525449},
issn = {0377-1237},
abstract = {BACKGROUND: Childhood traumatic (CT) events are more frequent in Bipolar Affective Disorder (BD) than in healthy individuals. As per existing studies, telomere shortening might be associated with psychiatric illnesses and aging-related disorders. One basis could be CT in BD aiding in telomere shortening.<br><br>METHODS: 100 BD patients and 100 healthy controls (HC) were matched for age and sex. All the participants were administered Childhood Trauma Questionnaire (CTQ). Subsequently, Quantitative Polymerase Chain Reaction (q-PCR) was performed in order to verify leukocyte telomere length (LTL) for both cases and controls.<br><br>RESULTS: Presence of subtypes of moderate to severe CT among cases revealed emotional abuse in 35%, physical abuse in 16%, and sexual abuse in 15%. BD patients had significantly shorter telomeres in comparison to HC. BD patients with CT had significantly shorter LTL as compared to healthy controls with CT. The association between CT and LTL was not statistically significant in cases as well as in controls.<br><br>CONCLUSIONS: Our study revealed presence of CT (moderate to severe) in 46% of BD patients and 12% in age and sex-matched healthy controls. All CT subtypes except sexual abuse were significantly higher among cases than in healthy controls. Mean score of LTL among cases including that with CT was significantly lower than the healthy controls.},
}
@article {pmid38519061,
year = {2024},
author = {Lieber, SB and Lipschultz, RA and Syed, S and Rajan, M and Venkatraman, S and Lin, M and Reid, MC and Lue, NF and Mandl, LA},
title = {Association of phenotypic frailty and hand grip strength with telomere length in SLE.},
journal = {Lupus science &amp; medicine},
volume = {11},
number = {1},
pages = {},
doi = {10.1136/lupus-2023-001008},
pmid = {38519061},
issn = {2053-8790},
abstract = {OBJECTIVE: Frailty and objective hand grip strength (one of the components of the frailty phenotype) are both risk factors for worse health outcomes in SLE. Whether telomere length, an established cellular senescence marker, is a biologic correlate of the frailty phenotype and hand grip strength in patients with SLE is not clear. First, we aimed to evaluate differences in telomere length between frail and non-frail women with SLE and then assessed whether frailty or hand grip strength is differentially associated with telomere length after adjusting for relevant confounders.<br><br>METHODS: Women &#x2265;18 years of age with validated SLE enrolled at a single medical centre. Fried frailty status (which includes hand grip strength), clinical characteristics and telomere length were assessed cross-sectionally. Differences between frail and non-frail participants were evaluated using Fisher's exact or Wilcoxon rank-sum tests. The associations between frailty and hand grip strength and telomere length were determined using linear regression.<br><br>RESULTS: Of the 150 enrolled participants, 131 had sufficient data for determination of frailty classification; 26% were frail with a median age of 45 years. There was a non-significant trend towards shorter telomere length in frail versus non-frail participants (p=0.07). Hand grip strength was significantly associated with telomere length (beta coefficient 0.02, 95%&#x2009;CI 0.004, 0.04), including after adjustment for age, SLE disease activity and organ damage, and comorbidity (beta coefficient 0.02, 95%&#x2009;CI 0.002, 0.04).<br><br>CONCLUSIONS: Decreased hand grip strength, but not frailty, was independently associated with shortened telomere length in a cohort of non-elderly women with SLE. Frailty in this middle-aged cohort may be multifactorial rather than strictly a manifestation of accelerated ageing.},
}
@article {pmid38518608,
year = {2024},
author = {Wei, B and Zhou, Y and Li, Q and Zhen, S and Wu, Q and Xiao, Z and Liao, J and Zhu, B and Duan, J and Yang, X and Liang, F},
title = {Outdoor fine particulate matter exposure and telomere length in humans: A systematic review and meta-analysis.},
journal = {Ecotoxicology and environmental safety},
volume = {275},
number = {},
pages = {116206},
doi = {10.1016/j.ecoenv.2024.116206},
pmid = {38518608},
issn = {1090-2414},
abstract = {Although the association between changes in human telomere length (TL) and ambient fine particulate matter (PM2.5) has been documented, there remains disagreement among the related literature. Our study conducted a systematic review and meta-analysis of epidemiological studies to investigate the health effects of outdoor PM2.5 exposure on human TL after a thorough database search. To quantify the overall effect estimates of TL changes associated with every 10 μg/m[3] increase in PM2.5 exposure, we focused on two main topics, which were outdoor long-term exposure and prenatal exposure of PM2.5. Additionally, we included a summary of short-term PM2.5 exposure and its impact on TL due to limited data availability. Our qualitative analysis included 20 studies with 483,600 participants. The meta-analysis showed a statistically significant association between outdoor PM2.5 exposure and shorter human TL, with pooled impact estimates (β) of -0.12 (95% CI: -0.20, -0.03, I[2]= 95.4%) for general long-term exposure and -0.07 (95% CI: -0.15, 0.00, I[2]= 74.3%) for prenatal exposure. In conclusion, our findings suggest that outdoor PM2.5 exposure may contribute to TL shortening, and noteworthy associations were observed in specific subgroups, suggesting the impact of various research variables. Larger, high-quality studies using standardized methodologies are necessary to strengthen these conclusions further.},
}
@article {pmid38516039,
year = {2024},
author = {Carver, AJ and Hing, B and Elser, BA and Lussier, SJ and Yamanashi, T and Howard, MA and Kawasaki, H and Shinozaki, G and Stevens, HE},
title = {Correlation of telomere length in brain tissue with peripheral tissues in living human subjects.},
journal = {Frontiers in molecular neuroscience},
volume = {17},
number = {},
pages = {1303974},
doi = {10.3389/fnmol.2024.1303974},
pmid = {38516039},
issn = {1662-5099},
abstract = {Telomeres are important to chromosomal stability, and changes in their length correlate with disease, potentially relevant to brain disorders. Assessing telomere length in human brain is invasive, but whether peripheral tissue telomere length correlates with that in brain is not known. Saliva, buccal, blood, and brain samples were collected at time points before, during, and after subjects undergoing neurosurgery (n = 35) for intractable epilepsy. DNA was isolated from samples and average telomere length assessed by qPCR. Correlations of telomere length between tissue samples were calculated across subjects. When data were stratified by sex, saliva telomere length correlated with brain telomere length in males only. Buccal telomere length correlated with brain telomere length when males and females were combined. These findings indicate that in living subjects, telomere length in peripheral tissues variably correlates with that in brain and may be dependent on sex. Peripheral tissue telomere length may provide insight into brain telomere length, relevant to assessment of brain disorder pathophysiology.},
}
@article {pmid38515829,
year = {2024},
author = {Chien, CW and Tang, YA and Jeng, SL and Pan, HA and Sun, HS},
title = {Blastocyst telomere length predicts successful implantation after frozen-thawed embryo transfer.},
journal = {Human reproduction open},
volume = {2024},
number = {2},
pages = {hoae012},
doi = {10.1093/hropen/hoae012},
pmid = {38515829},
issn = {2399-3529},
abstract = {STUDY QUESTION: Do embryos with longer telomere length (TL) at the blastocyst stage have a higher capacity to survive after frozen-thawed embryo transfer (FET)?<br><br>SUMMARY ANSWER: Digitally estimated TL using low-pass whole genome sequencing (WGS) data from the preimplantation genetic testing for aneuploidy (PGT-A) process demonstrates that blastocyst TL is the most essential factor associated with likelihood of implantation.<br><br>WHAT IS KNOWN ALREADY: The lifetime TL is established in the early cleavage cycles following fertilization through a recombination-based lengthening mechanism and starts erosion beyond the blastocyst stage. In addition, a telomerase-mediated slow erosion of TL in human fetuses has been observed from a gestational age of 6-11&#x2009;weeks. Finally, an abnormal shortening of telomeres is likely involved in embryo loss during early development.<br><br>STUDY DESIGN SIZE DURATION: Blastocyst samples were obtained from patients who underwent PGT-A and FET in an IVF center from March 2015 to May 2018. Digitally estimated mitochondrial copy number (mtCN) and TL were used to study associations with the implantation potential of each embryo.<br><br>In total, 965 blastocysts from 232 cycles (164 patients) were available to investigate the biological and clinical relevance of TL. A WGS-based workflow was applied to determine the ploidy of each embryo. Data from low-pass WGS-PGT-A were used to estimate the mtCN and TL for each embryo. Single-variant and multi-variant logistic regression, decision tree, and random forest models were applied to study various factors in association with the implantation potential of each embryo.<br><br>Of the 965 blastocysts originally available, only 216 underwent FET. While mtCN from the transferred embryos is significantly associated with the ploidy call of each embryo, mtCN has no role in impacting IVF outcomes after an embryo transfer in these women. The results indicate that mtCN is a marker of embryo aneuploidy. On the other hand, digitally estimated TL is the most prominent univariant factor and showed a significant positive association with pregnancy outcomes (P&#x2009;<&#x2009;0.01, odds ratio 79.1). We combined several maternal and embryo parameters to study the joint effects on successful implantation. The machine learning models, namely decision tree and random forest, were trained and yielded classification accuracy of 0.82 and 0.91, respectively. Taken together, these results support the vital role of TL in governing implantation potential, perhaps through the ability to control embryo survival after transfer.<br><br>The small sample size limits our study as only 216 blastocysts were transferred. The number was further reduced to 153 blastocysts, where pregnancy outcomes could be accurately traced. The other limitation of this study is that all data were collected from a single IVF center. The uniform and controlled operation of IVF cycles in a single center may cause selection bias.<br><br>We present novel findings to show that digitally estimated TL at the blastocyst stage is a predictor of pregnancy capacity after a FET cycle. As elective single-embryo transfer has become the mainstream direction in reproductive medicine, prioritizing embryos based on their implantation potential is crucial for clinical infertility treatment in order to reduce twin pregnancy rate and the time to pregnancy in an IVF center. The AI-powered, random forest prediction model established in this study thus provides a way to improve clinical practice and optimize the chances for people with fertility problems to achieve parenthood.<br><br>This study was supported by a grant from the National Science and Technology Council, Taiwan (MOST 108-2321-B-006-013 -). There were no competing interests.<br><br>TRIAL REGISTRATION NUMBER: N/A.},
}
@article {pmid38512957,
year = {2024},
author = {An, G and Zhao, X and Zhao, C},
title = {Unraveling the causal association between leukocyte telomere length and infertility: A two-sample Mendelian randomization study.},
journal = {PloS one},
volume = {19},
number = {3},
pages = {e0298997},
doi = {10.1371/journal.pone.0298997},
pmid = {38512957},
issn = {1932-6203},
abstract = {Infertility is a significant challenge in modern society, and observed studies have reported the association between telomere length and infertility. Whether this relationship is causal remains controversial.We employed two-sample mendelian randomization (MR) to investigate the causal relationship between leukocyte telomere length (LTL) and major causes of infertility, including male and female infertility, sperm abnormalities, and endometriosis. MR analyses were mainly performed using the inverse variance weighted (IVW) method and complemented with other MR methods.Our findings demonstrate a causal association between LTL and endometriosis (OR1.304, 95% CI (1.122,1.517), p = 0.001), suggesting its potential as a biomarker for this condition. However, we did not observe a significant causal relationship between LTL and other infertility causes.Our study presents compelling evidence on the relationship between LTL and endometriosis. Meanwhile, our study demonstrates that there is no causal relationship between LTL and infertility. This research contributes to the field by shedding light on the importance of LTL in the early diagnosis and intervention of endometriosis.},
}
@article {pmid38510147,
year = {2024},
author = {Keller, D and Stinus, S and Umlauf, D and Gourbeyre, E and Biot, E and Olivier, N and Mahou, P and Beaurepaire, E and Andrey, P and Crabbe, L},
title = {Non-random spatial organization of telomeres varies during the cell cycle and requires LAP2 and BAF.},
journal = {iScience},
volume = {27},
number = {4},
pages = {109343},
pmid = {38510147},
issn = {2589-0042},
abstract = {Spatial genome organization within the nucleus influences major biological processes and is impacted by the configuration of linear chromosomes. Here, we applied 3D spatial statistics and modeling on high-resolution telomere and centromere 3D-structured illumination microscopy images in cancer cells. We found a multi-scale organization of telomeres that dynamically evolved from a mixed clustered-and-regular distribution in early G1 to a purely regular distribution as cells progressed through the cell cycle. In parallel, our analysis revealed two pools of peripheral and internal telomeres, the proportions of which were inverted during the cell cycle. We then conducted a targeted screen using MadID to identify the molecular pathways driving or maintaining telomere anchoring to the nuclear envelope observed in early G1. Lamina-associated polypeptide (LAP) proteins were found transiently localized to telomeres in anaphase, a stage where LAP2α initiates the reformation of the nuclear envelope, and impacted telomere redistribution in the next interphase together with their partner barrier-to-autointegration factor (BAF).},
}
@article {pmid38509838,
year = {2024},
author = {Wolf, SE and Woodruff, MJ and Chang van Oordt, DA and Clotfelter, ED and Cristol, DA and Derryberry, EP and Ferguson, SM and Stanback, MT and Taff, CC and Vitousek, MN and Westneat, DF and Rosvall, KA},
title = {Among-population variation in telomere regulatory proteins and their potential role as hidden drivers of intraspecific variation in life history.},
journal = {The Journal of animal ecology},
volume = {},
number = {},
pages = {},
doi = {10.1111/1365-2656.14071},
pmid = {38509838},
issn = {1365-2656},
support = {T32 HD049336/NH/NIH HHS/United States ; },
abstract = {Biologists aim to explain patterns of growth, reproduction and ageing that characterize life histories, yet we are just beginning to understand the proximate mechanisms that generate this diversity. Existing research in this area has focused on telomeres but has generally overlooked the telomere's most direct mediator, the shelterin protein complex. Shelterin proteins physically interact with the telomere to shape its shortening and repair. They also regulate metabolism and immune function, suggesting a potential role in life history variation in the wild. However, research on shelterin proteins is uncommon outside of biomolecular work. Intraspecific analyses can play an important role in resolving these unknowns because they reveal subtle variation in life history within and among populations. Here, we assessed ecogeographic variation in shelterin protein abundance across eight populations of tree swallow (Tachycineta bicolor) with previously documented variation in environmental and life history traits. Using the blood gene expression of four shelterin proteins in 12-day-old nestlings, we tested the hypothesis that shelterin protein gene expression varies latitudinally and in relation to both telomere length and life history. Shelterin protein gene expression differed among populations and tracked non-linear variation in latitude: nestlings from mid-latitudes expressed nearly double the shelterin mRNA on average than those at more northern and southern sites. However, telomere length was not significantly related to latitude. We next assessed whether telomere length and shelterin protein gene expression correlate with 12-day-old body mass and wing length, two proxies of nestling growth linked to future fecundity and survival. We found that body mass and wing length correlated more strongly (and significantly) with shelterin protein gene expression than with telomere length. These results highlight telomere regulatory shelterin proteins as potential mediators of life history variation among populations. Together with existing research linking shelterin proteins and life history variation within populations, these ecogeographic patterns underscore the need for continued integration of ecology, evolution and telomere biology, which together will advance understanding of the drivers of life history variation in nature.},
}
@article {pmid38504468,
year = {2024},
author = {Hastings, WJ and Ye, Q and Wolf, SE and Ryan, CP and Das, SK and Huffman, KM and Kobor, MS and Kraus, WE and MacIsaac, JL and Martin, CK and Racette, SB and Redman, LM and Belsky, DW and Shalev, I},
title = {Effect of long-term caloric restriction on telomere length in healthy adults: CALERIE™ 2 trial analysis.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e14149},
doi = {10.1111/acel.14149},
pmid = {38504468},
issn = {1474-9726},
abstract = {Caloric restriction (CR) modifies lifespan and aging biology in animal models. The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE™) 2 trial tested translation of these findings to humans. CALERIE™ randomized healthy, nonobese men and premenopausal women (age 21-50y; BMI 22.0-27.9 kg/m[2]), to 25% CR or ad-libitum (AL) control (2:1) for 2 years. Prior analyses of CALERIE™ participants' blood chemistries, immunology, and epigenetic data suggest the 2-year CR intervention slowed biological aging. Here, we extend these analyses to test effects of CR on telomere length (TL) attrition. TL was quantified in blood samples collected at baseline, 12-, and 24-months by quantitative PCR (absolute TL; aTL) and a published DNA-methylation algorithm (DNAmTL). Intent-to-treat analysis found no significant differences in TL attrition across the first year, although there were trends toward increased attrition in the CR group for both aTL and DNAmTL measurements. When accounting for adherence heterogeneity with an Effect-of-Treatment-on-the-Treated analysis, greater CR dose was associated with increased DNAmTL attrition during the baseline to 12-month weight-loss period. By contrast, both CR group status and increased CR were associated with reduced aTL attrition over the month 12 to month 24 weight maintenance period. No differences were observed when considering TL change across the study duration from baseline to 24-months, leaving it unclear whether CR-related effects reflect long-term detriments to telomere fidelity, a hormesis-like adaptation to decreased energy availability, or measurement error and insufficient statistical power. Unraveling these trends will be a focus of future CALERIE™ analyses and trials.},
}
@article {pmid38503134,
year = {2024},
author = {Dos Santos, GA and Viana, NI and Pimenta, R and de Camargo, JA and Guimaraes, VR and Romão, P and Candido, P and Dos Santos, VG and Ghazarian, V and Reis, ST and Leite, KRM and Srougi, M},
title = {Upregulation of shelterin and CST genes and longer telomeres are associated with unfavorable prognostic characteristics in prostate cancer.},
journal = {Cancer genetics},
volume = {284-285},
number = {},
pages = {20-29},
doi = {10.1016/j.cancergen.2024.03.006},
pmid = {38503134},
issn = {2210-7762},
abstract = {INTRODUCTION: Search for new clinical biomarkers targets in prostate cancer (PC) is urgent. Telomeres might be one of these targets. Telomeres are the extremities of linear chromosomes, essential for genome stability and control of cell divisions. Telomere homeostasis relies on the proper functioning of shelterin and CST complexes. Telomeric dysfunction and abnormal expression of its components are reported in most cancers and are associated with PC. Despite this, there are only a few studies about the expression of the main telomere complexes and their relationship with PC progression. We aimed to evaluate the role of shelterin (POT1, TRF2, TPP1, TIN2, and RAP1) and CST (CTC1, STN1, and TEN1) genes and telomere length in the progression of PC.<br><br>METHODS: We evaluated genetic alterations of shelterin and CST by bioinformatics in samples of localized (n = 499) and metastatic castration-resistant PC (n = 444). We also analyzed the expression of the genes using TCGA (localized PC n = 497 and control n = 152) and experimental approaches, with surgical specimens (localized PC n = 81 and BPH n = 10) and metastatic cell lines (LNCaP, DU145, PC3 and PNT2 as control) by real-time PCR. Real-time PCR also determined the telomere length in the same experimental samples. All acquired data were associated with clinical parameters.<br><br>RESULTS: Genetic alterations are uncommon in PC, but POT1, TIN2, and TEN1 showed significantly more amplifications in the metastatic cancer. Except for CTC1 and TEN1, which are differentially expressed in localized PC samples, we did not detect an expression pattern relative to control and cell lines. Nevertheless, except for TEN1, the upregulation of all genes is associated with a worse prognosis in localized PC. We also found that increased telomere length is associated with disease aggressiveness in localized PC.<br><br>CONCLUSION: The upregulation of shelterin and CST genes creates an environment that favors telomere elongation, giving selective advantages for localized PC cells to progress to more aggressive stages of the disease.},
}
@article {pmid38499533,
year = {2024},
author = {Li, Y and Chen, J and Sun, T and Chen, Y and Fu, R and Liu, X and Xue, F and Liu, W and Ju, M and Dai, X and Dong, H and Li, H and Wang, W and Chi, Y and Zhang, L},
title = {Genetically determined telomere length and risk for haematologic diseases: results from large prospective cohorts and Mendelian Randomization analysis.},
journal = {Blood cancer journal},
volume = {14},
number = {1},
pages = {48},
pmid = {38499533},
issn = {2044-5385},
}
@article {pmid38498288,
year = {2024},
author = {Gürel, S and Pak, EN and Tek, NA},
title = {Aging Processes Are Affected by Energy Balance: Focused on the Effects of Nutrition and Physical Activity on Telomere Length.},
journal = {Current nutrition reports},
volume = {},
number = {},
pages = {},
pmid = {38498288},
issn = {2161-3311},
abstract = {PURPOSE OF REVIEW: The number and proportion of individuals aged 60 and over are increasing globally. The increase in the elderly population has important social and economic effects. Telomere length is an important marker for healthy aging. Here, we review the relevance between telomere length and energy balance by determining the effects of physical activity, nutrients, dietary patterns, and foods on healthy aging and telomere length with related studies.<br><br>RECENT FINDINGS: Evidence emphasizes the importance of telomere length and integrity for healthy aging. It also focuses on the importance of potential interventions such as physical activity and a healthy diet to improve this process. We suggest that ensuring energy balance with regular physical activity and healthy diets can contribute to the aging process by protecting telomere length. In addition, different methods in studies, short and inconsistent durations, different types of exercise, different diet patterns, and non-standard foods have led to conflicting results. More studies are needed to elucidate molecular-based mechanisms.},
}
@article {pmid38493659,
year = {2024},
author = {Zhang, Y and Zhu, Y and Zhang, X and Li, C and Fu, H and Lin, L and Yang, Z and Zhang, B},
title = {The association of sleep duration and leukocyte telomere length in middle-aged and young-old adults: A cross-sectional study of UK Biobank.},
journal = {Sleep medicine},
volume = {117},
number = {},
pages = {18-24},
doi = {10.1016/j.sleep.2024.02.043},
pmid = {38493659},
issn = {1878-5506},
abstract = {BACKGROUND: The relationships between sleep duration and aging-associated diseases are intricate. Leukocyte telomere length (LTL) is a biomarker of aging, while the association of sleep duration and LTL is unclear.<br><br>METHODS: The 310,091 study participants from UK Biobank were enrolled in this cross-sectional study. Restricted cubic splines (RCS) analysis was firstly performed to assess the nonlinear relationship between sleep duration and LTL. Sleep duration was then categorized into three groups: <7&#xa0;h (short sleep duration), 7-8&#xa0;h (reference group), and >8&#xa0;h (long sleep duration) and multiple linear regression was applied to analyze the association of short sleep and long sleep duration with LTL. We further performed subgroup analyses stratified by sex, age, chronotype and snoring.<br><br>RESULTS: RCS showed an inverted J-shaped relationship between sleep duration and LTL. Compared with the reference group, the inverse association of long sleep duration and LTL was statistically significant in fully-adjusted model (P&#xa0;=&#xa0;0.001). Subgroup analyses showed that this association was more apparent in people over 50 years (51-60&#xa0;y: P&#xa0;=&#xa0;0.002; >60&#xa0;y: P&#xa0;=&#xa0;0.005), in men (P&#xa0;=&#xa0;0.022), and in people preferred evening chronotype (P&#xa0;=&#xa0;0.001).<br><br>CONCLUSION: Compared with participants sleeping 7-8&#xa0;h, those sleep longer than 8&#xa0;h had shorter LTL in middle-aged and young-old adults. The negative association between long sleep duration and LTL was more apparent in older people, in men, and in people preferred evening chronotype.},
}
@article {pmid38493352,
year = {2024},
author = {Závodník, M and Pavlištová, V and Machelová, A and Lyčka, M and Mozgová, I and Caklová, K and Dvořáčková, M and Fajkus, J},
title = {KU70 and CAF-1 in Arabidopsis: Divergent roles in rDNA stability and telomere homeostasis.},
journal = {The Plant journal : for cell and molecular biology},
volume = {},
number = {},
pages = {},
doi = {10.1111/tpj.16718},
pmid = {38493352},
issn = {1365-313X},
support = {20-01331X//Grantov&#xe1; Agentura &#x10c;esk&#xe9; Republiky/ ; 23-06643S//Grantov&#xe1; Agentura &#x10c;esk&#xe9; Republiky/ ; },
abstract = {Deficiency in chromatin assembly factor-1 (CAF-1) in plants through dysfunction of its components, FASCIATA1 and 2 (FAS1, FAS2), leads to the specific and progressive loss of rDNA and telomere repeats in plants. This loss is attributed to defective repair mechanisms for the increased DNA breaks encountered during replication, a consequence of impaired replication-dependent chromatin assembly. In this study, we explore the role of KU70 in these processes. Our findings reveal that, although the rDNA copy number is reduced in ku70 mutants when compared with wild-type plants, it is not markedly affected by diverse KU70 status in fas1 mutants. This is consistent with our previous characterisation of rDNA loss in fas mutants as a consequence part of the single-strand annealing pathway of homology-dependent repair. In stark contrast to rDNA, KU70 dysfunction fully suppresses the loss of telomeres in fas1 plants and converts telomeres to their elongated and heterogeneous state typical for ku70 plants. We conclude that the alternative telomere lengthening pathway, known to be activated in the absence of KU70, overrides progressive telomere loss due to CAF-1 dysfunction.},
}
@article {pmid38493287,
year = {2024},
author = {Ojeda-Rodriguez, A and Rangel-Zuñiga, OA and Arenas-de Larriva, AP and Gutierrez-Mariscal, FM and Torres-Peña, JD and Romero-Cabrera, JL and Podadera-Herreros, A and García-Fernandez, H and Porras-Pérez, E and Luque, RM and Kales, SN and Perez-Martinez, P and Delgado-Lista, J and Yubero-Serrano, EM and Lopez-Miranda, J},
title = {Telomere length as biomarker of nutritional therapy for prevention of type 2 diabetes mellitus development in patients with coronary heart disease: CORDIOPREV randomised controlled trial.},
journal = {Cardiovascular diabetology},
volume = {23},
number = {1},
pages = {98},
pmid = {38493287},
issn = {1475-2840},
support = {MCIN/AEI/10.13039/501100011033//Ministerio de Ciencia e Innovaci&#xf3;n/ ; Grant PY20/00256//Consejer&#xed;a de Transformaci&#xf3;n Econ&#xf3;mica, Industria, Conocimiento y Universidades/ ; },
abstract = {BACKGROUND: Telomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years.<br><br>METHODS: The CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in C&#xf3;rdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements.<br><br>FINDINGS: 1002 patients (59.5&#xa0;&#xb1;&#xa0;8.7&#xa0;years and 82.5% men) were enrolled into Mediterranean diet (n&#x2009;=&#x2009;502) or a low-fat diet (n&#x2009;=&#x2009;500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL&#x2009;<&#x2009;percentile 20th) are more likely to experience T2DM than those at no risk of short telomeres (HR 1.65, p-value 0.023). In terms of diet, patients at high risk of short telomeres had a higher risk of T2DM incidence after consuming a low-fat diet compared to patients at no risk of short telomeres (HR 2.43, 95CI% 1.26 to 4.69, p-value 0.008), while no differences were observed in the Mediterranean diet group.<br><br>CONCLUSION: Patients with shorter TL presented a higher risk of developing T2DM. This association could be mitigated with a specific dietary pattern, in our case a Mediterranean diet, to prevent T2DM in patients with coronary heart disease.<br><br>TRIAL REGISTRATION: Clinicaltrials.gov number NCT00924937.},
}
@article {pmid38489874,
year = {2024},
author = {Liu, CC and Capart, MMM and Lin, JJ},
title = {Mismatch repair enzymes regulate telomere recombination in Saccharomycescerevisiae.},
journal = {Biochemical and biophysical research communications},
volume = {707},
number = {},
pages = {149768},
doi = {10.1016/j.bbrc.2024.149768},
pmid = {38489874},
issn = {1090-2104},
abstract = {DNA mismatch repair (MMR) is a crucial mechanism that ensures chromosome stability and prevents the development of various human cancers. Apart from its role in correcting mismatches during DNA replication, MMR also plays a significant role in regulating recombination between non-identical sequences, a process known as homeologous recombination. Telomeres, the protective ends of eukaryotic chromosomes, possess sequences that are not perfectly homologous. While telomerase primarily maintains telomere length in the yeast Saccharomyces cerevisiae, recombination between telomeres becomes a major pathway for length maintenance in cells lacking telomerase. This study investigates the participation of MMR in telomere recombination. Our findings reveal that mutations in MMR genes activate type I recombination. Notably, among the MMR proteins, MutSα (Msh2 and Msh6) and MutLα (Mlh1 and Pms1) exerted the most pronounced effects on telomere recombination. We also found that yeast cells containing simple human telomeric TTAGGG DNA sequences preferentially utilize type II recombination to maintain their telomeres, highlighting the influence of the heterogeneous nature of yeast telomeric sequences on type II recombination. Furthermore, our observations indicate that MMR activity is indispensable for its impact on telomere recombination. Collectively, these results contribute to a more comprehensive understanding of the role of MMR in telomere recombination.},
}
@article {pmid38487628,
year = {2024},
author = {, },
title = {Retraction: Obesity accelerates leukocyte telomere length shortening in apparently healthy adults: a meta-analysis.},
journal = {Frontiers in nutrition},
volume = {11},
number = {},
pages = {1390502},
doi = {10.3389/fnut.2024.1390502},
pmid = {38487628},
issn = {2296-861X},
abstract = {[This retracts the article DOI: 10.3389/fnut.2022.812846.].},
}
@article {pmid38485951,
year = {2024},
author = {Zhang, J and Ruiz, M and Bergh, PO and Henricsson, M and Stojanović, N and Devkota, R and Henn, M and Bohlooly-Y, M and Hernández-Hernández, A and Alsheimer, M and Borén, J and Pilon, M and Shibuya, H},
title = {Regulation of meiotic telomere dynamics through membrane fluidity promoted by AdipoR2-ELOVL2.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {2315},
pmid = {38485951},
issn = {2041-1723},
support = {StG-801659//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; 2018-03426//Vetenskapsr&#xe5;det (Swedish Research Council)/ ; KAW2019.0180//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; Al 1090/4-2//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 426173797 (INST 93/1003-1 FUGG)//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; },
abstract = {The cellular membrane in male meiotic germ cells contains a unique class of phospholipids and sphingolipids that is required for male reproduction. Here, we show that a conserved membrane fluidity sensor, AdipoR2, regulates the meiosis-specific lipidome in mouse testes by promoting the synthesis of sphingolipids containing very-long-chain polyunsaturated fatty acids (VLC-PUFAs). AdipoR2 upregulates the expression of a fatty acid elongase, ELOVL2, both transcriptionally and post-transcriptionally, to synthesize VLC-PUFA. The depletion of VLC-PUFAs and subsequent accumulation of palmitic acid in AdipoR2 knockout testes stiffens the cellular membrane and causes the invagination of the nuclear envelope. This condition impairs the nuclear peripheral distribution of meiotic telomeres, leading to errors in homologous synapsis and recombination. Further, the stiffened membrane impairs the formation of intercellular bridges and the germ cell syncytium, which disrupts the orderly arrangement of cell types within the seminiferous tubules. According to our findings we propose a framework in which the highly-fluid membrane microenvironment shaped by AdipoR2-ELOVL2 underpins meiosis-specific chromosome dynamics in testes.},
}
@article {pmid38481135,
year = {2024},
author = {Alanazi, AFR and Parkinson, GN and Haider, S},
title = {Structural Motifs at the Telomeres and Their Role in Regulatory Pathways.},
journal = {Biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.biochem.4c00023},
pmid = {38481135},
issn = {1520-4995},
abstract = {Telomeres are specialized structures, found at the ends of linear chromosomes in eukaryotic cells, that play a crucial role in maintaining the stability and integrity of genomes. They are composed of repetitive DNA sequences, ssDNA overhangs, and several associated proteins. The length of telomeres is linked to cellular aging in humans, and deficiencies in their maintenance are associated with various diseases. Key structural motifs at the telomeres serve to protect vulnerable chromosomal ends. Telomeric DNA also has the ability to form diverse complex DNA higher-order structures, including T-loops, D-loops, R-loops, G-loops, G-quadruplexes, and i-motifs, in the complementary C-rich strand. While many essential proteins at telomeres have been identified, the intricacies of their interactions and structural details are still not fully understood. This Perspective highlights recent advancements in comprehending the structures associated with human telomeres. It emphasizes the significance of telomeres, explores various telomeric structural motifs, and delves into the structural biology surrounding telomeres and telomerase. Furthermore, telomeric loops, their topologies, and the associated proteins that contribute to the safeguarding of telomeres are discussed.},
}
@article {pmid38478320,
year = {2024},
author = {Du, X and Guo, C and Zhang, C and Xu, B},
title = {Causal Association of Telomere Length and Loss of Bone: a Directional Mendelian Randomization Study of Multi-Outcomes.},
journal = {Applied biochemistry and biotechnology},
volume = {},
number = {},
pages = {},
pmid = {38478320},
issn = {1559-0291},
support = {Nos.82072491//National Natural Science Foundation of China/ ; Nos. 20JCYBJC00820//Natural Science Foundation of Tianjin City/ ; },
abstract = {This study employed a genome-wide association study (GWAS) to investigate the relationship between telomere length and marginal bone loss (MBL), a marker of bone health and aging. Telomere length, a biological indicator of aging, was analyzed alongside several serum markers of bone loss. Following a screen for appropriate instrumental variables, telomere length was designated as the exposure variable. We conducted the main analysis using random-effects inverse variance weighting (IVW) and supplemented it with MR Egger, weighted median, simple mode, and weighted mode analyses, employing a total of five methods. Positive outcomes underwent scrutiny through heterogeneity analysis, horizontal multiplicity analysis, and leave-one-out plot. Subsequently, the effective gene locus was chosen for a reverse MR analysis, with positive results serving as the exposure variable. We found a causal relationship between telomere length and the expression of osteocalcin (OC), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-12 (MMP-12), key markers of bone metabolism. Our findings suggest that telomere wear and shortening may contribute to increased activity of OC, MMP-3, and MMP-12, thus affecting bone metabolism. However, reverse Mendelian randomization analysis did not indicate a significant impact of OC, MMP-3, and MMP-12 on telomere length, implying a unidirectional relationship. Overall, this meta-analysis underscores the association between telomere length and bone loss, highlighting the importance of timing and duration of telomere wear and shortening in influencing bone metabolism.},
}
@article {pmid38475941,
year = {2024},
author = {Gao, Z and Santos, RB and Rupert, J and Van Drunen, R and Yu, Y and Eckel-Mahan, K and Kolonin, MG},
title = {Endothelial-specific telomerase inactivation causes telomere-independent cell senescence and multi-organ dysfunction characteristic of aging.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e14138},
doi = {10.1111/acel.14138},
pmid = {38475941},
issn = {1474-9726},
support = {1R01DK125922/DK/NIDDK NIH HHS/United States ; },
abstract = {It has remained unclear how aging of endothelial cells (EC) contributes to pathophysiology of individual organs. Cell senescence results in part from inactivation of telomerase (TERT). Here, we analyzed mice with Tert knockout specifically in EC. Tert loss in EC induced transcriptional changes indicative of senescence and tissue hypoxia in EC and in other cells. We demonstrate that EC-Tert-KO mice have leaky blood vessels. The blood-brain barrier of EC-Tert-KO mice is compromised, and their cognitive function is impaired. EC-Tert-KO mice display reduced muscle endurance and decreased expression of enzymes responsible for oxidative metabolism. Our data indicate that Tert-KO EC have reduced mitochondrial content and function, which results in increased dependence on glycolysis. Consistent with this, EC-Tert-KO mice have metabolism changes indicative of increased glucose utilization. In EC-Tert-KO mice, expedited telomere attrition is observed for EC of adipose tissue (AT), while brain and skeletal muscle EC have normal telomere length but still display features of senescence. Our data indicate that the loss of Tert causes EC senescence in part through a telomere length-independent mechanism undermining mitochondrial function. We conclude that EC-Tert-KO mice is a model of expedited vascular senescence recapitulating the hallmarks aging, which can be useful for developing revitalization therapies.},
}
@article {pmid38475782,
year = {2024},
author = {Li, J and Wang, W and Yang, Z and Qiu, L and Ren, Y and Wang, D and Li, M and Li, W and Gao, F and Zhang, J},
title = {Causal association of obesity with epigenetic aging and telomere length: a bidirectional mendelian randomization study.},
journal = {Lipids in health and disease},
volume = {23},
number = {1},
pages = {78},
pmid = {38475782},
issn = {1476-511X},
support = {C12021A03005//Scientific and technological innovation project of China Academy of Chinese Medical Sciences/ ; C12021A03005//Scientific and technological innovation project of China Academy of Chinese Medical Sciences/ ; },
abstract = {BACKGROUND: In observational studies, there exists an association between obesity and epigenetic age as well as telomere length. However, varying and partially conflicting outcomes have notably arisen from distinct studies on this topic. In the present study, two-way Mendelian randomization was used to identify potential causal associations between obesity and epigenetic age and telomeres.<br><br>METHODS: A genome-wide association study was conducted using data from individuals of European ancestry to investigate bidirectional Mendelian randomization (MR) regarding the causal relationships between obesity, as indicated by three obesity indicators (body mass index or BMI, waist circumference adjusted for BMI or WCadjBMI, and waist-to-hip ratio adjusted for BMI or WHRadjBMI), and four epigenetic age measures (HannumAge, HorvathAge, GrimAge, PhenoAge), as well as telomere length. To assess these causal associations, various statistical methods were employed, including Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Weighted Mode, and Simple Mode. To address the issue of multiple testing, we applied the Bonferroni correction. These methods were used to determine whether there is a causal link between obesity and epigenetic age, as well as telomere length, and to explore potential bidirectional relationships. Forest plots and scatter plots were generated to show causal associations between exposures and outcomes. For a comprehensive visualization of the results, leave-one-out sensitivity analysis plots, individual SNP-based forest plots for MR analysis, and funnel plots were included in the presentation of the results.<br><br>RESULTS: A strong causal association was identified between obesity and accelerated HannumAge, GrimAge, PhenoAge and telomere length shrinkage. The causal relationship between WCadjBMI and PhenoAge acceleration (OR: 2.099, 95%CI: 1.248-3.531, p&#x2009;=&#x2009;0.005) was the strongest among them. However, only the p-values for the causal associations of obesity with GrimAge, PhenoAge, and telomere length met the criteria after correction using the Bonferroni multiple test. In the reverse MR analysis, there were statistically significant causal associations between HorvathAge, PhenoAge and GrimAge and BMI, but these associations exhibited lower effect sizes, as indicated by their Odds Ratios (ORs). Notably, sensitivity analysis revealed the robustness of the study results.<br><br>CONCLUSIONS: The present findings reveal a causal relationship between obesity and the acceleration of epigenetic aging as well as the reduction of telomere length, offering valuable insights for further scientific investigations aimed at developing strategies to mitigate the aging process in humans.},
}
@article {pmid38467834,
year = {2024},
author = {Chen, S and Pan, C and Huang, J and Liu, T},
title = {ATR limits Rad18-mediated PCNA monoubiquitination to preserve replication fork and telomerase-independent telomere stability.},
journal = {The EMBO journal},
volume = {},
number = {},
pages = {},
pmid = {38467834},
issn = {1460-2075},
support = {2022YFA1302800//MOST | National Key Research and Development Program of China (NKPs)/ ; 2021YFA1101000//MOST | National Key Research and Development Program of China (NKPs)/ ; 31961160725//MOST | National Natural Science Foundation of China (NSFC)/ ; 31730021//MOST | National Natural Science Foundation of China (NSFC)/ ; 31971220//MOST | National Natural Science Foundation of China (NSFC)/ ; 32270769//MOST | National Natural Science Foundation of China (NSFC)/ ; 31970664//MOST | National Natural Science Foundation of China (NSFC)/ ; 31822031//MOST | National Natural Science Foundation of China (NSFC)/ ; },
abstract = {Upon replication fork stalling, the RPA-coated single-stranded DNA (ssDNA) formed behind the fork activates the ataxia telangiectasia-mutated and Rad3-related (ATR) kinase, concomitantly initiating Rad18-dependent monoubiquitination of PCNA. However, whether crosstalk exists between these two events and the underlying physiological implications of this interplay remain elusive. In this study, we demonstrate that during replication stress, ATR phosphorylates human Rad18 at Ser403, an adjacent residue to a previously unidentified PIP motif (PCNA-interacting peptide) within Rad18. This phosphorylation event disrupts the interaction between Rad18 and PCNA, thereby restricting the extent of Rad18-mediated PCNA monoubiquitination. Consequently, excessive accumulation of the tumor suppressor protein SLX4, now characterized as a novel reader of ubiquitinated PCNA, at stalled forks is prevented, contributing to the prevention of stalled fork collapse. We further establish that ATR preserves telomere stability in alternative lengthening of telomere (ALT) cells by restricting Rad18-mediated PCNA monoubiquitination and excessive SLX4 accumulation at telomeres. These findings shed light on the complex interplay between ATR activation, Rad18-dependent PCNA monoubiquitination, and SLX4-associated stalled fork processing, emphasizing the critical role of ATR in preserving replication fork stability and facilitating telomerase-independent telomere maintenance.},
}
@article {pmid38466631,
year = {2024},
author = {Stevers, NO and Costello, JF},
title = {Telomeres in glioma: Maintenance mechanisms to therapeutic potential.},
journal = {Neuro-oncology},
volume = {},
number = {},
pages = {},
doi = {10.1093/neuonc/noae052},
pmid = {38466631},
issn = {1523-5866},
}
@article {pmid38466455,
year = {2024},
author = {Eisenberg, DTA and Ryan, CP and Lee, NR and Carba, DB and MacIsaac, JL and Dever, K and Atashzay, P and Kobor, MS and Kuzawa, C},
title = {DNA methylation-based estimators of telomere length show low correspondence with paternal age at conception and other measures of external validity of telomere length.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {38466455},
issn = {2509-2723},
support = {R01AG061006//Office of Extramural Research, National Institutes of Health/ ; DK056350//Office of Extramural Research, National Institutes of Health/ ; DK078150//Office of Extramural Research, National Institutes of Health/ ; ES10126//Office of Extramural Research, National Institutes of Health/ ; RR20649//Office of Extramural Research, National Institutes of Health/ ; TW05596//Office of Extramural Research, National Institutes of Health/ ; BCS- 0962282//National Science Foundation/ ; BCS-1519110//National Science Foundation/ ; 8111//Wenner-Gren Foundation/ ; },
abstract = {In humans, DNA methylation (DNAm) based estimators of telomere length (TL) have been shown to better predict TL-associated variables (e.g., age, sex, and mortality) than TL itself. The biological significance of DNAm-based estimators of TL (DNAmTL) is unclear. In vitro DNAmTL shortens with cell replications, even when telomerase is maintaining TL. Telomerase is typically suppressed in humans, except in testes. Accordingly, sperm TL increases with age, and offspring with greater paternal age at conception (PAC) have longer TL. Thus, we expect that PAC associations with DNAmTL can shed light on whether in vivo cell replications in the presence of high telomerase activity (production of sperm) shorten DNAmTL or if PAC-lengthened TL causes lengthened DNAmTL. In a pre-registered analysis, using data from 1733 blood samples from the Philippines, we examined the association between paternal age at conception (PAC) and offspring DNAmTL. We did not find an association between PAC and DNAmTL but found a positive association of paternal grandfather's age at father's conception predicting grandchild's DNAmTL. In post hoc analyses, we examined how DNAmTL versus qPCR-measured TL (qPCR-TL) correlated with measures typically associated with TL. Contrary to previous findings, on almost all measures of external validity (correlations with parental TLs, southern blot TL, and age), qPCR-TL outperformed DNAmTL. The "kilobase" units of DNAm-based estimators of TL showed considerable deviations from southern blot-derived kilobase measures. Our findings suggest that DNAmTL is not a reliable index of inherited aspects of TL and underscores uncertainty about the biological meaning of DNAmTL.},
}
@article {pmid38466418,
year = {2024},
author = {Blanco, MB and Smith, DL and Greene, LK and Yoder, AD and Ehmke, EE and Lin, J and Klopfer, PH},
title = {Telomere dynamics during hibernation in a tropical primate.},
journal = {Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology},
volume = {},
number = {},
pages = {},
pmid = {38466418},
issn = {1432-136X},
abstract = {Hibernation is a widespread metabolic strategy among mammals for surviving periods of food scarcity. During hibernation, animals naturally alternate between metabolically depressed torpor bouts and energetically expensive arousals without ill effects. As a result, hibernators are promising models for investigating mechanisms that buffer against cellular stress, including telomere protection and restoration. In non-hibernators, telomeres, the protective structural ends of chromosomes, shorten with age and metabolic stress. In temperate hibernators, however, telomere shortening and elongation can occur in response to changing environmental conditions and associated metabolic state. We investigate telomere dynamics in a tropical hibernating primate, the fat-tailed dwarf lemur (Cheirogaleus medius). In captivity, these lemurs can hibernate when maintained under cold temperatures (11-15 °C) with limited food provisioning. We study telomere dynamics in eight fat-tailed dwarf lemurs at the Duke Lemur Center, USA, from samples collected before, during, and after the hibernation season and assayed via qPCR. Contrary to our predictions, we found that telomeres were maintained or even lengthened during hibernation, but shortened immediately thereafter. During hibernation, telomere lengthening was negatively correlated with time in euthermia. Although preliminary in scope, our findings suggest that there may be a preemptive, compensatory mechanism to maintain telomere integrity in dwarf lemurs during hibernation. Nevertheless, telomere shortening immediately afterward may broadly result in similar outcomes across seasons. Future studies could profitably investigate the mechanisms that offset telomere shortening within and outside of the hibernation season and whether those mechanisms are modulated by energy surplus or crises.},
}
@article {pmid38464183,
year = {2024},
author = {Smoom, R and May, CL and Skordalakes, E and Kaestner, KH and Tzfati, Y},
title = {Separation of telomere protection from length regulation by two different point mutations at amino acid 492 of RTEL1.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.02.26.582005},
pmid = {38464183},
abstract = {RTEL1 is an essential DNA helicase that plays multiple roles in genome stability and telomere length regulation. A variant of RTEL1 with a lysine at position 492 is associated with short telomeres in Mus spretus , while a conserved methionine at this position is found in M. musculus, which has ultra-long telomeres. In humans, a missense mutation at this position (RTEL1 [M492I]) causes a fatal telomere biology disease termed Hoyeraal-Hreidarsson syndrome (HHS). We previously described a M. musculus mouse model termed 'Telomouse', in which changing methionine 492 to a lysine (M492K) shortened the telomeres to their length in humans. Here, we report on the derivation of a mouse strain carrying the M492I mutation, termed 'HHS mouse'. The HHS mouse telomeres are not as short as those of Telomice but nevertheless they display higher levels of telomeric DNA damage, fragility and recombination, associated with anaphase bridges and micronuclei. These observations indicate that the two mutations separate critical functions of RTEL1: M492K mainly reduces the telomere length setpoint, while M492I predominantly disrupts telomere protection. The two mouse models enable dissecting the mechanistic roles of RTEL1 and the different contributions of short telomeres and DNA damage to telomere biology diseases, genomic instability, cancer, and aging.},
}
@article {pmid38463993,
year = {2024},
author = {Zhao, R and Xu, M and Wondisford, AR and Lackner, RM and Salsman, J and Dellaire, G and Chenoweth, DM and O'Sullivan, RJ and Zhao, X and Zhang, H},
title = {SUMO Promotes DNA Repair Protein Collaboration to Support Alterative Telomere Lengthening in the Absence of PML.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.02.29.582813},
pmid = {38463993},
abstract = {Alternative lengthening of telomeres (ALT) pathway maintains telomeres in a significant fraction of cancers associated with poor clinical outcomes. A better understanding of ALT mechanisms can provide a basis for developing new treatment strategies for ALT cancers. SUMO modification of telomere proteins plays a critical role in the formation of ALT telomere-associated PML bodies (APBs), where telomeres are clustered and DNA repair proteins are enriched to promote homology-directed telomere DNA synthesis in ALT. However, whether and how SUMO contributes to ALT beyond APB formation remains elusive. Here, we report that SUMO promotes collaboration among DNA repair proteins to achieve APB-independent telomere maintenance. By using ALT cancer cells with PML protein knocked out and thus devoid of APBs, we show that sumoylation is required for manifesting ALT features, including telomere clustering and telomeric DNA synthesis, independent of PML and APBs. Further, small molecule-induced telomere targeting of SUMO produces signatures of phase separation and ALT features in PML null cells in a manner depending on both sumoylation and SUMO interaction with SUMO interaction motifs (SIMs). Mechanistically, SUMO-induced effects are linked to the enrichment of DNA repair proteins, including Rad52, Rad51AP1, and BLM, to the SUMO-containing telomere foci. Finally, we find that Rad52 can undergo phase separation, enrich SUMO on telomeres, and promote telomere DNA synthesis in collaboration with the BLM helicase in a SUMO-dependent manner. Collectively, our findings suggest that, in addition to forming APBs, SUMO also promotes collaboration among DNA repair proteins to support telomere maintenance in ALT cells. Given the promising effects of sumoylation inhibitors in cancer treatment, our findings suggest their potential use in perturbing telomere maintenance in ALT cancer cells.},
}
@article {pmid38463625,
year = {2024},
author = {Jian, X and Sun, W and Zhang, J and Zhang, Q and Meng, X and Lu, H and Zheng, D and Wu, L and Wang, Y},
title = {Frailty mediating the causality between leucocyte telomere length and mortality: a cohort study of 440,551 UK Biobank participants.},
journal = {The EPMA journal},
volume = {15},
number = {1},
pages = {99-110},
pmid = {38463625},
issn = {1878-5077},
abstract = {INTRODUCTION: Previous studies reported leucocyte telomere length (LTL) and frailty were associated with mortality, but it remains unclear whether frailty serves as a mediator in the relationship between leucocyte telomere length and mortality risk. This study aimed to evaluate how measuring LTL and frailty can support early monitoring and prevention of risk of mortality from the prospective of predictive, preventive, and personalized medicine (PPPM/3PM).<br><br>METHODS: We included 440,551 participants from the UK Biobank between the baseline visit (2006-2010) and November 30, 2022. The time-dependent Cox proportional hazards model was conducted to assess the association between LTL and frailty index with the risk of mortality. Furthermore, we conducted causal mediation analyses to examine the extent to which frailty mediated the association between LTL and mortality.<br><br>RESULTS: During a median follow-up of 13.74&#xa0;years, each SD increase in LTL significantly decreased the risk of all-cause [hazard ratio (HR): 0.94, 95% confidence interval (CI): 0.93-0.95] and CVD-specific mortality (HR: 0.92, 95% CI: 0.90-0.95). The SD increase in FI elevated the risk of all-cause (HR: 1.35, 95% CI: 1.34-1.36), CVD-specific (HR: 1.47, 95% CI: 1.44-1.50), and cancer-specific mortality (HR: 1.22, 95% CI: 1.20-1.24). Frailty mediated approximately 10% of the association between LTL and all-cause and CVD-specific mortality.<br><br>CONCLUSIONS: Our results indicate that frailty mediates the effect of LTL on all-cause and CVD-specific mortality. There findings might be valuable to predict, prevent, and reduce mortality through primary prevention and healthcare in context of PPPM.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-024-00355-7.},
}
@article {pmid38461301,
year = {2024},
author = {Xu, M and Senanayaka, D and Zhao, R and Chigumira, T and Tripathi, A and Tones, J and Lackner, RM and Wondisford, AR and Moneysmith, LN and Hirschi, A and Craig, S and Alishiri, S and O'Sullivan, RJ and Chenoweth, DM and Reiter, NJ and Zhang, H},
title = {TERRA-LSD1 phase separation promotes R-loop formation for telomere maintenance in ALT cancer cells.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {2165},
pmid = {38461301},
issn = {2041-1723},
support = {U01CA260851//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; },
abstract = {The telomere repeat-containing RNA (TERRA) forms R-loops to promote homology-directed DNA synthesis in the alternative lengthening of telomere (ALT) pathway. Here we report that TERRA contributes to ALT via interacting with the lysine-specific demethylase 1A (LSD1 or KDM1A). We show that LSD1 localizes to ALT telomeres in a TERRA dependent manner and LSD1 function in ALT is largely independent of its demethylase activity. Instead, LSD1 promotes TERRA recruitment to ALT telomeres via RNA binding. In addition, LSD1 and TERRA undergo phase separation, driven by interactions between the RNA binding properties of LSD1 and the G-quadruplex structure of TERRA. Importantly, the formation of TERRA-LSD1 condensates enriches the R-loop stimulating protein Rad51AP1 and increases TERRA-containing R-loops at telomeres. Our findings suggest that LSD1-TERRA phase separation enhances the function of R-loop regulatory molecules for ALT telomere maintenance, providing a mechanism for how the biophysical properties of histone modification enzyme-RNA interactions impact chromatin function.},
}
@article {pmid38459464,
year = {2024},
author = {Li, Y and Lai, S and Kan, X},
title = {Causal relationship between immune cells and telomere length: mendelian randomization analysis.},
journal = {BMC immunology},
volume = {25},
number = {1},
pages = {19},
pmid = {38459464},
issn = {1471-2172},
support = {TJYX2DXK-068C//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; TJYX2DXK-068C//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; TJYX2DXK-068C//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; 22ZYYLCCG03//Tianjin Medical University General Hospital Clinical Research Program/ ; 22ZYYLCCG03//Tianjin Medical University General Hospital Clinical Research Program/ ; 22ZYYLCCG03//Tianjin Medical University General Hospital Clinical Research Program/ ; },
abstract = {BACKGROUND: The causal relationship between immune cells and telomere length remains controversial.<br><br>METHODS: Data on the immune cells were obtained from a previous study with 3,757 participants. Data on telomere length were obtained from the OpenGWAS database. Genome-Wide Association Study (GWAS) data were obtained and screened for eligible instrumental variables (IVs) using the TwoSampleMR package and the Phenoscanner database. To investigate the genetic causality between immune cells and telomere length, Mendelian randomization (MR) analysis and Bayesian weighted Mendelian randomization (BWMR) analysis were used.<br><br>RESULTS: MR analysis showed that there is indeed a genetic causal relationship between immune cells and telomere length. A total of 16 immune cells were successfully validated. A positive correlation was found between telomere length and immune cells such as CD28&#x2009;+&#x2009;CD45RA&#x2009;+&#x2009;CD8br %CD8br (OR&#x2009;=&#x2009;1.002, 95%CI: 1.000-1.003). A negative correlation was found between telomere length and immune cells such as Transitional AC (OR&#x2009;=&#x2009;0.991, 95%CI: 0.984-0.997) (P&#x2009;<&#x2009;0.05). Reverse MR analysis similarly confirmed that telomere length can affect four types of immune cells, including CD25 on IgD&#x2009;+&#x2009;CD24- (OR&#x2009;=&#x2009;1.291, 95%CI: 1.060-1.571), at the genetic level.<br><br>CONCLUSION: There is indeed a mutual genetic causality between immune cells and telomere length, which will provide theoretical basis and support for more subsequent clinical studies.},
}
@article {pmid38459383,
year = {2024},
author = {Darian, JC and Kundu, R and Rajaby, R and Sung, WK},
title = {Constructing telomere-to-telomere diploid genome by polishing haploid nanopore-based assembly.},
journal = {Nature methods},
volume = {},
number = {},
pages = {},
pmid = {38459383},
issn = {1548-7105},
abstract = {Draft genomes generated from Oxford Nanopore Technologies (ONT) long reads are known to have a higher error rate. Although existing genome polishers can enhance their quality, the error rate (including mismatches, indels and switching errors between paternal and maternal haplotypes) can be significant. Here, we develop two polishers, hypo-short and hypo-hybrid to address this issue. Hypo-short utilizes Illumina short reads to polish an ONT-based draft assembly, resulting in a high-quality assembly with low error rates and switching errors. Expanding on this, hypo-hybrid incorporates ONT long reads to further refine the assembly into a diploid representation. Leveraging on hypo-hybrid, we have created a diploid genome assembly pipeline called hypo-assembler. Hypo-assembler automates the generation of highly accurate, contiguous and nearly complete diploid assemblies using ONT long reads, Illumina short reads and optionally Hi-C reads. Notably, our solution even allows for the production of telomere-to-telomere diploid genomes with additional manual steps. As a proof of concept, we successfully assembled a fully phased telomere-to-telomere diploid genome of HG00733, achieving a quality value exceeding 50.},
}
@article {pmid38457472,
year = {2024},
author = {Gao, C},
title = {Investigating the association between blood metabolites and telomere length: A mendelian randomization study.},
journal = {PloS one},
volume = {19},
number = {3},
pages = {e0298172},
doi = {10.1371/journal.pone.0298172},
pmid = {38457472},
issn = {1932-6203},
abstract = {BACKGROUND: Telomere length refers to the protective cap at the end of chromosomes, and it plays a crucial role in many diseases. The objective of this study is to explore the relationship between blood metabolites and telomere length, aiming to identify novel biological factors that influence telomere length.<br><br>METHODS: In this study, we extracted genome-wide association study (GWAS) data for blood metabolites from a sample of 7824 Europeans. Additionally, GWAS data for telomere length were obtained from the Open GWAS database (GWAS ID: ieu-b-4879). The primary analysis of this study utilized the random inverse variance weighted (IVW) method. Complementary analyses were also conducted using the MR-Egger and weighted median approaches. Sensitivity analyses were performed to assess the robustness of the findings. These included the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. To investigate the possibility of reverse causation, reverse MR analysis was conducted. Additionally, multivariable MR was utilized to evaluate the direct effect of metabolites on telomere length.<br><br>RESULTS: The results suggested a potential association between 15-methylpalmitate, taurocholate, levulinate, and X-12712 and telomere length. MVMR analysis further showed that 15-methylpalmitate, taurocholate, and levulinate can directly influence telomere length, regardless of other metabolites.<br><br>CONCLUSIONS: This study suggests that 15-methylpalmitate, taurocholate, and levulinate are likely factors correlated with telomere length. These findings will contribute to the development of strategies for protecting telomeres, preventing related diseases, and establishing a new biological foundation for achieving healthy aging.},
}
@article {pmid38455184,
year = {2024},
author = {Praengam, K and Tuntipopipat, S and Muangnoi, C and Jangwangkorn, C and Piamkulvanich, O},
title = {Efficacy of a dietary supplement derived from five edible plants on telomere length in Thai adults: A randomized, double-blind, placebo-controlled trial.},
journal = {Food science &amp; nutrition},
volume = {12},
number = {3},
pages = {1592-1604},
doi = {10.1002/fsn3.3851},
pmid = {38455184},
issn = {2048-7177},
abstract = {Mylife/Mylife100® is a dietary supplement consisting of black sesame seed, guava fruit, mangosteen aril, pennywort leaves, and soy protein. These edible plants contain multiple high-potential bioactive compounds exerting various vital biological functions including antioxidants which contribute to delaying the rate of telomere shortening. Telomere length is associated with cellular aging and age-related diseases. This study aimed to assess the efficacy of Mylife/Mylife100® on telomere length through a randomized, double-blind placebo-controlled trial. The trial assessed the alteration of leukocyte telomere length after 32 adults aged 50-65 years received either Mylife/Mylife100® or placebo (five capsules/day) for 8-week supplementation. The results demonstrated a significant increase in mean telomere length from baseline (6313 bp) to the 8-week supplementation period (6655 bp; p < 0.05) in the group receiving the product, whereas no significant change was observed in the placebo group. Additionally, the product group exhibited a significant improvement in plasma total antioxidant capacity levels compared to the placebo group (mean change, +35 vs -38; p = 0.006). This study also showed a significant correlation between telomere length and % CD4 + T cells (r = +0.325; p = 0.00003), % CD8 + T cells (r = +0.156; p = 0.048), and visceral fat (r = - 0.349; p = 0.000006). The findings suggest that consuming this dietary supplement (Mylife/Mylife100®) for 8 weeks has a positive effect on cellular aging by lengthening telomeres possible through their antioxidant capacities. Oxidative stress and cellular aging are underlying predisease mechanisms that might be alleviated by supplementing with this product.},
}
@article {pmid38451181,
year = {2024},
author = {Fang, T and Zhang, Z and Ren, K and Zou, L},
title = {Genetically determined telomere length as a risk factor for hematological malignancies: evidence from Mendelian randomization analysis.},
journal = {Aging},
volume = {16},
number = {},
pages = {},
doi = {10.18632/aging.205625},
pmid = {38451181},
issn = {1945-4589},
abstract = {BACKGROUND: Over the past years, the exact correlation between telomere length and hematological malignancies was still not fully understood.<br><br>METHODS: We performed a two-sample Mendelian randomization study to investigate the causal relationship between telomere length and hematological malignancies. We selected genetic instruments associated with telomere length. The genetic associations for lymphoid and hematopoietic malignant neoplasms were obtained from the most recent publicly accessible FinnGen study R9 data. Inverse variant weighted (IVW) analysis was adopted as the primary method, and we also performed the weighted-median method and the MR-Egger, and MRPRESSO methods as sensitive analysis.<br><br>RESULTS: Significant associations have been observed between telomere length and primary lymphoid (IVW: OR = 1.52, P = 2.11 &#xd7; 10[-6]), Hodgkin lymphoma (IVW: OR = 1.64, P = 0.014), non-Hodgkin lymphoma (IVW: OR = 1.70, P = 0.002), B-cell lymphoma (IVW: OR = 1.57, P = 0.015), non-follicular lymphoma (IVW: OR = 1.58, P = 1.7 &#xd7; 10[-3]), mantle cell lymphoma (IVW: OR = 3.13, P = 0.003), lymphoid leukemia (IVW: OR = 2.56, P = 5.92E-09), acute lymphocytic leukemia (IVW: OR = 2.65, P = 0.021) and chronic lymphocytic leukemia (IVW: OR = 2.80, P = 8.21 &#xd7; 10[-6]), along with multiple myeloma (IVW: OR = 1.85, P = 0.016).<br><br>CONCLUSION: This MR study found a significant association between telomere length and a wide range of hematopoietic malignancies. But no substantial impact of lymphoma and hematopoietic malignancies on telomere length has been detected.},
}
@article {pmid38451028,
year = {2024},
author = {Etherington, GJ and Wu, PS and Oliferenko, S and Uhlmann, F and Nieduszynski, CA},
title = {Telomere-to-telomere Schizosaccharomyces japonicus genome assembly reveals hitherto unknown genome features.},
journal = {Yeast (Chichester, England)},
volume = {},
number = {},
pages = {},
doi = {10.1002/yea.3912},
pmid = {38451028},
issn = {1097-0061},
support = {/CRUK_/Cancer Research UK/United Kingdom ; cc2137/WT_/Wellcome Trust/United Kingdom ; },
abstract = {Schizosaccharomyces japonicus belongs to the single-genus class Schizosaccharomycetes, otherwise known as "fission yeasts." As part of a composite model system with its widely studied S. pombe sister species, S. japonicus has provided critical insights into the workings and the evolution of cell biological mechanisms. Furthermore, its divergent biology makes S. japonicus a valuable model organism in its own right. However, the currently available genome assembly contains gaps and has been unable to resolve centromeres and other repeat-rich chromosomal regions. Here we present a telomere-to-telomere long-read genome assembly of the S. japonicus genome. This includes the three megabase-length chromosomes, with centromeres hundreds of kilobases long, rich in 5S ribosomal RNA genes, transfer RNA genes, long terminal repeats, and short repeats. We identify a gene-sparse region on chromosome 2 that resembles a 331 kb centromeric duplication. We revise the genome size of S. japonicus to at least 16.6 Mb and possibly up to 18.12 Mb, at least 30% larger than previous estimates. Our whole genome assembly will support the growing S. japonicus research community and facilitate research in new directions, including centromere and DNA repeat evolution, and yeast comparative genomics.},
}
@article {pmid38450924,
year = {2024},
author = {Guo, X and Li, J and Qi, Y and Chen, J and Jiang, M and Zhu, L and Liu, Z and Wang, H and Wang, G and Wang, X},
title = {Telomere length and micronuclei trajectories in APP/PS1 mouse model of Alzheimer's disease: Correlating with cognitive impairment and brain amyloidosis in a sexually dimorphic manner.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e14121},
doi = {10.1111/acel.14121},
pmid = {38450924},
issn = {1474-9726},
support = {31900410//National Natural Science Foundation of China/ ; 32260148//National Natural Science Foundation of China/ ; 31860301//National Natural Science Foundation of China/ ; 202001AU070055//Yunnan Fundamental Research Projects/ ; 202101AT070112//Yunnan Fundamental Research Projects/ ; },
abstract = {Although studies have demonstrated that genome instability is accumulated in patients with Alzheimer's disease (AD), the specific types of genome instability linked to AD pathogenesis remain poorly understood. Here, we report the first characterization of the age- and sex-related trajectories of telomere length (TL) and micronuclei in APP/PS1 mice model and wild-type (WT) controls (C57BL/6). TL was measured in brain (prefrontal cortex, cerebellum, pituitary gland, and hippocampus), colon and skin, and MN was measured in bone marrow in 6- to 14-month-old mice. Variation in TL was attributable to tissue type, age, genotype and, to a lesser extent, sex. Compared to WT, APP/PS1 had a significantly shorter baseline TL across all examined tissues. TL was inversely associated with age in both genotypes and TL shortening was accelerated in brain of APP/PS1. Age-related increase of micronuclei was observed in both genotypes but was accelerated in APP/PS1. We integrated TL and micronuclei data with data on cognition performance and brain amyloidosis. TL and micronuclei were linearly correlated with cognition performance or Aβ40 and Aβ42 levels in both genotypes but to a greater extent in APP/PS1. These associations in APP/PS1 mice were dominantly driven by females. Together, our findings provide foundational knowledge to infer the TL and micronuclei trajectories in APP/PS1 mice during disease progression, and strongly support that TL attrition and micronucleation are tightly associated with AD pathogenesis in a female-biased manner.},
}
@article {pmid38447517,
year = {2024},
author = {Mu, C and Lin, M and Shao, Y and Liao, Q and Liang, J and Yu, C and Wu, X and Chen, M and Tang, Y and Zhou, L and Qiu, X and Pan, D and Huang, D},
title = {Associations between maternal serum neonicotinoid pesticide exposure during pregnancy and newborn telomere length: Effect modification by sampling season.},
journal = {Ecotoxicology and environmental safety},
volume = {273},
number = {},
pages = {116164},
doi = {10.1016/j.ecoenv.2024.116164},
pmid = {38447517},
issn = {1090-2414},
abstract = {BACKGROUND: An increasing amount of evidence suggests that telomere length (TL) at birth can predict lifespan and is associated with chronic diseases later in life, but newborn TL may be affected by environmental pollutants. Neonicotinoids (NEOs) are widely used worldwide, and despite an increasing number of studies showing that they may have adverse effects on birth in mammals and even humans, few studies have examined the effect of NEO exposure on newborn TLs.<br><br>OBJECTIVE: To investigate the effects of prenatal exposure to NEOs and the interactions between NEOs and sampling season on newborn TL.<br><br>METHODS: We conducted a prospective cohort study of 500 mother-newborn pairs from the Guangxi Zhuang Birth Cohort. Ultraperformance liquid chromatographymass spectrometry was used to detect ten NEOs in maternal serum, and fluorescence quantitative PCR was used to estimate the newborn TL. A generalized linear model (GLM) was used to evaluate the relationships between individual NEO exposures and TLs&#xa0;, and quantile g-computation (Qgcomp) model and Bayesian kernel machine regression (BKMR) model were used to evaluate the combined effect of mixtures of components.<br><br>RESULTS: The results of the GLM showed that compared with maternal TMX levels < LOD, maternal TMX levels < median were negatively correlated with newborn TL (-6.93%, 95% CI%: -11.92%, -1.66%), and the decrease in newborn TL was more pronounced in girls (-9.60%, 95% CI: -16.84%, -1.72%). Moreover, different kinds of maternal NEO exposure had different effects on newborn TL in different sampling seasons, and the effect was statistically significant in all seasons except in autumn. Mixed exposure analysis revealed a potential positive trend between NEOs and newborn TL, but the association was not statistically significant.<br><br>CONCLUSION: Prenatal exposure to TMX may&#xa0;shorten newborn TL, and this effect is more pronounced among female newborns. Furthermore, the relationship between NEO exposure and TL may be modified by the sampling season.},
}
@article {pmid38445359,
year = {2024},
author = {Azzalin, CM},
title = {TERRA and the alternative lengthening of telomeres: a dangerous affair.},
journal = {FEBS letters},
volume = {},
number = {},
pages = {},
doi = {10.1002/1873-3468.14844},
pmid = {38445359},
issn = {1873-3468},
support = {LCF/PR/HP21/52310016//'la Caixa' Foundation/ ; 2021.00143.CEECIND//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; PTDC/BIA-MOL/6624/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; PTDC/MED-ONC/7864/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; //Sturtup company/ ; },
abstract = {Eukaryotic telomeres are transcribed into the long noncoding RNA TERRA. A fraction of TERRA remains associated with telomeres by forming RNA:DNA hybrids dubbed telR-loops. TERRA and telR-loops are essential to promote telomere elongation in human cancer cells that maintain telomeres through a homology-directed repair pathway known as alternative lengthening of telomeres or ALT. However, TERRA and telR-loops compromise telomere integrity and cell viability if their levels are not finely tuned. The study of telomere transcription in ALT cells will enormously expand our understanding of the ALT mechanism and of how genome integrity is maintained. Moreover, telomere transcription, TERRA and telR-loops are likely to become exceptionally suited targets for the development of novel anti-cancer therapies.},
}
@article {pmid38443473,
year = {2024},
author = {Xu, J and Zhu, G and Zhang, H},
title = {Causal relationship between telomere length and sepsis: a bidirectional Mendelian randomization study.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {5397},
pmid = {38443473},
issn = {2045-2322},
support = {SKLKF202008//Open Project of the State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University/ ; 20181BAB205041//Jiangxi Provincial Natural Science Foundation/ ; },
abstract = {Numerous observational studies have elucidated a connection between leukocyte telomere length (LTL) and sepsis, yet its fundamental cause remains enigmatic. Thus, the current study's objective is to employ a bidirectional Mendelian randomization (MR) approach to scrutinize the causality between LTL and sepsis. We selected single nucleotide polymorphisms (SNPs) associated with LTL (n = 472,174) and sepsis from a genome-wide association study (GWAS), including Sepsis (n = 486,484, ncase = 11,643), Sepsis (28 day death in critical care) (n = 431,365, ncase = 347), Sepsis (under 75) (n = 462,869, ncase = 11,568), Sepsis (28 day death) (n = 486,484, ncase = 1896), and Sepsis (critical care) (n = 431,365, ncase = 1380), as instrumental variables (IVs). The inverse variance weighted (IVW) MR method was employed as the primary approach, and various sensitivity analyses were conducted to assess the validity of this instrument and potential pleiotropy. Using the IVW method, we uncovered a potential causal relationship between genetically predicted LTL reduction and increased susceptibility to sepsis, with an odds ratio (OR) of 1.161 [95% confidence interval (CI) 1.039-1.297, p = 0.008]. However, reverse MR analysis did not indicate any impact of sepsis on LTL. Our forward MR study highlights a potential causal relationship between LTL as an exposure and increased susceptibility to sepsis. Specifically, our findings suggest that individuals with genetically determined shorter LTL may be at an increased risk of developing sepsis. This may contribute to the development of novel diagnostic and therapeutic strategies for the prevention, diagnosis, and treatment of sepsis.},
}
@article {pmid38442010,
year = {2024},
author = {Souza-Talarico, JN and Chesak, S and Elizalde, N and Liu, W and Moon, C and Oberfrank, NDCF and Rauer, AJ and Takao, CL and Shaw, C and Saravanan, A and Longhi Palacio, FG and Buck, H},
title = {Exploring the interplay of psychological and biological components of stress response and telomere length in the transition from middle age to late adulthood: A systematic review.},
journal = {Stress and health : journal of the International Society for the Investigation of Stress},
volume = {},
number = {},
pages = {e3389},
doi = {10.1002/smi.3389},
pmid = {38442010},
issn = {1532-2998},
abstract = {Ageing and chronic stress have been linked to reduced telomere length (TL) in mixed-age groups. Whether stress response components are linked to TL during the midlife-to-late adulthood transition remains unclear. Our study aimed to synthesise evidence on the relationship between psychological and biological components of stress response on TL in middle-aged and older adults. We conducted a systematic review of studies obtained from six databases (PubMed, CINAHL, EMBASE, PsycINFO, Web of Science, and Scopus) and evaluated by two independent reviewers. Original research measuring psychological and biological components of stress response and TL in human individuals were included. From an initial pool of 614 studies, 15 were included (n = 9446 participants). Synthesis of evidence showed that higher psychological components of the stress response (i.e., global perceived stress or within a specific life domain and cognitive appraisal to social-evaluative stressors) were linked to shorter TL, specifically in women or under major life stressors. For the biological stress response, cortisol, dehydroepiandrosterone sulphate and IGF-1/cortisol imbalance, IL-6, MCP-1, blood pressure, and heart rate presented a significant association with TL, but this relationship depended on major life stressors and the stress context (manipulated vs. non-manipulated conditions). This comprehensive review showed that psychological and biological components of the stress response are linked to shorter TL, but mainly in women or those under a major life stressor and stress-induced conditions. The interaction between stressor attributes and psychological and biological reactions in the transition from middle to late adulthood still needs to be fully understood, and examining it is a critical step to expanding our understanding of stress's impact on ageing trajectories.},
}
@article {pmid38441835,
year = {2024},
author = {Olovnikov, IA},
title = {Telomeres in health and longevity: special issue in memory of Alexey Olovnikov.},
journal = {Biogerontology},
volume = {},
number = {},
pages = {},
pmid = {38441835},
issn = {1573-6768},
abstract = {In this special issue we commemorate theoretical biologist Alexey Olovnikov (1936-2022), whose theory of marginotomy has laid the foundation for the new field of biology that studies the molecular structure of telomeres and its role in health, longevity and aging. This issue contains a collection of reviews and research articles that discuss different aspects of telomere and telomerase research, ranging from telomere length dynamics in wild animal populations to problems of telomere maintenance during human space flight.},
}
@article {pmid38441152,
year = {2024},
author = {Henriques, CM and Ferreira, MG},
title = {Telomere length is an epigenetic trait - Implications for the use of telomerase-deficient organisms to model human disease.},
journal = {Disease models &amp; mechanisms},
volume = {17},
number = {3},
pages = {},
doi = {10.1242/dmm.050581},
pmid = {38441152},
issn = {1754-8411},
support = {/WT_/Wellcome Trust/United Kingdom ; },
abstract = {Telomere length, unlike most genetic traits, is epigenetic, in the sense that it is not fully coded by the genome. Telomeres vary in length and randomly assort to the progeny leaving some individuals with longer and others with shorter telomeres. Telomerase activity counteracts this by extending telomeres in the germline and during embryogenesis but sizeable variances remain in telomere length. This effect is exacerbated by the absence of fully active telomerase. Telomerase heterozygous animals (tert+/-) have reduced telomerase activity and their telomeres fail to be elongated to wild-type average length, meaning that - with every generation - they decrease. After a given number of successive generations of telomerase-insufficient crosses, telomeres become critically short and cause organismal defects that, in humans, are known as telomere biology disorders. Importantly, these defects also occur in wild-type (tert+/+) animals derived from such tert+/- incrosses. Despite these tert+/+ animals being proficient for telomerase, they have shorter than average telomere length and, although milder, develop phenotypes that are similar to those of telomerase mutants. Here, we discuss the impact of this phenomenon on human pathologies associated with telomere length, provide a brief overview of telomere biology across species and propose specific measures for working with telomerase-deficient zebrafish.},
}
@article {pmid38438580,
year = {2024},
author = {Qiu, YD and Yan, Q and Wang, Y and Ye, YF and Wang, Y and Wang, MY and Wang, PP and Zhang, SY and Wang, DL and Yan, H and Ruan, J and Zhao, YJ and Huang, LH and Cho, N and Wang, K and Zheng, XH and Liu, ZG},
title = {Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells.},
journal = {Acta pharmacologica Sinica},
volume = {},
number = {},
pages = {},
pmid = {38438580},
issn = {1745-7254},
abstract = {Telomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high expression is associated with poor prognosis. Flavokavain B derivative FKB04 potently inhibited TRF2 expression in liver cancer cells while having limited effects on the other five shelterin subunits. Moreover, FKB04 treatment induced telomere shortening and increased the amounts of telomere-free ends, leading to the destruction of T-loop structure. Consequently, FKB04 promoted liver cancer cell senescence without modulating apoptosis levels. In corroboration with these findings, FKB04 inhibited tumor cell growth by promoting telomeric TRF2 deficiency-induced telomere shortening in a mouse xenograft tumor model, with no obvious side effects. These results demonstrate that TRF2 is a potential therapeutic target for liver cancer and suggest that FKB04 may be a selective small-molecule inhibitor of TRF2, showing promise in the treatment of liver cancer.},
}
@article {pmid38435987,
year = {2024},
author = {Lunghi, E and Bilandžija, H},
title = {Telomere length and dynamics in Astyanax mexicanus cave and surface morphs.},
journal = {PeerJ},
volume = {12},
number = {},
pages = {e16957},
doi = {10.7717/peerj.16957},
pmid = {38435987},
issn = {2167-8359},
abstract = {BACKGROUND: Telomeres are non-coding DNA repeats at the chromosome ends and their shortening is considered one of the major causes of aging. However, they also serve as a biomarker of environmental exposures and their length and attrition is affected by various stressors. In this study, we examined the average telomere length in Astyanax mexicanus, a species that has both surface-dwelling and cave-adapted populations. The cave morph descended from surface ancestors and adapted to a markedly different environment characterized by specific biotic and abiotic stressors, many of which are known to affect telomere length. Our objective was to explore whether telomere length differs between the two morphs and whether it serves as a biological marker of aging or correlates with the diverse environments the morphs are exposed to.<br><br>METHODS: We compared telomere length and shortening between laboratory-reared Pach&#xf3;n cavefish and Rio Choy surface fish of A. mexicanus across different tissues and ages.<br><br>RESULTS: Astyanax mexicanus surface fish exhibited longer average telomere length compared to cavefish. In addition, we did not observe telomere attrition in either cave or surface form as a result of aging in adults up to 9 years old, suggesting that efficient mechanisms prevent telomere-mediated senescence in laboratory stocks of this species, at least within this time frame. Our results suggest that telomere length in Astyanax may be considered a biomarker of environmental exposures. Cavefish may have evolved shorter and energetically less costly telomeres due to the absence of potential stressors known to affect surface species, such as predator pressure and ultra-violet radiation. This study provides the first insights into telomere dynamics in Astyanax morphs and suggests that shorter telomeres may have evolved as an adaptation to caves.},
}
@article {pmid38435019,
year = {2024},
author = {Taylor, GT and McQueen, A and Eastwood, JR and Dupoué, A and Wong, BBM and Verhulst, S and Peters, A},
title = {No effect of testosterone or sexual ornamentation on telomere dynamics: A case study and meta-analyses.},
journal = {Ecology and evolution},
volume = {14},
number = {3},
pages = {e11088},
doi = {10.1002/ece3.11088},
pmid = {38435019},
issn = {2045-7758},
abstract = {Life-history theory predicts that reproductive investments are traded-off against self-maintenance. Telomeres, the protective caps on the ends of chromosomes, offer a promising avenue for assessing life-history trade-offs, as they shorten in response to stressors and are predictive of the remaining lifespan. In males, testosterone frequently mediates life-history trade-offs, in part, through its effects on sexual ornamentation, which is an important aspect of reproductive investment. However, studies of within-individual associations between telomere dynamics and sexual ornamentation are limited in number and have produced mixed results. Furthermore, most such studies have been observational, making it difficult to discern the nature of any causal relationship. To address this, we used short-acting testosterone implants in free-living male superb fairy-wrens (Malurus cyaneus) to stimulate the production of a sexual ornament: early moult into a costly blue breeding plumage. We found no evidence that elevated testosterone, and the consequent earlier moult into breeding plumage, accelerated telomere shortening. We therefore followed up with a systematic review and two meta-analyses (28 studies, 54 effect sizes) exploring the associations between telomeres and (1) testosterone and (2) sexual ornamentation. In line with our experimental findings, neither meta-analysis showed an overall correlation of testosterone or sexual ornamentation with telomere length or telomere dynamics. However, meta-regression showed that experimental, compared to observational, studies reported greater evidence of trade-offs. Our meta-analyses highlight the need for further experimental studies to better understand potential responses of telomere length or telomere dynamics to testosterone or sexual ornamentation.},
}
@article {pmid38434436,
year = {2024},
author = {Barcenilla, BB and Kundel, I and Hall, E and Hilty, N and Ulianich, P and Cook, J and Turley, J and Yerram, M and Min, JH and Castillo-González, C and Shippen, DE},
title = {Telomere dynamics and oxidative stress in Arabidopsis grown in lunar regolith simulant.},
journal = {Frontiers in plant science},
volume = {15},
number = {},
pages = {1351613},
doi = {10.3389/fpls.2024.1351613},
pmid = {38434436},
issn = {1664-462X},
abstract = {NASA envisions a future where humans establish a thriving colony on the Moon by 2050. Plants will be essential for this endeavor, but little is known about their adaptation to extraterrestrial bodies. The capacity to grow plants in lunar regolith would represent a major step towards this goal by minimizing the reliance on resources transported from Earth. Recent studies reveal that Arabidopsis thaliana can germinate and grow on genuine lunar regolith as well as on lunar regolith simulant. However, plants arrest in vegetative development and activate a variety of stress response pathways, most notably the oxidative stress response. Telomeres are hotspots for oxidative damage in the genome and a marker of fitness in many organisms. Here we examine A. thaliana growth on a lunar regolith simulant and the impact of this resource on plant physiology and on telomere dynamics, telomerase enzyme activity and genome oxidation. We report that plants successfully set seed and generate a viable second plant generation if the lunar regolith simulant is pre-washed with an antioxidant cocktail. However, plants sustain a higher degree of genome oxidation and decreased biomass relative to conventional Earth soil cultivation. Moreover, telomerase activity substantially declines and telomeres shorten in plants grown in lunar regolith simulant, implying that genome integrity may not be sustainable over the long-term. Overcoming these challenges will be an important goal in ensuring success on the lunar frontier.},
}
@article {pmid38431573,
year = {2024},
author = {Ding, K and Zhangwang, J and Lei, M and Xiong, C},
title = {Insight into telomere regulation: road to discovery and intervention in plasma drug-protein targets.},
journal = {BMC genomics},
volume = {25},
number = {1},
pages = {231},
pmid = {38431573},
issn = {1471-2164},
abstract = {BACKGROUND: Telomere length is a critical metric linked to aging, health, and disease. Currently, the exploration of target proteins related to telomere length is usually limited to the context of aging and specific diseases, which limits the discovery of more relevant drug targets. This study integrated large-scale plasma cis-pQTLs data and telomere length GWAS datasets. We used Mendelian randomization(MR) to identify drug target proteins for telomere length, providing essential clues for future precision therapy and targeted drug development.<br><br>METHODS: Using plasma cis-pQTLs data from a previous GWAS study (3,606 Pqtls associated with 2,656 proteins) and a GWAS dataset of telomere length (sample size: 472,174; GWAS ID:&#xa0;ieu-b-4879) from UK Biobank, using MR, external validation, and reverse causality testing, we identified essential drug target proteins for telomere length. We also&#xa0;performed co-localization, Phenome-wide association studies and enrichment analysis, protein-protein interaction network construction, search for existing intervening drugs, and potential drug/compound prediction for these critical targets to strengthen and expand our findings.<br><br>RESULTS: After Bonferron correction (p&#x2009;<&#x2009;0.05/734), RPN1 (OR: 0.96; 95%CI: (0.95, 0.97)), GDI2 (OR: 0.94; 95%CI: (0.92, 0.96)), NT5C (OR: 0.97; 95%CI: (0.95, 0.98)) had a significant negative causal association with telomere length; TYRO3 (OR: 1.11; 95%CI: (1.09, 1.15)) had a significant positive causal association with telomere length.&#xa0;GDI2 shared the same genetic variants with telomere length (coloc.abf-PPH 4&#x2009;>&#x2009;0.8).<br><br>CONCLUSION: Genetically determined plasma RPN1, GDI2, NT5C, and TYRO3 have significant causal effects on telomere length and can potentially be drug targets. Further exploration of the role and mechanism of these proteins/genes in regulating telomere length is needed.},
}
@article {pmid38431123,
year = {2024},
author = {Di, D and Zhou, H and Cui, Z and Zhang, J and Liu, Q and Yuan, T and Zhou, T and Luo, X and Ling, D and Wang, Q},
title = {Early-life tobacco smoke elevating later-life osteoporosis risk: Mediated by telomere length and interplayed with genetic predisposition.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2024.02.021},
pmid = {38431123},
issn = {2090-1224},
abstract = {INTRODUCTION: The growing prevalence of osteoporosis (OP) in an aging global population presents a significant public health concern. Tobacco smoke negatively affects bone turnover, leading to reduced bone mass and heightened OP and fracture risk. However, the impact of early-life tobacco smoke exposure on later-life OP risk remains unclear.<br><br>OBJECTIVES: This study was to explore the effects of early-life tobacco smoke exposure on incident OP risk in later life. The mediating role of telomere length (TL) and the interaction with genetic predisposition were also studied.<br><br>METHODS: Data on in utero tobacco smoke exposure (IUTSE) status and age of tobacco use initiation from the UK Biobank were used to estimate early-life tobacco smoke exposure. Incident OP cases were identified according to health-related records. Linear, Cox, and Laplace regression models were mainly used for data analysis.<br><br>RESULTS: Individuals with IUTSE showed a higher OP risk [hazard ratio (HR): 1.06, 95&#x202f;% confidence interval (CI): 1.01, 1.11] and experienced earlier OP onset by 0.30&#x202f;years [50th percentile difference&#x202f;=&#x202f;-0.30, 95&#x202f;% CI: -0.51, -0.09] compared to those without. Participants initiating tobacco smoke in childhood, adolescence, and adulthood had 1.41 times (95&#x202f;% CI: 1.23, 1.61), 1.17 times (95&#x202f;% CI:1.10, 1.24), and 1.14 times (95&#x202f;% CI: 1.07, 1.20) the risk of OP, respectively, compared to never smokers. They also experienced earlier OP onset by 2.16, 0.95, and 0.71&#x202f;years, sequentially. The TL significantly mediated the early-life tobacco exposure and OP association. Significant joint and interactive effects were detected between early-life tobacco smoke exposure and genetic elements.<br><br>CONCLUSIONS: Our findings implicate that early-life tobacco smoke exposure elevates the later-life OP risk, mediated by telomere length and interplayed with genetic predisposition. These findings highlight the importance of early-life intervention against tobacco smoke exposure and ageing status for precise OP prevention, especially in individuals with a high genetic risk.},
}
@article {pmid38430974,
year = {2024},
author = {Bories, C and Lejour, T and Adolphe, F and Kermasson, L and Couvé, S and Tanguy, L and Luszczewska, G and Watzky, M and Poillerat, V and Garnier, P and Groisman, R and Ferlicot, S and Richard, S and Saparbaev, M and Revy, P and Gad, S and Renaud, F},
title = {DCLRE1B/Apollo germline mutations associated with renal cell carcinoma impair telomere protection.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {},
number = {},
pages = {167107},
doi = {10.1016/j.bbadis.2024.167107},
pmid = {38430974},
issn = {1879-260X},
abstract = {Hereditary renal cell carcinoma (RCC) is caused by germline mutations in a subset of genes, including VHL, MET, FLCN, and FH. However, many familial RCC cases do not harbor mutations in the known predisposition genes. Using Whole Exome Sequencing, we identified two germline missense variants in the DCLRE1B/Apollo gene (Apollo[N246I] and Apollo[Y273H]) in two unrelated families with several RCC cases. Apollo encodes an exonuclease involved in DNA Damage Response and Repair (DDRR) and telomere integrity. We characterized these two functions in the human renal epithelial cell line HKC8. The decrease or inhibition of Apollo expression sensitizes these cells to DNA interstrand crosslink damage (ICLs). HKC8 Apollo[-/-] cells appear defective in the DDRR and present an accumulation of telomere damage. Wild-type and mutated Apollo forms could interact with TRF2, a shelterin protein involved in telomere protection. However, only Apollo[WT] can rescue the telomere damage in HKC8 Apollo[-/-] cells. Our results strongly suggest that Apollo[N246I] and Apollo[Y273H] are loss-of-function mutants that cause impaired telomere integrity and could lead to genomic instability. Altogether, our results suggest that mutations in Apollo could induce renal oncogenesis.},
}
@article {pmid38429270,
year = {2024},
author = {Spano, L and Marie-Claire, C and Godin, O and Lebras, A and Courtin, C and Laplanche, JL and Leboyer, M and Aouizerate, B and Lefrere, A and Belzeaux, R and Courtet, P and Olié, E and Dubertret, C and Schwan, R and Aubin, V and Roux, P and Polosan, M and Samalin, L and Haffen, E and , and Bellivier, F and Etain, B},
title = {Decreased telomere length in a subgroup of young individuals with bipolar disorders: replication in the FACE-BD cohort and association with the shelterin component POT1.},
journal = {Translational psychiatry},
volume = {14},
number = {1},
pages = {131},
pmid = {38429270},
issn = {2158-3188},
support = {2018//Fondation de France/ ; },
mesh = {Humans ; Aged ; Adult ; *Bipolar Disorder/genetics ; Telomere/genetics ; Telomere Shortening/genetics ; Aging ; *Aging, Premature ; Shelterin Complex ; Telomere-Binding Proteins/genetics ; },
abstract = {Bipolar disorder (BD) has been associated with premature cellular aging with shortened telomere length (TL) as compared to the general population. We recently identified a subgroup of young individuals with prematurely shortened TL. The aims of the present study were to replicate this observation in a larger sample and analyze the expression levels of genes associated with age or TL in a subsample of these individuals. TL was measured on peripheral blood DNA using quantitative polymerase chain reaction in a sample of 542 individuals with BD and clustering analyses were performed. Gene expression level of 29 genes, associated with aging or with telomere maintenance, was analyzed in RNA samples from a subsample of 129 individuals. Clustering analyses identified a group of young individuals (mean age 29.64 years), with shorter TL. None of the tested clinical variables were significantly associated with this subgroup. Gene expression level analyses showed significant downregulation of MYC, POT1, and CD27 in the prematurely aged young individuals compared to the young individuals with longer TL. After adjustment only POT1 remained significantly differentially expressed between the two groups of young individuals. This study confirms the existence of a subgroup of young individuals with BD with shortened TL. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening.},
}
@article {pmid38426330,
year = {2024},
author = {Bosquet Enlow, M and De Vivo, I and Petty, CR and Nelson, CA},
title = {Temperament and sex as moderating factors of the effects of exposure to maternal depression on telomere length in early childhood.},
journal = {Development and psychopathology},
volume = {},
number = {},
pages = {1-14},
doi = {10.1017/S0954579424000518},
pmid = {38426330},
issn = {1469-2198},
abstract = {Individual differences in sensitivity to context are posited to emerge early in development and to influence the effects of environmental exposures on a range of developmental outcomes. The goal of the current study was to examine the hypothesis that temperament characteristics and biological sex confer differential vulnerability to the effects of exposure to maternal depression on telomere length in early childhood. Telomere length has emerged as a potentially important biomarker of current and future health, with possible mechanistic involvement in the onset of various disease states. Participants comprised a community sample of children followed from infancy to age 3 years. Relative telomere length was assessed from DNA in saliva samples collected at infancy, 2 years, and 3 years. Maternal depressive symptoms and the child temperament traits of negative affectivity, surgency/extraversion, and regulation/effortful control were assessed via maternal report at each timepoint. Analyses revealed a 3-way interaction among surgency/extraversion, sex, and maternal depressive symptoms, such that higher surgency/extraversion was associated with shorter telomere length specifically among males exposed to elevated maternal depressive symptoms. These findings suggest that temperament and sex influence children's susceptibility to the effects of maternal depression on telomere dynamics in early life.},
}
@article {pmid38422914,
year = {2024},
author = {Kam, MLW and Chong, ST and Chan, SH and Swigris, JJ and Chew, EL and Tan, YH and Ngeow, JYY and Low, SY},
title = {First ever characterisation of the effects of short telomeres in a Singapore interstitial lung disease cohort.},
journal = {Respiratory investigation},
volume = {62},
number = {3},
pages = {348-355},
doi = {10.1016/j.resinv.2024.02.004},
pmid = {38422914},
issn = {2212-5353},
abstract = {BACKGROUND: Differences in disease behaviour and genotypes are described in Asian and Western interstitial lung disease (ILD) cohorts. Short leukocyte telomere length (LTL) correlates with poor outcomes in Western ILD cohorts but its significance in Asian populations is unknown. We aim to characterise the burden and clinical implications of short LTL in Singaporean ILD patients.<br><br>METHODS: Patients diagnosed with ILD at Singapore General Hospital were prospectively recruited and compared against 36 healthy controls. The primary outcome was transplant-free survival. Genomic DNA from peripheral blood was extracted and LTL measured using quantitative polymerase chain reaction assay (qPCR).<br><br>RESULTS: Amongst 165 patients, 37% had short LTL. There was a higher proportion of combined pulmonary fibrosis and emphysema (CPFE) patients with short LTL (n&#xa0;=&#xa0;21, 34.4% vs n&#xa0;=&#xa0;16, 15.4%; p&#xa0;<&#xa0;0.001). Short LTL patients had reduced survival at 12-, 24- and 36-months and median survival of 24 months (p&#xa0;<&#xa0;0.001) which remained significant following adjustment for smoking, GAP Stage and radiological UIP pattern (Hazard Ratio (HR), 2.74; 95%CI:1.46, 5.11; p&#xa0;=&#xa0;0.002). They had increased respiratory-related mortality and acute exacerbation incidences. Despite similar baseline lung function, short LTL patients had a faster decline in absolute forced vital capacity (FVC) of -105.3 (95% CI: 151.4, -59.1) mL/year compared to -58.2 (95% CI: 82.9, -33.6) mL/year (p&#xa0;<&#xa0;0.001) in normal LTL patients.<br><br>CONCLUSION: Short LTL correlated with increased mortality and faster lung function decline in our Singaporean ILD cohort with a magnitude similar to that in Western ILD cohorts. Further research is needed to integrate LTL assessment into clinical practice.},
}
@article {pmid38418884,
year = {2024},
author = {Takai, H and Aria, V and Borges, P and Yeeles, JTP and de Lange, T},
title = {CST-polymerase α-primase solves a second telomere end-replication problem.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {38418884},
issn = {1476-4687},
support = {R01 CA076027/CA/NCI NIH HHS/United States ; R50 CA243771/CA/NCI NIH HHS/United States ; },
abstract = {Telomerase adds G-rich telomeric repeats to the 3' ends of telomeres[1], counteracting telomere shortening caused by loss of telomeric 3' overhangs during leading-strand DNA synthesis ('the end-replication problem'[2]). Here we report a second end-replication problem that originates from the incomplete duplication of the C-rich telomeric repeat strand (C-strand) by lagging-strand DNA synthesis. This problem is resolved by fill-in synthesis mediated by polymerase α-primase bound to Ctc1-Stn1-Ten1 (CST-Polα-primase). In vitro, priming for lagging-strand DNA replication does not occur on the 3' overhang and lagging-strand synthesis stops in a zone of approximately 150 nucleotides (nt) more than 26 nt from the end of the template. Consistent with the in vitro data, lagging-end telomeres of cells lacking CST-Polα-primase lost 50-60 nt of telomeric CCCTAA repeats per population doubling. The C-strands of leading-end telomeres shortened by around 100 nt per population doubling, reflecting the generation of 3' overhangs through resection. The measured overall C-strand shortening in the absence of CST-Polα-primase fill-in is consistent with the combined effects of incomplete lagging-strand synthesis and 5' resection at the leading ends. We conclude that canonical DNA replication creates two telomere end-replication problems that require telomerase to maintain the G-rich strand and CST-Polα-primase to maintain the C-strand.},
}
@article {pmid38409427,
year = {2024},
author = {Inomata, S and Arima, H and Fukuda, T and Ozawa, H and Yamamoto, T},
title = {Smoking and diabetes cause telomere shortening among alcohol use disorder patients.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {4701},
pmid = {38409427},
issn = {2045-2322},
support = {19H05737//Grants-in-Aid for Scientific Research (KAKENHI)/ ; },
mesh = {Humans ; Telomere Shortening ; *Alcoholism/genetics ; Alcohol Drinking/adverse effects ; Smoking/adverse effects/genetics ; Telomere/genetics ; *Diabetes Mellitus/genetics ; Leukocytes ; },
abstract = {The length of telomeres located at the ends of chromosomes has attracted attention as an indicator of cellular and individual aging. Various diseases or stresses cause telomere shortening, and it has been reported that alcohol use disorder patients actually have shorter telomeres than healthy patients. However, the factors that contribute to the reduction in telomere length among alcohol use disorder patients have not been clarified in detail. Therefore, in this study, we explored the factors that reduce telomere length in alcohol use disorder patients. A questionnaire survey and a measurement of leukocyte telomere length were conducted among alcohol use disorder patients. The mean telomere length of leukocyte was measured by ∆∆Ct analysis using a real-time PCR. We compared the telomere length between alcohol use disorder patients and the control group (Japanese special health check-up examinee). Moreover, we searched for factors associated with telomere length from drinking/smoking characteristics and history of comorbidities. A total of 74 subjects had alcohol use disorder, and 68 were in the control group. Compared to the control group, alcohol use disorder patients had significantly shorter telomere lengths (p < 0.001). A multivariate analysis revealed that a longer duration of smoking resulted in a significantly shorter telomere length (p = 0.0129). In addition, a comparison of the telomere length between the groups with and without a history of suffering from each disease revealed that telomere length was significantly shorter in the group with diabetes than in the group without diabetes (p = 0.0371). This study reveals that in individuals with alcohol dependence, particularly, prolonged smoking habits and the presence of diabetes contribute to telomere shortening. Medication and support for abstinence from alcohol has been mainly provided for alcohol use disorder patients. Our findings demonstrate a potential support approach via smoking cessation programs and controlling diabetes, which may be helpful to suppress the shortening of healthy life expectancy among alcohol use disorder patients.},
}
@article {pmid38407308,
year = {2024},
author = {Sonmez, C and Toia, B and Eickhoff, P and Matei, AM and El Beyrouthy, M and Wallner, B and Douglas, ME and de Lange, T and Lottersberger, F},
title = {DNA-PK controls Apollo's access to leading-end telomeres.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae105},
pmid = {38407308},
issn = {1362-4962},
support = {AG016642/NH/NIH HHS/United States ; },
abstract = {The complex formed by Ku70/80 and DNA-PKcs (DNA-PK) promotes the synapsis and the joining of double strand breaks (DSBs) during canonical non-homologous end joining (c-NHEJ). In c-NHEJ during V(D)J recombination, DNA-PK promotes the processing of the ends and the opening of the DNA hairpins by recruiting and/or activating the nuclease Artemis/DCLRE1C/SNM1C. Paradoxically, DNA-PK is also required to prevent the fusions of newly replicated leading-end telomeres. Here, we describe the role for DNA-PK in controlling Apollo/DCLRE1B/SNM1B, the nuclease that resects leading-end telomeres. We show that the telomeric function of Apollo requires DNA-PKcs's kinase activity and the binding of Apollo to DNA-PK. Furthermore, AlphaFold-Multimer predicts that Apollo's nuclease domain has extensive additional interactions with DNA-PKcs, and comparison to the cryo-EM structure of Artemis bound to DNA-PK phosphorylated on the ABCDE/Thr2609 cluster suggests that DNA-PK can similarly grant Apollo access to the DNA end. In agreement, the telomeric function of DNA-PK requires the ABCDE/Thr2609 cluster. These data reveal that resection of leading-end telomeres is regulated by DNA-PK through its binding to Apollo and its (auto)phosphorylation-dependent positioning of Apollo at the DNA end, analogous but not identical to DNA-PK dependent regulation of Artemis at hairpins.},
}
@article {pmid38404592,
year = {2024},
author = {Xu, D and Ye, Z and Huang, Y and Zhu, K and Xu, H and Yu, J and Feng, Y and Zhao, X and Wang, L and Xu, H and Li, Q and Qin, M and Tang, Y and Zhang, X and Zhao, Y},
title = {Haplotype-resolved genome assembly of Corydalis yanhusuo, a traditional Chinese medicine with unusual telomere motif.},
journal = {Horticulture research},
volume = {11},
number = {2},
pages = {uhad296},
pmid = {38404592},
issn = {2662-6810},
}
@article {pmid38398126,
year = {2024},
author = {Gorria, T and Crous, C and Pineda, E and Hernandez, A and Domenech, M and Sanz, C and Jares, P and Muñoz-Mármol, AM and Arpí-Llucía, O and Melendez, B and Gut, M and Esteve, A and Esteve-Codina, A and Parra, G and Alameda, F and Carrato, C and Aldecoa, I and Mallo, M and de la Iglesia, N and Balana, C},
title = {The C250T Mutation of TERTp Might Grant a Better Prognosis to Glioblastoma by Exerting Less Biological Effect on Telomeres and Chromosomes Than the C228T Mutation.},
journal = {Cancers},
volume = {16},
number = {4},
pages = {},
pmid = {38398126},
issn = {2072-6694},
support = {665/C/2013//Fundaci&#xf3; La Marat&#xf3; TV3/ ; PI118/01062//Instituto de Salud Carlos III/ ; },
abstract = {UNLABELLED: The aim of this study was to determine how TERTp mutations impact glioblastoma prognosis.<br><br>MATERIALS AND METHODS: TERTp mutations were assessed in a retrospective cohort of 258 uniformly treated glioblastoma patients. RNA-sequencing and whole exome sequencing results were available in a subset of patients.<br><br>RESULTS: Overall, there were no differences in outcomes between patients with mutated TERTp-wt or TERTp. However, we found significant differences according to the type of TERTp mutation. Progression-free survival (mPFS) was 9.1 months for those with the C250T mutation and 7 months for those with either the C228T mutation or TERTp-wt (p = 0.016). Overall survival (mOS) was 21.9 and 15 months, respectively (p = 0.026). This differential effect was more pronounced in patients with MGMTp methylation (mPFS: p = 0.008; mOS: p = 0.021). Multivariate analysis identified the C250T mutation as an independent prognostic factor for longer mOS (HR 0.69; p = 0.044). We found no differences according to TERTp mutation status in molecular alterations common in glioblastoma, nor in copy number variants in genes related to alternative lengthening of telomeres. Nevertheless, in the gene enrichment analysis adjusted for MGMTp methylation status, some Reactome gene sets were differentially enriched, suggesting that the C250T mutation may exert a lesser effect on telomeres or chromosomes.<br><br>CONCLUSIONS: In our series, patients exhibiting the C250T mutation had a more favorable prognosis compared to those with either TERPp-wt or TERTp C228T mutations. Additionally, our findings suggest a reduced involvement of the C250T mutation in the underlying biological mechanisms related to telomeres.},
}
@article {pmid38397754,
year = {2024},
author = {Córdoba-Lanús, E and Montuenga, LM and Domínguez-de-Barros, A and Oliva, A and Mayato, D and Remírez-Sanz, A and Gonzalvo, F and Celli, B and Zulueta, JJ and Casanova, C},
title = {Oxidative Damage and Telomere Length as Markers of Lung Cancer Development among Chronic Obstructive Pulmonary Disease (COPD) Smokers.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {13},
number = {2},
pages = {},
pmid = {38397754},
issn = {2076-3921},
support = {PI 12/00355//Instituto de Salud Carlos III/ ; PI 13/007//Sociedad Espa&#xf1;ola de Neumolog&#xed;a y Cirug&#xed;a Tor&#xe1;cica/ ; Agust&#xed;n de Betancourt program//Cabildo de Tenerife/ ; CB21/13/00100//Centro de Investigaci&#xf3;n Biom&#xe9;dica en Red en Enfermedades Infecciosas/ ; 2018//Menarini S.A./ ; },
abstract = {Lung cancer (LC) constitutes an important cause of death among patients with Chronic Obstructive Pulmonary Disease (COPD). Both diseases may share pathobiological mechanisms related to oxidative damage and cellular senescence. In this study, the potential value of leucocyte telomere length, a hallmark of aging, and 8-OHdG concentrations, indicative of oxidative DNA damage, as risk biomarkers of LC was evaluated in COPD patients three years prior to LC diagnosis. Relative telomere length measured using qPCR and serum levels of 8-OHdG were determined at the baseline in 99 COPD smokers (33 with LC and 66 age-matched COPD without LC as controls). Of these, 21 COPD with LC and 42 controls had the biomarkers measured 3 years before. Single nucleotide variants (SNVs) in TERT, RTEL, and NAF1 genes were also determined. COPD cases were evaluated, which showed greater telomere length (p < 0.001) and increased serum 8-OHdG levels (p = 0.004) three years prior to LC diagnosis compared to the controls. This relationship was confirmed at the time of LC diagnosis. No significant association was found between the studied SNVs in cases vs. controls. In conclusion, this preliminary study shows that longer leucocyte telomere length and increased 8-OHdG serum levels can be useful as early biomarkers of the risk for future lung cancer development among COPD patients.},
}
@article {pmid38393686,
year = {2024},
author = {Wang, Y and Liu, Q and Liang, S and Yao, M and Zheng, H and Hu, D and Wang, Y},
title = {Genetically predicted telomere length and the risk of 11 hematological diseases: a Mendelian randomization study.},
journal = {Aging},
volume = {16},
number = {},
pages = {},
doi = {10.18632/aging.205583},
pmid = {38393686},
issn = {1945-4589},
abstract = {OBJECTIVE: Previous studies have demonstrated that various hematologic diseases (HDs) induce alterations in telomere length (TL). The aim of this study is to investigate whether genetically predicted changes in TL have an impact on the risk of developing HDs.<br><br>METHODS: GWAS data for TL and 11 HDs were extracted from the database. The R software package "TwoSampleMR" was employed to conduct a two-sample Mendelian randomization (MR) analysis, in order to estimate the influence of TL changes on the risk of developing the 11 HDs.<br><br>RESULTS: We examined the effect of TL changes on the risk of developing the 11 HDs. The IVW results revealed a significant causal association between genetically predicted longer TL and the risk of developing acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MANTLE), and hodgkin lymphoma (HODGKIN). However, there was no significant causal relationship observed between TL changes and the risk of developing chronic myeloid leukemia (CML), diffuse large b-cell lymphoma (DLBCL), marginal zone b-cell lymphoma (MARGINAL), follicular lymphoma (FOLLICULAR), monocytic leukemia (MONOCYTIC), and mature T/NK-cell lymphomas (TNK).<br><br>CONCLUSIONS: The MR analysis revealed a positive association between genetically predicted longer TL and an increased risk of developing ALL, AML, CLL, MANTLE, and HODGKIN. This study further supports the notion that cells with longer TL have greater proliferative and mutational potential, leading to an increased risk of certain HDs.},
}
@article {pmid38393627,
year = {2024},
author = {Kogure, GS and Verruma, CG and Santana, BA and Calado, RT and Ferriani, RA and Furtado, CLM and Dos Reis, RM},
title = {Obesity contributes to telomere shortening in polycystic ovary syndrome.},
journal = {Reproductive sciences (Thousand Oaks, Calif.)},
volume = {},
number = {},
pages = {},
pmid = {38393627},
issn = {1933-7205},
support = {2019/17618-3//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 2012/11566-2//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 2012/11069-9//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 2015/14031-0//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; },
abstract = {Polycystic ovary syndrome (PCOS) is a multifactorial disorder and obesity occurs in 38% to 88% of these women. Although hyperandrogenism may contribute to telomere lengthening, increased body mass index (BMI) is associated with telomere erosion. We sought to compare leukocyte telomere length (LTL) in PCOS women with normal, overweight, and obese BMI. We evaluated the relationship between LTL and clinical variables of PCOS and inflammatory biomarkers independent of BMI. A total of 348 women (243 PCOS and 105 non-PCOS) were evaluated for anthropometric measures, total testosterone, androstenedione, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), free androgen index (FAI), fasting insulin and glycemia, lipid profile, homocysteine, C-reactive protein (CRP) and homeostatic model of insulin resistance (HOMA-IR). LTL was measured by qPCR. The PCOS group presented higher weight, waist circumference, BMI, testosterone, LH, fasting insulin, FAI, and HOMA-IR, and lower E2, SHBG, and fasting glycemia measures compared with the non-PCOS. When stratified by BMI, LTL was increased in all subgroups in PCOS compared to non-PCOS. However, in the PCOS group, LTL was lower in overweight (P = 0.0187) and obese (P = 0.0018) compared to normal-weight women. The generalized linear model showed that BMI, androstenedione, homocysteine, and CRP were associated with telomere biology. Women with PCOS had longer LTL, however, overweight or obesity progressively contributes to telomere shortening and may affect reproductive outcomes of PCOS, while androstenedione may increase LTL.},
}
@article {pmid38389866,
year = {2024},
author = {Choudhary, D and Lekshmon, KS and Singh, C and Subramani, VN and Singh, Y and Mitra, S and Sekar, A and Malik, M and Bhagat, N and Shiva Kumar, SP and Taneja, S and Gupta, V and Ramachandran, R and Singh, S and Nada, R and Kenwar, D and Duseja, AK and Yadav, TD and Malhotra, P and Sharma, A},
title = {Simultaneous Liver and Kidney Transplantation in a Patient With Telomere Biology Disorder: A Case Study.},
journal = {Journal of clinical and experimental hepatology},
volume = {14},
number = {3},
pages = {101355},
pmid = {38389866},
issn = {0973-6883},
abstract = {Organ transplantation is the primary therapy for organ failure caused by telomere biology disorder (TBD). We describe the first documented case of simultaneous liver and kidney transplantation (SLKTx) for TBD, although the diagnosis of TBD was reached only three months following SLKTx. The patient was born prematurely, displayed growth retardation, and developed chronic kidney and liver diseases. His pre-SLKTx autoimmune, metabolic, and viral assessments were negative, and persistent pancytopenia (bone marrow cellularity 70-80%) was attributed to renal disease-associated bone marrow changes. Following SLKTx, he was discharged with stable graft function on tacrolimus and prednisolone. Although mycophenolate mofetil was discontinued on the second postoperative day, his pancytopenia persisted. Despite extensive evaluations, including drug, immune, nutritional, and viral assessments, all results were negative. A bone marrow biopsy conducted three months post-transplant revealed significant hypocellularity (40-50%). Whole genome sequencing revealed a likely pathogenic variant of the TINF2 gene. The patient was subsequently treated with danazol. At the nine-month follow-up post-SLKTx, he exhibited stable graft function and improved cell counts while maintaining triple-drug immunosuppression. Given the lack of uniform diagnostic criteria for TBD, healthcare providers must be vigilant with patients presenting with multi-organ failure and persistent cytopenias. Effective pre-transplant screening for TBD can lead to timely diagnoses, better management, and improved post-transplant outcomes.},
}
@article {pmid38386656,
year = {2024},
author = {Wolf, SE and Hastings, WJ and Ye, Q and Etzel, L and Apsley, AT and Chiaro, C and Heim, CC and Heller, T and Noll, JG and Schreier, HMC and Shenk, CE and Shalev, I},
title = {Cross-tissue comparison of telomere length and quality metrics of DNA among individuals aged 8 to 70 years.},
journal = {PloS one},
volume = {19},
number = {2},
pages = {e0290918},
pmid = {38386656},
issn = {1932-6203},
mesh = {Humans ; Child ; Adolescent ; *Leukocytes, Mononuclear/metabolism ; Cross-Sectional Studies ; *Mouth Mucosa ; Telomere/genetics ; DNA/genetics/metabolism ; },
abstract = {Telomere length (TL) is an important biomarker of cellular aging, yet its links with health outcomes may be complicated by use of different tissues. We evaluated within- and between-individual variability in TL and quality metrics of DNA across five tissues using a cross-sectional dataset ranging from 8 to 70 years (N = 197). DNA was extracted from all tissue cells using the Gentra Puregene DNA Extraction Kit. Absolute TL (aTL) in kilobase pairs was measured in buccal epithelial cells, saliva, dried blood spots (DBS), buffy coat, and peripheral blood mononuclear cells (PBMCs) using qPCR. aTL significantly shortened with age for all tissues except saliva and buffy coat, although buffy coat was available for a restricted age range (8 to 15 years). aTL did not significantly differ across blood-based tissues (DBS, buffy coat, PBMC), which had significantly longer aTL than buccal cells and saliva. Additionally, aTL was significantly correlated for the majority of tissue pairs, with partial Spearman's correlations controlling for age and sex ranging from ⍴ = 0.18 to 0.51. We also measured quality metrics of DNA including integrity, purity, and quantity of extracted DNA from all tissues and explored whether controlling for DNA metrics improved predictions of aTL. We found significant tissue variation: DNA from blood-based tissues had high DNA integrity, more acceptable A260/280 and A260/230 values, and greater extracted DNA concentrations compared to buccal cells and saliva. Longer aTL was associated with lower DNA integrity, higher extracted DNA concentrations, and higher A260/230, particularly for saliva. Model comparisons suggested that incorporation of quality DNA metrics improves models of TL, although relevant metrics vary by tissue. These findings highlight the merits of using blood-based tissues and suggest that incorporation of quality DNA metrics as control variables in population-based studies can improve TL predictions, especially for more variable tissues like buccal and saliva.},
}
@article {pmid38379260,
year = {2024},
author = {Margiana, R and Gupta, R and Al-Jewari, WM and Hjazi, A and Alsaab, HO and Mustafa, YF and Singh, R and Thaibt, R and Alkhayyat, S and Ibrahim, AJ},
title = {Evaluation of telomere length, reactive oxygen species, and apoptosis in spermatozoa of patients with oligospermia.},
journal = {Cell biochemistry and function},
volume = {42},
number = {2},
pages = {e3935},
doi = {10.1002/cbf.3935},
pmid = {38379260},
issn = {1099-0844},
mesh = {Humans ; Male ; *Oligospermia/genetics/metabolism ; Reactive Oxygen Species/metabolism ; Catalase/genetics/metabolism ; *Azoospermia/metabolism ; Semen/metabolism ; Spermatozoa/metabolism ; *Infertility, Male/genetics/diagnosis/metabolism ; Antioxidants/metabolism ; DNA Fragmentation ; Apoptosis ; Superoxide Dismutase/genetics/metabolism ; Telomere/metabolism ; RNA, Messenger/metabolism ; },
abstract = {50% of cases of infertility are caused by male factor, which acquired or congenital problems may bring on. Male infertility can be caused by oligospermia and asthenozoospermia, which are common. Since the same mutations that cause azoospermia in some people also cause oligozoospermia in others, oligozoospermia may be thought of as a less severe form of azoospermia. Studies have demonstrated telomere length, catalase activity, super oxide dismutase (SOD), and DNA fragmentation can be influential factors for male infertility. The amount of apoptosis, oxidative stress factors, telomere length, and DNA fragmentation were some aspects of healthy sperm that we chose to look into in this study and compare to oligospermia individuals. Oligospermia patients (n = 24) and fertile men (n = 27) semen samples were collected, and the apoptosis rate of sperms in both groups was analyzed (Flow cytometry). Also, gene expression of apoptotic and antiapoptotic markers and telomere length were examined (real-time polymerase chain reaction). The sperm DNA fragmentation kit was used to determine DNA fragmentation and to evaluate catalase and SOD activity; the specific kits and methods were utilized. Higher expression levels of caspase3 (p = .0042), caspase8 (p = .0145), caspase9 (p = .0275), and BAX (p = .0202) mRNA were observed in patients who had oligospermia. In contrast, lower mRNA expression of BCL-2 (p = .0009) was detected in this group. In addition, telomere length was decreased in the oligospermia group (p < .0001) compared to the health group. Moreover, the frequency of apoptosis is induced in patients (p = .0026). The catalase activity is low (p = .0008), but the SOD activity is high (p = .0015) in the patient group. As a result of our findings, we may list the sperm cell apoptosis rate, telomere length, the degree of sperm DNA fragmentation, and lastly, the measurement of significant and efficient oxidative stress markers like SOD and catalase in semen plasma among the principal diagnostic characteristics for oligospermia. Future studies will be better able to treat oligospermia by showing whether these indicators are rising or falling.},
}
@article {pmid38378028,
year = {2024},
author = {Mervic, A and Goricar, K and Blagus, T and Franko, A and Trebusak-Podkrajsek, K and Fikfak, MD and Dolzan, V and Kovac, V},
title = {Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases.},
journal = {Radiology and oncology},
volume = {58},
number = {1},
pages = {87-98},
pmid = {38378028},
issn = {1581-3207},
mesh = {Humans ; *Telomerase/genetics ; Case-Control Studies ; Retrospective Studies ; Polymorphism, Single Nucleotide ; Biomarkers ; Telomere/genetics ; Disease Progression ; },
abstract = {BACKGROUND: Asbestos exposure has been proposed as a risk factor for shorter telomere length. The aim of our study was to investigate whether telomere length in leukocytes and hTERT genetic polymorphisms may serve as potential biomarkers for the risk of developing asbestos-related diseases and as biomarkers of progression and chemotherapy response rate in malignant mesothelioma (MM).<br><br>SUBJECTS AND METHODS: We conducted two retrospective studies. In the first study, a case-control study, telomere length and hTERT polymorphisms were determined in patients with MM, subjects with pleural plaques and controls without the asbestos related disease, who were occupationally exposed to asbestos. In the second study, a longitudinal observational study, telomere length was also determined in samples from MM patients before and after chemotherapy. Telomere length was determined by monochromatic multiplex quantitative polymerase chain reaction (PCR), while competitive allele-specific PCR was used to genotype hTERT rs10069690, rs2736100 and rs2736098. Logistic regression and survival analysis were used in statistical analysis.<br><br>RESULTS: Patients with MM had shorter telomere length than subjects with pleural plaques (p < 0.001). After adjustment for age, rs2736098 CT, and rs10069690 TT and CT+TT genotypes were significantly associated with a higher risk of MM (padj = 0.023; padj = 0.026 and padj = 0.017), while rs2736100 AA and CA+AA genotypes conferred to a lower risk for MM compared to all other subjects (padj = 0.017, and padj = 0.026). Telomere length was not associated with a response to chemotherapy (p > 0.05) or time to disease progression (p > 0.05). Carriers of one or two polymorphic rs10069690 T alleles had a good response to chemotherapy (p = 0.039, and p = 0.048), these associations remained statistically significant after adjustment for age (padj = 0.019; padj = 0.017). Carriers of two polymorphic rs2736100 A alleles had a longer time to disease progression (p = 0.038).<br><br>CONCLUSIONS: Shorter telomere length and hTERT polymorphisms may serve as a biomarker for the risk of developing MM. Additionally, rs10069690 and rs2736100 polymorphisms, but not telomere length, were associated with a chemotherapy response or MM progression.},
}
@article {pmid38376914,
year = {2024},
author = {Choi, H and Cho, SW and Kim, HH and Yi, KH and Park, DJ and Park, YJ},
title = {Shortened telomere length in peripheral blood leukocytes is associated with cumulative radioactive iodine doses in patients with differentiated thyroid carcinoma.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.35256},
pmid = {38376914},
issn = {1097-0142},
support = {5120200513755//Ministry of Education of Korea/ ; NRF-2019R1A2C2084332//National Research Foundation of Korea/ ; 03-2014-0130//Seoul National University Hospital/ ; },
abstract = {BACKGROUND: Telomere length is associated with cancer risk and cancer aggressiveness. Radioactive iodine (RAI) therapy for thyroid cancer has raised concerns for second primary malignancy (SPM) in patients with high cumulative doses. The association between RAI dose and peripheral blood leukocyte telomere length was examined.<br><br>METHODS: A total of 425 patients were included who underwent total thyroidectomy and were followed up for at least 1&#xa0;year with or without RAI treatment. The relative telomere length (RTL) of the patients was assessed via a quantitative polymerase chain reaction amplification method. RAI doses were divided into five groups on the basis of cumulative dose, and a comparison was made among these groups.<br><br>RESULTS: The number of patients with RAI treatment was 287 (67.5%), and the cumulative RAI dose was 3.33&#xa0;GBq (range, 1.11-131.35 GBq). The mean RTL was significantly shorter in the highest RAI group (>22.2&#xa0;GBq) compared to both the no-RAI and lower dose groups. The association between RAI dose and RTL was positive in the lower RAI group (1.1-3.7&#xa0;GBq) and negative in the highest RAI group in both univariate and multivariate analyses. We observed 59 (13.9%) SPMs and 20 (4.7%) mortalities, and RTL did not show a significant risk effect for all-cause, thyroid cancer-specific, or SPM-specific mortality.<br><br>CONCLUSIONS: In patients with thyroid cancer who underwent total thyroidectomy, peripheral blood leukocyte telomere length exhibited a significant association with cumulative RAI dose higher than 22.2&#xa0;GBq. These results suggest the possibility of telomere length shortening in patients who undergo high-dose RAI treatment.},
}
@article {pmid38373547,
year = {2024},
author = {Shoeb, M and Meighan, T and Kodali, VK and Abadin, H and Faroon, O and Zarus, GM and Erdely, A and Antonini, JM},
title = {TERT-independent telomere elongation and shelterin dysregulation after pulmonary exposure to stainless-steel welding fume in-vivo.},
journal = {Environmental research},
volume = {250},
number = {},
pages = {118515},
doi = {10.1016/j.envres.2024.118515},
pmid = {38373547},
issn = {1096-0953},
abstract = {Telomeres are inert DNA sequences (TTAGGG) at the end of chromosomes that protect genetic information and maintain DNA integrity. Emerging evidence has demonstrated that telomere alteration can be closely related to occupational exposure and the development of various disease conditions, including cancer. However, the functions and underlying molecular mechanisms of telomere alteration and shelterin dysregulation after welding fume exposures have not been broadly defined. In this study, we analyzed telomere length and shelterin complex proteins in peripheral blood mononuclear cells (PBMCs) and in lung tissue recovered from male Sprague-Dawley rats following exposure by intratracheal instillation (ITI) to 2 mg/rat of manual metal arc-stainless steel (MMA-SS) welding fume particulate or saline (vehicle control). PBMCs and lung tissue were harvested at 30 d after instillation. Our study identified telomere elongation and shelterin dysregulation in PBMCs and lung tissue after welding fume exposure. Mechanistically, telomere elongation was independent of telomerase reverse transcriptase (TERT) activation. Collectively, our findings demonstrated that welding fume-induced telomere elongation was (a) TERT-independent and (b) associated with shelterin complex dysregulation. It is possible that an alteration of telomere length and its regulatory proteins may be utilized as predictive biomarkers for various disease conditions after welding fume exposure. This needs further investigation.},
}
@article {pmid38372947,
year = {2024},
author = {Warsame, F and Simonetto, DA},
title = {Telomere Biology Disorder: A Focus on Gastrointestinal and Hepatic Manifestations.},
journal = {Current hematologic malignancy reports},
volume = {19},
number = {2},
pages = {75-81},
pmid = {38372947},
issn = {1558-822X},
mesh = {Humans ; *Liver Cirrhosis ; Mutation ; *Hypertension, Portal ; Telomere/genetics ; Biology ; },
abstract = {PURPOSE OF REVIEW: Telomere biology disorders (TBD) encompass several illnesses caused by underlying mutations in telomere maintenance leading to premature telomere attrition and telomere dysfunction. These disorders have unique features but share common disease manifestations including pulmonary fibrosis, cirrhosis, and bone marrow failure. The goals of this article are to provide an overview of the gastrointestinal and hepatic manifestations of TBD, focusing on their pathophysiology, clinical disease states, and current management strategies.<br><br>RECENT FINDINGS: Telomere shortening has been observed in patients with chronic liver disease and is associated with a higher risk of progression to cirrhosis and portal hypertension. While the directionality of the association between telomere dysfunction and senescence on liver disease is not fully understood, research in TBD may provide clarity and could lead to future therapies for this increasingly prevalent disease. While treatment options remain limited in TBD-associated liver disease, recent studies point to the safety and efficacy of liver transplantation among patients with end-stage liver disease.},
}
@article {pmid38372835,
year = {2024},
author = {Wang, D and Lin, D and Yang, X and Wu, D and Li, P and Zhang, Z and Zhang, W and Guo, Y and Fu, S and Zhang, N},
title = {Alterations in leukocyte telomere length and mitochondrial DNA copy number in benzene poisoning patients.},
journal = {Molecular biology reports},
volume = {51},
number = {1},
pages = {309},
pmid = {38372835},
issn = {1573-4978},
support = {No.SZGSP015//Shenzhen Fund for Guangdong Provincial High- level Clinical Key Specialties/ ; No.KCXFZ20201221173602007//Science and Technology Planning Project of Shenzhen Municipality/ ; No.JCYJ20190808174815278//Science and Technology Planning Project of Shenzhen Municipality/ ; },
mesh = {Humans ; *DNA, Mitochondrial/genetics ; *Benzene ; DNA Copy Number Variations/genetics ; Leukocytes ; Hemoglobins ; Telomere/genetics ; },
abstract = {OBJECTIVE: The aim of this study is to examine and evaluate the impact of benzene poisoning on the relative content of the mitochondrial MT-ND1 gene and telomere length in individuals with occupational chronic benzene poisoning (CBP) compared to a control group. The study will analyze and gather data on the mitochondrial gene content and telomere length in cases of benzene poisoning, and investigate the relationship with blood routine parameters in order to contribute scientific experimental data for the prevention and treatment of CBP.<br><br>METHOD: The case group comprised 30 individuals diagnosed with occupational chronic benzene poisoning, whereas the control group consisted of 60 healthy individuals who underwent physical examinations at our hospital concurrently. Blood routine indicators were detected and analyzed, and the PCR method was employed to measure changes in mitochondrial MT-ND1 content and telomere length. Subsequently, a comparison and analysis of the aforementioned indicators was conducted.<br><br>RESULT: The case group exhibited a higher mitochondrial gene content (median 366.2, IQR 90.0 rate) compared to the control group (median 101.5, IQR 12.0 rate), with a statistically significant difference between the two groups (P&#x2009;<&#x2009;0.05). Additionally, the case group demonstrated lower white blood cell levels (3.78&#x2009;&#xb1;&#x2009;1.387&#x2009;&#xd7;&#x2009;10[9]/L) compared to the control group (5.74&#x2009;&#xb1;&#x2009;1.41&#x2009;&#xd7;&#x2009;10[9]/L), with a significant difference between the two groups (P&#x2009;<&#x2009;0.05). Furthermore, the case group displayed lower red blood cell levels (3.86&#x2009;&#xb1;&#x2009;0.65&#x2009;&#xd7;&#x2009;10[12]/L) compared to the control group (4.89&#x2009;&#xb1;&#x2009;0.65&#x2009;&#xd7;&#x2009;10[12]/L), with a significant difference between the two groups (P&#x2009;<&#x2009;0.05). The hemoglobin level in the case group (113.33&#x2009;&#xb1;&#x2009;16.34&#xa0;g/L) was lower than that in the control group (138.22&#x2009;&#xb1;&#x2009;13.22&#xa0;g/L). There was a significant difference between the two groups (P&#x2009;<&#x2009;0.05). Platelet levels in the case group (153.80&#x2009;&#xb1;&#x2009;58.31&#x2009;&#xd7;&#x2009;10[9]/L) is smaller than the control group (244.92&#x2009;&#xb1;&#x2009;51.99&#x2009;&#xd7;&#x2009;10[9]/L), there was a significant difference between the two groups (P&#x2009;<&#x2009;0.05). The average telomere length of the normal control group was 1.451&#x2009;&#xb1;&#x2009;0.475 (rate); The mean telomere length of individuals in the case group diagnosed with benzene poisoning was determined to be 1.237&#x2009;&#xb1;&#x2009;0.457 (rate). No significant correlation was observed between telomere length and three blood routine parameters, namely white blood cells (WBC), hemoglobin (HB), and platelets (PLT). However, a significant correlation was found between telomere length and red blood cell count (RBC). Additionally, a negative correlation was observed between mitochondrial gene content and white blood cell count (r&#x2009;=&#x2009;-&#x2009;0.314, P&#x2009;=&#x2009;0.026), as well as between mitochondrial gene content and red blood cell count (r&#x2009;=&#x2009;-&#x2009;0.226, P&#x2009;=&#x2009;0.032). Furthermore, a negative correlation was identified between mitochondrial gene content and hemoglobin (r = - 0.314, P = 0.028), and platelets (r = - 0.445, P = 0.001).<br><br>CONCLUSION: Individuals diagnosed with occupational chronic benzene poisoning exhibit a reduction in telomere length and an elevation in the relative content of the mitochondrial MT-ND1 gene. Moreover, a negative correlation is observed between the content of the mitochondrial MT-ND1 gene and four blood routine parameters, namely white blood cells (WBC), red blood cells (RBC), hemoglobin (HB), and platelets (PLT). Consequently, benzene exposure may potentially contribute to the onset of premature aging.},
}
@article {pmid38371225,
year = {2024},
author = {Shi, ZF and Li, KK and Chan, DT and Mao, Y and Ng, HK},
title = {Alternative lengthening of telomeres is seen in a proportion of oligodendrogliomas and is associated with a worse prognosis.},
journal = {Neuro-oncology advances},
volume = {6},
number = {1},
pages = {vdae006},
pmid = {38371225},
issn = {2632-2498},
}
@article {pmid38365850,
year = {2024},
author = {Hackenhaar, FS and Josefsson, M and Adolfsson, AN and Landfors, M and Kauppi, K and Hultdin, M and Adolfsson, R and Degerman, S and Pudas, S},
title = {Correction: Short leukocyte telomeres predict 25-year Alzheimer's disease incidence in non-APOE ε4-carriers.},
journal = {Alzheimer's research &amp; therapy},
volume = {16},
number = {1},
pages = {39},
pmid = {38365850},
issn = {1758-9193},
}
@article {pmid38365769,
year = {2024},
author = {Chen, M and Wang, Z and Xu, H and Teng, P and Li, W and Ma, L},
title = {Association between modifiable lifestyle factors and telomere length: a univariable and multivariable Mendelian randomization study.},
journal = {Journal of translational medicine},
volume = {22},
number = {1},
pages = {160},
pmid = {38365769},
issn = {1479-5876},
support = {82200269//Natural Science Foundation for Youth of China/ ; 82271812//Natural Science Foundation of China/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 2 ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Sleep Initiation and Maintenance Disorders ; Telomere/genetics ; Polymorphism, Single Nucleotide ; },
abstract = {BACKGROUND: Telomere length has long been recognized as a valuable biomarker of aging and is inversely correlated with chronological age. Various lifestyle factors have been implicated in telomere shortening or preservation; however, the association between lifestyle factors and telomere length remains controversial. To address this issue, we conducted a Mendelian randomization (MR) analysis to investigate the potential causal associations between multiple lifestyle factors and telomere length.<br><br>METHODS: Independent genetic variants strongly associated with lifestyle factors (tobacco smoking, sleep duration, insomnia, and physical activity) were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for telomere length was obtained from a GWAS comprising 472,174 European ancestries. Univariable and multivariable MR analyses were performed to assess the relationships.<br><br>RESULTS: The genetic liability to lifetime smoking was robustly associated with shorter telomere length (odd ratio [OR]: 0.882; 95% confidence interval [CI]: 0.847-0.918). Genetically predicted insomnia was also linked to shorter telomere length (OR: 0.972; 95% CI: 0.959-0.985), while no significant association was observed between sleep duration and telomere length. Furthermore, a suggestive association was found between moderate-to-vigorous physical activity and longer telomere length (OR: 1.680; 95% CI: 1.115-2.531). In multivariable MR analyses, adjusting for potential mediators such as body mass index, type 2 diabetes, alcohol consumption, and alcohol use disorder, the associations of lifetime smoking and insomnia with telomere length remained robust.<br><br>CONCLUSION: Our findings suggest that smoking and insomnia may contribute to telomere shortening, while physical activity may play a role in telomere length maintenance. These findings underscore the importance of managing positive risk factors and adopting a healthy lifestyle to promote telomere health.},
}
@article {pmid38359982,
year = {2024},
author = {Azeroglu, B and Ozbun, L and Pegoraro, G and Lazzerini Denchi, E},
title = {Native FISH: A low- and high-throughput assay to analyze the alternative lengthening of telomere (ALT) pathway.},
journal = {Methods in cell biology},
volume = {182},
number = {},
pages = {265-284},
doi = {10.1016/bs.mcb.2022.10.010},
pmid = {38359982},
issn = {0091-679X},
mesh = {Humans ; Animals ; *High-Throughput Screening Assays ; *Neoplasms ; DNA ; Telomere/genetics ; Fishes/genetics ; },
abstract = {Alternative lengthening of telomeres (ALT) is a telomerase-independent and recombination-based mechanism used by approximately 15% of human cancers to maintain telomere length and to sustain proliferation. ALT-positive cells display unique features that could be exploited for tailored cancer therapies. A key limitation for the development of ALT-specific treatments is the lack of an assay to detect ALT-positive cells that is easy to perform and that can be scaled up. One of the most broadly used assays for ALT detection, CCA (C-circle assay), does not provide single-cell information and it is not amenable to High-Throughput Screening (HTS). To overcome these limitations, we developed Native-FISH (N-FISH) as an alternative method to visualize ALT-specific single-stranded telomeric DNA. N-FISH produces single-cell data, can be applied to fixed tissues, does not require DNA isolation or amplification steps, and it can be miniaturized in a 384-well format. This protocol details the steps to perform N-FISH protocol both in a low- and high-throughput format to analyze ALT. While low-throughput N-FISH is useful to assay the ALT state of cell lines, we expect that the miniaturized N-FISH assay coupled with high-throughput imaging will be useful in functional genomics and chemical screens to identify novel cellular factors that regulate ALT and potential ALT therapeutic targets for cancer therapies directed against ALT-positive tumors, respectively.},
}
@article {pmid38359122,
year = {2024},
author = {Kinzig, CG and Zakusilo, G and Takai, KK and Myler, LR and de Lange, T},
title = {ATR blocks telomerase from converting DNA breaks into telomeres.},
journal = {Science (New York, N.Y.)},
volume = {383},
number = {6684},
pages = {763-770},
doi = {10.1126/science.adg3224},
pmid = {38359122},
issn = {1095-9203},
mesh = {Humans ; *Ataxia Telangiectasia Mutated Proteins/genetics/metabolism ; *DNA Breaks, Double-Stranded ; *Telomerase/genetics ; *Telomere/genetics/metabolism ; Genetic Techniques ; CRISPR-Associated Protein 9 ; HeLa Cells ; },
abstract = {Telomerase, the enzyme that maintains telomeres at natural chromosome ends, should be repressed at double-strand breaks (DSBs), where neotelomere formation can cause terminal truncations. We developed an assay to detect neotelomere formation at Cas9- or I-SceI-induced DSBs in human cells. Telomerase added telomeric repeats to DSBs, leading to interstitial telomeric repeat insertions or the formation of functional neotelomeres accompanied by terminal deletions. The threat that telomerase poses to genome integrity was minimized by ataxia telangiectasia and Rad3-related (ATR) kinase signaling, which inhibited telomerase at resected DSBs. In addition to acting at resected DSBs, telomerase used the extruded strand in the Cas9 enzyme-product complex as a primer for neotelomere formation. We propose that although neotelomere formation is detrimental in normal human cells, it may allow cancer cells to escape from breakage-fusion-bridge cycles.},
}
@article {pmid38357955,
year = {2024},
author = {Vazifehmand, R and Saeed Ali, D and Monem Homaie, F and Molaei Jalalvand, F and Othman, Z and Deming, C and Stanslas, J and Sekawi, Z},
title = {Effects of HSV-G47Δ Oncolytic Virus on Telomerase and Telomere Length Alterations in Glioblastoma Multiforme Cancer Stem Cells Under Hypoxia and Normoxia Conditions.},
journal = {Current cancer drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115680096274769240115165344},
pmid = {38357955},
issn = {1873-5576},
abstract = {BACKGROUND: Due to the existence of tumor stem cells with tumorigenicity properties and resistance patterns, treatment of glioblastoma is not easy. Hypoxia is a major concern in glioblastoma therapy. Telomerase activity and telomere length alterations have been known to play a critical role in glioblastoma progression and invasion.<br><br>OBJECTIVE: This study aimed to investigate the effects of HSV-G47&#x394; oncolytic virus on telomerase and telomere length alterations in U251GBMCSCs (U251-Glioblastoma cancer stem cells) under hypoxia and normoxia conditions.<br><br>METHODS: U251-CSCs were exposed to the HSV-G47&#x394; virus in optimized MOI (Multiplicity of infection= 1/14 hours). An absolute telomere length and gene expression of telomerase subunits were determined using an absolute human telomere length quantification PCR assay. Furthermore, a bioinformatics pathway analysis was carried out to evaluate physical and genetic interactions between dysregulated genes with other potential genes and pathways.<br><br>RESULTS: Data revealed that U251CSCs had longer telomeres when exposed to HSV-G47&#x394; in normoxic conditions but had significantly shorter telomeres in hypoxic conditions. Furthermore, hTERC, DKC1, and TEP1 genes were significantly dysregulated in hypoxic and normoxic microenvironments. The analysis revealed that the expression of TERF2 was significantly reduced in both microenvironments, and two critical genes from the MRN complex, MER11 and RAD50, were significantly upregulated in normoxic conditions. RAD50 showed a significant downregulation pattern in the hypoxic niche. Our results suggested that repair complex in the telomeric structure could be targeted by HSV-G47&#x394; in both microenvironments.<br><br>CONCLUSION: In the glioblastoma treatment strategy, telomerase and telomere complex could be potential targets for HSV-G47&#x394; in both microenvironments.},
}
@article {pmid38349865,
year = {2024},
author = {Cozzolino, M and Ergun, Y and Ristori, E and Garg, A and Imamoglu, G and Seli, E},
title = {Disruption of mitochondrial unfolded protein response results in telomere shortening in mouse oocytes and somatic cells.},
journal = {Aging},
volume = {16},
number = {3},
pages = {2047-2060},
doi = {10.18632/aging.205543},
pmid = {38349865},
issn = {1945-4589},
mesh = {Humans ; Female ; Animals ; Mice ; Telomere Shortening ; Oocytes/metabolism ; Aging/genetics ; Telomere/genetics/metabolism ; *Infertility, Female/metabolism ; Unfolded Protein Response/genetics ; *Telomerase/metabolism ; },
abstract = {Caseinolytic peptidase P (CLPP) plays a central role in mitochondrial unfolded protein response (mtUPR) by promoting the breakdown of misfolded proteins and setting in motion a cascade of reactions to re-establish protein homeostasis. Global germline deletion of Clpp in mice results in female infertility and accelerated follicular depletion. Telomeres are tandem repeats of 5'-TTAGGG-3' sequences found at the ends of the chromosomes. Telomeres are essential for maintaining chromosome stability during somatic cell division and their shortening is associated with cellular senescence and aging. In this study, we asked whether the infertility and ovarian aging phenotype caused by global germline deletion of Clpp is associated with somatic aging, and tested telomere length in tissues of young and aging mice. We found that impaired mtUPR caused by the lack of CLPP is associated with accelerated telomere shortening in both oocytes and somatic cells of aging mice. In addition, expression of several genes that maintain telomere integrity was decreased, and double-strand DNA breaks were increased in telomeric regions. Our results highlight how impaired mtUPR can affect telomere integrity and demonstrate a link between loss of mitochondrial protein hemostasis, infertility, and somatic aging.},
}
@article {pmid38349660,
year = {2023},
author = {Schnurr, E and Volz, KU and Mosetter, K and Ghanaati, S and Hueber, R and Preussler, C},
title = {Interaction of Telomere Length and Inflammatory Biomarkers Following Zirconia Implant Placement: A Case Series.},
journal = {The Journal of oral implantology},
volume = {49},
number = {5},
pages = {524-531},
doi = {10.1563/aaid-joi-D-22-00236},
pmid = {38349660},
issn = {0160-6972},
mesh = {Humans ; *Dental Implants ; Esthetics, Dental ; Biomarkers ; Cytokines ; Inflammation ; Anti-Inflammatory Agents ; *Zirconium ; },
abstract = {Zirconia implants have gained popularity for their aesthetic appeal and biocompatibility, making them a preferred choice for anterior teeth replacement. This study explores the interaction between telomere length and inflammatory biomarkers in seven cases of zirconia implant placement to gain insights into postoperative cellular aging, inflammatory responses, and long-term outcomes. Zirconia implants offer advantages over titanium implants, as they do not corrode or release metal ions, leading to potential inflammation and implant failure. Monitoring immune and inflammatory biomarkers is essential to assess inflammation initiation, severity, and progression. C-reactive protein (CRP) and pro-inflammatory cytokines, like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), play crucial roles in host immune responses, while anti-inflammatory cytokines, including interleukin-10 (IL-10), regulate and dampen immune responses. Achieving a delicate balance between pro- and anti-inflammatory cytokines is vital for maintaining a healthy immune response and preventing chronic inflammatory conditions. Telomeres, protective structures present at chromosome ends, influence cellular aging and mitochondrial function. Shorter telomeres are associated with impaired mitochondrial function, increased oxidative stress, and cellular senescence, while longer telomeres are linked to reduced inflammation and improved immune function. Understanding these mechanisms is essential for addressing age-related conditions and promoting overall well-being. In this case series, we investigated the interaction between telomere length and inflammatory biomarkers in patients who received zirconia dental implants. The study aims to improve our understanding of postoperative cellular aging, inflammatory responses, and the biocompatibility of zirconia implants, potentially leading to improved treatment protocols and patient outcomes. This innovative assessment of telomere length and inflammatory biomarkers in the context of zirconia implants provides novel insights into the field of dental implantology. By exploring the effects of zirconia implants on cellular health and inflammation, this study contributes to advancements in implant technology and patient care.},
}
@article {pmid38345296,
year = {2024},
author = {Connor, A and Deschamps, A and Busque, L and Tardif, JC and Bourgoin, V and Dubé, MP and Busseuil, D and D'Antono, B},
title = {Childhood maltreatment and leukocyte telomere length: Cardiac vagal activity influences the relation in older adults.},
journal = {Psychosomatic medicine},
volume = {},
number = {},
pages = {},
doi = {10.1097/PSY.0000000000001290},
pmid = {38345296},
issn = {1534-7796},
abstract = {OBJECTIVE: Childhood maltreatment is associated with shorter leukocyte telomere length (LTL). However, the influence of cardiac vagal control on this relation is unknown. We examined whether cardiac vagal control at rest and in response to stress moderates or cross-sectionally mediates the relationship between childhood maltreatment and LTL.<br><br>METHODS: Participants were 1179 men and women (aged 65 &#xb1; 7.2 years) suffering from coronary artery disease (CAD) or non-cardiovascular chronic disease. They completed a childhood maltreatment questionnaire and underwent a stress protocol while ECG was monitored. HF-HRV measures were obtained at rest, during stress, and post-stress in absolute and normalized units (nu). LTL was measured using qPCR. Mediation and moderation analyses were performed.<br><br>RESULTS: HF-HRV and HFnu measures did not mediate the childhood maltreatment-LTL relation. However, baseline HFnu (p = .027) and HFnu reactivity (p = .051) moderated the relation. Specifically, maltreatment was associated with significantly lower LTL among those with baseline HFnu at (b = -.059, p = .003) or below the mean (b = -.103, p < .001), but not among those with higher baseline HFnu. It was also associated with significantly lower LTL among participants who showed either blunted (b = -.058, p = .004) or increased HFnu (b = -.099, p = .001) responses to stress but not in those with large decreases in HFnu.<br><br>CONCLUSIONS: Childhood maltreatment was associated with lower LTL in those who showed a distinct cardiac vagal profile at baseline and in response to stress. The mechanisms and implications remain to be determined.},
}
@article {pmid38344651,
year = {2024},
author = {Wang, Z and Zhou, J and Pan, J and Cheng, W and Fang, J and Lv, Q and Lin, X and Cheng, W and Zhang, L and Cheng, K},
title = {Insights into the Superrosids phylogeny and flavonoid synthesis from the telomere-to-telomere gap-free genome assembly of Penthorum chinense Pursh.},
journal = {Horticulture research},
volume = {11},
number = {2},
pages = {uhad274},
pmid = {38344651},
issn = {2662-6810},
abstract = {The completion of the first telomere-to-telomere (T2T) genome assembly of Penthorum chinense Pursh (PC), a prominent medicinal plant in China, represents a significant achievement. This assembly spans a length of 257.5 Mb and consists of nine chromosomes. PC's notably smaller genome size in Saxifragales, compared to that of Paeonia ostii, can be attributed to the low abundance of transposable elements. By utilizing single-copy genes from 30 species, including 28 other Superrosids species, we successfully resolved a previously debated Superrosids phylogeny. Our findings unveiled Saxifragales as the sister group to the core rosids, with both being the sister group to Vitales. Utilizing previously characterized cytochrome P450 (CYP) genes, we predicted the compound classes that most CYP genes of PC are involved in synthesizing, providing insight into PC's potential metabolic diversity. Metabolomic and transcriptomic data revealed that the richest sources of the three most noteworthy medicinal components in PC are young leaves and flowers. We also observed higher activity of upstream genes in the flavonoid synthesis pathway in these plant parts. Additionally, through weighted gene co-expression network analysis, we identified gene regulatory networks associated with the three medicinal components. Overall, these findings deepen our understanding of PC, opening new avenues for further research and exploration.},
}
@article {pmid38344410,
year = {2024},
author = {Muthumalage, T and Goracci, C and Rahman, I},
title = {Club cell-specific telomere protection protein 1 (TPP1) protects against tobacco smoke-induced lung inflammation, xenobiotic metabolic dysregulation, and injurious responses.},
journal = {FASEB bioAdvances},
volume = {6},
number = {2},
pages = {53-71},
pmid = {38344410},
issn = {2573-9832},
abstract = {Inhaling xenobiotics, such as tobacco smoke is a major risk factor for pulmonary diseases, e.g., COPD/emphysema, interstitial lung disease, and pre-invasive diseases. Shelterin complex or telosome provides telomeric end protection during replication. Telomere protection protein 1 (TPP1) is one of the main six subunits of the shelterin complex supporting the telomere stability and genomic integrity. Dysfunctional telomeres and shelterin complex are associated as a disease mechanism of tobacco smoke-induced pulmonary damage and disease processes. The airway epithelium is critical to maintaining respiratory homeostasis and is implicated in lung diseases. Club cells (also known as clara cells) play an essential role in the immune response, surfactant production, and metabolism. Disrupted shelterin complex may lead to dysregulated cellular function, DNA damage, and disease progression. However, it is unknown if the conditional removal of TPP1 from Club cells can induce lung disease pathogenesis caused by tobacco smoke exposure. In this study, conditional knockout of Club-cell specific TPP1 demonstrated the instability of other shelterin protein subunits, such as TRF1, dysregulation of cell cycle checkpoint proteins, p53 and downstream targets, and dysregulation of telomeric genes. This was associated with age-dependent senescence-associated genes, increased DNA damage, and upregulated RANTES/IL13/IL33 mediated lung inflammation and injury network by cigarette smoke (CS). These phenomena are also associated with alterations in cytochrome P450 and glutathione transferases, upregulated molecular pathways promoting lung lesions, bronchial neoplasms, and adenocarcinomas. These findings suggest a pivotal role of TPP1 in maintaining lung homeostasis and injurious responses in response to CS. Thus, these data TPP1 may have therapeutic value in alleviating telomere-related chronic lung diseases.},
}
@article {pmid38340585,
year = {2024},
author = {Chen, Y and Ding, X and Aierken, A and Chen, Y and Li, Y},
title = {Related risk factors for age-dependent telomere shortening change with age from the perspective of life course.},
journal = {Archives of gerontology and geriatrics},
volume = {121},
number = {},
pages = {105349},
doi = {10.1016/j.archger.2024.105349},
pmid = {38340585},
issn = {1872-6976},
abstract = {BACKGROUND: Many related factors can accelerate the age-dependent telomere shortening, but some problems remain unresolved. This study aimed to assess the risk factors of telomere attrition at different age stages.<br><br>METHODS: This study was a population-based nationally representative survey study. All data were collected using a standard methodology by the national surveillance system. Quantitative polymerase chain reaction was used to measure relative leukocyte telomere length. Multiple linear regression analysis with age stratification was used to estimate the association of shortened telomere length with risk factors at the different age stages. Covariance analysis was used to compare the telomere length of category variables, and the model was adjusted for potentially confounders.<br><br>RESULTS: A total of 7,659 eligible participants aged 20 years or older with DNA specimens participated in the study. Related risk factors for age-dependent telomere shortening included gender, race-ethnicity, education levels, family income, health insurance, marital status, physical activity, smoking status, alcohol use, and self-reported greatest weight, which were associated with change in telomere length at different age stages.<br><br>CONCLUSIONS AND IMPLICATIONS: Related risk factors of telomere attrition were changed with age in life course. The evaluation of related risk factors for telomere attrition in terms of age may be a more accurate evaluation comparison with the specific age.},
}
@article {pmid38339395,
year = {2024},
author = {Gedvilaite, G and Kriauciuniene, L and Tamasauskas, A and Liutkeviciene, R},
title = {The Influence of Telomere-Related Gene Variants, Serum Levels, and Relative Leukocyte Telomere Length in Pituitary Adenoma Occurrence and Recurrence.},
journal = {Cancers},
volume = {16},
number = {3},
pages = {},
pmid = {38339395},
issn = {2072-6694},
abstract = {In this study, we examined 130 patients with pituitary adenomas (PAs) and 320 healthy subjects, using DNA samples from peripheral blood leukocytes purified through the DNA salting-out method. Real-time polymerase chain reaction (RT-PCR) was used to assess single nucleotide polymorphisms (SNPs) and relative leukocyte telomere lengths (RLTLs), while enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of TERF1, TERF2, TNKS2, CTC1, and ZNF676 in blood serum. Our findings reveal several significant associations. Genetic associations with pituitary adenoma occurrence: the TERF1 rs1545827 CT + TT genotypes were linked to 2.9-fold decreased odds of PA occurrence. Conversely, the TNKS2 rs10509637 GG genotype showed 6.5-fold increased odds of PA occurrence. Gender-specific genetic associations with PA occurrence: in females, the TERF1 rs1545827 CC + TT genotypes indicated 3.1-fold decreased odds of PA occurrence, while the TNKS2 rs10509637 AA genotype was associated with 4.6-fold increased odds. In males, the presence of the TERF1 rs1545827 T allele was associated with 2.2-fold decreased odds of PA occurrence, while the TNKS2 rs10509637 AA genotype was linked to a substantial 10.6-fold increase in odds. Associations with pituitary adenoma recurrence: the TNKS2 rs10509637 AA genotype was associated with 4.2-fold increased odds of PA recurrence. On the other hand, the TERF1 rs1545827 CT + TT genotypes were linked to 3.5-fold decreased odds of PA without recurrence, while the TNKS2 rs10509637 AA genotype was associated with 6.4-fold increased odds of PA without recurrence. Serum TERF2 and TERF1 levels: patients with PA exhibited elevated serum TERF2 levels compared to the reference group. Conversely, patients with PA had decreased TERF1 serum levels compared to the reference group. Relative leukocyte telomere length (RLTL): a significant difference in RLTL between the PA group and the reference group was observed, with PA patients having longer telomeres. Genetic associations with telomere shortening: the TERF1 rs1545827 T allele was associated with 1.4-fold decreased odds of telomere shortening. In contrast, the CTC1 rs3027234 TT genotype was linked to 4.8-fold increased odds of telomere shortening. These findings suggest a complex interplay between genetic factors, telomere length, and pituitary adenoma occurrence and recurrence, with potential gender-specific effects. Furthermore, variations in TERF1 and TNKS2 genes may play crucial roles in telomere length regulation and disease susceptibility.},
}
@article {pmid38338706,
year = {2024},
author = {Borghini, A and Ndreu, R and Canale, P and Campolo, J and Marinaro, I and Mercuri, A and Turchi, S and Andreassi, MG},
title = {Telomere Length, Mitochondrial DNA, and Micronucleus Yield in Response to Oxidative Stress in Peripheral Blood Mononuclear Cells.},
journal = {International journal of molecular sciences},
volume = {25},
number = {3},
pages = {},
pmid = {38338706},
issn = {1422-0067},
mesh = {*DNA, Mitochondrial/metabolism ; *Leukocytes, Mononuclear/metabolism ; Hydrogen Peroxide/toxicity ; DNA Copy Number Variations ; Mitochondria/genetics/metabolism ; Telomere Shortening ; Telomere/genetics/metabolism ; Oxidative Stress ; },
abstract = {Telomere shortening, chromosomal damage, and mitochondrial dysfunction are major initiators of cell aging and biomarkers of many diseases. However, the underlying correlations between nuclear and mitochondrial DNA alterations remain unclear. We investigated the relationship between telomere length (TL) and micronucleus (MN) and their association with mitochondrial DNA copy number (mtDNAcn) in peripheral blood mononuclear cells (PBMCs) in response to 100 μM and 200 μM of hydrogen peroxide (H2O2) at 44, 72, and 96 h. Significant TL shortening was observed after both doses of H2O2 and at all times (all p < 0.05). A concomitant increase in MN was found at 72 h (p < 0.01) and persisted at 96 h (p < 0.01). An increase in mtDNAcn (p = 0.04) at 200 µM of H2O2 was also found. In PBMCs treated with 200 µM H2O2, a significant inverse correlation was found between TL and MN (r = -0.76, p = 0.03), and mtDNA content was directly correlated with TL (r = 0.6, p = 0.04) and inversely related to MN (r = -0.78, p = 0.02). Telomere shortening is the main triggering mechanism of chromosomal damage in stimulated T lymphocytes under oxidative stress. The significant correlations between nuclear DNA damage and mtDNAcn support the notion of a telomere-mitochondria axis that might influence age-associated pathologies and be a target for the development of relevant anti-aging drugs.},
}
@article {pmid38337920,
year = {2024},
author = {Valeeva, LR and Sannikova, AV and Shafigullina, NR and Abdulkina, LR and Sharipova, MR and Shakirov, EV},
title = {Telomere Length Variation in Model Bryophytes.},
journal = {Plants (Basel, Switzerland)},
volume = {13},
number = {3},
pages = {},
pmid = {38337920},
issn = {2223-7747},
support = {GM127402/NH/NIH HHS/United States ; },
abstract = {The ends of linear chromosomes of most eukaryotes consist of protein-bound DNA arrays called telomeres, which play essential roles in protecting genome integrity. Despite general evolutionary conservation in function, telomeric DNA is known to drastically vary in length and sequence between different eukaryotic lineages. Bryophytes are a group of early diverging land plants that include mosses, liverworts, and hornworts. This group of ancient land plants recently emerged as a new model for important discoveries in genomics and evolutionary biology, as well as for understanding plant adaptations to a terrestrial lifestyle. We measured telomere length in different ecotypes of model bryophyte species, including Physcomitrium patens, Marchantia polymorpha, Ceratodon purpureus, and in Sphagnum isolates. Our data indicate that all analyzed moss and liverwort genotypes have relatively short telomeres. Furthermore, all analyzed ecotypes and isolates of model mosses and liverworts display evidence of substantial natural variation in telomere length. Interestingly, telomere length also differs between male and female strains of the dioecious liverwort M. polymorpha and dioecious moss C. purpureus. Given that bryophytes are extraordinarily well adapted to different ecological niches from polar to tropical environments, our data will contribute to understanding the impact of natural telomere length variation on evolutionary adaptations in this ancient land plant lineage.},
}
@article {pmid38336161,
year = {2024},
author = {Pili, MP and Cagliero, L and Panichi, V and Bordoni, M and Pansarasa, O and Cremaschi, G and Tonga, EB and Cappelletti, F and Provenzi, L},
title = {Exposure to pollution during the first thousand days and telomere length regulation: A literature review.},
journal = {Environmental research},
volume = {249},
number = {},
pages = {118323},
doi = {10.1016/j.envres.2024.118323},
pmid = {38336161},
issn = {1096-0953},
abstract = {Telomere length (TL) is a biomarker for cellular senescence and TL erosion is predictive of the risk for age-related diseases. Despite being genetically determined at birth, TL may be susceptible to modifications through epigenetic mechanisms. Pollutant agents are considered one of the major threats to both human and planetary health. Their ability to cross the placental barrier and induce oxidative stress in fetal cells is particularly concerning and it may be associated with early TL erosion. In consideration of the timely relevance of this topic, we conducted a literature review on the impact of prenatal exposure to pollutant agents on newborn TL. The search yielded a total of 1099 records, of which only 32 met the inclusion criteria for the review. These criteria included the participation of human subjects, a longitudinal design or collection of longitudinal data, reporting of original TL data, and a focus on exposure to pollutant agents. The majority of the studies reported a significant inverse association between prenatal exposure to pollutant agents and TL. Furthermore, the second trimester of pregnancy emerged as a special sensitive period for the occurrence of pollutant agent-driven TL modifications. Sex differences were inconsistently reported across studies. This review contributes to highlighting biochemical pathways for the threats of environmental pollution to human health. Future research is warranted to further highlight potential buffering mechanisms.},
}
@article {pmid38333665,
year = {2024},
author = {Schellnegger, M and Hofmann, E and Carnieletto, M and Kamolz, LP},
title = {Unlocking longevity: the role of telomeres and its targeting interventions.},
journal = {Frontiers in aging},
volume = {5},
number = {},
pages = {1339317},
pmid = {38333665},
issn = {2673-6217},
abstract = {Average life expectancy has been steadily increasing in developed countries worldwide. These demographic changes are associated with an ever-growing social and economic strain to healthcare systems as well as society. The aging process typically manifests as a decline in physiological and cognitive functions, accompanied by a rise in chronic diseases. Consequently, strategies that both mitigate age-related diseases and promote healthy aging are urgently needed. Telomere attrition, characterized by the shortening of telomeres with each cell division, paradoxically serves as both a protective mechanism and a contributor to tissue degeneration and age-related ailments. Based on the essential role of telomere biology in aging, research efforts aim to develop approaches designed to counteract telomere attrition, aiming to delay or reduce age-related diseases. In this review, telomere biology and its role in aging and age-related diseases is summarized along with recent approaches to interfere with telomere shortening aiming at well- and healthy-aging as well as longevity. As aging research enters a new era, this review emphasizes telomere-targeting therapeutics, including telomerase activators and tankyrase inhibitors, while also exploring the effects of antioxidative and anti-inflammatory agents, along with indirectly related approaches like statins.},
}
@article {pmid38332494,
year = {2024},
author = {Legan, AW and Mehl, HL and Wissotski, M and Adhikari, BN and Callicott, KA},
title = {Telomere-to-telomere genome assembly of the aflatoxin biocontrol agent Aspergillus flavus isolate La3279 isolated from maize in Nigeria.},
journal = {Microbiology resource announcements},
volume = {},
number = {},
pages = {e0069623},
doi = {10.1128/mra.00696-23},
pmid = {38332494},
issn = {2576-098X},
abstract = {Here, we report the complete genome of the non-aflatoxigenic Aspergillus flavus isolate La3279, which is an active ingredient of the aflatoxin biocontrol product Aflasafe. The chromosome-scale assembly clarifies the deletion pattern in the aflatoxin biosynthesis gene cluster and corrects a misidentified assembly previously published for this isolate.},
}
@article {pmid38326475,
year = {2024},
author = {Ohadi, H and Khalili, P and Abasnezhad Kasrineh, F and Esmaeili, OS and Esmaeili Ranjbar, F and Manshoori, A and Hajizadeh, MR and Jalali, Z},
title = {Umbilical cord blood thyroid hormones are inversely related to telomere length and mitochondrial DNA copy number.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {3164},
pmid = {38326475},
issn = {2045-2322},
mesh = {Humans ; Infant, Newborn ; Animals ; Male ; Female ; Pregnancy ; Child, Preschool ; *DNA, Mitochondrial/genetics ; *Fetal Blood ; DNA Copy Number Variations ; Thyroid Hormones ; Telomere/genetics ; Thyrotropin/genetics ; },
abstract = {Hypothyroidism has been linked to reduced mortality rate and increased lifespan and health span. Telomere shortening, enhanced oxidative stress, and reduced cellular mitochondrial content are important hallmarks of aging shown to be related to age-associated diseases. It was proposed that the status of these markers in early life can be predictive of lifespan and the predisposition to certain age-associated disease in adulthood. Animal studies indicated that prenatal injection of thyroid hormones affects postnatal telomere length. Here, we sought to determine whether thyroid hormones TSH and fT4 are related to the telomere length, mitochondrial DNA copy number (mtDNAcn), and oxidative stress resistance marker GPX in the cord blood of newborns. In this study, we analyzed 70 mothers (18-42 years) and neonate dyads born in 2022 at the Nik Nafs maternity Hospital in Rafsanjan. The relative telomere length (RTL) and mtDNAcn were measured in the genomic DNA of cord blood leukocytes using real-time PCR. GPX enzyme activity was measured in the serum using colorimetric assays. In this study the correlation between these markers and the cord blood TSH and fT4 hormones were assessed using regression models. We found a reverse relationship between TSH levels and RTL in the cord blood of neonates. Additionally, our results displayed increased TSH levels associated with enhanced GPX activity. Regarding the mitochondrial DNA copy number, we found an indirect relationship between fT4 level and mtDNAcn only in male newborns. Future analyses of various oxidative stress markers, mitochondrial biogenesis status, telomerase activity, and the level of DNA damage are warranted to demonstrate the underlying mechanism of our observations.},
}
@article {pmid38326339,
year = {2024},
author = {Sun, Z and Li, S and Liu, Y and Li, W and Liu, K and Cao, X and Lin, J and Wang, H and Wang, Q and Shao, C},
title = {Telomere-to-telomere gapless genome assembly of the Chinese sea bass (Lateolabrax maculatus).},
journal = {Scientific data},
volume = {11},
number = {1},
pages = {175},
pmid = {38326339},
issn = {2052-4463},
mesh = {Animals ; *Bass/genetics ; Genome ; Telomere/genetics ; Computational Biology ; Seafood ; },
abstract = {Chinese sea bass (Lateolabrax maculatus) is a highly sought-after commercial seafood species in Asian regions due to its excellent nutritional value. With the rapid advancement of bioinformatics, higher standards for genome analysis compared to previously published reference genomes are now necessary. This study presents a gapless assembly of the Chinese sea bass genome, which has a length of 632.75 Mb. The sequences were assembled onto 24 chromosomes with a coverage of over 99% (626.61 Mb), and telomeres were detected on 34 chromosome ends. Analysis using Merqury indicated a high level of accuracy, with an average consensus quality value of 54.25. The ONT ultralong and PacBio HiFi data were aligned with the assembly using minimap2, resulting in a mapping rate of 99.9%. The study also identified repeating elements in 20.90% (132.25 Mb) of the genome and inferred 22,014 protein-coding genes. These results establish meaningful groundwork for exploring the evolution of the Chinese sea bass genome and advancing molecular breeding techniques.},
}
@article {pmid38321948,
year = {2024},
author = {Audry, J and Zhang, H and Kerr, C and Berkner, KL and Runge, KW},
title = {Ccq1 restrains Mre11-mediated degradation to distinguish short telomeres from double-strand breaks.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkae044},
pmid = {38321948},
issn = {1362-4962},
support = {R01 HL152678/HL/NHLBI NIH HHS/United States ; R01 HL158007/HL/NHLBI NIH HHS/United States ; R01AG051601/NH/NIH HHS/United States ; },
abstract = {Telomeres protect chromosome ends and are distinguished from DNA double-strand breaks (DSBs) by means of a specialized chromatin composed of DNA repeats bound by a multiprotein complex called shelterin. We investigated the role of telomere-associated proteins in establishing end-protection by studying viable mutants lacking these proteins. Mutants were studied using a Schizosaccharomyces pombe model system that induces cutting of a 'proto-telomere' bearing telomere repeats to rapidly form a new stable chromosomal end, in contrast to the rapid degradation of a control DSB. Cells lacking the telomere-associated proteins Taz1, Rap1, Poz1 or Rif1 formed a chromosome end that was stable. Surprisingly, cells lacking Ccq1, or impaired for recruiting Ccq1 to the telomere, converted the cleaved proto-telomere to a rapidly degraded DSB. Ccq1 recruits telomerase, establishes heterochromatin and affects DNA damage checkpoint activation; however, these functions were separable from protection of the new telomere by Ccq1. In cells lacking Ccq1, telomere degradation was greatly reduced by eliminating the nuclease activity of Mre11 (part of the Mre11-Rad50-Nbs1/Xrs2 DSB processing complex), and higher amounts of nuclease-deficient Mre11 associated with the new telomere. These results demonstrate a novel function for S. pombe Ccq1 to effect end-protection by restraining Mre11-dependent degradation of the DNA end.},
}
@article {pmid38315384,
year = {2024},
author = {Pennington, KM and Simonetto, D and Taner, T and Mangaonkar, AA},
title = {Pulmonary, Hepatic, and Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Telomere Biology Disorders.},
journal = {Current hematologic malignancy reports},
volume = {},
number = {},
pages = {},
pmid = {38315384},
issn = {1558-822X},
abstract = {PURPOSE OF THE REVIEW: This study aimed to summarize evidence and provide consensus-based guidelines for management of transplantation in patients with telomere biology disorders (TBD). Specifically, this review focuses on clinical management of lung, liver, and bone marrow transplantation in TBD patients.<br><br>RECENT FINDINGS: TBD patients have specific unique biological vulnerabilities such as T cell immunodeficiency, susceptibility to infections, hypersensitivity to chemotherapy and radiation, and cytopenias. Furthermore, multiple organ involvement at diagnosis makes clinical management especially challenging due to higher degree of organ damage, and stress-induced telomeric crisis. Sequential and combined organ transplants, development of novel radiation and alkylator-free conditioning regimen, and use of novel drugs for graft-versus-host disease prophylaxis are some of the recent updates in the field. Multidisciplinary management is essential to optimize transplant outcomes in patients with TBD. In this review, we provide consensus-based transplant management guidelines for clinical management of transplant in TBD.},
}
@article {pmid38310618,
year = {2024},
author = {Borges, G and Benslimane, Y and Harrington, L},
title = {A CRISPR base editing approach for the functional assessment of telomere biology disorder-related genes in human health and aging.},
journal = {Biogerontology},
volume = {},
number = {},
pages = {},
pmid = {38310618},
issn = {1573-6768},
support = {FRN148936/CAPMC/CIHR/Canada ; },
abstract = {Telomere Biology Disorders (TBDs) are a group of rare diseases characterized by the presence of short and/or dysfunctional telomeres. They comprise a group of bone marrow failure syndromes, idiopathic pulmonary fibrosis, and liver disease, among other diseases. Genetic alterations (variants) in the genes responsible for telomere homeostasis have been linked to TBDs. Despite the number of variants already identified as pathogenic, an even more significant number must be better understood. The study of TBDs is challenging since identifying these variants is difficult due to their rareness, it is hard to predict their impact on the disease onset, and there are not enough samples to study. Most of our knowledge about pathogenic variants comes from assessing telomerase activity from patients and their relatives affected by a TBD. However, we still lack a cell-based model to identify new variants and to study the long-term impact of such variants on the genes involved in TBDs. Herein, we present a cell-based model using CRISPR base editing to mutagenize the endogenous alleles of 21 genes involved in telomere biology. We identified key residues in the genes encoding 17 different proteins impacting cell growth. We provide functional evidence for variants of uncertain significance in patients with TBDs. We also identified variants resistant to telomerase inhibition that, similar to cells expressing wild-type telomerase, exhibited increased tumorigenic potential using an in vitro tumour growth assay. We believe that such cell-based approaches will significantly advance our understanding of the biology of TBDs and may contribute to the development of new therapies for this group of diseases.},
}
@article {pmid38307343,
year = {2024},
author = {Ozturk, S},
title = {The close relationship between oocyte aging and telomere shortening, and possible interventions for telomere protection.},
journal = {Mechanisms of ageing and development},
volume = {218},
number = {},
pages = {111913},
doi = {10.1016/j.mad.2024.111913},
pmid = {38307343},
issn = {1872-6216},
abstract = {As women delay childbearing due to socioeconomic reasons, understanding molecular mechanisms decreasing oocyte quantity and quality during ovarian aging becomes increasingly important. The ovary undergoes biological aging at a higher pace when compared to other organs. As is known, telomeres play crucial roles in maintaining genomic integrity, and their shortening owing to increased reactive oxygen species, consecutive cellular divisions, genetic and epigenetic alterations is associated with loss of developmental competence of oocytes. Novel interventions such as antioxidant treatments and regulation of gene expression are being investigated to prevent or rescue telomere attrition and thereby oocyte aging. Herein, potential factors and molecular mechanisms causing telomere shortening in aging oocytes were comprehensively reviewed. For the purpose of extending reproductive lifespan, possible therapeutic interventions to protect telomere length were also discussed.},
}
@article {pmid38296763,
year = {2024},
author = {Akkar, I and Koyuncuoglu, G and Turgut, ZI and Dogan, MH and Kizilarslanoglu, MC},
title = {Comment on: Effect of a 3-year lifestyle intervention on telomere length in participants from PREDIMED-Plus.},
journal = {Clinical nutrition (Edinburgh, Scotland)},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.clnu.2024.01.018},
pmid = {38296763},
issn = {1532-1983},
}
@article {pmid38293941,
year = {2024},
author = {Salih, AM and Galazzo, IB and Menegaz, G and Altmann, A},
title = {Leukocyte Telomere Length and Cardiac Structure and Function: A Mendelian Randomization Study.},
journal = {Journal of the American Heart Association},
volume = {13},
number = {3},
pages = {e032708},
doi = {10.1161/JAHA.123.032708},
pmid = {38293941},
issn = {2047-9980},
mesh = {*Mendelian Randomization Analysis/methods ; *Heart ; Leukocytes ; Telomere/genetics ; Genome-Wide Association Study ; },
abstract = {BACKGROUND: Existing research demonstrates the association of shorter leukocyte telomere length with increased risk of age-related health outcomes including cardiovascular diseases. However, the direct causality of these relationships has not been definitively established. Cardiovascular aging at an organ level may be captured using image-derived phenotypes of cardiac anatomy and function.<br><br>METHODS AND RESULTS: In the current study, we use 2-sample Mendelian randomization to assess the causal link between leukocyte telomere length and 54 cardiac magnetic resonance imaging measures representing structure and function across the 4 cardiac chambers. Genetically predicted shorter leukocyte telomere length was causally linked to smaller ventricular cavity sizes including left ventricular end-systolic volume, left ventricular end-diastolic volume, lower left ventricular mass, and pulmonary artery. The association with left ventricular mass (&#x3b2;&#x2009;=0.217, Pfalse discovery rate=0.016) remained significant after multiple testing adjustment, whereas other associations were attenuated.<br><br>CONCLUSIONS: Our findings support a causal role for shorter leukocyte telomere length and faster cardiac aging, with the most prominent relationship with left ventricular mass.},
}
@article {pmid38288254,
year = {2024},
author = {Wang, X and Tu, M and Wang, Y and Zhang, Y and Yin, W and Fang, J and Gao, M and Li, Z and Zhan, W and Fang, Y and Song, J and Xi, Z and Wang, X},
title = {Telomere-to-telomere and gap-free genome assembly of a susceptible grapevine species (Thompson Seedless) to facilitate grape functional genomics.},
journal = {Horticulture research},
volume = {11},
number = {1},
pages = {uhad260},
pmid = {38288254},
issn = {2662-6810},
abstract = {Grapes are globally recognized as economically significant fruit trees. Among grape varieties, Thompson Seedless holds paramount influence for fresh consumption and for extensive applications in winemaking, drying, and juicing. This variety is one of the most efficient genotypes for grape genetic modification. However, the lack of a high-quality genome has impeded effective breeding efforts. Here, we present the high-quality reference genome of Thompson Seedless with all 19 chromosomes represented as 19 contiguous sequences (N50 = 27.1 Mb) with zero gaps and prediction of all telomeres and centromeres. Compared with the previous assembly (TSv1 version), the new assembly incorporates an additional 31.5 Mb of high-quality sequenced data with annotation of a total of 30 397 protein-coding genes. We also performed a meticulous analysis to identify nucleotide-binding leucine-rich repeat genes (NLRs) in Thompson Seedless and two wild grape varieties renowned for their disease resistance. Our analysis revealed a significant reduction in the number of two types of NLRs, TIR-NB-LRR (TNL) and CC-NB-LRR (CNL), in Thompson Seedless, which may have led to its sensitivity to many fungal diseases, such as powdery mildew, and an increase in the number of a third type, RPW8 (resistance to powdery mildew 8)-NB-LRR (RNL). Subsequently, transcriptome analysis showed significant enrichment of NLRs during powdery mildew infection, emphasizing the pivotal role of these elements in grapevine's defense against powdery mildew. The successful assembly of a high-quality Thompson Seedless reference genome significantly contributes to grape genomics research, providing insight into the importance of seedlessness, disease resistance, and color traits, and these data can be used to facilitate grape molecular breeding efforts.},
}
@article {pmid38285162,
year = {2024},
author = {Waitkus, MS and Erman, EN and Reitman, ZJ and Ashley, DM},
title = {Mechanisms of telomere maintenance and associated therapeutic vulnerabilities in malignant gliomas.},
journal = {Neuro-oncology},
volume = {},
number = {},
pages = {},
doi = {10.1093/neuonc/noae016},
pmid = {38285162},
issn = {1523-5866},
support = {K22 CA258965/CA/NCI NIH HHS/United States ; },
abstract = {A majority of cancers (~85%) activate the enzyme telomerase to maintain telomere length over multiple rounds of cellular division. Telomerase-negative cancers activate a distinct, telomerase-independent mechanism of telomere maintenance termed Alternative lengthening of telomeres (ALT). ALT uses homologous recombination to maintain telomere length and exhibits features of break-induced DNA replication. In malignant gliomas, the activation of either telomerase or ALT is nearly ubiquitous in pediatric and adult tumors, and the frequency with which these distinct telomere maintenance mechanisms is activated varies according to genetically-defined glioma subtypes. In this review, we summarize the current state of the field of telomere maintenance mechanisms (TMMs) and their relevance to glioma biology and therapy. We review the genetic alterations and molecular mechanisms leading to telomerase activation or ALT induction in pediatric and adult gliomas. With this background, we review emerging evidence on strategies for targeting TMMs for glioma therapy. Finally, we comment on critical gaps and issues for moving the field forward to translate our improved understanding of glioma telomere maintenance into better therapeutic strategies for patients.},
}
@article {pmid38279807,
year = {2024},
author = {Pereira, FSM and Thomasini, RL and Pereira, DS and Silva, TJ and Leite, CA and Reis, LGO and Câmara, VAA and da Costa, MBR and Bakir, JVS and Xavier, LS and Pereira, LSM and Parentoni, AN and Lacerda, ACR},
title = {Association Between the Length of Leukocyte Telomeres and Functional Performance of Older Adults: Observational Study.},
journal = {Rejuvenation research},
volume = {},
number = {},
pages = {},
doi = {10.1089/rej.2023.0050},
pmid = {38279807},
issn = {1557-8577},
abstract = {Despite current literature pointing to a link between shortened telomeres and aging, chronic diseases, and geriatric syndromes, the precise implications of this connection remain unclear. The aim of this exploratory, cross-sectional, observational study was to investigate the association between the relative telomere length (RTL) of peripheral blood leukocyte subtypes (mononuclear cells and granulocytes) and physical performance using the Short Physical Performance Battery (SPPB) in older adults. A cohort of 95 participants was recruited, which included men and women aged over 60 years (70.48 ± 5.5 years). It was found that mononuclear cell RTL was significantly lower than that of granulocytes (p < 0.0001). Moreover, individuals with good SPPB performance exhibited lower mononuclear cell RTL compared with those with moderate or poor performance. However, no significant differences were observed in granulocyte RTL between different SPPB performance groups. The global SPPB score showed an inverse correlation with mononuclear cell RTL, but this correlation was not present with granulocyte RTL. Similarly, the SPPB sit-to-stand domain correlated with mononuclear cell RTL, but no such correlation was found with granulocyte RTL. Our findings challenge conventional expectations, suggesting that shorter mononuclear cell RTL may be associated with favorable functional capacity. The variations in RTL between mononuclear cells and granulocytes highlight their distinct biological roles and turnover rates. A history of immune responses may influence mononuclear cell RTL dynamics, while telomerase activity may protect granulocyte RTL from significant shortening. The unexpected associations observed in mononuclear cell RTL emphasize the complex interplay between immune responses, cellular aging, and functional capacity in older adults.},
}
@article {pmid38278953,
year = {2024},
author = {Bi, G and Zhao, S and Yao, J and Wang, H and Zhao, M and Sun, Y and Hou, X and Haas, FB and Varshney, D and Prigge, M and Rensing, SA and Jiao, Y and Ma, Y and Yan, J and Dai, J},
title = {Near telomere-to-telomere genome of the model plant Physcomitrium patens.},
journal = {Nature plants},
volume = {10},
number = {2},
pages = {327-343},
pmid = {38278953},
issn = {2055-0278},
mesh = {*Centromere/genetics ; *Telomere/genetics ; Genome, Plant ; },
abstract = {The model plant Physcomitrium patens has played a pivotal role in enhancing our comprehension of plant evolution and development. However, the current genome harbours numerous regions that remain unfinished and erroneous. To address these issues, we generated an assembly using Oxford Nanopore reads and Hi-C mapping. The assembly incorporates telomeric and centromeric regions, thereby establishing it as a near telomere-to-telomere genome except a region in chromosome 1 that is not fully assembled due to its highly repetitive nature. This near telomere-to-telomere genome resolves the chromosome number at 26 and provides a gap-free genome assembly as well as updated gene models to aid future studies using this model organism.},
}
@article {pmid38276581,
year = {2024},
author = {Aon-Im, P and Monthakantirat, O and Daodee, S and Chulikhit, Y and Sriya, N and Boonyarat, C and Chumwangwapee, T and Khamphukdee, C and Kijjoa, A},
title = {Evaluation of the Impact of Alternanthera philoxeroides (Mart.) Griseb. Extract on Memory Impairment in D-Galactose-Induced Brain Aging in Mice through Its Effects on Antioxidant Enzymes, Neuroinflammation, and Telomere Shortening.},
journal = {Molecules (Basel, Switzerland)},
volume = {29},
number = {2},
pages = {},
pmid = {38276581},
issn = {1420-3049},
support = {RGNS 64-041//Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innova-tion, Thailand/ ; },
mesh = {Mice ; Animals ; *Antioxidants/metabolism ; *Galactose/metabolism ; Telomere Shortening ; Neuroinflammatory Diseases ; Maze Learning ; Aging ; Brain/metabolism ; Memory Disorders/chemically induced/drug therapy/metabolism ; Superoxide Dismutase/metabolism ; Cytokines/metabolism ; Oxidative Stress ; },
abstract = {Aging is a well-known factor that accelerates brain deterioration, resulting in impaired learning and memory functions. This current study evaluated the potential of an extract of Alternanthera philoxeroides (AP), an edible flavonoid-rich plant, to ameliorate D-galactose-induced brain aging in male mice. Chronic administration of D-galactose (150 mg/kg/day) in mice mimicked the characteristics of aging by accelerating senescence via downregulation of the following telomere-regulating factors: mouse telomerase reverse transcriptase (mTERT) and mouse telomeric repeat-binding factors 1 (mTRF1) and 2 (mTRF2). D-galactose also decreased the activities of the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD), while increasing expression of neuroinflammatory cytokines in the frontal cortex and hippocampus. Daily treatment of D-galactose-induced aging mice with AP at 250 and 500 mg/kg/day or vitamin E (100 mg/kg/day) significantly increased the activities of SOD and CAT, as well as expression of mTERT, mTRF1, and mTRF2, which are involved in telomere stabilization, but decreased the levels of proinflammatory cytokines IL-1β, IL-6, and TNF-α. In the behavioral portion of the study, AP improved aging-related cognitive deficits in short-term memory as shown by the Y-maze task and the novel object recognition test (NORT) and long-term memory as shown by the Morris water maze test (MWMT). The flavones kaempferol-O-glucoside (1), quercetin (2), alternanthin B (3), demethyltorosaflavone D (4), and chrysoeriol-7-O-rhamnoside (5), which could be responsible for the observed effects of AP in the D-galactose-induced aging mice, were identified by HPLC analysis.},
}
@article {pmid38275650,
year = {2024},
author = {Ojeda-Rodriguez, A and Alcala-Diaz, JF and Rangel-Zuñiga, OA and Arenas-de Larriva, AP and Gutierrez-Mariscal, FM and Torres-Peña, JD and Mora-Ortiz, M and Romero-Cabrera, JL and Luque, RM and Ordovas, JM and Perez-Martinez, P and Delgado-Lista, J and Yubero-Serrano, EM and Lopez-Miranda, J},
title = {Telomere Maintenance Is Associated with Type 2 Diabetes Remission in Response to a Long-Term Dietary Intervention without Non-Weight Loss in Patients with Coronary Heart Disease: From the CORDIOPREV Randomized Controlled Trial.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {13},
number = {1},
pages = {},
pmid = {38275650},
issn = {2076-3921},
support = {CEAS, 1/2016//Fundaci&#xf3;n Patrimonio Comunal Olivarero/ ; Grant AGL2015-67896-P; PID2019-104362RB-I00//Ministerio de Ciencia e Innovaci&#xf3;n/ ; Grant P20/00256//Consejer&#xed;a de Transformaci&#xf3;n Econ&#xf3;mica, Industria, Conocimiento y Universidades/ ; },
abstract = {In order to evaluate whether telomere maintenance is associated with type 2 diabetes remission, newly diagnosed type 2 diabetes patients without glucose-lowering treatment (183 out of 1002) from the CORDIOPREV study (NCT00924937) were randomized to consume a Mediterranean or low-fat diet. Patients were classified as Responders, those who reverted from type 2 diabetes during the 5 years of dietary intervention (n = 69), and Non-Responders, who did not achieve diabetes remission by the end of the follow-up period (n = 104). We found no differences in diabetes remission between the two diets, and we determined telomere length (TL) by measuring qPCR, telomerase activity using the TRAP assay, and direct redox balance based on the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSH) via colorimetric assay. Responders exhibited higher baseline TL in comparison with Non-Responders (p = 0.040), and a higher TL at baseline significantly predicted a higher probability of type 2 diabetes remission (OR 2.13; 95% CI, 1.03 to 4.41). After the dietary intervention, Non-Responders showed significant telomere shortening (-0.19, 95% CI -0.32 to 0.57; p = 0.005). Telomere shortening was significantly pronounced in type 2 diabetes patients with a worse profile of insulin resistance and/or beta-cell functionality: high hepatic insulin resistance fasting, a high disposition index (-0.35; 95% CI, -0.54 to -0.16; p < 0.001), and a low disposition index (-0.25; 95% CI, -0.47 to -0.01; p = 0.037). In addition, changes in TL were correlated to the GSH/GSSG ratio. Responders also showed increased telomerase activity compared with baseline (p = 0.048), from 0.16 (95% CI, 0.08 to 0.23) to 0.28 (95% CI, 0.15 to 0.40), with a more marked increase after the dietary intervention compared with Non-Responders (+0.07; 95% CI, -0.06-0.20; p = 0.049). To conclude, telomere maintenance may play a key role in the molecular mechanisms underlying type 2 diabetes remission in newly diagnosed patients. However, further larger-scale prospective studies are necessary to corroborate our findings.},
}
@article {pmid38270117,
year = {2023},
author = {Liao, P and Yan, B and Wang, C and Lei, P},
title = {Telomeres: Dysfunction, Maintenance, Aging and Cancer.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2023.1128},
pmid = {38270117},
issn = {2152-5250},
abstract = {Aging has emerged at the forefront of scientific research due to the growing social and economic costs associated with the growing aging global population. The defining features of aging involve a variety of molecular processes and cellular systems, which are interconnected and collaboratively contribute to the aging process. Herein, we analyze how telomere dysfunction potentially amplifies or accelerates the molecular and biochemical mechanisms underpinning each feature of aging and contributes to the emergence of age-associated illnesses, including cancer and neurodegeneration, via the perspective of telomere biology. Furthermore, the recently identified novel mechanistic actions for telomere maintenance offer a fresh viewpoint and approach to the management of telomeres and associated disorders. Telomeres and the defining features of aging are intimately related, which has implications for therapeutic and preventive approaches to slow aging and reduce the prevalence of age-related disorders.},
}
@article {pmid38269293,
year = {2024},
author = {Liao, Z and Zhang, T and Lei, W and Wang, Y and Yu, J and Wang, Y and Chai, K and Wang, G and Zhang, H and Zhang, X},
title = {A telomere-to-telomere reference genome of ficus (Ficus hispida) provides new insights into sex determination.},
journal = {Horticulture research},
volume = {11},
number = {1},
pages = {uhad257},
pmid = {38269293},
issn = {2662-6810},
abstract = {A high-quality reference genome is indispensable for resolving biologically essential traits. Ficus hispida is a dioecious plant. A complete Ficus reference genome will be crucial for understanding their sex evolution and important biological characteristics, such as aerial roots, mutualistic symbiosis with ficus-wasps, and fruiting from old stems. Here, we generated a telomere-to-telomere (T2T) genome for F. hispida using PacBio HiFi and Oxford Nanopore Ultra-long sequencing technologies. The genome contiguity and completeness has shown improvement compared with the previously released genome, with the annotation of six centromeres and 28 telomeres. We have refined our previously reported 2-Mb male-specific region into a 7.2-Mb genomic region containing 51 newly predicted genes and candidate sex-determination genes AG2 and AG3. Many of these genes showed extremely low expression, likely attributed to hypermethylation in the gene body and promoter regions. Gene regulatory networks (GRNs) revealed that AG2 and AG3 are related to the regulation of stamen development in male flowers, while the AG1 gene is responsible for regulating female flowers' defense responses and secondary metabolite processes. Comparative analysis of GRNs showed that the NAC, WRKY, and MYB transcription factor families dominate the female GRN, whereas the MADS and MYB transcription factor families are prevalent in the male GRN.},
}
@article {pmid38267053,
year = {2024},
author = {Aburada, N and Ito, J and Inoue, Y and Yamamoto, T and Hayashi, M and Teramoto, N and Okada, Y and Koshiishi, Y and Shirasuna, K and Iwata, H},
title = {Effect of paternal aging and vitrification on mitochondrial DNA copy number and telomere length of mouse blastocysts.},
journal = {The Journal of reproduction and development},
volume = {},
number = {},
pages = {},
doi = {10.1262/jrd.2023-079},
pmid = {38267053},
issn = {1348-4400},
abstract = {In this study, we examined the effects of paternal aging on the mitochondrial DNA copy number (mt-cn), telomere length (TL), and gene expression in mouse embryos. The effects of vitrification on the mt-cn and TL of the embryos derived from young and aged male parents (YF and AF, respectively) were examined. C57BL/6N male mice were used for embryo production at 13-23 and 50-55 weeks of age. Two-cell stage embryos were collected from the oviducts of superovulated female mice (8-15 weeks old) and cultured for 24 h until the 8-cell stage, followed by embryo vitrification. Fresh and vitrified-warmed embryos were incubated for 2 days until the blastocyst stage, and mt-cn and TL were investigated. The cell-free mitochondrial DNA copy number (cf-mt-cn) in the spent culture medium (SCM) of the embryos was then investigated. RNA sequencing of blastocysts revealed that metabolic pathways, including oxidative phosphorylation and mTOR pathways, were enriched in differentially expressed genes. The mt-cn and TL of AF-derived blastocysts were lower and shorter, respectively, than those of YF-derived blastocysts. Paternal aging did not affect the blastocyst rate after vitrification. Vitrification of the 8-cell stage embryos did not affect the mt-cn of the blastocysts. However, it increased the cf-mt-cn (cell-free mt-cn) in the SCM of both YF- and AF-derived embryos. Vitrification did not affect the TL of either YF- or AF-derived embryos. Thus, paternal aging affected the mt-cn and TL of the embryos, but vitrification did not affect these parameters in either age groups.},
}
@article {pmid38262198,
year = {2024},
author = {Lu, G and Fang, T and Li, X and Zhang, X and Li, H and Wu, N and Liu, F and Hao, W and Ye, QN and Cheng, L and Li, J and Li, F},
title = {Methamphetamine use shortens telomere length in male adults and rats.},
journal = {Drug and alcohol dependence},
volume = {256},
number = {},
pages = {111094},
doi = {10.1016/j.drugalcdep.2024.111094},
pmid = {38262198},
issn = {1879-0046},
mesh = {Humans ; Adult ; Animals ; Rats ; Male ; *Aging ; Diagnostic and Statistical Manual of Mental Disorders ; Leukocytes ; *Methamphetamine/pharmacology ; Telomere ; },
abstract = {BACKGROUND: Methamphetamine (MA) use increases the risk of age-related diseases. However, it remains uncertain whether MA use exhibits accelerated biological aging, as indicated by telomere length (TL), a proposed marker of aging. Here we conducted studies in both humans and rats to investigate the association between MA use and TL.<br><br>METHODS: We recruited 125 male MA users and 66 healthy controls, aged 30-40 years. MA users were diagnosed using DSM-5 criteria and categorized into two groups: non-severe (n = 78) and severe (n = 47) MA use disorder (MUD). MA-treated conditioned place preference (CPP) rats were utilized to validate our clinical investigations. TL was assessed using real-time polymerase chain reaction.<br><br>RESULTS: At clinical levels, MA users exhibited significantly shorter leukocyte TL compared to healthy controls. Among MA users, individuals with severe MUD had significantly shorter leukocyte TL than those with non-severe MUD. Importantly, both univariate and multivariate linear regression analyses demonstrated a negative association between the severity of MA use and leukocyte TL. In a rat model of MA-induced CPP, leukocyte TL was also significantly shortened after MA administration, especially in rats with higher CPP expression or reinstatement scores.<br><br>CONCLUSION: MA use shortened TL, and the severity of MA use was negatively correlated with TL. These findings provide new insights into the pathophysiology of accelerated aging caused by MA use and may have implications for identifying biomarkers and developing novel treatment strategies for MUD.},
}
@article {pmid38260456,
year = {2024},
author = {Cheng, D and Zhang, F and Porter, KI and Wang, S and Zhang, H and Davis, CJ and Robertson, GP and Zhu, J},
title = {Humanization of the mouse Tert gene reset telomeres to human length.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {38260456},
support = {R01 AG073423/AG/NIA NIH HHS/United States ; R21 OD021432/OD/NIH HHS/United States ; R35 GM149529/GM/NIGMS NIH HHS/United States ; },
abstract = {Telomeres undergo shortening with each cell division, serving as biomarkers of human aging, which is characterized by short telomeres and restricted telomerase expression in adult tissues. Contrarily, mice, featuring their longer telomeres and widespread telomerase activity, present limitations as models for understanding telomere-related human biology and diseases. To bridge this gap, we engineered a mouse strain with a humanized mTert gene, hmTert, wherein specific non-coding sequences were replaced with their human counterparts. The hmTert gene, encoding the wildtype mTert protein, was repressed in adult tissues beyond the gonads and thymus, closely resembling the regulatory pattern of the human TERT gene. Remarkably, the hmTert gene rescued telomere dysfunction in late generations of mTert-knockout mice. Through successive intercrosses of Tert[h/-] mice, telomere length progressively declined, stabilizing below 10-kb. Tert[h/h] mice achieved a human-like average telomere length of 10-12 kb, contrasting with the 50-kb length in wildtype C57BL/6J mice. Despite shortened telomeres, Tert[h/h] mice maintained normal body weight and cell homeostasis in highly proliferative tissues. Notably, colonocyte proliferation decreased significantly in Tert[h/h] mice during dextran sodium sulfate-induced ulcerative colitis-like pathology, suggesting limitations on cellular renewal due to short telomeres. Our findings underscore the genetic determination of telomere homeostasis in mice by the Tert gene. These mice, exhibiting humanized telomere homeostasis, serve as a valuable model for exploring fundamental questions related to human aging and cancer.},
}
@article {pmid38258326,
year = {2024},
author = {Romero-Haro, A&#xc1; and Mulder, E and Haussmann, MF and Tschirren, B},
title = {The association between age and telomere length is age-dependent: Evidence for a threshold model of telomere length maintenance.},
journal = {Journal of experimental zoology. Part A, Ecological and integrative physiology},
volume = {},
number = {},
pages = {},
doi = {10.1002/jez.2785},
pmid = {38258326},
issn = {2471-5646},
support = {/SNSF_/Swiss National Science Foundation/Switzerland ; },
abstract = {Telomere length and dynamics are commonly used biomarkers of somatic state, yet the role of telomeres underlying the aging process is still debated. Indeed, to date, empirical evidence for an association between age and telomere length is mixed. Here, we test if the age-dependency of the association between age and telomere length can provide a potential explanation for the reported inconsistencies across studies. To this end, we quantified telomere length by telomere restriction fragment analysis in two groups of Japanese quail (Coturnix japonica) that differed in their age distribution. One group consisted of young adults only, whereas the second group consisted of adults across a wide range of ages. In the young adults group, there was a highly significant negative association between telomere length and age, whereas no association between age and telomere length was found in the all-ages adults group. This difference between groups was not due to telomere length-dependent selective disappearance. Our results shows that the association between telomere length and age is age-dependent and suggest that the costs and benefits associated with telomere maintenance are dynamic across an individual's life course.},
}
@article {pmid38255792,
year = {2024},
author = {Dhillon, VS and Shahid, M and Deo, P and Fenech, M},
title = {Reduced SIRT1 and SIRT3 and Lower Antioxidant Capacity of Seminal Plasma Is Associated with Shorter Sperm Telomere Length in Oligospermic Men.},
journal = {International journal of molecular sciences},
volume = {25},
number = {2},
pages = {},
pmid = {38255792},
issn = {1422-0067},
mesh = {Humans ; Male ; Semen ; *Oligospermia/genetics ; Antioxidants ; *Sirtuin 3/genetics ; Sirtuin 1/genetics ; Spermatozoa ; Protamines ; Superoxide Dismutase/genetics ; },
abstract = {Infertility affects millions of couples worldwide and has a profound impact not only on their families, but also on communities. Telomere attrition has been associated with infertility, DNA damage and fragmentation. Oxidative stress has been shown to affect sperm DNA integrity and telomere length. Sirtuins such as SIRT1 and SIRT3 are involved in aging and oxidative stress response. The aim of the present study is to determine the role of SIRT1 and SIRT3 in regulating oxidative stress, telomere shortening, and their association with oligospermia. Therefore, we assessed the protein levels of SIRT1 and SIRT3, total antioxidant capacity (TAC), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase activity (CAT) in the seminal plasma of 272 patients with oligospermia and 251 fertile men. We also measured sperm telomere length (STL) and leukocyte telomere length (LTL) using a standard real-time quantitative PCR assay. Sperm chromatin and protamine deficiency were also measured as per standard methods. Our results for oligospermic patients demonstrate significant reductions in semen parameters, shorter STL and LTL, lower levels of SOD, TAC, CAT, SIRT1 and SIRT3 levels, and also significant protamine deficiency and higher levels of MDA and DNA fragmentation. We conclude that a shorter TL in sperms and leukocytes is associated with increased oxidative stress that also accounts for high levels of DNA fragmentation in sperms. Our results support the hypothesis that various sperm parameters in the state of oligospermia are associated with or caused by reduced levels of SIRT1 and SIRT3 proteins.},
}
@article {pmid38254712,
year = {2024},
author = {Musmaker, K and Wells, J and Tsai, MC and Comeron, JM and Malkova, A},
title = {Alternative Lengthening of Telomeres in Yeast: Old Questions and New Approaches.},
journal = {Biomolecules},
volume = {14},
number = {1},
pages = {},
pmid = {38254712},
issn = {2218-273X},
support = {R01 AG081263/AG/NIA NIH HHS/United States ; R01AG081263/AG/NIA NIH HHS/United States ; },
mesh = {*Saccharomyces cerevisiae/genetics ; *Telomere/genetics ; Computer Simulation ; DNA Repair ; Recombination, Genetic ; },
abstract = {Alternative lengthening of telomeres (ALT) is a homologous recombination-based pathway utilized by 10-15% of cancer cells that allows cells to maintain their telomeres in the absence of telomerase. This pathway was originally discovered in the yeast Saccharomyces cerevisiae and, for decades, yeast has served as a robust model to study ALT. Using yeast as a model, two types of ALT (RAD51-dependent and RAD51-independent) have been described. Studies in yeast have provided the phenotypic characterization of ALT survivors, descriptions of the proteins involved, and implicated break-induced replication (BIR) as the mechanism responsible for ALT. Nevertheless, many questions have remained, and answering them has required the development of new quantitative methods. In this review we discuss the historic aspects of the ALT investigation in yeast as well as new approaches to investigating ALT, including ultra-long sequencing, computational modeling, and the use of population genetics. We discuss how employing new methods contributes to our current understanding of the ALT mechanism and how they may expand our understanding of ALT in the future.},
}
@article {pmid38254667,
year = {2024},
author = {Li, B},
title = {Unwrap RAP1's Mystery at Kinetoplastid Telomeres.},
journal = {Biomolecules},
volume = {14},
number = {1},
pages = {},
pmid = {38254667},
issn = {2218-273X},
support = {R01 AI066095/AI/NIAID NIH HHS/United States ; R01 AI179972/AI/NIAID NIH HHS/United States ; },
mesh = {Animals ; *Telomere/genetics ; Epigenomics ; Eukaryota ; *RNA, Long Noncoding ; Mammals ; },
abstract = {Although located at the chromosome end, telomeres are an essential chromosome component that helps maintain genome integrity and chromosome stability from protozoa to mammals. The role of telomere proteins in chromosome end protection is conserved, where they suppress various DNA damage response machineries and block nucleolytic degradation of the natural chromosome ends, although the detailed underlying mechanisms are not identical. In addition, the specialized telomere structure exerts a repressive epigenetic effect on expression of genes located at subtelomeres in a number of eukaryotic organisms. This so-called telomeric silencing also affects virulence of a number of microbial pathogens that undergo antigenic variation/phenotypic switching. Telomere proteins, particularly the RAP1 homologs, have been shown to be a key player for telomeric silencing. RAP1 homologs also suppress the expression of Telomere Repeat-containing RNA (TERRA), which is linked to their roles in telomere stability maintenance. The functions of RAP1s in suppressing telomere recombination are largely conserved from kinetoplastids to mammals. However, the underlying mechanisms of RAP1-mediated telomeric silencing have many species-specific features. In this review, I will focus on Trypanosoma brucei RAP1's functions in suppressing telomeric/subtelomeric DNA recombination and in the regulation of monoallelic expression of subtelomere-located major surface antigen genes. Common and unique mechanisms will be compared among RAP1 homologs, and their implications will be discussed.},
}
@article {pmid38253555,
year = {2024},
author = {Eglenen-Polat, B and Kowash, RR and Huang, HC and Siteni, S and Zhu, M and Chen, K and Bender, ME and Mender, I and Stastny, V and Drapkin, BJ and Raj, P and Minna, JD and Xu, L and Shay, JW and Akbay, EA},
title = {A telomere-targeting drug depletes cancer initiating cells and promotes anti-tumor immunity in small cell lung cancer.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {672},
pmid = {38253555},
issn = {2041-1723},
support = {R01 CA276058/CA/NCI NIH HHS/United States ; U01 CA213338/CA/NCI NIH HHS/United States ; P30 CA142543/CA/NCI NIH HHS/United States ; P50 CA070907/CA/NCI NIH HHS/United States ; T32 CA124334/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Animals ; Mice ; *Small Cell Lung Carcinoma/drug therapy ; *Lung Neoplasms/drug therapy ; *Telomerase ; Drug Delivery Systems ; Telomere ; Deoxyguanosine/*analogs &amp; derivatives ; *Thionucleosides ; },
abstract = {There are few effective treatments for small cell lung cancer (SCLC) underscoring the need for innovative therapeutic approaches. This study focuses on exploiting telomerase, a critical SCLC dependency as a therapeutic target. A prominent characteristic of SCLC is their reliance on telomerase activity, a key enzyme essential for their continuous proliferation. Here we utilize a nucleoside analog, 6-Thio-2'-deoxyguanosine (6TdG) currently in phase II clinical trials, that is preferentially incorporated by telomerase into telomeres leading to telomere dysfunction. Using preclinical mouse and human derived models we find low intermittent doses of 6TdG inhibit tumor growth and reduce metastatic burden. Anti-tumor efficacy correlates with a reduction in a subpopulation of cancer initiating like cells (CICs) identified by their expression of L1CAM/CD133 and highest telomerase activity. 6TdG treatment also leads to activation of innate and adaptive anti-tumor responses. Mechanistically, 6TdG depletes CICs and induces type-I interferon signaling leading to tumor immune visibility by activating tumor cell STING signaling. We also observe increased sensitivity to irradiation after 6TdG treatment in both syngeneic and humanized SCLC xenograft models both of which are dependent on the presence of host immune cells. This study underscores the immune-enhancing and metastasis-reducing effects of 6TdG, employing a range of complementary in vitro and in vivo SCLC preclinical models providing a potential therapeutic approach to SCLC.},
}
@article {pmid38252370,
year = {2024},
author = {Monaghan, P},
title = {Linking telomere dynamics to evolution, life history and environmental change: perspectives, predictions and problems.},
journal = {Biogerontology},
volume = {},
number = {},
pages = {},
pmid = {38252370},
issn = {1573-6768},
support = {Adg 101020037//H2020 European Research Council/ ; },
abstract = {This perspectives paper considers the value of studying telomere biology outside of a biomedical context. I provide illustrative examples of the kinds of questions that evolutionary ecologists have addressed in studies of telomere dynamics in non-model species, primarily metazoan animals, and what this can contribute to our understanding of their evolution, life histories and health. I also discuss why the predicted relationships between telomere dynamics and life history traits, based on the detailed cellular studies in humans and model organisms, are not always found in studies in other species.},
}
@article {pmid38248925,
year = {2023},
author = {Wang, M and Meng, G and Yang, Y and Wang, X and Xie, R and Dong, C},
title = {Telomere-to-Telomere Genome Assembly of Tibetan Medicinal Mushroom Ganoderma leucocontextum and the First Copia Centromeric Retrotransposon in Macro-Fungi Genome.},
journal = {Journal of fungi (Basel, Switzerland)},
volume = {10},
number = {1},
pages = {},
pmid = {38248925},
issn = {2309-608X},
support = {2022YFD1200602//the National Key Research and Development Program of China project/ ; 21322916D//the Key Research and Development Program of Hebei Province/ ; KFJ-PTXM-016//CAS Engineering Laboratory for Advanced Microbial Technology of Agriculture/ ; },
abstract = {A complete telomere-to-telomere (T2T) genome has been a longstanding goal in the field of genomic research. By integrating high-coverage and precise long-read sequencing data using multiple assembly strategies, we present here the first T2T gap-free genome assembly of Ganoderma leucocontextum strain GL72, a Tibetan medicinal mushroom. The T2T genome, with a size of 46.69 Mb, consists 13 complete nuclear chromosomes and typical telomeric repeats (CCCTAA)n were detected at both ends of 13 chromosomes. The high mapping rate, uniform genome coverage, a complete BUSCOs of 99.7%, and base accuracy exceeding 99.999% indicate that this assembly represents the highest level of completeness and quality. Regions characterized by distinct structural attributes, including highest Hi-C interaction intensity, high repeat content, decreased gene density, low GC content, and minimal or no transcription levels across all chromosomes may represent potential centromeres. Sequence analysis revealed the first Copia centromeric retrotransposon in macro-fungi genome. Phylogenomic analysis identified that G. leucocontextum and G. tsugae diverged from the other Ganoderma species approximately 9.8-17.9 MYA. The prediction of secondary metabolic clusters confirmed the capability of this fungus to produce a substantial quantity of metabolites. This T2T gap-free genome will contribute to the genomic 'dark matter' elucidation and server as a great reference for genetics, genomics, and evolutionary studies of G. leucocontextum.},
}
@article {pmid38246982,
year = {2024},
author = {Campos-Sánchez, I and Navarrete-Muñoz, EM and Hurtado-Pomares, M and Júlvez, J and Lertxundi, N and Martens, DS and Fernández-Somoano, A and Riaño-Galán, I and Guxens, M and Ibarluzea, JM and Nawrot, T and Valera-Gran, D},
title = {Association between telomere length and neuropsychological function at 4-5 years in children from the INMA project: a cross-sectional study.},
journal = {European child &amp; adolescent psychiatry},
volume = {},
number = {},
pages = {},
pmid = {38246982},
issn = {1435-165X},
abstract = {Shortened telomere length (TL) has been associated with lower cognitive performance, different neurological diseases in adults, and certain neurodevelopmental disorders in children. However, the evidence about the association between TL and neuropsychological developmental outcomes in children from the general population is scarce. Therefore, this study aimed to explore the association between TL and neuropsychological function in children 4-5 years of age. We included 686 children from the INMA Project, a population-based birth cohort in Spain. Leucocyte TL was determined by quantitative PCR method, and neuropsychological outcomes were measured using the McCarthy Scales of Children's Abilities (MCSA). Multiple linear regression models were used to estimate associations adjusted for potential confounding variables. Main findings showed that a longer TL was associated with a higher mean working memory score (β = 4.55; 95% CI = 0.39, 8.71). In addition, longer TL was associated with a higher mean global quantitative score (β = 3.85; 95% CI = -0.19, 7.89), although the association was marginally significant. To our knowledge, this is the first study that shows a positive association between TL and better neuropsychological outcomes in children. Although further research is required to confirm these results, this study supports the hypothesis that TL is essential in protecting and maintaining a child's health, including cognitive functions such as working memory.},
}
@article {pmid38244620,
year = {2024},
author = {Sabol, A and Zhou, Y and Zhang, W and Ferreira, BCLB and Chen, J and Leblanc, RM and Catenazzi, A},
title = {Carbon nitride dots do not impair the growth, development, and telomere length of tadpoles.},
journal = {The Science of the total environment},
volume = {916},
number = {},
pages = {170176},
doi = {10.1016/j.scitotenv.2024.170176},
pmid = {38244620},
issn = {1879-1026},
mesh = {Animals ; Larva ; *Ecosystem ; *Wastewater ; Zebrafish ; Metamorphosis, Biological ; Anura ; Carbon/toxicity ; Telomere ; *Nitriles ; },
abstract = {Carbon nanoparticles, or carbon dots, can have many beneficial uses. However, we must consider whether they may have any potential negative side effects on wildlife or the ecosystem when these particles end up in wastewater. Early development stages of amphibians are particularly sensitive to contaminants, and exposure to carbon dots could disrupt their development and cause morbidity or death. Past studies have investigated short-term exposure to certain types of nanoparticles, but if these particles get into wastewater exposure may not be short term. Therefore, we tested whether chronic exposure to different concentrations of carbon dots affects the growth, metamorphosis, and telomere length of Cuban tree frog (Osteopilus septentrionalis) tadpoles. We exposed 12 groups of five tadpoles each to different concentrations of carbon dots and a control for three months and tracked survival, growth and metamorphosis. We used carbon nitride dots approximately 2 nm in size at concentrations of 0.01 mg/ml and 0.02 mg/ml, known to interrupt development in zebrafish embryos. After three months, we measured telomere length from tissue samples. We found no difference in tadpole survivorship, growth, development rate, or telomere length among any of the groups, suggesting that carbon dots at these concentrations do not disrupt tadpole development.},
}
@article {pmid38242305,
year = {2024},
author = {Zhou, G and Chai, J and Li, Q and Sun, P and Wang, Y and Wu, J and Zhang, J and Li, Y and Dong, W and Zhang, C and Yu, F and Yan, X and Ba, Y},
title = {U-shaped relationship between ozone exposure and preterm birth risk associated with preconception telomere length.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {344},
number = {},
pages = {123366},
doi = {10.1016/j.envpol.2024.123366},
pmid = {38242305},
issn = {1873-6424},
mesh = {Infant, Newborn ; Female ; Pregnancy ; Humans ; *Premature Birth/chemically induced/epidemiology ; *Air Pollutants/toxicity ; Environmental Monitoring ; *Ozone/toxicity ; Telomere ; },
abstract = {There are conflicting findings regarding the association of ozone (O3) exposure with preterm birth (PTB) occurrence. In the present study, two cohorts were combined to explore the relationship between maternal O3 exposure during pregnancy and PTB risk, and analyze the underlying mechanisms of this relationship in terms of alterations in the preconception telomere length. Cohort 1 included mothers who participated in the National Free Preconception Health Examination Project in Henan Province from 2014 to 2018 along with their newborns (n = 1,066,696). Cohort 2 comprised mothers who conceived between 2016 and 2018 and their newborns (n = 1871) from six areas in Henan Province. The telomere length was assessed in the peripheral blood of mothers at the preconception stage. Data on air pollutant concentrations were collected from environmental monitoring stations and individual exposures were assessed using an inverse distance-weighted model. O3 concentrations (100.60 ± 14.13 μg/m[3]) were lower in Cohort 1 than in Cohort 2 (114.09 ± 15.17 μg/m[3]). Linear analyses showed that PTB risk decreased with increasing O3 exposure concentrations in Cohort 1 but increased with increasing O3 exposure concentrations in Cohort 2. Nonlinear analyses revealed that PTB risk tended to decrease and then increase with increasing O3 exposure concentrations in both cohorts. Besides, PTB risk was reduced by 88% for each-unit increase in telomere length in those exposed to moderate O3 concentrations (92.4-123.7 μg/m[3], P < 0.05). While no significant association was observed between telomere length and PTB at extreme O3 concentration exposure during entire pregnancy (<92.4 or >123.7 μg/m[3], P > 0.05) in Cohort 2. These findings reveal a nonlinear (U-shaped) relationship between O3 exposure and PTB risk. Furthermore, telomere with elevated length was associated with decreased risk of PTB only when exposed to moderate concentrations of O3, but not when exposed to extreme concentrations of O3 during pregnancy.},
}
@article {pmid38240992,
year = {2024},
author = {Papageorgakopoulou, MA and Bania, A and Lagogianni, IA and Birmpas, K and Assimakopoulou, M},
title = {The Role of Glia Telomere Dysfunction in the Pathogenesis of Central Nervous System Diseases.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {38240992},
issn = {1559-1182},
abstract = {Maintaining the telomere length is decisive for the viability and homeostasis process of all the cells of an organism, including human glial cells. Telomere shortening of microglial cells has been widely associated with the onset and progression of neurodegenerative diseases such as Parkinson's and Alzheimer's disease. Additionally, traumatic brain injury appears to have a positive correlation with the telomere-shortening process of microglia, and telomere length can be used as a non-invasive biomarker for the clinical management of these patients. Moreover, telomere involvement through telomerase reactivation and homologous recombination also known as the alternative lengthening of telomeres (ALT) has been described in gliomagenesis pathways, and particular focus has been given in the translational significance of these mechanisms in gliomas diagnosis and prognostic classification. Finally, glia telomere shortening is implicated in some psychiatric diseases. Given that telomere dysfunction of glial cells is involved in the central nervous system (CNS) disease pathogenesis, it represents a promising drug target that could lead to the incorporation of new tools in the medicinal arsenal for the management of so far incurable conditions.},
}
@article {pmid38238005,
year = {2024},
author = {Wong, JY and Blechter, B and Hubbard, AK and Machiela, MJ and Shi, J and Gadalla, SM and Hu, W and Rahman, ML and Rothman, N and Lan, Q},
title = {Phenotypic and genetically predicted leucocyte telomere length and lung cancer risk in the prospective UK Biobank.},
journal = {Thorax},
volume = {79},
number = {3},
pages = {274-278},
doi = {10.1136/thorax-2023-220076},
pmid = {38238005},
issn = {1468-3296},
mesh = {Humans ; *Lung Neoplasms/epidemiology/genetics ; Biological Specimen Banks ; Prospective Studies ; UK Biobank ; Telomere Homeostasis/genetics ; *Adenocarcinoma ; Leukocytes ; Telomere/genetics ; },
abstract = {We investigated phenotypic leucocyte telomere length (LTL), genetically predicted LTL (gTL), and lung cancer risk among 371 890 participants, including 2829 incident cases, from the UK Biobank. Using multivariable Cox regression, we found dose-response relationships between longer phenotypic LTL (p-trendcontinuous=2.6×10[-5]), longer gTL predicted using a polygenic score with 130 genetic instruments (p-trendcontinuous=4.2×10[-10]), and overall lung cancer risk, particularly for adenocarcinoma. The associations were prominent among never smokers. Mendelian Randomization analyses supported causal associations between longer telomere length and lung cancer (HRper 1 SD gTL=1.87, 95% CI: 1.49 to 2.36, p=4.0×10[-7]), particularly adenocarcinoma (HRper 1 SD gTL=2.45, 95%CI: 1.69 to 3.57, p=6.5×10[-6]).},
}
@article {pmid38237997,
year = {2024},
author = {Zhang, D and Adegunsoye, A and Oldham, JM and Wolters, PJ and Garcia, CK and Newton, CA},
title = {Reply: Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease.},
journal = {The European respiratory journal},
volume = {63},
number = {1},
pages = {},
doi = {10.1183/13993003.02146-2023},
pmid = {38237997},
issn = {1399-3003},
mesh = {Humans ; *Pulmonary Fibrosis/genetics ; *Lung Diseases, Interstitial ; Immunosuppression Therapy ; Telomere ; },
}
@article {pmid38237995,
year = {2024},
author = {Mackintosh, JA and Chambers, DC},
title = {Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease.},
journal = {The European respiratory journal},
volume = {63},
number = {1},
pages = {},
doi = {10.1183/13993003.01806-2023},
pmid = {38237995},
issn = {1399-3003},
mesh = {Humans ; *Pulmonary Fibrosis/genetics ; *Lung Diseases, Interstitial/genetics ; Immunosuppression Therapy ; Telomere ; },
}
@article {pmid38237857,
year = {2024},
author = {Das, A and Giri, AK and Bhattacharjee, P},
title = {Targeting 'histone mark': Advanced approaches in epigenetic regulation of telomere dynamics in cancer.},
journal = {Biochimica et biophysica acta. Gene regulatory mechanisms},
volume = {1867},
number = {1},
pages = {195007},
doi = {10.1016/j.bbagrm.2024.195007},
pmid = {38237857},
issn = {1876-4320},
mesh = {Animals ; *Histones/metabolism ; *Epigenesis, Genetic ; Histone Code/genetics ; Telomere/genetics/metabolism ; Carcinogenesis/genetics ; Mammals/genetics ; },
abstract = {Telomere integrity is required for the maintenance of genome stability and prevention of oncogenic transformation of cells. Recent evidence suggests the presence of epigenetic modifications as an important regulator of mammalian telomeres. Telomeric and subtelomeric regions are rich in epigenetic marks that regulate telomere length majorly through DNA methylation and post-translational histone modifications. Specific histone modifying enzymes play an integral role in establishing telomeric histone codes necessary for the maintenance of structural integrity. Alterations of crucial histone moieties and histone modifiers cause deregulations in the telomeric chromatin leading to carcinogenic manifestations. This review delves into the significance of histone modifications and their influence on telomere dynamics concerning cancer. Additionally, it highlights the existing research gaps that hold the potential to drive the development of therapeutic interventions targeting the telomere epigenome.},
}
@article {pmid38237741,
year = {2024},
author = {Saxena, P and Srivastava, J and Rai, B and Tripathy, NK and Raza, S and Sinha, RA and Gupta, R and Yadav, S and Nityanand, S and Chaturvedi, CP},
title = {Elevated senescence in the bone marrow mesenchymal stem cells of acquired aplastic anemia patients: A possible implication of DNA damage responses and telomere attrition.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {1870},
number = {3},
pages = {167025},
doi = {10.1016/j.bbadis.2024.167025},
pmid = {38237741},
issn = {1879-260X},
mesh = {Humans ; *Anemia, Aplastic/genetics/metabolism ; *Telomerase/genetics/metabolism ; *Mesenchymal Stem Cells/metabolism ; Telomere/genetics ; DNA Repair ; },
abstract = {BACKGROUND: Bone marrow mesenchymal stem cells (BM-MSC) are an integral part of the BM niche that is essential to maintain hematopoietic homeostasis. In aplastic anemia (AA), a few studies have reported phenotypic defects in the BM-MSC, such as reduced proliferation, imbalanced differentiation, and apoptosis; however, the alterations at the molecular level need to be better characterized. Therefore, the current study aims to identify the causative factors underlying the compromised functions of AA BM-MSC that might eventually be contributing to the AA pathobiology.<br><br>METHODS: We performed RNA sequencing (RNA-Seq) using the Illumina platform to comprehend the distinction between the transcriptional landscape of AA and control BM-MSC. Further, we validated the alterations observed in senescence by Senescence- associated beta-galactosidase (SA -&#x3b2;-gal) assay, DNA damage by &#x3b3;H2AX staining, and telomere attrition by relative telomere length assessment and telomerase activity assay. We used qRT-PCR to analyze changes in some of the genes associated with these molecular mechanisms.<br><br>RESULTS: The transcriptome profiling revealed enrichment of senescence-associated genes and pathways in AA BM-MSC. The senescent phenotype of AA BM-MSC was accompanied by enhanced SA -&#x3b2;-gal activity and elevated expression of senescence associated genes TP53, PARP1, and CDKN1A. Further, we observed increased &#x3b3;H2AX foci indicating DNA damage, reduced telomere length, and diminished telomerase activity in the AA BM-MSC.<br><br>CONCLUSION: Our results highlight that AA BM-MSC have a senescent phenotype accompanied by other cellular defects like DNA damage and telomere attrition, which are most likely driving the senescent phenotype of AA BM-MSC thus hampering their hematopoiesis supporting properties as observed in AA.},
}
@article {pmid38236501,
year = {2024},
author = {Bukic, E and Dragovic, G and Toljic, B and Obradovic, B and Jadzic, J and Jevtovic, D and Milasin, JM},
title = {TERT single nucleotide polymorphism rs2736098 but not rs2736100 is associated with telomere length in HIV-infected patients on cART.},
journal = {Molecular biology reports},
volume = {51},
number = {1},
pages = {147},
pmid = {38236501},
issn = {1573-4978},
support = {200110/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; Polymorphism, Single Nucleotide/genetics ; *Telomerase/genetics ; Cross-Sectional Studies ; *HIV Infections/drug therapy/genetics ; Telomere/genetics ; },
abstract = {BACKGROUND: Continuous application of "combination antiretroviral therapy" (cART) has transformed Human immunodeficiency virus (HIV) infection into a manageable chronic disease; however, due to lasting inflammation and cumulative toxicity, progressive pathophysiological changes do occur and potentially lead to accelerated aging, among others, contributing to telomere shortening. The single nucleotide polymorphisms (SNP) rs2736100 and rs2736098 are particularly important for human telomerase (TERT) gene expression. The objective of this study was to evaluate the effects of clinical parameters and single nucleotide polymorphisms in TERT (rs2736100 and rs2736098) on telomere length in HIV-infected patients.<br><br>METHODS AND RESULTS: This cross-sectional study included 176 patients diagnosed with HIV infection. Relative telomere length (RTL) was determined by real-time polymerase chain reaction (qPCR), whereas genotyping was performed by polymerase chain reaction, followed by restriction fragment length polymorphism analysis (PCR-RFLP). The mean age of the patients (p&#x2009;=&#x2009;.904), time since HIV diagnosis (p&#x2009;=&#x2009;.220), therapy-related variables such as the cART regimen (0.761), and total cART duration (p&#x2009;=&#x2009;.096) did not significantly affect RTL. TERT rs2736100 genotype showed no association with RTL. However, TERT rs2736098 heterozygotes (GA) had significantly longer telomeres (P&#x2009;=&#x2009;.049) than both homozygotes (GG and AA).<br><br>CONCLUSIONS: Our findings support the fact that cellular aging in HIV-infected patients is influenced by the TERT rs2736098 polymorphism.},
}
@article {pmid38235989,
year = {2024},
author = {Kuszel, L and Trzeciak, T and Begier-Krasinska, B and Richter, M and Li, J and Czarny-Ratajczak, M},
title = {Sex-specific differences in telomere length of patients with primary knee osteoarthritis.},
journal = {Journal of cellular and molecular medicine},
volume = {28},
number = {3},
pages = {e18107},
pmid = {38235989},
issn = {1582-4934},
support = {P20 GM103629/GM/NIGMS NIH HHS/United States ; P20GM103629/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; *Osteoarthritis, Knee ; Telomere Shortening ; Telomere ; Leukocytes ; Pain ; },
abstract = {Accelerated telomere shortening is associated with age-related diseases, including osteoarthritis (OA). We aimed to determine the relative telomere length (TL) in leukocytes and cartilage of patients with primary knee OA and to investigate factors that may affect TL in OA. Relative TL measurements were performed using qPCR in leukocytes of 612 individuals (310 patients with primary knee OA undergoing total knee arthroplasty (TKA) and 302 unaffected controls). We also analysed cartilage in 57 of the 310 OA patients, measuring relative TL in severely affected and less affected (control) cartilage collected from the same knee. Cartilage TLs were compared to leukocyte TLs in all 57 patients. A significant sex-by-disease-status interaction was found in regard to relative TL. Controlling for age, the average difference of leukocyte TL between female OA patients versus female controls was 0.217 units greater than that between male OA patients versus male controls (95% CI; [0.014, 0.421]). Relative TL comparison of severely and less affected cartilage samples from the same joint showed attrition of telomeres corresponding to disease severity (0.345 mean TL difference with 95% CI of [0.151, 0.539]) in the joint. We also noted that both severely and less affected cartilage had shorter telomeres than leukocytes collected from the same patient. Severe and moderate pain in OA patients was associated with shorter TL in leukocytes, but there was no association with depression or smoking in leukocytes and cartilage. Our study indicates that sex is an important factor in OA contributing to leukocyte and cartilage TL and that pain in OA shows an inverse association only with leukocyte TL.},
}
@article {pmid38230426,
year = {2024},
author = {Hansson, A and Wapstra, E and While, GM and Olsson, M},
title = {Sex and early-life conditions shape telomere dynamics in an ectotherm.},
journal = {The Journal of experimental biology},
volume = {227},
number = {3},
pages = {},
doi = {10.1242/jeb.246512},
pmid = {38230426},
issn = {1477-9145},
support = {F20-0401//Helge Ax:son Johnsons Stiftelse/ ; //Nilsson-Ehle Endowments/ ; //Herbert &amp; Karin Jacobssons Foundation/ ; //Vetenskapsradet/ ; //Australian Research Council/ ; //Vetenskapsr&#xe5;det/ ; //G&#xf6;teborgs Universitet/ ; },
mesh = {Humans ; Animals ; Male ; Female ; *Telomerase/genetics ; Longevity/genetics ; Telomere Shortening ; *Lizards/metabolism ; Telomere/genetics/metabolism ; Telomere Homeostasis ; },
abstract = {Telomeres, the repetitive DNA regions that protect the ends of chromosomes, and their shortening have been linked to key life history trade-offs among growth, reproduction and lifespan. In contrast to most endotherms, many ectotherms can compensate for telomere shortening throughout life by upregulation of telomerase in somatic tissues. However, during development, marked by rapid growth and an increased sensitivity to extrinsic factors, the upregulation of telomerase may be overwhelmed, resulting in long-term impacts on telomere dynamics. In ectotherms, one extrinsic factor that may play a particularly important role in development is temperature. Here, we investigated the influence of developmental temperature and sex on early-life telomere dynamics in an oviparous ectotherm, Lacerta agilis. While there was no effect of developmental temperature on telomere length at hatching, there were subsequent effects on telomere maintenance capacity, with individuals incubated at warm temperatures exhibiting less telomere maintenance compared with cool-incubated individuals. Telomere dynamics were also sexually dimorphic, with females having longer telomeres and greater telomere maintenance compared with males. We suggest that selection drives this sexual dimorphism in telomere maintenance, in which females maximise their lifetime reproductive success by investing in traits promoting longevity such as maintenance, while males invest in short-term reproductive gains through a polygynous mating behaviour. These early-life effects, therefore, have the potential to mediate life-long changes to life histories.},
}
@article {pmid38229191,
year = {2024},
author = {Koemel, NA and Laouali, N and Senior, AM and Celermajer, DS and Grech, A and Solon-Biet, SM and Simpson, SJ and Raubenheimer, D and Gill, TP and Skilton, MR},
title = {The Relationship between Dietary Macronutrient Composition and Telomere Length Among US Adults.},
journal = {Advanced biology},
volume = {},
number = {},
pages = {e2300619},
doi = {10.1002/adbi.202300619},
pmid = {38229191},
issn = {2701-0198},
support = {GNT1149976//National Health and Medical Research Council/ ; },
abstract = {The role of dietary macronutrients and energy intake in the aging process has been well-established. However, previous research has mainly focused on the association between leukocyte telomere length (LTL) and individual macronutrients, while the effects of macronutrient composition on LTL remain unclear. This cross-sectional analysis involved 4130 US adults (44.8 ± 17.0 years; 51% female) from the National Health and Nutrition Examination Survey during 1999-2002. A single 24-h dietary recall is used to collect dietary data. The relationship between dietary macronutrient composition and LTL wasexamined using three-dimensional generalized additive models. After adjustment for age, sex, ethnicity, education, physical activity, BMI, and dietary quality, a three-dimensional association of macronutrient composition with LTL (P = 0.02) is revealed. Diets lower in protein (5-10%), higher in carbohydrates (75%), and lower in fat (15-20%) are associated with the longest LTL corresponding to 7.7 years of slower biological aging. Diets lowest in protein (5%) and carbohydrate (40%), while highest in dietary fat (55%) are associated with the shortest LTL, corresponding to accelerated biological aging of 4.4 years. The associations appeared magnified with higher energy intake. These findings support a complex relationship between dietary macronutrients and biological aging independent of diet quality.},
}
@article {pmid38225981,
year = {2024},
author = {Lan, L and Leng, L and Liu, W and Ren, Y and Reeve, W and Fu, X and Wu, Z and Zhang, X},
title = {The haplotype-resolved telomere-to-telomere carnation (Dianthus caryophyllus) genome reveals the correlation between genome architecture and gene expression.},
journal = {Horticulture research},
volume = {11},
number = {1},
pages = {uhad244},
pmid = {38225981},
issn = {2662-6810},
abstract = {Carnation (Dianthus caryophyllus) is one of the most valuable commercial flowers, due to its richness of color and form, and its excellent storage and vase life. The diverse demands of the market require faster breeding in carnations. A full understanding of carnations is therefore required to guide the direction of breeding. Hence, we assembled the haplotype-resolved gap-free carnation genome of the variety 'Baltico', which is the most common white standard variety worldwide. Based on high-depth HiFi, ultra-long nanopore, and Hi-C sequencing data, we assembled the telomere-to-telomere (T2T) genome to be 564 479 117 and 568 266 215 bp for the two haplotypes Hap1 and Hap2, respectively. This T2T genome exhibited great improvement in genome assembly and annotation results compared with the former version. The improvements were seen when different approaches to evaluation were used. Our T2T genome first informs the analysis of the telomere and centromere region, enabling us to speculate about specific centromere characteristics that cannot be identified by high-order repeats in carnations. We analyzed allele-specific expression in three tissues and the relationship between genome architecture and gene expression in the haplotypes. This demonstrated that the length of the genes, coding sequences, and introns, the exon numbers and the transposable element insertions correlate with gene expression ratios and levels. The insertions of transposable elements repress expression in gene regulatory networks in carnation. This gap-free finished T2T carnation genome provides a valuable resource to illustrate the genome characteristics and for functional genomics analysis in further studies and molecular breeding.},
}
@article {pmid38225201,
year = {2024},
author = {Speer, H and McKune, AJ and Woodward, AP},
title = {The long and the short of it: Salivary telomere length as a candidate biomarker for hypertension and age-related changes in blood pressure.},
journal = {Physiological reports},
volume = {12},
number = {1},
pages = {e15910},
pmid = {38225201},
issn = {2051-817X},
mesh = {Female ; Humans ; Aged ; Blood Pressure ; Bayes Theorem ; *Hypertension/diagnosis ; Biomarkers ; Telomere ; Telomere Shortening ; },
abstract = {Hypertension becomes more prevalent with increasing age. Telomere length (TL) has been proposed as a candidate biomarker and can be accessibly extracted from saliva. However, clarity is needed to evaluate the suitability of using TL as a predictor in such instances. This study investigated salivary TL in a cohort of older adults from the 2008 Health and Retirement Study (n = 3329; F: 58%, mean age: 69.4, SD: 10.3 years) to examine any associations with blood pressure (BP). A Bayesian robust regression model was fit using weakly informative priors to predict the effects of TL with age, sex, systolic BP (SBP), diastolic BP (DBP), and treatment status. There were small effects of treatment (β: -0.07, 95% CrI [-0.33, 0.19], pd: 71.91%) and sex (β: -0.10, 95% CrI [-0.27, 0.07], pd: >86.78%). Population effects showed a reduction of 0.01 log2 units in TL with each year of advancing age (95% CrI [-0.01, -0.00]). Conditional posterior predictions suggest that females, and treated individuals, experience greater change in TL with increasing age. Bayes R[2] was ~2%. TL declines with increasing age, differs between sexes, and appears to be influenced by antihypertensive drugs. Overall, all effects were weak. The data do not currently support the suitability of salivary TL as a biomarker to predict or understand any age-related changes in BP.},
}
@article {pmid38224126,
year = {2024},
author = {Dong, T and Yu, P and Zhao, J and Wang, J},
title = {Site specifically probing the unfolding process of human telomere i-motif DNA using vibrationally enhanced alkynyl stretch.},
journal = {Physical chemistry chemical physics : PCCP},
volume = {26},
number = {5},
pages = {3857-3868},
doi = {10.1039/d3cp05328h},
pmid = {38224126},
issn = {1463-9084},
mesh = {Humans ; *DNA/chemistry ; Base Pairing ; Temperature ; *Telomere ; Cytosine/chemistry ; Nucleic Acid Conformation ; },
abstract = {The microscopic unfolding process of a cytosine-rich DNA forming i-motif by hemi-protonated base pairs is related to gene regulation. However, the detailed thermal unfolding mechanism and the protonation/deprotonation status of site-specific cytosine in DNA in a physiological environment are still obscure. To address this issue, a vibration-enhanced C(?)C probe tagged on 5'E terminal cytosine of human telomere i-motif DNA was examined using linear and nonlinear infrared (IR) spectroscopies and quantum-chemistry calculations. The C(?)C probe extended into the major groove of the i-motif was found using nonlinear IR results only to introduce a minor steric effect on both steady-state structure and local structure dynamics; however, its IR absorption profile effectively reports the cleavage of the hemi-protonated base pair of C1-C13 upon the unfolding with C1 remaining protonated. The temperature mid-point (Tm) of the local transition reported using the C(?)C tag was slightly lower than the Tm of global transition, and the enthalpy of the former exceeds 60% of the global transition. It is shown that the base-pair unraveling is noncooperative, with outer base pairs breaking first and being likely the rate limiting step. Our results offered an in-depth understanding of the macroscopic unfolding characteristics of the i-motif DNA and provided a nonlinear IR approach to monitoring the local structural transition and dynamics of DNA and its complexes.},
}
@article {pmid38223236,
year = {2024},
author = {Burenkova, OV and Naumova, OY and Church, JA and Juranek, J and Fletcher, JM and Grigorenko, EL},
title = {Associations between telomere length, glucocorticoid receptor gene DNA methylation, volume of stress-related brain structures, and academic performance in middle-school-age children.},
journal = {Comprehensive psychoneuroendocrinology},
volume = {17},
number = {},
pages = {100223},
pmid = {38223236},
issn = {2666-4976},
support = {P20 HD091005/HD/NICHD NIH HHS/United States ; P50 HD052117/HD/NICHD NIH HHS/United States ; },
abstract = {BACKGROUND: The biological embedding theory posits that early life experiences can lead to enduring physiological and molecular changes impacting various life outcomes, notably academic performance. Studying previously revealed and objective biomarkers of early life stress exposure, such as telomere length (TL), glucocorticoid receptor gene DNA methylation (DNAme), and the volume of brain structures involved in the regulation of HPA axis functioning (the hippocampus, the amygdala, and the medial prefrontal cortex), in relation to academic performance is crucial. This approach provides an objective measure that surpasses the limitations of self-reported early life adversity and reveals potential molecular and neurological targets for interventions to enhance academic outcomes.<br><br>METHODS: The participants were 52 children of Mexican or Central American origin aged 11.6-15.6 years. DNA methylation levels and TL were analyzed in three cell sources: saliva, whole blood, and T cells derived from whole blood.<br><br>RESULTS: Overall, the concordance across three systems of stress-related biomarkers (TL, DNAme, and the brain) was observed to some extent, although it was less pronounced than we expected; no consistency in different cell sources was revealed. Each of the academic domains that we studied was characterized by a unique and distinct complex of associations with biomarkers, both in terms of the type of biomarker, the directionality of the observed effects, and the cell source of biomarkers. Furthermore, there were biomarker-by-sex interaction effects in predicting academic performance measures.<br><br>CONCLUSIONS: Assessed in an understudied youth sample, these preliminary data present new essential evidence for a deepened understanding of the biological mechanisms behind associations between exposure to early life stress and academic performance.},
}
@article {pmid38219218,
year = {2024},
author = {Ma, B and Martínez, P and Sánchez-Vázquez, R and Blasco, MA},
title = {Telomere dynamics in human pluripotent stem cells.},
journal = {Cell cycle (Georgetown, Tex.)},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/15384101.2023.2285551},
pmid = {38219218},
issn = {1551-4005},
abstract = {Pluripotent stem cells (PSCs) are a promising source of stem cells for regenerative therapies. Stem cell function depends on telomere maintenance mechanisms that provide them with the proliferative capacity and genome stability necessary to multiply and regenerate tissues. We show here that established human embryonic stem cells (hESCs) have stable telomere length that is dependent on telomerase but not on alternative mechanisms based on homologous recombination pathways. Here, we show that human-induced pluripotent stem cells (hiPSCs) reprogrammed from somatic cells show progressive telomere lengthening until reaching a length similar to ESCs. hiPSCs also acquire telomeric chromatin marks of ESCs including decreased abundance of tri-methylated histone H3K9 and H4K20 and HP1 heterochromatic marks, as well as of the shelterin component TRF2. These chromatin features are accompanied with increased abundance of telomere transcripts or TERRAs. We also found that telomeres of both hESCs and hiPSCs are well protected from DNA damage during telomere elongation and once full telomere length is achieved, and exhibit stable genomes. Collectively, this study highlights that hiPSCs acquire ESC features during reprogramming and reveals the telomere biology in human pluripotent stem cells (hPSCs).},
}
@article {pmid38214116,
year = {2024},
author = {Liu, X and Yuan, J and Liu, S and Wang, X and Tang, M and Meng, X and Li, Y and Chai, Y and Wang, Y and Tian, G and Liu, X and Zhou, H and Kou, C and Zhang, L and Yuan, Z and Zhang, H},
title = {The causal relationship between autoimmune thyroid disorders and telomere length: A Mendelian randomization and colocalization study.},
journal = {Clinical endocrinology},
volume = {100},
number = {3},
pages = {294-303},
doi = {10.1111/cen.15004},
pmid = {38214116},
issn = {1365-2265},
support = {82173624//National Natural Science Foundation of China/ ; 81872712//National Natural Science Foundation of China/ ; 82370793//National Natural Science Foundation of China/ ; 81670721//National Natural Science Foundation of China/ ; ZR2019ZD02//Natural Science Foundation of Shandong Province/ ; //Taishan Scholar Project of Shandong Province/ ; //Cheeloo Young Talent Program of Shandong University/ ; },
mesh = {Humans ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Graves Disease ; Telomere/genetics ; *Hypothyroidism/genetics ; *Thyroiditis, Autoimmune ; *Hashimoto Disease ; },
abstract = {This study aimed to evaluate whether there is a causal relationship between autoimmune thyroid disorders (AITDs) and telomere length (TL) in the European population and whether there is reverse causality. In this study, Mendelian randomization (MR) and colocalization analysis were conducted to assess the potential causal relationship between AITDs and TL using summary statistics from large-scale genome-wide association studies, followed by analysis of the relationship between TL and thyroid stimulating hormone and free thyroxine (FT4) to help interpret the findings. The inverse variance weighted (IVW) method was used to estimate the causal estimates. The weighted median, MR-Egger and leave-one-out methods were used as sensitivity analyses. The IVW method results showed a significant causal relationship between autoimmune hyperthyroidism and TL (β = -1.93 × 10[-2] ; p = 4.54 × 10[-5]). There was no causal relationship between autoimmune hypothyroidism and TL (β = -3.99 × 10[-3] ; p = 0.324). The results of the reverse MR analysis showed that genetically TL had a significant causal relationship on autoimmune hyperthyroidism (IVW: odds ratio (OR) = 0.49; p = 2.83 × 10[-4]) and autoimmune hypothyroidism (IVW: OR = 0.86; p = 7.46 × 10[-3]). Both horizontal pleiotropy and heterogeneity tests indicated the validity of our bidirectional MR study. Finally, colocalization analysis suggested that there were shared causal variants between autoimmune hyperthyroidism and TL, further highlighting the robustness of the results. In conclusion, autoimmune hyperthyroidism may accelerate telomere attrition, and telomere attrition is a causal factor for AITDs.},
}
@article {pmid38213617,
year = {2024},
author = {Lu, R and Nelson, CB and Rogers, S and Cesare, AJ and Sobinoff, AP and Pickett, HA},
title = {Distinct modes of telomere synthesis and extension contribute to Alternative Lengthening of Telomeres.},
journal = {iScience},
volume = {27},
number = {1},
pages = {108655},
pmid = {38213617},
issn = {2589-0042},
abstract = {Alternative lengthening of telomeres (ALT) is a homology-directed repair mechanism that becomes activated in a subset of cancers to maintain telomere length. One of the defining features of ALT cells is the prevalence of extrachromosomal telomeric repeat (ECTR) DNA. Here, we identify that ALT cells engage in two modes of telomere synthesis. Non-productive telomere synthesis occurs during the G2 phase of the cell cycle and is characterized by newly synthesized internal telomeric regions that are not retained in the subsequent G1, coinciding with an induction of ECTR DNA. Productive telomere synthesis occurs specifically during the transition from G2 to mitosis and is defined as the extension of the telomere termini. While many proteins associated with break-induced telomere synthesis function in both non-productive and productive telomere synthesis, POLH specifically promotes productive telomere lengthening and suppresses non-productive telomere synthesis. These findings delineate the mechanism and cell cycle regulation of ALT-mediated telomere synthesis and extension.},
}
@article {pmid38213291,
year = {2024},
author = {Barade, A and Lakshmi, KM and Korula, A and Abubacker, FN and Kulkarni, UP and Abraham, A and Mathews, V and George, B and Edison, ES},
title = {Comparison of telomere length in patients with bone marrow failure syndromes and healthy controls.},
journal = {European journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ejh.14173},
pmid = {38213291},
issn = {1600-0609},
support = {BT/PR17415/MED/12/724/2016//Department of Biotechnology, Ministry of Science and Technology, India/ ; },
abstract = {INTRODUCTION: During normal aging, telomeric DNA is gradually lost in dividing somatic cells, and critically short telomeres lead to replicative senescence, apoptosis, or chromosomal instability. We studied telomere length in bone marrow failure syndromes (BMFS) compared to normal healthy population.<br><br>METHODS: Peripheral blood was collected from the participants, and genomic DNA was extracted. Relative telomere length was measured using a quantitative polymerase chain reaction. Statistical analysis was performed using SPSS and GraphPad Prism 8.2 software.<br><br>RESULTS: The median age of normal Indian population was 31 (0-60) years. As expected, telomere length (TL) showed a decline with age and no difference in TL between males and females. The median age of 650 patients with aplastic anemia (AA) was 30 (1-60) years. TL was significantly shorter in patients with AA compared to healthy controls (p&#x2009;<&#x2009;.001). In FA and MDS patients, TL was significantly shorter than age-matched healthy controls (p&#x2009;=&#x2009;.028; p&#x2009;<&#x2009;.001), respectively. There was no difference between the median TL in age-matched AA and FA patients (p&#x2009;=&#x2009;.727). However, patients with MDS had shorter TL than age-matched AA (p&#x2009;=&#x2009;.031).<br><br>CONCLUSION: TL in BMF syndrome patients was significantly shorter than age-matched healthy controls.},
}
@article {pmid38205251,
year = {2024},
author = {Xue, J and Liu, Z and Liao, Y and Zhang, X and Liu, Y and Mo, L and Dong, R and Li, Q and Sun, X and Xie, J and Yang, P},
title = {Undersized telomeres in regulatory T cells link to the pathogenesis of allergic rhinitis.},
journal = {iScience},
volume = {27},
number = {1},
pages = {108615},
pmid = {38205251},
issn = {2589-0042},
abstract = {Telomeres are an important biomarker in the cell destiny. The relationship between telomeres and regulatory T cells (Tregs) has not yet been investigated. The objective of this study is to evaluate the link between Tregs' telomere length and allergic rhinitis (AR)'s pathogenesis. Here, we report that low telomerase activity and high endoplasmic reticulum stress status were observed in Tregs from AR patients, as shown in the results. Immune regulatory molecules levels were correlated with the length of Tregs' telomeres. The immune-suppressive functions of Tregs were associated with the telomere length/Telomerase reverse transcriptase/Telomerase protein component 1 status in Tregs. The levels of telomere length/telomerase in airway Tregs were reduced by sensitization. Endoplasmic reticulum stress signaling pathway of proline-rich receptor-like protein kinase-eukaryotic translation initiation factor 2A (eIF2a) was associated with the regulation of telomerase. Inhibiting eIF2a had an effect on upregulating telomerase activity in Tregs and mitigating experimental AR.},
}
@article {pmid38203842,
year = {2024},
author = {Vaquero-Sedas, MI and Vega-Palas, MA},
title = {A Nested PCR Telomere Fusion Assay Highlights the Widespread End-Capping Protection of Arabidopsis CTC1.},
journal = {International journal of molecular sciences},
volume = {25},
number = {1},
pages = {},
pmid = {38203842},
issn = {1422-0067},
support = {PID2020-115720GB-100//Ministerio de Ciencia e Innovaci&#xf3;n/ ; },
mesh = {*Arabidopsis/genetics ; In Situ Hybridization, Fluorescence ; Polymerase Chain Reaction ; Shelterin Complex ; *Telomere/genetics ; *Telomere-Binding Proteins/genetics ; *Arabidopsis Proteins/genetics ; },
abstract = {Telomeres protect the ends of linear eukaryotic chromosomes from being recognized as DNA double-strand breaks. Two major protein complexes are involved in the protection of telomeres: shelterin and CST. The dysfunction of these complexes can challenge the function of telomeres and lead to telomere fusions, breakage-fusion-bridge cycles, and cell death. Therefore, monitoring telomere fusions helps to understand telomeres biology. Telomere fusions are often analyzed by Fluorescent In Situ Hybridization (FISH) or PCR. Usually, both methods involve hybridization with a telomeric probe, which allows the detection of fusions containing telomeric sequences, but not of those lacking them. With the aim of detecting both types of fusion events, we have developed a nested PCR method to analyze telomere fusions in Arabidopsis thaliana. This method is simple, accurate, and does not require hybridization. We have used it to analyze telomere fusions in wild-type and mutant plants altered in CTC1, one of the three components of the Arabidopsis CST telomere capping complex. Our results show that null ctc1-2 mutant plants display fusions between all telomeric regions present in Arabidopsis chromosomes 1, 3 and 5, thus highlighting the widespread end-capping protection achieved by CTC1.},
}
@article {pmid38202757,
year = {2023},
author = {Xu, Y and Komiyama, M},
title = {G-Quadruplexes in Human Telomere: Structures, Properties, and Applications.},
journal = {Molecules (Basel, Switzerland)},
volume = {29},
number = {1},
pages = {},
pmid = {38202757},
issn = {1420-3049},
mesh = {Humans ; *G-Quadruplexes ; Guanine ; RNA/genetics ; Telomere/genetics ; DNA/genetics ; },
abstract = {G-quadruplexes, intricate four-stranded structures composed of G-tetrads formed by four guanine bases, are prevalent in both DNA and RNA. Notably, these structures play pivotal roles in human telomeres, contributing to essential cellular functions. Additionally, the existence of DNA:RNA hybrid G-quadruplexes adds a layer of complexity to their structural diversity. This review provides a comprehensive overview of recent advancements in unraveling the intricacies of DNA and RNA G-quadruplexes within human telomeres. Detailed insights into their structural features are presented, encompassing the latest developments in chemical approaches designed to probe these G-quadruplex structures. Furthermore, this review explores the applications of G-quadruplex structures in targeting human telomeres. Finally, the manuscript outlines the imminent challenges in this evolving field, setting the stage for future investigations.},
}
@article {pmid38198169,
year = {2024},
author = {Koh, JYP and Li, S and Koh, AS},
title = {Precision Measurement of Telomere Length as a Future Guide to Improve CVD Interventions.},
journal = {JAMA cardiology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamacardio.2023.5006},
pmid = {38198169},
issn = {2380-6591},
}
@article {pmid38194261,
year = {2024},
author = {Sánchez-González, JL and Sánchez-Rodríguez, JL and Varela-Rodríguez, S and González-Sarmiento, R and Rivera-Picón, C and Juárez-Vela, R and Tejada-Garrido, CI and Martín-Vallejo, J and Navarro-López, V},
title = {Effects of Physical Exercise on Telomere Length in Healthy Adults: Systematic Review, Meta-Analysis, and Meta-Regression.},
journal = {JMIR public health and surveillance},
volume = {10},
number = {},
pages = {e46019},
pmid = {38194261},
issn = {2369-2960},
mesh = {Adult ; Humans ; Databases, Factual ; *Exercise ; *Health Status ; Telomere ; },
abstract = {BACKGROUND: Physical exercise is one of the main nonpharmacological treatments for most pathologies. In addition, physical exercise is beneficial in the prevention of various diseases. The impact of physical exercise has been widely studied; however, existing meta-analyses have included diverse and heterogeneous samples. Therefore, to our knowledge, this is the first meta-analysis to evaluate the impact of different physical exercise modalities on telomere length in healthy populations.<br><br>OBJECTIVE: In this review, we aimed to determine the effect of physical exercise on telomere length in a healthy population through a meta-analysis of randomized controlled trials.<br><br>METHODS: A systematic review with meta-analysis and meta-regression of the published literature on the impact of physical exercise on telomere length in a healthy population was performed. PubMed, Cochrane Library, SCOPUS, Web of Science, and Embase databases were searched for eligible studies. Methodological quality was evaluated using the Risk Of Bias In Nonrandomized Studies of Interventions and the risk-of-bias tool for randomized trials. Finally, the certainty of our findings (closeness of the estimated effect to the true effect) was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE).<br><br>RESULTS: We included 9 trials that met the inclusion criteria with fair methodological quality. Random-effects model analysis was used to quantify the difference in telomere length between the exercise and sham groups. Meta-analysis showed that exercise did not significantly increase telomere length compared with the control intervention (mean difference=0.0058, 95% CI -0.05 to 0.06; P=.83). Subgroup analysis suggested that high-intensity interventional exercise significantly increased telomere length compared with the control intervention in healthy individuals (mean difference=0.15, 95% CI 0.03-0.26; P=.01). Furthermore, 56% of the studies had a high risk of bias. Certainty was graded from low to very low for most of the outcomes.<br><br>CONCLUSIONS: The findings of this systematic review and meta-analysis suggest that high-intensity interval training seems to have a positive effect on telomere length compared with other types of exercise such as resistance training or aerobic exercise in a healthy population.<br><br>TRIAL REGISTRATION: PROSPERO CRD42022364518; http://tinyurl.com/4fwb85ff.},
}
@article {pmid38192544,
year = {2024},
author = {Farrukh, S and Baig, S and Hussain, R and Imad, R and Kulsoom, O and Yousaf Rana, M},
title = {Identification of polymorphic alleles in TERC and TERT gene reprogramming the telomeres of newborn and legacy with parental health.},
journal = {Saudi journal of biological sciences},
volume = {31},
number = {2},
pages = {103897},
pmid = {38192544},
issn = {1319-562X},
abstract = {Telomere and telomerase genes (TERC and TERT) highlighted many novel genetic polymorphisms related to common diseases. This study explored the polymorphic alleles of TERC and TERT gene in parents-newborn (triad) and its association with telomere length (TL) and parental diseases (mother: Gestational Diabetes Mellitus (GDM), Preeclampsia, fathers: Diabetes, Hypertension). In this cross-sectional study, the blood samples (n = 612) were collected from parents-newborn triad (204 each) for TL (T/S ratio) quantification by using qPCR, and gene (TERC and TERT) polymorphism was detected by Sanger sequencing. The correlation analysis was used to find an association between paternal TL (T/S ratio) and newborn TL. The multivariate linear regression was applied to determine the effect of parents genes and diseases on newborn TL. A positive association (r = 0.42,0.39) (p < 0.0001) among parents and newborn TL was observed. In the diseased group, both TERC (rs10936599) and TERT (rs2736100) genes had a high frequency of allele C in newborns (OR = 0.94, P = 0.90, OR = 4.24, P = 0.012). However, among parents, TERT gene [Mother CC (B = 0.575; P = 0.196), Father CC (B = -0.739; P = 0.071)] was found significant contributing factor for Newborn TL. Diseased parents with T/T and A/C genotypes had longer newborn TL (2.82 ± 2.43, p < 0.022; 1.80 ± 1.20, p < 0.00) than the C/C genotype. Therefore, the study, confirmed that major allele C of TERC and TERT genes is associated with smaller TL in diseased parents-newborns of the targeted population.},
}
@article {pmid38190874,
year = {2024},
author = {Li, R and Wang, J and Wang, Y and Lin, X and Sun, C and Xu, L},
title = {Telomere length as a modifier in the relationship between phthalate metabolites exposure and glucose homeostasis.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {344},
number = {},
pages = {123309},
doi = {10.1016/j.envpol.2024.123309},
pmid = {38190874},
issn = {1873-6424},
mesh = {Environmental Exposure ; Nutrition Surveys ; Bayes Theorem ; Cross-Sectional Studies ; *Phthalic Acids/metabolism ; Glucose ; Homeostasis ; Telomere ; *Insulins ; *Environmental Pollutants/analysis ; },
abstract = {Given the rising concern over the potential impact of environmental factors on metabolic heath, we conducted a cross-sectional analysis among 645 adults aged 20 and older in the National Health and Nutrition Examination Survey (NHANES), examining the association between nine phthalate metabolites (Mono-n-butyl phthalate (MBP), Mono-ethyl phthalate (MEP), Mono-(2-ethyl)-hexyl phthalate (MEHP), Mono-benzyl phthalate (MBzP), Mono-n-methyl phthalate (MnMP), Mono-(3-carboxy propyl) phthalate (MCPP), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), Mono-isobutyl phthalate (MiBP)) and six glucose homeostasis indices (fasting glucose, fasting insulin, hemoglobin A1C (HbA1C), homeostatic model assessment of insulin resistance (HOMA-IR), single Point Insulin Sensitivity Estimator (SPISE), and HOMA-β). Latent Class Analysis identified three phthalate metabolites exposure patterns: high MEP-low MEOHP (n = 282), high MBzP-low MEHHP (n = 214), and high MEHHP, MEOHP (n = 149). The high MBzP-low MEHHP and high MEHHP, MEOHP, versus the high MEP-low MEOHP, exposure groups showed significantly higher levels of fasting insulin (β = 0.126, 95% CI: 0.023-0.228), SPISE (β = 0.091, 95% CI: 0.018-0.164), and HOMA-IR (β = 0.091, 95% CI: 0.018-0.164). In the shorter telomere length group, high MEHHP, MEOHP exposure showed an increase in SPISE levels (β = 0.153, 95% CI: 0.037-0.269), while in the overweight/obese subgroup, high MEHHP, MEOHP exposure was significantly positively associated with HOMA-IR (β = 0.392, 95% CI: 0.150-0.735). Bayesian kernel machine regression analyses showed positive associations between higher combined phthalate exposure and increased glucose homeostasis indices (fasting glucose, HbA1C, fasting insulin, SPISE, and HOMA-IR). The quantile of g-calculation analysis also supported the positive associations with HbA1C, HOMA-IR, and fasting insulin. Our findings indicate that phthalate exposure was positively associated with glucose homeostasis indices, which strengthen the call for proactive measures to reduce phthalate exposure and mitigate potential risks to glucose metabolism.},
}
@article {pmid38189870,
year = {2023},
author = {Kurashova, NA and Dashiev, BG and Kolesnikov, SI and Kolesnikova, LI},
title = {Oxidative Stress, Telomere Length and Telomerase Activity in Spermatogenesis Disorders (Review of Scientific Activity).},
journal = {Bulletin of experimental biology and medicine},
volume = {176},
number = {2},
pages = {115-122},
pmid = {38189870},
issn = {1573-8221},
mesh = {Humans ; Male ; *Infertility, Male/genetics ; Oxidative Stress/genetics ; Spermatogenesis/genetics ; *Telomerase/genetics ; Telomere/genetics/metabolism ; },
abstract = {The paper systematizes the available data on the study of oxidative stress, the relative length of telomeres, and telomerase activity in male infertility and disorders of spermatogenesis. The study of telomeres, the structures that protect chromosome ends and genome integrity, is of interest for researchers in various fields, from cell biology and epidemiology to ecology and evolutionary biology. The review includes our own data on the study of the relative length of telomeres, oxidative stress, and telomerase activity and reflects modern ideas about the importance of these structures both in the maintenance of genome stability during cell division and in gametogenesis and reproduction. Many studies indicate the role of oxidative stress in the pathogenesis of various diseases, including male infertility. In turn, studies of telomeres as a biomarker of male infertility are insufficient, and the results obtained are extremely controversial and require deeper knowledge about the mechanisms underlying the dynamics of telomere length.},
}
@article {pmid38187739,
year = {2024},
author = {Karimian, K and Groot, A and Huso, V and Kahidi, R and Tan, KT and Sholes, S and Keener, R and McDyer, JF and Alder, JK and Li, H and Rechtsteiner, A and Greider, CW},
title = {Human telomere length is chromosome specific and conserved across individuals.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {38187739},
support = {R35 CA209974/CA/NCI NIH HHS/United States ; T32 GM133391/GM/NIGMS NIH HHS/United States ; },
abstract = {Short telomeres cause age-related disease and long telomeres predispose to cancer; however, the mechanisms regulating telomere length are unclear. To probe these mechanisms, we developed a nanopore sequencing method, Telomere Profiling, that is easy to implement, precise, and cost effective with broad applications in research and the clinic. We sequenced telomeres from individuals with short telomere syndromes and found similar telomere lengths to the clinical FlowFISH assay. We mapped telomere reads to specific chromosome end and identified both chromosome end-specific and haplotype-specific telomere length distributions. In the T2T HG002 genome, where the average telomere length is 5kb, we found a remarkable 6kb difference in lengths between some telomeres. Further, we found that specific chromosome ends were consistently shorter or longer than the average length across 147 individuals. The presence of conserved chromosome end-specific telomere lengths suggests there are new paradigms in telomere biology that are yet to be explored. Understanding the mechanisms regulating length will allow deeper insights into telomere biology that can lead to new approaches to disease.},
}
@article {pmid38181239,
year = {2024},
author = {Zhang, Y and Wang, J and Zheng, M and Qu, H and Yang, S and Han, F and Yao, N and Li, W and Qu, J},
title = {Causal association between telomere length and colorectal polyps: A bidirectional two-sample Mendelian randomization study.},
journal = {Medicine},
volume = {103},
number = {1},
pages = {e36867},
pmid = {38181239},
issn = {1536-5964},
mesh = {Humans ; *Colonic Polyps/genetics ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Causality ; Telomere ; },
abstract = {We performed a bidirectional 2-sample Mendelian randomization (MR) design to explore the causal relation between telomere length (TL) and colorectal polyps. Genome-wide association study summary data of TL and colorectal polyps were extracted from the IEU open genome-wide association study database. Single nucleotide polymorphisms were served as instrumental variables at the significance threshold of P < 5 × 10-8. The inverse variance weighted method, MR-Egger method, and weight median method were performed for causal estimation in MR. Cochran Q test, MR-Egger intercept test, and leave-one-out analyses were performed to evaluate the pleiotropy of the MR results. One hundred and twenty-four single nucleotide polymorphisms were selected as instrumental variables. We found significant casual association between TL and colorectal polyps. Long TL increased the risk of colorectal polyps using the inverse variance weighted method [ukb-a-521: odds ratio (OR): 1.004, 95% confidence interval (CI): 1.001-1.007, P = .004; ukb-d-D12: OR: 1.008, CI: 1.004-1.012, P < .001; finn-b-CD2_BENIGN_COLORECANI_EXALLC2: OR: 1.170, CI: 1.027-1.332, P = .018]. Sensitivity analyses validated that the causality between TL and colorectal polyps was robust. The study provided a causal association between TL and colorectal polyps which indicated that TL might be served as a potential biomarker of colorectal polyps for screening and prevention. Nonetheless, the conclusions need further validation.},
}
@article {pmid38180812,
year = {2024},
author = {Vaid, R and Thombare, K and Mendez, A and Burgos-Panadero, R and Djos, A and Jachimowicz, D and Lundberg, KI and Bartenhagen, C and Kumar, N and Tümmler, C and Sihlbom, C and Fransson, S and Johnsen, JI and Kogner, P and Martinsson, T and Fischer, M and Mondal, T},
title = {METTL3 drives telomere targeting of TERRA lncRNA through m6A-dependent R-loop formation: a therapeutic target for ALT-positive neuroblastoma.},
journal = {Nucleic acids research},
volume = {},
number = {},
pages = {},
doi = {10.1093/nar/gkad1242},
pmid = {38180812},
issn = {1362-4962},
support = {2018-02224//Swedish Research Council/ ; 22-2341//Cancerfonden/ ; PR 2019-077//Barncancerfonden/ ; //Svenska L&#xe4;kares&#xe4;llskapet/ ; //&#xc5;ke Wibergs Stiftelse/ ; //Kungl Vetenskaps- och Vitterhets-Samh&#xe4;llet/ ; TJ 2019-0077//Barncancerfonden/ ; 23-0753 PT//Cancerfonden/ ; //Tore Nilsons Stiftelse and Bollan scholarship/ ; //Assar Gabrielsson Fond/ ; },
abstract = {Telomerase-negative tumors maintain telomere length by alternative lengthening of telomeres (ALT), but the underlying mechanism behind ALT remains poorly understood. A proportion of aggressive neuroblastoma (NB), particularly relapsed tumors, are positive for ALT (ALT+), suggesting that a better dissection of the ALT mechanism could lead to novel therapeutic opportunities. TERRA, a long non-coding RNA (lncRNA) derived from telomere ends, localizes to telomeres in a R-loop-dependent manner and plays a crucial role in telomere maintenance. Here we present evidence that RNA modification at the N6 position of internal adenosine (m6A) in TERRA by the methyltransferase METTL3 is essential for telomere maintenance in ALT+ cells, and the loss of TERRA m6A/METTL3 results in telomere damage. We observed that m6A modification is abundant in R-loop enriched TERRA, and the m6A-mediated recruitment of hnRNPA2B1 to TERRA is critical for R-loop formation. Our findings suggest that m6A drives telomere targeting of TERRA via R-loops, and this m6A-mediated R-loop formation could be a widespread mechanism employed by other chromatin-interacting lncRNAs. Furthermore, treatment of ALT+ NB cells with a METTL3 inhibitor resulted in compromised telomere targeting of TERRA and accumulation of DNA damage at telomeres, indicating that METTL3 inhibition may represent a therapeutic approach for ALT+ NB.},
}
@article {pmid38180375,
year = {2023},
author = {Maximov, VN and Ivanova, AA and Orlov, PS and Titarenko, AV and Maksimova, SV and Simonova, GI and Chervova, OA and Voevoda, MI and Malyutina, SK},
title = {[The relationship between the relative length of leukocyte telomeres and mtDNA copy number and acute coronary syndrome in a 15-year follow-up.].},
journal = {Advances in gerontology = Uspekhi gerontologii},
volume = {36},
number = {5},
pages = {748-755},
pmid = {38180375},
issn = {1561-9125},
mesh = {Aged ; Humans ; Middle Aged ; DNA, Mitochondrial/genetics ; *Acute Coronary Syndrome ; DNA Copy Number Variations ; Follow-Up Studies ; Telomere/genetics ; Leukocytes ; *Neoplasms ; },
abstract = {to study the association of relative leukocyte DNA telomere length with death from natural causes during a 15-year follow-up in a middle-aged and elderly Siberian population. Study of the association of the relative length of leukocyte telomeres (LTL) with fatal outcomes during a 15-year follow-up of a random population sample formed in 2003-2005 (n=9 360, 45-69 years old, Novosibirsk, HAPIEE project). The main group included the persons died from natural causes (except external) without a previous history of CVD and cancer (n=609); controls were stratified by sex and age (n=799). The analysis of relative LTL at baseline was performed using quantitative real-time PCR. We estimated the odds ratio of all-cause death per 1 decile shortening of LTD as a continuous variable in a multivariable-adjusted logistic regression. The carriers of shorter telomere carriers had an increased risk of death from natural causes over the next 15 years (OR=1,37, 95% CI 1,31-1,44) per decile of LTL decrease, regardless of other factors. The risk coefficients were similar for death from CVD (1,39), cancer (1,42), and other non-external causes (1,51). In studied middle-aged and elderly Siberian (Caucasoid) population cohort the LTL was an independent inverse predictor of the 15-year risk of death from natural causes.},
}
@article {pmid38176734,
year = {2024},
author = {Bertrand, A and Ba, I and Kermasson, L and Pirabakaran, V and Chable, N and Lainey, E and Ménard, C and Kallel, F and Picard, C and Hadiji, S and Coolen-Allou, N and Blanchard, E and de Villartay, JP and Moshous, D and Roelens, M and Callebaut, I and Kannengiesser, C and Revy, P},
title = {Characterization of novel mutations in the TEL-patch domain of the telomeric factor TPP1 associated with telomere biology disorders.},
journal = {Human molecular genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/hmg/ddad210},
pmid = {38176734},
issn = {1460-2083},
support = {ANR-10-IAHU-01//Agence Nationale de la Recherche/ ; //Fondation de la recherche m&#xe9;dicale/ ; //Centre National de la Recherche Scientifique/ ; },
abstract = {Telomeres are nucleoprotein structures that protect the chromosome ends from degradation and fusion. Telomerase is a ribonucleoprotein complex essential to maintain the length of telomeres. Germline defects that lead to short and/or dysfunctional telomeres cause telomere biology disorders (TBDs), a group of rare and heterogeneous Mendelian diseases including pulmonary fibrosis, dyskeratosis congenita, and Høyeraal-Hreidarsson syndrome. TPP1, a telomeric factor encoded by the gene ACD, recruits telomerase at telomere and stimulates its activity via its TEL-patch domain that directly interacts with TERT, the catalytic subunit of telomerase. TBDs due to TPP1 deficiency have been reported only in 11 individuals. We here report four unrelated individuals with a wide spectrum of TBD manifestations carrying either heterozygous or homozygous ACD variants consisting in the recurrent and previously described in-frame deletion of K170 (K170∆) and three novel missense mutations G179D, L184R, and E215V. Structural and functional analyses demonstrated that the four variants affect the TEL-patch domain of TPP1 and impair telomerase activity. In addition, we identified in the ACD gene several motifs associated with small deletion hotspots that could explain the recurrence of the K170∆ mutation. Finally, we detected in a subset of blood cells from one patient, a somatic TERT promoter-activating mutation that likely provides a selective advantage over non-modified cells, a phenomenon known as indirect somatic genetic rescue. Together, our results broaden the genetic and clinical spectrum of TPP1 deficiency and specify new residues in the TEL-patch domain that are crucial for length maintenance and stability of human telomeres in vivo.},
}
@article {pmid38171574,
year = {2024},
author = {Sakamoto, Y and Shiraishi, K and Kodama, S},
title = {Enhanced induction of abnormal telomere FISH signals in response to oxidative DNA damage.},
journal = {Journal of radiation research},
volume = {},
number = {},
pages = {},
doi = {10.1093/jrr/rrad102},
pmid = {38171574},
issn = {1349-9157},
support = {JP24651051//Japan Society for the Promotion of Science London/ ; },
abstract = {Telomere dysfunction induces chromosomal instability, which is a driving force in the development of cancers. To examine X-irradiation's effect on telomere integrity, we investigated X-ray-induced abnormalities in telomere signals detected by fluorescence in situ hybridization (telomere FISH) in mouse embryo fibroblast cells. The abnormalities were categorized as either extra telomere signals (ETSs) or loss of telomere signals (LTSs). The results indicated that low doses (0.3-0.5 Gy) of X-rays significantly induced ETS but not LTS and that ETS induction was saturated at doses above 0.5 Gy. In addition, treatment with hydrogen peroxide also induced ETS but not LTS. To clarify the involvement of radicals in inducing ETS, we examined the effect of ascorbic acid (AsA) on telomere FISH signals and found that pre-treatment with AsA (5 mM, 2 h), but not post-treatment, significantly suppressed the induction of ETS by X-irradiation. Importantly, neither pre- nor post-treatment with AsA affected X-ray-induced chromosome aberrations. These results suggest that oxidative DNA damage induced by radicals is involved in the induction of ETS. Furthermore, combined treatment with aphidicolin, a DNA replication inhibitor, elevated the induction of ETS by X-irradiation. This observation suggests that DNA replication stress, potentially triggered by oxidative DNA lesions within telomeres, may contribute to the induction of ETS resulting from X-irradiation. Based on these results, we propose that ETS is a sensitive biological marker of oxidative DNA damage in telomere structures.},
}
@article {pmid38167290,
year = {2024},
author = {Muyas, F and Rodriguez, MJG and Cascão, R and Afonso, A and Sauer, CM and Faria, CC and Cortés-Ciriano, I and Flores, I},
title = {The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {82},
pmid = {38167290},
issn = {2041-1723},
support = {/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; Telomere Homeostasis/genetics ; *Telomerase/genetics/metabolism ; *Neoplasms/genetics ; Telomere/genetics/metabolism ; Genomics ; },
abstract = {Telomere fusions (TFs) can trigger the accumulation of oncogenic alterations leading to malignant transformation and drug resistance. Despite their relevance in tumour evolution, our understanding of the patterns and consequences of TFs in human cancers remains limited. Here, we characterize the rates and spectrum of somatic TFs across >30 cancer types using whole-genome sequencing data. TFs are pervasive in human tumours with rates varying markedly across and within cancer types. In addition to end-to-end fusions, we find patterns of TFs that we mechanistically link to the activity of the alternative lengthening of telomeres (ALT) pathway. We show that TFs can be detected in the blood of cancer patients, which enables cancer detection with high specificity and sensitivity even for early-stage tumours and cancers of high unmet clinical need. Overall, we report a genomic footprint that enables characterization of the telomere maintenance mechanism of tumours and liquid biopsy analysis.},
}
@article {pmid38166713,
year = {2024},
author = {Zhao, XX and Bai, LL},
title = {Correlation between telomere shortening in maternal peripheral blood and fetal aneuploidy.},
journal = {BMC pregnancy and childbirth},
volume = {24},
number = {1},
pages = {2},
pmid = {38166713},
issn = {1471-2393},
support = {81660542//This work was supported by the Natural Science Foundation of China/ ; 2018MS08091//the Inner Mongolia Natural Science Fund/ ; },
mesh = {Female ; Humans ; *Trisomy/diagnosis/genetics ; *Down Syndrome/diagnosis/genetics ; Telomere Shortening ; Aneuploidy ; Fetus ; Fetal Blood ; },
abstract = {BACKGROUND: This study aimed to assess whether maternal telomere length is a more accurate predictor of trisomy 21 than maternal age while also exploring the factors influencing maternal and fetal telomere length.<br><br>METHODS: Forty mothers with fetuses carrying extra maternal copies of chromosome 21 were defined as trisomy 21 cases, and 18 mothers with normal karyotype fetuses were defined as controls. Telomere lengths of maternal blood lymphocytes and amniotic fluid cells were determined using real-time polymerase chain reaction. Fetal and maternal telomere lengths were compared between the two groups. Moreover, we analyzed the factors influencing maternal and fetal telomere length in the trisomy 21 pedigree. A logistic regression model was used to analyze the correlation between maternal telomere length and trisomy 21 risk. In addition, receiver operating characteristic (ROC) curve analysis was used to determine the accuracy of using maternal telomere length as an indicator of trisomy 21 risk.<br><br>RESULTS: The study revealed that both maternal and fetal telomere lengths were significantly shorter in trisomy 21 cases than in the controls. In the trisomy 21 group, the maternal age, occupation, and nationality showed no significant correlation with their telomere length; fetal telomere length exhibited a positive correlation with maternal telomere length. Furthermore, maternal telomere length shortening is associated with trisomy 21 (OR&#x2009;=&#x2009;0.311; 95% CI, 0.109-0.885, P&#x2009;<&#x2009;0.05). The results of ROC curve analysis indicated that a combined assessment of maternal age and maternal telomere length predicted fetal chromosome trisomy more effectively than a single assessment (area under the curve 0.808, 95% CI, 0.674-0.941, P&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Maternal age combined with maternal telomere length proved to be a superior predictor of trisomy risk. Additionally, maternal telomere length was found to influence fetal telomere length.},
}
@article {pmid38166034,
year = {2024},
author = {Wang, D and Li, C and Zhang, X and Li, Y and He, J and Guo, X},
title = {Leukocyte telomere length and sarcopenia-related traits: A bidirectional Mendelian randomization study.},
journal = {PloS one},
volume = {19},
number = {1},
pages = {e0296063},
pmid = {38166034},
issn = {1932-6203},
mesh = {Humans ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Sarcopenia/genetics ; Leukocytes ; Telomere/genetics ; *Diabetes Mellitus, Type 2 ; },
abstract = {Accumulating evidence indicated that leukocyte telomere length (LTL) was related to sarcopenia. However, it is still not clear whether the association of changes in LTL with sarcopenia is likely to be causal, or could be explained by reverse causality. Thus, we carried on bidirectional Mendelian randomization (MR) and multivariable MR analyses to identify the causal relationship between LTL and sarcopenia-related traits. Summary-level data and independent variants used as instruments came from large genome-wide association studies of LTL (472,174 participants), appendicular lean mass (450,243 participants), low grip strength (256,523 participants), and walking pace (450,967 participants). We identified suggestive association of longer LTL with larger appendicular lean mass [odds ratio (OR) = 1.053; 95% confidence interval (CI), 1.009-1.099; P = 0.018], and causal association of longer LTL with a lower risk of low grip strength (OR = 0.915; 95% CI, 0.860-0.974; P = 0.005). In the reverse MR analysis, we also observed a positive causal association between walking pace and LTL (OR = 1.252; 95% CI, 1.121-1.397; P < 0.001). Similar results can be repeated in sensitivity analyses. While in the multivariable MR analysis, the estimate of the impact of walking pace on LTL underwent a transformation after adjusting for T2DM (OR = 1.141; 95%CI: 0.989-1.317; P = 0.070). The current MR analysis supported a causal relationship between shorter telomere length and both low muscle mass and strength. Additionally, walking pace may affect LTL through T2DM.},
}
@article {pmid38165952,
year = {2024},
author = {Piani, LL and Reschini, M and Somigliana, E and Ferrari, S and Busnelli, A and Viganò, P and Favero, C and Albetti, B and Hoxha, M and Bollati, V},
title = {Correction: Peripheral mitochondrial DNA, telomere length and DNA methylation as predictors of live birth in in vitro fertilization cycles.},
journal = {PloS one},
volume = {19},
number = {1},
pages = {e0296603},
pmid = {38165952},
issn = {1932-6203},
abstract = {[This corrects the article DOI: 10.1371/journal.pone.0261591.].},
}
@article {pmid38165506,
year = {2024},
author = {Tire, B and Talibova, G and Ozturk, S},
title = {The crosstalk between telomeres and DNA repair mechanisms: an overview to mammalian somatic cells, germ cells, and preimplantation embryos.},
journal = {Journal of assisted reproduction and genetics},
volume = {41},
number = {2},
pages = {277-291},
pmid = {38165506},
issn = {1573-7330},
mesh = {Humans ; Animals ; Male ; Female ; *DNA Repair/genetics ; *Telomere/genetics ; DNA Damage ; Germ Cells ; Blastocyst ; Mammals ; },
abstract = {Telomeres are located at the ends of linear chromosomes and play a critical role in maintaining genomic stability by preventing premature activation of DNA repair mechanisms. Because of exposure to various genotoxic agents, telomeres can undergo shortening and genetic changes. In mammalian cells, the basic DNA repair mechanisms, including base excision repair, nucleotide excision repair, double-strand break repair, and mismatch repair, function in repairing potential damages in telomeres. If these damages are not repaired correctly in time, the unfavorable results such as apoptosis, cell cycle arrest, and cancerous transition may occur. During lifespan, mammalian somatic cells, male and female germ cells, and preimplantation embryos experience a number of telomeric damages. Herein, we comprehensively reviewed the crosstalk between telomeres and the DNA repair mechanisms in the somatic cells, germ cells, and embryos. Infertility development resulting from possible defects in this crosstalk is also discussed in the light of existing studies.},
}
@article {pmid38163559,
year = {2024},
author = {Li, C and Yang, J and Chu, L and Tian, J and Xiao, J and Huang, Y and Wang, Q and Guo, B and Huang, L and Hu, Y and Luo, Y},
title = {The function of Bazhen decoction in rescuing progeroid cell senescence via facilitating G-quadruplex resolving and telomere elongation.},
journal = {Journal of ethnopharmacology},
volume = {323},
number = {},
pages = {117694},
doi = {10.1016/j.jep.2023.117694},
pmid = {38163559},
issn = {1872-7573},
mesh = {Animals ; Mice ; *Werner Syndrome/genetics ; DNA Damage ; Telomere ; Cellular Senescence ; DNA Helicases/genetics ; },
abstract = {The Bazhen decoction is one of the most extensively used Traditional Chinese medicine (TCM) prescriptions for treatment of aging related diseases. However, due to the complexity of the components, the pharmacological mechanism of Bazhen decoction is still limited.<br><br>AIM OF THE STUDY: In this study, with the aim of helping the clinical precision medicine of TCM, we try out a systematic analysis for dissecting the molecular mechanism of complicated TCM prescription: Bazhen decoction. We identify the pharmacological mechanism of Bazhen decoction in telomere elongation as revealed by systematic analysis.<br><br>MATERIALS AND METHODS: By RNA sequencing and transcriptome analysis of Bazhen decoction treated wild type cells, we reveal the transcriptome profile induced by Bazhen decoction. We utilized the cells derived from Werner syndrome (WS) mice, which is known to be dysfunctional in telomere elongation due to the deficiency of DNA helicase Wrn. By Western blot, qPCR, Immunofluorescence, flow cytometry, telomere FISH, and SA-&#x3b2;-Gal staining, we verify the transcriptome data and confirm the pharmacological function of Bazhen decoction and its drug containing serum in telomere elongation and reversing progeroid cell senescence.<br><br>RESULTS: We reveal that Bazhen decoction may systematically regulate multiple anti-aging pathways, including stem cell regulation, protein homeostasis, cardiovascular function, neuronal function, anti-inflammation, anti-DNA damage induced stress, DNA helicase activity and telomere lengthening. We find that Bazhen decoction and its drug containing serum could up-regulate multiple DNA helicases and telomere regulating proteins. The increased DNA helicases promote the resolving of G-quadruplex (G4) structures, and facilitate DNA replication and telomere elongation. These improvements also endow the cellular resistance to DNA damages induced by replication stress, and rescue the WS caused cellular senescence.<br><br>CONCLUSIONS: Together these data suggest that Bazhen decoction up-regulate the expression of DNA helicases, thus facilitate G4 resolving and telomere maintenance, which rescue the progeroid cellular senescence and contribute to its anti-aging properties. Our data reveal a new molecular mechanism of Bazhen decoction in anti-aging related diseases via elongating telomere, this may shed light in the application of Bazhen decoction in multiple degenerative diseases caused by telomere erosion.},
}
@article {pmid38163245,
year = {2024},
author = {Zhu, Y and Meng, Y and Zhang, Y and Karlsson, IK and Hägg, S and Zhan, Y},
title = {Genetically determined telomere length and its association with chronic obstructive pulmonary disease and interstitial lung disease in biobank Japan: A Mendelian randomization study.},
journal = {Heliyon},
volume = {10},
number = {1},
pages = {e23415},
pmid = {38163245},
issn = {2405-8440},
abstract = {IMPORTANCE: Chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have been linked to shorter telomere length (TL). While understanding this association has critical clinical implications for respiratory diseases, previous studies exploring these associations were conducted in European populations. The present study aims to investigate this relationship in an Asian population.<br><br>OBJECTIVE: To examine the causal relationship between leukocyte TL and COPD and ILD in an Asian population.<br><br>DESIGN: Setting, and Participants: We used a genome-wide association study summary statistics-based two-sample Mendelian randomization (MR) design to investigate the association between leukocyte TL, genetically predicted by nine single-nucleotide polymorphisms and the risk of COPD and ILD. Participants were Japanese individuals enrolled in the Biobank Japan Project, including 3315 COPD patients and 806 ILD patients.<br><br>EXPOSURE: Leukocyte TL was genetically predicted by nine single-nucleotide polymorphisms.<br><br>RESULTS: The inverse-variance weighted estimates showed a significant inverse association between leukocyte TL and COPD (odds ratio [OR]&#xa0;=&#xa0;0.78; 95&#xa0;% confidence interval [CI]: 0.64, 0.95; P&#xa0;=&#xa0;0.01) and ILD (OR&#xa0;=&#xa0;0.29; 95&#xa0;% CI: 0.14, 0.61; P&#xa0;=&#xa0;0.001), respectively. All sensitivity analyses yielded consistent results. The MR-Egger regression intercept test showed no evidence of horizontal pleiotropy (Pintercept: COPD, 0.56; ILD: 0.70).<br><br>CONCLUSION: and Relevance: Our findings suggest that leukocyte telomere shortening may causally increase the risk of COPD and ILD. These results highlight the potential importance of TL for these respiratory diseases.},
}
@article {pmid38159192,
year = {2023},
author = {Del Valle, KT and Carmona, EM},
title = {Diagnosis and Management of Pulmonary Manifestations of Telomere Biology Disorders.},
journal = {Current hematologic malignancy reports},
volume = {},
number = {},
pages = {},
pmid = {38159192},
issn = {1558-822X},
abstract = {PURPOSE OF REVIEW: Telomere biology disorders (TBD) are a group of genetic disorders characterized by premature shortening of telomeres, resulting in accelerated aging of somatic cells. This often leads to major multisystem organ dysfunction, and TBDs have become increasingly recognized as a significant contributor to numerous disease processes within the past 10-15 years. Both research and clinical practice in this field are rapidly evolving.<br><br>RECENT FINDINGS: A subset of patients with TBD suffers from interstitial lung disease, most commonly pulmonary fibrosis. Often, the clinical presentation is indistinguishable from other forms of lung fibrosis. There are no pathognomonic radiographic or histological features, and a high level of suspicion is therefore required. Telomere evaluation is thus crucial to establishing the diagnosis. This review details the clinical presentation, objective evaluation, indicated genetic testing, and recommended management strategies for patients affected by interstitial lung disease associated with TBDs. Our goal is to empower pulmonologists and other healthcare professionals who care for these patients to provide appropriate and personalized care for this population.},
}
@article {pmid38150087,
year = {2023},
author = {Eppard, M and Passos, JF and Victorelli, S},
title = {Telomeres, cellular senescence, and aging: past and future.},
journal = {Biogerontology},
volume = {},
number = {},
pages = {},
pmid = {38150087},
issn = {1573-6768},
support = {R01AG068048/NH/NIH HHS/United States ; R01AG082708/NH/NIH HHS/United States ; },
abstract = {Over half a century has passed since Alexey Olovnikov's groundbreaking proposal of the end-replication problem in 1971, laying the foundation for our understanding of telomeres and their pivotal role in cellular senescence. This review paper delves into the intricate and multifaceted relationship between cellular senescence, the influence of telomeres in this process, and the far-reaching consequences of telomeres in the context of aging and age-related diseases. Additionally, the paper investigates the various factors that can influence telomere shortening beyond the confines of the end-replication problem and how telomeres can exert their impact on aging, even in the absence of significant shortening. Ultimately, this paper stands as a tribute to the pioneering work of Olovnikov, whose seminal contributions established the solid foundation upon which our ongoing explorations of telomeres and the aging process are based.},
}
@article {pmid38145728,
year = {2023},
author = {Zhang, X and Colicino, E and Cowell, W and Enlow, MB and Kloog, I and Coull, BA and Schwartz, JD and Wright, RO and Wright, RJ},
title = {Prenatal exposure to air pollution and BWGA Z-score: Modifying effects of placenta leukocyte telomere length and infant sex.},
journal = {Environmental research},
volume = {246},
number = {},
pages = {117986},
doi = {10.1016/j.envres.2023.117986},
pmid = {38145728},
issn = {1096-0953},
support = {R21 ES021318/ES/NIEHS NIH HHS/United States ; P30 ES023515/ES/NIEHS NIH HHS/United States ; UH3 OD023337/OD/NIH HHS/United States ; R01 HL095606/HL/NHLBI NIH HHS/United States ; R01 HL114396/HL/NHLBI NIH HHS/United States ; },
abstract = {BACKGROUND: Air pollutants, such as fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3), have been associated with adverse birth outcomes, including low birth weight, often exhibiting sex-specific effects. However, the modifying effect of placental telomere length (TL), reflecting cumulative lifetime oxidative stress in mothers, remains unexplored.<br><br>METHOD: Using data from a Northeastern U.S. birth cohort (n&#xa0;=&#xa0;306), we employed linear regression and weighted quantile sum models to assess trimester-average air pollution exposures and birth weight for gestational age (BWGA) z-scores. Placental TL, categorized by median split, was considered as an effect modifier. Interactions among air pollutants, placental TL, infant sex, and BWGA z-score were evaluated.<br><br>RESULTS: Without placental TL as a modifier, only 1[st] trimester O3 was significantly associated with BWGA z-scores (coefficient: 0.33, 95% CI: 0.03, 0.63). In models considering TL interactions, a significant modifying effect was observed between 3[rd] trimester NO2 and BWGA z-scores (interaction p-value&#xa0;=&#xa0;0.02). Specifically, a one interquartile range (1-IQR) increase in 3[rd] trimester NO2 was linked to a 0.28 (95% CI: 0.06, 0.52) change in BWGA z-score among shorter placental TL group, with no significant association among longer TL group. Among male infants, there were significant associations between 3[rd] trimester PM2.5 exposure and BWGA z-scores in the longer TL group (coefficient: -0.34, 95% CI: -0.61, -0.02), and between 1[st] trimester O3 exposure and BWGA z-scores among males in the shorter TL group (coefficient: 0.59, 95% CI: 0.06, 1.08). For females, only a negative association in 2[nd] trimester mixture model was observed within the longer TL group (coefficient: -0.10, 95% CI: -0.21, -0.01).<br><br>CONCLUSION: These findings highlight the need to consider the complex interactions among prenatal air pollutant exposures, placental TL, and fetal sex to better elucidate those at greatest risk for adverse birth outcomes.},
}
@article {pmid38144537,
year = {2023},
author = {, },
title = {Expression of concern: MRE11 and UBR5 co-operate to suppress RNF168-mediated fusion of dysfunctional telomeres.},
journal = {Frontiers in oncology},
volume = {13},
number = {},
pages = {1308554},
doi = {10.3389/fonc.2023.1308554},
pmid = {38144537},
issn = {2234-943X},
}
@article {pmid38141917,
year = {2024},
author = {Mishra, S and Stukken, CV and Drury, S and Nawrot, TS and Martens, DS},
title = {Prenatal air pollution exposure in relation to the telomere-mitochondrial axis of aging at birth: A systematic review.},
journal = {Environmental research},
volume = {244},
number = {},
pages = {117990},
doi = {10.1016/j.envres.2023.117990},
pmid = {38141917},
issn = {1096-0953},
mesh = {Infant, Newborn ; Pregnancy ; Female ; Humans ; Systematic Reviews as Topic ; Meta-Analysis as Topic ; *Air Pollution/adverse effects/analysis ; *Air Pollutants/toxicity/analysis ; Particulate Matter/analysis ; Telomere ; DNA, Mitochondrial ; Maternal Exposure/adverse effects ; Environmental Exposure/analysis ; },
abstract = {BACKGROUND: Telomere length (TL) and mitochondrial DNA (mtDNA) are central markers of vital biological mechanisms, including cellular aging. Prenatal air pollution exposure may impact molecular markers of aging leading to adverse health effects.<br><br>OBJECTIVE: To perform a systematic review on human population-based studies investigating the association between prenatal air pollution exposure and TL or mtDNA content at birth.<br><br>METHODOLOGY: Searches were undertaken on PubMed and Web of Science until July 2023. The framework of the review was based on the PRISMA-P guidelines.<br><br>RESULTS: Nineteen studies studied prenatal air pollution and TL or mtDNA content at birth. Studies investigating TL or mtDNA content measured at any other time or did not evaluate prenatal air pollution were excluded. Twelve studies (including 4381 participants with study sample range: 97 to 743 participants) investigated newborn TL and eight studies (including 3081 participants with study sample range: 120 to 743 participants) investigated mtDNA content at birth. Seven studies focused on particulate matter (PM2.5) exposure and newborn TL of which all, except two, showed an inverse association in at least one of the gestational trimesters. Of the eight studies on mtDNA content, four focused on PM2.5 air pollution with two of them reporting an inverse association. For PM2.5 exposure, observations on trimester-specific effects were inconsistent. Current literature showing associations with other prenatal air pollutants (including nitrogen oxides, sulfur dioxide, carbon monoxide and ozone) is inconsistent.<br><br>CONCLUSION: This review provides initial evidence that prenatal PM2.5 exposure impacts the telomere-mitochondrial axis of aging at birth. The current evidence did not reveal harmonious observations for trimester-specific associations nor showed consistent effects of other air pollutants. Future studies should elucidate the specific contribution of prenatal exposure to pollutants other than PM in relation to TL and mtDNA content at birth, and the potential later life health consequences.},
}
@article {pmid38137478,
year = {2023},
author = {Tesolato, S and Vicente-Valor, J and Jarabo, JR and Calatayud, J and Sáiz-Pardo, M and Nieto, A and Álvaro-Álvarez, D and Linares, MJ and Fraile, CA and Hernándo, F and Iniesta, P and Gómez-Martínez, AM},
title = {Role of Telomere Length in Survival of Patients with Idiopathic Pulmonary Fibrosis and Other Interstitial Lung Diseases.},
journal = {Biomedicines},
volume = {11},
number = {12},
pages = {},
pmid = {38137478},
issn = {2227-9059},
support = {2019 and 2020, respectively//"Neumomadrid" (Sociedad Madrile&#xf1;a de Neumolog&#xed;a y Cirug&#xed;a Tor&#xe1;cica), and "C&#xe1;tedra EPID Futuro UAM-Roche"./ ; },
abstract = {Interstitial lung diseases (ILDs) constitute a group of more than 200 disorders, with idiopathic pulmonary fibrosis (IPF) being one of the most frequent. Telomere length (TL) shortening causes loss of function of the lung parenchyma. However, little is known about its role as a prognostic factor in ILD patients. With the aim of investigating the role of TL and telomerase activity in the prognosis of patients affected by ILDs, we analysed lung tissue samples from 61 patients. We measured relative TL and telomerase activity by conventional procedures. Both clinical and molecular parameters were associated with overall survival by the Kaplan-Meier method. Patients with IPF had poorer prognosis than patients with other ILDs (p = 0.034). When patients were classified according to TL, those with shortened telomeres reported lower overall survival (p = 0.085); differences reached statistical significance after excluding ILD patients who developed cancer (p = 0.021). In a Cox regression analysis, TL behaved as a risk-modifying variable for death associated with rheumatic disease (RD) co-occurrence (p = 0.029). Also, in patients without cancer, ferritin was significantly increased in cases with RD and IPF co-occurrence (p = 0.032). In relation to telomerase activity, no significant differences were detected. In conclusion, TL in lung tissue emerges as a prognostic factor in ILD patients. Specifically, in cases with RD and IPF co-occurrence, TL can be considered as a risk-modifying variable for death.},
}
@article {pmid38136279,
year = {2023},
author = {Djos, A and Thombare, K and Vaid, R and Gaarder, J and Umapathy, G and Reinsbach, SE and Georgantzi, K and Stenman, J and Carén, H and Ek, T and Mondal, T and Kogner, P and Martinsson, T and Fransson, S},
title = {Telomere Maintenance Mechanisms in a Cohort of High-Risk Neuroblastoma Tumors and Its Relation to Genomic Variants in the TERT and ATRX Genes.},
journal = {Cancers},
volume = {15},
number = {24},
pages = {},
pmid = {38136279},
issn = {2072-6694},
support = {20-1213//the Swedish Cancer Society/ ; 19-566//the Swedish Cancer Society/ ; 19-139//the Swedish Childhood Cancer Foundation/ ; 22-156//the Swedish Childhood Cancer Foundation/ ; 17-122//the Swedish Childhood Cancer Foundation/ ; 18-99//the Swedish Childhood Cancer Foundation/ ; ALFGBG-447171//the Swedish state under the LUA/ALF agreement/ ; RB13-0204//the Swedish Foundation for Strategic Research/ ; SF//Sahlgrenska University hospital and Laboratory medicine research and development grant/ ; KAW 2018.0057//the Knut and Alice Wallenberg foundation/ ; },
abstract = {Tumor cells are hallmarked by their capacity to undergo unlimited cell divisions, commonly accomplished either by mechanisms that activate TERT or through the alternative lengthening of telomeres pathway. Neuroblastoma is a heterogeneous pediatric cancer, and the aim of this study was to characterize telomere maintenance mechanisms in a high-risk neuroblastoma cohort. All tumor samples were profiled with SNP microarrays and, when material was available, subjected to whole genome sequencing (WGS). Telomere length was estimated from WGS data, samples were assayed for the ALT biomarker c-circles, and selected samples were subjected to methylation array analysis. Samples with ATRX aberration in this study were positive for c-circles, whereas samples with either MYCN amplification or TERT re-arrangement were negative for c-circles. Both ATRX aberrations and TERT re-arrangement were enriched in 11q-deleted samples. An association between older age at diagnosis and 1q-deletion was found in the ALT-positive group. TERT was frequently placed in juxtaposition to a previously established gene in neuroblastoma tumorigenesis or cancer in general. Given the importance of high-risk neuroblastoma, means for mitigating active telomere maintenance must be therapeutically explored.},
}
@article {pmid38136206,
year = {2023},
author = {D'Angelo, S},
title = {Diet and Aging: The Role of Polyphenol-Rich Diets in Slow Down the Shortening of Telomeres: A Review.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {12},
pages = {},
pmid = {38136206},
issn = {2076-3921},
support = {DM737 of 25-06-2021; grant number: CUPI53C22001990001//Miur/ ; },
abstract = {The ends of human chromosomes are defended by DNA-protein complexes named telomeres, which inhibit the chromosomes from fusing with each other and from being known as a double-strand break by DNA reparation proteins. Telomere length is a marker of biological aging, and disfunction of telomeres is related to age-related syndromes. Telomere attrition has been shown to be accelerated by oxidative stress and inflammation. Telomere length has been proven to be positively linked with nutritional status in human and animal scientific research as several nutrients influence it through mechanisms that imitate their function in cellular roles including oxidative stress and inflammation. Data reported in this article support the idea that following a low-in-fat and rich-plant polyphenols food diet seems to be able to slow down the shortening of telomeres.},
}
@article {pmid38135140,
year = {2024},
author = {Wai, KM and Swe, T and Su Hninn, TS and Paing, AM and Naing, YL and Htay, ZW and Ihara, K},
title = {Prenatal exposure to environmental heavy metals and newborn telomere length: A systematic review and meta-analysis.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {343},
number = {},
pages = {123192},
doi = {10.1016/j.envpol.2023.123192},
pmid = {38135140},
issn = {1873-6424},
mesh = {Pregnancy ; Female ; Infant, Newborn ; Humans ; Cadmium/toxicity ; *Prenatal Exposure Delayed Effects ; Likelihood Functions ; Cohort Studies ; Telomere ; *Metals, Heavy/toxicity ; },
abstract = {Exposure to environmental heavy metals is associated with telomere length (TL) alteration. Available information regarding the effect of prenatal exposure to environmental pollutants on newborn TL is controversial. The aim of this study is to systematically review and conduct a meta-analysis of the existing epidemiological studies on the associations between prenatal metal exposure and newborn TL. A comprehensive literature search was performed using the online databases of PubMed, Web of Science, and ScienceDirect from their inception to December 1, 2023. Thirteen eligible studies were included from the overall initial identification of 3559 records. The effect size was expressed as standardized beta coefficients with 95% confidence intervals (CIs) by the restricted maximum-likelihood approach with a weighted random-effects model. Prenatal exposure to environmental heavy metals was associated with a shorter newborn TL (standardized beta = -0.04; 95% CI: -0.08, 0.00; p = 0.05). Subgroup analysis showed that prenatal exposure to cadmium was significantly, negatively associated with TL in newborns (standardized beta = -0.05; 95% CI: -0.10, -0.01; p = 0.021). Heavy metal exposure during the third trimester was significantly associated with a shorter TL in newborns (standardized beta = -0.05; 95% CI: -0.11, -0.01; p = 0.045). No significant association was found between the newborn's sex and exposure sample type. This study provides evidence for the negative effect of prenatal exposure to heavy metals on newborn TL. In particular, cadmium exposure and exposure during the third trimester of pregnancy are critical factors associated with heavy metal-induced TL shortening.},
}
@article {pmid38134301,
year = {2023},
author = {Niu, B and Wu, JX and Huang, XL and Lei, SF and Deng, FY},
title = {Telomere length is a driving hallmark for aging-related biochemical hallmarks: evidence from the shared genetic effect and causal inference.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/gerona/glad275},
pmid = {38134301},
issn = {1758-535X},
abstract = {Telomere shortening is an important sign and driving factor of aging, but its association mechanisms and causal effects with other aging-related biochemical hallmarks are largely unknown. This study first performed comprehensive genetic analyses (e.g., shared genetic analysis, pleiotropic analysis, gene enrichment analysis) to detect the underlying molecular mechanisms for the associations between TL and aging-related biochemical hallmarks. Then, further bidirectional MR analyses investigated the causal effects between TL and other biochemical hallmarks. The genetic correlations were negative between TL and GDF15 (P = 0.024), CRP (P = 0.007), HbA1c (P = 0.007) and RBC (P = 0.022), but positive between TL and IGF-1 (P = 0.002) and WBC (P = 0.007). The increased TL has causal effects on the low levels of GDF15 (P = 3.73E-06), SHBG (P = 6.30E-06), testosterone (P = 5.56E-07), FI (P = 2.67E-05), and RBC (P = 1.54E-05), but the higher levels of IGF-1 (P = 3.24E-07). In conclusion, the observed phenotypic correlations between TL and aging-related biochemical hallmarks may arise from a combination of shared genetic components and causal effects. TL is regarded as a driving hallmark for aging-related biochemical hallmarks.},
}
@article {pmid38129441,
year = {2023},
author = {Chang, Y and Zhou, Y and Zhou, J and Li, W and Cao, J and Jing, Y and Zhang, S and Shen, Y and Lin, Q and Fan, X and Yang, H and Dong, X and Zhang, S and Yi, X and Shuai, L and Shi, L and Liu, Z and Yang, J and Ma, X and Hao, J and Chen, K and Li, MJ and Wang, F and Huang, D},
title = {Unraveling the causal genes and transcriptomic determinants of human telomere length.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {8517},
pmid = {38129441},
issn = {2041-1723},
support = {32270717//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Adult ; Humans ; Female ; Pregnancy ; *Genome-Wide Association Study ; *Placenta/metabolism ; Telomere Shortening ; Telomere/genetics ; Gene Expression Profiling ; },
abstract = {Telomere length (TL) shortening is a pivotal indicator of biological aging and is associated with many human diseases. The genetic determinates of human TL have been widely investigated, however, most existing studies were conducted based on adult tissues which are heavily influenced by lifetime exposure. Based on the analyses of terminal restriction fragment (TRF) length of telomere, individual genotypes, and gene expressions on 166 healthy placental tissues, we systematically interrogate TL-modulated genes and their potential functions. We discover that the TL in the placenta is comparatively longer than in other adult tissues, but exhibiting an intra-tissue homogeneity. Trans-ancestral TL genome-wide association studies (GWASs) on 644,553 individuals identify 20 newly discovered genetic associations and provide increased polygenic determination of human TL. Next, we integrate the powerful TL GWAS with placental expression quantitative trait locus (eQTL) mapping to prioritize 23 likely causal genes, among which 4 are functionally validated, including MMUT, RRM1, KIAA1429, and YWHAZ. Finally, modeling transcriptomic signatures and TRF-based TL improve the prediction performance of human TL. This study deepens our understanding of causal genes and transcriptomic determinants of human TL, promoting the mechanistic research on fine-grained TL regulation.},
}
@article {pmid38110867,
year = {2023},
author = {Wang, H and Chen, X and Wang, S and Zhang, H},
title = {Exploration of the causal effects of leukocyte telomere length and four gastrointestinal diseases: a two-sample bidirectional Mendelian randomization study.},
journal = {BMC gastroenterology},
volume = {23},
number = {1},
pages = {446},
pmid = {38110867},
issn = {1471-230X},
support = {2020A1515011379//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2020A1515011379//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2020A1515011379//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2020A1515011379//Basic and Applied Basic Research Foundation of Guangdong Province/ ; },
mesh = {Humans ; *Irritable Bowel Syndrome/genetics ; Mendelian Randomization Analysis ; *Gastrointestinal Diseases/genetics ; *Gastroesophageal Reflux ; Leukocytes ; Telomere ; },
abstract = {BACKGROUND: To explore the underlying causality between leukocyte telomere length (LTL) and four gastrointestinal diseases, we designed a two-sample bidirectional Mendelian randomization study.<br><br>METHODS: Two-sample Mendelian randomization (MR) was used to explore genetic causality between LTL and four gastrointestinal diseases, including irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), gastrointestinal ulcers disease (GUD), and nonalcoholic fatty liver disease (NAFLD). We utilized inverse-variance weighted (IVW) as the primary method for MR analysis. Supplementary analyses were conducted using methods such as MR-Egger regression, weighted-median, Maximum Likelihood (MaxLik), Robust adjusted profile score (MR-RAPS), Contamination mixture (ConMix), and MR-mix. Cochran's Q was calculated to check for heterogeneity. The MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) were detected for pleiotropy.<br><br>RESULTS: The IVW analysis suggests that there may be a potential causal relationship between LTL and two diseases (odds ratio (OR): 1.062; 95% confidence interval (CI): 1.003, 1.124; p&#x2009;=&#x2009;0.038 for IBS and OR: 0.889; 95% CI: 0.798, 0.990; p&#x2009;=&#x2009;0.032 for GERD). However, other methods do not entirely align with the results of the IVW analysis. In the reverse MR analysis, we did not find statistically significant associations between LTL and these four diseases.<br><br>CONCLUSION: The current evidence does not definitively rule out a causal relationship between LTL and these four gastrointestinal diseases but suggests a potential association between LTL and IBS, or LTL and GERD. Exploring the relationship between gastrointestinal diseases and LTL may offer new insights into the onset, progression, and treatment of these diseases.},
}
@article {pmid38109000,
year = {2023},
author = {Savage, SA},
title = {Telomere length and cancer risk: finding Goldilocks.},
journal = {Biogerontology},
volume = {},
number = {},
pages = {},
pmid = {38109000},
issn = {1573-6768},
abstract = {Telomeres are the nucleoprotein complex at chromosome ends essential in genomic stability. Baseline telomere length (TL) is determined by rare and common germline genetic variants but shortens with age and is susceptible to certain environmental exposures. Cellular senescence or apoptosis are normally triggered when telomeres reach a critically short length, but cancer cells overcome these protective mechanisms and continue to divide despite chromosomal instability. Rare germline variants in telomere maintenance genes cause exceedingly short telomeres for age (< 1st percentile) and the telomere biology disorders, which are associated with elevated risks of bone marrow failure, myelodysplastic syndrome, acute myeloid leukemia, and squamous cell carcinoma of the head/neck and anogenital regions. Long telomeres due to rare germline variants in the same or different telomere maintenance genes are associated with elevated risks of other cancers, such as chronic lymphocytic leukemia or sarcoma. Early epidemiology studies of TL in the general population lacked reproducibility but new methods, including creation of a TL polygenic score using common variants, have found longer telomeres associated with excess risks of renal cell carcinoma, glioma, lung cancer, and others. It has become clear that when it comes to TL and cancer etiology, not too short, not too long, but "just right" telomeres are important in minimizing cancer risk.},
}
@article {pmid38106000,
year = {2023},
author = {Kumawat, S and Martinez, I and Logeswaran, D and Chen, H and Coughlan, JM and Chen, JJ and Yuan, Y and Sobel, JM and Choi, JY},
title = {Transposition, duplication, and divergence of the telomerase RNA underlies the evolution of Mimulus telomeres.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {38106000},
abstract = {Telomeres are nucleoprotein complexes with a crucial role of protecting chromosome ends. It consists of simple repeat sequences and dedicated telomere-binding proteins. Because of its vital functions, components of the telomere, for example its sequence, should be under strong evolutionary constraint. But across all plants, telomere sequences display a range of variation and the evolutionary mechanism driving this diversification is largely unknown. Here, we discovered in Monkeyflower (Mimulus) the telomere sequence is even variable between species. We investigated the basis of Mimulus telomere sequence evolution by studying the long noncoding telomerase RNA (TR), which is a core component of the telomere maintenance complex and determines the telomere sequence. We conducted total RNA-based de novo transcriptomics from 16 Mimulus species and analyzed reference genomes from 6 species, and discovered Mimulus species have evolved at least three different telomere sequences: (AAACCCT)n, (AAACCCG)n, and (AAACCG)n. Unexpectedly, we discovered several species with TR duplications and the paralogs had functional consequences that could influence telomere evolution. For instance, M. lewisii had two sequence-divergent TR paralogs and synthesized a telomere with sequence heterogeneity, consisting of AAACCG and AAACCCG repeats. Evolutionary analysis of the M. lewisii TR paralogs indicated it had arisen from a transposition-mediate duplication process. Further analysis of the TR from multiple Mimulus species showed the gene had frequently transposed and inserted into new chromosomal positions during Mimulus evolution. From our results, we propose the TR transposition, duplication, and divergence model to explain the evolutionary sequence turnovers in Mimulus and potentially all plant telomeres.},
}
@article {pmid38105195,
year = {2023},
author = {Kalmykova, AI and Sokolova, OA},
title = {Retrotransposons and Telomeres.},
journal = {Biochemistry. Biokhimiia},
volume = {88},
number = {11},
pages = {1739-1753},
doi = {10.1134/S0006297923110068},
pmid = {38105195},
issn = {1608-3040},
mesh = {Animals ; Humans ; *Retroelements ; Drosophila melanogaster/genetics ; RNA, Small Interfering/metabolism ; Drosophila/genetics ; *Drosophila Proteins/metabolism ; Telomere/genetics/metabolism ; DNA Transposable Elements ; },
abstract = {Transposable elements (TEs) comprise a significant part of eukaryotic genomes being a major source of genome instability and mutagenesis. Cellular defense systems suppress the TE expansion at all stages of their life cycle. Piwi proteins and Piwi-interacting RNAs (piRNAs) are key elements of the anti-transposon defense system, which control TE activity in metazoan gonads preventing inheritable transpositions and developmental defects. In this review, we discuss various regulatory mechanisms by which small RNAs combat TE activity. However, active transposons persist, suggesting these powerful anti-transposon defense mechanisms have a limited capacity. A growing body of evidence suggests that increased TE activity coincides with genome reprogramming and telomere lengthening in different species. In the Drosophila fruit fly, whose telomeres consist only of retrotransposons, a piRNA-mediated mechanism is required for telomere maintenance and their length control. Therefore, the efficacy of protective mechanisms must be finely balanced in order not only to suppress the activity of transposons, but also to maintain the proper length and stability of telomeres. Structural and functional relationship between the telomere homeostasis and LINE1 retrotransposon in human cells indicates a close link between selfish TEs and the vital structure of the genome, telomere. This relationship, which permits the retention of active TEs in the genome, is reportedly a legacy of the retrotransposon origin of telomeres. The maintenance of telomeres and the execution of other crucial roles that TEs acquired during the process of their domestication in the genome serve as a type of payment for such a "service."},
}
@article {pmid38105192,
year = {2023},
author = {Yegorov, YE},
title = {Olovnikov, Telomeres, and Telomerase. Is It Possible to Prolong a Healthy Life?.},
journal = {Biochemistry. Biokhimiia},
volume = {88},
number = {11},
pages = {1704-1718},
doi = {10.1134/S0006297923110032},
pmid = {38105192},
issn = {1608-3040},
mesh = {*Telomerase/genetics/metabolism ; Cellular Senescence/genetics ; Telomere Homeostasis ; Telomere/genetics/metabolism ; },
abstract = {The science of telomeres and telomerase has made tremendous progress in recent decades. In this review, we consider it first in a historical context (the Carrel-Hayflick-Olovnikov-Blackburn chain of discoveries) and then review current knowledge on the telomere structure and dynamics in norm and pathology. Central to the review are consequences of the telomere shortening, including telomere position effects, DNA damage signaling, and increased genetic instability. Cell senescence and role of telomere length in its development are discussed separately. Therapeutic aspects and risks of telomere lengthening methods including use of telomerase and other approaches are also discussed.},
}
@article {pmid38102621,
year = {2023},
author = {Moshfeghinia, R and Torabi, A and Mostafavi, S and Rahbar, S and Moradi, MS and Sadeghi, E and Mootz, J and Vardanjani, HM},
title = {Maternal psychological stress during pregnancy and newborn telomere length: a systematic review and meta-analysis.},
journal = {BMC psychiatry},
volume = {23},
number = {1},
pages = {947},
pmid = {38102621},
issn = {1471-244X},
mesh = {Infant ; Pregnancy ; Female ; Humans ; Infant, Newborn ; *Mothers ; *Telomere ; Stress, Psychological/complications ; Telomere Shortening ; Research Design ; },
abstract = {INTRODUCTION: Telomeres protect the ends of chromosomes, and shorter leukocyte telomeres are associated with major group diseases. Maternal psychological stress may be related to the shortening of telomeres in infants. This systematic review and meta-analysis set out to consolidate the varying effect sizes found in studies of maternal psychological stress and telomere length (TL) in newborns and identify moderators of the relationship between stress during pregnancy and newborn TL.<br><br>METHODS: Our systematic review was registered in Prospero. Six databases (PubMed, Scopus, Embase, PsycINFO, Web of Science, and CINAHL Complete) were searched for records in English from inception to February 10, 2023. Observational studies were included that measured the relationship of psychological stress of the mother during pregnancy on the TL of the newborn. The Newcastle-Ottawa quality assessment scale was used to assess the quality of the included studies. A random-effect model was selected. Statistical analysis performed by Stata software version 17.<br><br>RESULTS: Eight studies were included for qualitative and four for quantitative analysis. There was an inverse statistically significant relationship between maternal stress and newborn TL; A one score increase in maternal psychological stress resulted in a 0.04 decrease in the TL of the newborn (B&#x2009;=&#x2009;-0.04, 95% CI&#x2009;=&#x2009;[-0.08, 0.00], p&#x2009;=&#x2009;0.05). Selectivity analysis showed that the pooled effect size was sensitive to one study; After removing this study, the pooled effect size remained significant (B&#x2009;=&#x2009;-0.06, 95% CI&#x2009;=&#x2009;[-0. 10, -0.02], p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: Physiological and environmental factors can significantly affect the TL of newborns. Our results support a significant impact of maternal psychological stress on the TL of a newborn. This association demonstrates the significance of stress in influencing the telomere length, which can be a contributing factor in the infant's future. Therefore, recognizing this association is crucial for understanding and addressing potential health risks and necessitates the need for additional future studies to validate our findings.},
}
@article {pmid38099139,
year = {2023},
author = {Gómez-Blanco, D and Tobler, M and Hasselquist, D},
title = {Why and when should organisms elongate their telomeres? Elaborations on the 'excess resources elongation' and 'last resort elongation' hypotheses.},
journal = {Ecology and evolution},
volume = {13},
number = {12},
pages = {e10825},
pmid = {38099139},
issn = {2045-7758},
abstract = {Telomere length and telomere shortening are thought to be critical cellular attributes and processes that are related to an individual's life span and fitness. The general pattern across most taxa is that after birth telomere length gradually decreases with age. Telomere protection and restoration mechanisms are usually assumed to reduce the rate of shortening or at most keep telomere length constant. However, here we have compiled a list of 26 articles showing that there is an increasing number of studies reporting apparent elongation of telomeres (i.e., a net increase in TL from timet to timet+1) often in a considerable proportion of the individuals studied. Moreover, the few studies which have studied telomere elongation in detail show that increases in telomere length are unlikely to be due to measurement error alone. In this article, we argue that episodes of telomere elongation deserve more attention as they could reflect individual strategies to optimise life histories and maximise fitness, which may not be reflected in the overall telomere dynamics patterns. We propose that patterns of telomere (net) elongation may be partly determined by other factors than those causing telomere shortening, and therefore deserve analyses specifically targeted to investigate the occurrence of telomere elongation. We elaborate on two ecological hypotheses that have been proposed to explain patterns of telomere elongation (the 'excess resources elongation' and the 'last resort elongation' hypothesis) and we discuss the current evidence for (or against) these hypotheses and propose ways to test them.},
}
@article {pmid38095828,
year = {2024},
author = {Lasho, T and Patnaik, MM},
title = {Adaptive and Maladaptive Clonal Hematopoiesis in Telomere Biology Disorders.},
journal = {Current hematologic malignancy reports},
volume = {19},
number = {1},
pages = {35-44},
pmid = {38095828},
issn = {1558-822X},
mesh = {Humans ; *Telomerase/genetics/metabolism ; Clonal Hematopoiesis/genetics ; Telomere/genetics/metabolism ; Hematopoiesis/genetics ; Biology ; },
abstract = {PURPOSE OF REVIEW: Telomere biology disorders (TBDs) are germline-inherited conditions characterized by reduction in telomerase function, accelerated shortening of telomeres, predisposition to organ-failure syndromes, and increased risk of neoplasms, especially myeloid malignancies. In normal cells, critically short telomeres trigger apoptosis and/or cellular senescence. However, the evolutionary mechanism by which TBD-related telomerase-deficient cells can overcome this fitness constraint remains elusive.<br><br>RECENT FINDINGS: Preliminary data suggests the existence of adaptive somatic mosaic states characterized by variants in TBD-related genes and maladaptive somatic mosaic states that attempt to overcome hematopoietic fitness constraints by alternative methods leading to clonal hematopoiesis. TBDs are both rare and highly heterogeneous in presentation, and the association of TBD with malignant transformation is unclear. Understanding the clonal complexity and mechanisms behind TBD-associated molecular signatures that lead to somatic adaptation in the setting of defective hematopoiesis will help inform therapy and treatment for this set of diseases.},
}
@article {pmid38088914,
year = {2023},
author = {Kidd, E and Meimaridou, E and Williams, J and Metherell, LA and Walley, AJ and Fairbrother, UL},
title = {Choice of gDNA isolation method has a significant impact on average murine Telomere Length estimates.},
journal = {Preparative biochemistry &amp; biotechnology},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/10826068.2023.2288572},
pmid = {38088914},
issn = {1532-2297},
abstract = {Telomere Length (TL) and integrity is significantly associated with age-related disease, multiple genetic and environmental factors. We observe mouse genomic DNA (gDNA) isolation methods to have a significant impact on average TL estimates. The canonical qPCR method does not measure TL directly but via the ratio of telomere repeats to a single copy gene (SCG) generating a T/S ratio. We use a monochromatic-multiplex-qPCR (mmqPCR) method which multiplexes the PCR and enables quantification of the target and the single copy gene within the same qPCR reaction. We demonstrate that TL measurements, from murine gDNA, isolated via Spin Columns (SC) and Magnetic Beads (MB), generate significantly smaller T/S ratios compared to gDNA isolated via traditional phenol/chloroform methods. The former methods may impede correct TL estimation by producing non representative fragment sets and reducing qPCR efficacy. This work highlights discrepancies in TL measurements due to different extraction techniques. We recommend the use of gDNA isolation methods that are shown to preserve DNA length and integrity, such as phenol/chloroform isolation. We propose that widely used high throughput DNA isolation methodologies can create spurious associations within a sample set, thus creating misleading data. We suggest that published TL associations should be revisited in the light of these data.},
}
@article {pmid38088000,
year = {2024},
author = {Rivosecchi, J and Jurikova, K and Cusanelli, E},
title = {Telomere-specific regulation of TERRA and its impact on telomere stability.},
journal = {Seminars in cell &amp; developmental biology},
volume = {157},
number = {},
pages = {3-23},
doi = {10.1016/j.semcdb.2023.11.001},
pmid = {38088000},
issn = {1096-3634},
mesh = {*RNA, Long Noncoding/genetics ; Chromatin ; DNA ; Telomere/genetics ; },
abstract = {TERRA is a class of telomeric repeat-containing RNAs that are expressed from telomeres in multiple organisms. TERRA transcripts play key roles in telomere maintenance and their physiological levels are essential to maintain the integrity of telomeric DNA. Indeed, deregulated TERRA expression or its altered localization can impact telomere stability by multiple mechanisms including fueling transcription-replication conflicts, promoting resection of chromosome ends, altering the telomeric chromatin, and supporting homologous recombination. Therefore, a fine-tuned control of TERRA is important to maintain the integrity of the genome. Several studies have reported that different cell lines express substantially different levels of TERRA. Most importantly, TERRA levels markedly vary among telomeres of a given cell type, indicating the existence of telomere-specific regulatory mechanisms which may help coordinate TERRA functions. TERRA molecules contain distinct subtelomeric sequences, depending on their telomere of origin, which may instruct specific post-transcriptional modifications or mediate distinct functions. In addition, all TERRA transcripts share a repetitive G-rich sequence at their 3' end which can form DNA:RNA hybrids and fold into G-quadruplex structures. Both structures are involved in TERRA functions and can critically affect telomere stability. In this review, we examine the mechanisms controlling TERRA levels and the impact of their telomere-specific regulation on telomere stability. We compare evidence obtained in different model organisms, discussing recent advances as well as controversies in the field. Furthermore, we discuss the importance of DNA:RNA hybrids and G-quadruplex structures in the context of TERRA biology and telomere maintenance.},
}
@article {pmid38086788,
year = {2023},
author = {Braun, H and Xu, Z and Chang, F and Viceconte, N and Rane, G and Levin, M and Lototska, L and Roth, F and Hillairet, A and Fradera-Sola, A and Khanchandani, V and Sin, ZW and Yong, WK and Dreesen, O and Yang, Y and Shi, Y and Li, F and Butter, F and Kappei, D},
title = {ZNF524 directly interacts with telomeric DNA and supports telomere integrity.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {8252},
pmid = {38086788},
issn = {2041-1723},
mesh = {Humans ; *Telomeric Repeat Binding Protein 2/genetics ; *Telomere/genetics/metabolism ; Shelterin Complex ; Telomere-Binding Proteins/metabolism ; DNA/genetics/metabolism ; },
abstract = {Telomeres are nucleoprotein structures at the ends of linear chromosomes. In humans, they consist of TTAGGG repeats, which are bound by dedicated proteins such as the shelterin complex. This complex blocks unwanted DNA damage repair at telomeres, e.g. by suppressing nonhomologous end joining (NHEJ) through its subunit TRF2. Here, we describe ZNF524, a zinc finger protein that directly binds telomeric repeats with nanomolar affinity, and reveal base-specific sequence recognition by cocrystallization with telomeric DNA. ZNF524 localizes to telomeres and specifically maintains the presence of the TRF2/RAP1 subcomplex at telomeres without affecting other shelterin members. Loss of ZNF524 concomitantly results in an increase in DNA damage signaling and recombination events. Overall, ZNF524 is a direct telomere-binding protein involved in the maintenance of telomere integrity.},
}
@article {pmid38085929,
year = {2024},
author = {Lv, K and Wu, Y and Yang, G and Hao, X and Huang, S and Song, T and Yuan, Q},
title = {Leukocyte Telomere Length and the Risk of Prostate Cancer and Benign Prostatic Hyperplasia: Insights From UK Biobank and Mendelian Randomization Study.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {79},
number = {3},
pages = {},
doi = {10.1093/gerona/glad272},
pmid = {38085929},
issn = {1758-535X},
support = {20220484230//Beijing NOVA Program/ ; 2021YFC2009304//National Key Research and Development Program of China/ ; 23BJZ29//Logistics Health Special Project/ ; 22QNC016//Youth Innovation Science Foundation of PLA/ ; },
mesh = {Male ; Humans ; *Prostatic Hyperplasia/genetics ; Mendelian Randomization Analysis ; Biological Specimen Banks ; Reproducibility of Results ; UK Biobank ; *Prostatic Neoplasms/epidemiology/genetics ; Leukocytes ; Telomere ; Genome-Wide Association Study ; },
abstract = {BACKGROUND: Previous observational studies have been controversial regarding the association of leukocyte telomere length (LTL) with prostate cancer (PCa) and benign prostatic hyperplasia (BPH).<br><br>METHODS: First, we conducted an observational study utilizing UK Biobank data. The correlation between LTL and the risk of PCa and BPH was evaluated via multivariate-adjusted logistic regression. Then, we conducted a 2-sample Mendelian randomization to examine causal links between LTL (472&#xa0;174 individuals) and PCa as well as BPH. To verify the reliability of the primary analysis, we conducted a second analysis and sensitivity analyses.<br><br>RESULTS: In the UK Biobank study, individuals in the longer quartiles of LTL were observed to have a higher risk of PCa (1.155-fold to 1.349-fold, all p&#x2005;<&#x2005;.001) and BPH (1.119-fold to 1.212-fold, all p&#x2005;<&#x2005;.001) compared to those in the lowest quartile in multivariate-adjusted logistic regression. We observed that genetically predicted longer LTL resulted in a 1.427-fold risk of PCa (odds ratio [OR]&#x2005;=&#x2005;1.427, 95% confidence interval [CI]&#x2005;=&#x2005;1.197-1.702, p&#x2005;<&#x2005;.001) and 1.539-fold risk of BPH (OR&#x2005;=&#x2005;1.539, 95% CI&#x2005;=&#x2005;1.387-1.707, p&#x2005;<&#x2005;.001) in the primary analysis. In the second analysis, the results also indicated that longer LTL increased the genetic liability to both PCa (OR&#x2005;=&#x2005;1.338, 95% CI&#x2005;=&#x2005;1.189-1.507, p&#x2005;<&#x2005;.001) and BPH (OR&#x2005;=&#x2005;1.006, 95% CI&#x2005;=&#x2005;1.003-1.008, p&#x2005;<&#x2005;.001). Sensitivity analyses also supported the reliability of the results.<br><br>CONCLUSIONS: Our study provides convincing evidence supporting that longer LTL increases the risk of PCa and BPH in European individuals. Large-scale studies are needed to elucidate the potential mechanisms of LTL in PCa and BPH occurrence.},
}
@article {pmid38084376,
year = {2024},
author = {Sun, K and Li, M and Wu, Y and Wu, Y and Zeng, Y and Zhou, S and Peng, L and Shen, B},
title = {Exploring Causal Relationships between Leukocyte Telomere Length, Sex Hormone-Binding Globulin Levels, and Osteoporosis Using Univariable and Multivariable Mendelian Randomization.},
journal = {Orthopaedic surgery},
volume = {16},
number = {2},
pages = {320-328},
pmid = {38084376},
issn = {1757-7861},
support = {81974347//National Natural Science Foundation of China/ ; 82272561//National Natural Science Foundation of China/ ; 23NSFSC4104//Natural Science Foundation of Sichuan Province/ ; 2021M702351//Postdoctoral Research Foundation of China/ ; 2022YFS0050//Science and Technology Department of Sichuan Province/ ; 2022YFS0061//Science and Technology Department of Sichuan Province/ ; },
mesh = {Humans ; *Mendelian Randomization Analysis ; Sex Hormone-Binding Globulin/genetics ; Leukocytes ; *Osteoporosis/genetics ; Gonadal Steroid Hormones ; Telomere ; },
abstract = {OBJECTIVE: Recent evidence supports that leukocyte telomere length (LTL) may be positively associated with healthy living and inversely correlated with the risk of age-related diseases, including osteoporosis. Furthermore, it is important to note that sex hormone-binding globulin (SHBG) levels play a crucial role in the regulation of osteoporosis by influencing the availability of sex hormones. Hence, this study holds significant importance as it aims to unravel the roles of LTL and SHBG levels and determine which one acts as a predominant intermediary factor in influencing osteoporosis. Using Mendelian randomization (MR), we can gain valuable insights into the intricate relationships between aging, sex hormones, and bone health.<br><br>METHODS: Univariable and multivariable and MR analyses were employed in this study. First, we used genetic variants associated with both LTL, as determined from a study involving 472,174 European participants by Codd et al., and SHBG levels, as identified in a study conducted by Ruth et al. with 370,125 participants, as instrumental variables (IVs). Then we aimed to establish a causal relationship between LTL and SHBG levels and their potential impact on osteoporosis using univariable MR. Finally, we conducted multivariable MR to provide insights into the independent and combined effects of LTL, SHBG levels on osteoporosis risk. We used various MR methods, with the primary analysis employing the inverse-variance weighted (IVW) model.<br><br>RESULTS: Univariable MR analysis reveals a potential causal effect of longer LTL on reduced risk of osteoporosis [odds ratio (OR): 0.85; 95% confidence interval (CI): 0.73-0.99; p&#x2009;=&#x2009;0.03]. Conversely, higher genetically determined SHBG levels affect the risk of osteoporosis positively. (OR: 1.38; 95% CI: 1.09-1.75; p&#x2009;<&#x2009;0.01). We observed a negative causal effect for LTL on the occurrence of SHBG (OR: 0.96; 95% CI 0.94-0.98, p&#x2009;<&#x2009;0.01). After adjustment of using multivariable MR, the causal effect of LTL on osteoporosis (OR: 0.92; 95% CI: 0.84-1.03; p&#x2009;=&#x2009;0.14), and the effect of SHBG on osteoporosis (OR: 1.43; 95% CI: 1.16-1.75; p&#x2009;<&#x2009;0.01) were observed.<br><br>CONCLUSION: Longer LTL may confer a protective effect against osteoporosis. Additionally, the levels of SHBG appear to play a crucial role in mediating the relationship between LTL and osteoporosis. By understanding the interplay between these factors, we can gain valuable insights into the mechanisms underlying bone health and aging and potentially identify new avenues for prevention and intervention strategies.},
}
@article {pmid38077053,
year = {2023},
author = {Sanchez, SE and Gu, J and Golla, A and Martin, A and Shomali, W and Hockemeyer, D and Savage, SA and Artandi, SE},
title = {Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {38077053},
support = {R35 CA197563/CA/NCI NIH HHS/United States ; },
abstract = {Telomere length is an important biomarker of organismal aging and cellular replicative potential, but existing measurement methods are limited in resolution and accuracy. Here, we deploy digital telomere measurement by nanopore sequencing to understand how distributions of human telomere length change with age and disease. We measure telomere attrition and de novo elongation with unprecedented resolution in genetically defined populations of human cells, in blood cells from healthy donors and in blood cells from patients with genetic defects in telomere maintenance. We find that human aging is accompanied by a progressive loss of long telomeres and an accumulation of shorter telomeres. In patients with defects in telomere maintenance, the accumulation of short telomeres is more pronounced and correlates with phenotypic severity. We apply machine learning to train a binary classification model that distinguishes healthy individuals from those with telomere biology disorders. This sequencing and bioinformatic pipeline will advance our understanding of telomere maintenance mechanisms and the use of telomere length as a clinical biomarker of aging and disease.},
}
@article {pmid38077026,
year = {2023},
author = {Tan, KT and Slevin, MK and Leibowitz, ML and Garrity-Janger, M and Li, H and Meyerson, M},
title = {Neotelomeres and Telomere-Spanning Chromosomal Arm Fusions in Cancer Genomes Revealed by Long-Read Sequencing.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {38077026},
support = {R01 HG010040/HG/NHGRI NIH HHS/United States ; R35 CA197568/CA/NCI NIH HHS/United States ; U01 HG010961/HG/NHGRI NIH HHS/United States ; U41 HG010972/HG/NHGRI NIH HHS/United States ; },
abstract = {Alterations in the structure and location of telomeres are key events in cancer genome evolution. However, previous genomic approaches, unable to span long telomeric repeat arrays, could not characterize the nature of these alterations. Here, we applied both long-read and short-read genome sequencing to assess telomere repeat-containing structures in cancers and cancer cell lines. Using long-read genome sequences that span telomeric repeat arrays, we defined four types of telomere repeat variations in cancer cells: neotelomeres where telomere addition heals chromosome breaks, chromosomal arm fusions spanning telomere repeats, fusions of neotelomeres, and peri-centromeric fusions with adjoined telomere and centromere repeats. Analysis of lung adenocarcinoma genome sequences identified somatic neotelomere and telomere-spanning fusion alterations. These results provide a framework for systematic study of telomeric repeat arrays in cancer genomes, that could serve as a model for understanding the somatic evolution of other repetitive genomic elements.},
}
@article {pmid38074328,
year = {2023},
author = {Galindo-Lalana, C and Hoelzl, F and Zahn, S and Habold, C and Cornils, JS and Giroud, S and Smith, S},
title = {Seasonal variation in telomerase activity and telomere dynamics in a hibernating rodent, the garden dormouse (Eliomys quercinus).},
journal = {Frontiers in physiology},
volume = {14},
number = {},
pages = {1298505},
pmid = {38074328},
issn = {1664-042X},
abstract = {Telomere dynamics in hibernating species are known to reflect seasonal changes in somatic maintenance. Throughout hibernation, the periodic states of rewarming, known as inter-bout euthermia or arousals, are associated with high metabolic costs including shortening of telomeres. In the active season, if high energetic resources are available, telomere length can be restored in preparation for the upcoming winter. The mechanism for telomere elongation has not been clearly demonstrated, although the action of the ribonucleoprotein complex, telomerase, has been implicated in many species. Here we tested for levels of telomerase activity in the garden dormouse (Eliomys quercinus) at different seasonal time points throughout the year and across ages from liver tissues of male juveniles to adults. We found that telomerase is active at high levels across seasons (during torpor and inter-bout euthermia, plus in the active season) but that there was a substantial decrease in activity in the month prior to hibernation. Telomerase levels were consistent across age groups and were independent of feeding regime and time of birth (early or late born). The changes in activity levels that we detected were broadly associated with changes in telomere lengths measured in the same tissues. We hypothesise that i) telomerase is the mechanism used by garden dormice for maintenance of telomeres and that ii) activity is kept at high levels throughout the year until pre-hibernation when resources are diverted to increasing fat reserves for overwintering. We found no evidence for a decrease in telomerase activity with age or a final increase in telomere length which has been detected in other hibernating rodents.},
}
@article {pmid38074093,
year = {2023},
author = {Li, B},
title = {Telomere maintenance in African trypanosomes.},
journal = {Frontiers in molecular biosciences},
volume = {10},
number = {},
pages = {1302557},
pmid = {38074093},
issn = {2296-889X},
support = {R01 AI066095/AI/NIAID NIH HHS/United States ; R01 AI127562/AI/NIAID NIH HHS/United States ; R01 GM147378/GM/NIGMS NIH HHS/United States ; },
abstract = {Telomere maintenance is essential for genome integrity and chromosome stability in eukaryotic cells harboring linear chromosomes, as telomere forms a specialized structure to mask the natural chromosome ends from DNA damage repair machineries and to prevent nucleolytic degradation of the telomeric DNA. In Trypanosoma brucei and several other microbial pathogens, virulence genes involved in antigenic variation, a key pathogenesis mechanism essential for host immune evasion and long-term infections, are located at subtelomeres, and expression and switching of these major surface antigens are regulated by telomere proteins and the telomere structure. Therefore, understanding telomere maintenance mechanisms and how these pathogens achieve a balance between stability and plasticity at telomere/subtelomere will help develop better means to eradicate human diseases caused by these pathogens. Telomere replication faces several challenges, and the "end replication problem" is a key obstacle that can cause progressive telomere shortening in proliferating cells. To overcome this challenge, most eukaryotes use telomerase to extend the G-rich telomere strand. In addition, a number of telomere proteins use sophisticated mechanisms to coordinate the telomerase-mediated de novo telomere G-strand synthesis and the telomere C-strand fill-in, which has been extensively studied in mammalian cells. However, we recently discovered that trypanosomes lack many telomere proteins identified in its mammalian host that are critical for telomere end processing. Rather, T. brucei uses a unique DNA polymerase, PolIE that belongs to the DNA polymerase A family (E. coli DNA PolI family), to coordinate the telomere G- and C-strand syntheses. In this review, I will first briefly summarize current understanding of telomere end processing in mammals. Subsequently, I will describe PolIE-mediated coordination of telomere G- and C-strand synthesis in T. brucei and implication of this recent discovery.},
}
@article {pmid38071573,
year = {2024},
author = {Doyle, TJ and Juge, PA and Peljto, AL and Lee, S and Walts, AD and Esposito, AJ and Poli, S and Gill, R and Hatabu, H and Nishino, M and Dellaripa, PF and Weinblatt, ME and Shadick, NA and Demoruelle, MK and Sparks, JA and Rosas, IO and Granger, B and Deane, KD and Crestani, B and Wolters, PJ and Dieudé, P and Lee, JS},
title = {Short peripheral blood leukocyte telomere length in rheumatoid arthritis-interstitial lung disease.},
journal = {Thorax},
volume = {79},
number = {2},
pages = {182-185},
doi = {10.1136/thorax-2023-220022},
pmid = {38071573},
issn = {1468-3296},
support = {R01 HL155522/HL/NHLBI NIH HHS/United States ; R03 HL148484/HL/NHLBI NIH HHS/United States ; K23 HL119558/HL/NHLBI NIH HHS/United States ; R01 HL139897/HL/NHLBI NIH HHS/United States ; L30 HL149048/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Telomere Shortening ; Telomere/genetics ; *Arthritis, Rheumatoid/genetics/complications ; *Lung Diseases, Interstitial/complications ; Smoking ; },
abstract = {Shortened telomere lengths (TLs) can be caused by single nucleotide polymorphisms and loss-of-function mutations in telomere-related genes (TRG), as well as ageing and lifestyle factors such as smoking. Our objective was to determine if shortened TL is associated with interstitial lung disease (ILD) in individuals with rheumatoid arthritis (RA). This is the largest study to demonstrate and replicate that shortened peripheral blood leukocytes-TL is associated with ILD in patients with RA compared with RA without ILD in a multinational cohort, and short PBL-TL was associated with baseline disease severity in RA-ILD as measured by forced vital capacity percent predicted.},
}
@article {pmid38068836,
year = {2023},
author = {Lis, N and Lamnisos, D and Bograkou-Tzanetakou, A and Hadjimbei, E and Tzanetakou, IP},
title = {Preterm Birth and Its Association with Maternal Diet, and Placental and Neonatal Telomere Length.},
journal = {Nutrients},
volume = {15},
number = {23},
pages = {},
pmid = {38068836},
issn = {2072-6643},
mesh = {Infant, Newborn ; Humans ; Pregnancy ; Female ; *Placenta ; *Premature Birth/epidemiology ; Diet/adverse effects ; Family ; Telomere ; },
abstract = {Preterm birth (PTB), a multi-causal syndrome, is one of the global epidemics. Maternal nutrition, but also neonatal and placental telomere length (TL), are among the factors affecting PTB risk. However, the exact relationship between these factors and the PTB outcome, remains obscure. The aim of this review was to investigate the association between PTB, maternal nutrition, and placental-infant TL. Observational studies were sought with the keywords: maternal nutrition, placental TL, newborn, TL, and PTB. No studies were found that included all of the keywords simultaneously, and thus, the keywords were searched in dyads, to reach assumptive conclusions. The findings show that maternal nutrition affects PTB risk, through its influence on maternal TL. On the other hand, maternal TL independently affects PTB risk, and at the same time PTB is a major determinant of offspring TL regulation. The strength of the associations, and the extent of the influence from covariates, remains to be elucidated in future research. Furthermore, the question of whether maternal TL is simply a biomarker of maternal nutritional status and PTB risk, or a causative factor of PTB, to date, remains to be answered.},
}
@article {pmid38066848,
year = {2023},
author = {Niewisch, MR and Beier, F and Savage, SA},
title = {Clinical manifestations of telomere biology disorders in adults.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2023},
number = {1},
pages = {563-572},
pmid = {38066848},
issn = {1520-4383},
mesh = {Adult ; Humans ; Germ-Line Mutation ; *Hematologic Diseases ; *Neoplasms/diagnosis/genetics ; Telomere/genetics ; Biology ; },
abstract = {Telomere biology disorders (TBDs) are a spectrum of inherited bone marrow failure syndromes caused by impaired telomere function due to pathogenic germline variants in genes involved in telomere maintenance. TBDs can affect many organ systems and are often thought of as diseases of childhood. However, TBDs may present in mid- or even late adulthood with features similar to but not always the same as the childhood-onset TBDs. Adult-onset TBDs are often cryptic with isolated pulmonary, liver, or hematologic disease, or cancer, and may lack the classic disease-defining triad of abnormal skin pigmentation, nail dysplasia, and oral leukoplakia. Diagnostics include detection of very short leukocyte telomeres and germline genetic testing. Notably, adult-onset TBDs may show telomeres in the 1st to 10th percentile for age, and some cases may not have an identifiable genetic cause. TBD genetic etiology includes all modes of inheritance, with autosomal dominant the most frequent in adult-onset disease. Variable symptom onset due to incomplete penetrance, variable expressivity, and genetic anticipation add to the diagnostic challenges. Adult-onset TBDs are likely underrecognized, but their correct identification is of utmost importance, since affected patients are faced with numerous clinical complications, including but not limited to an increased risk of malignancies requiring close surveillance for early detection. Currently lung, liver, or hematopoietic cell transplants are the only curative therapeutic approaches but can be complicated by comorbidities, despite improved medical care. This review highlights the challenges of identifying adult-onset TBDs and addresses currently recommended clinical screening measures and therapy options.},
}
@article {pmid38066331,
year = {2023},
author = {Zhai, T and Zilli Vieira, CL and Vokonas, P and Baccarelli, AA and Nagel, ZD and Schwartz, J and Koutrakis, P},
title = {Annual space weather fluctuations and telomere length dynamics in a longitudinal cohort of older men: the Normative Aging Study.},
journal = {Journal of exposure science &amp; environmental epidemiology},
volume = {},
number = {},
pages = {},
pmid = {38066331},
issn = {1559-064X},
abstract = {BACKGROUND: Space weather has been associated with increased risk of cardiovascular diseases in space and flight crew. However, limited research has focused on the ground population, particularly among the elderly who are vulnerable to aging-related diseases.<br><br>OBJECTIVE: We evaluated the association between space weather alterations and biological aging using leukocyte telomere length as a biomarker in healthy elderly men.<br><br>METHODS: We used data from the Normative Aging Study, a longitudinal cohort of healthy elderly men in Massachusetts, USA. Leukocyte telomere length and health information were measured at in-person examinations approximately every three years, contributing to a total of 1,850 visits from 791 participants. Regional space weather information was collected daily, including cosmic ray-induced ionization, neutrons, sunspot number, interplanetary magnetic field, and Kp-index as our exposure of interest. We used mixed-effects models with a random intercept per individual to evaluate the associations between annual averages of space weather indicators and relative telomere length while accounting for participant demographics, environmental parameters, and secular trends.<br><br>RESULTS: The mean age at baseline was 72.36 years. A one-year increment in age is associated with a 1.21% reduction in leukocyte telomere length. In the fully adjusted model accounting for individual and environmental factors, an interquartile range (IQR) increase of annual cosmic ray induced ionization (110.0 ion pairs cm[-3] sec[-1]) was associated with a 17.64% (95%CI: -27.73%, -7.55%) decrease in leukocyte telomere length, equivalent to 15-years age increment. Solar and geomagnetic activities were associated with increased leukocyte telomere length, but the association became absent after adjusting for cosmic ray indicators.<br><br>IMPACT: Galactic cosmic rays may accelerate the aging process in populations on the Earth, despite the protection by the Earth's atmosphere and magnetic field. This research enhances our understanding of how changes in space weather can impact health, highlights potential risks from space to Earth's inhabitants, and helps inform health strategies for vulnerable populations.},
}
@article {pmid38065483,
year = {2024},
author = {Yang, X and Feng, F and Gao, D and Cai, L and Wan, C and Zhou, X and Zeng, Z},
title = {Analysis of telomere length and the relationship with neurocognitive functions in euthymic bipolar disorder: A cross-sectional pilot study.},
journal = {Journal of affective disorders},
volume = {347},
number = {},
pages = {630-634},
doi = {10.1016/j.jad.2023.12.021},
pmid = {38065483},
issn = {1573-2517},
mesh = {Humans ; *Bipolar Disorder/complications/genetics ; Pilot Projects ; Telomere Shortening ; Cross-Sectional Studies ; Telomere/genetics ; Biomarkers ; Neuropsychological Tests ; },
abstract = {BACKGROUND: Telomere shortening has been considered a potential biological marker related to disease susceptibility and aging in psychiatric disorders. However, the relationship between telomere length and bipolar disorder (BD-I and BD-II) is uncertain. Moreover, whether telomere shortening is an independent factor of cognitive impairment in BD patients is still inconclusive.<br><br>METHODS: We explore telomere length and cognitive function in patients with bipolar disorder and the relationship between them. We enrolled three groups (35 patients with euthymic BD-I, 18 with euthymic BD-II, and 38 healthy controls). Telomere length was measured by fluorescent quantitative polymerase chain reaction (q-PCR), and cognitive function was evaluated by the MATRICS Consensus Cognitive Battery (MCCB). SPSS 24.0 was used for statistical analysis.<br><br>RESULTS: The telomere length of euthymic patients with BD-I and BD-II was shorter than that of healthy controls (F&#xa0;=&#xa0;8.228, P&#xa0;=&#xa0;0.001, &#x3b7;[2]&#xa0;=&#xa0;0.176). Telomere length was not significantly different between BD-I and BD-II. Compared to HCs, poor performance was detected in attention and vigilance in BD-I patients (F&#xa0;=&#xa0;3.473, P&#xa0;=&#xa0;0.036). Working memory was positively correlated with telomere length in BD-II patients (Beta&#xa0;=&#xa0;0.5, P&#xa0;=&#xa0;0.041, Adjusted R[2]&#xa0;=&#xa0;0.2).<br><br>CONCLUSIONS: The current study provided evidence of shortened telomere length in euthymic BD patients, indicating that telomere shortening might be a promising biomarker of susceptibility to bipolar disorder. The telomere length predicted the working memory in BD-II patients. Further studies are needed to clarify the role of accelerated aging on cognitive functioning in a young group of patients with BD.},
}
@article {pmid38063002,
year = {2023},
author = {Belić, M and Sopić, M and Roksandić-Milenković, M and Ćeriman, V and Guzonijić, A and Vukašinović, A and Ostanek, B and Dimić, N and Jovanović, D and Kotur-Stevuljević, J},
title = {Correlation of Short Leukocyte Telomeres and Oxidative Stress with the Presence and Severity of Lung Cancer Explored by Principal Component Analysis.},
journal = {Folia biologica},
volume = {69},
number = {2},
pages = {59-68},
doi = {10.14712/fb2023069020059},
pmid = {38063002},
issn = {0015-5500},
support = {451-03-9/2021-14/200161//Ministarstvo Prosvete, Nauke i Tehnolo&#x161;kog Razvoja/ ; },
mesh = {Humans ; *Telomere Shortening ; *Lung Neoplasms/genetics/metabolism ; Principal Component Analysis ; Leukocytes/metabolism ; Oxidative Stress ; Telomere ; },
abstract = {Lung cancer (LC) is the second most common malignancy and leading cause of cancer death. The potential "culprit" for local and systemic telomere shortening in LC patients is oxidative stress. We investigated the correlation between the peripheral blood leukocyte (PBL) telomere length (TL) and the presence/severity of LC and oxidative stress, and its usefulness as LC diagnostic marker. PBL TL was measured in 89 LC patients and 83 healthy subjects using the modified Cawthon RTq-PCR method. The relative PBL TL, found to be a potential diagnostic marker for LC with very good accuracy (P < 0.001), was significantly shorter in patients compared to the control group (CG) (P < 0.001). Significantly shorter telomeres were found in patients with LC TNM stage IV than in patients with stages I-III (P = 0.014), in patients without therapy compared to those on therapy (P = 0.008), and in patients with partial response and stable/progressive disease compared to those with complete response (P = 0.039). The total oxidant status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB) and C-reactive protein (CRP) were significantly higher in patients compared to CG (P < 0.001) and correlated negatively with TL in both patients and CG (P < 0.001). PCA showed a relation between PAB and TL, and between the EGFR status and TL. Oxidative stress and PBL telomere shortening are probably associated with LC development and progression.},
}
@article {pmid38054014,
year = {2023},
author = {Pelletier, D and Blier, PU and Vézina, F and Dufresne, F and Paquin, F and Christen, F and Guillemette, M},
title = {Under pressure-exploring partner changes, physiological responses and telomere dynamics in northern gannets across varying breeding conditions.},
journal = {PeerJ},
volume = {11},
number = {},
pages = {e16457},
pmid = {38054014},
issn = {2167-8359},
mesh = {Humans ; Animals ; *Antioxidants ; *Birds/genetics ; Telomere/genetics ; Weight Loss/genetics ; Breeding ; Inflammation/genetics ; Oxygen ; },
abstract = {BACKGROUND: Life history theory predicts trade-offs between reproduction and survival in species like the northern gannet (Morus bassanus). During breeding, demanding foraging conditions lead them to expand their foraging range and diversify their diet, increasing the risk of reproductive failure. Changing partners may enhance breeding success but lead to more physiological costs.<br><br>METHODS: To investigate the physiological costs of reproduction upon partner changes, we measured and compared 21 biomarkers related to telomere dynamics, oxidative stress, inflammation, hematology, nutritional status, and muscle damage. We used a longitudinal approach with gannets (n&#xa0;=&#xa0;38) over three contrasting years (2017, 2018 and 2019).<br><br>RESULTS: Our results suggest that annual breeding conditions exert a greater influence on physiological changes than partnership status. Individuals that changed partner experienced greater short-term stress than retained partners. This transient increase in stress was marked by short-term increases in oxidative lipid damage, lower antioxidant capacity, signs of inflammation, and greater weight loss than individuals that retained partners. During favorable conditions, individuals that changed mates had stabilized telomere length, decreased antioxidant capacity, glucose concentration, and muscle damage, along with increased oxygen transport capacity. Conversely, unfavorable breeding conditions led to increased telomere attrition, stabilized antioxidant capacity, decreased inflammation susceptibility, diminished oxygen transport capacity, and increased muscle damage. In the cases where partners were retained, distinct physiological changes were observed depending on the year's conditions, yet the telomere dynamics remained consistent across both partnership status categories. During the favorable year, there was an increase in unsaturated fatty acids and oxygen transport capacity in the blood, coupled with a reduction in inflammation potential and protein catabolism. In contrast, during the unfavorable year in the retained mates, we observed an increase in oxidative DNA damage, antioxidant capacity, weight loss, but a decrease in inflammation susceptibility as observed in changed mates.<br><br>DISCUSSION: Our study shows that behavioral flexibility such as mate switching can help seabirds cope with the challenges of food scarcity during reproduction, but these coping strategies may have a negative impact on physiological status at the individual level. In addition, the marked reduction in telomere length observed during harsh conditions, coupled with the stabilization of telomere length in favorable conditions, highlights the long-term physiological impact of annual breeding conditions on seabirds. These findings underscore the effect on their potential survival and fitness, emphasizing that the influence of annual breeding conditions is greater than that of partnership status.},
}
@article {pmid38052712,
year = {2024},
author = {Volders, ELD and Meijer, C and Steeneken, LS and Lubberts, S and Zwart, N and van Roon, AM and Lefrandt, JD and de Jong, IJ and Demaria, M and Nuver, J and Gietema, JA},
title = {Change in telomere length and cardiovascular risk factors in testicular cancer survivors.},
journal = {Urologic oncology},
volume = {42},
number = {1},
pages = {24.e1-24.e8},
doi = {10.1016/j.urolonc.2023.10.010},
pmid = {38052712},
issn = {1873-2496},
mesh = {Male ; Humans ; *Cardiovascular Diseases/genetics ; *Metabolic Syndrome/complications/genetics ; *Testicular Neoplasms/drug therapy/genetics ; Prospective Studies ; Cisplatin/adverse effects ; Risk Factors ; Telomere Shortening ; Heart Disease Risk Factors ; Triglycerides ; Survivors ; Telomere/genetics ; *Hypogonadism/complications/genetics ; },
abstract = {BACKGROUND: Testicular cancer (TC) survivors cured with chemotherapy (CT) are prone to develop cardiovascular diseases, as part of an accelerated aging phenotype. A mechanism contributing to these events can be telomere shortening.<br><br>PATIENTS AND METHODS: In a prospective cohort of patients with disseminated TC who received cisplatin-based CT, mean absolute leukocyte telomere length (TL) was measured before and 1 year after start of treatment. Cardiovascular risk factors, including development of the metabolic syndrome and hypogonadism, were assessed before and up to 5 years after CT.<br><br>RESULTS: For the whole group (n&#x202f;=&#x202f;55), TL did not change 1 year after CT (5.7 (2.2-13.4) vs. 5.8 kb (1.6-19.2), P&#x202f;=&#x202f;0.335). At baseline, patients with a BMI >30 kg/m[2] (n = 12) had shorter TL (4.9 (2.2-13.4) vs. 6.3 kb (3.1-12.9), P = 0.045), while no age-dependent differences were measured. Patients with TL shortening after 1 year (n = 7) showed a significant increase in diastolic blood pressure (P = 0.007) and triglycerides (P = 0.003), compared to those with unchanged TL. There was no association between telomere shortening after 1 year or short TL at baseline (n = 7+11) and development of metabolic syndrome (25% vs. 21%; P = 0.777), or hypogonadism (38% vs. 17%; P = 0.120) after 5 years.<br><br>CONCLUSIONS: A small subset of TC patients treated with cisplatin-based CT showed telomere shortening 1 year after treatment. This shortening was associated to a rise in diastolic blood pressure and triglycerides, but not to newly developed metabolic syndrome and hypogonadism after 5 years.},
}
@article {pmid38047504,
year = {2024},
author = {Pepke, ML},
title = {Telomere length is not a useful tool for chronological age estimation in animals.},
journal = {BioEssays : news and reviews in molecular, cellular and developmental biology},
volume = {46},
number = {2},
pages = {e2300187},
doi = {10.1002/bies.202300187},
pmid = {38047504},
issn = {1521-1878},
mesh = {Animals ; *Telomere Shortening/genetics ; *Vertebrates/genetics ; Cell Division ; Oxidative Stress ; Telomere/genetics ; },
abstract = {Telomeres are short repetitive DNA sequences capping the ends of chromosomes. Telomere shortening occurs during cell division and may be accelerated by oxidative damage or ameliorated by telomere maintenance mechanisms. Consequently, telomere length changes with age, which was recently confirmed in a large meta-analysis across vertebrates. However, based on the correlation between telomere length and age, it was concluded that telomere length can be used as a tool for chronological age estimation in animals. Correlation should not be confused with predictability, and the current data and studies suggest that telomeres cannot be used to reliably predict individual chronological age. There are biological reasons for why there is large individual variation in telomere dynamics, which is mainly due to high susceptibility to a wide range of environmental, but also genetic factors, rendering telomeres unfeasible as a tool for age estimation. The use of telomeres for chronological age estimation is largely a misguided effort, but its occasional reappearance in the literature raises concerns that it will mislead resources in wildlife conservation.},
}
@article {pmid38047499,
year = {2024},
author = {Rai, R and Sodeinde, T and Boston, A and Chang, S},
title = {Telomeres cooperate with the nuclear envelope to maintain genome stability.},
journal = {BioEssays : news and reviews in molecular, cellular and developmental biology},
volume = {46},
number = {2},
pages = {e2300184},
doi = {10.1002/bies.202300184},
pmid = {38047499},
issn = {1521-1878},
support = {RO1GM141350/GF/NIH HHS/United States ; RO1GM141350/GM/NIGMS NIH HHS/United States ; RO1GM141350/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Humans ; *Nuclear Envelope/metabolism ; *Telomere/genetics/metabolism ; Telomere-Binding Proteins/chemistry/genetics/metabolism ; DNA/metabolism ; Genomic Instability ; Mammals/genetics ; },
abstract = {Mammalian telomeres have evolved safeguards to prevent their recognition as DNA double-stranded breaks by suppressing the activation of various DNA sensing and repair proteins. We have shown that the telomere-binding proteins TRF2 and RAP1 cooperate to prevent telomeres from undergoing aberrant homology-directed recombination by mediating t-loop protection. Our recent findings also suggest that mammalian telomere-binding proteins interact with the nuclear envelope to maintain chromosome stability. RAP1 interacts with nuclear lamins through KU70/KU80, and disruption of RAP1 and TRF2 function result in nuclear envelope rupture, promoting telomere-telomere recombination to form structures termed ultrabright telomeres. In this review, we discuss the importance of the interactions between shelterin components and the nuclear envelope to maintain telomere homeostasis and genome stability.},
}
@article {pmid38041119,
year = {2023},
author = {Xiong, L and Yang, G and Guo, T and Zeng, Z and Liao, T and Li, Y and Li, Y and Chen, F and Yang, S and Kang, L and Liang, Z},
title = {17-year follow-up of association between telomere length and all-cause mortality, cardiovascular mortality in individuals with metabolic syndrome: results from the NHANES database prospective cohort study.},
journal = {Diabetology &amp; metabolic syndrome},
volume = {15},
number = {1},
pages = {247},
pmid = {38041119},
issn = {1758-5996},
support = {No. 2021A374//administration of Traditional Chinese Medicine of Jiangxi Province, China (grant No. 2021A374)/ ; No. KCXFZ20201221173600001 and JCYJ20220818102605013//the Science and Technology Planning Project of Shenzhen City, Guangdong Province, China/ ; No. KCXFZ20201221173600001 and JCYJ20220818102605013//the Science and Technology Planning Project of Shenzhen City, Guangdong Province, China/ ; },
abstract = {BACKGROUND: The relationship between leukocyte telomere length (LTL) and mortality risk in individuals with metabolic syndrome (MetS) remains poorly understood. This study aimed to investigate the association between telomere length and long-term all-cause mortality, and cardiovascular disease (CVD) mortality, in individuals with MetS in the United States.<br><br>METHODS: A total of 1980 participants with MetS aged 18 years or older from the National Health and Nutrition Examination Survey (NHANES) prospective cohort study (1999-2002) were included in this cohort study. Medical records review was used to identify the cause of deaths as of December 2018. We employed Kaplan-Meier curves, fitted curves, and Cox proportional hazards regression models to estimate hazard ratios (HRs) for all-cause and CVD mortality, stratified by tertiles of LTL.<br><br>RESULTS: Over a median follow-up of 17.75 years of participants with metabolic syndrome, 819 deaths occurred, including 231 cardiovascular deaths. After adjusting for multiple covariates, participants with shorter telomere length had a significantly higher risk of all-cause mortality (HR, 1.33; 95% CI, 1.11-1.6) and CVD mortality (HR, 1.36; 95% CI, 0.96-1.93) compared with those in the highest tertile of telomere length. All-cause mortality (P&#x2009;<&#x2009;0.001) and cardiovascular disease mortality (P&#x2009;=&#x2009;0.028) followed a similar pattern across tertiles of telomere length.<br><br>CONCLUSION: In individuals with MetS, shorter telomere length is associated with increased risks of death from cardiovascular disease and all causes. The underlying mechanisms and clinical implications of these findings require additional investigation.},
}
@article {pmid38040384,
year = {2024},
author = {Prévot D'Alvise, N and Ascensio, E and Richard, S},
title = {Influence of EE2 exposure, age and sex on telomere length in European long-snouted seahorse (Hippocampus guttulatus).},
journal = {General and comparative endocrinology},
volume = {346},
number = {},
pages = {114419},
doi = {10.1016/j.ygcen.2023.114419},
pmid = {38040384},
issn = {1095-6840},
mesh = {Humans ; Male ; Animals ; Female ; Aged ; *Telomerase/genetics/metabolism ; *Smegmamorpha/genetics/metabolism ; Telomere Homeostasis ; Telomere/genetics/metabolism ; RNA, Messenger ; },
abstract = {After a Telomere Lengthening in juvenile stage, a progressive telomere shortening occurs with age despite higher telomerase level. Telomere Length (TL) may also reflect past physiological state such as a chronic chemical stress. Several studies have revealed a correlation between TL, ageing and/or sex in vertebrates, including teleosts; however, the patterns of telomere dynamics with telomerase mRNA expression, sex, lifespan or chemical stress in teleosts are unclear. The first aim of this study is to verify if telomere length is age and sex-dependent. The second aim is to consider if TL is a useful indicator of stress response in European long-snouted seahorse, Hippocampus guttulatus, an ectothermic and non-model system. We showed that after telomere lengthening during the juvenile stage, a telomeric attrition became significant in sexually mature individuals (p = 0.042). TL decreased in older seahorses despite the presence of somatic telomerase mRNA expression at all life stages studied. There was no difference in TL between males and females, but telomerase mRNA expression was consistently higher in females than males. Exposure to EE2 had no effect on TL in young seahorses, but was correlated with a significant increase in telomerase mRNA expression and various physiological disruptions. Here, a growth retardation of -10 % for body length (p = 0.016) and approximately -45 % for mass (p = 0.001) compared to healthy juvenile seahorses was observed. Our data suggest that telomere dynamics alone should not be used as a marker of EE2 exposure in juvenile seahorses.},
}
@article {pmid38039691,
year = {2024},
author = {Zhang, Y and Zhang, C and Zhang, C and Bin, X and Jiang, J and Huang, C},
title = {Leukocyte telomere length mediates the association between cadmium exposure and cognitive function in US older adults.},
journal = {Journal of psychiatric research},
volume = {169},
number = {},
pages = {166-173},
doi = {10.1016/j.jpsychires.2023.11.023},
pmid = {38039691},
issn = {1879-1379},
mesh = {Male ; Humans ; United States ; Middle Aged ; Aged ; Female ; Nutrition Surveys ; *Cadmium/toxicity ; *Cognition ; Leukocytes ; Telomere ; },
abstract = {BACKGROUND: Long-term exposure to cadmium-polluted environments may lead to shortened leukocyte telomere length and cognitive decline. This study aims to investigate (1) the associations among blood cadmium levels, leukocyte telomere length, and cognitive function, and (2) the mediating role of leukocyte telomere length between blood cadmium levels and cognitive function among older adults in the United States.<br><br>METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Cadmium exposure level was assessed by measuring cadmium levels in blood samples. Leukocyte telomere length was measured by quantitative polymerase chain reaction, and cognitive function was measured by the digit symbol substitution test (DSST).<br><br>RESULTS: A total of 2185 older adults aged over 60 were included in this study, comprising 1109 (49.65%) males. Elevated blood cadmium levels were significantly associated with the risk of a decline in cognitive function (&#x3b2;&#xa0;=&#xa0;- 2.842, p&#xa0;=&#xa0;0.018). Shorter leukocyte telomere lengths were significantly associated with a higher risk of a decline in cognitive function (&#x3b2;&#xa0;=&#xa0;4.144, p&#xa0;=&#xa0;0.020). The total indirect effect on the blood cadmium level and cognitive function via leukocyte telomere length was - 0.218 (p&#xa0;=&#xa0;0.012). The mediation effect was estimated to be 0.218/2.084&#xa0;&#xd7;&#xa0;100%&#xa0;=&#xa0;10.46%.<br><br>CONCLUSION: The findings suggest that cadmium exposure may increase the risk of cognitive impairment by causing shortened leukocyte telomere length.},
}
@article {pmid38035695,
year = {2023},
author = {Cottin, V and Kolb, M},
title = {Leukocyte telomere length: the dawn of a new era of personalised medicine in fibrotic interstitial lung diseases?.},
journal = {The European respiratory journal},
volume = {62},
number = {5},
pages = {},
doi = {10.1183/13993003.01852-2023},
pmid = {38035695},
issn = {1399-3003},
mesh = {Humans ; *Pulmonary Fibrosis/genetics/therapy ; Precision Medicine ; *Lung Diseases, Interstitial/genetics/therapy ; Fibrosis ; Leukocytes ; Immunosuppression Therapy ; Telomere/genetics ; },
}
@article {pmid38034012,
year = {2023},
author = {Bai, C and Shen, Z and Qiu, B and Zhang, S},
title = {Leukocyte telomere length is associated with increased risk of endometriosis: a bidirectional two-sample Mendelian randomization study.},
journal = {Frontiers in endocrinology},
volume = {14},
number = {},
pages = {1272200},
pmid = {38034012},
issn = {1664-2392},
mesh = {Female ; Humans ; *Endometriosis/genetics ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Leukocytes ; Telomere ; },
abstract = {BACKGROUND: Endometriosis (EMs) is a common gynecological disorder. Observational studies on the relationship between leukocyte telomere length (LTL) and EMs have shown conflicting results. The purpose of this study was to evaluate the precise causal relationship between LTL and EMs using Mendelian randomization (MR) methodology.<br><br>METHODS: We employed MR to assess the causal relationship between LTL and EMs. Summary data from several large-scale genome-wide association studies (GWAS) were used for bidirectional two-sample MR analysis. Sensitivity analyses were conducted to ensure the robustness of our results. All analyses were also replicated in another completely independent EMs dataset.<br><br>RESULTS: Our MR analysis indicated that genetically predicted longer LTL increased the risk of EMs (IVW: discovery, OR=1.169, 95%CI: 1.059-1.290, p=0.002; validation, OR=1.302, 95%CI: 1.140-1.487, p=0.000), while EMs had no causal impact on LTL (IVW: discovery, OR=1.013, 95%CI: 1.000-1.027, p=0.056; IVW: validation, OR=1.005, 95%CI: 0.995-1.015, p=0.363). Causal estimates were supported by various calculation models (including MR-Egger, Weighted median, MR-PRESSO, and MR-RAPS). Heterogeneity and pleiotropy analyses also indicated robustness of the results.<br><br>CONCLUSION: Our findings substantiate the idea that a genetically predicted longer LTL elevates the risk of EMs, with no influence of EMs on LTL risk. This research bolsters the causal link between LTL and EMs, overcoming the constraints of earlier observational studies. It implies that LTL may potentially function as a biomarker for EMs, opening up novel possibilities for EMs prevention and treatment.},
}
@article {pmid38030615,
year = {2023},
author = {Barcenilla, BB and Meyers, AD and Castillo-González, C and Young, P and Min, JH and Song, J and Phadke, C and Land, E and Canaday, E and Perera, IY and Bailey, SM and Aquilano, R and Wyatt, SE and Shippen, DE},
title = {Arabidopsis telomerase takes off by uncoupling enzyme activity from telomere length maintenance in space.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {7854},
pmid = {38030615},
issn = {2041-1723},
support = {R01 GM065383/GM/NIGMS NIH HHS/United States ; },
mesh = {Telomere Homeostasis ; *Arabidopsis/metabolism ; *Telomerase/genetics/metabolism ; *Arabidopsis Proteins/genetics/metabolism ; Telomere-Binding Proteins/metabolism ; Telomere/genetics/metabolism ; Plants/metabolism ; },
abstract = {Spaceflight-induced changes in astronaut telomeres have garnered significant attention in recent years. While plants represent an essential component of future long-duration space travel, the impacts of spaceflight on plant telomeres and telomerase have not been examined. Here we report on the telomere dynamics of Arabidopsis thaliana grown aboard the International Space Station. We observe no changes in telomere length in space-flown Arabidopsis seedlings, despite a dramatic increase in telomerase activity (up to 150-fold in roots), as well as elevated genome oxidation. Ground-based follow up studies provide further evidence that telomerase is induced by different environmental stressors, but its activity is uncoupled from telomere length. Supporting this conclusion, genetically engineered super-telomerase lines with enhanced telomerase activity maintain wildtype telomere length. Finally, genome oxidation is inversely correlated with telomerase activity levels. We propose a redox protective capacity for Arabidopsis telomerase that may promote survivability in harsh environments.},
}
@article {pmid38029531,
year = {2024},
author = {Zhou, Q and Wang, Y and Xin, C and Wei, X and Yao, Y and Xia, L},
title = {Identification of telomere-associated gene signatures to predict prognosis and drug sensitivity in glioma.},
journal = {Computers in biology and medicine},
volume = {168},
number = {},
pages = {107750},
doi = {10.1016/j.compbiomed.2023.107750},
pmid = {38029531},
issn = {1879-0534},
mesh = {Humans ; *Glioma/drug therapy/genetics ; Telomere/genetics ; *Brain Neoplasms/drug therapy/genetics ; Cluster Analysis ; Tumor Microenvironment ; Dual-Specificity Phosphatases ; Mitogen-Activated Protein Kinase Phosphatases ; },
abstract = {OBJECTIVE: Gliomas are a heterogeneous group of brain tumors with distinct biological and clinical properties, leading to significant mortality and morbidity. Emerging evidence shows telomere maintenance has implicated in glioma susceptibility and prognosis. In this study, we comprehensively analyzed gene signatures related to telomere maintenance in glioma and their predictive values for predicting the prognosis and drug sensitivity in glioma.<br><br>METHODS: We initially identified telomere-related genes differentially expressed between low-grade glioma (LGG) and glioblastoma (GBM) and accordingly developed a risk model by univariate and multivariate Cox analysis to assess the expressions of telomere-related genes across the risk groups. Finally, to assess these genes in immune function the anti-tumor medications often used in the clinical treatment of glioma, we computed immune cell infiltration analysis and drug sensitivity analysis.<br><br>RESULTS: The consensus clustering analysis identified 20 telomere-related genes which split LGG patients into two distinct subtypes. The patient survival, the expressions of key telomere-related DEGs, and immune cell infiltration significantly differed between Cluster 1 and Cluster 2. The LASSO risk model [riskScore=(0.086)*HOXA7+(0.242)*WEE1+(0.247)*IGF2BP3+(0.052)*DUSP10] showed significant differences regarding the 1-, 3-, 5-year overall survival, immune cell infiltration, and drug sensitivity between high- and low-risk groups. The predictive nomogram constructed to quantify the survival probability of each sample at 1, 3, and 5 years was consistent with the actual patient survival.<br><br>CONCLUSION: Our comprehensive characterization of telomere-associated gene signatures in glioma reveals their possible roles in the development, tumor microenvironment, and prognosis. The study provides some suggestive relationships between four telomere-related genes (HOXA7, WEE1, IGF2BP3, and DUSP10) and glioma prognosis.},
}
@article {pmid38029511,
year = {2024},
author = {Benites-Zapata, VA and Ulloque-Badaracco, JR and Alarcón-Braga, EA and Fernández-Alonso, AM and López-Baena, MT and Pérez-López, FR},
title = {Telomerase activity and telomere length in women with breast cancer or without malignancy: A systematic review and meta-analysis.},
journal = {Maturitas},
volume = {180},
number = {},
pages = {107882},
doi = {10.1016/j.maturitas.2023.107882},
pmid = {38029511},
issn = {1873-4111},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; *Telomerase/metabolism ; Telomere/metabolism ; },
abstract = {AIM: We performed a systematic review and meta-analysis to assess whether telomerase activity and telomere length are associated with breast cancer.<br><br>METHODS: PubMed, Web of Science, Embase, LILACS, Scielo, Embase, and CNKI databases were searched to obtain relevant articles published through May 10, 2023, following PRISMA guidelines and a registered PROSPERO protocol (CRD42022335402). We included observational studies reporting telomerase activity or telomere length in patients with breast cancer compared with women with benign lesions or normal tissue (control women). The Newcastle-Ottawa Scale was used to evaluate the quality of studies. Data were expressed as odds ratios (OR) and 95&#xa0;% confidence intervals (CI). Random effects and inverse variance methods were used to meta-analyze associations. The I[2] test was used to assess heterogeneity.<br><br>RESULTS: The meta-analysis of telomerase shows significantly greater activity in patients with breast cancer than in those without malignancies (OR&#xa0;=&#xa0;23.46, 95&#xa0;% CI 14.07-39.11, p&#xa0;<&#xa0;0.00001, I[2]&#xa0;=&#xa0;72&#xa0;%). There were non-significant differences in relative telomere length (OR&#xa0;=&#xa0;1.16, 95&#xa0;% CI&#xa0;=&#xa0;0.90-1.49, p&#xa0;=&#xa0;0.26, I[2]&#xa0;=&#xa0;86&#xa0;%) and leukocyte telomere length (OR&#xa0;=&#xa0;2.32, 95&#xa0;% CI&#xa0;=&#xa0;0.89-6.08, p&#xa0;=&#xa0;0.09, I[2]&#xa0;=&#xa0;98&#xa0;%) between women with and without breast cancer. In subgroup analyses by world regions of studies, both telomerase activity and telomere length displayed the same trends as in their respective meta-analyses. In sensitivity analyses, variables showed their respective same trends.<br><br>CONCLUSION: Telomerase activity is higher in patients with breast cancer than in women without malignancies. There were no significant differences in either relative telomere length or leukocyte telomere length in women with and without breast cancer. PROSPERO protocol CRD42022335402.},
}
@article {pmid38028989,
year = {2023},
author = {Qin, B},
title = {Can Antidiabetic Medications Affect Telomere Length in Patients with Type 2 Diabetes? A Mini-Review.},
journal = {Diabetes, metabolic syndrome and obesity : targets and therapy},
volume = {16},
number = {},
pages = {3739-3750},
pmid = {38028989},
issn = {1178-7007},
abstract = {The fight against aging is an eternal pursuit of humankind. The aging rate of patients with type 2 diabetes mellitus (T2DM) is higher than that of healthy individuals. Reducing the aging rate of patients with T2DM and extending their life expectancy are challenges that endocrinologists are eager to overcome. Many studies have shown that antidiabetic medications have potent anti-aging potential. Telomeres are repetitive DNA sequences located at the ends of chromosomes, and telomere shortening is a hallmark of aging. This review summarizes clinical trials that have explored the association between antidiabetic medications and telomere length (TL) in patients with T2DM and explore the mystery of delaying aging in patients with T2DM from the perspective of telomeres. Various antidiabetic medications may have different effects on TL in patients with T2DM. Metformin and sitagliptin may protect telomeres in patients with T2DM, while exogenous insulin may promote telomere shortening in patients with T2DM. The effect of acarbose and glyburide on TL in patients with T2DM is still uncertain due to the absence of evidence from longitudinal studies.},
}
@article {pmid38026244,
year = {2023},
author = {Almuraikhy, S and Sellami, M and Al-Amri, HS and Domling, A and Althani, AA and Elrayess, MA},
title = {Impact of Moderate Physical Activity on Inflammatory Markers and Telomere Length in Sedentary and Moderately Active Individuals with Varied Insulin Sensitivity.},
journal = {Journal of inflammation research},
volume = {16},
number = {},
pages = {5427-5438},
pmid = {38026244},
issn = {1178-7031},
abstract = {INTRODUCTION: Physical activity-associated immune response plays a crucial role in the aging process. This study aimed to determine the impact of short-term moderate physical activity on cytokine levels, oxidative stress markers, and telomere length in lean/overweight young subjects.<br><br>METHODS: Fasting blood samples were collected from 368 participants at Qatar Biobank. Based on their homeostatic model assessment of insulin resistance (HOMA-IR), participants were categorized as insulin sensitive (IS) or insulin resistant (IR). Subsequently, they were divided into four groups: sedentary IS (n = 90), sedentary IR (n = 90), moderately active IS (n = 94), and moderately active IR (n = 94). Moderate physical activity was defined as walking at least two days per week for more than 150 minutes, as determined by physical activity questionnaires. Serum samples were analyzed for circulating inflammatory cytokines (IL-1&#x3b2;, IL-1RA, IL-6, IL-10, IL-22, MCP-1/CCL2, TNF-&#x3b1;), as well as antioxidant enzyme levels (SOD and catalase). Telomere lengths were measured in the respective DNA samples.<br><br>RESULTS: Moderately active IR participants exhibited significantly lower SOD activity, while catalase activity did not show significant differences. Moderately active IS participants had higher IL-6 and IL-10 levels compared to sedentary IS participants, with no significant differences observed in the IR counterparts. Telomere length did not significantly differ between the physically active and sedentary groups.<br><br>CONCLUSION: This study highlights the potential anti-inflammatory and anti-oxidative stress effects of moderate physical activity in individuals with insulin sensitivity and insulin resistance. However, no significant changes in telomere length were observed, suggesting a complex relationship between physical activity and the aging process. Further research is needed to fully understand the underlying mechanisms and optimize the balance between anti-inflammation and anti-oxidation through exercise and lifestyle adjustments.},
}
@article {pmid38024356,
year = {2023},
author = {Messerlian, N and Zgheib, N and Chokor, FAZ and Nasrallah, M and Tamim, H and Nasreddine, L},
title = {Fructose intake and its association with relative telomere length: an exploratory study among healthy Lebanese adults.},
journal = {Frontiers in nutrition},
volume = {10},
number = {},
pages = {1270124},
pmid = {38024356},
issn = {2296-861X},
abstract = {INTRODUCTION: Shorter relative telomere length (RTL) has been associated with increased incidence of morbidity. Although still disputed, available evidence suggests that dietary factors, including sugar-sweetened beverages (SSB) may be linked with shorter RTL. It was argued that the link between SSB and RTL may be explained by the sugar content of these beverages, and specifically fructose given its impact on oxidative stress and the inflammatory response. However, none of the existing studies have examined the specific link between fructose intake and RTL. This exploratory study aimed at (1) assessing the intake of dietary fructose (total, added and natural) in Lebanese healthy adults and (2) examining dietary fructose as a predictor of short telomere length.<br><br>METHODS: Following a cross-sectional design (n = 282), anthropometric and biochemical data were collected. RTL was assessed by utilizing real-time polymerase chain reaction (RT-qPCR) to amplify both telomere and single-copy gene segments. Dietary intake was evaluated using a culture-specific food frequency questionnaire (FFQ). Intakes of added fructose, naturally-occurring fructose, and total fructose were estimated.<br><br>RESULTS: Mean intakes of added and natural fructose were of 39.03 &#xb1; 34.12 and 12.28 &#xb1; 8.59 g/day, respectively, representing 4.80 &#xb1; 3.56 and 1.78 &#xb1; 1.41% of total energy intake (EI). Mean total fructose intake was of 51.31 &#xb1; 35.55 g/day, contributing 6.58 &#xb1; 3.71% EI. Higher intakes of total and added fructose were significantly associated with shorter RTL 2nd RTL tertile as compared to the 3rd RTL tertile; relative risk ratio (RRR) = 3.10 [95% confidence interval (CI): 1.38, 6.94] and RRR = 2.33 (95% CI: 1.02, 5.36), respectively after adjustment for confounders identified using a directed acyclic graph (DAG).<br><br>CONCLUSION: In conclusion, although we could not observe a dose-dependent relation between fructose intakes and RTL shortening and although the study is limited by its small sample size, the findings suggest that total and added dietary fructose intakes may be associated with shorter RTL. Larger studies, of longitudinal nature, are needed to further confirm the study findings.},
}
@article {pmid38023918,
year = {2023},
author = {Wang, L and Li, LL and Chen, L and Zhang, RG and Zhao, SW and Yan, H and Gao, J and Chen, X and Si, YJ and Chen, Z and Liu, H and Xie, XM and Zhao, W and Han, B and Qin, X and Jia, KH},
title = {Telomere-to-telomere and haplotype-resolved genome assembly of the Chinese cork oak (Quercus variabilis).},
journal = {Frontiers in plant science},
volume = {14},
number = {},
pages = {1290913},
pmid = {38023918},
issn = {1664-462X},
abstract = {The Quercus variabilis, a deciduous broadleaved tree species, holds significant ecological and economical value. While a chromosome-level genome for this species has been made available, it remains riddled with unanchored sequences and gaps. In this study, we present a nearly complete comprehensive telomere-to-telomere (T2T) and haplotype-resolved reference genome for Q. variabilis. This was achieved through the integration of ONT ultra-long reads, PacBio HiFi long reads, and Hi-C data. The resultant two haplotype genomes measure 789 Mb and 768 Mb in length, with a contig N50 of 65 Mb and 56 Mb, and were anchored to 12 allelic chromosomes. Within this T2T haplotype-resolved assembly, we predicted 36,830 and 36,370 protein-coding genes, with 95.9% and 96.0% functional annotation for each haplotype genome. The availability of the T2T and haplotype-resolved reference genome lays a solid foundation, not only for illustrating genome structure and functional genomics studies but also to inform and facilitate genetic breeding and improvement of cultivated Quercus species.},
}
@article {pmid38023478,
year = {2023},
author = {Sun, M and Yao, C and Shu, Q and He, Y and Chen, G and Yang, G and Xu, S and Liu, Y and Xue, Z and Wu, J},
title = {Telomere-to-telomere pear (Pyrus pyrifolia) reference genome reveals segmental and whole genome duplication driving genome evolution.},
journal = {Horticulture research},
volume = {10},
number = {11},
pages = {uhad201},
pmid = {38023478},
issn = {2662-6810},
abstract = {Previously released pear genomes contain a plethora of gaps and unanchored genetic regions. Here, we report a telomere-to-telomere (T2T) gap-free genome for the red-skinned pear, 'Yunhong No. 1' (YH1; Pyrus pyrifolia), which is mainly cultivated in Yunnan Province (southwest China), the pear's primary region of origin. The YH1 genome is 501.20 Mb long with a contig N50 length of 29.26 Mb. All 17 chromosomes were assembled to the T2T level with 34 characterized telomeres. The 17 centromeres were predicted and mainly consist of centromeric-specific monomers (CEN198) and long terminal repeat (LTR) Gypsy elements (≥74.73%). By filling all unclosed gaps, the integrity of YH1 is markedly improved over previous P. pyrifolia genomes ('Cuiguan' and 'Nijisseiki'). A total of 1531 segmental duplication (SD) driven duplicated genes were identified and enriched in stress response pathways. Intrachromosomal SDs drove the expansion of disease resistance genes, suggesting the potential of SDs in adaptive pear evolution. A large proportion of duplicated gene pairs exhibit dosage effects or sub-/neo-functionalization, which may affect agronomic traits like stone cell content, sugar content, and fruit skin russet. Furthermore, as core regulators of anthocyanin biosynthesis, we found that MYB10 and MYB114 underwent various gene duplication events. Multiple copies of MYB10 and MYB114 displayed obvious dosage effects, indicating role differentiation in the formation of red-skinned pear fruit. In summary, the T2T gap-free pear genome provides invaluable resources for genome evolution and functional genomics.},
}
@article {pmid38023477,
year = {2023},
author = {Xu, XD and Zhao, RP and Xiao, L and Lu, L and Gao, M and Luo, YH and Zhou, ZW and Ye, SY and Qian, YQ and Fan, BL and Shang, X and Shi, P and Zeng, W and Cao, S and Wu, Z and Yan, H and Chen, LL and Song, JM},
title = {Telomere-to-telomere assembly of cassava genome reveals the evolution of cassava and divergence of allelic expression.},
journal = {Horticulture research},
volume = {10},
number = {11},
pages = {uhad200},
pmid = {38023477},
issn = {2662-6810},
abstract = {Cassava is a crucial crop that makes a significant contribution to ensuring human food security. However, high-quality telomere-to-telomere cassava genomes have not been available up to now, which has restricted the progress of haploid molecular breeding for cassava. In this study, we constructed two nearly complete haploid resolved genomes and an integrated, telomere-to-telomere gap-free reference genome of an excellent cassava variety, 'Xinxuan 048', thereby providing a new high-quality genomic resource. Furthermore, the evolutionary history of several species within the Euphorbiaceae family was revealed. Through comparative analysis of haploid genomes, it was found that two haploid genomes had extensive differences in linear structure, transcriptome features, and epigenetic characteristics. Genes located within the highly divergent regions and differentially expressed alleles are enriched in the functions of auxin response and the starch synthesis pathway. The high heterozygosity of cassava 'Xinxuan 048' leads to rapid trait segregation in the first selfed generation. This study provides a theoretical basis and genomic resource for molecular breeding of cassava haploids.},
}
@article {pmid38023474,
year = {2023},
author = {Zeng, T and He, Z and He, J and Lv, W and Huang, S and Li, J and Zhu, L and Wan, S and Zhou, W and Yang, Z and Zhang, Y and Luo, C and He, J and Wang, C and Wang, L},
title = {The telomere-to-telomere gap-free reference genome of wild blueberry (Vaccinium duclouxii) provides its high soluble sugar and anthocyanin accumulation.},
journal = {Horticulture research},
volume = {10},
number = {11},
pages = {uhad209},
pmid = {38023474},
issn = {2662-6810},
abstract = {Vaccinium duclouxii, endemic to southwestern China, is a berry-producing shrub or small tree belonging to the Ericaceae family, with high nutritive, medicinal, and ornamental value, abundant germplasm resources, and good edible properties. In addition, V. duclouxii exhibits strong tolerance to adverse environmental conditions, making it a promising candidate for research and offering wide-ranging possibilities for utilization. However, the lack of V. duclouxii genome sequence has hampered its development and utilization. Here, a high-quality telomere-to-telomere genome sequence of V. duclouxii was de novo assembled and annotated. All of 12 chromosomes were assembled into gap-free single contigs, providing the highest integrity and quality assembly reported so far for blueberry. The V. duclouxii genome is 573.67 Mb, which encodes 41 953 protein-coding genes. Combining transcriptomics and metabolomics analyses, we have uncovered the molecular mechanisms involved in sugar and acid accumulation and anthocyanin biosynthesis in V. duclouxii. This provides essential molecular information for further research on the quality of V. duclouxii. Moreover, the high-quality telomere-to-telomere assembly of the V. duclouxii genome will provide insights into the genomic evolution of Vaccinium and support advancements in blueberry genetics and molecular breeding.},
}
@article {pmid38022874,
year = {2023},
author = {Farrukh, S and Baig, S},
title = {Parental telomeres implications on immune senescence of newborns.},
journal = {American journal of clinical and experimental immunology},
volume = {12},
number = {5},
pages = {81-86},
pmid = {38022874},
issn = {2164-7712},
abstract = {Telomere, the biological chronometer, and its effect on the immune system considerably varies among individuals. During pregnancy, multiple risk factors affect telomere reprogramming during fetal life which can lead to health disparities in newborns. These changes may cause a long-term impact on the telomere genetics of the newborn and become a reason for lifelong health implications and immune senescence. Therefore, telomere shortening in parents due to genetic variation may act as a hallmark of immune senescence and aging in their newborns.},
}
@article {pmid38021281,
year = {2022},
author = {Srikanth, P and Chowdhury, AR and Low, GKM and Saraswathy, R and Fujimori, A and Banerjee, B and Martinez-Lopez, W and Hande, MP},
title = {Oxidative Damage Induced Telomere Mediated Genomic Instability in Cells from Ataxia Telangiectasia Patients.},
journal = {Genome integrity},
volume = {13},
number = {},
pages = {2},
pmid = {38021281},
issn = {2041-9414},
abstract = {Our cellular genome is susceptible to cytotoxic lesions which include single strand breaks and double strand breaks among other lesions. Ataxia telangiectasia mutated (ATM) protein was one of the first DNA damage sensor proteins to be discovered as being involved in DNA repair and as well as in telomere maintenance. Telomeres help maintain the stability of our chromosomes by protecting the ends from degradation. Cells from ataxia telangiectasia (AT) patients lack ATM and accumulate chromosomal alterations. AT patients display heightened susceptibility to cancer. In this study, cells from AT patients (called as AT [-/-] and AT [+/-] cells) were characterized for genome stability status and it was observed that AT [-/-] cells show considerable telomere attrition. Furthermore, DNA damage and genomic instability were compared between normal (AT [+/+] cells) and AT [-/-] cells exhibiting increased frequencies of spontaneous DNA damage and genomic instability markers. Both AT [-/-] and AT [+/-] cells were sensitive to sodium arsenite (1.5 and 3.0 μg/ml) and ionizing radiation-induced (2 Gy, gamma rays) oxidative stress. Interestingly, telomeric fragments were detected in the comet tails as revealed by comet-fluorescence in situ hybridization analysis, suggestive of telomeric instability in AT [-/-] cells upon exposure to sodium arsenite or radiation. Besides, there was an increase in the number of chromosome alterations in AT [-/-] cells following arsenite treatment or irradiation. In addition, complex chromosome aberrations were detected by multicolor fluorescence in situ hybridization in AT [-/-] cells in comparison to AT [+/-] and normal cells. Telomere attrition and chromosome alterations were detected even at lower doses of sodium arsenite. Peptide nucleic acid - FISH analysis revealed defective chromosome segregation in cells lacking ATM proteins. The data obtained in this study substantiates the role of ATM in telomere stability under oxidative stress.},
}
@article {pmid38020928,
year = {2023},
author = {Fernández-Álvarez, A},
title = {Beyond tradition: exploring the non-canonical functions of telomeres in meiosis.},
journal = {Frontiers in cell and developmental biology},
volume = {11},
number = {},
pages = {1278571},
pmid = {38020928},
issn = {2296-634X},
abstract = {The telomere bouquet is a specific chromosomal configuration that forms during meiosis at the zygotene stage, when telomeres cluster together at the nuclear envelope. This clustering allows cytoskeleton-induced movements to be transmitted to the chromosomes, thereby facilitating homologous chromosome search and pairing. However, loss of the bouquet results in more severe meiotic defects than can be attributed solely to recombination problems, suggesting that the bouquet's full function remains elusive. Despite its transient nature and the challenges in performing in vivo analyses, information is emerging that points to a remarkable suite of non-canonical functions carried out by the bouquet. Here, we describe how new approaches in quantitative cell biology can contribute to establishing the molecular basis of the full function and plasticity of the bouquet, and thus generate a comprehensive picture of the telomeric control of meiosis.},
}
@article {pmid38019799,
year = {2023},
author = {Balouchi, M and Huang, SH and McGrath, SL and Kobryn, K},
title = {The telomere resolvase, TelA, utilizes an underwound pre-cleavage intermediate to promote hairpin telomere formation.},
journal = {PloS one},
volume = {18},
number = {11},
pages = {e0294732},
pmid = {38019799},
issn = {1932-6203},
mesh = {*Recombinases/genetics ; *Bacterial Proteins/genetics ; DNA/chemistry ; Telomere/genetics ; Phosphates ; },
abstract = {The telomere resolvase, TelA, forms the hairpin telomeres of the linear chromosome of Agrobacterium tumefaciens in a process referred to as telomere resolution. Telomere resolution is a unique DNA cleavage and rejoining reaction that resolves replicated telomere junctions into a pair of hairpin telomeres. Telomere resolvases utilize a reaction mechanism with similarities to that of topoisomerase-IB enzymes and tyrosine recombinases. The reaction proceeds without the need for high-energy cofactors due to the use of a covalent, enzyme-cleaved DNA intermediate that stores the bond energy of the cleaved bonds in 3'-phosphotyrosyl linkages. The cleaved DNA strands are then refolded into a hairpin conformation and the 5'-OH ends of the refolded strands attack the 3'-phosphotyrosine linkages in order to rejoin the DNA strands into hairpin telomeres. Because this kind of reaction mechanism is, in principle, reversible it is unclear how TelA controls the direction of the reaction and propels the reaction to completion. We present evidence that TelA forms and/or stabilizes a pre-cleavage intermediate that features breakage of the four central basepairs between the scissile phosphates prior to DNA cleavage to help propel the reaction forwards, thus preventing abortive cleavage and rejoining cycles that regenerate the substrate DNA. We identify eight TelA sidechains, located in the hairpin-binding module and catalytic domains of TelA, implicated in this process. These mutants were deficient for telomere resolution on parental replicated telomere junctions but were rescued by introduction of substrate modifications that mimic unwinding of the DNA between the scissile phosphates.},
}
@article {pmid38018863,
year = {2024},
author = {Mostafa, H and Gutierrez-Tordera, L and Mateu-Fabregat, J and Papandreou, C and Bulló, M},
title = {Dietary fat, telomere length and cognitive function: unravelling the complex relations.},
journal = {Current opinion in lipidology},
volume = {35},
number = {1},
pages = {33-40},
pmid = {38018863},
issn = {1473-6535},
mesh = {Humans ; *Dietary Fats/adverse effects ; *Fatty Acids ; Fatty Acids, Monounsaturated ; Cognition ; Telomere/genetics ; },
abstract = {PURPOSE OF REVIEW: The review aims to explore the recent evidence on the associations between different dietary fat intake and cognitive function, and to understand the role of telomere length in this relationship.<br><br>RECENT FINDINGS: Clinical and preclinical studies included in this review suggest that dietary fat intake is associated with cognitive function and telomere length. High intake of saturated fats and trans fats, commonly found in ultra-processed foods, appears to have negative effects on cognitive function and telomere length, while other dietary fats, such as omega-3 polyunsaturated fatty acids and monounsaturated fatty acids are associated with improved cognitive performance and reduced telomere attrition. Controversial results related to omega-6 polyunsaturated fatty acids intake and its impact on cognitive function were found. Dietary fats may affect telomere length and cognition through oxidative stress, inflammation, and insulin resistance.<br><br>SUMMARY: The current review illustrated the relationship between dietary fat and cognitive function by focusing on the role of telomere length as a potential intermediator. More future studies are required, however, in order to develop targeted interventions aimed at preserving cognitive well-being throughout life.},
}
@article {pmid38017164,
year = {2023},
author = {Le Bras, A},
title = {Short telomeres in Telomice.},
journal = {Lab animal},
volume = {52},
number = {12},
pages = {285},
doi = {10.1038/s41684-023-01297-9},
pmid = {38017164},
issn = {1548-4475},
mesh = {*Telomere Shortening ; Telomere/genetics ; *Telomerase ; },
}
@article {pmid38014526,
year = {2023},
author = {Valipour, B and Davari, S and Farahzadi, R and Pourrasol, S and Mehran, N and Dizaji Asl, K and Altaha, SM and Hojjati, Z and Nozad Charoudeh, H},
title = {Inhibition of mitochondria induces apoptosis and reduces telomere length and activity in acute myeloid leukemia stem cells.},
journal = {Cell biochemistry and function},
volume = {41},
number = {8},
pages = {1477-1487},
doi = {10.1002/cbf.3888},
pmid = {38014526},
issn = {1099-0844},
support = {//Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran/ ; },
mesh = {Adult ; Child ; Humans ; Caspase 9/genetics ; bcl-2-Associated X Protein/metabolism ; *Tumor Suppressor Protein p53/metabolism ; Tigecycline/pharmacology/metabolism ; *Leukemia, Myeloid, Acute/genetics ; Apoptosis ; Antigens, CD34/metabolism ; Neoplastic Stem Cells/metabolism ; Mitochondria/metabolism ; Telomere/metabolism/pathology ; },
abstract = {Acute myeloid leukemia (AML) is a highly lethal hematological malignancy in adults and children. Abnormal proliferation of leukemia stem cells (LSC) with CD34[+] and CD38[-] phenotypes are the main clinical features of AML. Patients with AML face drug resistance and treatment failure due to a default in stem and progenitor cells. Therefore, defining LSC properties is necessary for targeting leukemia-initiating cells. Mitochondrial mass and activity increase in AML initiating cells compared with normal stem cells. This idea has offered the inhibition of the mitochondrial translation machinery to reduce the number of leukemia-initiating cells in patients with AML Tigecycline is an FDA-approved microbial antibiotic that inhibits oxidative phosphorylation in mitochondria, resulting in the suppression of leukemia cell proliferation with little toxicity to normal cells. Thus, the present study was conducted to evaluate whether LSC is influenced by mitochondrial inhibition. We measured the IC50 of tigecycline in KG-1a AML cell lines. KG-1a AML cell lines were separated into CD34[+] and CD34[-] cells by MACS. In the following, these cells were treated with 20 µM (IC50) tigecycline. The expression of Annexin/PI, Caspase 3, apoptotic genes (BCL2, BCLX, BAX, BAD, and P53) and proteins (P53, BAX, BCL2 and Caspase 9) was evaluated in CD34[+] , CD34[-] and KG-1a AML cells. In addition, the telomere length and expression of hTERT were evaluated in this study. The results indicated that BCl2 (gene and protein) and BCLX gene dramatically decreased. In addition, BAD, BAX, and P53 gene and protein expression significantly increased in CD34[+] AML cells compared to CD34[-] AML cells. The results also suggested that tigecycline induced intrinsic (Cleaved-caspase 9/Pro-Caspase 9 ratio) and p53-mediated apoptosis. Furthermore, hTERT gene expression and telomere length decreased in the tigecycline-treated groups. Taken together, our findings indicate that inhibition of mitochondrial activity with tigecycline can induce apoptosis in cancer stem cells and can be used as a novel method for cancer therapy.},
}
@article {pmid38008763,
year = {2023},
author = {San-Cristobal, R and de Toro-Martín, J and Guénard, F and Pérusse, L and Biron, S and Marceau, S and Lafortune Payette, A and Vohl, MC},
title = {Impact of maternal cardiometabolic status after bariatric surgery on the association between telomere length and adiposity in offspring.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {20771},
pmid = {38008763},
issn = {2045-2322},
mesh = {Child ; Female ; Humans ; Adiposity/genetics ; Obesity/complications ; *Bariatric Surgery ; Body Mass Index ; Telomere/genetics ; *Cardiovascular Diseases/genetics/complications ; },
abstract = {The impact of bariatric surgery on metabolic and inflammatory status are reflected in the epigenetic profile and telomere length mediated by the changes in the metabolic status of the patients. This study compared the telomere length of children born before versus after maternal bariatric surgery as a surrogate to test the influence of the mother's metabolic status on children's telomere length. DNA methylation telomere length (DNAmTL) was estimated from Methylation-EPIC BeadChip array data from a total of 24 children born before and after maternal bariatric surgery in the greater Quebec City area. DNAmTL was inversely associated with chronological age in children (r = - 0.80, p < 0.001) and significant differences were observed on age-adjusted DNAmTL between children born before versus after the maternal bariatric surgery. The associations found between body mass index and body fat percentage with DNAmTL in children born after the surgery were influenced by maternal triglycerides, TG/HDL-C ratio and TyG index. This study reports the impact of maternal bariatric surgery on offspring telomere length. The influence of maternal metabolic status on the association between telomere length and markers of adiposity in children suggests a putative modulating effect of bariatric surgery on the cardiometabolic risk in offspring.},
}
@article {pmid38008503,
year = {2023},
author = {Yu, TN and Cheng, EH and Lin, YP and Chen, YC and Huang, CC and Lee, TH and Lee, MS},
title = {Significantly shortened telomere length and altered androgen receptor level in cumulus cells from women with polycystic ovary syndrome.},
journal = {Taiwanese journal of obstetrics &amp; gynecology},
volume = {62},
number = {6},
pages = {845-851},
doi = {10.1016/j.tjog.2023.07.035},
pmid = {38008503},
issn = {1875-6263},
mesh = {Female ; Humans ; Aged ; Adult ; Cumulus Cells ; *Polycystic Ovary Syndrome/genetics/complications ; Receptors, Androgen/genetics ; *Infertility, Female/genetics/complications ; Prospective Studies ; Telomere Shortening/genetics ; Telomere/genetics ; RNA, Messenger ; Hormones ; },
abstract = {OBJECTIVE: The aim of this study was to investigate the correlation between hormone receptor levels and telomere length (TL) in infertile women with and without polycystic ovary syndrome (PCOS).<br><br>MATERIALS AND METHODS: This prospective cohort study recruited a total of 431 cumulus oocyte complex (COC) from 88 infertile women between July 2012 and June 2014. The participants were divided into three groups: young age (<38 years, n&#xa0;=&#xa0;42 and 227 COC), advanced age (&#x2265;38 years, n&#xa0;=&#xa0;33 and 107 COC) and PCOS patients (n&#xa0;=&#xa0;13 and 97 COC). Cumulus cells were collected from individual follicle during oocyte pick-up, and the mRNA levels of hormone receptors and TL were measured using real-time PCR.<br><br>RESULTS: The cumulus cells of PCOS patients demonstrated lower mRNA levels of LH receptor (75.57&#xa0;&#xb1;&#xa0;138.10 vs. 171.07&#xa0;&#xb1;&#xa0;317.68; p&#xa0;<&#xa0;0.01) and androgen receptor (1.13&#xa0;&#xb1;&#xa0;1.52 vs. 4.08&#xa0;&#xb1;&#xa0;9.57; p&#xa0;<&#xa0;0.01), as well as a shorter TL (2.39&#xa0;&#xb1;&#xa0;2.58 vs. 3.96&#xa0;&#xb1;&#xa0;4.72; p&#xa0;<&#xa0;0.01) compared to those of the young age group. In the young age group, only androgen receptor mRNA level showed a significant association with TL (rho&#xa0;=&#xa0;0.148, p&#xa0;=&#xa0;0.026), while FSH receptor mRNA level was the only factor associated with TL (rho&#xa0;=&#xa0;0.247, p&#xa0;=&#xa0;0.015) in PCOS patients. For advanced-aged patients, no significant relationship was observed between hormone receptor mRNA levels and TL. Alternative splicing of androgen receptors was identified in some PCOS patients but not in young age controls.<br><br>CONCLUSION: The findings suggest that the androgen receptor level and function may be altered in the cumulus cells of PCOS patients, leading to a shorter TL in cumulus cells in PCOS patients.},
}
@article {pmid38003036,
year = {2023},
author = {Tao, Y and He, C and Lin, D and Gu, Z and Pu, W},
title = {Comprehensive Identification of Mitochondrial Pseudogenes (NUMTs) in the Human Telomere-to-Telomere Reference Genome.},
journal = {Genes},
volume = {14},
number = {11},
pages = {},
pmid = {38003036},
issn = {2073-4425},
support = {82003360//Young Scientists Fund of the National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Pseudogenes/genetics ; *Mitochondria/genetics ; DNA, Mitochondrial/genetics ; Genome, Human ; Telomere ; },
abstract = {Practices related to mitochondrial research have long been hindered by the presence of mitochondrial pseudogenes within the nuclear genome (NUMTs). Even though partially assembled human reference genomes like hg38 have included NUMTs compilation, the exhaustive NUMTs within the only complete reference genome (T2T-CHR13) remain unknown. Here, we comprehensively identified the fixed NUMTs within the reference genome using human pan-mitogenome (HPMT) from GeneBank. The inclusion of HPMT serves the purpose of establishing an authentic mitochondrial DNA (mtDNA) mutational spectrum for the identification of NUMTs, distinguishing it from the polymorphic variations found in NUMTs. Using HPMT, we identified approximately 10% of additional NUMTs in three human reference genomes under stricter thresholds. And we also observed an approximate 6% increase in NUMTs in T2T-CHR13 compared to hg38, including NUMTs on the short arms of chromosomes 13, 14, and 15 that were not assembled previously. Furthermore, alignments based on 20-mer from mtDNA suggested the presence of more mtDNA-like short segments within the nuclear genome, which should be avoided for short amplicon or cell free mtDNA detection. Finally, through the assay of transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) on cell lines before and after mtDNA elimination, we concluded that NUMTs have a minimal impact on bulk ATAC-seq, even though 16% of sequencing data originated from mtDNA.},
}
@article {pmid38001857,
year = {2023},
author = {Coltell, O and Asensio, EM and Sorlí, JV and Ortega-Azorín, C and Fernández-Carrión, R and Pascual, EC and Barragán, R and González, JI and Estruch, R and Alzate, JF and Pérez-Fidalgo, A and Portolés, O and Ordovas, JM and Corella, D},
title = {Associations between the New DNA-Methylation-Based Telomere Length Estimator, the Mediterranean Diet and Genetics in a Spanish Population at High Cardiovascular Risk.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {11},
pages = {},
pmid = {38001857},
issn = {2076-3921},
support = {CIBER 06/03/035//The Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Econom&#xed;a y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER)/ ; PI21/00001//CIBER Fisiopatolog&#xed;a de la Obesidad y Nutrici&#xf3;n, Instituto de Salud Carlos III/ ; PROMETEO/2021/021//The Generalitat Valenciana/ ; PID2019-108858RB-I00//AEI 10.13039/501100011033 and by "ERDF A way of making Europe"/ ; },
abstract = {Biological aging is a relevant risk factor for chronic diseases, and several indicators for measuring this factor have been proposed, with telomere length (TL) among the most studied. Oxidative stress may regulate telomere shortening, which is implicated in the increased risk. Using a novel estimator for TL, we examined whether adherence to the Mediterranean diet (MedDiet), a highly antioxidant-rich dietary pattern, is associated with longer TL. We determined TL using DNA methylation algorithms (DNAmTL) in 414 subjects at high cardiovascular risk from Spain. Adherence to the MedDiet was assessed by a validated score, and genetic variants in candidate genes and at the genome-wide level were analyzed. We observed several significant associations (p < 0.05) between DNAmTL and candidate genes (TERT, TERF2, RTEL1, and DCAF4), contributing to the validity of DNAmTL as a biomarker in this population. Higher adherence to the MedDiet was associated with lower odds of having a shorter TL in the whole sample (OR = 0.93; 95% CI: 0.85-0.99; p = 0.049 after fully multivariate adjustment). Nevertheless, this association was stronger in women than in men. Likewise, in women, we observed a direct association between adherence to the MedDiet score and DNAmTL as a continuous variable (beta = 0.015; SE: 0.005; p = 0.003), indicating that a one-point increase in adherence was related to an average increase of 0.015 ± 0.005 kb in TL. Upon examination of specific dietary items within the global score, we found that fruits, fish, "sofrito", and whole grains exhibited the strongest associations in women. The novel score combining these items was significantly associated in the whole population. In the genome-wide association study (GWAS), we identified ten polymorphisms at the suggestive level of significance (p < 1 × 10[-5]) for DNAmTL (intergenics, in the IQSEC1, NCAPG2, and ABI3BP genes) and detected some gene-MedDiet modulations on DNAmTL. As this is the first study analyzing the DNAmTL estimator, genetics, and modulation by the MedDiet, more studies are needed to confirm these findings.},
}
@article {pmid38000989,
year = {2024},
author = {Qi, M and Yu, J and Ping, F and Xu, L and Li, W and Zhang, H and Li, Y},
title = {Leukocyte telomere length independently predicts hyperuricemia risk in a longitudinal study of the Chinese population.},
journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD},
volume = {34},
number = {1},
pages = {230-234},
doi = {10.1016/j.numecd.2023.10.004},
pmid = {38000989},
issn = {1590-3729},
mesh = {Humans ; Longitudinal Studies ; Prospective Studies ; *Uric Acid ; *Hyperuricemia/diagnosis/epidemiology/genetics ; Leukocytes ; Telomere/genetics ; },
abstract = {BACKGROUND AND AIMS: Leukocyte telomere length (LTL) has been correlated with uric acid levels, although results are inconsistent, and prospective studies are lacking. In this longitudinal, prospective cohort study, we aimed to assess whether a shorter LTL predicts the risk of hyperuricemia.<br><br>METHODS AND RESULTS: We conducted a longitudinal study in a Chinese cohort of 599 participants. Of these, 266 participants completed a 5.9-year follow-up from June 2014 to December 2021. LTL was assessed at baseline using real-time polymerase chain reaction. Hyperuricemia was defined as serum uric acid &#x2265;420&#xa0;mmol/L according to Chinese guidelines for diagnosis and treatment of hyperuricemia and gout. Participants who had developed hyperuricemia during follow-up (n&#xa0;=&#xa0;17) had shorter LTL at baseline. Baseline LTL was independently associated with the development of hyperuricemia at follow-up after adjusting for conventional hyperuricemia risk factors (odds ratio [OR] 2.347 [95% confidence interval [CI] 1.123, 4.906]; P&#xa0;=&#xa0;0.023). After grouping according to LTL tertiles, the incidence of hyperuricemia was 18.334-fold higher for the first than for the third tertile (OR 18.334 [95%CI 1.786, 191.272]; P&#xa0;=&#xa0;0.014, P for trend&#xa0;=&#xa0;0.050).<br><br>CONCLUSION: Our findings in a prospective cohort suggest that LTL could predict hyperuricemia risk, which might inform the timely prevention and treatment of hyperuricemia.},
}
@article {pmid37997988,
year = {2023},
author = {Zhang, N and Baker, EC and Welsh, TH and Riley, DG},
title = {Telomere Dynamics in Livestock.},
journal = {Biology},
volume = {12},
number = {11},
pages = {},
pmid = {37997988},
issn = {2079-7737},
support = {2019-67015-2957//United States Department of Agriculture/ ; },
abstract = {Telomeres are repeated sequences of nucleotides at the end of chromosomes. They deteriorate across mitotic divisions of a cell. In Homo sapiens this process of lifetime reduction has been shown to correspond with aspects of organismal aging and exposure to stress or other insults. The early impetus to characterize telomere dynamics in livestock related to the concern that aged donor DNA would result in earlier cell senescence and overall aging in cloned animals. Telomere length investigations in dairy cows included breed effects, estimates of additive genetic control (heritability 0.12 to 0.46), and effects of external stressors on telomere degradation across animal life. Evaluation of telomeres with respect to aging has also been conducted in pigs and horses, and there are fewer reports of telomere biology in beef cattle, sheep, and goats. There were minimal associations of telomere length with animal productivity measures. Most, but not all, work in livestock has documented an inverse relationship between peripheral blood cell telomere length and age; that is, a longer telomere length was associated with younger age. Because livestock longevity affects productivity and profitability, the role of tissue-specific telomere attrition in aging may present alternative improvement strategies for genetic improvement while also providing translational biomedical knowledge.},
}
@article {pmid37997496,
year = {2024},
author = {Park, S and Kim, DK},
title = {Comment on "Causal linkage of tobacco smoking with ageing: Mendelian randomization analysis towards telomere attrition and sarcopenia" by Park et al. - The authors reply.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {15},
number = {1},
pages = {453-454},
pmid = {37997496},
issn = {2190-6009},
mesh = {Humans ; *Sarcopenia ; Mendelian Randomization Analysis ; Tobacco Smoking ; Aging ; Telomere ; },
}
@article {pmid37994393,
year = {2024},
author = {Setia, N and Del Gaudio, D and Kandikatla, P and Arndt, K and Tjota, M and Wang, P and Segal, J and Alikhan, M and Hart, J},
title = {A novel telomere biology disease-associated gastritis identified through a whole exome sequencing-driven approach.},
journal = {The journal of pathology. Clinical research},
volume = {10},
number = {1},
pages = {e349},
pmid = {37994393},
issn = {2056-4538},
mesh = {Humans ; *Gastritis, Atrophic/genetics/pathology ; Exome Sequencing ; *Gastritis/genetics/pathology ; Biopsy ; Biology ; Exodeoxyribonucleases ; },
abstract = {A whole exome sequencing (WES)-driven approach to uncover the etiology of unexplained inflammatory gastritides has been underutilized by surgical pathologists. Here, we discovered the pathobiology of an unusual chronic atrophic gastritis in two unrelated patients using this approach. The gastric biopsies were notable for an unusual pattern of gastritis with persistent dense inflammation, loss of both parietal and neuroendocrine cells in the oxyntic mucosa, and sparing of the antral mucosa. The patients were found to harbor pathogenic variants in telomeropathic genes (POT1 and DCLRE1B). Clonality testing for one of the patients showed evidence of evolving clonality of TCR-gene rearrangement. Both patients showed significantly decreased numbers of stem/progenitor cells by immunohistochemistry, which appears to be responsible for the development of mucosal atrophy. No such cases of unusual chronic atrophic gastritis in the setting of telomeropathy have been previously reported. The loss of stem/progenitor cells suggests that stem/progenitor cell exhaustion in the setting of telomere dysfunction is the likely mechanism for development of this unusual chronic atrophic gastritis. The results underscore the need for close monitoring of these gastric lesions, with special regard to their neoplastic potential. This combined WES-driven approach has promise to identify the cause and mechanism of other uncharacterized gastrointestinal inflammatory disorders.},
}
@article {pmid37993053,
year = {2024},
author = {Robinson, LG and Kalmbach, K and Sumerfield, O and Nomani, W and Wang, F and Liu, L and Keefe, DL},
title = {Telomere dynamics and reproduction.},
journal = {Fertility and sterility},
volume = {121},
number = {1},
pages = {4-11},
doi = {10.1016/j.fertnstert.2023.11.012},
pmid = {37993053},
issn = {1556-5653},
mesh = {Male ; Female ; Humans ; Mice ; Animals ; Aged ; *Telomerase/genetics/metabolism ; Semen/metabolism ; Reproduction/genetics ; Aging/genetics ; Oocytes/metabolism ; Telomere/genetics ; },
abstract = {The oocyte, a long-lived, postmitotic cell, is the locus of reproductive aging in women. Female germ cells replicate only during fetal life and age throughout reproductive life. Mechanisms of oocyte aging include the accumulation of oxidative damage, mitochondrial dysfunction, and disruption of proteins, including cohesion. Nobel Laureate Bob Edwards also discovered a "production line" during oogonial replication in the mouse, wherein the last oocytes to ovulate in the adult-derived from the last oogonia to exit mitotic replication in the fetus. On the basis of this, we proposed a two-hit "telomere theory of reproductive aging" to integrate the myriad features of oocyte aging. The first hit was that oocytes remaining in older women traversed more cell cycles during fetal oogenesis. The second hit was that oocytes accumulated more environmental and endogenous oxidative damage throughout the life of the woman. Telomeres (Ts) could mediate both of these aspects of oocyte aging. Telomeres provide a "mitotic clock," with T attrition an inevitable consequence of cell division because of the end replication problem. Telomere's guanine-rich sequence renders them especially sensitive to oxidative damage, even in postmitotic cells. Telomerase, the reverse transcriptase that restores Ts, is better at maintaining than elongating T. Moreover, telomerase remains inactive during much of oogenesis and early development. Oocytes are left with short Ts, on the brink of viability. In support of this theory, mice with induced T attrition and women with naturally occurring telomeropathy suffer diminished ovarian reserve, abnormal embryo development, and infertility. In contrast, sperm are produced throughout the life of the male by a telomerase-active progenitor, spermatogonia, resulting in the longest Ts in the body. In mice, cleavage-stage embryos elongate Ts via "alternative lengthening of telomeres," a recombination-based mechanism rarely encountered outside of telomerase-deficient cancers. Many questions about Ts and reproduction are raised by these findings: does the "normal" T attrition observed in human oocytes contribute to their extraordinarily high rate of meiotic nondisjunction? Does recombination-based T elongation render embryos susceptible to mitotic nondisjunction (and mosaicism)? Can some features of Ts serve as markers of oocyte quality?},
}
@article {pmid37991243,
year = {2023},
author = {Wang, C and Huang, Y and Yang, Y and Li, R and Li, Y and Qiu, H and Wu, J and Shi, G and Ma, W and Songyang, Z},
title = {ILF3 safeguards telomeres from aberrant homologous recombination as a telomeric R-loop reader.},
journal = {Protein &amp; cell},
volume = {},
number = {},
pages = {},
doi = {10.1093/procel/pwad054},
pmid = {37991243},
issn = {1674-8018},
abstract = {Telomeres are specialized structures at the ends of linear chromosomes that protect genome stability. The telomeric repeat-containing RNA (TERRA) that is transcribed from subtelomeric regions can invade into double-stranded DNA regions and form RNA:DNA hybrid-containing structure called R-loop. In tumor cells, R-loop formation is closely linked to gene expression and the alternative lengthening of telomeres (ALT) pathway. Dysregulated R-loops can cause stalled replication forks and telomere instability. However, how R-loops are recognized and regulated, particularly at telomeres, is not well understood. We discovered that ILF3 selectively associates with telomeric R-loops and safeguards telomeres from abnormal homologous recombination. Knocking out ILF3 results in excessive R-loops at telomeres and triggers telomeric DNA damage responses (DDR). In addition, ILF3 deficiency disrupts telomere homeostasis and causes abnormalities in the ALT pathway. Using the proximity-dependent biotin identification (BioID) technology, we mapped the ILF3 interactome and discovered that ILF3 could interact with several DNA/RNA helicases, including DHX9. Importantly, ILF3 may aid in the resolution of telomeric R-loops through its interaction with DHX9. Our findings suggest that ILF3 may function as a reader of telomeric R-loops, helping to prevent abnormal homologous recombination and maintain telomere homeostasis.},
}
@article {pmid37988290,
year = {2023},
author = {Colin, L and Reyes, C and Berthezene, J and Maestroni, L and Modolo, L and Toselli, E and Chanard, N and Schaak, S and Cuvier, O and Gachet, Y and Coulon, S and Bernard, P and Tournier, S},
title = {Condensin positioning at telomeres by shelterin proteins drives sister-telomere disjunction in anaphase.},
journal = {eLife},
volume = {12},
number = {},
pages = {},
pmid = {37988290},
issn = {2050-084X},
support = {ANR-16-CE12-0015-TeloMito//Agence Nationale de la Recherche/ ; PJA20161204921//Fondation ARC pour la Recherche sur le Cancer/ ; PhD studentship//La ligue contre le cancer/ ; PJA 20191209370//Fondation ARC pour la Recherche sur le Cancer/ ; PhD studentship//La fondtion pour la recherche medicale/ ; },
mesh = {Shelterin Complex ; Anaphase ; Telomere-Binding Proteins/genetics/metabolism ; Telomere/metabolism ; *Schizosaccharomyces/genetics/metabolism ; *Schizosaccharomyces pombe Proteins/genetics/metabolism ; },
abstract = {The localization of condensin along chromosomes is crucial for their accurate segregation in anaphase. Condensin is enriched at telomeres but how and for what purpose had remained elusive. Here, we show that fission yeast condensin accumulates at telomere repeats through the balancing acts of Taz1, a core component of the shelterin complex that ensures telomeric functions, and Mit1, a nucleosome remodeler associated with shelterin. We further show that condensin takes part in sister-telomere separation in anaphase, and that this event can be uncoupled from the prior separation of chromosome arms, implying a telomere-specific separation mechanism. Consistent with a cis-acting process, increasing or decreasing condensin occupancy specifically at telomeres modifies accordingly the efficiency of their separation in anaphase. Genetic evidence suggests that condensin promotes sister-telomere separation by counteracting cohesin. Thus, our results reveal a shelterin-based mechanism that enriches condensin at telomeres to drive in cis their separation during mitosis.},
}
@article {pmid37987889,
year = {2023},
author = {Harley, J and Santosa, MM and Ng, CY and Grinchuk, OV and Hor, JH and Liang, Y and Lim, VJ and Tee, WW and Ong, DST and Ng, SY},
title = {Telomere shortening induces aging-associated phenotypes in hiPSC-derived neurons and astrocytes.},
journal = {Biogerontology},
volume = {},
number = {},
pages = {},
pmid = {37987889},
issn = {1573-6768},
abstract = {Telomere shortening is a well-established hallmark of cellular aging. Telomerase reverse transcriptase (TERT) plays a crucial role in maintaining the length of telomeres, which are specialised protective caps at the end of chromosomes. The lack of in vitro aging models, particularly for the central nervous system (CNS), has impeded progress in understanding aging and age-associated neurodegenerative diseases. In this study, we aimed to explore the possibility of inducing aging-associated features in cell types of the CNS using hiPSC (human induced pluripotent stem cell) technology. To achieve this, we utilised CRISPR/Cas9 to generate hiPSCs with a loss of telomerase function and shortened telomeres. Through directed differentiation, we generated motor neurons and astrocytes to investigate whether telomere shortening could lead to age-associated phenotypes. Our findings revealed that shortened telomeres induced age-associated characteristics in both motor neurons and astrocytes including increased cellular senescence, heightened inflammation, and elevated DNA damage. We also observed cell-type specific age-related morphology changes. Additionally, our study highlighted the fundamental role of TERT and telomere shortening in neural progenitor cell (NPC) proliferation and neuronal differentiation. This study serves as a proof of concept that telomere shortening can effectively induce aging-associated phenotypes, thereby providing a valuable tool to investigate age-related decline and neurodegenerative diseases.},
}
@article {pmid37986934,
year = {2023},
author = {Pierpoint, M and Floyd, W and Wisdom, AJ and Luo, L and Ma, Y and Waitkus, MS and Kirsch, DG},
title = {Loss of function of Atrx leads to activation of alternative lengthening of telomeres in a primary mouse model of sarcoma.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37986934},
support = {R35 CA197616/CA/NCI NIH HHS/United States ; },
abstract = {The development of a telomere maintenance mechanism is essential for immortalization in human cancer. While most cancers elongate their telomeres by expression of telomerase, 10-15% of human cancers use a pathway known as alternative lengthening of telomeres (ALT). In this work, we developed a genetically engineered primary mouse model of sarcoma in CAST/EiJ mice which displays multiple molecular features of ALT activation after CRISPR/Cas9 introduction of oncogenic Kras[G12D] and loss of function mutations of Trp53 and Atrx. In this model, we demonstrate that the loss of Atrx contributes to the development of ALT in an autochthonous tumor, and this process occurs independently of telomerase function by variation of mTR alleles. Furthermore, we find that telomere shortening from the loss of telomerase leads to higher chromosomal instability while loss of Atrx and activation of ALT lead to an increase in telomeric instability, telomere sister chromatid exchange, c-circle production, and formation of ALT-associated promyelocytic leukemia bodies (APBs). The development of this primary mouse model of ALT could enable future investigations into therapeutic vulnerabilities of ALT activation and its mechanism of action.},
}
@article {pmid37986388,
year = {2023},
author = {Zhang, W},
title = {Big data analysis identified a telomere-related signature predicting the prognosis and drug sensitivity in lung adenocarcinoma.},
journal = {Medicine},
volume = {102},
number = {46},
pages = {e35526},
pmid = {37986388},
issn = {1536-5964},
mesh = {Humans ; *RNA, Long Noncoding/genetics ; Prognosis ; *MicroRNAs/genetics ; Data Analysis ; *Adenocarcinoma ; Lung ; *Lung Neoplasms/drug therapy/genetics ; },
abstract = {Telomeres exert a critical role in chromosome stability and aberrant regulation of telomerase may result in telomeres dysfunction and genomic instability, which are involved in the occurrence of cancers. However, limited studies have been performed to fully clarify the immune infiltration and clinical significance of telomeres-related genes (TRGs) in lung adenocarcinoma (LUAD). The number of clusters of LUAD was determined by consensus clustering analysis. The prognostic signature was constructed and verified using TCGA and GSE42127 dataset with Least Absolute Shrinkage and Selection Operator cox regression analysis. The correlation between different clusters and risk-score and drug therapy response was analyzed using TIDE and IMvigor210 dataset. Using several miRNA and lncRNA related databases, we constructed a lncRNA-miRNA-mRNA regulatory axis. We identified 2 telomeres-related clusters in LUAD, which had distinct differences in prognostic stratification, TMB score, TIDE score, immune characteristics and signal pathways and biological effects. A prognostic model was developed based on 21 TRGs, which had a better performance in risk stratification and prognosis prediction compared with other established models. TRGs-based risk score could serve as an independent risk factor for LUAD. Survival prediction nomogram was also developed to promote the clinical use of TRGs risk score. Moreover, LUAD patients with high risk score had a high TMB score, low TIDE score and IC50 value of common drugs, suggesting that high risk score group might benefit from receiving immunotherapy, chemotherapy and target therapy. We also developed a lncRNA KCNQ1QT1/miR-296-5p/PLK1 regulatory axis. Our study identified 2 telomeres-related clusters and a prognostic model in LUAD, which could be helpful for risk stratification, prognosis prediction and treatment approach selection.},
}
@article {pmid37986353,
year = {2023},
author = {Li, W and Liu, C and Chen, Y and Dong, S and Zhang, M and Sun, J and Zhao, Z and Zuo, Y and Chen, S},
title = {Assessment of the relationship between telomere length and atherosclerosis: A Mendelian randomization study.},
journal = {Medicine},
volume = {102},
number = {46},
pages = {e35875},
pmid = {37986353},
issn = {1536-5964},
mesh = {Humans ; Mendelian Randomization Analysis ; *Atherosclerosis/genetics ; *Coronary Artery Disease/genetics ; Heart ; *Intracranial Arteriosclerosis ; Telomere/genetics ; Genome-Wide Association Study ; },
abstract = {To evaluate the causal relationship between genetically determined telomere length (TL) and atherosclerosis (AS). We performed a 2-sample Mendelian randomization (MR) study to assess the potential causal relationship between TL and AS (coronary AS, cerebral AS, peripheral atherosclerosis (PAD), and AS, excluding cerebral, coronary, and PAD). The TL phenotype contained 472,174 participants, and the 4 subtypes of AS had 361,194, 218,792, 168,832, and 213,140 participants, all of European ancestries. The single nucleotide polymorphisms (SNPs) of TL strongly associated with the 4 atherosclerotic subtypes included in this study were 101, 92, 91, and 92, respectively. The odds ratios (ORs) and 95% confidence interval (CI) between TL and coronary AS calculated using inverse variance weighted (IVW) were 0.993 (0.988, 0.997), and the results were statistically significant (P < .05). The results between TL and cerebral AS, PAD, and AS (excluding cerebral, coronary, and PAD) were not statistically significant (P > .05). "Egger-intercept test" showed that there was no horizontal pleiotropy (P > .05); "leave-one-out analysis" sensitivity analysis showed that the results were stable and there were no instrumental variables with strong effects on the results; "MR- pleiotropy residual sum and outlier (PRESSO) test" showed 1 outlier for coronary AS and no outliers for the remaining subgroups. The results of the 2-sample MR analysis showed a causal association between TL and coronary AS but not with cerebral AS, PAD, and AS (excluding cerebral, coronary, and PAD). This may elucidate the observation that various vascular regions can be affected by AS but highlights the propensity of coronary arteries to be more susceptible to AS development.},
}
@article {pmid37985967,
year = {2023},
author = {Serrano-León, IM and Prieto, P and Aguilar, M},
title = {Correction: Telomere and subtelomere high polymorphism might contribute to the specifcity of homologous recognition and pairing during meiosis in barley in the context of breeding.},
journal = {BMC genomics},
volume = {24},
number = {1},
pages = {694},
pmid = {37985967},
issn = {1471-2164},
}
@article {pmid37985282,
year = {2024},
author = {Mulet, A and González-Cabo, P and Pallardó, FV and Signes-Costa, J},
title = {Persistent Pulmonary Fibrotic Sequelae in Patients With Telomere Shortening One Year After Severe COVID-19.},
journal = {Archivos de bronconeumologia},
volume = {60},
number = {1},
pages = {62-64},
doi = {10.1016/j.arbres.2023.11.003},
pmid = {37985282},
issn = {1579-2129},
mesh = {Humans ; Telomere Shortening ; *COVID-19 ; *Idiopathic Pulmonary Fibrosis/genetics ; Disease Progression ; },
}
@article {pmid37983765,
year = {2023},
author = {Schmidt, KA and Simonetto, DA},
title = {The telomere tango: Liver disease in the genomic spotlight.},
journal = {Hepatology (Baltimore, Md.)},
volume = {},
number = {},
pages = {},
pmid = {37983765},
issn = {1527-3350},
}
@article {pmid37979607,
year = {2024},
author = {Garg, A and Seli, E},
title = {Leukocyte telomere length and DNA methylome as biomarkers of ovarian reserve and embryo aneuploidy: the intricate relationship between somatic and reproductive aging.},
journal = {Fertility and sterility},
volume = {121},
number = {1},
pages = {26-33},
doi = {10.1016/j.fertnstert.2023.11.011},
pmid = {37979607},
issn = {1556-5653},
mesh = {Female ; Humans ; *Ovarian Reserve/genetics ; Epigenome ; Aneuploidy ; Leukocytes/physiology ; *Infertility, Female/diagnosis/genetics ; Telomere/genetics ; Biomarkers ; },
abstract = {The average childbearing age among women continues to rise, leading to an increased prevalence of infertility and a subsequent increased use of assisted reproductive technologies (ARTs). Ovarian aging, especially diminished ovarian reserve and poor ovarian response, have been implicated as common causes of infertility. Telomere length and DNA methylation-based epigenetic clocks are established hallmarks of cellular aging; however, the interplay between somatic and ovarian aging remains unclear. There appears to be a lack of correlation between leukocyte telomere length and the DNA methylation age of somatic and ovarian cells. Both the telomere length and methylome of follicular somatic cells (granulosa and cumulus) appear to be unaffected by chronologic age, infertility, or processes that result in diminished ovarian reserve and poor ovarian response. As such, they are unlikely candidates as surrogate biomarkers of reproductive potential, response to stimulation, or ART outcome. Meanwhile, telomere or methylome changes in leukocytes associated with aging seem to correlate with reproductive function and may have the potential to aid the characterization of women with reproductive decline; however, current data are limited and larger studies evaluating this within an ART setting are warranted.},
}
@article {pmid37978541,
year = {2023},
author = {Liu, L and Luo, H and Sheng, Y and Kang, X and Peng, H and Luo, H and Fan, LL},
title = {A novel mutation of CTC1 leads to telomere shortening in a chinese family with interstitial lung disease.},
journal = {Hereditas},
volume = {160},
number = {1},
pages = {37},
pmid = {37978541},
issn = {1601-5223},
support = {82070003 and 82000079//National Natural Science Foundation of China/ ; 2021JJ30943, 2021JJ40849, 2023JJ20078//Natural Science Foundation of Hunan province/ ; 202203023480, 202103050563, and 202104022248//Hunan Province Health Commission Scientific Research Project/ ; },
mesh = {Humans ; *Telomere Shortening ; Telomere-Binding Proteins/genetics/metabolism ; East Asian People ; Mutation ; *Lung Diseases, Interstitial/genetics ; Telomere/genetics ; },
abstract = {Interstitial lung diseases (ILDs), or diffuse pulmonary lung disease, are a subset of lung diseases that primarily affect lung alveoli and the space around interstitial tissue and bronchioles. It clinically manifests as progressive dyspnea, and patients often exhibit a varied decrease in pulmonary diffusion function. Recently, variants in telomere biology-related genes have been identified as genetic lesions of ILDs. Here, we enrolled 82 patients with interstitial pneumonia from 2017 to 2021 in our hospital to explore the candidate gene mutations of these patients via whole-exome sequencing. After data filtering, a novel heterozygous mutation (NM_025099: p.Gly131Arg) of CTC1 was identified in two affected family members. As a component of CST (CTC1-STN1-TEN1) complex, CTC1 is responsible for maintaining telomeric structure integrity and has also been identified as a candidate gene for IPF, a special kind of chronic ILD with insidious onset. Simultaneously, real-time PCR revealed that two affected family members presented with short telomere lengths, which further confirmed the effect of the mutation in the CTC1 gene. Our study not only expanded the mutation spectrum of CTC1 and provided epidemiological data on ILDs caused by CTC1 mutations but also further confirmed the relationship between heterozygous mutations in CTC1 and ILDs, which may further contribute to understanding the mechanisms underlying ILDs.},
}
@article {pmid37976300,
year = {2023},
author = {Campa, D and Felici, A and Corradi, C and Peduzzi, G and Gentiluomo, M and Farinella, R and Rizzato, C},
title = {Long or short? Telomere length and pancreatic cancer and its precursor lesions, a narrative review.},
journal = {Mutagenesis},
volume = {},
number = {},
pages = {},
doi = {10.1093/mutage/gead034},
pmid = {37976300},
issn = {1464-3804},
abstract = {Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, with a survival approaching only 11% at five years after diagnosis. In the last 15 years, telomere length measured in leukocyte (LTL) has been studied in relation to PDAC risk. The majority of the studies reported an association between short LTL and increased PDAC risk, but the results are heterogeneous. Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) in the telomerase reverse transcriptase (TERT) gene as susceptibility loci for PDAC. Polygenic risk scores (PRS) computed using SNPs associated with LTL have been tested in relation to PDAC susceptibility with various methods and giving contrasting results. The aim of this review is to analyze all publications carried out specifically on LTL, considering LTL measured with qPCR and with genetic proxies, and PDAC risk. Additionally, we will give an overview of the most relevant associations between SNPs in telomere associated genes and PDAC, to answer the question shorter or longer? Which one of the two is associated with PDAC risk?},
}
@article {pmid37976136,
year = {2023},
author = {Zhao, Z and Shen, X and Zhao, S and Wang, J and Tian, Y and Wang, X and Tang, B},
title = {A novel telomere-related genes model for predicting prognosis and treatment responsiveness in diffuse large B-cell lymphoma.},
journal = {Aging},
volume = {15},
number = {22},
pages = {12927-12951},
pmid = {37976136},
issn = {1945-4589},
mesh = {Humans ; Prognosis ; *Lymphoma, Large B-Cell, Diffuse/drug therapy/genetics/pathology ; Monocytes ; Killer Cells, Natural ; Telomere/genetics/pathology ; Nuclear Proteins/genetics ; },
abstract = {Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous disease with diverse clinical and molecular features. Telomere maintenance is widely present in tumors, but there is a lack of relevant reports on the role of telomere-related genes (TRGs) in DLBCL. In this study, we used consensus clustering based on TRGs expression to identify two molecular clusters with distinct prognoses and immune cell infiltration. We developed a TRGs scoring model using univariate Cox regression and LASSO regression in the GSE10846 training cohort. DLBCL patients in the high-risk group had a worse prognosis than those in the low-risk group, as revealed by Kaplan-Meier curves. The scoring model was validated in the GSE10846 testing cohort and GSE87371 cohort, respectively. The high-risk group was characterized by elevated infiltration of activated DCs, CD56 dim natural killer cells, myeloid-derived suppressor cells, monocytes, and plasmacytoid DCs, along with reduced infiltration of activated CD4 T cells, Type 2 T helper cells, γδ T cells, NK cells, and neutrophils. Overexpression of immune checkpoints, such as PDCD1, CD274, and LAG3, was observed in the high-risk group. Furthermore, high-risk DLBCL patients exhibited increased sensitivity to bortezomib, rapamycin, AZD6244, and BMS.536924, while low-risk DLBCL patients showed sensitivity to cisplatin and ABT.263. Using RT-qPCR, we found that three protective model genes, namely TCEAL7, EPHA4, and ELOVL4, were down-regulated in DLBCL tissues compared with control tissues. In conclusion, our novel TRGs-based model has great predictive value for the prognosis of DLBCL patients and provides a promising direction for treatment optimization.},
}
@article {pmid37975773,
year = {2023},
author = {Tomé, S},
title = {[Nanopore and telomeres].},
journal = {Medecine sciences : M/S},
volume = {39 Hors s&#xe9;rie n&#xb0; 1},
number = {},
pages = {64},
doi = {10.1051/medsci/2023141},
pmid = {37975773},
issn = {1958-5381},
mesh = {Humans ; *Nanopores ; Telomere/genetics ; },
}
@article {pmid37971759,
year = {2023},
author = {},
title = {Boyraz B, Bellomo CM, Fleming MD, Cutler CS, Agarwal S. A novel TERC CR4/CR5 domain mutation causes telomere disease via decreased TERT binding. Blood. 2016;128(16):2089-2092.},
journal = {Blood},
volume = {142},
number = {20},
pages = {1758},
doi = {10.1182/blood.2023022677},
pmid = {37971759},
issn = {1528-0020},
mesh = {*RNA/genetics ; *Telomerase/metabolism ; Mutation ; Telomere/genetics/metabolism ; },
}
@article {pmid37971645,
year = {2024},
author = {Khaleda, L and Begum, SK and Apu, MAR and Chowdhury, RH and Alam, MJ and Datta, A and Rahman, MZ and Hosain, N and Al-Forkan, M},
title = {Arsenic-Induced Cardiovascular Diseases and their Correlation with Mitochondrial DNA Copy Number, Deletion, and Telomere Length in Bangladeshi Population.},
journal = {Cardiovascular toxicology},
volume = {24},
number = {1},
pages = {27-40},
pmid = {37971645},
issn = {1559-0259},
mesh = {Humans ; DNA, Mitochondrial/genetics ; *Arsenic/toxicity ; DNA Copy Number Variations ; *Cardiovascular Diseases/chemically induced/diagnosis/genetics ; Telomere/genetics ; },
abstract = {Arsenic contamination is a global health concern, primarily through contaminated groundwater and its entry into the food chain. The association between arsenic exposure and cardiovascular diseases (CVDs) is particularly alarming due to CVDs being the leading cause of death worldwide. Arsenic exposure has also been linked to changes in telomere length, mitochondrial DNA copy number (mtDNAcn), and deletion, further increasing the risk of CVDs. We aimed to determine whether arsenic exposure alters telomere length and mtDNAcn and deletion in a total of 50 CVD patients who underwent open heart surgery hailed from known arsenic-affected and unaffected areas in Bangladesh. Amount of arsenic was determined from the collected nails and cardiac tissues. Relative telomere length and mtDNAcn and deletion were quantified by qRT-PCR. The patients from arsenic-contaminated areas had higher average arsenic deposits in their fingers and toenails (P < 0.05) and higher cardiac tissue injury scores (P < 0.05). Moreover, approximately 1.5-fold shorter telomere length (P < 0.05, r = - 0.775), 1.2-fold decreased mtDNAcn (P < 0.05, r = - 0.797), and an 81-fold higher amount of mitochondrial DNA deletion (P < 0.05, r = 0.784) were observed in the patients who had higher arsenic deposition in their nails. Higher levels of arsenic exposure were found to be linked to shorter telomere length, decreased mtDNAcn, and increased mitochondrial DNA deletion in the patients from As-affected areas. It can also be anticipated that the correlation of arsenic exposure with telomere length, mtDNAcn, and deletion can be used as biomarkers for early diagnosis of arsenic-induced cardiovascular diseases.},
}
@article {pmid37966130,
year = {2024},
author = {Zavala-Paez, M and Holliday, J and Hamilton, JA},
title = {Leveraging whole-genome sequencing to estimate telomere length in plants.},
journal = {Molecular ecology resources},
volume = {24},
number = {2},
pages = {e13899},
doi = {10.1111/1755-0998.13899},
pmid = {37966130},
issn = {1755-0998},
support = {//Department of Ecosystem Science and Management at Pennsylvania State University/ ; //Huck Institutes of the Life Sciences/ ; NSF-PGR-1856450//National Science Foundation (NSF)/ ; //Pennsylvania State University's Intercollege Graduate Degree Program in Ecology/ ; //Schatz Center for Tree Molecular Genetics/ ; PEN04809//USDA National Institute of Food and Agriculture and Hatch Appropriations/ ; 7003639//USDA National Institute of Food and Agriculture and Hatch Appropriations/ ; },
mesh = {Humans ; *Plant Breeding ; Whole Genome Sequencing/methods ; *Genome ; Genotype ; Telomere/genetics ; },
abstract = {Changes in telomere length are increasingly used to indicate species' response to environmental stress across diverse taxa. Despite this broad use, few studies have explored telomere length in plants. Thus, evaluation of new approaches for measuring telomeres in plants is needed. Rapid advances in sequencing approaches and bioinformatic tools now allow estimation of telomere content from whole-genome sequencing (WGS) data, a proxy for telomere length. While telomere content has been quantified extensively using quantitative polymerase chain reaction (qPCR) and WGS in humans, no study to date has compared the effectiveness of WGS in estimating telomere length in plants relative to qPCR approaches. In this study, we use 100 Populus clones re-sequenced using short-read Illumina sequencing to quantify telomere length comparing three different bioinformatic approaches (Computel, K-seek and TRIP) in addition to qPCR. Overall, telomere length estimates varied across different bioinformatic approaches, but were highly correlated across methods for individual genotypes. A positive correlation was observed between WGS estimates and qPCR, however, Computel estimates exhibited the greatest correlation. Computel incorporates genome coverage into telomere length calculations, suggesting that genome coverage is likely important to telomere length quantification when using WGS data. Overall, telomere estimates from WGS provided greater precision and accuracy of telomere length estimates relative to qPCR. The findings suggest WGS is a promising approach for assessing telomere length and, as the field of telomere ecology evolves, may provide added value to assaying response to biotic and abiotic environments for plants needed to accelerate plant breeding and conservation management.},
}
@article {pmid37964387,
year = {2023},
author = {Kmiołek, T and Filipowicz, G and Bogucka, D and Wajda, A and Ejma-Multański, A and Stypińska, B and Modzelewska, E and Kaliberda, Y and Radkowski, M and Targowski, T and Wrona, J and Paradowska-Gorycka, A},
title = {Aging and the impact of global DNA methylation, telomere shortening, and total oxidative status on sarcopenia and frailty syndrome.},
journal = {Immunity &amp; ageing : I &amp; A},
volume = {20},
number = {1},
pages = {61},
pmid = {37964387},
issn = {1742-4933},
abstract = {Aging is a biological event that influences many organs and systems. Both sarcopenia and frailty syndrome refer to geriatric conditions with overlapping phenotypes. Many mechanisms are involved in the aging process such as DNA methylation telomeres which are susceptible to oxidative stress, and inflammations which result in telomere shortening, leading to chromosomal instability. The study aimed to determine the associations between these processes, frailty and sarcopenia syndrome. Global DNA methylation was analyzed using the ELISA method. Telomere length was analyzed using qPCR. Total oxidative status (TOS) was analyzed using a colorimetric method. The present study revealed that the main factor affecting methylation, telomeres length and level of total oxidant stress was age.},
}
@article {pmid37962763,
year = {2023},
author = {Liang, Y and Huang, P},
title = {Associations of telomere length with risk of mortality from influenza and pneumonia in US adults: a prospective cohort study of NHANES 1999-2002.},
journal = {Aging clinical and experimental research},
volume = {35},
number = {12},
pages = {3115-3125},
pmid = {37962763},
issn = {1720-8319},
mesh = {Humans ; Male ; Female ; Prospective Studies ; Nutrition Surveys ; *Influenza, Human/genetics ; *Pneumonia/genetics ; Telomere/genetics ; },
abstract = {BACKGROUND: Due to the ongoing Coronavirus disease 2019 (COVID-19) pandemic, interest has arisen to realize the relationship between telomere length (TL) and influenza and pneumonia mortality.<br><br>AIM: Our study attempted to investigate this correlation by analyzing information gathered from the National Health and Nutrition Examination Survey (NHANES) 1999-2002.<br><br>METHODS: A total of 7229 participants were involved in the conducted research. We utilized Cox proportional risk model analysis to determine the hazard ratio (HR) and 95% confidence interval (CI) for TL and influenza and pneumonia mortality.<br><br>RESULTS: During the average follow-up time of 204.10&#x2009;&#xb1;&#x2009;51.26 months, 33 (0.45%) participants died from influenza and pneumonia. After adjusting for multiple variables, shorter TL was associated with higher influenza-pneumonia mortality. In subgroup analyses stratified by sex, men exhibited stronger associations with influenza-pneumonia mortality than women (Model 1: HRmale: 0.014 vs HRfemale: 0.054; Model 2: HRmale: 0.082 vs HRfemale: 0.890; Model 3: HRmale: 0.072 vs HRfemale: 0.776). For subgroup analyses by visceral adiposity index (VAI), all statistically significant (P&#x2009;<&#x2009;0.05) models displayed an inverse relationship between TL and influenza and pneumonia mortality.<br><br>CONCLUSIONS: Our research provides further proof for the connection between shorter telomeres and higher influenza-pneumonia mortality. Larger prospective researches are essential to support our results and explain the underlying mechanisms.},
}
@article {pmid37962459,
year = {2023},
author = {Gold, NM and Okeke, MN and He, Y},
title = {Involvement of Inheritance in Determining Telomere Length beyond Environmental and Lifestyle Factors.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2023.1023},
pmid = {37962459},
issn = {2152-5250},
abstract = {All linear chromosomal ends have specific DNA-protein complexes called telomeres. Telomeres serve as a "molecular clock" to estimate the potential length of cell replication. Shortening of telomere length (TL) is associated with cellular senescence, aging, and various age-related diseases in humans. Here we reviewed the structure, function, and regulation of telomeres and the age-related diseases associated with telomere attrition. Among the various determinants of TL, we highlight the connection between TL and heredity to provide a new overview of genetic determinants for TL. Studies across multiple species have shown that maternal and paternal TL influence the TL of their offspring, and this may affect life span and their susceptibility to age-related diseases. Hence, we reviewed the linkage between TL and parental influences and the proposed mechanisms involved. More in-depth studies on the genetic mechanism for TL attrition are needed due to the potential application of this knowledge in human medicine to prevent premature frailty at its earliest stage, as well as promote health and longevity.},
}
@article {pmid37961611,
year = {2024},
author = {Takai, H and Aria, V and Borges, P and Yeeles, JTP and de Lange, T},
title = {CST-Polymeraseα-primase solves a second telomere end-replication problem.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37961611},
support = {R01 AG016642/AG/NIA NIH HHS/United States ; R35 CA210036/CA/NCI NIH HHS/United States ; R50 CA243771/CA/NCI NIH HHS/United States ; },
abstract = {Telomerase adds G-rich telomeric repeats to the 3' ends of telomeres[1], counteracting telomere shortening caused by loss of telomeric 3' overhangs during leading-strand DNA synthesis ("the end-replication problem"[2]). We report a second end-replication problem that originates from the incomplete duplication of the C-rich telomeric repeat strand by lagging-strand synthesis. This problem is solved by CST-Polymeraseα(Polα)-primase fill-in synthesis. In vitro, priming for lagging-strand DNA replication does not occur on the 3' overhang and lagging-strand synthesis stops in an ~150-nt zone more than 26 nt from the end of the template. Consistent with the in vitro data, lagging-end telomeres of cells lacking CST-Polα-primase lost ~50-60 nt of CCCTAA repeats per population doubling (PD). The C-strands of leading-end telomeres shortened by ~100 nt/PD, reflecting the generation of 3' overhangs through resection. The measured overall C-strand shortening in absence of CST-Polα-primase fill-in is consistent with the combined effects of incomplete lagging-strand synthesis and 5' resection at the leading-ends. We conclude that canonical DNA replication creates two telomere end-replication problems that require telomerase to maintain the G-strand and CST-Polα-primase to maintain the C-strand.},
}
@article {pmid37961382,
year = {2023},
author = {Agabekian, IA and Abdulkina, LR and Lushnenko, AY and Young, PG and Valeeva, LR and Boskovic, O and Lilly, EG and Sharipova, MR and Shippen, DE and Juenger, TE and Shakirov, EV},
title = {Arabidopsis AN3 and OLIGOCELLULA genes link telomere maintenance mechanisms with cell division and expansion control.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {37961382},
support = {R01 GM065383/GM/NIGMS NIH HHS/United States ; R01 GM127402/GM/NIGMS NIH HHS/United States ; },
abstract = {Telomeres are conserved chromosomal structures necessary for continued cell division and proliferation. In addition to the classical telomerase pathway, multiple other genes including those involved in ribosome metabolism and chromatin modification contribute to telomere length maintenance. We previously reported that Arabidopsis thaliana ribosome biogenesis genes OLI2/NOP2A, OLI5/RPL5A and OLI7/RPL5B have critical roles in telomere length regulation. These three OLIGOCELLULA genes were also shown to function in cell proliferation and expansion control and to genetically interact with the transcriptional co-activator ANGUSTIFOLIA3 (AN3). Here we show that AN3-deficient plants progressively lose telomeric DNA in early homozygous mutant generations, but ultimately establish a new shorter telomere length setpoint by the fifth mutant generation with a telomere length similar to oli2/nop2a - deficient plants. Analysis of double an3 oli2 mutants indicates that the two genes are epistatic for telomere length control. Telomere shortening in an3 and oli mutants is not caused by telomerase inhibition; wild type levels of telomerase activity are detected in all analyzed mutants in vitro. Late generations of an3 and oli mutants are prone to stem cell damage in the root apical meristem, implying that genes regulating telomere length may have conserved functional roles in stem cell maintenance mechanisms. Multiple instances of anaphase fusions in late generations of oli5 and oli7 mutants were observed, highlighting an unexpected effect of ribosome biogenesis factors on chromosome integrity. Overall, our data implicate AN3 transcription coactivator and OLIGOCELLULA proteins in the establishment of telomere length set point in plants and further suggest that multiple regulators with pleiotropic functions can connect telomere biology with cell proliferation and cell expansion pathways.},
}
@article {pmid37960914,
year = {2023},
author = {Xing, B and Yu, J and Liu, Y and He, S and Chen, X and Li, Z and He, L and Yang, N and Ping, F and Xu, L and Li, W and Zhang, H and Li, Y},
title = {High Dietary Zinc Intake Is Associated with Shorter Leukocyte Telomere Length, Mediated by Tumor Necrosis Factor-α: A Study of China Adults.},
journal = {The journal of nutrition, health &amp; aging},
volume = {27},
number = {10},
pages = {904-910},
doi = {10.1007/s12603-023-1992-z},
pmid = {37960914},
issn = {1760-4788},
mesh = {Humans ; *Tumor Necrosis Factor-alpha ; *Zinc ; Cross-Sectional Studies ; Diet ; Inflammation ; Superoxide Dismutase ; Leukocytes ; Telomere ; },
abstract = {OBJECTIVES: Diet can influence peripheral leukocyte telomere length (LTL), and various micronutrients have been reported to correlate with it. Zinc is known for its antioxidant properties and immunomodulatory effects. However, there are few epidemiological investigations on the relationship between dietary zinc intake and LTL. This study analyzed the association between dietary zinc and LTL and the potential role of inflammation and oxidative stress among them.<br><br>DESIGN: Cross-sectional and community-based study.<br><br>SETTING AND PARTICIPANTS: 599 participants from rural communities in the Changping suburb of Beijing, China, were recruited.<br><br>MEASUREMENTS: Serum lipid profile, glycosylated hemoglobin (HbA1c), oxidative stress marker, and inflammatory cytokines levels were measured. Detailed dietary data were obtained using a 24 h food recall. LTL was assessed using a real-time PCR assay. Spearman analysis, restricted cubic splines (RCS), and general linear regression models were used to determine the association between dietary zinc intake and LTL. Simple regulatory models were also applied to analyze the role of inflammation and oxidative stress among them.<br><br>RESULTS: A total of 482 subjects were ultimately included in this analysis. Spearman analysis showed that dietary zinc intake and zinc intake under energy density were negatively correlated with LTL (r=-0.142 and -0.126, all P <0.05) and positively correlated with tumor necrosis factor-&#x3b1; (TNF-&#x3b1;) (r=0.138 and 0.202, all P <0.05) while only dietary zinc without energy adjustment had a positive correlation with superoxide dismutase (SOD). RCS (P for non-linearity=0.933) and multiple linear regression (B=-0.084, P=0.009) indicated a negative linear association between dietary zinc and LTL. The adjustment of TNF-&#x3b1; rather than SOD could abolish the relationship. The mediation model suggested that the unfavorable effect of dietary zinc on LTL was mediated by TNF-&#x3b1;.<br><br>CONCLUSIONS: High dietary zinc may correlate with telomere attrition, and TNF-&#x3b1; can act as a mediator in this relationship. In the future, more extensive cohort studies are needed to further explore the relationship between dietary zinc and cellular aging and the specific mechanisms.},
}
@article {pmid37960150,
year = {2023},
author = {Zhu, G and Xu, J and Guo, G and Zhu, F},
title = {Association between Lipids, Apolipoproteins and Telomere Length: A Mendelian Randomization Study.},
journal = {Nutrients},
volume = {15},
number = {21},
pages = {},
pmid = {37960150},
issn = {2072-6643},
support = {81701899//Guanghua Guo/ ; 82160376//Guanghua Guo/ ; 2019YFA0110601//Feng Zhu/ ; },
mesh = {Cholesterol, LDL ; *Mendelian Randomization Analysis ; *Apolipoproteins/genetics ; Apolipoproteins B ; Triglycerides ; Telomere/genetics ; Genome-Wide Association Study ; },
abstract = {(1) Background: The relationship between lipids, apolipoproteins, and telomere length (TL) has been explored in previous studies; however, the causal relationship between the two remains unclear. This study aims to assess the causal relationship between lipids, apolipoproteins, and TL using the two-sample Mendelian randomization (MR) approach; (2) Methods: This study comprehensively employed both univariate MR (uvMR) and multivariate MR (mvMR) methods to genetically evaluate the associations between 21 exposures related to lipids and apolipoproteins and the outcome of TL. During the analysis process, we utilized various statistical methods, including Inverse Variance Weighting (IVW), Weighted Median, MR-Egger regression, MR-PRESSO, and outlier tests. Furthermore, to confirm the robustness of the results, we conducted several sensitivity analyses to explore potential heterogeneity; (3) Results: The uvMR analysis indicated that an increase in MUFA, MUFA/FA ratio, LDL-C, VLDL-C, total cholesterol, ApoB, and triglycerides (TG) was associated with an increase in TL. However, this relationship did not manifest in the mvMR analysis, suggesting that this association may be based on preliminary evidence; (4) Conclusions: MR analysis results suggest potential suggestive positive causal relationships between genetically predicted MUFA, MUFA/FA ratio, LDL-C, VLDL-C, total cholesterol, ApoB, and TG with TL.},
}
@article {pmid37958962,
year = {2023},
author = {Kalmykova, A},
title = {Telomere Checkpoint in Development and Aging.},
journal = {International journal of molecular sciences},
volume = {24},
number = {21},
pages = {},
pmid = {37958962},
issn = {1422-0067},
support = {075-15-2020-773/9//the Ministry of Science and Higher Education of the Russian Federation/ ; },
mesh = {Animals ; *RNA/metabolism ; *Telomere Homeostasis ; Drosophila/genetics ; Aging/genetics ; Telomere/genetics ; Genomic Instability ; },
abstract = {The maintenance of genome integrity through generations is largely determined by the stability of telomeres. Increasing evidence suggests that telomere dysfunction may trigger changes in cell fate, independently of telomere length. Telomeric multiple tandem repeats are potentially highly recombinogenic. Heterochromatin formation, transcriptional repression, the suppression of homologous recombination and chromosome end protection are all required for telomere stability. Genetic and epigenetic defects affecting telomere homeostasis may cause length-independent internal telomeric DNA damage. Growing evidence, including that based on Drosophila research, points to a telomere checkpoint mechanism that coordinates cell fate with telomere state. According to this scenario, telomeres, irrespective of their length, serve as a primary sensor of genome instability that is capable of triggering cell death or developmental arrest. Telomeric factors released from shortened or dysfunctional telomeres are thought to mediate these processes. Here, we discuss a novel signaling role for telomeric RNAs in cell fate and early development. Telomere checkpoint ensures genome stability in multicellular organisms but aggravates the aging process, promoting the accumulation of damaged and senescent cells.},
}
@article {pmid37958686,
year = {2023},
author = {Grzeczka, A and Graczyk, S and Kordowitzki, P},
title = {DNA Methylation and Telomeres-Their Impact on the Occurrence of Atrial Fibrillation during Cardiac Aging.},
journal = {International journal of molecular sciences},
volume = {24},
number = {21},
pages = {},
pmid = {37958686},
issn = {1422-0067},
mesh = {Humans ; Female ; *Atrial Fibrillation ; DNA Methylation ; Aging/pathology ; Heart Atria/pathology ; Telomere/genetics/pathology ; },
abstract = {Atrial fibrillation (AF) is the most common arrhythmia in humans. AF is characterized by irregular and increased atrial muscle activation. This high-frequency activation obliterates the synchronous work of the atria and ventricles, reducing myocardial performance, which can lead to severe heart failure or stroke. The risk of developing atrial fibrillation depends largely on the patient's history. Cardiovascular diseases are considered aging-related pathologies; therefore, deciphering the role of telomeres and DNA methylation (mDNA), two hallmarks of aging, is likely to contribute to a better understanding and prophylaxis of AF. In honor of Prof. Elizabeth Blackburn's 75th birthday, we dedicate this review to the discovery of telomeres and her contribution to research on aging.},
}
@article {pmid37958573,
year = {2023},
author = {Rodriguez-Martin, I and Villanueva-Martin, G and Guillen-Del-Castillo, A and Ortego-Centeno, N and Callejas, JL and Simeón-Aznar, CP and Martin, J and Acosta-Herrera, M},
title = {Contribution of Telomere Length to Systemic Sclerosis Onset: A Mendelian Randomization Study.},
journal = {International journal of molecular sciences},
volume = {24},
number = {21},
pages = {},
pmid = {37958573},
issn = {1422-0067},
support = {RD21/0002/0039//Instituto de Salud Carlos III/ ; CP21/00132//Instituto de Salud Carlos III/ ; PRE2019-087586//Ministerio de Ciencia e Innovaci&#xf3;n/ ; FPU21/02746//Ministerio de Universidades/ ; },
mesh = {Humans ; *Genome-Wide Association Study ; Mendelian Randomization Analysis ; Leukocytes ; *Scleroderma, Systemic/genetics ; Telomere/genetics ; Polymorphism, Single Nucleotide ; },
abstract = {Although previous studies have suggested a relationship between telomere shortening and systemic sclerosis (SSc), the association between these two traits remains poorly understood. The objective of this study was to assess the causal relationship between telomere length in leukocytes (LTL) and SSc using the two-sample Mendelian randomization approach, with the genome-wide association study data for both LTL and SSc. The results of inverse-variance weighted regression (OR = 0.716 [95% CI 0.528-0.970], p = 0.031) and the Mendelian randomization pleiotropy residual sum and outlier method (OR = 0.716 [95% CI 0.563-0.911], p = 0.035) indicate an association between telomere length and SSc. Specifically, longer genetically predicted LTL is associated with a reduced risk of SSc. Sensitivity tests highlight the significant roles of the variants rs10936599 and rs2736100 annotated to the TERC and TERT genes, respectively. Our findings suggest an influence of telomere length in leukocytes on the development of SSc.},
}
@article {pmid37957036,
year = {2024},
author = {Lu, X and Liu, L},
title = {Genome stability from the perspective of telomere length.},
journal = {Trends in genetics : TIG},
volume = {40},
number = {2},
pages = {175-186},
doi = {10.1016/j.tig.2023.10.013},
pmid = {37957036},
issn = {0168-9525},
mesh = {Animals ; *Retroelements ; Telomere/metabolism ; Genomic Instability ; Cell Division ; *Telomerase ; Cellular Senescence ; Mammals ; },
abstract = {Telomeres and their associated proteins protect the ends of chromosomes to maintain genome stability. Telomeres undergo progressive shortening with each cell division in mammalian somatic cells without telomerase, resulting in genome instability. When telomeres reach a critically short length or are recognized as a damage signal, cells enter a state of senescence, followed by cell cycle arrest, programmed cell death, or immortalization. This review provides an overview of recent advances in the intricate relationship between telomeres and genome instability. Alongside well-established mechanisms such as chromosomal fusion and telomere fusion, we will delve into the perspective on genome stability by examining the role of retrotransposons. Retrotransposons represent an emerging pathway to regulate genome stability through their interactions with telomeres.},
}
@article {pmid37953281,
year = {2023},
author = {Carvalho Borges, PC and Bouabboune, C and Escandell, JM and Matmati, S and Coulon, S and Ferreira, MG},
title = {Pot1 promotes telomere DNA replication via the Stn1-Ten1 complex in fission yeast.},
journal = {Nucleic acids research},
volume = {51},
number = {22},
pages = {12325-12336},
pmid = {37953281},
issn = {1362-4962},
support = {PTDC/BEX-BCM/5179/14//FCT/ ; //Howard Hughes Medical Institute IECS/ ; Action 2 - 2019//Universit&#xe9; C&#xf4;te d'Azur - Acad&#xe9;mie 4/ ; EQU201903007804//Fondation pour la Recherche M&#xe9;dicale/ ; //'Ligue Nationale Contre le Cancer' (LNCC)/ ; ANR-16-CE12 TeloMito//Agence Nationale de la Research/ ; },
mesh = {*DNA Replication ; DNA-Binding Proteins/metabolism ; *Schizosaccharomyces/metabolism ; *Schizosaccharomyces pombe Proteins/metabolism ; Shelterin Complex ; *Telomere/metabolism ; Telomere-Binding Proteins/metabolism ; *Chromosomes, Fungal/metabolism ; },
abstract = {Telomeres are nucleoprotein complexes that protect the chromosome-ends from eliciting DNA repair while ensuring their complete duplication. Pot1 is a subunit of telomere capping complex that binds to the G-rich overhang and inhibits the activation of DNA damage checkpoints. In this study, we explore new functions of fission yeast Pot1 by using a pot1-1 temperature sensitive mutant. We show that pot1 inactivation impairs telomere DNA replication resulting in the accumulation of ssDNA leading to the complete loss of telomeric DNA. Recruitment of Stn1 to telomeres, an auxiliary factor of DNA lagging strand synthesis, is reduced in pot1-1 mutants and overexpression of Stn1 rescues loss of telomeres and cell viability at restrictive temperature. We propose that Pot1 plays a crucial function in telomere DNA replication by recruiting Stn1-Ten1 and Polα-primase complex to telomeres via Tpz1, thus promoting lagging-strand DNA synthesis at stalled replication forks.},
}
@article {pmid37951311,
year = {2023},
author = {Banaszak, LG and Smith-Simmer, K and Shoger, K and Lovrien, L and Malik, A and Sandbo, N and Sultan, S and Guzy, R and Lowery, EM and Churpek, JE},
title = {Implementation of a prospective screening strategy to identify adults with a telomere biology disorder among those undergoing lung transplant evaluation for interstitial lung disease.},
journal = {Respiratory medicine},
volume = {220},
number = {},
pages = {107464},
doi = {10.1016/j.rmed.2023.107464},
pmid = {37951311},
issn = {1532-3064},
mesh = {Adult ; Humans ; Prospective Studies ; *Lung Diseases, Interstitial/diagnosis/genetics/surgery ; Telomere/genetics ; *Lung Transplantation ; Biology ; },
abstract = {INTRODUCTION: Patients with interstitial lung disease (ILD) secondary to telomere biology disorders (TBD) experience increased morbidity after lung transplantation. Identifying patients with TBD may allow for personalized management to facilitate better outcomes. However, establishing a TBD diagnosis in adults is challenging.<br><br>METHODS: A TBD screening questionnaire was introduced prospectively into the lung transplant evaluation. Patients with ILD screening positive were referred for comprehensive TBD phenotyping and concurrent telomere length measurement and germline genetic testing.<br><br>RESULTS: Of 98 patients, 32 (33%) screened positive. Eight patients (8% of total; 25% of patients with a positive screen) met strict TBD diagnostic criteria, requiring either critically short lymphocyte telomeres (<1st percentile) (n&#xa0;=&#xa0;4), a pathogenic variant in a TBD-associated gene (n&#xa0;=&#xa0;1), or both (n&#xa0;=&#xa0;3) along with a TBD clinical phenotype. Additional patients not meeting strict diagnostic criteria had histories consistent with TBD along with telomere lengths <10th percentile and/or rare variants in TBD-associated genes, highlighting a critical need to refine TBD diagnostic criteria for this patient population.<br><br>CONCLUSION: A TBD phenotype screening questionnaire in patients with ILD undergoing lung transplant evaluation has a diagnostic yield of 25%. Additional gene discovery, rare variant functional testing, and refined TBD diagnostic criteria are needed to realize the maximum benefit of testing for TBD in patients undergoing lung transplantation.},
}
@article {pmid37951043,
year = {2024},
author = {Nassour, J and Przetocka, S and Karlseder, J},
title = {Telomeres as hotspots for innate immunity and inflammation.},
journal = {DNA repair},
volume = {133},
number = {},
pages = {103591},
pmid = {37951043},
issn = {1568-7856},
support = {R01 CA227934/CA/NCI NIH HHS/United States ; R01 CA234047/CA/NCI NIH HHS/United States ; R01 AG077324/AG/NIA NIH HHS/United States ; R00 CA252447/CA/NCI NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; R01 CA228211/CA/NCI NIH HHS/United States ; K99 CA252447/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Aging/genetics ; *Telomere ; Inflammation ; Immunity, Innate ; Cellular Senescence ; },
abstract = {Aging is marked by the gradual accumulation of deleterious changes that disrupt organ function, creating an altered physiological state that is permissive for the onset of prevalent human diseases. While the exact mechanisms governing aging remain a subject of ongoing research, there are several cellular and molecular hallmarks that contribute to this biological process. This review focuses on two factors, namely telomere dysfunction and inflammation, which have emerged as crucial contributors to the aging process. We aim to discuss the mechanistic connections between these two distinct hallmarks and provide compelling evidence highlighting the loss of telomere protection as a driver of pro-inflammatory states associated with aging. By reevaluating the interplay between telomeres, innate immunity, and inflammation, we present novel perspectives on the etiology of aging and its associated diseases.},
}
@article {pmid37950187,
year = {2023},
author = {Hassanpour, H and Mirshokraei, P and Salehpour, M and Amiri, K and Ghareghani, P and Nasiri, L},
title = {Canine sperm motility is associated with telomere shortening and changes in expression of shelterin genes.},
journal = {BMC veterinary research},
volume = {19},
number = {1},
pages = {236},
pmid = {37950187},
issn = {1746-6148},
mesh = {Male ; Dogs ; Animals ; *Shelterin Complex ; *Telomere-Binding Proteins/genetics/metabolism ; Telomere Shortening ; Sperm Motility/genetics ; Semen ; },
abstract = {BACKGROUND: Motion quality is a critical property for essential functions. Several endogenous and exogenous factors are involved in sperm motility. Here, we measured the relative telomere length and evaluated the gene expression of its binding-proteins, shelterin complex (TRF1, TRF2, RAP1, POT1, TIN2, and TPP1) in sperm of dogs using relative quantitative real-time PCR. We compared them between two sperm subpopulations with poor and good motion qualities (separated by swim-up method). Telomere shortening and alterations of shelterin gene expression result from ROS, genotoxic insults, and genetic predisposition.<br><br>RESULTS: Sperm kinematic parameters were measured in two subpopulations and then telomeric index of each parameter was calculated. Telomeric index for linearity, VSL, VCL, STR, BCF, and ALH were significantly higher in sperms with good motion quality than in sperms with poor quality. We demonstrated that poor motion quality is associated with shorter telomere, higher expression of TRF2, POT1, and TIN2 genes, and lower expression of the RAP1 gene in dog sperm. The levels of TRF1 and TPP1 gene expression remained consistent despite variations in sperm quality and telomere length.<br><br>CONCLUSION: Data provided evidence that there are considerable changes in gene expression of many shelterin components (TRF2, TIN2, POT1and RAP1) associated with shortening telomere in the spermatozoa with poor motion quality. Possibly, the poor motion quality is the result of defects in the shelterin complex and telomere length. Our data suggests a new approach in the semen assessment and etiologic investigations of subfertility or infertility in male animals.},
}
@article {pmid37949346,
year = {2024},
author = {Randell, Z and Dehghanbanadaki, H and Fendereski, K and Jimbo, M and Aston, K and Hotaling, J},
title = {Sperm telomere length in male-factor infertility and reproduction.},
journal = {Fertility and sterility},
volume = {121},
number = {1},
pages = {12-25},
doi = {10.1016/j.fertnstert.2023.11.001},
pmid = {37949346},
issn = {1556-5653},
mesh = {Male ; Humans ; *Semen ; *Infertility, Male/diagnosis/genetics ; Spermatozoa ; Reproduction ; Telomere/genetics ; },
abstract = {The underlying reasons for male-factor infertility are often unknown. 30% of all men have unexplained semen analysis abnormalities. Moreover, 15%-40% of infertile men have normal semen analyses. There have been increasing efforts to identify causes and associations that may explain idiopathic male-factor infertility. Telomeres have become an area of considerable interest in the field because of the essential roles they have in cellular division and genome integrity. Research to date most consistently supports that men with infertility have shorter sperm telomere length (STL); however, associations between shorter STL and meaningful reproductive health outcomes are less consistent. There is a major need for additional studies to better identify the role of STL in male reproductive health and use the information to improve the counseling and treatment of couples with idiopathic male-factor infertility.},
}
@article {pmid37947937,
year = {2023},
author = {Ferrer, A and Stephens, ZD and Kocher, JA},
title = {Experimental and Computational Approaches to Measure Telomere Length: Recent Advances and Future Directions.},
journal = {Current hematologic malignancy reports},
volume = {18},
number = {6},
pages = {284-291},
pmid = {37947937},
issn = {1558-822X},
mesh = {Humans ; Forecasting ; *Telomere/genetics ; },
abstract = {PURPOSE OF REVIEW: The length of telomeres, protective structures at the chromosome ends, is a well-established biomarker for pathological conditions including multisystemic syndromes called telomere biology disorders. Approaches to measure telomere length (TL) differ on whether they estimate average, distribution, or chromosome-specific TL, and each presents their own advantages and limitations.<br><br>RECENT FINDINGS: The development of long-read sequencing and publication of the telomere-to-telomere human genome reference has allowed for scalable and high-resolution TL estimation in pre-existing sequencing datasets but is still impractical as a dedicated TL test. As sequencing costs continue to fall and strategies for selectively enriching telomere regions prior to sequencing improve, these approaches may become a promising alternative to classic methods. Measurement methods rely on probe hybridization, qPCR or more recently, computational methods using sequencing data. Refinements of existing techniques and new approaches have been recently developed but a test that is accurate, simple, and scalable is still lacking.},
}
@article {pmid37946752,
year = {2023},
author = {Yan, J and Jin, T and Wang, L},
title = {Hematopoietic stem cell transplantation of aplastic anemia by relative with mutations and normal telomere length: A case report.},
journal = {World journal of clinical cases},
volume = {11},
number = {29},
pages = {7200-7206},
pmid = {37946752},
issn = {2307-8960},
abstract = {BACKGROUND: Immunosuppressive therapy and matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) are the preferred treatments for aplastic anemia (AA).<br><br>CASE SUMMARY: In this report, we describe a 43-year-old male patient with severe AA who carried BRIP1 (also known as FANCJ), TINF2, and TCIRG1 mutations. Screening of the family pedigree revealed the same TINF2 mutation in his mother and older brother, with his older brother also carrying the BRIP1 variant and demonstrating normal telomere length and hematopoietic function. The patient was successfully treated with oral cyclosporine A, eltrombopag, and acetylcysteine, achieving remission 4 years after receiving MSD-HSCT from his older brother.<br><br>CONCLUSION: This case provides a valuable clinical reference for individuals with suspected pathogenic gene mutations, normal telomere length, and hematopoietic function, highlighting them as potential donors for patients with AA.},
}
@article {pmid37944684,
year = {2023},
author = {Rolles, B and Caballero-Oteyza, A and Proietti, M and Goldacker, S and Warnatz, K and Camacho-Ordonez, N and Prader, S and Schmid, JP and Vieri, M and Isfort, S and Meyer, R and Kirschner, M and Brümmendorf, TH and Beier, F and Grimbacher, B},
title = {Telomere biology disorders may manifest as common variable immunodeficiency (CVID).},
journal = {Clinical immunology (Orlando, Fla.)},
volume = {257},
number = {},
pages = {109837},
doi = {10.1016/j.clim.2023.109837},
pmid = {37944684},
issn = {1521-7035},
mesh = {Adult ; Humans ; *Common Variable Immunodeficiency/genetics ; *Telomerase/genetics/metabolism ; *Primary Immunodeficiency Diseases ; Telomere/genetics/metabolism/pathology ; *Dyskeratosis Congenita/genetics/diagnosis/pathology ; Biology ; },
abstract = {Telomere biology disorders (TBD) are caused by germline pathogenic variants in genes related to telomere maintenance and are characterized by critically short telomeres. In contrast to classical dyskeratosis congenita (DC), which is typically diagnosed in infancy, adult or late onset TBD frequently lack the typical DC triad and rather show variable organ manifestations and a cryptic disease course, thus complicating its diagnosis. Common variable immunodeficiency (CVID), on the other hand, is a primary antibody deficiency (PAD) syndrome. PADs are a heterogenous group of diseases characterized by hypogammaglobulinemia which occurs due to dysfunctional B lymphocytes and additional autoimmune and autoinflammatory complications. Genetic screening reveals a monogenic cause in a subset of CVID patients (15-35%). In our study, we screened the exomes of 491 CVID patients for the occurrence of TBD-related variants in 13 genes encoding for telomere/telomerase-associated proteins, which had previously been linked to the disease. We found 110/491 patients (22%) carrying 91 rare candidate variants in these 13 genes. Following the American College of Medical Genetics and Genomics (ACMG) guidelines, we classified two variants as benign, two as likely benign, 64 as variants of uncertain significance (VUS), four as likely pathogenic, and one heterozygous variant in an autosomal recessive disease gene as pathogenic. We performed telomere length measurement in 42 of the 110 patients with candidate variants and CVID. Two of these 42 patients showed significantly shorter telomeres compared to controls in both lymphocytes and granulocytes. Following the evaluation of the published literature and the patient's manifestations, we re-classified two VUS as likely pathogenic variants. Thus, 0.5-1% of all CVID patients in our study carry possibly pathogenic variants in telomere/telomerase-associated genes. Our data adds CVID to the broad clinical spectrum of cryptic adult-onset TBD. As the molecular diagnosis greatly impacts patient management and treatment strategies, we advise inclusion of all TBD-associated genes-despite their low prevalence-into the molecular screening of patients with antibody deficiencies.},
}
@article {pmid37943179,
year = {2023},
author = {Sato, MP and Iwakami, S and Fukunishi, K and Sugiura, K and Yasuda, K and Isobe, S and Shirasawa, K},
title = {Telomere-to-telomere genome assembly of an allotetraploid pernicious weed, Echinochloa phyllopogon.},
journal = {DNA research : an international journal for rapid publication of reports on genes and genomes},
volume = {30},
number = {5},
pages = {},
pmid = {37943179},
issn = {1756-1663},
support = {19H02955//KAKENHI/ ; //Kazusa DNA Research Institute Foundation/ ; },
mesh = {*Echinochloa ; Telomere/genetics ; *Oryza/genetics ; Phenotype ; Tetraploidy ; },
abstract = {Echinochloa phyllopogon is an allotetraploid pernicious weed species found in rice fields worldwide that often exhibit resistance to multiple herbicides. An accurate genome sequence is essential to comprehensively understand the genetic basis underlying the traits of this species. Here, the telomere-to-telomere genome sequence of E. phyllopogon was presented. Eighteen chromosome sequences spanning 1.0 Gb were constructed using the PacBio highly fidelity long technology. Of the 18 chromosomes, 12 sequences were entirely assembled into telomere-to-telomere and gap-free contigs, whereas the remaining six sequences were constructed at the chromosomal level with only eight gaps. The sequences were assigned to the A and B genome with total lengths of 453 and 520 Mb, respectively. Repetitive sequences occupied 42.93% of the A genome and 48.47% of the B genome, although 32,337, and 30,889 high-confidence genes were predicted in the A and B genomes, respectively. This suggested that genome extensions and gene disruptions caused by repeated sequence accumulation often occur in the B genome before polyploidization to establish a tetraploid genome. The highly accurate and comprehensive genome sequence could be a milestone in understanding the molecular mechanisms of the pernicious traits and in developing effective weed control strategies to avoid yield loss in rice production.},
}
@article {pmid37942318,
year = {2023},
author = {Pan, R and Xiao, M and Wu, Z and Liu, J and Wan, L},
title = {Associations of genetically predicted circulating levels of cytokines with telomere length: a Mendelian randomization study.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1276257},
pmid = {37942318},
issn = {1664-3224},
mesh = {Humans ; *Cytokines/genetics ; *Interleukin-7 ; Interleukin-2 Receptor alpha Subunit ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Reproducibility of Results ; Telomere/genetics ; },
abstract = {BACKGROUND: Telomere length (TL) has been regarded as a biomarker of aging, and TL shortening is associated with numerous chronic illnesses. The mounting evidence has shown that inflammatory cytokines are involved in maintaining or shortening TL, the causality of cytokines with TL remains unknown. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to estimate the underlying correlations of circulating inflammatory cytokines with TL.<br><br>METHODS: Genetic instrumental variables for inflammatory cytokines were identified through a genome-wide association study (GWAS) involving 8,293 European individuals. Summary statistics of TL were derived from a UK Bio-bank cohort comprising 472,174 samples of individuals with European descent. We employed the inverse-variance weighted (IVW) approach as our main analysis, and to ensure the reliability of our findings, we also conducted additional analyses including the weighted median, MR-Egger, MR pleiotropy residual sum and outlier test, and weighted model. Lastly, the reverse MR analyses were performed to estimate the likelihood of inverse causality between TL and the cytokines identified in the forward MR analysis. Cochran's Q test were employed to quantify the degree of heterogeneity.<br><br>RESULTS: After applying Bonferroni correction, a higher circulating level of Interleukin-7 (IL-7) was suggestively associated with TL maintaining (OR:1.01, 95%CI:1.00-1.02, P=0.032 by IVW method). The study also revealed suggestive evidence indicating the involvement of Interleukin-2 receptor, alpha subunit (IL-2R&#x3b1;) level was negatively associated with TL maintaining (OR:0.98, 95%CI:0.96-1.00, P=0.045 by IVW method), and the weighted median approach was consistent (OR:0.99, 95%CI:0.97-1.00, P=0.035). According to the findings of reverse MR analysis, no significant causal relationship between TL and cytokines was explored. Our analysis did not reveal any substantial heterogeneity in the Single nucleotide polymorphisms or horizontal pleiotropy.<br><br>CONCLUSIONS: Our MR analysis yielded suggestive evidence supporting the causality between circulating IL-7 and IL-2R&#x3b1; and telomere length, necessitating further investigations to elucidate the mechanisms by which these inflammatory cytokines may impact the progression of telomeres.},
}
@article {pmid37940980,
year = {2023},
author = {Tang, L and Li, D and Ma, Y and Cui, F and Wang, J and Tian, Y},
title = {The association between telomere length and non-alcoholic fatty liver disease: a prospective study.},
journal = {BMC medicine},
volume = {21},
number = {1},
pages = {427},
pmid = {37940980},
issn = {1741-7015},
mesh = {Humans ; *Non-alcoholic Fatty Liver Disease/epidemiology/genetics/complications ; Prospective Studies ; Risk Factors ; *Air Pollution ; Telomere/genetics ; },
abstract = {BACKGROUND: Research on the association between telomere length (TL) and incident non-alcoholic fatty liver disease (NAFLD) is limited. This study examined this association and further assessed how TL contributes to the association of NAFLD with its known risk factors.<br><br>METHODS: Quantitative PCR (polymerase chain reaction) was employed to assess leucocyte telomere length. Polygenic risk score (PRS) for NAFLD, air pollution score, and lifestyle index were constructed. Cox proportional hazard models were conducted to estimate the hazard ratios (HRs) and 95% confidence intervals.<br><br>RESULTS: Among 467,848 participants in UK Biobank, we identified 4809 NAFLD cases over a median follow-up of 12.83&#xa0;years. We found that long TL was associated with decreased risk of incident NAFLD, as each interquartile range increase in TL resulted in an HR of 0.93 (95% CI 0.89, 0.96). TL partly mediated the association between age and NAFLD (proportion mediated: 15.52%). When assessing the joint effects of TL and other risk factors, the highest risk of NAFLD was found in participants with low TL and old age, low TL and high air pollution score, low TL and unfavorable lifestyle, and low TL and high PRS, compared to each reference group. A positive addictive interaction was observed between high PRS and low TL, accounting for 14.57% (2.51%, 27.14%) of the risk of NAFLD in participants with low telomere length and high genetic susceptibility.<br><br>CONCLUSIONS: Long telomere length was associated with decreased risk of NAFLD incidence. Telomere length played an important role in NAFLD.},
}
@article {pmid37939053,
year = {2023},
author = {Kotecha, EA and Zhang, L and Aboklaish, A and Cousins, M and Hart, K and Kotecha, SJ and Watkins, WJ and Kotecha, S},
title = {Association of early and current life factors with telomere length in preterm-born children.},
journal = {PloS one},
volume = {18},
number = {11},
pages = {e0293589},
pmid = {37939053},
issn = {1932-6203},
support = {MR/M022552/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Infant, Newborn ; Male ; Infant ; Female ; Humans ; Child ; *Infant, Premature ; Gestational Age ; *Bronchopulmonary Dysplasia ; Fetal Growth Retardation ; Telomere/genetics ; },
abstract = {BACKGROUND: Telomeres shorten after each cell division. Since preterm-born babies are delivered early and often suffer from inflammatory conditions such as bronchopulmonary dysplasia (BPD), their telomere length may be altered.<br><br>OBJECTIVES: We assessed associations of early and current life factors with telomere length in saliva samples obtained from 7-12-year-old children born at &#x2264;34 weeks' gestation and term-born controls.<br><br>STUDY DESIGN: Relative telomere length was measured by qPCR on extracted DNA. Groups were compared using independent t-tests or ANOVA with post-hoc correction. Linear regression analysis was also used.<br><br>RESULTS: 534 children had satisfactory telomere data including 383 who were preterm-born (mean (SD) birthweight 1732g (558g), gestation 31.1 (2.6) weeks) and 151 term-born (3464g (510g); 39.8 (1.3) weeks). Telomere length was longer in children who had intrauterine growth restriction (IUGR) at birth: mean (SD): 464.6 (166.3) vs. 418.6 (110.7) in the no-IUGR group; in females: 440.2 (130.1) vs. 405.7 (101.5) in males; and in the least deprived group (397.8 (95.0) vs. 437.6 (121.9) most vs least deprivation quintile). Differences were most notable in females with IUGR. However, telomere length was not different between the preterm and term groups; the BPD and no BPD groups nor was it related to lung function or cardiovascular measurements. In multivariable regression analyses, telomere length was associated with sex, IUGR and deprivation with the greatest difference observed in females with IUGR.<br><br>CONCLUSIONS: Telomere length was associated with sex, IUGR and deprivation, especially in females with IUGR, but not with prematurity, BPD, lung function or cardiovascular measurements.},
}
@article {pmid37934624,
year = {2023},
author = {Sidali, S and Borie, R and Sicre de Fontbrune, F and El Husseini, K and Rautou, PE and Lainey, E and Goria, O and Crestani, B and Cadranel, J and Cottin, V and Bunel, V and Dumortier, J and Jacquemin, E and Reboux, N and Hirschi, S and Bourdin, A and Meszaros, M and Dharancy, S and Hilaire, S and Mallet, V and Reynaud-Gaubert, M and Terriou, L and Gottrand, F and Abou Chahla, W and Khan, JE and Carrier, P and Saliba, F and Rubbia-Brandt, L and Aubert, JD and Elkrief, L and de Lédinghen, V and Abergel, A and Olivier, T and Houssel, P and Jouneau, S and Wemeau, L and Bergeron, A and Leblanc, T and Ollivier-Hourmand, I and Nguyen Khac, E and Morisse-Pradier, H and Ba, I and Boileau, C and Roudot-Thoraval, F and Vilgrain, V and Bureau, C and Nunes, H and Naccache, JM and Durand, F and Francoz, C and Roulot, D and Valla, D and Paradis, V and Kannengiesser, C and Plessier, A},
title = {Liver disease in germline mutations of telomere-related genes: Prevalence, clinical, radiological, pathological features, outcome, and risk factors.},
journal = {Hepatology (Baltimore, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/HEP.0000000000000667},
pmid = {37934624},
issn = {1527-3350},
abstract = {BACKGROUND AND AIM: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases.<br><br>APPROACH AND RESULTS: Retrospective multicenter analysis of liver disease (transaminases > 30 IU/L and/or abnormal liver imaging) in patients with TRG mutations. Main measurements were characteristics, outcomes, and risk factors of liver disease in a TRG mutations cohort. The prevalence of liver disease was compared to a community-based control group (n = 1190) stratified for age and matched 1:3 for known risk factors of liver disease. Among 132 patients with TRG mutations, 95 (72%) had liver disease, with associated lung, blood, skin, rheumatological, and ophthalmological TRG diseases in 82%, 77%, 55%, 39%, and 30% of cases, respectively. Liver biopsy was performed in 52/95 patients, identifying porto-sinusoidal vascular disease in 48% and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12-54), ascites, hepato-pulmonary syndrome, variceal bleeding, and HCC occurred in 14%, 13%, 13%, and 2% of cases, respectively. Five-year liver transplantation-free survival was 69%. A FIB-4 score &#x2265; 3&#xb7;25 and &#x2265;1 risk factor for cirrhosis were associated with poor liver transplantation-free survival. Liver disease was more frequent in patients with TRG mutations than in the paired control group [80/396, (20%)], OR 12.9 (CI 95%: 7.8-21.3, p < 0.001).<br><br>CONCLUSIONS: TRG mutations significantly increase the risk of developing liver disease. Although symptoms may be mild, they may be associated with severe disease. Porto-sinusoidal vascular disease and cirrhosis were the most frequent lesions, suggesting that the mechanism of action is multifactorial.},
}
@article {pmid37930826,
year = {2023},
author = {Wang, Y and Zhu, W and Jang, Y and Sommers, JA and Yi, G and Puligilla, C and Croteau, DL and Yang, Y and Kai, M and Liu, Y},
title = {The RNA-binding motif protein 14 regulates telomere integrity at the interface of TERRA and telomeric R-loops.},
journal = {Nucleic acids research},
volume = {51},
number = {22},
pages = {12242-12260},
pmid = {37930826},
issn = {1362-4962},
support = {/AG/NIA NIH HHS/United States ; /AG/NIA NIH HHS/United States ; },
mesh = {Humans ; DNA/genetics ; R-Loop Structures ; RNA/genetics/metabolism ; RNA, Long Noncoding/genetics ; RNA-Binding Motifs ; *Telomere/genetics/metabolism ; *Telomere Homeostasis ; Neoplasms/genetics ; },
abstract = {Telomeric repeat-containing RNA (TERRA) and its formation of RNA:DNA hybrids (or TERRA R-loops), influence telomere maintenance, particularly in human cancer cells that use homologous recombination-mediated alternative lengthening of telomeres. Here, we report that the RNA-binding motif protein 14 (RBM14) is associated with telomeres in human cancer cells. RBM14 negatively regulates TERRA expression. It also binds to TERRA and inhibits it from forming TERRA R-loops at telomeres. RBM14 depletion has several effects, including elevated TERRA levels, telomeric R-loops, telomere dysfunction-induced DNA damage foci formation, particularly in the presence of DNA replication stress, pRPA32 accumulation at telomeres and telomere signal-free ends. Thus, RBM14 protects telomere integrity via modulating TERRA levels and its R-loop formation at telomeres.},
}
@article {pmid37927407,
year = {2023},
author = {He, S and Weng, D and Zhang, Y and Kong, Q and Wang, K and Jing, N and Li, F and Ge, Y and Xiong, H and Wu, L and Xie, DY and Feng, S and Yu, X and Wang, X and Shu, S and Mei, Z},
title = {A telomere-to-telomere reference genome provides genetic insight into the pentacyclic triterpenoid biosynthesis in Chaenomeles speciosa.},
journal = {Horticulture research},
volume = {10},
number = {10},
pages = {uhad183},
pmid = {37927407},
issn = {2662-6810},
abstract = {Chaenomeles speciosa (2n = 34), a medicinal and edible plant in the Rosaceae, is commonly used in traditional Chinese medicine. To date, the lack of genomic sequence and genetic studies has impeded efforts to improve its medicinal value. Herein, we report the use of an integrative approach involving PacBio HiFi (third-generation) sequencing and Hi-C scaffolding to assemble a high-quality telomere-to-telomere genome of C. speciosa. The genome comprised 650.4 Mb with a contig N50 of 35.5 Mb. Of these, 632.3 Mb were anchored to 17 pseudo-chromosomes, in which 12, 4, and 1 pseudo-chromosomes were represented by a single contig, two contigs, and four contigs, respectively. Eleven pseudo-chromosomes had telomere repeats at both ends, and four had telomere repeats at a single end. Repetitive sequences accounted for 49.5% of the genome, while a total of 45 515 protein-coding genes have been annotated. The genome size of C. speciosa was relatively similar to that of Malus domestica. Expanded or contracted gene families were identified and investigated for their association with different plant metabolisms or biological processes. In particular, functional annotation characterized gene families that were associated with the biosynthetic pathway of oleanolic and ursolic acids, two abundant pentacyclic triterpenoids in the fruits of C. speciosa. Taken together, this telomere-to-telomere and chromosome-level genome of C. speciosa not only provides a valuable resource to enhance understanding of the biosynthesis of medicinal compounds in tissues, but also promotes understanding of the evolution of the Rosaceae.},
}
@article {pmid37926899,
year = {2024},
author = {Zhao, L and Jin, W and Zhang, T and Lu, Y and Liu, Q and Cai, J and Luo, L and Teng, K and Guan, Q and Wu, S and Rong, J and Liang, YJ and Cao, J and Qin, L and Huang, C and Wang, X and Li, Y and Zhang, Z and Qin, J},
title = {Association between the dietary antioxidant index and relative telomere length of leucocytes in the Chinese population.},
journal = {The British journal of nutrition},
volume = {131},
number = {6},
pages = {1031-1040},
doi = {10.1017/S0007114523002544},
pmid = {37926899},
issn = {1475-2662},
mesh = {Humans ; Male ; Female ; *Antioxidants ; Cross-Sectional Studies ; *Vitamin E ; Telomere ; China ; },
abstract = {Dietary antioxidant indices (DAI) may be potentially associated with relative telomere length (RTL) of leucocytes. This study aimed to investigate the relationship between DAI and RTL. A cross-sectional study involving 1656 participants was conducted. A generalised linear regression model and a restricted cubic spline model were used to assess the correlation of DAI and its components with RTL. Generalised linear regression analysis revealed that DAI (β = 0·005, P = 0·002) and the intake of its constituents vitamin C (β = 0·043, P = 0·027), vitamin E (β = 0·088, P < 0·001), Se (β = 0·075, P = 0·003), and Zn (β = 0·075, P = 0·023) were significantly and positively correlated with RTL. Sex-stratified analysis showed that DAI (β = 0·006, P = 0·005) and its constituents vitamin E (β = 0·083, P = 0·012), Se (β = 0·093, P = 0·006), and Zn (β = 0·092, P = 0·034) were significantly and positively correlated with RTL among females. Meanwhile, among males, only vitamin E intake (β = 0·089, P = 0·013) was significantly and positively associated with RTL. Restricted cubic spline analysis revealed linear positive associations between DAI and its constituents' (vitamin E, Se and Zn) intake and RTL in the total population. Sex-stratified analysis revealed a linear positive correlation between DAI and its constituents' (vitamin E, Se and Zn) intake and RTL in females. Our study found a significant positive correlation between DAI and RTL, with sex differences.},
}
@article {pmid37926112,
year = {2023},
author = {Elbadry, MI and Tawfeek, A and Hirano, T and El-Mokhtar, MA and Kenawey, M and Helmy, AM and Ogawa, S and Mughal, MZ and Nannya, Y},
title = {A rare homozygous variant in TERT gene causing variable bone marrow failure, fragility fractures, rib anomalies and extremely short telomere lengths with high serum IgE.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.19176},
pmid = {37926112},
issn = {1365-2141},
abstract = {By whole exome sequencing, we identified a homozygous c.2086 C→T (p.R696C) TERT mutation in patients who present with a spectrum of variable bone marrow failure (BMF), raccoon eyes, dystrophic nails, rib anomalies, fragility fractures (FFs), high IgE level, extremely short telomere lengths (TLs), and skewed numbers of cytotoxic T cells with B and NK cytopenia. Haploinsufficiency in the other family members resulted in short TL and osteopenia. These patients also had the lowest bone mineral density Z-score compared to other BMF-patients. Danazol/zoledronic acid improved the outcomes of BMF and FFs. This causative TERT variant has been observed in one family afflicted with dyskeratosis congenita (DC), and thus, we also define a second report and new phenotype related to the variant which should be suspected in severe cases of DC with co-existent BMF, FFs, high IgE level and rib anomalies.},
}
@article {pmid37922882,
year = {2023},
author = {Miga, KH and Eichler, EE},
title = {Envisioning a new era: Complete genetic information from routine, telomere-to-telomere genomes.},
journal = {American journal of human genetics},
volume = {110},
number = {11},
pages = {1832-1840},
pmid = {37922882},
issn = {1537-6605},
support = {R01 HG010169/HG/NHGRI NIH HHS/United States ; R01 HG011274/HG/NHGRI NIH HHS/United States ; U01 HG010971/HG/NHGRI NIH HHS/United States ; U24 HG007497/HG/NHGRI NIH HHS/United States ; },
mesh = {Humans ; *Genomics ; Sequence Analysis, DNA ; *High-Throughput Nucleotide Sequencing ; Genome, Human/genetics ; Telomere/genetics ; },
abstract = {Advances in long-read sequencing and assembly now mean that individual labs can generate phased genomes that are more accurate and more contiguous than the original human reference genome. With declining costs and increasing democratization of technology, we suggest that complete genome assemblies, where both parental haplotypes are phased telomere to telomere, will become standard in human genetics. Soon, even in clinical settings where rigorous sample-handling standards must be met, affected individuals could have reference-grade genomes fully sequenced and assembled in just a few hours given advances in technology, computational processing, and annotation. Complete genetic variant discovery will transform how we map, catalog, and associate variation with human disease and fundamentally change our understanding of the genetic diversity of all humans.},
}
@article {pmid37925537,
year = {2023},
author = {Rosso, I and Jones-Weinert, C and Rossiello, F and Cabrini, M and Brambillasca, S and Munoz-Sagredo, L and Lavagnino, Z and Martini, E and Tedone, E and Garre', M and Aguado, J and Parazzoli, D and Mione, M and Shay, JW and Mercurio, C and d'Adda di Fagagna, F},
title = {Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {7086},
pmid = {37925537},
issn = {2041-1723},
support = {P30 CA142543/CA/NCI NIH HHS/United States ; P50 CA070907/CA/NCI NIH HHS/United States ; },
mesh = {*Telomere Homeostasis/genetics ; DNA Replication ; RNA ; Cell Survival/genetics ; Telomere/genetics/metabolism ; *Telomerase/genetics/metabolism ; },
abstract = {Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism activated in ~10-15% of cancers, characterized by telomeric damage. Telomeric damage-induced long non-coding RNAs (dilncRNAs) are transcribed at dysfunctional telomeres and contribute to telomeric DNA damage response (DDR) activation and repair. Here we observed that telomeric dilncRNAs are preferentially elevated in ALT cells. Inhibition of C-rich (teloC) dilncRNAs with antisense oligonucleotides leads to DNA replication stress responses, increased genomic instability, and apoptosis induction selectively in ALT cells. Cell death is dependent on DNA replication and is increased by DNA replication stress. Mechanistically, teloC dilncRNA inhibition reduces RAD51 and 53BP1 recruitment to telomeres, boosts the engagement of BIR machinery, and increases C-circles and telomeric sister chromatid exchanges, without increasing telomeric non-S phase synthesis. These results indicate that teloC dilncRNA is necessary for a coordinated recruitment of DDR factors to ALT telomeres and it is essential for ALT cancer cells survival.},
}
@article {pmid37924942,
year = {2024},
author = {Scorza, FA and Finsterer, J and Beltramim, L and Bombardi, LM and de Almeida, AG},
title = {Telomere Length and Pesticide Residues in Food: A Causal Link?.},
journal = {Journal of the Academy of Nutrition and Dietetics},
volume = {124},
number = {3},
pages = {311-312},
doi = {10.1016/j.jand.2023.11.002},
pmid = {37924942},
issn = {2212-2672},
mesh = {Humans ; *Pesticide Residues/analysis ; Fruit ; Telomere ; Food Contamination/analysis ; },
}
@article {pmid37921058,
year = {2023},
author = {Tsatsakis, A and Renieri, E and Tsoukalas, D and Buga, AM and Sarandi, E and Vakonaki, E and Fragkiadaki, P and Alegakis, A and Nikitovic, D and Calina, D and Spandidos, DA and Docea, AO},
title = {A novel nutraceutical formulation increases telomere length and activates telomerase activity in middle‑aged rats.},
journal = {Molecular medicine reports},
volume = {28},
number = {6},
pages = {},
pmid = {37921058},
issn = {1791-3004},
mesh = {Rats ; Animals ; *Telomerase/metabolism ; Leukocytes, Mononuclear/metabolism ; Telomere Shortening ; Dietary Supplements ; Telomere/metabolism ; },
abstract = {Telomeres are major contributors to cell fate and aging through their involvement in cell cycle arrest and senescence. The accelerated attrition of telomeres is associated with aging‑related diseases, and agents able to maintain telomere length (TL) through telomerase activation may serve as potential treatment strategies. The aim of the present study was to assess the potency of a novel telomerase activator on TL and telomerase activity in vivo. The administration of a nutraceutical formulation containing Centella asiatica extract, vitamin C, zinc and vitamin D3 in 18‑month‑old rats for a period of 3 months reduced the telomere shortening rate at the lower supplement dose and increased mean the TL at the higher dose, compared to pre‑treatment levels. TL was determined using the Q‑FISH method in peripheral blood mononuclear cells collected from the tail vein of the rats and cultured with RPMI‑1640 medium. In both cases, TLs were significantly longer compared to the untreated controls (P≤0.001). In addition, telomerase activity was increased in the peripheral blood mononuclear cells of both treatment groups. On the whole, the present study demonstrates that the nutraceutical formulation can maintain or even increase TL and telomerase activity in middle‑aged rats, indicating a potential role of this formula in the prevention and treatment of aging‑related diseases.},
}
@article {pmid37919818,
year = {2023},
author = {Prasad, A and Lin, J and Jelliffe-Pawlowski, L and Coleman-Phox, K and Rand, L and Wojcicki, JM},
title = {Sub-optimal maternal gestational gain is associated with shorter leukocyte telomere length at birth in a predominantly Latinx cohort of newborns.},
journal = {Maternal health, neonatology and perinatology},
volume = {9},
number = {1},
pages = {14},
pmid = {37919818},
issn = {2054-958X},
support = {Wojcicki//UCSF Preterm Birth Initiative/ ; Wojcicki//Little Giraffe Foundation/ ; },
abstract = {OBJECTIVE: To assess in utero exposures associated with leukocyte telomere length (LTL) at birth and maternal LTL in a primarily Latinx birth cohort.<br><br>STUDY DESIGN: Mothers and newborns were recruited postnatally before 24&#xa0;h of life. Newborn LTL was collected via heelstick at birth and maternal LTL was collected postnatally. LTL was determined by quantitative PCR. Using a longitudinal design, we evaluated associations between neonatal and maternal LTL and appropriate maternal gestational gain as indicated by the American College of Obstetrics and Gynecology (ACOG).<br><br>RESULT: Mean infant LTL was 2.02&#x2009;&#xb1;&#x2009;0.30&#xa0;T/S (n&#x2009;=&#x2009;386) and maternal LTL was 1.54&#x2009;&#xb1;&#x2009;0.26&#xa0;T/S (n&#x2009;=&#x2009;58). Independent risk factors for shorter LTL at birth included longer gestational duration (Coeff:-0.03, 95%CI: -0.05-0.01;p&#x2009;<&#x2009;0.01) and maternal gestational weight gain below ACOG recommendations (Coeff:-0.10, 95%CI: -0.18 - -0.02; p&#x2009;=&#x2009;0.01).<br><br>CONCLUSION: Gestational weight gain below ACOG recommendations may adversely impact neonatal health in Latinx infants as indicated by shorter LTL at birth.},
}
@article {pmid37919072,
year = {2023},
author = {Liu, J and Sha, S and Wang, J and Gu, X and Du, M and Lu, X},
title = {Development and Validation of a Prognosis-Prediction Signature for Patients with Lung Adenocarcinoma Based on 11 Telomere-Related Genes.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {28},
number = {10},
pages = {254},
doi = {10.31083/j.fbl2810254},
pmid = {37919072},
issn = {2768-6698},
mesh = {Humans ; *Adenocarcinoma of Lung/genetics ; *Lung Neoplasms/diagnosis/genetics ; Telomere/genetics ; B-Lymphocytes ; Tumor Microenvironment ; },
abstract = {BACKGROUND: The occurrence and progression of lung cancer are correlated with telomeres and telomerase. Telomere length is reduced in the majority of tumors, including lung cancers. Telomere length variations have been associated with lung cancer risk and may serve as therapeutic targets as well as predictive biomarkers for lung cancer. Nevertheless, the effects of telomere-associated genes on lung cancer prognosis have not been thoroughly studied. We aim to investigate the relationship between telomere-associated genes and lung cancer prognosis.<br><br>METHODS: The Cancer Genome Atlas and Genotype-Tissue Expression databases were used as training sets to build a predictive model. Three integrated Gene Expression Omnibus datasets served as validation sets. Using cluster consistency analysis and regression with the least absolute shrinkage and selection operator, we developed a telomere-related gene risk signature (TMGsig) based on 11 overall survival-related genes (RBBP8, PLK1, DSG2, HOXA7, ANAPC4, CSNK1E, SYAP1, ALDOA, PHF1, MUTYH, and PGS1).<br><br>RESULTS: The results indicated a negative outcome for the high-risk score group. Immunological microenvironment and somatic mutations differed between the high- and low-risk groups. A statistically significant difference existed between the low-risk and high-risk groups in terms of the expression levels of B cells and CD4 cells, and the risk score was essentially inversely linked with immune cell expression.<br><br>CONCLUSIONS: TMGsig can predict outcomes in patients with lung adenocarcinoma.},
}
@article {pmid37918674,
year = {2023},
author = {Ulak, M and Kvestad, I and Chandyo, RK and Schwinger, C and Basnet, S and Shrestha, M and Ranjitkar, S and Nguyen, LV and Corona-Pérez, D and De Vivo, I and Ueland, PM and McCann, A and Strand, TA},
title = {The Effect of Vitamin B12 Supplementation on Leukocyte Telomere Length in Mildly Stunted Nepalese Children: A Secondary Outcome of a Randomized Controlled Trial.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tjnut.2023.10.015},
pmid = {37918674},
issn = {1541-6100},
abstract = {BACKGROUND: Vitamin B12 is essential for deoxyribonucleic acid synthesis and genome stability. A deficiency of vitamin B12 is associated with telomere shortening, genomic aging, and increased risk of chronic disease and mortality.<br><br>OBJECTIVES: The study aims to determine the effect of vitamin B12 supplementation on leukocyte telomere length (LTL) in infants at risk of vitamin B12 deficiency.<br><br>METHODS: The study was a predefined secondary analysis of a randomized controlled trial enrolling 600 Nepalese infants aged 6 -11 mo, who were supplemented with 2 &#x3bc;g (2-3 recommended daily allowances) vitamin B12 or placebo daily for 1 y. At the end of the study, LTL was measured in 497 participants. Mean LTL was compared between the treatment arms in the full sample and predefined subgroups based on markers of vitamin B12 status, hemoglobin, sex, and growth indices.<br><br>RESULTS: LTL at end-study did not differ between the vitamin B12 and placebo arm with a standardized mean difference (95% confidence interval) of 0.04 (-0.14, 0.21). There was no effect of vitamin B12 on LTL in any of the subgroups.<br><br>CONCLUSIONS: Providing daily vitamin B12 for 1 y during infancy in a population at risk of vitamin B12 deficiency does not affect LTL. This trial was registered at clinicaltrials.gov as NCT02272842.},
}
@article {pmid37917279,
year = {2023},
author = {Medoro, A and Saso, L and Scapagnini, G and Davinelli, S},
title = {NRF2 signaling pathway and telomere length in aging and age-related diseases.},
journal = {Molecular and cellular biochemistry},
volume = {},
number = {},
pages = {},
pmid = {37917279},
issn = {1573-4919},
abstract = {The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is well recognized as a critical regulator of redox, metabolic, and protein homeostasis, as well as the regulation of inflammation. An age-associated decline in NRF2 activity may allow oxidative stress to remain unmitigated and affect key features associated with the aging phenotype, including telomere shortening. Telomeres, the protective caps of eukaryotic chromosomes, are highly susceptible to oxidative DNA damage, which can accelerate telomere shortening and, consequently, lead to premature senescence and genomic instability. In this review, we explore how the dysregulation of NRF2, coupled with an increase in oxidative stress, might be a major determinant of telomere shortening and age-related diseases. We discuss the relevance of the connection between NRF2 deficiency in aging and telomere attrition, emphasizing the importance of studying this functional link to enhance our understanding of aging pathologies. Finally, we present a number of compounds that possess the ability to restore NRF2 function, maintain a proper redox balance, and preserve telomere length during aging.},
}
@article {pmid37917220,
year = {2023},
author = {Chebly, A and Khalil, C and Kuzyk, A and Beylot-Barry, M and Chevret, E},
title = {T-cell lymphocytes' aging clock: telomeres, telomerase and aging.},
journal = {Biogerontology},
volume = {},
number = {},
pages = {},
pmid = {37917220},
issn = {1573-6768},
abstract = {Aging is the decline of physiological capabilities required for life maintenance and reproduction over time. The human immune cells, including T-cells lymphocytes, undergo dramatic aging-related changes, including those related to telomeres and telomerase. It was demonstrated that telomeres and telomerase play crucial roles in T-cell differentiation, aging, and diseases, including a well-documented link between short telomeres and telomerase activation demonstrated in several T-cells malignancies. Herein, we provide a comprehensive review of the literature regarding T-cells' telomeres and telomerase in health and age related-diseases.},
}
@article {pmid37915500,
year = {2023},
author = {Wei, M and Huang, Y and Mo, C and Wang, H and Zeng, Q and Yang, W and Chen, J and Zhang, X and Kong, Q},
title = {Telomere-to-telomere genome assembly of melon (Cucumis melo L. var. inodorus) provides a high-quality reference for meta-QTL analysis of important traits.},
journal = {Horticulture research},
volume = {10},
number = {10},
pages = {uhad189},
pmid = {37915500},
issn = {2662-6810},
abstract = {Melon is an important horticultural crop with extensive diversity in many horticultural groups. To explore its genomic diversity, it is necessary to assemble more high-quality complete genomes from different melon accessions. Meanwhile, a large number of QTLs have been mapped in several studies. Integration of the published QTLs onto a complete genome can provide more accurate information for candidate gene cloning. To address these problems, a telomere-to-telomere (T2T) genome of the elite melon landrace Kuizilikjiz (Cucumis melo L. var. inodorus) was de novo assembled and all the published QTLs were projected onto it in this study. The results showed that a high-quality Kuizilikjiz genome with the size of 379.2 Mb and N50 of 31.7 Mb was de novo assembled using the combination of short reads, PacBio high-fidelity long reads, Hi-C data, and a high-density genetic map. Each chromosome contained the centromere and telomeres at both ends. A large number of structural variations were observed between Kuizilikjiz and the other published genomes. A total of 1294 QTLs published in 67 studies were collected and projected onto the T2T genome. Several clustered, co-localized, and overlapped QTLs were determined. Furthermore, 20 stable meta-QTLs were identified, which significantly reduced the mapping intervals of the initial QTLs and greatly facilitated identification of the candidate genes. Collectively, the T2T genome assembly together with the numerous projected QTLs will not only broaden the high-quality genome resources but also provide valuable and abundant QTL information for cloning the genes controlling important traits in melon.},
}
@article {pmid37914069,
year = {2024},
author = {Pirtea, P and Keefe, DL and Ayoubi, JM and de Ziegler, D},
title = {Telomere length: a marker for reproductive aging?.},
journal = {Fertility and sterility},
volume = {121},
number = {1},
pages = {1-3},
doi = {10.1016/j.fertnstert.2023.10.027},
pmid = {37914069},
issn = {1556-5653},
mesh = {Female ; Humans ; *Aging/genetics ; *Reproduction/genetics ; Cellular Senescence/genetics ; Oocytes ; Telomere/genetics ; },
abstract = {The improvements accomplished in assisted reproductive technology have emphasized more than ever the role played by chronological age, notably for predicting oocyte quality. Studies in cellular aging have directed research on telomere length measurements as possible markers of functional aging and, notably, female reproductive outcomes. Although further research is still needed, encouraging results are already available on the possibility that leucocyte telomere length may be a useful parameter for assessing reproductive potential in aging women.},
}
@article {pmid37913757,
year = {2023},
author = {Al Awadhi, R and Alwehaidah, MS and Al Roomy, MS and Kapila, K},
title = {Relative Telomere length in cervical exfoliated cells among women with high- risk human papillomavirus.},
journal = {Pathobiology : journal of immunopathology, molecular and cellular biology},
volume = {},
number = {},
pages = {},
doi = {10.1159/000534917},
pmid = {37913757},
issn = {1423-0291},
abstract = {INTRODUCTION: This study investigates and compares the relative telomere length (RTL) outcome of high-risk (hr) human papillomavirus (HPV)-infected normal, low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL) cervical samples to HPV-free normal cervical samples.<br><br>METHODS: This study used archived cervical samples and obtained cytology and histology data. HPV genotyping was conducted using Sanger sequencing and RTL was performed using real-time quantitative polymerase chain reaction.<br><br>RESULTS: This study investigated 287 cervical samples, including 100 normal and hr-HPV-negative samples from the control group, 44 normal and hr-HPV-infected samples, and 143 SIL and hr-HPV-infected samples. The RTL in hr-HPV-infected samples, including the SIL and normal sample groups, were significantly longer than that in the control group. RTL in HSIL (5.13 &#xb1; 3.22) and LSIL (2.86 &#xb1; 2.81) were significantly different (P < 0.001). The RTL of cervical intraepithelial neoplasia (CIN1) lesion (3.53 &#xb1; 2.53) differed significantly (P < 0.001) when compared to CIN2 and CIN3 lesions combined. The risk of developing cervical cancer was associated with RTL and was decreased with RTL.<br><br>CONCLUSION: This study revealed the strong potential of the RTL test in identifying women at risk of developing cervical cancer.},
}
@article {pmid37903596,
year = {2024},
author = {Wang, F and Chang, L and Zhang, X and Jia, T and Wang, Y and Wang, Y and Liu, G},
title = {Effects of Polycyclic Aromatic Hydrocarbon Exposure and Telomere Length and their Interaction on Blood Lipids in Coal Miners.},
journal = {Journal of occupational and environmental medicine},
volume = {66},
number = {2},
pages = {111-117},
doi = {10.1097/JOM.0000000000003002},
pmid = {37903596},
issn = {1536-5948},
mesh = {Humans ; *Polycyclic Aromatic Hydrocarbons/adverse effects ; Bayes Theorem ; Telomere ; *Dyslipidemias ; Coal ; Biomarkers ; *Phenanthrenes ; },
abstract = {OBJECTIVE: This study aimed to investigate the effects of polycyclic aromatic hydrocarbon (PAH) exposure and telomere length on lipids in coal miners.<br><br>METHODS: Basic personal information of 637 coal miners was collected by questionnaire survey. Logistic regression, the Bayesian kernel machine regression model, and weighted quantile sum regression were used to analyze the effects of PAH metabolites and telomere length and their interactions on blood lipids.<br><br>RESULTS: High exposure to 9-hydroxyphenanthrene (OR = 1.586, 95% CI: 1.011-2.487) and telomere shortening (OR = 1.413, 95% CI: 1.005-1.985) were associated with dyslipidemia. Weighted quantile sum results showed that 9-hydroxyphenanthrene accounted for the largest proportion of dyslipidemia (weight = 0.66). The interaction results showed that high 9-hydroxyphenanthrene exposure and short telomeres were risk factors for dyslipidemia in coal miners (OR = 2.085, 95% CI: 1.121-3.879). Conclusions: Our findings suggest that 9-hydroxyphenanthrene and shorter telomeres are risk factors for dyslipidemia, and their interaction increases the risk of dyslipidemia.},
}
@article {pmid37900433,
year = {2023},
author = {Aghajanyan, V and Bhupathy, S and Sheikh, S and Nausheen, F},
title = {A Narrative Review of Telomere Length Modulation Through Diverse Yoga and Meditation Styles: Current Insights and Prospective Avenues.},
journal = {Cureus},
volume = {15},
number = {9},
pages = {e46130},
pmid = {37900433},
issn = {2168-8184},
abstract = {Mindfulness practices have demonstrated the potential to positively impact various aspects of human health associated with telomere length (TL) - a recognized marker of healthy aging and susceptibility to age-related diseases. This review seeks to conduct an in-depth comparative analysis, examining methodological variations, outcome assessments, strengths, weaknesses, and gaps across mindfulness-focused studies concerning TL and attrition rates. While emerging data tentatively suggest a positive connection between mindfulness practices and TL, a notable research gap pertains to establishing the clinically recommended dosage of yoga/meditation and mindfulness interventions to effectively influence TL. To address this gap, upcoming research should prioritize meticulous structuring, pedagogical precision, and vigilant monitoring of mindfulness interventions to yield psychological and physiological benefits across an appropriate timeframe and intensity. The amalgamation of yoga/meditation or mindfulness emerges as a promising avenue for enhancing the quality of life while counteracting the influence of telomere attrition in the spectrum of age-related diseases. The core objective of this review is to meticulously investigate the interplay between yoga/meditation and mindfulness practices and their potential impact on TL - an essential biomarker indicative of age-related health and well-being. To achieve this, our study methodically compares various methodological approaches, outcome measures, strengths, and limitations within relevant research endeavors focused on TL and attrition rates. Through this scrutiny, we highlight prevailing research gaps. Our analysis underscores the need for comprehensive research efforts aimed at establishing the optimal therapeutic regimen for yielding significant clinical effects on TL and overall health. In summation, our exploration emphasizes the urgency of further studies to unravel the most effective approaches for positively influencing TL and its implications for holistic health.},
}
@article {pmid37899647,
year = {2023},
author = {Yu, M and Yang, D and Chen, C and Xia, H},
title = {Effects of SETD2 on telomere length and malignant transformation property of Met-5A after one-month crocidolite exposure.},
journal = {Journal of environmental science and health. Part C, Toxicology and carcinogenesis},
volume = {41},
number = {3-4},
pages = {121-134},
doi = {10.1080/26896583.2023.2271822},
pmid = {37899647},
issn = {2689-6591},
mesh = {Humans ; *Aminobenzoates/metabolism/pharmacology ; *Asbestos, Crocidolite/toxicity/metabolism ; Cell Transformation, Neoplastic/chemically induced/metabolism/pathology ; Epithelium/metabolism/pathology ; Naphthalenes/metabolism/pharmacology ; *Histone-Lysine N-Methyltransferase/metabolism ; *Telomere Homeostasis ; },
abstract = {Crocidolite is a carcinogen contributing to the pathogenesis of malignant mesothelioma. This study aimed to characterize the possible telomere-related events mediating the malignant transformation of mesothelial cells with and without SETD2 under crocidolite exposure. The crocidolite concentration resulting in 90% viable SETD2 knockout Met-5A (Met-5A[SETD2-KO]) and Met-5A were estimated to be 0.71 μg/cm[2] and 1.8 μg/cm[2], respectively, during 72 h of exposure, which was further employed in chronical crocidolite exposure during a 72 h exposure interval per time up to 1 month. Chronical crocidolite-exposed Met-5A[SETD2-KO] (chronical Cro-Met-5A[SETD2-KO]) had higher colony formation and increased telomerase reverse transcriptase (TERT) protein levels than chronical crocidolite-exposed Met-5A (chronical Cro-Met-5A) and Met-5A[SETD2-KO]. Chronical Cro-Met-5A[SETD2-KO] had longer telomere length (TL) than chronical Cro-Met-5A, although there were no changes in TL for either chronical Cro-Met-5A or chronical Cro-Met-5A[SETD2-KO] compared with their corresponding cells without crocidolite exposure. BIBR 1532, an inhibitor targeting TERT, partially reduced colony formation and TL for chronical Cro-Met-5A[SETD2-KO], while BIBR 1532 reduced TL but had no effect on colony formation for chronical Cro-Met-5A. Therefore, SETD2 deficient mesothelial cells are susceptible to malignant transformation during chronical crocidolite exposure, and TERT-dependent TL modification likely partially drives SETD2 loss-mediated early onset of mesothelial malignant transformation.},
}
@article {pmid37897613,
year = {2024},
author = {Luo, H and Wang, X and You, C and Wu, X and Pan, D and Lv, Z and Li, T and Zhang, D and Shen, Z and Zhang, X and Liu, G and He, K and Ye, Q and Jia, Y and Zhao, Q and Deng, X and Cao, X and Song, X and Huang, G},
title = {Telomere-to-telomere genome of the allotetraploid legume Sesbania cannabina reveals transposon-driven subgenome divergence and mechanisms of alkaline stress tolerance.},
journal = {Science China. Life sciences},
volume = {67},
number = {1},
pages = {149-160},
pmid = {37897613},
issn = {1869-1889},
mesh = {*Sesbania/genetics ; *Fabaceae ; Manure ; Soil ; Vegetables/genetics ; Alkalies ; Telomere/genetics ; },
abstract = {Alkaline soils pose an increasing problem for agriculture worldwide, but using stress-tolerant plants as green manure can improve marginal land. Here, we show that the legume Sesbania cannabina is very tolerant to alkaline conditions and, when used as a green manure, substantially improves alkaline soil. To understand genome evolution and the mechanisms of stress tolerance in this allotetraploid legume, we generated the first telomere-to-telomere genome assembly of S. cannabina spanning ∼2,087 Mb. The assembly included all centromeric regions, which contain centromeric satellite repeats, and complete chromosome ends with telomeric characteristics. Further genome analysis distinguished A and B subgenomes, which diverged approximately 7.9 million years ago. Comparative genomic analysis revealed that the chromosome homoeologs underwent large-scale inversion events (>10 Mb) and a significant, transposon-driven size expansion of the chromosome 5A homoeolog. We further identified four specific alkali-induced phosphate transporter genes in S. cannabina; these may function in alkali tolerance by relieving the deficiency in available phosphorus in alkaline soil. Our work highlights the significance of S. cannabina as a green tool to improve marginal lands and sheds light on subgenome evolution and adaptation to alkaline soils.},
}
@article {pmid37896796,
year = {2023},
author = {Bräuer, JA and Hammerl, JA and El-Mustapha, S and Fuhrmann, J and Barac, A and Hertwig, S},
title = {The Novel Yersinia enterocolitica Telomere Phage vB_YenS_P840 Is Closely Related to PY54, but Reveals Some Striking Differences.},
journal = {Viruses},
volume = {15},
number = {10},
pages = {},
pmid = {37896796},
issn = {1999-4915},
mesh = {*Bacteriophages/genetics ; *Yersinia enterocolitica/genetics ; Prophages/genetics ; Lysogeny ; Telomere ; },
abstract = {Telomere phages are a small group of temperate phages, whose prophages replicate as a linear plasmid with covalently closed ends. They have been isolated from some Enterobacteriaceae and from bacterial species living in aquatic environments. Phage PY54 was the first Yersinia (Y.) enterocolitica telomere phage isolated from a nonpathogenic O:5 strain, but recently a second telomeric Yersinia phage (vB_YenS_P840) was isolated from a tonsil of a wild boar in Germany. Both PY54 and vB_YenS_P840 (P840) have a siphoviridal morphology and a similar genome organization including the primary immunity region immB and telomere resolution site telRL. However, whereas PY54 only possesses one prophage repressor for the lysogenic cycle, vB_YenS_P840 encodes two. The telRL region of this phage was shown to be processed by the PY54 protelomerase under in vivo conditions, but unlike with PY54, a flanking inverted repeat was not required for processing. A further substantial difference between the phages is their host specificity. While PY54 infects Y. enterocolitica strains belonging to the serotypes O:5 and O:5,27, vB_YenS_P840 exclusively lyses O:3 strains. As the tail fiber and tail fiber assembly proteins of the phages differ significantly, we introduced the corresponding genes of vB_YenS_P840 by transposon mutagenesis into the PY54 genome and isolated several mutants that were able to infect both serotypes, O:5,27 and O:3.},
}
@article {pmid37895262,
year = {2023},
author = {Ortega-Vázquez, A and Sánchez-Badajos, S and Ramírez-García, M&#xc1; and Alvarez-Luquín, D and López-López, M and Adalid-Peralta, LV and Monroy-Jaramillo, N},
title = {Longitudinal Changes in Mitochondrial DNA Copy Number and Telomere Length in Patients with Parkinson's Disease.},
journal = {Genes},
volume = {14},
number = {10},
pages = {},
pmid = {37895262},
issn = {2073-4425},
mesh = {Humans ; *DNA, Mitochondrial/genetics ; Case-Control Studies ; DNA Copy Number Variations/genetics ; *Parkinson Disease/genetics ; Telomere/genetics ; Mitochondria/genetics ; Biomarkers ; },
abstract = {Parkinson's disease (PD) pathophysiology includes mitochondrial dysfunction, neuroinflammation, and aging as its biggest risk factors. Mitochondrial DNA copy number (mtDNA-CN) and telomere length (TL) are biological aging markers with inconclusive results regarding their association with PD. A case-control study was used to measure TL and mtDNA-CN using qPCR in PBMCs. PD patients were naive at baseline (T0) and followed-up at one (T1) and two (T2) years after the dopaminergic treatment (DRT). Plasmatic cytokines were determined by ELISA in all participants, along with clinical parameters of patients at T0. While TL was shorter in patients vs. controls at all time points evaluated (p < 0.01), mtDNA-CN showed no differences. An increase in mtDNA-CN and TL was observed in treated patients vs. naive ones (p < 0.001). Our statistical model analyzed both aging markers with covariates, showing a strong correlation between them (r = 0.57, p < 0.01), and IL-17A levels positively correlating with mtDNA-CN only in untreated patients (r = 0.45, p < 0.05). TL and mtDNA-CN could be useful markers for monitoring inflammation progression or treatment response in PD. DRT might modulate TL and mtDNA-CN, reflecting a compensatory mechanism to counteract mitochondrial dysfunction in PD, but this needs further investigation.},
}
@article {pmid37892448,
year = {2023},
author = {Sato, M and Wai, KM and Itoh, K and Yang, Y and Uchikawa, Y and Ito, Y and Nakaji, S and Ihara, K},
title = {Does the Protective Effect of Zinc on Telomere Length Depend on the Presence of Hypertension or Type 2 Diabetes? Results from the Iwaki Health Promotion Project, Japan.},
journal = {Nutrients},
volume = {15},
number = {20},
pages = {},
pmid = {37892448},
issn = {2072-6643},
support = {JPMJCE1302//Japan Science and Technology Agency/ ; COI accelerating grant JPMJCA2201//Hirosaki University/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 2 ; Zinc/pharmacology ; Cross-Sectional Studies ; Japan ; *Hypertension ; Telomere ; },
abstract = {Telomeres, repeated TTAGGG sequences at chromosomal ends, shorten with age and indicate cellular lifespan. Zinc can protect against telomere damage through its anti-oxidative effect. Meanwhile, telomere shortening was correlated with metabolic diseases of hypertension and type 2 diabetes. The objective of this study was to investigate whether the association between zinc and telomere length differs by the presence or absence of hypertension/type 2 diabetes. This is a cross-sectional study with 1064 participants of the Iwaki area, Japan. Multiple linear regression models were performed to test the hypothesis. A higher serum zinc concentration was significantly associated with a longer G-tail length (β = 48.11, 95% confidence intervals [CI]: 25.69, 70.54, p < 0.001). By multivariate linear regression analysis, there was a significant positive association between zinc and G-tail length in both hypertensive (β = 46.84, 95%CI: 9.69, 84.0, p = 0.014) and non-hypertensive groups (β = 49.47, 95%CI: 20.75, 78.18, p = 0.001), while the association was significant only in the non-diabetes group (β = 50.82, 95%CI: 27.54, 74.11, p < 0.001). In conclusion, higher zinc concentration was significantly associated with longer G-tail length. The protective effect of zinc on G-tail did not differ by hypertension status; however, it disappeared in individuals with type 2 diabetes.},
}
@article {pmid37891926,
year = {2023},
author = {Reljic, D and Koller, A and Herrmann, HJ and Ekici, AB and Neurath, MF and Zopf, Y},
title = {Differential Effects of Very-Low-Volume Exercise Modalities on Telomere Length, Inflammation, and Cardiometabolic Health in Obese Metabolic Syndrome Patients: A Subanalysis from Two Randomized Controlled Trials.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {10},
pages = {},
pmid = {37891926},
issn = {2076-3921},
support = {MED1710//Hector-Stiftung/ ; N.N.//Manfred Roth Foundation/ ; N.N.//Research Foundation for Medicine at the University Hospital Erlangen/ ; N.N.//Deutsche Forschungsgemeinschaft and Friedrich-Alexander-University Erlangen-N&#xfc;rnberg: Funding program "Open Access Publication Funding"/ ; },
abstract = {Oxidative stress (OS) and inflammation are features of metabolic syndrome (MetS) that can contribute to the shortening of telomere length (TL), a marker of cellular ageing. Research indicates that exercise can positively influence MetS-associated conditions and TL. However, the effects of low-volume exercise types on TL are still unknown. We investigated the impact of very-low-volume high-intensity interval training (LV-HIIT), one-set resistance training (1-RT), and whole-body electromyostimulation (WB-EMS) on TL, inflammation, and cardiometabolic indices in 167 MetS patients. Data were derived from two randomized controlled trials where patients were allocated to an exercise group (2 sessions/week, for 12 weeks) or a control group. All groups received standard-care nutritional weight loss counselling. TL was determined as the T/S ratio (telomere to single-copy gene amount). All groups significantly reduced body weight (p < 0.05), but the T/S-ratio (p < 0.001) only increased with LV-HIIT. OS-related inflammatory markers (C-reactive protein, interleukin-6, and lipopolysaccharide-binding protein) only decreased (p < 0.05) following LV-HIIT. The MetS severity z-score improved with LV-HIIT (p < 0.001) and 1-RT (p = 0.014) but not with WB-EMS. In conclusion, very-low-volume exercise modalities have differential effects on telomeres, inflammation, and cardiometabolic health. Only LV-HIIT but not strength-based low-volume exercise increased TL in MetS patients, presumably due to superior effects on OS-related inflammatory markers.},
}
@article {pmid37890990,
year = {2024},
author = {Mori, JO and Keegan, J and Flynn, RL and Heaphy, CM},
title = {Alternative lengthening of telomeres: mechanism and the pathogenesis of cancer.},
journal = {Journal of clinical pathology},
volume = {77},
number = {2},
pages = {82-86},
doi = {10.1136/jcp-2023-209005},
pmid = {37890990},
issn = {1472-4146},
mesh = {Humans ; Telomere Homeostasis ; X-linked Nuclear Protein/genetics ; *Telomerase/genetics ; Telomere/genetics/metabolism ; *Neoplasms/genetics ; DNA Helicases/genetics ; Carrier Proteins ; },
abstract = {Telomere maintenance and elongation allows cells to gain replicative immortality and evade cellular senescence during cancer development. While most cancers use telomerase to maintain telomere lengths, a subset of cancers engage the alternative lengthening of telomeres (ALT) pathway for telomere maintenance. ALT is present in 5%-10% of all cancers, although the prevalence is dramatically higher in certain cancer types, including complex karyotype sarcomas, isocitrate dehydrogenase-mutant astrocytoma (WHO grade II-IV), pancreatic neuroendocrine tumours, neuroblastoma and chromophobe hepatocellular carcinomas. ALT is maintained through a homology-directed DNA repair mechanism. Resembling break-induced replication, this aberrant process results in dramatic cell-to-cell telomere length heterogeneity, widespread chromosomal instability and chronic replication stress. Additionally, ALT-positive cancers frequently harbour inactivating mutations in either chromatin remodelling proteins (ATRX, DAXX and H3F3A) or DNA damage repair factors (SMARCAL1 and SLX4IP). ALT can readily be detected in tissue by assessing the presence of unique molecular characteristics, such as large ultrabright nuclear telomeric foci or partially single-stranded telomeric DNA circles (C-circles). Importantly, ALT has been validated as a robust diagnostic and prognostic biomarker for certain cancer types and may even be exploited as a therapeutic target via small molecular inhibitors and/or synthetic lethality approaches.},
}
@article {pmid37886996,
year = {2023},
author = {Crocco, P and De Rango, F and Dato, S and La Grotta, R and Maletta, R and Bruni, AC and Passarino, G and Rose, G},
title = {The Shortening of Leukocyte Telomere Length Contributes to Alzheimer's Disease: Further Evidence from Late-Onset Familial and Sporadic Cases.},
journal = {Biology},
volume = {12},
number = {10},
pages = {},
pmid = {37886996},
issn = {2079-7737},
support = {PA.CRO.DE." PON ARS01_00568//Ministry of Education, University and Research/ ; },
abstract = {Telomeres are structures at the ends of eukaryotic chromosomes that help maintain genomic stability. During aging, telomere length gradually shortens, producing short telomeres, which are markers of premature cellular senescence. This may contribute to age-related diseases, including Alzheimer's disease (AD), and based on this, several studies have hypothesized that telomere shortening may characterize AD. Current research, however, has been inconclusive regarding the direction of the association between leukocyte telomere length (LTL) and disease risk. We assessed the association between LTL and AD in a retrospective case-control study of a sample of 255 unrelated patients with late-onset AD (LOAD), including 120 sporadic cases and 135 with positive family history for LOAD, and a group of 279 cognitively healthy unrelated controls, who were all from Calabria, a southern Italian region. Following regression analysis, telomeres were found significantly shorter in LOAD cases than in controls (48% and 41% decrease for sporadic and familial cases, respectively; p < 0.001 for both). Interestingly, LTL was associated with disease risk independently of the presence of conventional risk factors (e.g., age, sex, MMSE scores, and the presence of the APOE-ε4 allele). Altogether, our findings lend support to the notion that LTL shortening may be an indicator of the pathogenesis of LOAD.},
}
@article {pmid37884878,
year = {2023},
author = {Serrano-León, IM and Prieto, P and Aguilar, M},
title = {Telomere and subtelomere high polymorphism might contribute to the specificity of homologous recognition and pairing during meiosis in barley in the context of breeding.},
journal = {BMC genomics},
volume = {24},
number = {1},
pages = {642},
pmid = {37884878},
issn = {1471-2164},
support = {(N&#xba; expediente administrativo subvenci&#xf3;n: POEJ00028/ N.&#xba; expediente: AND21_IAS_M2_064) from Garant&#xed;a Juvenil-Andaluc&#xed;a 2022//Consejer&#xed;a de Universidad, Investigaci&#xf3;n e Innovaci&#xf3;n, Secretar&#xed;a General de Investigaci&#xf3;n e Innovaci&#xf3;n, Junta de Andaluc&#xed;a/Cofinanciaci&#xf3;n FEDER 91%/ ; },
mesh = {*Hordeum/genetics ; Chromosome Pairing ; Plant Breeding ; Meiosis/genetics ; Telomere/genetics ; Heterochromatin ; },
abstract = {Barley (Hordeum vulgare) is one of the most popular cereal crops globally. Although it is a diploid species, (2n = 2x = 14) the study of its genome organization is necessary in the framework of plant breeding since barley is often used in crosses with other cereals like wheat to provide them with advantageous characters. We already have an extensive knowledge on different stages of the meiosis, the cell division to generate the gametes in species with sexual reproduction, such as the formation of the synaptonemal complex, recombination, and chromosome segregation. But meiosis really starts with the identification of homologous chromosomes and pairing initiation, and it is still unclear how chromosomes exactly choose a partner to appropriately pair for additional recombination and segregation. In this work we present an exhaustive molecular analysis of both telomeres and subtelomeres of barley chromosome arms 2H-L, 3H-L and 5H-L. As expected, the analysis of multiple features, including transposable elements, repeats, GC content, predicted CpG islands, recombination hotspots, G4 quadruplexes, genes and targeted sequence motifs for key DNA-binding proteins, revealed a high degree of variability both in telomeres and subtelomeres. The molecular basis for the specificity of homologous recognition and pairing occurring in the early chromosomal interactions at the start of meiosis in barley may be provided by these polymorphisms. A more relevant role of telomeres and most distal part of subtelomeres is suggested.},
}
@article {pmid37883989,
year = {2023},
author = {, },
title = {Retraction: Zinc sulfate contributes to promote telomere length extension via increasing telomerase gene expression, telomerase activity and change in the TERT gene promoter CpG island methylation status of human adipose-derived mesenchymal stem cells.},
journal = {PloS one},
volume = {18},
number = {10},
pages = {e0292985},
pmid = {37883989},
issn = {1932-6203},
}
@article {pmid37882647,
year = {2024},
author = {Shiraishi, K and Takahashi, A and Momozawa, Y and Daigo, Y and Kaneko, S and Kawaguchi, T and Kunitoh, H and Matsumoto, S and Horinouchi, H and Goto, A and Honda, T and Shimizu, K and Torasawa, M and Takayanagi, D and Saito, M and Saito, A and Ohe, Y and Watanabe, SI and Goto, K and Tsuboi, M and Tsuchihara, K and Takata, S and Aoi, T and Takano, A and Kobayashi, M and Miyagi, Y and Tanaka, K and Suzuki, H and Maeda, D and Yamaura, T and Matsuda, M and Shimada, Y and Mizuno, T and Sakamoto, H and Yoshida, T and Goto, Y and Yoshida, T and Yamaji, T and Sonobe, M and Toyooka, S and Yoneda, K and Masago, K and Tanaka, F and Hara, M and Fuse, N and Nishizuka, SS and Motoi, N and Sawada, N and Nishida, Y and Kumada, K and Takeuchi, K and Tanno, K and Yatabe, Y and Sunami, K and Hishida, T and Miyazaki, Y and Ito, H and Amemiya, M and Totsuka, H and Nakayama, H and Yokose, T and Ishigaki, K and Nagashima, T and Ohtaki, Y and Imai, K and Takasawa, K and Minamiya, Y and Kobayashi, K and Okubo, K and Wakai, K and Shimizu, A and Yamamoto, M and Iwasaki, M and Matsuda, K and Inazawa, J and Shiraishi, Y and Nishikawa, H and Murakami, Y and Kubo, M and Matsuda, F and Kamatani, Y and Hamamoto, R and Matsuo, K and Kohno, T},
title = {Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses.},
journal = {Cancer communications (London, England)},
volume = {44},
number = {2},
pages = {287-293},
pmid = {37882647},
issn = {2523-3548},
support = {JP15ck0106096//Japan Agency for Medical Research and Development/ ; JP20km0105001//Japan Agency for Medical Research and Development/ ; JP20km0105002//Japan Agency for Medical Research and Development/ ; JP20km0105003//Japan Agency for Medical Research and Development/ ; JP20km0105004//Japan Agency for Medical Research and Development/ ; JPMJCR1689//Japan Science and Technology Agency/ ; JPMJCR18Y4//Japan Science and Technology Agency/ ; 17H06162//Japan Society for the Promotion of Science/ ; 20H03695//Japan Society for the Promotion of Science/ ; 17015018//Japan Society for the Promotion of Science/ ; 221S0001//Japan Society for the Promotion of Science/ ; 16H06277//Japan Society for the Promotion of Science/ ; 2020-J4//National Cancer Center Research and Development Fund/ ; 1989-2010//Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan/ ; },
mesh = {Humans ; Genome-Wide Association Study ; *Adenocarcinoma of Lung/genetics ; *Lung Neoplasms/genetics/pathology ; Whole Genome Sequencing ; Telomere/genetics/pathology ; },
}
@article {pmid37881605,
year = {2023},
author = {Kakridonis, F and Pneumatikos, SG and Vakonaki, E and Berdiaki, A and Tzatzarakis, MN and Fragkiadaki, P and Spandidos, DA and Baliou, S and Ioannou, P and Hatzidaki, E and Nikitovic, D and Tsatsakis, A and Vasiliadis, E},
title = {Telomere length as a predictive biomarker in osteoporosis (Review).},
journal = {Biomedical reports},
volume = {19},
number = {5},
pages = {87},
pmid = {37881605},
issn = {2049-9442},
abstract = {Telomeres are the ends of chromosomes that protect them from DNA damage. There is evidence to suggest that telomere shortening appears with advanced age. Since aging is a significant risk factor for developing age-related complications, it is plausible that telomere shortening may be involved in the development of osteoporosis. The present review summarizes the potential of telomere shortening as a biomarker for detecting the onset of osteoporosis. For the purposes of the present review, the following scientific databases were searched for relevant articles: PubMed/NCBI, Cochrane Library of Systematic Reviews, Scopus, Embase and Google Scholar. The present review includes randomized and non-randomized controlled studies and case series involving humans, irrespective of the time of their publication. In six out of the 11 included studies providing data on humans, there was at least a weak association between telomere length and osteoporosis, with the remaining studies exhibiting no such association. As a result, telomere shortening may be used as a biomarker or as part of a panel of biomarkers for tracking the onset and progression of osteoporosis.},
}
@article {pmid37879860,
year = {2023},
author = {Chrisman, B and He, C and Jung, JY and Stockham, N and Paskov, K and Washington, P and Petereit, J and Wall, DP},
title = {Localizing unmapped sequences with families to validate the Telomere-to-Telomere assembly and identify new hotspots for genetic diversity.},
journal = {Genome research},
volume = {33},
number = {10},
pages = {1734-1746},
pmid = {37879860},
issn = {1549-5469},
support = {U24 MH081810/MH/NIMH NIH HHS/United States ; R01 NS070911/NS/NINDS NIH HHS/United States ; R01 NS101158/NS/NINDS NIH HHS/United States ; U01 AG061356/AG/NIA NIH HHS/United States ; R01 AG017917/AG/NIA NIH HHS/United States ; P20 GM103440/GM/NIGMS NIH HHS/United States ; R01 MH064547/MH/NIMH NIH HHS/United States ; R01 NS095824/NS/NINDS NIH HHS/United States ; R01 NS101665/NS/NINDS NIH HHS/United States ; U54 GM104944/GM/NIGMS NIH HHS/United States ; P30 AG010161/AG/NIA NIH HHS/United States ; S10 OD011939/OD/NIH HHS/United States ; },
mesh = {Humans ; *Genomics ; *Genome, Human ; Algorithms ; Telomere/genetics ; Genetic Variation ; Sequence Analysis, DNA ; },
abstract = {Although it is ubiquitous in genomics, the current human reference genome (GRCh38) is incomplete: It is missing large sections of heterochromatic sequence, and as a singular, linear reference genome, it does not represent the full spectrum of human genetic diversity. To characterize gaps in GRCh38 and human genetic diversity, we developed an algorithm for sequence location approximation using nuclear families (ASLAN) to identify the region of origin of reads that do not align to GRCh38. Using unmapped reads and variant calls from whole-genome sequences (WGSs), ASLAN uses a maximum likelihood model to identify the most likely region of the genome that a subsequence belongs to given the distribution of the subsequence in the unmapped reads and phasings of families. Validating ASLAN on synthetic data and on reads from the alternative haplotypes in the decoy genome, ASLAN localizes >90% of 100-bp sequences with >92% accuracy and ∼1 Mb of resolution. We then ran ASLAN on 100-mers from unmapped reads from WGS from more than 700 families, and compared ASLAN localizations to alignment of the 100-mers to the recently released T2T-CHM13 assembly. We found that many unmapped reads in GRCh38 originate from telomeres and centromeres that are gaps in GRCh38. ASLAN localizations are in high concordance with T2T-CHM13 alignments, except in the centromeres of the acrocentric chromosomes. Comparing ASLAN localizations and T2T-CHM13 alignments, we identified sequences missing from T2T-CHM13 or sequences with high divergence from their aligned region in T2T-CHM13, highlighting new hotspots for genetic diversity.},
}
@article {pmid37873898,
year = {2023},
author = {Rehkopf, DH and Wojcicki, JM and Haydel, KF and Lin, J and Smith, DL and Kapphahn, KI and Robinson, TN},
title = {Changes in leukocyte telomere length among children with obesity participating in a behavioural weight control program.},
journal = {Pediatric obesity},
volume = {18},
number = {12},
pages = {e13082},
pmid = {37873898},
issn = {2047-6310},
support = {R01 HL096015/HL/NHLBI NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; ULI TR001085/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Female ; Child ; Male ; *Obesity/therapy ; Body Mass Index ; *Leukocytes ; Behavior Therapy ; Telomere ; },
abstract = {OBJECTIVE: To examine changes in leukocyte telomere length (LTL) during and after a behavioural weight control program for children with obesity.<br><br>METHODS: We measured LTL among a cohort of 158 children 8-12&#x2009;years of age with a body mass index greater than or equal to the 95th percentile for age and sex. Children were 55% female, 29% white, 52% Latinx, 8% Asian and 11% Pacific Islander, other or multiethnic. All children participated in a 6-month, family-based, group behavioural weight control program and were assessed before treatment, after treatment and 1&#x2009;year after the end of treatment. To test the sample population slope of LTL over the intervention and maintenance time periods, we fit spline mixed-effect regression models.<br><br>RESULTS: LTL increased an average of 0.09&#x2009;T/S&#x2009;units per year (95% confidence interval [CI] 0.04 to 0.13; p&#x2009;=&#x2009;0.0001) during the weight control program intervention period, followed by an average decline of -0.05&#x2009;T/S&#x2009;units per year (95% CI -0.08 to -0.03; p&#x2009;<&#x2009;0.0001) during the 1&#x2009;year of follow-up after the completion of the intervention. Among 26 social, psychological, behavioural and physiological factors we examined, we did not find any predictors of these changes.<br><br>CONCLUSIONS: LTL increased in response to a behavioural weight control program among children with obesity, suggesting an impact on biological health and cellular aging from participation in a behavioural weight control intervention. LTL may be a useful biomarker for assessing changes in response to behavioural interventions.},
}
@article {pmid37873235,
year = {2023},
author = {Paul, S and McCourt, PM and Le, LTM and Ryu, J and Czaja, W and Bode, AM and Contreras-Galindo, R and Dong, Z},
title = {Fyn-mediated phosphorylation of Menin disrupts telomere maintenance in stem cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37873235},
support = {R01 GM143428/GM/NIGMS NIH HHS/United States ; R21 CA259630/CA/NCI NIH HHS/United States ; },
abstract = {Telomeres protect chromosome ends and determine the replication potential of dividing cells. The canonical telomere sequence TTAGGG is synthesized by telomerase holoenzyme, which maintains telomere length in proliferative stem cells. Although the core components of telomerase are well-defined, mechanisms of telomerase regulation are still under investigation. We report a novel role for the Src family kinase Fyn, which disrupts telomere maintenance in stem cells by phosphorylating the scaffold protein Menin. Fyn phosphorylates Menin at tyrosine 603 (Y603), which increases Menin's SUMO1 modification, C-terminal stability, and importantly, its association with the telomerase RNA component (TR). We show that SUMO1-Menin decreases TR's association with telomerase subunit Dyskerin, suggesting that Fyn's phosphorylation of Menin induces telomerase subunit mislocalization and may compromise telomerase function at telomeres. Importantly, we find that Fyn inhibition reduces accelerated telomere shortening in human iPSCs harboring mutations for dyskeratosis congenita.},
}
@article {pmid37872177,
year = {2023},
author = {Smoom, R and May, CL and Ortiz, V and Tigue, M and Kolev, HM and Rowe, M and Reizel, Y and Morgan, A and Egyes, N and Lichtental, D and Skordalakes, E and Kaestner, KH and Tzfati, Y},
title = {Telomouse-a mouse model with human-length telomeres generated by a single amino acid change in RTEL1.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {6708},
pmid = {37872177},
issn = {2041-1723},
support = {R01 CA249929/CA/NCI NIH HHS/United States ; P30 DK019525/DK/NIDDK NIH HHS/United States ; R37 DK053839/DK/NIDDK NIH HHS/United States ; P30 DK050306/DK/NIDDK NIH HHS/United States ; P30 CA010815/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Mice ; Animals ; Disease Models, Animal ; *Genome ; Telomere/genetics ; Cell Proliferation ; *Neoplasms/genetics ; DNA Helicases/genetics ; },
abstract = {Telomeres, the ends of eukaryotic chromosomes, protect genome integrity and enable cell proliferation. Maintaining optimal telomere length in the germline and throughout life limits the risk of cancer and enables healthy aging. Telomeres in the house mouse, Mus musculus, are about five times longer than human telomeres, limiting the use of this common laboratory animal for studying the contribution of telomere biology to aging and cancer. We identified a key amino acid variation in the helicase RTEL1, naturally occurring in the short-telomere mouse species M. spretus. Introducing this variation into M. musculus is sufficient to reduce the telomere length set point in the germline and generate mice with human-length telomeres. While these mice are fertile and appear healthy, the regenerative capacity of their colonic epithelium is compromised. The engineered Telomouse reported here demonstrates a dominant role of RTEL1 in telomere length regulation and provides a unique model for aging and cancer.},
}
@article {pmid37872100,
year = {2024},
author = {Radhakrishna, U and Ratnamala, U and Jhala, DD and Uppala, LV and Vedangi, A and Saiyed, N and Patel, M and Vadsaria, N and Shah, SR and Rawal, RM and Mercuri, SR and McGonagle, D and Jemec, GBE and Damiani, G},
title = {Hidradenitis suppurativa associated telomere-methylome dysregulations in blood.},
journal = {Journal of the European Academy of Dermatology and Venereology : JEADV},
volume = {38},
number = {2},
pages = {393-403},
doi = {10.1111/jdv.19586},
pmid = {37872100},
issn = {1468-3083},
mesh = {Humans ; *Hidradenitis Suppurativa/genetics/epidemiology ; Epigenome ; Leukocytes, Mononuclear ; Comorbidity ; *Neoplasms ; Telomere/genetics ; Ligases ; },
abstract = {BACKGROUND: Hidradenitis suppurativa (HS) is a chronic debilitating disease with a significant burden of both organic and psychological comorbidities. It has been shown that certain telomere-related genes (TRGs) affect a wide range of diseases, including HS and its associated comorbidities, but their exact role in HS pathogenesis is still unknown.<br><br>OBJECTIVES: To determine whether TRG methylomes can be used as biomarkers in HS.<br><br>METHODS: Using the Illumina HumanMethylation450 BeadChip array, we examined methylation variations associated with TRGs in HS cases and age-, sex- and ethnicity-matched healthy controls. The study utilized integrated bioinformatics statistical methods, such as a false discovery rate (FDR), the area under the receiver operating characteristic curve (AUC) and principal component analysis.<br><br>RESULTS: There were a total of 585 different differentially methylated CpG sites identified in 585 TRGs associated with HS (474 hypomethylated and 111 hypermethylated) (FDR p-value&#x2009;<&#x2009;0.05). A number of these CpGs have been identified as being involved in increased pain sensitivity including EPAS1, AHR, CSNK1D, DNMT1, IKBKAP, NOS3, PLCB1 and PRDM16 genes; GABRB3 as a potential alcohol addiction marker; DDB1, NSMCE2 and HNRNPA2B1 associated with cancers. Pathway analysis identified 67 statistically significant pathways, including DNA repair, telomere maintenance, mismatch repair and cell cycle control (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSION: The disruption of TRGs leads to the shortening of telomeres, which is associated with HS progression, ageing, cellular senescence and an increased risk of various diseases, including cancer and associated comorbidities, such as metabolic syndrome, cardiovascular disease and inflammatory disorders. Further research is necessary to better understand the underlying mechanisms and establish causal links between TRGs and HS. The present study is the first effort to comprehend potential pathomechanisms of sporadic HS cases concentrating on PBMC methylome since ours.},
}
@article {pmid37870657,
year = {2024},
author = {Zhou, D and Sun, Y and Dong, C and Wang, Z and Zhao, J and Li, Z and Huang, G and Li, W},
title = {Folic acid alleviated oxidative stress-induced telomere attrition and inhibited apoptosis of neurocytes in old rats.},
journal = {European journal of nutrition},
volume = {63},
number = {1},
pages = {291-302},
pmid = {37870657},
issn = {1436-6215},
support = {81730091//National Natural Science Foundation of China/ ; 2021YJSB280//Tianjin Research Innovation Project for Postgraduate Students/ ; },
mesh = {Rats ; Male ; Animals ; *Folic Acid/pharmacology ; *Antioxidants/pharmacology ; Reactive Oxygen Species ; Rats, Sprague-Dawley ; Oxidative Stress ; Apoptosis ; 8-Hydroxy-2'-Deoxyguanosine ; Telomere ; },
abstract = {PURPOSE: Oxidative stress has been reported to cause telomere attrition, which triggers cell apoptosis. Apoptosis of neurocytes may play an essential role in the pathogenesis of neurodegenerative diseases. This study hypothesized that folic acid (FA) supplementation decreased neurocyte apoptosis by alleviating oxidative stress-induced telomere attrition in 25-month-old Sprague Dawley (SD) rats.<br><br>METHODS: Three-month-old male SD rats were randomly divided into four diet groups by different concentrations of folic acid in equal numbers, with intervention for 22&#xa0;months. Folate, homocysteine (Hcy), reactive oxygen species (ROS) levels, antioxidant activities, and telomere length in the brain tissues were tested at 11, 18, and 22&#xa0;months of intervention, and 8-hydroxy-deoxyguanosine (8-OHdG) levels, neurocyte apoptosis and telomere length in the cerebral cortex and hippocampal regions were tested during the 22-month intervention. An automated chemiluminescence system, auto-chemistry analyzer, Q-FISH, qPCR, and TUNEL assay were used in this study.<br><br>RESULTS: The rats had lower folate concentrations and higher Hcy, ROS, and 8-OHdG concentrations in brain tissue with aging. However, FA supplementation increased folate concentrations and antioxidant activities while decreasing Hcy, ROS, and 8-OHdG levels in rat brain tissue after 11, 18, and 22&#xa0;months of intervention. Furthermore, FA supplementation alleviated telomere length shortening and inhibited neurocyte apoptosis during the 22-month intervention.<br><br>CONCLUSION: FA supplementation alleviated oxidative stress-induced telomere attrition and inhibited apoptosis of neurocytes in 25-month-old rats.},
}
@article {pmid37864645,
year = {2023},
author = {Sung, JY and Lee, JW},
title = {Telomere maintenance mechanism subtype reveals different immune activity in vestibular schwannoma.},
journal = {Journal of neuro-oncology},
volume = {165},
number = {1},
pages = {113-126},
pmid = {37864645},
issn = {1573-7373},
mesh = {Humans ; *Telomerase/genetics/metabolism ; *Neuroma, Acoustic ; Telomere ; Telomere Homeostasis ; },
abstract = {BACKGROUND: The immortality of cancer cells relies on maintaining the length of telomeres, which prevents cellular senescence and enables unlimited replication. However, little is currently known about telomerase activity and the alternative lengthening of telomeres (ALT) in vestibular schwannomas. In this study we aimed to elucidate the role that telomerase and ALTs play in vestibular schwannomas.<br><br>METHODS: To address this gap, we conducted a study where we used the gene set variation analysis algorithm with bulk RNA-seq and single-cell RNA-seq to identify the characteristics of each group of patients with vestibular schwannomas, based on their telomere maintenance mechanism subtype.<br><br>RESULTS: Our findings suggest that patients with relatively high ALT-like groups have a better prognosis than those with relatively high telomerase groups. Specifically, we found that the high telomerase group had relatively higher antigen-presenting cell (APC) activity than the high ALT like group. At the single-cell level, microglia, neutrophils, and fibroblasts showed high telomerase activity and relatively high APC activity compared to other cell types. In addition, Schwann cells in the group with low ALT levels exhibited elevated immune activity at the single-cell level.<br><br>CONCLUSION: These results suggest that personalized drug therapy could be developed from the perspective of precision medicine for patients with relatively high telomerase activity and a high ALT-like group.},
}
@article {pmid37864620,
year = {2023},
author = {Ma, C and Li, X and Ding, W and Zhang, X and Chen, H and Feng, Y},
title = {Effects of hTERT transfection on the telomere and telomerase of Periplaneta americana cells in vitro.},
journal = {AMB Express},
volume = {13},
number = {1},
pages = {118},
pmid = {37864620},
issn = {2191-0855},
support = {32170168//National Natural Science Foundation of China/ ; 2019FB043//Yunnan Fundamental Research Projects/ ; },
abstract = {Telomere and telomerase are crucial factors in cell division and chromosome stability. Telomerase activity in most cells depends on the transcription control by the telomerase reverse transcriptase (TERT). The introduction of an exogenous human TERT (hTERT) in cultured cells could enhance telomerase activity and elongate the lifespan of various cells. Telomere elongation mechanisms vary between insects and are complex and unusual. Whether the use of exogenous hTERT can immortalize primary insect cells remains to be investigated. In this study, we used a recombinant virus expressing hTERT to infect primary cultured cells of Periplaneta americana and evaluated its effects on insect cell immortalization. We found that hTERT was successfully expressed and promoted the growth of P. americana cells, shortening their doubling time. This was due to the ability of hTERT to increase the activity of telomerase in P. americana cells, thus prolonging the telomeres. Our study lays the foundation for understanding the mechanisms of telomere elongation in P. americana, and suggests that the introduction of hTERT into insect cells could be an efficient way to establish certain insect cell lines.},
}
@article {pmid37864609,
year = {2023},
author = {Vaurs, M and Dolu, EB and Decottignies, A},
title = {Mitochondria and telomeres: hand in glove.},
journal = {Biogerontology},
volume = {},
number = {},
pages = {},
pmid = {37864609},
issn = {1573-6768},
abstract = {Born as an endosymbiont, the bacteria engulfed by the proto-eukaryotic cell more than 1.45 billion years ago progressively evolved as an important organelle with multiple interactions with the host cell. In particular, strong connections between mitochondria and the chromosome ends, the telomeres, led to propose a new theory of ageing in which dysfunctional telomeres and mitochondria are the main actors of a vicious circle reducing cell fitness and promoting cellular ageing. We review the evidences that oxidative stress and dysfunctional mitochondria damage telomeres and further discuss the interrelationship between telomere biology and mitochondria through the lens of telomerase which shuttles between the nucleus and mitochondria. Finally, we elaborate on the possible role of the mitochondrial genome on the inheritance of human telomere length through the expression of mitochondrial gene variants.},
}
@article {pmid37864481,
year = {2023},
author = {Badás, EP and Bauch, C and Boonekamp, JJ and Mulder, E and Verhulst, S},
title = {Ectoparasite presence and brood size manipulation interact to accelerate telomere shortening in nestling jackdaws.},
journal = {Molecular ecology},
volume = {32},
number = {24},
pages = {6913-6923},
doi = {10.1111/mec.17177},
pmid = {37864481},
issn = {1365-294X},
support = {8444403//European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie/ ; BA 5422/1-1//DFG fellowship/ ; 823.01.009//NWO/ ; 823.01.006//NWO/ ; },
mesh = {Animals ; *Crows ; Telomere Shortening/genetics ; Stress, Physiological ; Telomere/genetics ; },
abstract = {Early-life conditions impact fitness, but whether the combined effect of extrinsic stressors is additive or synergistic is not well known. This is a major knowledge gap because exposure to multiple stressors is frequent. Telomere dynamics may be instrumental when testing how stressors interact because many factors affect telomere shortening, and telomere shortening predicts survival. We evaluated the effect of manipulated brood size and natural infestation by the carnid fly Carnus hemapterus on nestling growth and telomere shortening of wild jackdaws (Corvus monedula). Telomere length, measured in blood using TRF, shortened on average by 264 bp, and on average, Carnus infection induced more telomere shortening. Further analyses showed that in enlarged broods, nestlings' telomeres shortened more when parasitized, while in reduced broods there was no effect of infection on telomere shortening. We conclude that there is a synergistic effect of number of siblings and Carnus infection on telomere shortening rate: blood-sucking parasites may negatively impact telomeres by increasing cell proliferation and/or physiological stress, and coping with infection may be less successful in enlarged broods with increased sibling competition. Larger nestlings had shorter telomeres independent of age, brood manipulation or infection. Growth was independent of infestation but in enlarged broods, nestlings were lighter at fledging. Our findings indicate that (i) evaluating consequences of early-life environmental conditions in isolation may not yield a full picture due to synergistic effects, and (ii) effects of environmental conditions may be cryptic, for example, on telomeres, with fitness consequences expressed beyond the temporal framework of the study.},
}
@article {pmid37859695,
year = {2023},
author = {Qi, M and Yu, J and Ping, F and Xu, L and Li, W and Zhang, H and Li, Y},
title = {Tumor necrosis factor-alpha mediates the negative association between telomere length and kidney dysfunction.},
journal = {International journal of medical sciences},
volume = {20},
number = {12},
pages = {1592-1599},
pmid = {37859695},
issn = {1449-1907},
mesh = {Humans ; Adult ; Middle Aged ; *Tumor Necrosis Factor-alpha/genetics/metabolism ; Prospective Studies ; Albuminuria/genetics ; Inflammation/pathology ; *Hypertension/genetics ; Kidney ; Telomere/genetics ; Leukocytes/metabolism/pathology ; },
abstract = {Aim/hypothesis: The relationship between peripheral blood leukocyte telomere length (LTL) and kidney dysfunction, especially in people with hypertension, remains unclear. No clinical study has explored the role of inflammation and oxidative stress in the relationship between LTL and kidney dysfunction. Therefore, we examined the relationship between baseline LTL and albuminuria progression and/or rapid renal function decline in Chinese patients with or without hypertension and investigated whether inflammation and oxidative stress played a mediating role in this relationship. Methods: We conducted a prospective study including 262 patients in a 7-year follow-up period from 2014 to 2021. Data on LTL, inflammation, oxidative markers, renal function, and urine protein levels were assessed. Kidney dysfunction was defined as either albuminuria progression, rapid decline in renal function, or the composite endpoint (albuminuria progression and rapid decline in renal function). Logistic regression and simple mediation models were used for the analysis. Results: In this cohort (mean age, 54.3±9.7 years; follow-up period, 5.9±1.1 years), 42(16.0%), 21(8.0%), and 59(22.5%) patients developed albuminuria progression, rapid eGFR decline, and the composite endpoint of kidney dysfunction, respectively. Logistic regression analysis showed that each standard deviation decrease of baseline LTL and the lower quartile (Q) of baseline LTL were significantly correlated with an increased risk of rapid decline in renal function (OR=1.83 [95% CI 1.07, 3.27] per 1SD, P=0.03; OR=7.57 [95% CI 1.25, 145.88] for Q1 vs. Q4, P for trend=0.031); and the composite endpoint of kidney dysfunction (OR=1.37 [95% CI 0.97, 1.96] per 1SD, borderline positive P=0.072; OR=2.96[95% CI 1.15, 8.2] for Q1 vs. Q4, P for trend=0.036). The mediating analysis showed that tumor necrosis factor (TNF)-a partly mediated the relationship between LTL and rapid decline in renal function (direct effect: β=0.046 95%CI [0.006, 0.090],P=0.02; indirect effect: β=0.013 95%CI [0.003, 0.020]), and the mediating proportion was 22.4%.In subgroup analyses, LTL was inversely associated with rapid decline in renal function or the composite endpoint of kidney dysfunction only in patients with hypertension (OR=49.07[3.72,211.12] vs.1.32[0.69,2.58] per 1SD, P for interaction=0.045;OR=3.10 [1.48, 7.52] vs.1.08[0.92,1.63] per 1SD, P for interaction=0.036). Conclusion: Baseline LTL could independently predict kidney dysfunction at follow-up, especially in participants with hypertension. TNF-a partially mediated the negative association between LTL and kidney dysfunction.},
}
@article {pmid37858982,
year = {2023},
author = {Rizzo, A and Maresca, C and D'Angelo, C and Porru, M and Di Vito, S and Salvati, E and Sacconi, A and Berardinelli, F and Sgura, A and Kuznetsov, S and Potdar, S and Hassinen, A and Stoppacciaro, A and Zizza, P and Biroccio, A},
title = {Drug repositioning strategy for the identification of novel telomere-damaging agents: A role for NAMPT inhibitors.},
journal = {Aging cell},
volume = {22},
number = {11},
pages = {e13944},
pmid = {37858982},
issn = {1474-9726},
support = {21579//Associazione Italiana per la Ricerca sul Cancro/ ; Ricerca Corrente 2022//Ministero della Salute/ ; },
mesh = {Humans ; *Triple Negative Breast Neoplasms ; Drug Repositioning ; Cell Death ; Apoptosis ; Telomere ; Telomeric Repeat Binding Protein 2/genetics ; Cell Line, Tumor ; },
abstract = {Drug repositioning strategy represents a valid tool to accelerate the pharmacological development through the identification of new applications for already existing compounds. In this view, we aimed at discovering molecules able to trigger telomere-localized DNA damage and tumor cell death. By applying an automated high-content spinning-disk microscopy, we performed a screening aimed at identifying, on a library of 527 drugs, molecules able to negatively affect the expression of TRF2, a key protein in telomere maintenance. FK866, resulting from the screening as the best candidate hit, was then validated at biochemical and molecular levels and the mechanism underlying its activity in telomere deprotection was elucidated both in vitro and in vivo. The results of this study allow us to discover a novel role of FK866 in promoting, through the production of reactive oxygen species, telomere loss and deprotection, two events leading to an accumulation of DNA damage and tumor cell death. The ability of FK866 to induce telomere damage and apoptosis was also demonstrated in advanced preclinical models evidencing the antitumoral activity of FK866 in triple-negative breast cancer-a particularly aggressive breast cancer subtype still orphan of targeted therapies and characterized by high expression levels of both NAMPT and TRF2. Overall, our findings pave the way to the development of novel anticancer strategies to counteract triple-negative breast cancer, based on the use of telomere deprotecting agents, including NAMPT inhibitors, that would rapidly progress from bench to bedside.},
}
@article {pmid37858268,
year = {2023},
author = {Sauty, SM and Yankulov, K},
title = {Analyses of POL30 (PCNA) reveal positional effects in transient repression or bi-modal active/silent state at the sub-telomeres of S. cerevisiae.},
journal = {Epigenetics &amp; chromatin},
volume = {16},
number = {1},
pages = {40},
pmid = {37858268},
issn = {1756-8935},
mesh = {Histone Chaperones/metabolism ; Histones/metabolism ; *Proliferating Cell Nuclear Antigen/genetics/metabolism ; *Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; *Telomere/genetics/metabolism ; },
abstract = {BACKGROUND: Classical studies on position effect variegation in Drosophila have demonstrated the existence of bi-modal Active/Silent state of the genes juxtaposed to heterochromatin. Later studies with irreversible methods for the detection of gene repression have revealed a similar phenomenon at the telomeres of Saccharomyces cerevisiae and other species. In this study, we used dual reporter constructs and a combination of reversible and non-reversible methods to present evidence for the different roles of PCNA and histone chaperones in the stability and the propagation of repressed states at the sub-telomeres of S. cerevisiae.<br><br>RESULTS: We show position dependent transient repression or bi-modal expression of reporter genes at the VIIL sub-telomere. We also show that mutations in the replicative clamp POL30 (PCNA) or the deletion of the histone chaperone CAF1 or the RRM3 helicase lead to transient de-repression, while the deletion of the histone chaperone ASF1 causes a shift from transient de-repression to a bi-modal state of repression. We analyze the physical interaction of CAF1 and RRM3 with PCNA and discuss the implications of these findings for our understanding of the stability and transmission of the epigenetic state of the genes.<br><br>CONCLUSIONS: There are distinct modes of gene silencing, bi-modal and transient, at the sub-telomeres of S. cerevisiae. We characterise the roles of CAF1, RRM3 and ASF1 in these modes of gene repression. We suggest that the interpretations of past and future studies should consider the existence of the dissimilar states of gene silencing.},
}
@article {pmid37857729,
year = {2023},
author = {Devrajani, T and Abid, S and Shaikh, H and Shaikh, I and Devrajani, DB and Memon, SM and Waryah, AM and Ujjan, ID and Syed, BM},
title = {Relationship between aging and control of metabolic syndrome with telomere shortening: a cross-sectional study.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {17878},
pmid = {37857729},
issn = {2045-2322},
mesh = {Humans ; Aged ; Adult ; Middle Aged ; *Telomere Shortening ; *Metabolic Syndrome/genetics/epidemiology ; Cross-Sectional Studies ; Aging/genetics ; Risk Factors ; Telomere/genetics ; },
abstract = {Aging is considered one of the major risk factors for several human disorders. The telomere plays a crucial role in regulating cellular responsiveness to stress and growth stimuli as well as maintaining the integrity of the Deoxyribonucleic Acid (DNA), and aging leads to the progressive decline in the telomere length (TL) due to continuous cell division. The aim of this study was to determine the relationship between TL and advancing age and the impact of metabolic syndrome (MetS) on TL. Firstly, we determined the association of advancing age and TL, by measuring telomere length (T/S ratio) in healthy volunteers (n = 90). The TL was compared between normal population and patients with metabolic syndrome (n = 298). The age matched controlled and uncontrolled MetS patients (n = 149) were also compared for their TL T/S ratio. The TL showed negative correlation with advancing age, whereas the significant change was observed at the cut-offs of 40 and 70 years defining 40 with longer TL and 70 as shorter TL. The longest T/S ratio at 2.46 was measured at the age range of 1 year in healthy volunteers, while elderly population showed considerably shorter TL. The patients older than 60 years with poor or uncontrolled MetS had shorter TL, as compared to the controlled MetS. In conclusion our findings suggest that TL was negatively correlated with advancing age. Uncontrolled metabolic syndrome appeared to have worsening effects on TL. Telomere length appears to have potential to be used a parameter to determine age. However, further large scale studies are recommended to make firm guidelines.},
}
@article {pmid37857262,
year = {2023},
author = {Yeung, SSY and Ma, SL and Wang, X and Chen, Y and Tsui, SKW and Tang, NLS and Woo, J},
title = {Telomere Length among Chinese Aged 75+ Years.},
journal = {Gerontology},
volume = {69},
number = {12},
pages = {1414-1423},
pmid = {37857262},
issn = {1423-0003},
mesh = {Male ; Female ; Humans ; Aged ; Aged, 80 and over ; *Sarcopenia/epidemiology/genetics ; *Frailty/epidemiology/genetics ; Cross-Sectional Studies ; East Asian People ; Biomarkers ; Telomere/genetics ; Telomere Shortening ; },
abstract = {INTRODUCTION: Telomere length (TL) is generally regarded as a biomarker of aging. TL, which is influenced by sociodemographic factors, has been shown to be inversely associated with morbidity. However, most studies examined the youngest, and whether the findings can be extended to older individuals is less clear. Further, few studies have examined these questions in Chinese older adults. This cross-sectional study examined TL and its associated factors in Chinese aged 75+ years in Hong Kong.<br><br>METHODS: Participants were from the Mr. and Ms. Osteoporosis cohort. A structured interview on sociodemographic factors and physical measurement was conducted. Frailty and sarcopenia status were respectively determined by Fried's criteria and the Asian Working Group for Sarcopenia definition. TL was measured by a molecular inversion probe-quantitative PCR assay and expressed as a novel telomere/a single copy reference gene (T/S) ratio. Adjusted binary logistic regressions were used to examine the associations between TL and the presence of multimorbidity, age-related diseases, frailty, and sarcopenia.<br><br>RESULTS: Among 555 participants (mean age 83.6 &#xb1; 3.8 years, 41.3% females), the mean T/S ratio was 1.01 &#xb1; 0.20. Males had a lower T/S ratio (0.97 &#xb1; 0.20) compared with females (1.07 &#xb1; 0.18) (p < 0.001). A lower education level was related to a longer TL (p = 0.016). Being a current smoker was related to a shorter TL (p = 0.007). TL was not significantly different across categories of age, subjective socioeconomic status, drinking status, physical activity level, and body mass index (p > 0.05). There were no associations between TL and the presence of multimorbidity, diabetes, stroke, cardiovascular diseases, cognitive impairment, frailty, and sarcopenia.<br><br>CONCLUSION: Among Chinese aged 75+ years, males had shorter TL compared with females. TL was not associated with age-related diseases, frailty, and sarcopenia in this age group. TL may not be a biological marker of aging among older individuals.},
}
@article {pmid37853446,
year = {2023},
author = {Liu, X and Ma, T and Yang, C and Li, J and Zhang, Y and Zhao, Y},
title = {Persistent dyslipidemia increases the longitudinal changes in telomere length.},
journal = {Lipids in health and disease},
volume = {22},
number = {1},
pages = {173},
pmid = {37853446},
issn = {1476-511X},
support = {2021BEG02026//the key R&amp;D projects in Ningxia Hui Autonomous Region/ ; No. 82060592//the National Natural Science Foundation of China/ ; },
mesh = {Humans ; Cross-Sectional Studies ; *Aging/genetics ; Real-Time Polymerase Chain Reaction ; *Leukocytes ; Telomere/genetics ; Lipids ; Longitudinal Studies ; },
abstract = {BACKGROUND AND AIMS: Leukocyte telomere length (LTL) as a 'biological clock' of aging is closely related to human health, its association with an aging-related disease, dyslipidemia, has been less studied and mainly focused on cross-sectional investigations.<br><br>METHODS: Two rounds of information and blood collections were conducted on a cohort of 1624 individuals residing in rural Ningxia, located in northwest China, with an average time gap of 9.8 years. The relative telomere length (RTL) of peripheral blood leukocytes was assessed using real-time quantitative PCR. To investigate the association between dyslipidemia, blood lipid levels, and alterations in RTL, multiple linear regression and generalized linear models were employed.<br><br>RESULTS: After conducting the follow-up analysis, it was observed that 83.3% of the participants in the study exhibited a reduction in telomere length, while 16.7% experienced an increase in telomere length. The results suggested that dyslipidemia at baseline or follow-up may increase longitudinal changes in telomere length, but it was more significant in the healthy group, especially in those aged &#x2265; 60 years. Furthermore, HDL-C levels in baseline and follow-up were found to be associated with longitudinal changes in telomere length, and lower HDL-C levels may be associated with increased longitudinal changes in telomere length.<br><br>CONCLUSIONS: The change in telomere length is correlated with dyslipidemia and its lipid indicators especially HDL-C. Persistent dyslipidemia and a reduction in HDL-C levels may be associated with elevated longitudinal fluctuations in telomere length.},
}
@article {pmid37851888,
year = {2023},
author = {Armanios, M},
title = {Familial Clonal Hematopoiesis in a Long Telomere Syndrome. Reply.},
journal = {The New England journal of medicine},
volume = {389},
number = {16},
pages = {1535-1536},
doi = {10.1056/NEJMc2309139},
pmid = {37851888},
issn = {1533-4406},
mesh = {Humans ; *Clonal Hematopoiesis ; *Hematopoiesis/genetics ; Mutation ; Telomere/genetics ; },
}
@article {pmid37851887,
year = {2023},
author = {Nakao, T and Natarajan, P},
title = {Familial Clonal Hematopoiesis in a Long Telomere Syndrome.},
journal = {The New England journal of medicine},
volume = {389},
number = {16},
pages = {1535},
pmid = {37851887},
issn = {1533-4406},
support = {K99 HL165024/HL/NHLBI NIH HHS/United States ; R01 HL148050/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Clonal Hematopoiesis ; *Hematopoiesis/genetics ; Mutation ; Telomere ; },
}
@article {pmid37849074,
year = {2024},
author = {Ertunc, O and Smearman, E and Zheng, Q and Hicks, JL and Brosnan-Cashman, JA and Jones, T and Gomes-Alexandre, C and Trabzonlu, L and Meeker, AK and De Marzo, AM and Heaphy, CM},
title = {Chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate.},
journal = {The Prostate},
volume = {84},
number = {2},
pages = {148-157},
pmid = {37849074},
issn = {1097-0045},
support = {P30 CA006973/CA/NCI NIH HHS/United States ; P50 CA058236/CA/NCI NIH HHS/United States ; U01 CA196390/CA/NCI NIH HHS/United States ; U54 CA274370/CA/NCI NIH HHS/United States ; },
mesh = {Male ; Humans ; In Situ Hybridization, Fluorescence/methods ; *Prostate ; In Situ Hybridization ; *Precancerous Conditions/diagnosis/genetics ; Telomere ; },
abstract = {BACKGROUND: Telomeres are terminal chromosomal elements that are essential for the maintenance of genomic integrity. The measurement of telomere content provides useful diagnostic and prognostic information, and fluorescent methods have been developed for this purpose. However, fluorescent-based tissue assays are cumbersome for investigators to undertake, both in research and clinical settings.<br><br>METHODS: A robust chromogenic in situ hybridization (CISH) approach was developed to visualize and quantify telomere content at single cell resolution in human prostate tissues, both frozen and formalin-fixed, paraffin-embedded (FFPE).<br><br>RESULTS: This new assay (telomere chromogenic in situ hybridization ["Telo-CISH"]) produces permanently stained slides that are viewable with a standard light microscope, thus avoiding the need for specialized equipment and storage. The assay is compatible with standard immunohistochemistry, thereby allowing simultaneous assessment of histomorphology, identification of specific cell types, and assessment of telomere status. In addition, Telo-CISH eliminates the problem of autofluorescent interference that frequently occurs with fluorescent-based methods. Using this new assay, we demonstrate successful application of Telo-CISH to help identify precancerous lesions in the prostate by the presence of markedly short telomeres specifically in the luminal epithelial cells.<br><br>CONCLUSIONS: In summary, with fewer restrictions on the types of tissues that can be tested, and increased histologic information provided, the advantages presented by this novel chromogenic assay should extend the applicability of tissue-based telomere length assessment in research and clinical settings.},
}
@article {pmid37848852,
year = {2023},
author = {Houminer-Klepar, N and Bord, S and Epel, E and Baron-Epel, O},
title = {Are pregnancy and parity associated with telomere length? A systematic review.},
journal = {BMC pregnancy and childbirth},
volume = {23},
number = {1},
pages = {733},
pmid = {37848852},
issn = {1471-2393},
mesh = {Pregnancy ; Child ; Humans ; Female ; *Aging ; *Reproduction ; Telomere ; Postpartum Period ; Biomarkers ; },
abstract = {BACKGROUND: Women's reproduction requires increased energy demands, which consequently may lead to cellular damage and aging. Hence, Telomere Length (TL), a biomarker of biological aging and health status may possibly serve as a biomarker of reproductive effort. The aim of this systematic review is to evaluate telomere dynamics throughout pregnancy and the association between parity and TL.<br><br>METHODS: A systematic search was conducted across seven databases including CINAHL, Cochrane, PsycINFO, Proquest, PubMed; Scopus; and Web of Science, using keywords and MeSH descriptors of parity and TL. Predefined inclusion and exclusion criteria were used to screen abstracts and titles. After the removal of duplicates, 3431 articles were included in the primary screening, narrowed to 194 articles included in the full-text screening. Consensus was reached for the&#xa0;14 studies that were included in the final review, and the Newcastle-Ottawa scale (NOS) was utilized to assess the quality of the selected studies. A mini meta-analysis utilized JASP 0.17.3 software and included 4 applicable studies, comprising a total of 2564 participants to quantitatively assess the estimated effect size of parity on TL.<br><br>RESULTS: Of the 11 studies reviewed on parity and TL, four demonstrated a negative correlation; one - a positive correlation and six -found no correlation. Studies demonstrating a negative correlation encompassed rigorous methodological practices possibly suggesting having more children is associated with enhanced telomere attrition. Of the four longitudinal studies assessing telomere dynamics throughout pregnancy, most found no change in TL from early pregnancy to postpartum suggesting pregnancy does not affect TL from early pregnancy to early postpartum. The meta-analysis revealed a negative, yet, non-significant effect, of the estimated effect size of parity on TL(ES&#x2009;=&#x2009;-0.009, p&#x2009;=&#x2009;0.126, CI -0.021, 0.03).<br><br>CONCLUSIONS: Studies assessing pregnancy, parity and TL yielded mixed results, most likely due to the different research methods utilized in each study. Improvements in study design to better understand the short-term effects of pregnancy on TL and the effect of parity on TL over time, include precise definitions of parity, comparisons of different age groups, inclusion of reproductive lifespan and statistically adjusting for potential confounders in the parity and TL relationship.},
}
@article {pmid37847171,
year = {2023},
author = {Chen, J and Zhang, D and Ren, X and Wang, P},
title = {A comprehensive prognostic and immunological analysis of telomere-related lncRNAs in kidney renal clear cell carcinoma.},
journal = {Aging},
volume = {15},
number = {20},
pages = {11012-11032},
pmid = {37847171},
issn = {1945-4589},
mesh = {Humans ; Prognosis ; *RNA, Long Noncoding/genetics ; *Carcinoma, Renal Cell/genetics ; Telomere/genetics ; *Kidney Neoplasms/genetics ; Kidney ; Tumor Microenvironment/genetics ; },
abstract = {Kidney renal clear cell carcinoma (KIRC) is one of the most prevalent malignant tumors of the urinary system, with a high recurrence and metastasis rate. Telomeres and long non-coding RNAs (lncRNAs) have been documented playing critical roles in cancer progression. However, the prognostic significance of telomere-related lncRNA (TRLs) in KIRC is less well-defined. The Cancer Genome Atlas database was applied to retrieve the expression profiles and corresponding clinical information of KIRC patients. To create the TRLs prognostic signature, univariate Cox regression, least absolute shrinkage and selection operator analyses were performed. The prognostic signature, comprised of nine prognostic TRLs, was developed and demonstrated superior prognostic ability for KIRC patients. Additionally, the risk score acted as an independent prognostic indicator. A nomogram incorporating age, grade, stage, and signature-based risk scores was also developed and exhibited excellent predictive accuracy. Several immune activities were associated with the signature, as determined by gene function analysis. Further analysis revealed differences in the status of immunity and the tumor microenvironment between low- and high-risk groups. Notably, KIRC patients with high-risk scores were more responsive to immunotherapy and chemotherapy. To summarize, our study developed a new prognostic signature consisting of nine telomere-related lncRNA that can precisely predict the prognosis of KIRC patients. The signature was shown to be of substantial value for the tumor microenvironment and tumor mutation burden, thereby contributing to a framework for the individualized treatment of patients.},
}
@article {pmid37844405,
year = {2023},
author = {Zhang, F and Du, H and Hu, C and Song, Y},
title = {A new prognostic risk model for acute myeloid leukemia patients based on telomere-related genes.},
journal = {Leukemia research},
volume = {135},
number = {},
pages = {107404},
doi = {10.1016/j.leukres.2023.107404},
pmid = {37844405},
issn = {1873-5835},
mesh = {Humans ; Prognosis ; *Leukemia, Myeloid, Acute/diagnosis/genetics/drug therapy ; Risk Factors ; Kaplan-Meier Estimate ; ROC Curve ; Aldehyde Dehydrogenase, Mitochondrial ; },
abstract = {Telomere maintenance is critical to ensure unlimited cancer cell proliferation, but the role of telomere-related genes in acute myeloid leukemia (AML) has not yet been thoroughly discussed. This study aims to develop a new prognostic risk model based on telomere-related genes and analyze potential mechanisms and targets. Cox regression analyses were used to build the prognostic risk model. Kaplan-Meier (KM) survival analysis and receiver operating characteristic (ROC) curve were used to assess the model performance. At the same time, we analyzed the relationship between the risk score and chemotherapy and immunotherapy and preliminarily explored possible mechanisms of immune resistance. The real-time polymerase chain reaction (PCR) was used to detect the prognosis gene expression levels. Finally, a prognostic signature of six telomere-related genes (TGPS6) including ALDH2, CDK18, DNMT3B, FRAT2, LGALSL, and RBL2 was constructed. The TGPS6 score was confirmed as an independent prognostic factor (HR 2.74, CI [2.13-3.53], p < 0.001) in AML and the five-year area under the ROC curve (AUC) value of the score in the training and validation set reached 0.74, 0.81 respectively. In addition, the TGPS6 perfected the European LeukemiaNet (ELN) 2017 prognosis risk stratification and performed well in both AML and cytogenetically normal AML (CN-AML) cohorts. The TGPS6 score also provided a reference for chemotherapy and immunotherapy in patients with AML.},
}
@article {pmid37843976,
year = {2023},
author = {Sze, S and Bhardwaj, A and Fnu, P and Azarm, K and Mund, R and Ring, K and Smith, S},
title = {TERRA R-loops connect and protect sister telomeres in mitosis.},
journal = {Cell reports},
volume = {42},
number = {10},
pages = {113235},
pmid = {37843976},
issn = {2211-1247},
support = {R01 GM129780/GM/NIGMS NIH HHS/United States ; R01 GM141292/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Tankyrases/genetics/metabolism ; R-Loop Structures ; Telomere/metabolism ; Mitosis ; RNA ; DNA ; },
abstract = {Resolution of cohesion between sister telomeres in human cells depends on TRF1-mediated recruitment of the polyADP-ribosyltransferase tankyrase to telomeres. In human aged cells, due to insufficient recruitment of TRF1/tankyrase to shortened telomeres, sisters remain cohered in mitosis. This persistent cohesion plays a protective role, but the mechanism by which sisters remain cohered is not well understood. Here we show that telomere repeat-containing RNA (TERRA) holds sister telomeres together through RNA-DNA hybrid (R-loop) structures. We show that a tankyrase-interacting partner, the RNA-binding protein C19orf43, is required for repression of TERRA R-loops. Persistent telomere cohesion in C19orf43-depleted cells is counteracted by RNaseH1, confirming that RNA-DNA hybrids hold sisters together. Consistent with a protective role for persistent telomere cohesion, depletion of C19orf43 in aged cells reduces DNA damage and delays replicative senescence. We propose that the inherent inability of shortened telomeres to recruit R-loop-repressing machinery permits a controlled onset of senescence.},
}
@article {pmid37843740,
year = {2024},
author = {Thai, NQN and LaCroix, AZ and Haring, B and Wactawski-Wende, J and Manson, JE and Posis, AIB and Shadyab, AH},
title = {The association of leukocyte telomere length with exceptional longevity among older women.},
journal = {GeroScience},
volume = {46},
number = {2},
pages = {2083-2092},
pmid = {37843740},
issn = {2509-2723},
support = {75N92021D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; },
mesh = {Humans ; Female ; Aged ; Aged, 80 and over ; *Longevity/genetics ; Prospective Studies ; Telomere ; Leukocytes ; *Stroke/epidemiology/genetics ; },
abstract = {The association of leukocyte telomere length (LTL) with survival to late life with intact mobility has not been adequately studied. This prospective cohort study consisted of 1451 postmenopausal women from a Women's Health Initiative ancillary study, who were eligible, because of birth year, to survive to age 90 as of March 6, 2021. LTL was measured by Southern blot at baseline (1993-1998). Associations between LTL and survival to age 90 were evaluated using logistic regression models adjusted for socio-demographic characteristics, health factors, and lifestyle factors. Multinominal logistic regression was utilized to examine associations of LTL with survival to age 90 with or without intact mobility. Mediation analysis examined the extent to which incident coronary heart disease and stroke-mediated the association between LTL and longevity. Overall, 76.7% of women were White, and 23.3% were Black; average age at baseline was 70.4±3.5 years. Relative to death before age 90, the odds of survival to age 90 were 60% higher (OR, 1.60; 95% CI, 1.28-2.01), the odds of survival to age 90 with mobility limitation were 72% higher (OR, 1.72; 95% CI, 1.33-2.21), and the odds of survival to age 90 with intact mobility were 44% higher (OR, 1.44; 95% CI, 1.06-1.95) for every one kilobase longer LTL. Absence of CHD, stroke, or CHD/stroke mediated the association of LTL with survival to age 90 by 11.1%, 37.4%, and 31.3%, respectively; however, these findings were not significant. Longer LTL was associated with higher odds of survival to age 90 among older women.},
}
@article {pmid37837282,
year = {2023},
author = {Westneat, DF and Young, RC and Cones, AG and Kucera, AC and Anacleto, A and Heidinger, BJ},
title = {Early-life telomeres are influenced by environments acting at multiple temporal and spatial scales.},
journal = {Molecular ecology},
volume = {32},
number = {22},
pages = {5959-5970},
doi = {10.1111/mec.17166},
pmid = {37837282},
issn = {1365-294X},
support = {IBN0542097//Division of Integrative Organismal Systems/ ; IBN9816989//Division of Integrative Organismal Systems/ ; IOS1257718//Division of Integrative Organismal Systems/ ; IOS1656194//Division of Integrative Organismal Systems/ ; IOS1656212//Division of Integrative Organismal Systems/ ; },
mesh = {Humans ; Animals ; *Telomere Shortening/genetics ; *Telomere/genetics ; Seasons ; Longevity ; },
abstract = {An individual's telomere length early in life may reflect or contribute to key life-history processes sensitive to environmental variation. Yet, the relative importance of genetic and environmental factors in shaping early-life telomere length is not well understood as it requires samples collected from multiple generations with known developmental histories. We used a confirmed pedigree and conducted an animal model analysis of telomere lengths obtained from nestling house sparrows (Passer domesticus) sampled over a span of 22 years. We found significant additive genetic variation for early-life telomere length, but it comprised a small proportion (9%) of the total biological variation. Three sources of environmental variation were important: among cohorts, among-breeding attempts within years, and among nestmates. The magnitude of variation among breeding attempts and among nestmates also differed by cohort, suggesting that interactive effects of environmental factors across time or spatial scales were important, yet we were unable to identify the specific causes of these interactions. The mean amount of precipitation during the breeding season positively predicted telomere length, but neither weather during a given breeding attempt nor date in the breeding season contributed to an offspring's telomere length. At the level of individual nestlings, offspring sex, size and mass at 10 days of age also did not predict telomere length. Environmental effects appear especially important in shaping early-life telomere length in some species, and more focus on how environmental factors that interact across scales may help to explain some of the variation observed among studies.},
}
@article {pmid37836587,
year = {2023},
author = {Petermann-Rocha, F and Valera-Gran, D and Prieto-Botella, D and Martens, DS and Gonzalez-Palacios, S and Riaño-Galán, I and Murcia, M and Irizar, A and Julvez, J and Santa-Marina, L and Tardón, A and Sunyer, J and Vioque, J and Nawrot, T and Navarrete-Muñoz, EM},
title = {Folic Acid Supplementation during Pregnancy and Its Association with Telomere Length in Children at Four Years: Results from the INMA Birth Cohort Study.},
journal = {Nutrients},
volume = {15},
number = {19},
pages = {},
pmid = {37836587},
issn = {2072-6643},
support = {27307C0010/ES/NIEHS NIH HHS/United States ; },
mesh = {Male ; Pregnancy ; Female ; Humans ; Child ; Cohort Studies ; *Folic Acid ; *Dietary Supplements ; Surveys and Questionnaires ; Telomere ; },
abstract = {This study examined the association between folic acid supplements (FAs) during different periods of pregnancy and offspring telomere length (TL) at age four in 666 children from the INMA study. FAs were self-reported using food-structured questionnaires during three periods of pregnancy (the first three months of pregnancy, from month fourth onward, and the whole pregnancy). For each period, the average daily dosage of FAs was categorised into (i) <400 μg/d, (ii) ≥400 to 999 μg/d, (iii) ≥1000 to 4999 μg/d, and (iv) ≥5000 μg/d. Leucocyte TL at age four was measured using quantitative PCR methods. Multiple robust linear log-level regression models were used to report the % difference among FA categories. During the first period, and compared with children whose mothers were classified in the reference group (<400 μg/d), children whose mothers took higher dosages of FAs showed shorter TL at age four (≥5000 μg/d). When the first and the second periods were mutually adjusted, children whose mothers self-reported ≥5000 μg/d during the first period of pregnancy had a statistically significant shorter TL than their counterparts (% difference: -7.28% [95% CI: -14.42 to -0.13]). Similar trends were observed for the whole period of pregnancy. When the analysis was stratified by sex, the association was more evident in boys (% difference: -13.5% [95% CI: -23.0 to -4.04]), whereas no association was observed in girls. This study suggests that high dosages of FAs in the first pregnancy period may be associated with a shorter TL in children at age four, particularly among boys. Further studies should confirm these results.},
}
@article {pmid37828426,
year = {2023},
author = {Liu, W and Chen, S and Xie, W and Wang, Q and Luo, Q and Huang, M and Gu, M and Lan, P and Chen, D},
title = {MCCC2 is a novel mediator between mitochondria and telomere and functions as an oncogene in colorectal cancer.},
journal = {Cellular &amp; molecular biology letters},
volume = {28},
number = {1},
pages = {80},
pmid = {37828426},
issn = {1689-1392},
support = {31970703//National Natural Science Foundation of China/ ; 2021A1515010544//Natural Science Foundation of Guangdong Province/ ; 2022A1515012472//Natural Science Foundation of Guangdong Province/ ; },
mesh = {Humans ; *Colorectal Neoplasms/genetics/metabolism ; Telomere/genetics/metabolism ; Oncogenes ; Mitochondria/metabolism ; Kaplan-Meier Estimate ; Cell Proliferation/genetics ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Cell Movement/genetics ; },
abstract = {BACKGROUND: The mitochondrial gene MCCC2, a subunit of the heterodimer of 3-methylcrotonyl-CoA carboxylase, plays a pivotal role in catabolism of leucine and isovaleric acid. The molecular mechanisms and prognostic value still need to be explored in the context of specific cancers, including colorectal cancer (CRC).<br><br>METHODS: In vitro and in vivo cell-based assays were performed to explore the role of MCCC2 in CRC cell proliferation, invasion, and migration. Mitochondrial morphology, membrane potential, intracellular reactive oxygen species (ROS), telomerase activity, and telomere length were examined and analyzed accordingly. Protein complex formation was detected by co-immunoprecipitation (CO-IP). Mitochondrial morphology was observed by transmission electron microscopy (TEM). The Cancer Genome Atlas (TCGA) CRC cohort analysis, qRT-PCR, and immunohistochemistry (IHC) were used to examine the MCCC2 expression level. The association between MCCC2 expression and various clinical characteristics was analyzed by chi-square tests. CRC patients' overall survival (OS) was analyzed by Kaplan-Meier analysis.<br><br>RESULTS: Ectopic overexpression of MCCC2 promoted cell proliferation, invasion, and migration, while MCCC2 knockdown (KD) or knockout (KO) inhibited cell proliferation, invasion, and migration. MCCC2 KD or KO resulted in reduced mitochondria numbers, but did not affect the gross ATP production in the cells. Mitochondrial fusion markers MFN1, MFN2, and OPA1 were all upregulated in MCCC2 KD or KO cells, which is in line with a phenomenon of more prominent mitochondrial fusion. Interestingly, telomere lengths of MCCC2 KD or KO cells were reduced more than control cells. Furthermore, we found that MCCC2 could specifically form a complex with telomere binding protein TRF2, and MCCC2 KD or KO did not affect the expression or activity of telomerase reverse transcriptase (TERT). Finally, MCCC2 expression was heightened in CRC, and patients with higher MCCC2 expression had favorable prognosis.<br><br>CONCLUSIONS: Together, we identified MCCC2 as a novel mediator between mitochondria and telomeres, and provided an additional biomarker for CRC stratification.},
}
@article {pmid37827695,
year = {2023},
author = {Wang, Q and Hou, K and Yang, J and Li, H and Li, C and Zhang, Y and Tian, J and Li, C and Guo, B and Jia, S and Luo, Y},
title = {Modified iPOND revealed the role of mutant p53 in promoting helicase function and telomere maintenance.},
journal = {Aging},
volume = {15},
number = {19},
pages = {10767-10784},
pmid = {37827695},
issn = {1945-4589},
mesh = {Animals ; Mice ; *DNA Replication ; Tumor Suppressor Protein p53/genetics/metabolism ; Werner Syndrome Helicase/genetics ; DNA Helicases/genetics/metabolism ; DNA/genetics ; Telomere/genetics/metabolism ; *Werner Syndrome ; RecQ Helicases/genetics/metabolism ; },
abstract = {The G-rich DNA, such as telomere, tends to form G-quadruplex (G4) structure, which slows down the replication fork progression, induces replication stress, and becomes the chromosome fragile sites. Here we described a molecular strategy that cells developed to overcome the DNA replication stress via DNA helicase regulation. The p53N236S (p53S) mutation has been found in the Werner syndrome mouse embryo fibroblast (MEFs) escaped from senescence, could be the driving force for cell escaping senescence. We revealed that the p53S could transcriptionally up-regulate DNA helicases expression, including Wrn, Blm, Timeless, Ddx, Mcm, Gins, Fanc, as well as telomere specific proteins Terf1, Pot1, through which p53S promoted the unwinding of G4 structures, and protected the cells from DNA replication stress induced by G4 stabilizer. By modified iPOND (isolation of proteins on nascent DNA) assay and telomere assay, we demonstrated that the p53S could promote the recruitment of those helicases to the DNA replication forks, facilitated the maintenance of telomere, and prevent the telomere dysfunction induced by G4 stabilizer. Interestingly, we did not observe the function of promoting G4 resolving and facilitating telomere lengthening in the cells with Li-Fraumeni Syndrome mutation-p53R172H (p53H), which suggests that this is the specific gain of function for p53S. Together our data suggest that the p53S could gain the new function of releasing the replication stress via regulating the helicase function and G4 structure, which benefits telomere lengthening. This strategy could be applied to the treatment of diseases caused by telomere replication stress.},
}
@article {pmid37826871,
year = {2023},
author = {Bernardinello, N and Crestani, B and Spagnolo, P and Ghanem, M and Homps-Legrand, M and Morer, L and Goletto, T and Frija-Masson, J and Bancal, C and Hurtado-Nedelec, M and de Chaisemartin, L and Debray, MP and Neukirch, C and Taillé, C and Ba, I and Kannengiesser, C and Lainey, E and Abels, A and Vankann, L and Beier, F and Borie, R},
title = {Is telomere length a predictor of long-term survival in patients with COVID-19 pneumonia?.},
journal = {Respiratory medicine and research},
volume = {84},
number = {},
pages = {101048},
doi = {10.1016/j.resmer.2023.101048},
pmid = {37826871},
issn = {2590-0412},
mesh = {Humans ; *COVID-19 ; Aging ; Telomere/genetics ; },
}
@article {pmid37824094,
year = {2023},
author = {Aviv, A},
title = {The "telomereless" erythrocytes and telomere-length dependent erythropoiesis.},
journal = {Aging cell},
volume = {22},
number = {12},
pages = {e13997},
pmid = {37824094},
issn = {1474-9726},
support = {U01 AG066529/AG/NIA NIH HHS/United States ; 1R56AG073226/NH/NIH HHS/United States ; U01AG066529/NH/NIH HHS/United States ; 1R01HL134840/NH/NIH HHS/United States ; },
mesh = {Adult ; Humans ; *Erythropoiesis/genetics ; *Erythrocytes ; Leukocytes ; Longevity ; Telomere ; },
abstract = {Approximately 25 trillion erythrocytes (red blood cells) circulate in the bloodstream of an adult human, surpassing the number of circulating leukocytes (white blood cells) by a factor of about 1000. Moreover, the erythrocyte turnover rate accounts for approximately 76% of the turnover rate of all circulating blood cells. This simple math shows that the hematopoietic system principally spends its telomere length-dependent replicative capacity on building and maintaining the erythrocyte blood pool. Erythropoiesis (red blood cell production) is thus the principal cause of telomere shortening with age in hematopoietic cells (HCs), a conclusion that holds significant implications for linking telomere length dynamics in HCs to health and lifespan of modern humans.},
}
@article {pmid37817598,
year = {2023},
author = {Power, ML and Ransome, RD and Riquier, S and Romaine, L and Jones, G and Teeling, EC},
title = {Hibernation telomere dynamics in a shifting climate: insights from wild greater horseshoe bats.},
journal = {Proceedings. Biological sciences},
volume = {290},
number = {2008},
pages = {20231589},
pmid = {37817598},
issn = {1471-2954},
mesh = {Humans ; Animals ; *Hibernation ; *Chiroptera/genetics ; Cross-Sectional Studies ; Body Temperature ; Telomere ; },
abstract = {Hibernation is linked with various hypotheses to explain the extended lifespan of hibernating mammals compared with their non-hibernating counterparts. Studies on telomeres, markers of ageing and somatic maintenance, suggest telomere shortening slows during hibernation, and lengthening may reflect self-maintenance with favourable conditions. Bats in temperate zones adjust body temperatures during winter torpor to conserve energy and exploit mild conditions for foraging. Climate change may impact the hibernation cycle of bats, but more research is needed regarding the role of telomeres in understanding their response to a changing climate. Here, relative telomere length (rTL) was measured in the long-lived greater horseshoe bat Rhinolophus ferrumequinum (n = 223 individuals) over three winters, considering climatic conditions. Cross-sectional analyses revealed between-individual variation in rTL with a strong year effect, likely linked to varying weather conditions and foraging success. Additionally, within-individual increases of rTL occurred in 51% of consecutive measurements, with evidence of increasing telomerase expression during hibernation in this species. These findings highlight the beneficial effects of hibernation on telomeres and potential consequences of changing climatic conditions for long-lived temperate bats. Understanding the interplay between hibernation, telomeres, and climate can provide insights into the adaptive capacity and survival of bat populations facing environmental challenges.},
}
@article {pmid37806951,
year = {2023},
author = {Veiko, NN and Ershova, ES and Porokhovnik, LN and Klimenko, MP and Klimenko, PA and Umriukhin, PE and Kostyuk, &#x415;V and Kurtser, MA and Agafonova, ON and Salimova, TA and Kutsev, SI and Izhevskaya, VL and Kostyuk, SV},
title = {Ribosomal, Telomere, and Mitochondrial Repeat Copy Number Variations in Female Genomes during Ovarian Stimulation and the Prediction of In Vitro Fertilization Outcome: A Pilot Study.},
journal = {Frontiers in bioscience (Scholar edition)},
volume = {15},
number = {3},
pages = {9},
doi = {10.31083/j.fbs1503009},
pmid = {37806951},
issn = {1945-0524},
support = {FGFF-2022-0007//State assignment of the Ministry of Science and Higher Education/ ; },
mesh = {Pregnancy ; Female ; Humans ; *DNA Copy Number Variations/genetics ; Pilot Projects ; *Fertilization in Vitro ; DNA, Mitochondrial/genetics ; DNA, Ribosomal ; Telomere ; Ovulation Induction/methods ; },
abstract = {INTRODUCTION: Individual risk assessment of assisted reproductive technologies is essential for personalized treatment strategies. Genetic and genomic indicators of the response to stress by cells could provide individual prognostic indicators for in vitro fertilization (IVF) success. Such indicators include the copy number of ribosomal genes (rDNA), which modulates the level of protein synthesis, and the abundance of mitochondrial DNA (mtDNA), which provides the cell with energy, while the content of telomere repeats (TRs) indicate the biological age.<br><br>MATERIALS AND METHODS: The contents of the three repeats in DNA isolated from blood leukocytes of 40 women before and after ovarian stimulation were assayed prior to IVF. Then, we divided the women into a successful IVF group, IVF+ (N = 17, 7 cases of twins), and a group of failed cases, IVF- (N = 23). The control group included 17 non-pregnant women with natural childbirth in the past. The nonradioactive quantitative hybridization (NQH) method was applied to assay the genome repeat contents.<br><br>RESULTS: The number of rDNA copies in the IVF+ group was significantly higher than in the IVF- group (p < 10-8). The number of mtDNA copies in the IVF+ group also exceeded those in the IVF- group (p < 0.001), whereas the TR content in the two groups differed, albeit, non-significantly (p < 0.03). Following the ovarian stimulation, the rDNA copy numbers did not change, while the contents of the mtDNA and TR varied significantly.<br><br>CONCLUSIONS: This pilot study has shown that rDNA abundance in blood leukocytes can be considered a stable and effective predictor. Very low numbers of ribosomal repeat copies (<330) entail a high risk of IVF failure. However, a combination of numerous mtDNA and TRs, provided that rDNA content is not very low, increases the probability of multiple pregnancies.},
}
@article {pmid37803147,
year = {2023},
author = {Hu, J and Lu, J and Lu, Q and Weng, W and Guan, Z and Wang, Z},
title = {Mendelian randomization and colocalization analyses reveal an association between short sleep duration or morning chronotype and altered leukocyte telomere length.},
journal = {Communications biology},
volume = {6},
number = {1},
pages = {1014},
pmid = {37803147},
issn = {2399-3642},
mesh = {*Sleep Duration ; *Chronotype ; Genome-Wide Association Study/methods ; Mendelian Randomization Analysis/methods ; Sleep/genetics ; Leukocytes ; Telomere/genetics ; },
abstract = {Observational studies suggest certain sleep traits are associated with telomere length, but the causal nature of these associations is unclear. The study aimed to determine the causal associations between 11 sleep-related traits and leukocyte telomere length (LTL) through two-sample Mendelian randomization and colocalization analyses using the summary statistics from large-scale genome-wide association studies. Univariable Mendelian randomization indicates that genetically determined short sleep is associated with decreased LTL, while morning chronotype is associated with increased LTL. Multivariable Mendelian randomization further supports the findings and colocalization analysis identifies shared common genetic variants for these two associations. No genetic evidence is observed for associations between other sleep-related traits and LTL. Sensitivity MR methods, reverse MR and re-running MR after removing potential pleiotropic genetic variants enhance the robustness of the results. These findings indicate that prioritizing morning chronotype and avoiding short sleep is beneficial for attenuating telomere attrition. Consequently, addressing sleep duration and chronotype could serve as practical intervention strategies.},
}
@article {pmid37802318,
year = {2023},
author = {Sienkiewicz, M and Sroka, K and Binienda, A and Jurk, D and Fichna, J},
title = {A new face of old cells: An overview about the role of senescence and telomeres in inflammatory bowel diseases.},
journal = {Ageing research reviews},
volume = {91},
number = {},
pages = {102083},
doi = {10.1016/j.arr.2023.102083},
pmid = {37802318},
issn = {1872-9649},
mesh = {Humans ; *Inflammatory Bowel Diseases/genetics/drug therapy ; Inflammation/pathology ; Cellular Senescence/genetics ; Aging/genetics/pathology ; Telomere/pathology ; },
abstract = {Cellular senescence is a pivotal factor contributing to aging and the pathophysiology of age-related diseases. Despite the presence of inflammation and abnormal immune system function in both inflammatory bowel diseases (IBD) and senescence, the relationship between the two remains largely unexplored. Therefore, our study aimed to investigate the intricate connection between cellular senescence, telomeres, and IBD. The review highlights the presence of senescence markers, particularly p16 and p21, in IBD patients, suggesting their potential association with disease progression and mucosal inflammation. We emphasize the critical role of macrophages in eliminating senescent cells and how disturbance in effective clearance may contribute to persistent senescence and inflammation in IBD. Additionally, we shed light on the involvement of telomeres in IBD, as their dysfunction impairs enterocyte function and disrupts colonic barrier integrity, potentially exacerbating the pathogenesis of the disease. Targeting senescence and telomere dysfunctions holds promise for the development of innovative therapeutic approaches to mitigate intestinal inflammation and alleviate symptoms in IBD patients. By unraveling the precise role of senescence in IBD, we can pave the way for the discovery of novel therapeutic interventions that effectively address the underlying mechanisms of intestinal inflammation, offering hope for improved management and treatment of IBD patients.},
}
@article {pmid37801568,
year = {2023},
author = {Butts, B and Hope, C and Herring, C and Mueller, K and Gary, RA},
title = {The Effects of Exercise on Telomere Length in Persons With Heart Failure.},
journal = {The Journal of cardiovascular nursing},
volume = {},
number = {},
pages = {},
pmid = {37801568},
issn = {1550-5049},
support = {T32 NR012715/NR/NINR NIH HHS/United States ; },
abstract = {BACKGROUND: Telomere length is reduced in persons with heart failure (HF). Inflammation is a putative mechanism contributing to telomere shortening. Although physical activity is known to increase telomere length, its effects in HF are unknown.<br><br>OBJECTIVE: The aim of this study was to examine the effects of exercise on telomere length and its relationship with interleukin (IL)-1&#x3b2; in persons with HF.<br><br>METHODS: This secondary analysis of a 3-month home-based aerobic exercise intervention measured total telomere length and IL-1&#x3b2; levels in persons with HF (69% with reduced ejection fraction).<br><br>RESULTS: Total telomere length increased and plasma IL-1&#x3b2; levels decreased in the exercise group from baseline to 3 months. Total telomere length was negatively associated with IL-1&#x3b2; at baseline (r = -0.441 P = .001).<br><br>CONCLUSIONS: The association between telomere length and IL-1&#x3b2; suggests a relationship between inflammation and cellular aging. Moderate-intensity exercise may help maintain cellular functions. Further research is needed to examine the effects on outcomes in persons with HF.},
}
@article {pmid37793222,
year = {2024},
author = {Yadav, PS and Kumar, D and Saini, M and Sharma, RK and Dua, S and Selokar, NL and Bansal, S and Punetha, M and Gupta, A and Kumar, R and Kumar, P},
title = {Evaluation of postnatal growth, hematology, telomere length and semen attributes of multiple clones and re-clone of superior buffalo breeding bulls.},
journal = {Theriogenology},
volume = {213},
number = {},
pages = {24-33},
doi = {10.1016/j.theriogenology.2023.09.024},
pmid = {37793222},
issn = {1879-3231},
mesh = {Male ; Female ; Animals ; Cattle/genetics ; *Semen ; Buffaloes/genetics ; Sperm Motility ; Spermatozoa ; *Hematology ; Telomere ; Semen Analysis/veterinary ; },
abstract = {The present study comprehensively evaluates the postnatal growth, hematology, telomere length, and semen attributes of multiple clones and re-clone derived from superior buffalo breeding bulls. To the best of our knowledge, we successfully produced multiple clones and a re-clone of an earlier cloned buffalo bull from an embryo developed from an adult bull's skin-derived cell for the first time. The cloned bulls' growth, blood hematology, plasma biochemistry, and telomere length were all shown to be normal at various stages of development. The bulls were used for semen production after being screened for testicular growth and training. Semen characteristics such as volume, concentration, and initial motility of fresh sperm as well as motility and kinetics characteristics such as straightness (STR), average lateral head displacement (ALH), and beat cross frequency (BCF) of frozen-thawed sperms of the cloned bulls were found to be similar to those of non-cloned bulls, including the donor bulls. Additionally, it was found that cloned bulls' functional sperm attributes, including acrosome intactness, mitochondrial membrane potential, and superoxide anion status, were comparable to those of non-cloned bulls. These characteristics are necessary for sperm to pass through the female reproductive system, penetrate the oocyte, and efficiently fertilize. Finally, this study adds to our understanding of the postnatal development, hematology, telomere length, and sperm characteristics of superior buffalo breeding bulls that have been cloned and re-cloned. The findings provide the groundwork for improving cloning practices, refining reproductive procedures, and optimizing the use of cloned genetic material in animal breeding and conservation.},
}
@article {pmid37792396,
year = {2023},
author = {Morbiato, E and Cattelan, S and Pilastro, A and Grapputo, A},
title = {Sperm production is negatively associated with muscle and sperm telomere length in a species subjected to strong sperm competition.},
journal = {Molecular ecology},
volume = {32},
number = {21},
pages = {5812-5822},
doi = {10.1111/mec.17158},
pmid = {37792396},
issn = {1365-294X},
support = {20178T2PSW//Ministry of University and Research/ ; C93C22002810006//NBFC-PNRR/ ; //PRID 2020/ ; },
mesh = {Animals ; Male ; *Semen ; Spermatozoa/physiology ; Sexual Behavior, Animal ; Reproduction/genetics ; Muscles ; *Poecilia/genetics ; },
abstract = {Life-history theory suggests that ageing is one of the costs of reproduction. Accordingly, a higher reproductive allocation is expected to increase the deterioration of both the somatic and the germinal lines through enhanced telomere attrition. In most species, males' reproductive allocation mainly regards traits that increase mating and fertilization success, that is sexually selected traits. In this study, we tested the hypothesis that a higher investment in sexually selected traits is associated with a reduced relative telomere length (RTL) in the guppy (Poecilia reticulata), an ectotherm species characterized by strong pre- and postcopulatory sexual selection. We first measured telomere length in both the soma and the sperm over guppies' lifespan to see whether there was any variation in telomere length associated with age. Second, we investigated whether a greater investment in pre- and postcopulatory sexually selected traits is linked to shorter telomere length in both the somatic and the sperm germinal lines, and in young and old males. We found that telomeres lengthened with age in the somatic tissue, but there was no age-dependent variation in telomere length in the sperm cells. Telomere length in guppies was significantly and negatively correlated with sperm production in both tissues and life stages considered in this study. Our findings indicate that telomere length in male guppies is strongly associated with their reproductive investment (sperm production), suggesting that a trade-off between reproduction and maintenance is occurring at each stage of males' life in this species.},
}
@article {pmid37790308,
year = {2024},
author = {Ahlers, NE and Lin, J and Weiss, SJ},
title = {WITHDRAWN: Exposure to Ambient Particulate Matter during Pregnancy: Implications for Infant Telomere Length.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.09.17.23295692},
pmid = {37790308},
abstract = {This manuscript has been withdrawn by the authors as it was submitted and made public without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The authors have an approved version for citation that is peer reviewed. Ahlers, N.E.; Lin, J.; Weiss, S.J. Exposure to Ambient Particulate Matter during Pregnancy: Implications for Infant Telomere Length. Air 2024, 2, 24-37. https://doi.org/10.3390/air2010002.},
}
@article {pmid37789444,
year = {2023},
author = {Wang, Y and Dong, M and Wu, Y and Zhang, F and Ren, W and Lin, Y and Chen, Q and Zhang, S and Yue, J and Liu, Y},
title = {Telomere-to-telomere and haplotype-resolved genome of the kiwifruit Actinidia eriantha.},
journal = {Molecular horticulture},
volume = {3},
number = {1},
pages = {4},
pmid = {37789444},
issn = {2730-9401},
support = {31972474//National Natural Science Foundation of China/ ; 31471157//National Natural Science Foundation of China/ ; },
abstract = {Actinidia eriantha is a characteristic fruit tree featuring with great potential for its abundant vitamin C and strong disease resistance. It has been used in a wide range of breeding programs and functional genomics studies. Previously published genome assemblies of A. eriantha are quite fragmented and not highly contiguous. Using multiple sequencing strategies, we get the haplotype-resolved and gap-free genomes of an elite breeding line "Midao 31" (MD), termed MDHAPA and MDHAPB. The new assemblies anchored to 29 pseudochromosome pairs with a length of 619.3 Mb and 611.7 Mb, as well as resolved 27 and 28 gap-close chromosomes in a telomere-to-telomere (T2T) manner. Based on the haplotype-resolved genome, we found that most alleles experienced purifying selection and coordinately expressed. Owing to the high continuity of assemblies, we defined the centromeric regions of A. eriantha, and identified the major repeating monomer, which is designated as Ae-CEN153. This resource lays a solid foundation for further functional genomics study and horticultural traits improvement in kiwifruit.},
}
@article {pmid37787873,
year = {2023},
author = {Ongie, L and Raj, HA and Stevens, KB},
title = {Genetic Counseling and Family Screening Recommendations in Patients with Telomere Biology Disorders.},
journal = {Current hematologic malignancy reports},
volume = {18},
number = {6},
pages = {273-283},
pmid = {37787873},
issn = {1558-822X},
mesh = {Humans ; *Genetic Counseling ; Telomere/genetics/metabolism ; *Telomerase/genetics/metabolism ; Genetic Testing ; Mutation ; },
abstract = {PURPOSE OF REVIEW: Telomere biology disorders (TBDs) encompass a spectrum of genetic diseases with a common pathogenesis of defects in telomerase function and telomere maintenance causing extremely short telomere lengths. Here, we review the current literature surrounding genetic testing strategies, cascade testing, reproductive implications, and the role of genetic counseling.<br><br>RECENT FINDINGS: The understanding of the genetic causes and clinical symptoms of TBDs continues to expand while genetic testing and telomere length testing are nuanced tools utilized in the diagnosis of this condition. Access to genetic counseling is becoming more abundant and is valuable in supporting patients and their families in making informed decisions. Patient resources and support groups are valuable to this community. Defining which populations should be offered genetic counseling and testing is imperative to provide proper diagnoses and medical management for not only the primary patient, but also their biological relatives.},
}
@article {pmid37786729,
year = {2023},
author = {Wang, YH and Liu, PZ and Liu, H and Zhang, RR and Liang, Y and Xu, ZS and Li, XJ and Luo, Q and Tan, GF and Wang, GL and Xiong, AS},
title = {Telomere-to-telomere carrot (Daucus carota) genome assembly reveals carotenoid characteristics.},
journal = {Horticulture research},
volume = {10},
number = {7},
pages = {uhad103},
pmid = {37786729},
issn = {2662-6810},
abstract = {Carrot (Daucus carota) is an Apiaceae plant with multi-colored fleshy roots that provides a model system for carotenoid research. In this study, we assembled a 430.40 Mb high-quality gapless genome to the telomere-to-telomere (T2T) level of "Kurodagosun" carrot. In total, 36 268 genes were identified and 34 961 of them were functionally annotated. The proportion of repeat sequences in the genome was 55.3%, mainly long terminal repeats. Depending on the coverage of the repeats, 14 telomeres and 9 centromeric regions on the chromosomes were predicted. A phylogenetic analysis showed that carrots evolved early in the family Apiaceae. Based on the T2T genome, we reconstructed the carotenoid metabolic pathway and identified the structural genes that regulate carotenoid biosynthesis. Among the 65 genes that were screened, 9 were newly identified. Additionally, some gene sequences overlapped with transposons, suggesting replication and functional differentiation of carotenoid-related genes during carrot evolution. Given that some gene copies were barely expressed during development, they might be functionally redundant. Comparison of 24 cytochrome P450 genes associated with carotenoid biosynthesis revealed the tandem or proximal duplication resulting in expansion of CYP gene family. These results provided molecular information for carrot carotenoid accumulation and contributed to a new genetic resource.},
}
@article {pmid37782440,
year = {2024},
author = {Liu, D and Aziz, NA and Imtiaz, MA and Pehlivan, G and Breteler, MMB},
title = {Associations of measured and genetically predicted leukocyte telomere length with vascular phenotypes: a population-based study.},
journal = {GeroScience},
volume = {46},
number = {2},
pages = {1947-1970},
pmid = {37782440},
issn = {2509-2723},
support = {432325352//Deutsche Forschungsgemeinschaft/ ; EXC 2151 - 390873048//Deutsche Forschungsgemeinschaft/ ; 2017006100345//China Scholarship Council/ ; },
mesh = {Humans ; Female ; Aged ; Aged, 80 and over ; Male ; Cohort Studies ; Longitudinal Studies ; Phenotype ; *Leukocytes/metabolism ; *Telomere/genetics ; },
abstract = {Shorter leukocyte telomere length (LTL) is associated with cardiovascular dysfunction. Whether this association differs between measured and genetically predicted LTL is still unclear. Moreover, the molecular processes underlying the association remain largely unknown. We used baseline data of the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany [56.2% women, age: 55.5 ± 14.0 years (range 30 - 95 years)]. We calculated genetically predicted LTL in 4180 participants and measured LTL in a subset of 1828 participants with qPCR. Using multivariable regression, we examined the association of measured and genetically predicted LTL, and the difference between measured and genetically predicted LTL (ΔLTL), with four vascular functional domains and the overall vascular health. Moreover, we performed epigenome-wide association studies of three LTL measures. Longer measured LTL was associated with better microvascular and cardiac function. Longer predicted LTL was associated with better cardiac function. Larger ΔLTL was associated with better microvascular and cardiac function and overall vascular health, independent of genetically predicted LTL. Several CpGs were associated (p < 1e-05) with measured LTL (n = 5), genetically predicted LTL (n = 8), and ΔLTL (n = 27). Genes whose methylation status was associated with ΔLTL were enriched in vascular endothelial signaling pathways and have been linked to environmental exposures, cardiovascular diseases, and mortality. Our findings suggest that non-genetic causes of LTL contribute to microvascular and cardiac function and overall vascular health, through an effect on the vascular endothelial signaling pathway. Interventions that counteract LTL may thus improve vascular function.},
}
@article {pmid37781376,
year = {2023},
author = {Roger, L and Miners, KL and Leonard, L and Grimstead, JW and Price, DA and Baird, DM and Ladell, K},
title = {T cell memory revisited using single telomere length analysis.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1100535},
pmid = {37781376},
issn = {1664-3224},
support = {/WT_/Wellcome Trust/United Kingdom ; C17199/A18246/CRUK_/Cancer Research UK/United Kingdom ; 093053/Z/10/Z/WT_/Wellcome Trust/United Kingdom ; 100326/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {*Memory T Cells ; Cell Differentiation ; Leukocyte Common Antigens/metabolism ; *Lymphocyte Activation ; Telomere/genetics ; },
abstract = {The fundamental basis of T cell memory remains elusive. It is established that antigen stimulation drives clonal proliferation and differentiation, but the relationship between cellular phenotype, replicative history, and longevity, which is likely essential for durable memory, has proven difficult to elucidate. To address these issues, we used conventional markers of differentiation to identify and isolate various subsets of CD8[+] memory T cells and measured telomere lengths in these phenotypically defined populations using the most sensitive technique developed to date, namely single telomere length analysis (STELA). Naive cells were excluded on the basis of dual expression of CCR7 and CD45RA. Memory subsets were sorted as CD27[+]CD45RA[+], CD27[int]CD45RA[+], CD27[-]CD45RA[+], CD27[+]CD45RA[int], CD27[-]CD45RA[int], CD27[+]CD45RA[-], and CD27[-]CD45RA[-] at >98% purity. The shortest median telomere lengths were detected among subsets that lacked expression of CD45RA, and the longest median telomere lengths were detected among subsets that expressed CD45RA. Longer median telomere lengths were also a feature of subsets that expressed CD27 in compartments defined by the absence or presence of CD45RA. Collectively, these data suggested a disconnect between replicative history and CD8[+] memory T cell differentiation, which is classically thought to be a linear process that culminates with revertant expression of CD45RA.},
}
@article {pmid37780571,
year = {2023},
author = {Chi, Z and Bai, X and Zhang, Z},
title = {Risk relationship between leukocyte telomere length and constipation: a Mendelian randomization study.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1177785},
pmid = {37780571},
issn = {2296-858X},
abstract = {OBJECTIVE: Some epidemiological studies have investigated the associations between aging and constipation, yet their outcomes are inconclusive, so we strive to ascertain whether aging is the cause of constipation.<br><br>METHODS: We conducted a two-sample Mendelian randomization (MR) analysis using publicly accessible genome-wide association study (GWAS) summary statistics. As a marker of cellular and biological aging, we employed 15 single-nucleotide polymorphisms as instrumental variables for leukocyte telomere length (LTL) as exposure and a GWAS for constipation in the Finnish database as an outcome. To select the instrumental variables strongly associated with the phenotype, we eliminated confounding factors and direct effects outcomes to determine the causal relationship of exposure factors on the outcome; the analysis was mainly performed using the random-effect inverse variance weighting method, MR-Egger, weighted median, and sensitivity analysis of the results.<br><br>RESULTS: Random effect inverse variance weighted odds ratio = 1.035 (95% CI 0.907-1.180), but p = 0.612, which was not statistically significant. Other statistical methods, such as MR-Egger and weighted median, also yielded non-significant results.<br><br>CONCLUSION: LTL as a proxy for aging does not necessarily indicate an increased likelihood of constipation. Further research is needed to explore the specific mechanisms of constipation.},
}
@article {pmid37777139,
year = {2023},
author = {Ogletree, SS and Huang, JH and Reif, D and Yang, L and Dunstan, C and Osakwe, N and Oh, JI and Hipp, JA},
title = {The relationship between greenspace exposure and telomere length in the National Health and Nutrition Examination Survey.},
journal = {The Science of the total environment},
volume = {905},
number = {},
pages = {167452},
doi = {10.1016/j.scitotenv.2023.167452},
pmid = {37777139},
issn = {1879-1026},
mesh = {Humans ; Nutrition Surveys ; *Parks, Recreational ; *Environmental Exposure ; Risk Factors ; Telomere ; },
abstract = {The exposome, reflecting the range of environmental exposures individuals encounter throughout their life, can influence a variety of health outcomes and can play a role in how the environment impacts our genes. Telomeres, genetic structures regulating cell growth and senescence, are one pathway through which the exposome may impact health. Greenspace exposure, representing the amount of green areas in one's neighborhood, is one component of the exposome and has been associated with multiple health benefits. To investigate the potential link between greenspace exposure and telomere length, we analyzed data from the 1999-2001 National Health and Nutrition Examination Survey (NHANES) sample. Our study examined individual, risk, and contextual factors. We found that greater greenspace exposure in one's neighborhood was associated with longer telomere lengths when considering individual and risk factors, suggesting a positive effect of living in greener neighborhoods. However, this relationship became non-significant when contextual factors, such as air pollution and deprivation, were included in the analysis. These findings highlight a complex relationship between greenspace and telomere length, warranting further research to explore contextual factors in detail.},
}
@article {pmid37773482,
year = {2023},
author = {Hou, X and Li, R and Wang, J and Wei, D and Yang, X and Liao, W and Yuchi, Y and Liu, X and Huo, W and Mao, Z and Liu, J and Wang, C and Hou, J},
title = {Gender-specific associations between mixture of polycyclic aromatic hydrocarbons and telomere length.},
journal = {Environmental geochemistry and health},
volume = {45},
number = {12},
pages = {9583-9598},
pmid = {37773482},
issn = {1573-2983},
support = {21IRTSTHN029//Science and Technology Innovation Team Support Plan of Colleges and Universities in Henan Province/ ; 222102320029//the Science and Technique Foundation of Henan Province/ ; 2016YFC0900803//the Foundation of National Key Program of Research and Development of China/ ; 2019M662548, 2021M702934//China Postdoctoral Science Foundation/ ; 2020GWFJJ01//the open project of Key Laboratory of Environment and health, ministry of Education/ ; },
mesh = {Male ; Humans ; Female ; *Polycyclic Aromatic Hydrocarbons/analysis ; Cohort Studies ; Gas Chromatography-Mass Spectrometry ; *Environmental Pollutants/toxicity/analysis ; Telomere/chemistry ; },
abstract = {Evidence shows the relationships of individual environmental PAHs by their urinary metabolites with relative telomere length (RTL), which may be affected by biological gender differences. Since plasma parent PAHs are not metabolized, it may reflect human exposure to PAHs more realistically in daily life. Thus, exploring joint associations between plasma parent PAHs and RTL is urgent, which may identify the major contributor to its adverse effect. In this study, 2577 participants were obtained from the Henan Rural Cohort. The level of PAHs in blood samples was detected by gas chromatography coupled with tandem mass spectrometry. RTL in blood samples was detected by quantitative polymerase chain reaction. Generalized linear models or quantile g-computation were performed to evaluate the associations between the individual or a mixture of PAHs and RTL. Results from generalized linear models showed that each unit increment in BghiP value corresponded to a 0.098 (95%CI: 0.067, 0.129) increment in RTL for men; each unit increment in BaP, BghiP and Flu value corresponded to a 0.041 (95%CI: 0.014, 0.068), 0.081 (95%CI: 0.055, 0.107) and 0.016 (95%CI: 0.005, 0.027) increment in RTL for women. Results from quantile-g computation revealed that each one-quantile increment in the mixture of 10 PAHs corresponded to a 0.057 (95%CI: 0.021, 0.094) and 0.047 (95%CI: 0.003, 0.091) increment in RTL values of women and men, but these associations were mainly ascribed to three PAHs for women (BaP, Flu and BghiP) and men (BaP, BghiP and Pyr), respectively. Similar results were found in smoking men and cooking women without smoking. Our study found that exposure to 10 PAHs mixture was positively associated with RTL across gender, mainly attributed to Flu, BaP and BghiP, implicating that gender-specific associations may be ascribed to tobacco and cooking smoke pollution. The findings provided clues for effective measures to control PAHs pollutants-related aging disease.Clinical trial registration The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375 .},
}
@article {pmid37773274,
year = {2023},
author = {Dutta, S},
title = {Unveiling the telomere-p53-PGC ageing axis.},
journal = {Nature reviews. Endocrinology},
volume = {19},
number = {12},
pages = {686},
pmid = {37773274},
issn = {1759-5037},
}
@article {pmid37771090,
year = {2023},
author = {Estep, KN and Tobias, JW and Fernandez, RJ and Beveridge, BM and Johnson, FB},
title = {Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair.},
journal = {Journal of molecular cell biology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jmcb/mjad058},
pmid = {37771090},
issn = {1759-4685},
abstract = {Although mechanisms of telomere protection are well-defined in differentiated cells, it is poorly understood how stem cells sense and respond to telomere dysfunction. In particular, the broader impact of telomeric double-strand breaks (DSBs) in these cells is poorly characterized. Here, we report on DNA damage signaling, cell cycle, and transcriptome-level changes in human induced pluripotent stem cells (iPSCs) in response to telomere-internal DSBs. We engineered human iPSCs with an inducible TRF1-FokI fusion protein to acutely induce DSBs at telomeres. Using this model, we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DDR, which leads to p53-independent cell cycle arrest in G2. Using CRISPR-Cas9 to cripple the catalytic domain of telomerase, we show that telomerase is largely dispensable for survival and lengthening of TRF1-FokI-cleaved telomeres, which instead are effectively repaired by robust homologous recombination (HR). In contrast to HR-based telomere maintenance in mouse embryonic stem cells, we find neither evidence that HR causes extension of telomeres beyond their initial lengths, nor an apparent role for ZSCAN4 in this process. Rather, HR-based repair of telomeric breaks is sufficient to maintain iPSC telomeres at a normal length which is compatible with sustained survival of the cells over several days of TRF1-FokI induction. Our findings suggest a previously unappreciated role for HR in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric damage.},
}
@article {pmid37770147,
year = {2023},
author = {Sutterlüty, H and Bargl, M and Holzmann, K},
title = {Quantifying telomere transcripts as tool to improve risk assessment for genetic instability and genotoxicity.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {891},
number = {},
pages = {503690},
doi = {10.1016/j.mrgentox.2023.503690},
pmid = {37770147},
issn = {1879-3592},
mesh = {Reactive Oxygen Species ; *Telomere/genetics ; *RNA, Long Noncoding/genetics ; DNA ; DNA Damage ; Risk Assessment ; },
abstract = {Telomere repeat-containing RNAs (TERRA) are transcribed from telomeres as long non-coding RNAs and are part of the telomere structure with protective function. The genetic stability of cells requires telomeric repeats at the ends of chromosomes. Maintenance of telomere length (TL) is essential for proliferative capacity and chromosomal integrity. In contrast, telomere shortening is a recognized risk factor for carcinogenesis and a biomarker of aging due to the cumulative effects of environmental exposures and life experiences such as trauma or stress. In this context, telomere repeats are lost due to cell proliferation, but are also susceptible to stress factors including reactive oxygen species (ROS) inducing oxidative base damage. Quantitative PCR (qPCR) of genomic DNA is an established method to analyze TL as a tool to detect genotoxic events. That same qPCR method can be applied to RNA converted into cDNA to quantify TERRA as a useful tool to perform high-throughput screenings. This short review summarizes relevant qPCR studies using both TL and TERRA quantification, provides an overall view of the molecular mechanisms of telomere protection against ROS by TERRA, and summarizes the presented studies comparing the results at DNA and RNA levels, which indicate that fluctuations at transcript level might reflect a short-term response. Therefore, we conclude that performing both of these measurements together will improve genotoxicity studies.},
}
@article {pmid37768599,
year = {2023},
author = {Bosquet Enlow, M and De Vivo, I and Petty, CR and Cayon, N and Nelson, CA},
title = {Associations among temperament characteristics and telomere length and attrition rate in early childhood.},
journal = {Developmental psychology},
volume = {},
number = {},
pages = {},
doi = {10.1037/dev0001635},
pmid = {37768599},
issn = {1939-0599},
support = {/NH/NIH HHS/United States ; },
abstract = {There is growing interest in telomere length as an indicator of current and future health. Although early childhood is a period of rapid telomere attrition, little is known about the factors that influence telomere biology during this time. Adult research suggests that telomere length is influenced by psychological characteristics. This study's goal was to test associations among repeated measures of temperament and telomere length in a community sample of children (N = 602; 52% male, 73% non-Hispanic White, middle-to-high socioeconomic status) from infancy to age 3 years. Relative telomere length was assessed from DNA in saliva samples collected at infancy (M = 8.4 months), 2 years (M = 24.9 months), and 3 years (M = 37.8 months). Temperament was assessed via maternal report questionnaires administered at infancy (Infant Behavior Report Questionnaire-Revised) and ages 2 and 3 years (Early Childhood Behavior Questionnaire). Temperament was operationalized in two ways: using the established domains of negative affectivity, surgency/extraversion, and regulation/effortful control and using person-centered scores that identified three groups of children with similar profiles across domains (emotionally and behaviorally regulated; emotionally and behaviorally dysregulated; introverted and overcontrolled). Analyses revealed that greater regulation/effortful control was associated with longer telomere length across time points. Additionally, higher surgency/extraversion, beginning in infancy, was associated with decreased rate of telomere attrition. There were no sex differences in the relations between temperament and telomere measures. These findings suggest that, as early as infancy, temperament may influence telomere biology, with a potential protective effect of positive temperament characteristics on telomere erosion. (PsycInfo Database Record (c) 2023 APA, all rights reserved).},
}
@article {pmid37767563,
year = {2023},
author = {Loe, TK and Lazzerini Denchi, E and Tricola, GM and Azeroglu, B},
title = {ALTercations at telomeres: stress, recombination and extrachromosomal affairs.},
journal = {Biochemical Society transactions},
volume = {51},
number = {5},
pages = {1935-1946},
doi = {10.1042/BST20230265},
pmid = {37767563},
issn = {1470-8752},
support = {ZIA BC011815/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; *Telomere Homeostasis ; *Telomere ; Recombination, Genetic ; },
abstract = {Approximately 15% of human cancers depend on the alternative lengthening of telomeres (ALT) pathway to maintain telomeres and proliferate. Telomeres that are elongated using ALT display unique features raising the exciting prospect of tailored cancer therapies. ALT-mediated telomere elongation shares several features with recombination-based DNA repair. Strikingly, cells that use the ALT pathway display abnormal levels of replication stress at telomeres and accumulate abundant extrachromosomal telomeric DNA. In this review, we examine recent findings that shed light on the ALT mechanisms and the strategies currently available to suppress this telomere elongation mechanism.},
}
@article {pmid37767490,
year = {2023},
author = {Sivasangari, K and Sivamaruthi, BS and Chaiyasut, C and Rajan, KE},
title = {Maternal stress-induced changes in adolescent and adult offspring: Neurobehavioural improvement and telomere maintenance.},
journal = {Heliyon},
volume = {9},
number = {10},
pages = {e20385},
pmid = {37767490},
issn = {2405-8440},
abstract = {Maternal stress (MS) during gestation is known to increase the risk for the development of behavioural and physiological disorders and advances cellular aging. In this study, we investigated whether the supplementation of standardized Bacopa monnieri extract (CDRI-08/BME) or l-Carnosine (L-C) to the mother exposed to social stress during gestation modify the effect on their offspring's neurobehaviour, antioxidant defence gene expression, telomere length, and telomere biology. To test this, timed pregnant rats were subjected to social stress during the gestational day (GD) 16-18. A subset of stressed pregnant rats received either BME [80 mg/kg in 0.5% gum acacia (per-orally; p.o)] or L-C [1 mg/kg (p.o)] every day from GD-10 to until their pup's attained postnatal day (PND)-23. We observed that MS induced anxiety-like behaviour, altered inter-limb coordination, antioxidant defence genes [Superoxide dismutase (SOD1,2), Catalase (CAT), Glutathione peroxidase-3 (GPX3)], telomerase reverse transcriptase (TERT), shelterin complex subunits (TRF1, RAP1B, POT1) protein level and shorten telomere length. Notably, supplementation of BME/L-C dampens the MS, thus the effect on neurobehaviour, antioxidant defence gene expression, and telomere biology is minimized in their offspring. Together, our results suggest that supplementation of BME/L-C during gestation dampens the MS and reduced oxidative stress-mediated changes in telomere shortening/biology and associated neurobehaviour in offspring born following MS.},
}
@article {pmid37762611,
year = {2023},
author = {Vukašinović, A and Klisic, A and Ostanek, B and Kafedžić, S and Zdravković, M and Ilić, I and Sopić, M and Hinić, S and Stefanović, M and Bogavac-Stanojević, N and Marc, J and Nešković, AN and Kotur-Stevuljević, J},
title = {Redox Status and Telomere-Telomerase System Biomarkers in Patients with Acute Myocardial Infarction Using a Principal Component Analysis: Is There a Link?.},
journal = {International journal of molecular sciences},
volume = {24},
number = {18},
pages = {},
pmid = {37762611},
issn = {1422-0067},
mesh = {Humans ; Antioxidants ; *Telomerase ; Biomarkers ; Serum Albumin ; Oxidation-Reduction ; *Myocardial Infarction ; },
abstract = {In the present study, we examined redox status parameters in arterial and venous blood samples, its potential to predict the prognosis of acute myocardial infarction (AMI) patients assessed through its impact on the comprehensive grading SYNTAX score, and its clinical accuracy. Potential connections between common blood biomarkers, biomarkers of redox status, leukocyte telomere length, and telomerase enzyme activity in the acute myocardial infarction burden were assessed using principal component analysis (PCA). This study included 92 patients with acute myocardial infarction. Significantly higher levels of advanced oxidation protein products (AOPP), superoxide anion (O2[•-]), ischemia-modified albumin (IMA), and significantly lower levels of total oxidant status (TOS) and total protein sulfhydryl (SH-) groups were found in arterial blood than in the peripheral venous blood samples, while biomarkers of the telomere-telomerase system did not show statistical significance in the two compared sample types (p = 0.834 and p = 0.419). To better understand the effect of the examined biomarkers in the AMI patients on SYNTAX score, those biomarkers were grouped using PCA, which merged them into the four the most contributing factors. The "cholesterol-protein factor" and "oxidative-telomere factor" were independent predictors of higher SYNTAX score (OR = 0.338, p = 0.008 and OR = 0.427, p = 0.035, respectively), while the ability to discriminate STEMI from non-STEMI patients had only the "oxidative-telomere factor" (AUC = 0.860, p = 0.008). The results show that traditional cardiovascular risk factors, i.e., high total cholesterol together with high total serum proteins and haemoglobin, are associated with severe disease progression in much the same way as a combination of redox biomarkers (pro-oxidant-antioxidant balance, total antioxidant status, IMA) and telomere length.},
}
@article {pmid37762576,
year = {2023},
author = {Han, X and Hirschel, A and Tsapekos, M and Perez, D and Vollmer, D},
title = {In Vitro Assessment of Gold Nanoparticles on Telomerase Activity and Telomere Length in Human Fibroblasts.},
journal = {International journal of molecular sciences},
volume = {24},
number = {18},
pages = {},
pmid = {37762576},
issn = {1422-0067},
support = {GF-AntiAging001//4Life Research/ ; },
mesh = {Infant, Newborn ; Humans ; Gold/pharmacology ; *Metal Nanoparticles ; *Telomerase/genetics ; Fibroblasts ; Telomere/genetics ; },
abstract = {Telomerase activity coincides with lengthening of the ends of chromosomes known as telomeres. Telomere length is used as a marker for cellular aging. Telomeres shorten over time as cells divide, and certain bioactive compounds such as gold nanoparticles (AuNPs) may slow the shortening of telomeres by increasing telomerase activity. The objective of the present study is to assess the effect of AuNPs on telomerase activity and telomere length in human fibroblasts. Telomerase activity was measured using enzyme-linked immunosorbent assay (ELISA) in primary human lung fibroblasts (IMR90) and using quantitative PCR-based telomeric repeat amplification protocol (Q-TRAP) in primary human dermal fibroblasts, neonatal (HDFn). Telomere length was determined by Telomere Analysis Technology (TAT[®])assay in HDFn. In IMR90, all AuNP treatments showed significant increases in telomerase activity when compared to earlier passages. HDFn treated with AuNPs at 0 ppm, 0.05 ppm, 0.5 ppm, or 5 ppm did not show significant differences in telomerase activity compared to the control group. Significant differences in telomere length in HDFn were observed at 2 weeks of 0.05 and 0.5 ppm AuNPs under oxidative culture conditions as compared to the control group. The study showed preliminary evidence that AuNPs may increase telomerase activity and decelerate the shortening of telomeres in human fibroblasts, suggesting its potential anti-aging effects, which warrants further investigation.},
}
@article {pmid37762556,
year = {2023},
author = {Hou, J and Yun, Y and Jeon, B and Baek, J and Kim, S},
title = {Ginsenoside F1-Mediated Telomere Preservation Delays Cellular Senescence.},
journal = {International journal of molecular sciences},
volume = {24},
number = {18},
pages = {},
pmid = {37762556},
issn = {1422-0067},
support = {2011-0031955//Intelligent Synthetic Biology Center of the Global Frontier Project, funded by the Ministry of Education, Science and Technology/ ; NRF-2021M3A9C4001028//Bio-Synergy Research Project of the Ministry of Sci-ence, ICT and Future Planning through the National Research Foundation/ ; P0014633//Advancement of Active Biomedical material Project, funded by the Ministry of Trade/ ; 321109041SB010//development of industrialization technology for crop virus and pest Project, funded by the Min-istry of Agriculture, Food and Rural Affairs/ ; 2021-153-0028-0019-002B//Multi-Department Research and Business Development Program, funded by Sejong city/ ; none//the KAIST Cross-Generation Collaborative Lab project/ ; P0021532//Center for mRNA/DNA Therapeutics Development and Production Project/ ; },
mesh = {Humans ; *Ginsenosides/pharmacology ; Cellular Senescence ; Preservation, Biological ; Syndrome ; },
abstract = {Telomeres play pivotal roles in processes closely related to somatic senescence and aging, making them a compelling target for interventions aimed at combating aging and age-related pathologies. Ginsenoside, a natural compound, has emerged as a potential remedy for promoting healthy aging, yet how it protects telomeres remains incompletely understood. Here, we show that treatment of F1 can effectively restore the level of TRF2, thereby preserving telomere integrity. This restoration leads to inhibition of the DNA damage response and improvements in mitochondrial function and, ultimately, delays in cellular senescence. Conversely, depletion of TRF2 causes mitochondrial dysfunction, accompanied by increased oxidative stress, autophagy inhibition, insufficient energy metabolism, and the onset of cellular senescence. These observations underscore the critical role of TRF2 in maintaining telomere integrity and direct association with the initiation of cellular senescence. We conduct a further analysis, suggesting F1 could bind in proximity to the TRF2 heterodimer interface, potentially enhancing dimerization stability. These findings suggest that F1 may be a promising natural remedy for anti-aging, and restoring TRF2 could potentially prevent telomere-dependent diseases commonly associated with the aging process.},
}
@article {pmid37759609,
year = {2023},
author = {Bukic, E and Milasin, J and Toljic, B and Jadzic, J and Jevtovic, D and Obradovic, B and Dragovic, G},
title = {Association between Combination Antiretroviral Therapy and Telomere Length in People Living with Human Immunodeficiency Virus.},
journal = {Biology},
volume = {12},
number = {9},
pages = {},
pmid = {37759609},
issn = {2079-7737},
abstract = {Long-term exposure to combination antiretroviral therapy (cART) may be associated with accelerated ageing. Telomere length is considered to be reliable aging biomarker. The aim of this study was to compare patients' relative telomere length (RTL) between and within different cART classes and to estimate the impact of certain HIV-related variables on RTL. The study was conducted in 176 HIV-infected male patients receiving cART, with ≤50 copies HIV RNA/mL plasma. RTL was determined from mononuclear cells by quantitative polymerase chain reaction. Standard statistical tests and unsupervised machine learning were performed. The mean RTL was 2.50 ± 1.87. There was no difference (p = 0.761) in RTL between therapeutic groups: two nucleoside reverse transcriptase inhibitors as the backbone treatment, combined with either integrase inhibitor, protease inhibitor, or non-nucleoside reverse transcriptase inhibitor (NNRTI). Machine learning results suggested duration of HIV infection, CD4+ T-cell count, and cART, including NNRTI, as potentially significant variables impacting RTL. Kendall's correlation test excluded duration of HIV infection (p = 0.220) and CD4+ T-cell count (p = 0.536) as significant. The Mann-Whitney test confirmed that cART containing NNRTI impacted RTL (p = 0.018). This was the first study to show that patients using efavirenz within cART had significantly shorter telomeres than patients using nevirapine.},
}
@article {pmid37757453,
year = {2023},
author = {},
title = {Correction to: Cancer-associated SMARCAL1 loss-of-function mutations promote alternative lengthening of telomeres and tumorigenesis in telomerase-negative glioblastoma cells.},
journal = {Neuro-oncology},
volume = {25},
number = {11},
pages = {2105},
doi = {10.1093/neuonc/noad180},
pmid = {37757453},
issn = {1523-5866},
support = {K22 CA258965/CA/NCI NIH HHS/United States ; 1K22CA258965-01A1/NH/NIH HHS/United States ; },
}
@article {pmid37756323,
year = {2023},
author = {Liu, J and Zheng, T and Chen, D and Huang, J and Zhao, Y and Ma, W and Liu, H},
title = {RBMX involves in telomere stability maintenance by regulating TERRA expression.},
journal = {PLoS genetics},
volume = {19},
number = {9},
pages = {e1010937},
pmid = {37756323},
issn = {1553-7404},
mesh = {*Exosomes/genetics ; Heterochromatin ; Nuclear Proteins ; *RNA, Long Noncoding/genetics ; Telomere/genetics ; Humans ; },
abstract = {Telomeric repeat-containing RNA (TERRA) is a class of long noncoding RNAs (lncRNAs) that are transcribed from subtelomeric to telomeric region of chromosome ends. TERRA is prone to form R-loop structures at telomeres by invading into telomeric DNA. Excessive telomere R-loops result in telomere instability, so the TERRA level needs to be delicately modulated. However, the molecular mechanisms and factors controlling TERRA level are still largely unknown. In this study, we report that the RNA binding protein RBMX is a novel regulator of TERRA level and telomere integrity. The expression level of TERRA is significantly elevated in RBMX depleted cells, leading to enhanced telomere R-loop formation, replication stress, and telomere instability. We also found that RBMX binds to TERRA and the nuclear exosome targeting protein ZCCHC8 simultaneously, and that TERRA degradation slows down upon RBMX depletion, implying that RBMX promotes TERRA degradation by regulating its transportation to the nuclear exosome, which decays nuclear RNAs. Altogether, these findings uncover a new role of RBMX in TERRA expression regulation and telomere integrity maintenance, and raising RBMX as a potential target of cancer therapy.},
}
@article {pmid37754816,
year = {2023},
author = {Borghini, A and Mercuri, A and Campolo, J and Parolini, M and Ndreu, R and Turchi, S and Andreassi, MG},
title = {Influence of Chromosome 9p21.3 rs1333049 Variant on Telomere Length and Their Interactive Impact on the Prognosis of Coronary Artery Disease.},
journal = {Journal of cardiovascular development and disease},
volume = {10},
number = {9},
pages = {},
pmid = {37754816},
issn = {2308-3425},
abstract = {BACKGROUND: Both telomere shortening and the chromosome 9p21.3 (Chr9p21) rs1333049 (G/C) variant are involved in coronary artery disease (CAD) risk, likely affecting mechanisms related to cell cycle arrest and vascular senescence. The aim of the study was to examine the link between Chr9p21 rs1333049 variant and leucocyte telomere length (LTL), as well as their interactive effect on the risk of major adverse cardiovascular events (MACEs).<br><br>METHODS: A cohort of 472 patients with angiographically proven and clinically stable CAD were included in the study. At baseline, the LTL, biochemical parameters, and genotype analysis of Chr9p21 rs1333049 variant were measured in all patients. The primary endpoint of this study was the occurrence of MACE defined as a composite of coronary-related death, nonfatal MI, and coronary revascularization.<br><br>RESULTS: On multivariable linear regression analysis, age (p = 0.02) and Chr9p21 rs1333049 variant (p = 0.002) were the only independent predictors of LTL levels. Carriers of the CC genotype of this SNP had shorter telomeres than GC carriers (p = 0.02) and GG carriers (p = 0.0005). After a follow-up with a mean period of 62 &#xb1; 19 months, 90 patients (19.1%) had MACE. Short LTL was an independent prognostic factor of MACE incidence (HR:2.2; 95% CI: 1.3-3.7; p = 0.005) after adjustment for potential confounders. There was a significant interaction (p = 0.01) between the LTL and rs1333049 variant, with patients with risk-allele C and short LTL having a higher risk (HR:5.8; 95% CI: 1.8-19.2; p = 0.004).<br><br>CONCLUSION: A strong relationship between LTL and Chr9p21 rs1333049 variant was identified, and they interactively affect the risk of poor prognosis in CAD patients.},
}
@article {pmid37754262,
year = {2023},
author = {Torres-Montaner, A},
title = {Interactions between the DNA Damage Response and the Telomere Complex in Carcinogenesis: A Hypothesis.},
journal = {Current issues in molecular biology},
volume = {45},
number = {9},
pages = {7582-7616},
pmid = {37754262},
issn = {1467-3045},
abstract = {Contrary to what was once thought, direct cancer originating from normal stem cells seems to be extremely rare. This is consistent with a preneoplastic period of telomere length reduction/damage in committed cells that becomes stabilized in transformation. Multiple observations suggest that telomere damage is an obligatory step preceding its stabilization. During tissue turnover, the telomeres of cells undergoing differentiation can be damaged as a consequence of defective DNA repair caused by endogenous or exogenous agents. This may result in the emergence of new mechanism of telomere maintenance which is the final outcome of DNA damage and the initial signal that triggers malignant transformation. Instead, transformation of stem cells is directly induced by primary derangement of telomere maintenance mechanisms. The newly modified telomere complex may promote survival of cancer stem cells, independently of telomere maintenance. An inherent resistance of stem cells to transformation may be linked to specific, robust mechanisms that help maintain telomere integrity.},
}
@article {pmid37753451,
year = {2023},
author = {Romero-Haro, AA and Figuerola, J and Alonso-Alvarez, C},
title = {Low Antioxidant Glutathione Levels Lead to Longer Telomeres: A Sex-Specific Link to Longevity?.},
journal = {Integrative organismal biology (Oxford, England)},
volume = {5},
number = {1},
pages = {obad034},
pmid = {37753451},
issn = {2517-4843},
abstract = {Telomeres are repetitive DNA sequences at the end of chromosomes that protect them from degradation. They have been the focus of intense research because short telomeres would predict accelerated ageing and reduced longevity in vertebrates. Oxidative stress is considered a physiological driver of the telomere shortening and, consequently, short lifespan. Among molecules fighting against oxidative stress, glutathione is involved in many antioxidant pathways. Literature supports that oxidative stress may trigger a compensatory "hormetic" response increasing glutathione levels and telomere length. Here, we tested the link between total glutathione concentration and telomere length in captive birds (zebra finches; Taeniopygia guttata). Total glutathione levels were experimentally decreased during birds' growth using a specific inhibitor of glutathione synthesis (buthionine sulfoximine; BSO). We monitored the birds' reproductive performance in an outdoor aviary during the first month of life, and their longevity for almost 9 years. Among control individuals, erythrocyte glutathione levels during development positively predicted erythrocyte telomere length in adulthood. However, BSO-treated females, but not males, showed longer telomeres than control females in adulthood. This counterintuitive finding suggests that females mounted a compensatory response. Such compensation agrees with precedent findings in the same population where the BSO treatment increased growth and adult body mass in females but not males. BSO did not influence longevity or reproductive output in any sex. However, early glutathione levels and adult telomere length interactively predicted longevity only among control females. Those females with "naturally" low (non-manipulated) glutathione levels at the nestling age but capable of producing longer telomeres in adulthood seem to live longer. The results suggest that the capability to mount a hormetic response triggered by low early glutathione levels can improve fitness via telomere length. Overall, the results may indicate a sex-specific link between glutathione and telomere values. Telomerase activity and sexual steroids (estrogens) are good candidates to explain the sex-biased mechanism underlying the early-life impact of oxidative stress on adult telomere length.},
}
@article {pmid37752708,
year = {2023},
author = {Shin, YA and Kim, JH},
title = {Effects of Cardiorespiratory Fitness on Cardiovascular Disease Risk Factors and Telomere Length by Age and Obesity.},
journal = {Journal of obesity &amp; metabolic syndrome},
volume = {32},
number = {3},
pages = {259-268},
pmid = {37752708},
issn = {2508-7576},
abstract = {BACKGROUND: This study investigates differences in telomere length according to obesity, cardiovascular disease (CVD) risk factors, and fitness level in South Korean males.<br><br>METHODS: The subjects of this study were males in their 10s to 50s (n=249). We measured obesity indices, CVD risk factors, leukocyte telomere length (LTL), and cardiorespiratory fitness (CRF). Correlation and regression analyses were performed to analyze the data.<br><br>RESULTS: Measurement of participants' obesity indices, CVD risk factors, and maximum oxygen intake and analyzing their correlations with LTL revealed that LTL and CRF decreased with age and the levels and numbers of obesity indices and CVD risk factors increased. The LTL showed differences according to whether subjects exhibited obesity or dyslipidemia and by CRF level. When all the variables that influence the LTL were adjusted, the LTL became shorter as the age and low-density lipoprotein cholesterol (LDL-C) level increased, and it became longer as the maximum rate of oxygen utilization (VO2max) increased. When the age and CVD risk factors that influence the LTL were adjusted according to obesity and CRF for the obese group, the LTL became shorter as the age and LDL-C level increased (P<0.01), and it became longer as VO2max increased (P<0.01).<br><br>CONCLUSION: We found that obesity influenced the LTL by increasing the levels of CVD risk factors and decreasing CRF, whereas maintaining high CRF could alleviate the effects of obesity and CVD risk factors according to age while maintaining and influencing the elongation of LTL.},
}
@article {pmid37752451,
year = {2023},
author = {Belyayev, A and Kalendar, R and Josefiová, J and Paštová, L and Habibi, F and Mahelka, V and Mandák, B and Krak, K},
title = {Telomere sequence variability in genotypes from natural plant populations: unusual block-organized double-monomer terminal telomeric arrays.},
journal = {BMC genomics},
volume = {24},
number = {1},
pages = {572},
pmid = {37752451},
issn = {1471-2164},
support = {20-20286S//Grantov&#xe1; Agentura &#x10c;esk&#xe9; Republiky/ ; },
mesh = {Humans ; *Arabidopsis/genetics ; In Situ Hybridization, Fluorescence ; Telomere/genetics ; Genotype ; Eukaryota ; },
abstract = {BACKGROUND: Telomeres are the nucleoprotein complexes that physically cap the ends of eukaryotic chromosomes. Most plants possess Arabidopsis-type telomere sequences (TSs). In addition to terminal TSs, more diverse interstitial TSs exists in plants. Although telomeres have been sufficiently studied, the actual diversity of TSs in land plants is underestimated.<br><br>RESULTS: We investigate genotypes from seven natural populations with contrasting environments of four Chenopodium species to reveal the variability in TSs by analyzing Oxford Nanopore reads. Fluorescent in situ hybridization was used to localize telomeric repeats on chromosomes. We identified a number of derivative monomers that arise in part of both terminal and interstitial telomeric arrays of a single genotype. The former presents a case of block-organized double-monomer telomers, where blocks of Arabidopsis-type TTTAGGG motifs were interspersed with blocks of derivative TTTAAAA motifs. The latter is an integral part of the satellitome with transformations specific to the inactive genome fraction.<br><br>CONCLUSIONS: We suggested two alternative models for the possible formation of derivative monomers from telomeric heptamer motifs of Arabidopsis-type. It was assumed that derivatization of TSs is a ubiquitous process in the plant genome but occurrence and frequencies of derivatives may be genotype-specific. We also propose that the formation of non-canonical arrays of TSs, especially at chromosomal termini, may be a source for genomic variability in nature.},
}
@article {pmid37751005,
year = {2023},
author = {Li, X and Duan, X and Wang, M and Wang, W},
title = {MEG3 polymorphisms associated with leukocyte telomere length in workers exposed to polycyclic aromatic hydrocarbons.},
journal = {Environmental science and pollution research international},
volume = {30},
number = {50},
pages = {108596-108605},
pmid = {37751005},
issn = {1614-7499},
mesh = {Humans ; *Polycyclic Aromatic Hydrocarbons/analysis ; *Occupational Exposure/analysis ; Telomere ; Leukocytes ; Polymorphism, Single Nucleotide ; *Coke/analysis ; },
abstract = {Long non-coding RNA maternally expressed gene 3 (MEG3) has been revealed to be involved in telomere length (TL) maintenance and homeostasis. However, it is unknown whether single-nucleotide polymorphisms (SNPs) in MEG3 could regulate TL in populations exposed to polycyclic aromatic hydrocarbons (PAHs). This study aimed to explore the effect of MEG3 genetic polymorphisms on TL in PAH-exposed populations. This study recruited 544 coke oven workers and 238 controls using random cluster sampling. The concentrations of four urinary OH-PAHs were measured by employing high-performance liquid chromatography. TL was measured by a quantitative polymerase chain reaction assay. The MEG3 genetic polymorphisms were detected using a Sequenom MassARRAY matrix-assisted laser desorption/ionization-time of flight mass spectrometry platform. The concentrations of four urinary OH-PAHs in the exposure group were significantly higher than those in the control group (P < 0.001). TL in the exposure group (4.57 ± 0.84) was significantly lower than in the control (5.00 ± 0.75), and TL had a negative correlation with OH-PAHs. The generalized linear model found that PAH exposure [β(95% CI) = -0.409(-0.537, -0.282), P < 0.001] and the CT+TT genotype in MEG3 rs10132552 [β(95% CI) = -0.299(-0.582, -0.017), P = 0.038] were associated with the decreased TL. In conclusion, PAH exposure and the CT+TT genotype in MEG3 rs10132552 may be the risk factors for TL reduction.},
}
@article {pmid37747680,
year = {2024},
author = {Kertes, DA and Clendinen, C and Duan, K and Rabinowitz, JA and Browning, C and Kvam, P},
title = {The Social Environment Matters for Telomere Length and Internalizing Problems During Adolescence.},
journal = {Journal of youth and adolescence},
volume = {53},
number = {1},
pages = {21-35},
pmid = {37747680},
issn = {1573-6601},
support = {R01 DA032371/DA/NIDA NIH HHS/United States ; R01DA032371/DA/NIDA NIH HHS/United States ; },
mesh = {Humans ; Adolescent ; Female ; *Depression/psychology ; *Emotions ; Anxiety/psychology ; Social Environment ; Telomere ; },
abstract = {Depression and anxiety symptoms are on the rise among adolescents. With increasing evidence that cellular aging may be associated with depressive and anxiety symptoms, there is an urgent need to identify the social environment context that may moderate this link. This study addresses this research gap by investigating the moderating role of the social environment on the relation between telomere length and emotional health among adolescents. Participants were 411 non-Hispanic (88.56%) Black (100%) adolescents (M = 14.23 years, SD = 1.85, female = 54%) in a major metropolitan city. Youth and parents reported on an array of social risk and protective factors, and youth provided DNA samples for telomere length measurement. Results demonstrated that the association of telomere length and anxiety symptoms was stronger among youth with higher perceived stress or lower school belongingness, and the association of telomere length with depressive symptoms was stronger under conditions of higher parent inter-partner psychological aggression. The results enhance our understanding of the complex associations between biological aging, the social environment, and mental health in adolescence.},
}
@article {pmid37745694,
year = {2023},
author = {Nonaka, K and Takubo, K and Aida, J and Watai, Y and Komatsu, A and Gomi, F and Shichi, Y and Yamazaki, Y and Ishiwata, T and Sasano, H and Arai, T},
title = {Accelerated telomere shortening in adrenal zona reticularis in patients with prolonged critical illness.},
journal = {Frontiers in endocrinology},
volume = {14},
number = {},
pages = {1244553},
pmid = {37745694},
issn = {1664-2392},
mesh = {Male ; Humans ; Female ; Aged, 80 and over ; Aged ; *Zona Reticularis ; *Critical Illness ; In Situ Hybridization, Fluorescence ; Telomere Shortening ; Cholesterol Esters ; },
abstract = {BACKGROUND: The number of patients with prolonged critical illness (PCI) has been increasing in many countries, and the adrenal gland plays an important role in maintaining homeostasis during PCI. Chronic disease burden is reportedly associated with shorter telomere lengths in human tissues. Telomere shortening in human somatic cells is largely dependent on cell divisions, and critically short telomeres lead to cellular dysfunction and aging. However, the association between PCI and telomere lengths in human adrenal cells is poorly understood. In this study, we investigated this association to assess whether the burden of PCI could accelerate the aging process in adrenal cells.<br><br>METHODS: Adrenocortical tissues from patients who died after PCI usually show a diffuse pattern of intracellular cholesterol ester depletion (i.e., lipid depletion). This study examined near-normal adrenal glands obtained from autopsied patients who died suddenly (control group) and lipid-depleted adrenal glands obtained from autopsied patients who died after PCI (PCI group). The control group included 7 men aged 80 to 94 years (mean age: 85.3 years) and 7 women aged 84 to 94 years (mean age: 87.7 years). The PCI group included 10 men aged 71 to 88 years (mean age: 78.8 years) and 8 women aged 77 to 95 years (mean age: 85.6 years). By using quantitative fluorescence in situ hybridization, relative telomere lengths (RTLs) were determined in the parenchymal cells of the three adrenocortical zones (zona glomerulosa, zona fasciculata, and zona reticularis [ZR]) and in the chromaffin cells of the medulla. The number of adrenal parenchymal cells was determined by immunohistochemistry and digital image analysis.<br><br>RESULTS: RTLs in ZR cells were significantly shorter in the PCI group than in the control group for both men and women (P = 0.0001 for men and P = 0.0012 for women). However, RTLs in the remaining three types of adrenal cells did not differ between the control and PCI groups for both men and women. The number of ZR cells was higher in the PCI group than in the control group for both men and women (P < 0.0001 for both men and women). The proportion of the number of ZR cells to the total number of adrenocortical parenchymal cells was also higher in the PCI group than in the control group (P < 0.0001 for both men and women). The Ki-67 proliferation index in ZR cells was higher in the PCI group than in the control group (P = 0.0039 for men and P = 0.0063 for women).<br><br>CONCLUSIONS: This study demonstrated ZR cell-specific telomere shortening in patients with adrenal lipid depletion who died after PCI. Our results suggest that the reactive proliferation of ZR cells accelerates the telomere shortening and aging process in ZR cells in these patients. The results of our study may contribute to the understanding of adrenal aging during PCI.},
}
@article {pmid37744360,
year = {2023},
author = {Guo, Y and Zhao, H and Wang, F and Xu, H and Liu, X and Hu, T and Wu, D},
title = {Telomere length as a marker of changes in body composition and fractures-an analysis of data from the NHANES 2001-2002.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1181544},
pmid = {37744360},
issn = {1664-3224},
mesh = {Humans ; Nutrition Surveys ; *Fractures, Bone/epidemiology ; Bone Density ; Body Composition ; Telomere ; },
abstract = {PURPOSE: There has been an association between changes in body composition, fracture incidence, and age in previous studies. Telomere length (TL) has been proposed as a biomarker of aging. However, the relationship between body composition, fractures, and TL has rarely been studied. Therefore, this study aimed to investigate the correlation between TL and body composition and fractures.Patients and methods: 20950 participants from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) were included in the final analysis. In NHANES, body compositions were measured with DXA, and TL was determined with quantitative PCR. Correlation analysis of TL and body composition was conducted using multivariate weighted linear regression and logistic regression models.<br><br>RESULTS: The results showed that TL positively correlated with bone mineral density (BMD) and bone mineral content (BMC) in most body parts. However, BMD and BMC were negatively connected with TL in the upper limbs and skull. Fat content was negatively associated with TL, while muscle content was positively linked to TL. In addition, TL's trend analysis results were consistent with the regression model when transformed from a continuous to a classified variable. An increase in TL was associated with a higher incidence of wrist fractures, while a decrease in spine fractures. The above correlation also has a certain degree of sex specificity.<br><br>CONCLUSION: Our study indicate that TL is associated with body composition as well as fractures, but further research is needed to confirm these contrasting associations in the skull, upper limbs, and wrists.},
}
@article {pmid37741970,
year = {2023},
author = {Moreno, E and Martínez-Sanz, J and Martín-Mateos, R and Díaz-Álvarez, J and Serrano-Villar, S and Burgos-Santamaría, D and Luna, L and Vivancos, MJ and Moreno-Zamora, A and Pérez-Elías, MJ and Moreno, S and Dronda, F and Montes, ML and Sánchez-Conde, M},
title = {Global DNA methylation and telomere length as markers of accelerated aging in people living with HIV and non-alcoholic fatty liver disease.},
journal = {BMC genomics},
volume = {24},
number = {1},
pages = {567},
pmid = {37741970},
issn = {1471-2164},
mesh = {Humans ; DNA Methylation ; *Non-alcoholic Fatty Liver Disease/genetics ; *HIV Infections/complications/genetics ; Leukocytes, Mononuclear ; Prospective Studies ; Aging/genetics ; *Aging, Premature ; Telomere/genetics ; },
abstract = {Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a comorbidity that generally increases in people living with HIV (PLWH). This condition is usually accompanied by persistent inflammation and premature immune system aging. In this prospective cohort study, we describe a straightforward methodology for quantifying biomarkers of aging, such as DNA methylation and telomere length, in PLWH and in the context of another relevant condition, such as MAFLD. Fifty-seven samples in total, thirty-eight from PLWH and nineteen from non-PLWH participants with or without MAFLD, were obtained and subjected to DNA extraction from peripheral blood mononuclear cells (PBMCs). Global DNA methylation and telomere length quantification were performed using an adapted enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. The quantification results were analysed and corrected by clinically relevant variables in this context, such as age, sex, and metabolic syndrome. Our results show an increased association of these biomarkers in PLWH regardless of their MAFLD status. Thus, we propose including the quantification of these age-related factors in studies of comorbidities. This will allow a better understanding of the effect of comorbidities of HIV infection and MAFLD and prevent their effects in these populations in the future.},
}
@article {pmid37737586,
year = {2023},
author = {Wood, ML and Neumann, R and Roy, P and Nair, V and Royle, NJ},
title = {Characterization of integrated Marek's disease virus genomes supports a model of integration by homology-directed recombination and telomere-loop-driven excision.},
journal = {Journal of virology},
volume = {97},
number = {10},
pages = {e0071623},
pmid = {37737586},
issn = {1098-5514},
support = {MIBTP 1645656//BBSRC-MIBTP/ ; },
mesh = {Animals ; *Chickens/virology ; *Genome, Viral/genetics ; *Herpesvirus 2, Gallid/genetics ; *Homologous Recombination ; *Marek Disease/genetics/virology ; Poultry Diseases/genetics/virology ; *Telomere/genetics ; Viral Vaccines/immunology ; Virus Activation ; Virus Latency ; *Virus Integration/genetics ; },
abstract = {Marek's disease virus (MDV) is a ubiquitous chicken pathogen that inflicts a large economic burden on the poultry industry, despite worldwide vaccination programs. MDV is only partially controlled by available vaccines, and the virus retains the ability to replicate and spread between vaccinated birds. Following an initial infection, MDV enters a latent state and integrates into host telomeres and this may be a prerequisite for malignant transformation, which is usually fatal. To understand the mechanism that underlies the dynamic relationship between integrated-latent and reactivated MDV, we have characterized integrated MDV (iMDV) genomes and their associated telomeres. This revealed a single orientation among iMDV genomes and the loss of some terminal sequences that is consistent with integration by homology-directed recombination and excision via a telomere-loop-mediated process.},
}
@article {pmid37737335,
year = {2023},
author = {Dratwa, M and Łacina, P and Butrym, A and Porzuczek, D and Mazur, G and Bogunia-Kubik, K},
title = {Telomere length and hTERT genetic variants as potential prognostic markers in multiple myeloma.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {15792},
pmid = {37737335},
issn = {2045-2322},
mesh = {Humans ; *Multiple Myeloma/genetics ; Prognosis ; Plasma Cells ; Alleles ; Telomere/genetics ; },
abstract = {Telomere dysfunction is a notable event observed in many cancers contributing to their genomic instability. A major factor controlling telomere stability is the human telomerase reverse transcriptase catalytic subunit (hTERT). Telomere shortening has been observed in multiple myeloma (MM), a plasma cell malignancy with a complex and heterogeneous genetic background. In the present study, we aimed to analyse telomere length and hTERT genetic variants as potential markers of risk and survival in 251 MM patients. We found that telomere length was significantly shorter in MM patients than in healthy individuals, and patients with more advanced disease (stage III according to the International Staging System) had shorter telomeres than patients with less advanced disease. MM patients with hTERT allele rs2736100 T were characterized with significantly shorter progression-free survival (PFS). Moreover, allele rs2736100 T was also found to be less common in patients with disease progression in response to treatment. hTERT rs2853690 T was associated with higher haemoglobin blood levels and lower C-reactive protein. In conclusion, our results suggest that telomere length and hTERT genetic variability may affect MM development and can be potential prognostic markers in this disease.},
}
@article {pmid37735501,
year = {2023},
author = {Ochi, S and Roy, B and Prall, K and Shelton, RC and Dwivedi, Y},
title = {Strong associations of telomere length and mitochondrial copy number with suicidality and abuse history in adolescent depressed individuals.},
journal = {Molecular psychiatry},
volume = {28},
number = {9},
pages = {3920-3929},
pmid = {37735501},
issn = {1476-5578},
support = {R01 MH107183/MH/NIMH NIH HHS/United States ; R01 MH124248/MH/NIMH NIH HHS/United States ; },
mesh = {Adult ; Humans ; Adolescent ; Child ; Suicidal Ideation ; *Depressive Disorder, Major/genetics ; DNA Copy Number Variations/genetics ; *Suicide ; DNA, Mitochondrial/genetics ; Telomere/genetics ; },
abstract = {Major depressive disorder (MDD) is highly prevalent in adolescents and is a major risk factor for suicidality. Recent evidence shows that accelerated cellular senescence/aging is associated with psychiatric illness, including depression, in adults. The present study examined if the relationships of telomere length (TL) and mitochondrial DNA copy number (mtDNAcn), two critical indicators of cellular senescence/aging, are altered in depressed adolescents and whether these alterations are associated with suicidality, early-life adversities, and other co-occuring factors. In genomic DNA isolated from 53 adolescents (ages 16-19, 19 MDD with suicide attempt/suicidal ideation [MDD + SI/SA], 14 MDD without SA/SI [MDD-SI/SA], and 20 healthy controls [HC]), TL and mtDNAcn were measured as the ratio between the number of telomere repeats and that of a single-copy nuclear-hemoglobin [HBG] gene or the amount of mtDNA (NADH dehydrogenase, subunit 1) relative to HBG. Our data show that TL was significantly lower, and mtDNAcn was significantly higher in the total MDD group than HC. TL was significantly lower and mtDNAcn was significantly higher in the MDD + SA/SI group than in the HC, whereas there were no differences in the MDD-SI/SA group. TL was positively correlated with mtDNAcn in both HC and MDD-SA/SI groups; however, TL was negatively correlated with mtDNAcn in MDD + SA/SI. Furthermore, TL was negatively correlated with the severity of both depression and anxiety, while mtDNAcn was positively correlated with the severity of prior emotional abuse. Our study indicates that cellular senescence is more advanced in depressed adolescents with suicidal ideation and that childhood emotional abuse may participate in such a process.},
}
@article {pmid37734859,
year = {2023},
author = {Lima, SM and Ren, X and Mu, L and Ochs-Balcom, HM and Palermo, T},
title = {Food Insecurity, telomere length and the potential modifying effects of social support in National Health and Nutrition Examination Survey.},
journal = {Public health nutrition},
volume = {26},
number = {12},
pages = {3005-3012},
pmid = {37734859},
issn = {1475-2727},
mesh = {Adult ; Humans ; Middle Aged ; Aged ; Nutrition Surveys ; Cross-Sectional Studies ; *Food Supply ; *Food Insecurity ; Social Support ; Telomere ; },
abstract = {OBJECTIVE: Telomere length (TL) is a posited pathway through which chronic stress results in biological dysregulation and subsequent adverse health outcomes. Food insecurity is associated with shorter TL. Social support, which is defined by the size and function of an individual's social network, is associated with better health outcomes. The present study assesses whether social support modifies the relationship between food security and TL.<br><br>DESIGN: Cross-sectional study design. Linear regression was used to assess the association between food insecurity and TL, stratified by social support level. A multiplicative interacted model was used to formally test modification.<br><br>SETTING: Data come from the National Health and Nutrition Examination Survey 1999-2000 and 2001-2002 waves.<br><br>PARTICIPANTS: Adults aged 60 years and older who have measurements for TL.<br><br>RESULTS: Our sample comprised 2674 participants, and 63&#xb7;5 % of the total sample had low social support, with 13&#xb7;3 % being food insecure. In fully adjusted models, food insecurity was negatively though modestly associated (P = 0&#xb7;13) with TL. Associations between food insecurity and TL were significantly modified by social support (interaction P = 0&#xb7;026), whereby food insecurity had a stronger effect among individuals with high social support (coefficient = -0&#xb7;099 (95 % CI: -0&#xb7;161, -0&#xb7;038)) compared to low social support (coefficient = -0&#xb7;001, (95 % CI: -0&#xb7;033, 0&#xb7;032)).<br><br>CONCLUSION: Food insecurity is modestly associated with shorter TL. Contrary to our hypothesis, food insecurity had more deleterious effects on TL among participants with high social support than low social support. Results may indicate that the food insecure population is a higher needs population, and increased social support reflects these needs rather than providing protective effects.},
}
@article {pmid37732945,
year = {2023},
author = {Gellert-Kristensen, H and Bojesen, SE and Tybjærg Hansen, A and Stender, S},
title = {Telomere length and risk of cirrhosis, hepatocellular carcinoma, and cholangiocarcinoma in 63,272 individuals from the general population.},
journal = {Hepatology (Baltimore, Md.)},
volume = {},
number = {},
pages = {},
pmid = {37732945},
issn = {1527-3350},
abstract = {BACKGROUND AND AIMS: Inherited short telomeres are associated with a risk of liver disease, whereas longer telomeres predispose to cancer. The association between telomere length and risk of HCC and cholangiocarcinoma remains unknown.<br><br>APPROACH AND RESULTS: We measured leukocyte telomere length using multiplex PCR in 63,272 individuals from the Danish general population. Telomere length and plasma ALT concentration were not associated (&#x3b2; = 4 &#xd7;10 -6 , p -value = 0.06) in a linear regression model, without any signs of a nonlinear relationship. We tested the association between telomere length and risk of cirrhosis, HCC, and cholangiocarcinoma using Cox regression. During a median follow-up of 11 years, 241, 76, and 112 individuals developed cirrhosis, HCC, and cholangiocarcinoma, respectively. Telomere length and risk of cirrhosis were inversely and linearly associated (p -value = 0.004, p for nonlinearity = 0.27). Individuals with telomeres in the shortest vs. longest quartile had a 2.25-fold higher risk of cirrhosis. Telomere length and risk of HCC were nonlinearly associated (p -value = 0.009, p -value for nonlinearity = 0.01). This relationship resembled an inverted J-shape, with the highest risk observed in individuals with short telomeres. Individuals with telomeres in the shortest versus longest quartile had a 2.29-fold higher risk of HCC. Telomere length was inversely and linearly associated with the risk of cholangiocarcinoma. Individuals with telomeres in the shortest versus longest quartile had a 1.86-fold higher risk of cholangiocarcinoma.<br><br>CONCLUSIONS: Shorter telomere length is associated with a higher risk of cirrhosis, HCC, and cholangiocarcinoma.},
}
@article {pmid37732532,
year = {2023},
author = {Hao, Y and Lv, M and Peng, J and Kuang, D and Zhang, Z and Zhang, Z and Wang, T and Yang, B and Wei, Z and Zhou, P and Zhang, Z and Cao, Y},
title = {Alteration of relative telomere length and telomerase reverse transcriptase expression in the granulosa cells of women during aging and assessment of in vitro fertilization outcomes.},
journal = {Molecular medicine reports},
volume = {28},
number = {5},
pages = {},
pmid = {37732532},
issn = {1791-3004},
mesh = {Adult ; Aged ; Female ; Humans ; Male ; Pregnancy ; Aging/genetics ; Aneuploidy ; Fertilization in Vitro ; Granulosa Cells ; Retrospective Studies ; Semen ; *Telomerase/genetics ; },
abstract = {Telomere attrition plays a critical role in the reproductive aging process in humans. Telomere length (TL) is typically regulated by telomerase, the main component of which is telomerase reverse transcriptase (TERT). The aim of the present study was to investigate the changes of relative TL (RTL) and TERT expression in granulosa cells (GCs) during aging and its association with reproduction. Clinical data on the frozen‑thawed embryo transfer cycles of older (>35 year old) and younger (≤35 year old) women from a single center over a 3‑year period were retrospectively analyzed. Preimplantation genetic testing for chromosome aneuploidies in older women during the same period was also analyzed. Following the analysis of the data, several biological characteristics of senescent GCs were explored. In addition, a total of 160 women who were undergoing their first fresh cycle of in vitro fertilization (IVF) or intracytoplasmic sperm injection were included in the study. GCs were collected from all participants. The changes of RTL and TERT expression in GCs during aging were investigated using quantitative PCR and western blotting. The associations of RTL and TERT with IVF outcomes were also assessed. The clinical data demonstrated that the pregnancy and live birth rates of women aged >35 years were ~20% lower than those of women aged ≤35 years, and the number of embryos with aneuploidy was 7‑fold of that without euploidy in the older age group. An aging‑induced change in follicle stimulating hormone receptor expression was observed. A shorter TL and increased TERT expression were detected in the older women. A significant inverse correlation between the expression levels of TERT and oocyte yield was identified. However, no association of RTL and TERT with blastocyst formation rate and the probability of clinical pregnancy was detected. It may be concluded that RTL and TERT alterations in GCs are potential determinants of ovarian aging. TERT expression in GCs appears to be a potential biomarker for the prediction of ovarian response, which provides a novel strategy for the assessment of female fertility.},
}
@article {pmid37732319,
year = {2023},
author = {, },
title = {Retraction: Leukocyte telomere length and obesity in children and adolescents: a systematic review and meta-analysis.},
journal = {Frontiers in genetics},
volume = {14},
number = {},
pages = {1285214},
doi = {10.3389/fgene.2023.1285214},
pmid = {37732319},
issn = {1664-8021},
abstract = {[This retracts the article DOI: 10.3389/fgene.2022.861101.].},
}
@article {pmid37727982,
year = {2024},
author = {Zhang, J and Zhang, F and Porter, KI and Dakup, PP and Wang, S and Robertson, GP and Gaddameedhi, S and Zhu, J},
title = {Telomere dysfunction in Tert knockout mice delays Braf[V600E] -induced melanoma development.},
journal = {International journal of cancer},
volume = {154},
number = {3},
pages = {548-560},
pmid = {37727982},
issn = {1097-0215},
support = {R01 AG073423/AG/NIA NIH HHS/United States ; R01 ES030113/ES/NIEHS NIH HHS/United States ; R35 GM149529/GM/NIGMS NIH HHS/United States ; 579152/MRA/Melanoma Research Alliance/United States ; },
mesh = {Animals ; Mice ; *Melanoma/genetics/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation ; *Proto-Oncogene Proteins B-raf/genetics/metabolism ; *Telomerase/genetics/metabolism ; Telomere/metabolism ; Tumor Suppressor Protein p53/genetics/metabolism ; Ultraviolet Rays/adverse effects ; },
abstract = {Telomerase activation is a crucial step in melanomagenesis, often occurring because of ultraviolet radiation (UVR)-induced mutations at the telomerase gene (TERT) promoter and rendering TERT transcription in response to the activated Raf-MAP kinase pathway by BRAF[V600E] mutation. Due to the excessively long telomeres in mice, this process does not occur during melanomagenesis in mouse models. To investigate the impact of telomere dysfunction on melanomagenesis, Braf[V600E] was induced in generations 1 and 4 (G1 and G4) of Tert[-/-] mice. Our findings revealed that, regardless of UVR exposure, melanoma development was delayed in G4 mice, which had shorter telomeres compared to G1 and wild-type C57BL/6J (G0) mice. Moreover, many G4 tumors displayed an accumulation of excessive DNA damage, as evidenced by increased γH2A.X staining. Tumors from UVR-exposed mice exhibited elevated p53 protein expression. Cultured tumor cells isolated from G4 mice displayed abundant chromosomal fusions and rearrangements, indicative of telomere dysfunction in these cells. Additionally, tumor cells derived from UVB-exposed mice exhibited constitutively elevated expression of mutant p53 proteins, suggesting that p53 was a target of UVB-induced mutagenesis. Taken together, our findings suggest that telomere dysfunction hampers melanomagenesis, and targeting telomere crisis-mediated genomic instability may hold promise for the prevention and treatment of melanoma.},
}
@article {pmid37725415,
year = {2024},
author = {Hassler, EM and Almer, G and Reishofer, G and Deutschmann, H and Mangge, H and Herrmann, M and Leber, SL and Gunzer, F and Langsenlehner, T and Renner, W},
title = {A sex-specific association of leukocyte telomere length with thigh muscle mass.},
journal = {Clinical chemistry and laboratory medicine},
volume = {62},
number = {1},
pages = {150-156},
pmid = {37725415},
issn = {1437-4331},
mesh = {Humans ; Male ; Female ; *Thigh ; *Telomere/genetics ; Leukocytes ; Muscles ; DNA/metabolism ; },
abstract = {OBJECTIVES: Telomeres are DNA-protein complexes at the ends of linear chromosomes that protect against DNA degradation. Telomeres shorten during normal cell divisions and therefore, telomere length is an indicator of mitotic-cell age. In humans, telomere shortening is a potential biomarker for disease risk, progression and premature death. Physical activity has been associated with longer leukocyte telomere length (LTL) in some studies. In the current study the relationship between LTL, thigh muscle mass and adipose tissue distribution was explored.<br><br>METHODS: We performed anthropometric measurements and magnetic resonance imaging (MRI) measurements of the thigh in 149 healthy subjects (77 male, 72 female). LTL was measured using qPCR. Additionally, the subjects answered a questionnaire concerning their training behaviour.<br><br>RESULTS: In male subjects, LTL was significantly associated with thigh muscle mass, independent of age and body mass index (p=0.006). In addition, a slight association of LTL with weekly endurance units in the male group was found. These relations could not be observed in females.<br><br>CONCLUSIONS: In conclusion, we observed a sex-specific association of LTL and thigh muscle mass in healthy males. The reason of this sex-specific association is currently unclear, but could be related to different training effects and/or hormonal pathways in men and women.},
}
@article {pmid37725013,
year = {2023},
author = {Liang, J and Cui, J and Cheng, J and Pan, Y and Zhang, R and Yang, S and Zou, L},
title = {SIRT6 Knockdown in Buffalo Fetal Fibroblasts Exacerbates Premature Senescence Caused by DNA and Telomere Damage.},
journal = {Cellular reprogramming},
volume = {25},
number = {6},
pages = {277-287},
doi = {10.1089/cell.2023.0048},
pmid = {37725013},
issn = {2152-4998},
mesh = {Animals ; *Buffaloes/genetics ; Cellular Senescence ; Fibroblasts/metabolism ; Fetus ; DNA/metabolism ; Telomere/metabolism ; *Sirtuins/genetics/metabolism ; },
abstract = {As a gene with antiaging functions, sirtuin6 (SIRT6) belonging to the sirtuin family plays a vital role in DNA repair, telomerase function, and cellular senescence, as well as maintains epigenomic stability and promotes longevity. However, its role in cell senescence in large animals, such as buffaloes, remains unknown. Fibroblasts are commonly used for somatic reprogramming, and their physiological characteristics affect the efficiency of this process. We aimed to elucidate the role of SIRT6 in cellular senescence and proliferation and analyze its effect on the biological function of buffalo fibroblasts to help improve the efficiency of buffalo somatic cell reprogramming. The expression of SIRT6 and related DNA damage was measured in buffalo fibroblasts obtained at different developmental stages (in the fetus and at 3 and 10 years of age), and the effect of SIRT6 knockdown on the senescence of buffalo fetal fibroblast was investigated. An inverse relationship was observed between SIRT6 expression and senescence in buffalo fibroblasts obtained from animals of various ages. This was accompanied by decreased cell growth, viability, and increased DNA damage. Short hairpin RNA-mediated SIRT6 knockdown accelerated the senescence of buffalo fetal fibroblasts. It blocked the cell cycle during in vitro cell culture, which further enhanced DNA damage, particularly with respect to the telomeres. Collectively, our findings suggest that SIRT6 expression was closely associated with buffalo senescence in fibroblasts. These findings serve as a foundation to better understand the cellular functions of SIRT6 and also aid in selecting donor cells for buffalo somatic cell reprogramming.},
}
@article {pmid37721487,
year = {2023},
author = {Wong, JYY and Shu, XO and Hu, W and Blechter, B and Shi, J and Wang, K and Cawthon, R and Cai, Q and Yang, G and Rahman, ML and Ji, BT and Gao, Y and Zheng, W and Rothman, N and Lan, Q},
title = {Associations between Longer Leukocyte Telomere Length and Increased Lung Cancer Risk among Never Smokers in Urban China.},
journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {32},
number = {12},
pages = {1734-1737},
pmid = {37721487},
issn = {1538-7755},
support = {ZIA HL006285/ImNIH/Intramural NIH HHS/United States ; UM1 CA173640/CA/NCI NIH HHS/United States ; R01 CA070867/CA/NCI NIH HHS/United States ; Z99 HL999999/ImNIH/Intramural NIH HHS/United States ; R01 CA082729/CA/NCI NIH HHS/United States ; ZIA CP010120/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Male ; Humans ; Female ; *Lung Neoplasms/etiology/genetics ; Prospective Studies ; China/epidemiology ; Smokers ; Telomere Homeostasis/genetics ; Leukocytes ; Lung ; Telomere/genetics ; Carcinogenesis ; },
abstract = {BACKGROUND: The complex relationship between measured leukocyte telomere length (LTL), genetically predicted LTL (gTL), and carcinogenesis is exemplified by lung cancer. We previously reported associations between longer pre-diagnostic LTL, gTL, and increased lung cancer risk among European and East Asian populations. However, we had limited statistical power to examine the associations among never smokers by gender and histology.<br><br>METHODS: To investigate further, we conducted nested case-control analyses on an expanded sample of never smokers from the prospective Shanghai Women's Health Studies (798 cases and 792 controls) and Shanghai Men's Health Studies (161 cases and 162 controls). We broke the case-control matching and used multivariable unconditional logistic regression models to estimate the ORs and 95% confidence intervals (CI) of incident lung cancer and adenocarcinoma (LUAD), in relation to LTL measured using quantitative PCR and gTL determined using a polygenic score. In addition, we conducted Mendelian randomization (MR) using MR-PRESSO.<br><br>RESULTS: We found striking dose-response relationships between longer LTL and gTL, and increased lung cancer risk among never-smoking women (P trendLTL = 4&#xd7;10-6; P trendgTL = 3&#xd7;10-4). Similarly, among never-smoking men, longer measured LTL was associated with over triple the risk compared with those with the shortest (OR, 3.48; 95% CI, 1.85-6.57). The overall results were similar for LUAD among women and men. MR analyses supported causal associations with LUAD among women (OR1 SD gTL, 1.19; 95% CI, 1.03-1.37; P = 0.03).<br><br>CONCLUSIONS: Longer pre-diagnostic LTL is associated with increased lung cancer risk among never smokers.<br><br>IMPACT: Our findings firmly support the role of longer telomeres in lung carcinogenesis.},
}
@article {pmid37718447,
year = {2023},
author = {Bhat, GR and Jamwal, RS and Sethi, I and Bhat, A and Shah, R and Verma, S and Sharma, M and Sadida, HQ and Al-Marzooqi, SK and Masoodi, T and Mirza, S and Haris, M and Macha, MA and Akil, ASA and Bhat, AA and Kumar, R},
title = {Associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the Jammu and Kashmir population of North India.},
journal = {BMC cancer},
volume = {23},
number = {1},
pages = {874},
pmid = {37718447},
issn = {1471-2407},
mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/genetics ; *Lung Neoplasms/epidemiology/genetics ; Telomere/genetics ; India/epidemiology ; Mass Spectrometry ; },
abstract = {BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes, playing a vital role in maintaining chromosomal integrity and stability. Dysregulation of telomeres has been implicated in the development of various cancers, including non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. Genetic variations within telomere maintenance genes may influence the risk of developing NSCLC. The present study aimed to evaluate the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India, and to investigate the relationship between telomere length and NSCLC risk.<br><br>METHODS: We employed the cost-effective and high-throughput MassARRAY MALDI-TOF platform to assess the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India. Additionally, we used TaqMan genotyping to validate our results. Furthermore, we investigated telomere length variation and its relation to NSCLC risk in the same population using dual-labeled fluorescence-based qPCR.<br><br>RESULTS: Our findings revealed significant associations of TERT rs10069690 and POT1 rs10228682 with NSCLC risk (adjusted p-values&#x2009;=&#x2009;0.019 and 0.002, respectively), while TERF2 rs251796 and rs2975843 showed no significant associations. The TaqMan genotyping validation further substantiated the associations of TERT rs10069690 and rs2242652 with NSCLC risk (adjusted p-values&#x2009;=&#x2009;0.02 and 0.003, respectively). Our results also demonstrated significantly shorter telomere lengths in NSCLC patients compared to controls (p&#x2009;=&#x2009;0.0004).<br><br>CONCLUSION: This study highlights the crucial interplay between genetic variation in telomere maintenance genes, telomere attrition, and NSCLC risk in the Jammu and Kashmir population of North India. Our findings suggest that TERT and POT1 gene variants, along with telomere length, may serve as potential biomarkers and therapeutic targets for NSCLC in this population. Further research is warranted to elucidate the underlying mechanisms and to explore the potential clinical applications of these findings.},
}
@article {pmid37716992,
year = {2023},
author = {Liu, X and Arshad, R and Wang, X and Li, WM and Zhou, Y and Ge, XJ and Huang, HR},
title = {The phased telomere-to-telomere reference genome of Musa acuminata, a main contributor to banana cultivars.},
journal = {Scientific data},
volume = {10},
number = {1},
pages = {631},
pmid = {37716992},
issn = {2052-4463},
support = {32070237, 31261140366//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Haploidy ; *Musa/genetics ; Telomere/genetics ; *Genome, Plant ; },
abstract = {Musa acuminata is a main wild contributor to banana cultivars. Here, we reported a haplotype-resolved and telomere-to-telomere reference genome of M. acuminata by incorporating PacBio HiFi reads, Nanopore ultra-long reads, and Hi-C data. The genome size of the two haploid assemblies was estimated to be 469.83 Mb and 470.21 Mb, respectively. Multiple assessments confirmed the contiguity (contig N50: 16.53 Mb and 18.58 Mb; LAI: 20.18 and 19.48), completeness (BUSCOs: 98.57% and 98.57%), and correctness (QV: 45.97 and 46.12) of the genome. The repetitive sequences accounted for about half of the genome size. In total, 40,889 and 38,269 protein-coding genes were annotated in the two haploid assemblies, respectively, of which 9.56% and 3.37% were newly predicted. Genome comparison identified a large reciprocal translocation involving 3 Mb and 10 Mb from chromosomes 01 and 04 within M. acuminata. This reference genome of M. acuminata provides a valuable resource for further understanding of subgenome evolution of Musa species, and precise genetic improvement of banana.},
}
@article {pmid37714858,
year = {2023},
author = {Tichy, ED and Lee, JH and Li, G and Estep, KN and Brad Johnson, F and Mourkioti, F},
title = {Impacts of radiation exposure, hindlimb unloading, and recovery on murine skeletal muscle cell telomere length.},
journal = {NPJ microgravity},
volume = {9},
number = {1},
pages = {76},
pmid = {37714858},
issn = {2373-8065},
support = {P30 AR069619/AR/NIAMS NIH HHS/United States ; R01 AR075914/AR/NIAMS NIH HHS/United States ; R01 HL146662/HL/NHLBI NIH HHS/United States ; },
abstract = {Astronauts are exposed to harsh conditions, including cosmic radiation and microgravity. Spaceflight elongates human telomeres in peripheral blood, which shorten upon return to Earth and approach baseline levels during postflight recovery. Astronauts also encounter muscle atrophy, losing up to 20% loss of muscle mass on spaceflights. Telomere length changes in muscle cells of astronauts remain unexplored. This study investigates telomere alterations in grounded mice experiencing radiation exposure and muscle atrophy, via a hindlimb unloading spaceflight mimicking model. We find telomere lengthening is present in muscle stem cells and in myofiber nuclei, but not in muscle-resident endothelial cells. We further assessed telomere length in the model following hindlimb unloading recovery. We find that telomere length failed to return to baseline values. Our results suggest a role for telomeres in muscle acclimatization, which is relevant for the well-being of astronauts in space, and upon their return to Earth.},
}
@article {pmid37713629,
year = {2023},
author = {Manzato, C and Larini, L and Oss Pegorar, C and Dello Stritto, MR and Jurikova, K and Jantsch, V and Cusanelli, E},
title = {TERRA expression is regulated by the telomere-binding proteins POT-1 and POT-2 in Caenorhabditis elegans.},
journal = {Nucleic acids research},
volume = {51},
number = {19},
pages = {10681-10699},
pmid = {37713629},
issn = {1362-4962},
support = {P40 OD010440/OD/NIH HHS/United States ; },
mesh = {Animals ; Caenorhabditis elegans/genetics/metabolism ; *Caenorhabditis elegans Proteins/genetics/metabolism ; DNA-Binding Proteins/genetics ; Meiosis ; *RNA, Long Noncoding/genetics ; *Telomerase/genetics ; Telomere/genetics/metabolism ; Telomere-Binding Proteins/genetics/metabolism ; },
abstract = {Several aspects of telomere biology are regulated by the telomeric repeat-containing RNA TERRA. While TERRA expression is conserved through evolution, species-specific mechanisms regulate its biogenesis and function. Here we report on the expression of TERRA in Caenorhabditis elegans. We show that C. elegans TERRA is regulated by the telomere-binding proteins POT-1 and POT-2 which repress TERRA in a telomere-specific manner. C. elegans TERRA transcripts are heterogeneous in length and form discrete nuclear foci, as detected by RNA FISH, in both postmitotic and germline cells; a fraction of TERRA foci localizes to telomeres. Interestingly, in germ cells, TERRA is expressed in all stages of meiotic prophase I, and it increases during pachytene, a stage in meiosis when homologous recombination is ongoing. We used the MS2-GFP system to study the spatiotemporal dynamics of single-telomere TERRA molecules. Single particle tracking revealed different types of motilities, suggesting complex dynamics of TERRA transcripts. Finally, we unveiled distinctive features of C. elegans TERRA, which is regulated by telomere shortening in a telomere-specific manner, and it is upregulated in the telomerase-deficient trt-1; pot-2 double mutant prior to activation of the alternative lengthening mechanism ALT. Interestingly, in these worms TERRA displays distinct dynamics with a higher fraction of fast-moving particles.},
}
@article {pmid37707950,
year = {2023},
author = {Jalan-Sakrikar, N and Anwar, A and Yaqoob, U and Gan, C and Lagnado, AB and Wixom, AQ and Jurk, D and Huebert, RC},
title = {Telomere dysfunction promotes cholangiocyte senescence and biliary fibrosis in primary sclerosing cholangitis.},
journal = {JCI insight},
volume = {8},
number = {20},
pages = {},
pmid = {37707950},
issn = {2379-3708},
support = {KL2 TR002379/TR/NCATS NIH HHS/United States ; P30 DK084567/DK/NIDDK NIH HHS/United States ; R01 DK117861/DK/NIDDK NIH HHS/United States ; },
mesh = {Humans ; Animals ; Mice ; *Cholangitis, Sclerosing/genetics/metabolism/pathology ; Liver/metabolism ; Bile Ducts/metabolism ; Fibrosis ; Telomere ; },
abstract = {Cellular senescence and biliary fibrosis are prototypical features of obliterative cholangiopathies, such as primary sclerosing cholangitis (PSC). Telomere dysfunction can lead to senescence either through telomere erosion or damaged telomeres. Our goal was to investigate a mechanistic relationship between telomere damage and biliary fibrosis in PSC. Telomere attrition was observed in the bile ducts of patients with PSC along with a reduction in telomerase reverse transcriptase (TERT) expression, compared with that in normal livers. Similarly, liver tissue from mouse models of biliary fibrosis showed telomere attrition with increased damage at telomeres measured as telomere-associated foci (TAF). Cellular models of senescence induction increased the TAF in cholangiocytes. This coincided with decreased TERT expression and increased senescence, which was rescued by modulating TERT levels. Epigenetic analysis revealed increased acquisition of repressive histone methylation at the TERT promoter, which correlated with decreased TERT transcription. Cholangiocyte-selective deletion of TERT in mice exacerbated fibrosis, whereas androgen therapy toward telomerase rescued liver fibrosis and liver function in a genetic mouse model of PSC. Our results demonstrate a mechanistic role for telomere dysfunction in cellular senescence and fibrosis that characterize PSC. This suggests that PSC may be, in part, a telomere biology disorder, and identifies TERT as a potential therapeutic target.},
}
@article {pmid37705928,
year = {2023},
author = {Cao, Z and Hou, Y and Xu, C},
title = {Leucocyte telomere length, brain volume and risk of dementia: a prospective cohort study.},
journal = {General psychiatry},
volume = {36},
number = {4},
pages = {e101120},
pmid = {37705928},
issn = {2517-729X},
abstract = {BACKGROUND: The evidence regarding the association between leucocyte telomere length (LTL) and brain health is sparse and inconclusive.<br><br>AIMS: To investigate the associations of LTL with brain structure and the risk of dementia based on a large-scale prospective study.<br><br>METHODS: LTL in the peripheral blood was measured by the quantitative polymerase chain reaction (qPCR) assay from 439&#x2009;961 individuals in the UK Biobank recruited between 2006 and 2010 and followed up until 2020. Electronic health records were used to record the incidence of dementia, including Alzheimer's disease (AD) and vascular dementia (VD). The brain structure, including total and regional brain volume, of 38&#x2009;740 participants was then assessed by magnetic resonance imaging (MRI).<br><br>RESULTS: During a median follow-up of 11.6 years, a total of 5 820 (1.3%) dementia cases were documented. The restricted cubic spline model showed significant overall associations between LTL and the risk of dementia and AD (p for overall <0.05). The multivariable adjusted hazard ratios (HRs) for the lowest LTL tertile compared with the highest LTL tertile were 1.14 (95% confidence interval (CI): 1.06 to 1.21) for dementia, 1.28 (95% CI: 1.12 to 1.46) for AD and 1.18 (95% CI: 0.98 to 1.42) for VD. Furthermore, we found that shorter LTL was associated with smaller total brain volume (&#x3b2;=-0.012 8, p=0.003), white matter volume (&#x3b2;=-0.022 4, p<0.001), hippocampus volume (&#x3b2;=-0.017 2, p<0.001), thalamus volume (&#x3b2;=-0.023 9, p<0.001) and accumbens (&#x3b2;=-0.015 5, p=0.001).<br><br>CONCLUSIONS: Shorter LTL is associated with total and regional brain structure and a higher risk of incident dementia and AD, implying the potential of telomere length as a predictive biomarker of brain health.},
}
@article {pmid37705399,
year = {2023},
author = {Houminer-Klepar, N and Bord, S and Epel, E and Lin, J and Sultan, L and Baron-Epel, O},
title = {Working Status of First-Time Postpartum Mothers and Telomere Length-A 1-Year Prospective Study.},
journal = {Journal of occupational and environmental medicine},
volume = {65},
number = {12},
pages = {1036-1044},
pmid = {37705399},
issn = {1536-5948},
mesh = {Female ; Humans ; *Mothers ; Prospective Studies ; *Postpartum Period ; Employment ; Telomere ; },
abstract = {OBJECTIVE: Transitioning to motherhood can create work family conflicts affecting mothers' health. Although employment is generally associated with longer telomeres, this may diminish during the early years of child-rearing. This study aimed to assess the impact of work reentry on telomere length (TL) among first-time mothers.<br><br>METHODS: In this 1-year prospective study, a total of 103 first-time postpartum mothers participated from two medical institutions in Northern Israel; they completed validated questionnaires, reported their current working status, and provided dried blood spots measuring TL.<br><br>RESULTS: We found that working status significantly predicted change in TL and was negatively correlated with change in TL over time (&#x3b2; = -0.245; 95% confidence interval, -0.169, -0.018; P = 0.016).<br><br>CONCLUSIONS: Identifying ideal timing of work reentry is recommended for first-time postpartum mother's optimal health and TL.},
}
@article {pmid37702332,
year = {2023},
author = {Rahman, ST and Waterhouse, M and Pham, H and Duarte Romero, B and Baxter, C and McLeod, DSA and English, DR and Ebeling, PR and Hartel, G and Armstrong, BK and O'Connell, RL and van der Pols, JC and Venn, AJ and Webb, PM and Wells, JK and Whiteman, DC and Pickett, HA and Neale, RE},
title = {Effects of Vitamin D Supplementation on Telomere Length: An Analysis of Data from the Randomised Controlled D-Health Trial.},
journal = {The journal of nutrition, health &amp; aging},
volume = {27},
number = {8},
pages = {609-616},
doi = {10.1007/s12603-023-1948-3},
pmid = {37702332},
issn = {1760-4788},
mesh = {Humans ; Aged ; Australia ; *Vitamins/pharmacology/therapeutic use ; *Vitamin D ; Calcifediol ; Telomere ; Dietary Supplements ; Randomized Controlled Trials as Topic ; },
abstract = {OBJECTIVES: Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio).<br><br>Participants were Australians aged 60-84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation.<br><br>RESULTS: The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was -0.001 (95% CI -0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration.<br><br>CONCLUSION: In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length.},
}
@article {pmid37701454,
year = {2023},
author = {Huang, HR and Liu, X and Arshad, R and Wang, X and Li, WM and Zhou, Y and Ge, XJ},
title = {Telomere-to-telomere haplotype-resolved reference genome reveals subgenome divergence and disease resistance in triploid Cavendish banana.},
journal = {Horticulture research},
volume = {10},
number = {9},
pages = {uhad153},
pmid = {37701454},
issn = {2662-6810},
abstract = {Banana is one of the most important crops of the world. Cavendish-type bananas, which have a monospecific Musa acuminata origin (AAA), account for around half of the global banana production, thereby are of great significance for human societies. However, until now, the high-quality haplotype-resolved reference genome was still undecoded for banana cultivars. Here, we reported the telomere-to-telomere (T2T) and haplotype-resolved reference genome of 'Baxijiao' (Cavendish) consisting of three haploid assemblies. The sizes of the three haploid assemblies were estimated to be 477.16 Mb, 477.18 Mb, and 469.57 Mb, respectively. Although with monospecific origins, the three haploid assemblies showed great differences with low levels of sequence collinearity. Several large reciprocal translocations were identified among chromosomes 1, 4, and 7. An expansion of gene families that might affect fruit quality and aroma was detected, such as those belonging to sucrose/disaccharide/oligosaccharide catabolic processes, sucrose metabolic process, starch metabolic process, and aromatic compound biosynthetic process. Besides, an expansion of gene families related to anther and pollen development was observed, which could be associated with parthenocarpy and sterility of the Cavendish cultivar. Finally, much fewer resistance genes were identified in 'Baxijiao' than in M. acuminata, particularly in the gene clusters in chromosomes 3 and 10, providing potential targets to explore for molecular analysis of disease resistance in banana. This T2T haplotype-resolved reference genome will thus be a valuable genetic resource for biological studies, molecular breeding, and genetic improvement of banana.},
}
@article {pmid37696218,
year = {2023},
author = {Han, D and Zhu, Y and Choudhry, AA and Cheng, J and Liang, H and Lin, F and Chang, Q and Liu, H and Pan, P and Zhang, Y},
title = {Association of telomere length with risk of lung cancer: A large prospective cohort study from the UK Biobank.},
journal = {Lung cancer (Amsterdam, Netherlands)},
volume = {184},
number = {},
pages = {107358},
doi = {10.1016/j.lungcan.2023.107358},
pmid = {37696218},
issn = {1872-8332},
mesh = {Female ; Humans ; *Lung Neoplasms/epidemiology/genetics ; Biological Specimen Banks ; Prospective Studies ; *Adenocarcinoma ; *Carcinoma, Squamous Cell ; Telomere/genetics ; United Kingdom/epidemiology ; },
abstract = {OBJECTIVES: Leukocyte telomere length (LTL) is associated with a wide variety of diseases, including cancer. However, findings regarding the association between LTL and the risk for lung cancer have been inconclusive and inconsistent across previous observational studies.<br><br>METHODS: This prospective cohort study included data from 425,146 participants 37-73&#xa0;years of age housed in the UK Biobank. Quantitative polymerase chain reaction (qPCR) was used to measure LTL in baseline DNA samples. A multivariate Cox proportional hazards model was used to evaluate the relationship between LTL and the risk for lung cancer.<br><br>RESULTS: An increase in LTL per interquartile range (IQR) was associated with a 9% increase in the risk for lung cancer (hazard ratio [HR] 1.09 [95% confidence interval (CI) 1.03-1.16]). Participants in the highest LTL quintile exhibited an approximately 25% elevated risk for developing lung cancer (HR 1.25 [95% CI 1.09-1.45]) compared with those in the lowest quintile. The relationship between per IQR increase in LTL and elevated risk for lung cancer was greater in the histological subtype of adenocarcinoma (HR 1.30 [95% CI 1.18-1.43]), female sex (HR 1.16 [95% CI 1.06-1.26]), non-smokers (HR 1.45 [95% CI 1.23-1.71]), and individuals with high genetic risk for lung cancer (HR 1.18 [95% CI 1.03-1.34]), respectively. Surprisingly, a per IQR increase in LTL was associated with increased risks for both lung adenocarcinoma (HR 1.56 [95% CI 1.24-1.96]) and squamous cell carcinoma (HR 2.01 [95% CI 1.13-3.56]) in never smokers.<br><br>CONCLUSIONS: Longer LTL was associated with an elevated risk for lung cancer, particularly for adenocarcinoma and squamous cell carcinoma in never smokers. The results suggest the potential of telomeres as non-invasive biomarkers for the early screening of lung cancer, particularly in non-smokers, who are typically overlooked.},
}
@article {pmid37693759,
year = {2023},
author = {Yu, W and Mei, Y and Lu, Z and Zhou, L and Jia, F and Chen, S and Wang, Z},
title = {The causal relationship between genetically determined telomere length and meningiomas risk.},
journal = {Frontiers in neurology},
volume = {14},
number = {},
pages = {1178404},
pmid = {37693759},
issn = {1664-2295},
abstract = {BACKGROUND: Studies have shown that longer leukocyte telomere length (LTL) is significantly associated with increased risk of meningioma. However, there is limited evidence concerning the causal association of LTL with benign and malignant meningiomas or with the location of benign tumors.<br><br>METHODS: We used three LTL datasets from different sources, designated by name and sample size as LTL-78592, LTL-9190, and LTL-472174. The linkage disequilibrium score (LDSC) was used to explore the association between LTL and meningioma. We utilized two-sample bidirectional Mendelian randomization (TSMR) to evaluate whether LTL is causally related to meningioma risk. We adjusted for confounders by conducting multivariable Mendelian randomization (MVMR).<br><br>RESULTS: In the LTL-78592, longer LTL was significantly associated with increased risk of malignant [odds ratio (OR)&#x2009;=&#x2009;5.14, p&#x2009;=&#x2009;1.04&#x2009;&#xd7;&#x2009;10[-5]], benign (OR&#x2009;=&#x2009;4.81, p&#x2009;<&#x2009;0.05), benign cerebral (OR&#x2009;=&#x2009;5.36, p&#x2009;<&#x2009;0.05), and benign unspecified meningioma (OR&#x2009;=&#x2009;8.26, p&#x2009;<&#x2009;0.05). The same results were obtained for the LTL-9190. In the LTL-472174, longer LTL was significantly associated with increased risk of malignant (OR&#x2009;=&#x2009;4.94, p&#x2009;<&#x2009;0.05), benign (OR&#x2009;=&#x2009;3.14, p&#x2009;<&#x2009;0.05), and benign cerebral meningioma (OR&#x2009;=&#x2009;3.59, p&#x2009;<&#x2009;0.05). Similar results were obtained in the MVMR. In contrast, only benign cerebral meningioma displayed a possible association with longer LTL (OR&#x2009;=&#x2009;1.01, p&#x2009;<&#x2009;0.05). No heterogeneity or horizontal pleiotropy was detected.<br><br>CONCLUSION: In brief, genetically predicted longer LTL may increase the risk of benign, malignant, and benign cerebral meningiomas, regardless of the LTL measure, in European populations.},
}
@article {pmid37690790,
year = {2023},
author = {},
title = {"Interstitial lung abnormalities are associated with decreased mean telomere length." R.K. Putman, G.T. Axelsson, S.Y. Ash, et al. Eur Respir J 2022; 60: 2101814.},
journal = {The European respiratory journal},
volume = {62},
number = {3},
pages = {},
doi = {10.1183/13993003.51814-2021},
pmid = {37690790},
issn = {1399-3003},
}
@article {pmid37689117,
year = {2023},
author = {Martinez, S and Jones, JD},
title = {A pilot study examining the relationship between chronic heroin use and telomere length among individuals of African ancestry.},
journal = {Pharmacology, biochemistry, and behavior},
volume = {231},
number = {},
pages = {173631},
pmid = {37689117},
issn = {1873-5177},
support = {R21 DA043199/DA/NIDA NIH HHS/United States ; T32 DA007294/DA/NIDA NIH HHS/United States ; },
mesh = {Humans ; Female ; Middle Aged ; Male ; *Telomere Shortening ; Pilot Projects ; *Heroin ; Cross-Sectional Studies ; Bayes Theorem ; Telomere/genetics ; },
abstract = {BACKGROUND: Prior research has suggested a possible link between heroin use and shortened telomere length (TL), a marker of cellular aging and genomic stability. We sought to replicate these findings by examining the relationship between TL and heroin use among individuals of African ancestry.<br><br>METHODS: This cross-sectional study examined TL among 57 participants [17.5&#xa0;% female; mean age 48.0 (&#xb1;6.80) years] of African ancestry with Opioid Use Disorder (OUD) and a mean heroin use duration of 18.2 (&#xb1;10.7) years. Quantitative polymerase chain reaction (qPCR) was used to calculate TL as the ratio between telomere repeat copy number (T) and a single-copy gene, copy number (S). The primary dependent variable was TL (T/S Ratio) measured in kilobase pairs. Covariates included heroin use years and personality traits. Using a hybrid approach, multiple linear regression and Bayesian linear regression examined the association of chronological age, heroin use years and personality traits with TL.<br><br>RESULTS: The multiple linear regression model fit the data well, R[2]&#xa0;=&#xa0;0.265, F(7,49)&#xa0;=&#xa0;2.53, p&#xa0;<&#xa0;.026. Chronological age (&#x3b2;&#xa0;=&#xa0;-0.36, p&#xa0;=&#xa0;.017), neuroticism (&#x3b2;&#xa0;=&#xa0;0.46, p&#xa0;=&#xa0;.044), and conscientiousness (&#x3b2;&#xa0;=&#xa0;0.52, p&#xa0;=&#xa0;.040) were significant predictors of TL. Bayesian linear regression provided moderate support for the alternate hypothesis that chronological age and TL are associated, BF[10]&#xa0;=&#xa0;5.77, R[2]&#xa0;=&#xa0;0.120. The posterior summary of the coefficient was M&#xa0;=&#xa0;0.719 (SD&#xa0;=&#xa0;0.278, 95&#xa0;% credible interval [-1.28, -0.163]).<br><br>CONCLUSIONS: Contrary to prior studies, these findings suggest that heroin use duration may not be significantly associated with TL among individuals of African ancestry, highlighting the need for more rigorous research to elucidate the complexity of this relationship.},
}
@article {pmid37688329,
year = {2023},
author = {Sullivan, DI and Bello, FM and Silva, AG and Redding, KM and Giordano, L and Hinchie, AM and Loughridge, KE and Mora, AL and Königshoff, M and Kaufman, BA and Jurczak, MJ and Alder, JK},
title = {Intact mitochondrial function in the setting of telomere-induced senescence.},
journal = {Aging cell},
volume = {22},
number = {10},
pages = {e13941},
pmid = {37688329},
issn = {1474-9726},
support = {F32 HL152503/HL/NHLBI NIH HHS/United States ; R01 DK114012/DK/NIDDK NIH HHS/United States ; R01 HL135062/HL/NHLBI NIH HHS/United States ; U54 AG075931/AG/NIA NIH HHS/United States ; },
mesh = {*Telomere/genetics ; *Telomere-Binding Proteins/metabolism ; Mitochondria/genetics/metabolism ; Cellular Senescence/genetics ; Fibroblasts/metabolism ; },
abstract = {Mitochondria play essential roles in metabolic support and signaling within all cells. Congenital and acquired defects in mitochondria are responsible for several pathologies, including premature entrance to cellar senescence. Conversely, we examined the consequences of dysfunctional telomere-driven cellular senescence on mitochondrial biogenesis and function. We drove senescence in vitro and in vivo by deleting the telomere-binding protein TRF2 in fibroblasts and hepatocytes, respectively. Deletion of TRF2 led to a robust DNA damage response, global changes in transcription, and induction of cellular senescence. In vitro, senescent cells had significant increases in mitochondrial respiratory capacity driven by increased cellular and mitochondrial volume. Hepatocytes with dysfunctional telomeres maintained their mitochondrial respiratory capacity in vivo, whether measured in intact cells or purified mitochondria. Induction of senescence led to the upregulation of overlapping and distinct genes in fibroblasts and hepatocytes, but transcripts related to mitochondria were preserved. Our results support that mitochondrial function and activity are preserved in telomere dysfunction-induced senescence, which may facilitate continued cellular functions.},
}
@article {pmid37686490,
year = {2023},
author = {Kreilmeier-Berger, T and Aupperle-Lellbach, H and Reifinger, M and Hörstke, NV and Holzmann, K and Kleiter, M},
title = {Alternative Lengthening of Telomeres Is Rare in Canine Histiocytic Sarcoma.},
journal = {Cancers},
volume = {15},
number = {17},
pages = {},
pmid = {37686490},
issn = {2072-6694},
abstract = {Cancer cells activate telomere maintenance mechanisms (TMMs) to overcome senescence and thus are targets for TMM-specific therapies. Telomerase-independent alternative lengthening of telomeres (ALT) is frequently utilized as a TMM in human sarcoma subtypes. Histiocytic sarcoma (HS) is a rare but aggressive tumor of hematopoietic origin with unknown ALT incidence in humans. ALT has been identified in canine HS, a tumor type comparable to human HS that occurs with high rates in certain canine breeds such as Bernese mountain dogs (BMDs). This retrospective study characterized the frequency of ALT in BMD and non-BMD patients diagnosed with HS as surrogates for humans. Formalin-fixed paraffin-embedded tumor samples from 63 dogs at two centers, including 47 BMDs, were evaluated for their ALT activity and relative telomere content (TC) using a radiolabel C-circle assay (CCA). Known ALT-positive samples served as controls. CCA-positive cases were validated via FISH. Two BMD samples showed ALT activity of 1-14% compared to controls. All other samples were ALT-negative. The TC did not correlate with the CCA results. ALT positivity was validated by the appearance of ultrabright telomere foci. Low ALT activity was present in 4% of BMDs with HS and therefore does not appear to be a common target for therapeutic approaches but can have diagnostic value.},
}
@article {pmid37682379,
year = {2023},
author = {Benitez-Roig, V and Martínez-Carpio, PA and Trelles, MA and Cosmina-Timircan, A and Arias-Salgado, EG and Perona, R},
title = {Clinical and laboratory results in vaginal wall restoration using a fractional-pixel-CO2 laser: histological findings and changes in the Ki67 protein and telomere length.},
journal = {Lasers in medical science},
volume = {38},
number = {1},
pages = {206},
pmid = {37682379},
issn = {1435-604X},
support = {PI20-00335//Instituto de Salud Carlos III/ ; },
mesh = {Humans ; Female ; *Carbon Dioxide ; *Hyaluronic Acid ; Ki-67 Antigen/genetics ; Prospective Studies ; Telomere/genetics ; },
abstract = {Thermal deposition of laser energy in the vaginal epithelium in genitourinary syndrome of menopause (GSM) results in clinical and biological effects, but many cellular and molecular changes indicating cell proliferation or senescence inhibition are unknown. The aim of this study is to evaluate the clinical efficacy of the fractional-pixel-CO2 laser in the possible improvement of GMS signs and symptoms that can be correlated with histological changes or with cellular or molecular indicators of restoration. A detailed prospective study was designed to assess 17 women diagnosed with GSM who were treated intravaginally with two laser sessions. Seven non-treated women diagnosed with GSM were used as controls. Three validated outcome questionnaires for assessment of quality of sexual life and urinary incontinence were performed. Vaginal biopsies were collected before the first laser treatment and 4 months following the second session. Histological status, elastin, collagen, and hyaluronic acid content of the biopsies were also evaluated. Cell proliferation was assessed by Ki67 staining. Telomere length (TL) was measured by qPCR. The results show an improvement of the clinical symptoms of GSM (p < 0.05), vaginal epithelium recovery and enhancement of collagen (p < 0.05), elastic fibers (p < 0.005), and hyaluronic acid (p < 0.0005) content in the lamina propria after fractional-pixel-CO2 laser treatment. The laser treatment induced a significant rise on the TL of vaginal epithelial cells (VECs), and a positive correlation was found between the improvements of the collagen and hyaluronic acid content and TL changes (r = 0.82, p < 0.05; r = 0.38, p < 0.05). The percentage of proliferative Ki67-positive VECs was increased in patients whose vaginal TL lengthened after laser treatment (p < 0.05). In conclusion, the results indicate that laser treatment may induce restoration of the vaginal epithelium which is associated to increased TL and proliferation in the VECs. Performing a TL assay could be a suitable tool to evaluate the efficacy of vaginal laser treatment.},
}
@article {pmid37673133,
year = {2023},
author = {Yin, F and Zhou, Y and Xie, D and Hu, J and Luo, X},
title = {Effects of nanomaterial exposure on telomere dysfunction, hallmarks of mammalian and zebrafish cell senescence, and zebrafish mortality.},
journal = {Ageing research reviews},
volume = {91},
number = {},
pages = {102062},
doi = {10.1016/j.arr.2023.102062},
pmid = {37673133},
issn = {1872-9649},
mesh = {Animals ; Humans ; *Zebrafish/metabolism ; *Telomerase/genetics ; Telomere/metabolism ; Shelterin Complex ; Cellular Senescence ; Mammals/metabolism ; },
abstract = {Environmental and occupational exposure to hazardous substances accelerates biological aging. However, the toxic effects of nanomaterials on telomere and cellular senescence (major hallmarks of the biological aging) remained controversial. This study was to synthesize all published evidence to explore the effects of nanomaterial exposure on the telomere change, cellular senescence and mortality of model animals. Thirty-five studies were included by searching electronic databases (PubMed, Embase and Web of Science). The pooled analysis by Stata 15.0 software showed that compared with the control, nanomaterial exposure could significantly shorten the telomere length [measured as kbp: standardized mean difference (SMD) = -1.88; 95% confidence interval (CI) = -3.13 - - 0.64; % of control: SMD = -1.26; 95%CI = -2.11- - 0.42; < 3 kbp %: SMD = 5.76; 95%CI = 2.92 - 8.60), increase the telomerase activity (SMD = -1.00; 95%CI = -1.74 to -0.26), senescence-associated β-galactosidase levels in cells (SMD = 8.20; 95%CI = 6.05 - 10.34) and zebrafish embryos (SMD = 7.32; 95%CI = 4.70 - 9.94) as well as the mortality of zebrafish (SMD = 3.83; 95%CI = 2.94 - 4.72)]. The expression levels of telomerase TERT, shelterin components (TRF1, TRF2 and POT1) and senescence biomarkers (p21, p16) were respectively identified to be decreased or increased in subgroup analyses. In conclusion, this meta-analysis demonstrates that nanomaterial exposure is associated with telomere attrition, cell senescence and organismal death.},
}
@article {pmid37671590,
year = {2023},
author = {Fan, G and Liu, Q and Bi, J and Qin, X and Fang, Q and Wang, Y and Song, L},
title = {Association between female-specific reproductive factors and leukocyte telomere length.},
journal = {Human reproduction (Oxford, England)},
volume = {38},
number = {11},
pages = {2239-2246},
doi = {10.1093/humrep/dead176},
pmid = {37671590},
issn = {1460-2350},
mesh = {Pregnancy ; Female ; Humans ; *Abortion, Spontaneous ; Stillbirth ; Leukocytes ; *Menopause, Premature ; Live Birth ; Contraceptives, Oral ; Menstruation Disturbances ; Telomere ; Chronic Disease ; },
abstract = {STUDY QUESTION: What are the associations between female-specific reproductive factors and leukocyte telomere length (LTL)?<br><br>SUMMARY ANSWER: Early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of oral contraceptives (OCs) and hormone replacement therapy (HRT) were associated with shorter LTL.<br><br>WHAT IS KNOWN ALREADY: Reproductive factors have been associated with age-related diseases, but their associations with cellular aging, as indicated by LTL, are unclear.<br><br>STUDY DESIGN, SIZE, DURATION: This population-based study included 224&#x200a;965 women aged 40-69&#x2009;years from the UK Biobank between 2006 and 2010.<br><br>Women aged 40-69 were included. Female-specific reproductive factors, including age at menarche, age at natural menopause, reproductive lifespan, number of live births, age at first live birth, history of stillbirth, history of miscarriage, and use of OCs and HRT were self-reported. LTL was measured using a validated polymerase chain reaction method. Multiple linear regression and restricted cubic spline models were applied to explore the association between each reproductive factor and LTL.<br><br>After adjustment for potential confounders, early menarche (<12&#x2009;years; percent change, per unit change in LTL Z score: -1.29%, 95% CI: -2.32%, -0.26%), early menopause (<45&#x2009;years; percent change: -7.18%, 95% CI: -8.87%, -5.45%), short reproductive lifespan (<30&#x2009;years; percent change: -6.10%, 95% CI: -8.14%, -4.01%), multiparity (percent change: -3.38%, 95% CI: -4.38%, -2.37%), early age at first live birth (<20&#x2009;years; percent change: -4.46%, 95% CI: -6.00%, -2.90%), and use of OCs (percent change: -1.10%, 95% CI: -2.18%, -0.02%) and HRT (percent change: -3.72%, 95% CI: -4.63%, -2.80%) were all significantly associated with shorter LTL. However, no significant association was found for history of miscarriage and stillbirth. We observed nonlinear relationships of age at menarche, age at natural menopause, reproductive lifespan, and age at first live birth with LTL (Pnonlinear < 0.05).<br><br>Considering that the participants were predominantly of European ethnicity, the findings may not be generalizable to women of other ethnic backgrounds.<br><br>Our findings suggest that early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of OCs and HRT were associated with shorter LTL, which has been linked to various chronic diseases. The accelerated shortening of telomeres may potentially contribute to the development of chronic diseases related to reproductive factors.<br><br>This study was funded by the National Natural Science Foundation of China (82003479, 82073660), Hubei Provincial Natural Science Foundation of China (2023AFB663), and the China Postdoctoral Science Foundation (2019M662646, 2020T130220). The authors have no competing interests to disclose.<br><br>TRIAL REGISTRATION NUMBER: N/A.},
}
@article {pmid37665761,
year = {2023},
author = {Ferrer, A and Lasho, T and Fernandez, JA and Steinauer, NP and Simon, RA and Finke, CM and Carmona, EM and Wylam, ME and Ongie, LJ and Burnap, BN and Arana Yi, C and Sproat, LZ and Foran, J and Badar, T and Mangaonkar, AA and Patnaik, MM},
title = {Patients with telomere biology disorders show context specific somatic mosaic states with high frequency of U2AF1 variants.},
journal = {American journal of hematology},
volume = {98},
number = {12},
pages = {E357-E359},
doi = {10.1002/ajh.27086},
pmid = {37665761},
issn = {1096-8652},
mesh = {Humans ; Splicing Factor U2AF/genetics ; *Telomere/genetics/metabolism ; Biology ; *Telomerase/genetics/metabolism ; },
abstract = {Somatic mosaic states in telomere biology disorders are characterized by somatic variants in the spliceosome and DNA damage response and repair pathways. A likely maladaptive response to short telomeres that may lead to increased hematological cancer.},
}
@article {pmid37662954,
year = {2023},
author = {Han, X and Yan, Z and Fan, K and Guan, X and Hu, B and Li, X and Ou, Y and Cui, B and An, L and Zhang, Y and Gong, J},
title = {The combined signatures of telomere and immune cell landscape provide a prognostic and therapeutic biomarker in glioma.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1220100},
pmid = {37662954},
issn = {1664-3224},
mesh = {Adult ; Humans ; Prognosis ; Biomarkers ; *Telomere/genetics ; *Glioma/diagnosis/genetics/therapy ; Central Nervous System ; Tumor Microenvironment/genetics ; },
abstract = {BACKGROUND: Gliomas, the most prevalent primary malignant tumors of the central nervous system in adults, exhibit slow growth in lower-grade gliomas (LGG). However, the majority of LGG cases progress to high-grade gliomas, posing challenges for prognostication. The tumor microenvironment (TME), characterized by telomere-related genes and immune cell infiltration, strongly influences glioma growth and therapeutic response. Therefore, our objective was to develop a Telomere-TME (TM-TME) classifier that integrates telomere-related genes and immune cell landscape to assess prognosis and therapeutic response in glioma.<br><br>METHODS: This study encompassed LGG patients from the TCGA and CCGA databases. TM score and TME score were derived from the expression signatures of telomere-related genes and the presence of immune cells in LGG, respectively. The TM-TME classifier was established by combining TM and TME scores to effectively predict prognosis. Subsequently, we conducted Kaplan-Meier survival estimation, univariate Cox regression analysis, and receiver operating characteristic curves to validate the prognostic prediction capacity of the TM-TME classifier across multiple cohorts. Gene Ontology (GO) analysis, biological processes, and proteomaps were performed to annotate the functional aspects of each subgroup and visualize the cellular signaling pathways.<br><br>RESULTS: The TM_low+TME_high subgroup exhibited superior prognosis and therapeutic response compared to other subgroups (P<0.001). This finding could be attributed to distinct tumor somatic mutations and cancer cellular signaling pathways. GO analysis indicated that the TM_low+TME_high subgroup is associated with the neuronal system and modulation of chemical synaptic transmission. Conversely, the TM_high+TME_low subgroup showed a strong association with cell cycle and DNA metabolic processes. Furthermore, the classifier significantly differentiated overall survival in the TCGA LGG cohort and served as an independent prognostic factor for LGG patients in both the TCGA cohort (P<0.001) and the CGGA cohort (P<0.001).<br><br>CONCLUSION: Overall, our findings underscore the significance of the TM-TME classifier in predicting prognosis and immune therapeutic response in glioma, shedding light on the complex immune landscape within each subgroup. Additionally, our results suggest the potential of integrating risk stratification with precision therapy for LGG.},
}
@article {pmid37660722,
year = {2024},
author = {Zhou, HH and Jin, B and Liao, Y and Hu, Y and Li, P and YangLha, T and Liu, Y and Xu, J and Wang, B and Zhu, M and Xiao, J and Liu, J and Nüssler, AK and Liu, L and Hao, X and Chen, J and Peng, Z and Yang, W},
title = {Associations of Various Physical Activities with Mortality and Life Expectancy are Mediated by Telomere Length.},
journal = {Journal of the American Medical Directors Association},
volume = {25},
number = {3},
pages = {431-438.e15},
doi = {10.1016/j.jamda.2023.08.002},
pmid = {37660722},
issn = {1538-9375},
mesh = {Adult ; Humans ; Middle Aged ; Prospective Studies ; *Exercise ; *Life Expectancy ; Longevity ; Telomere ; },
abstract = {OBJECTIVES: Physical activity (PA) and telomeres both contribute to healthy aging and longevity. To investigate the optimal dosage of various PA for longevity and the role of telomere length in PA and mortality.<br><br>DESIGN: Prospective cohort study.<br><br>SETTING AND PARTICIPANTS: A total of 333,865 adults (mean age of 56&#xa0;years) from the UK Biobank were analyzed.<br><br>METHODS: Walking, moderate PA (MPA), and vigorous PA (VPA) were self-reported via questionnaire, and leukocyte telomere length (LTL) was measured. Cox proportional hazards regression was used to predict all-cause mortality risk. A flexible parametric Royston-Parmar survival model was used to estimate life expectancy.<br><br>RESULTS: During a median follow-up of 13.8&#xa0;years, 19,789 deaths were recorded. Compared with the no-walking group, 90 to 720&#xa0;minutes/week of walking was similarly associated with 27% to 31% of lower mortality and about 6&#xa0;years of additional life expectancy. We observed nearly major benefits for mortality and life expectancy among those meeting the PA guidelines [151-300&#xa0;minutes/wk for MPA: hazard ratio (HR) 0.80, 95% CI 0.75-0.85, 3.40-3.42 additional life years; 76-150&#xa0;minutes/wk for VPA: HR 0.78, 95% CI 0.75-0.82, 2.61&#xa0;years (2.33-2.89)] vs the no-PA group. Similar benefits were also observed at 76-150 and 301-375&#xa0;minutes/wk of MPA (18%-19% lower mortality, 3.20-3.42 gained years) or 151-300&#xa0;minutes/wk of VPA (20%-26% lower mortality, 2.41-2.61 gained years). The associations between MPA, VPA, and mortality risk were slightly mediated by LTL (&#x2248;1% mediation proportion, both P < .001).<br><br>CONCLUSIONS AND IMPLICATIONS: Our study suggests a more flexible range of PA than the current PA guidelines, which could gain similar benefits and is easier to achieve: 90 to 720&#xa0;minutes/wk of walking, 75 to 375&#xa0;minutes/wk of MPA, and 75 to 300&#xa0;minutes/wk of VPA. Telomeres might be a potential mechanism by which PA promotes longevity.},
}
@article {pmid37658759,
year = {2023},
author = {Casagrande, S and Loveland, JL and Oefele, M and Boner, W and Lupi, S and Stier, A and Hau, M},
title = {Dietary nucleotides can prevent glucocorticoid-induced telomere attrition in a fast-growing wild vertebrate.},
journal = {Molecular ecology},
volume = {32},
number = {19},
pages = {5429-5447},
doi = {10.1111/mec.17114},
pmid = {37658759},
issn = {1365-294X},
mesh = {Humans ; Animals ; Adult ; *Telomere/genetics ; Glucocorticoids ; Nucleotides ; *Passeriformes/genetics ; Adenosine Triphosphate ; Telomere Shortening ; },
abstract = {Telomeres are chromosome protectors that shorten during eukaryotic cell replication and in stressful conditions. Developing individuals are susceptible to telomere erosion when their growth is fast and resources are limited. This is critical because the rate of telomere attrition in early life is linked to health and life span of adults. The metabolic telomere attrition hypothesis (MeTA) suggests that telomere dynamics can respond to biochemical signals conveying information about the organism's energetic state. Among these signals are glucocorticoids, hormones that promote catabolic processes, potentially impairing costly telomere maintenance, and nucleotides, which activate anabolic pathways through the cellular enzyme target of rapamycin (TOR), thus preventing telomere attrition. During the energetically demanding growth phase, the regulation of telomeres in response to two contrasting signals - one promoting telomere maintenance and the other attrition - provides an ideal experimental setting to test the MeTA. We studied nestlings of a rapidly developing free-living passerine, the great tit (Parus major), that either received glucocorticoids (Cort-chicks), nucleotides (Nuc-chicks) or a combination of both (NucCort-chicks), comparing these with controls (Cnt-chicks). As expected, Cort-chicks showed telomere attrition, while NucCort- and Nuc-chicks did not. NucCort-chicks was the only group showing increased expression of a proxy for TOR activation (the gene TELO2), of mitochondrial enzymes linked to ATP production (cytochrome oxidase and ATP-synthase) and a higher efficiency in aerobically producing ATP. NucCort-chicks had also a higher expression of telomere maintenance genes (shelterin protein TERF2 and telomerase TERT) and of enzymatic antioxidant genes (glutathione peroxidase and superoxide dismutase). The findings show that nucleotide availability is crucial for preventing telomere erosion during fast growth in stressful environments.},
}
@article {pmid37653240,
year = {2023},
author = {Roisné-Hamelin, F and Marcand, S},
title = {All roads lead to MRN regulation at telomeres: different paths to one solution.},
journal = {Nature structural &amp; molecular biology},
volume = {30},
number = {9},
pages = {1242-1243},
pmid = {37653240},
issn = {1545-9985},
}
@article {pmid37653239,
year = {2023},
author = {Myler, LR and Toia, B and Vaughan, CK and Takai, K and Matei, AM and Wu, P and Paull, TT and de Lange, T and Lottersberger, F},
title = {DNA-PK and the TRF2 iDDR inhibit MRN-initiated resection at leading-end telomeres.},
journal = {Nature structural &amp; molecular biology},
volume = {30},
number = {9},
pages = {1346-1356},
pmid = {37653239},
issn = {1545-9985},
support = {R01 AG016642/AG/NIA NIH HHS/United States ; R01 GM138548/GM/NIGMS NIH HHS/United States ; R35 CA210036/CA/NCI NIH HHS/United States ; R56 AG016642/AG/NIA NIH HHS/United States ; },
mesh = {Animals ; Mice ; *DNA-Activated Protein Kinase ; *DNA Breaks ; Endonucleases ; Telomere ; DNA ; },
abstract = {Telomeres replicated by leading-strand synthesis lack the 3' overhang required for telomere protection. Surprisingly, resection of these blunt telomeres is initiated by the telomere-specific 5' exonuclease Apollo rather than the Mre11-Rad50-Nbs1 (MRN) complex, the nuclease that acts at DNA breaks. Without Apollo, leading-end telomeres undergo fusion, which, as demonstrated here, is mediated by alternative end joining. Here, we show that DNA-PK and TRF2 coordinate the repression of MRN at blunt mouse telomeres. DNA-PK represses an MRN-dependent long-range resection, while the endonuclease activity of MRN-CtIP, which could cleave DNA-PK off of blunt telomere ends, is inhibited in vitro and in vivo by the iDDR of TRF2. AlphaFold-Multimer predicts a conserved association of the iDDR with Rad50, potentially interfering with CtIP binding and MRN endonuclease activation. We propose that repression of MRN-mediated resection is a conserved aspect of telomere maintenance and represents an ancient feature of DNA-PK and the iDDR.},
}
@article {pmid37650705,
year = {2023},
author = {Liu, M and Lan, Y and Zhang, H and Zhang, X and Wu, M and Yang, L and Zhou, J and Tong, M and Leng, L and Zheng, H and Li, J and Mi, X},
title = {Telomere length is associated with increased risk of cutaneous melanoma: a Mendelian randomization study.},
journal = {Melanoma research},
volume = {33},
number = {6},
pages = {475-481},
doi = {10.1097/CMR.0000000000000917},
pmid = {37650705},
issn = {1473-5636},
mesh = {Humans ; *Melanoma/genetics ; *Skin Neoplasms/genetics ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Telomere/genetics ; Melanoma, Cutaneous Malignant ; },
abstract = {The MR analysis using two TL GWAS datasets revealed strong and consistent evidence that long TL is causally associated with an increased risk of CM. The analysis of the Codd et al. dataset found that long TL significantly predicted an elevated risk of CM (IVW OR = 2.411, 95% CI 2.092-2.780, P = 8.05E-34). Similarly, the analysis of the Li et al. dataset yielded consistent positive results across all MR methods, providing further robustness to the causal relationship (IVW OR = 2.324, 95% CI 1.516-3.565, P = 1.11E-04). The study provides evidence for a causal association between TL and CM susceptibility, indicating that longer TL increases the risk of developing CM and providing insight into the unique telomere biology in melanoma pathogenesis. Telomere maintenance pathways may be a potential target for preventing and treating CM.},
}
@article {pmid37648073,
year = {2023},
author = {Greenland, JR and Guo, R and Lee, S and Tran, L and Kapse, B and Kukreja, J and Hays, SR and Golden, JA and Calabrese, DR and Singer, JP and Wolters, PJ},
title = {Short airway telomeres are associated with primary graft dysfunction and chronic lung allograft dysfunction.},
journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation},
volume = {42},
number = {12},
pages = {1700-1709},
pmid = {37648073},
issn = {1557-3117},
support = {R01 HL161048/HL/NHLBI NIH HHS/United States ; R01 HL139897/HL/NHLBI NIH HHS/United States ; U01 HL145435/HL/NHLBI NIH HHS/United States ; I01 CX002011/CX/CSRD VA/United States ; R01 HL151552/HL/NHLBI NIH HHS/United States ; IK2 BX005301/BX/BLRD VA/United States ; R01 HL134851/HL/NHLBI NIH HHS/United States ; U01 HL163242/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Primary Graft Dysfunction/genetics ; Lung ; *Lung Transplantation/adverse effects ; Allografts ; Fibrosis ; Telomere ; Retrospective Studies ; },
abstract = {Primary graft dysfunction (PGD) is a major risk factor for chronic lung allograft dysfunction (CLAD) following lung transplantation, but the mechanisms linking these pathologies are poorly understood. We hypothesized that the replicative stress induced by PGD would lead to erosion of telomeres, and that this telomere dysfunction could potentiate CLAD. In a longitudinal cohort of 72 lung transplant recipients with >6 years median follow-up time, we assessed tissue telomere length, PGD grade, and freedom from CLAD. Epithelial telomere length and fibrosis-associated gene expression were assessed on endobronchial biopsies taken at 2 to 4 weeks post-transplant by TeloFISH assay and nanoString digital RNA counting. Negative-binomial mixed-effects and Cox-proportional hazards models accounted for TeloFISH staining batch effects and subject characteristics including donor age. Increasing grade of PGD severity was associated with shorter airway epithelial telomere lengths (p = 0.01). Transcriptomic analysis of fibrosis-associated genes showed alteration in fibrotic pathways in airway tissue recovering from PGD, while telomere dysfunction was associated with inflammation and impaired remodeling. Shorter tissue telomere length was in turn associated with increased CLAD risk, with a hazard ratio of 1.89 (95% CI 1.16-3.06) per standard deviation decrease in airway telomere length, after adjusting for subject characteristics. PGD may accelerate telomere dysfunction, potentiating immune responses and dysregulated repair. Epithelial cell telomere dysfunction may represent one of several mechanisms linking PGD to CLAD.},
}
@article {pmid37645045,
year = {2023},
author = {Li, H and Durbin, R},
title = {Genome assembly in the telomere-to-telomere era.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {37645045},
issn = {2331-8422},
support = {/WT_/Wellcome Trust/United Kingdom ; R01 HG010040/HG/NHGRI NIH HHS/United States ; },
abstract = {De novo assembly is the process of reconstructing the genome sequence of an organism from sequencing reads. Genome sequences are essential to biology, and assembly has been a central problem in bioinformatics for four decades. Until recently, genomes were typically assembled into fragments of a few megabases at best but technological advances in long-read sequencing now enable near complete chromosome-level assembly, also known as telomere-to-telomere assembly, for many organisms. Here we review recent progress on assembly algorithms and protocols. We focus on how to derive near telomere-to-telomere assemblies and discuss potential future developments.},
}
@article {pmid37641324,
year = {2023},
author = {Häussler, S and Ghaffari, MH and Seibt, K and Sadri, H and Alaedin, M and Huber, K and Frahm, J and Dänicke, S and Sauerwein, H},
title = {Blood and liver telomere length, mitochondrial DNA copy number, and hepatic gene expression of mitochondrial dynamics in mid-lactation cows supplemented with l-carnitine under systemic inflammation.},
journal = {Journal of dairy science},
volume = {106},
number = {12},
pages = {9822-9842},
doi = {10.3168/jds.2023-23556},
pmid = {37641324},
issn = {1525-3198},
mesh = {Female ; Cattle ; Animals ; *Lactation/physiology ; Lipopolysaccharides/adverse effects ; Carnitine/metabolism ; DNA, Mitochondrial ; DNA Copy Number Variations ; Mitochondrial Dynamics ; Inflammation/veterinary ; Dietary Supplements ; Liver/metabolism ; Milk/metabolism ; Diet/veterinary ; Gene Expression ; Fibrinogen/adverse effects/metabolism ; RNA, Messenger/metabolism ; Mitochondrial Proteins/metabolism ; Telomere ; *Cattle Diseases/metabolism ; },
abstract = {The current study was conducted to examine the effect of l-carnitine (LC) supplementation on telomere length and mitochondrial DNA copy number (mtDNAcn) per cell in mid-lactation cows challenged by lipopolysaccharide (LPS) in blood and liver. The mRNA abundance of 31 genes related to inflammation, oxidative stress, and the corresponding stress response mechanisms, the mitochondrial quality control and the protein import system, as well as the phosphatidylinositol 3-kinase/protein kinase B pathway, were assessed using microfluidics integrated fluidic circuit chips (96.96 dynamic arrays). In addition to comparing the responses in cows with or without LC, our objectives were to characterize the oxidative and inflammatory status by assessing the circulating concentration of lactoferrin (Lf), haptoglobin (Hp), fibrinogen, derivates of reactive oxygen metabolites (dROM), and arylesterase activity (AEA), and to extend the measurement of Lf and Hp to milk. Pluriparous Holstein cows were assigned to either a control group (CON, n = 26) or an LC-supplemented group (CAR; 25 g LC/cow per day; d 42 ante partum to d 126 postpartum (PP), n = 27). On d 111 PP, each cow was injected intravenously with LPS (Escherichia coli O111:B4, 0.5 µg/kg). The mRNA abundance was examined in liver biopsies of d -11 and +1 relative to LPS administration. Plasma and milk samples were frequently collected before and after the challenge. After LPS administration, circulating plasma fibrinogen and serum dROM concentrations increased, whereas AEA decreased. Moreover, serum P4 initially increased by 3 h after LPS administration and declined thereafter irrespective of grouping. The Lf concentrations increased in both groups after LPS administration, with the CAR group showing greater concentrations in serum and milk than the CON group. After LPS administration, telomere length in blood increased, whereas mtDNAcn per cell decreased; however, both remained unaffected in liver. For mitochondrial protein import genes, the hepatic mRNA abundance of the translocase of the mitochondrial inner membrane (TIM)-17B was increased in CAR cows. Moreover, TIM23 increased in both groups after LPS administration. Regarding the mRNA abundance of genes related to stress response mechanisms, 7 out of 14 genes showed group × time interactions, indicating a (local) protective effect due to the dietary LC supplementation against oxidative stress in mid-lactating dairy cows. For mtDNAcn and telomere length, the effects of the LPS-induced inflammation were more pronounced than the dietary supplementation of LC. Dietary LC supplementation affected the response to LPS primarily by altering mitochondrial dynamics. Regarding mRNA abundance of genes related to the mitochondrial protein import system, the inner mitochondrial membrane translocase (TIM complex) seemed to be more sensitive to dietary LC than the outer mitochondrial membrane translocase (TOM complex).},
}
@article {pmid37634078,
year = {2023},
author = {Wang, L and Zhang, M and Li, M and Jiang, X and Jiao, W and Song, Q},
title = {A telomere-to-telomere gap-free assembly of soybean genome.},
journal = {Molecular plant},
volume = {16},
number = {11},
pages = {1711-1714},
doi = {10.1016/j.molp.2023.08.012},
pmid = {37634078},
issn = {1752-9867},
mesh = {*Glycine max/genetics ; *Telomere/genetics ; },
}
@article {pmid37628647,
year = {2023},
author = {Igoshin, AV and Yudin, NS and Romashov, GA and Larkin, DM},
title = {A Multibreed Genome-Wide Association Study for Cattle Leukocyte Telomere Length.},
journal = {Genes},
volume = {14},
number = {8},
pages = {},
pmid = {37628647},
issn = {2073-4425},
mesh = {Animals ; Cattle/genetics ; Cell Division ; *Genome-Wide Association Study ; *Leukocytes/physiology ; *Telomere/genetics/physiology ; },
abstract = {Telomeres are terminal DNA regions of chromosomes that prevent chromosomal fusion and degradation during cell division. In cattle, leukocyte telomere length (LTL) is associated with longevity, productive lifespan, and disease susceptibility. However, the genetic basis of LTL in this species is less studied than in humans. In this study, we utilized the whole-genome resequencing data of 239 animals from 17 cattle breeds for computational leukocyte telomere length estimation and subsequent genome-wide association study of LTL. As a result, we identified 42 significant SNPs, of which eight were found in seven genes (EXOC6B, PTPRD, RPS6KC1, NSL1, AGBL1, ENSBTAG00000052188, and GPC1) when using covariates for two major breed groups (Turano-Mongolian and European). Association analysis with covariates for breed effect detected 63 SNPs, including 13 in five genes (EXOC6B, PTPRD, RPS6KC1, ENSBTAG00000040318, and NELL1). The PTPRD gene, demonstrating the top signal in analysis with breed effect, was previously associated with leukocyte telomere length in cattle and likely is involved in the mechanism of alternative lengthening of telomeres. The single nucleotide variants found could be tested for marker-assisted selection to improve telomere-length-associated traits.},
}
@article {pmid37615075,
year = {2023},
author = {Ha, SJ and Kwag, E and Kim, S and Park, JH and Park, SJ and Yoo, HS},
title = {Effect of Traditional Korean Medicine Oncotherapy on the Survival, Quality of Life, and Telomere Length: A Prospective Cohort Study.},
journal = {Integrative cancer therapies},
volume = {22},
number = {},
pages = {15347354231154267},
pmid = {37615075},
issn = {1552-695X},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Female ; Humans ; *Quality of Life ; Prospective Studies ; Progression-Free Survival ; *Medicine, Korean Traditional ; Telomere/genetics ; Republic of Korea ; },
abstract = {A 4-year prospective cohort study on patients with lung, gastric, hepatic, colorectal, breast, uterine, and ovarian cancer was conducted at the East-West Cancer Center (EWCC) of Daejeon Korean Medicine Hospital in Daejeon, Korea. We divided patients into 2 groups based on how long they had been receiving TKM oncotherapy and compared event-free survival (EFS), telomere length change, and quality of life (QoL). The study collected data on 83 patients from October 2016 to June 2020 and discovered no statistical differences in EFS based on the duration of TKM oncotherapy. In the analysis of changes in QoL outcomes, there were no statistically significant group differences between the groups. After controlling for covariates that could affect telomere length, the long-term TKM oncotherapy group had a higher daily telomere attrition rate. The study of the relationship between telomere length and prognostic factors discovered that patients with advanced N stage at the time of diagnosis and who had previously received radiotherapy had shorter telomere length. When examining associations between SNP genotype and percentile score of telomere length, this study was able to confirm an association between telomere length and rs4387287. This study is significant because it is the first to assess the effects of TKM oncotherapy and investigate telomere length-related factors. To assess the effects of TKM oncotherapy on cancer patients' survival and QoL, a longer-term observational study with a larger sample size is required.},
}
@article {pmid37611374,
year = {2023},
author = {Dupoué, A and Mello, DF and Trevisan, R and Dubreuil, C and Queau, I and Petton, S and Huvet, A and Guével, B and Com, E and Pernet, F and Salin, K and Fleury, E and Corporeau, C},
title = {Intertidal limits shape covariation between metabolic plasticity, oxidative stress and telomere dynamics in Pacific oyster (Crassostrea gigas).},
journal = {Marine environmental research},
volume = {191},
number = {},
pages = {106149},
doi = {10.1016/j.marenvres.2023.106149},
pmid = {37611374},
issn = {1879-0291},
abstract = {In intertidal zones, species such as sessile shellfish exhibit extended phenotypic plasticity to face rapid environmental changes, but whether frequent exposure to intertidal limits of the distribution range impose physiological costs for the animal remains elusive. Here, we explored how phenotypic plasticity varied along foreshore range at multiple organization levels, from molecular to cellular and whole organism acclimatization, in the Pacific oyster (Crassostrea gigas). We exposed 7-month-old individuals for up to 16 months to three foreshore levels covering the vertical range for this species, representing 20, 50 and 80% of the time spent submerged monthly. Individuals at the upper range limit produced energy more efficiently, as seen by steeper metabolic reactive norms and unaltered ATP levels despite reduced mitochondrial density. By spending most of their time emerged, oysters mounted an antioxidant shielding concomitant with lower levels of pro-oxidant proteins and postponed age-related telomere attrition. Instead, individuals exposed at the lower limit range near subtidal conditions showed lower energy efficiencies, greater oxidative stress and shorter telomere length. These results unraveled the extended acclimatization strategies and the physiological costs of living too fast in subtidal conditions for an intertidal species.},
}
@article {pmid37610666,
year = {2023},
author = {Frydrychová, R&#x10c; and Konopová, B and Peska, V and Brejcha, M and Sábová, M},
title = {Telomeres and telomerase: active but complex players in life-history decisions.},
journal = {Biogerontology},
volume = {},
number = {},
pages = {},
pmid = {37610666},
issn = {1573-6768},
support = {LUAUS23128//Ministry of Education/ ; },
abstract = {Studies on human telomeres have established that telomeres exert a significant influence on lifespan and health of organisms. However, recent research has indicated that the original idea that telomeres affect lifespan in a universal and central manner across all eukaryotic species is an oversimplification. Indeed, findings from a variety of animal species revealed that the role of telomere biology in aging is more subtle and intricate than previously recognized. Here, we show how telomere biology varies depending on the taxon. We also show how telomere biology corresponds to basic life history traits and affects the life table of a species and investments in growth, body size, reproduction, and lifespan; telomeres are hypothesized to shape evolutionary perspectives for species in an active but complex manner. Our evaluation is based on telomere biology data from many examples from throughout the animal kingdom that vary according to the degree of organismal complexity and life history strategies.},
}
@article {pmid37608257,
year = {2023},
author = {Liu, C and Ding, K and Abdul, M and Sun, QC and Zhang, ZF and Dong, MM and Han, L and Dai, MS and Guan, HL and Han, Y and Liu, H and Chen, XF and Cao, JL},
title = {The relationship between longer leukocyte telomeres and dNCR in non-cardiac surgery patients: a retrospective analysis.},
journal = {BMC anesthesiology},
volume = {23},
number = {1},
pages = {284},
pmid = {37608257},
issn = {1471-2253},
mesh = {Aged ; Humans ; Retrospective Studies ; *Aging ; *Cognitive Dysfunction ; Leukocytes ; Telomere ; },
abstract = {BACKGROUND: Cognitive decline following surgery is a common concern among elderly individuals. Leukocyte telomere length (LTL) can be assessed as a biological clock connected to an individual lifespan. However, the mechanisms causing this inference are still not fully understood. As a result of this, LTL has the potential to be useful as an aging-related biomarker for assessing delayed neurocognitive recovery (dNCR) and related diseases.<br><br>METHODS: For this study, 196 individuals over 60 who were scheduled due to major non-cardiac surgical operations attended neuropsychological testing before surgery, followed by additional testing one week later. The finding of dNCR was based on a measured Z-score&#x2009;&#x2264;&#x2009;-1.96 on two or more separate tests. The frequency of dNCR was presented as the primary outcome of the study. Secondly, we evaluated the association between dNCR and preoperative LTL.<br><br>RESULTS: Overall, 20.4% [40/196; 95% confidence interval (CI), 14.7-26.1%] of patients exhibited dNCR 1-week post-surgery. Longer LTL was identified as a predictor for the onset of early cognitive impairment resulting in postoperative cognitive decline [odds ratio (OR), 14.82; 95% CI, 4.01-54.84; P&#x2009;<&#x2009;0.001], following adjustment of age (OR, 12.33; 95% CI, 3.29-46.24; P&#x2009;<&#x2009;0.001). The dNCR incidence based on LTL values of these patients, the area under the receiver operating characteristic (ROC) curve was 0.79 (95% CI, 0.722-0.859; P&#x2009;<&#x2009;0.001). At an optimal cut-off value of 0.959, LTL values offered respective specificity and sensitivity values of 64.7% and 87.5%.<br><br>CONCLUSIONS: In summary, the current study revealed that the incidence of dNCR was strongly associated with prolonged LTL. Furthermore, this biomarker could help identify high-risk patients and offer insight into the pathophysiology of dNCR.},
}
@article {pmid37606092,
year = {2023},
author = {Eastwood, JR and Dupoué, A and Verhulst, S and Cockburn, A and Peters, A},
title = {Cool, dry nights and short heatwaves during growth result in longer telomeres in temperate songbird nestlings.},
journal = {Molecular ecology},
volume = {32},
number = {19},
pages = {5382-5393},
doi = {10.1111/mec.17107},
pmid = {37606092},
issn = {1365-294X},
mesh = {Animals ; *Songbirds/genetics ; Climate ; Temperature ; *Passeriformes ; Telomere/genetics ; },
abstract = {Exposure to rising sublethal temperatures can affect development and somatic condition, and thereby Darwinian fitness. In the context of climate warming, these changes could have implications for population viability, but they can be subtle and consequently difficult to quantify. Using telomere length (TL) as a known biomarker of somatic condition in early life, we investigated the impact of pre-hatching and nestling climate on six cohorts of wild nestling superb fairy wrens (Malurus cyaneus) in temperate south-eastern Australia. Models incorporating only climate information from the nestling phase were best supported compared to those including the (pre-)laying to incubation phase (previously shown to affect mass) or both phases combined. This implies that nestling TL is most sensitive to ambient climate in the nestling phase. The top model showed a negative relationship between early-life TL and nestling mean daily minimum temperature when rainfall was low which gradually became positive with increasing rainfall. In addition, there was a positive relationship between TL and the frequency of hot days (daily maximum temperature ≥35°C), although these temperatures were rare and short-term. Including other pre-hatching and nestling period, climate variables (e.g., mean daily maximum temperature and mean diurnal temperature variability) did not improve the prediction of nestling TL. Overall, our results suggest that cooler nights when conditions are dry and short-term temperature spikes above 35°C during development are conducive for somatic maintenance. While these findings indicate a potential pathway for climate warming to impact wildlife fitness, they emphasize the need to elucidate the mechanisms underlying these complex associations.},
}
@article {pmid37602392,
year = {2024},
author = {Lyčka, M and Bubeník, M and Závodník, M and Peska, V and Fajkus, P and Demko, M and Fajkus, J and Fojtová, M},
title = {TeloBase: a community-curated database of telomere sequences across the tree of life.},
journal = {Nucleic acids research},
volume = {52},
number = {D1},
pages = {D311-D321},
pmid = {37602392},
issn = {1362-4962},
support = {20-01331X//Czech Science Foundation/ ; //CzechElib/ ; },
mesh = {Nucleotide Motifs ; Plants/genetics ; *Telomerase/genetics ; Telomere/genetics/metabolism ; *Databases, Genetic ; },
abstract = {Discoveries over the recent decade have demonstrated the unexpected diversity of telomere DNA motifs in nature. However, currently available resources, 'Telomerase database' and 'Plant rDNA database', contain just fragments of all relevant literature published over decades of telomere research as they have a different primary focus and limited updates. To fill this gap, we gathered data about telomere DNA sequences from a thorough literature screen as well as by analysing publicly available NGS data, and we created TeloBase (http://cfb.ceitec.muni.cz/telobase/) as a comprehensive database of information about telomere motif diversity. TeloBase is supplemented by internal taxonomy utilizing popular on-line taxonomic resources that enables in-house data filtration and graphical visualisation of telomere DNA evolutionary dynamics in the form of heat tree plots. TeloBase avoids overreliance on administrators for future data updates by having a simple form and community-curation system for application and approval, respectively, of new telomere sequences by users, which should ensure timeliness of the database and topicality. To demonstrate TeloBase utility, we examined telomere motif diversity in species from the fungal genus Aspergillus, and discovered (TTTATTAGGG)n sequence as a putative telomere motif in the plant family Chrysobalanaceae. This was bioinformatically confirmed by analysing template regions of identified telomerase RNAs.},
}
@article {pmid37601866,
year = {2023},
author = {Gorsi, HS and Gallardo-Rios, M and Savaşan, S},
title = {Short telomere length in autoimmune neutropenia of childhood: A mere coincidence or an association?.},
journal = {EJHaem},
volume = {4},
number = {3},
pages = {827-828},
pmid = {37601866},
issn = {2688-6146},
}
@article {pmid37600718,
year = {2023},
author = {Han, X and Wu, T and Liu, CY},
title = {Univariable and multivariable Mendelian randomization investigating the effects of telomere length on the risk of adverse pregnancy outcomes.},
journal = {Frontiers in endocrinology},
volume = {14},
number = {},
pages = {1225600},
pmid = {37600718},
issn = {1664-2392},
mesh = {Infant, Newborn ; Female ; Pregnancy ; Humans ; Pregnancy Outcome ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Premature Birth ; *Abortion, Spontaneous ; *Diabetes, Gestational ; Fetal Growth Retardation ; *Pre-Eclampsia/epidemiology/genetics ; Telomere/genetics ; },
abstract = {BACKGROUND: Numerous observational studies have revealed a correlation between telomere length (TL) and adverse pregnancy outcomes (APOs). However, the impacts of TL on APOs are still unclear.<br><br>METHODS: Mendelian randomization (MR) was carried out using summary data from genome-wide association studies (GWAS). Inverse variance weighted (IVW) was employed as the primary analysis to explore the causal relationship between TL and APOs. The exposure data came from a GWAS dataset of IEU analysis of the United Kingdom Biobank phenotypes consisting of 472,174 European participants. Summary-level data for five APOs were obtained from the GWAS datasets of the FinnGen consortium. We also performed multivariate MR (MVMR), adjusting for smoking, alcohol intake, body mass index (BMI), and number of live births. In addition, we conducted a series of rigorous analyses to further examine the validity of our MR findings.<br><br>RESULTS: After Bonferroni correction and rigorous quality control, univariable MR (UVMR) demonstrated that a shorter TL was significantly associated with an increased risk of spontaneous abortion (SA) (odds ratio [OR]: 0.815; 95% confidence interval [CI]: 0.714-0.930; P = 0.002) and preterm birth (PTB) (OR: 0.758; 95% CI: 0.632-0.908; P = 0.003) in the IVW model. There was a nominally significant relationship between TL and preeclampsia (PE) in the IVW model (OR: 0.799; 95% CI: 0.651-0.979; P = 0.031). However, no significant association was found between TL and gestational diabetes mellitus (GDM) (OR: 0.950; 95% CI: 0.804-1.122; P = 0.543) or fetal growth restriction (FGR) (OR: 1.187; 95% CI: 0.901-1.565; P = 0.223) among the five statistical models. Furthermore, we did not find a significant causal effect of APOs on TL in the reverse MR analysis. MVMR analysis showed that the causal effects of TL on SA remained significant after accounting for smoking, alcohol intake, BMI, and number of live births.<br><br>CONCLUSION: Our MR study provides robust evidence that shorter telomeres were associated with an increased risk of SA. Further work is necessary to investigate the potential mechanisms. UVMR and MVMR findings showed limited evidence that TL affects the risk of PTB, PE, GDM, and FGR, illustrating that the outcomes of previous observational studies may have been confounded.},
}
@article {pmid37599304,
year = {2023},
author = {Mo, W and Shu, Y and Liu, B and Long, Y and Li, T and Cao, X and Deng, X and Zhai, J},
title = {Single-molecule targeted accessibility and methylation sequencing of centromeres, telomeres and rDNAs in Arabidopsis.},
journal = {Nature plants},
volume = {9},
number = {9},
pages = {1439-1450},
pmid = {37599304},
issn = {2055-0278},
mesh = {*Arabidopsis/genetics ; Centromere/genetics ; Telomere/genetics ; DNA Methylation ; Chromatin/genetics ; DNA, Ribosomal ; },
abstract = {The short read-length of next-generation sequencing makes it challenging to characterize highly repetitive regions (HRRs) such as centromeres, telomeres and ribosomal DNAs. Based on recent strategies that combined long-read sequencing and exogenous enzymatic labelling of open chromatin, we developed single-molecule targeted accessibility and methylation sequencing (STAM-seq) in plants by further integrating nanopore adaptive sampling to investigate the HRRs in wild-type Arabidopsis and DNA methylation mutants that are defective in CG- or non-CG methylation. We found that CEN180 repeats show higher chromatin accessibility and lower DNA methylation on their forward strand, individual rDNA units show a negative correlation between their DNA methylation and accessibility, and both accessibility and CHH methylation levels are lower at telomere compared to adjacent subtelomeric region. Moreover, DNA methylation-deficient mutants showed increased chromatin accessibility at HRRs, consistent with the role of DNA methylation in maintaining heterochromatic status in plants. STAM-seq can be applied to study accessibility and methylation of repetitive sequences across diverse plant species.},
}
@article {pmid37598977,
year = {2023},
author = {Stylianakis, E and Chan, JPK and Law, PP and Jiang, Y and Khadayate, S and Karimi, MM and Festenstein, R and Vannier, JB},
title = {Mouse HP1γ regulates TRF1 expression and telomere stability.},
journal = {Life sciences},
volume = {331},
number = {},
pages = {122030},
doi = {10.1016/j.lfs.2023.122030},
pmid = {37598977},
issn = {1879-0631},
support = {MC_UP_1102/14/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Animals ; Humans ; Mice ; Chromatin ; DNA ; *Fibroblasts/metabolism ; RNA/genetics/metabolism ; *Telomere/genetics/metabolism ; Transcription Factors/genetics ; Telomeric Repeat Binding Protein 1/metabolism ; },
abstract = {AIMS: Telomeric repeat-containing RNAs are long non-coding RNAs generated from the telomeres. TERRAs are essential for the establishment of heterochromatin marks at telomeres, which serve for the binding of members of the heterochromatin protein 1 (HP1) protein family of epigenetic modifiers involved with chromatin compaction and gene silencing. While HP1γ is enriched on gene bodies of actively transcribed human and mouse genes, it is unclear if its transcriptional role is important for HP1γ function in telomere cohesion and telomere maintenance. We aimed to study the effect of mouse HP1γ on the transcription of telomere factors and molecules that can affect telomere maintenance.<br><br>MAIN METHODS: We investigated the telomere function of HP1&#x3b3; by using HP1&#x3b3; deficient mouse embryonic fibroblasts (MEFs). We used gene expression analysis of HP1&#x3b3; deficient MEFs and validated the molecular and mechanistic consequences of HP1&#x3b3; loss by telomere FISH, immunofluorescence, RT-qPCR and DNA-RNA immunoprecipitation (DRIP).<br><br>KEY FINDINGS: Loss of HP1&#x3b3; in primary MEFs led to a downregulation of various telomere and telomere-accessory transcripts, including the shelterin protein TRF1. Its downregulation is associated with increased telomere replication stress and DNA damage (&#x3b3;H2AX), effects more profound in females. We suggest that the source for the impaired telomere maintenance is a consequence of increased telomeric DNA-RNA hybrids and TERRAs arising at and from mouse chromosomes 18 and X.<br><br>SIGNIFICANCE: Our results suggest an important transcriptional control by mouse HP1&#x3b3; of various telomere factors including TRF1 protein and TERRAs that has profound consequences on telomere stability, with a potential sexually dimorphic nature.},
}
@article {pmid37598517,
year = {2023},
author = {Zhang, D and Chen, X and Huang, K and Zheng, Q and Fu, Y and Ma, J and Ren, X and Xu, B and Liu, P and Liu, J and Lu, S},
title = {Urinary essential and toxic metal mixtures, and type 2 diabetes mellitus: Telomere shortening as an intermediary factor?.},
journal = {Journal of hazardous materials},
volume = {459},
number = {},
pages = {132329},
doi = {10.1016/j.jhazmat.2023.132329},
pmid = {37598517},
issn = {1873-3336},
mesh = {Adult ; Humans ; *Diabetes Mellitus, Type 2 ; Mediation Analysis ; Telomere Shortening ; Bayes Theorem ; Cadmium/toxicity ; Cross-Sectional Studies ; Lead ; },
abstract = {The joint effect of metal mixtures on telomere function and type 2 diabetes mellitus (T2DM) is unclear. This large-scale cross-sectional study sought to assess the role of telomere length (TL) in the relationship between urinary essential and toxic metal mixtures, and T2DM in 7410 Chinese adults ≥ 60 years of age. Essential (Cr, Cu, Zn, Se) and non-essential metals (V, Al, Sb, Sn, Cd, Pb) in urine samples were quantified, while leukocyte TL was measured from blood samples. Restricted cubic splines regression showed nonlinear relationships between single metal and T2DM, and between TL and T2DM. Bayesian kernel machine regression and quantile-based g-computation showed that the overall status of urinary metals was positively associated with risk of developing T2DM, which was mainly explained by exposure to Pb, Cd, and Sb, excessive Se intake, and high excretion of Zn. Mediation analyses showed that shortened TL mediated 27.9% of the overall positive effect of metal exposure on T2DM, and this mediation was mainly explained by toxic metal exposure and excessive Se intake. Tobacco smoke exposure, extensive cooking at home, and black tea consumption were found to be important contributors of toxic metal exposures. Further studies are needed to explore the recommended Zn dosage for T2DM patients at different stages, which may ameliorate pancreatic senescence and glycemic progression.},
}
@article {pmid37596879,
year = {2023},
author = {Zhang, Y and Zhu, Y and Ye, M and Mao, Y and Zhan, Y},
title = {Telomere length and its association with systemic lupus erythematosus in an Asian population: A Mendelian randomization study.},
journal = {Lupus},
volume = {32},
number = {10},
pages = {1222-1226},
doi = {10.1177/09612033231195953},
pmid = {37596879},
issn = {1477-0962},
mesh = {Humans ; Asian ; Genome-Wide Association Study ; *Lupus Erythematosus, Systemic/genetics ; Mendelian Randomization Analysis ; *Telomere/genetics ; Telomere Shortening/genetics ; Genetic Predisposition to Disease ; },
abstract = {OBJECTIVES: To investigate whether shorter telomere length is a causal risk factor for systemic lupus erythematosus (SLE) in the Asian population.<br><br>METHODS: We applied the two-sample Mendelian randomization (MR) method to the pooled statistics from a genome-wide association study (GWAS) of 6,707 SLE cases and 16,047 controls. We selected nine single-nucleotide polymorphisms (SNPs) with genome-wide significance as instrumental variables for telomere length. The main analysis was carried out by the random-effects inverse-variance weighted (IVW) method. Horizontal pleiotropy was evaluated by the intercept of MR-Egger regression.<br><br>RESULTS: A potentially causal relationship between longer genetically predicted telomere length and increased risk of systemic lupus erythematosus (OR = 1.72, 95%CI: 1.21, 2.46, p = 0.01) was observed. The MR-Egger regression demonstrated an intercept proximal to zero (intercept = 0.017, p = 0.69), which does not provide evidence of the presence of horizontal pleiotropy.<br><br>CONCLUSIONS: Our findings provided evidence supporting a potential causal relationship between longer telomere length and increased risk of systemic lupus erythematosus.},
}
@article {pmid37595788,
year = {2023},
author = {He, Y and Chu, Y and Guo, S and Hu, J and Li, R and Zheng, Y and Ma, X and Du, Z and Zhao, L and Yu, W and Xue, J and Bian, W and Yang, F and Chen, X and Zhang, P and Wu, R and Ma, Y and Shao, C and Chen, J and Wang, J and Li, J and Wu, J and Hu, X and Long, Q and Jiang, M and Ye, H and Song, S and Li, G and Wei, Y and Xu, Y and Ma, Y and Chen, Y and Wang, K and Bao, J and Xi, W and Wang, F and Ni, W and Zhang, M and Yu, Y and Li, S and Kang, Y and Gao, Z},
title = {T2T-YAO: A Telomere-to-telomere Assembled Diploid Reference Genome for Han Chinese.},
journal = {Genomics, proteomics &amp; bioinformatics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.gpb.2023.08.001},
pmid = {37595788},
issn = {2210-3244},
abstract = {Since its initial release in 2001, the human reference genome has undergone continuous improvement in quality, and the recently released telomere-to-telomere version-T2T-CHM13-reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified, nearly homozygous genome of a hydatidiform mole cell line. To provide an authentic complete diploid human genome reference for the Han Chinese, the largest population in the world, we have assembled the genome of a male Han Chinese individual, T2T-YAO, which includes telomere-to-telomere assemblies of all the 22+X+M and 22+Y chromosomes in both haploid. The quality of T2T-YAO is much better than all currently available diploid assemblies, and its haploid version, T2T-YAO-hp, generated by selecting the better assembly for each autosome, reaches the top quality of fewer than one error per 29.5 Mb, even higher than that of T2T-CHM13. Derived from an individual living in the aboriginal region of the Han population, T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors. Each haplotype of T2T-YAO possesses ∼330 Mb exclusive sequences, ∼3100 unique genes, and tens of thousands of nucleotide and structural variations as compared to CHM13, highlighting the necessity of population-stratified reference genome. The construction of T2T-YAO, a truly accurate and authentic representative of the Chinese population, would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes, especially within the context of the unique variations of the Chinese population.},
}
@article {pmid37594236,
year = {2023},
author = {Rinne, GR and Carroll, JE and Guardino, CM and Shalowitz, MU and Ramey, SL and Schetter, CD},
title = {Parental preconception posttraumatic stress symptoms and maternal prenatal inflammation prospectively predict shorter telomere length in children.},
journal = {Psychosomatic medicine},
volume = {},
number = {},
pages = {},
pmid = {37594236},
issn = {1534-7796},
support = {U01 HD044207/HD/NICHD NIH HHS/United States ; R03 HD059584/HD/NICHD NIH HHS/United States ; R01 HD072021/HD/NICHD NIH HHS/United States ; U01 HD054791/HD/NICHD NIH HHS/United States ; U01 HD044245/HD/NICHD NIH HHS/United States ; U01 HD044253/HD/NICHD NIH HHS/United States ; U01 HD044226/HD/NICHD NIH HHS/United States ; U01 HD044219/HD/NICHD NIH HHS/United States ; T32 MH015750/MH/NIMH NIH HHS/United States ; U01 NR008929/NR/NINR NIH HHS/United States ; },
abstract = {OBJECTIVE: Parental trauma exposure and trauma-related distress can increase risk for adverse health outcomes in offspring, but the pathways implicated in intergenerational transmission are not fully explicated. Accelerated biological aging may be one mechanism underlying less favorable health in trauma-exposed individuals and their offspring. This study examines associations of preconception maternal and paternal posttraumatic stress disorder (PTSD) symptoms with child telomere length, and maternal prenatal C-reactive protein (CRP) as a biological mechanism.<br><br>METHODS: Mothers (n = 127) and a subset of the fathers (n = 84) reported on PTSD symptoms before conception. Mothers provided blood spots in the second and third trimester that were assayed for CRP. At age 4, children provided buccal cells for measurement of telomere length. Models adjusted for parental age, socioeconomic status, maternal pre-pregnancy BMI, child biological sex, and child age.<br><br>RESULTS: Mothers' PTSD symptoms were significantly associated with shorter child telomere length (&#x3b2; = -0.22, SE = 0.10, p = .023). Fathers' PTSD symptoms were also inversely associated with child telomere length (&#x3b2; = -0.21, SE = 0.11), though nonsignificant (p = .065). There was no significant indirect effect of mothers' PTSD symptoms on child telomere length through CRP in pregnancy, but higher second trimester CRP was significantly associated with shorter child telomere length (&#x3b2; = -0.35, SE = 0.18, p = .048).<br><br>CONCLUSIONS: Maternal symptoms of PTSD prior to conception and second trimester inflammation were associated with shorter telomere length in offspring in early childhood, independent of covariates. Findings indicate intergenerational transmission of parental trauma may occur in part through accelerated biological aging processes and provide further evidence that prenatal pro-inflammatory processes program child telomere length.Open Science Framework Pre-registration:https://osf.io/7c2d5/?view_only=cd0fb81f48db4b8f9c59fc8bb7b0ef97.},
}
@article {pmid37593897,
year = {2023},
author = {Luo, X and Ruan, Z and Liu, L},
title = {Causal relationship between telomere length and epilepsy: A bidirectional Mendelian randomization study.},
journal = {Epilepsia open},
volume = {8},
number = {4},
pages = {1432-1439},
pmid = {37593897},
issn = {2470-9239},
support = {2021A378//Science and Technology program of Jiangxi Provincial Administration of Traditional Chinese Medicine/ ; },
mesh = {Humans ; *Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Epilepsy/genetics ; Causality ; Telomere/genetics ; },
abstract = {OBJECTIVE: Observational studies have suggested a link between telomere length (TL) and epilepsy, but the direction of the effect and whether it is causal or not is still being debated. The objective of this study was to investigate the causal relationship between TL and epilepsy using Mendelian randomization (MR) analysis.<br><br>METHODS: We performed a bidirectional two-sample MR analysis using pooled statistics from genome-wide association studies (GWAS) of TL and epilepsy. Additionally, we conducted a replication analysis using data from another GWAS study on epilepsy to validate our findings. The final results were analyzed using five MR methods, with the inverse-variance weighted (IVW) method as the primary outcome. We applied methods such as radial MR, MR pleiotropy residual and outlier test and MR Steiger filters to exclude outliers. Sensitivity analyses were also conducted to assess heterogeneity and pleiotropy.<br><br>RESULTS: Our analysis found no evidence of a causal relationship between epilepsy and TL (all p-values >0.05). The sensitivity analysis confirms the robustness of these results.<br><br>SIGNIFICANCE: In summary, our study contradicts existing observational reports by not finding any evidence to support a causal relationship between epilepsy and TL. Further research is necessary to determine the underlying mechanism behind the association observed in observational studies.},
}
@article {pmid37592749,
year = {2023},
author = {Huang, X},
title = {A complete telomere-to-telomere assembly provides new reference genome for rice.},
journal = {Molecular plant},
volume = {16},
number = {9},
pages = {1370-1372},
doi = {10.1016/j.molp.2023.08.007},
pmid = {37592749},
issn = {1752-9867},
mesh = {*Oryza/genetics ; Telomere/genetics ; },
}
@article {pmid37591536,
year = {2023},
author = {Zhang, D and Adegunsoye, A and Oldham, JM and Kozlitina, J and Garcia, N and Poonawalla, M and Strykowski, R and Linderholm, AL and Ley, B and Ma, SF and Noth, I and Strek, ME and Wolters, PJ and Garcia, CK and Newton, CA},
title = {Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease.},
journal = {The European respiratory journal},
volume = {62},
number = {5},
pages = {},
pmid = {37591536},
issn = {1399-3003},
support = {K23 HL146942/HL/NHLBI NIH HHS/United States ; UL1 TR001105/TR/NCATS NIH HHS/United States ; R01 HL093096/HL/NHLBI NIH HHS/United States ; R01 HL139897/HL/NHLBI NIH HHS/United States ; UG3 HL145266/HL/NHLBI NIH HHS/United States ; K23 HL138190/HL/NHLBI NIH HHS/United States ; R56 HL158935/HL/NHLBI NIH HHS/United States ; K23 HL148498/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Azathioprine/adverse effects ; Retrospective Studies ; *Lung Diseases, Interstitial ; *Idiopathic Pulmonary Fibrosis ; Immunosuppressive Agents/therapeutic use ; *Connective Tissue Diseases ; Immunosuppression Therapy ; Telomere ; },
abstract = {BACKGROUND: Studies suggest a harmful pharmacogenomic interaction exists between short leukocyte telomere length (LTL) and immunosuppressants in idiopathic pulmonary fibrosis (IPF). It remains unknown if a similar interaction exists in non-IPF interstitial lung disease (ILD).<br><br>METHODS: A retrospective, multicentre cohort analysis was performed in fibrotic hypersensitivity pneumonitis (fHP), unclassifiable ILD (uILD) and connective tissue disease (CTD)-ILD patients from five centres. LTL was measured by quantitative PCR for discovery and replication cohorts and expressed as age-adjusted percentiles of normal. Inverse probability of treatment weights based on propensity scores were used to assess the association between mycophenolate or azathioprine exposure and age-adjusted LTL on 2-year transplant-free survival using weighted Cox proportional hazards regression incorporating time-dependent immunosuppressant exposure.<br><br>RESULTS: The discovery and replication cohorts included 613 and 325 patients, respectively. In total, 40% of patients were exposed to immunosuppression and 22% had LTL <10th percentile of normal. fHP and uILD patients with LTL <10th percentile experienced reduced survival when exposed to either mycophenolate or azathioprine in the discovery cohort (mortality hazard ratio (HR) 4.97, 95% CI 2.26-10.92; p<0.001) and replication cohort (mortality HR 4.90, 95% CI 1.74-13.77; p=0.003). Immunosuppressant exposure was not associated with differential survival in patients with LTL &#x2265;10th percentile. There was a significant interaction between LTL <10th percentile and immunosuppressant exposure (discovery pinteraction=0.013; replication pinteraction=0.011). Low event rate and prevalence of LTL <10th percentile precluded subgroup analyses for CTD-ILD.<br><br>CONCLUSION: Similar to IPF, fHP and uILD patients with age-adjusted LTL <10th percentile may experience reduced survival when exposed to immunosuppression.},
}
@article {pmid37591348,
year = {2023},
author = {Naudé, PJW and Stein, DJ and Lin, J and Zar, HJ},
title = {Investigating the association of prenatal psychological adversities with mother and child telomere length and neurodevelopment.},
journal = {Journal of affective disorders},
volume = {340},
number = {},
pages = {675-685},
doi = {10.1016/j.jad.2023.08.074},
pmid = {37591348},
issn = {1573-2517},
support = {222020/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; U01 MH115484/MH/NIMH NIH HHS/United States ; },
mesh = {Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; *Adverse Childhood Experiences ; Black People ; *Mothers ; Telomere ; Telomere Shortening ; Vitamins ; },
abstract = {BACKGROUND: Exposure to prenatal maternal psychological adversities can negatively affect the offspring's developing brain. Shortened telomere length (TL) has been implicated as a mechanism for the transgenerational effects of maternal psychological adversities on offspring. This study aimed to determine associations between prenatal psychological stressors and distress with maternal and early life TL, and associations between maternal, newborn and child TL with neurodevelopmental outcomes at 2 years of age.<br><br>METHODS: Follow-up TL was measured in a subgroup of African mothers (n&#xa0;=&#xa0;138) and their newborns (n&#xa0;=&#xa0;142) and children (n&#xa0;=&#xa0;96) at 2-years in the Drakenstein Child Health Study. Prenatal symptoms of depression, distress, intimate partner violence, posttraumatic stress-disorder and childhood trauma were measured at 27&#xa0;weeks gestation. Neurodevelopment was assessed at 2&#xa0;years using the Bayley Scales of Infant and Toddler Development III. TLs were measured in whole bloods from mothers and their children at 2-years, and cord bloods in newborns.<br><br>RESULTS: Maternal prenatal stressors and distress were not significantly associated with TL in mothers or their children at birth or at 2-years. Furthermore, maternal psychological measures were not associated with early-life attrition of TL. Longer TL in children at 2-years was associated (p&#xa0;=&#xa0;0.04) with higher motor functioning.<br><br>LIMITATIONS: Limited numbers of participants and single time-point psychological measures.<br><br>CONCLUSIONS: This study is the first to provide information on the association of early life TL with prenatal psychological adversities and neurodevelopmental outcomes in a population of low-income African mothers and their children.},
}
@article {pmid37591176,
year = {2023},
author = {Lu, ZH and Sun, B and Wang, YX and Wu, YR and Chen, YJ and Sun, SZ and Liang, SJ and Xu, S and Chang, H and Chen, HG and Zhang, J},
title = {Ozone exposure associates with sperm quality indicators: Sperm telomere length as a potential mediating factor.},
journal = {Journal of hazardous materials},
volume = {459},
number = {},
pages = {132292},
doi = {10.1016/j.jhazmat.2023.132292},
pmid = {37591176},
issn = {1873-3336},
mesh = {Humans ; Male ; *Semen Analysis ; Mediation Analysis ; Quality Indicators, Health Care ; Semen ; Spermatozoa ; Telomere ; *Ozone/toxicity ; },
abstract = {Evidence linking O3 exposure and human semen quality is limited and conflicting and the mechanism underlying the association remains unclear. Therefore, we investigated the associations between ambient O3 exposure and sperm quality parameters and explored the mediating role of sperm mitochondrial DNA copy number (mtDNAcn) and sperm telomere length (STL) among 1068 potential sperm donors who provided 5002 repeated semen samples over approximately 90 days. We found that every 10 μg/m[3] increase in O3 exposure was associated with a decrease in STL, sperm concentration, total count, total motile sperm number, and semen volume. However, O3 exposure was associated with increased total motility and progressive motility. The association for sperm quality parameters was stronger when exposure was measured at spermatogenesis stages I and II. For STL, the strongest association was observed when exposure was measured at spermatogenesis stage II. Additionally, we found that approximately 9% and 8% of the association between O3 exposure and sperm concentration and count was mediated by STL, respectively. In summary, our findings suggest that O3 pollution may affect sperm telomere length, eventually leading to reduced semen quality.},
}
@article {pmid37590305,
year = {2023},
author = {Vellingiri, B and Balasubramani, K and Iyer, M and Raj, N and Elangovan, A and Song, K and Yeo, HC and Jayakumar, N and Kinoshita, M and Thangarasu, R and Narayanasamy, A and Dayem, AA and Prajapati, VK and Gopalakrishnan, AV and Cho, SG},
title = {Role of Telomeres and Telomerase in Parkinson's Disease-A New Theranostics?.},
journal = {Advanced biology},
volume = {7},
number = {12},
pages = {e2300097},
doi = {10.1002/adbi.202300097},
pmid = {37590305},
issn = {2701-0198},
support = {340/2021//DST/INT/JSPS/P-/ ; 120217720//JPJSBP/ ; //technology exchange grant from Nakatani Foundation/ ; },
mesh = {Humans ; Aged ; *Parkinson Disease/diagnosis/genetics/therapy ; *Telomerase/genetics/metabolism ; Leukocytes, Mononuclear/metabolism ; Precision Medicine ; Telomere/genetics/metabolism ; },
abstract = {Parkinson's disease (PD) is a complex condition that is significantly influenced by oxidative stress and inflammation. It is also suggested that telomere shortening (TS) is regulated by oxidative stress which leads to various diseases including age-related neurodegenerative diseases like PD. Thus, it is anticipated that PD would result in TS of peripheral blood mononuclear cells (PBMCs). Telomeres protect the ends of eukaryotic chromosomes preserving them against fusion and destruction. The TS is a normal process because DNA polymerase is unable to replicate the linear ends of the DNA due to end replication complications and telomerase activity in various cell types counteracts this process. PD is usually observed in the aged population and progresses over time therefore, disparities among telomere length in PBMCs of PD patients are recorded and it is still a question whether it has any useful role. Here, the likelihood of telomere attrition in PD and its implications concerning microglia activation, ageing, oxidative stress, and the significance of telomerase activators are addressed. Also, the possibility of telomeres and telomerase as a diagnostic and therapeutic biomarker in PD is discussed.},
}
@article {pmid37589509,
year = {2023},
author = {Chen, H and Liang, W and Zheng, W and Li, F and Pan, X and Lu, Y},
title = {A novel telomere-related gene prognostic signature for survival and drug treatment efficiency prediction in lung adenocarcinoma.},
journal = {Aging},
volume = {15},
number = {16},
pages = {7956-7973},
pmid = {37589509},
issn = {1945-4589},
mesh = {Humans ; Prognosis ; Proteomics ; *Adenocarcinoma of Lung ; *Lung Neoplasms ; *Adenocarcinoma ; Aldehyde Dehydrogenase, Mitochondrial ; },
abstract = {OBJECTIVE: Telomere-related genes (TRGs) play a critical role in various types of tumors. However, there is a lack of comprehensive exploration of their relevance in lung cancer. This research aimed to verify the relationship between TRGs gene expression and the prognosis of patients with lung adenocarcinoma (LUAD), as well as the prediction of drug treatment efficiency.<br><br>METHODS: A total of 2093 TRGs were acquired from TelNet. The clinical information including age, tumor stage, follow up and outcome (death/survival) and TRGs expression profile of LUAD were obtained from the patients in The Cancer Genome Atlas (TCGA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. The two databases were used to construct and verify a prognostic model based on the expression of hubTRGs. The tumor mutation burden, immune infiltration and subtypes, as well as IC50 prediction of multiple targeted drugs were also evaluated in TRGs-divided risk groups.<br><br>RESULTS: A total of 335 TRGs were significantly differentially expressed in LUAD as compared with normal control. Among them, 9 TRGs (ABCC2, ABCC8, ALDH2, FOXP3, GNMT, JSRP1, MACF1, PLCD3, SULT4A1) were finally identified as hubGenes and used to construct a TRG risk score. The TRG risk score showed favorable performance in constructing a prognostic nomogram in predicting survival of LUAD, and the ROC curves at 1, 3 and 5 years were plotted and the AUROC values were 0.743, 0.754 and 0.735, respectively. Higher TRGs risk score correlated with worse immune subtypes and higher tumor mutation burden in LUAD tissues. In addition, the patients in TRG high risk group harbored a lower TIDE score which indicated potentially better response to immunotherapy.<br><br>CONCLUSION: This study proposed a broad molecular signature of telomere-related genes that can be used in further functional and therapeutic investigations, and also represents an integrated modality for characterizing critical molecules when exploring novel targets for lung cancer immunotherapy.},
}
@article {pmid37588048,
year = {2023},
author = {Zhu, S and Yang, M and Wang, T and Ding, Z},
title = {Causal relationships between telomere length and liver disease: a Mendelian randomization study.},
journal = {Frontiers in genetics},
volume = {14},
number = {},
pages = {1164024},
pmid = {37588048},
issn = {1664-8021},
abstract = {Background: Leukocyte telomere length and hepatic disorders have been linked in various research studies, although their causative association has not been clarified. This study investigated the causal relationship between the length of telomeres on peripheral blood leukocytes and certain liver disorders. Methods: Mendelian randomization (MR) analysis was used to examine the relationship between leukocyte telomere length and risk of liver disease using the publicly accessible worldwide gene-wide association study (GWAS) database. The weighted mode, weighted median, and inverse variance weighted (IVW) methods were employed as supplements to the IVW approach, which is the main analytical method. Results: Leukocytes with longer telomeres may have a lower risk of developing cirrhosis [OR = 0.645 (0.524, 0.795), p = 3.977E-05] and a higher chance of developing benign liver tumors [OR = 3.087 (1.721, 5.539), p = 1.567E-04]. There was no direct link between telomere length and fatty liver, hepatic fibrosis, or liver cancer. Our findings in the replication analysis agreed with those of the previous studies. Conclusion: Further research is needed to examine the mechanisms underlying the probable causal association between the length of leukocyte telomeres and cirrhosis and benign liver cancer.},
}
@article {pmid37586999,
year = {2023},
author = {He, Q and Lim, CJ},
title = {Models for human telomere C-strand fill-in by CST-Polα-primase.},
journal = {Trends in biochemical sciences},
volume = {48},
number = {10},
pages = {860-872},
pmid = {37586999},
issn = {0968-0004},
support = {DP2 GM150023/GM/NIGMS NIH HHS/United States ; R00 GM131023/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *DNA Primase ; *Telomerase ; Telomere ; Shelterin Complex ; Eukaryota ; },
abstract = {Telomere maintenance is essential for the genome integrity of eukaryotes, and this function is underpinned by the two-step telomeric DNA synthesis process: telomere G-overhang extension by telomerase and complementary strand fill-in by DNA polymerase alpha-primase (polα-primase). Compared to the telomerase step, the telomere C-strand fill-in mechanism is less understood. Recent studies have provided new insights into how telomeric single-stranded DNA-binding protein CTC1-STN1-TEN1 (CST) and polα-primase coordinate to synthesize the telomeric C-strand for telomere overhang fill-in. Cryogenic electron microscopy (cryo-EM) structures of CST-polα-primase complexes have provided additional insights into how they assemble at telomeric templates and de novo synthesize the telomere C-strand. In this review, we discuss how these latest findings coalesce with existing understanding to develop a human telomere C-strand fill-in mechanism model.},
}
@article {pmid37580799,
year = {2023},
author = {Brown, RL and Epel, EE and Lin, J and Dubal, DB and Prather, AA},
title = {Associations between klotho and telomere biology in high stress caregivers.},
journal = {Aging},
volume = {15},
number = {15},
pages = {7381-7396},
pmid = {37580799},
issn = {1945-4589},
support = {T32 MH019391/MH/NIMH NIH HHS/United States ; R21 HL117727/HL/NHLBI NIH HHS/United States ; R56 AG030424/AG/NIA NIH HHS/United States ; K08 HL112961/HL/NHLBI NIH HHS/United States ; K08 AG034531/AG/NIA NIH HHS/United States ; R01 AG030424/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; Female ; *Caregivers ; *Autism Spectrum Disorder ; Aging/genetics ; Biomarkers ; Telomere ; Biology ; Telomere Shortening ; },
abstract = {Aging biomarkers may be related to each other through direct co-regulation and/or through being regulated by common processes associated with chronological aging or stress. Klotho is an aging regulator that acts as a circulating hormone with critical involvement in regulating insulin signaling, phosphate homeostasis, oxidative stress, and age-related inflammatory functioning. Both klotho and telomere length are biomarkers of biological aging and decrease with age; however, the relationship between them is not well understood. Here we test the association between klotho levels and the telomere length of specific sorted immune cells among a healthy sample of mothers caregiving for a child with autism spectrum disorder (ASD; i.e., experiencing higher caregiving stress) or a child without ASD, covarying age and body mass index, in order to understand if high stress associated with caregiving for a child with an ASD may be involved in any association between these aging biomarkers. In 178 caregiving women (n = 90 high-stress mothers of children with ASD, n = 88 low-stress mothers of neurotypical children), we found that klotho levels were positively associated with telomere length in PBMCs (an effect driven by CD4+ and CD8+CD28- T cells) among high-stress mothers of children with an ASD but not among low-stress mothers of neurotypical children. There were no significant associations between klotho and telomerase activity in either group, across cell types assessed here. Our results suggest that klotho levels and telomere length may be associated through a coordinated downregulation of longevity factors occurring under higher stress caregiving conditions.},
}
@article {pmid37577643,
year = {2023},
author = {Lee, J and Lee, J and Sohn, EJ and Taglialatela, A and O'Sullivan, RJ and Ciccia, A and Min, J},
title = {Extrachromosomal Telomeres Derived from Excessive Strand Displacements.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37577643},
support = {K22 CA245259/CA/NCI NIH HHS/United States ; R01 CA197774/CA/NCI NIH HHS/United States ; R01 CA207209/CA/NCI NIH HHS/United States ; R01 CA262316/CA/NCI NIH HHS/United States ; },
abstract = {Alternative Lengthening of Telomeres (ALT) is a telomere maintenance mechanism mediated by break-induced replication (BIR), evident in approximately 15% of human cancers. A characteristic feature of ALT cancers is the presence of C-circles, circular single-stranded telomeric DNAs composed of C-rich sequences. Despite the fact that extrachromosomal C-rich single-stranded DNAs (ssDNAs), unique to ALT cells, are considered potential precursors of C-circles, their generation process remains undefined. Here, we introduce a highly sensitive method to detect single stranded telomeric DNA, called 4SET (Strand-Specific Southern-blot for Single-stranded Extrachromosomal Telomeres) assay. Utilizing 4SET, we are able to capture C-rich single stranded DNAs that are near 200 to 1500 nucleotides in size. Both linear C-rich ssDNAs and C-circles are abundant in the fractions of cytoplasm and nucleoplasm, which supports the idea that linear C-rich ssDNA accumulation may indeed precede C-circle formation. We also found that C-rich ssDNAs originate during Okazaki fragment processing during lagging strand DNA synthesis. The generation of C-rich ssDNA requires CST-PP (CTC1/STN1/TEN1-PRIMASE-Polymerase alpha) complex-mediated priming of the C-strand DNA synthesis and subsequent excessive strand displacement of the C-rich strand mediated by the DNA Polymerase delta and the BLM helicase. Our work proposes a new model for the generation of C-rich ssDNAs and C-circles during ALT-mediated telomere elongation.},
}
@article {pmid37570635,
year = {2023},
author = {Yamaguchi, I and Ikawa, K and Takimiya, N and Wang, A},
title = {Tetraphenylethene Derivatives Bearing Alkylammonium Substituents: Synthesis, Chemical Properties, and Application as BSA, Telomere DNA, and Hydroxyl Radical Sensors.},
journal = {Molecules (Basel, Switzerland)},
volume = {28},
number = {15},
pages = {},
pmid = {37570635},
issn = {1420-3049},
support = {20231181//Cooperative Research Program of "NJRC Mater. &amp; Dev."/ ; },
mesh = {*Serum Albumin, Bovine ; *Hydroxyl Radical ; DNA ; Telomere ; },
abstract = {Tetraphenylethene derivatives (TPEs) are used as luminescence probes for the detection of metal ions and biomolecules. These sensors function by monitoring the increase in the photoluminescence (PL) intensity of the TPEs resulting from aggregation-induced emission (AIE) upon interaction with the analytes. The AIE behavior of the sensors was investigated by measuring their PL. In this study, PL, PL lifetime, and confocal laser scanning microscopy measurements were carried out as part of our in-depth investigation of AIE behavior of TPEs for the detection of biomolecules and radical species. We used 1,1,2,2-tetrakis(4-((trimethylammonium)alkoxy)phenyl)tetraphenylethene tetrabromide (TPE-C(m)N[+]Me3Br[-], m = 2, 4, and 6, where m denotes the number of methylene groups in the alkyl chain) and TPE-C(m)N[+]Me3TCNQ[-•] (TCNQ[-•] is the 7,7',8,8'-tetracyanoquinodimethane anion radical) as luminescent probes for the detection of bovine serum albumin (BSA), DNA, and the hydroxyl radical ([•]OH) generated from Fenton's reagent. The sensing performance of TPE-C(m)N[+]Me3Br[-] for BSA and DNA was found to depend on the length of the alkyl chains (m). UV-vis and PL measurements revealed that the responses of TPE-C(m)N[+]Me3Br[-] and TPE-C(4)N[+]TCNQ[-•] to Fenton's reagent depended on the solvent. The electrochemical properties of the TPE derivatives prepared in this study were additionally investigated via cyclic voltammetry.},
}
@article {pmid37569497,
year = {2023},
author = {Li, XH and Sun, MH and Jiang, WJ and Zhou, D and Lee, SH and Heo, G and Chen, Z and Cui, XS},
title = {ZSCAN4 Regulates Zygotic Genome Activation and Telomere Elongation in Porcine Parthenogenetic Embryos.},
journal = {International journal of molecular sciences},
volume = {24},
number = {15},
pages = {},
pmid = {37569497},
issn = {1422-0067},
support = {2022R1A2C300769//National Research Foundation of Korea/ ; },
mesh = {Animals ; Mice ; Swine ; *Transcription Factors/genetics/metabolism ; *Telomere/genetics/metabolism ; Telomere Shortening ; DNA-Binding Proteins/metabolism ; Zygote/metabolism ; Embryonic Development/genetics ; Gene Expression Regulation, Developmental ; },
abstract = {Zinc finger and SCAN domain-containing 4 (ZSCAN4), a DNA-binding protein, maintains telomere length and plays a key role in critical aspects of mouse embryonic stem cells, including maintaining genomic stability and defying cellular senescence. However, the effect of ZSCAN4 in porcine parthenogenetic embryos remains unclear. To investigate the function of ZSCAN4 and the underlying mechanism in porcine embryo development, ZSCAN4 was knocked down via dsRNA injection in the one-cell stage. ZSCAN4 was highly expressed in the four- and five- to eight-cell stages in porcine embryos. The percentage of four-cell stage embryos, five- to eight-cell stage embryos, and blastocysts was lower in the ZSCAN4 knockdown group than in the control group. Notably, depletion of ZSCAN4 induced the protein expression of DNMT1 and 5-Methylcytosine (5mC, a methylated form of the DNA base cytosine) in the four-cell stage. The H3K27ac level and ZGA genes expression decreased following ZSCAN4 knockdown. Furthermore, ZSCAN4 knockdown led to DNA damage and shortened telomere compared with the control. Additionally, DNMT1-dsRNA was injected to reduce DNA hypermethylation in ZSCAN4 knockdown embryos. DNMT1 knockdown rescued telomere shortening and developmental defects caused by ZSCAN4 knockdown. In conclusion, ZSCAN4 is involved in the regulation of transcriptional activity and is essential for maintaining telomere length by regulating DNMT1 expression in porcine ZGA.},
}
@article {pmid37567392,
year = {2023},
author = {Ye, Q and Apsley, AT and Etzel, L and Hastings, WJ and Kozlosky, JT and Walker, C and Wolf, SE and Shalev, I},
title = {Telomere length and chronological age across the human lifespan: A systematic review and meta-analysis of 414 study samples including 743,019 individuals.},
journal = {Ageing research reviews},
volume = {90},
number = {},
pages = {102031},
pmid = {37567392},
issn = {1872-9649},
support = {T32 AG049676/AG/NIA NIH HHS/United States ; U01 ES030949/ES/NIEHS NIH HHS/United States ; U24 AG066528/AG/NIA NIH HHS/United States ; },
mesh = {Aged ; Humans ; *Longevity ; Cross-Sectional Studies ; *Telomere Shortening ; Aging/genetics ; Telomere ; },
abstract = {Telomere attrition is a proposed hallmark of aging. To evaluate the association of telomere length (TL) with chronological age across the human lifespan, we conducted a systematic review and meta-analysis of 414 study samples comprising 743,019 individuals aged 0-112 years. We examined both cross-sectional and longitudinal data, and evaluated the impact of various biological and methodological factors including sex, health status, tissue types, DNA extraction procedures, and TL measurement methods. The pooled corrected correlation between TL and age from cross-sectional samples was -0.19 (95%CI: -0.22 to -0.15), which weakened with increased chronological age (β = 0.003, p < 0.001). Z-score change rates of TL across the lifespan showed a gradual decrease in shortening rate until around age 50 and remained at a relatively stable rate towards the elderly period. A greater attrition rate was observed in longitudinal than cross-sectional evaluations. For TL measured in base pairs, the median change rate of TL was -23 bp/year in cross-sectional samples and -38 bp/year in longitudinal samples. Methodological factors including TL measurement methods and tissue types impacted the TL-age correlation, while sex or disease status did not. This meta-analysis revealed the non-linear shortening trend of TL across the human lifespan and provides a reference value for future studies. Results also highlight the importance of methodological considerations when using TL as an aging biomarker.},
}
@article {pmid37564879,
year = {2023},
author = {Nose, D and Shiga, Y and Takahashi, RU and Yamamoto, Y and Suematsu, Y and Kuwano, T and Sugihara, M and Kanda, M and Tahara, H and Miura, SI},
title = {Association Between Telomere G-Tail Length and Coronary Artery Disease or Statin Treatment in Patients With Cardiovascular Risks - A Cross-Sectional Study.},
journal = {Circulation reports},
volume = {5},
number = {8},
pages = {338-347},
pmid = {37564879},
issn = {2434-0790},
abstract = {Background: The utility of telomere G-tail length to predict coronary artery disease (CAD) remains controversial. CAD results from coronary artery narrowing due to cholesterol and lipid accumulation, augmented by inflammatory cells and other factors. This study explored the significance of telomere G-tail length in suspected CAD patients. Methods and Results: In all, 95 patients with suspected CAD or ≥1 cardiac risk factor underwent coronary computed tomography angiography (CCTA). We measured leukocyte telomere length and G-tail length using a hybrid protection method, and diagnosed the presence of CAD using CCTA. Associations between G-tail length and the presence of CAD, the number of stenosed coronary arteries, and brachial-ankle pulse wave velocity (baPWV) were analyzed. No significant difference was observed in G-tail length when comparing groups with or without CAD or statin treatment. However, in the non-statin group, G-tail length was significantly shorter in patients with 3-vessel disease compared with 1-vessel disease. Dividing the group using a baPWV of 1,300 cm/s, telomere G-tail length was significantly shorter in the high-risk (baPWV ≥1,300 cm/s) group. Conclusions: The clinical utility of telomere G-tail length as a CAD risk indicator seems limited. There was a trend for longer telomere G-tail length in the statin-treated group. Moreover, telomere G-tail length was reduced in patients at high-risk of cardiovascular events, aligning with the trend of a shortening in telomere G-tail length with CAD severity.},
}
@article {pmid37560909,
year = {2023},
author = {Takasugi, T and Gu, P and Liang, F and Staco, I and Chang, S},
title = {Pot1b -/- tumors activate G-quadruplex-induced DNA damage to promote telomere hyper-elongation.},
journal = {Nucleic acids research},
volume = {51},
number = {17},
pages = {9227-9247},
pmid = {37560909},
issn = {1362-4962},
support = {R01 GM141350/GM/NIGMS NIH HHS/United States ; T32 GM007205/GM/NIGMS NIH HHS/United States ; F30 CA254123/CA/NCI NIH HHS/United States ; },
mesh = {Mice ; Humans ; Animals ; *Shelterin Complex ; Telomere-Binding Proteins/genetics/metabolism ; Telomere/genetics/metabolism ; DNA Damage ; Replication Protein A/metabolism ; *Sarcoma ; DNA-Binding Proteins/genetics ; },
abstract = {Malignant cancers must activate telomere maintenance mechanisms to achieve replicative immortality. Mutations in the human Protection of Telomeres 1 (POT1) gene are frequently detected in cancers with abnormally long telomeres, suggesting that the loss of POT1 function disrupts the regulation of telomere length homeostasis to promote telomere elongation. However, our understanding of the mechanisms leading to elongated telomeres remains incomplete. The mouse genome encodes two POT1 proteins, POT1a and POT1b possessing separation of hPOT1 functions. We performed serial transplantation of Pot1b-/- sarcomas to better understand the role of POT1b in regulating telomere length maintenance. While early-generation Pot1b-/- sarcomas initially possessed shortened telomeres, late-generation Pot1b-/- cells display markedly hyper-elongated telomeres that were recognized as damaged DNA by the Replication Protein A (RPA) complex. The RPA-ATR-dependent DNA damage response at telomeres promotes telomerase recruitment to facilitate telomere hyper-elongation. POT1b, but not POT1a, was able to unfold G-quadruplex present in hyper-elongated telomeres to repress the DNA damage response. Our findings demonstrate that the repression of the RPA-ATR DDR is conserved between POT1b and human POT1, suggesting that similar mechanisms may underly the phenotypes observed in human cancers harboring human POT1 mutations.},
}
@article {pmid37560336,
year = {2023},
author = {Teng, Y and Huang, DQ and Li, RX and Yi, C and Zhan, YQ},
title = {Association Between Telomere Length and Risk of Lung Cancer in an Asian Population: A Mendelian Randomization Study.},
journal = {World journal of oncology},
volume = {14},
number = {4},
pages = {277-284},
pmid = {37560336},
issn = {1920-454X},
abstract = {BACKGROUND: Several traditional observational studies and Mendelian randomization (MR) studies have indicated an association between leukocyte telomere length (LTL) and the risk of lung cancer in the European population. However, the results in the Asian population are still unclear. The objective was to reveal the genetic causal association between LTL and the risk of lung cancer in the Asian population.<br><br>METHODS: We conducted a two-sample MR analysis using summary statistics. Instrumental variables (IVs) were obtained from the genome-wide association studies (GWAS) of LTL (n = 23,096) and lung cancer (n = 212,453) of Asian ancestry. We applied the random-effects inverse-variance weighted (IVW) model as the main method. As well, several other models were performed as complementary methods to assess the impact of potential MR assumption violations, including MR-Egger regression, weighted median, and weighted mode models.<br><br>RESULTS: We included eight single-nucleotide polymorphisms (SNPs) as IVs for LTL and found that LTL was significantly associated with the risk of lung cancer in the IVW model (odds ratio (OR): 1.60; 95% confidence interval (CI): 1.31 - 1.97; P = 5.96 &#xd7; 10[-6]), which was in line with the results in the weighted median and weighted mode models. However, the relationship was not statistically significant in the MR-Egger regression model (OR: 1.44; 95% CI: 0.92 - 2.26; P = 0.160). Sensitivity analyses indicated the robustness of the results.<br><br>CONCLUSIONS: This two-sample MR study confirmed that longer telomere length significantly increased the risk of lung cancer in the Asian population, which was in accord with findings in the Western population.},
}
@article {pmid37560017,
year = {2023},
author = {Lin, Y and Ye, C and Li, X and Chen, Q and Wu, Y and Zhang, F and Pan, R and Zhang, S and Chen, S and Wang, X and Cao, S and Wang, Y and Yue, Y and Liu, Y and Yue, J},
title = {quarTeT: a telomere-to-telomere toolkit for gap-free genome assembly and centromeric repeat identification.},
journal = {Horticulture research},
volume = {10},
number = {8},
pages = {uhad127},
pmid = {37560017},
issn = {2662-6810},
abstract = {A high-quality genome is the basis for studies on functional, evolutionary, and comparative genomics. The majority of attention has been paid to the solution of complex chromosome structures and highly repetitive sequences, along with the emergence of a new 'telomere-to-telomere (T2T) assembly' era. However, the bioinformatic tools for the automatic construction and/or characterization of T2T genome are limited. Here, we developed a user-friendly web toolkit, quarTeT, which currently includes four modules: AssemblyMapper, GapFiller, TeloExplorer, and CentroMiner. First, AssemblyMapper is designed to assemble phased contigs into the chromosome-level genome by referring to a closely related genome. Then, GapFiller would endeavor to fill all unclosed gaps in a given genome with the aid of additional ultra-long sequences. Finally, TeloExplorer and CentroMiner are applied to identify candidate telomere and centromere as well as their localizations on each chromosome. These four modules can be used alone or in combination with each other for T2T genome assembly and characterization. As a case study, by adopting the entire modular functions of quarTeT, we have achieved the Actinidia chinensis genome assembly that is of a quality comparable to the reported genome Hongyang v4.0, which was assembled with the addition of manual handling. Further evaluation of CentroMiner by searching centromeres in Arabidopsis thaliana and Oryza sativa genomes showed that quarTeT is capable of identifying all the centromeric regions that have been previously detected by experimental methods. Collectively, quarTeT is an efficient toolkit for studies of large-scale T2T genomes and can be accessed at http://www.atcgn.com:8080/quarTeT/home.html without registration.},
}
@article {pmid37550565,
year = {2023},
author = {Tang, L and Li, D and Wang, J and Su, B and Tian, Y},
title = {Ambient air pollution, genetic risk and telomere length in UK biobank.},
journal = {Journal of exposure science &amp; environmental epidemiology},
volume = {},
number = {},
pages = {},
pmid = {37550565},
issn = {1559-064X},
abstract = {BACKGROUND: Telomere length (TL) is a biomarker of genomic aging. The evidence on the association between TL and air pollution was inconsistent. Besides, the modification effect of genetic susceptibility on the air pollution-TL association remains unknown.<br><br>OBJECTIVE: We aimed to evaluate the association of ambient air pollution with TL and further assess the modification effect of genetic susceptibility.<br><br>METHODS: 433,535 participants with complete data of TL and air pollutants in UK Biobank were included. Annual average exposure of NO2, NOx, PM10 and PM2.5 was estimated by&#xa0;applying land use regression models. Genetic risk score (GRS) was constructed using reported telomere-related SNPs. Leukocyte TL was measured by quantitative polymerase chain reaction (qPCR). Multivariable linear regression models were employed to conduct associational analyses.<br><br>RESULTS: Categorical exposure models and RCS models both indicated U-shaped (for NO2 and NOx) and L-shaped (for PM10 and PM2.5) correlations between air pollution and TL. In comparison to the lowest quartile, the 2nd and 3rd quartile of NO2 (q2: -1.3% [-2.1%, -0.4%]; q3: -1.2% [-2.0%, -0.3%], NOx (q2: -1.3% [-2.1%, -0.5%]; q3: -1.4% [-2.2%, -0.5%]), PM2.5 (q2: -0.8% [-1.7%, 0.0%]; q3: -1.3% [-2.2%, -0.5%]), and the third quartile of PM10 (q3: -1.1% [-1.9%, -0.2%]) were inversely associated with TL. The highest quartile of NO2 was positively correlated with TL (q4: 1.0% [0.0%, 2.0%]), whereas the negative correlation between the highest quartile of other pollutants and TL was also attenuated and no longer significant. In the genetic analyses, synergistic interactions were observed between the 4th quartile of three air pollutants (NO2, NOx, and PM2.5) and genetic risk.<br><br>IMPACT STATEMENT: Our study for the first time revealed a non-linear trend for the association between air pollution and telomere length. The genetic analyses suggested synergistic interactions between air pollution and genetic risk on the&#xa0;air pollution-TL association. These findings may shed new light on air pollution's health effects, offer suggestions for identifying at-risk individuals, and provide hints regarding further investigation into gene-environment interactions.},
}
@article {pmid37549582,
year = {2023},
author = {Ojeda-Rodriguez, A and Alcala-Diaz, JF and Rangel-Zuñiga, OA and Arenas-de Larriva, AP and Gutierrez-Mariscal, FM and Gómez-Luna, P and Torres-Peña, JD and Garcia-Rios, A and Romero-Cabrera, JL and Malagon, MM and Perez-Martinez, P and Ordovas, JM and Delgado-Lista, J and Yubero-Serrano, EM and Lopez-Miranda, J},
title = {Association between telomere length and intima-media thickness of both common carotid arteries in patients with coronary heart disease: From the CORDIOPREV randomized controlled trial.},
journal = {Atherosclerosis},
volume = {380},
number = {},
pages = {117193},
doi = {10.1016/j.atherosclerosis.2023.117193},
pmid = {37549582},
issn = {1879-1484},
mesh = {Humans ; Carotid Intima-Media Thickness ; *Carotid Artery Diseases/diagnostic imaging/epidemiology/complications ; Risk Factors ; *Coronary Disease/complications ; Carotid Artery, Common/diagnostic imaging ; *Diet, Mediterranean ; Telomere ; Carotid Arteries/diagnostic imaging ; },
abstract = {BACKGROUND AND AIMS: A critical telomere length (TL) is associated with cardiovascular mortality. Dietary habits have been demonstrated to affect cardiovascular risk. However, it remains unclear how exactly TL determines the response to specific dietary approaches in the reduction of arterial injury. We aimed to evaluate whether TL was associated with the progression of arterial injury (assessed by intima-media thickness of both common carotid arteries: IMT-CC), after long-term consumption of two healthy dietary models in patients with coronary heart disease (CHD).<br><br>METHODS: From the 1002 CHD patients of the CORDIOPREV study, 903 completed IMT-CC and TL evaluation at baseline and were randomized to follow a Mediterranean diet or a low-fat diet for 5 years.<br><br>RESULTS: Patients at risk of short TL (TL&#xa0;<&#xa0;20th percentile) presented an elevated IMT-CC, (0.79&#xa0;&#xb1;&#xa0;0.17 vs patients at non-risk 0.74&#xa0;&#xb1;&#xa0;0.17 p&#xa0;<&#xa0;0.001). TL and IMT-CC showed an inverse association (&#x3b2;&#xa0;=&#xa0;-0.035, p&#xa0;=&#xa0;0.002). Patients who consumed a Mediterranean diet, regardless of the risk of short TL, showed a significant decrease in IMT-CC, with a higher reduction in those patients with risk of short TL (-0.03&#xa0;&#xb1;&#xa0;0.11, p&#xa0;=&#xa0;0.036). TL (&#x3b2;&#xa0;=&#xa0;0.019, p&#xa0;=&#xa0;0.024), age (&#x3b2;&#xa0;=&#xa0;-0.001, p&#xa0;=&#xa0;0.031), energy intake (&#x3b2;&#xa0;=&#xa0;-0.000, p&#xa0;=&#xa0;0.036), use of statins (&#x3b2;&#xa0;=&#xa0;-0.027, p&#xa0;=&#xa0;0.028) and allocation into the Mediterranean diet (vs low-fat diet) (&#x3b2;&#xa0;=&#xa0;-0.024, p&#xa0;=&#xa0;0.003) were significant contributors to changes in IMT-CC.<br><br>CONCLUSIONS: Patients who had a reduced TL exhibited a greater decrease in IMT-CC after consuming a Mediterranean diet.},
}
@article {pmid37548940,
year = {2023},
author = {Kordowitzki, P and Graczyk, S and Mechsner, S and Sehouli, J},
title = {Shedding Light on the Interaction Between Rif1 and Telomeres in Ovarian Cancer.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2023.0716},
pmid = {37548940},
issn = {2152-5250},
abstract = {Ovarian cancer, more precisely high-grade serous ovarian cancer, is one of the most lethal ageindependent gynecologic malignancies in women worldwide, regardless of age. There is mounting evidence that there is a link between telomeres and the RIF1 protein and the proliferation of cancer cells. Telomeres are hexameric (TTAGGG) tandem repeats at the tip of chromosomes that shorten as somatic cells divide, limiting cell proliferation and serving as an important barrier in preventing cancer. RIF1 (Replication Time Regulation Factor 1) plays, among other factors, an important role in the regulation of telomere length. Interestingly, RIF1 appears to influence the DNA double-strand break (DSB) repair pathway. However, detailed knowledge regarding the interplay between RIF1 and telomeres and their degree of engagement in epithelial ovarian cancer (EOC) is still elusive, despite the fact that such knowledge could be of relevance in clinical practice to find novel biomarkers. In this review, we provide an update of recent literature to elucidate the relation between telomere biology and the RIF1 protein during the development of ovarian cancer in women.},
}
@article {pmid37548421,
year = {2023},
author = {Tahara, T and Shijimaya, T and Yamazaki, J and Tomiyama, T and Fukui, T and Naganuma, M},
title = {Telomere Shortening of Barrett's Esophagus and Esophageal Adenocarcinoma in Japanese Patients.},
journal = {Cancer investigation},
volume = {41},
number = {7},
pages = {640-645},
doi = {10.1080/07357907.2023.2245897},
pmid = {37548421},
issn = {1532-4192},
mesh = {Humans ; *Barrett Esophagus/pathology ; Telomere Shortening ; East Asian People ; Telomere/pathology ; *Esophageal Neoplasms/pathology ; *Adenocarcinoma/pathology ; },
abstract = {Telomere shortening is deeply involved in many types of cancer. Telomere length of esophageal adenocarcinoma (EAC) and Barrett's esophagus (BE) was examined in Japanese patients. Among BE from cancer free patients (Cancer free), BE from patients with EAC (Adjacent) and EAC tissue (Cancer), Cancer free group presented the longest telomeres, while Cancer group presented the shortest telomeres and Adjacent group presented intermediate telomeres. Direction of endoscopic biopsy, 2 o'clock direction was also significantly associated with shorter telomere length in non-neoplastic BE (p = 0.027). Shortened telomere highlighted the impact of this molecular change in early carcinogenesis in EAC.},
}
@article {pmid37544968,
year = {2024},
author = {Xiang, M and Pilling, LC and Melzer, D and Kirk, B and Duque, G and Liu, R and Kuchel, GA and Wood, AR and Metcalf, B and Diniz, BS and Hillsdon, M and Kuo, CL},
title = {Does physical activity moderate the association between shorter leukocyte telomere length and incident coronary heart disease? Data from 54,180 UK Biobank participants.},
journal = {GeroScience},
volume = {46},
number = {1},
pages = {1331-1342},
pmid = {37544968},
issn = {2509-2723},
support = {P30 AG067988/AG/NIA NIH HHS/United States ; R21 NR018963/NR/NINR NIH HHS/United States ; P30AG067988/AG/NIA NIH HHS/United States ; R21NR018963-01A1/NR/NINR NIH HHS/United States ; },
mesh = {Humans ; *Biological Specimen Banks ; UK Biobank ; *Coronary Disease/epidemiology/genetics ; Leukocytes ; Telomere/genetics ; Exercise ; },
abstract = {Telomere shortening is a biological aging hallmark. The effect of short telomere length may be targeted by increased physical activity to reduce the risk of multiple aging-related diseases, including coronary heart disease (CHD). The objective was to assess the moderation effect of accelerometer-based physical activity (aPA) on the association between shorter leukocyte telomere length (LTL) relatively in the population sample and incident CHD. Data were from the UK Biobank participants with well-calibrated accelerometer data for at least 6.5 days (n = 54,180). Relative mean LTL at baseline (5-6 years prior to aPA assessment) was measured in T/S ratio, using a multiplex quantitative polymerase chain reaction (qPCR) technology, by comparing the amount of the telomere amplification product (T) to that of a single-copy gene (S). aPA measures included total number of events (at least 10-s continued physical activity > 32 milligravities [mg]), total volume, mean duration, mean intensity, and peak intensity of all events. LTL, aPA measures, and their interactions were associated with incident CHD (mean follow-up 6.8 years) using Cox proportional hazards models adjusting for covariates. Longer LTL (relative to the sample distribution) was associated with reduced incidence of CHD (adjusted hazard ratio [aHR] = 0.94 per standard deviation [SD] increase in LTL, [95% CI, 0.90 to 0.99], P = .010). Incidence of CHD was reduced by higher total volume of aPA (aHR = 0.82 per SD increase in LTL, [95% CI, 0.71 to 0.95], P = .010) but increased by higher total number of events (aHR = 1.11 per SD increase in LTL, [95% CI, 1.02 to 1.21], P = .020) after controlling for other aPA measures and covariates. However, none of the interactions between LTL and aPA measures was statistically significant (P = .171).},
}
@article {pmid37544465,
year = {2023},
author = {Snyder, ME and Anderson, MR and Benvenuto, LJ and Sutton, RM and Bondonese, A and Koshy, R and Burke, R and Clifford, S and Craig, A and Iasella, CJ and Hannan, SJ and Popescu, I and Zhang, Y and Sanchez, PG and Alder, JK and McDyer, JF},
title = {Impact of age and telomere length on circulating T cells and rejection risk after lung transplantation for idiopathic pulmonary fibrosis.},
journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation},
volume = {42},
number = {12},
pages = {1666-1677},
pmid = {37544465},
issn = {1557-3117},
support = {R00 HL151750/HL/NHLBI NIH HHS/United States ; R01 HL135062/HL/NHLBI NIH HHS/United States ; R01 HL133184/HL/NHLBI NIH HHS/United States ; R01 HL167901/HL/NHLBI NIH HHS/United States ; K23 HL151759/HL/NHLBI NIH HHS/United States ; R35 HL139860/HL/NHLBI NIH HHS/United States ; K99 HL151750/HL/NHLBI NIH HHS/United States ; R01 HL166265/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Infant ; Leukocytes, Mononuclear ; CD8-Positive T-Lymphocytes ; *Idiopathic Pulmonary Fibrosis/genetics/surgery ; *Lung Transplantation ; Telomere ; Receptors, Antigen, T-Cell/genetics ; },
abstract = {BACKGROUND: Most idiopathic pulmonary fibrosis (IPF) lung transplant recipients (IPF-LTRs) have short telomere (ST) length. Inherited mutations in telomere-related genes are associated with the development of T cell immunodeficiency. Despite this, IPF-LTRs with telomere-related rare variants are not protected from acute cellular rejection (ACR). We set out to determine the impact of both age and telomere length on the circulating T cell compartment and ACR burden of IPF-LTRs.<br><br>METHODS: We identified 106 IPF-LTRs who had telomere length testing using flowFISH (57 with short telomeres and 49 with long telomeres) as well as a subset from both cohorts who had cryopreserved PBMC at least 1 time point, 6 months posttransplantation. Circulating T cells from before transplantation and at 6 and 12 months posttransplantation were analyzed using multiparameter flow cytometry to study phenotype and functional capacity, and bulk T cell receptor sequencing was performed to study repertoire diversity. Linear regression was used to study the relationship of age and telomere length on early (within 1 year) and late (between 1 and 2 years) ACR.<br><br>RESULTS: IPF-LTRs with ST were found to have premature "aging" of their circulating T cell compartment, with age-agnostic elevations in posttransplant terminal differentiation of CD8[+] T cells, increased granzyme B positivity of both CD8[+] and CD4[+] T cells, upregulation of the exhaustion marker, CD57, and chemotactic protein CCR5, and enhanced T cell receptor clonal expansion. Additionally, we found a significant decline in early ACR burden with increasing age, but only in the ST cohort.<br><br>CONCLUSIONS: IPF-LTRs with ST have premature "aging" of their circulating T cell compartment posttransplantation and a clear age-related decline in ACR burden.},
}
@article {pmid37543795,
year = {2023},
author = {Zou, J and Chu, S and Bao, Q and Zhang, Y},
title = {Telomere maintenance genes-derived prognosis signature characterizes immune landscape and predicts prognosis of head and neck squamous cell carcinoma.},
journal = {Medicine},
volume = {102},
number = {31},
pages = {e34586},
pmid = {37543795},
issn = {1536-5964},
mesh = {Humans ; Squamous Cell Carcinoma of Head and Neck/genetics ; Prognosis ; *Nomograms ; Immunotherapy ; *Head and Neck Neoplasms/genetics/therapy ; },
abstract = {Telomere dysfunction has been identified as a biological marker of cancer progression in several types of cancer, including Head and Neck Squamous Cell Carcinoma (HNSCC). This study aimed to characterize the telomere maintenance genes (TMG)-related signature in prognosis and treatment response in HNSCC. The transcriptome and clinical data of HNSCC were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases, respectively. Non-negative matrix factorization (NMF) was used to identify molecular subtypes derived from TMG. Gene set enrichment analysis (GSEA) was performed to analyze the differentially expressed pathways between subtypes, and a risk score model derived from TMG was established. Kaplan-Meier survival analysis was used to evaluate inter-group prognostic features, and the correlation between TMG-derived molecular subtypes and risk score model with immune infiltration, immunotherapy, and chemosensitivity was assessed. Two HNSCC subtypes were identified based on 59 TMG-related genes, which exhibit significant heterogeneity in prognosis, immune cell infiltration, and treatment response. Additionally, a TMG-derived risk signature containing 9 genes was developed to assess the prognosis of HNSCC patients. The signature had significant predictive ability for HNSCC prognosis and was significantly correlated with immune cell infiltration and immunotherapy response. A nomogram integrating the risk signature, N stage and radiotherapy was constructed to predict 1-, 3-, and 5-year overall survival (OS) of HNSCC patients, which had better performance than other prognostic models and included TMG-derived risk score, radiotherapy, and N stage. This study identified TMG-derived molecular subtypes in HNSCC and developed a novel prognostic score model, highlighting the potential value of TMG in HNSCC prognosis and immunotherapy.},
}
@article {pmid37543429,
year = {2023},
author = {Jiang, T and Mo, X and Zhan, R and Zhang, Y},
title = {Causal pathway from telomere length to occurrence and 28-day mortality of sepsis: an observational and mendelian randomization study.},
journal = {Aging},
volume = {15},
number = {15},
pages = {7727-7740},
pmid = {37543429},
issn = {1945-4589},
mesh = {Humans ; *Mendelian Randomization Analysis/methods ; Genome-Wide Association Study ; Causality ; Polymorphism, Single Nucleotide ; Telomere/genetics ; *Sepsis/genetics ; },
abstract = {BACKGROUND: Telomeres are considered to be a physiological marker of aging. Elucidating relationship between telomere length and sepsis is an essential step towards understanding the biological processes involved in sepsis and its salvation. Mendelian randomization studies based on SNPs have given us new insights into genetic susceptibility to disease.<br><br>OBJECTIVES: To explore the causal pathway from telomere length to occurrence and 28-day mortality of sepsis.<br><br>METHODS: Leveraging genetic information resource of UK Biobank, we captured three groups of large-scale GWAS data: leukocyte telomere length (LTL), sepsis and all-cause death of 28-day. Study design consisted of three parts: forward analysis, reverse analysis and one-way analysis. Genetic instrumental variables were selected for different analyses under the premise that three MR core assumptions were satisfied. Causality was determined by means of IVW.<br><br>RESULTS: In forward analysis, we did not observe a significant causal pathway from sepsis to LTL under IVW model: &#x3b2; (SE) was -0.0051 (0.0075) with a p-value of 0.499. In reverse analysis, based on the IVW model, the OR (95% CI) was 0.89 (0.80-0.99) and the p-values was 0.043; based on the results of leave out method and single SNP analysis, we obtained seven key SNPs. There were results of IVW model in the one-way analysis: &#x3b2; (SE) was -0.0287(0.1261).<br><br>CONCLUSIONS: Short LTL increases susceptibility to sepsis, but sepsis does not shorten telomere length. LTL does not affect sepsis 28-day all-cause mortality and does not serve as a causal intermediate in gene regulation during the progression of sepsis to 28-day death.},
}
@article {pmid37534393,
year = {2023},
author = {Lombardi, F and Sanfilippo, A and Fabbiani, M and Borghetti, A and Ciccullo, A and Tamburrini, E and Di Giambenedetto, S},
title = {Blood telomere length gain in people living with HIV switching to dolutegravir plus lamivudine versus continuing triple regimen: a longitudinal, prospective, matched, controlled study.},
journal = {The Journal of antimicrobial chemotherapy},
volume = {78},
number = {9},
pages = {2315-2322},
pmid = {37534393},
issn = {1460-2091},
mesh = {Adult ; Humans ; Lamivudine/therapeutic use/pharmacology ; *HIV Infections/drug therapy ; *Anti-HIV Agents/therapeutic use/pharmacology ; Prospective Studies ; Oxazines/pharmacology ; Heterocyclic Compounds, 3-Ring/therapeutic use/pharmacology ; Pyridones/pharmacology ; Telomere ; Viral Load ; },
abstract = {BACKGROUND: Blood telomere length (BTL) is a validated biomarker of aging. ART reduces immunosenescence and has benefits in terms of BTL in people living with HIV (PLWH). However, it has also been observed that ART containing NRTIs, such as tenofovir or abacavir, which are potent inhibitors of human telomerase activity in vitro, might negatively affect BTL. Here we investigated the effects on BTL 1 year after switching to a dual therapy (DT) with dolutegravir + lamivudine versus maintaining a standard triple therapy (TT) with a two-NRTI backbone and an anchor drug.<br><br>METHODS: This was a longitudinal, prospective, matched, controlled study that included virologically suppressed adults on stable three-drug ART who either switched at baseline (BL) to DT or maintained TT. The DT and TT groups were 1:1 matched for age, sex, years since HIV diagnosis, years on ART and anchor drug. BTL was assessed by a monochrome multiplex qPCR at BL and after 48 weeks (W48).<br><br>RESULTS: We enrolled 120 PLWH, i.e. 60 participants in each group. At BL, the BTL means were comparable between the two groups (P&#x200a;=&#x200a;0.973). At W48, viro-immunological status was stable and an overall increase in the mean BTL was observed, i.e., +0.161 (95%CI, 0.054-0.268) (P&#x200a;=&#x200a;0.004). However, the within-group analysis showed a significant mean BTL gain in the DT group (P&#x200a;=&#x200a;0.003) but not in the TT group (P&#x200a;=&#x200a;0.656).<br><br>CONCLUSIONS: In this setting of virologically suppressed PLWH, simplifying to dolutegravir&#x200a;+&#x200a;lamivudine was associated with a higher gain in BTL than maintaining triple therapy after the 1 year follow-up. These findings suggest that as a simplification strategy dolutegravir&#x200a;+&#x200a;lamivudine might have a positive effect on BTL.},
}
@article {pmid37534392,
year = {2023},
author = {Naspolini, NF and Sichieri, R and Barbosa Cunha, D and Alves Pereira, R and Faerstein, E},
title = {Dietary patterns, obesity markers and leukocyte telomere length among Brazilian civil servants: cross-sectional results from the Pro-Saude study - CORRIGENDUM.},
journal = {Public health nutrition},
volume = {26},
number = {10},
pages = {2180},
pmid = {37534392},
issn = {1475-2727},
}
@article {pmid37532653,
year = {2024},
author = {Hourvitz, N and Awad, A and Tzfati, Y},
title = {The many faces of the helicase RTEL1 at telomeres and beyond.},
journal = {Trends in cell biology},
volume = {34},
number = {2},
pages = {109-121},
doi = {10.1016/j.tcb.2023.07.002},
pmid = {37532653},
issn = {1879-3088},
mesh = {Humans ; *DNA Helicases/genetics/metabolism ; *Genome ; Phenotype ; Telomere/genetics/metabolism ; },
abstract = {Regulator of telomere elongation 1 (RTEL1) is known as a DNA helicase that is important for telomeres and genome integrity. However, the diverse phenotypes of RTEL1 dysfunction, the wide spectrum of symptoms caused by germline RTEL1 mutations, and the association of RTEL1 mutations with cancers suggest that RTEL1 is a complex machine that interacts with DNA, RNA, and proteins, and functions in diverse cellular pathways. We summarize the proposed functions of RTEL1 and discuss their implications for telomere maintenance. Studying RTEL1 is crucial for understanding the complex interplay between telomere maintenance and other nuclear pathways, and how compromising these pathways causes telomere biology diseases, various aging-associated pathologies, and cancer.},
}
@article {pmid37531260,
year = {2023},
author = {Sullivan, SM and Cole, B and Lane, J and Meredith, JJ and Langer, E and Hooten, AJ and Roesler, M and McGraw, KL and Pankratz, N and Poynter, JN},
title = {Predicted leukocyte telomere length and risk of myeloid neoplasms.},
journal = {Human molecular genetics},
volume = {32},
number = {20},
pages = {2996-3005},
pmid = {37531260},
issn = {1460-2083},
support = {R01 CA142714/CA/NCI NIH HHS/United States ; R01 CA142714/NH/NIH HHS/United States ; },
mesh = {Humans ; *Genome-Wide Association Study ; Genetic Predisposition to Disease ; Risk Factors ; Leukocytes/metabolism ; Genetic Risk Score ; Telomere/genetics ; *Leukemia, Myeloid, Acute/genetics/metabolism ; Mendelian Randomization Analysis ; },
abstract = {Maintenance of telomere length has long been established to play a role in the biology of cancer and several studies suggest that it may be especially important in myeloid malignancies. To overcome potential bias in confounding and reverse causation of observational studies, we use both a polygenic risk score (PRS) and inverse-variance weighted (IVW) Mendelian randomization (MR) analyses to estimate the relationship between genetically predicted leukocyte telomere length (LTL) and acute myeloid leukemia (AML) risk in 498 cases and 2099 controls and myelodysplastic syndrome (MDS) risk in 610 cases and 1759 controls. Genetic instruments derived from four recent studies explaining 1.23-4.57% of telomere variability were considered. We used multivariable logistic regression to estimate odds ratios (OR, 95% confidence intervals [CI]) as the measure of association between individual single-nucleotide polymorphisms and myeloid malignancies. We observed a significant association between a PRS of longer predicted LTL and AML using three genetic instruments (OR = 4.03 per ~1200 base pair [bp] increase in LTL, 95% CI: 1.65, 9.85 using Codd et al. [Codd, V., Nelson, C.P., Albrecht, E., Mangino, M., Deelen, J., Buxton, J.L., Hottenga, J.J., Fischer, K., Esko, T., Surakka, I. et al. (2013) Identification of seven loci affecting mean telomere length and their association with disease. Nat. Genet., 45, 422-427 427e421-422.], OR = 3.48 per one-standard deviation increase in LTL, 95% CI: 1.74, 6.97 using Li et al. [Li, C., Stoma, S., Lotta, L.A., Warner, S., Albrecht, E., Allione, A., Arp, P.P., Broer, L., Buxton, J.L., Alves, A.D.S.C. et al. (2020) Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length. Am. J. Hum. Genet., 106, 389-404.] and OR = 2.59 per 1000 bp increase in LTL, 95% CI: 1.03, 6.52 using Taub et al. [Taub, M.A., Conomos, M.P., Keener, R., Iyer, K.R., Weinstock, J.S., Yanek, L.R., Lane, J., Miller-Fleming, T.W., Brody, J.A., Raffield, L.M. et al. (2022) Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed. Cell Genom., 2.] genetic instruments). MR analyses further indicated an association between LTL and AML risk (PIVW ≤ 0.049) but not MDS (all PIVW ≥ 0.076). Findings suggest variation in genes relevant to telomere function and maintenance may be important in the etiology of AML but not MDS.},
}
@article {pmid37530521,
year = {2023},
author = {Singh, P and Gazy, I and Kupiec, M},
title = {Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader.},
journal = {eLife},
volume = {12},
number = {},
pages = {},
pmid = {37530521},
issn = {2050-084X},
mesh = {Saccharomyces cerevisiae/genetics/metabolism ; Proliferating Cell Nuclear Antigen/genetics ; *Telomerase/metabolism ; Telomere-Binding Proteins/genetics/metabolism ; Protein Binding ; Telomere/metabolism ; *Saccharomyces cerevisiae Proteins/metabolism ; Carrier Proteins/metabolism ; },
abstract = {Telomeres cap and protect the linear eukaryotic chromosomes. Telomere length is determined by an equilibrium between positive and negative regulators of telomerase activity. A systematic screen for yeast mutants that affect telomere length maintenance in the yeast Saccharomyces cerevisiae revealed that mutations in any of ~500 genes affects telomere length. One of the genes that, when mutated, causes telomere elongation is ELG1, which encodes an unloader of PCNA, the processivity factor for replicative DNA polymerases. PCNA can undergo SUMOylation on two conserved residues, K164 and K127, or ubiquitination at lysine 164. These modifications have already been implicated in genome stability processes. We report that SUMOylated PCNA acts as a signal that positively regulates telomerase activity. We also uncovered physical interactions between Elg1 and the CST (Cdc13-Stn1-Ten) complex and addressed the mechanism by which Elg1 and Stn1 negatively regulates telomere elongation, coordinated by SUMO. We discuss these results with respect to how chromosomal replication and telomere elongation are coordinated.},
}
@article {pmid37527721,
year = {2023},
author = {Sebastiano, M and Jouanneau, W and Blévin, P and Angelier, F and Parenteau, C and Pallud, M and Ribout, C and Gernigon, J and Lemesle, JC and Robin, F and Pardon, P and Budzinski, H and Labadie, P and Chastel, O},
title = {Physiological effects of PFAS exposure in seabird chicks: A multi-species study of thyroid hormone triiodothyronine, body condition and telomere length in South Western France.},
journal = {The Science of the total environment},
volume = {901},
number = {},
pages = {165920},
doi = {10.1016/j.scitotenv.2023.165920},
pmid = {37527721},
issn = {1879-1026},
abstract = {There is growing evidence that poly and perfluoroalkyl substances (PFAS) exposure leads to the disruption of thyroid hormones including thyroxine (T4) and triiodothyronine (T3), and may affect telomeres, repetitive nucleotide sequences which protect chromosome ends. Many seabird species are long-lived top predators thus exhibit high contaminant levels, and PFAS-disrupting effects on their physiology have been documented especially in relation to the endocrine system in adults. On the contrary, studies on the developmental period (i.e., chicks), during which exposure to environmental contaminants may have a greater impact on physiological traits, remain scarce to this date. We carried out a multi-species study with the aim to assess whether and to which extent chicks of four gull species (herring gull, great and lesser black-backed gull, yellow-legged gull) in South Western France are contaminated by PFAS, and to bring further evidence about their potential physiological consequences. Linear PFOS showed concentrations of concern as it was generally >10 times higher than the other PFAS, and exceeded a threshold toxicity level (calculated from previous studies in birds) in almost all sampled chicks. Nonetheless, in herring gull male chicks, total T3 levels were significantly and negatively associated with perfluorodecanoate (PFDA) and perfluorododecanoate (PFDoDA) and positively associated with perfluorotetradecanoate (PFTeDA) in female chicks. Total T3 levels were also positively associated with PFDoDA in great black backed gull male chicks and with perfluorotridecanoate (PFTrDA) in lesser black backed gull chicks. In lesser and great black-backed gulls, both females and males showed significant negative associations between several PFAS and their body condition, and a positive association between telomere length and L-PFOS in the yellow-legged gull was also found. These results corroborate previous findings and need to be further explored as they suggest that PFAS may interfere with the physiological status of chicks during the developmental period, potentially inducing long-lasting consequences.},
}
@article {pmid37526508,
year = {2023},
author = {Zhao, P and Deng, B and Kang, Q and Ni, M and Yang, B and Xue, M and Zhang, Y and Gao, R and Chen, Y and Li, Y and Zhang, L and Cheng, W and Zhao, M and Wang, J},
title = {Recipients with acute myeloid leukemia with a long telomere and donors with a short telomere have a higher relapse rate within 1-year post-transplantation.},
journal = {Minerva medica},
volume = {},
number = {},
pages = {},
doi = {10.23736/S0026-4806.23.08742-6},
pmid = {37526508},
issn = {1827-1669},
}
@article {pmid37526331,
year = {2023},
author = {Guo, M and Songyang, Z and Xiong, Y},
title = {ChArmTelo Enables Large-Scale Chromosome Arm-Level Telomere Analysis across Human Populations and in Cancer Patients.},
journal = {Small methods},
volume = {7},
number = {11},
pages = {e2300385},
doi = {10.1002/smtd.202300385},
pmid = {37526331},
issn = {2366-9608},
support = {92249303//National Natural Science Foundation of China/ ; 2021A1515110972//Guangdong Basic and Applied Basic Research Foundation/ ; },
mesh = {Animals ; Humans ; *Arm ; Telomere/genetics ; DNA Replication ; Algorithms ; *Liver Neoplasms ; },
abstract = {Telomeres are structures protecting chromosome ends. However, a scalable and cost-effective method to investigate chromosome arm-level (ChArm) telomeres (Telos) in large-scale projects is still lacking, hindering intensive investigation of high-resolution telomeres across cancers and other diseases. Here, ChArmTelo, the first computational toolbox to analyze telomeres at chromosome arm level in human and other animal species, using 10X linked-read and similar technologies, is presented. ChArmTelo currently consists of two algorithms, TeloEM and TeloKnow, for arm-level telomere length (TL) analysis. The algorithms are demonstrated by comprehensive analysis of chromosome arm-level telomere lengths (chArmTLs) in nearly 400 whole genome sequencing samples (WGS) from human populations and animals, including healthy and cancer samples. Notably, considerable performance improvement contributed by using the latest complete telomere-to-telomere reference genome (CHM13v2), compared to hg38, is shown. ChArmTelo reveals population-specific chArmTL differences and liver cancer signatures of chArmTLs and that DNA replication origin disruption may contribute to cancer by affecting TLs. Importantly, ChArmTelo can be readily applied to tens of thousands of cancer and healthy samples with published WGS data.},
}
@article {pmid37524789,
year = {2023},
author = {O'Donnell, S and Yue, JX and Saada, OA and Agier, N and Caradec, C and Cokelaer, T and De Chiara, M and Delmas, S and Dutreux, F and Fournier, T and Friedrich, A and Kornobis, E and Li, J and Miao, Z and Tattini, L and Schacherer, J and Liti, G and Fischer, G},
title = {Telomere-to-telomere assemblies of 142 strains characterize the genome structural landscape in Saccharomyces cerevisiae.},
journal = {Nature genetics},
volume = {55},
number = {8},
pages = {1390-1399},
pmid = {37524789},
issn = {1546-1718},
mesh = {*Saccharomyces cerevisiae/genetics ; Phylogeny ; *Genome ; Genomics ; Telomere/genetics ; },
abstract = {Pangenomes provide access to an accurate representation of the genetic diversity of species, both in terms of sequence polymorphisms and structural variants (SVs). Here we generated the Saccharomyces cerevisiae Reference Assembly Panel (ScRAP) comprising reference-quality genomes for 142 strains representing the species' phylogenetic and ecological diversity. The ScRAP includes phased haplotype assemblies for several heterozygous diploid and polyploid isolates. We identified circa (ca.) 4,800 nonredundant SVs that provide a broad view of the genomic diversity, including the dynamics of telomere length and transposable elements. We uncovered frequent cases of complex aneuploidies where large chromosomes underwent large deletions and translocations. We found that SVs can impact gene expression near the breakpoints and substantially contribute to gene repertoire evolution. We also discovered that horizontally acquired regions insert at chromosome ends and can generate new telomeres. Overall, the ScRAP demonstrates the benefit of a pangenome in understanding genome evolution at population scale.},
}
@article {pmid37519381,
year = {2023},
author = {Dasanayaka, NN and Sirisena, ND and Samaranayake, N},
title = {Associations of meditation with telomere dynamics: a case-control study in healthy adults.},
journal = {Frontiers in psychology},
volume = {14},
number = {},
pages = {1222863},
pmid = {37519381},
issn = {1664-1078},
abstract = {INTRODUCTION: Telomeres are protective end caps of chromosomes which naturally shorten with each cell division and thus with age. Short telomeres have been associated with many age-related diseases. Meditation has come to the fore as a mind-body practice which could influence the telomere dynamics underlying these phenomena. We previously reported meditation to be associated with higher telomerase levels, mindfulness and quality of life. Here, reporting on the same study population, we describe associations between long-term meditation and telomere length (TL), expression of hTERT and hTR genes and methylation of the promoter region of hTERT gene.<br><br>METHODS: Thirty healthy meditators and matched non-meditators were recruited. TL was measured using quantitative PCR, gene expression was assessed using reverse transcriptase PCR, and methylation level was quantified by bisulfite-specific PCR followed by Sanger sequencing. Comparisons between meditators and controls were carried out using t-tests, while Pearson correlation was used to identify correlations, and regression was used to identify predictors.<br><br>RESULTS: Males comprised 63.4% of each group with an average age of 43&#x2009;years. On average, they had meditated daily for 5.82&#x2009;h (&#xb1;3.45) for 6.8&#x2009;years (&#xb1;3.27). Meditators had longer relative TLs (p =&#x2009;0.020), and TL decreased with age (p <&#x2009;0.001) but was not associated with other socio-demographic variables. Regression analysis showed that age (p <&#x2009;0.001) and duration of meditation (p =&#x2009;0.003) significantly predicted TL. The meditators showed higher relative expression of hTERT (p =&#x2009;0.020) and hTR (p =&#x2009;0.029) genes while the methylation level of the promoter region of hTERT gene was significantly lower when compared to non-meditators (p <&#x2009;0.001). Negative correlations were identified between the methylation level of the promoter region of hTERT gene and the expression of the hTERT gene (p =&#x2009;0.001) and duration of meditation (p =&#x2009;0.001).<br><br>CONCLUSION: The findings suggest that meditation as a lifestyle practice has multi-level beneficial effects on telomere dynamics with potential to promote healthy aging.},
}
@article {pmid37515613,
year = {2023},
author = {Cai, Y and Guo, H and Zhou, J and Zhu, G and Qu, H and Liu, L and Shi, T and Ge, S and Qu, Y},
title = {An alternative extension of telomeres related prognostic model to predict survival in lower grade glioma.},
journal = {Journal of cancer research and clinical oncology},
volume = {149},
number = {15},
pages = {13575-13589},
pmid = {37515613},
issn = {1432-1335},
support = {81630027//National Natural Science Foundation of China/ ; },
abstract = {OBJECTIVE: The alternative extension of the telomeres (ALT) mechanism is activated in lower grade glioma (LGG), but the role of the ALT mechanism has not been well discussed. The primary purpose was to demonstrate the significance of the ALT mechanism in prognosis estimation for LGG patients.<br><br>METHOD: Gene expression and clinical data of LGG patients were collected from the Chinese Glioma Genome Atlas (CGGA) and the Cancer Genome Atlas (TCGA) cohort, respectively. ALT-related genes obtained from the TelNet database and potential prognostic genes related to ALT were selected by LASSO regression to calculate an ALT-related risk score. Multivariate Cox regression analysis was performed to construct a prognosis signature, and a nomogram was used to represent this signature. Possible pathways of the ALT-related risk score are explored by enrichment analysis.<br><br>RESULT: The ALT-related risk score was calculated based on the LASSO regression coefficients of 22 genes and then divided into high-risk and low-risk groups according to the median. The ALT-related risk score is an independent predictor of LGG (HR and 95% CI in CGGA cohort: 5.70 (3.79, 8.58); in TCGA cohort: 1.96 (1.09, 3.54)). ROC analysis indicated that the model contained ALT-related risk score was superior to conventional clinical features (AUC: 0.818 vs 0.729) in CGGA cohorts. The results in the TCGA cohort also shown a powerful ability of ALT-related risk score (AUC: 0.766 vs 0.691). The predicted probability and actual probability of the nomogram are consistent. Enrichment analysis demonstrated that the ALT mechanism was involved in the cell cycle, DNA repair, immune processes, and others.<br><br>CONCLUSION: ALT-related risk score based on the 22-gene is an important factor in predicting the prognosis of LGG patients.},
}
@article {pmid37511119,
year = {2023},
author = {Dmitrenko, OP and Abramova, OI and Karpova, NS and Nurbekov, MK and Arshinova, ES},
title = {Relative Telomere Length Is Associated with the Risk of Development and Severity of the Course of Age-Related Macular Degeneration in the Russian Population.},
journal = {International journal of molecular sciences},
volume = {24},
number = {14},
pages = {},
pmid = {37511119},
issn = {1422-0067},
support = {&#x2116; FGFU-2022-0011: &#xab;Identification of significant bioindicators of various disorders of body functions&#xbb;.//The work was carried out within the framework of the state task of the Federal State Budgetary Institution "Research Institute of Pathology and Pathophysiology" &#x2116; FGFU-2022-0011: &#xab;Identification of significant bioindicators of various disorders of body fu/ ; },
mesh = {Male ; Humans ; Female ; *Telomere/genetics ; Aging/pathology ; Risk Factors ; *Macular Degeneration/genetics ; Biomarkers ; Disease Progression ; },
abstract = {One of the most significant factors for age-related macular degeneration (AMD) development is considered to be aging, the processes of which are closely associated with telomere shortening. The different forms, indicators of aggressiveness, and intensities of AMD can be observed in the same age group, confirming the need to find a biomarker for early diagnosis and be capable of monitoring the progression of the pathological process. Therefore, we investigated whether the relative telomere length (RTL) has any connection with the risk of development of disease and its progression. RTL was measured using RT-PCR in 166 people, including 96 patients with AMD. RTL was significantly lower in patients with AMD. Women were more likely to develop AMD than men (odds ratio (OR) = 9.53 × 10[6] vs. OR = 1.04 × 10[8], respectively). The decrease in RTL in patients reliably correlated with the progression of AMD, and the smallest RTL was observed in late-stage patients. RTL < 0.8 is a significant risk factor for disease progression. The results of our research showed that RTL may be considered as a potential biomarker and a promising predictor of disease progression in patients with early AMD.},
}
@article {pmid37508101,
year = {2023},
author = {O'Daniel, SE and Kochan, KJ and Long, CR and Riley, DG and Randel, RD and Welsh, TH},
title = {Comparison of Telomere Length in Age-Matched Primiparous and Multiparous Brahman Cows.},
journal = {Animals : an open access journal from MDPI},
volume = {13},
number = {14},
pages = {},
pmid = {37508101},
issn = {2076-2615},
support = {USDA-NIFA grant 2019-67015-2957//United States Department of Agriculture/ ; },
abstract = {Physiological and psychological stressors have been associated with the attrition of telomeres, which are the protective caps of chromosomes. This study compares the telomere length (TL) in 4-year-old Brahman cows grouped by the first parity (n = 8) and the second parity (n = 11). The cows were bled via jugular venipuncture, weighed, and had their body condition scores recorded at Day -28 prior to calving and at Day + 7 and Day + 28 post-calving. The duration of labor (Dlabor) and parturition ease were recorded. The peripheral leukocytes were isolated, the leukocyte blood count with differential was recorded, and the genomic DNA was extracted. The relative quantity of telomere products, which is proportional to the average TL, was determined via multiplex quantitative PCR using the ratio (T/S ratio) of bovine telomere and β-globulin DNA. Standards of the bovine telomere (10[12]-10[7] dilution series) and β-globulin (10[9]-10[4] dilution series) genes were utilized to produce relative copy numbers. The samples were assayed in triplicate and were included if the triplicate Cq difference was less than 0.25 cycles. The parity was the fixed effect, and the random effects included the sire and day repeated with the cow as the subject. Statistical significance was not observed in the leukocyte number or type (p > 0.1). A reduction in the TL of approximately 9225 telomeric copies was found between Parity 1 and Parity 2 (p = 0.02). A trend was found between the TL and Dlabor (p = 0.06). The stress of parturition and raising the first calf of a cow's life may be responsible for TL attenuation. Parity may be considered a stressor of cow longevity.},
}
@article {pmid37502897,
year = {2023},
author = {Bazan, N and Bhattacharjee, S and Kala-Bhattacharjee, S and Ledet, A and Mukherjee, P},
title = {Elovanoids are neural resiliency epigenomic regulators targeting histone modifications, DNA methylation, tau phosphorylation, telomere integrity, senescence programming, and dendrite integrity.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {37502897},
support = {R01 EY005121/EY/NEI NIH HHS/United States ; },
abstract = {Cellular identity, developmental reorganization, genomic structure modulation, and susceptibility to diseases are determined by epigenomic regulation by multiple signaling interplay. Here we demonstrate that elovanoids (ELVs), mediators derived from very-long-chain polyunsaturated fatty acids (VLC-PUFAs, n-3, C > 28), and their precursors in neurons in culture overcome the damage triggered by oligomeric amyloid-beta (OAβ), erastin (ferroptosis-dependent cell death), or other insults that target epigenomic signaling. We uncover that ELVs counteract damage targeting histones H3K9 and H3K27 methylation and acetylation; tau hyperphosphorylation (pThr181, pThr217, pThr231, and pSer202/pThr205 (AT8)); senescence gene programming (p16INK4a, p27KIP, p21CIP1, and p53); DNA methylation (DNAm) modifying enzymes: TET (DNA hydroxymethylase), DNA methyltransferase, DNA demethylase, and DNAm (5mC) phenotype. Moreover, ELVs revert OAβ-triggered telomere length (TL) attrition as well as upregulation of telomerase reverse transcriptase (TERT) expression fostering dendrite protection and neuronal survival. Thus, ELVs modulate epigenomic resiliency by pleiotropic interrelated signaling.},
}
@article {pmid37496110,
year = {2023},
author = {Sung, S and Kim, E and Niida, H and Kim, C and Lee, J},
title = {Distinct characteristics of two types of alternative lengthening of telomeres in mouse embryonic stem cells.},
journal = {Nucleic acids research},
volume = {51},
number = {17},
pages = {9122-9143},
pmid = {37496110},
issn = {1362-4962},
mesh = {Animals ; Mice ; *Mouse Embryonic Stem Cells/metabolism ; Mutation ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere Homeostasis ; },
abstract = {Telomere length must be maintained in actively dividing cells to avoid cellular arrest or death. In the absence of telomerase activity, activation of alternative lengthening of telomeres (ALT) allows the maintenance of telomeric length and prolongs the cellular lifespan. Our previous studies have established two types of ALT survivors from mouse embryonic stem cells. The key differences between these ALT survivors are telomere-constituting sequences: non-telomeric sequences and canonical telomeric repeats, with each type of ALT survivors being referred to as type I and type II, respectively. We explored how the characteristics of the two types of ALT lines reflect their fates using multi-omics approaches. The most notable gene expression signatures of type I and type II ALT cell lines were chromatin remodelling and DNA repair, respectively. Compared with type II cells, type I ALT cells accumulated more mutations and demonstrated persistent telomere instability. These findings indicate that cells of the same origin have separate routes for survival, thus providing insights into the plasticity of crisis-suffering cells and cancers.},
}
@article {pmid37495394,
year = {2023},
author = {Cai, SW and de Lange, T},
title = {CST-Polα/Primase: the second telomere maintenance machine.},
journal = {Genes &amp; development},
volume = {37},
number = {13-14},
pages = {555-569},
pmid = {37495394},
issn = {1549-5477},
support = {R35 CA210036/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Humans ; *Telomerase/metabolism ; DNA Primase/genetics ; Telomere-Binding Proteins/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere Homeostasis ; DNA Replication ; Mammals/genetics ; },
abstract = {It has been known for decades that telomerase extends the 3' end of linear eukaryotic chromosomes and dictates the telomeric repeat sequence based on the template in its RNA. However, telomerase does not mitigate sequence loss at the 5' ends of chromosomes, which results from lagging strand DNA synthesis and nucleolytic processing. Therefore, a second enzyme is needed to keep telomeres intact: DNA polymerase α/Primase bound to Ctc1-Stn1-Ten1 (CST). CST-Polα/Primase maintains telomeres through a fill-in reaction that replenishes the lost sequences at the 5' ends. CST not only serves to maintain telomeres but also determines their length by keeping telomerase from overelongating telomeres. Here we discuss recent data on the evolution, structure, function, and recruitment of mammalian CST-Polα/Primase, highlighting the role of this complex and telomere length control in human disease.},
}
@article {pmid37494011,
year = {2023},
author = {Aung, N and Wang, Q and van Duijvenboden, S and Burns, R and Stoma, S and Raisi-Estabragh, Z and Ahmet, S and Allara, E and Wood, A and Di Angelantonio, E and Danesh, J and Munroe, PB and Young, A and Harvey, NC and Codd, V and Nelson, CP and Petersen, SE and Samani, NJ},
title = {Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure.},
journal = {JAMA cardiology},
volume = {8},
number = {9},
pages = {808-815},
pmid = {37494011},
issn = {2380-6591},
support = {MR/L003120/1/MRC_/Medical Research Council/United Kingdom ; BRC-1215-20014/DH_/Department of Health/United Kingdom ; RE/18/1/34212/BHF_/British Heart Foundation/United Kingdom ; FS/17/81/33318/BHF_/British Heart Foundation/United Kingdom ; PG/21/10619/BHF_/British Heart Foundation/United Kingdom ; BTRU-2014-10024/DH_/Department of Health/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; SP/16/4/32697/BHF_/British Heart Foundation/United Kingdom ; BCDSA\100005/BHF_/British Heart Foundation/United Kingdom ; MR/M012816/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_21001/MRC_/Medical Research Council/United Kingdom ; NIHR203312/DH_/Department of Health/United Kingdom ; RG/13/13/30194/BHF_/British Heart Foundation/United Kingdom ; BRC-1215-20010/DH_/Department of Health/United Kingdom ; RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; MC_PC_21003/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Male ; Middle Aged ; Humans ; Female ; Cross-Sectional Studies ; Phenotype ; *Heart Failure/genetics ; Leukocytes ; Telomere/genetics ; },
abstract = {IMPORTANCE: Longer leukocyte telomere length (LTL) is associated with a lower risk of adverse cardiovascular outcomes. The extent to which variation in LTL is associated with intermediary cardiovascular phenotypes is unclear.<br><br>OBJECTIVE: To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes.<br><br>This is a population-based cross-sectional study of UK Biobank participants recruited from 2006 to 2010. LTL was measured using a quantitative polymerase chain reaction method. Cardiovascular measurements were derived from cardiovascular magnetic resonance using machine learning. The median (IQR) duration of follow-up was 12.0 (11.3-12.7) years. The associations of LTL with imaging measurements and incident heart failure (HF) were evaluated by multivariable regression models. Genetic associations between LTL and significantly associated traits were investigated by mendelian randomization. Data were analyzed from January to May 2023.<br><br>EXPOSURE: LTL.<br><br>MAIN OUTCOMES AND MEASURES: Cardiovascular imaging traits and HF.<br><br>RESULTS: Of 40&#x202f;459 included participants, 19 529 (48.3%) were men, and the mean (SD) age was 55.1 (7.6) years. Longer LTL was independently associated with a pattern of positive cardiac remodeling (higher left ventricular mass, larger global ventricular size and volume, and higher ventricular and atrial stroke volumes) and a lower risk of incident HF (LTL fourth quartile vs first quartile: hazard ratio, 0.86; 95% CI, 0.81-0.91; P&#x2009;=&#x2009;1.8&#x2009;&#xd7;&#x2009;10-6). Mendelian randomization analysis suggested a potential causal association between LTL and left ventricular mass, global ventricular volume, and left ventricular stroke volume.<br><br>CONCLUSIONS AND RELEVANCE: In this cross-sectional study, longer LTL was associated with a larger heart with better cardiac function in middle age, which could potentially explain the observed lower risk of incident HF.},
}
@article {pmid37493024,
year = {2023},
author = {Li, T and Zhang, M and Li, Y and Han, X and Tang, L and Ma, T and Zhao, X and Zhao, R and Wang, Y and Bai, X and Zhang, K and Geng, X and Sui, L and Feng, X and Zhang, Q and Zhao, Y and Liu, Y and Stewart, JA and Wang, F},
title = {Cooperative interaction of CST and RECQ4 resolves G-quadruplexes and maintains telomere stability.},
journal = {EMBO reports},
volume = {24},
number = {9},
pages = {e55494},
pmid = {37493024},
issn = {1469-3178},
mesh = {Humans ; *DNA Replication ; Telomere-Binding Proteins/genetics ; *G-Quadruplexes ; Telomere Homeostasis ; Telomere/metabolism ; },
abstract = {Human CST (CTC1-STN1-TEN1) is a ssDNA-binding complex that interacts with the replisome to aid in stalled fork rescue. We previously found that CST promotes telomere replication to maintain genomic integrity via G-quadruplex (G4) resolution. However, the detailed mechanism by which CST resolves G4s in vivo and whether additional factors are involved remains unclear. Here, we identify RECQ4 as a novel CST-interacting partner and show that RECQ4 can unwind G4 structures in vitro using a FRET assay. Moreover, G4s accumulate at the telomere after RECQ4 depletion, resulting in telomere dysfunction, including the formation of MTSs, SFEs, and TIFs, suggesting that RECQ4 is crucial for telomere integrity. Furthermore, CST is also required for RECQ4 telomere or chromatin localization in response to G4 stabilizers. RECQ4 is involved in preserving genomic stability by CST and RECQ4 disruption impairs restart of replication forks stalled by G4s. Overall, our findings highlight the essential roles of CST and RECQ4 in resolving G-rich regions, where they collaborate to resolve G4-induced replication deficiencies and maintain genomic homeostasis.},
}
@article {pmid37491556,
year = {2024},
author = {Pérez-López, FR and López-Baena, MT and Ulloque-Badaracco, JR and Benites-Zapata, VA},
title = {Telomere Length in Patients with Gestational Diabetes Mellitus and Normoglycemic Pregnant Women: a Systematic Review and Meta-analysis.},
journal = {Reproductive sciences (Thousand Oaks, Calif.)},
volume = {31},
number = {1},
pages = {45-55},
pmid = {37491556},
issn = {1933-7205},
mesh = {Infant ; Humans ; Pregnancy ; Female ; *Diabetes, Gestational/diagnosis ; Pregnant Women ; Birth Weight ; Cholesterol ; Telomere ; },
abstract = {We performed a systematic review and meta-analysis of studies assessing telomere length in blood leukocytes or mononuclear cells in women with gestational diabetes mellitus (GDM) and normoglycemic pregnant women (NPW) and their infants. The review protocol was registered in PROSPERO (CRD42022300950). Searches were conducted in PubMed, Embase, LILACS, CNKI, and Wang Fang, from inception through November 2022. The primary outcomes were maternal and offspring telomere length. The Newcastle-Ottawa Scale was used to assess the quality of included studies. Random-effect meta-analyses were applied to estimate standardized mean differences (SMDs) and their 95% confidence interval (CI). The meta-analysis of four studies showed no significant maternal telomere length difference (SMD = -0.80, 95% CI: -1.66, 0.05) in women with GDM compared to NPW. In the sensibility analysis omitting one study with a small sample of women, the telomere length becomes significantly reduced in women with GDM (SMD = -1.10, 95% CI: -2.18, -0.02). GDM patients had increased glucose (SMD = 0.28, 95% CI: 0.09, 0.46) and glycosylated hemoglobin than NPW (SMD = 0.62, 95% CI: 0.23, 1.01) while total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides did not display differences between women with and without GDM. There was no significant difference in cord blood telomere length in offspring from women with GDM and NPW (SMD = 0.11, 95% CI: -0.52, 0.30). Cord blood insulin levels (SMD = 0.59, 95% CI: 0.33, 0.85) and birthweight (SMD = 0.59, 95% CI: 0.39, 0.79) were higher in offspring from pregnant women with GDM than in those from NPW. There were no significant differences in maternal and offspring telomere length between pregnancies with and without GDM.},
}
@article {pmid37489893,
year = {2023},
author = {Hoferichter, F and Jentsch, A and Maas, L and Hageman, G},
title = {Burnout among high school students is linked to their telomere length and relatedness with peers.},
journal = {Stress (Amsterdam, Netherlands)},
volume = {26},
number = {1},
pages = {2240909},
doi = {10.1080/10253890.2023.2240909},
pmid = {37489893},
issn = {1607-8888},
mesh = {Female ; Humans ; Male ; *Burnout, Psychological/genetics ; *Students ; Telomere/genetics ; Adolescent ; Interpersonal Relations ; Peer Group ; },
abstract = {School burnout is a serious concern, as it impairs students' health and academic success. According to the Conservation of Resources Theory, burnout results from the depletion of personal coping resources and can be counteracted by supportive social relationships. However, it is not yet clear how students' relatedness with their peers is linked to their burnout. Next to students' self-reported fatigue, biomarkers such as telomere length (TL), which presents an indicator of aging, complement stress research. To identify school-related factors that may prevent students from experiencing burnout and to link TL to students' self-reported burnout, the current study investigated how relatedness with peers as well as TL at the beginning of the school year explained students' burnout at the end of the school year. The sample included 78 students (Mage = 13.7 ± 0.7 years; 48% girls). Results of multilevel analysis in Mplus indicate that, over the school year, students with higher TL and those who experienced relatedness with their peers reported lower levels of burnout. Moreover, students who felt related to their peers exhibited a longer TL. The study implies that students' relatedness with their peers may be a promising setscrew to prevent students' burnout and support their physical health. This is one of the first studies to link TL with school-related variables such as burnout and relatedness to peers in a non-clinical student sample, providing a baseline for interventions and future interdisciplinary studies in the field of education and stress.},
}
@article {pmid37489536,
year = {2023},
author = {Schuermans, A and Nakao, T and Uddin, MM and Hornsby, W and Ganesh, S and Shadyab, AH and Liu, S and Haring, B and Shufelt, CL and Taub, MA and Mathias, RA and Kooperberg, C and Reiner, AP and Bick, AG and Manson, JE and Natarajan, P and Honigberg, MC},
title = {Age at Menopause, Leukocyte Telomere Length, and Coronary Artery Disease in Postmenopausal Women.},
journal = {Circulation research},
volume = {133},
number = {5},
pages = {376-386},
pmid = {37489536},
issn = {1524-4571},
support = {75N92021D00002/HL/NHLBI NIH HHS/United States ; R01 HL130733/HL/NHLBI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; K08 HL166687/HL/NHLBI NIH HHS/United States ; U01 HL120393/HL/NHLBI NIH HHS/United States ; HHSN268201500014C/HL/NHLBI NIH HHS/United States ; R01 HL141944/HL/NHLBI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; HHSN268201800001C/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; R01 HL146500/HL/NHLBI NIH HHS/United States ; HHSN268201000001I/HL/NHLBI NIH HHS/United States ; DP5 OD029586/OD/NIH HHS/United States ; R01 HL120393/HL/NHLBI NIH HHS/United States ; R01 HL148050/HL/NHLBI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; },
mesh = {Adult ; Female ; Humans ; *Coronary Artery Disease/epidemiology/genetics ; Leukocytes ; Menopause/genetics ; *Menopause, Premature ; Postmenopause/genetics ; Telomere/genetics ; },
abstract = {BACKGROUND: Premature menopause is a risk factor for accelerated cardiovascular aging, but underlying mechanisms remain incompletely understood. This study investigated the role of leukocyte telomere length (LTL), a marker of cellular aging and genomic instability, in the association of premature menopause with cardiovascular disease.<br><br>METHODS: Participants from the UK Biobank and Women's Health Initiative with complete reproductive history and LTL measurements were included. Primary analyses tested the association between age at menopause and LTL using multivariable-adjusted linear regression. Secondary analyses stratified women by history of gynecologic surgery. Mendelian randomization was used to infer causal relationships between LTL and age at natural menopause. Multivariable-adjusted Cox regression and mediation analyses tested the joint associations of premature menopause and LTL with incident coronary artery disease.<br><br>RESULTS: This study included 130&#x2005;254 postmenopausal women (UK Biobank: n=122&#x2005;224; Women's Health Initiative: n=8030), of whom 4809 (3.7%) had experienced menopause before age 40. Earlier menopause was associated with shorter LTL (meta-analyzed &#xdf;=-0.02 SD/5 years of earlier menopause [95% CI, -0.02 to -0.01]; P=7.2&#xd7;10[-12]). This association was stronger and significant in both cohorts for women with natural/spontaneous menopause (meta-analyzed &#xdf;=-0.04 SD/5 years of earlier menopause [95% CI, -0.04 to -0.03]; P<2.2&#xd7;10[-16]) and was independent of hormone therapy use. Mendelian randomization supported a causal association of shorter genetically predicted LTL with earlier age at natural menopause. LTL and age at menopause were independently associated with incident coronary artery disease, and mediation analyses indicated small but significant mediation effects of LTL in the association of menopausal age with coronary artery disease.<br><br>CONCLUSIONS: Earlier age at menopause is associated with shorter LTL, especially among women with natural menopause. Accelerated telomere shortening may contribute to the heightened cardiovascular risk associated with premature menopause.},
}
@article {pmid37487414,
year = {2023},
author = {Sun, P and Wei, P and Liu, H and Wu, J and Gross, ND and Sikora, AG and Wei, Q and Shete, S and Zafereo, ME and Liu, J and Li, G},
title = {GWAS-identified telomere length associated genetic variants predict risk of recurrence of HPV-positive oropharyngeal cancer after definitive radiotherapy.},
journal = {EBioMedicine},
volume = {94},
number = {},
pages = {104722},
pmid = {37487414},
issn = {2352-3964},
mesh = {Humans ; Genome-Wide Association Study ; *Papillomavirus Infections/complications/genetics ; *Oropharyngeal Neoplasms/genetics ; Squamous Cell Carcinoma of Head and Neck ; *Carcinoma, Squamous Cell/genetics ; *Head and Neck Neoplasms ; Telomere/genetics ; Polymorphism, Single Nucleotide ; Leukocytes ; },
abstract = {BACKGROUND: Lymphocyte telomere length (LTL)-related genetic variants may modulate LTL and affect recurrence of squamous cell carcinoma of the oropharynx (SCCOP).<br><br>METHODS: A total of 1013 patients with incident SCCOP were recruited and genotyped for 16 genome-wide association study (GWAS)-identified TL-related polymorphisms. Of these patients, 489 had tumour HPV16 status determination. Univariate and multivariate analyses were performed to evaluate associations.<br><br>FINDINGS: Of the 16&#xa0;TL-related polymorphisms, four were significantly associated with LTL: rs1920116, rs3027234, rs6772228, and rs11125529, and the patients with putatively favourable genotypes had approximately 1.5-3 times the likelihood of shorter LTL compared with patients with the corresponding risk genotypes. Moreover, patients with one to four favourable genotypes of the four combined polymorphisms had approximately 3-11 times the likelihood of shorter LTL compared with patients with no favourable genotype. The four LTL-related polymorphisms were significantly associated with approximately 40% reduced risk (for favourable genotypes) or doubled risk (for risk genotypes) of recurrence, and similar but more pronounced associations were observed in patients with tumour HPV16-positive SCCOP. Similarly, patients with one to four risk genotypes had significantly approximately 2.5-4 times increased recurrence risk compared with patients with no risk genotype, and similar but more pronounced associations were observed in patients with tumour HPV16-positive SCCOP.<br><br>INTERPRETATION: Four LTL-related polymorphisms individually or jointly modify LTL and risk of recurrence of SCCOP, particularly HPV-positive SCCOP. These LTL-related polymorphisms could have potential to further stratify patients with HPV-positive SCCOP for individualized treatment and better survival.<br><br>FUNDING: Not applicable.},
}
@article {pmid37478811,
year = {2023},
author = {Marti, A and Fernández de la Puente, M and Canudas, S and Zalba, G and Razquin, C and Valle-Hita, C and Fitó, M and Martínez-González, M&#xc1; and García-Calzón, S and Salas-Salvadó, J},
title = {Effect of a 3-year lifestyle intervention on telomere length in participants from PREDIMED-Plus: A randomized trial.},
journal = {Clinical nutrition (Edinburgh, Scotland)},
volume = {42},
number = {9},
pages = {1581-1587},
doi = {10.1016/j.clnu.2023.06.030},
pmid = {37478811},
issn = {1532-1983},
mesh = {Male ; Humans ; Female ; Middle Aged ; Aged ; Risk Factors ; *Cardiovascular Diseases/prevention &amp; control ; *Metabolic Syndrome ; Life Style ; Telomere ; *Diet, Mediterranean ; },
abstract = {BACKGROUND &amp; AIMS: Short telomeres have been observed in chronic disease patients. Identifying environmental and lifestyle factors that could reduce telomere attrition is crucial for disease prevention. The aim of this work was to determine whether weight-loss induced by an energy-reduced Mediterranean diet (erMedDiet) and physical activity (PA) could modify telomere length (TL).<br><br>METHODS: In 317 randomized non-smoker participants (mean age, 65.8&#xa0;&#xb1;&#xa0;4.98 years) with metabolic syndrome from two "Prevenci&#xf3;n con Dieta Mediterr&#xe1;nea-Plus" (PREDIMED-Plus) trial centers, we evaluated MedDiet adherence, PA, anthropometric variables and TL at baseline and after a 3-year intervention using an intensive lifestyle program (IG) with an erMedDiet and PA or an unrestricted MedDiet without PA promotion (CG).<br><br>RESULTS: Participants in the IG displayed greater 3-year weight reductions (-3.7&#xa0;&#xb1;&#xa0;4&#xa0;kg, P&#xa0;<&#xa0;0.001) compared to those in the CG. No differences in TL changes between groups were observed in the cohort as a whole. However, an interaction was observed between the intervention group and sex for TL changes (pinteraction&#xa0;=&#xa0;0.039). Women in the IG showed an increase in TL after 3-y (+0.25&#xa0;&#xb1;&#xa0;0.9, relative units) compared to women in the CG (-0.07&#xa0;&#xb1;&#xa0;1.0) (pANCOVA&#xa0;=&#xa0;0.036), whereas no differences between groups were observed in men. Women in the IG had a lower risk of telomere shortening after the intervention (OR&#xa0;=&#xa0;0.17, 95%CI: 0.05-0.64, p&#xa0;=&#xa0;0.008) compared to women in the CG.<br><br>CONCLUSIONS: A 3-year lifestyle intervention based on an erMedDiet and PA slowed telomere shortening in women but not in men.<br><br>TRIAL REGISTRATION: ISRCTN, ISRCTN89898870. Registered 24 July 2014- Retrospectively registered, https://www.isrctn.com/ISRCTN89898870.},
}
@article {pmid37477674,
year = {2023},
author = {Çakır, S},
title = {The Effect of Royal Jelly on Telomere Length and Some Biochemical Parameters in Wistar Albino Rats with Liver Damage Caused by Carbon Tetrachloride.},
journal = {Journal of medicinal food},
volume = {26},
number = {8},
pages = {580-585},
doi = {10.1089/jmf.2023.0042},
pmid = {37477674},
issn = {1557-7600},
mesh = {Rats ; Animals ; Bees ; Rats, Wistar ; *Carbon Tetrachloride/adverse effects ; Cholesterol, LDL ; *Liver Diseases/drug therapy ; Antioxidants/pharmacology/therapeutic use ; Liver ; Aspartate Aminotransferases ; },
abstract = {Royal jelly (RJ) is a natural bee product that has been used for therapeutic purposes since ancient times. The therapeutic properties of this product, which has rich biological content, are still being investigated with new approaches. In this study, the effect of RJ on telomere length, some antioxidant parameters, and lipid profile was examined. This study will contribute to the literature as it is the first to evaluate the effect of RJ on the length of telomeres in damaged liver tissues. In the study, the levels of serum triglyceride, total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), aspartate transaminase (AST), alanine transaminase (ALT), telomerase, 8'-hydroxy-2'-deoxyguanosine (8-OHdG), and paraoxonase-1 (PON1) were investigated with enzyme-linked immunosorbent assay method and telomere lengths were investigated by real-time quantitative polymerase chain reaction. The increased TC, LDL-C levels, and AST and ALT activities in the serum after carbon tetrachloride (CCl4) administration approached the control level after RJ administration. PON1 activity decreased in groups with CCl4. PON1 activity increased after RJ administration. The level of 8-OHdG, which increased groups with CCl4, decreased after RJ administration. According to the results of telomere length analysis in liver tissues, telomere lengths in damaged tissues were significantly shortened with CCl4 application and increased with RJ application. Based on the findings of the study, it was concluded that RJ may have therapeutic effects on telomere lengths and some biochemistry parameters.},
}
@article {pmid37477641,
year = {2023},
author = {Reddy, V and Hwang, C and Reddy, GP and Kim, SH},
title = {A Novel Role of Prostate-Specific Membrane Antigen in Telomere Stability in Prostate Cancer Cells.},
journal = {Molecular cancer research : MCR},
volume = {21},
number = {11},
pages = {1176-1185},
doi = {10.1158/1541-7786.MCR-23-0075},
pmid = {37477641},
issn = {1557-3125},
support = {W81XWH-17-1-0305//U.S. Department of Defense (DOD)/ ; W81XWH-22-1-0400//U.S. Department of Defense (DOD)/ ; },
mesh = {Male ; Humans ; *Prostate/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Antigens, Surface/genetics ; Glutamate Carboxypeptidase II/genetics ; *Prostatic Neoplasms/metabolism ; Phosphorylation ; Telomere/genetics/metabolism ; Cell Line, Tumor ; },
abstract = {UNLABELLED: Prostate-specific membrane antigen (PSMA) expression increases with prostate cancer grade and progression; however, the role of PSMA in prostate cancer progression remains poorly understood. Telomere stability is essential for the survival and genome stability of cancer cells. We found massive telomere DNA damage in PSMA-negative prostate cancer cells (PC-3 and DU145) compared with PSMA-positive prostate cancer (LNCaP) cells. The ectopic expression of PSMA suppressed telomere DNA damage in PC3 cells. PSMA inhibitor, 2-PMPA, and PSMA knockdown induced telomere DNA damage in PSMA-positive LNCaP cells but not in PSMA-negative PC-3 cells, suggesting that PSMA plays a critical role in telomere stability in prostate cancer cells. In addition, we observed that inhibition of PSMA or inhibition of glutamate receptor, which mediates PSMA-dependent activation of AKT, suppressed AKT phosphorylation, and caused telomere DNA damage. Furthermore, 2-PMPA-induced telomere DNA damage in LNCaP cells was associated with telomere aberrations, such as telomere-telomere fusions, sister-chromatid telomere fusions, and telomere breakages. AKT is reported to promote cell growth by stabilizing telomere association with telomere-binding proteins TRF1 and TPP1. We observed that TRF1 and TPP1 transfection of LNCaP cells attenuated the inhibitory effect of 2-PMPA on cell growth and telomere DNA damage. Together, these observations indicate that PSMA role in maintaining telomere stability in prostate cancer cells is mediated by AKT. Thus, these studies reveal an important role of PSMA in maintaining telomere stability that can promote cell survival and, thereby, prostate cancer progression.<br><br>IMPLICATIONS: Role of PSMA in telomere stability suggests a strong correlation between PSMA expression and prostate cancer progression.},
}
@article {pmid37477196,
year = {2023},
author = {Aoulad Fares, D and Wiegel, RE and Eggink, AJ and van Meurs, JBJ and Willemsen, SP and Danser, AHJ and Steegers-Theunissen, RPM},
title = {First-trimester maternal renin-angiotensin-aldosterone system activation and the association with maternal telomere length after natural and IVF/ICSI conceived pregnancies: the Rotterdam periconception cohort.},
journal = {Hypertension in pregnancy},
volume = {42},
number = {1},
pages = {2238086},
doi = {10.1080/10641955.2023.2238086},
pmid = {37477196},
issn = {1525-6065},
mesh = {Pregnancy ; Male ; Female ; Humans ; Pregnancy Trimester, First ; *Sperm Injections, Intracytoplasmic ; *Renin-Angiotensin System ; Renin ; Aldosterone ; Semen ; Fertilization ; Fertilization in Vitro ; Telomere ; },
abstract = {OBJECTIVE: To study associations between the first-trimester maternal determinants of renin-angiotensin-aldosterone system (RAAS) activation and telomere length (TL) in pregnancies conceived natural and after IVF/ICSI.<br><br>METHODS: In 145 pregnancies of the Rotterdam Periconception cohort renin, prorenin and aldosterone concentrations were measured in maternal blood at 9 weeks gestational age (GA). TL was measured by qPCR at 20 weeks GA.<br><br>RESULTS: A significantly negative correlation was found between renin and TL, which was attenuated for prorenin but not observed for aldosterone. Maternal TL was significantly shorter in pregnancies conceived after in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) compared to natural pregnancies.<br><br>CONCLUSION: The negative association between first-trimester maternal renin and maternal TL, and the shorter maternal TL in women after IVF/ICSI treatment compared to natural pregnancies, substantiates the role of excessive RAAS activation.},
}
@article {pmid37474692,
year = {2023},
author = {Kurashova, NA and Vanyarkina, AS and Petrova, AG and Rychkova, LV and Kolesnikov, SI and Darenskaya, MA and Moskaleva, EV and Kolesnikova, LI},
title = {Length of Leukocyte Telomeres in Newborns of HIV-Infected Mothers.},
journal = {Bulletin of experimental biology and medicine},
volume = {175},
number = {2},
pages = {260-264},
pmid = {37474692},
issn = {1573-8221},
mesh = {Pregnancy ; Female ; Infant, Newborn ; Humans ; Mothers ; Infectious Disease Transmission, Vertical/prevention &amp; control ; Cross-Sectional Studies ; *HIV Infections/drug therapy/genetics/prevention &amp; control ; Leukocytes ; Telomere/genetics ; *Pregnancy Complications, Infectious/genetics ; },
abstract = {We studied the relative length of telomeres in newborns with unrealized perinatal transmission of HIV (zero viral load according to PCR results). A cross-sectional survey of 62 newborns of HIV-infected mothers (Apgar score 8); the control group consisted of 80 healthy newborns (Apgar score 8). DNA extracted from whole venous blood samples was analyzed. In newborns of HIV-infected mothers, the relative length of telomeres was significantly lower (0.69 (0.66; 0.72)) than in newborns of the control group (1.1 (0.97; 1.22)) (p<0.001). No significant differences in the relative length of telomeres were found between newborns of mothers with a viral load at the time of delivery and with undetectable viral load: 0.69 (0.66; 0.73) and 0.69 (0.63; 0.72). These findings indicate that HIV-infection in mothers or exposure to antiretroviral therapy has an impact on the relative telomere length in leukocytes of newborns.},
}
@article {pmid37469277,
year = {2023},
author = {Lee, GO and Mora-Plazas, M and Marín, C and Villamor, E},
title = {Leukocyte telomere length predicts subsequent infectious morbidity among Colombian schoolchildren.},
journal = {American journal of human biology : the official journal of the Human Biology Council},
volume = {35},
number = {10},
pages = {e23966},
doi = {10.1002/ajhb.23966},
pmid = {37469277},
issn = {1520-6300},
support = {//ASISA Foundation/ ; },
abstract = {OBJECTIVE: Telomere length (TL) attrition is related to chronic disease risk. However, less is known on whether TL predicts infectious outcomes, especially in childhood. We examined whether leukocyte TL (LTL) was associated with subsequent infectious morbidity in schoolchildren.<br><br>METHODS: We assessed LTL in 717 Colombian children 5-12&#x2009;years-old at the beginning of a school year and followed them through the year for daily occurrence of common infection symptoms and doctor visits. We estimated adjusted incidence rate ratios (IRR) with 95% confidence intervals (CI) of gastrointestinal and respiratory syndromes for quartiles of standardized LTL Z score and per unit LTL Z score.<br><br>RESULTS: A longer LTL was associated with increased incidence of all infectious morbidity syndromes considered. Adjusted IRR (95% CI) per unit LTL Z score were 1.55 (1.20, 2.00) for diarrhea with vomiting, 1.34 (1.13, 1.60) for cough with fever, 1.70 (1.28, 2.28) for ear infection, and 1.66 (1.36, 2.02) for doctor visits with symptoms.<br><br>CONCLUSIONS: Longer LTL is related to increased incidence of common infectious morbidities in middle childhood.},
}
@article {pmid37463174,
year = {2023},
author = {Zhou, H and Xie, C and Xie, Y and He, Y and Chen, Y and Zhang, C and Zhang, Y and Zhao, Y and Liu, H},
title = {UBQLN1 deficiency mediates telomere shortening and IPF through interacting with RPA1.},
journal = {PLoS genetics},
volume = {19},
number = {7},
pages = {e1010856},
pmid = {37463174},
issn = {1553-7404},
mesh = {Humans ; Animals ; Mice ; *Telomere Shortening/genetics ; HeLa Cells ; *Idiopathic Pulmonary Fibrosis/genetics/epidemiology/pathology ; Telomere Homeostasis ; Telomere/genetics ; Replication Protein A/genetics ; Autophagy-Related Proteins/genetics ; Adaptor Proteins, Signal Transducing/genetics ; },
abstract = {Premature telomere shortening is a known factor correlated to idiopathic pulmonary fibrosis (IPF) occurrence, which is a chronic, progressive, age-related disease with high mortality. The etiology of IPF is still unknown. Here, we found that UBQLN1 plays a key role in telomere length maintenance and is potentially relevant to IPF. UBQLN1 involves in DNA replication by interacting with RPA1 and shuttling it off from the replication fork. The deficiency of UBQLN1 retains RPA1 at replication fork, hinders replication and thus causes cell cycle arrest and genome instability. Especially at telomere regions of the genome, where more endogenous replication stress exists because of G rich sequences, UBQLN1 depletion leads to rapid telomere shortening in HeLa cells. It revealed that UBQLN1 depletion also shortens telomere length at mouse lung and accelerates mouse lung fibrosis. In addition, the UBQLN1 expression level in IPF patients is downregulated and correlated to poor prognosis. Altogether, these results uncover a new role of UBQLN1 in ensuring DNA replication and maintaining telomere stability, which may shed light on IPF pathogenesis and prevention.},
}
@article {pmid37459977,
year = {2023},
author = {Mlakar, V and Birkenæs, V and Elvsaashagen, T and Ormerod, MBEG and Quintana, DS and Ueland, T and Melle, I and Lagerberg, TV and Djurovic, S and Martin-Ruiz, C and Steen, NE and Andreassen, OA and Aas, M},
title = {Telomere length and verbal learning in bipolar disorders.},
journal = {Journal of affective disorders},
volume = {339},
number = {},
pages = {555-560},
doi = {10.1016/j.jad.2023.07.087},
pmid = {37459977},
issn = {1573-2517},
support = {MR/WO27720/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; *Bipolar Disorder/drug therapy ; Telomere Shortening ; Telomere ; Neuropsychological Tests ; Memory, Short-Term ; Verbal Learning ; },
abstract = {INTRODUCTION: Recent studies indicate accelerated ageing processes, shorter telomere length and poorer cognitive functioning in patients with bipolar disorder. The neurobiology underlying cognitive function in bipolar disorder is yet to be established. We anticipated that accelerated ageing as indicated by shortened telomere length, would be associated with reduced cognitive performance in bipolar disorder, particularly for ageing sensitive functions such as memory and learning.<br><br>METHODS: The study consisted of 647 participants (bipolar disorder [n&#xa0;=&#xa0;246] and healthy controls [n&#xa0;=&#xa0;401]). All participants underwent a standardized neuropsychological test battery, including working memory, executive functioning, processing speed, verbal learning, and verbal memory. Leucocyte telomere length was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio). The T/S ratio was used as an estimate of the mean telomere length of each participant. All analyses were adjusted for medication, Daily Defined Dose (DDD), chronological age, sex, and ethnicity.<br><br>RESULTS: Patients had shorter telomere lengths than healthy controls (Cohen's d&#xa0;=&#xa0;0.11, p&#xa0;=&#xa0;0.01). Within patients', a positive association was observed for verbal learning and telomere length (&#x3b2;&#xa0;=&#xa0;0.14, p&#xa0;=&#xa0;0.025), along with a trend for verbal memory and telomere length (&#x3b2;&#xa0;=&#xa0;0.11, p&#xa0;=&#xa0;0.07). No other associations were observed for telomere length and cognitive functioning in the patient or the control group (p&#xa0;>&#xa0;0.1).<br><br>CONCLUSION: Our study may suggest poorer brain health in bipolar disorder as indexed by shorter telomere length and reduced learning correlates. However, the role of telomere length on cognitive functioning in bipolar disorder seems limited.},
}
@article {pmid37455385,
year = {2023},
author = {Neyaz, A and Crotty, R and Rickelt, S and Pankaj, A and Stojanova, M and Michelakos, TP and Sekigami, Y and Kontos, F and Parrack, PH and Patil, DT and Heaphy, CM and Ferrone, CR and Deshpande, V},
title = {Predicting recurrence in pancreatic neuroendocrine tumours: role of ARX and alternative lengthening of telomeres (ALT).},
journal = {Histopathology},
volume = {83},
number = {4},
pages = {546-558},
doi = {10.1111/his.14996},
pmid = {37455385},
issn = {1365-2559},
mesh = {Humans ; *Neuroendocrine Tumors/diagnosis/pathology ; *Pancreatic Neoplasms/diagnosis/pathology ; Disease-Free Survival ; Telomere/pathology ; Transcription Factors ; Homeodomain Proteins ; },
abstract = {BACKGROUND: While many pancreatic neuroendocrine tumours (PanNET) show indolent behaviour, predicting the biological behaviour of small nonfunctional PanNETs remains a challenge. Nonfunctional PanNETs with an epigenome and transcriptome that resemble islet alpha cells (ARX-positive) are more aggressive than neoplasms that resemble islet beta cells (PDX1-positive). In this study, we explore the ability of immunohistochemistry for ARX and PDX1 and telomere-specific fluorescence in situ hybridisation (FISH) for alternative lengthening of telomeres (ALT) to predict recurrence.<br><br>METHODS: Two hundred fifty-six patients with PanNETs were identified, and immunohistochemistry for ARX and PDX1 was performed. Positive staining was defined as strong nuclear staining in >5% of tumour cells. FISH for ALT was performed in a subset of cases.<br><br>RESULTS: ARX reactivity correlated with worse disease-free survival (DFS) (P&#x2009;=&#x2009;0.011), while there was no correlation between PDX1 reactivity and DFS (P&#x2009;=&#x2009;0.52). ALT-positive tumours (n&#x2009;=&#x2009;63, 31.8%) showed a significantly lower DFS (P&#x2009;<&#x2009;0.0001) than ALT-negative tumours (n&#x2009;=&#x2009;135, 68.2%). ARX reactivity correlated with ALT positivity (P&#x2009;<&#x2009;0.0001). Among nonfunctional tumours, recurrence was noted in 18.5% (30/162) of ARX-positive tumours and 7.5% (5/67) of ARX-negative tumours. Among WHO grade 1 and 2 PanNETs with &#x2264;2&#x2009;cm tumour size, 14% (6/43) of ARX-positive tumours recurred compared to 0 of 33 ARX-negative tumours and 33.3% (3/9) ALT-positive tumours showed recurrence versus 4.4% (2/45) ALT-negative tumours.<br><br>CONCLUSION: Immunohistochemistry for ARX and ALT FISH status may aid in distinguishing biologically indolent cases from aggressive small low-grade PanNETs, and help to identify patients who may preferentially benefit from surgical intervention.},
}
@article {pmid37454741,
year = {2023},
author = {Zhou, M and Cui, Y and Zuo, S and Peng, Q and Liu, Y and Li, X and Yang, Y and He, Q and Yu, X and Zhou, J and He, Z and He, Q},
title = {ZBTB40 is a telomere-associated protein and protects telomeres in human ALT cells.},
journal = {The Journal of biological chemistry},
volume = {299},
number = {9},
pages = {105053},
pmid = {37454741},
issn = {1083-351X},
mesh = {Humans ; Cell Line, Tumor ; *Telomere/genetics/metabolism ; Telomere Homeostasis/genetics ; Protein Binding ; DNA/metabolism ; Nuclear Bodies/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; Gene Knockdown Techniques ; Gene Knockout Techniques ; Apoptosis/genetics ; },
abstract = {Alternative lengthening of telomeres (ALTs) mechanism is activated in some somatic, germ cells, and human cancer cells. However, the key regulators and mechanisms of the ALT pathway remain elusive. Here we demonstrated that ZBTB40 is a novel telomere-associated protein and binds to telomeric dsDNA through its N-terminal BTB (BR-C, ttk and bab) or POZ (Pox virus and Zinc finger) domain in ALT cells. Notably, the knockout or knockdown of ZBTB40 resulted in the telomere dysfunction-induced foci and telomere lengthening in the ALT cells. The results also show that ZBTB40 is associated with ALT-associated promyelocytic leukemia nuclear bodies, and the loss of ZBTB40 induces the accumulation of the ALT-associated promyelocytic leukemia nuclear bodies in U2OS cells. Taken together, our results implicate that ZBTB40 is a key player of telomere protection and telomere lengthening regulation in human ALT cells.},
}
@article {pmid37452322,
year = {2023},
author = {Yue, K and Yao, X},
title = {Prognostic model based on telomere-related genes predicts the risk of oral squamous cell carcinoma.},
journal = {BMC oral health},
volume = {23},
number = {1},
pages = {484},
pmid = {37452322},
issn = {1472-6831},
mesh = {Humans ; Squamous Cell Carcinoma of Head and Neck/genetics ; *Carcinoma, Squamous Cell/pathology ; *Mouth Neoplasms/pathology ; Prognosis ; Biomarkers, Tumor/genetics ; *Head and Neck Neoplasms/genetics ; Gene Expression Regulation, Neoplastic/genetics ; },
abstract = {BACKGROUND: This study investigated a potential prognostic model based on telomere-related genes (TRGs) for the clinical prediction of oral squamous cell carcinoma (OSCC).<br><br>METHODS: Gene expression data and associated clinical phenotypes were obtained from online databases. Differentially expressed (DE)-TRGs were identified between OSCC and normal samples, followed by protein-protein interaction and enrichment analyses. Subsequently, the prognostic genes explored based on the DE-TRGs and survival data were applied in the establishment of the current prognostic model, and an integrated analysis was performed between high- and low-risk groups using a prognostic model. The expression of certain prognostic genes identified in the present study was validated using qPCR analysis and/or western blot in OSCC cell lines and clinical samples.<br><br>RESULTS: 169 DE-TRGs were identified between the OSCC samples and controls. DE-TRGs are mainly involved in functions such as hypoxia response and pathways such as the cell cycle. Eight TRGs (CCNB1, PDK4, PLOD2, RACGAP1, MET, PLK1, KPNA2, and CCNA2) associated with OSCC survival and prognosis were used to construct a prognostic model. qPCR analysis and western blot showed that most of the eight prognostic genes were consistent with the current bioinformatics results. Analysis of the high- and low-risk groups for OSCC determined by the prognostic model showed that the current prognostic model was reliable.<br><br>CONCLUSIONS: A novel prognostic model for OSCC was constructed by TRGs. PLOD2 and APLK1 may participate in the progression of OSCC via responses to hypoxia and cell cycle pathways, respectively. TRGs, including KPNA2 and CCNA2, may serve as novel prognostic biomarkers for OSCC.},
}
@article {pmid37447170,
year = {2023},
author = {Ren, Q and Zhang, G and Dong, C and Li, Z and Zhou, D and Huang, L and Li, W and Huang, G and Yan, J},
title = {Parental Folate Deficiency Inhibits Proliferation and Increases Apoptosis of Neural Stem Cells in Rat Offspring: Aggravating Telomere Attrition as a Potential Mechanism.},
journal = {Nutrients},
volume = {15},
number = {13},
pages = {},
pmid = {37447170},
issn = {2072-6643},
support = {82003439//National Natural Science Foundation of China/ ; 2019KJ166//Scientific Research Program of Tianjin Municipal Education Commission/ ; 2022KJ203//Scientific Research Program of Tianjin Municipal Education Commission/ ; },
mesh = {Animals ; Rats ; *Telomerase ; Telomere Shortening ; Telomere ; Folic Acid/pharmacology ; *Folic Acid Deficiency ; *Neural Stem Cells ; Apoptosis ; Cell Proliferation ; },
abstract = {The effect of maternal folate status on the fetal central nervous system (CNS) is well recognized, while evidence is emerging that such an association also exists between fathers and offspring. The biological functions of telomeres and telomerase are also related to neural cell proliferation and apoptosis. The study aimed to investigate the effect of parental folate deficiency on the proliferation and apoptosis of neural stem cells (NSCs) in neonatal offspring and the role of telomeres in this effect. In this study, rats were divided into four groups: maternal folate-deficient and paternal folate-deficient diet (D-D) group; maternal folate-deficient and paternal folate-normal diet (D-N) group; maternal folate-normal and paternal folate-deficient diet (N-D) group; and the maternal folate-normal and paternal folate-normal diet (N-N) group. The offspring were sacrificed at postnatal day 0 (PND0), and NSCs were cultured from the hippocampus and striatum tissues of offspring for future assay. The results revealed that parental folate deficiency decreased folate levels, increased homocysteine (Hcy) levels of the offspring's brain tissue, inhibited proliferation, increased apoptosis, shortened telomere length, and aggravated telomere attrition of offspring NSCs in vivo and in vitro. In vitro experiments further showed that offspring NSCs telomerase activity was inhibited due to parental folate deficiency. In conclusion, parental folate deficiency inhibited the proliferation and increased apoptosis of offspring NSCs, maternal folate deficiency had more adverse effects than paternal, and the mechanisms may involve the telomere attrition of NSCs.},
}
@article {pmid37445605,
year = {2023},
author = {Pendina, AA and Krapivin, MI and Sagurova, YM and Mekina, ID and Komarova, EM and Tikhonov, AV and Golubeva, AV and Gzgzyan, AM and Kogan, IY and Efimova, OA},
title = {Telomere Length in Human Spermatogenic Cells as a New Potential Predictor of Clinical Outcomes in ART Treatment with Intracytoplasmic Injection of Testicular Spermatozoa.},
journal = {International journal of molecular sciences},
volume = {24},
number = {13},
pages = {},
pmid = {37445605},
issn = {1422-0067},
support = {18-75-10046//Russian Science Foundation/ ; },
mesh = {Pregnancy ; Female ; Humans ; Male ; *Azoospermia/genetics/therapy/pathology ; Sperm Retrieval ; Retrospective Studies ; Semen ; Spermatozoa ; Testis/pathology ; },
abstract = {Predicting the clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles that use the testicular spermatozoa of azoospermic patients presents a challenge. Thus, the development of additional approaches to assessing the competence of a testicular-sperm-derived embryo without causing damage to gametes or the embryo is necessary. One of the key parameters in determining such developmental competence is telomere length (TL). We aimed to analyze TLs in spermatogenic cells from the testicular biopsy samples of azoospermic patients and determine how this parameter influences embryo competence for pre- and post-implantation development. Using Q-FISH, we studied the TL of the chromosomes in spermatogonia and spermatocytes I from the TESE biopsy samples of 30 azoospermic patients. An increase in TL was detected during the differentiation from spermatogonia to spermatocytes I. The patients' testicular spermatozoa were used in 37 ICSI cycles that resulted in 22 embryo transfers. Nine pregnancies resulted, of which, one was ectopic and eight ended in birth. The analysis of embryological outcomes revealed a dependence between embryo competence for development to the blastocyst stage and the TL in spermatogenic cells. The TLs in spermatogonia and spermatocytes I in the testicular biopsy samples were found to be higher in patients whose testicular sperm ICSI cycles resulted in a birth. Therefore, the length of telomeres in spermatogenic cells can be considered as a potential prognostic criterion in assessing the competence of testicular-sperm-derived embryos for pre- and post-implantation development. The results of this study provide the basis for the development of a laboratory test for the prediction of testicular sperm ICSI cycle outcomes.},
}
@article {pmid37444460,
year = {2023},
author = {Dhillon, VS and Deo, P and Fenech, M},
title = {The Relationship between Telomere Length and Nucleoplasmic Bridges and Severity of Disease in Prostate Cancer Patients.},
journal = {Cancers},
volume = {15},
number = {13},
pages = {},
pmid = {37444460},
issn = {2072-6694},
abstract = {Telomeres are repetitive nucleotide (TTAGGG) sequences that stabilize the chromosome ends and play an important role in the prevention of cancer initiation and progression. Nucleoplasmic bridges (NPBs) are formed when chromatids remain joined together during mitotic anaphase either due to mis-repair of DNA breaks or due to chromatid end fusion as a result of telomere loss or telomere dysfunction. We tested the hypotheses that (i) telomere length (TL) is shorter in prostate cancer (PC) patients relative to healthy age-matched individuals, (ii) TL differs in different stages of PC and (iii) shorter TL is significantly correlated with NPBs formation in PC cases. TL was measured in whole blood by well-established quantitative PCR method and the frequency of NPBs was measured in lymphocytes using cytokinesis-block micronucleus cytome (CBMNcyt) assay. Our results indicate that TL is shorter and NPBs are increased in PC patients relative to age-matched healthy controls. Furthermore, TL was significantly shorter (p = 0.03) in patients with a Gleason score more than 7 and there was also a significant trend of decreasing TL across all three stages (p trend = 0.01; Gleason score <7, 7 and >7). Furthermore, TL was significantly inversely correlated with NPB frequency in PC patients (r = -0.316; p = 0.001) but not in controls (r = 0.163; p = 0.06) and their relationships became stronger with higher Gleason scores. More studies are required that can confirm our observations and explore mechanistic differences in the role of telomeres in NPB formation in PC cases relative to non-cancer cases.},
}
@article {pmid37433812,
year = {2023},
author = {Zhang, X and Yu, Q and Wu, Y and Zhang, Y and He, Y and Wang, R and Yu, X and Li, S},
title = {Glc7/PP1 dephosphorylates histone H3T11 to regulate autophagy and telomere silencing in response to nutrient availability.},
journal = {Cell discovery},
volume = {9},
number = {1},
pages = {71},
pmid = {37433812},
issn = {2056-5968},
support = {31970578//National Natural Science Foundation of China (National Science Foundation of China)/ ; 31872812//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2021CFA013//Natural Science Foundation of Hubei Province (Hubei Provincial Natural Science Foundation)/ ; 2019CFA077//Natural Science Foundation of Hubei Province (Hubei Provincial Natural Science Foundation)/ ; },
abstract = {How cells adapt their gene expression to nutritional changes remains poorly understood. Histone H3T11 is phosphorylated by pyruvate kinase to repress gene transcription. Here, we identify the protein phosphatase 1 (PP1), Glc7 as the enzyme that specifically dephosphorylates H3T11. We also characterize two novel Glc7-containing complexes and reveal their roles in regulating gene expression upon glucose starvation. Specifically, the Glc7-Sen1 complex dephosphorylates H3T11 to activate the transcription of autophagy-related genes. The Glc7-Rif1-Rap1 complex dephosphorylates H3T11 to derepress the transcription of telomere-proximal genes. Upon glucose starvation, Glc7 expression is up-regulated and more Glc7 translocates into the nucleus to dephosphorylate H3T11, leading to induction of autophagy and derepressed transcription of telomere-proximal genes. Furthermore, the functions of PP1/Glc7 and the two Glc7-containing complexes are conserved in mammals to regulate autophagy and telomere structure. Collectively, our results reveal a novel mechanism that regulate gene expression and chromatin structure in response to glucose availability.},
}
@article {pmid37433224,
year = {2023},
author = {Ibrahim, KG and Chivandi, E and Erlwanger, KH and Brooksbank, RL},
title = {Neonatal administration of fenofibrate had no developmental programming effect on the lipid profile and relative leucocyte telomere lengths of adolescent rats fed a high-fructose diet postnatally.},
journal = {Canadian journal of physiology and pharmacology},
volume = {101},
number = {11},
pages = {565-573},
doi = {10.1139/cjpp-2022-0528},
pmid = {37433224},
issn = {1205-7541},
mesh = {Male ; Rats ; Animals ; Female ; *Fenofibrate/pharmacology ; Fructose/adverse effects ; Rats, Sprague-Dawley ; Diet ; Cholesterol ; Triglycerides ; },
abstract = {Telomere length, a marker of ageing, is susceptible to developmental programming that may cause its accelerated attrition. Metabolic syndrome triggers telomere attrition. Fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, is protective against telomere attrition. We investigated the impact of fenofibrate administered during suckling on the lipid profile and leucocyte telomere lengths of rats fed a high-fructose diet post-weaning. Suckling Sprague-Dawley pups (n = 119) were allocated to four groups and gavaged with either 10 mL·kg[-1] body mass 0.5% dimethyl sulfoxide, 100 mg·kg[-1] body mass fenofibrate, fructose (20%, w / v), or a combination of fenofibrate and fructose for 15 days. Upon weaning, each of the initial groups was split into two subgroups: one had plain water while the other had fructose solution (20%, w / v) to drink for 6 weeks. Blood was collected for DNA extraction and relative leucocyte telomere length determination by real-time PCR. Plasma triglycerides and cholesterol were also quantified. The treatments had no effect (p > 0.05) on body mass, cholesterol concentration, and relative leucocyte telomere lengths in both sexes. Post-weaning fructose increased triglyceride concentrations (p < 0.05) in female rats. Fenofibrate administered during suckling did not affect ageing nor did it prevent high fructose-induced hypertriglyceridaemia in female rats.},
}
@article {pmid37432588,
year = {2023},
author = {Yung, Y and Maydan, SA and Bart, Y and Orvieto, R and Aizer, A},
title = {Human granulosa cells of poor ovarian responder patients display telomeres shortening.},
journal = {Journal of assisted reproduction and genetics},
volume = {40},
number = {8},
pages = {1943-1947},
pmid = {37432588},
issn = {1573-7330},
mesh = {Female ; Humans ; Aged ; *Fertilization in Vitro ; *Granulosa Cells ; Ovary ; Oocyte Retrieval ; Telomere/genetics ; Ovulation Induction ; },
abstract = {OBJECTIVE: We aimed to compare the telomere length in granulosa cells of the young normal and poor ovarian responder patients and elderly patients undergoing ovarian stimulation for IVF.<br><br>METHODS: The main outcome measures granulosa cells telomere Length in the 3 study groups of patients undergoing IVF treatment in our center. 1) young normal responder patients (<&#x2009;35&#xa0;years); 2) young (<&#x2009;35&#xa0;years) poor ovarian responder patients; and 3) Elderly patients (40-45&#xa0;years). Granulosa cells were obtained at the time of oocyte retrieval. Granulosa cells telomere length was assessed by absolute human telomere length quantification qPCR Assay.<br><br>RESULTS: The telomere length of the young normal responder was significantly longer as compared to young poor ovarian responder (15.5 vs 9.6&#xa0;KB, p&#x2009;<&#x2009;0.001) and the elderly patients (15.5 vs 10.66&#xa0;KB, p&#x2009;<&#x2009;0.002). No significant difference was observed in the telomere length between the young poor ovarian responder and the elderly patients.<br><br>CONCLUSIONS: Granulosa cells telomere length of the young normal responder was found to be significantly longer than young poor ovarian responder or elderly patients, highlighting the role of telomere length as a predictor, or contributor to poor oocyte yield following IVF treatment.},
}
@article {pmid37424625,
year = {2023},
author = {Karaviti, E and Kontogiannis, A and Anastopoulos, A and Kotteas, E and Gomatou, G},
title = {An overview of the role of telomeres and telomerase in pre‑neoplastic lesions (Review).},
journal = {Molecular and clinical oncology},
volume = {19},
number = {2},
pages = {61},
pmid = {37424625},
issn = {2049-9469},
abstract = {Telomeres are tandem repeats of DNA sequences protecting the end of linear chromosomes. Replicative senescence due to telomere attrition is considered a tumor-preventing mechanism in differentiated somatic cells. However, telomere shortening is associated with genome instability and several disease entities. During carcinogenesis, the development of a telomere maintenance mechanism, predominately through the activation of the telomerase enzyme, represents a hallmark of cancer, since it enables cancer cells to avert senescence and divide indefinitely. Although research of the involvement of telomeres and telomerase in various malignant neoplasms has gained a large amount of interest, the timing and relevance of their role in pre-neoplastic lesions remain to be determined. The present narrative review aims to summarize the evidence regarding the role of telomeres and telomerase in pre-neoplasia across different types of tissues.},
}
@article {pmid37421961,
year = {2023},
author = {Luo, S and Wong, ICK and Chui, CSL and Zheng, J and Huang, Y and Schooling, CM and Yeung, SLA},
title = {Effects of putative metformin targets on phenotypic age and leukocyte telomere length: a mendelian randomisation study using data from the UK Biobank.},
journal = {The lancet. Healthy longevity},
volume = {4},
number = {7},
pages = {e337-e344},
doi = {10.1016/S2666-7568(23)00085-5},
pmid = {37421961},
issn = {2666-7568},
mesh = {Humans ; *Metformin/pharmacology/therapeutic use ; *Diabetes Mellitus, Type 2/drug therapy/genetics/metabolism ; Biological Specimen Banks ; Cross-Sectional Studies ; Biomarkers ; Hemoglobin A/genetics ; Transcription Factors/genetics/therapeutic use ; Telomere/genetics/metabolism ; United Kingdom ; },
abstract = {BACKGROUND: Metformin, a first-line medication for type 2 diabetes, might also have a protective effect against ageing-related diseases, but so far little experimental evidence is available. We sought to assess the target-specific effect of metformin on biomarkers of ageing in the UK Biobank.<br><br>METHODS: In this drug target mendelian randomisation study, we assessed the target-specific effect of four putative targets of metformin (AMPK, ETFDH, GPD1, and PEN2), involving ten genes. Genetic variants with evidence of causation of gene expression, glycated haemoglobin A1c (HbA1c), and colocalisation were used as instruments mimicking the target-specific effect of metformin via HbA1c lowering. The biomarkers of ageing considered were phenotypic age (PhenoAge) and leukocyte telomere length. To triangulate the evidence, we also assessed the effect of HbA1c on the outcomes using a polygenic mendelian randomisation design and assessed the effect of metformin use on these outcomes using a cross-sectional observational design.<br><br>FINDINGS: GPD1-induced HbA1c lowering was associated with younger PhenoAge (&#x3b2; -5&#xb7;26, 95% CI -6&#xb7;69 to -3&#xb7;83) and longer leukocyte telomere length (&#x3b2; 0&#xb7;28, 0&#xb7;03 to 0&#xb7;53), and AMPK&#x3b3;2 (PRKAG2)-induced HbA1c lowering was associated with younger PhenoAge (&#x3b2; -4&#xb7;88, -7&#xb7;14 to -2&#xb7;62) but not with longer leukocyte telomere length. Genetically predicted HbA1c lowering was associated with younger PhenoAge (&#x3b2; -0&#xb7;96 per SD lowering of HbA1c, 95% CI -1&#xb7;19 to -0&#xb7;74) but not associated with leukocyte telomere length. In the propensity score matched analysis, metformin use was associated with younger PhenoAge (&#x3b2; -0&#xb7;36, 95% CI -0&#xb7;59 to -0&#xb7;13) but not with leukocyte telomere length.<br><br>INTERPRETATION: This study provides genetic validation evidence that metformin might promote healthy ageing via targets GPD1 and AMPK&#x3b3;2 (PRKAG2), and the effect could be in part due to its glycaemic property. Our findings support further clinical research into metformin and longevity.<br><br>FUNDING: Healthy Longevity Catalyst Award, National Academy of Medicine, and Seed Fund for Basic Research, The University of Hong Kong.},
}
@article {pmid37419142,
year = {2024},
author = {Heleniak, C and Goff, B and Gabard-Durnam, LJ and Telzer, EH and Humphreys, KL and Lumian, DS and Flannery, JE and Caldera, C and Shapiro, M and Louie, JY and Shen, F and Vannucci, A and Jain, M and Glatt, CE and Tottenham, N},
title = {Telomere Erosion and Depressive Symptoms Across Development Following Institutional Care.},
journal = {Journal of the American Academy of Child and Adolescent Psychiatry},
volume = {63},
number = {3},
pages = {365-375},
doi = {10.1016/j.jaac.2023.06.011},
pmid = {37419142},
issn = {1527-5418},
mesh = {Adult ; Child ; Child, Preschool ; Adolescent ; Humans ; *Depression/genetics/diagnosis ; Longitudinal Studies ; *Telomere Shortening ; Psychopathology ; Telomere ; },
abstract = {OBJECTIVE: A large literature has identified exposure to early caregiving adversities as a potent risk for developing affective psychopathology, with depression, in particular, increasing across childhood into adolescence. Evidence suggests telomere erosion, a marker of biological aging, may underlie associations between adverse early-life experiences and later depressive behavior; yet, little is understood about this association during development.<br><br>METHOD: The current accelerated longitudinal study examined concurrent telomere length and depressive symptoms concurrently, 2 and 4 years later, from the preschool period through adolescence among children exposed (n&#xa0;=116) and not exposed (n&#xa0;= 242) to early previous institutional (PI) care.<br><br>RESULTS: PI care was associated with shorter telomeres on average and with quadratic age-related growth in depressive symptoms, indicating a steeper association between PI care and depressive symptoms in younger age groups that leveled off in adolescence. Contrary to studies in adult samples, telomere length was not associated with depressive symptoms, and it did not predict future symptoms.<br><br>CONCLUSION: These findings indicate that early caregiving disruptions increase the risk for both accelerated biological aging and depressive symptoms, although these variables did not correlate with each other during this age range.},
}
@article {pmid37415075,
year = {2023},
author = {Loh, NY and Rosoff, D and Noordam, R and Christodoulides, C},
title = {Investigating the impact of metabolic syndrome traits on telomere length: a Mendelian randomization study.},
journal = {Obesity (Silver Spring, Md.)},
volume = {31},
number = {8},
pages = {2189-2198},
pmid = {37415075},
issn = {1930-739X},
support = {FS/16/45/32359/BHF_/British Heart Foundation/United Kingdom ; },
mesh = {Humans ; *Metabolic Syndrome/epidemiology/genetics/metabolism ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Aging ; Telomere/genetics ; Leukocytes/metabolism ; },
abstract = {OBJECTIVE: Observational studies have reported bidirectional associations between metabolic syndrome (MetS) traits and short leukocyte telomere length (LTL), a TL marker in somatic tissues and a proposed risk factor for age-related degenerative diseases. However, in Mendelian randomization studies, longer LTL has been paradoxically associated with higher MetS risk. This study investigated the hypothesis that shorter LTL might be a consequence of metabolic dysfunction.<br><br>METHODS: This study undertook univariable and multivariable Mendelian randomization. As instrumental variables for MetS traits, all of the genome-wide significant independent signals identified in genome-wide association studies for anthropometric, glycemic, lipid, and blood pressure traits conducted in European individuals were used. Summary-level data for LTL were obtained from a genome-wide association study conducted in the UK Biobank.<br><br>RESULTS: Higher BMI was associated with shorter LTL (&#x3b2;&#x2009;=&#x2009;-0.039, 95% CI:&#x2009;-0.058 to -0.020, p&#x2009;=&#x2009;5&#x2009;&#xd7;&#x2009;10[-5]) equivalent to 1.70&#x2009;years of age-related LTL change. In contrast, higher low-density lipoprotein cholesterol was associated with longer LTL (&#x3b2;&#x2009;=&#x2009;0.022, 95% CI:&#x2009;0.007 to 0.037, p&#x2009;=&#x2009;0.003) equivalent to 0.96&#x2009;years of age-related LTL change. Mechanistically, increased low-grade systemic inflammation, as measured by circulating C-reactive protein, and lower circulating linoleic acid levels might link higher BMI to shorter LTL.<br><br>CONCLUSIONS: Overweight and obesity might promote the development of aging-related degenerative diseases by accelerating telomere shortening.},
}
@article {pmid37405953,
year = {2023},
author = {},
title = {Erratum: Fluorescence In Situ Hybridization on DNA Halo Preparations to Reveal Whole Chromosomes, Telomeres and Gene Loci.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {196},
pages = {},
doi = {10.3791/6564},
pmid = {37405953},
issn = {1940-087X},
abstract = {An erratum was issued for: Fluorescence In Situ Hybridization on DNA Halo Preparations to Reveal Whole Chromosomes, Telomeres and Gene Loci. The Authors section was updated from: Lauren S. Godwin[1] Joanna M. Bridger[1] Helen A. Foster[2] [1]Laboratory of Nuclear and Genomic Health, Centre for Genome Engineering and Maintenance, Division of Biosciences, Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London [2]Biosciences, Department of Clinical, Pharmaceutical and Biological Science, School of Life and Medical Sciences, University of Hertfordshire to: Lauren S. Godwin[1] Emily Roberts[2] Joanna M. Bridger[1] Helen A. Foster[2] [1]Laboratory of Nuclear and Genomic Health, Centre for Genome Engineering and Maintenance, Division of Biosciences, Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London [2]Biosciences, Department of Clinical, Pharmaceutical and Biological Science, School of Life and Medical Sciences, University of Hertfordshire.},
}
@article {pmid37400833,
year = {2023},
author = {Tire, B and Ozturk, S},
title = {Potential effects of assisted reproductive technology on telomere length and telomerase activity in human oocytes and early embryos.},
journal = {Journal of ovarian research},
volume = {16},
number = {1},
pages = {130},
pmid = {37400833},
issn = {1757-2215},
mesh = {Humans ; *Telomerase/genetics ; Oocytes/metabolism ; Germ Cells/metabolism ; Reproductive Techniques, Assisted ; Telomere/genetics/metabolism ; },
abstract = {Telomeres are repetitive DNA sequences at eukaryotic chromosome ends and function in maintaining genome integrity and stability. These unique structures undergo shortening due to various factors including biological aging, consecutive DNA replication, oxidative stress, and genotoxic agents. Shortened telomeres can be lengthened by the enzyme telomerase and alternative lengthening of telomeres in germ cells, early embryos, stem cells, and activated lymphocytes. If telomeres reach to critical length, it may lead to genomic instability, chromosome segregation defects, aneuploidy, and apoptosis. These phenotypes also occur in the oocytes and early embryos, produced using assisted reproductive technologies (ARTs). Thus, a number of studies have examined the potential effects of ART applications such as ovarian stimulation, culture conditions, and cryopreservation procedures on telomeres. Herein, we comprehensively reviewed impacts of these applications on telomere length and telomerase activity in ART-derived oocytes and embryos. Further, we discussed use of these parameters in ART centers as a biomarker in determining oocyte and embryo quality.},
}
@article {pmid37397566,
year = {2023},
author = {Kung, SC and Dixon, O and Kentwell, S and Vasireddy, RS and Rodgers, J and Ding, Y and Rahman, T and Tallis, C and Yang, IA and Mackintosh, JA},
title = {Telomere biology disorder presenting acutely with pulmonary fibrosis and hepatopulmonary syndrome in a young adult male.},
journal = {Respirology case reports},
volume = {11},
number = {8},
pages = {e01182},
pmid = {37397566},
issn = {2051-3380},
abstract = {A 33-year-old man presented with acute dyspnoea and profound hypoxaemia, and had clubbing, greying of hair, orthodeoxia and fine inspiratory crackles. CT chest showed established pulmonary fibrosis in a usual interstitial pneumonia pattern. Additional investigations revealed a small patent foramen ovale, pancytopenia, and oesophageal varices and portal hypertensive gastropathy from liver cirrhosis. Telomere length testing demonstrated short telomeres (<1st percentile), confirming the diagnosis of a telomere biology disorder. An interstitial lung disease gene panel identified a pathogenic variant in TERT (c.1700C>T, p.(Thr567Met)) and a variant of uncertain significance in PARN (c.1159G>A, p.(Gly387Arg)). Combined lung and liver transplantation was deemed not suitable due to frailty and severe hepatopulmonary syndrome, and he died 56 days after presentation. Early recognition of the short telomere syndrome is important, and its multi-organ involvement poses challenges to management. Genetic screening may be important in younger patients with pulmonary fibrosis or in unexplained liver cirrhosis.},
}
@article {pmid37395529,
year = {2023},
author = {Ton, R and Boner, W and Raveh, S and Monaghan, P and Griffith, SC},
title = {Effects of heat waves on telomere dynamics and parental brooding effort in nestlings of the zebra finch (Taeniopygia castanotis) transitioning from ectothermy to endothermy.},
journal = {Molecular ecology},
volume = {32},
number = {17},
pages = {4911-4920},
doi = {10.1111/mec.17064},
pmid = {37395529},
issn = {1365-294X},
mesh = {Animals ; Hot Temperature ; *Passeriformes/physiology ; Body Temperature Regulation ; Telomere/genetics ; *Finches/genetics ; },
abstract = {Heat waves are predicted to be detrimental for organismal physiology with costs for survival that could be reflected in markers of biological state such as telomeres. Changes in early life telomere dynamics driven by thermal stress are of particular interest during the early post-natal stages of altricial birds because nestlings quickly shift from being ectothermic to endothermic after hatching. Telomeres of ectothermic and endothermic organisms respond differently to environmental temperature, but few investigations within species that transition from ectothermy to endothermy are available. Also, ambient temperature influences parental brooding behaviour, which will alter the temperature experienced by offspring and thereby, potentially, their telomeres. We exposed zebra finch nestlings to experimental heat waves and compared their telomere dynamics to that of a control group at 5, 12 and 80 days of age that encapsulate the transition from the ectothermic to the endothermic thermoregulatory stage; we also recorded parental brooding, offspring sex, mass, growth rates, brood size and hatch order. Nestling mass showed an inverse relationship with telomere length, and nestlings exposed to heat waves showed lower telomere attrition during their first 12 days of life (ectothermic stage) compared to controls. Additionally, parents of heated broods reduced the time they spent brooding offspring (at 5 days old) compared to controls. Our results indicate that the effect of heat waves on telomere dynamics likely varies depending on age and thermoregulatory stage of the offspring in combination with parental brooding behaviour during growth.},
}
@article {pmid37392813,
year = {2023},
author = {Hannan, SJ and Iasella, CJ and Sutton, RM and Popescu, ID and Koshy, R and Burke, R and Chen, X and Zhang, Y and Pilewski, JM and Hage, CA and Sanchez, PG and Im, A and Farah, R and Alder, JK and McDyer, JF},
title = {Lung transplant recipients with telomere-mediated pulmonary fibrosis have increased risk for hematologic complications.},
journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons},
volume = {23},
number = {10},
pages = {1590-1602},
doi = {10.1016/j.ajt.2023.06.014},
pmid = {37392813},
issn = {1600-6143},
support = {R01 HL135062/HL/NHLBI NIH HHS/United States ; R01 HL166265/HL/NHLBI NIH HHS/United States ; R01 HL133184/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Retrospective Studies ; Transplant Recipients ; *Telomerase/genetics/metabolism ; Lung/metabolism ; *Idiopathic Pulmonary Fibrosis/genetics/surgery/pathology ; Telomere/genetics/metabolism/pathology ; },
abstract = {Idiopathic pulmonary fibrosis lung transplant recipients (IPF-LTRs) are enriched for short telomere length (TL) and telomere gene rare variants. A subset of patients with nontransplant short-TL are at increased risk for bone marrow (BM) dysfunction. We hypothesized that IPF-LTRs with short-TL and/or rare variants would be at increased risk for posttransplant hematologic complications. Data were extracted from a retrospective cohort of 72 IPF-LTRs and 72 age-matched non-IPF-LTR controls. Genetic assessment was done using whole genome sequencing or targeted sequence panel. TL was measured using flow cytometry and fluorescence in-situ hybridization (FlowFISH) and TelSeq software. The majority of the IPF-LTR cohort had short-TL, and 26% of IPF-LTRs had rare variants. Compared to non-IPF controls, short-TL IPF-LTRs were more likely to have immunosuppression agents discontinued due to cytopenias (P = .0375), and BM dysfunction requiring BM biopsy was more prevalent (29% vs 4%, P = .0003). IPF-LTRs with short-TL and rare variants had increased requirements for transfusion and growth factor support. Multivariable logistic regression demonstrated that short-TL, rare variants, and lower pretransplant platelet counts were associated with BM dysfunction. Pretransplant TL measurement and genetic testing for rare telomere gene variants identified IPF-LTRs at increased risk for hematologic complications. Our findings support stratification for telomere-mediated pulmonary fibrosis in lung transplant candidates.},
}
@article {pmid37392033,
year = {2023},
author = {Zhang, R and Wu, M and Ma, M and Liu, B and Zhang, X and Wei, N and Wang, T and Lv, Y and Xu, C and Wang, J and Zhang, Y and Liu, F},
title = {Genetic evidence for the causal linkage between telomere length and aortic aneurysm risk: A Mendelian randomisation study.},
journal = {European journal of clinical investigation},
volume = {53},
number = {11},
pages = {e14056},
doi = {10.1111/eci.14056},
pmid = {37392033},
issn = {1365-2362},
support = {2022JZ-47//Key Basic Natural Science Foundation of Shaanxi Province/ ; 2020ZDLSF01-08//Key Industrial Innovation Chain Project in Shaanxi Province of China/ ; 2021ZDLSF02-03//Key Industrial Innovation Chain Project in Shaanxi Province of China/ ; 2021-03-22-001//Key Program for the Traditional Chinese Medicine Inheritance and Innovation and "Qin Medicine" Development/ ; 2022SF-476//Natural Science Foundation of Shaanxi Province/ ; 2021JQ-911//Natural Science Foundation of Shaanxi Province/ ; 2022D024//Shaanxi Provincial Health and Health Research Fund Project/ ; },
abstract = {BACKGROUND: Evidence of a clear causal relationship between telomere length and aortic aneurysms is limited by the potential for confounding or reverse causation effects. In this study, we used a Mendelian randomisation (MR) approach to investigate this putative causal association.<br><br>METHODS: In total, 118 telomere length-associated single-nucleotide polymorphisms, identified in 472,174 individuals of European ancestry, were used as the instrumental variables. Summary statistics for genome-wide association studies of aortic aneurysms were obtained from the FinnGen consortium. For the primary MR analyses, the inverse-variance weighted random-effects method was used and was supplemented with multivariable MR, weighted median and MR-Egger approaches. The MR-Egger intercept test, Cochran's Q test and 'leave-one-out' sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneity and stability of the genetic variants. Forward and reverse MR analyses were performed.<br><br>RESULTS: All forward univariable MR analyses showed that longer telomere lengths decreased aortic aneurysm risks (total aortic aneurysms: OR&#x2009;=&#x2009;0.80, 95% CI 0.67-0.96, p&#x2009;=&#x2009;.015; thoracic aortic aneurysms: OR&#x2009;=&#x2009;0.82, 95% CI 0.68-0.98, p&#x2009;=&#x2009;.026; abdominal aortic aneurysms: OR&#x2009;=&#x2009;0.525, 95% CI 0.398-0.69, p&#x2009;<&#x2009;.001), whereas all reverse MR analyses suggested the absence of aortic aneurysm liability on telomere length. The sensitivity analysis results were robust, and no evidence of horizontal pleiotropy was observed.<br><br>CONCLUSIONS: Our results support a possible causal association between telomere length and aortic aneurysms, providing new insights into the involvement of telomere biology in this condition and offering a potential avenue for targeted therapeutic interventions.},
}
@article {pmid37391893,
year = {2023},
author = {Závodník, M and Fajkus, P and Franek, M and Kopecký, D and Garcia, S and Dodsworth, S and Orejuela, A and Kilar, A and Ptáček, J and Mátl, M and Hýsková, A and Fajkus, J and Peška, V},
title = {Telomerase RNA gene paralogs in plants - the usual pathway to unusual telomeres.},
journal = {The New phytologist},
volume = {239},
number = {6},
pages = {2353-2366},
doi = {10.1111/nph.19110},
pmid = {37391893},
issn = {1469-8137},
mesh = {*Telomerase/genetics/metabolism ; Telomere/genetics ; RNA/genetics/metabolism ; Plants/metabolism ; },
abstract = {Telomerase, telomeric DNA and associated proteins together represent a complex, finely tuned and functionally conserved mechanism that ensures genome integrity by protecting and maintaining chromosome ends. Changes in its components can threaten an organism's viability. Nevertheless, molecular innovation in telomere maintenance has occurred multiple times during eukaryote evolution, giving rise to species/taxa with unusual telomeric DNA sequences, telomerase components or telomerase-independent telomere maintenance. The central component of telomere maintenance machinery is telomerase RNA (TR) as it templates telomere DNA synthesis, its mutation can change telomere DNA and disrupt its recognition by telomere proteins, thereby leading to collapse of their end-protective and telomerase recruitment functions. Using a combination of bioinformatic and experimental approaches, we examine a plausible scenario of evolutionary changes in TR underlying telomere transitions. We identified plants harbouring multiple TR paralogs whose template regions could support the synthesis of diverse telomeres. In our hypothesis, formation of unusual telomeres is associated with the occurrence of TR paralogs that can accumulate mutations, and through their functional redundancy, allow for the adaptive evolution of the other telomere components. Experimental analyses of telomeres in the examined plants demonstrate evolutionary telomere transitions corresponding to TR paralogs with diverse template regions.},
}
@article {pmid37391503,
year = {2023},
author = {Chen, S and Hu, S and Zhou, B and Cheng, B and Tong, H and Su, D and Li, X and Chen, Y and Zhang, G},
title = {Telomere-related prognostic biomarkers for survival assessments in pancreatic cancer.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {10586},
pmid = {37391503},
issn = {2045-2322},
mesh = {Humans ; Prognosis ; *Pancreatic Neoplasms/diagnosis/genetics ; Telomere/genetics ; Biomarkers ; Tumor Microenvironment/genetics ; },
abstract = {Human telomeres are linked to genetic instability and a higher risk of developing cancer. Therefore, to improve the dismal prognosis of pancreatic cancer patients, a thorough investigation of the association between telomere-related genes and pancreatic cancer is required. Combat from the R package "SVA" was performed to correct the batch effects between the TCGA-PAAD and GTEx datasets. After differentially expressed genes (DEGs) were assessed, we constructed a prognostic risk model through univariate Cox regression, LASSO-Cox regression, and multivariate Cox regression analysis. Data from the ICGC, GSE62452, GSE71729, and GSE78229 cohorts were used as test cohorts for validating the prognostic signature. The major impact of the signature on the tumor microenvironment and its response to immune checkpoint drugs was also evaluated. Finally, PAAD tissue microarrays were fabricated and immunohistochemistry was performed to explore the expression of this signature in clinical samples. After calculating 502 telomere-associated DEGs, we constructed a three-gene prognostic signature (DSG2, LDHA, and RACGAP1) that can be effectively applied to the prognostic classification of pancreatic cancer patients in multiple datasets, including TCGA, ICGC, GSE62452, GSE71729, and GSE78229 cohorts. In addition, we have screened a variety of tumor-sensitive drugs targeting this signature. Finally, we also found that protein levels of DSG2, LDHA, and RACGAP1 were upregulated in pancreatic cancer tissues compared to normal tissues by immunohistochemistry analysis. We established and validated a telomere gene-related prognostic signature for pancreatic cancer and confirmed the upregulation of DSG2, LDHA, and RACGAP1 expression in clinical samples, which may provide new ideas for individualized immunotherapy.},
}
@article {pmid37382785,
year = {2023},
author = {Berteli, TS and Wang, F and Navarro, PA and Kohlrausch, FB and Keefe, DL},
title = {A pilot study of LINE-1 copy number and telomere length with aging in human sperm.},
journal = {Journal of assisted reproduction and genetics},
volume = {40},
number = {8},
pages = {1845-1854},
pmid = {37382785},
issn = {1573-7330},
support = {88887.371487/2019-00//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 88887.597054/2021-00//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 204747/2018-0//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; },
mesh = {Humans ; Male ; Aged ; Pilot Projects ; *DNA Copy Number Variations ; *Semen ; Spermatozoa/physiology ; Telomere/genetics ; Telomere Homeostasis/genetics ; },
abstract = {PURPOSE: Unlike other cells in the body, in sperm, telomere length (TL) increases with age. TL can regulate nearby genes, and the subtelomeric region is rich in retrotransposons. We hypothesized that age-related telomere lengthening in sperm might suppress Long Interspersed Element 1 (LINE-1/L1), the only competent retrotransposon in humans.<br><br>METHODS: We measured L1 copy number (L1-CN) and sperm telomere length (STL) from young and older men to evaluate the relationship between age, TL and L1-CN. We also evaluated L1-CN and TL in individual sperm to determine whether these variables influence sperm morphology. STL was assayed by Multiplex quantitative polymerase chain reaction method (mmqPCR) and L1-CN by Quantitative polymerase chain reaction (qPCR).<br><br>RESULTS: We found that STL increased, and L1-CN decreased significantly with paternal age. STL in normal single sperm was significantly higher than in abnormal sperm. L1-CN did not differ between normal and abnormal sperm. Furthermore, morphologically normal sperm have longer telomeres than abnormal sperm.<br><br>CONCLUSIONS: Elongation of telomeres in the male germline could repress retrotransposition, which tends to increase with cellular aging. More studies in larger cohorts across a wide age span are needed to confirm our conclusions and explore their biological and clinical significance.},
}
@article {pmid37380710,
year = {2023},
author = {Thayer, Z and Becares, L and Marks, E and Ly, K and Walker, C},
title = {Maternal racism experience and cultural identity in relation to offspring telomere length.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {10458},
pmid = {37380710},
issn = {2045-2322},
mesh = {Child, Preschool ; Female ; Humans ; Pregnancy ; *Maori People ; Mothers ; Parents ; *Racism ; *Social Identification ; *Telomere ; },
abstract = {Racism is a determinant of individual and offspring health. Accelerated telomere shortening, an indicator of cellular aging, is a potential mechanism through which parental experience of racism could affect offspring. Here we longitudinally evaluated the relationship between maternal lifetime experience of an ethnically-motivated verbal or physical attack, as reported in pregnancy, with offspring telomere length in 4.5-year-old children. We also explored the potential association between positive feelings about one's culture and offspring telomere length. Data come from a nationally representative, multi-ethnic birth cohort in Aotearoa New Zealand (NZ) (Māori N = 417, Pacific N = 364, Asian N = 381). In models adjusting for covariates, including socioeconomic status and health status, Māori mothers who experienced an ethnically-motivated physical attack had children with significantly shorter telomere length than children of Māori mothers who did not report an attack (B = - 0.20, p = 0.01). Conversely, Māori mothers who had positive feelings about their culture had offspring with significantly longer telomeres (B = 0.25, p = 0.02). Our results suggest that ethnicity-based health inequities are shaped by racism, with impacts for clinical care and policy. Future research should also evaluate the potential protective effects of positive cultural identity.},
}
@article {pmid37380632,
year = {2023},
author = {Silva, B and Arora, R and Bione, S and Azzalin, CM},
title = {Author Correction: TERRA transcription destabilizes telomere integrity to initiate break-induced replication in human ALT cells.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {3829},
doi = {10.1038/s41467-023-39584-1},
pmid = {37380632},
issn = {2041-1723},
}
@article {pmid37376725,
year = {2023},
author = {Hu, Y and You, X and Zhang, Z and Zhao, H},
title = {Telomere-Associated Gene Signatures Correlate with Prognosis, Tumor Microenvironment, and Chemosensitivity in Breast Cancer.},
journal = {Medical science monitor : international medical journal of experimental and clinical research},
volume = {29},
number = {},
pages = {e939921},
pmid = {37376725},
issn = {1643-3750},
mesh = {Humans ; Female ; *Breast Neoplasms/drug therapy/genetics ; Tumor Microenvironment/genetics ; Prognosis ; Breast ; Cluster Analysis ; },
abstract = {BACKGROUND Telomeres are strongly associated with cancer, as their shortening over time is associated with an increased risk of tumor growth and progression. However, the prognostic value of telomere-related genes (TRGs) in breast cancer has not been systematically elucidated. MATERIAL AND METHODS The transcriptome and clinical data of breast cancer were downloaded from TCGA and GEO databases, and prognostic TRGs were identified by differential expression analysis and univariate and multivariate Cox regression analyses. Gene set enrichment analysis (GSEA) of different risk groups was performed. Molecular subtypes of breast cancer were constructed by consensus clustering analysis, and the differences in immune infiltration and chemotherapy sensitivity between subtypes were analyzed. RESULTS Differential expression analysis revealed 86 significantly differentially expressed TRGs in breast cancer, of which 43 were significantly associated with breast cancer prognosis. A predictive risk signature consisting of 6 tumor-related genes (TRGs) was developed, which can accurately stratify patients with breast cancer into 2 distinct groups with significantly different prognoses. Significantly different risk scores were found among different racial groups, treatment groups, and pathological features groups. GSEA results showed that patients in the low-risk group had activated immune responses and repressed cilium-related biological processes. Consistent clustering analysis based on these 6 TRGs obtained 2 molecular models with significant prognosis differences, which revealed distinct immune infiltration and chemotherapy sensitivity. CONCLUSIONS This study conducted a systematic investigation of the expression pattern of TRGs in breast cancer and its prognostic and clustering implications, thereby offering a reference for utilizing it to predict prognosis and evaluate treatment response.},
}
@article {pmid37374216,
year = {2023},
author = {Abu-Awwad, SA and Craina, M and Gluhovschi, A and Ciordas, PD and Marian, C and Boscu, L and Bernad, E and Iurciuc, M and Abu-Awwad, A and Iurciuc, S and Maghiari, AL},
title = {Linking Pregnancy and Long-Term Health: The Impact of Cardiovascular Risk on Telomere Shortening in Pregnant Women.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {59},
number = {6},
pages = {},
pmid = {37374216},
issn = {1648-9144},
mesh = {Child ; Humans ; Female ; Pregnancy ; *Pregnant Women ; Telomere Shortening ; *Cardiovascular Diseases/genetics ; Cesarean Section ; Risk Factors ; Heart Disease Risk Factors ; },
abstract = {Background and Objectives: Telomeres are repetitive DNA sequences located at the end of chromosomes that play a crucial role in maintaining chromosomal stability. Shortening of telomeres has been associated with an increased risk of cardiovascular disease. The aim of this study was to investigate whether the length of telomeres in pregnant women with cardiovascular risk is shorter compared to those without cardiovascular risk. Materials and Methods: A total of 68 participants were enrolled, including 30 pregnant women with cardiovascular risk and 38 without cardiovascular risk, who were followed-up during their pregnancy between 2020 and 2022 at the Obstetrical and Gynecology Department of the "Pius Brînzeu" Emergency County Clinical Hospital in Timişoara, Romania. All included women underwent delivery via cesarean section at the same medical institution. The telomere length was measured in each participant using quantitative Polymerase chain reaction (PCR). Results: The results showed that the telomere length was negatively correlated with cardiovascular risk in pregnant women, with significantly shorter telomeres observed in the cardiovascular risk group (mean telomere length = 0.3537) compared to the group without cardiovascular risk (mean telomere length = 0.5728) (p = 0.0458). Conclusions: These findings suggest that cardiovascular risk during pregnancy may be associated with accelerated telomere shortening, which could have implications for the long-term health of both the mother and the child. Further research is needed to investigate the potential mechanisms underlying this association and to identify interventions that may mitigate the negative effects of cardiovascular risk on the telomere length during pregnancy.},
}
@article {pmid37373801,
year = {2023},
author = {Coskun, M and Altinova, AE and Babayeva, A and Sel, AT and Yapar, D and Karaca, M and Yalcin, MM and Akturk, M and Toruner, FB and Karakoc, MA and Yetkin, I},
title = {Leukocyte Telomere Length and Neuregulin-4 Levels in Female Patients with Acromegaly: The Relationship between Disease Activity and Body Fat Distribution.},
journal = {Journal of clinical medicine},
volume = {12},
number = {12},
pages = {},
pmid = {37373801},
issn = {2077-0383},
support = {123-21//Endocrinology and Metabolism Training Coordination Association/ ; },
abstract = {The study aimed to examine leukocyte telomere length (LTL) and serum neuregulin-4 levels and their relationship with disease activity, co-morbidities and body fat distribution in female acromegaly patients. Forty female patients with acromegaly and thirty-nine age and body mass index (BMI) similar healthy female volunteers were included in the study. Patients were classified into two groups: active acromegaly (AA) and controlled acromegaly (CA). The quantitative polymerase chain reaction (PCR) method was used to study LTL, and T/S ratio < 1 was accepted as shortened telomere length. Neuregulin-4 was studied by ELISA. There was no difference in median LTL between acromegaly and the control group (p = 0.530). The percentage of T/S < 1 in patients with acromegaly (60.0%) was similar to that of the control group (43.6%) (p = 0.144). However, serum neuregulin-4 was significantly higher in patients with acromegaly than those in the control group (p = 0.037). There were no significant differences concerning LTL, percentage of T/S < 1 and neuregulin-4 levels between active and controlled acromegaly groups (p > 0.05). Neuregulin-4 correlated positively with fasting glucose, triglyceride (TG), triglyceride/glucose (TyG) index, and lean body mass in the acromegaly group. A negative correlation was observed between LTL and neuregulin-4 in the control group (p = 0.039). When the factors affecting neuregulin-4 were evaluated by multivariate linear regression analysis with an enter method, TG (β: 0.316, p = 0.025) was independently and positively associated with neuregulin-4. Our findings indicate that acromegaly is associated with unchanged LTL and high neuregulin-4 levels in female patients. However, the relationship between acromegaly, the aging process, and neuregulin-4 involves complex mechanisms, and further studies are needed.},
}
@article {pmid37373080,
year = {2023},
author = {Saretzki, G},
title = {Role of Telomeres and Telomerase in Cancer and Aging.},
journal = {International journal of molecular sciences},
volume = {24},
number = {12},
pages = {},
pmid = {37373080},
issn = {1422-0067},
mesh = {Humans ; *Telomerase/genetics/metabolism ; Aging/genetics ; Telomere/genetics/metabolism ; *Neoplasms/genetics ; },
abstract = {Seventeen papers published in 2019 and early 2020 demonstrate the ongoing interest and research concerning telomeres and telomerase in aging and cancer [...].},
}
@article {pmid37372458,
year = {2023},
author = {Raseley, K and Jinwala, Z and Zhang, D and Xiao, M},
title = {Single-Molecule Telomere Assay via Optical Mapping (SMTA-OM) Can Potentially Define the ALT Positivity of Cancer.},
journal = {Genes},
volume = {14},
number = {6},
pages = {},
pmid = {37372458},
issn = {2073-4425},
mesh = {Humans ; Telomere Homeostasis/genetics ; *Telomerase/genetics/metabolism ; Cell Line ; *Neoplasms/genetics ; DNA Replication ; },
abstract = {Telomeres play an essential role in protecting the ends of linear chromosomes and maintaining the integrity of the human genome. One of the key hallmarks of cancers is their replicative immortality. As many as 85-90% of cancers activate the expression of telomerase (TEL+) as the telomere maintenance mechanism (TMM), and 10-15% of cancers utilize the homology-dependent repair (HDR)-based Alternative Lengthening of Telomere (ALT+) pathway. Here, we performed statistical analysis of our previously reported telomere profiling results from Single Molecule Telomere Assay via Optical Mapping (SMTA-OM), which is capable of quantifying individual telomeres from single molecules across all chromosomes. By comparing the telomeric features from SMTA-OM in TEL+ and ALT+ cancer cells, we demonstrated that ALT+ cancer cells display certain unique telomeric profiles, including increased fusions/internal telomere-like sequence (ITS+), fusions/internal telomere-like sequence loss (ITS-), telomere-free ends (TFE), super-long telomeres, and telomere length heterogeneity, compared to TEL+ cancer cells. Therefore, we propose that ALT+ cancer cells can be differentiated from TEL+ cancer cells using the SMTA-OM readouts as biomarkers. In addition, we observed variations in SMTA-OM readouts between different ALT+ cell lines that may potentially be used as biomarkers for discerning subtypes of ALT+ cancer and monitoring the response to cancer therapy.},
}
@article {pmid37372380,
year = {2023},
author = {Wang, F and McCulloh, DH and Chan, K and Wiltshire, A and McCaffrey, C and Grifo, JA and Keefe, DL},
title = {The Landscape of Telomere Length and Telomerase in Human Embryos at Blastocyst Stage.},
journal = {Genes},
volume = {14},
number = {6},
pages = {},
pmid = {37372380},
issn = {2073-4425},
mesh = {Humans ; *Telomerase/genetics/metabolism ; Blastocyst/metabolism ; Embryo, Mammalian/metabolism ; Aneuploidy ; Telomere/genetics/metabolism ; },
abstract = {The telomere length of human blastocysts exceeds that of oocytes and telomerase activity increases after zygotic activation, peaking at the blastocyst stage. Yet, it is unknown whether aneuploid human embryos at the blastocyst stage exhibit a different profile of telomere length, telomerase gene expression, and telomerase activity compared to euploid embryos. In present study, 154 cryopreserved human blastocysts, donated by consenting patients, were thawed and assayed for telomere length, telomerase gene expression, and telomerase activity using real-time PCR (qPCR) and immunofluorescence (IF) staining. Aneuploid blastocysts showed longer telomeres, higher telomerase reverse transcriptase (TERT) mRNA expression, and lower telomerase activity compared to euploid blastocysts. The TERT protein was found in all tested embryos via IF staining with anti-hTERT antibody, regardless of ploidy status. Moreover, telomere length or telomerase gene expression did not differ in aneuploid blastocysts between chromosomal gain or loss. Our data demonstrate that telomerase is activated and telomeres are maintained in all human blastocyst stage embryos. The robust telomerase gene expression and telomere maintenance, even in aneuploid human blastocysts, may explain why extended in vitro culture alone is insufficient to cull out aneuploid embryos during in vitro fertilization.},
}
@article {pmid37371908,
year = {2023},
author = {Warman, DJ and Jia, H and Kato, H},
title = {Effects of Thyme (Thymus vulgaris L.) Essential Oil on Aging-Induced Brain Inflammation and Blood Telomere Attrition in Chronologically Aged C57BL/6J Mice.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {6},
pages = {},
pmid = {37371908},
issn = {2076-3921},
abstract = {Chronological aging is commonly accompanied by chronic low-grade inflammation (or "inflammaging"), a contributor to the development of age-related chronic diseases. Aging increases oxidative stress that accelerates telomere shortening, leading to cell senescence and the generation of senescence-associated secretory phenotype (SASP) that exacerbates inflammation. Dietary antioxidants may help protect telomeres and attenuate inflammation. Thyme essential oil (TEO), reported for its potency against neuroinflammation, was fed to chronologically aged C57BL/6J mice for 24 weeks. The TEO diet showed notable impacts on the hippocampus, indicated by lower expression of the aging-related gene p16[INK4A] (p = 0.0783) and significantly lower expression of cyclin D kinase Cdk4 and Cdk6 (p < 0.05) compared to the age-matched control mice. The TEO group also showed significantly lower gene expression of the pro-inflammatory cytokine Il6 (p < 0.05) in the hippocampus and lower Il1b expression in the liver and cerebellum (p < 0.05). In vitro experiments conducted on NIH-3T3 cells expressing SASP revealed the dose-dependent anti-inflammatory activity of TEO. Remarkably, TEO diet-fed mice showed higher survival rates and significantly longer blood telomere lengths than the control mice. Monoterpene antioxidants in TEO, particularly thymol and p-cymene, may primarily contribute to the anti-inflammatory and telomere-protecting activities of TEO.},
}
@article {pmid37371596,
year = {2023},
author = {Kuse, R and Ishii, K},
title = {Flexible Attachment and Detachment of Centromeres and Telomeres to and from Chromosomes.},
journal = {Biomolecules},
volume = {13},
number = {6},
pages = {},
pmid = {37371596},
issn = {2218-273X},
mesh = {*Centromere/genetics ; *Telomere/genetics ; Cell Division ; },
abstract = {Accurate transmission of genomic information across multiple cell divisions and generations, without any losses or errors, is fundamental to all living organisms. To achieve this goal, eukaryotes devised chromosomes. Eukaryotic genomes are represented by multiple linear chromosomes in the nucleus, each carrying a centromere in the middle, a telomere at both ends, and multiple origins of replication along the chromosome arms. Although all three of these DNA elements are indispensable for chromosome function, centromeres and telomeres possess the potential to detach from the original chromosome and attach to new chromosomal positions, as evident from the events of telomere fusion, centromere inactivation, telomere healing, and neocentromere formation. These events seem to occur spontaneously in nature but have not yet been elucidated clearly, because they are relatively infrequent and sometimes detrimental. To address this issue, experimental setups have been developed using model organisms such as yeast. In this article, we review some of the key experiments that provide clues as to the extent to which these paradoxical and elusive features of chromosomally indispensable elements may become valuable in the natural context.},
}
@article {pmid37370681,
year = {2023},
author = {Umaru, B and Sengupta, S and Senthil Kumar, S and Drissi, R},
title = {Alternative Lengthening of Telomeres in Pediatric High-Grade Glioma and Therapeutic Implications.},
journal = {Cancers},
volume = {15},
number = {12},
pages = {},
pmid = {37370681},
issn = {2072-6694},
support = {None//The Cure Starts Now Foundation/ ; },
abstract = {Pediatric high-grade gliomas (pHGGs), including diffuse intrinsic pontine glioma (DIPG), are highly aggressive tumors with dismal prognoses despite multimodal therapy including surgery, radiation therapy, and chemotherapy. To achieve cellular immortality cancer cells must overcome replicative senescence and apoptosis by activating telomere maintenance mechanisms (TMMs) through the reactivation of telomerase activity or using alternative lengthening of telomere (ALT) pathways. Although the ALT phenotype is more prevalent in pHGGs compared to adult HGGs, the molecular pathway and the prognostic significance of ALT activation are not well understood in pHGGs. Here, we report the heterogeneity of TMM in pHGGs and their association with genetic alterations. Additionally, we show that sensitivity to the protein kinase ataxia telangiectasia- and RAD3-related protein (ATR) inhibitor and the ATR downstream target CHK1 is not specific to pHGG ALT-positive cells. Together, these findings underscore the need for novel therapeutic strategies to target ALT in pHGG tumors.},
}
@article {pmid37368589,
year = {2023},
author = {Kuo, CL and Liu, R and Godoy, LDC and Pilling, LC and Fortinsky, RH and Brugge, D},
title = {Association between Residential Exposure to Air Pollution and Incident Coronary Heart Disease Is Not Mediated by Leukocyte Telomere Length: A UK Biobank Study.},
journal = {Toxics},
volume = {11},
number = {6},
pages = {},
pmid = {37368589},
issn = {2305-6304},
support = {R21 NR018963/NR/NINR NIH HHS/United States ; R01ES030289/ES/NIEHS NIH HHS/United States ; P30AG067988/AG/NIA NIH HHS/United States ; R21NR018963-01A1/NR/NINR NIH HHS/United States ; P30 AG067988/AG/NIA NIH HHS/United States ; R01 ES030289/ES/NIEHS NIH HHS/United States ; },
abstract = {Higher air pollution exposure and shorter leukocyte telomere length (LTL) are both associated with increased risk of coronary heart disease (CHD), and share plausible mechanisms, including inflammation. LTL may serve as a biomarker of air pollution exposure and may be intervened with to reduce the risk of CHD. To the best of our knowledge, we are the first to test the mediation effect of LTL in the relationship between air pollution exposure and incident CHD. Using the UK Biobank (UKB) data (n = 317,601), we conducted a prospective study linking residential air pollution exposure (PM2.5, PM10, NO2, NOx) and LTL to incident CHD during a mean follow-up of 12.6 years. Cox proportional hazards models and generalized additive models with penalized spline functions were used to model the associations of pollutant concentrations and LTL with incident CHD. We found non-linear associations of air pollution exposure with LTL and CHD. Pollutant concentrations in the lower range were decreasingly associated with longer LTL and reduced risk of CHD. The associations between lower pollutant concentrations and reduced risk of CHD, however, were minimally mediated by LTL (<3%). Our findings suggest that air pollution influences CHD through pathways that do not involve LTL. Replication is needed with improved measurements of air pollution that more accurately assesses personal exposure.},
}
@article {pmid37360685,
year = {2023},
author = {Boyle, C and Lansdorp, PM and Edelstein-Keshet, L},
title = {Predicting the number of lifetime divisions for hematopoietic stem cells from telomere length measurements.},
journal = {iScience},
volume = {26},
number = {7},
pages = {107053},
pmid = {37360685},
issn = {2589-0042},
abstract = {How many times does a typical hematopoietic stem cell (HSC) divide to maintain a daily production of over 1011 blood cells over a human lifetime? It has been predicted that relatively few, slowly dividing HSCs occupy the top of the hematopoietic hierarchy. However, tracking HSCs directly is extremely challenging due to their rarity. Here, we utilize previously published data documenting the loss of telomeric DNA repeats in granulocytes, to draw inferences about HSC division rates, the timing of major changes in those rates, as well as lifetime division totals. Our method uses segmented regression to identify the best candidate representations of the telomere length data. Our method predicts that, on average, an HSC divides 56 times over an 85-year lifespan (with lower and upper bounds of 36 and 120, respectively), with half of these divisions during the first 24 years of life.},
}
@article {pmid37356355,
year = {2023},
author = {Caria, P and Pilotto, S and D'Alterio, MN and Fronza, M and Murgia, F and Frau, J and Fenu, G and Dettori, T and Frau, DV and Atzori, L and Angioni, S and Cocco, E and Lorefice, L},
title = {Leukocyte telomere length in women with multiple sclerosis: Comparison with healthy women during pregnancy and puerperium.},
journal = {Journal of neuroimmunology},
volume = {381},
number = {},
pages = {578137},
doi = {10.1016/j.jneuroim.2023.578137},
pmid = {37356355},
issn = {1872-8421},
mesh = {Pregnancy ; Female ; Humans ; *Multiple Sclerosis/genetics ; In Situ Hybridization, Fluorescence ; Postpartum Period ; Leukocytes ; Telomere ; },
abstract = {OBJECTIVES: Several studies indicated leukocyte telomere length (LTL) as a biomarker of multiple sclerosis (MS) evolution. This study aimed to investigate LTL in women with multiple sclerosis (MS) compared to that in healthy women (HW) across different reproductive phases, and to evaluate its relationship with MS activity.<br><br>METHODS: Blood samples were collected from women with MS and HW during the fertile phase, pregnancy, and puerperium. LTL was determined using quantitative fluorescence in situ hybridization (Q-FISH).<br><br>RESULTS: Blood samples from 68 women with MS (22 during fertile life, 23 during pregnancy, and 23 post-partum) and 52 HW (23 during fertile life, 20 during pregnancy, and 9 post-partum) were analyzed. During pregnancy, LTL in MS women and HW was 84.7&#xa0;&#xb1;&#xa0;10.5 and 77.6&#xa0;&#xb1;&#xa0;11.5, respectively (p&#xa0;<&#xa0;0.005). Regression analysis showed that shorter LTL was associated with pregnancy in HW (p&#xa0;=&#xa0;0.021); this relationship was not observed in MS women, for whom shorter LTL was related to a higher EDSS (p&#xa0;=&#xa0;0.036). A longitudinal analysis was performed in eight MS women, showing LTL shortening from pregnancy to puerperium (p&#xa0;=&#xa0;0.003), which was related to MS reactivation (p&#xa0;=&#xa0;0.042).<br><br>CONCLUSION: Our results highlight the possible associations between LTL, reproductive biological phases, and MS activity after delivery.},
}
@article {pmid37354000,
year = {2023},
author = {Raj, HA and Lai, TP and Niewisch, MR and Giri, N and Wang, Y and Spellman, SR and Aviv, A and Gadalla, SM and Savage, SA},
title = {The distribution and accumulation of the shortest telomeres in telomere biology disorders.},
journal = {British journal of haematology},
volume = {203},
number = {5},
pages = {820-828},
pmid = {37354000},
issn = {1365-2141},
support = {ZIA CP010144/ImNIH/Intramural NIH HHS/United States ; Z01 CP010144/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; Biology ; *Bone Marrow Failure Disorders ; *Dyskeratosis Congenita/genetics ; *Pancytopenia ; Telomere/genetics ; Telomere Shortening ; },
abstract = {Individuals with telomere biology disorders (TBDs) have very short telomeres, high risk of bone marrow failure (BMF), and reduced survival. Using data from TBD patients, a mean leukocyte Southern blot telomere length (TL) of 5 kilobases (kb) was estimated as the 'telomere brink' at which human survival is markedly reduced. However, the shortest telomere, not the mean TL, signals replicative senescence. We used the Telomere Shortest Length Assay (TeSLA) to tally TL of all 46 chromosomes in blood-derived DNA and examined its relationship with TBDs. Patients (n = 18) had much shorter mean TL (TeSmTL) (2.54 ± 0.41 kb vs. 4.48 ± 0.52 kb, p < 0.0001) and more telomeres <3 kb than controls (n = 22) (70.43 ± 8.76% vs. 33.05 ± 6.93%, p < 0.0001). The proportion of ultrashort telomeres (<1.6 kb) was also higher in patients than controls (39.29 ± 10.69% vs. 10.40 ± 4.09%, p < 0.0001). TeS <1.6 kb was associated with severe (n = 11) compared with non-severe (n = 7) BMF (p = 0.027). Patients with multi-organ manifestations (n = 10) had more telomeres <1.6 kb than those with one affected organ system (n = 8) (p = 0.029). Findings suggest that TBD clinical manifestations are associated with a disproportionately higher number of haematopoietic cell telomeres reaching a telomere brink, whose length at the single telomere level is yet to be determined.},
}
@article {pmid37353495,
year = {2023},
author = {Rampersaud, R and Wu, GWY and Reus, VI and Lin, J and Blackburn, EH and Epel, ES and Hough, CM and Mellon, SH and Wolkowitz, OM},
title = {Shorter telomere length predicts poor antidepressant response and poorer cardiometabolic indices in major depression.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {10238},
pmid = {37353495},
issn = {2045-2322},
support = {R01 MH083784/MH/NIMH NIH HHS/United States ; UL1 RR024131/RR/NCRR NIH HHS/United States ; TL1 TR001871/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; *Depressive Disorder, Major/drug therapy/genetics ; Leukocytes, Mononuclear/metabolism ; Depression ; *Telomerase/genetics ; Telomere Shortening ; Selective Serotonin Reuptake Inhibitors/therapeutic use ; Antidepressive Agents/therapeutic use ; Telomere/metabolism ; *Cardiovascular Diseases/drug therapy ; },
abstract = {Telomere length (TL) is a marker of biological aging, and shorter telomeres have been associated with several medical and psychiatric disorders, including cardiometabolic dysregulation and Major Depressive Disorder (MDD). In addition, studies have shown shorter TL to be associated with poorer response to certain psychotropic medications, and our previous work suggested shorter TL and higher telomerase activity (TA) predicts poorer response to Selective Serotonin Reuptake Inhibitor (SSRI) treatment. Using a new group of unmedicated medically healthy individuals with MDD (n = 48), we sought to replicate our prior findings demonstrating that peripheral blood mononuclear cell (PBMC) TL and TA predict response to SSRI treatment and to identify associations between TL and TA with biological stress mediators and cardiometabolic risk indices. Our results demonstrate that longer pre-treatment TL was associated with better response to SSRI treatment (β = .407 p = .007). Additionally, we observed that TL had a negative relationship with allostatic load (β = - .320 p = .017) and a cardiometabolic risk score (β = - .300 p = .025). Our results suggest that PBMC TL reflects, in part, the cumulative effects of physiological stress and cardiovascular risk in MDD and may be a biomarker for predicting SSRI response.},
}
@article {pmid37352282,
year = {2023},
author = {Wan, B and Lu, L and Lv, C},
title = {Mendelian randomization study on the causal relationship between leukocyte telomere length and prostate cancer.},
journal = {PloS one},
volume = {18},
number = {6},
pages = {e0286219},
pmid = {37352282},
issn = {1932-6203},
mesh = {Male ; Humans ; *Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Prostatic Neoplasms/genetics ; Leukocytes ; Polymorphism, Single Nucleotide ; Telomere/genetics ; },
abstract = {BACKGROUND: Leukocyte telomere length (LTL) is related to prostate cancer (PCa). However, the causal relationship between them remains unknown. This study was aimed at identifying the causal direction between LTL and PCa with Mendelian randomization (MR).<br><br>METHODS: Single-nucleotide polymorphisms associated with LTL were identified from a genome-wide association study (GWAS) involving 472,174 individuals. Summary-level data of PCa-related GWAS were extracted from four cohorts comprising 456,717 individuals. An inverse-variance-weighted (IVW) algorithm was used for MR. Sensitivity analyses were performed with MR-Egger regression, IVW regression, leave-one-out test, and MR-Pleiotropy Residual Sum and Outlier analyses. A meta-analysis was also performed to compute the average genetically determined effect of LTL on PCa.<br><br>RESULTS: A long LTL was associated with an increased risk of PCa in all cohorts, with odds ratios of 1.368 (95% confidence interval [CI]: 1.247 to 1.500, P = 2.84&#xd7;10-11), 1.503 (95% CI: 1.243 to 1.816, P = 2.57&#xd7;10-5), 1.722 (95% CI: 1.427 to 2.077, P = 1.48&#xd7;10-8), and 1.358 (95% CI: 1.242 to 1.484, P = 1.73&#xd7;10-11) in the IVW analysis. Sensitivity analyses showed that the genetically determined effect of LTL on PCa was stable and reliable. The meta-analysis showed that the genetically determined per 1-standard deviation rise in LTL correlated significantly with an average 40.6% increase in the PCa risk, with an average odds ratio of 1.406 (95% CI: 1.327 to 1.489, P < 0.001).<br><br>CONCLUSION: The results of this study supported the causal hypothesis that the genetically determined longer LTL was associated with a higher risk of PCa. This finding could serve as a basis for therapeutic strategies for PCa.},
}
@article {pmid37352164,
year = {2023},
author = {Gao, S and Rohr, JK and de Vivo, I and Ramsay, M and Krieger, N and Kabudula, CW and Farrell, MT and Bassil, DT and Harriman, NW and Corona-Perez, D and Pesic, K and Berkman, LF},
title = {Telomere Length, Health, and Mortality in a Cohort of Older Black South African Adults.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {78},
number = {11},
pages = {1983-1990},
pmid = {37352164},
issn = {1758-535X},
support = {069683/Z/02/Z/WT_/Wellcome Trust/United Kingdom ; 085477/Z/08/Z/WT_/Wellcome Trust/United Kingdom ; 058893/Z/99/A/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; P01 AG041710/AG/NIA NIH HHS/United States ; 085477/B/08/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; Female ; Aged ; Longitudinal Studies ; South Africa/epidemiology ; *Aging/genetics ; *Life Expectancy ; Biomarkers ; Telomere ; },
abstract = {Telomere length (TL) may be a biomarker of aging processes as well as age-related diseases. However, most studies of TL and aging are conducted in high-income countries. Less is known in low- and middle-income countries (LMICs) such as South Africa, where life expectancy remains lower despite population aging. We conducted a descriptive analysis of TL in a cohort of older adults in rural South Africa. TL was assayed from venous blood draws using quantitative polymerase chain reaction (T/S ratio). We examined the correlation between TL and biomarkers, demographic characteristics, mental/cognitive health measures, and physical performance measures in a subsample of the Wave 1 2014-2015 "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa" (HAALSI) cohort (n = 510). We used logistic regression to measure the association between TL and mortality through Wave 3 (2021-2022). In bivariate analyses, TL was significantly correlated with age (r = -0.29, p < .0001), self-reported female sex (r = 0.13, p = .002), mortality (r = -0.1297, p = .003), diastolic blood pressure (r = 0.09, p = .037), pulse pressure (r = -0.09, p = .045), and being a grandparent (r = -0.17, p = .0001). TL was significantly associated with age (β = -0.003; 95% confidence interval [CI] = -0.005, -0.003). TL was significantly associated in unadjusted multivariate analyses with mortality, but the relationship between TL and mortality was attenuated after adjusting for age (odds ratio [OR] = 0.19; 95% CI = 0.03, 1.27) and other covariates (OR = 0.17; 95% CI = 0.02, 1.19). Our study is the first analysis of TL in an older adult South African population. Our results corroborate existing relationships between TL and age, sex, cardiometabolic disease, and mortality found in higher-income countries.},
}
@article {pmid37351101,
year = {2023},
author = {Xie, Q and Liu, T and Zhang, X and Ding, Y and Fan, X},
title = {Construction of a telomere-related gene signature to predict prognosis and immune landscape for glioma.},
journal = {Frontiers in endocrinology},
volume = {14},
number = {},
pages = {1145722},
pmid = {37351101},
issn = {1664-2392},
mesh = {Humans ; *Endothelial Cells ; Prognosis ; *Glioma/genetics ; Immunotherapy ; B-Lymphocytes ; },
abstract = {BACKGROUND: Glioma is one of the commonest malignant tumors of the brain. However, glioma present with a poor clinical prognosis. Therefore, specific detection markers and therapeutic targets need to be explored as a way to promote the survival rate of BC patients. Therefore, we need to search for quality immune checkpoints to support the efficacy of immunotherapy for glioma.<br><br>METHODS: We first recognized differentially expressed telomere-related genes (TRGs) and accordingly developed a risk model by univariate and multivariate Cox analysis. The accuracy of the model is then verified. We evaluated the variations in immune function and looked at the expression levels of immune checkpoint genes. Finally, to assess the anti-tumor medications often used in the clinical treatment of glioma, we computed the half inhibitory concentration of pharmaceuticals.<br><br>RESULTS: We finally identified nine TRGs and built a risk model. Through the validation of the model, we found good agreement between the predicted and observed values. Then, we found 633 differentially expressed genes between various risk groups to identify the various molecular pathways between different groups. The enrichment of CD4+ T cells, CD8+ T cells, fibroblasts, endothelial cells, macrophages M0, M1, and M2, mast cells, myeloid dendritic cells, and neutrophils was favorably correlated with the risk score, but the enrichment of B cells and NK cells was negatively correlated with the risk score. The expression of several immune checkpoint-related genes differed significantly across the risk groups. Finally, in order to create individualized treatment plans for diverse individuals, we searched for numerous chemotherapeutic medications for patients in various groups.<br><br>CONCLUSION: The findings of this research provide evidence that TRGs may predict a patient's prognosis for glioma, assist in identifying efficient targets for glioma immunotherapy, and provide a foundation for an efficient, customized approach to treating glioma patients.},
}
@article {pmid37350340,
year = {2023},
author = {Vohra, V and Cheng, MZ and Xue, QL and Simonsick, EM and Lane, AP and Agrawal, Y and Rowan, NR},
title = {The Association of Multiple Sensory Impairment and Telomere Length: The Health ABC Study.},
journal = {The Laryngoscope},
volume = {133},
number = {11},
pages = {3132-3138},
pmid = {37350340},
issn = {1531-4995},
support = {P30 AG021334/AG/NIA NIH HHS/United States ; R01 DC016106/DC/NIDCD NIH HHS/United States ; ZIA AG000964/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; *Aging ; *Hearing ; Smell ; Telomere ; },
abstract = {OBJECTIVES: The objective of this study was to characterize the associations of sensory impairments, including olfaction (OI), vision (VI), hearing (HI), and touch (TI), with telomere length (TL) in a group of community-dwelling older adults who participated in the Health ABC study.<br><br>METHODS: Across 1603 participants, OI was classified with the Brief Smell Identification Test (<11), HI with pure-tone averages (<25 dB), VI with visual acuity (20/50 or worse), and TI with monofilament testing (inability to detect three of four touches). Shorter TL was defined as the lowest quartile of sample TLs. Adjusted multivariable regressions were used to examine the cross-sectional association between the modality, severity, and number of sensory impairments with TL.<br><br>RESULTS: Participants had an average age of 77.4&#x2009;&#xb1;&#x2009;2.84&#x2009;years, and 89.7% (n&#x2009;=&#x2009;1438) had at least one or more sensory impairments. Severe OI (odds ratio [OR]&#x2009;=&#x2009;1.73, 95% confidence interval [CI]&#x2009;=&#x2009;[1.19, 2.6]) was independently associated with increased odds of shorter TL. Additionally, having one (OR&#x2009;=&#x2009;2.79, 95% CI&#x2009;=&#x2009;[1.69, 4.70]), two (OR&#x2009;=&#x2009;2.5, 95% CI&#x2009;=&#x2009;[1.51, 4.26]), three (OR&#x2009;=&#x2009;3.04, 95% CI&#x2009;=&#x2009;[1.79, 5.36]), or four impairments (OR&#x2009;=&#x2009;3.72, 95% CI&#x2009;=&#x2009;[1.52, 7.33]) was associated with increased odds of shorter TL in a dose-dependent manner.<br><br>CONCLUSION: Severe OI and TI appear to be particularly robust markers of shortened TL. Additionally, multiple sensory impairment is strongly associated with shortened TL, suggesting that sensory dysfunction may represent a unique biomarker of unhealthy aging.<br><br>LEVEL OF EVIDENCE: Level II Laryngoscope, 133:3132-3138, 2023.},
}
@article {pmid37348955,
year = {2023},
author = {Jessberger, R},
title = {Rolf Jessberger: cohesin, telomeres, &amp; germ cells.},
journal = {Life science alliance},
volume = {6},
number = {7},
pages = {},
pmid = {37348955},
issn = {2575-1077},
mesh = {Male ; Humans ; *Germ Cells ; *Telomere/genetics ; Cohesins ; },
abstract = {Rolf Jessberger is Professor and Chairman at the Institute of Physiological Chemistry, and Faculty of Medicine at the Technische Universität Dresden. We asked him about his recent article published in Life Science Alliance (LSA) and his experience in science thus far.},
}
@article {pmid37345011,
year = {2023},
author = {Amin, A and Morello, M and Petrara, MR and Rizzo, B and Argenton, F and De Rossi, A and Giunco, S},
title = {Short-Term TERT Inhibition Impairs Cellular Proliferation via a Telomere Length-Independent Mechanism and Can Be Exploited as a Potential Anticancer Approach.},
journal = {Cancers},
volume = {15},
number = {10},
pages = {},
pmid = {37345011},
issn = {2072-6694},
support = {5x1000 2017 - Cancer Genomics Research Platform//Istituto Oncologico Veneto/ ; Department of Surgery, Oncology and Gastroenterology DOR 2021 and BIRD 2021 to SG//University of Padua/ ; },
abstract = {Telomerase reverse transcriptase (TERT), the catalytic component of telomerase, may also contribute to carcinogenesis via telomere-length independent mechanisms. Our previous in vitro and in vivo studies demonstrated that short-term telomerase inhibition by BIBR1532 impairs cell proliferation without affecting telomere length. Here, we show that the impaired cell cycle progression following short-term TERT inhibition by BIBR1532 in in vitro models of B-cell lymphoproliferative disorders, i.e., Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines (LCLs), and B-cell malignancies, i.e., Burkitt's lymphoma (BL) cell lines, is characterized by a significant reduction in NF-κB p65 nuclear levels leading to the downregulation of its target gene MYC. MYC downregulation was associated with increased expression and nuclear localization of P21, thus promoting its cell cycle inhibitory function. Consistently, treatment with BIBR1532 in wild-type zebrafish embryos significantly decreased Myc and increased p21 expression. The combination of BIBR1532 with antineoplastic drugs (cyclophosphamide or fludarabine) significantly reduced xenografted cells' proliferation rate compared to monotherapy in the zebrafish xenograft model. Overall, these findings indicate that short-term inhibition of TERT impairs cell growth through the downregulation of MYC via NF-κB signalling and supports the use of TERT inhibitors in combination with antineoplastic drugs as an efficient anticancer strategy.},
}
@article {pmid37342644,
year = {2023},
author = {Thakur, M and Patil, Y and Philip, ST and Hamdule, T and Thimmapuram, J and Vyas, N and Thakur, K},
title = {Impact of Heartfulness meditation practice on anxiety, perceived stress, well-being, and telomere length.},
journal = {Frontiers in psychology},
volume = {14},
number = {},
pages = {1158760},
pmid = {37342644},
issn = {1664-1078},
abstract = {OBJECTIVE: Exhaustion, stress, and burnout have all been found to be reduced using techniques like yoga and meditation. This study was carried out to check the effectiveness of Heartfulness practice (a form of meditation) on certain psychological and genetic variables.<br><br>METHODS: A total of 100 healthy individuals (aged 18-24) were recruited and randomized into two groups-Heartfulness intervention and control group. The intervention was carried out for 03&#x2009;months. Participants from both groups were analysed for their cortisol levels and telomere length before and after the intervention. Psychometric measures of anxiety, perceived stress, well-being and mindfulness were carried out using Beck Anxiety Inventory (BAI), Perceived Stress Scale (PSS), WHO-Well-being Index (WHO-WBI) and Five Facet Mindfulness Questionnaire (FFMQ).<br><br>RESULTS: The cortisol levels in the meditators group significantly decreased (p&#x2009;<&#x2009;0.001) after the intervention as compared to the non-meditators group, whereas, the telomere length increased in the mediators group. This increase was not significant (p&#x2009;>&#x2009;0.05). Anxiety and perceived stress also decreased post intervention, and well-being as well as mindfulness increased, as assessed by the questionnaire tools, although the decrease in perceived stress was statistically insignificant (p&#x2009;>&#x2009;0.05). A negative correlation was observed between telomere length and cortisol (stress biomarker), whereas a positive correlation was found between telomere length and well-being.<br><br>CONCLUSION: Our data provide evidence that Heartfulness meditation practice can improve our mental health. Additionally, telomere length is shown to be affected by cortisol levels, and this meditation practice can also help to increase telomere length, and thereby slow down cellular aging. However, future studies with larger sample size are required to confirm our observations.},
}
@article {pmid37342445,
year = {2023},
author = {Li, K and Dai, M and Sacirovic, M and Zemmrich, C and Pagonas, N and Ritter, O and Grisk, O and Lubomirov, LT and Lauxmann, MA and Bramlage, P and Persson, AB and Buschmann, E and Buschmann, I and Hillmeister, P},
title = {Leukocyte telomere length and mitochondrial DNA copy number associate with endothelial function in aging-related cardiovascular disease.},
journal = {Frontiers in cardiovascular medicine},
volume = {10},
number = {},
pages = {1157571},
pmid = {37342445},
issn = {2297-055X},
abstract = {BACKGROUND: We investigated the association between leukocyte telomere length, mitochondrial DNA copy number, and endothelial function in patients with aging-related cardiovascular disease (CVD).<br><br>METHODS: In total 430 patients with CVD and healthy persons were enrolled in the current study. Peripheral blood was drawn by routine venipuncture procedure. Plasma and peripheral blood mononuclear cells (PBMCs) were collected. Cell-free genomic DNA (cfDNA) and leukocytic genomic DNA (leuDNA) were extracted from plasma and PBMCs, respectively. Relative telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) were analyzed using quantitative polymerase chain reaction. Endothelial function was evaluated by measuring flow-mediated dilation (FMD). The correlation between TL of cfDNA (cf-TL), mtDNA-CN of cfDNA (cf-mtDNA), TL of leuDNA (leu-TL), mtDNA-CN of leuDNA (leu-mtDNA), age, and FMD were analyzed based on Spearman's rank correlation. The association between cf-TL, cf-mtDNA, leu-TL, leu-mtDNA, age, gender, and FMD were explored using multiple linear regression analysis.<br><br>RESULTS: cf-TL positively correlated with cf-mtDNA (r&#x2009;=&#x2009;0.1834, P&#x2009;=&#x2009;0.0273), and leu-TL positively correlated with leu-mtDNA (r&#x2009;=&#x2009;0.1244, P&#x2009;=&#x2009;0.0109). In addition, both leu-TL (r&#x2009;=&#x2009;0.1489, P&#x2009;=&#x2009;0.0022) and leu-mtDNA (r&#x2009;=&#x2009;0.1929, P&#x2009;<&#x2009;0.0001) positively correlated with FMD. In a multiple linear regression analysis model, both leu-TL (&#x3b2;&#x2009;=&#x2009;0.229, P&#x2009;=&#x2009;0.002) and leu-mtDNA (&#x3b2;&#x2009;=&#x2009;0.198, P&#x2009;=&#x2009;0.008) were positively associated with FMD. In contrast, age was inversely associated with FMD (&#x3b2;&#x2009;=&#x2009;-0.426, P&#x2009;<&#x2009;0.0001).<br><br>CONCLUSION: TL positively correlates mtDNA-CN in both cfDNA and leuDNA. leu-TL and leu-mtDNA can be regarded as novel biomarkers of endothelial dysfunction.},
}
@article {pmid37342232,
year = {2023},
author = {Kliszczak, M and Moralli, D and Jankowska, JD and Bryjka, P and Subha Meem, L and Goncalves, T and Hester, SS and Fischer, R and Clynes, D and Green, CM},
title = {Loss of FAM111B protease mutated in hereditary fibrosing poikiloderma negatively regulates telomere length.},
journal = {Frontiers in cell and developmental biology},
volume = {11},
number = {},
pages = {1175069},
pmid = {37342232},
issn = {2296-634X},
abstract = {Hereditary fibrosing poikiloderma (HFP) is a rare human dominant negative disorder caused by mutations in the FAM111B gene that encodes a nuclear trypsin-like serine protease. HFP patients present with symptoms including skin abnormalities, tendon contractures, myopathy and lung fibrosis. We characterized the cellular roles of human FAM111B using U2OS and MCF7 cell lines and report here that the protease interacts with components of the nuclear pore complex. Loss of FAM111B expression resulted in abnormal nuclear shape and reduced telomeric DNA content suggesting that FAM111B protease is required for normal telomere length; we show that this function is independent of telomerase or recombination driven telomere extension. Even though FAM111B-deficient cells were proficient in DNA repair, they showed hallmarks of genomic instability such as increased levels of micronuclei and ultra-fine DNA bridges. When mutated as in HFP, FAM111B was more frequently localized to the nuclear envelope, suggesting that accumulation of the mutated protease at the nuclear periphery may drive the disease pathology.},
}
@article {pmid37340856,
year = {2023},
author = {Chen, C and Yang, K and Nan, H and Unverzagt, F and McClure, LA and Irvin, MR and Judd, S and Cushman, M and Kamin Mukaz, D and Klaunig, JE and D'Alton, ME and Kahe, K},
title = {Associations of Telomere Length and Change With Cognitive Decline Were Modified by Sex and Race: The REGARDS Study.},
journal = {American journal of Alzheimer's disease and other dementias},
volume = {38},
number = {},
pages = {15333175231175797},
doi = {10.1177/15333175231175797},
pmid = {37340856},
issn = {1938-2731},
support = {RF1 AG056111/AG/NIA NIH HHS/United States ; U01 NS041588/NS/NINDS NIH HHS/United States ; },
mesh = {Female ; Humans ; Biomarkers ; *Cognition ; Executive Function ; *Cognitive Dysfunction/genetics ; Telomere/genetics ; },
abstract = {INTRODUCTION: We examined the associations of baseline telomere length (TL) and TL change with cognitive function over time in older US adults, as well as differences by sex and race.<br><br>METHODS: A total of 1820 cognitively healthy individuals (median baseline age: 63&#xa0;years) were included. Telomere length was measured using qPCR-based method at baseline and among 614 participants in the follow-up examination 10&#xa0;years later. Cognitive function was assessed by a four-test battery every 2&#xa0;years.<br><br>RESULTS: In multivariable-adjusted linear mixed models, longer baseline TL and smaller attrition/lengthening of TL over time were associated with better Animal Fluency Test score. Longer baseline TL was also linearly associated with better Letter Fluency Test score. The observed associations were consistently more pronounced in women than men and in Black compared to White participants.<br><br>DISCUSSION: Telomere length may be a biomarker that predicts long-term verbal fluency and executive function, particularly in women and Black Americans.},
}
@article {pmid37338562,
year = {2023},
author = {Polonio, AM and Medrano, M and Chico-Sordo, L and Córdova-Oriz, I and Cozzolino, M and Montans, J and Herraiz, S and Seli, E and Pellicer, A and García-Velasco, JA and Varela, E},
title = {Impaired telomere pathway and fertility in Senescence-Accelerated Mice Prone 8 females with reproductive senescence.},
journal = {Aging},
volume = {15},
number = {11},
pages = {4600-4624},
pmid = {37338562},
issn = {1945-4589},
mesh = {Male ; Female ; Mice ; Animals ; *Telomerase/genetics/metabolism ; Aging/genetics ; Fertility/physiology ; *Infertility ; Telomere/metabolism ; },
abstract = {Ovarian aging is the main cause of infertility and telomere attrition is common to both aging and fertility disorders. Senescence-Accelerated Mouse Prone 8 (SAMP8) model has shortened lifespan and premature infertility, reflecting signs of reproductive senescence described in middle-aged women. Thus, our objective was to study SAMP8 female fertility and the telomere pathway at the point of reproductive senescence. The lifespan of SAMP8 and control mice was monitored. Telomere length (TL) was measured by in situ hybridization in blood and ovary. Telomerase activity (TA) was analyzed by telomere-repeat amplification protocol, and telomerase expression, by real-time quantitative PCR in ovaries from 7-month-old SAMP8 and controls. Ovarian follicles at different stages of maturation were evaluated by immunohistochemistry. Reproductive outcomes were analyzed after ovarian stimulation. Unpaired t-test or Mann-Whitney test were used to calculate p-values, depending on the variable distribution. Long-rank test was used to compare survival curves and Fisher's exact test was used in contingency tables. Median lifespan of SAMP8 females was reduced compared to SAMP8 males (p = 0.0138) and control females (p < 0.0001). In blood, 7-month-old SAMP8 females presented lower mean TL compared to age-matched controls (p = 0.041). Accordingly, the accumulation of short telomeres was higher in 7-month-old SAMP8 females (p = 0.0202). Ovarian TA was lower in 7-month-old SAMP8 females compared to controls. Similarly, telomerase expression was lower in the ovaries of 7-month-old SAMP8 females (p = 0.04). Globally, mean TL in ovaries and granulosa cells (GCs) were similar. However, the percentage of long telomeres in ovaries (p = 0.004) and GCs (p = 0.004) from 7-month-old SAMP8 females was lower compared to controls. In early-antral and antral follicles, mean TL of SAMP8 GCs was lower than in age-matched controls (p = 0.0156 for early-antral and p = 0.0037 for antral follicles). Middle-aged SAMP8 showed similar numbers of follicles than controls, although recovered oocytes after ovarian stimulation were lower (p = 0.0068). Fertilization rate in oocytes from SAMP8 was not impaired, but SAMP8 mice produced significantly more morphologically abnormal embryos than controls (27.03% in SAMP8 vs. 1.22% in controls; p < 0.001). Our findings suggest telomere dysfunction in SAMP8 females, at the time of reproductive senescence.},
}
@article {pmid37335484,
year = {2023},
author = {Lyčka, M and Fajkus, P and Jenner, LP and Sýkorová, E and Fojtová, M and Peska, V},
title = {Identification of the Sequence and the Length of Telomere DNA.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2672},
number = {},
pages = {285-302},
pmid = {37335484},
issn = {1940-6029},
mesh = {*DNA/genetics ; *Telomere/genetics ; Telomere-Binding Proteins/genetics ; DNA Breaks, Double-Stranded ; },
abstract = {Telomeres are essential nucleoprotein structures at the very ends of linear eukaryote chromosomes. They shelter the terminal genome territories against degradation and prevent the natural chromosome ends from being recognized by repair mechanisms as double-strand DNA breaks.There are two basic characteristics of telomeric DNA, its sequence and its length. The telomere sequence is important as a "landing area" for specific telomere-binding proteins, which function as signals and moderate the interactions required for correct telomere function. While the sequence forms the proper "landing surface" of telomeric DNA, its length is similarly important. Too short or exceptionally long telomere DNA cannot perform its function properly. In this chapter, methods for the investigation of these two basic telomere DNA characteristics are described, namely, telomere motif identification and telomere length measurement.},
}
@article {pmid37333916,
year = {2023},
author = {Zhang, T and Sun, Y and Wei, J and Zhao, G and Hao, W and Lv, Z and Chen, X and Liu, Y and Wei, F},
title = {Shorter telomere length in children with autism spectrum disorder is associated with oxidative stress.},
journal = {Frontiers in psychiatry},
volume = {14},
number = {},
pages = {1209638},
pmid = {37333916},
issn = {1664-0640},
abstract = {OBJECTIVE: Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder caused by a complex interaction between genetic and environmental risk factors. The balance between antioxidant capacity and oxidative stress (OS) induced free radicals may be crucial during the pathophysiological development of ASD.<br><br>METHODS: In this study, 96 children with ASD who met the diagnostic and statistical manual of mental disorders were collected, and the number of children in the typical development (TD) group was matched by 1:1. Digital PCR (dPCR) for telomere length (TL) expression in ASD in peripheral blood leukocytes. Urine levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) content were measured by tandem triple quadrupole mass spectrometry and corrected by urinary creatinine levels. The levels of superoxide dismutase (SOD), catalase (CAT), and capacity (AOC) were detected by kits.<br><br>RESULTS: The TL of the ASD group was shorter than the TD group (p&#x2009;<&#x2009;0.01) and had some accurate predictive significance for the identification of ASD (AUC&#x2009;=&#x2009;0.632, 95% CI: 0.533-0.710, p =&#x2009;0.002). Both 8-OHdG content and SOD activity in the ASD group were significantly higher than those in the TD group (p&#x2009;<&#x2009;0.05). Shortened TL (Monofactor: 2.20 (1.22, 3.96), p =&#x2009;0.009; Multifactor: 2.22 (1.22, 4.00), p =&#x2009;0.008) and reduced CAT activity (Monofactor: 2.31 (1.28, 4.17), p =&#x2009;0.006; Multifactor: 2.31 (1.28, 4.18), p =&#x2009;0.006) are risk factors for the development of ASD, while reduced 8-OHdG content (Monofactor: 0.29 (0.14, 0.60), p =&#x2009;0.001; Multifactor: 0.27 (0.13, 0.57), p =&#x2009;0.001) and reduced SOD activity (Monofactor: 0.55 (0.31, 0.98), p =&#x2009;0.042; Multifactor: 0.54 (0.30, 0.98), p =&#x2009;0.042) are protective factors for the development of ASD.<br><br>CONCLUSION: In this study, TL and OS were significantly different between the ASD group and the TD group. As guanine-rich telomere sequences were likely damaged by oxygen free radicals, creating OS, which is a factor in the incidence and progression of ASDs. In conclusion, oxidative damage occurs in the bodies of children with ASD, which may lead to sustained disease progression and severe clinical manifestations. We assume that timely supplementation of antioxidants is very likely to be a potential treatment for early intervention in children with ASD. Identification and detection of OS-related biomarkers may contribute to early diagnosis and timely interventions in young patients with ASD.},
}
@article {pmid37332563,
year = {2023},
author = {Cheng, H and Asri, M and Lucas, J and Koren, S and Li, H},
title = {Scalable telomere-to-telomere assembly for diploid and polyploid genomes with double graph.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {37332563},
issn = {2331-8422},
support = {K99 HG012798/HG/NHGRI NIH HHS/United States ; R01 HG010040/HG/NHGRI NIH HHS/United States ; U01 HG010971/HG/NHGRI NIH HHS/United States ; U41 HG010972/HG/NHGRI NIH HHS/United States ; },
abstract = {Despite recent advances in the length and the accuracy of long-read data, building haplotype-resolved genome assemblies from telomere to telomere still requires considerable computational resources. In this study, we present an efficient de novo assembly algorithm that combines multiple sequencing technologies to scale up population-wide telomere-to-telomere assemblies. By utilizing twenty-two human and two plant genomes, we demonstrate that our algorithm is around an order of magnitude cheaper than existing methods, while producing better diploid and haploid assemblies. Notably, our algorithm is the only feasible solution to the haplotype-resolved assembly of polyploid genomes.},
}
@article {pmid37329271,
year = {2023},
author = {Barcın-Güzeldere, HK and Aksoy, M and Demircan, T and Yavuz, M and Beler, M},
title = {Association between the anthropometric measurements and dietary habits on telomere shortening in healthy older adults: A-cross-sectional study.},
journal = {Geriatrics &amp; gerontology international},
volume = {23},
number = {7},
pages = {565-572},
doi = {10.1111/ggi.14620},
pmid = {37329271},
issn = {1447-0594},
mesh = {Male ; Humans ; Female ; Aged ; *Telomere Shortening ; Cross-Sectional Studies ; *Diet ; Feeding Behavior ; Leukocytes ; Telomere/genetics ; },
abstract = {AIM: This study aimed to evaluate the effect of anthropometric measurements and dietary habits on telomere length in healthy older residents in rural and urban areas.<br><br>METHODS: This was a cross-sectional study. The study population included 81 healthy older individuals aged &#x2265;80&#x2009;years. A quantitative food frequency questionnaire was used to determine dietary habits. Anthropometric measurements were taken by researchers. The telomere length of individuals was determined from leukocytes using quantitative polymerase chain reaction.<br><br>RESULTS: Urban women had longer telomeres than rural women (P&#x2009;<&#x2009;0.05). Rural men had significantly higher hip circumference, middle-upper arm circumference and fat-free mass than urban men (P&#x2009;<&#x2009;0.05). It was shown that while fresh vegetable consumption was higher in rural areas, carbonated drink consumption was higher in urban areas (P&#x2009;<&#x2009;0.05). In women, homemade bread and sugar consumption were higher in rural areas, and honey consumption was higher in urban (P&#x2009;<&#x2009;0.05). Red meat, milk-based dessert and pastry consumption explain telomere shortening by 22.5%, 24.8% and 17.9%, respectively. In addition, the model based on anthropometric measurements also contributes to explaining telomere shortening by 42.9%.<br><br>CONCLUSION: Red meat, milk-based dessert and pastry consumption, and waist circumference, hip circumference, waist-to-hip ratio and waist-to-height ratio are associated with telomere length. Longer telomeres are associated with a healthy, balanced, adequate diet and maintaining a healthy body weight/proportion, and they are crucial for achieving healthy aging. Geriatr Gerontol Int 2023; 23: 565-572.},
}
@article {pmid37328426,
year = {2024},
author = {Fernández de la Puente, M and Salas-Huetos, A and Valle-Hita, C and Babio, N and Murphy, MM and Canudas, S and Salas-Salvadó, J},
title = {Is telomere length a biomarker of sperm quality? A systematic review and meta-analysis of observational studies.},
journal = {Andrology},
volume = {12},
number = {2},
pages = {277-288},
doi = {10.1111/andr.13482},
pmid = {37328426},
issn = {2047-2927},
support = {CEX2021-001234-M//MICIN/AEI/FEDER, UE/ ; PI21/01447//Instituto de Salud Carlos III/ ; PI21/01447//European Union/ ; 2021/11-No.Exp.8004330008-2021-0022642//Diputaci&#xf3; de Tarragona/ ; },
mesh = {Humans ; Male ; *Semen Analysis ; Semen ; Cross-Sectional Studies ; Spermatozoa ; *Infertility, Male/diagnosis/genetics ; Telomere ; Biomarkers ; },
abstract = {BACKGROUND: Telomeres are essential for the integrity of chromosome ends during cell division and their involvement in different processes linked to aging has been established. These chromosome components are involved in spermatogenesis and seem to play an important role in fertilization and embryo development. Telomere length is shortened with each cell division. Recently, short sperm telomere length has been proposed as a potential biomarker of male infertility.<br><br>OBJECTIVES: To conduct a systematic review and meta-analysis of studies exploring the association between spermatozoa and/or leukocyte telomere length with sperm quality parameters and different infertility conditions.<br><br>MATERIAL AND METHODS: A systematic review and meta-analysis was conducted with studies from Medline-PUBMED and Cochrane Library databases until May 2022. Eligible studies included cohort, cross-sectional and case-control studies, and telomere length in spermatozoa and/or leukocytes cells was defined as the exposure. Semen quality parameters or infertility conditions (e.g., oligozoospermia, asthenozoospermia, teratozoospermia, or other spermatogenic impairment combinations) were defined as the outcomes.<br><br>RESULTS: Twenty-three observational studies were included. In the qualitative analysis, high heterogeneity was observed between studies regarding the associations between telomere length and semen parameters in different normozoospermic/fertile and oligozoospermic/infertile populations. In the meta-analysis, spermatozoa and leukocyte telomere length were shorter in infertile individuals than in fertile individuals (mean difference [95% confidence interval]: -1.43 [-1.66 to -1.21], p-value <0.001&#xa0;and -1.67 [-2.02 to -1.31], p-value <0.001, respectively). Moreover, in terms of sperm telomere length, these differences were also significant between individuals with a normal seminogram and individuals with a low quantity of spermatozoa in the ejaculate (-0.97 [-1.32, -0.61], p-value <0.001).<br><br>CONCLUSION: The current systematic review and meta-analysis suggests the potential role of spermatozoa or leukocyte telomere length as a reliable biomarker of semen quality, which may help distinguish between infertility conditions beyond the routine semen analysis.},
}
@article {pmid37322622,
year = {2023},
author = {Ma, TL and Chang, KF and Huang, XF and Lai, HC and Hsiao, CY and Tsai, NM},
title = {Angelica sinensis extract induces telomere dysfunction, cell cycle arrest, and mitochondria-mediated apoptosis in human glioblastoma cells.},
journal = {The Chinese journal of physiology},
volume = {66},
number = {3},
pages = {119-128},
doi = {10.4103/cjop.CJOP-D-23-00024},
pmid = {37322622},
issn = {0304-4920},
mesh = {Humans ; Mice ; Animals ; *Glioblastoma/drug therapy/metabolism/pathology ; *Telomerase/metabolism/pharmacology/therapeutic use ; Apoptosis ; Cell Cycle Checkpoints ; Cell Cycle ; Cell Proliferation ; Telomere/metabolism/pathology ; Mitochondria ; Cell Line, Tumor ; },
abstract = {Glioblastoma (GB) is one of the most aggressive and malignant tumors of the central nervous system. Conventional treatment for GB requires surgical resection followed by radiotherapy combined with temozolomide chemotherapy; however, the median survival time is only 12-15 months. Angelica sinensis Radix (AS) is commonly used as a traditional medicinal herb or a food/dietary supplement in Asia, Europe, and North America. This study aimed to investigate the effect of AS-acetone extract (AS-A) on the progression of GB and the potential mechanisms underlying its effects. The results indicated that AS-A used in this study showed potency in growth inhibition of GB cells and reduction of telomerase activity. In addition, AS-A blocked the cell cycle at the G0/G1 phase by regulating the expression of p53 and p16. Furthermore, apoptotic morphology, such as chromatin condensation, DNA fragmentation, and apoptotic bodies, was observed in AS-A-treated cells, induced by the activation of the mitochondria-mediated pathway. In an animal study, AS-A reduced tumor volume and prolonged lifespans of mice, with no significant changes in body weight or obvious organ toxicity. This study confirmed the anticancer effects of AS-A by inhibiting cell proliferation, reducing telomerase activity, altering cell cycle progression, and inducing apoptosis. These findings suggest that AS-A has great potential for development as a novel agent or dietary supplement against GB.},
}
@article {pmid37322399,
year = {2023},
author = {Tang, W and Zhan, W and Chen, Q},
title = {The mediating role of telomere length in multi-pollutant exposure associated with metabolic syndrome in adults.},
journal = {Environmental science and pollution research international},
volume = {30},
number = {34},
pages = {82068-82082},
doi = {10.1007/s11356-023-28017-7},
pmid = {37322399},
issn = {1614-7499},
mesh = {Telomere ; *Environmental Pollutants ; *Metabolic Syndrome/epidemiology ; *Environmental Pollution ; Humans ; Male ; Female ; Polycyclic Aromatic Hydrocarbons/analysis ; *Environmental Exposure/statistics &amp; numerical data ; Nutrition Surveys ; Metals ; },
abstract = {Metabolic syndrome is a chronic and complex disease characterized by environmental and genetic factors. However, the underlying mechanisms remain unclear. This study assessed the relationship between exposure to a mixture of environmental chemicals and metabolic syndrome (MetS) and further examined whether telomere length (TL) moderated these relationships. A total of 1265 adults aged > 20 years participated in the study. Data on multiple pollutants (polycyclic aromatic hydrocarbons, phthalates, and metals), MetS, leukocyte telomere length (LTL), and confounders were provided in the 2001-2002 National Health and Nutrition Examination Survey. The correlations between multi-pollutant exposure, TL, and MetS in the males and females were separately assessed using principal component analysis (PCA), logistic and extended linear regression models, Bayesian kernel machine regression (BKMR), and mediation analysis. Four factors were generated in PCA that accounted for 76.2% and 77.5% of the total environmental pollutants in males and females, respectively. The highest quantiles of PC2 and PC4 were associated with the risk of TL shortening (P < 0.05). We observed that the relationship between PC2, PC4, and MetS risk was significant in the participants with median TL levels (P for trend = 0.04 for PC2, and P for trend = 0.01 for PC4). Furthermore, mediation analysis revealed that TL could explain 26.1% and 17.1% of the effects of PC2 and PC4 associated with MetS in males, respectively. The results of BKMR model revealed that these associations were mainly driven by 1-PYE (cPIP = 0.65) and Cd (cPIP = 0.29) in PC2. Meanwhile, TL could explain 17.7% of the mediation effects of PC2 associated with MetS in the females. However, the relationships between pollutants and MetS were sparse and inconsistent in the females. Our findings suggest that the effects of the risk of MetS associated with mixed exposure to multiple pollutants are mediated by TL, and this mediating effect in the males is more pronounced than that in the females.},
}
@article {pmid37322109,
year = {2023},
author = {Chen, J and Wang, Z and Tan, K and Huang, W and Shi, J and Li, T and Hu, J and Wang, K and Wang, C and Xin, B and Zhao, H and Song, W and Hufford, MB and Schnable, JC and Jin, W and Lai, J},
title = {A complete telomere-to-telomere assembly of the maize genome.},
journal = {Nature genetics},
volume = {55},
number = {7},
pages = {1221-1231},
pmid = {37322109},
issn = {1546-1718},
mesh = {*Zea mays/genetics ; *Genomics ; Repetitive Sequences, Nucleic Acid/genetics ; Genome, Plant ; Telomere/genetics ; Sequence Analysis, DNA ; High-Throughput Nucleotide Sequencing ; },
abstract = {A complete telomere-to-telomere (T2T) finished genome has been the long pursuit of genomic research. Through generating deep coverage ultralong Oxford Nanopore Technology (ONT) and PacBio HiFi reads, we report here a complete genome assembly of maize with each chromosome entirely traversed in a single contig. The 2,178.6 Mb T2T Mo17 genome with a base accuracy of over 99.99% unveiled the structural features of all repetitive regions of the genome. There were several super-long simple-sequence-repeat arrays having consecutive thymine-adenine-guanine (TAG) tri-nucleotide repeats up to 235 kb. The assembly of the entire nucleolar organizer region of the 26.8 Mb array with 2,974 45S rDNA copies revealed the enormously complex patterns of rDNA duplications and transposon insertions. Additionally, complete assemblies of all ten centromeres enabled us to precisely dissect the repeat compositions of both CentC-rich and CentC-poor centromeres. The complete Mo17 genome represents a major step forward in understanding the complexity of the highly recalcitrant repetitive regions of higher plant genomes.},
}
@article {pmid37316451,
year = {2023},
author = {Liu, M and Yang, C and Pan, Y and Sun, G},
title = {Comment on 'Causal linkage of tobacco smoking with ageing: Mendelian randomization analysis towards telomere attrition and sarcopenia' by Park et al.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {14},
number = {4},
pages = {1912-1914},
pmid = {37316451},
issn = {2190-6009},
mesh = {Humans ; *Sarcopenia ; Mendelian Randomization Analysis ; Tobacco Smoking ; Aging ; Telomere ; },
}
@article {pmid37299586,
year = {2023},
author = {Novau-Ferré, N and Rojas, M and Gutierrez-Tordera, L and Arcelin, P and Folch, J and Papandreou, C and Bulló, M},
title = {Lipoprotein Particle Profiles Associated with Telomere Length and Telomerase Complex Components.},
journal = {Nutrients},
volume = {15},
number = {11},
pages = {},
pmid = {37299586},
issn = {2072-6643},
mesh = {Humans ; *Telomerase/metabolism ; Telomere Shortening ; Cellular Senescence/genetics ; Oxidative Stress ; Telomere/metabolism ; },
abstract = {Telomere length (TL) is a well-known marker of age-related diseases. Oxidative stress and inflammation increase the rate of telomere shortening, triggering cellular senescence. Although lipoproteins could have anti-inflammatory and proinflammatory functional properties, the relationship between lipoprotein particles with TL and telomerase activity-related genes has not been investigated much. In this study, we assessed the associations of lipoprotein subfractions with telomere length, TERT, and WRAP53 expression in a total of 54 pre-diabetic subjects from the EPIRDEM study. We regressed TL, TERT, and WRAP53 on 12 lipoprotein subclasses, employing a Gaussian linear regression method with Lasso penalty to determine a lipoprotein profile associated with telomere-related parameters. The covariates included age, sex, body mass index (BMI), dyslipidemia, statin consumption, and physical activity leisure time. We identified a lipoprotein profile composed of four lipoprotein subfractions associated with TL (Pearson r = 0.347, p-value = 0.010), two lipoprotein subfractions associated with TERT expression (Pearson r = 0.316, p-value = 0.020), and five lipoprotein subfractions associated with WRAP53 expression (Pearson r = 0.379, p-value =0.005). After adjusting for known confounding factors, most lipoprotein profiles maintained the association with TL, TERT, and WRAP53. Overall, medium and small-sized HDL particles were associated with shorter telomeres and lower expression of TERT and WRAP53. Large HDL particles were associated with longer telomere and lower expression of WRAP53, but not with TERT. Our results suggest that the lipoprotein profiles are associated with telomere length, TERT, and WRAP53 expression and should be considered when assessing the risk of chronic diseases.},
}
@article {pmid37299559,
year = {2023},
author = {Uziel, O and Dickstein, H and Beery, E and Lewis, Y and Loewenthal, R and Uziel, E and Shochat, Z and Weizman, A and Stein, D},
title = {Differences in Telomere Length between Adolescent Females with Anorexia Nervosa Restricting Type and Anorexia Nervosa Binge-Purge Type.},
journal = {Nutrients},
volume = {15},
number = {11},
pages = {},
pmid = {37299559},
issn = {2072-6643},
mesh = {Humans ; Female ; Adolescent ; *Anorexia Nervosa/psychology ; *Feeding and Eating Disorders ; Hospitalization ; Surveys and Questionnaires ; Telomere ; *Bulimia Nervosa/psychology ; },
abstract = {Physiological and psychological distress may accelerate cellular aging, manifested by shortening of telomere length (TL). The present study focused on TL shortening in anorexia nervosa (AN), an illness combining physiological and psychological distress. For that purpose, we measured TL in 44 female adolescents with AN at admission to inpatient treatment, in a subset of 18 patients also at discharge, and in 22 controls. No differences in TL were found between patients with AN and controls. At admission, patients with AN-binge/purge type (AN-B/P; n = 18) showed shorter TL compared with patients with AN-restricting type (AN-R; n = 26). No change in TL was found from admission to discharge, despite an improvement in body mass index standard deviation score (BMI-SDS) following inpatient treatment. Older age was the only parameter assessed to be correlated with greater TL shortening. Several methodological changes have to be undertaken to better understand the putative association of shorter TL with B/P behaviors, including increasing the sample size and the assessment of the relevant pathological eating disorder (ED) and non-ED psychological correlates in the two AN subtypes.},
}
@article {pmid37298208,
year = {2023},
author = {Feng, SW and Wu, ZS and Chiu, YL and Huang, SM},
title = {Exploring the Functional Roles of Telomere Maintenance 2 in the Tumorigenesis of Glioblastoma Multiforme and Drug Responsiveness to Temozolomide.},
journal = {International journal of molecular sciences},
volume = {24},
number = {11},
pages = {},
pmid = {37298208},
issn = {1422-0067},
support = {MND-MAB-D-112069 to S-M Huang//the Ministry of National Defense-Medical Affairs Bureau/ ; A1111035 to S-M Huang//Teh-Tzer Study Group for Human Medical Research Foundation/ ; },
mesh = {Adult ; Humans ; Temozolomide/pharmacology/therapeutic use ; *Glioblastoma/drug therapy/genetics/metabolism ; Reactive Oxygen Species/metabolism ; *Telomerase/genetics/metabolism ; *Glioma/metabolism ; *Brain Neoplasms/drug therapy/genetics/metabolism ; *Central Nervous System Neoplasms/drug therapy ; Carcinogenesis/genetics ; Cell Transformation, Neoplastic ; RNA, Messenger ; Telomere/metabolism ; Cell Line, Tumor ; Antineoplastic Agents, Alkylating/pharmacology/therapeutic use ; Drug Resistance, Neoplasm/genetics ; },
abstract = {Glioblastoma multiforme (GBM) is a grade IV human glioma. It is the most malignant primary central nervous system tumor in adults, accounting for around 15% of intracranial neoplasms and 40-50% of all primary malignant brain tumors. However, the median survival time of GBM patients is still less than 15 months, even after treatment with surgical resection, concurrent chemoradiotherapy, and adjuvant chemotherapy with temozolomide (TMZ). Telomere maintenance 2 (TELO2) mRNA is highly expressed in high-grade glioma patients, and its expression correlates with shorter survival outcomes. Hence, it is urgent to address the functional role of TELO2 in the tumorigenesis and TMZ treatment of GBM. In this study, we knocked down TELO2 mRNA in GBM8401 cells, a grade IV GBM, compared with TELO2 mRNA overexpression in human embryonic glial SVG p12 cells and normal human astrocyte (NHA) cells. We first analyzed the effect of TELO2 on the Elsevier pathway and Hallmark gene sets in GBM8401, SVG p12, and NHA via an mRNA array analysis. Later, we further examined and analyzed the relationship between TELO2 and fibroblast growth factor receptor 3, cell cycle progression, epithelial-mesenchymal transient (EMT), reactive oxygen species (ROS), apoptosis, and telomerase activity. Our data showed that TELO2 is involved in several functions of GBM cells, including cell cycle progression, EMT, ROS, apoptosis, and telomerase activity. Finally, we examined the crosstalk between TELO2 and the responsiveness of TMZ or curcumin mediated through the TELO2-TTI1-TTI2 complex, the p53-dependent complex, the mitochondrial-related complex, and signaling pathways in GBM8401 cells. In summary, our work provides new insight that TELO2 might modulate target proteins mediated through the complex of phosphatidylinositol 3-kinase-related kinases in its involvement in cell cycle progression, EMT, and drug response in GBM patients.},
}
@article {pmid37294548,
year = {2023},
author = {Martínez, P and Sánchez-Vazquez, R and Saha, A and Rodriguez-Duque, MS and Naranjo-Gonzalo, S and Osorio-Chavez, JS and Villar-Ramos, AV and Blasco, MA},
title = {Short telomeres in alveolar type II cells associate with lung fibrosis in post COVID-19 patients with cancer.},
journal = {Aging},
volume = {15},
number = {11},
pages = {4625-4641},
pmid = {37294548},
issn = {1945-4589},
mesh = {Humans ; Mice ; Animals ; *Pulmonary Fibrosis/pathology ; *COVID-19/pathology ; SARS-CoV-2 ; Alveolar Epithelial Cells ; Lung/pathology ; *Neoplasms/pathology ; Telomere/pathology ; },
abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic. The severity of COVID-19 increases with each decade of life, a phenomenon that suggest that organismal aging contributes to the fatality of the disease. In this regard, we and others have previously shown that COVID-19 severity correlates with shorter telomeres, a molecular determinant of aging, in patient's leukocytes. Lung injury is a predominant feature of acute SARS-CoV-2 infection that can further progress to lung fibrosis in post-COVID-19 patients. Short or dysfunctional telomeres in Alveolar type II (ATII) cells are sufficient to induce pulmonary fibrosis in mouse and humans. Here, we analyze telomere length and the histopathology of lung biopsies from a cohort of alive post-COVID-19 patients and a cohort of age-matched controls with lung cancer. We found loss of ATII cellularity and shorter telomeres in ATII cells concomitant with a marked increase in fibrotic lung parenchyma remodeling in post- COVID-19 patients compared to controls. These findings reveal a link between presence of short telomeres in ATII cells and long-term lung fibrosis sequel in Post-COVID-19 patients.},
}
@article {pmid37293446,
year = {2023},
author = {Ignatieva, EV and Yudin, NS and Larkin, DM},
title = {Compilation and functional classification of telomere length-associated genes in humans and other animal species.},
journal = {Vavilovskii zhurnal genetiki i selektsii},
volume = {27},
number = {3},
pages = {283-292},
doi = {10.18699/VJGB-23-34},
pmid = {37293446},
issn = {2500-0462},
abstract = {Telomeres are the terminal regions of chromosomes that ensure their stability while cell division. Telomere shortening initiates cellular senescence, which can lead to degeneration and atrophy of tissues, so the process is associated with a reduction in life expectancy and predisposition to a number of diseases. An accelerated rate of telomere attrition can serve as a predictor of life expectancy and health status of an individual. Telomere length is a complex phenotypic trait that is determined by many factors, including the genetic ones. Numerous studies (including genome-wide association studies, GWAS) indicate the polygenic nature of telomere length control. The objective of the present study was to characterize the genetic basis of the telomere length regulation using the GWAS data obtained during the studies of various human and other animal populations. To do so, a compilation of the genes associated with telomere length in GWAS experiments was collected, which included information on 270 human genes, as well as 23, 22, and 9 genes identified in the cattle, sparrow, and nematode, respectively. Among them were two orthologous genes encoding a shelterin protein (POT1 in humans and pot-2 in C. elegans). Functional analysis has shown that telomere length can be influenced by genetic variants in the genes encoding: (1) structural components of telomerase; (2) the protein components of telomeric regions (shelterin and CST complexes); (3) the proteins involved in telomerase biogenesis and regulating its activity; (4) the proteins that regulate the functional activity of the shelterin components; (5) the proteins involved in telomere replication and/or capping; (6) the proteins involved in the alternative telomere lengthening; (7) the proteins that respond to DNA damage and are responsible for DNA repair; (8) RNA-exosome components. The human genes identified by several research groups in populations of different ethnic origins are the genes encoding telomerase components such as TERC and TERT as well as STN1 encoding the CST complex component. Apparently, the polymorphic loci affecting the functions of these genes may be the most reliable susceptibility markers for telomere-related diseases. The systematized data about the genes and their functions can serve as a basis for the development of prognostic criteria for telomere length-associated diseases in humans. Information about the genes and processes that control telomere length can be used for marker-assisted and genomic selection in the farm animals, aimed at increasing the duration of their productive lifetime.},
}
@article {pmid37290379,
year = {2023},
author = {Ford, JL and Pickler, R and Browning, CR and Tarrence, J and Anderson, AM and Kertes, DA},
title = {Associations of depression and anxiety and adolescent telomere length.},
journal = {Psychoneuroendocrinology},
volume = {155},
number = {},
pages = {106310},
pmid = {37290379},
issn = {1873-3360},
support = {R01 DA032371/DA/NIDA NIH HHS/United States ; P2C HD058484/HD/NICHD NIH HHS/United States ; P2C HD042849/HD/NICHD NIH HHS/United States ; R21 DA034960/DA/NIDA NIH HHS/United States ; R01 NR019008/NR/NINR NIH HHS/United States ; R01 MD011727/MD/NIMHD NIH HHS/United States ; },
mesh = {Adult ; Humans ; Male ; Adolescent ; Female ; Child ; *Depression/genetics ; Prospective Studies ; *Anxiety/genetics ; Cellular Senescence ; Telomere ; Telomere Shortening ; },
abstract = {BACKGROUND: Telomere length (TL), a biomarker of cellular aging, is influenced by adverse life experiences. Although depression and anxiety are associated with shorter TL in adults, the relationship in younger ages has received little attention. We examined relationships between depression and anxiety diagnoses and symptomatology and TL in adolescence, an important developmental window for early intervention. Sex differences in relationships were also examined.<br><br>METHODS: Wave 1 survey and TL data from the Adolescent Health and Development in Context study were analyzed (N&#xa0;=&#xa0;995). Depression and anxiety diagnosis were parent-reported measures categorized as: current diagnosis, prior diagnosis, and never diagnosed (reference category). Depressive symptoms were measured via adolescent-report using nine items from the Center for Epidemiologic Studies-Depression scale, short form. Anxiety symptoms were measured via adolescent-report using eight items from the pediatric anxiety scale obtained from the Patient-Reported Outcomes Measurement Information System. Genomic DNA was isolated from 500&#xa0;&#x3bc;L saliva via ethanol precipitation. Genomic DNA TL was assessed using monoplexed quantitative polymerase chain reactions. Relative T/S quantities were calculated in accordance with established procedures. Covariates included sociodemographic factors (sex, age, race/ethnicity, caregiver marital status and education level, and household income), pubertal development, and season of collection. Descriptive and multivariable linear regression analyses were conducted, including an examination of sex as a moderator in the relationships between depression, anxiety, and TL.<br><br>RESULTS: In multivariable analysis, adolescents with a current depression diagnosis (b = -0.26, p&#xa0;<&#xa0;.05), but not a prior diagnosis (b =0.05, p&#xa0;>&#xa0;.05) had shorter TL than those who were never diagnosed; higher depressive symptom scores were associated with shorter TL (b = -0.12, p&#xa0;<&#xa0;.05). No significant associations were found between anxiety diagnosis and TL; however, higher anxiety symptom scores were associated with shorter TL (b = -0.14, p&#xa0;<&#xa0;.01). Sex did not significantly moderate any of the relationships between depression, anxiety and TL.<br><br>CONCLUSIONS: Depression and anxiety were associated with shorter TL in this diverse community sample of adolescents and the findings highlight the potential for impaired mental health to contribute to cellular senescence as early as adolescence. Prospective research on the long-term effect of depression and anxiety occurring earlier in the life span on TL over time is needed, including examination of potential mechanisms that may accelerate or buffer the negative effects of impaired mental health on TL.},
}
@article {pmid37288975,
year = {2023},
author = {Kim, JJ and Ahn, A and Ying, J and Hickman, E and Ludlow, AT},
title = {Exercise as a Therapy to Maintain Telomere Function and Prevent Cellular Senescence.},
journal = {Exercise and sport sciences reviews},
volume = {51},
number = {4},
pages = {150-160},
pmid = {37288975},
issn = {1538-3008},
support = {R00 CA197672/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Telomerase/genetics/metabolism ; Telomere/metabolism ; Cellular Senescence/genetics ; },
abstract = {Exercise transiently impacts the expression, regulation, and activity of TERT/telomerase to maintain telomeres and protect the genome from insults. By protecting the telomeres (chromosome ends) and the genome, telomerase promotes cellular survival and prevents cellular senescence. By increasing cellular resiliency, via the actions of telomerase and TERT, exercise promotes healthy aging.},
}
@article {pmid37288004,
year = {2022},
author = {Wang, Z and Li, J and Liu, J and Wang, L and Lu, Y and Liu, JP},
title = {Molecular mechanism of anionic stabilizer for telomere G-quadruplex.},
journal = {Biophysics reports},
volume = {8},
number = {4},
pages = {225-238},
pmid = {37288004},
issn = {2364-3420},
abstract = {Telomere DNA assumes a high-order G-quadruplex (G4) structure, stabilization of which prevents telomere lengthening by telomerase in cancer. Through applying combined molecular simulation methods, an investigation on the selective binding mechanism of anionic phthalocyanine 3,4',4'',4'''-tetrasulfonic acid (APC) and human hybrid (3 + 1) G4s was firstly performed at the atomic level. Compared to the groove binding mode of APC and the hybrid type I (hybrid-I) telomere G4, APC preferred to bind to the hybrid type II (hybrid-II) telomere G4 via end-stacking interactions, which showed much more favorable binding free energies. Analyses of the non-covalent interaction and binding free energy decomposition revealed a decisive role of van der Waals interaction in the binding of APC and telomere hybrid G4s. And the binding of APC and hybrid-II G4 that showed the highest binding affinity adopted the end-stacking binding mode to form the most extensive van der Waals interactions. These findings add new knowledge to the design of selective stabilizers targeting telomere G4 in cancer.},
}
@article {pmid37286532,
year = {2023},
author = {Rai, R and Biju, K and Sun, W and Sodeinde, T and Al-Hiyasat, A and Morgan, J and Ye, X and Li, X and Chen, Y and Chang, S},
title = {Author Correction: Homology directed telomere clustering, ultrabright telomere formation and nuclear envelope rupture in cells lacking TRF2[B] and RAP1.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {3319},
doi = {10.1038/s41467-023-39144-7},
pmid = {37286532},
issn = {2041-1723},
support = {R01 GM141350/GM/NIGMS NIH HHS/United States ; },
}
@article {pmid37284908,
year = {2023},
author = {Altundag, K},
title = {The association of telomere length with exercise and diet might be time-dependent in breast cancer survivors.},
journal = {Breast cancer research and treatment},
volume = {200},
number = {3},
pages = {401},
pmid = {37284908},
issn = {1573-7217},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/complications ; *Cancer Survivors ; Diet ; Exercise ; Telomere/genetics ; },
}
@article {pmid37284700,
year = {2023},
author = {Martha, SR and Tolentino, EJ and Bugajski, AA and Thompson, HJ},
title = {Telomere Length Associates With Symptom Severity After Mild Traumatic Brain Injury in Older Adults.},
journal = {Neurotrauma reports},
volume = {4},
number = {1},
pages = {350-358},
pmid = {37284700},
issn = {2689-288X},
abstract = {The objectives were to compare differences in telomere length (TL) among younger (21-54 years) and older adults (≥55) with mild traumatic brain injury (mTBI) to non-injured controls and to examine the association between TL and the severity of post-concussive symptoms over time. We performed a quantitative polymerase chain reaction to determine the TL (Kb/genome) of peripheral blood mononuclear cell samples (day 0, 3 months, and 6 months) from 31 subjects. The Rivermead Post-Concussion Symptoms Questionnaire was used to assess symptoms. Group-by-time comparisons of TL and symptom severity were evaluated with repeated-measures analysis of variance. Multiple linear regression examined the relationship between TL, group (mTBI and non-injured controls), and symptom severity total and subscale scores. Significant aging-related differences in TL were found within mTBI groups by time (day 0, 3 months, and 6 months; p = 0.025). Older adults with mTBI experienced significant worsening of changes in total symptom severity scores over time (day 0, 3 months, and 6 months; p = 0.016). Shorter TLs were associated with higher total symptom burden among each of the four groups at day 0 (baseline; p = 0.035) and 3 months (p = 0.038). Shorter TL was also associated with higher cognitive symptom burden among the four groups at day 0 (p = 0.008) and 3 months (p = 0.008). Shorter TL was associated with higher post-injury symptom burden to 3 months in both older and younger persons with mTBI. Large-scale, longitudinal studies of factors associated with TL may be useful to delineate the mechanistic underpinnings of higher symptom burden in adults with mTBI.},
}
@article {pmid37284584,
year = {2023},
author = {Zhang, X and Tong, G},
title = {Antigen-presenting cells maintain T cells proliferation through vesicle transfer of telomeres: A new approach to telomere extension.},
journal = {MedComm},
volume = {4},
number = {3},
pages = {e270},
pmid = {37284584},
issn = {2688-2663},
}
@article {pmid37278929,
year = {2023},
author = {Diukov, Y and Bachinskaya, N and Dzobak, A and Kholin, V and Kyriachenko, Y and Barsukov, O and Zabuha, O and Krasnienkov, D},
title = {Association of Telomere Length with Cognitive Impairment.},
journal = {Journal of molecular neuroscience : MN},
volume = {73},
number = {6},
pages = {448-455},
pmid = {37278929},
issn = {1559-1166},
mesh = {Male ; Humans ; Female ; Aged ; Leukocytes, Mononuclear ; *Depressive Disorder, Major ; *Cognitive Dysfunction/genetics ; *Alzheimer Disease/genetics/diagnosis ; Telomere/genetics ; },
abstract = {Telomere attrition is attributed to Alzheimer's disease (AD), major depressive disorder, stress levels, physical inactivity, short sleep duration, and reduced educational abilities. In this article, we tried to assess the association between the telomere length in peripheral blood leukocytes and level of cognitive impairment and its dependence on age and sex. Healthy subjects and patients with amnestic mild cognitive impairment (aMCI) and different AD stages were recruited in the study. All patients were assessed by the same standard diagnostic procedure, including neurological examination-Mini-Mental State Examination (MMSE). Blood samples from 66 subjects (18 men and 48 women, mean age 71.2 ± 0.56 years) were collected for DNA extraction from peripheral mononuclear cells (PBMC). Relative telomere length (RTL) was measured by monochrome multiplex polymerase chain reaction. The data obtained in the study indicate that RTL in PBMCs has a statistically significant association with MMSE score (p < 0.02). Moreover, the sex-specific difference was observed for the association between telomere length and various parameters of MMSE. Also, it has been found that a decrease in RTL by one unit is associated with an increase in the odds to get AD at a ratio of 2.54 (95% CI, 1.25 to 5.17). The results obtained in this research are in coherence with other studies that telomere length may be a valuable biomarker of cognitive decline. However, the potential need for longitudinal studies of telomere length, in order to estimate the influence of hereditary and environmental factors, remains.},
}
@article {pmid37277368,
year = {2023},
author = {Kroupa, M and Kubecek, O and Tomasova, K and Hanak, P and Krupova, M and Cervena, K and Siskova, A and Rosendorf, J and Hosek, P and Vodickova, L and Vodicka, P and Liska, V and John, S and Vymetalkova, V and Petera, J},
title = {The dynamics of telomere length in primary and metastatic colorectal cancer lesions.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {9097},
pmid = {37277368},
issn = {2045-2322},
mesh = {Humans ; *Colonic Neoplasms ; *Rectal Neoplasms ; Prognosis ; *Liver Neoplasms ; Telomere/genetics/pathology ; *Colorectal Neoplasms/pathology ; Telomere Shortening ; },
abstract = {Telomeric sequences, the structures comprised of hexanucleotide repeats and associated proteins, play a pivotal role in chromosome end protection and preservation of genomic stability. Herein we address telomere length (TL) dynamics in primary colorectal cancer (CRC) tumour tissues and corresponding liver metastases. TL was measured by multiplex monochrome real-time qPCR in paired samples of primary tumours and liver metastases along with non-cancerous reference tissues obtained from 51 patients diagnosed with metastatic CRC. Telomere shortening was observed in the majority of primary tumour tissues compared to non-cancerous mucosa (84.1%, p < 0.0001). Tumours located within the proximal colon had shorter TL than those in the rectum (p < 0.05). TL in liver metastases was not significantly different from that in primary tumours (p = 0.41). TL in metastatic tissue was shorter in the patients diagnosed with metachronous liver metastases than in those diagnosed with synchronous liver metastases (p = 0.03). The metastatic liver lesions size correlated with the TL in metastases (p < 0.05). Following the neoadjuvant treatment, the patients with rectal cancer had shortened telomeres in tumour tissue than prior to the therapy (p = 0.01). Patients with a TL ratio between tumour tissue and the adjacent non-cancerous mucosa of ≥ 0.387 were associated with increased overall survival (p = 0.01). This study provides insights into TL dynamics during progression of the disease. The results show TL differences in metastatic lesions and may help in clinical practice to predict the patient's prognosis.},
}
@article {pmid37276942,
year = {2023},
author = {Rafiq, M and Liaquat, A and Javed, A and Ullah Shah, S and Hussain, R and Akram, Z and Jawad Khan, M},
title = {Association of leukocyte telomere attrition in coronary artery disease in Pakistani population: A case-control study with meta-analysis.},
journal = {Clinica chimica acta; international journal of clinical chemistry},
volume = {547},
number = {},
pages = {117416},
doi = {10.1016/j.cca.2023.117416},
pmid = {37276942},
issn = {1873-3492},
mesh = {Humans ; *Coronary Artery Disease/diagnosis/genetics ; Case-Control Studies ; Pakistan ; Telomere/genetics ; Leukocytes ; Cholesterol ; },
abstract = {BACKGROUND: Coronary arteries disease (CAD) is one of the primary causes of mortality worldwide. Genetic, epigenetic and environmental factors have been hypothesized in the pathogenesis of CAD. Leukocyte telomere length (LTL) has been proposed as a potential biomarker for early detection of atherosclerosis. Telomere is the DNA-Protein structure that maintains stability and integrity of chromosomes and is associated with the aging-related cellular mechanisms. This study is designed to investigate the association of LTL with CAD pathogenesis.<br><br>MATERIAL AND METHOD: This prospective case-control study included 100 patients and 100 control individuals. DNA was extracted from the peripheral blood samples, and LTL was measured using real-time PCR. Data were normalized with single copy gene and presented as relative telomere length T/S ratio. Comprehensive meta-analysis was conducted to ascertain the pivotal role of telomere length in CAD pathology across multiple populations.<br><br>RESULTS: Our results showed shorter telomere length in CAD patients as compared to control. The correlation analysis revealed a significant (P-value <0.01) negative correlation between telomere length with basal metabolic index (BMI), total cholesterol, and low-density lipoprotein cholesterol (LDL-C) and a positive correlation with high-density lipoprotein cholesterol (HDL-C). Meta-analysis results indicated a significantly shorter telomere length in the Asian population and a non-significant shorter telomere length in other populations. Receiver operator curve (ROC) analysis demonstrated an area under the curve (AUC) of 0.814 with cut-off value of 0.691 exhibited sensitivity of 72.2%, and specificity of 79.1%, for the diagnosis of CAD.<br><br>CONCLUSION: In conclusion, LTL is associated with the onset of CAD and could be used as a diagnostic predictor to screen individuals with CAD.},
}
@article {pmid37274248,
year = {2023},
author = {Roka, K and Solomou, EE and Kattamis, A},
title = {Telomere biology: from disorders to hematological diseases.},
journal = {Frontiers in oncology},
volume = {13},
number = {},
pages = {1167848},
pmid = {37274248},
issn = {2234-943X},
abstract = {Variations in the length of telomeres and pathogenic variants involved in telomere length maintenance have been correlated with several human diseases. Recent breakthroughs in telomere biology knowledge have contributed to the identification of illnesses named "telomeropathies" and revealed an association between telomere length and disease outcome. This review emphasizes the biology and physiology aspects of telomeres and describes prototype diseases in which telomeres are implicated in their pathophysiology. We also provide information on the role of telomeres in hematological diseases ranging from bone marrow failure syndromes to acute and chronic leukemias.},
}
@article {pmid37273887,
year = {2023},
author = {Mahmoodpoor, A and Sanaie, S and Eskandari, M and Behrouzi, N and Taghizadeh, M and Roudbari, F and Emamalizadeh, B and Sohrabifar, N and Kazeminasab, S},
title = {Association between leukocyte telomere length and COVID-19 severity.},
journal = {The Egyptian journal of medical human genetics},
volume = {24},
number = {1},
pages = {37},
pmid = {37273887},
issn = {2090-2441},
abstract = {BACKGROUND: Inter-individual variations in the clinical manifestations of SARS-CoV-2 infection are among the challenging features of COVID-19. The known role of telomeres in cell proliferation and immune competency highlights their possible function in infectious diseases. Variability in telomere length is an invaluable parameter in the heterogeneity of the clinical presentation of diseases.<br><br>RESULT: In this study, our aim was to investigate the possible association between leukocyte telomere length (LTL) and COVID-19 severity. LTL was measured in 100 patients with moderate and severe forms of COVID-19 using the quantitative PCR (q-PCR) method. Statistical analysis confirmed a strong inverse correlation between relative LTL and COVID-19 severity.<br><br>CONCLUSIONS: These findings suggest that LTL can be a useful parameter for predicting disease severity in patients, as individuals with short telomeres may have a higher risk of developing severe COVID-19.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s43042-023-00415-z.},
}
@article {pmid37268182,
year = {2023},
author = {Wolf, SE and Shalev, I},
title = {The shelterin protein expansion of telomere dynamics: Linking early life adversity, life history, and the hallmarks of aging.},
journal = {Neuroscience and biobehavioral reviews},
volume = {152},
number = {},
pages = {105261},
pmid = {37268182},
issn = {1873-7528},
support = {R01 NR019610/NR/NINR NIH HHS/United States ; R03 AG071549/AG/NIA NIH HHS/United States ; T32 AG049676/AG/NIA NIH HHS/United States ; U01 ES030949/ES/NIEHS NIH HHS/United States ; },
mesh = {Humans ; *Adverse Childhood Experiences ; Shelterin Complex ; Telomere/metabolism ; Telomere-Binding Proteins/genetics/chemistry/metabolism ; Proteins/metabolism ; Aging/genetics ; },
abstract = {Aging is characterized by functional decline occurring alongside changes to several hallmarks of aging. One of the hallmarks includes attrition of repeated DNA sequences found at the ends of chromosomes called telomeres. While telomere attrition is linked to morbidity and mortality, whether and how it causally contributes to lifelong rates of functional decline is unclear. In this review, we propose the shelterin-telomere hypothesis of life history, in which telomere-binding shelterin proteins translate telomere attrition into a range of physiological outcomes, the extent of which may be modulated by currently understudied variation in shelterin protein levels. Shelterin proteins may expand the breadth and timing of consequences of telomere attrition, e.g., by translating early life adversity into acceleration of the aging process. We consider how the pleiotropic roles of shelterin proteins provide novel insights into natural variation in physiology, life history, and lifespan. We highlight key open questions that encourage the integrative, organismal study of shelterin proteins that enhances our understanding of the contribution of the telomere system to aging.},
}
@article {pmid37263999,
year = {2023},
author = {Rouan, A and Pousse, M and Djerbi, N and Porro, B and Bourdin, G and Carradec, Q and Hume, BC and Poulain, J and Lê-Hoang, J and Armstrong, E and Agostini, S and Salazar, G and Ruscheweyh, HJ and Aury, JM and Paz-García, DA and McMinds, R and Giraud-Panis, MJ and Deshuraud, R and Ottaviani, A and Morini, LD and Leone, C and Wurzer, L and Tran, J and Zoccola, D and Pey, A and Moulin, C and Boissin, E and Iwankow, G and Romac, S and de Vargas, C and Banaigs, B and Boss, E and Bowler, C and Douville, E and Flores, M and Reynaud, S and Thomas, OP and Troublé, R and Thurber, RV and Planes, S and Allemand, D and Pesant, S and Galand, PE and Wincker, P and Sunagawa, S and Röttinger, E and Furla, P and Voolstra, CR and Forcioli, D and Lombard, F and Gilson, E},
title = {Telomere DNA length regulation is influenced by seasonal temperature differences in short-lived but not in long-lived reef-building corals.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {3038},
pmid = {37263999},
issn = {2041-1723},
mesh = {Animals ; *Anthozoa/genetics ; Coral Reefs ; Temperature ; Seasons ; DNA/genetics ; },
abstract = {Telomeres are environment-sensitive regulators of health and aging. Here,we present telomere DNA length analysis of two reef-building coral genera revealing that the long- and short-term water thermal regime is a key driver of between-colony variation across the Pacific Ocean. Notably, there are differences between the two studied genera. The telomere DNA lengths of the short-lived, more stress-sensitive Pocillopora spp. colonies were largely determined by seasonal temperature variation, whereas those of the long-lived, more stress-resistant Porites spp. colonies were insensitive to seasonal patterns, but rather influenced by past thermal anomalies. These results reveal marked differences in telomere DNA length regulation between two evolutionary distant coral genera exhibiting specific life-history traits. We propose that environmentally regulated mechanisms of telomere maintenance are linked to organismal performances, a matter of paramount importance considering the effects of climate change on health.},
}
@article {pmid37262296,
year = {2023},
author = {Puglisi, CJ and McDonough, J and Bianco-Miotto, T and Grieger, JA},
title = {General Practitioners perspectives on infant telomere length screening after a pregnancy complication: a qualitative analysis.},
journal = {Family practice},
volume = {},
number = {},
pages = {},
doi = {10.1093/fampra/cmad064},
pmid = {37262296},
issn = {1460-2229},
support = {APP2000905//National Health and Medical Research Council/ ; },
abstract = {BACKGROUND: Pregnancy complications can impact the mother and child's health in the short and longterm resulting in an increased risk of chronic disease later in life. Telomere length is a biomarker of future cardiometabolic diseases and may offer a novel way of identifying offspring most at risk for future chronic diseases.<br><br>OBJECTIVE(S): To qualitatively explore General Practitioners' (GPs) perspectives on the feasibility and uptake for recommending a telomere screening test in children who were born after a pregnancy complication.<br><br>METHODS: Twelve semi-structured interviews were conducted with GPs within metropolitan Adelaide, South Australia. Interviews were audio recorded, transcribed verbatim, and analysed for codes and themes.<br><br>RESULTS: Two themes were generated: ethical considerations and practical considerations. Ethically, the GP participants discussed barriers including consenting on behalf of a child, parental guilt, and the impact of health insurance, whereas viewing it for health promotion was a facilitator. For practical considerations, barriers included the difficulty in identifying people eligible for screening, maintaining medical communication between service providers, and time and financial constraints, whereas linking screening for telomere length with existing screening would facilitate uptake.<br><br>CONCLUSIONS: GPs were generally supportive of potential telomere screening in infants, particularly via a saliva test that could be embedded in current antenatal care. However, several challenges, such as lack of knowledge, ethical considerations, and time and financial constraints, need to be overcome before such a test could be implemented into practice.},
}
@article {pmid37261700,
year = {2023},
author = {Haridoss, M and Ayyasamy, L and Bagepally, BS},
title = {Is COVID-19 severity associated with telomere length? A systematic review and meta-analysis.},
journal = {Virus genes},
volume = {59},
number = {4},
pages = {489-498},
pmid = {37261700},
issn = {1572-994X},
mesh = {Humans ; *COVID-19 ; Telomere Shortening/genetics ; Telomere/genetics ; },
abstract = {Telomere shortening, a marker of cellular aging, has been linked to hospitalization and the severity of COVID-19. In this systematic review and meta-analysis, the mean difference in telomere length between non-severe and severe COVID-19 individuals was pooled to determine the association between short telomeres and COVID-19 severity. Relevant studies were retrieved through searches conducted in PubMed-Medline, Scopus, EMBASE, Medrxiv, Biorxiv, EuroPMC, and SSRN databases up to November 2022. Selected studies were systematically reviewed and assessed for risk of bias using AXIS tool. The standardized mean difference in telomere length between non-severe and severe COVID-19 was pooled using random-effects model. A total of thirteen studies were included in the review, out of which seven (1332 patients with the severe COVID-19 disease and 6321 patients with non-severe COVID-19) were eligible for meta-analysis. The estimated pooled mean difference in Leukocyte telomere length between severe COVID-19 and non-severe COVID-19 was 0.39 (95% CI - 0.02 to 0.81, I[2] = 93.5%) with substantial heterogeneity. Our findings do not provide clear evidence for association of shorter telomere length and severe COVID-19 disease. More extensive studies measuring absolute telomere length with age and gender adjustments are needed to draw definitive conclusions on the potential causal association between telomere shortening and COVID-19 severity.},
}
@article {pmid37260287,
year = {2023},
author = {Kim, Y and Lin, J and Epel, ES and Carver, CS},
title = {A Lens on Caregiver Stress in Cancer: Longitudinal Investigation of Cancer-Related Stress and Telomere Length Among Family Caregivers of Adult Patients With Cancer.},
journal = {Psychosomatic medicine},
volume = {85},
number = {6},
pages = {527-534},
pmid = {37260287},
issn = {1534-7796},
support = {R01 NR016838/NR/NINR NIH HHS/United States ; },
mesh = {Humans ; Adult ; Female ; Middle Aged ; Male ; *Caregivers/psychology ; Stress, Psychological/psychology ; Cellular Senescence ; Family ; Telomere ; *Colorectal Neoplasms ; },
abstract = {OBJECTIVE: Family members are typically the primary caregivers of patients with chronic illnesses. Family caregivers of adult relatives with cancer are a fast-growing population, yet the physical consequences of their stress due to the cancer in the family have been poorly understood. This study examined the bidirectional relations of the perceived stress of family caregivers of individuals recently diagnosed with cancer and leukocyte cellular aging indexed by telomere length for 2 years.<br><br>METHODS: Family caregivers (N = 168; mean age = 51 years, 70% female, 46% Hispanic, 36% spouse to the patient) of patients with colorectal cancer provided psychological data and peripheral blood samples approximately 4 (T1), 12 (T2), and 21 months (T3) after diagnosis. Time-lagged cross-panel modeling was used to test the associations of perceived cancer-related stress and telomere length, controlling for age, sex, and body mass index.<br><br>RESULTS: Cancer-related stress was highest at T1 and decreased by 1 year. Greater cancer-related stress predicted longer telomere length at subsequent assessments for 2 years (&#x3b2; &#x2265; 0.911, p &#x2264; .019). However, telomere length did not change significantly for 2 years overall and did not prospectively predict cancer-related stress over this period.<br><br>CONCLUSIONS: Findings suggest the need to better understand how the perceived stress of colorectal cancer caregivers, which tends to be intense for a relatively short period compared with dementia caregiving, may impact immune cell distributions and telomere length. These findings emphasize the need for further knowledge about psychobiological mechanisms of how cancer caregiving may impact cellular aging.},
}
@article {pmid37259830,
year = {2023},
author = {Nichele, S and Bonfim, C and Junior, LGD and Loth, G and Kuwahara, C and Trennephol, J and Funke, VAM and Marinho, DE and Koliski, A and Rodrigues, AM and Mousquer, RTG and Fasth, A and Lima, ACM and Calado, RT and Pasquini, R},
title = {Hematopoietic cell transplantation for telomere biology diseases: A retrospective single-center cohort study.},
journal = {European journal of haematology},
volume = {111},
number = {3},
pages = {423-431},
doi = {10.1111/ejh.14023},
pmid = {37259830},
issn = {1600-0609},
mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Retrospective Studies ; Cohort Studies ; *Graft vs Host Disease/etiology ; Unrelated Donors ; Telomere/genetics ; Biology ; Transplantation Conditioning/adverse effects ; },
abstract = {BACKGROUND: Telomere biology diseases (TBD) result from defective telomere maintenance, leading to bone marrow failure. The only curative treatment for aplastic anemia related to TBD is a hematopoietic cell transplant (HCT). Although reduced-intensity conditioning (RIC) regimens decrease transplant-related mortality, non-hematological phenotypes represent a major challenge and are associated with poor long-term follow-up outcomes.<br><br>OBJECTIVE: To describe the outcome of TBD patients transplanted for marrow failure.<br><br>STUDY DESIGN: This is a retrospective, single-center study describing the outcomes of 32 consecutive transplants on 29 patients between 1993 and 2019.<br><br>RESULTS: The median age at transplantation was 14&#x2009;years (range, 3-30&#x2009;years). Most patients received a RIC regimen (n&#x2009;=&#x2009;28) and bone marrow (BM) from an unrelated donor (n&#x2009;=&#x2009;16). Four patients received a haploidentical transplant. Chimerism was available for 27 patients with a median time to neutrophil recovery of 20&#x2009;days (13-36&#x2009;days). Primary graft failure occurred in one patient, whereas second graft failure occurred in two. Acute GVHD grade II-IV and moderate to severe chronic GVHD occurred in 22% of patients at risk. Fourteen patients were alive after HCT at the last follow-up (median, 6&#x2009;years; 1.4-19&#x2009;years). The 5-year overall survival was better after matched sibling donor (MSD) transplantation compared to other hematopoietic stem cell sources (88.9% vs. 47.7%; p&#x2009;=&#x2009;.05; CI&#x2009;=&#x2009;95%). Overall, 15 patients died after HCT, most of them (n&#x2009;=&#x2009;11) after the first year of transplant, due to non-hematological disease progression or complication of chronic GVHD.<br><br>CONCLUSIONS: Hematopoietic cell transplantation is a potentially curative treatment option for TBD, nonetheless the poor outcome reflects the progression of non-hematologic disease manifestations, which should be considered when transplantation is indicated.},
}
@article {pmid37259606,
year = {2023},
author = {Bloom, SI and Liu, Y and Tucker, JR and Islam, MT and Machin, DR and Abdeahad, H and Thomas, TG and Bramwell, RC and Lesniewski, LA and Donato, AJ},
title = {Endothelial cell telomere dysfunction induces senescence and results in vascular and metabolic impairments.},
journal = {Aging cell},
volume = {22},
number = {8},
pages = {e13875},
pmid = {37259606},
issn = {1474-9726},
support = {F31 AG076312/AG/NIA NIH HHS/United States ; R00 AT010017/AT/NCCIH NIH HHS/United States ; R01 AG048366/AG/NIA NIH HHS/United States ; R01 AG060395/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; Animals ; Mice ; *Endothelial Cells/metabolism ; *Telomere ; Cellular Senescence/genetics ; Shelterin Complex ; Telomeric Repeat Binding Protein 2/genetics/metabolism ; Inflammation/genetics/metabolism ; },
abstract = {In advanced age, increases in oxidative stress and inflammation impair endothelial function, which contributes to the development of cardiovascular disease (CVD). One plausible source of this oxidative stress and inflammation is an increase in the abundance of senescent endothelial cells. Cellular senescence is a cell cycle arrest that occurs in response to various damaging stimuli. In the present study, we tested the hypothesis that advanced age results in endothelial cell telomere dysfunction that induces senescence. In both human and mouse endothelial cells, advanced age resulted in an increased abundance of dysfunctional telomeres, characterized by activation of DNA damage signaling at telomeric DNA. To test whether this results in senescence, we selectively reduced the telomere shelterin protein telomere repeat binding factor 2 (Trf2) from endothelial cells of young mice. Trf2 reduction increased endothelial cell telomere dysfunction and resulted in cellular senescence. Furthermore, induction of endothelial cell telomere dysfunction increased inflammatory signaling and oxidative stress, resulting in impairments in endothelial function. Finally, we demonstrate that endothelial cell telomere dysfunction-induced senescence impairs glucose tolerance. This likely occurs through increases in inflammatory signaling in the liver and adipose tissue, as well as reductions in microvascular density and vasodilation to metabolic stimuli. Cumulatively, the findings of the present study identify age-related telomere dysfunction as a mechanism that leads to endothelial cell senescence. Furthermore, these data provide compelling evidence that senescent endothelial cells contribute to age-related increases in oxidative stress and inflammation that impair arterial and metabolic function.},
}
@article {pmid37258936,
year = {2023},
author = {Huang, P and Li, Q},
title = {Comments on the effects of exercise and diet on oxidative stress and telomere length in breast cancer survivors.},
journal = {Breast cancer research and treatment},
volume = {200},
number = {3},
pages = {399},
pmid = {37258936},
issn = {1573-7217},
mesh = {Humans ; Female ; *Breast Neoplasms/genetics ; *Cancer Survivors ; Diet ; Oxidative Stress ; Telomere/genetics ; },
}
@article {pmid37258109,
year = {2023},
author = {Ashe, JJ and Evans, MK and Zonderman, AB and Waldstein, SR},
title = {Absent Relations of Religious Coping to Telomere Length in African American and White Women and Men.},
journal = {Experimental aging research},
volume = {},
number = {},
pages = {1-23},
pmid = {37258109},
issn = {1096-4657},
support = {R01 AG034161/AG/NIA NIH HHS/United States ; ZIA AG000513/ImNIH/Intramural NIH HHS/United States ; },
abstract = {OBJECTIVES: This study investigated whether race and sex moderated the relations of religious coping to telomere length (TL), a biomarker of cellular aging implicated in race-related health disparities.<br><br>METHODS: Participant data were drawn from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, which included 252 socioeconomically diverse African American and White men and women aged (30-64&#x2009;years old). Cross-sectional multivariable regression analyses examined interactive associations of religious coping, race, and sex to TL, adjusting for other sociodemographic characteristics.<br><br>RESULTS: Religious coping was unrelated to TL in this sample (p's > .05). There were no notable race or sex differences. Post hoc exploratory analyses similarly found that neither secular social support coping use nor substance use coping was associated with TL.<br><br>CONCLUSION: There was no evidence to support that religious coping use provided protective effects to TL in this sample of African American and White women and men. Nevertheless, future studies should use more comprehensive assessments of religious coping and intersectional identities to provide an in-depth examination of religiosity/spirituality as a potential culturally salient protective factor in cellular aging among African Americans in the context of specific chronic stressors such as discrimination.},
}
@article {pmid37254630,
year = {2023},
author = {Liu, R and Xiang, M and Pilling, LC and Melzer, D and Wang, L and Manning, KJ and Steffens, DC and Bowden, J and Fortinsky, RH and Kuchel, GA and Rhee, TG and Diniz, BS and Kuo, CL},
title = {Mid-life leukocyte telomere length and dementia risk: An observational and mendelian randomization study of 435,046 UK Biobank participants.},
journal = {Aging cell},
volume = {22},
number = {7},
pages = {e13808},
pmid = {37254630},
issn = {1474-9726},
support = {P30 AG067988/AG/NIA NIH HHS/United States ; R21 NR018963/NR/NINR NIH HHS/United States ; R21NR018963-01A1S1/NR/NINR NIH HHS/United States ; },
mesh = {Humans ; *Alzheimer Disease/genetics/pathology ; Mendelian Randomization Analysis ; Biological Specimen Banks ; Leukocytes ; Telomere/genetics/pathology ; United Kingdom ; },
abstract = {Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data (n = 43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology. Longer TL was associated with a lower risk of incident AD/ADRD (adjusted Hazard Ratio [aHR] per SD = 0.93, 95% CI 0.90-0.96, p = 3.37 × 10[-7]). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume, lower total volume of white matter hyperintensities, and higher fractional anisotropy and lower mean diffusivity in the fornix. In conclusion, longer TL is inversely associated with AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. However, the relationships between genetically determined TL and the outcomes above were not statistically significant based on the results from Mendelian randomization analysis results. Our findings add to the literature of prioritizing risk for AD/ADRD. The causality needs to be ascertained in mechanistic studies.},
}
@article {pmid37246640,
year = {2023},
author = {Fernandes, RV and Lingner, J},
title = {The THO complex counteracts TERRA R-loop-mediated telomere fragility in telomerase+ cells and telomeric recombination in ALT+ cells.},
journal = {Nucleic acids research},
volume = {51},
number = {13},
pages = {6702-6722},
pmid = {37246640},
issn = {1362-4962},
mesh = {Humans ; *Telomerase/genetics/metabolism ; R-Loop Structures ; Telomere/genetics/metabolism ; Telomere Homeostasis ; *RNA, Long Noncoding/genetics ; Recombination, Genetic ; },
abstract = {Telomeres are the nucleoprotein structures at the ends of linear chromosomes. Telomeres are transcribed into long non-coding Telomeric Repeat-Containing RNA (TERRA), whose functions rely on its ability to associate with telomeric chromatin. The conserved THO complex (THOC) was previously identified at human telomeres. It links transcription with RNA processing, decreasing the accumulation of co-transcriptional DNA:RNA hybrids throughout the genome. Here, we explore the role of THOC at human telomeres, as a regulator of TERRA localization to chromosome ends. We show that THOC counteracts TERRA association with telomeres via R-loops formed co-transcriptionally and also post-transcriptionally, in trans. We demonstrate that THOC binds nucleoplasmic TERRA, and that RNaseH1 loss, which increases telomeric R-loops, promotes THOC occupancy at telomeres. Additionally, we show that THOC counteracts lagging and mainly leading strand telomere fragility, suggesting that TERRA R-loops can interfere with replication fork progression. Finally, we observed that THOC suppresses telomeric sister-chromatid exchange and C-circle accumulation in ALT cancer cells, which maintain telomeres by recombination. Altogether, our findings reveal crucial roles of THOC in telomeric homeostasis through the co- and post-transcriptional regulation of TERRA R-loops.},
}
@article {pmid37245595,
year = {2023},
author = {Zhu, X and Li, Z and Wang, Z and Guo, C and Qian, Y and Wang, Z and Li, X and Wei, Y},
title = {Associations between exposure to ambient air pollution and changes in blood telomeres in young people: A repeated-measure study.},
journal = {Chemosphere},
volume = {336},
number = {},
pages = {139053},
doi = {10.1016/j.chemosphere.2023.139053},
pmid = {37245595},
issn = {1879-1298},
mesh = {Humans ; Adolescent ; Nitrogen Dioxide/analysis ; Environmental Exposure/analysis ; *Air Pollution/analysis ; *Air Pollutants/toxicity/analysis ; Particulate Matter/toxicity/analysis ; *Ozone/toxicity/analysis ; Sulfur Dioxide/analysis ; Telomere ; China ; },
abstract = {Telomere length (TL) is one of the early biomarkers of aging. Air pollutants play an important role in promoting the aging process. However, few studies have explored how they adversely affect human health by altering telomeres. This study aims to investigate the associations between telomere alterations and exposure to ambient air pollutants, thereby shedding light on the intrinsic and profound link between these pollutants and aging. We recruited 26 healthy young people and conducted 7 repeated measure studies from 2019 to 2021, and TL and telomerase (TA) in the blood samples. We analyzed the associations between air pollutants, including ozone (O3), particulate matter in diameter smaller than 2.5 μm (PM2.5) and 10 μm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO) and telomere variability, and explored the lagged effects by linear mixed-effects model. The result showed that short-term exposure to O3 was negatively associated with TL, and this effect in the lag days went up to around 0. In contrast, the associations between O3 and TA presented positive tendency and gradually decreased to around 0 in the lag days. The association between PM2.5 and TL showed positive tendency and gradually decreased to negative. There was no statistically significant association between PM2.5 and TA. Other pollutants (PM10, NO2, SO2, CO) showed similar patterns of variation to that of PM2.5. Our findings suggest that short-term exposure to O3 shortens TL, which can be gradually recovered through activating TA activity, while exposure to PM2.5, PM10, NO2, SO2 and CO lengthens TL and then becomes shorter over time. This implies that the human body has some ability to self-repair telomere changes after exposure to air pollutants, and predictably, when this exposure exceeds a certain threshold, it cannot be repaired, leading to aging of the body.},
}
@article {pmid37239399,
year = {2023},
author = {Gouhier, C and Pons-Rejraji, H and Dollet, S and Chaput, L and Bourgne, C and Berger, M and Pereira, B and Tchirkov, A and Brugnon, F},
title = {Freezing Does Not Alter Sperm Telomere Length despite Increasing DNA Oxidation and Fragmentation.},
journal = {Genes},
volume = {14},
number = {5},
pages = {},
pmid = {37239399},
issn = {2073-4425},
mesh = {Male ; Animals ; Freezing ; *Spermatozoa ; *Semen Analysis/methods ; DNA ; Telomere/genetics ; },
abstract = {Correlations were reported between sperm telomere length (STL) and male fertility, sperm DNA fragmentation, and oxidation. Sperm freezing is widely used for assisted reproductive techniques, fertility preservation, and sperm donation. However, its impact on STL remains unknown. For this study, semen surplus from patients who underwent routine semen analysis were used. The impact of slow freezing on STL was analyzed by performing qPCR before and after freezing. Sperm populations with different STL were evaluated using Q-FISH. The relationship between sperm DNA oxidation, DNA fragmentation, and STL was assessed in fresh and frozen sperm samples. No significant impact of slow freezing on STL was observed, neither measured by qPCR nor Q-FISH. However, Q-FISH allowed for the distinguishing of sperm populations with different STLs within individual sperm samples. Slow freezing induced different STL distributions for some of the analyzed sperm samples, but no correlation was found between STL and sperm DNA fragmentation or oxidation. Slow freezing does not alter STL despite increasing sperm DNA oxidation and fragmentation. As STL alterations could be transmitted to offspring, the lack of impact of the slow freezing method on STL ensures the safety of this procedure.},
}
@article {pmid37239390,
year = {2023},
author = {Hill, C and Duffy, S and Kettyle, LM and McGlynn, L and Sandholm, N and Salem, RM and Thompson, A and Swan, EJ and Kilner, J and Rossing, P and Shiels, PG and Lajer, M and Groop, PH and Maxwell, AP and McKnight, AJ and On Behalf Of The Genie Consortium, },
title = {Differential Methylation of Telomere-Related Genes Is Associated with Kidney Disease in Individuals with Type 1 Diabetes.},
journal = {Genes},
volume = {14},
number = {5},
pages = {},
pmid = {37239390},
issn = {2073-4425},
support = {MC_PC_20026/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; Aged ; *Diabetes Mellitus, Type 1/complications/genetics ; *Diabetic Nephropathies/genetics/metabolism ; *Kidney Failure, Chronic/genetics ; DNA Methylation/genetics ; Telomere/genetics/metabolism ; },
abstract = {Diabetic kidney disease (DKD) represents a major global health problem. Accelerated ageing is a key feature of DKD and, therefore, characteristics of accelerated ageing may provide useful biomarkers or therapeutic targets. Harnessing multi-omics, features affecting telomere biology and any associated methylome dysregulation in DKD were explored. Genotype data for nuclear genome polymorphisms in telomere-related genes were extracted from genome-wide case-control association data (n = 823 DKD/903 controls; n = 247 end-stage kidney disease (ESKD)/1479 controls). Telomere length was established using quantitative polymerase chain reaction. Quantitative methylation values for 1091 CpG sites in telomere-related genes were extracted from epigenome-wide case-control association data (n = 150 DKD/100 controls). Telomere length was significantly shorter in older age groups (p = 7.6 × 10[-6]). Telomere length was also significantly reduced (p = 6.6 × 10[-5]) in DKD versus control individuals, with significance remaining after covariate adjustment (p = 0.028). DKD and ESKD were nominally associated with telomere-related genetic variation, with Mendelian randomisation highlighting no significant association between genetically predicted telomere length and kidney disease. A total of 496 CpG sites in 212 genes reached epigenome-wide significance (p ≤ 10[-8]) for DKD association, and 412 CpG sites in 193 genes for ESKD. Functional prediction revealed differentially methylated genes were enriched for Wnt signalling involvement. Harnessing previously published RNA-sequencing datasets, potential targets where epigenetic dysregulation may result in altered gene expression were revealed, useful as potential diagnostic and therapeutic targets for intervention.},
}
@article {pmid37238614,
year = {2023},
author = {Chieffi Baccari, G and Iurato, G and Santillo, A and Dale, B},
title = {Male Germ Cell Telomeres and Chemical Pollutants.},
journal = {Biomolecules},
volume = {13},
number = {5},
pages = {},
pmid = {37238614},
issn = {2218-273X},
mesh = {Male ; Humans ; *Seeds ; Telomere/genetics ; Germ Cells/metabolism ; Spermatozoa ; *Infertility, Male ; },
abstract = {In recent decades, male infertility has been correlated with the shortening of sperm telomeres. Telomeres regulate the reproductive lifespan by mediating the synapsis and homologous recombination of chromosomes during gametogenesis. They are composed of thousands of hexanucleotide DNA repeats (TTAGGG) that are coupled to specialized shelterin complex proteins and non-coding RNAs. Telomerase activity in male germ cells ensures that the telomere length is maintained at maximum levels during spermatogenesis, despite telomere shortening due to DNA replication or other genotoxic factors such as environmental pollutants. An emerging body of evidence has associated an exposure to pollutants with male infertility. Although telomeric DNA may be one of the important targets of environmental pollutants, only a few authors have considered it as a conventional parameter for sperm function. The aim of this review is to provide comprehensive and up-to-date data on the research carried out so far on the structure/function of telomeres in spermatogenesis and the influence of environmental pollutants on their functionality. The link between pollutant-induced oxidative stress and telomere length in germ cells is discussed.},
}
@article {pmid37236462,
year = {2023},
author = {Zhang, Q and Han, XZ and Burraco, P and Hao, X and Teng, LW and Liu, ZS and Zhang, FS and Du, WG},
title = {Telomere length, oxidative stress and their links with growth and survival in a lizard facing climate warming.},
journal = {The Science of the total environment},
volume = {891},
number = {},
pages = {164424},
doi = {10.1016/j.scitotenv.2023.164424},
pmid = {37236462},
issn = {1879-1026},
mesh = {Humans ; Animals ; *Lizards/physiology ; Telomere Shortening ; Telomere ; Temperature ; Climate Change ; Oxidative Stress ; },
abstract = {Higher temperatures enhance ectothermic metabolism and development, which can reduce individual health and life expectancy, and therefore increase their vulnerability to climate warming. However, the mechanistic causes and consequences of such a temperature-driven impact remain unclear. Our study aimed to address two questions: (1) does climate warming alter early-life growth and physiology, and, if so, what are the associated carry-over effects in terms of reduced survival, increased oxidative stress and telomere shortening? (2) can oxidative stress and telomere dynamics at early life stages predict the effect of climate warming on individual survival? To answer these questions, we conducted a longitudinal experiment under semi-natural conditions where we exposed multiocellated racerunner (Eremias multiocellata) to warming conditions from juvenile to adult stages. We found that exposure to climate warming enhanced growth rates, induced oxidative stress, and shortened telomere length of juvenile lizards. Warming conditions did not induce carry-over effects in terms of altered growth rate or physiology but resulted in increased mortality risk in the later life. Intriguingly, telomere shortening in young individuals was associated with mortality risk later in life. This study improves our mechanistic understanding of how global warming impacts on ectotherms' life-history traits, which encourages the inclusion of physiological information in assessing species vulnerability to climate change.},
}
@article {pmid37235262,
year = {2023},
author = {Zhou, F and Guo, C and Wang, L and Zhang, G and Wang, J and Chen, W and Cui, K and Tan, Y and Zhou, Z},
title = {Mono-(2-ethylhexyl) Phthalate (MEHP)-Induced Telomere Structure and Function Disorder Mediates Cell Cycle Dysregulation and Apoptosis via c-Myc and Its Upstream Transcription Factors in a Mouse Spermatogonia-Derived (GC-1) Cell Line.},
journal = {Toxics},
volume = {11},
number = {5},
pages = {},
pmid = {37235262},
issn = {2305-6304},
support = {2018YFC1004201//Ministry of Science and Technology/ ; },
abstract = {As a typical environmental endocrine disrupting chemical (EDC), di-(2-ethylhexyl) phthalate (DEHP) is thought to be related to reproductive disorders, especially in males. Growing evidence suggests that various EDCs may result in an impaired telomere structure and function, which is associated with male infertility. However, the adverse effect of DEHP on telomeres in male reproductive cells has rarely been studied, and the related mechanisms remain unclear. In this study, we tested the effects of mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of DEHP, on telomere dysfunction in mouse spermatogonia-derived cells (GC-1) and the potential role of TERT and c-Myc in MEHP-induced spermatogenic cell damage. Results showed that MEHP induced cell viability inhibition, G0/G1 phase cell cycle arrest, and apoptosis in GC-1 cells in a dose-dependent manner. Shortened telomeres, reduced telomerase activity, and decreased expression of TERT, c-Myc, and upstream transcription factors of c-Myc were also observed in the MEHP-treated cells. In conclusion, it can be concluded that TERT-mediated telomere dysfunction may contribute to MEHP-induced G0/G1 phase cell cycle arrest and apoptosis in GC-1 cells through the impairment of c-Myc and its upstream transcription factors.},
}
@article {pmid37232505,
year = {2023},
author = {Chen, B and Yan, Y and Wang, H and Xu, J},
title = {Association between genetically determined telomere length and health-related outcomes: A systematic review and meta-analysis of Mendelian randomization studies.},
journal = {Aging cell},
volume = {22},
number = {7},
pages = {e13874},
pmid = {37232505},
issn = {1474-9726},
mesh = {Humans ; Mendelian Randomization Analysis/methods ; *Arthritis, Rheumatoid ; *Glioma ; *Hypertension ; Telomere/genetics ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; },
abstract = {Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains unclear. We performed a systematic review and meta-analysis of current evidence from Mendelian randomization (MR) studies on the association between LTL and health-related outcomes. We searched PubMed, Embase, and Web of Science up to April 2022 to identify eligible MR studies. We graded the evidence level of each MR association based on the results of the main analysis and four sensitive MR methods, MR-Egger, weighted median, MR-PRESSO, and multivariate MR. Meta-analyses of published MR studies were also performed. A total of 62 studies with 310 outcomes and 396 MR associations were included. Robust evidence level was observed for the association between longer LTL and increased risk of 24 neoplasms (the strongest magnitude for osteosarcoma, GBM, glioma, thyroid cancer, and non-GBM glioma), six genitourinary and digestive system outcomes of excessive or abnormal growth, hypertension, metabolic syndrome, multiple sclerosis, and clonal hematopoiesis of indeterminate potential. Robust inverse association was observed for coronary heart disease, chronic kidney disease, rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic pulmonary fibrosis, and facial aging. Meta-analyses of MR studies suggested that genetically determined LTL was associated with 12 neoplasms and 9 nonneoplasm outcomes. Evidence from published MR studies supports that LTL plays a causal role in various neoplastic and nonneoplastic diseases. Further research is required to elucidate the underlying mechanisms and to bring insight into the potential prediction, prevention, and therapeutic applications of telomere length.},
}
@article {pmid37232367,
year = {2023},
author = {Tsatsakis, A and Oikonomopoulou, T and Nikolouzakis, TK and Vakonaki, E and Tzatzarakis, M and Flamourakis, M and Renieri, E and Fragkiadaki, P and Iliaki, E and Bachlitzanaki, M and Karzi, V and Katsikantami, I and Kakridonis, F and Hatzidaki, E and Tolia, M and Svistunov, AA and Spandidos, DA and Nikitovic, D and Tsiaoussis, J and Berdiaki, A},
title = {Role of telomere length in human carcinogenesis (Review).},
journal = {International journal of oncology},
volume = {63},
number = {1},
pages = {},
pmid = {37232367},
issn = {1791-2423},
mesh = {Humans ; *Neoplasms/genetics/pathology ; Telomere/genetics/metabolism ; Carcinogenesis ; Chromosomal Instability ; DNA ; *Telomerase/genetics ; },
abstract = {Cancer is considered the most important clinical, social and economic issue regarding cause‑specific disability‑adjusted life years among all human pathologies. Exogenous, endogenous and individual factors, including genetic predisposition, participate in cancer triggering. Telomeres are specific DNA structures positioned at the end of chromosomes and consist of repetitive nucleotide sequences, which, together with shelterin proteins, facilitate the maintenance of chromosome stability, while protecting them from genomic erosion. Even though the connection between telomere status and carcinogenesis has been identified, the absence of a universal or even a cancer‑specific trend renders consent even more complex. It is indicative that both short and long telomere lengths have been associated with a high risk of cancer incidence. When evaluating risk associations between cancer and telomere length, a disparity appears to emerge. Even though shorter telomeres have been adopted as a marker of poorer health status and an older biological age, longer telomeres due to increased cell growth potential are associated with the acquirement of cancer‑initiating somatic mutations. Therefore, the present review aimed to comprehensively present the multifaceted pattern of telomere length and cancer incidence association.},
}
@article {pmid37231745,
year = {2023},
author = {Naspolini, NF and Sichieri, R and Barbosa Cunha, D and Alves Pereira, R and Faerstein, E},
title = {Dietary patterns, obesity markers and leukocyte telomere length among Brazilian civil servants: cross-sectional results from the Pro-Saude study.},
journal = {Public health nutrition},
volume = {26},
number = {10},
pages = {2076-2082},
pmid = {37231745},
issn = {1475-2727},
mesh = {Humans ; Cross-Sectional Studies ; *Leptin ; Brazil ; Cohort Studies ; *Adiponectin ; Obesity ; Diet ; Leukocytes ; Telomere ; Feeding Behavior ; },
abstract = {OBJECTIVE: Dietary patterns express the combination and variety of foods in the diet. The partial least squares method allows extracting dietary patterns related to a specific health outcome. Few studies have evaluated obesity-related dietary patterns associated with telomeres length. This study aims to identify dietary patterns explaining obesity markers and to assess their association with leukocyte telomere length (LTL), a biological marker of the ageing process.<br><br>DESIGN: Cross-sectional study.<br><br>SETTING: University campuses in the state of Rio de Janeiro, Brazil.<br><br>PARTICIPANTS: 478 participants of a civil servants' cohort study with data on food consumption, obesity measurements (total body fat, visceral fat, BMI, leptin and adiponectin) and blood samples.<br><br>RESULTS: Three dietary patterns were extracted: (1) fast food and meat; (2) healthy and (3) traditional pattern, which included rice and beans, the staple foods most consumed in Brazil. All three dietary patterns explained 23&#xb7;2 % of food consumption variation and 10&#xb7;7 % of the obesity-related variables. The fast food and meat pattern were the first factor extracted, explaining 11-13 % variation of the obesity-related response variables (BMI, total body fat and visceral fat), leptin and adiponectin showed the lowest percentage (4&#xb7;5-0&#xb7;1 %). The healthy pattern mostly explained leptin and adiponectin variations (10&#xb7;7 and 3&#xb7;3 %, respectively). The traditional pattern was associated with LTL (&#x3b2; = 0&#xb7;0117; 95 % CI 0&#xb7;0001, 0&#xb7;0233) after adjustment for the other patterns, age, sex, exercise practice, income and energy intake.<br><br>CONCLUSION: Leukocyte telomere length was longer among participants eating a traditional dietary pattern that combines fruit, vegetables and beans.},
}
@article {pmid37231173,
year = {2023},
author = {Jacome Burbano, MS and Robin, JD and Bauwens, S and Martin, M and Donati, E and Martínez, L and Lin, P and Sacconi, S and Magdinier, F and Gilson, E},
title = {Non-canonical telomere protection role of FOXO3a of human skeletal muscle cells regulated by the TRF2-redox axis.},
journal = {Communications biology},
volume = {6},
number = {1},
pages = {561},
pmid = {37231173},
issn = {2399-3642},
mesh = {Humans ; *Telomere ; *Telomeric Repeat Binding Protein 2/genetics ; Cellular Senescence ; Aging/metabolism ; Muscle Fibers, Skeletal ; Muscle, Skeletal ; },
abstract = {Telomeric repeat binding factor 2 (TRF2) binds to telomeres and protects chromosome ends against the DNA damage response and senescence. Although the expression of TRF2 is downregulated upon cellular senescence and in various aging tissues, including skeletal muscle tissues, very little is known about the contribution of this decline to aging. We previously showed that TRF2 loss in myofibers does not trigger telomere deprotection but mitochondrial dysfunction leading to an increased level of reactive oxygen species. We show here that this oxidative stress triggers the binding of FOXO3a to telomeres where it protects against ATM activation, revealing a previously unrecognized telomere protective function of FOXO3a, to the best of our knowledge. We further showed in transformed fibroblasts and myotubes that the telomere properties of FOXO3a are dependent on the C-terminal segment of its CR2 domain (CR2C) but independent of its Forkhead DNA binding domain and of its CR3 transactivation domain. We propose that these non-canonical properties of FOXO3a at telomeres play a role downstream of the mitochondrial signaling induced by TRF2 downregulation to regulate skeletal muscle homeostasis and aging.},
}
@article {pmid37230863,
year = {2023},
author = {Liu, Q and Song, L and Fan, G and Wu, M and Bi, J and Xu, L and Xiong, C and Xia, W and Cao, Z and Xu, S and Wang, Y},
title = {Associations of self-reported sleep duration and sleep quality during pregnancy with newborn telomere length.},
journal = {Sleep health},
volume = {9},
number = {4},
pages = {475-481},
doi = {10.1016/j.sleh.2023.03.001},
pmid = {37230863},
issn = {2352-7226},
mesh = {Child ; Pregnancy ; Humans ; Infant, Newborn ; Female ; Cohort Studies ; Self Report ; *Sleep Quality ; *Sleep Duration ; Parturition ; Telomere ; },
abstract = {BACKGROUND: Telomere length (TL) at birth is considered a potential biomarker for lifelong health. Although maternal sleep disturbance has been linked to a series of adverse pregnancy outcomes, evidence on the effect of maternal sleep on newborn TL remains scarce. Therefore, we aim to investigate the association of maternal sleep duration and sleep quality with newborn TL.<br><br>METHODS: A total of 742 mother-newborn pairs were recruited from Wuhan Children's Hospital between November 2013 and March 2015. Cord blood TL was measured using real-time quantitative polymerase chain reaction. Maternal sleep duration and quality during late pregnancy were obtained via questionnaires. Multivariate linear regression models were used to estimate the effects of maternal sleep duration and sleep quality on newborn TL.<br><br>RESULTS: A total of 742 maternal-newborn pairs were included in the analyses. Mothers sleeping &#x2265;10&#xa0;hours had a 9.30% (95% CI: 2.09%, 15.99%) shorter newborn TL than those sleeping 7-<9&#xa0;hours. However, the association in mothers with short sleep duration (<7&#xa0;hours) did not reach statistical significance. Compared to mothers with good sleep quality, those with poor sleep quality had a 9.91% (95% CI: 4.06%, 15.40%) shorter newborn TL. We observed a joint effect of sleep duration and sleep quality on newborn telomere shortening. Women with sleep duration &#x2265;10&#xa0;hours and poor sleep quality were most likely to have newborns with short TL (percent change:-19.66%, 95% CI: -28.42, -9.84%).<br><br>CONCLUSIONS: Long sleep duration and poor sleep quality during late pregnancy were associated with shorter newborn TL.},
}
@article {pmid37230028,
year = {2023},
author = {Giunco, S and Padovan, M and Angelini, C and Cavallin, F and Cerretti, G and Morello, M and Caccese, M and Rizzo, B and d'Avella, D and Puppa, AD and Chioffi, F and De Bonis, P and Zagonel, V and De Rossi, A and Lombardi, G},
title = {Prognostic role and interaction of TERT promoter status, telomere length and MGMT promoter methylation in newly diagnosed IDH wild-type glioblastoma patients.},
journal = {ESMO open},
volume = {8},
number = {3},
pages = {101570},
pmid = {37230028},
issn = {2059-7029},
mesh = {Humans ; Prognosis ; *Glioblastoma/genetics ; Isocitrate Dehydrogenase/genetics ; Retrospective Studies ; Methylation ; Prospective Studies ; *Brain Neoplasms/diagnosis ; Telomere ; *Telomerase/genetics ; DNA Modification Methylases/genetics ; Tumor Suppressor Proteins/genetics ; DNA Repair Enzymes/genetics ; },
abstract = {BACKGROUND: The clinical relevance of promoter mutations and single nucleotide polymorphism rs2853669 of telomerase reverse transcriptase (TERT) and telomere length in patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) patients remains unclear. Moreover, some studies speculated that TERT promoter status might influence the prognostic role of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in newly diagnosed GBM. We carried out a large study to investigate their clinical impact and their interaction in newly diagnosed GBM patients.<br><br>PATIENTS AND METHODS: We included 273 newly diagnosed IDH wild-type GBM patients who started treatment at Veneto Institute of Oncology IOV - IRCCS (Padua, Italy) from December 2016 to January 2020. TERT promoter mutations (-124 C>T and&#xa0;-146 C>T) and SNP rs2853669 (-245 T>C), relative telomere length (RTL) and MGMT methylation status were retrospectively assessed in this prospective cohort of patients.<br><br>RESULTS: Median overall survival (OS) of 273 newly diagnosed IDH wild-type GBM patients was 15 months. TERT promoter was mutated in 80.2% of patients, and most had the rs2853669 single nucleotide polymorphism as T/T genotype (46.2%). Median RTL was 1.57 (interquartile range 1.13-2.32). MGMT promoter was methylated in 53.4% of cases. At multivariable analysis, RTL and TERT promoter mutations were not associated with OS or progression-free survival (PFS). Notably, patients C carrier of rs2853669 (C/C+C/T genotypes) showed a better PFS compared with those with the T/T genotype (hazard ratio 0.69, P&#xa0;= 0.007). In terms of OS and PFS, all interactions between MGMT, TERT and RTL and between TERT and rs2853669 genotype were not statistically significant.<br><br>CONCLUSIONS: Our findings suggest the presence of the C variant allele at the rs2853669 of the TERT promoter as an attractive independent prognostic biomarker of disease progression in IDH wild-type GBM patients. RTL and TERT promoter mutational status were not correlated to survival regardless of MGMT methylation status.},
}
@article {pmid37230009,
year = {2023},
author = {Pan, Y and Hu, C and Hou, LJ and Chen, YL and Shi, J and Liu, JC and Zhou, JQ},
title = {Swc4 protects nucleosome-free rDNA, tDNA and telomere loci to inhibit genome instability.},
journal = {DNA repair},
volume = {127},
number = {},
pages = {103512},
doi = {10.1016/j.dnarep.2023.103512},
pmid = {37230009},
issn = {1568-7856},
mesh = {Humans ; *Nucleosomes ; Histones/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; DNA, Ribosomal ; Chromatin ; Saccharomyces cerevisiae/genetics/metabolism ; Telomere/genetics/metabolism ; Genomic Instability ; Chromatin Assembly and Disassembly ; Histone Acetyltransferases/genetics ; Transcription Factors/genetics ; },
abstract = {In the baker's yeast Saccharomyces cerevisiae, NuA4 and SWR1-C, two multisubunit complexes, are involved in histone acetylation and chromatin remodeling, respectively. Eaf1 is the assembly platform subunit of NuA4, Swr1 is the assembly platform and catalytic subunit of SWR1-C, while Swc4, Yaf9, Arp4 and Act1 form a functional module, and is present in both NuA4 and SWR1 complexes. ACT1 and ARP4 are essential for cell survival. Deletion of SWC4, but not YAF9, EAF1 or SWR1 results in a severe growth defect, but the underlying mechanism remains largely unknown. Here, we show that swc4Δ, but not yaf9Δ, eaf1Δ, or swr1Δ cells display defects in DNA ploidy and chromosome segregation, suggesting that the defects observed in swc4Δ cells are independent of NuA4 or SWR1-C integrity. Swc4 is enriched in the nucleosome-free regions (NFRs) of the genome, including characteristic regions of RDN5s, tDNAs and telomeres, independently of Yaf9, Eaf1 or Swr1. In particular, rDNA, tDNA and telomere loci are more unstable and prone to recombination in the swc4Δ cells than in wild-type cells. Taken together, we conclude that the chromatin associated Swc4 protects nucleosome-free chromatin of rDNA, tDNA and telomere loci to ensure genome integrity.},
}
@article {pmid37226085,
year = {2023},
author = {Raee, P and Shams Mofarahe, Z and Nazarian, H and Abdollahifar, MA and Ghaffari Novin, M and Aghamiri, S and Ghaffari Novin, M},
title = {Male obesity is associated with sperm telomere shortening and aberrant mRNA expression of autophagy-related genes.},
journal = {Basic and clinical andrology},
volume = {33},
number = {1},
pages = {13},
pmid = {37226085},
issn = {2051-4190},
abstract = {BACKGROUND: Obesity is regarded a global public health crisis. It has been implicated in a variety of health problems, but when it comes to male fertility, how and to what extent obesity affects it are poorly understood. Accordingly, semen samples from 32 individuals with obesity (body mass index (BMI) ≥ 30 kg/m[2]) and 32 individuals with normal weight (BMI: 18.5-25 kg/m[2]) were obtained. Here, for the first time, we examined the association between obesity, relative sperm telomere length (STL) and autophagy-related mRNA levels such as Beclin1, AMPKa1, ULK1, BAX, and BCL2. Each group was also evaluated for conventional semen parameters, sperm apoptotic changes, DNA fragmentation index (DFI), sperm chromatin maturation, and reactive oxygen species (ROS) levels.<br><br>RESULTS: Based on our findings, there was a marked reduction in relative STL in individuals with obesity as compared to the normal-weight group. We also found a significant negative correlation between relative STL and age, BMI, DFI, percentage of sperm with immature chromatin, and intracellular ROS levels in patients with obesity. In the normal-weight group, relative STL was only negatively correlated with DFI and intracellular ROS levels. Regarding mRNA expression, there was considerable upregulation of Beclin1, ULK1, and BCL2 in the group with obesity compared to the normal-weight group. Obesity was also found to be associated with a considerable decline in semen volume, total sperm count, progressive motility, and viability in comparison to normal-weight individuals. Furthermore, obesity was associated with considerably higher percentages of DFI, sperm with immature chromatin, late-stage apoptosis, and elevated ROS levels.<br><br>CONCLUSION: According to our findings, obesity is associated with sperm telomere shortening and aberrant autophagy-related mRNA expression. It should be emphasized that telomere shortening in sperm may be an indirect consequence of obesity due to the oxidative stress associated with the condition. Nevertheless, further investigation is required for a more comprehensive understanding.},
}
@article {pmid37216436,
year = {2023},
author = {Aix, E and Gallinat, A and Yago-Díez, C and Lucas, J and Gómez, MJ and Benguría, A and Freitag, P and Cortez-Toledo, E and Fernández de Manuel, L and García-Cuasimodo, L and Sánchez-Iranzo, H and Montoya, MC and Dopazo, A and Sánchez-Cabo, F and Mercader, N and López, JE and Fleischmann, BK and Hesse, M and Flores, I},
title = {Telomeres Fuse During Cardiomyocyte Maturation.},
journal = {Circulation},
volume = {147},
number = {21},
pages = {1634-1636},
doi = {10.1161/CIRCULATIONAHA.122.062229},
pmid = {37216436},
issn = {1524-4539},
mesh = {Humans ; *Myocytes, Cardiac ; Cell Proliferation ; *Telomere/genetics ; },
}
@article {pmid37216007,
year = {2023},
author = {Allaire, P and He, J and Mayer, J and Moat, L and Gerstenberger, P and Wilhorn, R and Strutz, S and Kim, DSL and Zeng, C and Cox, N and Shay, JW and Denny, J and Bastarache, L and Hebbring, S},
title = {Genetic and clinical determinants of telomere length.},
journal = {HGG advances},
volume = {4},
number = {3},
pages = {100201},
pmid = {37216007},
issn = {2666-2477},
support = {R01 GM130715/GM/NIGMS NIH HHS/United States ; R01 LM010685/LM/NLM NIH HHS/United States ; UL1 TR002373/TR/NCATS NIH HHS/United States ; R01 GM114128/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; Aged ; *Leukocytes ; *Telomere/genetics ; Calcium-Binding Proteins/genetics ; Eye Proteins/genetics ; Membrane Proteins/genetics ; },
abstract = {Many epidemiologic studies have identified important relationships between leukocyte telomere length (LTL) with genetics and health. Most of these studies have been significantly limited in scope by focusing predominantly on individual diseases or restricted to GWAS analysis. Using two large patient populations derived from Vanderbilt University and Marshfield Clinic biobanks linked to genomic and phenomic data from medical records, we investigated the inter-relationship between LTL, genomics, and human health. Our GWAS confirmed 11 genetic loci previously associated with LTL and two novel loci in SCNN1D and PITPNM1. PheWAS of LTL identified 67 distinct clinical phenotypes associated with both short and long LTL. We demonstrated that several diseases associated with LTL were related to one another but were largely independent from LTL genetics. Age of death was correlated with LTL independent of age. Those with very short LTL (<-1.5 standard deviation [SD]) died 10.4 years (p < 0.0001) younger than those with average LTL (±0.5 SD; mean age of death = 74.2 years). Likewise, those with very long LTL (>1.5 SD) died 1.9 years (p = 0.0175) younger than those with average LTL. This is consistent with the PheWAS results showing diseases associating with both short and long LTL. Finally, we estimated that the genome (12.8%) and age (8.5%) explain the largest proportion of LTL variance, whereas the phenome (1.5%) and sex (0.9%) explained a smaller fraction. In total, 23.7% of LTL variance was explained. These observations provide the rationale for expanded research to understand the multifaceted correlations between TL biology and human health over time, leading to effective LTL usage in medical applications.},
}
@article {pmid37215005,
year = {2023},
author = {Cai, SW and Takai, H and Walz, T and de Lange, T},
title = {POT1 recruits and regulates CST-Polα/Primase at human telomeres.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37215005},
support = {R35 CA210036/CA/NCI NIH HHS/United States ; R50 CA243771/CA/NCI NIH HHS/United States ; },
abstract = {Telomere maintenance requires extension of the G-rich telomeric repeat strand by telomerase and fill-in synthesis of the C-rich strand by Polα/Primase. Telomeric Polα/Primase is bound to Ctc1-Stn1-Ten1 (CST), a single-stranded DNA-binding complex. Like mutations in telomerase, mutations affecting CST-Polα/Primase result in pathological telomere shortening and cause a telomere biology disorder, Coats plus (CP). We determined cryogenic electron microscopy structures of human CST bound to the shelterin heterodimer POT1/TPP1 that reveal how CST is recruited to telomeres by POT1. Phosphorylation of POT1 is required for CST recruitment, and the complex is formed through conserved interactions involving several residues mutated in CP. Our structural and biochemical data suggest that phosphorylated POT1 holds CST-Polα/Primase in an inactive auto-inhibited state until telomerase has extended the telomere ends. We propose that dephosphorylation of POT1 releases CST-Polα/Primase into an active state that completes telomere replication through fill-in synthesis.},
}
@article {pmid37214874,
year = {2023},
author = {Granger, SL and Sharma, R and Kaushik, V and Razzaghi, M and Honda, M and Bhat, DS and Wlodarski, MW and Antony, E and Spies, M},
title = {Human hnRNPA1 reorganizes telomere-bound Replication Protein A.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.05.09.540056},
pmid = {37214874},
support = {R01 GM130746/GM/NIGMS NIH HHS/United States ; R01 GM133967/GM/NIGMS NIH HHS/United States ; R35 GM149320/GM/NIGMS NIH HHS/United States ; S10 OD030343/OD/NIH HHS/United States ; },
abstract = {UNLABELLED: Human replication protein A (RPA) is a heterotrimeric ssDNA binding protein responsible for many aspects of cellular DNA metabolism. The binding and dissociation of the four individual DNA binding domains (DBDs) from DNA result in configurational dynamics of the RPA-DNA complexes. This dynamics is essential for replacement of RPA by downstream proteins in various cellular metabolic pathways. RPA plays several important functions at telomeres where it binds to and melts telomeric G-quadruplexes, non-canonical DNA structures formed at the G-rich telomeric ssDNA overhangs. Here, we combine single-molecule total internal reflection fluorescence microscopy (smTIRFM) and mass photometry (MP) with biophysical and biochemical analyses to demonstrate that heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) specifically remodels RPA bound to telomeric ssDNA by dampening the RPA configurational dynamics and forming a stable ternary complex. Uniquely, among hnRNPA1 target RNAs, telomeric repeat-containing RNA (TERRA) is selectively capable of releasing hnRNPA1 from the RPA-telomeric DNA complex. We speculate that this telomere specific RPA-DNA-hnRNPA1 complex is an important structure in telomere protection.<br><br>ONE SENTENCE SUMMARY: At the single-stranded ends of human telomeres, the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) binds to and modulates conformational dynamics of the ssDNA binding protein RPA forming a ternary complex which is controlled by telomeric repeat-containing RNA (TERRA).},
}
@article {pmid37213605,
year = {2023},
author = {Cai, X and Ning, C and Fan, L and Li, Y and Wang, L and He, H and Dong, T and Cai, Y and Zhang, M and Lu, Z and Chen, C and Shi, K and Ye, T and Zhong, R and Tian, J and Li, H and Li, H and Zhu, Y and Miao, X},
title = {Triclosan is associated with breast cancer via oxidative stress and relative telomere length.},
journal = {Frontiers in public health},
volume = {11},
number = {},
pages = {1163965},
pmid = {37213605},
issn = {2296-2565},
mesh = {Humans ; Female ; *Triclosan/adverse effects ; *Breast Neoplasms ; Leukocytes, Mononuclear ; Case-Control Studies ; Oxidative Stress ; 8-Hydroxy-2'-Deoxyguanosine ; Telomere ; },
abstract = {INTRODUCTION: Triclosan (TCS), a widely prescribed broad-spectrum antibacterial agent, is an endocrine-disrupting chemical. The relationship and biological mechanisms between TCS exposure and breast cancer (BC) are disputed. We aimed to examine the correlation between urinary TCS exposure and BC risk and estimated the mediating effects of oxidative stress and relative telomere length (RTL) in the above association.<br><br>METHODS: This case-control study included 302 BC patients and 302 healthy individuals in Wuhan, China. We detected urinary TCS, three common oxidative stress biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2&#x3b1; (8-isoPGF2&#x3b1;), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], and RTL in peripheral blood mononuclear cells.<br><br>RESULTS: Significant associations were observed between log-transformed urinary concentrations of TCS, 8-OHdG, HNE-MA, 8-isoPGF2&#x3b1;, RTL, and BC risk, with the odds ratios (95% confidence intervals) being 1.58 (1.32-1.91), 3.08 (1.55-6.23), 3.39 (2.45-4.77), 3.99 (2.48-6.54), and 1.67 (1.35-2.09), respectively. Continuous TCS exposure was significantly positively correlated with RTL, HNE-MA, and 8-isoPGF2&#x3b1; (all p<0.05) but not with 8-OHdG (p = 0.060) after adjusting for covariates. The mediated proportions of 8-isoPGF22&#x3b1; and RTL in the relationship between TCS and BC risk were 12.84% and 8.95%, respectively (all p<0.001).<br><br>DISCUSSION: In conclusion, our study provides epidemiological evidence to confirmed the deleterious effects of TCS on BC and indicated the mediating effect of oxidative stress and RTL on the correlation between TCS and BC risk. Moreover, exploring the contribution of TCS to BC can clarify the biological mechanisms of TCS exposure, provide new clues for the pathogenesis of BC, which is of great significance to improving public health systems.},
}
@article {pmid37211520,
year = {2023},
author = {Ämmälä, AJ and Suvisaari, J and Kananen, L and Lönnqvist, J and Ripatti, S and Pirkola, S and Paunio, T and Hovatta, I},
title = {Corrigendum to Childhood adversities are associated with shorter leukocyte telomere length at adult age in a population-based study [Psychoneuroendocrinology (2021) 130 105276].},
journal = {Psychoneuroendocrinology},
volume = {153},
number = {},
pages = {106286},
doi = {10.1016/j.psyneuen.2023.106286},
pmid = {37211520},
issn = {1873-3360},
}
@article {pmid37211230,
year = {2023},
author = {Gu, Z and Niu, Z and Yan, Z and Fan, Y and Sun, J and Zhao, X and Duan, X and Yao, W and Yang, Y and Wang, W},
title = {Chain-mediating effect of interaction between telomeres and mitochondria under oxidative stress in coke oven workers.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {331},
number = {Pt 1},
pages = {121855},
doi = {10.1016/j.envpol.2023.121855},
pmid = {37211230},
issn = {1873-6424},
mesh = {Humans ; Antioxidants/analysis ; *Coke/analysis ; DNA, Mitochondrial/genetics ; Mitochondria/genetics ; *Occupational Exposure/analysis ; Oxidative Stress ; *Polycyclic Aromatic Hydrocarbons/analysis ; Telomere ; },
abstract = {Coke oven emissions (COEs) exposure leads to oxidative stress, an imbalance between oxidant production and antioxidant defence in the body, which then leads to shortened relative telomere length (RTL) and reduced mitochondrial DNA copy number (mtDNAcn), ultimately leading to ageing and disease. By analysing the relationship among COEs, oxidative stress, RTL and mtDNAcn, we investigated the chain-mediating effects of oxidative stress and telomeres on mitochondrial damage and mitochondria on telomere damage in coke oven workers. A total of 779 subjects were included in the study. Cumulative COEs exposure concentrations were estimated, and the RTL and mtDNAcn of peripheral blood leukocytes were measured using real-time fluorescence quantitative PCR. Total antioxidant capacity (T-AOC) was measured to reflect the level of oxidative stress. The data were statistically analysed using SPSS 21.0 software and discussed using mediation effect analysis. After adjusting for age, sex, smoking, drinking and BMI, generalised linear model revealed dose-response associations between COEs and T-AOC, RTL and mtDNAcn, respectively. (Ptrend < 0.05). The results of chain-mediating effect showed that the proportion of the chain-mediating effect of "CED-COEs→T-AOC→ RTL→mtDNAcn" was 0.82% (β = -0.0005, 95% CI = [-0.0012, -0.0001]), and the proportion of the chain-mediating effect of "CED-COEs→T-AOC→ mtDNAcn → RTL ″ was 2.64% (β = -0.0013, 95% CI = [-0.0025, -0.0004]). After oxidative stress is induced by COEs, mitochondria and telomeres may interact with each other while leading further to potential bodily damage. This study provides clues to explore the association between mitochondria and telomeres.},
}
@article {pmid37209418,
year = {2024},
author = {Wang, W and Huang, N and Zhuang, Z and Song, Z and Li, Y and Dong, X and Xiao, W and Zhao, Y and Jia, J and Liu, Z and Qi, L and Huang, T},
title = {Identifying Potential Causal Effects of Telomere Length on Health Outcomes: A Phenome-Wide Investigation and Mendelian Randomization Study.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {79},
number = {1},
pages = {},
doi = {10.1093/gerona/glad128},
pmid = {37209418},
issn = {1758-535X},
support = {2020YFC2003401//National Key Research and Development Program of China/ ; },
mesh = {Humans ; *Genome-Wide Association Study ; Mendelian Randomization Analysis ; Phenotype ; *Myocardial Infarction/epidemiology/genetics ; Telomere/genetics ; Polymorphism, Single Nucleotide ; },
abstract = {BACKGROUND: Telomere length has been linked to various health outcomes. To comprehensively investigate the causal effects of telomere length throughout the human disease spectrum, we conducted a phenome-wide Mendelian randomization study (MR-PheWAS) and a systematic review of MR studies.<br><br>METHODS: We conducted a PheWAS to screen for associations between telomere length and 1 035 phenotypes in the UK Biobank (n = 408 354). The exposure of interest was the genetic risk score (GRS) of telomere length. Observed associations passing multiple testing corrections were assessed for causality by 2-sample MR analysis. A systematic review of MR studies on telomere length was performed to harmonize the published evidence and complement our findings.<br><br>RESULTS: Of the 1 035 phenotypes tested, PheWAS identified 29 and 78 associations of telomere length GRS at a Bonferroni- and false discovery rate-corrected threshold; 24 and 66 distinct health outcomes were causal in the following principal MR analysis. The replication MR using data from the FinnGen study provided evidence of causal effects of genetically instrumented telomere length on 28 out of 66 outcomes, including decreased risks of 5 diseases in respiratory diseases, digestive diseases, and myocardial infarction, and increased risks of 23 diseases, mainly comprised neoplasms, diseases of the genitourinary system, and essential hypertension. A systematic review of 53 MR studies found evidence to support 16 out of the 66 outcomes.<br><br>CONCLUSIONS: This large-scale MR-PheWAS identified a wide range of health outcomes that were possibly affected by telomere length, and suggested that susceptibility to telomere length may vary across disease categories.},
}
@article {pmid37204126,
year = {2023},
author = {Liao, S and Zhou, Q and Zhang, Y},
title = {Association of ABCA1 R219K polymorphism and telomere length in a Chinese rural population: possible linking to systemic inflammation.},
journal = {Journal of genetics},
volume = {102},
number = {},
pages = {},
pmid = {37204126},
issn = {0973-7731},
mesh = {Humans ; Gene Frequency ; *East Asian People ; *Rural Population ; Genetic Predisposition to Disease ; Polymorphism, Genetic ; Genotype ; Inflammation ; Polymorphism, Single Nucleotide ; ATP Binding Cassette Transporter 1/genetics ; },
abstract = {The ATP-binding cassette transporter A1 (ABCA1) gene polymorphisms have been shown to be associated with various human diseases and pathological conditions such as cardiovascular disease and Alzheimer's disease. However, these associations remain unclear and inconclusive. Interestingly, short telomere length was also observed in these diseases. In the present study, our aims were to investigate the interaction between two selected ABCA1 polymorphisms (-565C/T and R219K) and telomere length in a Chinese rural population including 1629 subjects and explore the underlying mechanisms. Genotyping was conducted using Taqman SNP Genotyping Assays. Mean relative leukocyte telomere length was measured using monochrome multiplex quantitative PCR method. We found that the telomere length of R219K RR genotype was significantly shorter than RK or KK genotypes (1.242 ± 0.198 vs 1.271 ± 0.207, P = 0.027 and 1.242 ± 0.198 vs 1.276 ± 0.209, P = 0.021, respectively). While the neutrophil to lymphocyte ratio (NLR) of R219K RR genotype was significantly higher than KK genotype (1.929 ± 0.826 vs 1.768 ± 0.893, P = 0.019). In the general linear models after adjustments for confounding factors, the KK and RK genotypes were both significantly associated with telomere length and NLR. A significant association was also observed for K allele carrier genotypes when compared with RR genotype for telomere length and NLR. In conclusion, the R219K polymorphism of ABCA1 was independently associated with telomere length. R219K K allele could be protective against shortening of telomeres and inflammation.},
}
@article {pmid37193737,
year = {2023},
author = {Carlund, O and Norberg, A and Osterman, P and Landfors, M and Degerman, S and Hultdin, M},
title = {DNA methylation variations and epigenetic aging in telomere biology disorders.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {7955},
pmid = {37193737},
issn = {2045-2322},
mesh = {*DNA Methylation ; *DNA ; Epigenesis, Genetic ; Telomere/genetics ; Biology ; },
abstract = {Telomere Biology Disorders (TBDs) are characterized by mutations in telomere-related genes leading to short telomeres and premature aging but with no strict correlation between telomere length and disease severity. Epigenetic alterations are also markers of aging and we aimed to evaluate whether DNA methylation (DNAm) could be part of the pathogenesis of TBDs. In blood from 35 TBD cases, genome-wide DNAm were analyzed and the cases were grouped based on relative telomere length (RTL): short (S), with RTL close to normal controls, and extremely short (ES). TBD cases had increased epigenetic age and DNAm alterations were most prominent in the ES-RTL group. Thus, the differentially methylated (DM) CpG sites could be markers of short telomeres but could also be one of the mechanisms contributing to disease phenotype since DNAm alterations were observed in symptomatic, but not asymptomatic, cases with S-RTL. Furthermore, two or more DM-CpGs were identified in four genes previously linked to TBD or telomere length (PRDM8, SMC4, VARS, and WNT6) and in three genes that were novel in telomere biology (MAS1L, NAV2, and TM4FS1). The DM-CpGs in these genes could be markers of aging in hematological cells, but they could also be of relevance for the progression of TBD.},
}
@article {pmid37191632,
year = {2023},
author = {Bhala, S and Savage, SA},
title = {What is the future of telomere length testing in telomere biology disorders?.},
journal = {Expert review of hematology},
volume = {16},
number = {7},
pages = {475-478},
pmid = {37191632},
issn = {1747-4094},
support = {ZIA CP010144/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; Telomere/genetics/metabolism ; *Telomerase ; Biology ; *Dyskeratosis Congenita ; },
}
@article {pmid37189188,
year = {2023},
author = {Byrjalsen, A and Brainin, AE and Lund, TK and Andersen, MK and Jelsig, AM},
title = {Size matters in telomere biology disorders ‒ expanding phenotypic spectrum in patients with long or short telomeres.},
journal = {Hereditary cancer in clinical practice},
volume = {21},
number = {1},
pages = {7},
pmid = {37189188},
issn = {1731-2302},
abstract = {The end of each chromosome consists of a DNA region termed the telomeres. The telomeres serve as a protective shield against degradation of the coding DNA sequence, as the DNA strand inevitably ‒ with each cell division ‒ is shortened. Inherited genetic variants cause telomere biology disorders when located in genes (e.g. DKC1, RTEL1, TERC, TERT) playing a role in the function and maintenance of the telomeres. Subsequently patients with telomere biology disorders associated with both too short or too long telomeres have been recognized. Patients with telomere biology disorders associated with short telomeres are at increased risk of dyskeratosis congenita (nail dystrophy, oral leukoplakia, and hyper- or hypo-pigmentation of the skin), pulmonary fibrosis, hematologic disease (ranging from cytopenia to leukemia) and in rare cases very severe multiorgan manifestations and early death. Patients with telomere biology disorders associated with too long telomeres have in recent years been found to confer an increased risk of melanoma and chronic lymphocytic leukemia. Despite this, many patients have an apparently isolated manifestation rendering telomere biology disorders most likely underdiagnosed. The complexity of telomere biology disorders and many causative genes makes it difficult to design a surveillance program which will ensure identification of early onset disease manifestation without overtreatment.},
}
@article {pmid37188431,
year = {2023},
author = {Li, S and Liu, Z and Zhang, J and Li, L},
title = {Links between telomere dysfunction and hallmarks of aging.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {888},
number = {},
pages = {503617},
doi = {10.1016/j.mrgentox.2023.503617},
pmid = {37188431},
issn = {1879-3592},
mesh = {Humans ; Aging/genetics ; *Neoplasms/genetics ; Telomere/genetics ; *Telomerase ; },
abstract = {Aging is characterized by the gradual loss of physiological integrity, leading to impaired function and increased risk of death. This deterioration is the main risk factor for the great majority of chronic diseases, which account for most of the morbidity, death and medical expenses. The hallmarks of aging comprise diverse molecular mechanisms and cell systems, which are interrelated and coordinated to drive the aging process. This review focuses on telomere to analyze the interrelationships between telomere dysfunction and other aging hallmarks and their relative contributions to the initiation and progression of age-related diseases (such as neurodegeneration, cardiovascular disease, and cancer), which will contribute to determine drug targets, improve human health in the aging process with minimal side effects and provide information for the prevention and treatment of age-related diseases.},
}
@article {pmid37186136,
year = {2023},
author = {Kurokochi, H and Tajima, N and Sato, MP and Yoshitake, K and Asakawa, S and Isobe, S and Shirasawa, K},
title = {Telomere-to-telomere genome assembly of matsutake (Tricholoma matsutake).},
journal = {DNA research : an international journal for rapid publication of reports on genes and genomes},
volume = {30},
number = {3},
pages = {},
pmid = {37186136},
issn = {1756-1663},
abstract = {Here, we report the first telomere-to-telomere genome assembly of matsutake (Tricholoma matsutake), which consists of 13 sequences (spanning 161.0 Mb) and a 76 kb circular mitochondrial genome. All the 13 sequences were supported with telomeric repeats at the ends. GC-rich regions are located at the middle of the sequences and are enriched with long interspersed nuclear elements (LINEs). Repetitive sequences including long-terminal repeats (LTRs) and LINEs occupy 71.6% of the genome. A total of 21,887 potential protein-coding genes were predicted. The genomic data reported in this study served not only matsutake gene sequences but also genome structures and intergenic sequences. The information gained would be a great reference for exploring the genetics, genomics, and evolutionary study of matsutake in the future, and ultimately facilitate the conservation of this vulnerable genetic resource.},
}
@article {pmid37185424,
year = {2023},
author = {Delmonico, L and Bines, J and Nascimento, CMD and Fernandes, PV and Barbosa, IS and Ribeiro, GB and de Paula, BHR and Silvestre, RT and Ornellas, MHF and Alves, G and Lage, C},
title = {Nuclear and Cytoplasmic hTERT, Tumor-Infiltrating Lymphocytes, and Telomere Elongation Leukocytes Are Independent Factors in the Response to Neoadjuvant Treatment in HER2-Enriched Breast Cancer.},
journal = {Current oncology (Toronto, Ont.)},
volume = {30},
number = {4},
pages = {4094-4109},
pmid = {37185424},
issn = {1718-7729},
mesh = {Female ; Humans ; *Breast Neoplasms/drug therapy/genetics/pathology ; Lymphocytes, Tumor-Infiltrating/metabolism/pathology ; Neoadjuvant Therapy/methods ; Prognosis ; Receptor, ErbB-2/genetics/metabolism ; },
abstract = {HER2-enriched tumors are responsible for 20% of breast tumors and have high rates of immune infiltrates in the tumor stroma that respond favorably to neoadjuvant chemotherapy. In the context of tumors, telomeres control cell death and prevent tumor cells from replicating discontinuously, leading to their immortalization. This study aimed to evaluate the presence of tumor-infiltrating lymphocytes, hTERT expression, hTERT promoter mutation, and leukocyte telomere length in HER2-enriched breast tumors. A total of 103 cases were evaluated, 19 with pathologic complete response. The TILs percentage was above ≥10 in 44 cases (43%) and significantly present in patients ≥50 years of age. hTERT staining positivity was mostly nuclear, significantly present in the non-pCR group, and associated with a lower survival rate. Leukocyte telomeres were elongated for HER2-enriched tumors, and in multivariate analysis, shortening was associated with an increased risk of death. Overall, our results show that the nuclear and cytoplasmic presence of hTERT may indicate a worse prognosis and that leukocyte telomere elongation is a protective factor.},
}
@article {pmid37184208,
year = {2023},
author = {Vittal, A and Niewisch, MR and Bhala, S and Kudaravalli, P and Rahman, F and Hercun, J and Kleiner, DE and Savage, SA and Koh, C and Heller, T and Giri, N},
title = {Progression of liver disease and portal hypertension in dyskeratosis congenita and related telomere biology disorders.},
journal = {Hepatology (Baltimore, Md.)},
volume = {78},
number = {6},
pages = {1777-1787},
pmid = {37184208},
issn = {1527-3350},
support = {ZIA CP010190/ImNIH/Intramural NIH HHS/United States ; ZIA DK075008/ImNIH/Intramural NIH HHS/United States ; ZIA DK075150/ImNIH/Intramural NIH HHS/United States ; ZIC BC010685/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Humans ; Male ; Female ; *Dyskeratosis Congenita/complications/genetics ; *Digestive System Diseases ; Telomere/metabolism ; *Hypertension, Portal/genetics/complications ; *Vascular Diseases/complications ; Disease Progression ; Biology ; Mutation ; *Telomerase/genetics/metabolism ; },
abstract = {BACKGROUND AND AIMS: Dyskeratosis congenita (DC) and related telomere biology disorders (TBD) are characterized by very short telomeres and multisystem organ involvement including liver disease. Our study aimed to characterize baseline hepatic abnormalities in patients with DC/TBD and determine risk factors associated with liver disease progression.<br><br>APPROACH AND RESULTS: A retrospective review was performed on a cohort of 58 patients (39 males) with DC/TBD who were prospectively evaluated at a single institute from 2002 to 2019. The median age at initial assessment was 18 (1.4-67.6) years, and median follow-up duration was 6 (1.4-8.2) years. Patients with autosomal or X-linked recessive inheritance and those with heterozygous TINF2 DC were significantly younger, predominantly male, and more likely to have DC-associated mucocutaneous triad features and severe bone marrow failure compared with autosomal dominant-non- TINF2 DC/TBD patients. Liver abnormality (defined at baseline assessment by laboratory and/or radiological findings) was present in 72.4% of patients with predominantly cholestatic pattern of liver enzyme elevation. Clinically significant liver disease and portal hypertension developed in 17.2% of patients during the 6-year follow-up; this progression was mainly seen in patients with recessive or TINF2 -associated DC. Significant risk factors associated with progression included the presence of pulmonary or vascular disease.<br><br>CONCLUSIONS: Our experience shows a high prevalence of cholestatic pattern of liver abnormality with progression to portal hypertension in patients with DC/TBD. Presence of pulmonary and/or vascular disease in patients with recessive or TINF2 DC was an important predictor of liver disease progression, suggesting the need for increased vigilance and monitoring for complications in these patients.},
}
@article {pmid37183325,
year = {2023},
author = {Zade, NH and Khattar, E},
title = {POT1 mutations cause differential effects on telomere length leading to opposing disease phenotypes.},
journal = {Journal of cellular physiology},
volume = {238},
number = {6},
pages = {1237-1255},
doi = {10.1002/jcp.31034},
pmid = {37183325},
issn = {1097-4652},
mesh = {Mutation/genetics ; Phenotype ; *Shelterin Complex ; *Telomere/genetics/metabolism ; *Telomere-Binding Proteins/genetics/metabolism ; Humans ; },
abstract = {The protection of telomere protein (POT1) is a telomere-binding protein and is an essential component of the six-membered shelterin complex, which is associated with the telomeres. POT1 directly binds to the 3' single-stranded telomeric overhang and prevents the activation of DNA damage response at telomeres thus preventing the telomere-telomere fusions and genomic instability. POT1 also plays a pivotal role in maintaining telomere length by regulating telomerase-mediated telomere elongation. Mutations in POT1 proteins result in three different telomere phenotypes, which include long, short, or aberrant telomere length. Long telomeres predispose individuals to cancer, while short or aberrant telomere phenotypes result in pro-aging diseases referred to as telomeropathies. Here, we review the function of POT1 proteins in telomere length hemostasis and how the spectrum of mutations reported in POT1 can be segregated toward developing very distinct disease phenotypes of cancer and telomeropathies.},
}
@article {pmid37179160,
year = {2023},
author = {De Rosa, M and Opresko, PL},
title = {Translating the telomeres.},
journal = {Trends in genetics : TIG},
volume = {39},
number = {8},
pages = {593-595},
doi = {10.1016/j.tig.2023.04.009},
pmid = {37179160},
issn = {0168-9525},
mesh = {*RNA, Long Noncoding/genetics ; Telomere/genetics/metabolism ; },
abstract = {Telomeres are transcribed into long noncoding telomeric repeat-containing RNA (TERRA). Or so we thought. Recently, Al-Turki and Griffith provided evidence that TERRA can code for valine-arginine (VR) or glycine-leucine (GL) dipeptide repeat proteins by undergoing repeat-associated non-ATG (RAN) translation. This finding uncovers a new mechanism by which telomeres can impact cellular function.},
}
@article {pmid37173827,
year = {2023},
author = {Morland, F and Ewen, JG and Simons, MJP and Brekke, P and Hemmings, N},
title = {Early-life telomere length predicts life-history strategy and reproductive senescence in a threatened wild songbird.},
journal = {Molecular ecology},
volume = {32},
number = {14},
pages = {4031-4043},
doi = {10.1111/mec.16981},
pmid = {37173827},
issn = {1365-294X},
support = {216405/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Animals ; Female ; Longevity ; *Songbirds/genetics ; Aging ; *Passeriformes ; Telomere/genetics ; Reproduction/genetics ; Telomere Shortening/genetics ; },
abstract = {Telomeres are well known for their associations with lifespan and ageing across diverse taxa. Early-life telomere length can be influenced by developmental conditions and has been shown positively affect lifetime reproductive success in a limited number of studies. Whether these effects are caused by a change in lifespan, reproductive rate or perhaps most importantly reproductive senescence is unclear. Using long-term data on female breeding success from a threatened songbird (the hihi, Notiomystis cincta), we show that the early-life telomere length of individuals predicts the presence and rate of future senescence of key reproductive traits: clutch size and hatching success. In contrast, senescence of fledging success is not associated with early-life telomere length, which may be due to the added influence of biparental care at this stage. Early-life telomere length does not predict lifespan or lifetime reproductive success in this species. Females may therefore change their reproductive allocation strategy depending on their early developmental conditions, which we hypothesise are reflected in their early-life telomere length. Our results offer new insights on the role that telomeres play in reproductive senescence and individual fitness and suggest telomere length can be used as a predictor for future life history in threatened species.},
}
@article {pmid37172909,
year = {2023},
author = {McLester-Davis, LWY and Estrada, P and Hastings, WJ and Kataria, LA and Martin, NA and Siebeneicher, JT and Tristano, RI and Mayne, CV and Horlick, RP and O'Connell, SS and Drury, SS},
title = {A review and meta-analysis: Cross-tissue telomere length correlations in healthy humans.},
journal = {Ageing research reviews},
volume = {88},
number = {},
pages = {101942},
doi = {10.1016/j.arr.2023.101942},
pmid = {37172909},
issn = {1872-9649},
support = {U24 AG066528/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; Databases, Factual ; *Telomere ; },
abstract = {BACKGROUND AND AIM: Tissue source has been shown to exert a significant effect on the magnitude of associations between telomere length and various health outcomes and exposures. The purpose of the present qualitative review and meta-analysis is to describe and investigate the impact of study design and methodological features on the correlation between telomere lengths measured in different tissues from the same healthy individual.<br><br>METHODS: This meta-analysis included studies published from 1988 to 2022. Databases searched included PubMed, Embase, and Web of Science and studies were identified using the keywords "telomere length" and "tissues" or "tissue." A total of 220 articles of 7856 initially identified studies met inclusion criteria for qualitative review, of which 55 met inclusion criteria for meta-analysis in R RESULTS: Studies meeting inclusion criteria for meta-analysis tended to have enhanced demographic and methodological reporting relative to studies only included in the qualitative review. A total of 463 pairwise correlations reported for 4324 unique individuals and 102 distinct tissues were extracted from the 55 studies and subject to meta-analysis, resulting in a significant effect size z&#xa0;=&#xa0;0.66 (p&#xa0;<&#xa0;0.0001) and meta-correlation coefficient of r&#xa0;=&#xa0;0.58. Meta-correlations were significantly moderated by sample size and telomere length measurement methodology, with studies of smaller size and those using hybridization-based analyses exhibiting the largest meta-correlation. Tissue source also significantly moderated the meta-correlation, wherein correlations between samples of a different lineage (e.g., blood vs. non-blood) or collection method (e.g., peripheral vs. surgical) were lower than correlations between samples of the same lineage or collection method.<br><br>CONCLUSION: These results suggest that telomere lengths measured within individuals are generally correlated, but future research should be intentional in selecting a tissue for telomere length measurement that is most biologically relevant to the exposure or outcome investigated and balance this with the feasibility of obtaining the sample in sufficient numbers of individuals.},
}
@article {pmid37170112,
year = {2023},
author = {Wu, W and Li, C and Zhu, X and Liu, X and Li, P and Wan, R and Wu, X and Chen, S},
title = {Genetic association of telomere length, obesity and tobacoo smoking with idiopathic pulmonary fibrosis risk.},
journal = {BMC public health},
volume = {23},
number = {1},
pages = {868},
pmid = {37170112},
issn = {1471-2458},
mesh = {Humans ; *Genome-Wide Association Study ; Obesity/epidemiology/genetics ; *Idiopathic Pulmonary Fibrosis/epidemiology/genetics ; Smoking/adverse effects/epidemiology ; Tobacco Smoking ; Telomere/genetics ; Polymorphism, Single Nucleotide ; },
abstract = {BACKGROUND: Due to the inadequacy of published evidence, association of telomere length (TL), obesity and tobacco smoking with idiopathic pulmonary fibrosis (IPF) remains unclear. The aim of the study was to explore whether these exposures genetically affected the risk of the disease.<br><br>METHODS: Genetic variants from genome-wide association studies for TL, body mass index (BMI), body fat percentage (BFP) and tobacco smoking (including maternal smoking) were used as instrumental variables. Inverse-variance weighted were mainly adopted to determine the genetic association of these exposures with IPF. All analyses were conducted by R-software (version 3.6.1).<br><br>RESULTS: Firstly, longer TL was associated with the decreased risk of IPF (OR&#x2009;=&#x2009;0.475 per SD increase in TL, 95%CI&#x2009;=&#x2009;0.336&#x2009;~&#x2009;0.670, P<0.001). Secondly, higher levels of BMI and BFP were related to the increased risk of the disease (OR&#x2009;=&#x2009;1.425 per SD increase in BMI level, 95%CI&#x2009;=&#x2009;1.114&#x2009;~&#x2009;1.823, P&#x2009;=&#x2009;0.005; OR&#x2009;=&#x2009;1.702 per SD increase in BFP level, 95%CI&#x2009;=&#x2009;1.202&#x2009;~&#x2009;2.409, P&#x2009;=&#x2009;0.003). Thirdly, maternal smoking was implicated in the increased risk of the disease (OR&#x2009;=&#x2009;13.183 per SD increase in the prevalence of maternal smoking, 95%CI&#x2009;=&#x2009;1.820&#x2009;~&#x2009;95.484, P&#x2009;=&#x2009;0.011).<br><br>CONCLUSION: TL should be a genetic risk factor for IPF. Obesity and exposure to tobacco smoking as a fetus might also contribute to the development of this fibrotic diseases. These findings should be verified by future studies.},
}
@article {pmid37169669,
year = {2023},
author = {Mastrosimini, MG and Manfrin, E and Remo, A and De Bellis, M and Parisi, A and Pedron, S and Luchini, C and Brunelli, M and Ammendola, S and Bernardoni, L and Conti Bellocchi, MC and Gabbrielli, A and Facciorusso, A and Pea, A and Landoni, L and Scarpa, A and Crinò, SF},
title = {Endoscopic ultrasound fine-needle biopsy to assess DAXX/ATRX expression and alternative lengthening of telomeres status in non-functional pancreatic neuroendocrine tumors.},
journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]},
volume = {23},
number = {4},
pages = {429-436},
doi = {10.1016/j.pan.2023.05.002},
pmid = {37169669},
issn = {1424-3911},
mesh = {Humans ; X-linked Nuclear Protein/genetics/metabolism ; *Neuroendocrine Tumors/diagnosis/genetics/surgery ; Retrospective Studies ; Biopsy, Fine-Needle ; In Situ Hybridization, Fluorescence ; *Intellectual Disability ; *alpha-Thalassemia ; Reproducibility of Results ; *Pancreatic Neoplasms/diagnosis/genetics/surgery ; Telomere/genetics/metabolism/pathology ; Molecular Chaperones/genetics ; Co-Repressor Proteins/genetics ; },
abstract = {BACKGROUND/OBJECTIVES: Death domain-associated protein (DAXX) and/or α-thalassemia/mental retardation X-linked (ATRX) chromatin remodeling genes mutations and alternative lengthening of telomeres (ALT) activation are associated with more aggressive behavior of non-functional pancreatic neuroendocrine tumors (NF-PanNETs). We aimed to evaluate the reliability of such markers on endoscopic-ultrasound fine-needle biopsy (EUS-FNB) specimens.<br><br>METHODS: Patients who underwent EUS-FNB and subsequent surgical resection for PanNETs between January 2017 and December 2019 were retrospectively identified. Immunohistochemistry (IHC) to evaluate DAXX/ATRX expression and fluorescence in situ hybridization (FISH) for ALT status were performed. Primary outcome was the concordance rate of markers expression between EUS-FNB and surgical specimens. Secondary aims were association between markers and lesion aggressiveness, their diagnostic performance in predicting aggressiveness, and agreement of preoperative and post-surgical Ki67-based grading.<br><br>RESULTS: Forty-one NF-PanNETs (mean diameter 36.1&#xa0;&#xb1;&#xa0;26.5&#xa0;mm) were included. Twenty-four showed features of lesion aggressiveness. Concordance of expressions of DAXX, ATRX, and ALT status between EUS-FNB and surgical specimens were 95.1% (&#x3ba;&#xa0;=&#xa0;0.828; p&#xa0;<&#xa0;0.001), 92.7% (&#x3ba;&#xa0;=&#xa0;0.626; p&#xa0;<&#xa0;0.001), and 100% (&#x3ba;&#xa0;=&#xa0;1; p&#xa0;<&#xa0;0.001), respectively. DAXX/ATRX loss and ALT-positivity were significantly (p&#xa0;<&#xa0;0.05) associated with metastatic lymphnodes and lymphovascular invasion. The combination of all tumor markers (DAXX/ATRX loss&#xa0;+&#xa0;ALT-positivity&#xa0;+&#xa0;grade 2) reached an accuracy of 73.2% (95%CI 57.1-85.8) in identifying aggressive lesions. Pre- and post-operative ki-67-based grading was concordant in 80.5% of cases (k&#xa0;=&#xa0;0.573; p&#xa0;<&#xa0;0.001).<br><br>CONCLUSION: DAXX/ATRX expression and ALT status can be accurately evaluated in a preoperative setting on EUS-FNB samples, potentially improving the identification of patients with increased risk and poorer prognosis.},
}
@article {pmid37165507,
year = {2023},
author = {Maiese, K},
title = {The Implications of Telomere Length: Advanced Aging, Cell Senescence, MRI Phenotypes, Stem Cells and Alzheimer's Disease.},
journal = {Current neurovascular research},
volume = {20},
number = {2},
pages = {171-174},
doi = {10.2174/1567202620666230510150337},
pmid = {37165507},
issn = {1875-5739},
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging/genetics ; Cellular Senescence ; Phenotype ; Telomere ; Stem Cells ; },
}
@article {pmid37165138,
year = {2023},
author = {Mannherz, W and Agarwal, S},
title = {Publisher Correction: Thymidine nucleotide metabolism controls human telomere length.},
journal = {Nature genetics},
volume = {55},
number = {7},
pages = {1251},
doi = {10.1038/s41588-023-01418-7},
pmid = {37165138},
issn = {1546-1718},
}
@article {pmid37163741,
year = {2023},
author = {Ida, CM and Jenkins, RB},
title = {SMARCAL1: Expanding the spectrum of genes associated with alternative lengthening of telomeres.},
journal = {Neuro-oncology},
volume = {25},
number = {9},
pages = {1576-1577},
pmid = {37163741},
issn = {1523-5866},
mesh = {Humans ; *Telomerase/genetics ; *Glioblastoma ; Telomere/genetics/metabolism ; Mutation ; Carcinogenesis ; DNA Helicases/genetics/metabolism ; },
}
@article {pmid37160859,
year = {2023},
author = {Yang, D and Chen, X and Cao, W and Xu, C and Chang, L and Long, G},
title = {Association between mixed exposure of polycyclic aromatic hydrocarbons and telomere length in general population: NHANES 2001-2002.},
journal = {Environmental science and pollution research international},
volume = {30},
number = {27},
pages = {71131-71140},
pmid = {37160859},
issn = {1614-7499},
mesh = {Adult ; Humans ; Young Adult ; *Polycyclic Aromatic Hydrocarbons/metabolism ; Nutrition Surveys ; Bayes Theorem ; *Phenanthrenes ; Fluorenes ; Telomere ; Biomarkers ; },
abstract = {Although an association between single polycyclic aromatic hydrocarbons (PAHs) adult exposure and telomere length has been reported, the evidence of mixed PAHs (1-napthol, 2-napthol, 3-fluorene, 2-fluorene, 3-phenanthrene, 1-phenanthrene, 2-phenanthrene, and 1-pyrene) exposure and telomere length in the adult general population is still not clear. A total of 1460 adults over the age of 20 years provided urine information on 8 PAHs and selected covariates from the 2001-2002 National Health and Nutrition Examination Survey (NHANES). Bayesian nuclear machine regression (BKMR) was conducted to analyze these associations of telomere length in multiple PAH-exposed environments. Linear regression is mainly used for correlation analysis of PAHs with selected covariate adjustments. Restricted cubic spline (RCS) is used to estimate the correlation between selected PAHs and telomere length. After adjusting for potential covariates, PAHs mixed exposure was negatively associated with telomere length. The linear regression results showed that 2-napthol and 2-fluorene were negatively correlated with telomere length. Telomere length decreased by 1.0% in the fully adjusted model per increment of one unit in the base-10-logarithm-transformed 2-napthol and 2-fluorene concentrations (P = 0.030 and 0.049, respectively). However, the other 6 PAH metabolites were not significantly different. In addition, RCS results showed that 2-napthol has a marginal dose effect relationship with telomere length. Our present study suggested that PAHs are negatively associated with telomere length in the general population of the USA. Considering that the low level of PAHs exposure in the general population can also induce reduced telomere length and potential health risks, future research is needed to explore potential mechanisms.},
}
@article {pmid37160312,
year = {2023},
author = {Biswas, U and Deb Mallik, T and Pschirer, J and Lesche, M and Sameith, K and Jessberger, R},
title = {Cohesin SMC1β promotes closed chromatin and controls TERRA expression at spermatocyte telomeres.},
journal = {Life science alliance},
volume = {6},
number = {7},
pages = {},
pmid = {37160312},
issn = {2575-1077},
mesh = {Male ; *Chromatin/genetics ; *RNA, Long Noncoding/genetics ; Spermatocytes ; Telomere/genetics ; Animals ; *Cell Cycle Proteins ; Cohesins ; },
abstract = {Previous data showed that meiotic cohesin SMC1β protects spermatocyte telomeres from damage. The underlying reason, however, remained unknown as the expressions of telomerase and shelterin components were normal in Smc1β [-/-] spermatocytes. Here. we report that SMC1β restricts expression of the long noncoding RNA TERRA (telomeric repeat containing RNA) in spermatocytes. In somatic cell lines increased TERRA was reported to cause telomere damage through altering telomere chromatin structure. In Smc1β [-/-] spermatocytes, we observed strongly increased levels of TERRA which accumulate on damaged chromosomal ends, where enhanced R-loop formation was found. This suggested a more open chromatin configuration near telomeres in Smc1β [-/-] spermatocytes, which was confirmed by ATAC-seq. Telomere-distal regions were not affected by the absence of SMC1β but RNA-seq revealed increased transcriptional activity in telomere-proximal regions. Thus, SMC1β promotes closed chromatin specifically near telomeres and limits TERRA expression in spermatocytes.},
}
@article {pmid37156332,
year = {2023},
author = {Hart, M and Conrad, J and Barrett, E and Legg, K and Ivey, G and Lee, PHU and Yung, YC and Shim, JW},
title = {X-linked hydrocephalus genes: Their proximity to telomeres and high A + T content compared to Parkinson's disease.},
journal = {Experimental neurology},
volume = {366},
number = {},
pages = {114433},
pmid = {37156332},
issn = {1090-2430},
support = {P20 GM103434/GM/NIGMS NIH HHS/United States ; P20 GM121299/GM/NIGMS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; },
mesh = {Mice ; Rats ; Humans ; Animals ; *Parkinson Disease/genetics ; Thymine ; Genes, X-Linked ; Telomere/genetics ; *Hydrocephalus/genetics ; Mutation ; },
abstract = {Proximity to telomeres (i) and high adenine and thymine (A + T) content (ii) are two factors associated with high mutation rates in human chromosomes. We have previously shown that >100 human genes when mutated to cause congenital hydrocephalus (CH) meet either factor (i) or (ii) at 91% matching, while two factors are poorly satisfied in human genes associated with familial Parkinson's disease (fPD) at 59%. Using the sets of mouse, rat, and human chromosomes, we found that 7 genes associated with CH were located on the X chromosome of mice, rats, and humans. However, genes associated with fPD were in different autosomes depending on species. While the contribution of proximity to telomeres in the autosome was comparable in CH and fPD, high A + T content played a pivotal contribution in X-linked CH (43% in all three species) than in fPD (6% in rodents or 13% in humans). Low A + T content found in fPD cases suggests that PARK family genes harbor roughly 3 times higher chances of methylations in CpG sites or epigenetic changes than X-linked genes.},
}
@article {pmid37154569,
year = {2023},
author = {Jain, M and Madeka, S and Khattar, E},
title = {Optimization of Performance Parameters of the TAGGG Telomere Length Assay.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {194},
pages = {},
doi = {10.3791/65288},
pmid = {37154569},
issn = {1940-087X},
mesh = {Humans ; *Aging ; Telomere/genetics/metabolism ; *Telomerase/genetics/metabolism ; Oxidative Stress ; },
abstract = {Telomeres are repetitive sequences which are present at chromosomal ends; their shortening is a characteristic feature of human somatic cells. Shortening occurs due to a problem with end replication and the absence of the telomerase enzyme, which is responsible for maintaining telomere length. Interestingly, telomeres also shorten in response to various internal physiological processes, like oxidative stress and inflammation, which may be impacted due to extracellular agents like pollutants, infectious agents, nutrients, or radiation. Thus, telomere length serves as an excellent biomarker of aging and various physiological health parameters. The TAGGG telomere length assay kit is used to quantify average telomere lengths using the telomere restriction fragment (TRF) assay and is highly reproducible. However, it is an expensive method, and because of this, it is not employed routinely for large sample numbers. Here, we describe a detailed protocol for an optimized and cost-effective measurement of telomere length using Southern blots or TRF analysis and non-radioactive chemiluminescence-based detection.},
}
@article {pmid37150235,
year = {2023},
author = {Gregório, C and Thakur, S and Camara Rivero, R and Márcia Dos Santos Machado, S and Cuenin, C and Carreira, C and White, V and Cree, IA and Vukojevic, K and Glavina Durdov, M and Bersch Osvaldt, A and Ashton-Prolla, P and Herceg, Z and Talukdar, FR},
title = {Telomere length assessment and molecular characterization of TERT gene promoter in periampullary carcinomas.},
journal = {Gene},
volume = {873},
number = {},
pages = {147460},
doi = {10.1016/j.gene.2023.147460},
pmid = {37150235},
issn = {1879-0038},
mesh = {Humans ; *Telomerase/genetics/metabolism ; *Carcinoma/genetics ; Telomere Shortening ; Promoter Regions, Genetic ; Telomere/genetics/metabolism ; Mutation ; Telomere Homeostasis/genetics ; },
abstract = {Genetic and epigenetic alterations of the telomere maintenance machinery like telomere length and telomerase reverse transcriptase (encoded by TERT gene) are reported in several human malignancies. However, there is limited knowledge on the status of the telomere machinery in periampullary carcinomas (PAC) which are rare and heterogeneous groups of cancers arising from different anatomic sites around the ampulla of Vater. In the current study, we investigated the relative telomere length (RTL) and the most frequent genetic and epigenetic alterations in the TERT promoter in PAC and compared it with tumor-adjacent nonpathological duodenum (NDu). We found shorter RTLs (1.27 vs 1.33, P = 0.01) and lower TERT protein expression (p = 0.04) in PAC tissues as compared to the NDu. Although we did not find any mutation at two reactivating hotspot mutation sites of the TERT promoter, we detected polymorphism in 45% (9/20) of the cases at rs2853669 (T > C). Also, we found a hypermethylated region in the TERT promoter of PACs consisting of four CpGs (cg10896616 with Δβ 7%; cg02545192 with Δβ 9%; cg03323598 with Δβ 19%; and cg07285213 with Δβ 15%). In conclusion, we identified shorter telomeres with DNA hypermethylation in the TERT promoter region and lower TERT protein expression in PAC tissues. These results could be used further to investigate molecular pathology and develop theranostics for PAC.},
}
@article {pmid37149932,
year = {2023},
author = {Carson, LM and Flynn, RL},
title = {Highlighting vulnerabilities in the alternative lengthening of telomeres pathway.},
journal = {Current opinion in pharmacology},
volume = {70},
number = {},
pages = {102380},
pmid = {37149932},
issn = {1471-4973},
support = {R01 CA201446/CA/NCI NIH HHS/United States ; R01 CA214880/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Telomere Homeostasis ; DNA Replication ; *Neoplasms/drug therapy/genetics/metabolism ; Telomere/metabolism ; },
abstract = {The alternative lengthening of telomeres (ALT) pathway is a telomere elongation mechanism found in a small but often aggressive subset of cancers. Dependent on break-induced replication, telomere extension in ALT-positive cells relies on a baseline level of DNA replication stress to initiate elongation events. This results in an elevated level of DNA damage and presents a possible vulnerability to be exploited in the development of ALT-targeted cancer therapies. Currently, there are no treatment options that target the ALT mechanism or that are specific for ALT-positive tumors. Here, we review recent developments and promising directions in the development of ALT-targeted therapeutics, many of which involve tipping the balance towards inhibition or exacerbation of ALT activity to selectively target these cells.},
}
@article {pmid37149272,
year = {2023},
author = {Deregowska, A and Lewinska, A and Warzybok, A and Stoklosa, T and Wnuk, M},
title = {Telomere loss is accompanied by decreased pool of shelterin proteins TRF2 and RAP1, elevated levels of TERRA and enhanced glycolysis in imatinib-resistant CML cells.},
journal = {Toxicology in vitro : an international journal published in association with BIBRA},
volume = {90},
number = {},
pages = {105608},
doi = {10.1016/j.tiv.2023.105608},
pmid = {37149272},
issn = {1879-3177},
mesh = {Humans ; *Shelterin Complex ; Imatinib Mesylate/pharmacology ; Telomere-Binding Proteins/genetics/metabolism ; Telomeric Repeat Binding Protein 2 ; Telomere/metabolism ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; },
abstract = {Telomere length may be maintained by telomerase nucleoprotein complex and shelterin complex, namely TRF1, TRF2, TIN2, TPP1, POT1 and RAP1 proteins and modulated by TERRA expression. Telomere loss is observed during progression of chronic myeloid leukemia (CML) from the chronic phase (CML-CP) to the blastic phase (CML-BP). The introduction of tyrosine kinase inhibitors (TKIs), such as imatinib (IM), has changed outcome for majority of patients, however, a number of patients treated with TKIs may develop drug resistance. The molecular mechanisms underlying this phenomenon are not fully understood and require further investigation. In the present study, we demonstrate that IM-resistant BCR::ABL1 gene-positive CML K-562 and MEG-A2 cells are characterized by decreased telomere length, lowered protein levels of TRF2 and RAP1 and increased expression of TERRA in comparison to corresponding IM-sensitive CML cells and BCR::ABL1 gene-negative HL-60 cells. Furthermore, enhanced activity of glycolytic pathway was observed in IM-resistant CML cells. A negative correlation between a telomere length and advanced glycation end products (AGE) was also revealed in CD34[+] cells isolated from CML patients. In conclusion, we suggest that affected expression of shelterin complex proteins, namely TRF2 and RAP1, TERRA levels, and glucose consumption rate may promote telomere dysfunction in IM-resistant CML cells.},
}
@article {pmid37146910,
year = {2023},
author = {Thompson, AJ and Henrich, CC},
title = {Maternal depression and child telomere length: The role of genetic sensitivity.},
journal = {Journal of affective disorders},
volume = {334},
number = {},
pages = {77-82},
doi = {10.1016/j.jad.2023.04.103},
pmid = {37146910},
issn = {1573-2517},
support = {R01 HD036916/HD/NICHD NIH HHS/United States ; R01 HD039135/HD/NICHD NIH HHS/United States ; R01 HD040421/HD/NICHD NIH HHS/United States ; },
mesh = {Humans ; Child ; Child, Preschool ; Female ; *Telomere Shortening/genetics ; *Family ; Telomere/genetics ; Mothers/psychology ; },
abstract = {BACKGROUND: The stress of a mother's depression may increasingly tax psychobiological systems that help children with self-regulation, increasing children's allostatic load over time. Some evidence supports children exposed to maternal depression tend to have shorter telomeres and tend to have more somatic and psychological problems. Children having one or more A1 alleles of dopamine receptor 2 (DRD2, rs1800497), tend to have greater sensitivity to maternal depression and could experience more adverse child outcomes that contribute to greater allostatic load.<br><br>METHODS: Using the Future Families and Child Wellbeing dataset, secondary-data analyses were used to test the effect of repeated exposure to maternal depression during early childhood on children's telomere length during middle childhood moderated by children's DRD2 genotype (N&#xa0;=&#xa0;2884).<br><br>RESULTS: Greater maternal depression was not significantly associated with shorter child telomere length and this association was not moderated by DRD2 genotypes while controlling for factors associated with child telomere length.<br><br>IMPLICATIONS: The effect of maternal depression on children's TL may not be significant in populations from diverse racial-ethnic and family backgrounds during middle childhood. These findings could help further our current understanding psychobiological systems affected by maternal depression that result in adverse child outcomes.<br><br>LIMITATIONS: Even though this study used a relatively large and diverse sample, replication of DRD2 moderation in even larger samples is an important next step.},
}
@article {pmid37142951,
year = {2023},
author = {Mascarenhas Dos Santos, AC and Julian, AT and Liang, P and Juárez, O and Pombert, JF},
title = {Telomere-to-Telomere genome assemblies of human-infecting Encephalitozoon species.},
journal = {BMC genomics},
volume = {24},
number = {1},
pages = {237},
pmid = {37142951},
issn = {1471-2164},
support = {R15AI128627//National Institute of Allergy and Infectious Diseases/ ; R15AI128627//National Institute of Allergy and Infectious Diseases/ ; R15AI128627//National Institute of Allergy and Infectious Diseases/ ; },
mesh = {Humans ; *Encephalitozoon/genetics ; Epigenesis, Genetic ; Heterochromatin/genetics ; Genome, Fungal ; *Microsporidia ; Telomere/genetics ; },
abstract = {BACKGROUND: Microsporidia are diverse spore forming, fungal-related obligate intracellular pathogens infecting a wide range of hosts. This diversity is reflected at the genome level with sizes varying by an order of magnitude, ranging from less than 3 Mb in Encephalitozoon species (the smallest known in eukaryotes) to more than 50 Mb in Edhazardia spp. As a paradigm of genome reduction in eukaryotes, the small Encephalitozoon genomes have attracted much attention with investigations revealing gene dense, repeat- and intron-poor genomes characterized by a thorough pruning of molecular functions no longer relevant to their obligate intracellular lifestyle. However, because no Encephalitozoon genome has been sequenced from telomere-to-telomere and since no methylation data is available for these species, our understanding of their overall genetic and epigenetic architectures is incomplete.<br><br>METHODS: In this study, we sequenced the complete genomes from telomere-to-telomere of three human-infecting Encephalitozoon spp. -E. intestinalis ATCC 50506, E. hellem ATCC 50604 and E. cuniculi ATCC 50602- using short and long read platforms and leveraged the data generated as part of the sequencing process to investigate the presence of epigenetic markers in these genomes. We also used a mixture of sequence- and structure-based computational approaches, including protein structure prediction, to help identify which Encephalitozoon proteins are involved in telomere maintenance, epigenetic regulation, and heterochromatin formation.<br><br>RESULTS: The Encephalitozoon chromosomes were found capped by TTAGG 5-mer telomeric repeats followed by telomere associated repeat elements (TAREs) flanking hypermethylated ribosomal RNA (rRNA) gene loci featuring 5-methylcytosines (5mC) and 5-hemimethylcytosines (5hmC), themselves followed by lesser methylated subtelomeres and hypomethylated chromosome cores. Strong nucleotide biases were identified between the telomeres/subtelomeres and chromosome cores with significant changes in GC/AT, GT/AC and GA/CT contents. The presence of several genes coding for proteins essential to telomere maintenance, epigenetic regulation, and heterochromatin formation was further confirmed in the Encephalitozoon genomes.<br><br>CONCLUSION: Altogether, our results strongly support the subtelomeres as sites of heterochromatin formation in Encephalitozoon genomes and further suggest that these species might shutdown their energy-consuming ribosomal machinery while dormant as spores by silencing of the rRNA genes using both 5mC/5hmC methylation and facultative heterochromatin formation at these loci.},
}
@article {pmid37141574,
year = {2023},
author = {Wang, Z and Liu, J and Chen, H and Qiu, X and Xie, L and Kaniskan, H&#xdc; and Chen, X and Jin, J and Wei, W},
title = {Telomere Targeting Chimera Enables Targeted Destruction of Telomeric Repeat-Binding Factor Proteins.},
journal = {Journal of the American Chemical Society},
volume = {145},
number = {19},
pages = {10872-10879},
doi = {10.1021/jacs.3c02783},
pmid = {37141574},
issn = {1520-5126},
support = {R35 CA253027/CA/NCI NIH HHS/United States ; R01 CA218600/CA/NCI NIH HHS/United States ; R01 CA230854/CA/NCI NIH HHS/United States ; R01 CA260666/CA/NCI NIH HHS/United States ; R01 CA268384/CA/NCI NIH HHS/United States ; R01 CA268519/CA/NCI NIH HHS/United States ; S10 OD025132/OD/NIH HHS/United States ; S10 OD028504/OD/NIH HHS/United States ; },
mesh = {*Telomeric Repeat Binding Protein 1/genetics/metabolism ; *Telomere/metabolism ; Proteins/genetics ; Cell Line ; Proteasome Endopeptidase Complex/metabolism ; },
abstract = {Telomeres are naturally shortened after each round of cell division in noncancerous normal cells, while the activation of telomerase activity to extend telomere in the cancer cell is essential for cell transformation. Therefore, telomeres are regarded as a potential anticancer target. In this study, we report the development of a nucleotide-based proteolysis-targeting chimera (PROTAC) designed to degrade TRF1/2 (telomeric repeat-binding factor 1/2), which are the key components of the shelterin complex (telosome) that regulates the telomere length by directly interacting with telomere DNA repeats. The prototype telomere-targeting chimeras (TeloTACs) efficiently degrade TRF1/2 in a VHL- and proteosome-dependent manner, resulting in the shortening of telomeres and suppressed cancer cell proliferation. Compared to the traditional receptor-based off-target therapy, TeloTACs have potential application in a broad spectrum of cancer cell lines due to their ability to selectively kill cancer cells that overexpress TRF1/2. In summary, TeloTACs provide a nucleotide-based degradation approach for shortening the telomere and inhibiting tumor cell growth, representing a promising avenue for cancer treatment.},
}
@article {pmid37140180,
year = {2023},
author = {Robertson, CM and Xue, Y and Chowdhury, S and Maringele, L},
title = {A CDK-Dependent Phosphorylation of a Novel Domain of Rif1 Regulates its Function during Telomere Damage and Other Types of Stress.},
journal = {Molecular and cellular biology},
volume = {43},
number = {5},
pages = {185-199},
pmid = {37140180},
issn = {1098-5549},
support = {/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {DNA Replication ; Phosphorylation ; *Repressor Proteins/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; *Telomere/metabolism ; *Telomere-Binding Proteins/genetics/metabolism ; },
abstract = {Rif1 mediates telomere length, DNA replication, and DNA damage responses in budding yeast. Previous work identified several posttranslational modifications of Rif1, however none of these was shown to mediate the molecular or cellular responses to DNA damage, including telomere damage. We searched for such modifications using immunoblotting methods and the cdc13-1 and tlc1Δ models of telomere damage. We found that Rif1 is phosphorylated during telomere damage, and that serines 57 and 110 within a novel phospho-gate domain (PGD) of Rif1 are important for this modification, in cdc13-1 cells. The phosphorylation of Rif1 appeared to inhibit its accumulation on damaged chromosomes and the proliferation of cells with telomere damage. Moreover, we found that checkpoint kinases were upstream of this Rif1 phosphorylation and that the Cdk1 activity was essential for maintaining it. Apart from telomere damage, S57 and S110 were essential for Rif1 phosphorylation during the treatment of cells with genotoxic agents or during mitotic stress. We propose a speculative "Pliers" model to explain the role of the PGD phosphorylation during telomere and other types of damage.},
}
@article {pmid37140166,
year = {2023},
author = {DeBoy, EA and Tassia, MG and Schratz, KE and Yan, SM and Cosner, ZL and McNally, EJ and Gable, DL and Xiang, Z and Lombard, DB and Antonarakis, ES and Gocke, CD and McCoy, RC and Armanios, M},
title = {Familial Clonal Hematopoiesis in a Long Telomere Syndrome.},
journal = {The New England journal of medicine},
volume = {388},
number = {26},
pages = {2422-2433},
pmid = {37140166},
issn = {1533-4406},
support = {T32 GM136577/GM/NIGMS NIH HHS/United States ; R01 CA225027/CA/NCI NIH HHS/United States ; R01CA225027/CA/NCI NIH HHS/United States ; F31 HG012495/HG/NHGRI NIH HHS/United States ; K08 HL163468/HL/NHLBI NIH HHS/United States ; R01 HL119476/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Aging/genetics ; *Clonal Hematopoiesis/genetics ; Heterozygote ; Loss of Function Mutation/genetics ; Mutation ; *Neoplasms/genetics ; Shelterin Complex/genetics ; Syndrome ; *Telomere/genetics/physiology ; Telomere Homeostasis/genetics ; Telomere-Binding Proteins/genetics ; },
abstract = {BACKGROUND: Telomere shortening is a well-characterized cellular aging mechanism, and short telomere syndromes cause age-related disease. However, whether long telomere length is advantageous is poorly understood.<br><br>METHODS: We examined the clinical and molecular features of aging and cancer in persons carrying heterozygous loss-of-function mutations in the telomere-related gene POT1 and noncarrier relatives.<br><br>RESULTS: A total of 17 POT1 mutation carriers and 21 noncarrier relatives were initially included in the study, and a validation cohort of 6 additional mutation carriers was subsequently recruited. A majority of the POT1 mutation carriers with telomere length evaluated (9 of 13) had long telomeres (>99th percentile). POT1 mutation carriers had a range of benign and malignant neoplasms involving epithelial, mesenchymal, and neuronal tissues in addition to B- and T-cell lymphoma and myeloid cancers. Five of 18 POT1 mutation carriers (28%) had T-cell clonality, and 8 of 12 (67%) had clonal hematopoiesis of indeterminate potential. A predisposition to clonal hematopoiesis had an autosomal dominant pattern of inheritance, as well as penetrance that increased with age; somatic DNMT3A and JAK2 hotspot mutations were common. These and other somatic driver mutations probably arose in the first decades of life, and their lineages secondarily accumulated a higher mutation burden characterized by a clocklike signature. Successive generations showed genetic anticipation (i.e., an increasingly early onset of disease). In contrast to noncarrier relatives, who had the typical telomere shortening with age, POT1 mutation carriers maintained telomere length over the course of 2 years.<br><br>CONCLUSIONS: POT1 mutations associated with long telomere length conferred a predisposition to a familial clonal hematopoiesis syndrome that was associated with a range of benign and malignant solid neoplasms. The risk of these phenotypes was mediated by extended cellular longevity and by the capacity to maintain telomeres over time. (Funded by the National Institutes of Health and others.).},
}
@article {pmid37140164,
year = {2023},
author = {Vassiliou, G},
title = {Telomere Length and Clonal Hematopoiesis.},
journal = {The New England journal of medicine},
volume = {388},
number = {26},
pages = {2481-2484},
doi = {10.1056/NEJMe2303022},
pmid = {37140164},
issn = {1533-4406},
mesh = {Humans ; *Clonal Hematopoiesis/genetics ; *Hematopoiesis/genetics ; Mutation ; *Telomere/genetics ; Telomere Homeostasis/genetics ; },
}
@article {pmid37140004,
year = {2023},
author = {Gavia-García, G and Rosado-Pérez, J and Arista-Ugalde, TL and Aguiñiga-Sánchez, I and Santiago-Osorio, E and Mendoza-Núñez, VM},
title = {The consumption of Sechium edule (chayote) has antioxidant effect and prevents telomere attrition in older adults with metabolic syndrome.},
journal = {Redox report : communications in free radical research},
volume = {28},
number = {1},
pages = {2207323},
pmid = {37140004},
issn = {1743-2928},
mesh = {Humans ; Aged ; *Antioxidants/therapeutic use/metabolism ; *Metabolic Syndrome/drug therapy ; Lipid Peroxides ; Hydrogen Peroxide ; Telomere/metabolism ; },
abstract = {OBJECTIVE: To determine the effect of the consumption of Sechium edule (1.5 g/day) for six months on oxidative stress (OxS) and inflammation markers and its association with telomere length (TL) in older adults with metabolic syndrome (MetS).<br><br>METHODS: The study was conducted in a sample of 48 older adults: placebo (EP) and experimental (EG) groups. Lipoperoxides, protein carbonylation, 8-OHdG, total oxidant status (TOS), SOD, GPx, H2O2 inhibition, total antioxidant status (TAS), inflammatory cytokines (IL6, IL10, TNF-&#x3b1;), and TL were measured before and six months post-treatment.<br><br>RESULTS: We found a significant decrease in the levels of lipoperoxides, protein carbonylation, 8-OHdG, TOS in the EG in comparison PG. Likewise, a significante increase of TAS, IL-6, and IL-10 levels was found at six months post-treatment in EG in comparison with PG. TL showed a statistically significant decrease in PG compared to post-treatment EG.<br><br>CONCLUSIONS: Our findigns showed that the supplementation of Sechium edule has antioxidant, and anti-inflammatory effects, and diminushion of shortening of telomeric DNA in older adults with MetS. This would be the first study that shows that the intervention with Sechium edule has a possible geroprotective effect by preventing telomeres from shortening as usually happens in these patients. Therefore, suggesting a protection of telomeric DNA and genomic DNA.},
}
@article {pmid37139235,
year = {2023},
author = {Whittemore, K and Fossel, M},
title = {Editorial: Telomere length and species lifespan.},
journal = {Frontiers in genetics},
volume = {14},
number = {},
pages = {1199667},
pmid = {37139235},
issn = {1664-8021},
}
@article {pmid37139230,
year = {2023},
author = {Liu, M and Luo, P and Liu, L and Wei, X and Bai, X and Li, J and Wu, L and Luo, M},
title = {Immune-mediated inflammatory diseases and leukocyte telomere length: A Mendelian randomization study.},
journal = {Frontiers in genetics},
volume = {14},
number = {},
pages = {1129247},
pmid = {37139230},
issn = {1664-8021},
abstract = {Objective: To elucidate the potential causality of leukocyte telomere length (LTL) with immune-mediated inflammatory diseases (IMIDs), we conducted a Mendelian randomization (MR) study. Methods: The genetically predicted causation between LTL and IMIDs was evaluated using a two-sample MR method. We analyzed 16 major IMIDs, which included systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD), ankylosing spondylitis (AS), sicca syndrome (SS), rheumatoid arthritis (RA), type 1 diabetes (T1D), primary sclerosing cholangitis (PSC), idiopathic pulmonary fibrosis (IPF), atopic dermatitis (AD), sarcoidosis, hypothyroidism, hyperthyroidism, psoriasis, and childhood asthma. The random-effects inverse-variance weighted (IVW) method was performed as the main analytical approach in MR. Various sensitivity analyses, including MR-Egger, MR robust adjusted profile score (MR-RAPS), weighted median, MR pleiotropy residual sum and outlier (MR-PRESSO) methods, weighted mode, radial plot, and radial regression, were used to guarantee the robustness of the results and detect horizontal pleiotropy. Cochran's Q value was calculated to check for heterogeneity, and the MR Steiger approach was used to test the causal direction. Results: The MR results indicated significant inverse associations of LTL with risks of psoriasis (OR: 0.77, 95% CI: 0.66-0.89, and p = 3.66 × 10[-4]), SS (OR: 0.75, CI: 0.58-0.98, and p = 0.03), RA (OR: 0.77, 95% CI: 0.68-0.88, and p = 9.85 × 10[-5]), hypothyroidism (OR: 0.84, 95% CI: 0.78-0.91, and p = 7,08 × 10[-6]), hyperthyroidism (OR: 0.60, 95% CI: 0.44-0.83, and p = 1.90 × 10[-3]), sarcoidosis (OR: 0.67, 95% CI: 0.54-0.83, and p = 2.60 × 10[-4]), and IPF (OR: 0.41, 95% CI: 0.29-0.58, and p = 4.11 × 10[-7]) in the FinnGen study. We observed that longer LTL was associated with an increased risk of AS susceptibility (OR: 1.51, 95% CI: 1.18-1.94, and p = 9.66 × 10[-4]). The results of the IVW method showed no causal relationship between TL and SLE (OR: 0.92, 95% CI: 0.62-1.38, and p = 0.69) in the FinnGen study; however, a significantly positive correlation was shown between LTL and SLE in another larger GWAS (OR: 1.87, 95% CI: 1.37-2.54, and p = 8.01 × 10[-5]). Conclusion: Our findings reveal that abnormal LTL has the potential to increase the risk of IMIDs. Therefore, it could be treated as a predictor and may provide new potential treatment targets for IMIDs. However, the change of LTL may not be the direct cause of IMIDs. Further studies should aim at the pathogenic mechanism or potential protective effects of LTL in IMIDs.},
}
@article {pmid37132239,
year = {2023},
author = {Voituron, Y and Guillaume, O and Dumet, A and Zahn, S and Criscuolo, F},
title = {Temperature-independent telomere lengthening with age in the long-lived human fish (Proteus anguinus).},
journal = {Proceedings. Biological sciences},
volume = {290},
number = {1998},
pages = {20230503},
pmid = {37132239},
issn = {1471-2954},
mesh = {Animals ; Humans ; Adult ; *Longevity ; *Telomere Homeostasis ; Temperature ; Telomere ; Telomere Shortening ; Mammals ; Fishes ; },
abstract = {Despite a number of studies showing a negative relationship between age and telomere length, the universality of this pattern has been recently challenged, mainly in ectothermic animals exhibiting diverse effects of age on telomere shortening. However, data on ectotherms may be strongly affected by the thermal history of the individuals. We thus investigated the age-related changes in relative telomere length in the skin of a small but long-lived amphibian living naturally in a stable thermal environment over its entire life, allowing comparison with other homeothermic animals like birds and mammals. The present data showed a positive relation between telomere length and individual age, independent of sex and body size. A segmented analysis highlighted a breakpoint in the telomere length-age relationship, suggesting that telomere length reached a plateau at the age of 25 years. Further studies focusing on the biology of animals that live much longer than expected based on body mass will contribute to our better understanding of how ageing processes evolved and may also bring innovation for extending human health span.},
}
@article {pmid37131110,
year = {2023},
author = {Kalal, AA and Shetty, RA and Manjappa, AB and Kulkarni, NV and Shetty, P},
title = {Prognostic significance of dysregulation of shelterin complex and its correlation with telomere length and cytogenetics in multiple myeloma.},
journal = {Journal, genetic engineering &amp; biotechnology},
volume = {21},
number = {1},
pages = {50},
pmid = {37131110},
issn = {2090-5920},
abstract = {BACKGROUND: MM (multiple myeloma) is a bone marrow disease with the accumulation of malignant plasma cells characterized by the neoplastic transformation of differentiated B cells. The onset and progression of cancer are greatly influenced by telomere dysfunction. We aimed to study the biomarker potential and prognostic significance of shelterin complex and hTERT. Telomere length and gene expression were measured using real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and these results were further correlated with clinical parameters.<br><br>RESULTS: Our study showed increased expression of all genes in complex, hTERT, and TL in MM (n&#x2009;=&#x2009;72) in comparison with controls (n&#x2009;=&#x2009;31). TRF2 (P&#x2009;=&#x2009;0.025) and hTERT (P&#x2009;=&#x2009;0.0002) displayed significant association among cytogenetic analysis. The receiver operative curve showed POT1 and RAP1 with a greater area under the curve (AUC). RAP1 (P&#x2009;=&#x2009;0.020) and hTERT (P&#x2009;=&#x2009;0.037) displayed to be independent prognostic markers for overall survival. Clinical parameters and genes were observed to be significantly correlated.<br><br>CONCLUSION: Our study findings showed variation in telomere-associated genes and suggest the participation of these genes as prognostic markers in MM. These results all together highlight the evaluation and role of genes involved in telomeric alteration and TL, providing the opportunity to study new therapeutic approaches in patients with MM.},
}
@article {pmid37130870,
year = {2023},
author = {Zhao, N and Yin, G and Liu, C and Zhang, W and Shen, Y and Wang, D and Lin, Z and Yang, J and Mao, J and Guo, R and Zhang, Y and Wang, F and Liu, Z and Lu, X and Liu, L},
title = {Critically short telomeres derepress retrotransposons to promote genome instability in embryonic stem cells.},
journal = {Cell discovery},
volume = {9},
number = {1},
pages = {45},
pmid = {37130870},
issn = {2056-5968},
support = {32030033//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32070858//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Telomeres, at the ends of chromosomes, protect chromosomes from fusion and preserve genomic stability. However, the molecular mechanisms underlying telomere attrition-induced genome instability remain to be understood. We systematically analyzed the expression of retrotransposons and performed genomic sequencing of different cell and tissue types with telomeres of varying lengths due to telomerase deficiency. We found that critically short telomeres altered retrotransposon activity to promote genomic instability in mouse embryonic stem cells, as evidenced by elevated numbers of single nucleotide variants, indels and copy number variations (CNVs). Transpositions of retrotransposons such as LINE1 resulting from the short telomeres can also be found in these genomes with elevated number of mutations and CNVs. Retrotransposon activation is linked to increased chromatin accessibility, and reduced heterochromatin abundance correlates with short telomeres. Re-elongation of telomeres upon recovery of telomerase partly represses retrotransposons and heterochromatin accumulation. Together, our findings suggest a potential mechanism by which telomeres maintain genomic stability by suppressing chromatin accessibility and retrotransposon activity.},
}
@article {pmid37129365,
year = {2023},
author = {Schreglmann, SR and Goncalves, T and Grant-Peters, M and Kia, DA and Soreq, L and Ryten, M and Wood, NW and Bhatia, KP and Tomita, K},
title = {Age-related telomere attrition in the human putamen.},
journal = {Aging cell},
volume = {22},
number = {7},
pages = {e13861},
pmid = {37129365},
issn = {1474-9726},
support = {C36439/A12097/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Humans ; *Putamen ; Cross-Sectional Studies ; *Telomere Shortening ; Risk Factors ; Telomere/genetics ; },
abstract = {Age is a major risk factor for neurodegenerative diseases. Shortening of leucocyte telomeres with advancing age, arguably a measure of "biological" age, is a known phenomenon and epidemiologically correlated with age-related disease. The main mechanism of telomere shortening is cell division, rendering telomere length in post-mitotic cells presumably stable. Longitudinal measurement of human brain telomere length is not feasible, and cross-sectional cortical brain samples so far indicated no attrition with age. Hence, age-related changes in telomere length in the brain and the association between telomere length and neurodegenerative diseases remain unknown. Here, we demonstrate that mean telomere length in the putamen, a part of the basal ganglia, physiologically shortens with age, like leukocyte telomeres. This was achieved by using matched brain and leukocyte-rich spleen samples from 98 post-mortem healthy human donors. Using spleen telomeres as a reference, we further found that mean telomere length was brain region-specific, as telomeres in the putamen were significantly shorter than in the cerebellum. Expression analyses of genes involved in telomere length regulation and oxidative phosphorylation revealed that both region- and age-dependent expression pattern corresponded with region-dependent telomere length dynamics. Collectively, our results indicate that mean telomere length in the human putamen physiologically shortens with advancing age and that both local and temporal gene expression dynamics correlate with this, pointing at a potential mechanism for the selective, age-related vulnerability of the nigro-striatal network.},
}
@article {pmid37128641,
year = {2023},
author = {Aguilera, P and Dubarry, M and Géli, V and Simon, MN},
title = {NPCs and APBs: two HUBs of non-canonical homology-based recombination at telomeres?.},
journal = {Cell cycle (Georgetown, Tex.)},
volume = {22},
number = {10},
pages = {1163-1168},
pmid = {37128641},
issn = {1551-4005},
mesh = {Humans ; *Saccharomyces cerevisiae/genetics/metabolism ; Nuclear Pore/metabolism ; *Telomerase/metabolism ; Homologous Recombination ; Telomere/genetics/metabolism ; Telomere Homeostasis ; },
abstract = {Apart from a few rare exceptions, the maintenance of functional telomeres by recombination-based mechanisms is restricted to accidental and/or pathological situations. Originally described in the yeast S. cerevisiae, this mode of telomere repair has gained interest with the discovery of telomerase negative cancers that use alternative lengthening of telomeres (ALT cancer) dependent on homologous recombination. In both yeast and humans, it has been shown that recombination at telomeres is spatially regulated and occurs preferentially at the nuclear pore complexes (NPCs) in yeast and at ALT-associated promyelocytic leukemia nuclear bodies (APBs) in human cells. Here, we discuss the potential relationships between these two membrane-less structures and their role in enabling unconventional recombination pathways.},
}
@article {pmid37127563,
year = {2023},
author = {Doherty, T and Dempster, E and Hannon, E and Mill, J and Poulton, R and Corcoran, D and Sugden, K and Williams, B and Caspi, A and Moffitt, TE and Delany, SJ and Murphy, TM},
title = {A comparison of feature selection methodologies and learning algorithms in the development of a DNA methylation-based telomere length estimator.},
journal = {BMC bioinformatics},
volume = {24},
number = {1},
pages = {178},
pmid = {37127563},
issn = {1471-2105},
support = {18/CRT/6183/SFI_/Science Foundation Ireland/Ireland ; },
mesh = {Algorithms ; *Telomere Homeostasis ; *DNA Methylation ; *Epigenomics/methods ; Regression Analysis ; Machine Learning ; Humans ; },
abstract = {BACKGROUND: The field of epigenomics holds great promise in understanding and treating disease with advances in machine learning (ML) and artificial intelligence being vitally important in this pursuit. Increasingly, research now utilises DNA methylation measures at cytosine-guanine dinucleotides (CpG) to detect disease and estimate biological traits such as aging. Given the challenge of high dimensionality of DNA methylation data, feature-selection techniques are commonly employed to reduce dimensionality and identify the most important subset of features. In this study, our aim was to test and compare a range of feature-selection methods and ML algorithms in the development of a novel DNA methylation-based telomere length (TL) estimator. We utilised both nested cross-validation and two independent test sets for the comparisons.<br><br>RESULTS: We found that principal component analysis in advance of elastic net regression led to the overall best performing estimator when evaluated using a nested cross-validation analysis and two independent test cohorts. This approach achieved a correlation between estimated and actual TL of 0.295 (83.4% CI [0.201, 0.384]) on the EXTEND test data set. Contrastingly, the baseline model of elastic net regression with no prior feature reduction stage performed less well in general-suggesting a prior feature-selection stage may have important utility. A previously developed TL estimator, DNAmTL, achieved a correlation of 0.216 (83.4% CI [0.118, 0.310]) on the EXTEND data. Additionally, we observed that different DNA methylation-based TL estimators, which have few common CpGs, are associated with many of the same biological entities.<br><br>CONCLUSIONS: The variance in performance across tested approaches shows that estimators are sensitive to data set heterogeneity and the development of an optimal DNA methylation-based estimator should benefit from the robust methodological approach used in this study. Moreover, our methodology which utilises a range of feature-selection approaches and ML algorithms could be applied to other biological markers and disease phenotypes, to examine their relationship with DNA methylation and predictive value.},
}
@article {pmid37122888,
year = {2023},
author = {Fattahi, M and Maghsudlu, M and Hasan Sheikhha, M},
title = {Is sperm telomere length altered in teratozoospermia specimens? A case-control study.},
journal = {International journal of reproductive biomedicine},
volume = {21},
number = {3},
pages = {229-236},
pmid = {37122888},
issn = {2476-4108},
abstract = {BACKGROUND: Male factor infertility is a multifactorial defect, and many of its etiologies are unknown. Teratozoospermia is determined by the existence of over 85% morphologically abnormal spermatozoa in semen which are almost incompetent in fertilization function. One of the most novel issues in genetic alterations studies is the variation of sperm telomere lengths (STL) and its collaboration with male infertility. The present study has been focused on STL alterations in teratozoospermia.<br><br>OBJECTIVE: Investigation of differences in telomere length of teratozoospermia specimens and sperms with normal parameters.<br><br>MATERIALS AND METHODS: In this case-control study, 60 men referred to Arak Fertility Clinic, Markazi province, Iran from November 2017 to February 2018 were categorized into teratozoospermia and normozoospermic groups. Sperm genomic DNA extraction was conducted, and STL were evaluated using quantitative polymerase chain reaction.<br><br>RESULTS: Statistical evaluation of relative telomere length was calculated by the ratio of telomere to single-copy gene for teratozoospermia and normal specimens. Results significantly demonstrated that relative telomere length in teratozoospermia samples is nearly 3 times shorter than in normal samples (p > 0.001).<br><br>CONCLUSION: Our results represent the reduction of telomeres length in teratozoospermia and suggest that this alteration might be one of the factors contributing to the sperm fertility potential of this kind of specimen. However, defining relevant molecular processes requires further detailed investigations.},
}
@article {pmid37119805,
year = {2023},
author = {Ngo, K and Gittens, TH and Gonzalez, DI and Hatmaker, EA and Plotkin, S and Engle, M and Friedman, GA and Goldin, M and Hoerr, RE and Eichman, BF and Rokas, A and Benton, ML and Friedman, KL},
title = {A comprehensive map of hotspots of de novo telomere addition in Saccharomyces cerevisiae.},
journal = {Genetics},
volume = {224},
number = {2},
pages = {},
pmid = {37119805},
issn = {1943-2631},
support = {T32 GM137793/GM/NIGMS NIH HHS/United States ; R01 AI153356/AI/NIAID NIH HHS/United States ; R35 GM136401/GM/NIGMS NIH HHS/United States ; T34 GM136451/GM/NIGMS NIH HHS/United States ; R01 GM123292/GM/NIGMS NIH HHS/United States ; F31 EY033235/EY/NEI NIH HHS/United States ; },
mesh = {Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; Telomere-Binding Proteins/genetics/metabolism ; Telomere/genetics/metabolism ; DNA Repair ; *Telomerase/genetics/metabolism ; },
abstract = {Telomere healing occurs when telomerase, normally restricted to chromosome ends, acts upon a double-strand break to create a new, functional telomere. De novo telomere addition (dnTA) on the centromere-proximal side of a break truncates the chromosome but, by blocking resection, may allow the cell to survive an otherwise lethal event. We previously identified several sequences in the baker's yeast, Saccharomyces cerevisiae, that act as hotspots of dnTA [termed Sites of Repair-associated Telomere Addition (SiRTAs)], but the distribution and functional relevance of SiRTAs is unclear. Here, we describe a high-throughput sequencing method to measure the frequency and location of telomere addition within sequences of interest. Combining this methodology with a computational algorithm that identifies SiRTA sequence motifs, we generate the first comprehensive map of telomere-addition hotspots in yeast. Putative SiRTAs are strongly enriched in subtelomeric regions where they may facilitate formation of a new telomere following catastrophic telomere loss. In contrast, outside of subtelomeres, the distribution and orientation of SiRTAs appears random. Since truncating the chromosome at most SiRTAs would be lethal, this observation argues against selection for these sequences as sites of telomere addition per se. We find, however, that sequences predicted to function as SiRTAs are significantly more prevalent across the genome than expected by chance. Sequences identified by the algorithm bind the telomeric protein Cdc13, raising the possibility that association of Cdc13 with single-stranded regions generated during the response to DNA damage may facilitate DNA repair more generally.},
}
@article {pmid37119246,
year = {2023},
author = {Kong, PL and Looi, LM and Cheah, PL},
title = {Potential utility of telomere length assessment in breast cancer in a diagnostic histopathology setting.},
journal = {The Malaysian journal of pathology},
volume = {45},
number = {1},
pages = {51-63},
pmid = {37119246},
issn = {0126-8635},
mesh = {Humans ; Female ; *Breast Neoplasms/diagnosis/genetics/metabolism ; In Situ Hybridization, Fluorescence ; Prognosis ; Telomere/metabolism/pathology ; Receptors, Antigen, T-Cell ; },
abstract = {INTRODUCTION: Telomeres shorten with cell cycling but are restored above mortality threshold in many cancers making them potentially exploitable for differentiating malignant from benign tissues, and for cancer evaluation.<br><br>MATERIALS AND METHODS: We assessed telomeres in a diagnostic histopathology setting using quantitative fluorescence in situ hybridisation on 33 fibroadenoma (FA) and 73 invasive breast carcinoma of no special type (IBC-NST) (prototypes of benign and malignant breast tumours, respectively) with paired benign, non-lesional breast tissues (BNL). Telomere lengths were expressed as telomere/chromosome-2-centromere ratio (TCR). The telomere length cut-off for malignancy was also determined.<br><br>RESULTS: Mean TCR of IBC-NST was significantly shorter than FA and BNL (p<0.001). Mean TCR of FA was shorter than BNL but not significantly (p>0.05). TCR cut-off for IBC-NST based on FA was &#x2264;0.29 (sensitivity=75.3%; specificity=78.8%), and &#x2264;0.30 based on BNL (sensitivity=76.7%; specificity=89.0%). TCR of IBC-NST did not differ in relation to histological grade, nodal and hormonal status (p>0.05) but was significantly shorter in HER2-overexpressing cancers (p<0.05).<br><br>CONCLUSION: We have demonstrated a first-step to the development of methodologybased cut-off values of mean telomere length for distinguishing benign from malignant breast tissues. Telomere length may not value-add to the standard prognostic and predictive parameters, but has potential in relation to HER2.},
}
@article {pmid37118904,
year = {2023},
author = {Lai, TP and Verhulst, S and Savage, SA and Gadalla, SM and Benetos, A and Toupance, S and Factor-Litvak, P and Susser, E and Aviv, A},
title = {Buildup from birth onward of short telomeres in human hematopoietic cells.},
journal = {Aging cell},
volume = {22},
number = {6},
pages = {e13844},
pmid = {37118904},
issn = {1474-9726},
support = {R21 ES023582/ES/NIEHS NIH HHS/United States ; KL2 TR003018/TR/NCATS NIH HHS/United States ; R01 HD071180/HD/NICHD NIH HHS/United States ; U01 AG066529/AG/NIA NIH HHS/United States ; P30 ES009089/ES/NIEHS NIH HHS/United States ; },
mesh = {Male ; Aged, 80 and over ; Female ; Humans ; *Telomere Shortening ; *Longevity ; Cell Division ; Telomere/genetics ; },
abstract = {Telomere length (TL) limits somatic cell replication. However, the shortest among the telomeres in each nucleus, not mean TL, is thought to induce replicative senescence. Researchers have relied on Southern blotting (SB), and techniques calibrated by SB, for precise measurements of TL in epidemiological studies. However, SB provides little information on the shortest telomeres among the 92 telomeres in the nucleus of human somatic cells. Therefore, little is known about the accumulation of short telomeres with age, or whether it limits the human lifespan. To fill this knowledge void, we used the Telomere-Shortest-Length-Assay (TeSLA), a method that tallies and measures single telomeres of all chromosomes. We charted the age-dependent buildup of short telomeres (<3 kb) in human hematopoietic cells from 334 individuals (birth-89 years) from the general population, and 18 patients with dyskeratosis congenita-telomere biology disorders (DC/TBDs), whose hematopoietic cells have presumably reached or are close to their replicative limit. For comparison, we also measured TL with SB. We found that in hematopoietic cells, the buildup of short telomeres occurs in parallel with the shortening with age of mean TL. However, the proportion of short telomeres was lower in octogenarians from the general population than in patients with DC/TBDs. At any age, mean TL was longer and the proportion of short telomeres lower in females than in males. We conclude that though converging to the TL-mediated replicative limit, hematopoietic cell telomeres are unlikely to reach this limit during the lifespan of most contemporary humans.},
}
@article {pmid37115645,
year = {2023},
author = {Singh, M and MacKenzie, D and Desai, S and Batista, N and Zhang, D},
title = {Diagnostic Biomarkers and Therapeutic Targets of Alternative Lengthening of Telomeres-Positive Cancers.},
journal = {Genetic testing and molecular biomarkers},
volume = {27},
number = {4},
pages = {123-125},
doi = {10.1089/gtmb.2023.29069.mas},
pmid = {37115645},
issn = {1945-0257},
mesh = {Humans ; *Neoplasms/diagnosis/genetics/therapy ; Telomere/genetics/metabolism ; Biomarkers ; *Telomerase/genetics/metabolism ; },
}
@article {pmid37114543,
year = {2023},
author = {Moraes, IB and Paiva, IM and Moreira-Júnior, RE and Sartori, BM and Franco, RR and Espindola, FS and Murgas, LDS and Brunialti-Godard, AL},
title = {Ethanol Preference Leads to Alterations in Telomere Length, Mitochondria Copy Number, and Antioxidant Enzyme Activity in Zebrafish Brains.},
journal = {Frontiers in bioscience (Landmark edition)},
volume = {28},
number = {4},
pages = {73},
doi = {10.31083/j.fbl2804073},
pmid = {37114543},
issn = {2768-6698},
mesh = {Animals ; *Antioxidants/pharmacology ; Zebrafish/genetics/metabolism ; *Alcoholism ; DNA Copy Number Variations ; Catalase/genetics/metabolism/pharmacology ; Superoxide Dismutase/genetics/metabolism ; Ethanol ; Brain/metabolism ; Mitochondria/metabolism ; DNA, Mitochondrial/genetics ; Telomere/genetics/metabolism ; Oxidative Stress ; },
abstract = {BACKGROUND: The motivations for and effects of ethanol consumption vary considerably among individuals, and as such, a significant proportion of the population is prone to substance abuse and its negative consequences in the physical, social, and psychological spheres. In a biological context, the characterization of these phenotypes provides clues for understanding the neurological complexity associated with ethanol abuse behavior. Therefore, the objective of this research was to characterize four ethanol preference phenotypes described in zebrafish: Light, Heavy, Inflexible, and Negative Reinforcement.<br><br>METHODS: To do this, we evaluated the telomere length, mtDNA copy number using real-time quantitative PCR (qPCR), and the activity of these antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the brain, and the interactions between these biomarkers. Changes observed in these parameters were associated with ethanol consumption and alcohol abuse.<br><br>RESULTS: The Heavy, Inflexible, and Negative Reinforcement phenotypes showed ethanol preference. This was particularly the case with the Inflexible phenotype, which was the group with the greatest ethanol preference. These three phenotypes showed telomere shortening as well as high SOD/CAT and/or GPx activities, while the Heavy phenotype also showed an increase in the mtDNA copy number. However, the Light phenotype, containing individuals without ethanol preference, did not demonstrate any changes in the analyzed parameters even after being exposed to the drug. Additionally, the PCA analysis showed a tendency to cluster the Light and Control groups differently from the other ethanol preference phenotypes. There was also a negative correlation between the results of the relative telomere length and SOD and CAT activity, providing further evidence of the biological relationship between these parameters.<br><br>CONCLUSIONS: Our results showed differential molecular and biochemistry patterns in individuals with ethanol preference, suggesting that the molecular and biochemical basis of alcohol abuse behavior extends beyond its harmful physiological effects, but rather is correlated with preference phenotypes.},
}
@article {pmid37113976,
year = {2023},
author = {Duncan, E and Papatheodoulou, M and Metcalfe, NB and McLennan, D},
title = {Does pre-spawning catch and release angling affect offspring telomere dynamics in Atlantic salmon?.},
journal = {Conservation physiology},
volume = {11},
number = {1},
pages = {coad018},
pmid = {37113976},
issn = {2051-1434},
abstract = {The practice of 'catch and release' (C&amp;R) angling confers a balance between animal welfare, conservation efforts and preserving the socio-economic interests of recreational angling. However, C&amp;R angling can still cause exhaustion and physical injury, and often exposes the captured fish to the stress of air exposure. Therefore, the true conservation success of C&amp;R angling depends on whether the angled individuals then survive to reproduction and whether there are any persisting effects on subsequent generations. Here we tested the hypothesis that the stress of C&amp;R angling is then passed on to offspring. We experimentally manipulated the C&amp;R experience of wild adult salmon prior to the spawning season. These parental fish either underwent a C&amp;R simulation (which involved exercise with/without air exposure) or were left as control individuals. We then measured the telomere length of the arising offspring (at the larval stage of development) since previous studies have linked a shorter telomere length with reduced fitness/longevity and the rate of telomere loss is thought to be influenced by stress. Family-level telomere length was positively related to rate of growth. However, the telomere lengths of the salmon offspring were unrelated to the C&amp;R experience of their parents. This may be due to there being no intergenerational effect of parental stress exposure on offspring telomeres, or to any potential effects being buffered by the significant telomere elongation mechanisms that are thought to occur during the embryonic and larval stages of development. While this may suggest that C&amp;R angling has a minimal intergenerational effect on offspring fitness, there have been numerous other reports of negative C&amp;R effects, therefore we should still be aiming to mitigate and refine such practices, in order to minimize their impacts on fish populations.},
}
@article {pmid37113742,
year = {2023},
author = {Yang, Q and Nie, Z and Zhu, Y and Hao, M and Liu, S and Ding, X and Wang, F and Wang, F and Geng, X},
title = {Inhibition of TRF2 Leads to Ferroptosis, Autophagic Death, and Apoptosis by Causing Telomere Dysfunction.},
journal = {Oxidative medicine and cellular longevity},
volume = {2023},
number = {},
pages = {6897268},
pmid = {37113742},
issn = {1942-0994},
mesh = {Apoptosis/genetics ; *Autophagic Cell Death ; Cell Proliferation ; *Ferroptosis/genetics ; Telomere ; Telomeric Repeat Binding Protein 2/metabolism ; },
abstract = {BACKGROUND: Gastric cancer (GC) is an aggressive malignancy with a high mortality rate and poor prognosis. Telomeric repeat-binding factor 2 (TRF2) is a critical telomere protection protein. Emerging evidence indicates that TRF2 may be an essential treatment option for GC; however, the exact mechanism remains largely unknown.<br><br>OBJECTIVE: We aimed to explore the role of TRF2 in GC cells. The function and molecular mechanisms of TRF2 in the pathogenesis of GC were mainly discussed in this study.<br><br>METHODS: Relevant data from GEPIA and TCGA databases regarding TRF2 gene expression and its prognostic significance in GC samples were analyzed. Analysis of 53BP1 foci at telomeres by immunofluorescence, metaphase spreads, and telomere-specific FISH analysis was carried out to explore telomere damage and dysfunction after TRF2 depletion. CCK8 cell proliferation, trypan blue staining, and colony formation assay were performed to evaluate cell survival. Apoptosis and cell migration were determined with flow cytometry and scratch-wound healing assay, respectively. qRT-PCR and Western blotting were carried out to analyze the mRNA and protein expression levels after TRF2 depletion on apoptosis, autophagic death, and ferroptosis.<br><br>RESULTS: By searching with GEPIA and TCGA databases, the results showed that the expression levels of TRF2 were obviously elevated in the samples of GC patients, which was associated with adverse prognosis. Knockdown of TRF2 suppressed the cell growth, proliferation, and migration in GC cells, causing significant telomere dysfunction. Apoptosis, autophagic death, and ferroptosis were also triggered in this process. The pretreatment of chloroquine (autophagy inhibitor) and ferrostatin-1 (ferroptosis inhibitor) improved the survival phenotypes of GC cells.<br><br>CONCLUSION: Our data suggest that TRF2 depletion can inhibit cell growth, proliferation, and migration through the combined action of ferroptosis, autophagic death, and apoptosis in GC cells. The results indicate that TRF2 might be used as a potential target to develop therapeutic strategies for treating GC.},
}
@article {pmid37113487,
year = {2023},
author = {Wang, X and Wen, J and Qu, Q and Gu, S and Zhang, L and Li, Y and Qi, X},
title = {Association of weight range with telomere length: A retrospective cohort study.},
journal = {Frontiers in endocrinology},
volume = {14},
number = {},
pages = {1106283},
pmid = {37113487},
issn = {1664-2392},
mesh = {Adult ; Humans ; Nutrition Surveys ; Retrospective Studies ; *Aging ; *Telomere Shortening ; Telomere/genetics ; },
abstract = {OBJECTIVE: Previous research has shown a significant association between weight and telomere length, but did not take into consideration weight range. The study was to investigate the association of weight range with telomere length.<br><br>METHODS: Data of 2918 eligible participants aged 25-84 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 cycle were analyzed. Information about demographic variables, lifestyle factors, anthropometric variables, and medical comorbidities were included. Univariate and multivariate linear regression model with adjustments for potential confounders were employed to determine the association between weight range and telomere length. A non-parametrically restricted cubic spline model was used to illustrate the possible non-linear relationship.<br><br>RESULTS: In univariate linear regression, BMImax, BMI range, and weight range all revealed significant negative associations with telomere length. However, annual rate of BMI/weight range showed a significant positive associations with telomere length. There was no significant association between telomere length and BMImin. After adjusting for potential confounders, the inverse associations persisted in BMImax (&#x3b2;=-0.003, P<0.001), BMI range (&#x3b2;=-0.002, P=0.003), and weight range (&#x3b2;=-0.001, P=0.001). Furthermore, annual rate of BMI range (&#x3b2;=-0.026, P=0.009) and weight range (&#x3b2;=-0.010, P=0.007) presented negative associations with telomere length, after adjusting for covariates in Model 2-4. The association between BMImin (&#x3b2; =-0.002, P=0.237) and telomere length still could not reach statistical significance in multivariate linear regression model. The results of restricted cubic spline analysis showed that BMImax (P for nonlinear =0.026), BMI range (P for nonlinear =0.022), weight range (P for nonlinear =0.035), annual rate of BMI range (P for nonlinear =0.030), and annual rate of weight range (P for nonlinear =0.027) all had nonlinear inverse associations with telomere length.<br><br>CONCLUSIONS: The study suggests that weight range is inversely associated with telomere length in U.S. adults. Larger weight fluctuation may accelerate telomere shortening and aging.},
}
@article {pmid37107603,
year = {2023},
author = {Adwan Shekhidem, H and Sharvit, L and Huffman, DM and Manov, I and Atzmon, G and Shams, I},
title = {Damage-Free Shortening of Telomeres Is a Potential Strategy Supporting Blind Mole-Rat Longevity.},
journal = {Genes},
volume = {14},
number = {4},
pages = {},
pmid = {37107603},
issn = {2073-4425},
mesh = {Animals ; Telomere Shortening/genetics ; Mole Rats/genetics/metabolism ; *Spalax/genetics/metabolism ; Longevity/genetics ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Shelterin Complex ; },
abstract = {Telomere shortening or loss of shelterin components activates DNA damage response (DDR) pathways, leading to a replicative senescence that is usually coupled with a senescence-associated secretory phenotype (SASP). Recent studies suggested that telomere aberration that activates DDR may occur, irrespective of telomere length or loss of shelterin complex. The blind mole-rat (Spalax) is a subterranean rodent with exceptional longevity, and its cells demonstrate an uncoupling of senescence and SASP inflammatory components. Herein, we evaluated Spalax relative telomere length, telomerase activity, and shelterin expression, along with telomere-associated DNA damage foci (TAFs) levels with cell passage. We show that telomeres shorten in Spalax fibroblasts similar to the process in rats, and that the telomerase activity is lower. Moreover, we found lower DNA damage foci at the telomeres and a decline in the mRNA expression of two shelterin proteins, known as ATM/ATR repressors. Although additional studies are required for understanding the underling mechanism, our present results imply that Spalax genome protection strategies include effective telomere maintenance, preventing early cellular senescence induced by persistent DDR, thereby contributing to its longevity and healthy aging.},
}
@article {pmid37107534,
year = {2023},
author = {Pennarun, G and Picotto, J and Bertrand, P},
title = {Close Ties between the Nuclear Envelope and Mammalian Telomeres: Give Me Shelter.},
journal = {Genes},
volume = {14},
number = {4},
pages = {},
pmid = {37107534},
issn = {2073-4425},
mesh = {Animals ; Humans ; *Nuclear Envelope/genetics/metabolism ; *Telomere/genetics/metabolism ; DNA Replication/genetics ; Telomere-Binding Proteins/genetics/metabolism ; Meiosis ; Mammals/genetics/metabolism ; },
abstract = {The nuclear envelope (NE) in eukaryotic cells is essential to provide a protective compartment for the genome. Beside its role in connecting the nucleus with the cytoplasm, the NE has numerous important functions including chromatin organization, DNA replication and repair. NE alterations have been linked to different human diseases, such as laminopathies, and are a hallmark of cancer cells. Telomeres, the ends of eukaryotic chromosomes, are crucial for preserving genome stability. Their maintenance involves specific telomeric proteins, repair proteins and several additional factors, including NE proteins. Links between telomere maintenance and the NE have been well established in yeast, in which telomere tethering to the NE is critical for their preservation and beyond. For a long time, in mammalian cells, except during meiosis, telomeres were thought to be randomly localized throughout the nucleus, but recent advances have uncovered close ties between mammalian telomeres and the NE that play important roles for maintaining genome integrity. In this review, we will summarize these connections, with a special focus on telomere dynamics and the nuclear lamina, one of the main NE components, and discuss the evolutionary conservation of these mechanisms.},
}
@article {pmid37106187,
year = {2023},
author = {Lanna, A and D'Ambra, C},
title = {Detection of Telomere Transfer at Immunological Synapse.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2654},
number = {},
pages = {251-261},
pmid = {37106187},
issn = {1940-6029},
mesh = {*Immunological Synapses/metabolism ; Telomere/genetics/metabolism ; DNA Replication ; Telomere-Binding Proteins/metabolism ; Cellular Senescence ; *Telomerase/genetics ; },
abstract = {Eukaryotes solve the DNA-end replication problem synthesizing hexameric chromosome ends known as telomeres. Recent studies have uncovered unexpected functions of telomeres in linking synaptic signaling and vesicle transport, with at least one pathway directly involved in transferring telomeres through the immune synapse. These emerging forms of cellular communication may originate a new class of antiaging interventions based on telomere transplants.},
}
@article {pmid37105990,
year = {2023},
author = {Broderick, R and Cherdyntseva, V and Nieminuszczy, J and Dragona, E and Kyriakaki, M and Evmorfopoulou, T and Gagos, S and Niedzwiedz, W},
title = {Pathway choice in the alternative telomere lengthening in neoplasia is dictated by replication fork processing mediated by EXD2's nuclease activity.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {2428},
pmid = {37105990},
issn = {2041-1723},
support = {A24881/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Humans ; Telomere Homeostasis ; DNA Replication ; Telomere Shortening ; DNA Repair ; *Telomerase/genetics ; Telomere/genetics/metabolism ; *Neoplasms/genetics ; DNA Helicases/genetics/metabolism ; },
abstract = {Telomerase-independent cancer proliferation via the alternative lengthening of telomeres (ALT) relies upon two distinct, largely uncharacterized, break-induced-replication (BIR) processes. How cancer cells initiate and regulate these terminal repair mechanisms is unknown. Here, we establish that the EXD2 nuclease is recruited to ALT telomeres to direct their maintenance. We demonstrate that EXD2 loss leads to telomere shortening, elevated telomeric sister chromatid exchanges, C-circle formation as well as BIR-mediated telomeric replication. We discover that EXD2 fork-processing activity triggers a switch between RAD52-dependent and -independent ALT-associated BIR. The latter is suppressed by EXD2 but depends specifically on the fork remodeler SMARCAL1 and the MUS81 nuclease. Thus, our findings suggest that processing of stalled replication forks orchestrates elongation pathway choice at ALT telomeres. Finally, we show that co-depletion of EXD2 with BLM, DNA2 or POLD3 confers synthetic lethality in ALT cells, identifying EXD2 as a potential druggable target for ALT-reliant cancers.},
}
@article {pmid37105911,
year = {2023},
author = {Dang, MJ and Li, T and Zhao, LL and Li, Y and Wang, XY and Wu, YL and Lu, JL and Lu, ZW and Yang, Y and Feng, YX and Wang, HY and Jian, YT and Fan, SH and Jiang, Y and Zhang, GL},
title = {Leukocyte Telomere Length and Lacunar Stroke: A Mendelian Randomization Study.},
journal = {Biomedical and environmental sciences : BES},
volume = {36},
number = {4},
pages = {367-370},
doi = {10.3967/bes2023.042},
pmid = {37105911},
issn = {2214-0190},
mesh = {Humans ; *Stroke, Lacunar ; Mendelian Randomization Analysis ; Leukocytes ; Telomere/genetics ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; },
}
@article {pmid37104965,
year = {2023},
author = {de Punder, K and Heim, C and Martens, DS and Wadhwa, PD and Entringer, S},
title = {Maximal telomerase activity capacity (mTAC) underlies the link between the cortisol response to stress and telomere length.},
journal = {Psychoneuroendocrinology},
volume = {153},
number = {},
pages = {106120},
pmid = {37104965},
issn = {1873-3360},
support = {R01 AG050455/AG/NIA NIH HHS/United States ; R01 HD060628/HD/NICHD NIH HHS/United States ; R01 HD065825/HD/NICHD NIH HHS/United States ; },
mesh = {Male ; Humans ; Female ; *Telomerase/metabolism ; Leukocytes, Mononuclear/metabolism ; Hydrocortisone ; Telomere/metabolism ; },
abstract = {Exposure to various forms of stress has been associated with shorter telomere length (TL). However, the molecular underpinnings of this effect are poorly understood. Based on an understanding of the key role of the reverse transcriptase enzyme telomerase in regulating TL, and building upon our previous work in developing and validating a biomarker of the capacity of cells to express telomerase (maximal telomerase activity capacity (mTAC)), we examine here the hypotheses that mTAC is positively associated with TL and that the effect of stress on TL is mediated by individual differences in mTAC. In a proof-of-principle study of 28 healthy women and men we quantified the cortisol response to a standardized stress challenge, the Trier Social Stress Test (TSST), and we concurrently assessed peripheral blood mononuclear cell (PBMC) mTAC and TL. Our results indicated that higher mTAC levels were associated with longer TL (r = 0.50, p = .01). Moreover, mediational analysis suggested that the effect of the cortisol stress response on TL was mediated by mTAC (completely standardized β = -0.17, bootstrap CI95 %: -0.44 to -0.01). Thus, our findings support the premise that individual differences in the capacity of cells to up-regulate telomerase may represent a key mediator in the link between stress and TL.},
}
@article {pmid37104389,
year = {2023},
author = {McKnight, I and Raines, R and White, H and Nosoudi, N and Lee, C and Lee, PHU and Shim, JW},
title = {Mutability of druggable kinases and pro-inflammatory cytokines by their proximity to telomeres and A+T content.},
journal = {PloS one},
volume = {18},
number = {4},
pages = {e0283470},
pmid = {37104389},
issn = {1932-6203},
support = {P20 GM103434/GM/NIGMS NIH HHS/United States ; P20 GM121299/GM/NIGMS NIH HHS/United States ; U54 GM104942/GM/NIGMS NIH HHS/United States ; },
mesh = {Child ; Humans ; Animals ; Mice ; *Cytokines/genetics/therapeutic use ; Genomics/methods ; Mutation ; *Neoplasms/genetics ; Telomere/genetics ; },
abstract = {Mutations of protein kinases and cytokines are common and can cause cancer and other diseases. However, our understanding of the mutability in these genes remains rudimentary. Therefore, given previously known factors which are associated with high mutation rates, we analyzed how many genes encoding druggable kinases match (i) proximity to telomeres or (ii) high A+T content. We extracted this genomic information using the National Institute of Health Genome Data Viewer. First, among 129 druggable human kinase genes studied, 106 genes satisfied either factors (i) or (ii), resulting in an 82% match. Moreover, a similar 85% match rate was found in 73 genes encoding pro-inflammatory cytokines of multisystem inflammatory syndrome in children. Based on these promising matching rates, we further compared these two factors utilizing 20 de novo mutations of mice exposed to space-like ionizing radiation, in order to determine if these seemingly random mutations were similarly predictable with this strategy. However, only 10 of these 20 murine genetic loci met (i) or (ii), leading to only a 50% match. When compared with the mechanisms of top-selling FDA approved drugs, this data suggests that matching rate analysis on druggable targets is feasible to systematically prioritize the relative mutability-and therefore therapeutic potential-of the novel candidates.},
}
@article {pmid37102475,
year = {2023},
author = {Penrice, DD and Jalan-Sakrikar, N and Jurk, D and Passos, JF and Simonetto, DA},
title = {Telomere dysfunction in chronic liver disease: The link from aging.},
journal = {Hepatology (Baltimore, Md.)},
volume = {},
number = {},
pages = {},
pmid = {37102475},
issn = {1527-3350},
support = {KL2 TR002379/TR/NCATS NIH HHS/United States ; U01 DK130181/DK/NIDDK NIH HHS/United States ; U01 AA026886/AA/NIAAA NIH HHS/United States ; R01 AG068182/AG/NIA NIH HHS/United States ; UG3 CA268103/CA/NCI NIH HHS/United States ; R01 AG068048/AG/NIA NIH HHS/United States ; P30 DK084567/DK/NIDDK NIH HHS/United States ; },
}
@article {pmid37096215,
year = {2023},
author = {Tometten, M and Kirschner, M and Meyer, R and Begemann, M and Halfmeyer, I and Vieri, M and Kricheldorf, K and Maurer, A and Platzbecker, U and Radsak, M and Schafhausen, P and Corbacioglu, S and Höchsmann, B and Matthias Wilk, C and Hinze, C and Chromik, J and Heuser, M and Kreuter, M and Koschmieder, S and Panse, J and Isfort, S and Kurth, I and Brümmendorf, TH and Beier, F},
title = {Identification of Adult Patients With Classical Dyskeratosis Congenita or Cryptic Telomere Biology Disorder by Telomere Length Screening Using Age-modified Criteria.},
journal = {HemaSphere},
volume = {7},
number = {5},
pages = {e874},
pmid = {37096215},
issn = {2572-9241},
abstract = {Telomere biology disorders (TBD) result from premature telomere shortening due to pathogenic germline variants in telomere maintenance-associated genes. In adults, TBD are characterized by mono/oligosymptomatic clinical manifestations (cryptic TBD) contributing to severe underdiagnosis. We present a prospective multi-institutional cohort study where telomere length (TL) screening was performed in either newly diagnosed patients with aplastic anemia (AA) or if TBD was clinically suspected by the treating physician. TL of 262 samples was measured via flow-fluorescence in situ hybridization (FISH). TL was considered suspicious once below the 10th percentile of normal individuals (standard screening) or if below 6.5 kb in patients >40 years (extended screening). In cases with shortened TL, next generation sequencing (NGS) for TBD-associated genes was performed. The patients referred fell into 6 different screening categories: (1) AA/paroxysmal nocturnal hemoglobinuria, (2) unexplained cytopenia, (3) dyskeratosis congenita, (4) myelodysplastic syndrome/acute myeloid leukemia, (5) interstitial lung disease, and (6) others. Overall, TL was found to be shortened in 120 patients (n = 86 standard and n = 34 extended screening). In 17 of the 76 (22.4%) standard patients with sufficient material for NGS, a pathogenic/likely pathogenic TBD-associated gene variant was identified. Variants of uncertain significance were detected in 17 of 76 (22.4%) standard and 6 of 29 (20.7%) extended screened patients. Expectedly, mutations were mainly found in TERT and TERC. In conclusion, TL measured by flow-FISH represents a powerful functional in vivo screening for an underlying TBD and should be performed in every newly diagnosed patient with AA as well as other patients with clinical suspicion for an underlying TBD in both children and adults.},
}
@article {pmid37094463,
year = {2023},
author = {Ruan, Y and Lv, W and Li, S and Cheng, Y and Wang, D and Zhang, C and Shimizu, K},
title = {Identification of telomere-related genes associated with aging-related molecular clusters and the construction of a diagnostic model in Alzheimer's disease based on a bioinformatic analysis.},
journal = {Computers in biology and medicine},
volume = {159},
number = {},
pages = {106922},
doi = {10.1016/j.compbiomed.2023.106922},
pmid = {37094463},
issn = {1879-0534},
mesh = {Humans ; *Alzheimer Disease/genetics/metabolism ; *Neurodegenerative Diseases ; Aging/genetics ; Telomere/genetics/metabolism/pathology ; Computational Biology ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease that is strongly associated with aging. Telomeres are DNA sequences that protect chromosomes from damage and shorten with age. Telomere-related genes (TRGs) may play a role in AD's pathogenesis.<br><br>OBJECTIVES: To identify TRGs related to aging clusters in AD patients, explore their immunological characteristics, and build a TRG-based prediction model for AD and AD subtypes.<br><br>METHODS: We analyzed the gene expression profiles of 97 AD samples from the GSE132903 dataset, using aging-related genes (ARGs) as clustering variables. We also assessed immune-cell infiltration in each cluster. We performed a weighted gene co-expression network analysis to identify cluster-specific differentially expressed TRGs. We compared four machine-learning models (random forest, generalized linear model [GLM], gradient boosting model, and support vector machine) for predicting AD and AD subtypes based on TRGs and validated TRGs by conducting an artificial neural network (ANN) analysis and a nomogram model.<br><br>RESULTS: We identified two aging clusters in AD patients with distinct immunological features: Cluster A had higher immune scores than Cluster B. Cluster A and the immune system are intimately associated, and this association could affect immunological function and result in AD via the digestive system. The GLM predicted AD and AD subtypes most accurately and was validated by the ANN analysis and nomogram model.<br><br>CONCLUSION: Our analyses revealed novel TRGs associated with aging clusters in AD patients and their immunological characteristics. We also developed a promising prediction model based on TRGs for assessing AD risk.},
}
@article {pmid37090094,
year = {2023},
author = {Zhou, Y and Xiong, J and Shu, Z and Dong, C and Gu, T and Sun, P and He, S and Jiang, M and Xia, Z and Xue, J and Khan, WU and Chen, F and Cheng, ZM},
title = {The telomere-to-telomere genome of Fragaria vesca reveals the genomic evolution of Fragaria and the origin of cultivated octoploid strawberry.},
journal = {Horticulture research},
volume = {10},
number = {4},
pages = {uhad027},
pmid = {37090094},
issn = {2662-6810},
abstract = {Fragaria vesca, commonly known as wild or woodland strawberry, is the most widely distributed diploid Fragaria species and is native to Europe and Asia. Because of its small plant size, low heterozygosity, and relative ease of genetic transformation, F. vesca has been a model plant for fruit research since the publication of its Illumina-based genome in 2011. However, its genomic contribution to octoploid cultivated strawberry remains a long-standing question. Here, we de novo assembled and annotated a telomere-to-telomere, gap-free genome of F. vesca 'Hawaii 4', with all seven chromosomes assembled into single contigs, providing the highest completeness and assembly quality to date. The gap-free genome is 220 785 082 bp in length and encodes 36 173 protein-coding gene models, including 1153 newly annotated genes. All 14 telomeres and seven centromeres were annotated within the seven chromosomes. Among the three previously recognized wild diploid strawberry ancestors, F. vesca, F. iinumae, and F. viridis, phylogenomic analysis showed that F. vesca and F. viridis are the ancestors of the cultivated octoploid strawberry F. × ananassa, and F. vesca is its closest relative. Three subgenomes of F. × ananassa belong to the F. vesca group, and one is sister to F. viridis. We anticipate that this high-quality, telomere-to-telomere, gap-free F. vesca genome, combined with our phylogenomic inference of the origin of cultivated strawberry, will provide insight into the genomic evolution of Fragaria and facilitate strawberry genetics and molecular breeding.},
}
@article {pmid37087699,
year = {2023},
author = {Voirin, CJ and Tsunekage, T and Liu, Y and Alexy, KF and Levin, II},
title = {Brood size is associated with apparent telomere lengthening in nestling barn swallows.},
journal = {Oecologia},
volume = {202},
number = {1},
pages = {29-40},
pmid = {37087699},
issn = {1432-1939},
support = {1856254//Division of Integrative Organismal Systems/ ; },
mesh = {Animals ; *Swallows ; Telomere Homeostasis ; Telomere ; Reproduction ; Telomere Shortening ; },
abstract = {Early life for animals is often a time of rapid growth and development. In a resource-limited environment, life history theory predicts that there must be trade-offs between resource sinks in ways that optimize future survival and reproductive success. Telomeres have emerged as putative indicators of these early life trade-offs, but there are conflicting accounts as to how developmental traits and conditions impact telomere length and dynamics. For 2 years, we studied the nestlings of a breeding population of barn swallows from day 6 to day 12 of life, measuring various ontogenetic factors to understand to what extent they explain variation in telomere length and dynamics. We unexpectedly found that telomeres lengthened between the two sampling points. Nestlings in large broods had shorter telomeres, but surprisingly, individuals that grew faster from day 6 to day 12 had longer telomeres and more telomere lengthening. Nestlings with higher mass relative to their nestmates on d6 had shorter telomeres, suggesting that the relatively fast growth barn swallows experience early in development is more costly than the relatively slower growth later in development. These effects were only found in the first year of study. Telomere lengthening may be due to the initiation of new hematopoietic cell lines during development or the expression of telomerase early in life. Favorable early life conditions and high parental investment could allow for more growth with little to no cost to telomere length or dynamics.},
}
@article {pmid37085672,
year = {2023},
author = {Piñeiro-Hermida, S and Bosso, G and Sánchez-Vázquez, R and Martínez, P and Blasco, MA},
title = {Telomerase deficiency and dysfunctional telomeres in the lung tumor microenvironment impair tumor progression in NSCLC mouse models and patient-derived xenografts.},
journal = {Cell death and differentiation},
volume = {30},
number = {6},
pages = {1585-1600},
pmid = {37085672},
issn = {1476-5403},
mesh = {Humans ; Mice ; Animals ; *Carcinoma, Non-Small-Cell Lung/genetics/pathology ; *Lung Neoplasms/pathology ; *Telomerase/genetics/metabolism ; Heterografts ; Tumor Microenvironment ; Telomere/metabolism ; Lung/metabolism ; Cell Line, Tumor ; },
abstract = {Non-small cell lung cancer (NSCLC) is a leading cause of cancer death. Tumor progression depends on interactions of cancer cells with the tumor microenvironment. Here, we find increased copy number and mRNA expression of the catalytic subunit of telomerase, TERT, in tumors from NSCLC patients, contributing to a lower survival. Moreover, TERT expression in NSCLC patients from the TCGA cohort is mainly associated to the reduced infiltration of CD8[+] T lymphocytes, as well as to increased infiltration of myeloid-derived suppressor cells (MDSCs). We also show that TERT deficiency and dysfunctional telomeres induced by 6-thio-dG treatment in mice reduced lung tumor implantation and vascularization, increased DNA damage response, cell cycle arrest and apoptosis, as well as reduced proliferation, inflammation, lung tumor immunosupression and invasion upon induction of a Lewis lung carcinoma (LLC). Furthermore, 6-thio-dG-treated human NSCLC xenografts exhibited increased telomere damage, cell cycle arrest and apoptosis, as well as reduced proliferation, resulting in a reduced tumor growth. Our results show that targeting telomeres might be an effective therapeutic strategy in NSCLC.},
}
@article {pmid37083294,
year = {2023},
author = {},
title = {Telomere Shortening Induces T-cell Dysfunction and Squamous Cell Cancers.},
journal = {Cancer discovery},
volume = {13},
number = {6},
pages = {1287},
doi = {10.1158/2159-8290.CD-RW2023-059},
pmid = {37083294},
issn = {2159-8290},
mesh = {Humans ; Telomere Shortening ; *Carcinoma, Squamous Cell/genetics/pathology ; T-Lymphocytes/metabolism ; Telomere/genetics/metabolism/pathology ; *Telomerase/genetics/metabolism ; },
abstract = {Patients with short telomere syndromes are predisposed to squamous cell carcinomas due to T-cell dysfunction.},
}
@article {pmid37079368,
year = {2023},
author = {Cortez Cardoso Penha, R and Smith-Byrne, K and Atkins, JR and Haycock, PC and Kar, S and Codd, V and Samani, NJ and Nelson, C and Milojevic, M and Gabriel, AAG and Amos, C and Brennan, P and Hung, RJ and Kachuri, L and Mckay, JD},
title = {Common genetic variations in telomere length genes and lung cancer: a Mendelian randomisation study and its novel application in lung tumour transcriptome.},
journal = {eLife},
volume = {12},
number = {},
pages = {},
pmid = {37079368},
issn = {2050-084X},
support = {K99 CA246076/CA/NCI NIH HHS/United States ; U19 CA203654/CA/NCI NIH HHS/United States ; C18281/A29019/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Humans ; Female ; Male ; Transcriptome ; Genome-Wide Association Study ; Risk Factors ; *Lung Neoplasms/genetics/metabolism ; *Adenocarcinoma of Lung/genetics/metabolism ; Leukocytes/metabolism ; Telomere/genetics/metabolism ; Genetic Variation ; RNA Splicing Factors/metabolism ; Transcription Factors/metabolism ; },
abstract = {BACKGROUND: Genome-wide association studies (GWASs) have identified genetic susceptibility variants for both leukocyte telomere length (LTL) and lung cancer susceptibility. Our study aims to explore the shared genetic basis between these traits and investigate their impact on somatic environment of lung tumours.<br><br>METHODS: We performed genetic correlation, Mendelian randomisation (MR), and colocalisation analyses using the largest available GWASs summary statistics of LTL (N=464,716) and lung cancer (N=29,239 cases and 56,450 controls). Principal components analysis based on RNA-sequencing data was used to summarise gene expression profile in lung adenocarcinoma cases from TCGA (N=343).<br><br>RESULTS: Although there was no genome-wide genetic correlation between LTL and lung cancer risk, longer LTL conferred an increased risk of lung cancer regardless of smoking status in the MR analyses, particularly for lung adenocarcinoma. Of the 144 LTL genetic instruments, 12 colocalised with lung adenocarcinoma risk and revealed novel susceptibility loci, including MPHOSPH6, PRPF6, and POLI. The polygenic risk score for LTL was associated with a specific gene expression profile (PC2) in lung adenocarcinoma tumours. The aspect of PC2 associated with longer LTL was also associated with being female, never smokers, and earlier tumour stages. PC2 was strongly associated with cell proliferation score and genomic features related to genome stability, including copy number changes and telomerase activity.<br><br>CONCLUSIONS: This study identified an association between longer genetically predicted LTL and lung cancer and sheds light on the potential molecular mechanisms related to LTL in lung adenocarcinomas.<br><br>FUNDING: Institut National du Cancer (GeniLuc2017-1-TABAC-03-CIRC-1-TABAC17-022), INTEGRAL/NIH (5U19CA203654-03), CRUK (C18281/A29019), and Agence Nationale pour la Recherche (ANR-10-INBS-09).},
}
@article {pmid37077333,
year = {2023},
author = {Zheng, B and Fu, J},
title = {Telomere dysfunction in some pediatric congenital and growth-related diseases.},
journal = {Frontiers in pediatrics},
volume = {11},
number = {},
pages = {1133102},
pmid = {37077333},
issn = {2296-2360},
abstract = {Telomere wear and dysfunction may lead to aging-related diseases. Moreover, increasing evidence show that the occurrence, development, and prognosis of some pediatric diseases are also related to telomere dysfunction. In this review, we systematically analyzed the relationship between telomere biology and some pediatric congenital and growth-related diseases and proposed new theoretical basis and therapeutic targets for the treatment of these diseases.},
}
@article {pmid37074465,
year = {2023},
author = {Saradadevi, GP and Fultz, D and Ramgopal, MK and Subramanian, AT and Prince, G and Thakur, V and Mohannath, G},
title = {Structural variation among assembled genomes facilitates development of rapid and low-cost NOR-linked markers and NOR-telomere junction mapping in Arabidopsis.},
journal = {Plant cell reports},
volume = {42},
number = {6},
pages = {1059-1069},
pmid = {37074465},
issn = {1432-203X},
support = {SB-S2-RJN-062-2017//DST-SERB, Government of India/ ; CRG/2020/002855//DST-SERB, Government of India/ ; BT/RLF/Re-Entry/47/2015//Department of Biotechnology, Ministry of Science and Technology, India/ ; },
mesh = {*Arabidopsis/genetics ; Genome-Wide Association Study ; Chromosome Mapping ; Base Sequence ; Telomere ; },
abstract = {Genome-wide structural variants we identified and new NOR-linked markers we developed would be useful for future genome-wide association studies (GWAS), and for new gene/trait mapping purposes. Bioinformatic alignment of the assembled genomes of Col-0 and Sha ecotypes of Arabidopsis thaliana revealed ~ 13,000 genome-wide structural variants involving simple insertions or deletions and repeat contractions or expansions. Using some of these structural variants, we developed new, rapid, and low-cost PCR-based molecular markers that are genetically linked to the nucleolus organizer regions (NORs). A. thaliana has two NORs, one each on chromosome 2 (NOR2) and chromosome 4 (NOR4). Both NORs are ~ 4 Mb each, and hundreds of 45S ribosomal RNA (rRNA) genes are tandemly arrayed at these loci. Using previously characterized recombinant inbred lines (RILs) derived from Sha x Col-0 crosses, we validated the utility of the newly developed NOR-linked markers in genetically mapping rRNA genes and the associated telomeres to either NOR2 or NOR4. Lastly, we sequenced Sha genome using Oxford Nanopore Technology (ONT) and used the data to obtain sequences of NOR-telomere junctions, and with the help of RILs, we mapped them as new genetic markers to their respective NORs (NOR2-TEL2N and NOR4-TEL4N). The structural variants obtained from this study would serve as valuable data for genome-wide association studies (GWAS), and to rapidly design more genome-wide genetic (molecular) markers for new gene/trait mapping purposes.},
}
@article {pmid37070671,
year = {2023},
author = {Mender, I and Siteni, S and Barron, S and Flusche, AM and Kubota, N and Yu, C and Cornelius, C and Tedone, E and Maziveyi, M and Grichuk, A and Venkateswaran, N and Conacci-Sorrell, M and Hoshida, Y and Kang, R and Tang, D and Gryaznov, S and Shay, JW},
title = {Activating an Adaptive Immune Response with a Telomerase-Mediated Telomere Targeting Therapeutic in Hepatocellular Carcinoma.},
journal = {Molecular cancer therapeutics},
volume = {22},
number = {6},
pages = {737-750},
pmid = {37070671},
issn = {1538-8514},
support = {P50 CA070907/CA/NCI NIH HHS/United States ; R01CA229275/NH/NIH HHS/United States ; R01CA211070/NH/NIH HHS/United States ; R01 CA255621/CA/NCI NIH HHS/United States ; R01 CA233794/CA/NCI NIH HHS/United States ; P30 CA142543/CA/NCI NIH HHS/United States ; R01CA245548/BC/NCI NIH HHS/United States ; R01CA160417/NH/NIH HHS/United States ; },
mesh = {Humans ; *Carcinoma, Hepatocellular/drug therapy/genetics ; *Telomerase/genetics ; *Liver Neoplasms/drug therapy/genetics ; Telomere/genetics ; Adaptive Immunity ; },
abstract = {A select group of patients with hepatocellular carcinomas (HCC) benefit from surgical, radiologic, and systemic therapies that include a combination of anti-angiogenic and immune-checkpoint inhibitors. However, because HCC is generally asymptomatic in its early stages, this not only leads to late diagnosis, but also to therapy resistance. The nucleoside analogue 6-thio-dG (THIO) is a first-in-class telomerase-mediated telomere-targeting anticancer agent. In telomerase expressing cancer cells, THIO is converted into the corresponding 5'-triphosphate, which is efficiently incorporated into telomeres by telomerase, activating telomere damage responses and apoptotic pathways. Here, we show how THIO is effective in controlling tumor growth and, when combined with immune checkpoint inhibitors, is even more effective in a T-cell-dependent manner. We also show telomere stress induced by THIO increases both innate sensing and adaptive antitumor immunity in HCC. Importantly, the extracellular high-mobility group box 1 protein acts as a prototypical endogenous DAMP (Damage Associated Molecular Pattern) in eliciting adaptive immunity by THIO. These results provide a strong rationale for combining telomere-targeted therapy with immunotherapy.},
}
@article {pmid37066381,
year = {2023},
author = {Ertunc, O and Smearman, E and Zheng, Q and Hicks, JL and Brosnan-Cashman, JA and Jones, T and Gomes-Alexandre, C and Trabzonlu, L and Meeker, AK and De Marzo, AM and Heaphy, CM},
title = {Chromogenic detection of telomere lengths in situ aids the identification of precancerous lesions in the prostate.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37066381},
support = {P30 CA006973/CA/NCI NIH HHS/United States ; P50 CA058236/CA/NCI NIH HHS/United States ; U01 CA196390/CA/NCI NIH HHS/United States ; U54 CA274370/CA/NCI NIH HHS/United States ; },
abstract = {Telomeres are terminal chromosomal elements that are essential for the maintenance of genomic integrity. The measurement of telomere content provides useful diagnostic and prognostic information, and fluorescent methods have been developed for this purpose. However, fluorescent-based tissue assays are cumbersome for investigators to undertake, both in research and clinical settings. Here, a robust chromogenic in situ hybridization (CISH) approach was developed to visualize and quantify telomere content at single cell resolution in human prostate tissues, both frozen and formalin-fixed, paraffin-embedded (FFPE). This new assay ("Telo-CISH") produces permanently stained slides that are viewable with a standard light microscope, thus avoiding the need for specialized equipment and storage. The assay is compatible with standard immunohistochemistry, thereby allowing simultaneous assessment of histomorphology, identification of specific cell types, and assessment of telomere status. In addition, Telo-CISH eliminates the problem of autofluorescent interference that frequently occurs with fluorescent-based methods. Using this new assay, we demonstrate successful application of Telo-CISH to help identify precancerous lesions in the prostate by the presence of markedly short telomeres specifically in the luminal epithelial cells. In summary, with fewer restrictions on the types of tissues that can be tested, and increased histologic information provided, the advantages presented by this novel chromogenic assay should extend the applicability of tissue-based telomere length assessment in research and clinical settings.},
}
@article {pmid37065841,
year = {2023},
author = {Francis, M and Lindrose, A and O'Connell, S and Tristano, RI and McGarvey, C and Drury, S},
title = {The interaction of socioeconomic stress and race on telomere length in children: A systematic review and meta-analysis.},
journal = {SSM - population health},
volume = {22},
number = {},
pages = {101380},
pmid = {37065841},
issn = {2352-8273},
support = {U24 AG066528/AG/NIA NIH HHS/United States ; },
abstract = {RATIONALE: Proposed mechanisms relating early life exposures to poor health suggest that biologic indicators of risk are observable in childhood. Telomere length (TL) is a biomarker of aging, psychosocial stress, and a range of environmental exposures. In adults, exposure to early life adversity, including low socioeconomic status (SES), is predictive of shorter TL. However, results in pediatric populations have been mixed. Defining the true relation between TL and SES in childhood is expected to enhance the understanding of the biological pathways through which socioeconomic factors influence health across the life span.<br><br>OBJECTIVE: The aim of this meta-analysis was to systematically review and quantitatively assess the published literature to better understand how SES, race, and TL are related in pediatric populations.<br><br>METHODS: Studies in the United States in any pediatric population with any measure of SES were included and identified through the following electronic databases: PubMed, EMBASE, Web of Science, Medline, Socindex, CINAHL, and Psychinfo. Analysis utilized a multi-level random-effects meta-analysis accounting for multiple effect sizes within a study.<br><br>RESULTS: Thirty-two studies were included with a total of 78 effect sizes that were categorized into income-based, education-based, and composite indicators. Only three studies directly tested the relation between SES and TL as the primary study aim. In the full model, there was a significant relation between SES and TL (r&#xa0;=&#xa0;0.0220 p&#xa0;=&#xa0;0.0286). Analysis by type of SES categorization identified a significant moderating effect of income on TL (r&#xa0;=&#xa0;0.0480, 95% CI: 0.0155 to 0.0802, p&#xa0;=&#xa0;0.0045) but no significant effect for education or composite SES.<br><br>CONCLUSIONS: There is an overall association between SES and TL that is predominately due to the association with income-based SES measures implicating income disparities as a key target for efforts to address health inequity across the life span. Identification of associations between family income and biological changes in children that predict life-span health risk provides key data to support public health policies addressing economic inequality in families and presents a unique opportunity to assess the effect of prevention efforts at the biologic level.},
}
@article {pmid37061546,
year = {2023},
author = {Lai, KY and Webster, C and Kumari, S and Gallacher, JEJ and Sarkar, C},
title = {The associations of socioeconomic status with incident dementia and Alzheimer's disease are modified by leucocyte telomere length: a population-based cohort study.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {6163},
pmid = {37061546},
issn = {2045-2322},
support = {MR/T0333771/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; *Alzheimer Disease/epidemiology/genetics ; Cohort Studies ; Aging ; Social Class ; Telomere/genetics ; },
abstract = {Socio-economic status (SES) and biological aging are risk factors for dementia, including Alzheimer's disease, however, it is less clear if the associations with SES vary sufficiently across different biological age strata. We used data from 331,066 UK Biobank participants aged 38-73 with mean follow-up of 12 years to examine if associations between SES (assessed by educational attainment, employment status and household income) and dementia and Alzheimer's disease are modified by biological age (assessed by leucocyte telomere length: LTL). Diagnosis of events was ascertained through hospital admissions data. Cox regressions were used to estimate hazard ratios [HRs]. A consistent dose-response relationship was found, with participants in low SES and shorter LTL strata (double-exposed group) reporting 3.28 (95% confidence interval [CI] 2.57-4.20) and 3.44 (95% CI 2.35-5.04) times higher risks of incident dementia and Alzheimer's disease respectively, compared to those of high SES and longer LTL (least-exposed group). Of interest is a synergistic interaction between SES and LTL to increase risk of dementia (RERI 0.57, 95% CI 0.07-1.06) and Alzheimer's disease (RERI 0.79, 95% CI 0.02-1.56). Our findings that SES and biological age (LTL) are synergistic risk factors of dementia and Alzheimer's disease may suggest the need to target interventions among vulnerable sub-groups.},
}
@article {pmid37060569,
year = {2023},
author = {Savoca, V and Rivosecchi, J and Gaiatto, A and Rossi, A and Mosca, R and Gialdini, I and Zubovic, L and Tebaldi, T and Macchi, P and Cusanelli, E},
title = {TERRA stability is regulated by RALY and polyadenylation in a telomere-specific manner.},
journal = {Cell reports},
volume = {42},
number = {4},
pages = {112406},
doi = {10.1016/j.celrep.2023.112406},
pmid = {37060569},
issn = {2211-1247},
mesh = {*RNA, Long Noncoding/metabolism ; Polyadenylation ; RNA, Messenger/genetics/metabolism ; Telomere/metabolism ; },
abstract = {Telomeric repeat-containing RNA (TERRA) is a long non-coding RNA transcribed from telomeres that plays key roles in telomere maintenance. A fraction of TERRA is polyadenylated, and the presence of the poly(A) tail influences TERRA localization and stability. However, the mechanisms of TERRA biogenesis remain mostly elusive. Here, we show that the stability of TERRA transcripts is regulated by the RNA-binding protein associated with lethal yellow mutation (RALY). RALY depletion results in lower TERRA levels, impaired localization of TERRA at telomeres, and ultimately telomere damage. Importantly, we show that TERRA polyadenylation is telomere specific and that RALY preferentially stabilizes non-polyadenylated TERRA transcripts. Finally, we report that TERRA interacts with the poly(A)-binding protein nuclear 1 (PABPN1). Altogether, our results indicate that TERRA stability is regulated by the interplay between RALY and PABPN1, defined by the TERRA polyadenylation state. Our findings also suggest that different telomeres may trigger distinct TERRA-mediated responses.},
}
@article {pmid37059728,
year = {2023},
author = {Rai, R and Biju, K and Sun, W and Sodeinde, T and Al-Hiyasat, A and Morgan, J and Ye, X and Li, X and Chen, Y and Chang, S},
title = {Homology directed telomere clustering, ultrabright telomere formation and nuclear envelope rupture in cells lacking TRF2[B] and RAP1.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {2144},
pmid = {37059728},
issn = {2041-1723},
support = {5R01GM141350/GM/NIGMS NIH HHS/United States ; R01 CA202816/CA/NCI NIH HHS/United States ; },
mesh = {Lamin Type A/metabolism ; *Nuclear Envelope/metabolism ; Telomere/genetics/metabolism ; Telomere-Binding Proteins/metabolism ; *Telomeric Repeat Binding Protein 2/genetics/metabolism ; rap1 GTP-Binding Proteins/metabolism ; },
abstract = {Double-strand breaks (DSBs) due to genotoxic stress represent potential threats to genome stability. Dysfunctional telomeres are recognized as DSBs and are repaired by distinct DNA repair mechanisms. RAP1 and TRF2 are telomere binding proteins essential to protect telomeres from engaging in homology directed repair (HDR), but how this occurs remains unclear. In this study, we examined how the basic domain of TRF2 (TRF2[B]) and RAP1 cooperate to repress HDR at telomeres. Telomeres lacking TRF2[B] and RAP1 cluster into structures termed ultrabright telomeres (UTs). HDR factors localize to UTs, and UT formation is abolished by RNaseH1, DDX21 and ADAR1p110, suggesting that they contain DNA-RNA hybrids. Interaction between the BRCT domain of RAP1 and KU70/KU80 is also required to repress UT formation. Expressing TRF2[∆B] in Rap1[-/-] cells resulted in aberrant lamin A localization in the nuclear envelope and dramatically increased UT formation. Expressing lamin A phosphomimetic mutants induced nuclear envelope rupturing and aberrant HDR-mediated UT formation. Our results highlight the importance of shelterin and proteins in the nuclear envelope in repressing aberrant telomere-telomere recombination to maintain telomere homeostasis.},
}
@article {pmid37046606,
year = {2023},
author = {Sohn, EJ and Goralsky, JA and Shay, JW and Min, J},
title = {The Molecular Mechanisms and Therapeutic Prospects of Alternative Lengthening of Telomeres (ALT).},
journal = {Cancers},
volume = {15},
number = {7},
pages = {},
pmid = {37046606},
issn = {2072-6694},
support = {K22 CA245259/CA/NCI NIH HHS/United States ; },
abstract = {As detailed by the end replication problem, the linear ends of a cell's chromosomes, known as telomeres, shorten with each successive round of replication until a cell enters into a state of growth arrest referred to as senescence. To maintain their immortal proliferation capacity, cancer cells must employ a telomere maintenance mechanism, such as telomerase activation or the Alternative Lengthening of Telomeres pathway (ALT). With only 10-15% of cancers utilizing the ALT mechanism, progress towards understanding its molecular components and associated hallmarks has only recently been made. This review analyzes the advances towards understanding the ALT pathway by: (1) detailing the mechanisms associated with engaging the ALT pathway as well as (2) identifying potential therapeutic targets of ALT that may lead to novel cancer therapeutic treatments. Collectively, these studies indicate that the ALT molecular mechanisms involve at least two distinct pathways induced by replication stress and damage at telomeres. We suggest exploiting tumor dependency on ALT is a promising field of study because it suggests new approaches to ALT-specific therapies for cancers with poorer prognosis. While substantial progress has been made in the ALT research field, additional progress will be required to realize these advances into clinical practices to treat ALT cancers and improve patient prognoses.},
}
@article {pmid37046137,
year = {2023},
author = {Kuan, XY and Fauzi, NSA and Ng, KY and Bakhtiar, A},
title = {Exploring the Causal Relationship Between Telomere Biology and Alzheimer's Disease.},
journal = {Molecular neurobiology},
volume = {60},
number = {8},
pages = {4169-4183},
pmid = {37046137},
issn = {1559-1182},
support = {FRGS/1/2021/SKK03/MUSM/03/1//Kementerian Pendidikan Malaysia/ ; REU00335//Monash University Malaysia/ ; },
mesh = {Humans ; *Alzheimer Disease/genetics/metabolism ; Telomere/genetics/metabolism ; Aging/genetics ; Telomere Shortening ; Biology ; },
abstract = {Telomeres, also known as the "protective caps" of our chromosomes, shorten with each cell cycle due to the end replication problem. This process, termed telomere attrition, is associated with many age-related disorders, such as Alzheimer's disease (AD). Despite the numerous studies conducted in this field, the role of telomere attrition in the onset of the disease remains unclear. To investigate the causal relationship between short telomeres and AD, this review aims to highlight the primary factors that regulate telomere length and maintain its integrity, with an additional outlook on the role of oxidative stress, which is commonly associated with aging and molecular damage. Although some findings thus far might be contradictory, telomere attrition likely plays a crucial role in the progression of AD due to its close association with oxidative stress. The currently available treatments for AD are only symptomatic without affecting the progression of the disease. The components of telomere biology discussed in this paper have previously been studied as an alternative treatment option for several diseases and have exhibited promising in vitro and in vivo results. Hence, this should provide a basis for future research to develop a potential therapeutic strategy for AD. (Created with BioRender.com).},
}
@article {pmid37042812,
year = {2023},
author = {Sosa Ponce, ML and Remedios, MH and Moradi-Fard, S and Cobb, JA and Zaremberg, V},
title = {SIR telomere silencing depends on nuclear envelope lipids and modulates sensitivity to a lysolipid.},
journal = {The Journal of cell biology},
volume = {222},
number = {7},
pages = {},
pmid = {37042812},
issn = {1540-8140},
support = {MOP-82736//CIHR/Canada ; },
mesh = {Membrane Proteins/metabolism ; *Nuclear Envelope/genetics/metabolism ; Phospholipid Ethers/metabolism ; Repressor Proteins/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; *Silent Information Regulator Proteins, Saccharomyces cerevisiae/genetics/metabolism ; *Telomere/genetics/metabolism ; Transcription Factors/genetics/metabolism ; },
abstract = {The nuclear envelope (NE) is important in maintaining genome organization. The role of lipids in communication between the NE and telomere regulation was investigated, including how changes in lipid composition impact gene expression and overall nuclear architecture. Yeast was treated with the non-metabolizable lysophosphatidylcholine analog edelfosine, known to accumulate at the perinuclear ER. Edelfosine induced NE deformation and disrupted telomere clustering but not anchoring. Additionally, the association of Sir4 at telomeres decreased. RNA-seq analysis showed altered expression of Sir-dependent genes located at sub-telomeric (0-10 kb) regions, consistent with Sir4 dispersion. Transcriptomic analysis revealed that two lipid metabolic circuits were activated in response to edelfosine, one mediated by the membrane sensing transcription factors, Spt23/Mga2, and the other by a transcriptional repressor, Opi1. Activation of these transcriptional programs resulted in higher levels of unsaturated fatty acids and the formation of nuclear lipid droplets. Interestingly, cells lacking Sir proteins displayed resistance to unsaturated-fatty acids and edelfosine, and this phenotype was connected to Rap1.},
}
@article {pmid37041499,
year = {2023},
author = {Baird, A and Gomes, M and Souza, CA and Magner, K and Alvarez, G},
title = {Short Telomere Syndrome presenting with pulmonary fibrosis, liver cirrhosis and hepatopulmonary syndrome: a case report.},
journal = {BMC pulmonary medicine},
volume = {23},
number = {1},
pages = {114},
pmid = {37041499},
issn = {1471-2466},
mesh = {Male ; Humans ; *Hepatopulmonary Syndrome/complications/therapy ; Telomere Shortening ; Telomere ; Liver Cirrhosis/complications ; Fibrosis ; *Idiopathic Pulmonary Fibrosis/complications ; *Lung Diseases, Interstitial/complications ; },
abstract = {BACKGROUND: Idiopathic pulmonary fibrosis is thought to result from aberrant post-injury activation of epithelial cells leading to fibroblast proliferation and activation. A number of genetic aetiologies have been implicated in this disease process, including, among others, the short telomere syndromes. Short telomere syndromes follow an autosomal dominant pattern of inheritance resulting in shortened telomere length, which consequently leads to accelerated cell death. Organs with rapid cell turnover are most affected.<br><br>CASE PRESENTATION: We describe a case of a 53-year-old man with a chief complaint of cough and dyspnea on exertion. His presentation was otherwise significant for features of accelerated aging, including a history of osteoporosis and early greying, and a family history of pulmonary fibrosis in his father. Pulmonary function testing revealed a restrictive pattern with severely reduced diffusion capacity and high resolution CT of the chest showed diffuse lung disease with mild fibrosis, in pattern suggesting an alternative diagnosis to IPF. Biopsy of the lung was in keeping with&#xa0;chronic fibrosing interstitial pneumonia. Imaging of the abdomen showed splenomegaly, hepatic cirrhosis and portal hypertension. Transthoracic contrast echocardiogram showed intrapulmonary shunting consistent with hepatopulmonary syndrome. Given the constellation of early aging, idiopathic pulmonary fibrosis, cryptogenic cirrhosis and a family history of pulmonary fibrosis in this patient, the Short Telomere Syndrome was suspected. Peripheral blood was sent for Flow-cytometry FISH, which demonstrated granulocyte telomere length below the 10[th] percentile for the patient's age, consistent with a diagnosis of Short Telomere Syndrome in this clinical context. Targeted genetic testing of mutations known to be associated with short telomere was negative though it was acknowledged that the full spectrum of disease-causing mutations remains unknown. Given the extensive fibrosis on biopsy and his progressive hypoxemia he was treated with mycophenolate and prednisone. Ultimately, he developed progressive respiratory failure and underwent double lung and concurrent liver transplant 18&#xa0;months after the initial diagnosis was made.<br><br>CONCLUSIONS: Short Telomere Syndrome is a rare cause of end stage organ disease and testing lacks sensitivity making diagnosis challenging. Organ transplant is still the mainstay of treatment. Nevertheless, disease identification is important because of implications for family member screening and the possibility of future treatment options.},
}
@article {pmid37037617,
year = {2023},
author = {Schratz, KE and Flasch, DA and Atik, CC and Cosner, ZL and Blackford, AL and Yang, W and Gable, DL and Vellanki, PJ and Xiang, Z and Gaysinskaya, V and Vonderheide, RH and Rooper, LM and Zhang, J and Armanios, M},
title = {T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to squamous cancers.},
journal = {Cancer cell},
volume = {41},
number = {4},
pages = {807-817.e6},
pmid = {37037617},
issn = {1878-3686},
support = {P30 CA006973/CA/NCI NIH HHS/United States ; R01 CA225027/CA/NCI NIH HHS/United States ; F32 HL142207/HL/NHLBI NIH HHS/United States ; T32 CA009071/CA/NCI NIH HHS/United States ; R01 CA229803/CA/NCI NIH HHS/United States ; T32 GM007309/GM/NIGMS NIH HHS/United States ; K08 HL163468/HL/NHLBI NIH HHS/United States ; R01 HL119476/HL/NHLBI NIH HHS/United States ; },
mesh = {Animals ; Mice ; Telomere/genetics/metabolism ; *Carcinoma, Squamous Cell/genetics ; Chromosomal Instability ; Mutation ; *Telomerase/genetics/metabolism ; T-Lymphocytes/metabolism ; },
abstract = {Patients with short telomere syndromes (STS) are predisposed to developing cancer, believed to stem from chromosome instability in neoplastic cells. We tested this hypothesis in a large cohort assembled over the last 20 years. We found that the only solid cancers to which patients with STS are predisposed are squamous cell carcinomas of the head and neck, anus, or skin, a spectrum reminiscent of cancers seen in patients with immunodeficiency. Whole-genome sequencing showed no increase in chromosome instability, such as translocations or chromothripsis. Moreover, STS-associated cancers acquired telomere maintenance mechanisms, including telomerase reverse transcriptase (TERT) promoter mutations. A detailed study of the immune status of patients with STS revealed a striking T cell immunodeficiency at the time of cancer diagnosis. A similar immunodeficiency that impaired tumor surveillance was documented in mice with short telomeres. We conclude that STS patients’ predisposition to solid cancers is due to T cell exhaustion rather than autonomous defects in the neoplastic cells themselves.},
}
@article {pmid37034403,
year = {2023},
author = {Howpay Manage, SA and Zhu, J and Fleming, AM and Burrows, CJ},
title = {Promoters vs. telomeres: AP-endonuclease 1 interactions with abasic sites in G-quadruplex folds depend on topology.},
journal = {RSC chemical biology},
volume = {4},
number = {4},
pages = {261-270},
pmid = {37034403},
issn = {2633-0679},
support = {P30 CA042014/CA/NCI NIH HHS/United States ; R01 CA090689/CA/NCI NIH HHS/United States ; R35 GM145237/GM/NIGMS NIH HHS/United States ; },
abstract = {The DNA repair endonuclease APE1 is responsible for the cleavage of abasic sites (AP) in DNA as well as binding AP in promoter G-quadruplex (G4) folds in some genes to regulate transcription. The present studies focused on the topological properties of AP-bearing G4 folds and how they impact APE1 interaction. The human telomere sequence with a tetrahydrofuran model (F) of an AP was folded in K[+]- or Na[+]-containing buffers to adopt hybrid- or basket-folds, respectively. Endonuclease and binding assays were performed with APE1 and the G4 substrates, and the data were compared to prior work with parallel-stranded VEGF and NEIL3 promoter G4s to identify topological differences. The APE1-catalyzed endonuclease assays led to the conclusion that telomere G4 folds were slightly better substrates than the promoter G4s, but the yields were all low compared to duplex DNA. In the binding assays, G4 topological differences were observed in which APE1 bound telomere G4s with dissociation constants similar to single-stranded DNA, and promoter G4s were bound with nearly ten-fold lower values similar to duplex DNA. An in-cellulo assay with the telomere G4 in a model promoter bearing a lesion failed to regulate transcription. These data support a hypothesis that G4 topology in gene promoters is a critical feature that APE1 recognizes for gene regulation.},
}
@article {pmid37033949,
year = {2023},
author = {Wei, D and Jiang, Y and Cheng, J and Wang, H and Sha, K and Zhao, J},
title = {Assessing the association of leukocyte telomere length with ankylosing spondylitis and rheumatoid arthritis: A bidirectional Mendelian randomization study.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1023991},
pmid = {37033949},
issn = {1664-3224},
mesh = {Humans ; *Spondylitis, Ankylosing/genetics/complications ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Arthritis, Rheumatoid/genetics ; Leukocytes ; Telomere/genetics ; },
abstract = {BACKGROUND: Telomere length shortening can cause senescence and apoptosis in various immune cells, resulting in immune destabilization and ageing of the organism. In this study, we aimed to systematically assess the causal relationship of leukocyte telomere length (LTL) with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) using a Mendelian randomization study.<br><br>METHODS: LTL (n=472174) was obtained from the UK Biobank genome-wide association study pooled data. AS (n=229640), RA (n=212472) were obtained from FinnGen database. MR-Egger, inverse variance weighting, and weighted median methods were used to estimate the effects of causes. Cochran's Q test, MR Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots were used to look at sensitivity, heterogeneity, and multiple effects. Forward MR analysis considered LTL as the exposure and AS, RA as the outcome. Reverse MR analysis considered AS, RA as the exposure and LTL as the outcome.<br><br>RESULTS: In the forward MR analysis, inverse variance-weighted and weighted median analysis results indicated that longer LTL might be associated with increased risk of AS (IVW: OR = 1.55, 95% CI: 1.14-2.11, p = 0.006). MR Egger regression analysis showed no pleiotropy between instrumental variables (IVs) (Egger intercept= 0.008, p = 0.294). The leave-one-out analysis showed that each single nucleotide polymorphism (SNP) of AS was robust to each outcome. No significant causal effects were found between AS, RA and LTL in the reverse MR analysis.<br><br>CONCLUSION: Longer LTL may be related with an increased risk of developing AS, and these findings provide a foundation for future clinical research on the causal association between LTL and AS.},
}
@article {pmid37031574,
year = {2023},
author = {Flor-Alemany, M and Acosta-Manzano, P and Migueles, JH and Varela-López, A and Baena-García, L and Quiles, JL and Aparicio, VA},
title = {Influence of an exercise intervention plus an optimal Mediterranean diet adherence during pregnancy on the telomere length of the placenta. The GESTAFIT project.},
journal = {Placenta},
volume = {136},
number = {},
pages = {42-45},
doi = {10.1016/j.placenta.2023.04.002},
pmid = {37031574},
issn = {1532-3102},
mesh = {Humans ; Female ; Pregnancy ; *Placenta ; *Diet, Mediterranean ; Telomere Shortening ; Telomere ; Exercise Therapy ; },
abstract = {We aimed to investigate whether the effects of exercise on placental relative telomere length (RTL) after delivery are modulated by the Mediterranean diet [MD] adherence in 65 pregnant women (control n = 34, exercise n = 31). No differences were found in placental RTL between the exercise and the control groups (p = 0.557). The interaction-term between exercise and MD adherence with placental RTL was significant (p = 0.001). Specifically, women in the exercise group showed longer placental RTL after birth compared to controls (referent group), only for those women with a high MD adherence (mean difference = 0.467, p=0.010). A concurrent-exercise training plus an optimal MD adherence during pregnancy might prevent the placental RTL shortening.},
}
@article {pmid37028414,
year = {2023},
author = {Gaela, VM and Chen, LY},
title = {Ends end it via mitochondria: A telomere-dependent tumor suppressive mechanism acts during replicative crisis.},
journal = {Molecular cell},
volume = {83},
number = {7},
pages = {1027-1029},
doi = {10.1016/j.molcel.2023.03.012},
pmid = {37028414},
issn = {1097-4164},
mesh = {Humans ; Telomere/metabolism ; DNA Replication ; *RNA, Long Noncoding ; *Neoplasms/metabolism ; Mitochondria/metabolism ; },
abstract = {Nassour et al.[1] report that telomere dysfunction communicates with mitochondria via the ZBP1-TERRA-MAVS axis. This pathway activates a detrimental innate immune response that may promote the elimination of cells prone to oncogenic transformation during replicative crisis, thus serving as a telomere-dependent tumor-suppressive mechanism.},
}
@article {pmid37025175,
year = {2023},
author = {González-Amor, M and Dorado, B and Andrés, V},
title = {Emerging roles of interferon-stimulated gene-15 in age-related telomere attrition, the DNA damage response, and cardiovascular disease.},
journal = {Frontiers in cell and developmental biology},
volume = {11},
number = {},
pages = {1128594},
pmid = {37025175},
issn = {2296-634X},
abstract = {Population aging and age-related cardiovascular disease (CVD) are becoming increasingly prevalent worldwide, generating a huge medical and socioeconomic burden. The complex regulation of aging and CVD and the interaction between these processes are crucially dependent on cellular stress responses. Interferon-stimulated gene-15 (ISG15) encodes a ubiquitin-like protein expressed in many vertebrate cell types that can be found both free and conjugated to lysine residues of target proteins via a post-translational process termed ISGylation. Deconjugation of ISG15 (deISGylation) is catalyzed by the ubiquitin-specific peptidase 18 (USP18). The ISG15 pathway has mostly been studied in the context of viral and bacterial infections and in cancer. This minireview summarizes current knowledge on the role of ISG15 in age-related telomere shortening, genomic instability, and DNA damage accumulation, as well as in hypertension, diabetes, and obesity, major CVD risk factors prevalent in the elderly population.},
}
@article {pmid37024489,
year = {2023},
author = {Kusuma, FK and Prabhu, A and Tieo, G and Ahmed, SM and Dakle, P and Yong, WK and Pathak, E and Madan, V and Jiang, YY and Tam, WL and Kappei, D and Dröge, P and Koeffler, HP and Jeitany, M},
title = {Signalling inhibition by ponatinib disrupts productive alternative lengthening of telomeres (ALT).},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {1919},
pmid = {37024489},
issn = {2041-1723},
support = {R01 CA200992/CA/NCI NIH HHS/United States ; },
mesh = {*Telomere ; Cell Survival ; *Signal Transduction/drug effects ; Gene Expression Regulation ; DNA Repair ; DNA Replication ; JNK Mitogen-Activated Protein Kinases/metabolism ; Humans ; Animals ; Mice ; Cell Line, Tumor ; },
abstract = {Alternative lengthening of telomeres (ALT) supports telomere maintenance in 10-15% of cancers, thus representing a compelling target for therapy. By performing anti-cancer compound library screen on isogenic cell lines and using extrachromosomal telomeric C-circles, as a bona fide marker of ALT activity, we identify a receptor tyrosine kinase inhibitor ponatinib that deregulates ALT mechanisms, induces telomeric dysfunction, reduced ALT-associated telomere synthesis, and targets, in vivo, ALT-positive cells. Using RNA-sequencing and quantitative phosphoproteomic analyses, combined with C-circle level assessment, we find an ABL1-JNK-JUN signalling circuit to be inhibited by ponatinib and to have a role in suppressing telomeric C-circles. Furthermore, transcriptome and interactome analyses suggest a role of JUN in DNA damage repair. These results are corroborated by synergistic drug interactions between ponatinib and either DNA synthesis or repair inhibitors, such as triciribine. Taken together, we describe here a signalling pathway impacting ALT which can be targeted by a clinically approved drug.},
}
@article {pmid37021555,
year = {2023},
author = {Wang, H and Ma, T and Zhang, X and Chen, W and Lan, Y and Kuang, G and Hsu, SJ and He, Z and Chen, Y and Stewart, J and Bhattacharjee, A and Luo, Z and Price, C and Feng, X},
title = {CTC1 OB-B interaction with TPP1 terminates telomerase and prevents telomere overextension.},
journal = {Nucleic acids research},
volume = {51},
number = {10},
pages = {4914-4928},
pmid = {37021555},
issn = {1362-4962},
support = {R01 GM041803/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; Cell Line ; DNA, Single-Stranded/genetics ; Mutation ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere Homeostasis ; Telomere-Binding Proteins/genetics/metabolism ; },
abstract = {CST (CTC1-STN1-TEN1) is a telomere associated complex that binds ssDNA and is required for multiple steps in telomere replication, including termination of G-strand extension by telomerase and synthesis of the complementary C-strand. CST contains seven OB-folds which appear to mediate CST function by modulating CST binding to ssDNA and the ability of CST to recruit or engage partner proteins. However, the mechanism whereby CST achieves its various functions remains unclear. To address the mechanism, we generated a series of CTC1 mutants and studied their effect on CST binding to ssDNA and their ability to rescue CST function in CTC1-/- cells. We identified the OB-B domain as a key determinant of telomerase termination but not C-strand synthesis. CTC1-ΔB expression rescued C-strand fill-in, prevented telomeric DNA damage signaling and growth arrest. However, it caused progressive telomere elongation and the accumulation of telomerase at telomeres, indicating an inability to limit telomerase action. The CTC1-ΔB mutation greatly reduced CST-TPP1 interaction but only modestly affected ssDNA binding. OB-B point mutations also weakened TPP1 association, with the deficiency in TPP1 interaction tracking with an inability to limit telomerase action. Overall, our results indicate that CTC1-TPP1 interaction plays a key role in telomerase termination.},
}
@article {pmid37021005,
year = {2023},
author = {Domínguez-de-Barros, A and Sifaoui, I and Borecka, Z and Dorta-Guerra, R and Lorenzo-Morales, J and Castro-Fuentes, R and Córdoba-Lanús, E},
title = {An approach to the effects of longevity, sexual maturity, and reproduction on telomere length and oxidative stress in different Psittacidae species.},
journal = {Frontiers in genetics},
volume = {14},
number = {},
pages = {1156730},
pmid = {37021005},
issn = {1664-8021},
abstract = {Introduction: Aging is a multifactorial process that includes molecular changes such as telomere shortening. Telomeres shorten progressively with age in vertebrates, and their shortening rate has a significant role in determining the lifespan of a species. However, DNA loss can be enhanced by oxidative stress. The need for novel animal models has recently emerged as a tool to gather more information about the human aging process. Birds live longer than other mammals of the same size, and Psittacidae species are the most persevering of them, due to special key traits. Methods: We aimed to determine telomere length by qPCR, and oxidative stress status using colorimetric and fluorescence methods in different species of the order Psittaciformes with different lifespans. Results: We found that telomeres shorten with age for both long- and short-lived birds (p < 0.001 and p = 0.004, respectively), with long-lived birds presenting longer telomeres than short-lived ones (p = 0.001). In addition, short-lived birds accumulated more oxidative stress products than long-lived birds (p = 0.013), who showed a better antioxidant capacity (p < 0.001). Breeding was found related to telomere shortening in all species (p < 0.001 and p = 0.003 for long- and short-lived birds). Short-lived birds, especially breeding females, increased their oxidative stress products when breeding (p = 0.021), whereas long-lived birds showed greater resistance and even increased their antioxidant capacity (p = 0.002). Conclusion: In conclusion, the relationship between age and telomere length in Psittacidae was verified. The influence of breeding increased cumulative oxidative damage in short-lived species, while long-lived species may counteract this damage.},
}
@article {pmid37020849,
year = {2023},
author = {Lu, L and Zeng, H and Wan, B and Sun, M},
title = {Leukocyte telomere length and bipolar disorder risk: evidence from Mendelian randomization analysis.},
journal = {PeerJ},
volume = {11},
number = {},
pages = {e15129},
pmid = {37020849},
issn = {2167-8359},
mesh = {Humans ; *Bipolar Disorder ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Leukocytes ; Telomere ; },
abstract = {OBJECTIVE: We aim to test whether leukocyte telomere length (LTL) is causally associated with the risk of bipolar disorder (BD) using the Mendelian randomization (MR) method.<br><br>METHODS: Results of a genome-wide association study (GWAS) conducted with 472,174 individuals of European descent were used to screen for single-nucleotide polymorphisms (SNPs) related with LTL traits. Summary-level data for BD (7,647 cases and 27,303 controls) were obtained from UK Biobank. An inverse-variance-weighted (IVW) method was employed as the primary MR analysis. Sensitivity analyses were conducted via MR-Egger, maximum likelihood, MR-pleiotropy residual sum outlier (MR-PRESSO), and MR-robust adjusted profile score (MR-RAPS) methods. Finally, the MR Steiger test was utilized to validate the hypothesized relationship between exposure and outcome.<br><br>RESULTS: Two-sample MR analysis revealed inverse relationships between genetically predicted LTL and BD risk (IVW OR [odds ratio] = 0.800, 95% CI [0.647-0.989] P = 0.039). Genetically predicted LTL exhibits a consistent connection with BD across five MR methods. Sensitivity analyses showed that the genetically determined effect of LTL on BD was stable and reliable. Furthermore, the MR Steiger test demonstrated that LTL was causal for BD rather than the opposite (P < 0.001).<br><br>CONCLUSION: Our findings show that genetically determined LTL reduces the risk of BD. More research is required to clarify the mechanisms underlying this apparent causal connection. In addition, these findings may be useful for developing strategies for the prevention and treatment of BD.},
}
@article {pmid37018627,
year = {2023},
author = {Ling, X and Cui, H and Chen, Q and Yang, W and Zou, P and Yang, H and Zhou, N and Deng, J and Liu, J and Cao, J and Ao, L},
title = {Sperm telomere length is associated with sperm nuclear DNA integrity and mitochondrial DNA abnormalities among healthy male college students in Chongqing, China.},
journal = {Human reproduction (Oxford, England)},
volume = {38},
number = {6},
pages = {1036-1046},
doi = {10.1093/humrep/dead065},
pmid = {37018627},
issn = {1460-2350},
mesh = {Humans ; Male ; *DNA, Mitochondrial/genetics/metabolism ; *Semen ; Prospective Studies ; Follow-Up Studies ; Cross-Sectional Studies ; Spermatozoa/metabolism ; Semen Analysis ; Mitochondria/genetics ; Telomere ; Students ; },
abstract = {STUDY QUESTION: Is sperm telomere length (STL) associated with sperm nuclear DNA damage and mitochondrial DNA abnormalities?<br><br>SUMMARY ANSWER: Sperm telomere length is related to sperm nuclear DNA integrity and mitochondrial DNA abnormalities in healthy young college students.<br><br>WHAT IS KNOWN ALREADY: Many studies have revealed the correlations between sperm genetic alterations in both the nucleus and mitochondria and sperm functionality, however, the possible associations between the telomere, an important component of chromosome, and conventional indicators of mitochondrial DNA and nuclear DNA changes have not been investigated.<br><br>STUDY DESIGN, SIZE, DURATION: A prospective cohort study, Male Reproductive Health in Chongqing College Students (MARHCS), was conducted from June 2013 to June 2015. We pooled data collected from the follow-up study in 2014 and a total of 444 participants were included.<br><br>STL was measured by quantitative (Q)-PCR. Sperm nuclear DNA integrity was determined using sperm chromatin structure assay (SCSA) and comet assay. Mitochondrial DNA damage was assessed by mitochondrial DNA copy number (mtDNAcn) evaluated with Q-PCR, and mtDNA integrity was determined with long PCR.<br><br>The univariable-linear regression analysis revealed that STL was significantly positively correlated with markers of sperm nuclear DNA damage including the DNA fragmentation index (DFI) and comet parameters (the percentage of DNA in the tail, tail length, comet length, and tail moment). Additionally, STL was also significantly positively correlated with mtDNAcn and significantly negatively correlated with mtDNA integrity. After adjustment for potential confounders, these relationships remained appreciable. Moreover, we investigated potential effects of biometric factors, including age, parental age at conception, and BMI on STL and found that STL was increased with paternal age at conception.<br><br>A mechanistic explanation of the correlation between STL, sperm nuclear DNA integrity, and mtDNA abnormalities cannot be provided with a cross-sectional study design, so well-designed longitudinal studies are still necessary. In addition, a single semen samples were provided and were not all obtained at the same time point, which may increase the intraindividual bias in this study.<br><br>The findings extend the literature including assessment of mitochondrial dysfunction, sperm nuclear DNA damage, and telomere length and provide new insights into the relevance of STL in male reproduction.<br><br>This work was supported by the National Natural Science Foundation of China (No. 82073590), the National Natural Science Foundation of China (No. 81903363), the National Natural Science Foundation of China (No. 82130097), and the National Key R&amp;D Program of China (2022YFC2702900). The authors declare no conflicts of interest.<br><br>TRIAL REGISTRATION NUMBER: N/A.},
}
@article {pmid37014460,
year = {2023},
author = {Salem, S and Ashaat, E},
title = {Association of Relative Telomere Length and LINE-1 Methylation with Autism but not with Severity.},
journal = {Journal of autism and developmental disorders},
volume = {},
number = {},
pages = {},
pmid = {37014460},
issn = {1573-3432},
support = {33432//Science and Technology Development Fund (STDF)/ Egypt/ ; },
abstract = {Autism is associated with genomic instability, which is regulated by telomere length (TL) and index of global methylation (LINE-1). This study will determine relative TL (RTL) and LINE-1 methylation percentage for 69 patients and 33 control subjects to evaluate their potential role as biomarkers for autism. The results displayed a significant decrease of both RTL and LINE-1 methylation in autistic cases relative to controls (P < 0.001). Analysis of receiver operating characteristics curve revealed that both of RTL and LINE-1 methylation percentage have the ability to serve as autism biomarkers (area under the curve = 0.817 and 0.889, respectively). The statistical analysis revealed positive correlation between the two biomarkers (correlation coefficient = 0.439 and P < 0.001).},
}
@article {pmid37013192,
year = {2023},
author = {Moreno, SP and Fusté, JM and Kaiser, M and Li, JSZ and Nassour, J and Haggblom, C and Denchi, EL and Karlseder, J},
title = {TZAP overexpression induces telomere dysfunction and ALT-like activity in ATRX/DAXX-deficient cells.},
journal = {iScience},
volume = {26},
number = {4},
pages = {106405},
pmid = {37013192},
issn = {2589-0042},
support = {R01 CA234047/CA/NCI NIH HHS/United States ; },
abstract = {The appropriate regulation of telomere length homeostasis is crucial for the maintenance of genome integrity. The telomere-binding protein TZAP has been suggested to regulate telomere length by promoting t-circle and c-circle excisions through telomere trimming, yet the molecular mechanisms by which TZAP functions at telomeres are not understood. Using a system based on TZAP overexpression, we show that efficient TZAP recruitment to telomeres occurs in the context of open telomeric chromatin caused by loss of ATRX/DAXX independently of H3.3 deposition. Moreover, our data indicate that TZAP binding to telomeres induces telomere dysfunction and ALT-like activity, resulting in the generation of t-circles and c-circles in a Bloom-Topoisomerase IIIα-RMI1-RMI2 (BTR)-dependent manner.},
}
@article {pmid37012261,
year = {2023},
author = {Wojcicki, JM and Gill, RM and Wilson, L and Lin, J and Rosenthal, P},
title = {Shorter leukocyte telomere length protects against NAFLD progression in children.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {5446},
pmid = {37012261},
issn = {2045-2322},
support = {U01 DK061732/DK/NIDDK NIH HHS/United States ; U01 DK061718/DK/NIDDK NIH HHS/United States ; U01 DK061737/DK/NIDDK NIH HHS/United States ; U01 DK061713/DK/NIDDK NIH HHS/United States ; U01 DK061738/DK/NIDDK NIH HHS/United States ; U01 DK061728/DK/NIDDK NIH HHS/United States ; U01 DK061734/DK/NIDDK NIH HHS/United States ; U24 DK061730/DK/NIDDK NIH HHS/United States ; U01 DK061730/DK/NIDDK NIH HHS/United States ; P30 DK098722/DK/NIDDK NIH HHS/United States ; },
mesh = {Adult ; Child ; Humans ; Disease Progression ; Inflammation/pathology ; Leukocytes/pathology ; Liver Cirrhosis/complications ; *Non-alcoholic Fatty Liver Disease/pathology ; Telomere/genetics/pathology ; },
abstract = {Leukocyte telomere length (LTL) gets shorter with each cell division and is also sensitive to reactive oxygen species damage and inflammatory processes. Studies in adults with non-alcoholic fatty liver disease (NAFLD) have found that increased fibrosis but not ALT levels are associated with shorter LTL. Few pediatric studies have been conducted; as such, we sought to evaluate potential associations between LTL and liver disease and liver disease progression in pediatric patients. Using data from the Treatment of NAFLD in Children (TONIC) randomized controlled trial, we assessed the potential predictive relationship between LTL and liver disease progression based on two successive liver biopsies over 96 weeks. We assessed the potential relationship between LTL and child age, sex, and race/ethnicity and features of liver disease including components of histology. We subsequently evaluated predictors for improvement in non-alcoholic steatohepatitis (NASH) at 96 weeks including LTL. We also assessed predictors of lobular inflammation improvement at 96 weeks using multivariable models. Mean LTL at baseline was 1.33 ± 0.23 T/S. Increasing lobular and portal inflammation were associated with longer LTL. In multivariable models, greater lobular inflammation at baseline was associated with longer LTL (Coeff 0.03, 95% CI 0.006-0.13; p = 0.03). Longer LTL at baseline was associated with worsening lobular inflammation at 96 weeks (Coeff 2.41, 95% CI 0.78-4.04; p < 0.01). There was no association between liver fibrosis and LTL. The association between LTL and pediatric NASH does not parallel adults with no association between fibrosis stage and NASH. Conversely, longer LTL was associated with more lobular inflammation at baseline and increased lobular inflammation over the 96-week period. Longer LTL in children may indicate greater risk for future complications from NASH.},
}
@article {pmid37010429,
year = {2023},
author = {Zhu, M and Wu, C and Wu, X and Song, G and Li, M and Wang, Q},
title = {POP1 promotes the progression of breast cancer through maintaining telomere integrity.},
journal = {Carcinogenesis},
volume = {44},
number = {3},
pages = {252-262},
doi = {10.1093/carcin/bgad017},
pmid = {37010429},
issn = {1460-2180},
mesh = {Female ; Humans ; *Apoptosis Regulatory Proteins/metabolism ; Cell Cycle Checkpoints ; Cell Line, Tumor ; Cell Proliferation/genetics ; *Endoribonucleases ; Gene Expression Regulation, Neoplastic ; *Ribonucleoproteins/metabolism ; Telomere/genetics ; *Triple Negative Breast Neoplasms/genetics ; },
abstract = {Breast cancer is one of the most common and disastrous neoplasm for women worldwide, especially triple-negative breast cancer (TNBC). Emerging evidences have demonstrated that RNase subunits are closely related to the occurrence and development of malignant tumors. However, the functions and underlying molecular mechanisms of Processing of Precursor 1 (POP1), a core component of RNase subunits, in breast cancer development have not been fully defined. Our study identified the POP1was upregulated in breast cancer cell lines and tissues and patients with higher POP1 expression were associated with poor outcomes. Overexpression of POP1 promoted cell progression in breast cancer cells, whereas silencing of POP1 induced cell cycle arrest. Moreover, Xenograft model reproduced its growth regulatory roles in breast cancer in vivo. Mechanistically, POP1 interacted and activated the telomerase complex by stabilizing the telomerase RNA component (TERC), thus protecting telomeres from shortening during division. Collectively, our findings demonstrate POP1 may as a novel prognostic marker and a therapeutic target for the management of breast cancer.},
}
@article {pmid37003649,
year = {2023},
author = {Luna-Carrascal, J and Olivero-Verbel, J and Acosta-Hoyos, AJ and Quintana-Sosa, M},
title = {Auto repair workers exposed to PM2.5 particulate matter in Barranquilla, Colombia: Telomere length and hematological parameters.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {887},
number = {},
pages = {503597},
doi = {10.1016/j.mrgentox.2023.503597},
pmid = {37003649},
issn = {1879-3592},
mesh = {Humans ; *Particulate Matter/toxicity ; Colombia ; Glutathione Transferase/genetics ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; *Occupational Exposure/adverse effects/analysis ; Genotype ; Telomere ; },
abstract = {Exposure to 2.5 µm particulate matter (PM2.5) in automotive repair shops is associated with risks to health. We evaluated the effects of occupational exposure to PM2.5 among auto repair-shop workers. Blood and urine samples were collected from 110 volunteers from Barranquilla, Colombia: 55 active workers and 55 controls. PM2.5 concentrations were assessed at each of the sampling sites and chemical content was analyzed by SEM-EDS electron microscopy. The biological samples obtained were peripheral blood (hematological profiling, DNA extraction) and urine (malondialdehyde concentration). Telomere length was assessed by qPCR and polymorphisms in the glutathione transferase genes GSTT1 and GSTM1 by PCR-RFLP, with confirmation by allelic exclusion. White blood cell (WBC), lymphocyte (LYM%) and platelet (PLT) counts and the malondialdehyde concentration were higher (4.10 ± 0.93) in the exposed group compared to the control group (1.56 ± 0.96). TL was shorter (5071 ± 891) in the exposed individuals compared to the control group (6271 ± 805). White blood cell (WBC) and platelet counts were positively associated with exposure. Age and TBARS were correlated with TL in exposed individuals. The GSTT1 gene alleles were not in Hardy-Weinberg (H-W) equilibrium. The GSTM1 gene alleles were in H-W equilibrium and allelic exclusion analysis confirmed the presence of heterozygous GSTM1 genotypes. SEM-EDS analysis showed the presence of potentially toxic elements, including Mg, Al, Fe, Mn, Rh, Zn, and Cu. Auto repair shop workers showed effects that may be associated with exposure to mixtures of pollutants present in PM2.5. The GSTM1 and GSTT1 genes had independent modulatory effects.},
}
@article {pmid37003504,
year = {2023},
author = {Jones, CY and Williams, CL and Moreno, SP and Morris, DK and Mondello, C and Karlseder, J and Bertuch, AA},
title = {Hyperextended telomeres promote formation of C-circle DNA in telomerase positive human cells.},
journal = {The Journal of biological chemistry},
volume = {299},
number = {5},
pages = {104665},
pmid = {37003504},
issn = {1083-351X},
support = {R01 CA211653/CA/NCI NIH HHS/United States ; R01 CA228211/CA/NCI NIH HHS/United States ; R01 CA234047/CA/NCI NIH HHS/United States ; T32 GM008307/GM/NIGMS NIH HHS/United States ; R01 CA227934/CA/NCI NIH HHS/United States ; R01 AG077324/AG/NIA NIH HHS/United States ; R01 GM077509/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; DNA Helicases/metabolism ; *DNA, Circular ; *Telomerase/metabolism ; *Telomere/genetics/metabolism ; Telomere Homeostasis ; Cell Line ; HeLa Cells ; DNA Replication ; Hydroxyurea ; DNA Repair ; },
abstract = {Telomere length maintenance is crucial to cancer cell immortality. Up to 15% of cancers utilize a telomerase-independent, recombination-based mechanism termed alternative lengthening of telomeres (ALT). Currently, the primary ALT biomarker is the C-circle, a type of circular DNA with extrachromosomal telomere repeats (cECTRs). How C-circles form is not well characterized. We investigated C-circle formation in the human cen3tel cell line, a long-telomere, telomerase+ (LTT+) cell line with progressively hyper-elongated telomeres (up to ∼100 kb). cECTR signal was observed in 2D gels and C-circle assays but not t-circle assays, which also detect circular DNA with extrachromosomal telomere repeats. Telomerase activity and C-circle signal were not separable in the analysis of clonal populations, consistent with C-circle production occurring within telomerase+ cells. We observed similar cECTR results in two other LTT+ cell lines, HeLa1.3 (∼23 kb telomeres) and HeLaE1 (∼50 kb telomeres). In LTT+ cells, telomerase activity did not directly impact C-circle signal; instead, C-circle signal correlated with telomere length. LTT+ cell lines were less sensitive to hydroxyurea than ALT+ cell lines, suggesting that ALT status is a stronger contributor to replication stress levels than telomere length. Additionally, the DNA repair-associated protein FANCM did not suppress C-circles in LTT+ cells as it does in ALT+ cells. Thus, C-circle formation may be driven by telomere length, independently of telomerase and replication stress, highlighting limitations of C-circles as a stand-alone ALT biomarker.},
}
@article {pmid37002420,
year = {2023},
author = {Zlotorynski, E},
title = {RPA dynamics at telomeres.},
journal = {Nature reviews. Molecular cell biology},
volume = {24},
number = {5},
pages = {310},
pmid = {37002420},
issn = {1471-0080},
mesh = {*Telomere/genetics/metabolism ; *DNA-Binding Proteins/metabolism ; DNA, Single-Stranded ; },
}
@article {pmid36999631,
year = {2023},
author = {Liu, CC and Chan, HR and Su, GC and Hsieh, YZ and Lei, KH and Kato, T and Yu, TY and Kao, YW and Cheng, TH and Chi, P and Lin, JJ},
title = {Flap endonuclease Rad27 cleaves the RNA of R-loop structures to suppress telomere recombination.},
journal = {Nucleic acids research},
volume = {51},
number = {9},
pages = {4398-4414},
pmid = {36999631},
issn = {1362-4962},
mesh = {DNA Helicases/genetics ; DNA, Single-Stranded ; *Flap Endonucleases/genetics/metabolism ; *R-Loop Structures ; Recombination, Genetic ; RNA/genetics ; Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {The long non-coding telomeric RNA transcript TERRA, in the form of an RNA-DNA duplex, regulates telomere recombination. In a screen for nucleases that affects telomere recombination, mutations in DNA2, EXO1, MRE11 and SAE2 cause severe delay in type II survivor formation, indicating that type II telomere recombination is mediated through a mechanism similar to repairing double-strand breaks. On the other hand, mutation in RAD27 results in early formation of type II recombination, suggesting that RAD27 acts as a negative regulator in telomere recombination. RAD27 encodes a flap endonuclease that plays a role in DNA metabolism, including replication, repair and recombination. We demonstrate that Rad27 suppresses the accumulation of the TERRA-associated R-loop and selectively cleaves TERRA of R-loop and double-flapped structures in vitro. Moreover, we show that Rad27 negatively regulates single-stranded C-rich telomeric DNA circles (C-circles) in telomerase-deficient cells, revealing a close correlation between R-loop and C-circles during telomere recombination. These results demonstrate that Rad27 participates in telomere recombination by cleaving TERRA in the context of an R-loop or flapped RNA-DNA duplex, providing mechanistic insight into how Rad27 maintains chromosome stability by restricting the accumulation of the R-loop structure within the genome.},
}
@article {pmid36999210,
year = {2023},
author = {Gao, M and Zheng, G and Li, Y and Zhang, Y and Hu, P and Pan, Y},
title = {Telomere length in multiple cancer: insight into recurrence risk from a meta-analysis.},
journal = {Journal of gastroenterology and hepatology},
volume = {38},
number = {6},
pages = {844-853},
doi = {10.1111/jgh.16186},
pmid = {36999210},
issn = {1440-1746},
support = {82004039//National Natural Science Foundation of China/ ; 82204420//National Natural Science Foundation of China/ ; BK20220474//Natural Science Foundation of Jiangsu Province/ ; 22KJB310004//Natural Science Foundation of the Jiangsu Higher Education Institutions of China/ ; SKLNMKF202202//Open Project of the State Key Laboratory of Natural Medicines/ ; NZY82004039//Natural Science Foundation for Young Scholars of Nanjing University of Chinese Medicine/ ; XPT82204420//Funding Supporting Projects of National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Neoplasm Recurrence, Local/genetics ; *Gastrointestinal Neoplasms/genetics ; Telomere/genetics ; },
abstract = {BACKGROUND: Several studies have revealed the relationships between telomere length and the risk and mortality of numerous cancers. This meta-analysis aims to insightfully clarify the potential relationship between telomere length and the recurrence of multiple cancers.<br><br>METHODS: PubMed database was used to search and identify interrelated citations. These reports investigated the relationship between telomere length and various cancer recurrences. Meta-analysis pooled data from studies that reported risk ratio (RR) of 95 (CI&#xa0;=&#xa0;95%) confidence intervals and/or P-values. The cancer recurrence was investigated from an overall standpoint to the multiple levels of subtypes of cancers.<br><br>RESULTS: The meta-analysis involved 5907 recurrent multiple cancer patients from 13 cohort studies. Compared to these cancer recurrence cases and the telomere length differences, there was no significant correlation between telomere length and cancer recurrence risk (short telomeres vs long telomeres; RR&#xa0;=&#xa0;0.93, 95% CI: 0.72-1.20, P&#xa0;=&#xa0;0.59). Additionally, a negative association was observed between telomere length and cancer recurrence in gastrointestinal cancer and a positive association in head and neck cancer, while telomere length had little effect on the recurrence of hematological malignancies and genitourinary cancer in this analysis.<br><br>CONCLUSION: There was no significant relationship between recurrence and telomere length in 5907 cases in 13 studies. However, there was a correlation between specific tumors. These results suggested that telomere length as a recurrence marker or telomere length to determine the possibility of recurrence must be evaluated on the specific type of cancer.},
}
@article {pmid36997693,
year = {2023},
author = {Bryan, TM},
title = {Nucleotide metabolism regulates human telomere length via telomerase activation.},
journal = {Nature genetics},
volume = {55},
number = {4},
pages = {532-533},
pmid = {36997693},
issn = {1546-1718},
mesh = {Humans ; *Telomerase/genetics ; Telomere Homeostasis/genetics ; Telomere/genetics ; Nucleotides/genetics ; },
}
@article {pmid36993206,
year = {2023},
author = {Ngo, K and Gittens, TH and Gonzalez, DI and Hatmaker, EA and Plotkin, S and Engle, M and Friedman, GA and Goldin, M and Hoerr, RE and Eichman, BF and Rokas, A and Benton, ML and Friedman, KL},
title = {A comprehensive map of hotspots of de novo telomere addition in Saccharomyces cerevisiae.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {36993206},
support = {T34 GM136451/GM/NIGMS NIH HHS/United States ; R35 GM136401/GM/NIGMS NIH HHS/United States ; T32 GM137793/GM/NIGMS NIH HHS/United States ; R01 AI153356/AI/NIAID NIH HHS/United States ; R01 GM123292/GM/NIGMS NIH HHS/United States ; F31 EY033235/EY/NEI NIH HHS/United States ; },
abstract = {Telomere healing occurs when telomerase, normally restricted to chromosome ends, acts upon a double-strand break to create a new, functional telomere. De novo telomere addition on the centromere-proximal side of a break truncates the chromosome but, by blocking resection, may allow the cell to survive an otherwise lethal event. We previously identified several sequences in the baker’s yeast, Saccharomyces cerevisiae , that act as hotspots of de novo telomere addition (termed Sites of Repair-associated Telomere Addition or SiRTAs), but the distribution and functional relevance of SiRTAs is unclear. Here, we describe a high-throughput sequencing method to measure the frequency and location of telomere addition within sequences of interest. Combining this methodology with a computational algorithm that identifies SiRTA sequence motifs, we generate the first comprehensive map of telomere-addition hotspots in yeast. Putative SiRTAs are strongly enriched in subtelomeric regions where they may facilitate formation of a new telomere following catastrophic telomere loss. In contrast, outside of subtelomeres, the distribution and orientation of SiRTAs appears random. Since truncating the chromosome at most SiRTAs would be lethal, this observation argues against selection for these sequences as sites of telomere addition per se. We find, however, that sequences predicted to function as SiRTAs are significantly more prevalent across the genome than expected by chance. Sequences identified by the algorithm bind the telomeric protein Cdc13, raising the possibility that association of Cdc13 with single-stranded regions generated during the response to DNA damage may facilitate DNA repair more generally.},
}
@article {pmid36991019,
year = {2023},
author = {Li, F and Wang, Y and Hwang, I and Jang, JY and Xu, L and Deng, Z and Yu, EY and Cai, Y and Wu, C and Han, Z and Huang, YH and Huang, X and Zhang, L and Yao, J and Lue, NF and Lieberman, PM and Ying, H and Paik, J and Zheng, H},
title = {Histone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {1756},
pmid = {36991019},
issn = {2041-1723},
support = {P30 CA010815/CA/NCI NIH HHS/United States ; R01 CA140652/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Cell Line ; DNA ; Telomere Homeostasis/genetics ; Telomere/genetics/metabolism ; *Neoplasms/genetics ; *Telomerase/genetics ; Cysteine Endopeptidases/metabolism ; *F-Box Proteins/genetics ; Jumonji Domain-Containing Histone Demethylases/genetics/metabolism ; },
abstract = {Telomere length maintenance is essential for cellular immortalization and tumorigenesis. 5% - 10% of human cancers rely on a recombination-based mechanism termed alternative lengthening of telomeres (ALT) to sustain their replicative immortality, yet there are currently no targeted therapies. Through CRISPR/Cas9-based genetic screens in an ALT-immortalized isogenic cellular model, here we identify histone lysine demethylase KDM2A as a molecular vulnerability selectively for cells contingent on ALT-dependent telomere maintenance. Mechanistically, we demonstrate that KDM2A is required for dissolution of the ALT-specific telomere clusters following recombination-directed telomere DNA synthesis. We show that KDM2A promotes de-clustering of ALT multitelomeres through facilitating isopeptidase SENP6-mediated SUMO deconjugation at telomeres. Inactivation of KDM2A or SENP6 impairs post-recombination telomere de-SUMOylation and thus dissolution of ALT telomere clusters, leading to gross chromosome missegregation and mitotic cell death. These findings together establish KDM2A as a selective molecular vulnerability and a promising drug target for ALT-dependent cancers.},
}
@article {pmid36989559,
year = {2023},
author = {Ali, JH and Abdeen, Z and Azmi, K and Berman, T and Jager, K and Barnett-Itzhaki, Z and Walter, M},
title = {Influence of exposure to pesticides on telomere length and pregnancy outcome: Diethylphosphates but not Dimethylphosphates are associated with accelerated telomere attrition in a Palestinian cohort.},
journal = {Ecotoxicology and environmental safety},
volume = {256},
number = {},
pages = {114801},
doi = {10.1016/j.ecoenv.2023.114801},
pmid = {36989559},
issn = {1090-2414},
mesh = {Humans ; Female ; Pregnancy ; *Pesticides/metabolism ; Birth Weight ; Arabs ; *Environmental Pollutants/metabolism ; Organophosphorus Compounds/urine ; Organophosphates/metabolism ; Vegetables/metabolism ; },
abstract = {Exposure to environmental pesticides during pregnancy is associated with adverse health outcomes such as low birth weight and impaired neuro-development. In this study, we assessed maternal leukocyte telomere lengths (TL) in Palestinian pregnant women and compared the data with urinary organophosphate concentrations, demographic, lifestyle and dietary factors, birth weight, body length, gestational age, and head circumference. Women with high urine levels of creatinine adjusted diethylphosphate(DE)derived pesticide metabolites DEP, DETP or DEDTP had shorter telomeres (p = 0.05). Women living in proximity to agricultural fields had shorter telomeres compared to women not living in proximity to agricultural fields (p = 0.011). Regular consumption of organic food was associated with shorter telomeres (p = 0.01), whereas the consumption of other vegetables such as artichokes was rather associated with longer telomeres. By contrast, urine levels of dimethylphosphate(DM)-derived pesticide metabolites DMTP and DMDTP were associated with lower birth weight (p = 0.05) but not with shrter telomeres. In conclusion organophosphate pesticides and living in proximity to agriculture are associated with shorter TL, likely due to higher consumption of contaminated fruits and vegetables and/or the transport of pesticides to non-treatment sites. DE and DM substituted pesticides seem to have different effects on telomeres and development.},
}
@article {pmid36989538,
year = {2023},
author = {Valeeva, LR and Abdulkina, LR and Agabekian, IA and Shakirov, EV},
title = {Telomere biology and ribosome biogenesis: structural and functional interconnections.},
journal = {Biochemistry and cell biology = Biochimie et biologie cellulaire},
volume = {101},
number = {5},
pages = {394-409},
doi = {10.1139/bcb-2022-0383},
pmid = {36989538},
issn = {1208-6002},
mesh = {Humans ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Mutation ; Ribosomes/genetics/metabolism ; Eukaryota/genetics ; Biology ; },
abstract = {Telomeres are nucleoprotein structures that play a pivotal role in the protection and maintenance of eukaryotic chromosomes. Telomeres and the enzyme telomerase, which replenishes telomeric DNA lost during replication, are important factors necessary to ensure continued cell proliferation. Cell proliferation is also dependent on proper and efficient protein synthesis, which is carried out by ribosomes. Mutations in genes involved in either ribosome biogenesis or telomere biology result in cellular abnormalities and can cause human genetic diseases, defined as ribosomopathies and telomeropathies, respectively. Interestingly, recent discoveries indicate that many of the ribosome assembly and rRNA maturation factors have additional noncanonical functions in telomere biology. Similarly, several key proteins and enzymes involved in telomere biology, including telomerase, have unexpected roles in rRNA transcription and maturation. These observations point to an intriguing cross-talk mechanism potentially explaining the multiple pleiotropic symptoms of mutations in many causal genes identified in various telomeropathy and ribosomopathy diseases. In this review, we provide a brief summary of eukaryotic telomere and rDNA loci structures, highlight several universal features of rRNA and telomerase biogenesis, evaluate intriguing interconnections between telomere biology and ribosome assembly, and conclude with an assessment of overlapping features of human diseases of telomeropathies and ribosomopathies.},
}
@article {pmid36986204,
year = {2023},
author = {Kuo, CL and Kirk, B and Xiang, M and Pilling, LC and Kuchel, GA and Kremer, R and Duque, G},
title = {Very Low and High Levels of Vitamin D Are Associated with Shorter Leukocyte Telomere Length in 148,321 UK Biobank Participants.},
journal = {Nutrients},
volume = {15},
number = {6},
pages = {},
pmid = {36986204},
issn = {2072-6643},
support = {NR018963-01A1/NH/NIH HHS/United States ; },
mesh = {Humans ; Middle Aged ; Aged ; *Biological Specimen Banks ; *Vitamin D ; Vitamins ; Leukocytes ; Telomere ; United Kingdom ; },
abstract = {Background: Shorter leukocyte telomere length (LTL) is observed in multiple age-related diseases, which are also associated with vitamin D deficiency (i.e., osteosarcopenia, neurocognitive disorders, cancer, osteoarthritis, etc.), suggesting a close association between vitamin D and LTL. In this study, we examined the relationship between vitamin D levels and LTL in older participants of the UK Biobank. Methods: Data were collected from the UK Biobank. Participants aged 60 and older (n = 148,321) were included. Baseline LTL was measured using a multiplex qPCR technique and expressed as the ratio of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Serum 25-hydroxyvitamin D (25OHD) was stratified by z score and linked to LTL in a linear regression model adjusting for covariates. Results: Compared to the medium level, a low (in the range of 16.6 nmol/L, 29.7 nmol/L) or extremely low (≤16.6 nmol/L) level of serum 25OHD was associated with shorter LTL: 0.018 SD (standardized β = -0.018, 95% CI -0.033 to -0.003, p = 0.022) and 0.048 SD (standardized β = -0.048, 95% CI -0.083 to -0.014, p = 0.006), respectively. Additionally, the high serum 25OHD groups (>95.9 nmol/L) had 0.038 SD (standardized β = -0.038, 95% CI -0.072 to -0.004, p = 0.030) shorter mean LTL than the group with medium 25OHD levels. The associations above were adjusted for multiple variables. Conclusions: In this population-based study, we identified an inverted U-shape relationship between LTL and vitamin D status. Our findings could be affected by unmeasured confounders. Whether high or low vitamin D-associated shorter LTL is mechanistically related to age-related conditions remains to be elucidated.},
}
@article {pmid36986083,
year = {2023},
author = {Wei, Y and Li, Z and Lai, H and Lu, P and Zhang, B and Song, L and Zhang, L and Shen, M},
title = {Instant Coffee Is Negatively Associated with Telomere Length: Finding from Observational and Mendelian Randomization Analyses of UK Biobank.},
journal = {Nutrients},
volume = {15},
number = {6},
pages = {},
pmid = {36986083},
issn = {2072-6643},
support = {12171387//National Natural Science Foundation of China/ ; 2018M631134//China Postdoctoral Science Foundation/ ; 2020T130095ZX//China Postdoctoral Science Foundation/ ; 20210307//Young Talent Support Program of Shaanxi University Association for Science and Technology/ ; },
mesh = {Humans ; *Aging/genetics ; Biological Specimen Banks ; Genome-Wide Association Study ; *Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; *Telomere/genetics ; United Kingdom ; *Coffee/adverse effects ; },
abstract = {Telomere length, as a biomarker of accelerated aging, is closely related to many chronic diseases. We aimed to explore the association between coffee consumption and telomere length. Our study included 468,924 participants from the UK Biobank. Multivariate linear models (observational analyses) were conducted to evaluate the associations of coffee intake, instant coffee intake, and filtered coffee intake with telomere length. In addition, we evaluated the causality of these associations in Mendelian randomization (MR) analyses by four methods (inverse-variance weighted (IVW), MR pleiotropy residual sum and outlier (MR-PRESSO), MR-Egger, and weighted median). Observational analyses indicated that coffee intake and instant coffee intake were negatively correlated with telomere length, which was equal to 0.12 year of age-related decrease in telomere length for each additional cup of coffee intake (p < 0.001), and 0.38 year of age-related decrease in telomere length for each additional cup of instant coffee intake (p < 0.001), respectively. There was no significant correlation between filtered coffee and telomere length (p = 0.862). Mendelian randomization analyses supported the results of observational analyses. Coffee intake was found to have a causal effect on telomere length through weighted median analysis (p = 0.022), and instant coffee intake had a causal effect on telomere length through IVW analysis (p = 0.019) and MR-PRESSO analysis (p = 0.028). No causal relationship was found between filtered coffee intake and telomere length (p > 0.05). Coffee intake, particularly instant coffee, was found to have an important role in shortening telomere length.},
}
@article {pmid36982772,
year = {2023},
author = {M'Kacher, R and Colicchio, B and Junker, S and El Maalouf, E and Heidingsfelder, L and Plesch, A and Dieterlen, A and Jeandidier, E and Carde, P and Voisin, P},
title = {High Resolution and Automatable Cytogenetic Biodosimetry Using In Situ Telomere and Centromere Hybridization for the Accurate Detection of DNA Damage: An Overview.},
journal = {International journal of molecular sciences},
volume = {24},
number = {6},
pages = {},
pmid = {36982772},
issn = {1422-0067},
mesh = {Humans ; Cytogenetics ; *Centromere/genetics ; *Telomere/genetics ; Chromosome Aberrations ; Radiometry/methods ; DNA Damage/genetics ; Cytogenetic Analysis ; Lymphocytes ; },
abstract = {In the event of a radiological or nuclear accident, or when physical dosimetry is not available, the scoring of radiation-induced chromosomal aberrations in lymphocytes constitutes an essential tool for the estimation of the absorbed dose of the exposed individual and for effective triage. Cytogenetic biodosimetry employs different cytogenetic assays including the scoring of dicentrics, micronuclei, and translocations as well as analyses of induced premature chromosome condensation to define the frequency of chromosome aberrations. However, inherent challenges using these techniques include the considerable time span from sampling to result, the sensitivity and specificity of the various techniques, and the requirement of highly skilled personnel. Thus, techniques that obviate these challenges are needed. The introduction of telomere and centromere (TC) staining have successfully met these challenges and, in addition, greatly improved the efficiency of cytogenetic biodosimetry through the development of automated approaches, thus reducing the need for specialized personnel. Here, we review the role of the various cytogenetic dosimeters and their recent improvements in the management of populations exposed to genotoxic agents such as ionizing radiation. Finally, we discuss the emerging potentials to exploit these techniques in a wider spectrum of medical and biological applications, e.g., in cancer biology to identify prognostic biomarkers for the optimal triage and treatment of patients.},
}
@article {pmid36982042,
year = {2023},
author = {Prieto-Botella, D and Martens, DS and Valera-Gran, D and Subiza-Pérez, M and Tardón, A and Lozano, M and Casas, M and Bustamante, M and Jimeno-Romero, A and Fernández-Somoano, A and Llop, S and Vrijheid, M and Nawrot, TS and Navarrete-Muñoz, EM},
title = {Sedentary Behaviour and Telomere Length Shortening during Early Childhood: Evidence from the Multicentre Prospective INMA Cohort Study.},
journal = {International journal of environmental research and public health},
volume = {20},
number = {6},
pages = {},
pmid = {36982042},
issn = {1660-4601},
mesh = {Child ; Humans ; Child, Preschool ; Cohort Studies ; *Sedentary Behavior ; Prospective Studies ; Longitudinal Studies ; *Telomere ; Leukocytes ; },
abstract = {Sedentary behaviour (SB) may be related to telomere length (TL) attrition due to a possible pro-inflammatory effect. This study examined the association between parent-reported sedentary behaviour (SB) and leukocyte TL at the age of 4 and telomere tracking from 4 to 8 years. In the Spanish birth cohort Infancia y Medio Ambiente (INMA) project, we analysed data from children who attended follow-up visits at age 4 (n = 669) and 8 (n = 530). Multiple robust regression models were used to explore the associations between mean daily hours of SB (screen time, other sedentary activities, and total SB) at 4 years categorised into tertiles and TL at 4 years and difference in TL rank between age 4 and 8, respectively. At the age of 4, the results showed that children with the highest screen time (1.6-5.0 h/day) had a shorter TL of -3.9% (95% CI: -7.4, -0.4; p = 0.03) compared with children in the lowest tertile (0.0-1.0 h/day). Between 4 and 8 years, a higher screen time (highest tertile group vs. lowest tertile) was associated with a decrease in the LTL rank of -1.9% (95% CI: -3.8, -0.1; p = 0.03) from 4 to 8 years. Children exposed to a higher screen time at 4 years were more prone to have shorter TL at 4 and between 4 and 8 years of age. This study supports the potential negative effect of SB during childhood on cellular longevity.},
}
@article {pmid36981836,
year = {2023},
author = {Duchaine, CS and Brisson, C and Diorio, C and Talbot, D and Maunsell, E and Carmichael, PH and Giguère, Y and Gilbert-Ouimet, M and Trudel, X and Ndjaboué, R and Vézina, M and Milot, A and Mâsse, B and Dionne, CE and Laurin, D},
title = {Work-Related Psychosocial Factors and Global Cognitive Function: Are Telomere Length and Low-Grade Inflammation Potential Mediators of This Association?.},
journal = {International journal of environmental research and public health},
volume = {20},
number = {6},
pages = {},
pmid = {36981836},
issn = {1660-4601},
support = {201403MOP-32544-BCA-CFBA-52569 to DL and CB, and 201810GSD-422016-DRB-CFBA-280487 to CSD//CIHR/Canada ; },
mesh = {Male ; Humans ; Female ; Longitudinal Studies ; *Stress, Psychological/psychology ; *Cognition ; Inflammation ; Telomere ; },
abstract = {The identification of modifiable factors that could maintain cognitive function is a public health priority. It is thought that some work-related psychosocial factors help developing cognitive reserve through high intellectual complexity. However, they also have well-known adverse health effects and are considered to be chronic psychosocial stressors. Indeed, these stressors could increase low-grade inflammation and promote oxidative stress associated with accelerated telomere shortening. Both low-grade inflammation and shorter telomeres have been associated with a cognitive decline. This study aimed to evaluate the total, direct, and indirect effects of work-related psychosocial factors on global cognitive function overall and by sex, through telomere length and an inflammatory index. A random sample of 2219 participants followed over 17 years was included in this study, with blood samples and data with cognitive function drawn from a longitudinal study of 9188 white-collar workers (51% female). Work-related psychosocial factors were evaluated according to the Demand-Control-Support and the Effort-Reward Imbalance (ERI) models. Global cognitive function was evaluated with the validated Montreal Cognitive Assessment (MoCA). Telomere length and inflammatory biomarkers were measured using standardised protocols. The direct and indirect effects were estimated using a novel mediation analysis method developed for multiple correlated mediators. Associations were observed between passive work or low job control, and shorter telomeres among females, and between low social support at work, ERI or iso-strain, and a higher inflammatory index among males. An association was observed with higher cognitive performance for longer telomeres, but not for the inflammatory index. Passive work overall, and low reward were associated with lower cognitive performance in males; whereas, high psychological demand in both males and females and high job strain in females were associated with a higher cognitive performance. However, none of these associations were mediated by telomere length or the inflammatory index. This study suggests that some work-related psychosocial factors could be associated with shorter telomeres and low-grade inflammation, but these associations do not explain the relationship between work-related psychosocial factors and global cognitive function. A better understanding of the biological pathways, by which these factors affect cognitive function, could guide future preventive strategies to maintain cognitive function and promote healthy aging.},
}
@article {pmid36980987,
year = {2023},
author = {Holesova, Z and Krasnicanova, L and Saade, R and Pös, O and Budis, J and Gazdarica, J and Repiska, V and Szemes, T},
title = {Telomere Length Changes in Cancer: Insights on Carcinogenesis and Potential for Non-Invasive Diagnostic Strategies.},
journal = {Genes},
volume = {14},
number = {3},
pages = {},
pmid = {36980987},
issn = {2073-4425},
mesh = {Humans ; *Neoplasms/diagnosis/genetics ; Carcinogenesis/genetics ; Telomere Homeostasis/genetics ; DNA ; Telomere/genetics ; },
abstract = {Telomere dynamics play a crucial role in the maintenance of chromosome integrity; changes in telomere length may thus contribute to the development of various diseases including cancer. Understanding the role of telomeric DNA in carcinogenesis and detecting the presence of cell-free telomeric DNA (cf-telDNA) in body fluids offer a potential biomarker for novel cancer screening and diagnostic strategies. Liquid biopsy is becoming increasingly popular due to its undeniable benefits over conventional invasive methods. However, the organization and function of cf-telDNA in the extracellular milieu are understudied. This paper provides a review based on 3,398,017 cancer patients, patients with other conditions, and control individuals with the aim to shed more light on the inconsistent nature of telomere lengthening/shortening in oncological contexts. To gain a better understanding of biological factors (e.g., telomerase activation, alternative lengthening of telomeres) affecting telomere homeostasis across different types of cancer, we summarize mechanisms responsible for telomere length maintenance. In conclusion, we compare tissue- and liquid biopsy-based approaches in cancer assessment and provide a brief outlook on the methodology used for telomere length evaluation, highlighting the advances of state-of-the-art approaches in the field.},
}
@article {pmid36980962,
year = {2023},
author = {da Mota, THA and Camargo, R and Biojone, ER and Guimarães, AFR and Pittella-Silva, F and de Oliveira, DM},
title = {The Relevance of Telomerase and Telomere-Associated Proteins in B-Acute Lymphoblastic Leukemia.},
journal = {Genes},
volume = {14},
number = {3},
pages = {},
pmid = {36980962},
issn = {2073-4425},
mesh = {Child ; Humans ; *Telomerase/genetics/metabolism ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; *Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Telomere Shortening ; Telomere/genetics/metabolism ; },
abstract = {Telomeres and telomerase are closely linked to uncontrolled cellular proliferation, immortalization and carcinogenesis. Telomerase has been largely studied in the context of cancer, including leukemias. Deregulation of human telomerase gene hTERT is a well-established step in leukemia development. B-acute lymphoblastic leukemia (B-ALL) recovery rates exceed 90% in children; however, the relapse rate is around 20% among treated patients, and 10% of these are still incurable. This review highlights the biological and clinical relevance of telomerase for B-ALL and the implications of its canonical and non-canonical action on signaling pathways in the context of disease and treatment. The physiological role of telomerase in lymphocytes makes the study of its biomarker potential a great challenge. Nevertheless, many works have demonstrated that high telomerase activity or hTERT expression, as well as short telomeres, correlate with poor prognosis in B-ALL. Telomerase and related proteins have been proven to be promising pharmacological targets. Likewise, combined therapy with telomerase inhibitors may turn out to be an alternative strategy for B-ALL.},
}
@article {pmid36980890,
year = {2023},
author = {Zeinoun, B and Teixeira, MT and Barascu, A},
title = {TERRA and Telomere Maintenance in the Yeast Saccharomyces cerevisiae.},
journal = {Genes},
volume = {14},
number = {3},
pages = {},
pmid = {36980890},
issn = {2073-4425},
mesh = {*Saccharomyces cerevisiae/genetics/metabolism ; *RNA, Long Noncoding/metabolism ; Transcription, Genetic ; Telomere/genetics/metabolism ; Heterochromatin ; },
abstract = {Telomeres are structures made of DNA, proteins and RNA found at the ends of eukaryotic linear chromosomes. These dynamic nucleoprotein structures protect chromosomal tips from end-to-end fusions, degradation, activation of damage checkpoints and erroneous DNA repair events. Telomeres were thought to be transcriptionally silent regions because of their constitutive heterochromatin signature until telomeric long non-coding RNAs (LncRNAs) were discovered. One of them, TERRA (TElomeric Repeat-containing RNA), starts in the subtelomeric regions towards the chromosome ends from different telomeres and has been extensively studied in many evolutionarily distant eukaryotes. Changes in TERRA's expression can lead to telomeric dysfunction, interfere with the replicative machinery and impact telomere length. TERRA also co-localizes in vivo with telomerase, and can form RNA:DNA hybrid structures called R-loops, which have been implicated in the onset of senescence and the alternative lengthening of telomere (ALT) pathway. Yet, the molecular mechanisms involving TERRA, as well as its function, remain elusive. Here, we review the current knowledge of TERRA transcription, structure, expression, regulation and its multiple telomeric and extra-telomeric functions in the budding yeast Saccharomyces cerevisiae.},
}
@article {pmid36980881,
year = {2023},
author = {Hill, C and Duffy, S and Coulter, T and Maxwell, AP and McKnight, AJ},
title = {Harnessing Genomic Analysis to Explore the Role of Telomeres in the Pathogenesis and Progression of Diabetic Kidney Disease.},
journal = {Genes},
volume = {14},
number = {3},
pages = {},
pmid = {36980881},
issn = {2073-4425},
support = {MC_PC_15025/MRC_/Medical Research Council/United Kingdom ; MC_PC_20026/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; *Diabetic Nephropathies/genetics/metabolism ; Gene Expression Regulation ; Epigenesis, Genetic/genetics ; Epigenomics ; Telomere/genetics/metabolism ; *Diabetes Mellitus/genetics ; },
abstract = {The prevalence of diabetes is increasing globally, and this trend is predicted to continue for future decades. Research is needed to uncover new ways to manage diabetes and its co-morbidities. A significant secondary complication of diabetes is kidney disease, which can ultimately result in the need for renal replacement therapy, via dialysis or transplantation. Diabetic kidney disease presents a substantial burden to patients, their families and global healthcare services. This review highlights studies that have harnessed genomic, epigenomic and functional prediction tools to uncover novel genes and pathways associated with DKD that are useful for the identification of therapeutic targets or novel biomarkers for risk stratification. Telomere length regulation is a specific pathway gaining attention recently because of its association with DKD. Researchers are employing both observational and genetics-based studies to identify telomere-related genes associated with kidney function decline in diabetes. Studies have also uncovered novel functions for telomere-related genes beyond the immediate regulation of telomere length, such as transcriptional regulation and inflammation. This review summarises studies that have revealed the potential to harness therapeutics that modulate telomere length, or the associated epigenetic modifications, for the treatment of DKD, to potentially slow renal function decline and reduce the global burden of this disease.},
}
@article {pmid36979904,
year = {2023},
author = {Caslini, C and Serna, A},
title = {Telomere Transcription in MLL-Rearranged Leukemia Cell Lines: Increased Levels of TERRA Associate with Lymphoid Lineage and Are Independent of Telomere Length and Ploidy.},
journal = {Biomedicines},
volume = {11},
number = {3},
pages = {},
pmid = {36979904},
issn = {2227-9059},
abstract = {Telomere transcription into telomeric repeat-containing RNA (TERRA) is an integral component of all aspects of chromosome end protection consisting of telomerase- or recombination-dependent telomere elongation, telomere capping, and the preservation of the (sub)telomeric heterochromatin structure. The chromatin modifier and transcriptional regulator MLL binds to telomeres and regulates TERRA transcription in telomere length homeostasis and response to telomere dysfunction. MLL fusion proteins (MLL-FPs), the product of MLL rearrangements in leukemia, also bind to telomeric chromatin. However, an effect on telomere transcription in MLL-rearranged (MLL-r) leukemia has not yet been evaluated. Here, we show increased UUAGGG repeat-containing RNA levels in MLL-r acute lymphoblastic leukemia (ALL) when compared to non-MLL-r ALL and myeloid leukemia. MLL rearrangements do not affect telomere length and UUAGGG repeat-containing RNA levels correlate with mean telomere length and reflect increased levels of TERRA. Furthermore, high levels of TERRA in MLL-r ALL occur in the presence of telomerase activity and are independent of ploidy, an underestimated source of variation on the overall transcriptome size in a cell. This MLL rearrangement-dependent and lymphoid lineage-associated increase in levels of TERRA supports a sustained telomere transcription by MLL-FPs that correlates with marked genomic stability previously reported in pediatric MLL-r ALL.},
}
@article {pmid36979709,
year = {2023},
author = {Cuevas Diaz, P and Nicolini, H and Nolasco-Rosales, GA and Juarez Rojop, I and Tovilla-Zarate, CA and Rodriguez Sanchez, E and Genis-Mendoza, AD},
title = {Telomere Shortening in Three Diabetes Mellitus Types in a Mexican Sample.},
journal = {Biomedicines},
volume = {11},
number = {3},
pages = {},
pmid = {36979709},
issn = {2227-9059},
abstract = {This study aimed to explore the role of telomere length in three different diabetes types: latent autoimmune diabetes of adulthood (LADA), latent autoimmune diabetes in the young (LADY), and type 2 diabetes mellitus (T2DM). A total of 115 patients were included, 72 (62.61%) had LADA, 30 (26.09%) had T2DM, and 13 (11.30%) had LADY. Telomere length was measured using real-time Polymerase Chain Reaction. For statistical analysis, we used the ANOVA test, X2 test, and the Mann-Whitney U test. Patients with T2DM had higher BMI compared to LADA and LADY groups, with a BMI average of 31.32 kg/m[2] (p = 0.0235). While the LADA group had more patients with comorbidities, there was not a statistically significant difference (p = 0.3164, p = 0.3315, p = 0.3742 for each of the previously mentioned conditions). There was a difference between those patients with T2DM who took metformin plus any other oral antidiabetic agent and those who took metformin plus insulin, the ones who had longer telomeres. LADA patients had shorter telomeres compared to T2DM patients but not LADY patients. Furthermore, T2DM may have longer telomeres thanks to the protective effects of both metformin and insulin, despite the higher BMI in this group.},
}
@article {pmid36979008,
year = {2023},
author = {Ferk, F and Mišík, M and Ernst, B and Prager, G and Bichler, C and Mejri, D and Gerner, C and Bileck, A and Kundi, M and Langie, S and Holzmann, K and Knasmueller, S},
title = {Impact of Bariatric Surgery on the Stability of the Genetic Material, Oxidation, and Repair of DNA and Telomere Lengths.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {3},
pages = {},
pmid = {36979008},
issn = {2076-3921},
support = {AP00692OFF//Richard and Ethel Herzfeld Foundation/ ; CA15132//European Cooperation in Science and Technology/ ; },
abstract = {Obesity causes genetic instability, which plays a key-role in the etiology of cancer and aging. We investigated the impact of bariatric surgery (BS) on DNA repair, oxidative DNA damage, telomere lengths, alterations of antioxidant enzymes and, selected proteins which reflect inflammation. The study was realized with BS patients (n = 35). DNA damage, base oxidation, BER, and NER were measured before and 1 month and 6 months after surgery with the single-cell gel electrophoresis technique. SOD and GPx were quantified spectrophotometrically, malondealdehyde (MDA) was quantified by HPLC. Telomere lengths were determined with qPCR, and plasma proteome profiling was performed with high-resolution mass spectrophotometry. Six months after the operations, reduction of body weight by 27.5% was observed. DNA damage decreased after this period, this effect was paralleled by reduced formation of oxidized DNA bases, a decline in the MDA levels and of BER and NER, and an increase in the telomere lengths. The activities of antioxidant enzymes were not altered. Clear downregulation of certain proteins (CRP, SAA1) which reflect inflammation and cancer risks was observed. Our findings show that BS causes reduced oxidative damage of DNA bases, possibly as a consequence of reduction of inflammation and lipid peroxidation, and indicate that the surgery has beneficial long-term health effects.},
}
@article {pmid36978826,
year = {2023},
author = {Levstek, T and Trebušak Podkrajšek, K},
title = {Telomere Attrition in Chronic Kidney Diseases.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {3},
pages = {},
pmid = {36978826},
issn = {2076-3921},
support = {P1-0170//Slovenian Research Agency/ ; },
abstract = {Telomeres are dynamic DNA nucleoprotein structures located at the end of chromosomes where they maintain genomic stability. Due to the end replication problem, telomeres shorten with each cell division. Critically short telomeres trigger cellular senescence, which contributes to various degenerative and age-related diseases, including chronic kidney diseases (CKDs). Additionally, other factors such as oxidative stress may also contribute to accelerated telomere shortening. Indeed, telomeres are highly susceptible to oxidative damage due to their high guanine content. Here, we provide a comprehensive review of studies examining telomere length (TL) in CKDs to highlight the association between TL and the development and progression of CKDs in humans. We then focus on studies investigating TL in patients receiving kidney replacement therapy. The mechanisms of the relationship between TL and CKD are not fully understood, but a shorter TL has been associated with decreased kidney function and the progression of nephropathy. Interestingly, telomere lengthening has been observed in some patients in longitudinal studies. Hemodialysis has been shown to accelerate telomere erosion, whereas the uremic milieu is not reversed even in kidney transplantation patients. Overall, this review aims to provide insights into the biological significance of telomere attrition in the pathophysiology of kidney disease, which may contribute to the development of new strategies for the management of patients with CKDs.},
}
@article {pmid36973214,
year = {2023},
author = {Zhang, KJ and Zhang, ZH},
title = {[Progress in the study of alternative lengthening of telomeres and prognosis of pancreatic neuroendocrine tumors].},
journal = {Zhonghua bing li xue za zhi = Chinese journal of pathology},
volume = {52},
number = {4},
pages = {431-434},
doi = {10.3760/cma.j.cn112151-20220701-00570},
pmid = {36973214},
issn = {0529-5807},
mesh = {Humans ; *Neuroendocrine Tumors/genetics ; Prognosis ; X-linked Nuclear Protein/genetics ; *Pancreatic Neoplasms/genetics/pathology ; Telomere/genetics/pathology ; },
}
@article {pmid36968845,
year = {2023},
author = {Zhang, H and Kong, W and Xie, Y and Zhao, X and Luo, D and Chen, S and Pan, Z},
title = {Telomere-related genes as potential biomarkers to predict endometriosis and immune response: Development of a machine learning-based risk model.},
journal = {Frontiers in medicine},
volume = {10},
number = {},
pages = {1132676},
pmid = {36968845},
issn = {2296-858X},
abstract = {INTRODUCTION: Endometriosis (EM) is an aggressive, pleomorphic, and common gynecological disease. Its clinical presentation includes abnormal menstruation, dysmenorrhea, and infertility, which seriously affect the patient's quality of life. However, the pathogenesis underlying EM and associated regulatory genes are unknown.<br><br>METHODS: Telomere-related genes (TRGs) were uploaded from TelNet. RNA-sequencing (RNA-seq) data of EM patients were obtained from three datasets (GSE5108, GSE23339, and GSE25628) in the GEO database, and a random forest approach was used to identify telomere signature genes and build nomogram prediction models. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to identify the pathways involved in the action of the signature genes. Finally, the CAMP database was used to screen drugs for potential use in EM treatment.<br><br>RESULTS: Fifteen total genes were screened as EM-telomere differentially expressed genes. Further screening by machine learning obtained six genes as characteristic predictive of EM. Immuno-infiltration analysis of the telomeric genes showed that expressions including macrophages and natural killer cells were significantly higher in cluster A. Further enrichment analysis showed that the differential genes were mainly enriched in biological pathways like cell cycle and extracellular matrix. Finally, the Connective Map database was used to screen 11 potential drugs for EM treatment.<br><br>DISCUSSION: TRGs play a crucial role in EM development, and are associated with immune infiltration and act on multiple pathways, including the cell cycle. Telomere signature genes can be valuable predictive markers for EM.},
}
@article {pmid36967999,
year = {2023},
author = {Wan, B and Ma, N and Lv, C},
title = {Identifying effects of genetic obesity exposure on leukocyte telomere length using Mendelian randomization.},
journal = {PeerJ},
volume = {11},
number = {},
pages = {e15085},
pmid = {36967999},
issn = {2167-8359},
mesh = {Humans ; *Genome-Wide Association Study ; *Mendelian Randomization Analysis ; Leukocytes ; Obesity/genetics ; Telomere/genetics ; },
abstract = {BACKGROUND: Observational studies have shown that obesity is closely associated with leukocyte telomere length (LTL). However, the causal relationship between obesity and LTL remains unclear. This study investigated the causal relationship between obesity and LTL through the Mendelian randomization approach.<br><br>MATERIALS AND METHODS: The genome-wide association study (GWAS) summary data of several studies on obesity-related traits with a sample size of more than 600,000 individuals were extracted from the UK Biobank cohort. The summary-level data of LTL-related GWAS (45 6,717 individuals) was obtained from the IEU Open GWAS database. An inverse-variance-weighted (IVW) algorithm was utilized as the primary MR analysis method. Sensitivity analyses were conducted via MR-Egger regression, IVW regression, leave-one-out test, MR-pleiotropy residual sum, and outlier methods.<br><br>RESULTS: High body mass index was correlated with a short LTL, and the odds ratio (OR) was 0.957 (95% confidence interval [CI] 0.942-0.973, p = 1.17E-07). The six body fat indexes (whole body fat mass, right leg fat mass, left leg fat mass, right arm fat mass, left arm fat mass, and trunk fat mass) were consistently inversely associated with LTL. Multiple statistical sensitive analysis approaches showed that the adverse effect of obesity on LTL was steady and dependable.<br><br>CONCLUSION: The current study provided robust evidence supporting the causal assumption that genetically caused obesity is negatively associated with LTL. The findings may facilitate the formulation of persistent strategies for maintaining LTL.},
}
@article {pmid36966355,
year = {2023},
author = {Wang, H and Ni, J and Guo, X and Xue, J and Wang, X},
title = {Effects of folate on telomere length and chromosome stability of human fibroblasts and melanoma cells in vitro: a comparison of folic acid and 5-methyltetrahydrofolate.},
journal = {Mutagenesis},
volume = {38},
number = {3},
pages = {160-168},
doi = {10.1093/mutage/gead007},
pmid = {36966355},
issn = {1464-3804},
mesh = {Humans ; Folic Acid/pharmacology ; *Telomerase/genetics/metabolism ; Telomere/metabolism ; Chromosomal Instability ; Fibroblasts/metabolism ; *Melanoma ; },
abstract = {Telomere length (TL), which is maintained by human telomerase reverse transcriptase (hTERT; component of telomerase) and/or TRF1/TRF2 (core components of shelterin) via different mechanisms, is essential for chromosomal stability and cell survival. Folates comprise a group of essential B9 vitamin that involve in DNA synthesis and methylation. This study aimed to evaluate the effects of folic acid (FA) and 5-methyltetrahydrofolate (5-MeTHF) on TL, chromosome stability, and cell survival of telomerase-negative BJ and telomerase-positive A375 cells in vitro. BJ and A375 cells were cultured in modified medium with FA or 5-MeTHF (22.6 or 2260 nM) for 28 days. TL and mRNA expression were determined by RT-qPCR. Chromosome instability (CIN) and cell death were measured by CBMN-Cyt assay. Results showed that abnormal TL elongation was observed in FA and 5-MeTHF deficient BJ cells. The TL of A375 cells showed no obvious alterations under the FA-deficient condition but was significantly elongated under the 5-MeTHF-deficient condition. In both BJ and A375 cells, FA and 5-MeTHF deficiency caused decreased TRF1, TRF2, and hTERT expression, increased CIN and cell death; while a high concentration of 5-MeTHF induced elongated TL, elevated CIN, increased TRF1 and TRF2 expression and decreased hTERT expression, when compared with the FA counterpart. These findings concluded that folate deficiency induced TL instability in both telomerase-negative and -positive cells, and FA was more efficient in maintaining TL and chromosome stability compared with 5-MeTHF.},
}
@article {pmid36960859,
year = {2023},
author = {Maggio, J and Cardama, GA and Armando, RG and Balcone, L and Sobol, NT and Gomez, DE and Mengual Gómez, DL},
title = {Key role of PIN1 in telomere maintenance and oncogenic behavior in a human glioblastoma model.},
journal = {Oncology reports},
volume = {49},
number = {5},
pages = {},
doi = {10.3892/or.2023.8528},
pmid = {36960859},
issn = {1791-2431},
mesh = {Humans ; Animals ; Mice ; *Glioblastoma/pathology ; NF-kappa B/genetics/metabolism ; *Telomerase/metabolism ; Polymerase Chain Reaction ; Telomere/genetics/metabolism ; Cell Line, Tumor ; NIMA-Interacting Peptidylprolyl Isomerase/genetics/metabolism ; },
abstract = {PIN1 is the only known enzyme capable of recognizing and isomerizing the phosphorylated Serine/Threonine‑Proline motif. Through this mechanism, PIN1 controls diverse cellular functions, including telomere maintenance. Both PIN1 overexpression and its involvement in oncogenic pathways are involved in several cancer types, including glioblastoma (GBM), a lethal disease with poor therapeutic resources. However, knowledge of the role of PIN1 in GBM is limited. Thus, the present work aimed to study the role of PIN1 as a telomere/telomerase regulator and its contribution to tumor biology. PIN1 knockout (KO) LN‑229 cell variant using CRISPR/Cas9 was developed and compared with PIN1 LN‑229 expressing cells. To study the effect of PIN1 absence, status of NF‑κB pathway was evaluated by luciferase reporter gene assay and quantitative PCR. Results revealed that PIN1 deletion in GBM cells diminished the active levels of NF‑κB and decrease the transcription of il‑8 and htert genes. Then, telomere/telomerase related processes were studied by RQ‑TRAP assay and telomere length determination by qPCR, obtaining a reduction both in telomerase activity as in telomere length in PIN1 KO cells. In addition, measurement of SA β‑galactosidase and caspase‑3 activities revealed that loss of PIN1 triggers senescence and apoptosis. Finally, migration, cell cycle progression and tumorigenicity were studied by flow cytometry/western blot, Transwell assay and in vivo experiments, respectively. PIN1 deletion decreased migration as well as cell cycle progression by increasing doubling time and also resulted in the loss of LN‑229 cell ability to form tumors in mice. These results highlight the role of PIN1 in telomere homeostasis and GBM progression, which supports PIN1 as a potential molecular target for the development of novel therapeutic agents for GBM treatment.},
}
@article {pmid36959362,
year = {2023},
author = {Mannherz, W and Agarwal, S},
title = {Thymidine nucleotide metabolism controls human telomere length.},
journal = {Nature genetics},
volume = {55},
number = {4},
pages = {568-580},
pmid = {36959362},
issn = {1546-1718},
support = {R33 HL154133/HL/NHLBI NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; T32 GM007226/GM/NIGMS NIH HHS/United States ; T32 GM144273/GM/NIGMS NIH HHS/United States ; R01 DK107716/DK/NIDDK NIH HHS/United States ; },
mesh = {Humans ; *Telomerase/genetics ; SAM Domain and HD Domain-Containing Protein 1/genetics/metabolism ; Nucleotides/genetics ; Telomere Homeostasis/genetics ; Thymidine ; Telomere/genetics ; },
abstract = {Telomere length in humans is associated with lifespan and severe diseases, yet the genetic determinants of telomere length remain incompletely defined. Here we performed genome-wide CRISPR-Cas9 functional telomere length screening and identified thymidine (dT) nucleotide metabolism as a limiting factor in human telomere maintenance. Targeted genetic disruption using CRISPR-Cas9 revealed multiple telomere length control points across the thymidine nucleotide metabolism pathway: decreasing dT nucleotide salvage via deletion of the gene encoding nuclear thymidine kinase (TK1) or de novo production by knockout of the thymidylate synthase gene (TYMS) decreased telomere length, whereas inactivation of the deoxynucleoside triphosphohydrolase-encoding gene SAMHD1 lengthened telomeres. Remarkably, supplementation with dT alone drove robust telomere elongation by telomerase in cells, and thymidine triphosphate stimulated telomerase activity in a substrate-independent manner in vitro. In induced pluripotent stem cells derived from patients with genetic telomere biology disorders, dT supplementation or inhibition of SAMHD1 promoted telomere restoration. Our results demonstrate a critical role of thymidine metabolism in controlling human telomerase and telomere length, which may be therapeutically actionable in patients with fatal degenerative diseases.},
}
@article {pmid36949104,
year = {2023},
author = {Meesters, M and Van Eetvelde, M and Martens, DS and Nawrot, TS and Dewulf, M and Govaere, J and Opsomer, G},
title = {Prenatal environment impacts telomere length in newborn dairy heifers.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {4672},
pmid = {36949104},
issn = {2045-2322},
mesh = {Pregnancy ; Humans ; Animals ; Cattle ; Female ; Animals, Newborn ; Parity ; *Parturition ; Humidity ; *Telomere/genetics ; Lactation ; },
abstract = {Telomere length is associated with longevity and survival in multiple species. In human population-based studies, multiple prenatal factors have been described to be associated with a newborn's telomere length. In the present study, we measured relative leukocyte telomere length in 210 Holstein Friesian heifers, within the first ten days of life. The dam's age, parity, and milk production parameters, as well as environmental factors during gestation were assessed for their potential effect on telomere length. We found that for both primi- and multiparous dams, the telomere length was 1.16% shorter for each day increase in the calf's age at sampling (P = 0.017). The dam's age at parturition (P = 0.045), and the median temperature-humidity index (THI) during the third trimester of gestation (P = 0.006) were also negatively associated with the calves' TL. Investigating multiparous dams separately, only the calf's age at sampling was significantly and negatively associated with the calves' TL (P = 0.025). Results of the present study support the hypothesis that in cattle, early life telomere length is influenced by prenatal factors. Furthermore, the results suggest that selecting heifers born in winter out of young dams might contribute to increased longevity in dairy cattle.},
}
@article {pmid36947528,
year = {2023},
author = {Topiwala, A and Nichols, TE and Williams, LZJ and Robinson, EC and Alfaro-Almagro, F and Taschler, B and Wang, C and Nelson, CP and Miller, KL and Codd, V and Samani, NJ and Smith, SM},
title = {Telomere length and brain imaging phenotypes in UK Biobank.},
journal = {PloS one},
volume = {18},
number = {3},
pages = {e0282363},
pmid = {36947528},
issn = {1932-6203},
support = {216462/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; 215573/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; 202788/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; R01 EB026859/EB/NIBIB NIH HHS/United States ; BRC-1215-20014/DH_/Department of Health/United Kingdom ; 100309/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; MR/M012816/1/MRC_/Medical Research Council/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /BHF_/British Heart Foundation/United Kingdom ; BRC-1215-20010/DH_/Department of Health/United Kingdom ; },
mesh = {Humans ; *Neurodegenerative Diseases ; Biological Specimen Banks ; Brain/diagnostic imaging ; Phenotype ; Telomere/genetics ; Neuroimaging ; United Kingdom ; *Dementia/diagnostic imaging/genetics ; Leukocytes ; },
abstract = {Telomeres form protective caps at the ends of chromosomes, and their attrition is a marker of biological aging. Short telomeres are associated with an increased risk of neurological and psychiatric disorders including dementia. The mechanism underlying this risk is unclear, and may involve brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized. Here we show that leucocyte telomere length (LTL) is associated with multi-modal MRI phenotypes in 31,661 UK Biobank participants. Longer LTL is associated with: i) larger global and subcortical grey matter volumes including the hippocampus, ii) lower T1-weighted grey-white tissue contrast in sensory cortices, iii) white-matter microstructure measures in corpus callosum and association fibres, iv) lower volume of white matter hyperintensities, and v) lower basal ganglia iron. Longer LTL was protective against certain related clinical manifestations, namely all-cause dementia (HR 0.93, 95% CI: 0.91-0.96), but not stroke or Parkinson's disease. LTL is associated with multiple MRI endophenotypes of neurodegenerative disease, suggesting a pathway by which longer LTL may confer protective against dementia.},
}
@article {pmid36946056,
year = {2023},
author = {Zhou, Z and Lo, CKM and Chan, KL and Chung, RSY and Pell, JP and Minnis, H and Shiels, PG and Ip, P and Ho, FK},
title = {Child maltreatment and telomere length in middle and older age: retrospective cohort study of 141 748 UK Biobank participants.},
journal = {The British journal of psychiatry : the journal of mental science},
volume = {223},
number = {2},
pages = {377-381},
doi = {10.1192/bjp.2023.33},
pmid = {36946056},
issn = {1472-1465},
mesh = {Adult ; Aged ; Humans ; Middle Aged ; Biological Specimen Banks ; Retrospective Studies ; *Telomere ; United Kingdom/epidemiology ; *Adult Survivors of Child Abuse ; },
abstract = {BACKGROUND: There is evidence that child maltreatment is associated with shorter telomere length in early life.<br><br>AIMS: This study aims to examine if child maltreatment is associated with telomere length in middle- and older-age adults.<br><br>METHOD: This was a retrospective cohort study of 141 748 UK Biobank participants aged 37-73 years at recruitment. Leukocyte telomere length was measured with quantitative polymerase chain reaction, and log-transformed and scaled to have unit standard deviation. Child maltreatment was recalled by participants. Linear regression was used to analyse the association.<br><br>RESULTS: After adjusting for sociodemographic characteristics, participants with three or more types of maltreatment presented with the shortest telomere lengths (&#x3b2; = -0.05, 95% CI -0.07 to -0.03; P < 0.0001), followed by those with two types of maltreatment (&#x3b2; = -0.02, 95% CI -0.04 to 0.00; P = 0.02), referent to those who had none. When adjusted for depression and post-traumatic stress disorder, the telomere lengths of participants with three or more types of maltreatment were still shorter (&#x3b2; = -0.04, 95% CI -0.07 to -0.02; P = 0.0008). The telomere lengths of those with one type of maltreatment were not significantly different from those who had none. When mutually adjusted, physical abuse (&#x3b2; = -0.05, 95% CI -0.07 to -0.03; P < 0.0001) and sexual abuse (&#x3b2; = -0.02, 95% CI -0.04 to 0.00; P = 0.02) were independently associated with shorter telomere length.<br><br>CONCLUSIONS: Our findings showed that child maltreatment is associated with shorter telomere length in middle- and older-aged adults, independent of sociodemographic and mental health factors.},
}
@article {pmid36944821,
year = {2023},
author = {Herrera-Moreno, JF and Prada, D and Baccarelli, AA},
title = {Early Environment and Telomeres: a Long-Term Toxic Relationship.},
journal = {Current environmental health reports},
volume = {10},
number = {2},
pages = {112-124},
pmid = {36944821},
issn = {2196-5412},
support = {R01 ES025225/ES/NIEHS NIH HHS/United States ; R01 ES032242/ES/NIEHS NIH HHS/United States ; R35 ES031688/ES/NIEHS NIH HHS/United States ; R01 AG069120/AG/NIA NIH HHS/United States ; R01 AG058704/AG/NIA NIH HHS/United States ; R01 ES027747/ES/NIEHS NIH HHS/United States ; P30 ES009089/ES/NIEHS NIH HHS/United States ; },
mesh = {Child ; Female ; Pregnancy ; Humans ; Child, Preschool ; Aged ; Environmental Exposure/adverse effects/analysis ; *Air Pollutants/analysis ; *Polycyclic Aromatic Hydrocarbons/toxicity/analysis ; Aging/genetics ; Telomere/chemistry ; },
abstract = {PURPOSE OF REVIEW: Telomere length (TL) shortening is a hallmark of biological aging. While studies have extensively focused on the impact of environmental exposures on TL in older populations, consistent evidence indicates that prenatal environmental exposures to air pollutants, polycyclic aromatic hydrocarbons, metals, and endocrine-disrupting chemicals influence TL shortening. Here, we summarize evidence linking prenatal environmental exposures with children's TL and discuss potential long-term effects.<br><br>RECENT FINDINGS: Current evidence shows that prenatal environmental exposures alter TL and identify pregnancy as a critical window of susceptibility for telomere damage in children. However, results vary across studies, possibly depending on the source, exposure time window, and stage evaluated. Additional research is needed to investigate whether early TL alterations mediate long-term health effects of offspring. Prenatal environmental exposures induce early childhood changes in TL. Based on known links between TL and biological aging, these alterations may have long-term impact on individuals' health throughout life.},
}
@article {pmid36943406,
year = {2023},
author = {Connor, A and Starnino, L and Busque, L and Tardif, JC and Bourgoin, V and Dubé, MP and Busseuil, D and D'Antono, B},
title = {Childhood maltreatment and leukocyte telomere length in men and women with chronic illness: an evaluation of moderating and mediating influences.},
journal = {Psychological medicine},
volume = {53},
number = {13},
pages = {6242-6252},
pmid = {36943406},
issn = {1469-8978},
support = {MOP # 111015//CIHR/Canada ; },
mesh = {Male ; Humans ; Female ; Aged ; Child ; Aging ; *Coronary Artery Disease ; Chronic Disease ; Leukocytes/physiology ; Telomere ; *Child Abuse ; },
abstract = {BACKGROUND: Childhood maltreatment can result in lifelong psychological and physical sequelae, including coronary artery disease (CAD). Mechanisms leading to increased risk of illness may involve emotional dysregulation and shortened leukocyte telomere length (LTL).<br><br>METHODS: To evaluate whether (1) childhood maltreatment is associated with shorter LTL among older adults with CAD or other chronic illnesses; (2) sex and/or CAD status influence these results; and (3) symptoms of anxiety, depression, and stress moderate or mediate the association between childhood maltreatment and LTL, men and women (N = 1247; aged 65 &#xb1; 7.2 years) with and without CAD completed validated questionnaires on childhood maltreatment, symptoms of depression, anxiety, and perceived stress. LTL was measured using quantitative polymerase chain reaction. Analyses included bivariate correlations, hierarchical regressions, and moderation/mediation analyses, controlling for sociodemographic and lifestyle variables.<br><br>RESULTS: Childhood maltreatment was associated with significantly shorter LTL (r = -0.059, p = 0.038, b = -0.016, p = 0.005). This relation was not moderated by depression, anxiety, nor perceived stress, though there was mitigated evidence for absence of a maltreatment-LTL relation in men with CAD. Stress perception (but not anxiety or depression) partially mediated the relation between childhood maltreatment and LTL [Indirect effect, b = -0.0041, s.e. = 0.002, 95% CI (-0.0085 to -0.0002)].<br><br>CONCLUSIONS: Childhood maltreatment was associated with accelerated biological aging independently of patient characteristics. Emotional dysregulation resulting in chronic stress may contribute to this process. Whether stress management or other interventions may help prevent or slow premature aging in those who have suffered maltreatment requires study.},
}
@article {pmid36943300,
year = {2023},
author = {Wang, B and Shi, X and Gao, J and Liao, R and Fu, J and Bai, J and Cui, H},
title = {SCARECROW maintains the stem cell niche in Arabidopsis roots by ensuring telomere integrity.},
journal = {Plant physiology},
volume = {192},
number = {2},
pages = {1115-1131},
pmid = {36943300},
issn = {1532-2548},
mesh = {*Arabidopsis/genetics/metabolism ; *Arabidopsis Proteins/genetics/metabolism ; Plant Roots/genetics/metabolism ; Stem Cell Niche/genetics ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {Stem cells are the ultimate source of cells for various tissues and organs and thus are essential for postembryonic plant growth and development. SCARECROW (SCR) is a plant-specific transcription regulator well known for its role in stem cell renewal in plant roots, but the mechanism by which SCR exerts this function remains unclear. To address this question, we carried out a genetic screen for mutants that no longer express SCR in the stem cell niche of Arabidopsis (Arabidopsis thaliana) roots and characterized 1 of these mutants. Molecular genetics methods allowed us to pinpoint the causal mutation in this mutant in TELOMERIC PATHWAYS IN ASSOCIATION WITH STN 1 (TEN1), encoding a factor that protects telomere ends. Interestingly, TEN1 expression was dramatically reduced in the scr mutant. Telomerase and STN1 and CONSERVED TELOMERE MAINTENANCE COMPONENT 1 (CTC1), components of the same protein complex as TEN1, were also dramatically downregulated in scr. Loss of STN1, CTC1, and telomerase caused defects in root stem cells. These results together suggest that SCR maintains root stem cells by promoting expression of genes that ensure genome integrity. Supporting this conclusion, we demonstrated that the scr mutant accumulates more DNA damage than wild-type Arabidopsis and that this problem is aggravated after exposure to zeocin, a DNA damage reagent. Finally, we identified 2 previously uncharacterized motifs in TEN1 and provide evidence that a conserved amino acid residue in 1 of the motifs is indispensable for TEN1 function. SCR thus provides a connection between genome integrity and stem cell maintenance in Arabidopsis roots.},
}
@article {pmid36940725,
year = {2023},
author = {Rose, AM and Goncalves, T and Cunniffe, S and Geiller, HEB and Kent, T and Shepherd, S and Ratnaweera, M and O'Sullivan, RJ and Gibbons, RJ and Clynes, D},
title = {Induction of the alternative lengthening of telomeres pathway by trapping of proteins on DNA.},
journal = {Nucleic acids research},
volume = {51},
number = {13},
pages = {6509-6527},
pmid = {36940725},
issn = {1362-4962},
support = {P30 CA047904/CA/NCI NIH HHS/United States ; /MRC_/Medical Research Council/United Kingdom ; R01 CA207209/CA/NCI NIH HHS/United States ; /DH_/Department of Health/United Kingdom ; R01 CA262316/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; DNA ; *Neoplasms/genetics ; Telomerase/genetics ; *Telomere/genetics/metabolism ; Telomere Homeostasis ; X-linked Nuclear Protein/genetics/metabolism ; },
abstract = {Telomere maintenance is a hallmark of malignant cells and allows cancers to divide indefinitely. In some cancers, this is achieved through the alternative lengthening of telomeres (ALT) pathway. Whilst loss of ATRX is a near universal feature of ALT-cancers, it is insufficient in isolation. As such, other cellular events must be necessary - but the exact nature of the secondary events has remained elusive. Here, we report that trapping of proteins (such as TOP1, TOP2A and PARP1) on DNA leads to ALT induction in cells lacking ATRX. We demonstrate that protein-trapping chemotherapeutic agents, such as etoposide, camptothecin and talazoparib, induce ALT markers specifically in ATRX-null cells. Further, we show that treatment with G4-stabilising drugs cause an increase in trapped TOP2A levels which leads to ALT induction in ATRX-null cells. This process is MUS81-endonuclease and break-induced replication dependent, suggesting that protein trapping leads to replication fork stalling, with these forks being aberrantly processed in the absence of ATRX. Finally, we show ALT-positive cells harbour a higher load of genome-wide trapped proteins, such as TOP1, and knockdown of TOP1 reduced ALT activity. Taken together, these findings suggest that protein trapping is a fundamental driving force behind ALT-biology in ATRX-deficient malignancies.},
}
@article {pmid36934410,
year = {2023},
author = {D'Aronco, G and Ferraro, P and Sassano, V and Dagostino, C and Biancotto, M and Palumbo, E and Presot, E and Russo, A and Bianchi, V and Rampazzo, C},
title = {SAMHD1 restricts the deoxyguanosine triphosphate pool contributing to telomere stability in telomerase-positive cells.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {37},
number = {4},
pages = {e22883},
doi = {10.1096/fj.202300122R},
pmid = {36934410},
issn = {1530-6860},
mesh = {Humans ; Deoxyguanine Nucleotides ; *Monomeric GTP-Binding Proteins/metabolism ; *SAM Domain and HD Domain-Containing Protein 1/genetics ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {SAMHD1 (Sterile alpha motif and histidine/aspartic acid domain-containing protein 1) is a dNTP triphosphohydrolase crucial in the maintenance of balanced cellular dNTP pools, which support genome integrity. In SAMHD1 deficient fibroblasts isolated from Aicardi-Goutières Syndrome (AGS) patients, all four DNA precursors are increased and markedly imbalanced with the largest effect on dGTP, a key player in the modulation of telomerase processivity. Here, we present data showing that SAMHD1, by restricting the dGTP pool, contributes to telomere maintenance in hTERT-immortalized human fibroblasts from AGS patients as well as in telomerase positive cancer cell lines. Only in cells expressing telomerase, the lack of SAMHD1 causes excessive lengthening of telomeres and telomere fragility, whereas primary fibroblasts lacking both SAMHD1 and telomerase enter normally into senescence. Telomere lengthening observed in SAMHD1 deficient but telomerase proficient cells is a gradual process, in accordance with the intrinsic property of telomerase of adding only a few tens of nucleotides for each cycle. Therefore, only a prolonged exposure to high dGTP content causes telomere over-elongation. hTERT-immortalized AGS fibroblasts display also high fragility of chromosome ends, a marker of telomere replication stress. These results not only demonstrate the functional importance of dGTP cellular level but also reveal the critical role played by SAMHD1 in restraining telomerase processivity and safeguarding telomere stability.},
}
@article {pmid36933050,
year = {2023},
author = {Brown, JC and Sturgeon, K and Sarwer, DB and Troxel, AB and DeMichele, AM and Denlinger, CS and Schmitz, KH},
title = {The effects of exercise and diet on oxidative stress and telomere length in breast cancer survivors.},
journal = {Breast cancer research and treatment},
volume = {199},
number = {1},
pages = {109-117},
pmid = {36933050},
issn = {1573-7217},
support = {U54 CA155850/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Female ; *Breast Neoplasms/genetics/therapy ; *Cancer Survivors ; Diet ; Oxidative Stress ; Telomere/genetics ; },
abstract = {PURPOSE: Cancer and its treatments accelerate biological aging. This analysis tested the hypothesis that exercise and diet reduce oxidative stress and prevent telomere shortening in breast cancer survivors.<br><br>METHODS: In a 2&#xa0;&#xd7;&#xa0;2 factorial design, 342 breast cancer survivors who were insufficiently physically active and had overweight or obesity at enrollment were randomized to one of four treatment groups for 52&#xa0;weeks: control, exercise alone, diet alone, or exercise plus diet. The endpoints of this analysis were the change from baseline to week 52 in 8-iso-prostaglandin F2&#x3b1; (8-iso-PGF2&#x3b1;) and lymphocyte telomere length.<br><br>RESULTS: Baseline telomere length was shorter than age-adjusted normative values (median difference:&#x2009;-&#x2009;1.8 kilobases; 95% CI&#x2009;-&#x2009;2.4,&#x2009;-&#x2009;1.1); equivalent to 21&#xa0;years (95% CI 17, 25) of accelerated chronological aging. Compared to control, exercise alone did not change 8-iso-PGF2&#x3b1; [9.9%; 95% confidence interval (CI)&#x2009;-&#x2009;1.0, 20.8] or telomere length (13.8%; 95% CI&#x2009;-&#x2009;15.6, 43.3). Compared to control, diet alone was associated with reduced 8-iso-PGF2&#x3b1; (-&#x2009;10.5%; 95% CI&#x2009;-&#x2009;19.5,&#x2009;-&#x2009;1.5) but did not change telomere length (12.1%; 95% CI&#xa0;-&#x2009;17.2, 41.3). Compared to control, exercise plus diet was associated with reduced 8-iso-PGF2&#x3b1; (-&#x2009;9.8%; 95% CI&#x2009;-&#x2009;18.7,&#x2009;-&#x2009;0.9) but did not change telomere length (-&#x2009;8.5%; 95% CI&#x2009;-&#x2009;32.1, 15.2). Change in 8-iso-PGF2&#x3b1; did not correlate with change in telomere length (r&#x2009;=&#x2009;0.07; 95% CI&#x2009;-&#x2009;0.07, 0.20).<br><br>CONCLUSION: In breast cancer survivors, diet alone or exercise plus diet were associated with reduced oxidative stress but did not change telomere length. This analysis may inform future trials that aim to optimize healthy aging in cancer survivors.},
}
@article {pmid36933034,
year = {2023},
author = {Meng, Q and Shao, B and Zhao, D and Fu, X and Wang, J and Li, H and Zhou, Q and Gao, T},
title = {Loss of SUN1 function in spermatocytes disrupts the attachment of telomeres to the nuclear envelope and contributes to non-obstructive azoospermia in humans.},
journal = {Human genetics},
volume = {142},
number = {4},
pages = {531-541},
pmid = {36933034},
issn = {1432-1203},
support = {82201762//National Natural Science Foundation of China/ ; 82201765//National Natural Science Foundation of China/ ; BK20220200//Natural Science Foundation of Jiangsu Province/ ; LCZX202109//Suzhou science and technology development plan/ ; CJ20220143//the Science and Technology Project of Changzhou/ ; Z2021048//the Science and Technology Project of Jiangsu Health Committee/ ; },
mesh = {Male ; Humans ; *Nuclear Envelope/genetics ; *Azoospermia/pathology ; Microtubule-Associated Proteins/genetics ; Spermatocytes/metabolism/pathology ; Telomere/pathology ; Membrane Proteins/genetics/metabolism ; Nuclear Proteins/genetics/metabolism ; },
abstract = {One of the most severe forms of infertility in humans, caused by gametogenic failure, is non-obstructive azoospermia (NOA). Approximately, 20-30% of men with NOA may have single-gene mutations or other genetic variables that cause this disease. While a range of single-gene mutations associated with infertility has been identified in prior whole-exome sequencing (WES) studies, current insight into the precise genetic etiology of impaired human gametogenesis remains limited. In this paper, we described a proband with NOA who experienced hereditary infertility. WES analyses identified a homozygous variant in the SUN1 (Sad1 and UNC84 domain containing 1) gene [c. 663C > A: p.Tyr221X] that segregated with infertility. SUN1 encodes a LINC complex component essential for telomeric attachment and chromosomal movement. Spermatocytes with the observed mutations were incapable of repairing double-strand DNA breaks or undergoing meiosis. This loss of SUN1 functionality contributes to significant reductions in KASH5 levels within impaired chromosomal telomere attachment to the inner nuclear membrane. Overall, our results identify a potential genetic driver of NOA pathogenesis and provide fresh insight into the role of the SUN1 protein as a regulator of prophase I progression in the context of human meiosis.},
}
@article {pmid36932659,
year = {2023},
author = {Wang, H and Ni, J and Guo, X and Xue, J and Wang, X},
title = {Effects of folate on telomere length and chromosome stability of human fibroblasts and melanoma cells in vitro: a comparison of folic acid and 5-methyltetrahydrofolate.},
journal = {Mutagenesis},
volume = {38},
number = {2},
pages = {100-108},
doi = {10.1093/mutage/gead004},
pmid = {36932659},
issn = {1464-3804},
mesh = {Humans ; Folic Acid/pharmacology ; *Telomerase/genetics/metabolism ; Telomere/metabolism ; Chromosomal Instability ; Fibroblasts/metabolism ; *Melanoma ; },
abstract = {Telomere length (TL), which is maintained by human telomerase reverse transcriptase (hTERT; component of telomerase) and/or TRF1/TRF2 (core components of shelterin) via different mechanisms, is essential for chromosomal stability and cell survival. Folates comprise a group of essential B9 vitamin that involve in DNA synthesis and methylation. This study aimed to evaluate the effects of folic acid (FA) and 5-methyltetrahydrofolate (5-MeTHF) on TL, chromosome stability, and cell survival of telomerase-negative BJ and telomerase-positive A375 cells in vitro. BJ and A375 cells were cultured in modified medium with FA or 5-MeTHF (22.6 or 2260 nM) for 28 days. TL and mRNA expression were determined by RT-qPCR. Chromosome instability (CIN) and cell death were measured by CBMN-Cyt assay. Results showed that abnormal TL elongation was observed in FA- and 5-MeTHF-deficient BJ cells. The TL of A375 cells showed no obvious alterations under the FA-deficient condition but was significantly elongated under the 5-MeTHF-deficient condition. In both BJ and A375 cells, FA and 5-MeTHF deficiency caused decreased TRF1, TRF2, and hTERT expression, increased CIN and cell death; while a high concentration of 5-MeTHF induced elongated TL, elevated CIN, increased TRF1 and TRF2 expression, and decreased hTERT expression, when compared with the FA counterpart. These findings concluded that folate deficiency induced TL instability in both telomerase-negative and -positive cells, and FA was more efficient in maintaining TL and chromosome stability compared with 5-MeTHF.},
}
@article {pmid36932145,
year = {2023},
author = {Adegunsoye, A and Newton, CA and Oldham, JM and Ley, B and Lee, CT and Linderholm, AL and Chung, JH and Garcia, N and Zhang, D and Vij, R and Guzy, R and Jablonski, R and Bag, R and Voogt, RS and Ma, SF and Sperling, AI and Raghu, G and Martinez, FJ and Strek, ME and Wolters, PJ and Garcia, CK and Pierce, BL and Noth, I},
title = {Telomere length associates with chronological age and mortality across racially diverse pulmonary fibrosis cohorts.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {1489},
pmid = {36932145},
issn = {2041-1723},
support = {K23 HL148498/HL/NHLBI NIH HHS/United States ; R01 HL139897/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Pulmonary Fibrosis ; Ethnicity ; Proportional Hazards Models ; Racial Groups ; Telomere/genetics ; Leukocytes ; },
abstract = {Pulmonary fibrosis (PF) is characterized by profound scarring and poor survival. We investigated the association of leukocyte telomere length (LTL) with chronological age and mortality across racially diverse PF cohorts. LTL measurements among participants with PF stratified by race/ethnicity were assessed in relation to age and all-cause mortality, and compared to controls. Generalized linear models were used to evaluate the age-LTL relationship, Cox proportional hazards models were used for hazard ratio estimation, and the Cochran-Armitage test was used to assess quartiles of LTL. Standardized LTL shortened with increasing chronological age; this association in controls was strengthened in PF (R = -0.28; P < 0.0001). In PF, age- and sex-adjusted LTL below the median consistently predicted worse mortality across all racial groups (White, HR = 2.21, 95% CI = 1.79-2.72; Black, HR = 2.22, 95% CI = 1.05-4.66; Hispanic, HR = 3.40, 95% CI = 1.88-6.14; and Asian, HR = 2.11, 95% CI = 0.55-8.23). LTL associates uniformly with chronological age and is a biomarker predictive of mortality in PF across racial groups.},
}
@article {pmid36922555,
year = {2023},
author = {Pepke, ML and Kvalnes, T and Wright, J and Araya-Ajoy, YG and Ranke, PS and Boner, W and Monaghan, P and Sæther, BE and Jensen, H and Ringsby, TH},
title = {Longitudinal telomere dynamics within natural lifespans of a wild bird.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {4272},
pmid = {36922555},
issn = {2045-2322},
mesh = {Animals ; *Animals, Wild/genetics ; *Longevity/genetics ; Birds/genetics ; Telomere Homeostasis ; Telomere Shortening/genetics ; Telomere/genetics ; },
abstract = {Telomeres, the nucleotide sequences that protect the ends of eukaryotic chromosomes, shorten with each cell division and telomere loss may be influenced by environmental factors. Telomere length (TL) decreases with age in several species, but little is known about the sources of genetic and environmental variation in the change in TL (∆TL) in wild animals. In this study, we tracked changes in TL throughout the natural lifespan (from a few months to almost 9 years) of free-living house sparrows (Passer domesticus) in two different island populations. TL was measured in nestlings and subsequently up to four times during their lifetime. TL generally decreased with age (senescence), but we also observed instances of telomere lengthening within individuals. We found some evidence for selective disappearance of individuals with shorter telomeres through life. Early-life TL positively predicted later-life TL, but the within-individual repeatability in TL was low (9.2%). Using genetic pedigrees, we found a moderate heritability of ∆TL (h[2] = 0.21), which was higher than the heritabilities of early-life TL (h[2] = 0.14) and later-life TL measurements (h[2] = 0.15). Cohort effects explained considerable proportions of variation in early-life TL (60%), later-life TL (53%), and ∆TL (37%), which suggests persistent impacts of the early-life environment on lifelong telomere dynamics. Individual changes in TL were independent of early-life TL. Finally, there was weak evidence for population differences in ∆TL that may be linked to ecological differences in habitat types. Combined, our results show that individual telomere biology is highly dynamic and influenced by both genetic and environmental variation in natural conditions.},
}
@article {pmid36911306,
year = {2023},
author = {Wolf, SE and Zhang, S and Clotfelter, ED},
title = {Experimental ectoparasite removal has a sex-specific effect on nestling telomere length.},
journal = {Ecology and evolution},
volume = {13},
number = {3},
pages = {e9861},
pmid = {36911306},
issn = {2045-7758},
abstract = {Parasites are a strong selective force that can influence fitness-related traits. The length of chromosome-capping telomeres can be used to assess the long-term costs of parasitism, as telomere loss accelerates in response to environmental stressors and often precedes poorer survival prospects. Here, we explored the sex-specific effects of ectoparasite removal on morphology and telomere length in nestling tree swallows (Tachycineta bicolor). To do so, we experimentally removed blow fly (Protocalliphora spp.) larvae from nests using Permethrin, a broad-spectrum insecticide. Compared to water-treated controls, insecticide treatment of nests had a sex-biased effect on blood telomere length: ectoparasite removal resulted in significantly longer telomeres in males but not females. While this treatment did not influence nestling body mass, it was associated with reduced feather development regardless of sex. This may reflect a relaxed pressure to fledge quickly in the absence of parasites, or alternatively, could be a negative side effect of permethrin on morphology. Exploring robust sex-specific telomere dynamics in response to early-life environmental pressures such as parasitism will shed light on sexual dimorphism in adult life histories and aging.},
}
@article {pmid36910209,
year = {2023},
author = {Liu, J and Zhao, S and Li, Z and Zhang, Z and Zhao, B and Guan, G and Yin, H and Luo, J},
title = {Activation of telomerase activity and telomere elongation of host cells by Theileria annulata infection.},
journal = {Frontiers in microbiology},
volume = {14},
number = {},
pages = {1128433},
pmid = {36910209},
issn = {1664-302X},
abstract = {Theileria annulata-transformed cells share many phenotypes with cancer cells, including uncontrolled proliferation, immortalization, and dissemination. Telomeres are DNA-protein complex at the end of eukaryotic chromosomes that function to maintain genome stability and cell replicative capacity. Telomere length maintenance is primarily dependent on telomerase activity. In up to 90% of human cancer cells, telomerase is reactivated through expression of its catalytic subunit TERT. However, the effect of T. annulata infection on telomere and telomerase activity in bovine cells has not yet been described. In the present study, we confirmed that telomere length and telomerase activity are upregulated after T. annulata infection in three types of cell lines. This change depends on the presence of parasites. After eliminating Theileria from cells with antitheilerial drug buparvaquone, telomerase activity and the expression level of bTERT were decreased. In addition, inhibition of bHSP90 by novobiocin led to decreased AKT phosphorylation levels and telomerase activity, indicating that the bHSP90-AKT complex is a potent factor modulates telomerase activity in T. annulata-infected cells.},
}
@article {pmid36902458,
year = {2023},
author = {Shepelev, N and Dontsova, O and Rubtsova, M},
title = {Post-Transcriptional and Post-Translational Modifications in Telomerase Biogenesis and Recruitment to Telomeres.},
journal = {International journal of molecular sciences},
volume = {24},
number = {5},
pages = {},
pmid = {36902458},
issn = {1422-0067},
support = {21-64-00006//Russian Science Foundation/ ; },
mesh = {Animals ; Humans ; *Telomerase/metabolism ; *Neoplasms ; Saccharomyces cerevisiae/metabolism ; Telomere/metabolism ; Protein Processing, Post-Translational ; },
abstract = {Telomere length is associated with the proliferative potential of cells. Telomerase is an enzyme that elongates telomeres throughout the entire lifespan of an organism in stem cells, germ cells, and cells of constantly renewed tissues. It is activated during cellular division, including regeneration and immune responses. The biogenesis of telomerase components and their assembly and functional localization to the telomere is a complex system regulated at multiple levels, where each step must be tuned to the cellular requirements. Any defect in the function or localization of the components of the telomerase biogenesis and functional system will affect the maintenance of telomere length, which is critical to the processes of regeneration, immune response, embryonic development, and cancer progression. An understanding of the regulatory mechanisms of telomerase biogenesis and activity is necessary for the development of approaches toward manipulating telomerase to influence these processes. The present review focuses on the molecular mechanisms involved in the major steps of telomerase regulation and the role of post-transcriptional and post-translational modifications in telomerase biogenesis and function in yeast and vertebrates.},
}
@article {pmid36894693,
year = {2023},
author = {Spegg, V and Panagopoulos, A and Stout, M and Krishnan, A and Reginato, G and Imhof, R and Roschitzki, B and Cejka, P and Altmeyer, M},
title = {Phase separation properties of RPA combine high-affinity ssDNA binding with dynamic condensate functions at telomeres.},
journal = {Nature structural &amp; molecular biology},
volume = {30},
number = {4},
pages = {451-462},
pmid = {36894693},
issn = {1545-9985},
mesh = {*Replication Protein A/chemistry ; *Telomere/metabolism ; RNA/metabolism ; DNA, Single-Stranded ; Protein Binding ; DNA Replication ; },
abstract = {RPA has been shown to protect single-stranded DNA (ssDNA) intermediates from instability and breakage. RPA binds ssDNA with sub-nanomolar affinity, yet dynamic turnover is required for downstream ssDNA transactions. How ultrahigh-affinity binding and dynamic turnover are achieved simultaneously is not well understood. Here we reveal that RPA has a strong propensity to assemble into dynamic condensates. In solution, purified RPA phase separates into liquid droplets with fusion and surface wetting behavior. Phase separation is stimulated by sub-stoichiometric amounts of ssDNA, but not RNA or double-stranded DNA, and ssDNA gets selectively enriched in RPA condensates. We find the RPA2 subunit required for condensation and multi-site phosphorylation of the RPA2 N-terminal intrinsically disordered region to regulate RPA self-interaction. Functionally, quantitative proximity proteomics links RPA condensation to telomere clustering and integrity in cancer cells. Collectively, our results suggest that RPA-coated ssDNA is contained in dynamic RPA condensates whose properties are important for genome organization and stability.},
}
@article {pmid36890798,
year = {2023},
author = {Moustakli, E and Zikopoulos, A and Sakaloglou, P and Bouba, I and Sofikitis, N and Georgiou, I},
title = {Functional association between telomeres, oxidation and mitochondria.},
journal = {Frontiers in reproductive health},
volume = {5},
number = {},
pages = {1107215},
pmid = {36890798},
issn = {2673-3153},
abstract = {Prior research has substantiated the vital role of telomeres in human fertility. Telomeres are prerequisites for maintaining the integrity of chromosomes by preventing the loss of genetic material following replication events. Little is known about the association between sperm telomere length and mitochondrial capacity involving its structure and functions. Mitochondria are structurally and functionally distinct organelles that are located on the spermatozoon's midpiece. Mitochondria produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS), which is necessary for sperm motility and generate reactive oxygen species (ROS). While a moderate concentration of ROS is critical for egg-sperm fusion, and fertilization, excessive ROS generation is primarily related to telomere shortening, sperm DNA fragmentation, and alterations in the methylation pattern leading to male infertility. This review aims to highlight the functional connection between mitochondria biogenesis and telomere length in male infertility, as mitochondrial lesions have a damaging impact on telomere length, leading both to telomere lengthening and reprogramming of mitochondrial biosynthesis. Furthermore, it aims to shed light on how both inositol and antioxidants can positively affect male fertility.},
}
@article {pmid36890680,
year = {2023},
author = {Chen, Z and Shen, Y and He, J and Shen, Y and Zhu, W and Wu, X and Xiao, M},
title = {Longer leukocyte telomere length increases cardiovascular mortality in type 2 diabetes patients.},
journal = {Journal of diabetes},
volume = {15},
number = {4},
pages = {325-331},
pmid = {36890680},
issn = {1753-0407},
mesh = {Humans ; *Diabetes Mellitus, Type 2/complications ; Nutrition Surveys ; *Cardiovascular Diseases ; *Neoplasms ; Leukocytes ; Telomere/genetics ; },
abstract = {AIMS: Leukocyte telomere length (LTL), as a biomarker of biological aging, is associated with the prevalence and complications of diabetes. This study aims to investigate the associations between LTL and all-cause and cause-specific mortality in patients with type 2 diabetes.<br><br>METHODS: All participants with baseline LTL records were included from the National Health and Nutrition Examination Survey 1999-2002. Death status and its causes were ascertained for National Death Index based on International Classification of Diseases, Tenth Revision code. Cox proportional hazards regression models were established to estimate the hazard ratios (HRs) of LTL associating with all-cause and cause-specific mortality.<br><br>RESULTS: The study enrolled 804 diabetic patients with the mean follow-up of 14.9&#x2009;&#xb1;&#x2009;2.59&#x2009;years. There were 367 (45.6%) all-cause deaths, 80 (10.0%) cardiovascular deaths, and 42 (5.2%) cancer-related deaths. Longer LTL was associated with reduced all-cause mortality, whereas this association disappeared after adjusting for other variables. Compared with the lowest tertiles of LTL, the multivariable-adjusted hazard ratio of cardiovascular mortality was 2.11 (95% confidence interval [CI] 1.31-3.39; p&#x2009;<&#x2009;.05) in the highest tertiles. In terms of cancer mortality, the highest tertile was negatively correlated with the risk of cancer mortality (HR 0.58 [95% CI 0.37, 0.91], p&#x2009;<&#x2009;.05).<br><br>CONCLUSION: In conclusion, LTL was independently associated with the risk of cardiovascular mortality in patients with type 2 diabetes and was negatively correlated with the risk of cancer mortality. Telomere length may be a predictor of cardiovascular mortality in diabetes.},
}
@article {pmid36883676,
year = {2023},
author = {Becher, OJ},
title = {A new path to alternative lengthening of telomeres?.},
journal = {Neuro-oncology},
volume = {25},
number = {7},
pages = {1343-1344},
pmid = {36883676},
issn = {1523-5866},
support = {R01 CA197313/CA/NCI NIH HHS/United States ; R01 CA258636/CA/NCI NIH HHS/United States ; R01s CA197313/GF/NIH HHS/United States ; },
mesh = {Humans ; Child ; DNA Mismatch Repair ; Telomere/genetics/metabolism ; *Telomerase/genetics/metabolism ; Mutation ; *Glioma ; X-linked Nuclear Protein/genetics ; },
}
@article {pmid36880214,
year = {2023},
author = {Yang, C and Wu, X and Chen, S and Xiang, B},
title = {Association between telomere length and hepatocellular carcinoma risk: A Mendelian randomization study.},
journal = {Cancer medicine},
volume = {12},
number = {8},
pages = {9937-9944},
pmid = {36880214},
issn = {2045-7634},
mesh = {Humans ; *Carcinoma, Hepatocellular/genetics ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; *Liver Neoplasms/genetics ; Polymorphism, Single Nucleotide ; Telomere/genetics ; },
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer threatening the public health globally. Although HCC has been associated with the telomere length (TL), the causal relationship between them is not well understood. Therefore, we attempted to explore the linear causal relationship between TL and HCC through Mendelian randomization (MR) analysis among Asian and European populations.<br><br>METHODS: The summary statistics of TL-associated single nucleotide polymorphisms (SNPs) were obtained from a genome-wide association study (GWAS) in the Asian population (N = 23,096). The data of TL-associated SNPs in the European population (N&#xa0;=&#xa0;472,174) and the GWAS summary statistics of HCC in the Asian population (1866 cases, 195,745 controls) as well as the European population (168 cases, 372,016 controls) were downloaded from the public GWAS database. Two-sample MR was performed using inverse variance weighting (IVW), weighted median estimate, MR-Egger regression, weighted-mode estimate, and simple-mode estimate methods. Sensitivity analysis was performed to text the primary results' robustness.<br><br>RESULTS: Nine SNPs associated with TL in Asian populations and 98 SNPs in European populations were selected as instrumental variables. No linear causal relationship between heritable TL and the HCC risk was recorded in the Asian (IVW analysis odds ratio [OR]&#xa0;=&#xa0;1.023, 95% confidence interval [CI] 0.745, 1.405, p&#xa0;=&#xa0;0.887) and European populations (IVW analysis OR&#xa0;=&#xa0;0.487, 95% CI 0.180, 1.320, p&#xa0;=&#xa0;0.157). Other methods also achieved similar outcomes. Sensitivity analysis was performed and revealed no heterogeneity and horizontal pleiotropy.<br><br>CONCLUSIONS: No linear causal association was recorded between heritable TL and HCC in Asian and European populations.},
}
@article {pmid36879937,
year = {2023},
author = {Kumari, R and Suneja, A and Mehndiratta, M and Guleria, K and Malik, R},
title = {Maternal Serum Vitamin E Levels and its Association with Cord Blood Telomere Length and Mitochondrial DNA Copy Number in Preterm Premature Rupture of Membranes.},
journal = {Journal of obstetrics and gynaecology of India},
volume = {73},
number = {1},
pages = {9-14},
pmid = {36879937},
issn = {0971-9202},
abstract = {BACKGROUND AND OBJECTIVE: Oxidative stress is one of the pathophysiological factors of pPROM and Vit. E being antioxidant may have preventive role. Study was conducted to estimate maternal serum vitamin E levels and cord blood oxidative stress markers in pPROM cases.<br><br>METHODS: This was a case-control study including 40 pPROM cases and 40 controls. Maternal serum vitamin E levels were measured at recruitment. Cord blood was collected at delivery for estimation of telomere length and mtDNA copy number as oxidative stress markers. Levels were compared using student's t test or Mann Whitney test. For correlation Pearson coefficient was used.<br><br>RESULTS: Maternal serum vitamin E levels were normal in pPROM cases. Cord blood telomere length was more in pPROM than controls (428.99&#x2009;&#xb1;&#x2009;290.65 vs 322.35&#x2009;&#xb1;&#x2009;180.33) (p value 0.05). Cord blood mtDNA copy number was more in pPROM than controls (516.46&#x2009;&#xb1;&#x2009;443.55 vs 384.77&#x2009;&#xb1;&#x2009;328.27) (p value 0.13) though it was not significant. mtDNA copy number had negative correlation with Vit. E levels but it was statistically not significant (p value 0.49). There was no association of vitamin E levels with telomere length (p value 0.95).<br><br>INTERPRETATION AND CONCLUSION: pPROM was not associated with vitamin E deficiency. There was insignificant oxidative stress in cord blood as measured by mtDNA copy number but cord blood telomere length measurement did not detect any oxidative stress in pPPROM cases.},
}
@article {pmid36876055,
year = {2023},
author = {Goldstein, AM and Qin, R and Chu, EY and Elder, DE and Massi, D and Adams, DJ and Harms, PW and Robles-Espinoza, CD and Newton-Bishop, JA and Bishop, DT and Harland, M and Holland, EA and Cust, AE and Schmid, H and Mann, GJ and Puig, S and Potrony, M and Alos, L and Nagore, E and Millán-Esteban, D and Hayward, NK and Broit, N and Palmer, JM and Nathan, V and Berry, EG and Astiazaran-Symonds, E and Yang, XR and Tucker, MA and Landi, MT and Pfeiffer, RM and Sargen, MR},
title = {Association of germline variants in telomere maintenance genes (POT1, TERF2IP, ACD, and TERT) with spitzoid morphology in familial melanoma: A multi-center case series.},
journal = {JAAD international},
volume = {11},
number = {},
pages = {43-51},
pmid = {36876055},
issn = {2666-3287},
support = {MR/V000292/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {BACKGROUND: Spitzoid morphology in familial melanoma has been associated with germline variants in POT1, a telomere maintenance gene (TMG), suggesting a link between telomere biology and spitzoid differentiation.<br><br>OBJECTIVE: To assess if familial melanoma cases associated with germline variants in TMG (POT1, ACD, TERF2IP, and TERT) commonly exhibit spitzoid morphology.<br><br>METHODS: In this case series, melanomas were classified as having spitzoid morphology if at least 3 of 4 dermatopathologists reported this finding in &#x2265;25% of tumor cells. Logistic regression was used to calculate odds ratios (OR) of spitzoid morphology compared to familial melanomas from unmatched noncarriers that were previously reviewed by a National Cancer Institute dermatopathologist.<br><br>RESULTS: Spitzoid morphology was observed in 77% (23 of 30), 75% (3 of 4), 50% (2 of 4), and 50% (1 of 2) of melanomas from individuals with germline variants in POT1, TERF2IP, ACD, and TERT, respectively. Compared to noncarriers (n&#xa0;=&#xa0;139 melanomas), POT1 carriers (OR&#xa0;=&#xa0;225.1, 95% confidence interval: 51.7-980.5; P&#xa0;<&#xa0;.001) and individuals with TERF2IP, ACD, and TERT variants (OR&#xa0;=&#xa0;82.4, 95% confidence interval: 21.3-494.6; P&#xa0;<&#xa0;.001) had increased odds of spitzoid morphology.<br><br>LIMITATIONS: Findings may not be generalizable to nonfamilial melanoma cases.<br><br>CONCLUSION: Spitzoid morphology in familial melanoma could suggest germline alteration of TMG.},
}
@article {pmid36873417,
year = {2023},
author = {Sha, Z and Hou, T and Zhou, T and Dai, Y and Bao, Y and Jin, Q and Ye, J and Lu, Y and Wu, L},
title = {Causal relationship between atrial fibrillation and leukocyte telomere length: A two sample, bidirectional Mendelian randomization study.},
journal = {Frontiers in cardiovascular medicine},
volume = {10},
number = {},
pages = {1093255},
pmid = {36873417},
issn = {2297-055X},
abstract = {BACKGROUND: Atrial fibrillation (AF) is an age-related disease, while telomeres play a central role in aging. But the relationship between AF and telomere length (LTL) is still controversial. This study aims to examine the potential causal association between AF and LTL by using Mendelian randomization (MR).<br><br>METHODS: Bidirectional two-sample MR, expression and protein quantitative trait loci (eQTL and pQTL)-based MR were performed using genetic variants from United Kingdom Biobank, FinnGen, and a meta-analysis study, which comprised nearly 1 million participants in the Atrial Fibrillation Study and 470,000 participants in the Telomere Length Study. Apart from the inverse variance weighted (IVW) approach as the main MR analysis, complementary analysis approaches and sensitivity analysis were applied.<br><br>RESULTS: The forward MR revealed a significant causal estimate for the genetically predicted AF with LTL shortening [IVW: odds ratio (OR)&#x2009;=&#x2009;0.989, p&#x2009;=&#x2009;0.007; eQTL-IVW: OR&#x2009;=&#x2009;0.988, p&#x2009;=&#x2009;0.005; pQTL-IVW: OR&#x2009;=&#x2009;0.975, p&#x2009;<&#x2009;0.005]. But in the reverse MR analysis, genetically predicted LTL has no significant correlation with AF (IVW: OR&#x2009;=&#x2009;0.995, p&#x2009;=&#x2009;0.916; eQTL-IVW: OR&#x2009;=&#x2009;0.999, p&#x2009;=&#x2009;0.995; pQTL-IVW: OR&#x2009;=&#x2009;1.055, p&#x2009;=&#x2009;0.570). The FinnGen replication data yielded similar findings. Sensitivity analysis ensured the stability of the results.<br><br>CONCLUSION: The presence of AF leads to LTL shortening rather than the other way around. Aggressive intervention for AF may delay the telomere attrition.},
}
@article {pmid36871092,
year = {2023},
author = {Deręgowska, A and Pępek, M and Solarska, I and Machnicki, MM and Pruszczyk, K and Dudziński, M and Niesiobędzka-Krężel, J and Seferyńska, I and Sawicki, W and Wnuk, M and Stokłosa, T},
title = {The interplay between telomeric complex members and BCR::ABL1 oncogenic tyrosine kinase in the maintenance of telomere length in chronic myeloid leukemia.},
journal = {Journal of cancer research and clinical oncology},
volume = {149},
number = {10},
pages = {7103-7112},
pmid = {36871092},
issn = {1432-1335},
support = {2015/19/B/NZ5/03501//Narodowe Centrum Nauki/ ; },
mesh = {Humans ; Bone Marrow/metabolism ; Cell Cycle Proteins/genetics ; Fusion Proteins, bcr-abl/genetics ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics/pathology ; Nuclear Proteins/genetics ; *Tankyrases/genetics/metabolism ; *Telomerase/genetics/metabolism ; Telomere/metabolism ; },
abstract = {PURPOSE: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by recurrent genetic aberration in leukemic stem cells, namely Philadelphia chromosome caused by reciprocal translocation t(9;22)(q34;q11). In our study, we analyzed the telomeric complex expression and function in the molecular pathogenesis of CML.<br><br>METHODS: We employed CD34+&#x2009;primary leukemic cells, comprising both leukemic stem and progenitor cell populations, isolated from peripheral blood or bone marrow of CML patients in chronic and blastic phase to analyze the telomere length and telomeric-associated proteins.<br><br>RESULTS: The reduction in telomere length during disease progression was correlated with increased expression of BCR::ABL1 transcript and the dynamic changes were neither associated with the enzymatic activity of telomerase nor with gene copy number and expression of telomerase subunits. Increased expression of BCR::ABL1 was positively correlated with expression of TRF2, RAP1, TPP1, DKC1, TNKS1, and TNKS2 genes.<br><br>CONCLUSIONS: The dynamics of telomere length changes in CD34+&#x2009;CML cells is dependent on the expression level of BCR::ABL, which promotes the expression of certain shelterins including RAP1 and TRF2, as well as TNKS, and TNKS2, and results in telomere shortening regardless of telomerase activity. Our results may allow better understanding of the mechanisms responsible for the genomic instability of leukemic cells and CML progression.},
}
@article {pmid36868694,
year = {2023},
author = {Chakraborty, A and Roy, S and Hande, MP and Banerjee, B},
title = {Telomere attrition and genomic instability in unexplained recurrent pregnancy loss in humans: A preliminary study.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {886},
number = {},
pages = {503580},
doi = {10.1016/j.mrgentox.2022.503580},
pmid = {36868694},
issn = {1879-3592},
mesh = {Female ; Pregnancy ; Humans ; Retrospective Studies ; *Genomic Instability ; Mutation ; *DNA Damage ; Telomere ; },
abstract = {Genome instability is defined as an elevated rate of DNA damage and mutations as a result of exposure to potential direct and indirect mutagens. This current investigation was designed to elucidate the genomic instability among couples experiencing unexplained recurrent pregnancy loss (uRPL). A cohort of 1272 individuals with history of unexplained RPL with normal karyotype was retrospectively screened for levels of intracellular ROS production, baseline genomic instability and telomere functionality. The experimental outcome was compared with 728 fertile control individuals. In this study, it was perceived that individuals with uRPL exhibited higher intracellular oxidative stress, along with higher basal levels of genomic instability as compared with the fertile controls. This observation elucidates the role of genomic instability as well as involvement of telomeres in cases of uRPL. It was also observed that higher oxidative stress might be associated with DNA damage and telomere dysfunction resulting in genomic instability among subjects with unexplained RPL. This study highlighted the assessment of genomic instability status in individuals experiencing uRPL.},
}
@article {pmid36864251,
year = {2023},
author = {Maresca, C and Dello Stritto, A and D'Angelo, C and Petti, E and Rizzo, A and Vertecchi, E and Berardinelli, F and Bonanni, L and Sgura, A and Antoccia, A and Graziani, G and Biroccio, A and Salvati, E},
title = {PARP1 allows proper telomere replication through TRF1 poly (ADP-ribosyl)ation and helicase recruitment.},
journal = {Communications biology},
volume = {6},
number = {1},
pages = {234},
pmid = {36864251},
issn = {2399-3642},
support = {21579//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; 17121//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; },
mesh = {ADP-Ribosylation ; DNA Damage ; DNA Helicases ; *Shelterin Complex ; *Telomere/genetics ; Poly (ADP-Ribose) Polymerase-1/metabolism ; },
abstract = {Telomeres are nucleoprotein structures at eukaryotic chromosome termini. Their stability is preserved by a six-protein complex named shelterin. Among these, TRF1 binds telomere duplex and assists DNA replication with mechanisms only partly clarified. Here we found that poly (ADP-ribose) polymerase 1 (PARP1) interacts and covalently PARylates TRF1 in S-phase modifying its DNA affinity. Therefore, genetic and pharmacological inhibition of PARP1 impairs the dynamic association of TRF1 and the bromodeoxyuridine incorporation at replicating telomeres. Inhibition of PARP1 also affects the recruitment of WRN and BLM helicases in TRF1 containing complexes during S-phase, triggering replication-dependent DNA-damage and telomere fragility. This work unveils an unprecedented role for PARP1 as a "surveillant" of telomere replication, which orchestrates protein dynamics at proceeding replication fork.},
}
@article {pmid36860927,
year = {2023},
author = {Sun, H and Chen, G and Guo, B and Lv, S and Yuan, G},
title = {Potential clinical treatment prospects behind the molecular mechanism of alternative lengthening of telomeres (ALT).},
journal = {Journal of Cancer},
volume = {14},
number = {3},
pages = {417-433},
pmid = {36860927},
issn = {1837-9664},
abstract = {Normal somatic cells inevitably experience replicative stress and senescence during proliferation. Somatic cell carcinogenesis can be prevented in part by limiting the reproduction of damaged or old cells and removing them from the cell cycle [1, 2]. However, Cancer cells must overcome the issues of replication pressure and senescence as well as preserve telomere length in order to achieve immortality, in contrast to normal somatic cells [1, 2]. Although telomerase accounts for the bulk of telomere lengthening methods in human cancer cells, there is a non-negligible portion of telomere lengthening pathways that depend on alternative lengthening of telomeres (ALT) [3]. For the selection of novel possible therapeutic targets for ALT-related disorders, a thorough understanding of the molecular biology of these diseases is crucial [4]. The roles of ALT, typical ALT tumor cell traits, the pathophysiology and molecular mechanisms of ALT tumor disorders, such as adrenocortical carcinoma (ACC), are all summarized in this work. Additionally, this research compiles as many of its hypothetically viable but unproven treatment targets as it can (ALT-associated PML bodies (APB), etc.). This review is intended to contribute as much as possible to the development of research, while also trying to provide a partial information for prospective investigations on ALT pathways and associated diseases.},
}
@article {pmid36859557,
year = {2023},
author = {Chen, J and Wu, S and Wu, Y and Zhuang, P and Zhang, Y and Jiao, J},
title = {Long-term dietary DHA intervention prevents telomere attrition and lipid disturbance in telomerase-deficient male mice.},
journal = {European journal of nutrition},
volume = {62},
number = {4},
pages = {1867-1878},
pmid = {36859557},
issn = {1436-6215},
support = {LR18C200001//Natural Science Foundation of Zhejiang Province/ ; },
mesh = {Animals ; Mice ; Male ; *Docosahexaenoic Acids/pharmacology ; *Telomerase/genetics ; Glycerol ; Mice, Inbred C57BL ; Telomere ; Phosphates ; Mice, Knockout ; Mammals/genetics/metabolism ; },
abstract = {PURPOSE: Previous evidence indicated anti-ageing potential of docosahexaenoic acid (DHA), but the underlying mechanism remains unclear. We investigated protective effect of DHA on telomere attrition and lipid disturbance in male mice with premature ageing caused by telomerase deficiency.<br><br>METHODS: Wild-type (WT) and fourth-generation telomerase-deficient (G4 Terc[-/-], Terc knockout, KO) male mice (C57BL/6, 2&#xa0;months old) were fed control diet (WT-C and KO-C groups) or DHA-enriched diet containing 0.80% DHA by weight (WT-DHA and KO-DHA groups) for 10&#xa0;months. The ageing phenotypes and metabolic level [carbon dioxide emission, oxygen consumption, and respiratory exchange ratio (RER)] were assessed at the end of the experiment. Telomere length in various tissues and the hepatic gene and protein expression for regulating lipid synthesis and lipolysis were measured. Data were tested using one- or two-factor ANOVA.<br><br>RESULTS: In KO male mice, DHA prevented weight loss, corrected high RER, and reduced fat loss. Telomere shortening was reduced by 22.3%, 25.5%, and 13.5% in heart, liver, and testes of the KO-DHA group compared with those in the KO-C group. The KO-DHA group exhibited higher gene transcription involved in glycerol-3-phosphate pathway [glycerol-3-phosphate acyltransferase (Gpat)], lower gene expression of &#x3b2;-oxidation [carnitine palmitoyltransferase 1a (Cpt1a)], and upregulation of proteins in lipid synthesis [mammalian target of rapamycin complex 1 (mTORC1) and sterol responsive element binding protein 1 (SREBP1)] in liver than the KO-C group.<br><br>CONCLUSION: Long-term DHA intervention attenuates telomere attrition and promotes lipid synthesis via the tuberous sclerosis complex 2 (TSC2)-mTORC1-SREBP1 pathway in KO male mice.},
}
@article {pmid36855016,
year = {2023},
author = {Chen, X and Hao, Z and Pan, H and Liu, W and Lu, L and Zhang, M and He, X and Yi, H and Tang, S},
title = {Relationship between common telomere length-related genetic variations, telomere length, and risk of antituberculosis drug-induced hepatotoxicity in Chinese Han population: As assessed for causality using the updated Roussel Uclaf Causality Assessment Method.},
journal = {Fundamental &amp; clinical pharmacology},
volume = {37},
number = {4},
pages = {858-867},
doi = {10.1111/fcp.12885},
pmid = {36855016},
issn = {1472-8206},
support = {82073614//National Natural Science Foundation of China/ ; 2021//Zhenjiang "Jinshan Doctor" Talent Training Program/ ; SH2021055//Zhenjiang Key Technologies Research and Development Program (Social Development)/ ; },
mesh = {Humans ; *Antitubercular Agents/adverse effects ; Case-Control Studies ; *Chemical and Drug Induced Liver Injury/etiology/genetics ; East Asian People ; Genetic Predisposition to Disease ; Leukocytes ; Polymorphism, Single Nucleotide ; Telomere/genetics ; Causality ; },
abstract = {Antituberculosis drug-induced hepatotoxicity (ATDH) is a significant threat to tuberculosis control, and two recent studies indicated that leukocyte telomere length (LTL) might be a potential biomarker for ATDH. This study aimed to investigate the relationship between common telomere length-related genetic variations, LTL, and risk of ATDH in Eastern Chinese antituberculosis treatment patients. A 1:4 matched case-control study was conducted among 79 ATDH cases assessed for causality using the updated RUCAM and 316 controls. LTL was determined by quantitative real-time PCR, and nine SNPs involved in telomere biology reported by previous GWAS were assessed. Conditional logistic regression model was used to estimate the association between genotypes and risk of ATDH with odds ratios (ORs) and 95% confidence intervals (CIs). The average RUCAM score of cases was 7.1. The average LTL in cases was significantly shorter than that in controls (median = 1.239 vs. 1.481, P = 0.032). Differences in the distribution of LTL were statistically significant among three genotypes of SNP rs2736098 (CC vs. CT vs. TT, median = 1.544 vs. 1.356 vs. 1.337, P = 0.026) and rs2853677 (AA vs. AG vs. GG, median = 1.511 vs. 1.544 vs. 1.159, P = 0.005) in TERT. SNP rs7675998 in NAF1 was statistically associated with the risk of ATDH under the dominant model (adjusted OR = 1.725, 95% CI: 1.021-2.913, P = 0.042). This is the first study to investigate the relationship of LTL, common telomere length-related variations, and risk of ATDH. SNP rs2736098 and rs2853677 in TERT were significantly associated with LTL, and SNP rs7675998 in NAF1 may be associated with ATDH in Chinese population.},
}
@article {pmid36852686,
year = {2023},
author = {Zhang, H and Lai, X and Fang, Q and Ma, L and Liu, M and Yang, H and Guo, W and He, M and Yang, L and Zhang, X},
title = {Independent and Joint Association of Leukocyte Telomere Length and Lifestyle Score With Incident Stroke.},
journal = {Stroke},
volume = {54},
number = {5},
pages = {e199-e200},
doi = {10.1161/STROKEAHA.122.041126},
pmid = {36852686},
issn = {1524-4628},
mesh = {Humans ; *Aging ; Life Style ; *Stroke ; Leukocytes ; Telomere ; },
}
@article {pmid36851065,
year = {2023},
author = {Wu, X and Li, P and Tao, J and Chen, X and Zhang, A},
title = {Subchronic Low-Dose Methylmercury Exposure Accelerated Cerebral Telomere Shortening in Relevant with Declined Urinary aMT6s Level in Rats.},
journal = {Toxics},
volume = {11},
number = {2},
pages = {},
pmid = {36851065},
issn = {2305-6304},
support = {U1812403//National Natural Science Foundation of China/ ; },
abstract = {Methylmercury (MeHg) is a global pollutant with established toxic effects on the central nervous system (CNS). However, early events and early-warning biomarkers of CNS damage following exposure to low-dose MeHg are still lacking. This study aimed to investigate whether subchronic low-dose MeHg exposure had adverse effects on the cerebral telomere length, as well as serum melatonin and its urinary metabolite 6-sulfatoxymelatonin (aMT6s) in rats. Sixteen male Sprague Dawley rats were divided into two groups. Group I was the control group. In group II, rats were exposed to MeHg by gavage at a dose of 0.1 mg/kg/day for 3 months. This study revealed that MeHg exposure resulted in impairment of learning and memory ability, a slightly reduced number of neurons and an irregular arrangement of neurons in the hippocampus. It also significantly accelerated telomere shortening in the cerebral cortex, hippocampus and hypothalamus. Moreover, MeHg exposure decreased the levels of melatonin in serum and aMT6s in urine, partly by suppressing the synthesis of 5-hydroxytryptamine (5-HT) in the brain but promoted the expression of melatonin-catalyzing AANAT and ASMT. Importantly, cerebral telomere length was positively correlated with MT and aMT6s after MeHg exposure. These results suggested that the shortened telomere length in the brain may be an early event in MeHg-induced CNS toxicity, and the level of aMT6s in urine may serve as an early-warning biomarker for MeHg-induced CNS damage.},
}
@article {pmid36849001,
year = {2023},
author = {Liu, S and Nong, W and Ji, L and Zhuge, X and Wei, H and Luo, M and Zhou, L and Chen, S and Zhang, S and Lei, X and Huang, H},
title = {The regulatory feedback of inflammatory signaling and telomere/telomerase complex dysfunction in chronic inflammatory diseases.},
journal = {Experimental gerontology},
volume = {174},
number = {},
pages = {112132},
doi = {10.1016/j.exger.2023.112132},
pmid = {36849001},
issn = {1873-6815},
mesh = {Humans ; *Telomerase/metabolism ; NF-kappa B ; Feedback ; Telomere ; Inflammation ; },
abstract = {Inflammation is believed to play a role in the progression of numerous human diseases. Research has shown that inflammation and telomeres are involved in a feedback regulatory loop: inflammation increases the rate of telomere attrition, leading to telomere dysfunction, while telomere components also participate in regulating the inflammatory response. However, the specific mechanism behind this feedback loop between inflammatory signaling and telomere/telomerase complex dysfunction has yet to be fully understood. This review presents the latest findings on this topic, with a particular focus on the detailed regulation and molecular mechanisms involved in the progression of aging, various chronic inflammatory diseases, cancers, and different stressors. Several feedback loops between inflammatory signaling and telomere/telomerase complex dysfunction, including NF-κB-TERT feedback, NF-κB-RAP1 feedback, NF-κB-TERC feedback, STAT3-TERT feedback, and p38 MAPK-shelterin complex-related gene feedback, are summarized. Understanding the latest discoveries of this feedback regulatory loop can help identify novel potential drug targets for the suppression of various inflammation-associated diseases.},
}
@article {pmid36847305,
year = {2024},
author = {Levy, MA and Tian, J and Gandelman, M and Cheng, H and Tsapekos, M and Crego, SR and Maddela, R and Sinnott, R},
title = {A Multivitamin Mixture Protects against Oxidative Stress-Mediated Telomere Shortening.},
journal = {Journal of dietary supplements},
volume = {21},
number = {1},
pages = {53-70},
doi = {10.1080/19390211.2023.2179153},
pmid = {36847305},
issn = {1939-022X},
mesh = {Humans ; *Telomere Shortening ; *Hydrogen Peroxide ; Oxidative Stress ; Vitamins/pharmacology ; Aging/metabolism ; },
abstract = {Telomeres are nucleotide repeat sequences located at the end of chromosomes that protect them from degradation and maintain chromosomal stability. Telomeres shorten with each cell division; hence telomere length is associated with aging and longevity. Numerous lifestyle factors have been identified that impact the rate of telomere shortening; high vitamin consumption has been associated with longer telomere length, whereas oxidative stress is associated with telomere shortening. In this paper, we sought to determine if a multivitamin mixture containing both vitamins and a blend of polyphenolic compounds, could reduce telomere shortening consequent to an oxidative stress (10 uM H2O2 for 8 weeks) in a primary fibroblast cell culture model. Under conditions of oxidative stress, the median and 20[th] percentile telomere length were significantly greater (p < 0.05), and the percentage of critically short telomeres (<3000 bp) was significantly less (p < 0.05) in cells treated with the multivitamin mixture at 4, 15 and 60 ug/ml compared to control (0 ug/ml). Median and 20[th] percentile telomere shortening rate was also reduced under the same conditions (p < 0.05). Taken together, these findings demonstrate that the multivitamin mixture protects against oxidative stress-mediated telomere shortening in cell culture, findings which may have implications in human health.},
}
@article {pmid36847070,
year = {2023},
author = {Pepke, ML and Ringsby, TH and Eisenberg, DTA},
title = {The evolution of early-life telomere length, pace-of-life and telomere-chromosome length dynamics in birds.},
journal = {Molecular ecology},
volume = {32},
number = {11},
pages = {2898-2912},
doi = {10.1111/mec.16907},
pmid = {36847070},
issn = {1365-294X},
mesh = {*Birds/classification/genetics ; Animals ; *Telomere Homeostasis ; *Chromosome Structures/genetics ; *Phylogeny ; Genome Size/genetics ; Cytogenetic Analysis ; *Life History Traits ; },
abstract = {Telomeres, the short DNA sequences that protect chromosome ends, are an ancient molecular structure, which is highly conserved across most eukaryotes. Species differ in their telomere lengths, but the causes of this variation are not well understood. Here, we demonstrate that mean early-life telomere length is an evolutionary labile trait across 57 bird species (representing 35 families in 12 orders) with the greatest trait diversity found among passerines. Among these species, telomeres are significantly shorter in fast-lived than in slow-lived species, suggesting that telomere length may have evolved to mediate trade-offs between physiological requirements underlying the diversity of pace-of-life strategies in birds. This association was attenuated when excluding studies that may include interstitial telomeres in the estimation of mean telomere length. Curiously, within some species, larger individual chromosome size predicts longer telomere lengths on that chromosome, leading to the hypothesis that telomere length also covaries with chromosome length across species. We show that longer mean chromosome length or genome size tends to be associated with longer mean early-life telomere length (measured across all chromosomes) within a phylogenetic framework constituting up to 31 bird species. These associations were strengthened when excluding highly influential outliers. However, sensitivity analyses suggested that they were susceptible to sample size effects and not robust to the exclusion of studies that may include interstitial telomeres. Combined, our analyses generalize patterns previously found within a few species and provide potential adaptive explanations for the 10-fold variation in telomere lengths observed among birds.},
}
@article {pmid36843839,
year = {2023},
author = {Zhang, X and Zhang, C and Zhou, D and Zhang, T and Chen, X and Ren, J and He, C and Meng, F and Zhou, Q and Yang, Q and Dai, C and Lin, G and Zeng, S and Leng, L},
title = {Telomeres cooperate in zygotic genome activation by affecting DUX4/Dux transcription.},
journal = {iScience},
volume = {26},
number = {3},
pages = {106158},
pmid = {36843839},
issn = {2589-0042},
abstract = {Zygotic genome activation (ZGA) is initiated once the genome chromatin state is organized in the newly formed zygote. Telomeres are specialized chromatin structures at the ends of chromosomes and are reset during early embryogenesis, while the details and significance of telomere changes in preimplantation embryos remain unclear. We demonstrated that the telomere length was shortened in the minor ZGA stage and significantly elongated in the major ZGA stage of human and mouse embryos. Expression of the ZGA pioneer factor DUX4/Dux was negatively correlated with the telomere length. ATAC sequencing data revealed that the chromatin accessibility peaks on the DUX4 promoter region (i.e., the subtelomere of chromosome 4q) were transiently augmented in human minor ZGA. Reduction of telomeric heterochromatin H3K9me3 in the telomeric region also synergistically activated DUX4 expression with p53 in human embryonic stem cells. We propose herein that telomeres regulate the expression of DUX4/Dux through chromatin remodeling and are thereby involved in ZGA.},
}
@article {pmid36834938,
year = {2023},
author = {Martel-Martel, A and Corchete, LA and Martí, M and Vidal-Tocino, R and Hurtado, E and Álvaro, E and Jiménez, F and Jiménez-Toscano, M and Balaguer, F and Sanz, G and López, I and Hernández-Villafranca, S and Ballestero, A and Vivas, A and Melone, S and Pastor, C and Brandáriz, L and Gómez-Marcos, MA and Cruz-Hernández, JJ and Perea, J and González-Sarmiento, R},
title = {Telomere Length as a New Risk Marker of Early-Onset Colorectal Cancer.},
journal = {International journal of molecular sciences},
volume = {24},
number = {4},
pages = {},
pmid = {36834938},
issn = {1422-0067},
support = {PI20/0974//Instituto de Salud Carlos III/ ; PI20/01569//Instituto de Salud Carlos III/ ; },
mesh = {Humans ; Middle Aged ; *Colorectal Neoplasms/diagnosis/genetics ; Incidence ; *Telomere/genetics/metabolism ; Biomarkers, Tumor ; *Early Detection of Cancer/methods ; },
abstract = {Early-onset colorectal cancer (EOCRC; age younger than 50 years) incidence has been steadily increasing in recent decades worldwide. The need for new biomarkers for EOCRC prevention strategies is undeniable. In this study, we aimed to explore whether an aging factor, such as telomere length (TL), could be a useful tool in EOCRC screening. The absolute leukocyte TL from 87 microsatellite stable EOCRC patients and 109 healthy controls (HC) with the same range of age, was quantified by Real Time Quantitative PCR (RT-qPCR). Then, leukocyte whole-exome sequencing (WES) was performed to study the status of the genes involved in TL maintenance (hTERT, TERC, DKC1, TERF1, TERF2, TERF2IP, TINF2, ACD, and POT1) in 70 sporadic EOCRC cases from the original cohort. We observed that TL was significantly shorter in EOCRC patients than in healthy individuals (EOCRC mean: 122 kb vs. HC mean: 296 kb; p < 0.001), suggesting that telomeric shortening could be associated with EOCRC susceptibility. In addition, we found a significant association between several SNPs of hTERT (rs79662648), POT1 (rs76436625, rs10263573, rs3815221, rs7794637, rs7784168, rs4383910, and rs7782354), TERF2 (rs251796 and rs344152214), and TERF2IP (rs7205764) genes and the risk of developing EOCRC. We consider that the measurement of germline TL and the status analysis of telomere maintenance related genes polymorphisms at early ages could be non-invasive methods that could facilitate the early identification of individuals at risk of developing EOCRC.},
}
@article {pmid36834592,
year = {2023},
author = {Fujiwara-Tani, R and Takagi, T and Mori, S and Kishi, S and Nishiguchi, Y and Sasaki, T and Ikeda, M and Nagai, K and Bhawal, UK and Ohmori, H and Fujii, K and Kuniyasu, H},
title = {Short Telomere Lesions with Dysplastic Metaplasia Histology May Represent Precancerous Lesions of Helicobacter pylori-Positive Gastric Mucosa.},
journal = {International journal of molecular sciences},
volume = {24},
number = {4},
pages = {},
pmid = {36834592},
issn = {1422-0067},
support = {19K16564//Ministry of Education, Culture, Sports, Science and Technology/ ; 20K21659//Ministry of Education, Culture, Sports, Science and Technology/ ; 20K18007//Ministry of Education, Culture, Sports, Science and Technology/ ; 21K10143//Ministry of Education, Culture, Sports, Science and Technology/ ; },
mesh = {Humans ; *Helicobacter pylori ; *Stomach Neoplasms/pathology ; *Helicobacter Infections/complications ; In Situ Hybridization, Fluorescence ; Gastric Mucosa/metabolism ; *Precancerous Conditions/pathology ; Hyperplasia/metabolism ; Metaplasia/metabolism ; Telomere/pathology ; },
abstract = {Gastric cancers are strongly associated with Helicobacter pylori infection, with intestinal metaplasia characterizing the background mucosa in most cases. However, only a subset of intestinal metaplasia cases proceed to carcinogenesis, and the characteristics of high-risk intestinal metaplasia that link it with gastric cancer are still unclear. We examined telomere reduction in five gastrectomy specimens using fluorescence in situ hybridization, and identified areas with localized telomere loss (outside of cancerous lesions), which were designated as short telomere lesions (STLs). Histological analyses indicated that STLs were characteristic of intestinal metaplasia accompanied by nuclear enlargement but lacking structural atypia, which we termed dysplastic metaplasia (DM). A review of gastric biopsy specimens from 587 H. pylori-positive patients revealed 32 cases of DM, 13 of which were classified as high-grade based on the degree of nuclear enlargement. All high-grade DM cases exhibited a telomere volume reduced to less than 60% of that of lymphocytes, increased stemness, and telomerase reverse transcriptase (TERT) expression. Two patients (15%) exhibited low levels of p53 nuclear retention. After a 10-year follow-up, 7 (54%) of the high-grade DM cases had progressed to gastric cancer. These results suggest that DM is characterized by telomere shortening, TERT expression, and stem cell proliferation, and high-grade DM is a high-grade intestinal metaplasia that likely represents a precancerous lesion of gastric cancer. High-grade DM is expected to effectively prevent progression to gastric cancer in H. pylori-positive patients.},
}
@article {pmid36834587,
year = {2023},
author = {Deng, S and Yang, M and Su, J and Cui, N and Wu, S and Zhang, G and Wang, L and Hou, Y and Chai, Y and Yu, B},
title = {Heat-Killed Staphylococcus aureus Induces Bone Mass Loss through Telomere Erosion.},
journal = {International journal of molecular sciences},
volume = {24},
number = {4},
pages = {},
pmid = {36834587},
issn = {1422-0067},
support = {81830079//the Major Program of National Natural Science Foundation of China/ ; 82102623//the National Natural Science Foundation of China/ ; 82002352//the National Natural Science Foundation of China/ ; 2020A1515010145//Natural Science Foundation of Guangdong Province/ ; 2019A1515110053//Natural Science Foundation of Guangdong Province/ ; 2020M682798//China Postdoctoral Science Foundation/ ; 202201011340//the Science and Technology Program of Guangzhou/ ; },
mesh = {Animals ; Mice ; Staphylococcus aureus ; Hot Temperature ; *Staphylococcal Infections ; Inflammation ; Bone Marrow Cells ; Telomere ; *Telomerase ; Cellular Senescence ; },
abstract = {The mechanism of systemic osteoporosis caused by chronic infection is not completely clear, and there is a lack of reasonable interventions for this disease. In this study, heat-killed S. aureus (HKSA) was applied to simulate the inflammation caused by the typical clinical pathogen and to explore the mechanism of systemic bone loss caused by it. In this study, we found that the systemic application of HKSA caused bone loss in mice. Further exploration found that HKSA caused cellular senescence, telomere length shortening, and telomere dysfunction-induced foci (TIF) in limb bones. As a well-known telomerase activator, cycloastragenol (CAG) significantly alleviated HKSA-induced telomere erosion and bone loss. These results suggested that telomere erosion in bone marrow cells is a possible mechanism of HKSA-induced bone loss. CAG may protect against HKSA-induced bone loss by alleviating telomere erosion in bone marrow cells.},
}
@article {pmid36833352,
year = {2023},
author = {Fattet, AJ and Chaillot, M and Koscinski, I},
title = {Telomere Length, a New Biomarker of Male (in)Fertility? A Systematic Review of the Literature.},
journal = {Genes},
volume = {14},
number = {2},
pages = {},
pmid = {36833352},
issn = {2073-4425},
mesh = {Humans ; Male ; *Semen ; *Infertility, Male ; Fertility ; Telomere ; Biomarkers ; },
abstract = {Male factors are suspected in around half cases of infertility, of which up to 40% are diagnosed as idiopathic. In the context of a continuously increased resort to ART and increased decline of semen parameters, it is of greatest interest to evaluate an additional potential biomarker of sperm quality. According to PRISMA guidelines, this systematic review of the literature selected studies evaluating telomere length in sperm and/or in leukocytes as a potential male fertility biomarker. Twenty-two publications (3168 participants) were included in this review of experimental evidence. For each study, authors determined if there was a correlation between telomere length and semen parameters or fertility outcomes. Of the 13 studies concerning sperm telomere length (STL) and semen parameters, ten found an association between short STL and altered parameters. Concerning the impact of STL on ART results, the data are conflicting. However, eight of the 13 included studies about fertility found significantly longer sperm telomeres in fertile men than in infertile men. In leukocytes, the seven studies reported conflicting findings. Shorter sperm telomeres appear to be associated with altered semen parameters or male infertility. Telomere length may be considered as a new molecular marker of spermatogenesis and sperm quality, and thus is related to male fertility potential. However, additional studies are needed to define the place of the STL in the assessment of individual fertility.},
}
@article {pmid36833275,
year = {2023},
author = {Barnes, RP and Thosar, SA and Opresko, PL},
title = {Telomere Fragility and MiDAS: Managing the Gaps at the End of the Road.},
journal = {Genes},
volume = {14},
number = {2},
pages = {},
pmid = {36833275},
issn = {2073-4425},
support = {R35 ES030396/ES/NIEHS NIH HHS/United States ; K99 ES033771/ES/NIEHS NIH HHS/United States ; R01 CA207342/CA/NCI NIH HHS/United States ; },
mesh = {*DNA Replication ; *DNA/metabolism ; Mitosis ; Phenotype ; Telomere/metabolism ; },
abstract = {Telomeres present inherent difficulties to the DNA replication machinery due to their repetitive sequence content, formation of non-B DNA secondary structures, and the presence of the nucleo-protein t-loop. Especially in cancer cells, telomeres are hot spots for replication stress, which can result in a visible phenotype in metaphase cells termed "telomere fragility". A mechanism cells employ to mitigate replication stress, including at telomeres, is DNA synthesis in mitosis (MiDAS). While these phenomena are both observed in mitotic cells, the relationship between them is poorly understood; however, a common link is DNA replication stress. In this review, we will summarize what is known to regulate telomere fragility and telomere MiDAS, paying special attention to the proteins which play a role in these telomere phenotypes.},
}
@article {pmid36831502,
year = {2023},
author = {Pauleck, S and Sinnott, JA and Zheng, YL and Gadalla, SM and Viskochil, R and Haaland, B and Cawthon, RM and Hoffmeister, A and Hardikar, S},
title = {Association of Telomere Length with Colorectal Cancer Risk and Prognosis: A Systematic Review and Meta-Analysis.},
journal = {Cancers},
volume = {15},
number = {4},
pages = {},
pmid = {36831502},
issn = {2072-6694},
support = {K07 CA222060//National Cancer Institute/ ; U01ES031786//National Cancer Institute/ ; P30CA042014//National Cancer Institute/ ; intramural program//National Cancer Institute/ ; Promotionsstipendium//DGHO/ ; Promotionsstipendium//Stiftung Lebensblicke/ ; },
abstract = {(1) Background: Colorectal cancer risk and survival have previously been associated with telomere length in peripheral blood leukocytes and tumor tissue. A systematic review and meta-analysis of the literature was conducted. The PubMed, Embase, and Web of Science databases were searched through March 2022. (2) Methods: Relevant studies were identified through database searching following PRISMA guidelines. Risk estimates were extracted from identified studies; meta-analyses were conducted using random effects models. (3) Results: Fourteen studies were identified (eight on risk; six on survival) through systematic review. While no association was observed between circulating leukocyte telomere length and the risk of colorectal cancer [overall OR (95% CI) = 1.01 (0.82-1.24)], a worse survival for those with shorter telomeres in leukocytes and longer telomeres in tumor tissues was observed [Quartile1/Quartile2-4 overall HR (95% CI) = 1.41 (0.26-7.59) and 0.82 (0.69-0.98), respectively]. (4) Conclusions: Although there was no association with colorectal cancer risk, a poorer survival was observed among those with shorter leukocyte telomere length. Future larger studies evaluating a potentially non-linear relationship between telomeres and colorectal cancer are needed.},
}
@article {pmid36831134,
year = {2023},
author = {Hernández-Álvarez, D and Rosado-Pérez, J and Gavia-García, G and Arista-Ugalde, TL and Aguiñiga-Sánchez, I and Santiago-Osorio, E and Mendoza-Núñez, VM},
title = {Aging, Physical Exercise, Telomeres, and Sarcopenia: A Narrative Review.},
journal = {Biomedicines},
volume = {11},
number = {2},
pages = {},
pmid = {36831134},
issn = {2227-9059},
abstract = {Human aging is a gradual and adaptive process characterized by a decrease in the homeostatic response, leading to biochemical and molecular changes that are driven by hallmarks of aging, such as oxidative stress (OxS), chronic inflammation, and telomere shortening. One of the diseases associated with the hallmarks of aging, which has a great impact on functionality and quality of life, is sarcopenia. However, the relationship between telomere length, sarcopenia, and age-related mortality has not been extensively studied. Moderate physical exercise has been shown to have a positive effect on sarcopenia, decreasing OxS and inflammation, and inducing protective effects on telomeric DNA. This results in decreased DNA strand breaks, reduced OxS and IA, and activation of repair pathways. Higher levels of physical activity are associated with an apparent increase in telomere length. This review aims to present the current state of the art of knowledge on the effect of physical exercise on telomeric maintenance and activation of repair mechanisms in sarcopenia.},
}
@article {pmid36830739,
year = {2023},
author = {Ueno, M},
title = {Exploring Genetic Interactions with Telomere Protection Gene pot1 in Fission Yeast.},
journal = {Biomolecules},
volume = {13},
number = {2},
pages = {},
pmid = {36830739},
issn = {2218-273X},
support = {20K06488//MEXT/JSPS KAKENHI/ ; },
mesh = {Humans ; *Schizosaccharomyces/metabolism ; Shelterin Complex ; *Schizosaccharomyces pombe Proteins/metabolism ; Telomere-Binding Proteins/genetics/metabolism ; Chromosomes, Fungal ; Telomere/metabolism ; },
abstract = {The regulation of telomere length has a significant impact on cancer risk and aging in humans. Circular chromosomes are found in humans and are often unstable during mitosis, resulting in genome instability. Some types of cancer have a high frequency of a circular chromosome. Fission yeast is a good model for studying the formation and stability of circular chromosomes as deletion of pot1 (encoding a telomere protection protein) results in rapid telomere degradation and chromosome fusion. Pot1 binds to single-stranded telomere DNA and is conserved from fission yeast to humans. Loss of pot1 leads to viable strains in which all three fission yeast chromosomes become circular. In this review, I will introduce pot1 genetic interactions as these inform on processes such as the degradation of uncapped telomeres, chromosome fusion, and maintenance of circular chromosomes. Therefore, exploring genes that genetically interact with pot1 contributes to finding new genes and/or new functions of genes related to the maintenance of telomeres and/or circular chromosomes.},
}
@article {pmid36829978,
year = {2023},
author = {Péntek, S and Várnagy, &#xc1; and Farkas, B and Mauchart, P and Gödöny, K and Varjas, T and Kőszegi, T and Kaltenecker, P and Jakabfi-Csepregi, R and Kovács, K and Bódis, J and Sulyok, E},
title = {Telomere Length and Telomerase Activity of Granulosa Cells and Follicular Fluid in Women Undergoing In Vitro Fertilization.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {12},
number = {2},
pages = {},
pmid = {36829978},
issn = {2076-3921},
abstract = {This study aimed to evaluate the interrelationship between telomere length, telomerase activity and oxidative DNA damage in patients undergoing in vitro fertilization (IVF). This single-center, observational clinical study comprised 102 unselected, consecutive patients with various infertility diagnoses. Granulosa cells (GCs) and follicular fluid (FF) were analyzed simultaneously for telomere functions and for the marker of oxidative DNA damage, 8-hydroxy-2-deoxyguanosine (8-OHdG). An Absolute Human Telomere Lengths Quantification qPCR Assay kit and Telomerase Activity Quantification qPCR Assay kit (Nucleotestbio, Budapest, Hungary), as well as an 8-OHdG ELISA kit (Abbexa Ltd., Cambridge, United Kingdom) were used for analyses. Similar telomere lengths were found in GCs and FF, however telomerase activity was markedly depressed, while 8-OHdG levels were markedly elevated in FF compared with those in GCs (p < 0.01). Telomere lengths were independent of telomerase activity both in GCs and FF. However, GC 8-OHdG was inversely related to telomerase activity in GCs and FF (p < 0.05). Importantly, 8-OHdG levels both in GCs and FF had significant negative impact on the number of the retrieved and MII oocytes (p < 0.01), whereas FF 8-OHdG was negatively related further to the number of fertilized oocytes and blastocysts (p < 0.01). In conclusion, we could not confirm the direct association of telomere function and reproductive potential. However, oxidative DNA damage, as mainly reflected by 8-OHdG, adversely affected early markers of IVF outcome and clinical pregnancies.},
}
@article {pmid36826621,
year = {2023},
author = {Stock, AJ and Ayyar, S and Kashyap, A and Wang, Y and Yanai, H and Starost, MF and Tanaka-Yano, M and Bodogai, M and Sun, C and Wang, Y and Gong, Y and Puligilla, C and Fang, EF and Bohr, VA and Liu, Y and Beerman, I},
title = {Boosting NAD ameliorates hematopoietic impairment linked to short telomeres in vivo.},
journal = {GeroScience},
volume = {45},
number = {4},
pages = {2213-2228},
pmid = {36826621},
issn = {2509-2723},
support = {Intramural Funding/AG/NIA NIH HHS/United States ; Intramural Funding/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; Animals ; Mice ; NAD ; Telomere/metabolism ; *Dyskeratosis Congenita/genetics/metabolism ; Inflammation ; *Hematopoietic Stem Cell Transplantation ; },
abstract = {Short telomeres are a defining feature of telomere biology disorders (TBDs), including dyskeratosis congenita (DC), for which there is no effective general cure. Patients with TBDs often experience bone marrow failure. NAD, an essential metabolic coenzyme, is decreased in models of DC. Herein, using telomerase reverse transcriptase null (Tert[-/-]) mice with critically short telomeres, we investigated the effect of NAD supplementation with the NAD precursor, nicotinamide riboside (NR), on features of health span disrupted by telomere impairment. Our results revealed that NR ameliorated body weight loss in Tert[-/-] mice and improved telomere integrity and telomere dysfunction-induced systemic inflammation. NR supplementation also mitigated myeloid skewing of Tert[-/-] hematopoietic stem cells. Furthermore, NR alleviated villous atrophy and inflammation in the small intestine of Tert[-/-] transplant recipient mice. Altogether, our findings support NAD intervention as a potential therapeutic strategy to enhance aspects of health span compromised by telomere attrition.},
}
@article {pmid36811398,
year = {2023},
author = {Eastwood, JR and Dupoué, A and Delhey, K and Verhulst, S and Cockburn, A and Peters, A},
title = {When does early-life telomere length predict survival? A case study and meta-analysis.},
journal = {Molecular ecology},
volume = {32},
number = {11},
pages = {3000-3013},
doi = {10.1111/mec.16894},
pmid = {36811398},
issn = {1365-294X},
mesh = {Animals ; *Longevity/genetics ; Telomere Shortening ; Telomere/genetics ; *Songbirds/genetics ; Research Design ; Mammals/genetics ; },
abstract = {Suboptimal conditions during development can shorten telomeres, the protective DNA caps on the end of chromosomes. Shorter early-life telomere length (TL) can indicate reduced somatic maintenance, leading to lower survival and shorter lifespan. However, despite some clear evidence, not all studies show a relationship between early-life TL and survival or lifespan, which may be due to differences in biology or study design (e.g., survival period measured). In superb fairy-wrens (Malurus cyaneus), we assessed whether early-life TL predicts mortality across different life-history stages (fledgling, juvenile, adult). However, in contrast to a similar study on a congener, early-life TL did not predict mortality across any life stage in this species. We then performed a meta-analysis including 32 effect sizes from 23 studies (15 birds and three mammals) to quantify the effect of early-life TL on mortality whilst taking into consideration potential sources of biological and methodological variation. Overall, the effect of early-life TL on mortality was significant, corresponding to a 15% reduction in mortality risk with each standard deviation increase in TL. However, the effect became weaker when correcting for publication bias. Contrary to our predictions, there was no evidence that effects of early-life TL on mortality varied with species lifespan or the period over which survival was measured. However, negative effects of early-life TL on mortality risk were pervasive throughout life. These results imply that effects of early-life TL on mortality are more likely to be context-dependent than age-dependent, although substantial power and publication bias issues highlight the need for more research.},
}
@article {pmid36810772,
year = {2023},
author = {Strzyz, P},
title = {From shortening telomeres to replicative crisis.},
journal = {Nature reviews. Molecular cell biology},
volume = {24},
number = {4},
pages = {239},
pmid = {36810772},
issn = {1471-0080},
mesh = {*Telomere/genetics/metabolism ; Cellular Senescence ; DNA Replication/genetics ; Telomere Shortening ; *Telomerase/metabolism ; },
}
@article {pmid36809211,
year = {2023},
author = {Li, Z and Cai, K and Sun, Y and Zhou, D and Yan, J and Luo, S and Huang, G and Gao, Y and Li, W},
title = {Folic acid protects against age-associated apoptosis and telomere attrition of neural stem cells in senescence-accelerated mouse prone 8.},
journal = {Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme},
volume = {48},
number = {5},
pages = {393-402},
doi = {10.1139/apnm-2022-0111},
pmid = {36809211},
issn = {1715-5320},
mesh = {Mice ; Male ; Animals ; *Folic Acid/pharmacology ; In Situ Hybridization, Fluorescence ; Aging ; *Neural Stem Cells ; Apoptosis ; Telomere ; },
abstract = {Folic acid (FA) could improve cognitive performance and attenuate brain cell injury in the aging brain; FA supplementation is also associated with inhibiting neural stem cell (NSC) apoptosis. However, its role in age-associated telomere attrition remains unclear. We hypothesized that FA supplementation attenuates age-associated apoptosis of NSCs in mice via alleviating telomere attrition in senescence-accelerated mouse prone 8 (SAMP8). In this study, 4-month-old male SAMP8 mice were assigned equal numbers to four different diet groups (n = 15). Fifteen age-matched senescence-accelerated mouse resistant 1 mice, fed with the FA-normal diet, were used as the standard aging control group. After FA treatment for 6 months, all mice were sacrificed. NSC apoptosis, proliferation, oxidative damage, and telomere length were evaluated by immunofluorescence and Q-fluorescent in situ hybridization. The results showed that FA supplementation inhibited age-associated NSC apoptosis and prevented telomere attrition in the cerebral cortex of SAMP8 mice. Importantly, this effect might be explained by the decreased levels of oxidative damage. In conclusion, we demonstrate it may be one of the mechanisms by which FA inhibits age-associated NSC apoptosis by alleviating telomere length shortening.},
}
@article {pmid36805596,
year = {2023},
author = {Turkalo, TK and Maffia, A and Schabort, JJ and Regalado, SG and Bhakta, M and Blanchette, M and Spierings, DCJ and Lansdorp, PM and Hockemeyer, D},
title = {A non-genetic switch triggers alternative telomere lengthening and cellular immortalization in ATRX deficient cells.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {939},
pmid = {36805596},
issn = {2041-1723},
mesh = {Humans ; Telomere Homeostasis/genetics ; Telomere/genetics ; Cell Differentiation/genetics ; *Telomerase/genetics ; *Pluripotent Stem Cells ; X-linked Nuclear Protein/genetics ; },
abstract = {Alternative Lengthening of Telomeres (ALT) is an aberrant DNA recombination pathway which grants replicative immortality to approximately 10% of all cancers. Despite this high prevalence of ALT in cancer, the mechanism and genetics by which cells activate this pathway remain incompletely understood. A major challenge in dissecting the events that initiate ALT is the extremely low frequency of ALT induction in human cell systems. Guided by the genetic lesions that have been associated with ALT from cancer sequencing studies, we genetically engineered primary human pluripotent stem cells to deterministically induce ALT upon differentiation. Using this genetically defined system, we demonstrate that disruption of the p53 and Rb pathways in combination with ATRX loss-of-function is sufficient to induce all hallmarks of ALT and results in functional immortalization in a cell type-specific manner. We further demonstrate that ALT can be induced in the presence of telomerase, is neither dependent on telomere shortening nor crisis, but is rather driven by continuous telomere instability triggered by the induction of differentiation in ATRX-deficient stem cells.},
}
@article {pmid36805537,
year = {2023},
author = {Han, MH and Lee, EH and Park, HH and Choi, SH and Koh, SH},
title = {Relationship between telomere shortening and early subjective depressive symptoms and cognitive complaints in older adults.},
journal = {Aging},
volume = {15},
number = {4},
pages = {914-931},
pmid = {36805537},
issn = {1945-4589},
mesh = {Aged ; Humans ; Cognition ; *Cognitive Dysfunction/psychology ; *Depression/psychology ; Surveys and Questionnaires ; Telomere ; Telomere Shortening ; Middle Aged ; },
abstract = {Telomere length (TL) has been reported to be associated with depression and cognitive impairment in elderly. Early detection of depression and cognitive impairment is important to delay disease progression. Therefore, we aimed to identify whether TL is associated with early subjective depressive symptoms and cognitive complaints among healthy elderly subjects. This study was a multicenter, outcome assessor-blinded, 24-week, randomized controlled trial (RCT). Measurement of questionnaire and physical activity scores and blood sample analyses were performed at baseline and after six months of follow-up in all study participants. Linear regression analyses were performed to identify whether early subjective depressive symptoms, cognitive complaints, and several blood biomarkers are associated with TL. Altogether, 137 relatively healthy elderly individuals (60-79 years old) were enrolled in this prospective RCT. We observed an approximate decrease of 0.06 and 0.11-0.14 kbps of TL per one point increase in the geriatric depression scale and cognitive complaint interview scores, respectively, at baseline and after six months of follow-up. We also found an approximate decrease of 0.08-0.09 kbps of TL per one point increase in interleukin (IL)-6 levels at baseline and after six months of follow-up. Our study showed that both early subjective depressive symptoms and cognitive complaints were associated with a relatively shorter TL in relatively healthy elderly individuals. In addition, based on our findings, we believe that IL-6 plays an important role in the relationship between shortening TL and early subjective depressive symptoms and cognitive complaints.},
}
@article {pmid36798520,
year = {2022},
author = {Li, Y and Yang, S and Liao, M and Zheng, Z and Li, M and Wei, X and Liu, M and Yang, L},
title = {Association between genetically predicted leukocyte telomere length and non-scarring alopecia: A two-sample Mendelian randomization study.},
journal = {Frontiers in immunology},
volume = {13},
number = {},
pages = {1072573},
pmid = {36798520},
issn = {1664-3224},
mesh = {Humans ; *Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Alopecia Areata ; Leukocytes ; Telomere/genetics ; },
abstract = {BACKGROUND: The most commonly acknowledged non-scarring alopecia are androgenetic alopecia (AGA) and alopecia areata (AA). Previous studies have revealed various risk factors associated with alopecia. However, the relationship between leukocyte telomere length (LTL) and non-scarring alopecia remains unclear.<br><br>METHODS: A two-sample Mendelian randomization (MR) analysis was performed to evaluate the causality between genetically predicted LTL and the risk of non-scarring alopecia. MR analyses were performed using the inverse variance-weighted (IVW) method and complemented with other MR methods.<br><br>RESULTS: The summary statistics of the genome-wide association studies (GWAS) for AGA and AA were obtained from the FinnGen biobank, which included 119,185 and 211,428 individuals, respectively. A total of 126 single nucleotide polymorphisms (SNPs) with genome-wide significance were selected as the instrumental variables for LTL. The MR analyses suggested a causal relationship between LTL and AGA, and the risk of AGA increased by 3.19 times as the genetically predicted LTL was shortened by one standard deviation in log transformed form under the IVW method (OR&#xa0;=&#xa0;4.19, 95% CI&#xa0;=&#xa0;1.20-14.61, p&#xa0;=&#xa0;0.024). The other MR methods also demonstrated a similar trend of the effect of LTL on AGA. There was no causal relationship between LTL and AA (p&#xa0;>&#xa0;0.05). Sensitivity analyses further demonstrated that the current results were less likely to be affected by confounders and bias.<br><br>CONCLUSION: Our results suggested a potential causal relationship between LTL and AGA, and shortened LTL was associated with an increased risk of AGA.},
}
@article {pmid36798426,
year = {2023},
author = {Li, F and Wang, Y and Hwang, I and Jang, JY and Xu, L and Deng, Z and Yu, EY and Cai, Y and Wu, C and Han, Z and Huang, YH and Huang, X and Zhang, L and Yao, J and Lue, NF and Lieberman, PM and Ying, H and Paik, J and Zheng, H},
title = {Histone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2023.02.10.528023},
pmid = {36798426},
abstract = {Telomere length maintenance is essential for cellular immortalization and tumorigenesis. 5% - 10% of human cancers rely on a recombination-based mechanism termed alternative lengthening of telomeres (ALT) to sustain their replicative immortality, yet there are currently no targeted therapies. Through CRISPR/Cas9-based genetic screens in an ALT-immortalized isogenic cellular model, here we identify histone lysine demethylase KDM2A as a molecular vulnerability selectively for cells contingent on ALT-dependent telomere maintenance. Mechanistically, we demonstrate that KDM2A is required for dissolution of the ALT-specific telomere clusters following homology-directed telomere DNA synthesis. We show that KDM2A promotes de-clustering of ALT multitelomeres through facilitating isopeptidase SENP6-mediated SUMO deconjugation at telomeres. Inactivation of KDM2A or SENP6 impairs post-recombination telomere de-SUMOylation and thus dissolution of ALT telomere clusters, leading to gross chromosome missegregation and mitotic cell death. These findings together establish KDM2A as a selective molecular vulnerability and a promising drug target for ALT-dependent cancers.},
}
@article {pmid36797576,
year = {2023},
author = {Han, M and Liu, S and Ji, JR and Wu, YF and Chang, KW and Zhang, JY and Wei, JN},
title = {[Interaction of polycyclic aromatic hydrocarbon DNA adducts and telomere length on missed abortion].},
journal = {Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]},
volume = {57},
number = {2},
pages = {193-199},
doi = {10.3760/cma.j.cn112150-20220322-00274},
pmid = {36797576},
issn = {0253-9624},
support = {201901D111206//Shanxi Provincial Basic Research Project of China/ ; 2020086//Shanxi Provincial Health Commission Scientific Research Project of China/ ; },
mesh = {Humans ; Female ; Pregnancy ; Young Adult ; Adult ; DNA Adducts ; *Abortion, Missed/chemically induced ; *Polycyclic Aromatic Hydrocarbons ; *Abortion, Spontaneous/chemically induced ; Telomere/chemistry ; },
abstract = {Objective: To analyze the contribution and interaction of polycyclic aromatic hydrocarbons (PAH)-DNA adducts and changes of telomere length (TL) on missed abortion. Methods: From March to December 2019, patients with missed abortion in the First Hospital of Shanxi Medical University and pregnant women with normal pregnancy but voluntary abortion in the same department during the same period were selected and divided into a case group and a control group. Questionnaire was used to investigate the general situation and the pregnancy situation of the subjects. The abortion villi were collected and the content of PAH-DNA adducts and TL was detected. Logistic regression model was used to analyze the associated factors of missed abortion. R epiR package and Mediation package were used to analyze the effect and relationship between PAH-DNA adducts and TL on missed abortion. Results: The age of the subjects was(29.92±5.69)years old. The M(Q1,Q3)of PAH-DNA adducts was 453.75(404.61, 504.72) pg/ml. The M(Q1,Q3)of TL was 1.21(0.77, 1.72). The content of PAH-DNA adducts in the case group was higher than that in the control group (Z=-2.10, P=0.036), while the TL was lower than that in the control group (Z=-4.05, P<0.001). Multivariate logistic regression showed that low, medium and high levels of PAH-DNA adducts (OR=3.17,95%CI:1.41-7.14;OR=2.85,95%CI:1.25-6.52;OR=2.46,95%CI:1.07-5.64), and long, medium and short levels of TL (OR=2.50,95%CI:1.11-5.63;OR=3.32,95%CI:1.45-7.56;OR=3.22,95%CI:1.42-7.26) were all risk factors for missed abortion. The medium level of PAH-DNA adducts had a 2.76-fold higher risk of shortened TL than those with the lowest level, and no mediating role of TL was found. The stratified analysis showed that when the TL level was longer (>1.21), the low and high levels of PAH-DNA adducts were associated with missed abortion (all P<0.05); when the TL level was shorter (<1.21), the medium level of PAH-DNA adducts was associated with abortion (P=0.025). At lower levels of PAH-DNA adducts, no effect of TL on missed abortion was observed, while, at higher levels, TL was strongly associated with missed abortion (OR=7.50,95%CI:1.95-28.82;OR=6.04,95%CI:1.54-23.65;OR=9.05,95%CI:2.34-35.04). The interaction analysis found that the AP was 0.72 (95%CI: 0.46-0.99), and the SI was 5.21 (95%CI: 2.30-11.77). Conclusion: The high level of PAH-DNA adducts and shortened TL may increase the risk of missed abortion, and there may be a positive additive interaction between the two factors on missed abortion.},
}
@article {pmid36797493,
year = {2023},
author = {Rautiainen, M and Nurk, S and Walenz, BP and Logsdon, GA and Porubsky, D and Rhie, A and Eichler, EE and Phillippy, AM and Koren, S},
title = {Telomere-to-telomere assembly of diploid chromosomes with Verkko.},
journal = {Nature biotechnology},
volume = {41},
number = {10},
pages = {1474-1482},
pmid = {36797493},
issn = {1546-1696},
support = {F32 GM134558/GM/NIGMS NIH HHS/United States ; R01 HG010169/HG/NHGRI NIH HHS/United States ; Z99 HG999999/ImNIH/Intramural NIH HHS/United States ; R01 HG002385/HG/NHGRI NIH HHS/United States ; },
mesh = {Humans ; Sequence Analysis, DNA/methods ; *Diploidy ; *Genomics/methods ; Genome, Human/genetics ; Telomere/genetics ; High-Throughput Nucleotide Sequencing/methods ; },
abstract = {The Telomere-to-Telomere consortium recently assembled the first truly complete sequence of a human genome. To resolve the most complex repeats, this project relied on manual integration of ultra-long Oxford Nanopore sequencing reads with a high-resolution assembly graph built from long, accurate PacBio high-fidelity reads. We have improved and automated this strategy in Verkko, an iterative, graph-based pipeline for assembling complete, diploid genomes. Verkko begins with a multiplex de Bruijn graph built from long, accurate reads and progressively simplifies this graph by integrating ultra-long reads and haplotype-specific markers. The result is a phased, diploid assembly of both haplotypes, with many chromosomes automatically assembled from telomere to telomere. Running Verkko on the HG002 human genome resulted in 20 of 46 diploid chromosomes assembled without gaps at 99.9997% accuracy. The complete assembly of diploid genomes is a critical step towards the construction of comprehensive pangenome databases and chromosome-scale comparative genomics.},
}
@article {pmid36779965,
year = {2023},
author = {Bountziouka, V and Hansell, AL and Nelson, CP and Codd, V and Samani, NJ},
title = {Large-Scale Analysis of the Association between Air Pollutants and Leucocyte Telomere Length in the UK Biobank.},
journal = {Environmental health perspectives},
volume = {131},
number = {2},
pages = {27701},
pmid = {36779965},
issn = {1552-9924},
support = {MR/M012816/1/MRC_/Medical Research Council/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; SP/16/4/32697/BHF_/British Heart Foundation/United Kingdom ; BRC-1215-20010/DH_/Department of Health/United Kingdom ; },
mesh = {*Air Pollutants ; Biological Specimen Banks ; Telomere ; United Kingdom ; Leukocytes ; },
}
@article {pmid36778189,
year = {2023},
author = {Yue, J and Chen, Q and Wang, Y and Zhang, L and Ye, C and Wang, X and Cao, S and Lin, Y and Huang, W and Xian, H and Qin, H and Wang, Y and Zhang, S and Wu, Y and Wang, S and Yue, Y and Liu, Y},
title = {Telomere-to-telomere and gap-free reference genome assembly of the kiwifruit Actinidia chinensis.},
journal = {Horticulture research},
volume = {10},
number = {2},
pages = {uhac264},
pmid = {36778189},
issn = {2662-6810},
abstract = {Kiwifruit is an economically and nutritionally important fruit crop with extremely high contents of vitamin C. However, the previously released versions of kiwifruit genomes all have a mass of unanchored or missing regions. Here, we report a highly continuous and completely gap-free reference genome of Actinidia chinensis cv. 'Hongyang', named Hongyang v4.0, which is the first to achieve two de novo haploid-resolved haplotypes, HY4P and HY4A. HY4P and HY4A have a total length of 606.1 and 599.6 Mb, respectively, with almost the entire telomeres and centromeres assembled in each haplotype. In comparison with Hongyang v3.0, the integrity and contiguity of Hongyang v4.0 is markedly improved by filling all unclosed gaps and correcting some misoriented regions, resulting in ~38.6-39.5 Mb extra sequences, which might affect 4263 and 4244 protein-coding genes in HY4P and HY4A, respectively. Furthermore, our gap-free genome assembly provides the first clue for inspecting the structure and function of centromeres. Globally, centromeric regions are characterized by higher-order repeats that mainly consist of a 153-bp conserved centromere-specific monomer (Ach-CEN153) with different copy numbers among chromosomes. Functional enrichment analysis of the genes located within centromeric regions demonstrates that chromosome centromeres may not only play physical roles for linking a pair of sister chromatids, but also have genetic features for participation in the regulation of cell division. The availability of the telomere-to-telomere and gap-free Hongyang v4.0 reference genome lays a solid foundation not only for illustrating genome structure and functional genomics studies but also for facilitating kiwifruit breeding and improvement.},
}
@article {pmid36776610,
year = {2023},
author = {Cai, Y and Zhong, YD and Zhang, H and Lu, PL and Liang, YY and Hu, B and Wu, H},
title = {Association between dietary vitamin C and telomere length: A cross-sectional study.},
journal = {Frontiers in nutrition},
volume = {10},
number = {},
pages = {1025936},
pmid = {36776610},
issn = {2296-861X},
abstract = {BACKGROUND: Currently, telomere length is known to reflect the replication potential and longevity of cells, and many studies have reported that telomere length is associated with age-related diseases and biological aging. Studies have also shown that vitamin C acts as an oxidant and free radical scavenger to protect cells from oxidative stress and telomere wear, thus achieving anti-aging effects. At present, there are few and incomplete studies on the relationship between vitamin C and telomere length, so this study aims to explore the relationship between vitamin C and telomere length.<br><br>METHODS: This study used cross-sectional data from the National Health and Nutrition Examination Surveys (NHANES) database from 1999 to 2002, a total of 7,094 participants were selected from all races in the United States. Male participants accounted for 48.2% and female participants accounted for 51.8%. The correlation between vitamin C and telomere length was assessed using a multiple linear regression model, and the effect of dietary vitamin C on telomere length was obtained after adjusting for confounding factors such as age, gender, race, body mass index (BMI), and poverty income ratio (PIR).<br><br>RESULTS: This cross-sectional study showed that vitamin C was positively correlated with telomere length, with greater dietary vitamin C intake associated with longer telomeres (&#x3b2; = 0.03, 95% CI: 0.01-0.05, P = 0.003).<br><br>CONCLUSION: This study shows that vitamin C intake is positively correlated with human telomere length, which is of guiding significance for our clinical guidance on people's health care, but our study need to be confirmed by more in-depth and comprehensive other research results.},
}
@article {pmid36767300,
year = {2023},
author = {Pasha, Q and Rain, M and Tasnim, S and Kanipakam, H and Thinlas, T and Mohammad, G},
title = {The Telomere-Telomerase System Is Detrimental to Health at High-Altitude.},
journal = {International journal of environmental research and public health},
volume = {20},
number = {3},
pages = {},
pmid = {36767300},
issn = {1660-4601},
mesh = {Humans ; Altitude ; *Altitude Sickness/genetics ; Biomarkers ; Case-Control Studies ; *Telomerase/genetics ; *Telomere/genetics ; *DNA Damage/genetics ; },
abstract = {The hypobaric-hypoxia environment at high-altitude (HA, >2500 m) may influence DNA damage due to the production of reactive molecular species and high UV radiation. The telomere system, vital to chromosomal integrity and cellular viability, is prone to oxidative damages contributing to the severity of high-altitude disorders such as high-altitude pulmonary edema (HAPE). However, at the same time, it is suggested to sustain physical performance. This case-control study, comprising 210 HAPE-free (HAPE-f) sojourners, 183 HAPE-patients (HAPE-p) and 200 healthy highland natives (HLs) residing at ~3500 m, investigated telomere length, telomerase activity, and oxidative stress biomarkers. Fluidigm SNP genotyping screened 65 single nucleotide polymorphisms (SNPs) in 11 telomere-maintaining genes. Significance was attained at p ≤ 0.05 after adjusting for confounders and correction for multiple comparisons. Shorter telomere length, decreased telomerase activity and increased oxidative stress were observed in HAPE patients; contrarily, longer telomere length and elevated telomerase activity were observed in healthy HA natives compared to HAPE-f. Four SNPs and three haplotypes are associated with HAPE, whereas eight SNPs and nine haplotypes are associated with HA adaptation. Various gene-gene interactions and correlations between/among clinical parameters and biomarkers suggested the presence of a complex interplay underlining HAPE and HA adaptation physiology. A distinctive contribution of the telomere-telomerase system contributing to HA physiology is evident in this study. A normal telomere system may be advantageous in endurance training.},
}
@article {pmid36759506,
year = {2023},
author = {Falcinelli, M and Dell'Omo, G and Grassi, E and Mariella, E and Leto, SM and Scardellato, S and Lorenzato, A and Arena, S and Bertotti, A and Trusolino, L and Bardelli, A and d'Adda di Fagagna, F},
title = {Colorectal cancer patient-derived organoids and cell lines harboring ATRX and/or DAXX mutations lack Alternative Lengthening of Telomeres (ALT).},
journal = {Cell death &amp; disease},
volume = {14},
number = {2},
pages = {96},
pmid = {36759506},
issn = {2041-4889},
mesh = {Humans ; X-linked Nuclear Protein/genetics/metabolism ; *Intellectual Disability ; Telomere Homeostasis/genetics ; *alpha-Thalassemia ; Co-Repressor Proteins/genetics/metabolism ; *Telomerase/genetics/metabolism ; Mutation/genetics ; Cell Line ; Telomere/genetics/metabolism ; Organoids/metabolism ; *Colorectal Neoplasms/genetics ; Molecular Chaperones/genetics/metabolism ; },
abstract = {Telomere maintenance is necessary to maintain cancer cell unlimited viability. However, the mechanisms maintaining telomere length in colorectal cancer (CRC) have not been extensively investigated. Telomere maintenance mechanisms (TMM) include the re-expression of telomerase or alternative lengthening of telomeres (ALT). ALT is genetically associated with somatic alterations in alpha-thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes. Cells displaying ALT present distinctive features including C-circles made of telomeric DNA, long and heterogenous telomeric tracts, and telomeric DNA co-localized with promyelocytic leukemia (PML) bodies forming so-called ALT-associated PML bodies (APBs). Here, we identified mutations in ATRX and/or DAXX genes in an extensive collection of CRC samples including 119 patient-derived organoids (PDOs) and 232 established CRC cell lines. C-circles measured in CRC PDOs and cell lines showed low levels overall. We also observed that CRC PDOs and cell lines did not display a significant accumulation of APBs or long telomeres with no appreciable differences between wild-type and mutated ATRX/DAXX samples. Overall, our extensive analyses indicate that CRC is not prone to engage ALT, even when carrying genetic lesions in ATRX and/or DAXX, and support the notion that ATRX/DAXX genomic footprints are not reliable predictors of ALT.},
}
@article {pmid36758285,
year = {2023},
author = {Vostatek, R and Hohensinner, P and Nopp, S and Haider, P and Englisch, C and Pointner, J and Pabinger, I and Ay, C},
title = {Association of telomere length and mitochondrial DNA copy number, two biomarkers of biological aging, with the risk of venous thromboembolism.},
journal = {Thrombosis research},
volume = {223},
number = {},
pages = {168-173},
doi = {10.1016/j.thromres.2023.01.031},
pmid = {36758285},
issn = {1879-2472},
mesh = {Male ; Humans ; Female ; *DNA, Mitochondrial/genetics ; *Venous Thromboembolism ; DNA Copy Number Variations ; Case-Control Studies ; Telomere ; Aging/genetics ; Mitochondria ; Biomarkers ; },
abstract = {BACKGROUND: Venous thromboembolism (VTE) is the third most common cardiovascular disease and occurs in all age groups, albeit the risk increases considerably with age. Previous research indicates mitochondrial dysfunction and telomere shortening in cardiovascular aging. However, in the context of VTE this has not been investigated in detail.<br><br>AIM: We aimed to explore biomarkers reflecting biological aging (i.e. human mitochondrial DNA copy number (mtDNA) and telomere length) and their association with VTE.<br><br>METHODS: mtDNA and telomere length were measured in a case-control study of 116 patients with a history of VTE and 128 age- and sex-matched healthy individuals from isolated blood using a qPCR-based assay kit. Cases had at least one unprovoked VTE event and were enrolled no earlier than 3&#xa0;months after the last VTE event.<br><br>RESULTS: The mtDNA copy number was significantly lower in VTE cases compared to controls (median [IQR]: 663 per diploid cells [78.75-2204.5] vs. 2832 per diploid cells [724-4350]; p&#xa0;<&#xa0;0.001). After adjustment for age, sex, BMI, and smoking, mtDNA copy number was independently associated with VTE risk (odds ratio per increase in 400 mtDNA per diploid cell: 0.889, 95%CI 0.834-0.947). mtDNA copy numbers were significantly different between women and men (2375 [455-3737] women vs. 893 [152-3154] men; p&#xa0;<&#xa0;0.001). The analysis of telomere length showed no significant difference between patients and healthy controls.<br><br>CONCLUSION: Lower mtDNA levels were found in patients with VTE compared to controls, indicating an association of biological aging with risk of VTE.},
}
@article {pmid36755096,
year = {2023},
author = {Nassour, J and Aguiar, LG and Correia, A and Schmidt, TT and Mainz, L and Przetocka, S and Haggblom, C and Tadepalle, N and Williams, A and Shokhirev, MN and Akincilar, SC and Tergaonkar, V and Shadel, GS and Karlseder, J},
title = {Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis.},
journal = {Nature},
volume = {614},
number = {7949},
pages = {767-773},
pmid = {36755096},
issn = {1476-4687},
support = {P01 AG073084/AG/NIA NIH HHS/United States ; RF1 AG064049/AG/NIA NIH HHS/United States ; R01 CA228211/CA/NCI NIH HHS/United States ; R01 CA234047/CA/NCI NIH HHS/United States ; P30 AG068635/AG/NIA NIH HHS/United States ; R01 AR069876/AR/NIAMS NIH HHS/United States ; P30 AR041940/AR/NIAMS NIH HHS/United States ; K99 CA252447/CA/NCI NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; R01 AG077324/AG/NIA NIH HHS/United States ; R01 CA227934/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; DNA/biosynthesis/genetics/metabolism ; *DNA Replication ; *Mitochondria/genetics/metabolism ; Neoplasms/genetics/pathology ; RNA, Long Noncoding/biosynthesis/genetics/metabolism ; *Telomere/genetics/metabolism ; Interferons ; Immunity, Innate ; Autophagy ; *Signal Transduction ; },
abstract = {Cancers arise through the accumulation of genetic and epigenetic alterations that enable cells to evade telomere-based proliferative barriers and achieve immortality. One such barrier is replicative crisis-an autophagy-dependent program that eliminates checkpoint-deficient cells with unstable telomeres and other cancer-relevant chromosomal aberrations[1,2]. However, little is known about the molecular events that regulate the onset of this important tumour-suppressive barrier. Here we identified the innate immune sensor Z-DNA binding protein 1 (ZBP1) as a regulator of the crisis program. A crisis-associated isoform of ZBP1 is induced by the cGAS-STING DNA-sensing pathway, but reaches full activation only when associated with telomeric-repeat-containing RNA (TERRA) transcripts that are synthesized from dysfunctional telomeres. TERRA-bound ZBP1 oligomerizes into filaments on the outer mitochondrial membrane of a subset of mitochondria, where it activates the innate immune adapter protein mitochondrial antiviral-signalling protein (MAVS). We propose that these oligomerization properties of ZBP1 serve as a signal amplification mechanism, where few TERRA-ZBP1 interactions are sufficient to launch a detrimental MAVS-dependent interferon response. Our study reveals a mechanism for telomere-mediated tumour suppression, whereby dysfunctional telomeres activate innate immune responses through mitochondrial TERRA-ZBP1 complexes to eliminate cells destined for neoplastic transformation.},
}
@article {pmid36751991,
year = {2023},
author = {Marriott, RJ and Murray, K and Budgeon, CA and Codd, V and Hui, J and Arscott, GM and Beilby, JP and Hankey, GJ and Wittert, GA and Wu, FCW and Yeap, BB},
title = {Serum testosterone and sex hormone-binding globulin are inversely associated with leucocyte telomere length in men: a cross-sectional analysis of the UK Biobank study.},
journal = {European journal of endocrinology},
volume = {188},
number = {2},
pages = {},
doi = {10.1093/ejendo/lvad015},
pmid = {36751991},
issn = {1479-683X},
support = {//Western Australian Health Translation Network/ ; //University of Western Australia/ ; //Government of Western Australia/ ; },
mesh = {Humans ; Male ; Middle Aged ; *Biological Specimen Banks ; Cross-Sectional Studies ; *Sex Hormone-Binding Globulin/analysis ; Telomere ; Testosterone ; United Kingdom ; },
abstract = {OBJECTIVE: Older men on an average have lower testosterone concentrations, compared with younger men, and more age-related comorbidities. Whether lower testosterone concentrations contribute to biological ageing remains unclear. Shorter telomeres are a marker for biological age. We tested the hypothesis that testosterone concentrations are associated with leucocyte telomere length (LTL), in middle- to older-aged men.<br><br>DESIGN: Cross-sectional analysis of the UK Biobank study, involving community-dwelling men aged 40-69 years.<br><br>METHODS: Serum testosterone and sex hormone-binding globulin (SHBG) were assayed. Free testosterone was calculated (cFT). Leucocyte telomere length was measured using polymerase chain reaction. Multivariable models were used to assess associations of hormones with standardised LTL.<br><br>RESULTS: In 167 706 men, median age 58 years, adjusting for sociodemographic, lifestyle, and medical factors, total testosterone was inversely associated with standardised LTL, which was 0.09 longer (95% confidence interval [CI], 0.08-0.10, P < .001) in men with total testosterone at median of lowest quintile [Q1] vs highest [Q5]. This relationship was attenuated after additional adjustment for SHBG (0.03 longer, CI = 0.02-0.05, P = .003). The association between cFT and LTL was similar in direction but lower in magnitude. In multivariable analysis, SHBG was inversely associated with standardised LTL, which was 0.12 longer (CI = 0.10-0.13, P < .001) for SHBG at median Q1 vs Q5. Results were similar with testosterone included in the model (0.10 longer, CI = 0.08-0.12, P < .001).<br><br>CONCLUSIONS: Total testosterone and SHBG were independently and inversely associated with LTL. Men with higher testosterone or SHBG had shorter telomeres, arguing against a role for testosterone to slow biological ageing in men.},
}
@article {pmid36750187,
year = {2023},
author = {Burraco, P and Hernandez-Gonzalez, M and Metcalfe, NB and Monaghan, P},
title = {Ageing across the great divide: tissue transformation, organismal growth and temperature shape telomere dynamics through the metamorphic transition.},
journal = {Proceedings. Biological sciences},
volume = {290},
number = {1992},
pages = {20222448},
pmid = {36750187},
issn = {1471-2954},
mesh = {Animals ; Temperature ; *Aging ; *Metamorphosis, Biological ; Larva ; Telomere ; },
abstract = {Telomere attrition is considered a useful indicator of cellular and whole-organism ageing rate. While approximately 80% of animal species undergo metamorphosis that includes extensive tissue transformations (involving cell division, apoptosis, de-differentiation and de novo formation of stem cells), the effect on telomere dynamics is unknown. We measured telomeres in Xenopus laevis developing from larvae to adults under contrasting environmental temperatures. Telomere dynamics were linked to the degree of tissue transformation during development. Average telomere length in gut tissue increased dramatically during metamorphosis, when the gut shortens by 75% and epithelial cells de-differentiate into stem cells. In the liver (retained from larva) and hindlimb muscle (newly formed before metamorphosis), telomeres gradually shortened until adulthood, likely due to extensive cell division. Tail muscle telomere lengths were constant until tail resorption, and those in heart (retained from larva) showed no change over time. Telomere lengths negatively correlated with larval growth, but for a given growth rate, telomeres were shorter in cooler conditions, suggesting that growing in the cold is more costly. Telomere lengths were not related to post-metamorphic growth rate. Further research is now needed to understand whether telomere dynamics are a good indicator of ageing rate in species undergoing metamorphosis.},
}
@article {pmid36747763,
year = {2023},
author = {Jones, CY and Williams, CL and Moreno, SP and Morris, DK and Mondello, C and Karlseder, J and Bertuch, AA},
title = {Hyperextended telomeres promote C-circle formation in telomerase positive human cells.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {36747763},
abstract = {Telomere length maintenance is crucial to cancer cell immortality. Up to 15% of cancers utilize a telomerase-independent, recombination-based mechanism termed alternative lengthening of telomeres (ALT). The primary ALT biomarker is the C-circle, a type of circular DNA with extrachromosomal telomere repeats (cECTRs). How C-circles form is not well characterized. To investigate C-circle formation in telomerase+ cells, we studied the human cen3tel cell line, in which telomeres progressively hyper-elongated post TERT -immortalization. cECTR signal was observed in 2D gels and C-circle assays but not t-circle assays, which also detect cECTRs. Telomerase activity and C-circle signal were not separable in the analysis of clonal populations, consistent with C-circle production occurring within telomerase+ cells. Two other long telomere, telomerase+ (LTT+) cell lines, HeLa1.3 (~23 kb telomeres) and HeLaE1 (~50 kb telomeres), had similar cECTR properties. Telomerase activity did not directly impact C-circle signal in LTT+ cells; instead, C-circle signal correlated with telomere length. LTT+ lines were less sensitive to hydroxyurea than an ALT+ cell line, suggesting that ALT status is a stronger contributor to replication stress levels than telomere length. Additionally, FANCM did not suppress C-circles in LTT+ cells as it does in ALT+ cells. Thus, C-circle formation may be driven by telomere length, independently of telomerase and replication stress, highlighting limitations of C-circles as a stand-alone ALT biomarker.},
}
@article {pmid36747657,
year = {2023},
author = {Landa, I and Thornton, CE and Xu, B and Haase, J and Krishnamoorthy, GP and Hao, J and Knauf, JA and Herbert, ZT and Blasco, MA and Ghossein, R and Fagin, JA},
title = {Telomerase reactivation induces progression of mouse Braf [V600E] -driven thyroid cancers without telomere lengthening.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {36747657},
support = {R01 CA050706/CA/NCI NIH HHS/United States ; K22 CA230381/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA249663/CA/NCI NIH HHS/United States ; P30 CA006516/CA/NCI NIH HHS/United States ; },
abstract = {Mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the paradigm of a cross-cancer alteration in a non-coding region. TERT promoter mutations (TPMs) are biomarkers of poor prognosis in several tumors, including thyroid cancers. TPMs enhance TERT transcription, which is otherwise silenced in adult tissues, thus reactivating a bona fide oncoprotein. To study TERT deregulation and its downstream consequences, we generated a Tert mutant promoter mouse model via CRISPR/Cas9 engineering of the murine equivalent locus (Tert [-123C>T]) and crossed it with thyroid-specific Braf [V600E] -mutant mice. We also employed an alternative model of Tert overexpression (K5-Tert). Whereas all Braf [V600E] animals developed well-differentiated papillary thyroid tumors, 29% and 36% of Braf [V600E] +Tert [-123C>T] and Braf [V600E] +K5-Tert mice progressed to poorly differentiated thyroid cancers at week 20, respectively. Braf+Tert tumors showed increased mitosis and necrosis in areas of solid growth, and older animals from these cohorts displayed anaplastic-like features, i.e., spindle cells and macrophage infiltration. Murine Tert promoter mutation increased Tert transcription in vitro and in vivo , but temporal and intra-tumoral heterogeneity was observed. RNA-sequencing of thyroid tumor cells showed that processes other than the canonical Tert-mediated telomere maintenance role operate in these specimens. Pathway analysis showed that MAPK and PI3K/AKT signaling, as well as processes not previously associated with this tumor etiology, involving cytokine and chemokine signaling, were overactivated. Braf+Tert animals remained responsive to MAPK pathway inhibitors. These models constitute useful pre-clinical tools to understand the cell-autonomous and microenvironment-related consequences of Tert-mediated progression in advanced thyroid cancers and other aggressive tumors carrying TPMs.},
}
@article {pmid36729832,
year = {2023},
author = {Pires, VB and Lohner, N and Wagner, T and Wagner, CB and Wilkens, M and Hajikazemi, M and Paeschke, K and Butter, F and Luke, B},
title = {RNA-DNA hybrids prevent resection at dysfunctional telomeres.},
journal = {Cell reports},
volume = {42},
number = {2},
pages = {112077},
doi = {10.1016/j.celrep.2023.112077},
pmid = {36729832},
issn = {2211-1247},
mesh = {*RNA/genetics ; *Telomere/genetics ; DNA ; Telomere Shortening ; DNA, Single-Stranded ; },
abstract = {At critically short telomeres, stabilized TERRA RNA-DNA hybrids drive homology-directed repair (HDR) to delay replicative senescence. However, even at long- and intermediate-length telomeres, not subject to HDR, transient TERRA RNA-DNA hybrids form, suggestive of additional roles. We report that telomeric RNA-DNA hybrids prevent Exo1-mediated resection when telomeres become non-functional. We used the well-characterized cdc13-1 allele, where telomere resection can be induced in a temperature-dependent manner, to demonstrate that ssDNA generation at telomeres is either prevented or augmented when RNA-DNA hybrids are stabilized or destabilized, respectively. The viability of cdc13-1 cells is affected by the presence or absence of hybrids accordingly. Telomeric hybrids do not affect the shortening rate of bulk telomeres. We suggest that TERRA hybrids require dynamic regulation to drive HDR at short telomeres; hybrid presence may initiate HDR through replication stress, whereby their removal allows strand resection.},
}
@article {pmid36726239,
year = {2023},
author = {Van Ommen, CE and Hsieh, AYY and Albert, AY and Kimmel, ER and Cote, HCF and Maan, EJ and Prior, JC and Pick, N and Murray, MCM and , },
title = {Lower anti-Müllerian hormone levels are associated with HIV in reproductive age women and shorter leukocyte telomere length among late reproductive age women.},
journal = {AIDS (London, England)},
volume = {37},
number = {5},
pages = {769-778},
pmid = {36726239},
issn = {1473-5571},
support = {//CIHR/Canada ; },
mesh = {Pregnancy ; Humans ; Female ; Adult ; Aged ; Child ; Adolescent ; Young Adult ; Middle Aged ; *Anti-Mullerian Hormone ; Cross-Sectional Studies ; *HIV Infections ; Leukocytes ; Telomere ; },
abstract = {OBJECTIVES: We sought to better understand factors associated with ovarian aging in women with HIV (WWH).<br><br>DESIGN: HIV has been associated with diminished fertility, younger age at menopause, and shorter leukocyte telomere length (LTL), a marker of cellular aging. We herein examine cross-sectional and longitudinal associations between LTL, anti-M&#xfc;llerian hormone (AMH), and HIV.<br><br>METHODS: We included WWH and HIV-negative women 12-50&#x200a;years of age in the CARMA cohort with one or more study visit(s). LTL and AMH were measured by qPCR and ELISA, respectively. Women were analyzed in peak reproductive (<35&#x200a;years) vs. late reproductive (&#x2265;35&#x200a;years) life phases. Using multivariable mixed-effect linear or logistic regressions, we assessed factors associated with AMH and &#x394;AMH/year while adjusting for relevant confounders.<br><br>RESULTS: WWH had shorter LTL and lower AMH levels compared to HIV-negative controls despite being of similar age. After adjusting for relevant factors, HIV was associated with 20% lower AMH levels in women under 35 years of age and shorter LTL was associated with AMH levels below 2&#x200a;ng/ml among women aged 35 years or older. Longitudinally, &#x394;AMH/year was largely related to initial AMH level among older women, and to age in younger women.<br><br>CONCLUSIONS: Factors associated with AMH change across women's reproductive lifespan. Lower AMH among peak reproductive aged WWH suggests that HIV may have an initial detrimental effect on ovarian reserve, an observation that may warrant counseling around pregnancy planning. In women aged 35 years or older, the association between shorter LTL and lower AMH suggests that the immune and reproductive aging connections are more important in this age group.},
}
@article {pmid36719921,
year = {2023},
author = {Eguchi, A and Gonzalez, AFGS and Torres-Bigio, SI and Koleckar, K and Birnbaum, F and Zhang, JZ and Wang, VY and Wu, JC and Artandi, SE and Blau, HM},
title = {TRF2 rescues telomere attrition and prolongs cell survival in Duchenne muscular dystrophy cardiomyocytes derived from human iPSCs.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {120},
number = {6},
pages = {e2209967120},
pmid = {36719921},
issn = {1091-6490},
support = {R01 HL159340/HL/NHLBI NIH HHS/United States ; R01 HL130020/HL/NHLBI NIH HHS/United States ; R25 HL147666/HL/NHLBI NIH HHS/United States ; R01 HL126527/HL/NHLBI NIH HHS/United States ; R01 HL123968/HL/NHLBI NIH HHS/United States ; R01 HL146690/HL/NHLBI NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; R01 HL134776/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Cardiomyopathy, Dilated/genetics ; Cell Survival ; Dystrophin/genetics ; *Heart Failure/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; *Muscular Dystrophy, Duchenne/metabolism ; Myocytes, Cardiac/metabolism ; Telomere/genetics/metabolism ; },
abstract = {Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by the lack of dystrophin. Heart failure, driven by cardiomyocyte death, fibrosis, and the development of dilated cardiomyopathy, is the leading cause of death in DMD patients. Current treatments decrease the mechanical load on the heart but do not address the root cause of dilated cardiomyopathy: cardiomyocyte death. Previously, we showed that telomere shortening is a hallmark of DMD cardiomyocytes. Here, we test whether prevention of telomere attrition is possible in cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPSC-CMs) and if preventing telomere shortening impacts cardiomyocyte function. We observe reduced cell size, nuclear size, and sarcomere density in DMD iPSC-CMs compared with healthy isogenic controls. We find that expression of just one telomere-binding protein, telomeric repeat-binding factor 2 (TRF2), a core component of the shelterin complex, prevents telomere attrition and rescues deficiencies in cell size as well as sarcomere density. We employ a bioengineered platform to micropattern cardiomyocytes for calcium imaging and perform Southern blots of telomere restriction fragments, the gold standard for telomere length assessments. Importantly, preservation of telomere lengths in DMD cardiomyocytes improves their viability. These data provide evidence that preventing telomere attrition ameliorates deficits in cell morphology, activation of the DNA damage response, and premature cell death, suggesting that TRF2 is a key player in DMD-associated cardiac failure.},
}
@article {pmid36717449,
year = {2022},
author = {Morgunova, VV and Sokolova, OA and Sizova, TV and Malaev, LG and Babaev, DS and Kwon, DA and Kalmykova, AI},
title = {Dysfunction of Lamin B and Physiological Aging Cause Telomere Instability in Drosophila Germline.},
journal = {Biochemistry. Biokhimiia},
volume = {87},
number = {12},
pages = {1600-1610},
doi = {10.1134/S000629792212015X},
pmid = {36717449},
issn = {1608-3040},
mesh = {Animals ; *Lamin Type B/genetics/metabolism ; *Drosophila/genetics ; Heterochromatin ; Drosophila melanogaster/genetics ; Aging/genetics ; Telomere/genetics/metabolism ; Germ Cells ; },
abstract = {Chromatin spatial organization in the nucleus is essential for the genome functioning and regulation of gene activity. The nuclear lamina and lamina-associated proteins, lamins, play a key role in this process. Lamin dysfunction leads to the decompaction and transcriptional activation of heterochromatin, which is associated with the premature aging syndrome. In many cell types, telomeres are located at the nuclear periphery, where their replication and stability are ensured by the nuclear lamina. Moreover, diseases associated with defects in lamins and telomeres have similar manifestations and resemble physiological aging. Understanding molecular changes associated with aging at the organismal level is especially important. In this study, we compared the effects caused by the mutation in lamin B and physiological aging in the germline of the model organism Drosophila melanogaster. We have shown that the impaired localization of lamin B leads to the heterochromatin decompaction and transcriptional activation of some transposable elements and telomeric repeats. Both DNA damage and activation of homologous recombination in the telomeres were observed in the germ cells of lamin B mutants. The instability of repeat-enriched heterochromatin can be directly related to the genome destabilization, germ cell death, and sterility observed in lamin B mutants. Similar processes were observed in Drosophila germline in the course of physiological aging, which indicates a close link between the maintenance of the heterochromatin stability at the nuclear periphery and mechanisms of aging.},
}
@article {pmid36714994,
year = {2023},
author = {Hsu, BY and Cossin-Sevrin, N and Stier, A and Ruuskanen, S},
title = {Prenatal thyroid hormones accelerate postnatal growth and telomere shortening in wild great tits.},
journal = {The Journal of experimental biology},
volume = {226},
number = {6},
pages = {},
pmid = {36714994},
issn = {1477-9145},
mesh = {Pregnancy ; Animals ; Female ; Telomere Shortening ; Aging ; Fetal Development ; *Passeriformes ; *Songbirds ; Vitamins ; Telomere ; Thyroid Hormones ; Hormones ; },
abstract = {The early-life environment is known to affect later-life health and disease, which could be mediated by the early-life programming of telomere length, a key hallmark of ageing. According to the fetal programming of telomere biology hypothesis, variation in prenatal exposure to hormones is likely to influence telomere length. Yet, the contribution of key metabolic hormones, i.e. thyroid hormones (THs), has been largely ignored. We recently showed that in contrast to predictions, exposure to elevated prenatal THs increased postnatal telomere length in wild collared flycatchers, but the generality of such effect, the underlying proximate mechanisms and consequences for survival have not been investigated. We therefore conducted a comprehensive study evaluating the impact of THs on potential drivers of telomere dynamics (growth, post-natal THs, mitochondria and oxidative stress), telomere length and medium-term survival using wild great tits as a model system. While prenatal THs did not significantly affect telomere length a week after hatching (i.e. day 7), they influenced postnatal telomere shortening (i.e. shorter telomeres at day 14 and the following winter) but not apparent survival. Circulating THs, mitochondrial density or oxidative stress biomarkers were not significantly influenced, whereas the TH-supplemented group showed accelerated growth, which may explain the observed delayed effect on telomeres. We discuss several alternative hypotheses that may explain the contrast with our previous findings in flycatchers. Given that shorter telomeres in early life tend to be carried until adulthood and are often associated with decreased survival prospects, the effects of prenatal THs on telomeres may have long-lasting effects on senescence.},
}
@article {pmid36714598,
year = {2022},
author = {Yuan, Y and Tan, Y and Qiu, X and Luo, H and Li, Y and Li, R and Yang, X},
title = {Sperm telomere length as a novel biomarker of male infertility and embryonic development: A systematic review and meta-analysis.},
journal = {Frontiers in endocrinology},
volume = {13},
number = {},
pages = {1079966},
pmid = {36714598},
issn = {1664-2392},
mesh = {Pregnancy ; Female ; Humans ; Male ; *Semen Analysis ; Semen ; *Infertility, Male/diagnosis/genetics ; Spermatozoa ; Telomere ; Biomarkers ; Observational Studies as Topic ; },
abstract = {BACKGROUND: Telomeres have an essential role in maintaining the integrity and stability of the human chromosomal genome and preserving essential DNA biological functions. Several articles have been published on the association of STL with male semen parameters and clinical pregnancy. The results, however, are either inconclusive or inconsistent. Therefore, this meta-analysis aimed to systematically assess the accuracy and clinical value of sperm telomere length (STL) as a new marker for diagnosing male infertility and predicting the quality of embryonic development.<br><br>METHODS: We performed a comprehensive systematic search for relevant publications in PubMed, the Cochrane Library, Web of Science, Embase, Scopus, and Ovid, from database build to August 2022. All experimental studies exploring the association of STL with male semen quality, male infertility, or embryonic development were included.<br><br>RESULTS: Overall, Twelve prospective observational cohort studies (1700 patients) were eligible for inclusion in the meta-analysis. The meta-analysis showed a positive linear correlation between STL and semen parameters. The optimal cut-off value for STL diagnosing male infertility was 1.0, with a sensitivity and specificity of 80%. Regarding STL and embryonic development, the clinical pregnancy rate was associated with longer STL, and there was no significant difference between the two groups regarding fertilization rate.<br><br>CONCLUSION: Our study showed that STL has good diagnostic and predictive value for male fertility and clinical pregnancy and could be used as a new biomarker for diagnosing male infertility and predicting embryonic development.<br><br>https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022303333.},
}
@article {pmid36707451,
year = {2023},
author = {Valdiani, A and Ofoghi, H},
title = {Enzymatic approaches against SARS-CoV-2 infection with an emphasis on the telomere-associated enzymes.},
journal = {Biotechnology letters},
volume = {45},
number = {3},
pages = {333-345},
pmid = {36707451},
issn = {1573-6776},
mesh = {Humans ; *COVID-19 ; SARS-CoV-2/genetics ; Pandemics/prevention &amp; control ; *Middle East Respiratory Syndrome Coronavirus ; },
abstract = {The pandemic phase of coronavirus disease 2019 (COVID-19) appears to be over in most countries. However, the unexpected behaviour and unstable nature of coronaviruses, including temporary hiatuses, re-emergence, emergence of new variants, and changing outbreak epicentres during the COVID-19 pandemic, have been frequently reported. The mentioned trend shows the fact that in addition to vaccine development, different strategies should be considered to deal effectively with this disease, in long term. In this regard, the role of enzymes in regulating immune responses to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has recently attracted much attention. Moreover, several reports confirm the association of short telomeres with sever COVID-19 symptoms. This review highlights the role of several enzymes involved in telomere length (TL) regulation and explains their relevance to SARS-CoV-2 infection. Apparently, inhibition of telomere shortening (TS) through inhibition and/or activation of these enzymes could be a potential target in the treatment of COVID-19, which may also lead to a reduction in disease severity.},
}
@article {pmid36705478,
year = {2023},
author = {},
title = {Heritable Defects in Mitotic and Telomere Function Confer Sarcoma Risk.},
journal = {Cancer discovery},
volume = {13},
number = {3},
pages = {529},
doi = {10.1158/2159-8290.CD-RW2023-016},
pmid = {36705478},
issn = {2159-8290},
mesh = {Humans ; *Sarcoma/genetics ; Telomere/genetics ; },
abstract = {Mitotic and telomere function pathways were identified to play a role in sarcoma susceptibility.},
}
@article {pmid36703827,
year = {2022},
author = {Wai, KM and Swe, T and Myar, MT and Aisyah, CR and Hninn, TSS},
title = {Telomeres susceptibility to environmental arsenic exposure: Shortening or lengthening?.},
journal = {Frontiers in public health},
volume = {10},
number = {},
pages = {1059248},
pmid = {36703827},
issn = {2296-2565},
mesh = {*Arsenic/metabolism ; *Telomerase/genetics/metabolism ; Telomere/metabolism ; },
abstract = {Maintaining telomere length plays a crucial role in regulating cellular life span. Telomere lengthening or shortening is one of the important biomarkers which could predict the preceding or present diseases. Meanwhile, the impact of environmental arsenic exposure on telomere length has increasingly concerned. Although previous studies demonstrated the effects of arsenic on telomere length, the findings were unclear on whether telomere shortens or lengthens by arsenic exposure. Thus, this manuscript summarized and discussed the telomere length alteration following arsenic exposure and the possible does-response effect of arsenic on telomere length. The present review suggested that different age groups may respond differently to arsenic exposure, and the dose-response effect of arsenic could be a critical factor in its effect on telomere length. Moreover, speciation analysis of arsenic could be more informative in identifying the effect of arsenic on telomere length.},
}
@article {pmid36702776,
year = {2023},
author = {Hoerr, RE and Eng, A and Payen, C and Di Rienzi, SC and Raghuraman, MK and Dunham, MJ and Brewer, BJ and Friedman, KL},
title = {Hotspot of de novo telomere addition stabilizes linear amplicons in yeast grown in sulfate-limiting conditions.},
journal = {Genetics},
volume = {224},
number = {2},
pages = {},
pmid = {36702776},
issn = {1943-2631},
support = {R01 GM123292/GM/NIGMS NIH HHS/United States ; R35 GM122497/GM/NIGMS NIH HHS/United States ; T32 GM137793/GM/NIGMS NIH HHS/United States ; R01GM123292/NH/NIH HHS/United States ; },
mesh = {Humans ; Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; *Telomerase/genetics/metabolism ; Sulfates/metabolism ; DNA Copy Number Variations ; Telomere-Binding Proteins/genetics ; Telomere/genetics/metabolism ; Sulfate Transporters/genetics/metabolism ; },
abstract = {Evolution is driven by the accumulation of competing mutations that influence survival. A broad form of genetic variation is the amplification or deletion of DNA (≥50 bp) referred to as copy number variation (CNV). In humans, CNV may be inconsequential, contribute to minor phenotypic differences, or cause conditions such as birth defects, neurodevelopmental disorders, and cancers. To identify mechanisms that drive CNV, we monitored the experimental evolution of Saccharomyces cerevisiae populations grown under sulfate-limiting conditions. Cells with increased copy number of the gene SUL1, which encodes a primary sulfate transporter, exhibit a fitness advantage. Previously, we reported interstitial inverted triplications of SUL1 as the dominant rearrangement in a haploid population. Here, in a diploid population, we find instead that small linear fragments containing SUL1 form and are sustained over several generations. Many of the linear fragments are stabilized by de novo telomere addition within a telomere-like sequence near SUL1 (within the SNF5 gene). Using an assay that monitors telomerase action following an induced chromosome break, we show that this region acts as a hotspot of de novo telomere addition and that required sequences map to a region of <250 base pairs. Consistent with previous work showing that association of the telomere-binding protein Cdc13 with internal sequences stimulates telomerase recruitment, mutation of a four-nucleotide motif predicted to associate with Cdc13 abolishes de novo telomere addition. Our study suggests that internal telomere-like sequences that stimulate de novo telomere addition can contribute to adaptation by promoting genomic plasticity.},
}
@article {pmid36702689,
year = {2023},
author = {Heaphy, CM and Singhi, AD},
title = {Reprint of: The Diagnostic and Prognostic Utility of Incorporating DAXX, ATRX, and Alternative Lengthening of Telomeres (ALT) to the Evaluation of Pancreatic Neuroendocrine Tumors (PanNETs).},
journal = {Human pathology},
volume = {132},
number = {},
pages = {1-11},
pmid = {36702689},
issn = {1532-8392},
support = {R37 CA263622/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Neuroendocrine Tumors/diagnosis/genetics/pathology ; Prognosis ; X-linked Nuclear Protein/genetics ; In Situ Hybridization, Fluorescence ; *Intellectual Disability ; *alpha-Thalassemia ; Nuclear Proteins/genetics ; *Pancreatic Neoplasms/diagnosis/genetics/metabolism ; Telomere/pathology ; Co-Repressor Proteins ; Telomere Homeostasis ; Molecular Chaperones ; },
abstract = {Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and an ill-defined pathobiology. Although many PanNETs are indolent and remain stable for years, a subset may behave aggressively and metastasize widely. Thus, the increasing and frequent detection of PanNETs presents a treatment dilemma. Current prognostic systems are susceptible to interpretation errors, sampling issues, and do not accurately reflect the clinical behavior of these neoplasms. Hence, additional biomarkers are needed to improve the prognostic stratification of patients diagnosed with a PanNET. Recent studies have identified alterations in death domain-associated protein 6 (DAXX) and alpha-thalassemia/mental retardation X-linked (ATRX), as well as alternative lengthening of telomeres (ALT), as promising prognostic biomarkers. This review summarizes the identification, clinical utility, and specific nuances in testing for DAXX/ATRX by immunohistochemistry and ALT by telomere-specific fluorescence in situ hybridization in PanNETs. Furthermore, a discussion on diagnostic indications for DAXX, ATRX, and ALT status is provided to include the distinction between PanNETs and pancreatic neuroendocrine carcinomas (PanNECs), and determining pancreatic origin for metastatic neuroendocrine tumors in the setting of an unknown primary.},
}
@article {pmid36700322,
year = {2023},
author = {Uzuncakmak, SK and Dirican, E and Ozcan, H and Takim, U},
title = {Relation of ATPase6 Mutations and Telomere Length in Schizophrenia Patients.},
journal = {Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology},
volume = {21},
number = {1},
pages = {162-170},
pmid = {36700322},
issn = {1738-1088},
abstract = {OBJECTIVE: Schizophrenia is a serious mental disorder. Mutations in mitochondrial genes can change energy metabolism. Telomere is a tandem sequence at the end of chromosomes. Shorter telomere length has been shown in schizophrenia. The aim of this study was to determine the relationship between ATPase6 gene mutations and telomere length in schizophrenia patients.<br><br>METHODS: Blood samples of 34 patients and 34 healthy controls were used. In this study conventional PCR, Sanger sequencing technic and real-time PCR were utilized.<br><br>RESULTS: Five different mutations (A8860G, A8836, G8697A, C8676T, and A8701G) in the ATPase6 gene were identified in schizophrenia patients. The most seen mutation was A8860G (94%). Telomere length analysis indicated the relation of ATPase6 gene mutations and telomere length variations (p = 0.001). Patients carrying the A8860G mutation had shorter telomere lengths than patients carrying other mutations. Comparing telomere length between schizophrenia patients and healthy controls revealed that the mean telomere length of schizophrenia patients was shorter than healthy controls (p = 0.006). The demographic analysis demonstrated a significant relationship between marital status and telomere length (p = 0.011). Besides that, the duration of the illness is another factor that impacts telomere length (p = 0.044). There is no significant relation between telomere length and other clinical and demographic characteristics including education status, age, gender, etc.<br><br>CONCLUSION: In conclusion, telomere length and ATPase6 gene mutations have a significant relation. Studies with larger patient populations and investigation of other mitochondrial gene mutations will make the clearer link between telomere length and mitochondrial mutations.},
}
@article {pmid36699384,
year = {2022},
author = {Holmes, O and Nones, K and Tang, YH and Loffler, KA and Lee, M and Patch, AM and Dagg, RA and Lau, LMS and Leonard, C and Wood, S and Xu, Q and Pickett, HA and Reddel, RR and Barbour, AP and Grimmond, SM and Waddell, N and Pearson, JV},
title = {qmotif: determination of telomere content from whole-genome sequence data.},
journal = {Bioinformatics advances},
volume = {2},
number = {1},
pages = {vbac005},
pmid = {36699384},
issn = {2635-0041},
abstract = {MOTIVATION: Changes in telomere length have been observed in cancer and can be indicative of mechanisms involved in carcinogenesis. Most methods used to estimate telomere length require laboratory analysis of DNA samples. Here, we present qmotif, a fast and easy tool that determines telomeric repeat sequences content as an estimate of telomere length directly from whole-genome sequencing.<br><br>RESULTS: qmotif shows similar results to quantitative PCR, the standard method for high-throughput clinical telomere length quantification. qmotif output correlates strongly with the output of other tools for determining telomere sequence content, TelSeq and TelomereHunter, but can run in a fraction of the time-usually under a minute.<br><br>qmotif is implemented in Java and source code is available at https://github.com/AdamaJava/adamajava, with instructions on how to build and use the application available from https://adamajava.readthedocs.io/en/latest/.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics Advances online.},
}
@article {pmid36696951,
year = {2023},
author = {Park, S and Kim, SG and Lee, S and Kim, Y and Cho, S and Kim, K and Kim, YC and Han, SS and Lee, H and Lee, JP and Joo, KW and Lim, CS and Kim, YS and Kim, DK},
title = {Causal linkage of tobacco smoking with ageing: Mendelian randomization analysis towards telomere attrition and sarcopenia.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {14},
number = {2},
pages = {955-963},
pmid = {36696951},
issn = {2190-6009},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; 3020220160//Seoul National University Hospital/ ; //Ministry of Health &amp; Welfare, Republic of Korea/ ; 2021R1A2C2094586//Korean government (MSIT, Ministry of Science and ICT)/ ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; Mendelian Randomization Analysis ; *Sarcopenia ; Hand Strength ; *Frailty ; Tobacco Smoking ; Telomere/genetics ; },
abstract = {BACKGROUND: Ageing traits and frailty are important health issues in modern medicine. Evidence supporting the causal effects of tobacco smoking on various ageing traits is required.<br><br>METHODS: This study performed Mendelian randomization (MR) analysis instrumenting 377 genetic variants associated with being an ever-smoker at a genome-wide significance level to test the causal estimates from tobacco smoking. The outcome data were obtained from 337&#x2009;138 white British ancestry participants from the UK Biobank. Leucocyte telomere length, appendicular lean mass index, subjective walking pace, handgrip strength,&#xa0;and wristband accelerometry-determined physical activity degree were collected as ageing-related outcomes. Summary-level MR analysis was performed using the inverse variance-weighted method and pleiotropy-robust MR methods, including weighted median and MR-Egger. Observational association between the outcome traits and phenotypically being an ever-smoker was also investigated.<br><br>RESULTS: Summary-level MR analysis indicated that a higher genetic predisposition for tobacco smoking was significantly associated with shorter leucocyte telomere length (twofold increase in prevalence of smoking towards standardized Z-score, -0.041 [-0.054, -0.028]), lower appendicular lean mass index (-0.007 [-0.010, -0.005]), slower walking pace (ordinal category, -0.047 [-0.054, -0.033]) and lower time spent on moderate-to-vigorous physical activity (hours per week, -0.39 [-0.56, -0.23]). The causal estimates were non-significant towards handgrip strength phenotype (kg, 0.074 [-0.055, 0.204]). Pleiotropy-robust MR results generally supported the main causal estimates. The observational findings also showed significant association between being an ever-smoker and the ageing traits.<br><br>CONCLUSIONS: Genetically predicted and observational tobacco smoking status are significantly associated with poor ageing phenotypes. Healthcare providers may continue to reduce tobacco use, which may be helpful in reducing the burden of ageing and frailty.},
}
@article {pmid36691437,
year = {2023},
author = {Sabot, D and Lovegrove, R and Stapleton, P},
title = {The association between sleep quality and telomere length: A systematic literature review.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {28},
number = {},
pages = {100577},
pmid = {36691437},
issn = {2666-3546},
abstract = {Several sleep parameters present an elevated risk for processes that contribute to cellular aging. Short sleep duration, sleep apnoea, and insomnia are significantly associated with shorter telomeres, a biological marker of cellular aging. However, there has been no review or analysis of studies that have examined the association between the psychological construct of sleep quality and telomere length. The present study aimed to provide a systematic review of the association between sleep quality and telomere length. A systematic review of English articles was conducted using MEDLINE/PubMed, PsycINFO, Google Scholar, and Web of Science electronic databases, with the final search conducted on 3rd September 2021. Search terms included sleep quality, poor sleep, insomnia, sleep difficulties, sleep issue*, non-restorative sleep, telomere*, cellular aging, and immune cell telomere length. Study eligibility criteria included human participants aged 18 years or older and a reproducible methodology. Study appraisal and synthesis were completed using a systematic search in line with a PICOS approach (P = Patient, problem, or population; I = Intervention, prognostic factor, exposure; C = Comparison, control, or comparator; O = Outcomes; S = Study designs). Twenty-two studies met review inclusion criteria. Qualitative synthesis of the literature indicated insufficient evidence overall to support a significant association between sleep quality and telomere length. Limitations across studies were addressed, such as the assessment of examined constructs. Findings highlight important targets for future research, including the standardised operationalisation of the sleep quality construct and experimental study designs. Research in this area has clinical significance by identifying possible mechanisms that increase the risk for age-related disease and mortality. PROSPERO Registration No.: CRD 42021233139.},
}
@article {pmid36690926,
year = {2023},
author = {Kim, JS and Manichaikul, AW and Hoffman, EA and Balte, P and Anderson, MR and Bernstein, EJ and Madahar, P and Oelsner, EC and Kawut, SM and Wysoczanski, A and Laine, AF and Adegunsoye, A and Ma, JZ and Taub, MA and Mathias, RA and Rich, SS and Rotter, JI and Noth, I and Garcia, CK and Barr, RG and Podolanczuk, AJ},
title = {MUC5B, telomere length and longitudinal quantitative interstitial lung changes: the MESA Lung Study.},
journal = {Thorax},
volume = {78},
number = {6},
pages = {566-573},
pmid = {36690926},
issn = {1468-3296},
support = {K23 HL140199/HL/NHLBI NIH HHS/United States ; N01HC95169/HL/NHLBI NIH HHS/United States ; 75N92020D00007/HL/NHLBI NIH HHS/United States ; K23 HL146942/HL/NHLBI NIH HHS/United States ; 75N92020D00005/HL/NHLBI NIH HHS/United States ; N01HC95168/HL/NHLBI NIH HHS/United States ; R01 HL077612/HL/NHLBI NIH HHS/United States ; N01HC95162/HL/NHLBI NIH HHS/United States ; HHSN268201000021C/HL/NHLBI NIH HHS/United States ; N01HC95165/HL/NHLBI NIH HHS/United States ; N01HC95167/HL/NHLBI NIH HHS/United States ; N01HC95163/HL/NHLBI NIH HHS/United States ; 75N92020D00002/HL/NHLBI NIH HHS/United States ; U01 HL120393/HL/NHLBI NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; R01 HL117626/HL/NHLBI NIH HHS/United States ; HHSN268201000001I/HL/NHLBI NIH HHS/United States ; N01HC95161/HL/NHLBI NIH HHS/United States ; 75N92020D00001/HL/NHLBI NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; R01 HL120393/HL/NHLBI NIH HHS/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; 75N92020D00004/HL/NHLBI NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; R01 HL093081/HL/NHLBI NIH HHS/United States ; R01 HL105756/HL/NHLBI NIH HHS/United States ; N01HC95159/HL/NHLBI NIH HHS/United States ; R01 HL121270/HL/NHLBI NIH HHS/United States ; K23 AR075112/AR/NIAMS NIH HHS/United States ; 75N92020D00003/HL/NHLBI NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; HHSN268201500003I/HL/NHLBI NIH HHS/United States ; N01HC95164/HL/NHLBI NIH HHS/United States ; 75N92020D00006/HL/NHLBI NIH HHS/United States ; UL1 TR001079/TR/NCATS NIH HHS/United States ; N01HC95166/HL/NHLBI NIH HHS/United States ; K23 HL150301/HL/NHLBI NIH HHS/United States ; UL1 TR000040/TR/NCATS NIH HHS/United States ; R01 HL131565/HL/NHLBI NIH HHS/United States ; N01HC95160/HL/NHLBI NIH HHS/United States ; },
mesh = {Adult ; Humans ; *Lung/diagnostic imaging ; *Lung Diseases, Interstitial/diagnostic imaging/genetics/complications ; Genotype ; Telomere/genetics ; Mucin-5B/genetics ; },
abstract = {BACKGROUND: The MUC5B promoter variant (rs35705950) and telomere length are linked to pulmonary fibrosis and CT-based qualitative assessments of interstitial abnormalities, but their associations with longitudinal quantitative changes of the lung interstitium among community-dwelling adults are unknown.<br><br>METHODS: We used data from participants in the Multi-Ethnic Study of Atherosclerosis with high-attenuation areas (HAAs, Examinations 1-6 (2000-2018)) and MUC5B genotype (n=4552) and telomere length (n=4488) assessments. HAA was defined as the per cent of imaged lung with attenuation of -600 to -250 Hounsfield units. We used linear mixed-effects models to examine associations of MUC5B risk allele (T) and telomere length with longitudinal changes in HAAs. Joint models were used to examine associations of longitudinal changes in HAAs with death and interstitial lung disease (ILD).<br><br>RESULTS: The MUC5B risk allele (T) was associated with an absolute change in HAAs of 2.60% (95% CI 0.36% to 4.86%) per 10 years overall. This association was stronger among those with a telomere length below an age-adjusted percentile of 5% (p value for interaction=0.008). A 1% increase in HAAs per year was associated with 7% increase in mortality risk (rate ratio (RR)=1.07, 95%&#x2009;CI 1.02 to 1.12) for overall death and 34% increase in ILD (RR=1.34, 95%&#x2009;CI 1.20 to 1.50). Longer baseline telomere length was cross-sectionally associated with less HAAs from baseline scans, but not with longitudinal changes in HAAs.<br><br>CONCLUSIONS: Longitudinal increases in HAAs were associated with the MUC5B risk allele and a higher risk of death and ILD.},
}
@article {pmid36689342,
year = {2023},
author = {Liu, H and Xu, C and Diplas, BH and Brown, A and Strickland, LM and Yao, H and Ling, J and McLendon, RE and Keir, ST and Ashley, DM and He, Y and Waitkus, MS},
title = {Cancer-associated SMARCAL1 loss-of-function mutations promote alternative lengthening of telomeres and tumorigenesis in telomerase-negative glioblastoma cells.},
journal = {Neuro-oncology},
volume = {25},
number = {9},
pages = {1563-1575},
pmid = {36689342},
issn = {1523-5866},
support = {K22 CA258965/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Telomerase/genetics/metabolism ; *Glioblastoma/genetics ; Telomere Homeostasis ; Mutation ; Telomere/genetics/metabolism ; Carcinogenesis ; Cell Transformation, Neoplastic/genetics ; DNA Helicases/genetics/metabolism ; },
abstract = {BACKGROUND: Telomere maintenance mechanisms are required to enable the replicative immortality of malignant cells. While most cancers activate the enzyme telomerase, a subset of cancers uses telomerase-independent mechanisms termed alternative lengthening of telomeres (ALT). ALT occurs via homology-directed-repair mechanisms and is frequently associated with ATRX mutations. We previously showed that a subset of adult glioblastoma (GBM) patients with ATRX-expressing ALT-positive tumors harbored loss-of-function mutations in the SMARCAL1 gene, which encodes an annealing helicase involved in replication fork remodeling and the resolution of replication stress. However, the causative relationship between SMARCAL1 deficiency, tumorigenesis, and de novo telomere synthesis is not understood.<br><br>METHODS: We used a patient-derived ALT-positive GBM cell line with native SMARCAL1 deficiency to investigate the role of SMARCAL1 in ALT-mediated de novo telomere synthesis, replication stress, and gliomagenesis in vivo.<br><br>RESULTS: Inducible rescue of SMARCAL1 expression suppresses ALT indicators and inhibits de novo telomere synthesis in GBM and osteosarcoma cells, suggesting that SMARCAL1 deficiency plays a functional role in ALT induction in cancers that natively lack SMARCAL1 function. SMARCAL1-deficient ALT-positive cells can be serially propagated in vivo in the absence of detectable telomerase activity, demonstrating that the SMARCAL1-deficient ALT phenotype maintains telomeres in a manner that promotes tumorigenesis.<br><br>CONCLUSIONS: SMARCAL1 deficiency is permissive to ALT and promotes gliomagenesis. Inducible rescue of SMARCAL1 in ALT-positive cell lines permits the dynamic modulation of ALT activity, which will be valuable for future studies aimed at understanding the mechanisms of ALT and identifying novel anticancer therapeutics that target the ALT phenotype.},
}
@article {pmid36689071,
year = {2023},
author = {Yin, H and Pickering, JG},
title = {Telomere Length: Implications for Atherogenesis.},
journal = {Current atherosclerosis reports},
volume = {25},
number = {3},
pages = {95-103},
pmid = {36689071},
issn = {1534-6242},
support = {FDN-143326//CIHR/Canada ; PJT-180604//CIHR/Canada ; },
mesh = {Humans ; *Atherosclerosis/genetics ; Telomere Shortening ; *Cardiovascular System ; Risk Factors ; Telomere ; Leukocytes ; },
abstract = {PURPOSE OF REVIEW: The purpose of the study is to explore the evidence linking telomere length with atherosclerotic ischemic disease.<br><br>RECENT FINDINGS: There has been a recent expansion in strategies for measuring telomere length, including analyzing genome sequence data and capitalizing on genomic loci that associate with telomere length. These, together with more established approaches, have been used to generate a more complete picture of telomere length relationships with ischemic disease. Whereas earlier meta-analyses suggested an association between short leukocyte telomeres and ischemic disease, several recent large population studies now provide particularly compelling data, including an association with cardiovascular mortality. In addition, whether short leukocyte telomeres might be causally related to ischemic disease has been interrogated using Mendelian randomization strategies, which point to shorter leukocyte telomeres as a determining risk factor. Importantly however, the wide, interindividual variability in telomere length still means that a single assessment of leukocyte telomere length in an individual does not reliably report on a biological aging process. In this regard, recent multi-tissue analyses of telomere length dynamics are providing both new mechanistic insights into how telomere length and shortening rates may participate in atherogenesis and risk prediction opportunities. The balance of evidence indicates that short leukocyte telomeres confer a risk for atherosclerotic cardiovascular disease. Moreover, an integrated analysis of telomere lengths in leukocytes and other tissues may provide a window into individualized telomere dynamics, raising new prospects for risk management.},
}
@article {pmid36685927,
year = {2022},
author = {Xiao, Y and Xu, D and Jiang, C and Huili, Y and Nie, S and Zhu, H and Fan, G and Guan, X},
title = {Telomere maintenance-related genes are important for survival prediction and subtype identification in bladder cancer.},
journal = {Frontiers in genetics},
volume = {13},
number = {},
pages = {1087246},
pmid = {36685927},
issn = {1664-8021},
abstract = {Background: Bladder cancer ranks among the top three in the urology field for both morbidity and mortality. Telomere maintenance-related genes are closely related to the development and progression of bladder cancer, and approximately 60%-80% of mutated telomere maintenance genes can usually be found in patients with bladder cancer. Methods: Telomere maintenance-related gene expression profiles were obtained through limma R packages. Of the 359 differential genes screened, 17 prognostically relevant ones were obtained by univariate independent prognostic analysis, and then analysed by LASSO regression. The best result was selected to output the model formula, and 11 model-related genes were obtained. The TCGA cohort was used as the internal group and the GEO dataset as the external group, to externally validate the model. Then, the HPA database was used to query the immunohistochemistry of the 11 model genes. Integrating model scoring with clinical information, we drew a nomogram. Concomitantly, we conducted an in-depth analysis of the immune profile and drug sensitivity of the bladder cancer. Referring to the matrix heatmap, delta area plot, consistency cumulative distribution function plot, and tracking plot, we further divided the sample into two subtypes and delved into both. Results: Using bioinformatics, we obtained a prognostic model of telomere maintenance-related genes. Through verification with the internal and the external groups, we believe that the model can steadily predict the survival of patients with bladder cancer. Through the HPA database, we found that three genes, namely ABCC9, AHNAK, and DIP2C, had low expression in patients with tumours, and eight other genes-PLOD1, SLC3A2, RUNX2, RAD9A, CHMP4C, DARS2, CLIC3, and POU5F1-were highly expressed in patients with tumours. The model had accurate predictive power for populations with different clinicopathological features. Through the nomogram, we could easily assess the survival rate of patients. Clinicians can formulate targeted diagnosis and treatment plans for patients based on the prediction results of patient survival, immunoassays, and drug susceptibility analysis. Different subtypes help to further subdivide patients for better treatment purposes. Conclusion: According to the results obtained by the nomogram in this study, combined with the results of patient immune-analysis and drug susceptibility analysis, clinicians can formulate diagnosis and personalized treatment plans for patients. Different subtypes can be used to further subdivide the patient for a more precise treatment plan.},
}
@article {pmid36684585,
year = {2022},
author = {Semeraro, MD and Beltrami, AP and Kharrat, F and Almer, G and Sedej, S and Renner, W and Gruber, HJ and Curcio, F and Herrmann, M},
title = {The impact of moderate endurance exercise on cardiac telomeres and cardiovascular remodeling in obese rats.},
journal = {Frontiers in cardiovascular medicine},
volume = {9},
number = {},
pages = {1080077},
pmid = {36684585},
issn = {2297-055X},
abstract = {INTRODUCTION: Hypercaloric nutrition and physical inactivity cause obesity, a potential driver of myocardial apoptosis and senescence that may accelerate cardiac aging. Although physical activity reduces mortality, its impact on myocardial aging is insufficiently understood. Here we investigated the effects of a hypercaloric high-fat diet (HFD) and regular exercise training on cardiac cells telomeres and histomorphometric indices of cardiac aging.<br><br>METHODS: Ninety-six 4-months old female Sprague-Dawley rats were fed for 10 months normal (ND) or a HFD diet. Half of the animals in each group performed 30 min treadmill-running sessions on 5 consecutive days per week. At study end, cardiomyocyte cross-sectional area (CSA), interstitial collagen content, vascular density, apoptotic and senescent cells, relative telomere length (RTL), and expression of telomerase-reverse transcriptase (Tert) as marker of telomere-related senescence and apoptosis were analyzed.<br><br>RESULTS: Compared to ND, the HFD group developed obesity, higher CSA, lower capillary density and tended to have more apoptotic cardiomyocytes and interstitials cells. Myocardial RTL and the expression of Terf-1 and Terf-2 were comparable in sedentary HFD and ND animals. In the HFD group, regular moderate endurance exercise improved myocardial vascularization, but had no effect on CSA or apoptosis. Notably, the combination of exercise and HFD increased senescence when compared to sedentary ND or HFD, and reduced RTL when compared to exercise ND animals. Exercising HFD animals also showed a trend toward higher Tert expression compared to all other groups. In addition, exercise reduced Terf-1 expression regardless of diet.<br><br>CONCLUSION: HFD-induced obesity showed no effects on myocardial telomeres and induced only mild morphologic alterations. Summarized, long-term moderate endurance exercise partially reverses HFD-induced effects but may even trigger cardiac remodeling in the context of obesity.},
}
@article {pmid36674498,
year = {2023},
author = {Dhillon, VS and Deo, P and Thomas, P and Fenech, M},
title = {Low Magnesium in Conjunction with High Homocysteine and Less Sleep Accelerates Telomere Attrition in Healthy Elderly Australian.},
journal = {International journal of molecular sciences},
volume = {24},
number = {2},
pages = {},
pmid = {36674498},
issn = {1422-0067},
mesh = {Humans ; Aged ; *Magnesium ; Australia ; *Vitamin B 12 ; Folic Acid ; Telomere/genetics ; Sleep ; Micronutrients ; Homocysteine ; },
abstract = {The relationship between sleep and micronutrients, including magnesium, is implicated in its regulation. The effects of low magnesium and other micronutrients on sleep disruption and telomere loss are not well understood. The present study was carried out in 172 healthy elderly subjects from South Australia. Plasma micronutrients including magnesium were measured. Each participant provided information about their sleep hours (<7 h or ≥7 h). Lymphocyte telomere length (TL) was measured by real-time qPCR assay. Plasma magnesium level was significantly low in subjects who sleep less than 7 h (p = 0.0002). TL was significantly shorter in people who are low in magnesium and sleep less than 7 h (p = 0.01). Plasma homocysteine (Hcy) is negatively associated with magnesium (r = −0.299; p < 0.0001). There is a significant interaction effect of magnesium and Hcy on sleep duration (p = 0.04) and TL (p = 0.003). Our results suggest that inadequate magnesium levels have an adverse impact on sleep and telomere attrition rate in cognitively normal elderly people, and this may be exacerbated by low levels of vitamin B12 and folate that elevate Hcy concentration.},
}
@article {pmid36674427,
year = {2023},
author = {López-Armas, GDC and Ramos-Márquez, ME and Navarro-Meza, M and Macías-Islas, M&#xc1; and Saldaña-Cruz, AM and Zepeda-Moreno, A and Siller-López, F and Cruz-Ramos, JA},
title = {Leukocyte Telomere Length Predicts Severe Disability in Relapsing-Remitting Multiple Sclerosis and Correlates with Mitochondrial DNA Copy Number.},
journal = {International journal of molecular sciences},
volume = {24},
number = {2},
pages = {},
pmid = {36674427},
issn = {1422-0067},
support = {259639//University of Guadalajara/ ; },
mesh = {Humans ; *Multiple Sclerosis, Relapsing-Remitting/genetics ; *Multiple Sclerosis/genetics ; DNA, Mitochondrial/genetics ; DNA Copy Number Variations ; Leukocytes ; Telomere/genetics ; },
abstract = {Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of neurological disability and neural damage. Our objective was to assess the LTL and mtDNA-CN in relapsing-remitting MS (RRMS). We included 10 healthy controls, 75 patients with RRMS, 50 of whom had an Expanded Disability Status Scale (EDSS) from 0 to 3 (mild to moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). We use the Real-Time Polymerase Chain Reaction (qPCR) technique to quantify absolute LTL and absolute mtDNA-CN. ANOVA test show differences between healthy control vs. severe disability RRMS and mild-moderate RRMS vs. severe disability RRMS (p = 0.0130). LTL and mtDNA-CN showed a linear correlation in mild-moderate disability RRMS (r = 0.378, p = 0.007). Furthermore, we analyzed LTL between RRMS groups with a ROC curve, and LTL can predict severe disability (AUC = 0.702, p = 0.0018, cut-off < 3.0875 Kb, sensitivity = 75%, specificity = 62%), whereas the prediction is improved with a logistic regression model including LTL plus age (AUC = 0.762, p = 0.0001, sensitivity = 79.17%, specificity = 80%). These results show that LTL is a biomarker of disability in RRMS and is correlated with mtDNA-CN in mild-moderate RRMS patients.},
}
@article {pmid36669753,
year = {2023},
author = {Bountziouka, V and Nelson, CP and Wang, Q and Musicha, C and Codd, V and Samani, NJ},
title = {Dietary Patterns and Practices and Leucocyte Telomere Length: Findings from the UK Biobank.},
journal = {Journal of the Academy of Nutrition and Dietetics},
volume = {123},
number = {6},
pages = {912-922.e26},
doi = {10.1016/j.jand.2023.01.008},
pmid = {36669753},
issn = {2212-2672},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MR/M012816/1/MRC_/Medical Research Council/United Kingdom ; BRC-1215-20010/DH_/Department of Health/United Kingdom ; SP/16/4/32697/BHF_/British Heart Foundation/United Kingdom ; },
mesh = {Humans ; Cross-Sectional Studies ; *Biological Specimen Banks ; *Diet, Mediterranean ; Telomere ; United Kingdom ; },
abstract = {BACKGROUND: Shorter telomere length (TL) is associated with risk of several age-related diseases and decreased life span, but the extent to which dietary patterns and practices associate with TL is uncertain.<br><br>OBJECTIVE: This study aimed to investigate the association of dietary patterns and practices and leucocyte TL (LTL).<br><br>DESIGN: This was a cross-sectional study.<br><br>PARTICIPANTS AND SETTING: Data collected voluntarily from up to 422,797 UK Biobank participants, during 2006-2010.<br><br>MAIN OUTCOME MEASURES: LTL was measured as a ratio of the telomere repeat number to a single-copy gene and was loge-transformed and standardized (z-LTL).<br><br>Adherence a priori to a Mediterranean-style diet was assessed through the MedDietScore. Principal component analysis was used to a posteriori extract the "Meat" and "Prudent" dietary patterns. Additional dietary practices considered were the self-reported adherence to "Vegetarian" diet, "Eating 5-a-day of fruit and vegetables" and "Abstaining from eggs/dairy/wheat/sugar." Associations between quintiles of dietary patterns or adherence to dietary practices with z-LTL were investigated through multivariable linear regression models (adjusted for demographic, lifestyle, and clinical characteristics).<br><br>RESULTS: Adherence to the "Mediterranean" and the "Prudent" patterns, was positively associated with LTL, with an effect magnitude in z-LTL of 0.020 SD and 0.014 SD, respectively, for the highest vs the lowest quintile of adherence to the pattern (both P values < 0.05). Conversely, a reversed association between quintile of the "Meat" pattern and LTL was observed, with z-LTL being on average shorter by 0.025 SD (P&#xa0;= 6.12&#xd7;10[-05]) for participants in the highest quintile of the pattern compared with the lowest quintile. For adherents to "5-a-day" z-LTL was on average longer by 0.027 SD (P&#xa0;= 5.36&#xd7;10[-09]), and for "abstainers," LTL was shorter by 0.016 SD (P&#xa0;= 2.51&#xd7;10[-04]). The association of LTL with a vegetarian diet was nonsignificant after adjustment for demographic, lifestyle, and clinical characteristics.<br><br>CONCLUSIONS: Several dietary patterns and practices associated with beneficial health effects are significantly associated with longer LTL. However, the magnitude of the association was small, and any clinical relevance is uncertain.},
}
@article {pmid36658792,
year = {2023},
author = {Park, HS and Im, K and Shin, DY and Yoon, SS and Kwon, S and Kim, SW and Lee, DS},
title = {Telomere integrated scoring system of myelodysplastic syndrome.},
journal = {Journal of clinical laboratory analysis},
volume = {37},
number = {3},
pages = {e24839},
pmid = {36658792},
issn = {1098-2825},
support = {NRF-2017R1A2A1A17069780//National Research Foundation of Korea/ ; NRF-2020R1A3B3079653//Ministry of Science and ICT(MSIT) of the Republic of Korea and the National Research Foundation of Korea/ ; },
mesh = {Humans ; Aged ; Retrospective Studies ; Prognosis ; *Myelodysplastic Syndromes ; Mutation ; Telomere ; },
abstract = {INTRODUCTION: Recently, multigene target sequencing is widely performed for the purpose of prognostic prediction and application of targeted therapy. Here, we proposed a new scoring system that encompasses gene variations, telomere length, and Revised International Prognostic Scoring System (IPSS-R) together in Asian myelodysplastic syndrome.<br><br>METHODS: We developed a new scoring model of these variables: age&#xa0;&#x2265;&#x2009;65&#x2009;years&#x2009;+&#x2009;IPSS-R score&#x2009;+&#x2009;ASXL1 mutation&#x2009;+&#x2009;TP53 mutation&#x2009;+&#x2009;Telomere length (<5.37). According to this new scoring system, patients were divided into four groups: very good score cutoff (&#x2264;3.0), good (3.0-4.5), poor (4.5-7.0), and very poor (>7.0).<br><br>RESULTS: The median OS was 170.1, 100.4, 46.0, and 12.0&#xa0;months for very good, good, poor, and very poor, retrospectively (p&#x2009;<&#x2009;0.001). Meanwhile, according to the conventional IPSS-R scoring system, the median OS was 141.3, 50.2, 93.0, 36.0, and 16.2&#xa0;months for very low, low, intermediate, high, and very high, retrospectively (p&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: The newly developed model incorporating molecular variations and TL yielded more clear separations of the survival curves. By adding the presence of gene mutation and telomere length to the existing IPSS-R, its predictive ability can be further improved in myelodysplastic syndrome.},
}
@article {pmid36657619,
year = {2023},
author = {Armstrong, E and Boonekamp, J},
title = {Does oxidative stress shorten telomeres in vivo? A meta-analysis.},
journal = {Ageing research reviews},
volume = {85},
number = {},
pages = {101854},
doi = {10.1016/j.arr.2023.101854},
pmid = {36657619},
issn = {1872-9649},
mesh = {Humans ; *Oxidative Stress ; *Aging/genetics ; Telomere ; Telomere Shortening ; },
abstract = {Telomere attrition is considered a hallmark of ageing. Untangling the proximate causes of telomere attrition may therefore reveal important aspects about the ageing process. In a landmark paper in 2002 Thomas von Zglinicki demonstrated that oxidative stress accelerates telomere attrition in cell culture. In the next 20 years, oxidative stress became firmly embedded into modern theories of ageing and telomere attrition. However, a recent surge of in vivo studies reveals an inconsistent pattern questioning the unequivocal role of oxidative stress in telomere length and telomere attrition (henceforth referred to as telomere dynamics), in living organisms. Here we report the results of the first formal meta-analysis on the association between oxidative stress and telomere dynamics in vivo, representing 37 studies, 4969 individuals, and 18,677 correlational measurements. The overall correlation between oxidative stress markers and telomere dynamics was indistinguishable from zero (r = 0.027). This result was independent of the type of oxidative stress marker, telomere dynamic, or taxonomic group. However, telomere measurement method affected the analysis and the subset of TRF-based studies showed a significant overall correlation (r = 0.09), supporting the prediction that oxidative stress accelerates telomere attrition. The correlation was more pronounced in short-lived species and during the adult life phase, when ageing becomes apparent. We then performed an additional meta-analysis of interventional studies (n = 7) manipulating oxidative stress. This revealed a significant effect of treatment on telomere dynamics (d=0.36). Our findings provide new support for the hypothesis that oxidative stress causes telomere attrition in living organisms.},
}
@article {pmid36656928,
year = {2023},
author = {Ballinger, ML and Pattnaik, S and Mundra, PA and Zaheed, M and Rath, E and Priestley, P and Baber, J and Ray-Coquard, I and Isambert, N and Causeret, S and van der Graaf, WTA and Puri, A and Duffaud, F and Le Cesne, A and Seddon, B and Chandrasekar, C and Schiffman, JD and Brohl, AS and James, PA and Kurtz, JE and Penel, N and Myklebost, O and Meza-Zepeda, LA and Pickett, H and Kansara, M and Waddell, N and Kondrashova, O and Pearson, JV and Barbour, AP and Li, S and Nguyen, TL and Fatkin, D and Graham, RM and Giannoulatou, E and Green, MJ and Kaplan, W and Ravishankar, S and Copty, J and Powell, JE and Cuppen, E and van Eijk, K and Veldink, J and Ahn, JH and Kim, JE and Randall, RL and Tucker, K and Judson, I and Sarin, R and Ludwig, T and Genin, E and Deleuze, JF and , and Haber, M and Marshall, G and Cairns, MJ and Blay, JY and , and Thomas, DM and Tattersall, M and Neuhaus, S and Lewis, C and Tucker, K and Carey-Smith, R and Wood, D and Porceddu, S and Dickinson, I and Thorne, H and James, P and Ray-Coquard, I and Blay, JY and Cassier, P and Le Cesne, A and Duffaud, F and Penel, N and Isambert, N and Kurtz, JE and Puri, A and Sarin, R and Ahn, JH and Kim, JE and Ward, I and Judson, I and van der Graaf, W and Seddon, B and Chandrasekar, C and Rickar, R and Hennig, I and Schiffman, J and Randall, RL and Silvestri, A and Zaratzian, A and Tayao, M and Walwyn, K and Niedermayr, E and Mang, D and Clark, R and Thorpe, T and MacDonald, J and Riddell, K and Mar, J and Fennelly, V and Wicht, A and Zielony, B and Galligan, E and Glavich, G and Stoeckert, J and Williams, L and Djandjgava, L and Buettner, I and Osinki, C and Stephens, S and Rogasik, M and Bouclier, L and Girodet, M and Charreton, A and Fayet, Y and Crasto, S and Sandupatla, B and Yoon, Y and Je, N and Thompson, L and Fowler, T and Johnson, B and Petrikova, G and Hambridge, T and Hutchins, A and Bottero, D and Scanlon, D and Stokes-Denson, J and Génin, E and Campion, D and Dartigues, JF and Deleuze, JF and Lambert, JC and Redon, R and Ludwig, T and Grenier-Boley, B and Letort, S and Lindenbaum, P and Meyer, V and Quenez, O and Dina, C and Bellenguez, C and Le Clézio, CC and Giemza, J and Chatel, S and Férec, C and Le Marec, H and Letenneur, L and Nicolas, G and Rouault, K},
title = {Heritable defects in telomere and mitotic function selectively predispose to sarcomas.},
journal = {Science (New York, N.Y.)},
volume = {379},
number = {6629},
pages = {253-260},
doi = {10.1126/science.abj4784},
pmid = {36656928},
issn = {1095-9203},
support = {P50 CA272170/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Genetic Predisposition to Disease ; Genetic Variation ; Germ Cells ; Melanoma/genetics ; *Mitosis/genetics ; *Sarcoma/genetics ; Shelterin Complex/genetics ; *Telomere/genetics ; *Germ-Line Mutation ; },
abstract = {Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify pathways specific to mesenchymal cancers, we performed whole-genome germline sequencing on 1644 sporadic cases and 3205 matched healthy elderly controls. Using an extreme phenotype design, a combined rare-variant burden and ontologic analysis identified two sarcoma-specific pathways involved in mitotic and telomere functions. Variants in centrosome genes are linked to malignant peripheral nerve sheath and gastrointestinal stromal tumors, whereas heritable defects in the shelterin complex link susceptibility to sarcoma, melanoma, and thyroid cancers. These studies indicate a specific role for heritable defects in mitotic and telomere biology in risk of sarcomas.},
}
@article {pmid36652742,
year = {2023},
author = {Lv, BB and Yang, CL and Tan, ZX and Zheng, L and Li, MD and Jiang, YL and Liu, L and Tang, MM and Hua, DX and Yang, J and Xu, DX and Zhao, H and Fu, L},
title = {Association between cadmium exposure and pulmonary function reduction: Potential mediating role of telomere attrition in chronic obstructive pulmonary disease patients.},
journal = {Ecotoxicology and environmental safety},
volume = {251},
number = {},
pages = {114548},
doi = {10.1016/j.ecoenv.2023.114548},
pmid = {36652742},
issn = {1090-2414},
mesh = {Humans ; Cadmium/toxicity ; *Telomerase ; Forced Expiratory Volume ; *Pulmonary Disease, Chronic Obstructive ; Lung ; },
abstract = {BACKGROUND: Environmental cadmium (Cd) exposure is linked to pulmonary function injury in the general population. But, the association between blood Cd concentration and pulmonary function has not been investigated thoroughly in chronic obstructive pulmonary disease (COPD) patients, and the potential mechanisms are unclear.<br><br>METHODS: All eligible 789 COPD patients were enrolled from Anhui COPD cohort. Blood specimens and clinical information were collected. Pulmonary function test was conducted. The subunit of telomerase, telomerase reverse transcriptase (TERT), was determined through enzyme linked immunosorbent assay (ELISA). Blood Cd was measured via inductively coupled-mass spectrometer (ICP-MS).<br><br>RESULTS: Blood Cd was negatively and dose-dependently associated with pulmonary function. Each 1-unit increase of blood Cd was associated with 0.861&#xa0;L decline in FVC, 0.648&#xa0;L decline in FEV1, 5.938 % decline in FEV1/FVC %, and 22.098 % decline in FEV1 % among COPD patients, respectively. Age, current-smoking, self-cooking and higher smoking amount aggravated Cd-evoked pulmonary function decrease. Additionally, there was an inversely dose-response association between Cd concentration and TERT in COPD patients. Elevated TERT obviously mediated 29.53 %, 37.50 % and 19.48 % of Cd-evoked FVC, FEV1, and FEV1 % declines in COPD patients, respectively.<br><br>CONCLUSION: Blood Cd concentration is strongly associated with the decline of pulmonary function and telomerase activity among COPD patients. Telomere attrition partially mediates Cd-induced pulmonary function decline, suggesting an underlying mechanistic role of telomere attrition in pulmonary function decline from Cd exposure in COPD patients.},
}
@article {pmid36651908,
year = {2023},
author = {James, EN and Sagi-Kiss, V and Bennett, M and Mycielska, ME and Karen-Ng, LP and Roberts, T and Matta, S and Dokal, I and Bundy, JG and Parkinson, EK},
title = {Dyskeratosis Congenita Links Telomere Attrition to Age-Related Systemic Energetics.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {78},
number = {5},
pages = {780-789},
pmid = {36651908},
issn = {1758-535X},
support = {MR/P018440/1/MRC_/Medical Research Council/United Kingdom ; R452/1115/DMT_/The Dunhill Medical Trust/United Kingdom ; },
mesh = {Humans ; Animals ; Mice ; *Dyskeratosis Congenita/genetics/metabolism ; *Telomerase/genetics/metabolism ; *Diabetes Mellitus, Type 2 ; Telomere/genetics/metabolism ; Mutation ; Citrates ; Lactates ; Nuclear Proteins/metabolism ; Cell Cycle Proteins/genetics/metabolism ; },
abstract = {The underlying mechanisms of plasma metabolite signatures of human aging and age-related diseases are not clear but telomere attrition and dysfunction are central to both. Dyskeratosis congenita (DC) is associated with mutations in the telomerase enzyme complex (TERT, TERC, and DKC1) and progressive telomere attrition. We analyzed the effect of telomere attrition on senescence-associated metabolites in fibroblast-conditioned media and DC patient plasma. Samples were analyzed by gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. We showed extracellular citrate was repressed by canonical telomerase function in vitro and associated with DC leukocyte telomere attrition in vivo, leading to the hypothesis that altered citrate metabolism detects telomere dysfunction. However, elevated citrate and senescence factors only weakly distinguished DC patients from controls, whereas elevated levels of other tricarboxylic acid cycle (TCA) metabolites, lactate, and especially pyruvate distinguished them with high significance. The DC plasma signature most resembled that of patients with loss of function pyruvate dehydrogenase complex mutations and that of older subjects but significantly not those of type 2 diabetes, lactic acidosis, or elevated mitochondrial reactive oxygen species. Additionally, our data are consistent with further metabolism of citrate and lactate in the liver and kidneys. Citrate uptake in certain organs modulates age-related disease in mice and our data have similarities with age-related disease signatures in humans. Our results have implications for the role of telomere dysfunction in human aging in addition to its early diagnosis and the monitoring of anti-senescence therapeutics, especially those designed to improve telomere function.},
}
@article {pmid36651296,
year = {2023},
author = {Storchova, R and Palek, M and Palkova, N and Veverka, P and Brom, T and Hofr, C and Macurek, L},
title = {Phosphorylation of TRF2 promotes its interaction with TIN2 and regulates DNA damage response at telomeres.},
journal = {Nucleic acids research},
volume = {51},
number = {3},
pages = {1154-1172},
pmid = {36651296},
issn = {1362-4962},
mesh = {DNA Damage ; Phosphorylation ; Proteomics ; *Shelterin Complex ; Telomere/metabolism ; *Telomere-Binding Proteins/metabolism ; *Telomeric Repeat Binding Protein 2 ; Humans ; },
abstract = {Protein phosphatase magnesium-dependent 1 delta (PPM1D) terminates the cell cycle checkpoint by dephosphorylating the tumour suppressor protein p53. By targeting additional substrates at chromatin, PPM1D contributes to the control of DNA damage response and DNA repair. Using proximity biotinylation followed by proteomic analysis, we identified a novel interaction between PPM1D and the shelterin complex that protects telomeric DNA. In addition, confocal microscopy revealed that endogenous PPM1D localises at telomeres. Further, we found that ATR phosphorylated TRF2 at S410 after induction of DNA double strand breaks at telomeres and this modification increased after inhibition or loss of PPM1D. TRF2 phosphorylation stimulated its interaction with TIN2 both in vitro and at telomeres. Conversely, induced expression of PPM1D impaired localisation of TIN2 and TPP1 at telomeres. Finally, recruitment of the DNA repair factor 53BP1 to the telomeric breaks was strongly reduced after inhibition of PPM1D and was rescued by the expression of TRF2-S410A mutant. Our results suggest that TRF2 phosphorylation promotes the association of TIN2 within the shelterin complex and regulates DNA repair at telomeres.},
}
@article {pmid36650155,
year = {2023},
author = {Tham, CY and Poon, L and Yan, T and Koh, JYP and Ramlee, MK and Teoh, VSI and Zhang, S and Cai, Y and Hong, Z and Lee, GS and Liu, J and Song, HW and Hwang, WYK and Teh, BT and Tan, P and Xu, L and Koh, AS and Osato, M and Li, S},
title = {High-throughput telomere length measurement at nucleotide resolution using the PacBio high fidelity sequencing platform.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {281},
pmid = {36650155},
issn = {2041-1723},
mesh = {Humans ; *Telomere/genetics ; *Shelterin Complex ; Aging ; },
abstract = {Telomeres are specialized nucleoprotein structures at the ends of linear chromosomes. The progressive shortening of steady-state telomere length in normal human somatic cells is a promising biomarker for age-associated diseases. However, there remain substantial challenges in quantifying telomere length due to the lack of high-throughput method with nucleotide resolution for individual telomere. Here, we describe a workflow to capture telomeres using newly designed telobaits in human culture cell lines as well as clinical patient samples and measure their length accurately at nucleotide resolution using single-molecule real-time (SMRT) sequencing. Our results also reveal the extreme heterogeneity of telomeric variant sequences (TVSs) that are dispersed throughout the telomere repeat region. The presence of TVSs disrupts the continuity of the canonical (5'-TTAGGG-3')n telomere repeats, which affects the binding of shelterin complexes at the chromosomal ends and telomere protection. These findings may have profound implications in human aging and diseases.},
}
@article {pmid36649908,
year = {2023},
author = {Lambert-Lanteigne, P and Young, A and Autexier, C},
title = {Complex interaction network revealed by mutation of human telomerase 'insertion in fingers' and essential N-terminal domains and the telomere protein TPP1.},
journal = {The Journal of biological chemistry},
volume = {299},
number = {3},
pages = {102916},
pmid = {36649908},
issn = {1083-351X},
support = {PJT-166130//CIHR/Canada ; },
mesh = {Humans ; Cell Line ; Mutation ; *Telomerase/chemistry/metabolism ; Telomere/chemistry/metabolism ; *Telomere-Binding Proteins/chemistry/metabolism ; *Shelterin Complex/chemistry/metabolism ; },
abstract = {In the majority of human cancer cells, cellular immortalization depends on the maintenance of telomere length by telomerase. An essential step required for telomerase function is its recruitment to telomeres, which is regulated by the interaction of the telomere protein, TPP1, with the telomerase essential N-terminal (TEN) domain of the human telomerase reverse transcriptase, hTERT. We previously reported that the hTERT 'insertion in fingers domain' (IFD) recruits telomerase to telomeres in a TPP1-dependent manner. Here, we use hTERT truncations and the IFD domain containing mutations in conserved residues or premature aging disease-associated mutations to map the interactions between the IFD and TPP1. We find that the hTERT-IFD domain can interact with TPP1. However, deletion of the IFD motif in hTERT lacking the N-terminus and the C-terminal extension does not abolish interaction with TPP1, suggesting the IFD is not essential for hTERT interaction with TPP1. Several conserved residues in the central IFD-TRAP region that we reported regulate telomerase recruitment to telomeres, and cell immortalization compromise interaction of the hTERT-IFD domain with TPP1 when mutated. Using a similar approach, we find that the IFD domain interacts with the TEN domain but is not essential for intramolecular hTERT interactions with the TEN domain. IFD-TEN interactions are not disrupted by multiple amino acid changes in the IFD or TEN, thus highlighting a complex regulation of IFD-TEN interactions as suggested by recent cryo-EM structures of human telomerase.},
}
@article {pmid36649354,
year = {2023},
author = {Schneper, LM and Drake, AJ and Dunstan, T and Kotenko, I and Notterman, DA and Piyasena, C},
title = {Characteristics of salivary telomere length shortening in preterm infants.},
journal = {PloS one},
volume = {18},
number = {1},
pages = {e0280184},
pmid = {36649354},
issn = {1932-6203},
support = {R01 HD076592/HD/NICHD NIH HHS/United States ; },
mesh = {Infant ; Female ; Humans ; Infant, Newborn ; *Infant, Premature ; *Telomere Shortening ; Gestational Age ; Maternal Age ; Telomere/genetics ; },
abstract = {OBJECTIVE: To examine the association between gestational age, telomere length (TL) and rate of shortening in newborns.<br><br>STUDY DESIGN: Genomic DNA was isolated from buccal samples of 39 term infants at birth and one year and 32 preterm infants at birth, term-adjusted age (40 weeks post-conception) and age one-year corrected for gestational duration. Telomere length was measured by quantitative real-time PCR. Demographic and clinical data were collected during clinic or research visits and from hospital records. Socioeconomic status was estimated using the deprivation category (DEPCAT) scores derived from the Carstairs score of the subject's postal code.<br><br>RESULTS: At birth, preterm infants had longer telomeres than infants born at term. However, there was no difference in telomere length between preterm infants and term infants at one year of age, implying that the rate of telomere shortening was greater in pre-term than term infants. Interestingly, TL at age 40 weeks post-conception in preterm infants was significantly longer than term infant TL at birth, suggesting that time since conception is not the only factor that affects rate of shortening. Several factors, including sex, fetal growth restriction, maternal age, maternal booking body mass index (BMI), mother education level and DEPCAT score, also differed between the preterm and term groups.<br><br>CONCLUSIONS: Preterm infants have longer telomeres than term infants at birth. In the studied cohort, the rate of telomere shortening was greater in the premature group compared with the term infants. This finding agrees with previous studies using cord blood, suggesting that the longer TL in premature infants detected at birth do not persist and demonstrating that use of saliva DNA is acceptable for studies of telomere dynamics in infants. However, that the TL at age 40 weeks post-conception in preterm is longer than term infants at birth suggests that biological factors other than time since conception also affect rate of shortening.},
}
@article {pmid36643758,
year = {2023},
author = {Fu, A and Zheng, Y and Guo, J and Grierson, D and Zhao, X and Wen, C and Liu, Y and Li, J and Zhang, X and Yu, Y and Ma, H and Wang, Q and Zuo, J},
title = {Telomere-to-telomere genome assembly of bitter melon (Momordica charantia L. var. abbreviata Ser.) reveals fruit development, composition and ripening genetic characteristics.},
journal = {Horticulture research},
volume = {10},
number = {1},
pages = {uhac228},
pmid = {36643758},
issn = {2662-6810},
abstract = {Momordica charantia L. var. abbreviata Ser. (Mca), known as bitter gourd or bitter melon, is a Momordica variety with medicinal value and belongs to the Cucurbitaceae family. In view of the lack of genomic information on bitter gourd and other Momordica species and to promote Mca genomic research, we assembled a 295.6-Mb telomere-to-telomere (T2T) high-quality Mca genome with six gap-free chromosomes after Hi-C correction. This genome is anchored to 11 chromosomes, which is consistent with the karyotype information, and comprises 98 contigs (N50 of 25.4 Mb) and 95 scaffolds (N50 of 25.4 Mb). The Mca genome harbors 19 895 protein-coding genes, of which 45.59% constitute predicted repeat sequences. Synteny analysis revealed variations involved in fruit quality during the divergence of bitter gourd. In addition, assay for transposase-accessible chromatin by high-throughput sequencing and metabolic analysis showed that momordicosides and other substances are characteristic of Mca fruit pulp. A combined transcriptomic and metabolomic analysis revealed the mechanisms of pigment accumulation and cucurbitacin biosynthesis in Mca fruit peels, providing fundamental molecular information for further research on Mca fruit ripening. This report provides a new genetic resource for Momordica genomic studies and contributes additional insights into Cucurbitaceae phylogeny.},
}
@article {pmid36642039,
year = {2023},
author = {Zong, ZQ and Chen, SW and Wu, Y and Gui, SY and Zhang, XJ and Hu, CY},
title = {Ambient air pollution exposure and telomere length: a systematic review and meta-analysis.},
journal = {Public health},
volume = {215},
number = {},
pages = {42-55},
doi = {10.1016/j.puhe.2022.11.022},
pmid = {36642039},
issn = {1476-5616},
mesh = {Child ; Adult ; Female ; Pregnancy ; Humans ; Nitrogen Dioxide/analysis ; Environmental Exposure ; *Air Pollution/analysis ; *Air Pollutants/adverse effects/analysis ; Particulate Matter/adverse effects/analysis ; Telomere/chemistry ; },
abstract = {OBJECTIVE: This study aimed to provide evidence of the associations between pre- and post-birth and adulthood air pollution exposure with telomere length.<br><br>STUDY DESIGN: The databases of PubMed, Embase, and Web of Science were searched up to June 1st, 2022 in order to include relevant observational studies and perform a systematic review and meta-analysis.<br><br>METHODS: The random-effects meta-analysis was grouped by air pollutant and exposure window (pre- and post-birth and adulthood) to evaluate the summary effect estimate. Cochran's Q and I[2] statistics were used to evaluate the heterogeneity among the included studies. The quality of individual studies was evaluated using the national toxicology program/office of health assessment and translation risk of bias rating tool.<br><br>RESULTS: We identified 18 studies, covering 8506 children and 2263 adults from multiple countries. We found moderate evidence that particulate matter less than 2.5&#xa0;&#x3bc;m (PM2.5) exposure during the entire pregnancy (-0.043, 95% CI:&#xa0;-0.067,&#xa0;-0.018), nitrogen dioxide (NO2) exposure during the first trimester (-0.016, 95% confidence interval [CI]:&#xa0;-0.027,&#xa0;-0.005), long-term adulthood PM2.5 exposure were associated with shortening telomere length. Mild to high between-study heterogeneity was observed for the most tested air pollutant-telomere length combinations in different exposure windows.<br><br>CONCLUSIONS: This systematic review and meta-analysis provides the evidence which strongly supports that prenatal PM2.5 and NO2 exposures were related to reduced telomere length, while prenatal sulfur dioxide (SO2) and carbon monoxide (CO) exposures, childhood PM2.5, particulate matter less than 10&#xa0;&#x3bc;m (PM10), NO2 exposures and short-term adulthood PM2.5 and PM10 exposures were not associated with telomere length. Further high-quality studies are needed to elaborate our suggestive associations.},
}
@article {pmid36641077,
year = {2023},
author = {Siegel, SR and Ulrich, M and Logue, SF},
title = {Comparison qPCR study for selecting a valid single copy gene for measuring absolute telomere length.},
journal = {Gene},
volume = {860},
number = {},
pages = {147192},
doi = {10.1016/j.gene.2023.147192},
pmid = {36641077},
issn = {1879-0038},
mesh = {Humans ; Gene Dosage ; *Interferon-beta/genetics ; *Polymerase Chain Reaction/methods ; Reference Standards ; *Telomere/genetics ; *Telomere Shortening/genetics ; },
abstract = {Telomere shortening is a well-known biomarker for biological aging. A previous review of the methods used to measure telomere length (TL) noted how challenging it is to compare results from different studies using diverse methodological techniques. The most commonly used high throughput method for measuring average TL is the quantitative PCR (qPCR) method, where there are two protocols available; the relative TL and the absolute TL (aTL) method. All qPCR methods have similarities in that they use two different primer sets to measure the telomere repeat sequence (TTAGGG)n and a single copy gene region to calculate the average TL, (T/S) ratio. The difference between the relative TL and the aTL assay lies with the introduction of duplex oligomer standards to identify TL in kilobase pairs rather than using the traditional relative TL, T/S ratio method. Problems were noted using 36B4 (RPLP0), which was originally used as a suitable single copy gene qPCR assay. A previous aTL publication attempted to replace the 36B4 (RPLP0) single copy gene using the Interferon beta 1 gene (IFNB1) but results showed a lack of agreement with the TL results when compared to the DNAmTL assay. Here, we compare the two single copy gene assays previously used for the aTL assay and offer an alternative IFNB1 single copy gene assay without non-specific priming amplification to provide more consistent diploid copy number determination and a more robust and reproducible assay for measuring absolute TL.},
}
@article {pmid36636341,
year = {2023},
author = {Guo, YZ and Zhang, Y and Wang, Q and Yu, J and Wan, QH and Huang, J and Fang, SG},
title = {Alternative telomere maintenance mechanism in Alligator sinensis provides insights into aging evolution.},
journal = {iScience},
volume = {26},
number = {1},
pages = {105850},
pmid = {36636341},
issn = {2589-0042},
abstract = {Lifespan is a life-history trait that undergoes natural selection. Telomeres are hallmarks of aging, and shortening rate predicts species lifespan, making telomere maintenance mechanisms throughout different lifespans a worthy topic for study. Alligators are suitable for the exploration of anti-aging molecular mechanisms, because they exhibit low or even negligible mortality in adults and no significant telomere shortening. Telomerase reverse transcriptase (TERT) expression is absent in the adult Alligator sinensis, as in humans. Selection analyses on telomere maintenance genes indicated that ATM, FANCE, SAMHD1, HMBOX1, NAT10, and MAP3K4 experienced positive selection on A. sinensis. Repressed pleiotropic ATM kinase in A. sinensis suggests their fitness optimum shift. In ATM downstream, Alternative Lengthening of Telomeres (ALT)-related genes were clustered in a higher expression pattern in A. sinensis, which covers 10-15% of human cancers showing no telomerase activities. In summary, we demonstrated how telomere shortening, telomerase activities, and ALT contributed to anti-aging strategies.},
}
@article {pmid36635307,
year = {2023},
author = {Romero-Zamora, D and Hayashi, MT},
title = {A non-catalytic N-terminus domain of WRN prevents mitotic telomere deprotection.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {645},
pmid = {36635307},
issn = {2045-2322},
mesh = {Werner Syndrome Helicase/genetics/metabolism ; *Exodeoxyribonucleases/genetics ; *Telomeric Repeat Binding Protein 2 ; RecQ Helicases/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {Telomeric ends form a loop structure (T-loop) necessary for the repression of ATM kinase activation throughout the normal cell cycle. However, cells undergoing a prolonged mitotic arrest are prone to lose the T-loop, resulting in Aurora B kinase-dependent mitotic telomere deprotection, which was proposed as an anti-tumor mechanism that eliminates precancerous cells from the population. The mechanism of mitotic telomere deprotection has not been elucidated. Here, we show that WRN, a RECQ helicase family member, can suppress mitotic telomere deprotection independently of its exonuclease and helicase activities. Truncation of WRN revealed that N-terminus amino acids 168-333, a region that contains a coiled-coil motif, is sufficient to suppress mitotic telomere deprotection without affecting both mitotic Aurora B-dependent spindle checkpoint and ATM kinase activity. The suppressive activity of the WRN[168-333] fragment is diminished in cells partially depleted of TRF2, while WRN is required for complete suppression of mitotic telomere deprotection by TRF2 overexpression. Finally, we found that phosphomimetic but not alanine mutations of putative Aurora B target sites in the WRN[168-333] fragment abolished its suppressive effect. Our findings reveal a non-enzymatic function of WRN, which may be regulated by phosphorylation in cells undergoing mitotic arrest. We propose that WRN enhances the protective function of TRF2 to counteract the hypothetical pathway that resolves the mitotic T-loop.},
}
@article {pmid36634459,
year = {2023},
author = {Vulsteke, JB and Smith, V and Bonroy, C and Derua, R and Blockmans, D and De Haes, P and Vanderschueren, S and Lenaerts, JL and Claeys, KG and Wuyts, WA and Verschueren, P and Vanhandsaeme, G and Piette, Y and De Langhe, E and Bossuyt, X},
title = {Identification of new telomere- and telomerase-associated autoantigens in systemic sclerosis.},
journal = {Journal of autoimmunity},
volume = {135},
number = {},
pages = {102988},
doi = {10.1016/j.jaut.2022.102988},
pmid = {36634459},
issn = {1095-9157},
mesh = {Humans ; Autoantigens ; *Telomerase/metabolism ; *Scleroderma, Systemic ; Autoantibodies ; Telomere ; Nuclear Proteins/metabolism ; Cell Cycle Proteins/metabolism ; ATPases Associated with Diverse Cellular Activities/metabolism ; Carrier Proteins ; DNA Helicases/metabolism ; DNA-Binding Proteins/metabolism ; RNA-Binding Proteins ; },
abstract = {PURPOSE: In up to 20% of patients with systemic sclerosis (SSc) no known autoantibody specificity can be identified. Recently discovered autoantigens, such as telomeric repeat binding factor 1 (TERF1), as well as established autoantigens, like RuvBL1/2, are associated with telomere and telomerase biology. We aimed to identify new telomere- and telomerase-associated autoantigens in patients with SSc without known autoantibody specificity.<br><br>METHODS: Unlabelled protein immunoprecipitation combined with gel-free liquid chromatography-tandem mass spectrometry (IP-MS) was performed with sera of 106 patients with SSc from two tertiary referral centres that had a nuclear pattern on HEp-2 indirect immunofluorescence without previously identified autoantibody. Telomere- or telomerase-associated proteins or protein complexes precipitated by individual sera were identified. Candidate autoantigens were confirmed through immunoprecipitation-western blot (IP-WB). A custom Luminex xMAP assay for 5 proteins was evaluated with sera from persons with SSc (n&#xa0;=&#xa0;467), other systemic autoimmune rheumatic diseases (n&#xa0;=&#xa0;923), non-rheumatic disease controls (n&#xa0;=&#xa0;187) and healthy controls (n&#xa0;=&#xa0;199).<br><br>RESULTS: Eight telomere- and telomerase-associated autoantigens were identified in a total of 11 index patients, including the THO complex (n&#xa0;=&#xa0;3, all with interstitial lung disease and two with cardiac involvement), telomeric repeat-binding factor 2 (TERF2, n&#xa0;=&#xa0;1), homeobox-containing protein 1 (HMBOX1, n&#xa0;=&#xa0;2), regulator of chromosome condensation 1 (RCC1, n&#xa0;=&#xa0;1), nucleolar and coiled-body phosphoprotein 1 (NOLC1, n&#xa0;=&#xa0;1), dyskerin (DKC1, n&#xa0;=&#xa0;1), probable 28S rRNA (cytosine(4447)-C(5))-methyltransferase (NOP2, n&#xa0;=&#xa0;1) and nuclear valosin-containing protein-like (NVL, n&#xa0;=&#xa0;2). A Luminex xMAP assay for THO complex subunit 1 (THOC1), TERF2, NOLC1, NOP2 and NVL revealed high reactivity in all index patients, but also in other patients with SSc and disease controls. However, the reactivity by xMAP assay in these other patients was not confirmed by IP-WB.<br><br>CONCLUSION: IP-MS revealed key telomere- and telomerase-associated proteins and protein complexes as autoantigens in patients with SSc.},
}
@article {pmid36627320,
year = {2023},
author = {Sohn, I and Shin, C and Baik, I},
title = {Associations of green tea, coffee, and soft drink consumption with longitudinal changes in leukocyte telomere length.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {492},
pmid = {36627320},
issn = {2045-2322},
mesh = {Male ; Humans ; Female ; *Coffee ; *Tea ; Carbonated Beverages ; Leukocytes ; Telomere ; },
abstract = {Whether beverage consumption is associated with longitudinal observation of telomere length remains unclear. We evaluated the association of green tea, coffee, and soft drink consumption with 6-year changes in leukocyte telomere length (LTL). The study included 1952 participants who provided whole blood samples for LTL assays during the baseline (year 2011-2012) and follow-up (year 2017-2018) periods and reported baseline information on consumption of green tea, coffee, and soft drinks. Robust regression analysis was used to analyze the association adjusted for potential confounding variables. In the results, an inverse association between green tea consumption and LTL changes from baseline, which indicate telomere shortening, was found; regression coefficient [95% confidence interval] was - 0.097 [- 0.164, - 0.029] for participants who daily consumed at least 1 cup of green tea compared with non-consumers (p value = 0.006). This association was stronger among women (versus men) and younger participants aged 50-64 years (versus older). However, a positive association between soft drink consumption and LTL shortening was observed among women (p value < 0.05). Coffee consumption was not associated with LTL changes. These findings suggested that green tea consumption may be protective against telomere shortening reflecting biological aging whereas coffee and soft drink consumption may not.},
}
@article {pmid36617609,
year = {2023},
author = {Montoya, M and Uchino, BN},
title = {Social support and telomere length: a meta-analysis.},
journal = {Journal of behavioral medicine},
volume = {46},
number = {4},
pages = {556-565},
pmid = {36617609},
issn = {1573-3521},
support = {R01 HL137606/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Social Support ; *Telomere ; },
abstract = {Previous studies have shown that lower social support is associated with higher all-cause mortality (Holt-Lunstad et al. in PLoS ONE Medicine 7:e1000316, 2010). While social support has been associated with system-specific biological measures (e.g., cardiovascular), there is the need to elucidate more general biological mechanisms linking social support to health risk across a number of diseases. In this meta-analytic review, the link between social support and telomere length (Cawthon et al. in Lancet 361:393-395, 2003) was conducted based on the updated PRISMA guidelines (Page et al., 2021). Across 17 studies, higher social support was not significantly related to longer telomere length (Zr = 0.010, 95% CI [- 0.028, 0.047], p > 0.05). The confidence interval indicated that the bulk of plausible values were small to null associations. Little evidence for bias was found as shown by funnel plots and Kendall's Tau. Moderator analyses focusing on the measure of support, health of sample, age, type of assay specimen, and gender were not significant. In conclusion, this review showed no significant relationship between social support and telomere length and highlights important future directions.},
}
@article {pmid36612286,
year = {2022},
author = {Faugeras, E and Véronèse, L and Jeannin, G and Janicot, H and Bailly, S and Bay, JO and Pereira, B and Cayre, A and Penault-Llorca, F and Cachin, F and Merle, P and Tchirkov, A},
title = {Telomere Status of Advanced Non-Small-Cell Lung Cancer Offers a Novel Promising Prognostic and Predictive Biomarker.},
journal = {Cancers},
volume = {15},
number = {1},
pages = {},
pmid = {36612286},
issn = {2072-6694},
abstract = {Telomere length appears to correlate with survival in early non-small-cell lung cancer (NSCLC), but the prognostic impact of telomere status in advanced NSCLC remains undetermined. Our purpose was to evaluate telomere parameters as prognostic and predictive biomarkers in advanced NSCLC. In 79 biopsies obtained before treatment, we analyzed the telomere length and expression of TERT and shelterin complex genes (TRF1, TRF2, POT1, TPP1, RAP1, and TIN2), using quantitative PCR. Non-responders to first-line chemotherapy were characterized by shorter telomeres and low RAP1 expression (p = 0.0035 and p = 0.0069), and tended to show higher TERT levels (p = 0.058). In multivariate analysis, short telomeres were associated with reduced event-free (EFS, p = 0.0023) and overall survival (OS, p = 0.00041). TERT and TRF2 overexpression correlated with poor EFS (p = 0.0069 and p = 0.00041) and OS (p = 0.0051 and p = 0.007). Low RAP1 and TIN2 expression-levels were linked to reduced EFS (p = 0.00032 and p = 0.0069) and OS (p = 0.000051 and p = 0.02). Short telomeres were also associated with decreased survival after nivolumab therapy (p = 0.097). Evaluation of telomere status in advanced NSCLC emerges as a useful biomarker that allows for the selection of patient groups with different clinical evolutions, to establish personalized treatment.},
}
@article {pmid36612269,
year = {2022},
author = {García-Martínez, S and González-Gamo, D and Tesolato, SE and Barabash, A and de la Serna, SC and Domínguez-Serrano, I and Dziakova, J and Rivera, D and Torres, AJ and Iniesta, P},
title = {Telomere Length and Telomerase Activity in Subcutaneous and Visceral Adipose Tissues from Obese and Non-Obese Patients with and without Colorectal Cancer.},
journal = {Cancers},
volume = {15},
number = {1},
pages = {},
pmid = {36612269},
issn = {2072-6694},
support = {PI15/01199 and PI19/00073//Instituto de Salud Carlos III/ ; },
abstract = {To investigate the molecular mechanisms that link obesity and colorectal cancer (CRC), we analyzed parameters related to telomere function in subcutaneous and visceral adipose tissues (SAT and VAT), including subjects with and without CRC, who were classified according to their body mass index (BMI). Adipose tissues were obtained from 147 patients who had undergone surgery. A total of 66 cases corresponded to CRC patients, and 81 subjects were not affected by cancer. Relative telomere length was established by qPCR, and telomerase activity was determined by a method based on the telomeric repeat amplification protocol. Our results indicated longer telomeres in patients affected by CRC, both in SAT and VAT, when compared to the group of subjects without CRC. Tumor local invasion was associated with telomere length (TL) in SAT. Considering the BMI values, significant differences were found in the TL of both adipose tissues between subjects affected by CRC and those without cancer. Overweight subjects showed the greatest differences, with longer telomeres in the group of CRC patients, and a higher number of cases with telomerase reactivation in the VAT of subjects without cancer. In conclusion, parameters related to telomere function in adipose tissue could be considered as potential biomarkers in the evaluation of CRC and obesity.},
}
@article {pmid36609582,
year = {2023},
author = {Rolles, B and Ferreira, MSV and Vieri, M and Rheinwalt, KP and Schmitz, SM and Alizai, PH and Neumann, U and Brümmendorf, TH and Beier, F and Ulmer, TF and Tometten, M},
title = {Telomere length dynamics measured by flow-FISH in patients with obesity undergoing bariatric surgery.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {304},
pmid = {36609582},
issn = {2045-2322},
mesh = {Humans ; *Quality of Life ; Obesity/surgery ; *Bariatric Surgery ; Telomere ; },
abstract = {Obesity has negative effects on comorbidities, health-related quality of life and survival. Telomere length (TL) changes after bariatric surgery have been reported, but the studies are contradictory, and analyses using state-of-the art techniques for TL measurement, such as flow-FISH, are sparse. We measured TL dynamics via flow-FISH in patients undergoing bariatric surgery and compared their TL with 105 healthy individuals. Patients with obesity who underwent bariatric surgery were included. Lymphocyte and granulocyte absolute and age-adjusted (aa) TL were analyzed by flow-FISH before (preoperative cohort, n = 45) and after surgery (follow-up cohort, n = 35) at month 5.5 ± 3.9 (mean ± standard deviation [SD]). The initial lymphocyte aaTL was significantly shorter (-0.37 kb ± 0.18 kb, P = 0.045) in patients with obesity, while the granulocyte aaTL was not different from that in the healthy comparison population (0.28 kb ± 0.17 kb, P = 0.11). The telomere dynamics after surgery showed an increase in mean TL in both lymphocytes and granulocytes of patients with a pronounced BMI loss of ≥ 10 kg/m[2]. We did not find any association between TL increase after surgery and age, sex or the type of procedure selected for bariatric surgery. We confirmed that patients suffering from obesity have significantly shorter lymphocyte TL using flow-FISH. Along with and dependent on the degree of weight reduction after bariatric surgery, TL significantly increased in both lymphocytes and granulocytes after a mean of 5.5 months. Our results show that bariatric surgery affects not only body weight but also biomarkers of aging, such as TL.},
}
@article {pmid36607563,
year = {2023},
author = {Troxel, WM and Madrigano, J and Haas, AC and Dubowitz, T and Rosso, AL and Prather, AA and Ghosh-Dastidar, M and Weinstein, AM and Butters, MA and Presto, A and Gary-Webb, TL},
title = {Examining the Cross-sectional Association Between Neighborhood Conditions, Discrimination, and Telomere Length in a Predominantly African American Sample.},
journal = {Journal of racial and ethnic health disparities},
volume = {10},
number = {6},
pages = {3159-3167},
pmid = {36607563},
issn = {2196-8837},
support = {R01 HL131531/HL/NHLBI NIH HHS/United States ; R01-HL131531-S2/HL/NHLBI NIH HHS/United States ; R01 AG072652/AG/NIA NIH HHS/United States ; K23 AG076663/AG/NIA NIH HHS/United States ; AG072652/AG/NIA NIH HHS/United States ; NHLBI R01 HL131531/HL/NHLBI NIH HHS/United States ; R01 CA149105/CA/NCI NIH HHS/United States ; NHLBI R01 HL131531/HL/NHLBI NIH HHS/United States ; R01-HL131531-S2/HL/NHLBI NIH HHS/United States ; AG072652/AG/NIA NIH HHS/United States ; },
mesh = {Aged ; Humans ; *Aging ; *Black or African American ; Cross-Sectional Studies ; Particulate Matter ; *Telomere ; *Neighborhood Characteristics ; *Racism ; Air Pollution ; },
abstract = {Disproportionate exposure to adverse neighborhood conditions and greater discrimination may contribute to health disparities among African Americans (AAs). We examined whether adverse neighborhood conditions, alone or in conjunction with discrimination, associate with shorter leukocyte telomere length among a predominantly AA cohort. The sample included 200 residents from two low-income neighborhoods (96% AA; mean age = 67 years). Perceived neighborhood conditions and discrimination were surveyed in 2018, and objective neighborhood conditions (total crime rate, neighborhood walkability, ambient air pollution (PM2.5, black carbon)) were collected in 2017/2018. Relative telomere length (T/S; ratio of telomeric DNA to a single-gene copy) was assessed from blood samples. Linear regression models estimated the main effects of each neighborhood condition and discrimination and their interactions on the T/S ratio. Less walkable neighborhoods were associated with shorter telomeres. Higher air pollution (PM2.5) was associated with shorter telomeres among those experiencing greater discrimination. Findings highlight the importance of understanding the intersecting influences of historic and contemporary sources of systemic racism and how they contribute to accelerated aging among adults.},
}
@article {pmid36607418,
year = {2023},
author = {Hassanpour, H and Farhadi, N and Bahadoran, S and Akbari, MR},
title = {Cardiac telomere attrition following changes in the expression of shelterin genes in pulmonary hypertensive chickens.},
journal = {British poultry science},
volume = {64},
number = {3},
pages = {370-376},
doi = {10.1080/00071668.2022.2163877},
pmid = {36607418},
issn = {1466-1799},
mesh = {Animals ; *Chickens/genetics/metabolism ; *Telomere-Binding Proteins/genetics/metabolism ; Shelterin Complex ; Telomere/metabolism ; Heart ; },
abstract = {1. The alterations of relative telomere length and expression of shelterin genes (TRF1, TRF2, RAP1, POT1, and TPP1) were evaluated from the chickens' right heart ventricle in the early and last stages of cold-induced pulmonary hypertension (PHS) at 21 and 42 d of age.2. The relative telomere length in the right ventricular tissues was significantly shorter in the PHS group of broilers than in the control group at 42 d, but did not statistically change at 21 d of age. There was a significant negative correlation between relative telomere length and RV:TV ratio in the broilers at 42 d of age.3. The relative expression of POT1, RAP1 and TPP1 genes in the right ventricular tissues was significantly lower in the PHS group than in the control group at 21 d. The relative expression of the TRF2 gene was only higher in the PHS group of broilers than control at 42 d. The mRNA level of the TRF2 gene exhibited a significant positive correlation with RV:TV ratio at 42 d.4. It was concluded that most shelterin genes are dysregulated in the early stage of PHS (right ventricular hypertrophy) while telomere attrition occurs only at the last stage (heart dilation/failure).},
}
@article {pmid36605550,
year = {2022},
author = {Ask, TF and Sütterlin, S},
title = {Prefrontally modulated vagal neuroimmunomodulation is associated with telomere length.},
journal = {Frontiers in neuroscience},
volume = {16},
number = {},
pages = {1063162},
pmid = {36605550},
issn = {1662-4548},
abstract = {BACKGROUND: Accumulated senescent cells are proposed to be one of the main drivers of age-related pathology such as dementia and cancer through disruption of tissue structure and function. We recently proposed the Neuro-Immuno-Senescence Integrative Model (NISIM), which relates prefrontally modulated vagal tone and subsequent balance between vagal and sympathetic input to the spleen to inflammatory responses leading to generation of reactive oxygen species and oxidative telomere damage.<br><br>AIM: In this study, we assess inflammation as a mediator in the relationship between prefrontally modulated vagal tone and leukocyte telomere length (LTL). We also assess the relationship between a recently proposed index of vagal neuroimmunomodulation (vagal tone/inflammation ratio; NIM index) and telomere length.<br><br>METHODS: This study uses participant data from a large nationally representative longitudinal study since 1974 with a total of 45,000 Norwegian residents so far. A sub-sample of 131 participants from which ultrashort recordings (30 s) of vagal tone, c reactive protein, and LTL could be obtained were included in the study. Relationships were analyzed with Pearson's correlations and hierarchical multiple linear regression using either vagal tone and CRP or the NIM index to predict telomere length.<br><br>RESULTS: Vagal tone was a significant positive predictor of telomere length but this was not mediated by c reactive protein, even after controlling for confounders. The NIM index was a significant positive predictor of telomere length, also when controlling for confounders. In a follow-up analysis simultaneously comparing telomere length between groups with high and low values of vagal tone, and between groups with high and low NIM index values, telomere length was only significantly different between NIM index groups.<br><br>CONCLUSION: This is the first study suggesting that prefrontally modulated vagal neuroimmunomodulation is associated with telomere length thus supporting the NISIM. Results indicate that the NIM index is a more sensitive indicator of vagal neuroimmunomodulation than vagal tone and CRP in isolation.},
}
@article {pmid36604719,
year = {2023},
author = {Liu, Q and Li, Z and Huang, L and Zhou, D and Fu, J and Duan, H and Wang, Z and Yang, T and Zhao, J and Li, W and Liu, H and Ma, F and Sun, C and Wang, G and Du, Y and Zhang, M and Chen, Y and Huang, G},
title = {Telomere and mitochondria mediated the association between dietary inflammatory index and mild cognitive impairment: A prospective cohort study.},
journal = {Immunity &amp; ageing : I &amp; A},
volume = {20},
number = {1},
pages = {1},
pmid = {36604719},
issn = {1742-4933},
abstract = {BACKGROUND: Diet and chronic inflammation might play a major role in the pathogenesis of mild cognitive impairment (MCI). In addition, peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) might mediate the relationship between inflammation and MCI risk. The purpose of the present study is to evaluate whether inflammatory potential of diet assessed by dietary inflammatory index (DII), chronic inflammation, peripheral blood LTL, and mtDNAcn were associated with the risk of MCI.<br><br>RESULTS: A population-based cohort study was conducted with a total of 2944 participants. During a median follow-up of 2 years, 438 (14.90%) individuals were new-onset MCI. After adjustment, a higher score of DII (hazard ratio [HR]: 1.056, 95% CI: 1.005, 1.109), a higher log systemic immune inflammation index (SII) (HR: 1.333, 95% CI: 1.089, 1.633) and log system inflammation response index (SIRI) (HR: 1.487, 95% CI: 1.024, 2.161) predicted elevated risk of MCI. An increased mtDNAcn (HR: 0.843, 95% CI: 0.712, 0.997), but not LTL, predicted a decreased risk of MCI. Negative associations of log SII with LTL (&#x3b2;:-0.359, 95% CI: -0.445, -0.273) and mtDNAcn (&#x3b2;:-0.048, 95% CI: -0.090, -0.006) were found. Additionally, negative associations of log SIRI with LTL (&#x3b2;: -0.035, 95% CI: -0.052, -0.017) and mtDNAcn (&#x3b2;:-0.136, 95% CI: -0.216, -0.056) were also found. Path analysis suggested that SIRI, LTL, and mtDNAcn, in series, have mediation roles in the association between DII score and MCI risk.<br><br>CONCLUSIONS: Higher DII, SII, and SIRI might predict a greater risk of MCI, while a longer LTL and an increased mtDNAcn were linked to a reduced risk of MCI among the older population. LTL and mtDNAcn could play mediation roles in the association between DII and MCI risk.},
}
@article {pmid36603485,
year = {2023},
author = {Duan, X and Huang, T and Zhang, D and Wei, Y and Li, L and Yao, W and Cui, L and Zhou, X and Yang, Y and Wang, W and Zhao, J},
title = {Effect and interaction of TNKS genetic polymorphisms and environmental factors on telomere damage in COEs-exposure workers.},
journal = {Ecotoxicology and environmental safety},
volume = {250},
number = {},
pages = {114489},
doi = {10.1016/j.ecoenv.2022.114489},
pmid = {36603485},
issn = {1090-2414},
mesh = {Humans ; *Coke/adverse effects ; DNA Damage ; *Occupational Exposure/adverse effects/analysis ; *Polycyclic Aromatic Hydrocarbons/toxicity/analysis ; Polymorphism, Genetic ; *Tankyrases/genetics ; Telomere/genetics ; },
abstract = {Coke oven emissions (COEs) contain many carcinogenic polycyclic aromatic hydrocarbons (PAHs). Telomere damage is an early biological marker reflecting long-term COEs-exposure. Whereas, whether the genetic variations of telomere-regulated gene TNKS have an effect on the COEs-induced telomere damage is unknown. So we detected the environmental exposure levels, relative telomere length (RTL), and TNKS genetic polymorphisms among 544 COEs-exposure workers and 238 healthy participants. We found that the RTL of the wild homozygous GG genotype in rs1055328 locus was statistically shorter compared with the CG+CC genotype for the healthy participants using covariance analysis(P = 0.008). In the Generalized linear model (GLM) analysis, TNKS rs1055328 GG could accelerate telomere shortening (P = 0.011); and the interaction between TNKS rs1055328 GG and COEs-exposure had an effect on RTL (P = 0.002). In conclusion, this study was the first to discover the role of TNKS rs1055328 locus in COEs-induced telomere damage, and proved that chromosomal damage was a combined consequence of environmental and genetic factors.},
}
@article {pmid36601105,
year = {2022},
author = {Hu, J and Song, J and Chen, Z and Yang, J and Shi, Q and Jin, F and Pang, Q and Chang, X and Tian, Y and Luo, Y and Chen, L},
title = {Reverse causal relationship between periodontitis and shortened telomere length: Bidirectional two-sample Mendelian random analysis.},
journal = {Frontiers in immunology},
volume = {13},
number = {},
pages = {1057602},
pmid = {36601105},
issn = {1664-3224},
mesh = {Humans ; Causality ; *Chronic Periodontitis ; *Genome-Wide Association Study ; Telomere/genetics ; Telomere Shortening ; },
abstract = {BACKGROUND: Observational studies have demonstrated a link between shortened telomere lengths(TL) and chronic periodontitis. However, whether the shortened TL is the cause or the result of periodontitis is unknown.Therefore, our objective was to investigate a bidirectional causal relationship between periodontitis and TL using a two-sample Mendel randomized (MR) study.<br><br>METHODS: A two-sample bidirectional MR analysis using publicly available genome-wide association study (GWAS) data was used. As the primary analysis, inverse variance weighting (IVW) was employed. To identify pleiotropy, we used leave-one-out analysis, MR-Egger, Weighted median, Simple mode, Weighted mode, and MR pleiotropy residual sum and outlier (MR-PRESSO).<br><br>RESULTS: In reverse MR results, a genetic prediction of short TL was causally associated with a higher risk of periodontitis (IVW: odds ratio [OR]: 1.0601, 95% confidence interval [CI]: 1.0213 to 1.1002; P =0.0021) and other complementary MR methods. In the forward MR analysis, periodontitis was shown to have no significant effect on TL (IVW: p = 0.7242), with consistent results for the remaining complementary MR. No pleiotropy was detected in sensitivity analysis (all P>0.05).<br><br>CONCLUSION: Our MR studies showed a reverse causal relationship, with shorten TL being linked to a higher risk of periodontitis, rather than periodontitis shorten that TL. Future research is needed to investigate the relationship between cell senescence and the disease.},
}
@article {pmid36592269,
year = {2023},
author = {Seki, Y and Aczel, D and Torma, F and Jokai, M and Boros, A and Suzuki, K and Higuchi, M and Tanisawa, K and Boldogh, I and Horvath, S and Radak, Z},
title = {No strong association among epigenetic modifications by DNA methylation, telomere length, and physical fitness in biological aging.},
journal = {Biogerontology},
volume = {24},
number = {2},
pages = {245-255},
pmid = {36592269},
issn = {1573-6768},
mesh = {Humans ; Aged ; Aged, 80 and over ; *DNA Methylation ; *Aging/physiology ; Epigenesis, Genetic ; Physical Fitness ; Telomere ; },
abstract = {Cellular senescence is greatly accelerated by telomere shortening, and the steps forward in human aging are strongly influenced by environmental and lifestyle factors, whether DNA methylation (DNAm) is affected by exercise training, remains unclear. In the present study, we investigated the relationships between physiological functions, maximal oxygen uptake (VO2max), vertical jump, working memory, telomere length (TL) assessed by RT-PCR, DNA methylation-based estimation of TL (DNAmTL), and DNA methylation-based biomarkers of aging of master rowers (N = 146) and sedentary subjects (N = 95), aged between 37 and 85 years. It was found that the TL inversely correlated with chronological age. We could not detect an association between telomere length and VO2max, vertical jump, and working memory by RT-PCR method, while these physiological test results showed a correlation with DNAmTL. DNAmGrimAge and DNAmPhenoAge acceleration were inversely associated with telomere length assessed by both methods. It appears that there are no strong beneficial effects of exercise or physiological fitness on telomere shortening, however, the degree of DNA methylation is associated with telomere length.},
}
@article {pmid36591268,
year = {2022},
author = {Lv, Z and Cui, J and Zhang, J},
title = {Associations between serum urate and telomere length and inflammation markers: Evidence from UK Biobank cohort.},
journal = {Frontiers in immunology},
volume = {13},
number = {},
pages = {1065739},
pmid = {36591268},
issn = {1664-3224},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; Biological Specimen Banks ; Biomarkers/blood ; Genome-Wide Association Study ; *Hyperuricemia/blood/genetics/immunology ; *Inflammation/blood/genetics/immunology ; Insulin-Like Growth Factor I ; Interleukin-6 ; *Telomere/genetics/immunology ; Tumor Necrosis Factor-alpha ; United Kingdom ; *Uric Acid/blood/immunology ; *Gout/blood/immunology ; },
abstract = {OBJECTIVE: Hyperuricemia and gout have become gradually more common. The effect of serum urate on organism aging and systematic inflammation is not determined. This study aims to evaluate whether serum urate is causally associated with cellular aging markers and serum inflammation markers.<br><br>METHODS: A Mendelian randomization study was performed on summary-level data from the largest published genome-wide association studies. Single nucleotide polymorphisms with a genome-wide significance level were selected as instrumental variables for leukocyte telomere length (LTL), and serum soluble makers of inflammation (CRP, IL-6, TNF-&#x3b1;, and IGF-1). Standard inverse variance weighted (IVW) method was used as the primary statistical method. The weighted median, MR-Egger regression, and MR-PRESSO methods were used for sensitivity analysis.<br><br>RESULTS: An inverse causal association of genetically predicted serum urate levels and LTL was found using IVW method (OR: 0.96, 95%CI 0.95, 0.97; &#x3b2;=-0.040; SE=0.0072; P=4.37&#xd7;10[-8]). The association was also supported by MR results using MR-Egger method and weighted median method. The MR-PRESSO analysis and leave-one-out sensitivity analysis supported the robustness of the combined results. In terms of other aging-related serum biomarkers, there was no evidence supporting a causal effect of serum urate on CRP, IL-6, TNF-&#x3b1;, or IGF-1 levels.<br><br>CONCLUSIONS: Serum urate levels are negatively associated with telomere length but are not associated with serum soluble indicators of inflammation. Telomere length may be a critical marker that reflects urate-related organismal aging and may be a mechanism in the age-related pathologies and mortality caused by hyperuricemia.},
}
@article {pmid36589292,
year = {2022},
author = {Al Khleifat, A and Iacoangeli, A and Jones, AR and van Vugt, JJFA and Moisse, M and Shatunov, A and Zwamborn, RAJ and van der Spek, RAA and Cooper-Knock, J and Topp, S and van Rheenen, W and Kenna, B and Van Eijk, KR and Kenna, K and Byrne, R and López, V and Opie-Martin, S and Vural, A and Campos, Y and Weber, M and Smith, B and Fogh, I and Silani, V and Morrison, KE and Dobson, R and van Es, MA and McLaughlin, RL and Vourc'h, P and Chio, A and Corcia, P and de Carvalho, M and Gotkine, M and Panades, MP and Mora, JS and Shaw, PJ and Landers, JE and Glass, JD and Shaw, CE and Basak, N and Hardiman, O and Robberecht, W and Van Damme, P and van den Berg, LH and Veldink, JH and Al-Chalabi, A},
title = {Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data.},
journal = {Frontiers in cellular neuroscience},
volume = {16},
number = {},
pages = {1050596},
pmid = {36589292},
issn = {1662-5102},
support = {MR/L501529/1/MRC_/Medical Research Council/United Kingdom ; R56 NS073873/NS/NINDS NIH HHS/United States ; R01 NS073873/NS/NINDS NIH HHS/United States ; MC_PC_17214/MRC_/Medical Research Council/United Kingdom ; 171/ALZS_/Alzheimer's Society/United Kingdom ; MCLAUGHLIN/OCT15/957-799/MNDA_/Motor Neurone Disease Association/United Kingdom ; ALCHALABI-DOBSON/APR14/829-791/MNDA_/Motor Neurone Disease Association/United Kingdom ; G0600974/MRC_/Medical Research Council/United Kingdom ; MR/R024804/1/MRC_/Medical Research Council/United Kingdom ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive weakness of voluntary muscles, with death following from neuromuscular respiratory failure, typically within 3 to 5 years. There is a strong genetic contribution to ALS risk. In 10% or more, a family history of ALS or frontotemporal dementia is obtained, and the Mendelian genes responsible for ALS in such families have now been identified in about 50% of cases. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. Sex and age are risk factors for ALS and we therefore investigated telomere length in ALS.<br><br>METHODS: Samples were from Project MinE, an international ALS whole genome sequencing consortium that includes phenotype data. For validation we used donated brain samples from motor cortex from people with ALS and controls. Ancestry and relatedness were evaluated by principal components analysis and relationship matrices of DNA microarray data. Whole genome sequence data were from Illumina HiSeq platforms and aligned using the Isaac pipeline. TelSeq was used to quantify telomere length using whole genome sequence data. We tested the association of telomere length with ALS and ALS survival using Cox regression.<br><br>RESULTS: There were 6,580 whole genome sequences, reducing to 6,195 samples (4,315 from people with ALS and 1,880 controls) after quality control, and 159 brain samples (106 ALS, 53 controls). Accounting for age and sex, there was a 20% (95% CI 14%, 25%) increase of telomere length in people with ALS compared to controls (p = 1.1 &#xd7; 10[-12]), validated in the brain samples (p = 0.03). Those with shorter telomeres had a 10% increase in median survival (p = 5.0&#xd7;10[-7]). Although there was no difference in telomere length between sporadic ALS and familial ALS (p=0.64), telomere length in 334 people with ALS due to expanded C9orf72 repeats was shorter than in those without expanded C9orf72 repeats (p = 5.0&#xd7;10[-4]).<br><br>DISCUSSION: Although telomeres shorten with age, longer telomeres are a risk factor for ALS and worsen prognosis. Longer telomeres are associated with ALS.},
}
@article {pmid38426924,
year = {2023},
author = {Timina, MF and Pavlova, LE and Kirgintsev, RM and Agumava, AA},
title = {[Changes in telomere length in leukocytes of male rhesus macaques of different ages.].},
journal = {Advances in gerontology = Uspekhi gerontologii},
volume = {36},
number = {6},
pages = {859-863},
pmid = {38426924},
issn = {1561-9125},
mesh = {Humans ; Animals ; Male ; *Aging/genetics ; Macaca mulatta/genetics ; Phylogeny ; *Telomere/genetics ; Leukocytes ; DNA ; },
abstract = {Telomeres are specialized terminal sections of chromosomes that ensure the stability of the latter. DNA duplication during cell division is associated with telomere shortening due to the phenomenon of terminal underreplication. As cells divide, shortening of telomere length is considered to be one of the most important causes of cell aging. Estimation of telomere length still remains the subject of scientific research in gerontology and it is not used in clinical practice. Most often, rodents are used as a model object for studying the aging process, but the neuroendocrine mechanisms that influence, among other things, the regulation of the aging process differ in rodents and humans. The model objects closest in phylogenetic relation to humans are monkeys. In particular, Rhesus macaques is one of the representatives of the Old World most often used in biomedical research. However, data on age-related changes in telomere length in monkeys are extremely scarce. We studied the absolute average length of telomeres in DNA from blood leukocytes of 29 clinically healthy male rhesus monkeys aged from 4 to 24 years using quantitative PCR-method. The data obtained did not correspond to the normal distribution and the correlation analysis showed the absence of a significant dependence of telomere length on the age of the animals (rs=0,27; p>0,05). Thus, our study does not confirm the dependence of changes in the average length of telomeres of blood leukocytes with age.},
}
@article {pmid36586020,
year = {2023},
author = {Liu, Y and Song, L and Wu, M and Bi, J and Wang, L and Liu, Q and Xiong, C and Cao, Z and Xu, S and Wang, Y},
title = {Association between rare earth element exposure during pregnancy and newborn telomere length.},
journal = {Environmental science and pollution research international},
volume = {30},
number = {13},
pages = {38751-38760},
pmid = {36586020},
issn = {1614-7499},
support = {82073660//National Natural Science Foundation of China/ ; 82003479//National Natural Science Foundation of China/ ; 2019M662646//Postdoctoral Research Foundation of China/ ; 2020T130220//Postdoctoral Research Foundation of China/ ; },
mesh = {Pregnancy ; Infant, Newborn ; Female ; Humans ; *Maternal Exposure ; Cohort Studies ; Parturition ; Mothers ; *Metals, Rare Earth ; Telomere ; China ; },
abstract = {Telomere length (TL) is considered a marker of biological aging and lifetime health, and some epidemiological studies report that the environmental exposures may influence TL at birth. We aimed to investigate the associations between prenatal rare earth elements (REE) exposure and newborn TL. A total of 587 mother-newborn pairs were recruited during 2013 to 2015 in Wuhan, China. Maternal urinary concentrations of REE collected during three trimesters were measured by inductively coupled plasma mass spectrometry. Quantitative real-time polymerase chain reaction was used to measure relative cord blood TL. The trimester-specific associations between prenatal REE exposure and cord blood TL were evaluated using multiple informant models. Weighted quantile sum regression was used to estimate the mixture effect of urinary REE on cord blood TL. After adjustment for potential confounders, per doubling of urinary REE (Dy, Yb, Pr, Nd, and Tm) concentrations (μg/g creatinine) during the second trimester was respectively associated with 1.94% (95% CI 0.19%, 3.72%), 2.10% (95% CI 0.31%, 3.92%), 2.11% (95% CI 0.35%, 3.89%), 2.08% (95% CI 0.01%, 4.20%), and 1.38% (95% CI 0.09%, 2.70%) increase in cord blood TL. Furthermore, exposure to the mixture of REE during the second trimester was also significantly associated with increased cord blood TL (percent change 1.20%, 95% CI 0.30%, 2.11%). However, these associations were not statistically significant in the first and third trimesters. This study provides new evidence on the potential effect of prenatal REE exposure on the initial (newborn) setting of offspring's telomere biology. Further epidemiological studies are warranted to confirm our findings.},
}
@article {pmid36585257,
year = {2023},
author = {Mei, Q and Yu, Q and Li, X and Chen, J and Yu, X},
title = {Regulation of telomere silencing by the core histones-autophagy-Sir2 axis.},
journal = {Life science alliance},
volume = {6},
number = {3},
pages = {},
pmid = {36585257},
issn = {2575-1077},
mesh = {*Histones/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; Gene Silencing ; Saccharomyces cerevisiae/genetics/metabolism ; Telomere/genetics/metabolism ; Silent Information Regulator Proteins, Saccharomyces cerevisiae/genetics/metabolism ; Sirtuin 2/genetics/metabolism ; Histone-Lysine N-Methyltransferase/metabolism ; },
abstract = {Telomeres contain compacted heterochromatin, and genes adjacent to telomeres are subjected to transcription silencing. Maintaining telomere structure integrity and transcription silencing is important to prevent the occurrence of premature aging and aging-related diseases. How telomere silencing is regulated during aging is not well understood. Here, we find that the four core histones are reduced during yeast chronological aging, leading to compromised telomere silencing. Mechanistically, histone loss promotes the nuclear export of Sir2 and its degradation by autophagy. Meanwhile, reducing core histones enhances the autophagy pathway, which further accelerates autophagy-mediated Sir2 degradation. By screening the histone mutant library, we identify eight histone mutants and one histone modification (histone methyltransferase Set1-catalyzed H3K4 trimethylation) that regulate telomere silencing by modulating the core histones-autophagy-Sir2 axis. Overall, our findings reveal core histones and autophagy as causes of aging-coupled loss of telomere silencing and shed light on dynamic regulation of telomere structure during aging.},
}
@article {pmid36582083,
year = {2022},
author = {Dondoladze, K and Nikolaishvili, M and Museliani, T and Jikia, G},
title = {EFFECT OF RADIATION ON AGING PROCESSES AND TELOMERE LENGTH.},
journal = {Problemy radiatsiinoi medytsyny ta radiobiolohii},
volume = {27},
number = {},
pages = {107-119},
doi = {10.33145/2304-8336-2022-27-107-119},
pmid = {36582083},
issn = {2313-4607},
mesh = {*Antioxidants ; *Cellular Senescence/genetics ; Oxidative Stress ; Telomere/genetics ; },
abstract = {Telomeres are the ending areas of chromosomes - protective «caps» that ensure the stability of chromosomes. Telomere shortening is one of the most important biological signs of aging and is involved in cellular aging and the «mitotic clock» mechanism. One of the known mechanisms of the impact of radiation on the aging process is damage to telomeres by free radicals. Oxidative stress has a toxic effect on telomere length. The increase in free radicals occurs under the action of both ionizing and nonionizing radiation, although antioxidant mechanisms are often able to neutralize harmful free radicals. Low doses of nonionizing and ionizing radiation even cause the activation of antioxidant systems, however, when the body is exposed to radiation at a high dose or for a long time, or if pathological processes with oxidative stress occur in the body, damage to cells becomes more noticeable, and aging processes accelerate. Maintaining telomere length and a normal rate of aging is important for health. In this review, we want to discuss the role of ionizing and nonionizing radiation in cellular aging, in particular, in the shortening of telomere length.},
}
@article {pmid36579443,
year = {2023},
author = {Clé, DV and Catto, LFB and Gutierrez-Rodrigues, F and Donaires, FS and Pinto, AL and Santana, BA and Darrigo, LG and Valera, ET and Koenigkam-Santos, M and Baddini-Martinez, J and Young, NS and Martinez, EZ and Calado, RT},
title = {Effects of nandrolone decanoate on telomere length and clinical outcome in patients with telomeropathies: a prospective trial.},
journal = {Haematologica},
volume = {108},
number = {5},
pages = {1300-1312},
pmid = {36579443},
issn = {1592-8721},
mesh = {Humans ; In Situ Hybridization, Fluorescence ; *Lung Diseases, Interstitial ; Nandrolone Decanoate ; Prospective Studies ; Retrospective Studies ; Telomere ; },
abstract = {Androgens have been reported to elongate telomeres in retrospective and prospective trials with patients with telomeropathies, mainly with bone marrow failure. In our single-arm prospective clinical trial (clinicaltrials gov. Identifier: NCT02055456), 17 patients with short telomeres and/or germline pathogenic variants in telomere biology genes associated with at least one cytopenia and/or radiologic diagnosis of interstitial lung disease were treated with 5 mg/kg of intramuscular nandrolone decanoate every 15 days for 2 years. Ten of 13 evaluable patients (77%) showed telomere elongation at 12 months by flow-fluorescence in situ hybridization (average increase, 0.87 kb; 95% confidence interval: 0.20-1.55 kb; P=0.01). At 24 months, all ten evaluable patients showed telomere elongation (average increase, 0.49 kb; 95% confidence interval: 0.24-1.23 kb; P=0.18). Hematologic response was achieved in eight of 16 patients (50%) with marrow failure at 12 months, and in ten of 16 patients (63%) at 24 months. Seven patients had interstitial lung disease at baseline, and two and three had pulmonary response at 12 and 24 months, respectively. Two patients died due to pulmonary failure during treatment. In the remaining evaluable patients, the pulmonary function remained stable or improved, but showed consistent decline after cessation of treatment. Somatic mutations in myeloid neoplasm-related genes were present in a minority of patients and were mostly stable during drug treatment. The most common adverse events were elevations in liver function test levels in 88%, acne in 59%, and virilization in 59%. No adverse events grade ≥4 was observed. Our findings indicate that nandrolone decanoate elongates telomeres in patients with telomeropathies, which correlated with clinical improvement in some cases and tolerable adverse events.},
}
@article {pmid36579149,
year = {2022},
author = {Wang, J and Hao, Y and Zhu, Z and Liu, B and Zhang, X and Wei, N and Wang, T and Lv, Y and Xu, C and Ma, M and Zhang, Y and Liu, F},
title = {Causality of telomere length associated with calcific aortic valvular stenosis: A Mendelian randomization study.},
journal = {Frontiers in medicine},
volume = {9},
number = {},
pages = {1077686},
pmid = {36579149},
issn = {2296-858X},
abstract = {BACKGROUND: Observational studies have shown that calcific aortic valve stenosis (CAVS) is associated with a shorter telomere length (TL). However, the results of observational studies are often influenced by confounding factors and reverse causal associations; it is unclear whether there is a causal relationship between TL and CAVS. This study aimed to investigate the causal relationship between TL and CAVS.<br><br>MATERIALS AND METHODS: Genome-wide association study (GWAS) data on TL (n = 472,174) and CAVS (n = 311,437) were used to assess the effect of TL on CAVS. All the participants were of European ancestry. Three Mendelian randomization (MR) methods, namely, MR-Egger, weighted median, and inverse variance weighted (IVW), were used to assess the potential causal effect of TL on CAVS. Heterogeneity was assessed using Cochran's Q statistic. Leave-one-out and MR-Egger regression methods were used for sensitivity and pleiotropy analyses. Forward and reverse MR analyses were performed.<br><br>RESULTS: In total, 118 valid and independent TL genetic instrumental variants were extracted from the GWAS dataset. MR analysis showed that TL was negatively associated with CAVS (odds ratios [OR] = 0.727, 95% confidence interval [CI]: 0.565-0.936, and P = 0.013 by weighted median; OR = 0.763, 95% CI: 0.634-0.920, and P = 0.005 by IVW; OR = 0.757, 95% CI: 0.549-1.044, and P = 0.055 by MR-Egger). Sensitivity and pleiotropy analyses showed that the results of this study were relatively stable and that there was no significant pleiotropy. Reverse MR analyses consistently suggested the absence of causal effects of CAVS liability on TL levels.<br><br>CONCLUSION: A causal relationship between the shortening of TL and the development of CAVS in the European population was suggested in this study, and a theoretical basis was provided to investigate the pathogenesis of CAVS.},
}
@article {pmid36575046,
year = {2022},
author = {Yang, X and Benny, PA and Cervera-Marzal, E and Wu, B and Lassiter, CB and Astern, J and Garmire, LX},
title = {Placental telomere length shortening is not associated with severe preeclampsia but the gestational age.},
journal = {Aging},
volume = {15},
number = {2},
pages = {353-370},
pmid = {36575046},
issn = {1945-4589},
mesh = {Pregnancy ; Humans ; Female ; *Placenta ; *Pre-Eclampsia/genetics ; Retrospective Studies ; Gestational Age ; Telomere Shortening ; Telomere ; },
abstract = {Variations in telomere length (TL) have been associated with aging, stress, and many diseases. Placenta TL is an essential molecular component influencing the outcome of birth. Previous investigations into the relationship between placenta TL and preeclampsia (PE) have produced conflicting findings. We conducted a retrospective case-control analysis in this study to address the disparity. We used placenta samples from 224 births received from Hawaii Biorepository (HiBR) between 2006 and 2013, comprising 129 healthy full-term controls and 95 severe PE samples. The average absolute placental TL was calculated using the quantitative polymerase chain reaction (qPCR) technique. We utilized multiple linear regressions to associate placental TL with severe PE and other demographic, clinical and physiological data. The outcome demonstrates that the placental TL of severe PE cases did not significantly differ from that of healthy controls. Instead, there is a strong correlation between gestational age and placenta TL shortening. Placental TL also exhibits racial differences: (1) Latino moms' TL is significantly longer than non-Latino mothers' (p=0.009). (2) Caucasian patients with severe PE have shorter TL than non-Caucasian patients (p=0.0037). This work puts the long-standing question of whether severe PE influences placental TL to rest. Placental TL is not related to severe PE but is negatively associated with gestational age and is also affected by race.},
}
@article {pmid36574746,
year = {2023},
author = {Van Der Stukken, C and Nawrot, TS and Wang, C and Lefebvre, W and Vanpoucke, C and Plusquin, M and Roels, HA and Janssen, BG and Martens, DS},
title = {The association between ambient particulate matter exposure and the telomere-mitochondrial axis of aging in newborns.},
journal = {Environment international},
volume = {171},
number = {},
pages = {107695},
doi = {10.1016/j.envint.2022.107695},
pmid = {36574746},
issn = {1873-6750},
mesh = {Humans ; Infant, Newborn ; Female ; Pregnancy ; Particulate Matter/analysis ; Tumor Suppressor Protein p53/analysis/pharmacology ; Placenta/chemistry ; Maternal Exposure/adverse effects ; *Air Pollution/adverse effects/analysis ; Aging ; Mitochondria/chemistry ; DNA, Mitochondrial/analysis ; Telomere ; *Air Pollutants/analysis ; },
abstract = {BACKGROUND: Particulate matter (PM) is associated with aging markers at birth, including telomeres and mitochondria. It is unclear whether markers of the core-axis of aging, i.e. tumor suppressor p53 (p53) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), are associated with prenatal air pollution and whether there are underlying mechanisms.<br><br>METHODS: 556 mother-newborn pairs from the ENVIRONAGE birth cohort were recruited at the East Limburg Hospital in Genk (Belgium). In placenta and cord blood, telomere length (TL) and mitochondrial DNA content (mtDNAc) were measured using quantitative real-time polymerase chain reaction (qPCR). In cord plasma, p53 and PGC-1&#x3b1; protein levels were measured using ELISA. Daily ambient PM2.5 concentrations during gestation were calculated using a spatial temporal interpolation model. Distributed lag models (DLMs) were applied to assess the association between prenatal PM2.5 exposure and each molecular marker. Mediation analysis was performed to test for underlying mechanisms.<br><br>RESULTS: A 5&#xa0;&#xb5;g/m[3] increment in PM2.5 exposure was associated with -11.23&#xa0;% (95&#xa0;% CI: -17.36&#xa0;% to -4.65&#xa0;%, p&#xa0;=&#xa0;0.0012) and -7.34&#xa0;% (95&#xa0;% CI: -11.56&#xa0;% to -2.92&#xa0;%, p&#xa0;=&#xa0;0.0014) lower placental TL during the entire pregnancy and second trimester respectively, and with -12.96&#xa0;% (95&#xa0;% CI: -18.84&#xa0;% to -6.64&#xa0;%, p&#xa0;<&#xa0;0.001) lower placental mtDNAc during the third trimester. Furthermore, PM2.5&#xa0;exposure was associated with a 12.42&#xa0;% (95&#xa0;% CI: -1.07&#xa0;% to 27.74&#xa0;%, p&#xa0;=&#xa0;0.059) higher cord plasma p53 protein level and a -3.69&#xa0;% (95&#xa0;% CI: -6.97&#xa0;% to -0.31&#xa0;%, p&#xa0;=&#xa0;0.033) lower cord plasma PGC-1&#x3b1; protein level during the third trimester. Placental TL mediated 65&#xa0;% of the negative and 17&#xa0;% of the positive association between PM2.5 and placental mtDNAc and cord plasma p53 protein levels, respectively.<br><br>CONCLUSION: Ambient PM2.5 exposure during pregnancy is associated with markers of the core-axis of aging, with TL as a mediating factor. This study strengthens the hypothesis of the air pollution induced core-axis of aging, and may unravel a possible underlying mediating mechanism in an early-life epidemiological context.},
}
@article {pmid36573392,
year = {2023},
author = {Ardestani, SK and Jamali, T and Taravati, A and Behboudi, H and Vaez-Mahdavi, MR and Faghihzadeh, E and Ghazanfari, T},
title = {Changes in hormones, Leukocyte Telomere Length (LTL), and p16[INK4a] expression in SM-exposed individuals in favor of the cellular senescence.},
journal = {Drug and chemical toxicology},
volume = {46},
number = {6},
pages = {1235-1241},
doi = {10.1080/01480545.2022.2150205},
pmid = {36573392},
issn = {1525-6014},
mesh = {Humans ; Male ; *Mustard Gas/toxicity ; Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism ; Hydrocortisone/metabolism ; Iran ; Cellular Senescence ; Leukocytes/metabolism ; Telomere ; Testosterone/metabolism ; },
abstract = {Sulfur mustard (SM) is a chemical warfare agent with well-known severe toxic effects and may cause long-term debilitating injuries. We aimed to evaluate aging and longevity in Iranian SM-exposed survivors using some endocrine and molecular biomarkers for the first time. Dehydroepiandrosterone (DHEA), prolactin (PRL), cortisol, testosterone, and luteinizing hormone (LH) were measured in 289 male SM-veterans and 66 age-matched males using the ELISA method. Leukocyte Telomere Length (LTL) measurement and p16[INK4a] expression were measured in the peripheral blood leukocytes of 55 males who were exposed to SM. We found a significantly lower serum DHEAS level and higher serum PRL level in SM-exposed groups (without any related to the severity of lung injuries) compared to healthy controls, but no significant difference in serum levels of cortisol, testosterone, and LH. The molar ratio of DHEAS/cortisol was significantly higher in controls compared to the SM-exposed individuals especially those with severe lung damage. Some biological parameters of allostatic load score such as DHEAS and DHEAS/cortisol ratio significantly decreased long-term after the SM exposure. Additionally, we found that LTL was shorter in SM-exposed veterans rather than unexposed controls while p16[INK4a] gene expression significantly increased in these groups. It seems that DHEAS, DHEAS/cortisol ratio, LTL, and p16[INK4a] gene expression have changed significantly in favor of cellular senescence in SM-exposed patients. Therefore, it seems that SM exposure increases biological age compared to chronological age in SM-exposed survivors.},
}
@article {pmid36567450,
year = {2023},
author = {Matsuda, Y and Ye, J and Yamakawa, K and Mukai, Y and Azuma, K and Wu, L and Masutomi, K and Yamashita, T and Daigo, Y and Miyagi, Y and Yokose, T and Oshima, T and Ito, H and Morinaga, S and Kishida, T and Minamoto, T and Kojima, M and Kaneko, S and Haba, R and Kontani, K and Kanaji, N and Okano, K and Muto-Ishizuka, M and Yokohira, M and Saoo, K and Imaida, K and Suizu, F},
title = {Association of longer telomere length in cancer cells and cancer-associated fibroblasts with worse prognosis.},
journal = {Journal of the National Cancer Institute},
volume = {115},
number = {2},
pages = {208-218},
pmid = {36567450},
issn = {1460-2105},
mesh = {Humans ; *Carcinoma, Renal Cell ; *Cancer-Associated Fibroblasts/pathology ; In Situ Hybridization, Fluorescence ; Prognosis ; Telomere Shortening ; Telomere ; *Carcinoma, Squamous Cell/pathology ; *Liver Neoplasms/pathology ; *Kidney Neoplasms ; Telomere Homeostasis ; },
abstract = {BACKGROUND: Telomere dysfunction has been reported to be directly involved in carcinogenesis owing to chromosomal instability and immortalization; however, the clinicopathological significance of telomeres remains controversial. We have shown that telomere shortening occurs in normal-appearing duct cells at initiation and then continues during the progression of pancreatic cancer. In this study, we determined the clinicopathological and prognostic value of telomere length (TL) in cancer progression.<br><br>METHODS: TL in both cancer cells and cancer-associated fibroblasts (CAFs) was analyzed by high-throughput quantitative fluorescence in situ hybridization using a previously reported cohort comprising 1434 cases of adenocarcinoma (ADC), squamous cell carcinoma (SCC), adenosquamous carcinoma, hepatocellular carcinoma, and renal cell carcinoma (RCC), which are known cancers with a statistically significantly low incidence of alternative lengthening of telomeres. Cases were divided into 2 groups as follows: longer and shorter telomeres, according to the median TL of cancer cells and CAFs. The statistical significance of TL in cancer cells and CAFs on clinicopathological characteristics and prognosis was analyzed.<br><br>RESULTS: There was a close association between TL in cancer cells and CAFs. Longer telomeres in cancer cells and CAFs were associated with aggressive features such as advanced stage, high mitosis score and nuclear score, poorly differentiated cancer, and desmoplastic stroma in ADC. Furthermore, a longer TL was an independent prognostic factor for ADC, SCC, and RCC.<br><br>CONCLUSIONS: Longer telomeres are associated with worse prognosis in ADC, SCC, and RCC. Thus, TL is a novel biomarker for the diagnosis of aggressive cancers with poor prognoses.},
}
@article {pmid36563016,
year = {2023},
author = {D'Angiolo, M and Yue, JX and De Chiara, M and Barré, BP and Giraud Panis, MJ and Gilson, E and Liti, G},
title = {Telomeres are shorter in wild Saccharomyces cerevisiae isolates than in domesticated ones.},
journal = {Genetics},
volume = {223},
number = {3},
pages = {},
pmid = {36563016},
issn = {1943-2631},
mesh = {*Saccharomyces cerevisiae/genetics/metabolism ; Telomere/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics ; Telomere-Binding Proteins/genetics ; Base Sequence ; },
abstract = {Telomeres are ribonucleoproteins that cap chromosome-ends and their DNA length is controlled by counteracting elongation and shortening processes. The budding yeast Saccharomyces cerevisiae has been a leading model to study telomere DNA length control and dynamics. Its telomeric DNA is maintained at a length that slightly varies between laboratory strains, but little is known about its variation at the species level. The recent publication of the genomes of over 1,000 S. cerevisiae strains enabled us to explore telomere DNA length variation at an unprecedented scale. Here, we developed a bioinformatic pipeline (YeaISTY) to estimate telomere DNA length from whole-genome sequences and applied it to the sequenced S. cerevisiae collection. Our results revealed broad natural telomere DNA length variation among the isolates. Notably, telomere DNA length is shorter in those derived from wild rather than domesticated environments. Moreover, telomere DNA length variation is associated with mitochondrial metabolism, and this association is driven by wild strains. Overall, these findings reveal broad variation in budding yeast's telomere DNA length regulation, which might be shaped by its different ecological life-styles.},
}
@article {pmid36555658,
year = {2022},
author = {Sagris, M and Theofilis, P and Antonopoulos, AS and Tsioufis, K and Tousoulis, D},
title = {Telomere Length: A Cardiovascular Biomarker and a Novel Therapeutic Target.},
journal = {International journal of molecular sciences},
volume = {23},
number = {24},
pages = {},
pmid = {36555658},
issn = {1422-0067},
mesh = {Humans ; *Cardiovascular System ; Telomere Shortening ; *Atherosclerosis/genetics ; Biomarkers ; *Telomerase/genetics ; Telomere/genetics ; },
abstract = {Coronary artery disease (CAD) is a multifactorial disease with a high prevalence, particularly in developing countries. Currently, the investigation of telomeres as a potential tool for the early detection of the atherosclerotic disease seems to be a promising method. Telomeres are repetitive DNA sequences located at the extremities of chromosomes that maintain genetic stability. Telomere length (TL) has been associated with several human disorders and diseases while its attrition rate varies significantly in the population. The rate of TL shortening ranges between 20 and 50 bp and is affected by factors such as the end-replication phenomenon, oxidative stress, and other DNA-damaging agents. In this review, we delve not only into the pathophysiology of TL shortening but also into its association with cardiovascular disease and the progression of atherosclerosis. We also provide current and future treatment options based on TL and telomerase function, trying to highlight the importance of these cutting-edge developments and their clinical relevance.},
}
@article {pmid36541551,
year = {2023},
author = {Stundon, JL and Ijaz, H and Gaonkar, KS and Kaufman, RS and Jin, R and Karras, A and Vaksman, Z and Kim, J and Corbett, RJ and Lueder, MR and Miller, DP and Guo, Y and Santi, M and Li, M and Lopez, G and Storm, PB and Resnick, AC and Waanders, AJ and MacFarland, SP and Stewart, DR and Diskin, SJ and Rokita, JL and Cole, KA},
title = {Alternative lengthening of telomeres (ALT) in pediatric high-grade gliomas can occur without ATRX mutation and is enriched in patients with pathogenic germline mismatch repair (MMR) variants.},
journal = {Neuro-oncology},
volume = {25},
number = {7},
pages = {1331-1342},
pmid = {36541551},
issn = {1523-5866},
support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; K12 HD043245/HD/NICHD NIH HHS/United States ; U2C-CA233285/NH/NIH HHS/United States ; },
mesh = {Humans ; Child ; DNA Mismatch Repair ; Telomere Homeostasis/genetics ; X-linked Nuclear Protein/genetics ; *Glioma/genetics ; *Brain Neoplasms/genetics/pathology ; Mutation ; Telomere/genetics/pathology ; },
abstract = {BACKGROUND: To achieve replicative immortality, most cancers develop a telomere maintenance mechanism, such as reactivation of telomerase or alternative lengthening of telomeres (ALT). There are limited data on the prevalence and clinical significance of ALT in pediatric brain tumors, and ALT-directed therapy is not available.<br><br>METHODS: We performed C-circle analysis (CCA) on 579 pediatric brain tumors that had corresponding tumor/normal whole genome sequencing through the Open Pediatric Brain Tumor Atlas (OpenPBTA). We detected ALT in 6.9% (n&#xa0;=&#xa0;40/579) of these tumors and completed additional validation by ultrabright telomeric foci in situ on a subset of these tumors. We used CCA to validate TelomereHunter for computational prediction of ALT status and focus subsequent analyses on pediatric high-grade gliomas (pHGGs) Finally, we examined whether ALT is associated with recurrent somatic or germline alterations.<br><br>RESULTS: ALT is common in pHGGs (n&#xa0;=&#xa0;24/63, 38.1%), but occurs infrequently in other pediatric brain tumors (<3%). Somatic ATRX mutations occur in 50% of ALT+ pHGGs and in 30% of ALT- pHGGs. Rare pathogenic germline variants in mismatch repair (MMR) genes are significantly associated with an increased occurrence of ALT.<br><br>CONCLUSIONS: We demonstrate that ATRX is mutated in only a subset of ALT+ pHGGs, suggesting other mechanisms of ATRX loss of function or alterations in other genes may be associated with the development of ALT in these patients. We show that germline variants in MMR are associated with the development of ALT in patients with pHGG.},
}
@article {pmid36536359,
year = {2022},
author = {Wong, KK and Cheng, F and Lim, CKP and Tam, CHT and Tutino, G and Yuen, LY and Wang, CC and Hou, Y and Chan, MHM and Ho, CS and Joglekar, MV and Hardikar, AA and Jenkins, AJ and Metzger, BE and Lowe, WL and Tam, WH and Ma, RCW},
title = {Early emergence of sexual dimorphism in offspring leukocyte telomere length was associated with maternal and children's glucose metabolism-a longitudinal study.},
journal = {BMC medicine},
volume = {20},
number = {1},
pages = {490},
pmid = {36536359},
issn = {1741-7015},
support = {R01 HD034242/HD/NICHD NIH HHS/United States ; R01 HD034243/HD/NICHD NIH HHS/United States ; },
mesh = {Male ; Pregnancy ; Female ; Humans ; Adult ; Child ; Longitudinal Studies ; *Diabetes Mellitus, Type 2 ; Sex Characteristics ; Leukocytes ; Insulin/metabolism ; Glucose/metabolism ; Telomere ; },
abstract = {BACKGROUND: Leukocyte telomere length (LTL) is suggested to be a biomarker of biological age and reported to be associated with metabolic diseases such as type 2 diabetes. Glucose metabolic traits including glucose and insulin levels have been reported to be associated with LTL in adulthood. However, there is relatively little research focusing on children's LTL and the association with prenatal exposures. This study investigates the relationship between maternal and offspring glucose metabolism with offspring LTL in early life.<br><br>METHODS: This study included 882 mother-child pairs from the HAPO Hong Kong Field Centre, with children evaluated at age 7.0 &#xb1; 0.4 (mean &#xb1; SD) years. Glucose metabolic traits including maternal post-load glucose during pregnancy, children's glucose and insulin levels, and their derived indices at follow-up were measured or calculated. Offspring LTL was assessed using real-time polymerase chain reaction.<br><br>RESULTS: Sex- and age-adjusted children's LTL was found to be associated with children's HOMA-IR (&#x3b2;=-0.046 &#xb1; 0.016, p=0.005). Interestingly, both children's and maternal post-load glucose levels were positively associated with children's LTL. However, negative associations were observed between children's LTL and children's OGTT insulin levels. In addition, the LTL in females was more strongly associated with pancreatic beta-cell function whilst LTL in males was more strongly associated with OGTT glucose levels.<br><br>CONCLUSIONS: Our findings suggest a close association between maternal and offspring glucose metabolic traits with early life LTL, with the offspring sex as an important modifier of the disparate relationships in insulin production and response.},
}
@article {pmid36533316,
year = {2023},
author = {Derenzini, E and Gueli, A and Risso, A and Bruna, R and Gottardi, D and Cignetti, A and Pileri, S and Avvedimento, EV and Tarella, C},
title = {Long telomeres at baseline and male sex are main determinants of telomere loss following chemotherapy exposure in lymphoma patients.},
journal = {Hematological oncology},
volume = {41},
number = {3},
pages = {335-342},
doi = {10.1002/hon.3118},
pmid = {36533316},
issn = {1099-1069},
support = {//Fondazione Cariplo/ ; //Piaggio/ ; //Banca del Piemonte/ ; },
mesh = {Adult ; Humans ; Male ; Female ; Young Adult ; Middle Aged ; Aged ; *Lymphoma/drug therapy/genetics ; Telomere Shortening ; Telomere ; },
abstract = {Although chemotherapy (CHT) exposure is an established cause of telomere attrition, determinants of telomere length (TL) dynamics after chemotherapy are poorly defined. In this study, we analyzed granulocyte telomere dynamics in 34 adult lymphoma patients undergoing first-line CHT. TL was measured by southern blot at each CHT cycle and after 1 year from CHT completion. Median age was 59 yrs (range 22-77). Median number of CHT cycles was 6 (range 3-6). The majority of patients (79%, n = 27) experienced TL shortening following CHT exposure. Mean telomere loss was 673 base pairs (bp) by cycle 6. Telomere shortening was an early event as 87% of the total telomere loss (mean 586 bp) occurred by the end of cycle 3, with no significant recovery after 1 year. A significant correlation was observed between baseline TL and total or fractional telomere loss (p < 0.001), with telomere shortening by cycle 3 observed predominantly in male patients with long telomeres at pre-treatment evaluation. Stratifying the analysis by gender and age only young women (<51 years of age) did not show significant telomere shortening following chemotherapy exposure. These findings indicate that gender and baseline TL are major determinants of TL dynamics following chemotherapy exposure in lymphoma patients.},
}
@article {pmid36526187,
year = {2023},
author = {Zamora-Camacho, FJ and Burraco, P and Zambrano-Fernández, S and Aragón, P},
title = {Ammonium effects on oxidative stress, telomere length, and locomotion across life stages of an anuran from habitats with contrasting land-use histories.},
journal = {The Science of the total environment},
volume = {862},
number = {},
pages = {160924},
doi = {10.1016/j.scitotenv.2022.160924},
pmid = {36526187},
issn = {1879-1026},
mesh = {Animals ; Humans ; *Ammonium Compounds/pharmacology ; Antioxidants ; Ecosystem ; Hydrogen Peroxide ; Larva ; Life Cycle Stages ; Locomotion/physiology ; *Oxidative Stress/physiology ; Ranidae ; *Telomere/metabolism ; },
abstract = {Understanding the mechanistic implications behind wildlife responses to global changes is a central topic in eco-evolutionary research. In particular, anthropic pollution is known to impact wild populations across the globe, which may have even stronger consequences for species with complex life cycles. Among vertebrates, amphibians represent a paradigmatic example of metamorphosis, and their characteristics make them highly vulnerable to pollution. Here, we tested for differences in the redox status, telomere length, and locomotor performance across life stages of green frogs (Pelophylax perezi) from agrosystem and natural habitats, both constitutively and in response to an experimental ammonium exposure (10 mg/L). We found that larvae from the agrosystem constitutively showed an enhanced redox status (better antioxidant balance against H2O2, lower lipid peroxidation) but shorter telomeres as compared to larvae from the natural environment. The larval redox response to ammonium was, overall, similar in both habitats. In contrast, after metamorphosis, the redox status of individuals from the natural habitat seemed to cope better with ammonium exposure (denoted by lower lipid peroxidation), and differences between habitats in telomere length were no longer present. Intriguingly, while the swimming performance of larvae did not correlate with individual's physiology, metamorphs with lower glutathione reductase activity and longer telomeres had a better jumping performance. This may suggest that locomotor performance is both traded off with the production of reactive oxygen species and potentiated directly by longer telomeres or indirectly by the mechanisms that buffer their shortening. Overall, our study suggests that contrasting land-use histories can drive divergence in physiological pathways linked to individual health and lifespan. Since this pattern was life-stage dependent, divergent habitat conditions can have contrasting implications across the ontogenetic development of species with complex life cycles.},
}
@article {pmid36525974,
year = {2023},
author = {Warecki, B and Bast, I and Tajima, M and Sullivan, W},
title = {Connections between sister and non-sister telomeres of segregating chromatids maintain euploidy.},
journal = {Current biology : CB},
volume = {33},
number = {1},
pages = {58-74.e5},
pmid = {36525974},
issn = {1879-0445},
support = {R35 GM139595/GM/NIGMS NIH HHS/United States ; S10 OD023528/OD/NIH HHS/United States ; },
mesh = {Animals ; *Chromatids/genetics ; Drosophila melanogaster/genetics ; Telomere/genetics ; Anaphase ; DNA ; Chromosome Segregation ; Cell Cycle Proteins/genetics ; *Drosophila Proteins/genetics ; },
abstract = {The complete separation of sister chromatids during anaphase is a fundamental requirement for successful mitosis. Therefore, divisions with either persistent DNA-based connections or lagging chromosome fragments threaten aneuploidy if unresolved. Here, we demonstrate the existence of an anaphase mechanism in normally dividing cells in which pervasive connections between telomeres of segregating chromosomes aid in rescuing lagging chromosome fragments. We observe that in a large proportion of Drosophila melanogaster neuronal stem cell divisions, early anaphase sister and non-sister chromatids remain connected by thin telomeric DNA threads. Normally, these threads are resolved in mid-to-late anaphase via a spatial mechanism. However, we find that the presence of a nearby unrepaired DNA break recruits histones, BubR1 kinase, Polo kinase, Aurora B kinase, and BAF to the telomeric thread of the broken chromosome, stabilizing it. Stabilized connections then aid lagging chromosome rescue. These results suggest a model in which pervasive anaphase telomere-telomere connections that are normally resolved quickly can instead be stabilized to retain wayward chromosome fragments. Thus, the liability of persistent anaphase inter-chromosomal connections in normal divisions may be offset by their ability to maintain euploidy in the face of chromosome damage and genome loss.},
}
@article {pmid36522605,
year = {2022},
author = {Wang, C and Gu, Y and Zhou, J and Zang, J and Ling, X and Li, H and Hu, L and Xu, B and Zhang, B and Qin, N and Lv, H and Duan, W and Jiang, Y and He, Y and Jiang, T and Chen, C and Han, X and Zhou, K and Xu, B and Liu, X and Tao, S and Jiang, Y and Du, J and Dai, J and Diao, F and Lu, C and Guo, X and Huo, R and Liu, J and Lin, Y and Xia, Y and Jin, G and Ma, H and Shen, H and Hu, Z},
title = {Leukocyte telomere length in children born following blastocyst-stage embryo transfer.},
journal = {Nature medicine},
volume = {28},
number = {12},
pages = {2646-2653},
pmid = {36522605},
issn = {1546-170X},
mesh = {Pregnancy ; Humans ; Female ; Animals ; Mice ; *Pregnancy Outcome ; *Premature Birth ; Embryo Transfer ; Reproductive Techniques, Assisted ; Blastocyst ; Leukocytes ; Telomere/genetics ; },
abstract = {Perinatal and childhood adverse outcomes associated with assisted reproductive technology (ART) has been reported, but it remains unknown whether the initial leukocyte telomere length (LTL), which is an indicator of age-related phenotypes in later life, is affected. Here, we estimated the LTLs of 1,137 individuals from 365 families, including 202 children conceived by ART and 205 children conceived spontaneously from two centers of the China National Birth Cohort, using whole-genome sequencing (WGS) data. One-year-old children conceived by ART had shorter LTLs than those conceived spontaneously (beta, -0.36; P = 1.29 × 10[-3]) after adjusting for plurality, sex and other potential confounding factors. In particular, blastocyst-stage embryo transfer was associated with shorter LTL (beta, -0.54, P = 2.69 × 10[-3]) in children conceived by ART. The association was validated in 586 children conceived by ART from five centers using different LTL quantification methods (that is, WGS or qPCR). Blastocyst-stage embryo transfer resulted in shorter telomere lengths in mice at postnatal day 1 (P = 2.10 × 10[-4]) and mice at 6 months (P = 0.042). In vitro culturing of mice embryos did not result in shorter telomere lengths in the late cleavage stage, but it did suppress telomerase activity in the early blastocyst stage. Our findings demonstrate the need to evaluate the long-term consequences of ART, particularly for aging-related phenotypes, in children conceived by ART.},
}
@article {pmid36514516,
year = {2022},
author = {Akay, GG},
title = {Telomeres and Psychological Stress: Perspective on Psychopathologies.},
journal = {Noro psikiyatri arsivi},
volume = {59},
number = {4},
pages = {330-337},
pmid = {36514516},
issn = {1300-0667},
abstract = {INTRODUCTION: Telomeres are specialized DNA-protein complexes located at the ends of all chromosomes and act as a "molecular clock" to determine the replicative lifespan of the cells. Recent studies indicate that life-long exposure to stress, starting from the prenatal period, causes many diseases to emerge at an early age, and telomeres may be possible mediators in this process. This article aims to review the relationship between the stress-telomere-disease triad and the potential role of telomere dysfunction in psychopathologies in the light of current literature.<br><br>METHODS: A literature search was conducted along the lines of a narrative review. PubMed and Web of Science databases were used to identify all types of articles published from inception to January 2022. After the title/abstract search, articles available in full text and English were selected based on key findings, the applicability of the method used to test the hypothesis, limitations, interpretation of the results, and impact of the results in the field. A total of 73 records were included in this narrative review.<br><br>RESULTS: The fact that some age-related chronic diseases, such as cardiovascular diseases and type 2 diabetes, are seen more frequently and at an earlier age in certain psychopathologies including depression, bipolar disorder, and schizophrenia suggests that these disorders are premature ageing syndromes. Although there are some conflicting results in the literature, in line with this hypothesis, the presence of shortened telomeres reported in these psychopathologies and the impact of lifelong exposure to stress on this process are remarkable.<br><br>CONCLUSION: Many of the studies point to an association and do not tell much about the causality. Hence, the elucidation of the biological processes underlying the relationship between psychological stress, dysfunctional telomeres and complex, common age-related diseases, as well as psychiatric disorders is important and further studies are needed at the cellular level.},
}
@article {pmid36513246,
year = {2023},
author = {Ito, J and Kageyama, M and Hara, S and Sato, T and Shirasuna, K and Iwata, H},
title = {Paternal aging impacts mitochondrial DNA content and telomere length in mouse embryos.},
journal = {Mitochondrion},
volume = {68},
number = {},
pages = {105-113},
doi = {10.1016/j.mito.2022.12.002},
pmid = {36513246},
issn = {1872-8278},
mesh = {Male ; Animals ; Cattle ; Mice ; *DNA, Mitochondrial/genetics ; *Telomere/genetics ; Mitochondria/genetics ; Aging/genetics ; Blastocyst ; },
abstract = {Mitochondrial DNA (mtDNA) copy number and telomere length (TL) in blastocysts derived from the same male mice at young (10-19-week-old) and aged (40-49-week-old) time points and mtDNA and TL in the hearts of offspring derived from young and aged male mice were examined. Paternal aging correlated with reduced mtDNA and TL in blastocysts. mtDNA and TL were significantly correlated, which was also observed in bovine blastocysts. Moreover, mtDNA in the heart of offspring was reduced in male mice with paternal aging. In conclusion, paternal aging affects embryonic mtDNA and TL, potentially impacting their offspring.},
}
@article {pmid36513120,
year = {2022},
author = {Misino, S and Busch, A and Wagner, CB and Bento, F and Luke, B},
title = {TERRA increases at short telomeres in yeast survivors and regulates survivor associated senescence (SAS).},
journal = {Nucleic acids research},
volume = {50},
number = {22},
pages = {12829-12843},
pmid = {36513120},
issn = {1362-4962},
mesh = {Humans ; *RNA, Long Noncoding/genetics ; *Saccharomyces cerevisiae/genetics/metabolism ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; *Telomere Shortening ; },
abstract = {Cancer cells achieve immortality by employing either homology-directed repair (HDR) or the telomerase enzyme to maintain telomeres. ALT (alternative lengthening of telomeres) refers to the subset of cancer cells that employ HDR. Many ALT features are conserved from yeast to human cells, with the yeast equivalent being referred to as survivors. The non-coding RNA TERRA, and its ability to form RNA-DNA hybrids, has been implicated in ALT/survivor maintenance by promoting HDR. It is not understood which telomeres in ALT/survivors engage in HDR, nor is it clear which telomeres upregulate TERRA. Using yeast survivors as a model for ALT, we demonstrate that HDR only occurs at telomeres when they become critically short. Moreover, TERRA levels steadily increase as telomeres shorten and decrease again following HDR-mediated recombination. We observe that survivors undergo cycles of senescence, in a similar manner to non-survivors following telomerase loss, which we refer to as survivor associated senescence (SAS). Similar to 'normal' senescence, we report that RNA-DNA hybrids slow the rate of SAS, likely through the elongation of critically short telomeres, however decreasing the rate of telomere shortening may contribute to this effect. In summary, TERRA RNA-DNA hybrids regulate telomere dysfunction-induced senescence before and after survivor formation.},
}
@article {pmid36508921,
year = {2023},
author = {Nasiri, L and Vaez-Mahdavi, MR and Hassanpour, H and Ghazanfari, T and Kaboudanian Ardestani, S and Askari, N and Mohseni Majd, MA and Rahimlou, B},
title = {Increased serum lipofuscin associated with leukocyte telomere shortening in veterans: a possible role for sulfur mustard exposure in delayed-onset accelerated cellular senescence.},
journal = {International immunopharmacology},
volume = {114},
number = {},
pages = {109549},
doi = {10.1016/j.intimp.2022.109549},
pmid = {36508921},
issn = {1878-1705},
mesh = {Humans ; Male ; *Mustard Gas/toxicity ; *Chemical Warfare Agents/toxicity ; Telomere Shortening ; Lipofuscin ; *Veterans ; Leukocytes ; Cellular Senescence ; Transforming Growth Factor beta ; },
abstract = {BACKGROUND: Sulfur mustard (SM) is a toxic gas that causes chronic inflammation and oxidative stress leading to cell senescence. This study aimed to evaluate two indicators of biological aging (i.e., serum lipofuscin level and leukocyte telomere length) and assess their relationship based on the severity of SM exposure in the long term.<br><br>METHODS: The study was performed on two groups of male participants. 1) SM-exposed group (exposed to SM once in 1987), 73 volunteers. 2) Non-exposed group, 16 healthy volunteers. The SM-exposed group was categorized into three subgroups based on the severity of SM exposure and body damage (asymptom, mild, and severe). The blood sample was prepared from members of each group. The serum lipofuscin, TGF-&#x3b2;, malondialdehyde (MDA), c-reactive protein (CRP), and leukocyte telomere length (TL) were measured in all participants.<br><br>RESULTS: The MDA level was increased in the SM-exposed group (mean = 39.6 &#xb5;M, SD = 16.5) compared to the non-exposed group (mean = 21.1 &#xb5;M, SD = 10.3) (P < 0.05). The CRP level was also increased in the SM-exposed group (mean = 5.12 mg/l, SD = 3.36) compared to the non-exposed group (mean = 3.51 mg/l, SD = 1.21), while the TGF-&#x3b2; level was decreased (P < 0.05) in the SM-exposed group (mean = 52.6 pg/ml, SD = 18.7) compared to the non-exposed group (mean = 68.9 pg/ml, SD = 13.8). The relative TL was shorter in the SM-exposed group (mean = 0.40, SD = 0.28) than in the non-exposed group (mean = 2.25, SD = 1.41) (P < 0.05). The lipofuscin level was higher in the total SM-exposed group (mean = 1.44 ng/ml, SD = 0.685) than in the non-exposed group (mean = 0.88 ng/ml, SD = 0.449) (P < 0.05). The MDA and CRP levels were increased in the SM-exposed subgroups of asymptom, mild, and severe than the non-exposed group, while TGF-&#x3b2; level and TL were decreased in those subgroups. The lipofuscin level was higher in the SM-exposed subgroups of mild and severe than in the non-exposed group. The regression analysis determined a negative correlation between lipofuscin level and TL. The lipofuscin/TL ratio was higher in the total SM-exposed group (mean = 6.36, SD = 5.342) than in the non-exposed group (mean = 0.51, SD=0.389). This ratio was also higher in the SM-exposed subgroups of asymptom, mild, and severe than in the non-exposed group. The lipofuscin/TL ratio did not differ between mild and severe subgroups.<br><br>CONCLUSION: The delayed toxicity of SM is associated with chronic oxidative stress, continuous inflammatory stimulation, increased lipofuscin, and telomere shortening. Future studies are needed to verify the suitability of serum lipofuscin to telomere length ratio in determining the severity of SM toxicity.},
}
@article {pmid36502996,
year = {2023},
author = {Zhang, Y and Liu, J and Li, X and Zhou, G and Sang, Y and Zhang, M and Gao, L and Xue, J and Zhao, M and Yu, H and Zhou, X},
title = {Dietary selenium excess affected spermatogenesis via DNA damage and telomere-related cell senescence and apoptosis in mice.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {171},
number = {},
pages = {113556},
doi = {10.1016/j.fct.2022.113556},
pmid = {36502996},
issn = {1873-6351},
mesh = {Mice ; Male ; Animals ; *Selenium/pharmacology ; Semen ; Spermatogenesis ; Cellular Senescence ; Apoptosis ; DNA Damage ; *Malnutrition ; Telomere ; },
abstract = {Selenium (Se) is a vital microelement for spermatogenesis and male fertility. The aim of this study was to investigate the effects of Se on the male reproductive function and possible mechanisms. Fourty male mice were randomly divided into 0, 0.1, 0.3 and 0.9 mg/kg Se supplementation groups and given with Se dietary intervention for 12 weeks. Our data showed that excessive Se intake damaged the tissue structure of testes and epididymides of the mice, resulting in decreased sperm quality and quantity. Moreover, excessive Se induced oxidative stress, causing DNA damage and activated DNA damage repair factors (Mre11/Rad50/Nbs1), and also disrupted telomere function by shortening telomere length and decreasing TERT expression. Se excess activated the senescence pathway p53/p21/p16, leading to germ cell senescence, and inhibited cell proliferation by suppressing the Sirt1/Foxo1/c-Myc pathway. All of this led to spermatogenic cell apoptosis, thereby causing a decrease of sperm quantity and quality. In conclusion, excessive Se caused reproductive toxicity via inducing telomere dysfunction due to DNA damage, leading to germ cellular senescence and apoptosis in the testes of male mice. Our research provide new proof to explain the underlying mechanism of male reproductive toxicity triggered by excessive Se intake.},
}
@article {pmid36501220,
year = {2022},
author = {Toupance, S and Karampatsou, SI and Labat, C and Genitsaridi, SM and Tragomalou, A and Kassari, P and Soulis, G and Hollander, A and Charmandari, E and Benetos, A},
title = {Longitudinal Association of Telomere Dynamics with Obesity and Metabolic Disorders in Young Children.},
journal = {Nutrients},
volume = {14},
number = {23},
pages = {},
pmid = {36501220},
issn = {2072-6643},
support = {ANR-15-IDEX-04-LUE//Agence Nationale de la Recherche/ ; FHU project CARTAGE-PROFILES//French National Alliance for Life Sciences and Health/ ; },
mesh = {Adult ; Adolescent ; Child ; Humans ; Child, Preschool ; *Pediatric Obesity/genetics/metabolism ; Telomere ; Telomere Shortening ; Leukocytes/metabolism ; *Diabetes Mellitus, Type 2/genetics/metabolism ; },
abstract = {In adults, short leukocyte telomere length (LTL) is associated with metabolic disorders, such as obesity and diabetes mellitus type 2. These associations could stem from early life interactions between LTL and metabolic disorders. To test this hypothesis, we explored the associations between LTL and metabolic parameters as well as their evolution over time in children with or without obesity at baseline. Seventy-three (n = 73) children attending our Outpatient Clinic for the Prevention and Management of Overweight and Obesity in Childhood and Adolescence, aged 2-10 years (mean ± SD: 7.6 ± 2.0 years), were followed for 2 to 4 years. Anthropometric, clinical, and biological (including LTL by Southern blot) measurements were performed annually. Baseline LTL correlated negatively with BMI (p = 0.02), fat percentage (p = 0.01), and blood glucose (p = 0.0007). These associations persisted after adjustments for age and sex. No associations were found between LTL attrition during the follow-up period and any of the metabolic parameters. In young children, obesity and metabolic disturbances were associated with shorter telomeres but were not associated with more pronounced LTL attrition. These results suggest that short telomeres contribute to the development of obesity and metabolic disorders very early in life, which can have a major impact on health.},
}
@article {pmid36498467,
year = {2022},
author = {Mulet, A and Signes-Costa, J},
title = {Idiopathic Pulmonary Fibrosis and Telomeres.},
journal = {Journal of clinical medicine},
volume = {11},
number = {23},
pages = {},
pmid = {36498467},
issn = {2077-0383},
abstract = {Idiopathic pulmonary fibrosis is an interstitial lung disease of unknown etiology with a highly compromised prognosis and a significant mortality rate within a few years of diagnosis. Despite being idiopathic, it has been shown that telomeric shortening could play an important role in its etiopathogenesis. Mutations in telomere-related genes have been identified, but they are not always present despite telomere shortening. On the other hand, this telomeric shortening has been linked to a worse prognosis of the disease independently of other clinical factors, implying it may serve as a biomarker.},
}
@article {pmid36497103,
year = {2022},
author = {Vilkeviciute, A and Gedvilaite, G and Banevicius, M and Kriauciuniene, L and Zaliuniene, D and Dobiliene, O and Liutkeviciene, R},
title = {Relative Leukocyte Telomere Length and Genetic Variants in Telomere-Related Genes and Serum Levels Role in Age-Related Macular Degeneration.},
journal = {Cells},
volume = {11},
number = {23},
pages = {},
pmid = {36497103},
issn = {2073-4409},
mesh = {Humans ; Telomeric Repeat Binding Protein 1/genetics/metabolism ; *Telomerase/genetics/metabolism ; Leukocytes/metabolism ; *Macular Degeneration/genetics ; DNA ; *Tankyrases ; },
abstract = {UNLABELLED: Telomere shortening is well known to be associated with ageing. Age is the most decisive risk factor for age-related macular degeneration (AMD) development. The older the individual, the higher the AMD risk. For this reason, we aimed to find any associations between telomere length, distribution of genetic variants in telomere-related genes (TERT, TERT-CLPTM1, TRF1, TRF2, and TNKS2), and serum TERF-1 and TERF2 levels on AMD development.<br><br>METHODS: Our study enrolled 342 patients with AMD and 177 healthy controls. Samples of DNA from peripheral blood leukocytes were extracted by DNA salting-out method. The genotyping of TERT rs2736098, rs401681 in TERT-CLPTM1 locus, TRF1 rs1545827, rs10107605, TNKS2 rs10509637, rs10509639, and TRF2 rs251796 and relative leukocyte telomere length (T/S) measurement were carried out using the real-time polymerase chain reaction method. Serum TERF-1 and TERF2 levels were measured by enzymatic immunoassay (ELISA).<br><br>RESULTS: We found longer telomeres in early AMD patients compared to the control group. Additionally, we revealed that minor allele C at TRF1 rs10107605 was associated with decreases the odds of both early and exudative AMD. Each minor allele G at TRF2 rs251796 and TRF1 rs1545827 C/T genotype and C/T+T/T genotypes, compared to the C/C genotype, increases the odds of having shorter telomeres. Furthermore, we found elevated TERF1 serum levels in the early AMD group compared to the control group.<br><br>CONCLUSIONS: In conclusion, these results suggest that relative leukocyte telomere length and genetic variants of TRF1 and TRF2 play a role in AMD development. Additionally, TERF1 is likely to be associated with early AMD.},
}
@article {pmid36497039,
year = {2022},
author = {Farrukh, S and Baig, S and Hussain, R and Imad, R and Khalid, M},
title = {Parental Genetics Communicate with Intrauterine Environment to Reprogram Newborn Telomeres and Immunity.},
journal = {Cells},
volume = {11},
number = {23},
pages = {},
pmid = {36497039},
issn = {2073-4409},
support = {Ref No. 20-15896/NRPU/R&amp;D/HEC/2021 2021//Higher Education Commission/ ; Ref no. Biochemistry.242.14/5/21)//ziauddin university/ ; },
mesh = {Female ; Humans ; Infant, Newborn ; Pregnancy ; Genotype ; Mothers ; *Telomerase/genetics ; *Telomere/genetics ; Telomere Shortening/genetics ; Fathers ; Male ; *Immunity/genetics ; Maternal Inheritance ; Paternal Inheritance ; },
abstract = {Telomeres, markers for cellular senescence, have been found substantially influenced by parental inheritance. It is well known that genomic stability is preserved by the DNA repair mechanism through telomerase. This study aimed to determine the association between parents−newborn telomere length (TL) and telomerase gene (TERT), highlighting DNA repair combined with TL/TERT polymorphism and immunosenescence of the triad. The mother−father−newborn triad blood samples (n = 312) were collected from Ziauddin Hospitals, Pakistan, between September 2021 and June 2022. The telomere length (T/S ratio) was quantified by qPCR, polymorphism was identified by Sanger sequencing, and immunosenescence by flow cytometry. The linear regression was applied to TL and gene association. The newborns had longest TL (2.51 ± 2.87) and strong positive association (R = 0.25, p ≤ 0.0001) (transgenerational health effects) with mothers’ TL (1.6 ± 2.00). Maternal demographics—socioeconomic status, education, and occupation—showed significant effects on TL of newborns (p < 0.015, 0.034, 0.04, respectively). The TERT risk genotype CC (rs2736100) was predominant in the triad (0.6, 0.5, 0.65, respectively) with a strong positive association with newborn TL (β = 2.91, <0.0011). Further analysis highlighted the expression of KLRG 1+ in T-cells with shorter TL but less frequent among newborns. The study concludes that TERT, parental TL, antenatal maternal health, and immunity have a significantly positive effect on the repair of newborn TL.},
}
@article {pmid36496180,
year = {2023},
author = {Nelson, N and Feurstein, S and Niaz, A and Truong, J and Holien, JK and Lucas, S and Fairfax, K and Dickinson, J and Bryan, TM},
title = {Functional genomics for curation of variants in telomere biology disorder associated genes: A systematic review.},
journal = {Genetics in medicine : official journal of the American College of Medical Genetics},
volume = {25},
number = {3},
pages = {100354},
doi = {10.1016/j.gim.2022.11.021},
pmid = {36496180},
issn = {1530-0366},
mesh = {Humans ; *Genetic Variation/genetics ; *Genetic Testing ; Genome, Human ; Genomics ; Telomere/genetics ; },
abstract = {PURPOSE: Patients with an underlying telomere biology disorder (TBD) have variable clinical presentations, and they can be challenging to diagnose clinically. A genomic diagnosis for patients presenting with TBD is vital for optimal treatment. Unfortunately, many variants identified during diagnostic testing are variants of uncertain significance. This complicates management decisions, delays treatment, and risks nonuptake of potentially curative therapies. Improved application of functional genomic evidence may reduce variants of uncertain significance classifications.<br><br>METHODS: We systematically searched the literature for published functional assays interrogating TBD gene variants. When possible, established likely benign/benign and likely pathogenic/pathogenic variants were used to estimate the assay sensitivity, specificity, positive predictive value, negative predictive value, and odds of pathogenicity.<br><br>RESULTS: In total, 3131 articles were screened and 151 met inclusion criteria. Sufficient data to enable a PS3/BS3 recommendation were available for TERT variants only. We recommend that PS3 and BS3 can be applied at a moderate and supportive level, respectively. PS3/BS3 application was limited by a lack of assay standardization and limited inclusion of benign variants.<br><br>CONCLUSION: Further assay standardization and assessment of benign variants are required for optimal use of the PS3/BS3 criterion for TBD gene variant classification.},
}
@article {pmid36485133,
year = {2022},
author = {Savage, SA},
title = {Dyskeratosis congenita and telomere biology disorders.},
journal = {Hematology. American Society of Hematology. Education Program},
volume = {2022},
number = {1},
pages = {637-648},
pmid = {36485133},
issn = {1520-4383},
mesh = {Humans ; Child ; *Dyskeratosis Congenita/genetics/pathology ; Telomere/genetics/pathology ; Germ-Line Mutation ; Bone Marrow Failure Disorders ; *Anemia, Aplastic ; },
abstract = {Numerous genetic discoveries and the advent of clinical telomere length testing have led to the recognition of a spectrum of telomere biology disorders (TBDs) beyond the classic dyskeratosis congenita (DC) triad of nail dysplasia, abnormal skin pigmentation, and oral leukoplakia occurring with pediatric bone marrow failure. Patients with DC/TBDs have very short telomeres for their age and are at high risk of bone marrow failure, cancer, pulmonary fibrosis (PF), pulmonary arteriovenous malformations, liver disease, stenosis of the urethra, esophagus, and/or lacrimal ducts, avascular necrosis of the hips and/or shoulders, and other medical problems. However, many patients with TBDs do not develop classic DC features; they may present in middle age and/or with just 1 feature, such as PF or aplastic anemia. TBD-associated clinical manifestations are progressive and attributed to aberrant telomere biology caused by the X-linked recessive, autosomal dominant, autosomal recessive, or de novo occurrence of pathogenic germline variants in at least 18 different genes. This review describes the genetics and clinical manifestations of TBDs and highlights areas in need of additional clinical and basic science research.},
}
@article {pmid36483815,
year = {2022},
author = {Picos-Cárdenas, VJ and Beltrán-Ontiveros, SA and Cruz-Ramos, JA and Contreras-Gutiérrez, JA and Arámbula-Meraz, E and Angulo-Rojo, C and Guadrón-Llanos, AM and Leal-León, EA and Cedano-Prieto, DM and Meza-Espinoza, JP},
title = {Novel TINF2 gene mutation in dyskeratosis congenita with extremely short telomeres: A case report.},
journal = {World journal of clinical cases},
volume = {10},
number = {33},
pages = {12440-12446},
pmid = {36483815},
issn = {2307-8960},
abstract = {BACKGROUND: Dyskeratosis congenita is a rare disease characterized by bone marrow failure and a clinical triad of oral leukoplakia, nail dystrophy, and abnormal skin pigmentation. The genetics of dyskeratosis congenita include mutations in genes involved in telomere maintenance, including TINF2.<br><br>CASE SUMMARY: Here, we report a female patient who presented thrombocytopenia, anemia, reticulate hyperpigmentation, dystrophy in fingernails and toenails, and leukoplakia on the tongue. A histopathological study of the skin showed dyskeratocytes; however, a bone marrow biopsy revealed normal cell morphology. The patient was diagnosed with dyskeratosis congenita, but her family history did not reveal significant antecedents. Whole-exome sequencing showed a novel heterozygous punctual mutation in exon 6 from the TINF2 gene, namely, NM_001099274.1:c.854delp.(Val285Alafs*32). An analysis of telomere length showed short telomeres relative to the patient's age.<br><br>CONCLUSION: The disease in this patient was caused by a germline novel mutation of TINF2 in one of her parents.},
}
@article {pmid36481818,
year = {2022},
author = {Sieverling, L and Hong, C and Koser, SD and Ginsbach, P and Kleinheinz, K and Hutter, B and Braun, DM and Cortés-Ciriano, I and Xi, R and Kabbe, R and Park, PJ and Eils, R and Schlesner, M and , and Brors, B and Rippe, K and Jones, DTW and Feuerbach, L and , },
title = {Author Correction: Genomic footprints of activated telomere maintenance mechanisms in cancer.},
journal = {Nature communications},
volume = {13},
number = {1},
pages = {7574},
doi = {10.1038/s41467-022-32328-7},
pmid = {36481818},
issn = {2041-1723},
}
@article {pmid36473858,
year = {2022},
author = {He, F and Yu, Q and Wang, M and Wang, R and Gong, X and Ge, F and Yu, X and Li, S},
title = {SESAME-catalyzed H3T11 phosphorylation inhibits Dot1-catalyzed H3K79me3 to regulate autophagy and telomere silencing.},
journal = {Nature communications},
volume = {13},
number = {1},
pages = {7526},
pmid = {36473858},
issn = {2041-1723},
mesh = {*Histones ; *Sesamum ; Autophagy ; },
abstract = {The glycolytic enzyme, pyruvate kinase Pyk1 maintains telomere heterochromatin by phosphorylating histone H3T11 (H3pT11), which promotes SIR (silent information regulator) complex binding at telomeres and prevents autophagy-mediated Sir2 degradation. However, the exact mechanism of action for H3pT11 is poorly understood. Here, we report that H3pT11 directly inhibits Dot1-catalyzed H3K79 tri-methylation (H3K79me3) and uncover how this histone crosstalk regulates autophagy and telomere silencing. Mechanistically, Pyk1-catalyzed H3pT11 directly reduces the binding of Dot1 to chromatin and inhibits Dot1-catalyzed H3K79me3, which leads to transcriptional repression of autophagy genes and reduced autophagy. Despite the antagonism between H3pT11 and H3K79me3, they work together to promote the binding of SIR complex at telomeres to maintain telomere silencing. Furthermore, we identify Reb1 as a telomere-associated factor that recruits Pyk1-containing SESAME (Serine-responsive SAM-containing Metabolic Enzyme) complex to telomere regions to phosphorylate H3T11 and prevent the invasion of H3K79me3 from euchromatin into heterochromatin to maintain telomere silencing. Together, these results uncover a histone crosstalk and provide insights into dynamic regulation of silent heterochromatin and autophagy in response to cell metabolism.},
}
@article {pmid36469522,
year = {2022},
author = {Martinez, D and Lavebratt, C and Millischer, V and de Jesus R de Paula, V and Pires, T and Michelon, L and Camilo, C and Esteban, N and Pereira, A and Schalling, M and Vallada, H},
title = {Shorter telomere length and suicidal ideation in familial bipolar disorder.},
journal = {PloS one},
volume = {17},
number = {12},
pages = {e0275999},
pmid = {36469522},
issn = {1932-6203},
mesh = {Humans ; *Bipolar Disorder/genetics ; Suicidal Ideation ; Telomere/genetics ; Leukocytes ; *Suicide ; Telomere Shortening/genetics ; },
abstract = {Bipolar Disorder (BD) has recently been related to a process of accelerated aging, with shortened leukocyte telomere length (LTL) in this population. It has also been observed that the suicide rate in BD patients is higher than in the general population, and more recently the telomere length variation has been described as shorter in suicide completers compared with control subjects. Objectives The aim of the present study was to investigate if there is an association between LTL and BD in families where two or more members have BD including clinical symptomatology variables, along with suicide behavior. Methods Telomere length and single copy gene ratio (T/S ratio) was measured using quantitative polymerase chain reaction in a sample of 143 relatives from 22 families, of which 60 had BD. The statistical analysis was performed with a polygenic mixed model. Results LTL was associated with suicidal ideation (p = 0.02) as that there is an interaction between suicidal ideation and course of the disorder (p = 0.02). The estimated heritability for LTL in these families was 0.68. In addition, covariates that relate to severity of disease, i.e. suicidal ideation and course of the disorder, showed an association with shorter LTL in BD patients. No difference in LTL between BD patients and healthy relatives was observed. Conclusion LTL are shorter in subjects with familial BD suggesting that stress related sub-phenotypes possibly accelerate the process of cellular aging and correlate with disease severity and suicidal ideation.},
}
@article {pmid36466397,
year = {2022},
author = {Shi, H and Li, X and Yu, H and Shi, W and Lin, Y and Zhou, Y},
title = {Potential effect of dietary zinc intake on telomere length: A cross-sectional study of US adults.},
journal = {Frontiers in nutrition},
volume = {9},
number = {},
pages = {993425},
pmid = {36466397},
issn = {2296-861X},
abstract = {BACKGROUND: Telomere length, which is related to chronic diseases and premature mortality, is influenced by dietary factors. Zinc is known as a dietary antioxidant micronutrient, however, its impact on telomere length remains unclear.<br><br>OBJECTIVE: We aimed to examine the potential effect of dietary zinc intake on telomere length among middle-aged and older individuals in the US.<br><br>MATERIALS AND METHODS: Our study included 3,793 US participants aged 45 years and older from the 1999 to 2002 National Health and Nutrition Examination Survey (NHANES). 24-h dietary recall interviews were employed to evaluate zinc consumption. Leukocyte telomere length was assessed by real-time quantitative polymerase chain reaction (qPCR). We adopted generalized linear models to investigate the effect of dietary zinc intake on telomere length, and subgroup analyses were further applied. We further evaluated the dose-response relationship using restricted cubic spline analysis.<br><br>RESULTS: Among the 3,793 participants, the average telomere length was 0.926 &#xb1; 0.205 (T/S ratio) or 5509.5 &#xb1; 494.9 (bp). After adjusting for major confounders, every 5 mg increment in dietary zinc consumption was related to 0.64% (95% CI: 0.17%, 1.10%) longer telomere length. In the subgroup analyses, significant relationships were found in females (Percentage change: 1.11%; 95% CI: 0.48%, 1.75%), obese (Percentage change: 0.88%; 95% CI: 0.26%, 1.50%), and low energy intake individuals (Percentage change: 0.99%; 95% CI: 0.51%, 1.46%). Additionally, we revealed a positive linear relationship between dietary zinc intake and telomere length (P for non-linearity = 0.636).<br><br>CONCLUSION: Our study revealed that elevated dietary zinc intake was significantly related to longer telomere length among adults aged 45 years and older in the US. And the association was more pronounced in females, obese, and low energy intake individuals.},
}
@article {pmid36466075,
year = {2022},
author = {Krasnienkov, DS and Gorodna, OV and Kaminska, TM and Podolskiy, VV and Podolskiy, VV and Nechyporenko, MV and Antypkin, YG and Livshits, LA},
title = {Analysis of Relative Average Length of Telomeres in Leukocytes of Women with COVID-19.},
journal = {Cytology and genetics},
volume = {56},
number = {6},
pages = {526-529},
pmid = {36466075},
issn = {0095-4527},
abstract = {Coronavirus disease (COVID-19) is an acute infectious disease of the respiratory tract caused by a new SARS-CoV-2 coronavirus. A global vaccination program against SARS-CoV-2 continues, and the incidence of COVID-19 worldwide is significantly decreasing. However, among millions of those who survived COVID-19, numerous groups will need assistance due to increased clinical consequences after COVID-19. Currently, there is a need to search for molecular biomarkers for monitoring the onset and progression of post-COVID syndrome. For this purpose, the relative average length of chromosome regions was studied in the groups of women of reproductive age: in the group of patients (n = 64) recovered from COVID-19 and in the control group (n = 42) of women of the same age. The analysis was carried out using a method of multiplex monochrome quantitative real-time PCR on DNA samples isolated from the peripheral blood leukocytes. According to the results of the study, it was established that the relative average length of chromosomes in the peripheral blood leukocytes was statistically significantly lower in the group of patients with COVID-19 than in the control group (p < 0.05). The results obtained allow one to state that the observed shortening of the relative average length of telomeres in the group of patients that recovered from COVID-19 can indicate that SARS-CoV-2 infection can directly cause the erosion of telomeres in the blood cells, particularly, in leukocytes. Thus, the determination of the relative average length of telomeres can be an informative prognostic marker for estimating the risk of the severity of COVID-19 disease and the development of post-COVID syndrome.},
}
@article {pmid36462796,
year = {2022},
author = {Zizza, A and Panico, A and Grassi, T and Recchia, V and Grima, P and De Giglio, O and Bagordo, F},
title = {Is telomere length in buccal or salivary cells a useful biomarker of exposure to air pollution? A review.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {883-884},
number = {},
pages = {503561},
doi = {10.1016/j.mrgentox.2022.503561},
pmid = {36462796},
issn = {1879-3592},
mesh = {Adult ; Child ; Humans ; *Air Pollution/adverse effects ; Biomarkers ; Soot ; Telomere ; *Pesticides ; Carbon ; },
abstract = {Telomeres are repetitive DNA-protein sequences located at the end of chromosomes and play an essential role in preserving information in our genome by protecting against end-to-end fusion, nucleolytic degradation, breakage, and inappropriate recombination. The telomeres shorten with aging and this process can be affected by oxidative stress and inflammation. Environmental and occupational factors may contribute to telomere length (TL) shortening, as demonstrated by an increasing number of studies. In particular, air pollution was associated with aging-related health outcomes and molecular alterations, such as telomeric shortening. Leukocytes are widely used for TL measurement. However, buccal and salivary cells have more intimate contact with airborne pollutants and are easier to sample. The objective of this review was to identify whether salivary or buccal TL represents a valid marker for evaluating the effects of pollution on health. The reviewed studies investigated the association between TL and occupational exposure (genotoxic substances in mechanical workers, and pesticides in pesticides applicators), residential traffic exposure (NOx, NO2, PM2.5, PM10, and black carbon), and household air pollution (PM2.5 and black carbon from biomass stoves). The studies involved adults and children. Although few studies have yet been carried out, almost all reported a negative association between salivary or buccal TL and exposure to air pollutants stating that it could be a good indicator of occupational or airborne pollution exposure. However, further research is needed to evaluate the effect of acute versus long-term exposure on salivary or buccal TL as well as the role of confounding factors. Moreover, most of the reviewed studies were conducted on healthy adults, so it is important to deeply investigate how TL is associated with all-cause mortality such as cancer, diabetes, cardiovascular disease, and respiratory disease, how it can be affected during childhood, and which changes over time can be associated with diseases' onset in adulthood.},
}
@article {pmid36461827,
year = {2023},
author = {Safaee, MM and Lin, J and Smith, DL and Fury, M and Scheer, JK and Burke, JF and Bravate, C and Lambert, D and Ames, CP},
title = {Association of telomere length with risk of complications in adult spinal deformity surgery: a pilot study of 43 patients.},
journal = {Journal of neurosurgery. Spine},
volume = {38},
number = {3},
pages = {331-339},
doi = {10.3171/2022.10.SPINE22605},
pmid = {36461827},
issn = {1547-5646},
mesh = {Humans ; Adult ; Female ; Aged ; Middle Aged ; Pilot Projects ; Follow-Up Studies ; *Frailty ; *Scoliosis/surgery ; Postoperative Complications ; Quality of Life ; Retrospective Studies ; },
abstract = {OBJECTIVE: Risk stratification is a critical element of surgical planning. Early tools were fairly crude, while newer instruments incorporate disease-specific elements and markers of frailty. It is unknown if discrepancies between chronological and cellular age can guide surgical planning or treatment. Telomeres are DNA-protein complexes that serve an important role in protecting genomic DNA. Their shortening is a consequence of aging and environmental exposures, with well-established associations with diseases of aging and mortality. There are compelling data to suggest that telomere length can provide insight toward overall health. The authors sought to determine potential associations between telomere length and postoperative complications.<br><br>METHODS: Adults undergoing elective surgery for spinal deformity were prospectively enrolled. Telomere length was measured from preoperative whole blood using quantitative polymerase chain reaction and expressed as the ratio of telomere (T) to single-copy gene (S) abundance (T/S ratio), with higher T/S ratios indicating longer telomere length. Demographic and patient data included age, BMI, and results for the following rating scales: the Adult Spinal Deformity Frailty Index (ASD-FI), Oswestry Disability Index (ODI), Scoliosis Research Society-22r (SRS-22r), American Society of Anesthesiology (ASA) classification, and Charlson Comorbidity Index (CCI). Operative and postoperative complication data (medical or surgical within 90 days) were also collected.<br><br>RESULTS: Forty-three patients were enrolled, including 31 women (53%), with a mean age of 66 years and a mean BMI of 28.5. The mean number of levels fused was 11, with 21 (48.8%) combined anterior-posterior approaches. Twenty-two patients (51.2%) had a medical or surgical complication. Patients with a postoperative complication had a significantly lower T/S ratio (0.712 vs 0.813, p = 0.008), indicating shorter telomere length, despite a mild difference in age compared with patients without a postoperative complication (68 vs 63 years, p = 0.069). Patients with complications also had higher CCI scores than patients without complications (2.3 vs 3.8, p = 0.004). There were no significant differences in sex, BMI, ASD-FI score, ASA class, preoperative ODI and SRS-22r scores, number of levels fused, or use of three-column osteotomies. In a multivariate model including age, frailty, ASA class, use of an anterior-posterior approach, CCI score, and telomere length, the authors found that short telomere length was significantly associated with postoperative complications. Patients whose telomere length fell in the shortest quartile had the highest risk (OR 18.184, p = 0.030).<br><br>CONCLUSIONS: Short telomere length was associated with an increased risk of postoperative complications despite only a mild difference in chronological age. Increasing comorbidity scores also trended toward significance. Larger prospective studies are needed; however, these data provide a compelling impetus to investigate the role of biological aging as a component of surgical risk stratification.},
}
@article {pmid36458548,
year = {2023},
author = {Virseda-Berdices, A and Concostrina-Martinez, L and Martínez-González, O and Blancas, R and Resino, S and Ryan, P and Martin-Vicente, M and Brochado-Kith, O and Blanca-López, N and Mallol Poyato, MJ and López Matamala, B and Martín Parra, C and Jiménez-Sousa, M&#xc1; and Fernández-Rodríguez, A},
title = {Relative telomere length impact on mortality of COVID-19: Sex differences.},
journal = {Journal of medical virology},
volume = {95},
number = {1},
pages = {e28368},
pmid = {36458548},
issn = {1096-9071},
mesh = {Humans ; Male ; Female ; Aged ; *Sex Characteristics ; *COVID-19 ; Prognosis ; Telomere Shortening ; Telomere ; },
abstract = {Increasing age is associated with severity and higher mortality of COVID-19. Telomere shortening is associated with higher risk of infections and may be used to identify those patients who are more likely to die. We evaluated the association between relative telomere length (RTL) and COVID-19 mortality. RTL was measured in patients hospitalized because of COVID-19. We used Kaplan-Meier method to analyze survival probabilities, and Cox regression to investigate the association between RTL and mortality (30 and 90 days). Six hundred and eight patients were included in the analysis (mean age =72.5 years, 41.1% women, and 53.8% Caucasic). During the study period, 75 people died from COVID-19 and 533 survived. Lower RTL was associated with a higher risk of death in women either at 30 (adjusted hazard ratio [HR] (aHR) = 3.33; 95% confidence interval [CI] = 1.05-10.00; p = 0.040) and at 90 days (aHR = 3.57; 95%CI = 1.23-11.11; p = 0.019). Lower RTL was associated with a higher risk of dying of COVID-19 in women. This finding suggests that RTL has an essential role in the prognosis of this subset of the population.},
}
@article {pmid36457292,
year = {2023},
author = {Mayer, SE and Guan, J and Lin, J and Hamlat, E and Parker, JE and Brownell, K and Price, C and Mujahid, M and Tomiyama, AJ and Slavich, GM and Laraia, BA and Epel, ES},
title = {Intergenerational effects of maternal lifetime stressor exposure on offspring telomere length in Black and White women.},
journal = {Psychological medicine},
volume = {53},
number = {13},
pages = {6171-6182},
pmid = {36457292},
issn = {1469-8978},
support = {R01 HD073568/HD/NICHD NIH HHS/United States ; R00 AG062778/AG/NIA NIH HHS/United States ; R56 HL141878/HL/NHLBI NIH HHS/United States ; R01 AG059677/AG/NIA NIH HHS/United States ; K99 AG062778/AG/NIA NIH HHS/United States ; K12 HD051958/HD/NICHD NIH HHS/United States ; R56 AG059677/AG/NIA NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Child ; Female ; Humans ; Pregnancy ; Maternal Exposure ; *Mothers/psychology ; Prospective Studies ; Telomere/physiology ; *Telomere Shortening/physiology ; White People/psychology ; Intergenerational Relations/ethnology ; Black or African American/psychology ; Young Adult ; Middle Aged ; },
abstract = {BACKGROUND: Although maternal stressor exposure has been associated with shorter telomere length (TL) in offspring, this literature is based largely on White samples. Furthermore, timing of maternal stressors has rarely been examined. Here, we examined how maternal stressors occurring during adolescence, pregnancy, and across the lifespan related to child TL in Black and White mothers.<br><br>METHOD: Mothers (112 Black; 110 White; Mage = 39) and their youngest offspring (n = 222; Mage = 8) were part of a larger prospective cohort study, wherein mothers reported their stressors during adolescence (assessed twice during adolescence for the past year), pregnancy (assessed in midlife for most recent pregnancy), and across their lifespan (assessed in midlife). Mother and child provided saliva for TL measurement. Multiple linear regression models examined the interaction of maternal stressor exposure and race in relation to child TL, controlling for maternal TL and child gender and age. Race-stratified analyses were also conducted.<br><br>RESULTS: Neither maternal adolescence nor lifespan stressors interacted with race in relation to child TL. In contrast, greater maternal pregnancy stressors were associated with shorter child TL, but this effect was present for children of White but not Black mothers. Moreover, this effect was significant for financial but not social pregnancy stressors. Race-stratified models revealed that greater financial pregnancy stressors predicted shorter telomeres in offspring of White, but not Black mothers.<br><br>CONCLUSIONS: Race and maternal stressors interact and are related to biological aging across generations, but these effects are specific to certain races, stressors, and exposure time periods.},
}
@article {pmid36447745,
year = {2021},
author = {Aiello, A and Accardi, G and Alì, S and Caruso, C and Chen, M and De Vivo, I and Ligotti, ME and Scapagnini, G and Davinelli, S and Candore, G},
title = {Possible Association of Telomere Length With Sleep Duration. A Preliminary Pilot Study in a Sicilian Cohort with Centenarians.},
journal = {Translational medicine @ UniSa},
volume = {24},
number = {1},
pages = {24-29},
pmid = {36447745},
issn = {2239-9747},
abstract = {Telomere length (TL) is considered a biomarker of ageing although this topic is still debated. Also, sleep pattern changes are physiological part of the normal ageing process. In fact, it is widely recognized that sleep duration declines with age, leading to dysregulation of circadian rhythms. The aim of our study was to analyse the possible association of sleep duration with TL in a sample of 135 subjects with ages ranging from 20 to 111 years, recruited from Palermo and neighbouring municipalities in Sicily (Italy). Preliminary data suggest that relative TL (RTL) decreases with age in both men and women. However, at older ages, the difference between men and women tends to narrow. Nonagenarian and centenarian women do not show RTL values significantly different from those observed in adult and old women (40-89 years aged). Moreover, to analyse the relationship between TL and sleep, we stratified sleep duration into greater or lesser than 8-h periods. We found that centenarians, who daily sleep 8 hours or more, have longer RTL than centenarians who sleep fewer than 8 hours. Although the relatively small sample size of centenarians, we provide preliminary evidence that sleep duration may affect the RTL of centenarians. To the best of our knowledge, this is the first study to examine the relationship between centenarians, RTL and sleep duration. Further studies with greater sample size of centenarians are required to replicate and extend these data.},
}
@article {pmid36442845,
year = {2022},
author = {Ni, W and Wolf, K and Breitner, S and Zhang, S and Nikolaou, N and Ward-Caviness, CK and Waldenberger, M and Gieger, C and Peters, A and Schneider, A},
title = {Higher Daily Air Temperature Is Associated with Shorter Leukocyte Telomere Length: KORA F3 and KORA F4.},
journal = {Environmental science &amp; technology},
volume = {56},
number = {24},
pages = {17815-17824},
pmid = {36442845},
issn = {1520-5851},
mesh = {Adult ; Humans ; *Air Pollution/analysis ; Temperature ; Cohort Studies ; Leukocytes ; Telomere ; },
abstract = {Higher air temperature is associated with increased age-related morbidity and mortality. To date, short-term effects of air temperature on leukocyte telomere length have not been investigated in an adult population. We aimed to examine the short-term associations between air temperature and leukocyte telomere length in an adult population-based setting, including two independent cohorts. This population-based study involved 5864 participants from the KORA F3 (2004-2005) and F4 (2006-2008) cohort studies conducted in Augsburg, Germany. Leukocyte telomere length was assessed by a quantitative PCR-based method. We estimated air temperature at each participant's residential address through a highly resolved spatiotemporal model. We conducted cohort-specific generalized additive models to explore the short-term effects of air temperature on leukocyte telomere length at lags 0-1, 2-6, 0-6, and 0-13 days separately and pooled the estimates by fixed-effects meta-analysis. Our study found that between individuals, an interquartile range (IQR) increase in daily air temperature was associated with shorter leukocyte telomere length at lags 0-1, 2-6, 0-6, and 0-13 days (%change: -2.96 [-4.46; -1.43], -2.79 [-4.49; -1.07], -4.18 [-6.08; -2.25], and -6.69 [-9.04; -4.27], respectively). This meta-analysis of two cohort studies showed that between individuals, higher daily air temperature was associated with shorter leukocyte telomere length.},
}
@article {pmid36440190,
year = {2022},
author = {Lan, B and Bai, Y and Chang, X and Zhang, X},
title = {Independent and joint effect of relative telomere length and type 2 diabetes on all-cause mortality in American adults.},
journal = {Frontiers in endocrinology},
volume = {13},
number = {},
pages = {1035017},
pmid = {36440190},
issn = {1664-2392},
mesh = {Adult ; Humans ; Male ; United States ; Female ; *Diabetes Mellitus, Type 2/genetics ; Nutrition Surveys ; Telomere/genetics ; Leukocytes ; Proportional Hazards Models ; },
abstract = {OBJECTIVE: The joint effect of leukocyte telomere length (LTL) and type 2 diabetes (T2D) on the risk of all-cause death has been sparsely explored. The study designed to examine the joint effect of T2D and LTL on the probability of death in American adults.<br><br>METHODS: A cohort of 6862 adults with LTL measurements and with or without T2D from the NHANES 1999-2002 with follow-up information until 2015 was studied. Quantitative PCR was used to measure the length of telomeres relative to standard reference DNA (T/S ratio). Individuals were grouped into three tertiles according to the LTL levels, with the first tertile demonstrating the lowest one and used as the reference group. The effects of LTL and T2D status on death were evaluated using Kaplan-Meier curves along with log-rank test. Three Cox proportional hazards models with adjustment for various confounders were used to examine the links between TL and all-cause death possibility using adjusted hazard ratios (HRs).<br><br>RESULTS: Adults in the sample averaged 45.54 years of age, with 49.51% being male. After a median follow-up period of 14.4 years, 1543 (22.5%) individuals died from all cause. The probability of all-cause mortality was higher among individuals with LTL in the highest tertile than individuals in the lowest tertile (aHR = 0.89; 95%CI: 0.77-1.03); however, the difference did not reach the level of statistical significance (P = 0.11). Conversely, the individuals with T2D had a higher probability of death than individuals without (aHR = 1.26; 95%CI: 1.06-1.50; P = 0.0092). When LTL and T2D status were investigated jointly, subjects in the highest TLT tertile and with T2D had the highest probability of mortality compared with their counterparts (aHR = 1.34; 95%CI: 1.07-1.68; P = 0.0101). However, there was no independent effect of low TLT on mortality as demonstrated among individuals with diabetes (aHR = 1.14; 95%CI: 0.95-1.38; P = 0.1662).<br><br>CONCLUSION: The joint effect of TLT and T2D was larger than the sum of the independent effects on the risk of all-cause death. Participants with high TLT and diabetes showed the highest possibility of death compared with other groups.},
}
@article {pmid36437769,
year = {2022},
author = {Zhao, G and Guo, D and Li, L and Yang, C and Dong, J},
title = {The Association between Dietary Magnesium Intake and Telomere Length in Adults with Hypertension.},
journal = {The journal of nutrition, health &amp; aging},
volume = {26},
number = {11},
pages = {1010-1015},
doi = {10.1007/s12603-022-1856-y},
pmid = {36437769},
issn = {1760-4788},
mesh = {Male ; Humans ; Female ; Nutrition Surveys ; *Magnesium ; *Hypertension/genetics ; Uric Acid ; Telomere ; },
abstract = {BACKGROUND: Dietary micronutrients are significantly associated with telomere length, as shown in multiple studies. However, no study has investigated the association between magnesium intake and telomere length in adults with hypertension.<br><br>METHODS: Participants were included from the National Health and Nutrition Examination Survey (NHANES) in 1999-2000 and 2001-2002. Dietary magnesium intake was assessed using the 24 - hour recall method and the telomere length of leukocytes was measured using polymerase chain reaction (PCR). A multivariate regression model was then used to assess the association between dietary magnesium intake and telomere length in adults with hypertension.<br><br>RESULTS: Our final analysis included 2199 hypertensive adults (46.79% males) with a mean dietary magnesium intake of 254.82&#xb1;133.47 mg/day. Linear regression, adjusted for race, sex, age, smoking, uric acid, and other variables, showed that every 1 mg increase in dietary magnesium intake was associated with a 0.20 (95% CI: 0.01, 0.39, p = 0.043) longer telomere length in all participants. In the &#x2265;45 years age group, there was a statistically significant association between the telomere length and dietary magnesium (95% CI: 0.16, 0.63, p <0.001).<br><br>CONCLUSIONS: This study suggests that increased magnesium intake is associated with a longer telomere length in hypertensive adults, especially in those &#x2265;45 years of age. However, further research is needed to determine a causal relationship.},
}
@article {pmid36437244,
year = {2022},
author = {Maciejewska, N and Olszewski, M and Jurasz, J and Baginski, M and Stasevych, M and Zvarych, V and Folini, M and Zaffaroni, N},
title = {Teloxantron inhibits the processivity of telomerase with preferential DNA damage on telomeres.},
journal = {Cell death &amp; disease},
volume = {13},
number = {11},
pages = {1005},
pmid = {36437244},
issn = {2041-4889},
mesh = {Humans ; *Telomerase ; Telomere ; DNA Damage ; *Lung Neoplasms ; Anthraquinones/pharmacology ; Cell Line, Tumor ; *Bone Neoplasms ; },
abstract = {Telomerase reactivation is one of the hallmarks of cancer, which plays an important role in cellular immortalization and the development and progression of the tumor. Chemical telomerase inhibitors have been shown to trigger replicative senescence and apoptotic cell death both in vitro and in vivo. Due to its upregulation in various cancers, telomerase is considered a potential target in cancer therapy. In this study, we identified potent, small-molecule telomerase inhibitors using a telomerase repeat amplification protocol assay. The results of the assay are the first evidence of telomerase inhibition by anthraquinone derivatives that do not exhibit G-quadruplex-stabilizing properties. The stability of telomerase in the presence of its inhibitor was evaluated under nearly physiological conditions using a cellular thermal shift assay. Our data showed that the compound induced aggregation of the catalytic subunit (hTERT) of human telomerase, and molecular studies confirmed the binding of the hit compound with the active site of the enzyme. The ability of new derivatives to activate DNA double-strand breaks (DSBs) was determined by high-resolution microscopy and flow cytometry in tumor cell lines differing in telomere elongation mechanism. The compounds triggered DSBs in TERT-positive A549 and H460 lung cancer cell lines, but not in TERT-negative NHBE normal human bronchial epithelial and ALT-positive U2OS osteosarcoma cell lines, which indicates that the induction of DSBs was dependent on telomerase inhibition. The observed DNA damage activated DNA damage response pathways involving ATM/Chk2 and ATR/Chk1 cascades. Additionally, the compounds induced apoptotic cell death through extrinsic and intrinsic pathways in lung cancer cells. Taken together, our study demonstrated that anthraquinone derivatives can be further developed into novel telomerase-related anticancer agents.},
}
@article {pmid36435475,
year = {2023},
author = {Tao, HY and He, SM and Zhao, CY and Wang, Y and Sheng, WJ and Zhen, YS},
title = {Antitumor efficacy of a recombinant EGFR-targeted fusion protein conjugate that induces telomere shortening and telomerase downregulation.},
journal = {International journal of biological macromolecules},
volume = {226},
number = {},
pages = {1088-1099},
doi = {10.1016/j.ijbiomac.2022.11.225},
pmid = {36435475},
issn = {1879-0003},
mesh = {Animals ; Mice ; Humans ; Recombinant Fusion Proteins/genetics/pharmacology/metabolism ; *Telomerase/genetics/metabolism ; ErbB Receptors/metabolism ; Down-Regulation ; Telomere Shortening ; Cell Line, Tumor ; Xenograft Model Antitumor Assays ; *Immunoconjugates/pharmacology ; Telomere/metabolism ; },
abstract = {OBJECTIVE: To prepare a recombinant EGFR-targeted fusion protein drug conjugate acting on telomere and telomerase; and evaluate its antitumor efficacy.<br><br>METHODS: We prepared a recombinant fusion protein Fv-LDP-D3 which consists of the Fv fragment of an anti-EGFR monoclonal antibody (MAb), the apoprotein of lidamycin (LDP), and the third domain (D3) of human serum albumin (HSA); then generated the conjugate Fv-LDP-D3&#x223c;AE by integrating the active enediyne chomophore (AE) of lidamycin. Accordingly, in vitro and in vivo experiments were performed.<br><br>RESULTS: As shown, Fv-LDP-D3 specifically bound to EGFR highly-expressing cancer cells and intensely entered K-Ras mutant cells via enhanced macropinocytosis. By in vivo imaging, Fv-LDP-D3 displayed intense accumulation and persistent retention in tumor-site. Furthermore, the conjugate Fv-LDP-D3&#x223c;AE displayed highly potent cytotoxicity to cancer cells with IC50 at 0.1&#xa0;nM level. The conjugate induced telomere shortening and downregulation of telomerase and EGFR pathway related proteins. Fv-LDP-D3&#x223c;AE exhibited prominent antitumor efficacy against human colorectal cancer xenograft accompanying with significant increase of serum IFN-&#x3b2; in athymic mice.<br><br>CONCLUSION: The recombinant fusion protein conjugate that exhibits the capability of tumor-targeting drug delivery can induce telomere shortening and telomerase downregulation. The investigation may lay the foundation for the development of MAb-HSA domain-based fusion protein drug conjugates.},
}
@article {pmid36427630,
year = {2022},
author = {Jenkins, AJ and Syreeni, A and Mutter, S and Januszewski, AS and Groop, PH},
title = {Telomeres in clinical diabetes research - Moving towards precision medicine in diabetes care?.},
journal = {Diabetes research and clinical practice},
volume = {194},
number = {},
pages = {110178},
doi = {10.1016/j.diabres.2022.110178},
pmid = {36427630},
issn = {1872-8227},
mesh = {Humans ; *Precision Medicine ; Telomere/genetics ; Telomere Shortening ; *Diabetes Mellitus/genetics/therapy ; Biomarkers ; },
abstract = {The early prediction of health outcomes for people with diabetes mellitus is desirable, as are adjunct therapies to reduce the related chronic complications and risk of premature death. The length of telomeres, protective caps on chromosome ends, is influenced by genetic and acquired factors, and shorter telomeres have been associated with and predictive of adverse cardiometabolic outcomes. Many studies have shown associations between telomere length in white blood cells (WBC) and diabetes per se and its chronic complications, and some studies show that telomeres do not always progressively shorten in people with diabetes. With the pandemic of diabetes and taking into consideration the calculations of residual risk using existent risk equations, additional tests to stratify subject risk are desirable. In this evolving era of precision medicine for people with diabetes, this 'global biomarker' of WBC telomere length may be useful to help predict health outcomes, to monitor health status, and may be a therapeutic target. We comment on the field of telomere investigations in diabetes, including recommending areas for further clinical research.},
}
@article {pmid36427074,
year = {2023},
author = {Goswami, J and MacArthur, TA and Ramachandran, D and Mahony, CR and Howick, AS and Price-Troska, T and Thompson, RJ and Spears, GM and Bailey, KR and Patnaik, MS and Passos, JF and Park, MS and Ferrer, A},
title = {TELOMERE LENGTH OF PERIPHERAL BLOOD MONONUCLEAR CELLS IS ASSOCIATED WITH DISCHARGE DISPOSITION IN OLDER TRAUMA PATIENTS.},
journal = {Shock (Augusta, Ga.)},
volume = {59},
number = {3},
pages = {327-333},
pmid = {36427074},
issn = {1540-0514},
support = {R38 HL150086/HL/NHLBI NIH HHS/United States ; T32 AG049672/AG/NIA NIH HHS/United States ; UM1 HL120877/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Male ; Aged ; Female ; *Leukocytes, Mononuclear ; *Thrombin ; Patient Discharge ; Blood Coagulation ; Telomere ; },
abstract = {Introduction: Little is known regarding peripheral blood mononuclear cell telomere length (PBMC-TL) and response to traumatic injury. The objective of this study was to characterize the role of PBMC-TL in coagulation and clinical outcomes after injury. Methods: Plasma and buffy coats were prospectively collected from trauma patients and healthy volunteers. DNA was purified and PBMC-TL quantified by quantitative polymerase chain reaction. Thrombin generation kinetics were expressed as lag time (in minutes), peak height (in nanometers), time to peak (in minutes), and endogenous thrombin potential (in nM × min). Results are in median and quartiles [Q1, Q3]. P < 0.05 was considered significant (Wilcoxon rank sum testing). Results: Forty-two younger patients (21 [20, 22] years, 69% were male) and 39 older patients (62 [61, 64] years, 79% were male) were included. There was no significant difference in Clinical Frailty Scores between groups. Younger patients had longer total PBMC-TL (0.40 Mb [0.30, 0.49] vs. 0.29 Mb [0.23, 0.33], P < 0.001) and longer average PBMC-TL per chromosome (4.3 kb [3.3, 5.3] vs. 3.2 kb [2.5, 3.7], P < 0.001). When older patients were stratified by 50th percentile of PBMC-TL, there were no differences in thrombin generation; however, those with shorter telomeres were less likely to be discharged home (29% vs. 77%, P = 0.004). Older patients in the bottom quartile of PBMC-TL had shorter lag time (2.78 min [2.33, 3.00] vs. 3.33 min [3.24, 3.89], P = 0.030) and were less likely to be discharged home (22% vs. 90%, P = 0.006) than those in the top quartile of PBMC-TL. Multivariable logistic regression models revealed both increased age and shorter PBMC-TL to be independent predictors of discharge disposition other than home. Conclusion: In older trauma patients, shorter PBMC-TL is associated with accelerated initiation of thrombin generation and lower likelihood of being discharged to home.},
}
@article {pmid36421025,
year = {2023},
author = {PerezGrovas-Saltijeral, A and Ochoa-Morales, A and Jara-Prado, A and Velázquez-Cruz, R and Rivera-Paredez, B and Dávila-OrtizdeMontellano, D and Benítez-Alonso, EO and Santamaría-Olmedo, M and Sevilla-Montoya, R and Marfil-Marín, E and Valdés-Flores, M and Martínez-Ruano, L and Camacho-Molina, A and Hidalgo-Bravo, A},
title = {Unraveling the role of relative telomere length and CAG expansion on initial symptoms of juvenile Huntington disease.},
journal = {European journal of neurology},
volume = {30},
number = {3},
pages = {612-621},
doi = {10.1111/ene.15644},
pmid = {36421025},
issn = {1468-1331},
mesh = {Adult ; Humans ; *Huntington Disease/genetics/diagnosis ; Trinucleotide Repeats/genetics ; Telomere ; Age of Onset ; },
abstract = {BACKGROUND AND PURPOSE: Juvenile-onset Huntington disease (JHD) is defined when symptoms initiate before 20 years of age. Mechanisms explaining differences between juvenile and adult onset are not fully understood. Our aim was to analyze the distribution of initial symptoms in a cohort of JHD patients and to explore its relationship with CAG expansion and relative telomere length (RTL).<br><br>METHODS: A total of 84 JHD patients and 54 neurologically healthy age and sex matched individuals were recruited. CAG length was measured by southern blot or triplet repeat primed polymerase chain reaction. RTL was measured using the Cawthon method.<br><br>RESULTS: Psychiatric symptoms were most frequent when considering the entire cohort. When divided into onset before or after 10&#x2009;years, cognitive symptoms were more frequent in the youngest, whilst in the older group psychiatric symptoms prevailed. Motor symptoms were rare in the youngest and epilepsy was observed only in this group as well as a larger CAG expansion. RTL analysis revealed shorter telomeres in JHD patients compared to controls. This difference is not influenced by age, initial symptoms, time of disease or CAG expansion.<br><br>CONCLUSIONS: To the best of our knowledge this is the largest cohort of JHD patients reported. Psychiatric manifestations deserve special attention when JHD is suspected and epilepsy is especially important in the youngest patients. Initial symptoms seem to be influenced by CAG expansion and therefore age of onset. RTL is significantly reduced in JHD patients which can influence the characteristic neurodegeneration of JHD and contribute to the clinical discrepancy between adult and juvenile forms of Huntington disease.},
}
@article {pmid36416860,
year = {2023},
author = {Jezek, M and Sun, W and Negesse, MY and Smith, ZM and Orosz, A and Green, EM},
title = {Set1 regulates telomere function via H3K4 methylation-dependent and -independent pathways and calibrates the abundance of telomere maintenance factors.},
journal = {Molecular biology of the cell},
volume = {34},
number = {1},
pages = {ar6},
pmid = {36416860},
issn = {1939-4586},
support = {R01 GM124342/GM/NIGMS NIH HHS/United States ; R25 GM055036/GM/NIGMS NIH HHS/United States ; T32 GM144876/GM/NIGMS NIH HHS/United States ; },
mesh = {Methylation ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; Histone-Lysine N-Methyltransferase/genetics/metabolism ; Histones/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Telomere/metabolism ; Telomere-Binding Proteins/metabolism ; },
abstract = {Set1 is an H3K4 methyltransferase that comprises the catalytic subunit of the COMPASS complex and has been implicated in transcription, DNA repair, cell cycle control, and numerous other genomic functions. Set1 also promotes proper telomere maintenance, as cells lacking Set1 have short telomeres and disrupted subtelomeric gene repression; however, the precise role for Set1 in these processes has not been fully defined. In this study, we have tested mutants of Set1 and the COMPASS complex that differentially alter H3K4 methylation status, and we have attempted to separate catalytic and noncatalytic functions of Set1. Our data reveal that Set1-dependent subtelomeric gene repression relies on its catalytic activity toward H3K4, whereas telomere length is regulated by Set1 catalytic activity but likely independent of the H3K4 substrate. Furthermore, we uncover a role for Set1 in calibrating the abundance of critical telomere maintenance proteins, including components of the telomerase holoenzyme and members of the telomere capping CST (Cdc13-Stn1-Ten1) complex, through both transcriptional and posttranscriptional pathways. Altogether, our data provide new insights into the H3K4 methylation-dependent and -independent roles for Set1 in telomere maintenance in yeast and shed light on possible roles for Set1-related methyltransferases in other systems.},
}
@article {pmid36406126,
year = {2022},
author = {Peretz, I and Kupiec, M and Sharan, R},
title = {A comparative analysis of telomere length maintenance circuits in fission and budding yeast.},
journal = {Frontiers in genetics},
volume = {13},
number = {},
pages = {1033113},
pmid = {36406126},
issn = {1664-8021},
abstract = {The natural ends of the linear eukaryotic chromosomes are protected by telomeres, which also play an important role in aging and cancer development. Telomere length varies between species, but it is strictly controlled in all organisms. The process of Telomere Length Maintenance (TLM) involves many pathways, protein complexes and interactions that were first discovered in budding and fission yeast model organisms (Saccharomyces cerevisiae, Schizosaccharomyces pombe). In particular, large-scale systematic genetic screens in budding yeast uncovered a network of ≈ 500 genes that, when mutated, cause telomeres to lengthen or to shorten. In contrast, the TLM network in fission yeast remains largely unknown and systematic data is still lacking. In this work we try to close this gap and develop a unified interpretable machine learning framework for TLM gene discovery and phenotype prediction in both species. We demonstrate the utility of our framework in pinpointing the pathways by which TLM homeostasis is maintained and predicting novel TLM genes in fission yeast. The results of this study could be used for better understanding of telomere biology and serve as a step towards the adaptation of computational methods based on telomeric data for human prognosis.},
}
@article {pmid36404192,
year = {2023},
author = {Vinayagamurthy, S and Bagri, S and Mergny, JL and Chowdhury, S},
title = {Telomeres expand sphere of influence: emerging molecular impact of telomeres in non-telomeric functions.},
journal = {Trends in genetics : TIG},
volume = {39},
number = {1},
pages = {59-73},
pmid = {36404192},
issn = {0168-9525},
support = {IA/S/18/2/504021/WTDBT_/DBT-Wellcome Trust India Alliance/India ; },
mesh = {*Telomere/genetics/metabolism ; DNA/metabolism ; *G-Quadruplexes ; Heterochromatin ; },
abstract = {Although the impact of telomeres on physiology stands well established, a question remains: how do telomeres impact cellular functions at a molecular level? This is because current understanding limits the influence of telomeres to adjacent subtelomeric regions despite the wide-ranging impact of telomeres. Emerging work in two distinct aspects offers opportunities to bridge this gap. First, telomere-binding factors were found with non-telomeric functions. Second, locally induced DNA secondary structures called G-quadruplexes are notably abundant in telomeres, and gene regulatory regions genome wide. Many telomeric factors bind to G-quadruplexes for non-telomeric functions. Here we discuss a more general model of how telomeres impact the non-telomeric genome - through factors that associate at telomeres and genome wide - and influence cell-intrinsic functions, particularly aging, cancer, and pluripotency.},
}
@article {pmid36402910,
year = {2022},
author = {Roberts, EK and Boss, J and Mukherjee, B and Salerno, S and Zota, A and Needham, BL},
title = {Persistent organic pollutant exposure contributes to Black/White differences in leukocyte telomere length in the National Health and Nutrition Examination Survey.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {19960},
pmid = {36402910},
issn = {2045-2322},
support = {R01 AG033592/AG/NIA NIH HHS/United States ; U24 AG066528/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; Adult ; Persistent Organic Pollutants ; *Polychlorinated Biphenyls/toxicity ; Nutrition Surveys ; Cross-Sectional Studies ; White People ; Leukocytes ; *Environmental Pollutants/toxicity ; Telomere/genetics ; },
abstract = {Despite racial disparities in diseases of aging and premature mortality, non-Hispanic Black Americans tend to have longer leukocyte telomere length (LTL), a biomarker of cellular aging, than non-Hispanic White Americans. Previous findings suggest that exposure to certain persistent organic pollutants (POPs) is both racially-patterned and associated with longer LTL. We examine whether Black/White differences in LTL are explained by differences in exposure to 15 POPs by estimating the indirect effect (IE) of self-reported race on LTL that is mediated through nine polychlorinated biphenyls (PCBs), three furans, and three dioxins, as well as their mixtures. Our study population includes 1,251 adults from the 1999-2000 and 2001-2002 cycles of the cross-sectional National Health and Nutrition Examination Survey. We characterized single-pollutant mediation effects by constructing survey-weighted linear regression models. We also implemented various approaches to quantify a global mediation effect of all POPs, including unpenalized linear regression, ridge regression, and examination of three summary exposure scores. We found support for the hypothesis that exposure to PCBs partially mediates Black/White differences in LTL. In single-pollutant models, there were significant IEs of race on LTL through six individual PCBs (118, 138, 153, 170, 180, and 187). Ridge regression (0.013, CI 0.001, 0.023; 26.0% mediated) and models examining summative exposure scores with linear combinations derived from principal components analysis (0.019, CI 0.009, 0.029; 34.8% mediated) and Toxic Equivalency Quotient (TEQ) scores (0.016, CI 0.005, 0.026; 28.8% mediated) showed significant IEs when incorporating survey weights. Exposures to individual POPs and their mixtures, which may arise from residential and occupational segregation, may help explain why Black Americans have longer LTL than their White counterparts, providing an environmental explanation for counterintuitive race differences in cellular aging.},
}
@article {pmid36401358,
year = {2022},
author = {Wang, L and Yin, H and Huang, S and Huang, S and Huang, C and Zhang, Z and Liu, H},
title = {Bortezomib induces cellular senescence in A549 lung cancer cells by stimulating telomere shortening.},
journal = {Human &amp; experimental toxicology},
volume = {41},
number = {},
pages = {9603271221124094},
doi = {10.1177/09603271221124094},
pmid = {36401358},
issn = {1477-0903},
mesh = {Humans ; Bortezomib/pharmacology/therapeutic use ; *Lung Neoplasms/drug therapy/genetics ; *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics ; A549 Cells ; Telomere Shortening ; *Antineoplastic Agents/pharmacology/therapeutic use ; Cell Line, Tumor ; Cellular Senescence ; },
abstract = {Bortezomib (BTZ) is a first-generation proteasome inhibitor with anti-tumor properties for multiple myeloma and mantle cell lymphoma. Increasing evidence has shown that BTZ exhibits toxic effects on diverse tumor cells, including non-small cell lung cancer (NSCLC) cells. However, the mechanism has not been fully evaluated. Here, we examined the regulatory effect of BTZ on cellular senescence, a potent tumor suppressive mechanism, in NSCLC cell lines. SA-β-gal staining assay showed that BTZ caused a significant increase in β-Gal positive A549 cells. BTZ also induced cell cycle arrest on G0/G1 phase in A549 cells. Furthermore, telomerase activity was markedly reduced in A549 cells treated with BTZ. BTZ reduced the expression levels of hTERT, and the key proteins binding to telomeric DNA, including POT1 and TIN2. It also induced the expressions of the cell cycle-associated tumor suppressors p53 and p21 in A549 cells. Moreover, hTERT overexpression abolished the effects of BTZ on A549 cells. These results show that BTZ induced cellular senescence by stimulating telomere shortening. Our results provide experimental data for the potential clinical application of BTZ in NSCLC treatment.},
}
@article {pmid36400982,
year = {2023},
author = {Jin, M and Huang, JD},
title = {New mechanism to promote long-term T-cell immunity by telomere transfer from antigen-presenting cells.},
journal = {Cellular &amp; molecular immunology},
volume = {20},
number = {2},
pages = {117-118},
pmid = {36400982},
issn = {2042-0226},
mesh = {*T-Lymphocytes ; *Antigen-Presenting Cells ; Antigen Presentation ; Telomere ; },
}
@article {pmid36399511,
year = {2022},
author = {Chen, L and Zhang, C and Ma, W and Huang, J and Zhao, Y and Liu, H},
title = {METTL3-mediated m6A modification stabilizes TERRA and maintains telomere stability.},
journal = {Nucleic acids research},
volume = {50},
number = {20},
pages = {11619-11634},
pmid = {36399511},
issn = {1362-4962},
mesh = {*RNA, Long Noncoding/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere Shortening ; Homologous Recombination ; DNA ; Telomere Homeostasis ; },
abstract = {Telomeric repeat-containing RNA (TERRA) is a type of long non-coding RNA transcribed from telomeres, and it forms R-loops by invasion into telomeric DNA. Since either an excessive or inadequate number of R-loops leads to telomere instability, the TERRA levels need to be delicately modulated. In this study, we found that m6A modification presents on the subtelomeric regions of TERRA and stabilizes it, and the loss of METTL3 impacts telomere stability. Mechanically, the m6A modification on TERRA is catalyzed by METTL3, recognized and stabilized by the m6A reader YTHDC1. Knockdown of either METTL3 or YTHDC1 enhances TERRA degradation. The m6A-modified TERRA forms R-loops and promotes homologous recombination which is essential for the alternative lengthening of telomeres (ALT) pathway in cancer cells. METTL3 depletion leads to R-loop reduction, telomere shortening and instability. Altogether, these findings reveal that METTL3 protects telomeres by catalyzing m6A modification on TERRA, indicating that inhibition or deletion of METTL3 is potentially a new avenue for ALT cancer therapy.},
}
@article {pmid36399449,
year = {2022},
author = {Salih, A and Galazzo, IB and Petersen, SE and Lekadir, K and Radeva, P and Menegaz, G and Altmann, A},
title = {Telomere length is causally connected to brain MRI image derived phenotypes: A mendelian randomization study.},
journal = {PloS one},
volume = {17},
number = {11},
pages = {e0277344},
pmid = {36399449},
issn = {1932-6203},
support = {MR/L016311/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {*Mendelian Randomization Analysis ; *Brain/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Phenotype ; Telomere ; },
abstract = {Recent evidence suggests that shorter telomere length (TL) is associated with neuro degenerative diseases and aging related outcomes. The causal association between TL and brain characteristics represented by image derived phenotypes (IDPs) from different magnetic resonance imaging (MRI) modalities remains unclear. Here, we use two-sample Mendelian randomization (MR) to systematically assess the causal relationships between TL and 3,935 brain IDPs. Overall, the MR results suggested that TL was causally associated with 193 IDPs with majority representing diffusion metrics in white matter tracts. 68 IDPs were negatively associated with TL indicating that longer TL causes decreasing in these IDPs, while the other 125 were associated positively (longer TL leads to increased IDPs measures). Among them, ten IDPs have been previously reported as informative biomarkers to estimate brain age. However, the effect direction between TL and IDPs did not reflect the observed direction between aging and IDPs: longer TL was associated with decreases in fractional anisotropy and increases in axial, radial and mean diffusivity. For instance, TL was positively associated with radial diffusivity in the left perihippocampal cingulum tract and with mean diffusivity in right perihippocampal cingulum tract. Our results revealed a causal role of TL on white matter integrity which makes it a valuable factor to be considered when brain age is estimated and investigated.},
}
@article {pmid36396857,
year = {2023},
author = {Hong, Z and Lin, X and Zhou, Y and Zheng, G and Liao, X and Wei, Q and Zhang, Z and Liang, J},
title = {Lean body mass but not body fat mass is related with leukocyte telomere length in children.},
journal = {International journal of obesity (2005)},
volume = {47},
number = {1},
pages = {67-74},
pmid = {36396857},
issn = {1476-5497},
mesh = {Male ; Female ; Humans ; Child ; Cross-Sectional Studies ; *Body Composition/physiology ; *Bone Density/physiology ; Absorptiometry, Photon ; Telomere ; },
abstract = {OBJECTIVES: The aim of this study was to investigate the relationship between body composition and leukocyte telomere length (LTL) in healthy Chinese children aged 6-11 years.<br><br>METHODS: This cross-sectional study enrolled 406 healthy children (175 girls and 231 boys). The relative telomere length in their peripheral blood leukocytes was determined via quantitative polymerase chain reaction. Dual-energy X-ray absorptiometry was used to determine body fat content and regional fat distribution, appendicular skeletal muscle mass (ASM), bone mineral density (BMD) and bone mineral content (BMC) at the total body (TB) and total body less head (TBLH) levels, and total body lean mass (TBLM) was then determined. ASM/height[2] (ASMI) was also calculated.<br><br>RESULTS: After adjusting for potential covariates, multiple linear regression analyses revealed that neither body fat content nor regional body fat distribution were significantly associated with LTL (&#x3b2;&#x2009;=&#x2009;-8.48&#x2009;&#xd7;&#x2009;10[-6]-1.44&#x2009;&#xd7;&#x2009;10[-1], p&#x2009;=&#x2009;0.227-0.959). However, ASM, ASMI, TB BMC/TB BMD, TBLH BMC/TBLH BMD and TBLM were positively associated with LTL (&#x3b2;&#x2009;=&#x2009;8.95&#x2009;&#xd7;&#x2009;10[-6]-4.95&#x2009;&#xd7;&#x2009;10[-1], p&#x2009;=&#x2009;0.005-0.035). Moreover, analysis of covariance revealed there was a statistically significant dose-dependent positive association between LTL and ASM, TB BMC/BMD, TBLH BMC/BMD, and TBLM (p-trend&#x2009;=&#x2009;0.002-0.025).<br><br>CONCLUSIONS: Skeletal muscle mass and bone mass but not body fat content or distribution were significantly associated with LTL in this pediatric population.},
}
@article {pmid36394537,
year = {2022},
author = {Vicari, MR and Bruschi, DP and Cabral-de-Mello, DC and Nogaroto, V},
title = {Telomere organization and the interstitial telomeric sites involvement in insects and vertebrates chromosome evolution.},
journal = {Genetics and molecular biology},
volume = {45},
number = {3 Suppl 1},
pages = {e20220071},
pmid = {36394537},
issn = {1415-4757},
abstract = {Telomere has a central role in chromosomal stability events. Chromosome ends organized in telomere-loop prevent activation of DNA damage response (DDR) mechanisms, thus keeping the chromosome structure organized. On the other hand, free chromosome ends, dysfunctional telomeres, and interstitial telomeric sequences (ITS) can trigger chromosome rearrangements. Here, the telomere organization, function, and maintenance mechanisms, in addition to ITS types and their involvement in chromosome changes, were revisited. Despite a general (TTAGGG)n sequence being present in vertebrate telomeres, insects show more diversification of their telomere motif. The relation between ITS and chromosome rearrangements was observed in insects and vertebrates, demonstrating different types of genome organization and distribution. Some ITS cannot be considered relicts of chromosome rearrangements because probable they were inserted during a double-strand break repair mechanism. On the other hand, the involvement of telomere sequences participating or triggering chromosome rearrangements or organizing satellite DNA components in several species groups is evident. The genomic assembling advances and applying other methodologies over ITS, and their flanking regions, can help to understand the telomere participation in the chromosomal evolution in species groups with highly diversified karyotypes.},
}
@article {pmid36394204,
year = {2022},
author = {Yuan, X and Yuan, H and Zhang, N and Liu, T and Xu, D},
title = {Thyroid carcinoma-featured telomerase activation and telomere maintenance: Biology and translational/clinical significance.},
journal = {Clinical and translational medicine},
volume = {12},
number = {11},
pages = {e1111},
pmid = {36394204},
issn = {2001-1326},
mesh = {Humans ; *Telomerase/genetics/metabolism ; *Thyroid Neoplasms/diagnosis/genetics ; Telomere/genetics/metabolism ; Telomere Homeostasis/genetics ; Biology ; },
abstract = {BACKGROUND: Telomerase is a ribonucleoprotein complex consisting of a catalytic component telomerase reverse transcriptase (TERT), internal RNA template and other co-factors, and its essential function is to synthesize telomeric DNA, repetitive TTAGGG sequences at the termini of linear chromosomes. Telomerase is silent in normal human follicular thyroid cells, primarily due to the TERT gene being tightly repressed. During the development and progression of thyroid carcinomas (TCs), TERT induction and telomerase activation is in general required to maintain telomere length, thereby conferring TC cells with immortal and aggressive phenotypes.<br><br>METHODS: The genomic alterations of the TERT loci including TERT promoter's gain-of-function mutations, copy number gain, fusion and rearrangements, have recently been identified in TCs as mechanisms to induce TERT expression and to activate telomerase. Importantly, numerous studies have consistently shown that TERT promoter mutations and TERT expression occur in all TC subtypes, and are robustly associated with TC malignancy, aggressiveness, treatment failure and poor outcomes. Therefore, the assessment of TERT promoter mutations and TERT expression is highly valuable in TC diagnostics, prognosis, treatment decision, and follow-up design. In addition, the TERT promoter is frequently hypermethylated in TC cells and tumors, which is required to activate TERT transcription and telomerase. Dysregulation of other components in the telomerase complex similarly upregulate telomerase. Moreover, shortened telomeres lead to altered gene expression and metabolism, thereby actively promoting TC aggressiveness. Here we summarize recent findings in TCs to provide the landscape of TC-featured telomere/telomerase biology and discuss underlying implications in TC precision medicine.<br><br>CONCLUSION: Mechanistic insights into telomerase activation and TERT induction in TCs are important both biologically and clinically. The TERT gene aberration and expression-based molecular classification of TCs is proposed, and for such a purpose, the standardization of the assay and evaluation system is required. Moreover, the TERT-based system and 2022 WHO TC classification may be combined to improve TC care.},
}
@article {pmid36385813,
year = {2022},
author = {Liu, Y and Ye, X and Wang, Z and Zong, S and Cui, Y},
title = {In Situ Super-Resolution Imaging of Telomeres with DNA-PAINT.},
journal = {ACS omega},
volume = {7},
number = {44},
pages = {40512-40519},
pmid = {36385813},
issn = {2470-1343},
abstract = {Telomeres are located at the ends of chromosomes and play an important role in maintaining the integrity of chromosomes and controlling the cycle of cell division. Studies have shown that abnormal telomere length may lead to the occurrence of some diseases. Therefore, accurate measurement of telomere length will be helpful for the prediction and diagnosis of related diseases. DNA point accumulation for imaging in nanoscale topography (PAINT) is an optical super-resolution technology that relies on the instantaneous binding of the fluorescent DNA imaging strand to the target epitope. Here, we present the first demonstration of DNA-PAINT-based in situ super-resolution imaging of telomeres as well as centromeres. For DNA-PAINT imaging, Cy5-labeled telomere DNA (5'-Cy5-TTTTTCCCTAACCCTAA-3') and Cy3-labeled centromere DNA (5'-Cy3-TTTTTAGCTTCTGTCTAGTTT-3') are utilized as the imager strands. Through an improved permeabilization strategy that we proposed, the imager strands can bind with intracellular telomeres and centromeres with high specificity, realizing super-resolution imaging of telomeres and centromeres. To check the applicability of DNA-PAINT in evaluating telomere length, we conducted an experiment using azidothymidine (AZT)-treated tumor cells as the imaging target. The DNA-PAINT imaging results clearly revealed the telomerase inhibition effect of AZT. Compared with single-molecule localization microscopy (SMLM) with peptide nucleic acid (PNA)-based fluorescence in situ hybridization (FISH), our method has the advantages of low cost, low toxicity, and simple equipment. Such a DNA-PAINT-based imaging strategy holds great potential in measuring telomere length with high accuracy, which would play an important role in the study of telomere-related diseases such as cancer.},
}
@article {pmid36374285,
year = {2022},
author = {Kohlrausch, FB and Wang, F and Luo, D and Mahn, R and Keefe, DL},
title = {Telomere fusions as a signal of term placental aging? A pilot study.},
journal = {Reproduction &amp; fertility},
volume = {3},
number = {4},
pages = {L9-L11},
pmid = {36374285},
issn = {2633-8386},
mesh = {Animals ; Humans ; Female ; Pregnancy ; Pilot Projects ; *Placenta ; },
abstract = {The placenta plays an essential role at the beginning of life, nourishing and supporting the fetus, but its life span is limited. In late pregnancy, the placenta develops signs of aging, including inflammation and impaired function, which may complicate pregnancy. Placentas also show another sign of aging - cells with extra or missing chromosomes. Chromosomally abnormal cells could gather in the placenta if they get stranded there and/or if the cells do not separate normally. Chromosome separation goes wrong in aging cells when the DNA sequences, which protect the ends of the chromosomes, erode. When chromosomes lose their protective caps, they fuse which leads to abnormal numbers of chromosomes. In this pilot study, for the first time, we found fusions between the caps in a human placenta when it reaches full term. More studies are needed to decide whether this has an influence on how the placenta works and outcomes of pregnancy.},
}
@article {pmid36372149,
year = {2023},
author = {Liu, C and Chen, YJ and Sun, B and Chen, HG and Mustieles, V and Messerlian, C and Sun, Y and Meng, TQ and Lu, WQ and Pan, XF and Xiong, CL and Hou, J and Wang, YX},
title = {Blood trihalomethane concentrations in relation to sperm mitochondrial DNA copy number and telomere length among 958 healthy men.},
journal = {Environmental research},
volume = {216},
number = {Pt 4},
pages = {114737},
doi = {10.1016/j.envres.2022.114737},
pmid = {36372149},
issn = {1096-0953},
mesh = {Humans ; Male ; *Semen Analysis ; Semen/chemistry ; DNA, Mitochondrial ; DNA Copy Number Variations ; Trihalomethanes/toxicity ; Spermatozoa ; Telomere ; *Water Pollutants, Chemical/analysis ; },
abstract = {BACKGROUND: In animal and human studies, exposure to trihalomethanes (THMs) has been associated with reduced semen quality. However, the underlying mechanisms remain poorly understood.<br><br>OBJECTIVE: To investigate the associations of blood THM concentrations with sperm mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) among healthy men.<br><br>METHODS: We recruited 958 men who volunteered as potential sperm donors. A single blood sample was collected from each participant at recruitment and measured for chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) concentrations. Within a 90-day follow-up, the last semen sample provided by each participant was quantified for sperm mtDNAcn and TL. We used multivariable linear regression models to assess the associations between blood THM concentrations and sperm mtDNAcn and TL. We also performed stratified analyses according to the time intervals between baseline blood THM determinations and semen collection (i.e., 0-9, 10-14, 15-69, or >69 days) to explore potential windows of susceptibility.<br><br>RESULTS: After adjusting for potential confounders, we found inverse associations between quartiles (or categories) of blood TBM, brominated THM (Br-THM, the sum of BDCM, DBCM, and TBM), and total THM (TTHM, the sum of all four THMs) concentrations and sperm mtDNAcn (all P for trend&#x2264;0.03). Besides, we found inverse associations between quartiles of blood TCM, Br-THM, chlorinated THM (Cl-THM, the sum of TCM, BDCM, and DBCM), and TTHM concentrations and sperm TL (all P for trend<0.10). Stratified analyses showed stronger associations between Br-THM concentrations and sperm mtDNAcn determined 15-69 days since baseline exposure determinations, and between blood TCM and TTHM concentrations and sperm TL determined >69 days since baseline exposure determinations.<br><br>CONCLUSION: Exposure to THMs may be associated with sperm mitochondrial and telomeric dysfunction.},
}
@article {pmid36371747,
year = {2023},
author = {Yu, HJ and Ho, M and Chau, PH and Geng, L and Fong, DYT},
title = {Salivary telomere length and the risks of prediabetes and diabetes among middle-aged and older adults: findings from the Health and Retirement Study.},
journal = {Acta diabetologica},
volume = {60},
number = {2},
pages = {273-283},
pmid = {36371747},
issn = {1432-5233},
mesh = {Male ; Middle Aged ; Humans ; Aged ; Retirement ; Overweight ; *Prediabetic State/epidemiology/genetics ; Obesity/complications/epidemiology ; *Diabetes Mellitus/epidemiology/genetics ; Telomere Shortening ; Telomere/genetics ; *Cardiovascular Diseases ; },
abstract = {AIM: To assess the association of telomere length (TL) with prediabetes/diabetes and to explore the potential factors affecting TL among individuals with prediabetes/diabetes by weight status.<br><br>METHODS: This study included 3,379 eligible adults (aged 45-85&#xa0;years, males: 42%) from the US Health and Retirement Study in 2008. TL was assayed using quantitative PCR of saliva (T/S ratio). Linear and nonlinear associations between TL and prediabetes/diabetes were assessed using the logistic regression and restricted cubic spline model, respectively, adjusting for TL-plate numbers, age, sex, race, body mass index, lifestyles, diabetes medications, and cardiometabolic parameters (blood pressure, C-reactive protein, and total cholesterol). Multiple linear regression was used for testing any factors associated with TL.<br><br>RESULTS: Among 3,379 participants, 868 (25.7%) had prediabetes with a mean TL of 1.34&#x2009;&#xb1;&#x2009;0.37 (T/S ratio) and 858 (25.4%) had diabetes with a mean TL of 1.36&#x2009;&#xb1;&#x2009;0.43 (T/S ratio). Neither linear nor nonlinear association of TL with prediabetes/diabetes was significant by weight status. Age was negatively associated with TL in both normal-weight (&#x3b2;&#x2009;=&#x2009;-&#x2009;0.002, p&#x2009;=&#x2009;0.025) and overweight/obese (&#x3b2;&#x2009;=&#x2009;-&#x2009;0.002, p&#x2009;=&#x2009;0.006) prediabetes, but non-significant in normal-weight and overweight/obese diabetes. BMI and cardiometabolic parameters were not associated with TL in prediabetes/diabetes by weight status.<br><br>CONCLUSIONS: Salivary TL was not associated with prediabetes/diabetes among the US middle-aged and older adults. Further longitudinal studies are required to establish the link between TL and diabetes development and to identify potential factors affecting TL shortening, particularly in normal-weight diabetic patients.},
}
@article {pmid36370823,
year = {2023},
author = {Yasir, S and Thompson, S and Chen, ZE and Knudson, R and Knutson, D and Kloft-Nelson, S and Graham, RP and Jain, D and Simon, SM and Wu, TT and Torbenson, M},
title = {Alternative lengthening of telomeres in primary hepatic neoplasms.},
journal = {Human pathology},
volume = {131},
number = {},
pages = {79-86},
pmid = {36370823},
issn = {1532-8392},
support = {P50 CA210964/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Carcinoma, Hepatocellular/genetics/pathology ; *Hemangiosarcoma/genetics/pathology ; In Situ Hybridization, Fluorescence ; *Liver Neoplasms/genetics/pathology ; *Cholangiocarcinoma/genetics/pathology ; *Carcinosarcoma/pathology ; Bile Ducts, Intrahepatic/pathology ; *Bile Duct Neoplasms/genetics/pathology ; Telomere/genetics/pathology ; },
abstract = {The alternative lengthening of telomeres (ALT) phenotype is characterized by ultra-bright telomeres on fluorescence in situ hybridization (FISH) and is a marker of a unique mechanism of telomere maintenance in tumors. ALT does not occur in normal tissues. ALT has been described in hepatocellular carcinoma (5-10%) and in primary hepatic angiosarcomas (75%). To study the frequency of ALT in other primary hepatic tumors, a wide range of primary hepatic neoplasms were retrieved. The tumors included the following: intrahepatic and hilar cholangiocarcinomas (N = 110), hepatic adenomas (N = 35), hepatocellular carcinomas (N = 30), fibrolamellar carcinomas (n = 11), combined cholangiocarcinoma-hepatocellular carcinomas (N = 8), carcinosarcoma (N = 10), hepatoblastomas (N = 5), hemangiomas (N = 4), angiosarcomas (N = 8), epithelioid hemangioendotheliomas (N = 10), calcified nested stromal epithelial tumor (N = 2), embryonal sarcoma (N = 2), rhabdoid tumor (N = 1), bile duct adenoma (N = 1), and angiomyolipoma (N = 1). For epithelial tumors, ALT-FISH was positive in one carcinosarcoma (10% of cases), one cholangiocarcinoma (1% of cases), and one combined hepatocellular carcinoma-cholangiocarcinoma (13% of cases). In the hepatocellular carcinoma component of both the carcinosarcoma and the combined hepatocellular carcinoma-cholangiocarcinoma, the tumor cells showed patchy marked nuclear pleomorphism akin to that described previously for chromophobe hepatocellular carcinoma, which are typically ALT FISH positive. The ALT-positive cholangiocarcinoma also showed patchy, striking nuclear pleomorphism. For soft tissue tumors, ALT was positive in two angiosarcomas (N = 2; 25% of cases). In summary, this study shows that ALT-FISH is positive in rare carcinosarcomas, cholangiocarcinomas, and combined cholangiocarcinoma-hepatocellular carcinoma. ALT is not a significant mechanism of telomere maintenance in hepatocellular adenomas or fibrolamellar carcinomas and was negative in all other tested primary hepatic neoplasms. ALT-FISH is also positive in a subset of primary hepatic angiosarcomas.},
}
@article {pmid36364907,
year = {2022},
author = {Nonsa-Ard, R and Aneknan, P and Tong-Un, T and Honsawek, S and Leelayuwat, N},
title = {Effects of Irvingia gabonensis Extract on Metabolism, Antioxidants, Adipocytokines, Telomere Length, and Aerobic Capacity in Overweight/Obese Individuals.},
journal = {Nutrients},
volume = {14},
number = {21},
pages = {},
pmid = {36364907},
issn = {2072-6643},
support = {N/A//Blackmores Limited and Exercise and Sport Sciences Development and Research Group, Khon Kaen University, Khon Kaen, Thailand./ ; },
mesh = {Humans ; Adipokines ; Adiponectin ; *Antioxidants/therapeutic use ; Ascorbic Acid/therapeutic use ; Dietary Supplements ; Double-Blind Method ; Inflammation/drug therapy ; Obesity/drug therapy ; *Overweight ; Plant Extracts/pharmacology/therapeutic use ; Polyesters/therapeutic use ; Telomere ; },
abstract = {We investigated the effects of Irvingia gabonensis (IG) kernel extract on the metabolism, adiposity indices, redox status, inflammation, adipocytokines, blood leukocyte relative telomere length (RTL), and aerobic capacity of overweight/obese individuals. All participants used the first 12-week phase to monitor body weight. They were then randomly divided into two groups: (1) 300 mg IG or (2) placebo (PLA). Both groups took one tablet per day for 12 weeks. The variables were measured before supplementation and after 3, 6, and 12 weeks of supplementation. RTL and aerobic capacity were measured before and after 12 weeks. Compared with the PLA, the IG increased plasma vitamin C after supplementation at 6 (p < 0.01) and 12 weeks (p < 0.05) and serum adiponectin after 3 weeks (p < 0.05). Compared with before supplementation, plasma malondialdehyde in the IG and serum leptin in the PLA were decreased after 12-week supplementation, without any differences between the groups. There were no differences between groups with respect to metabolism, inflammation, RTL, and aerobic capacity after the supplementation. We suggest that 12-week daily IG supplementation improved plasma vitamin C and adiponectin. The findings show the possible mechanism contributing to the effect of IG supplementation on a reduction in obesity-related complications.},
}
@article {pmid36362235,
year = {2022},
author = {Scarabino, D and Veneziano, L and Mantuano, E and Arisi, I and Fiore, A and Frontali, M and Corbo, RM},
title = {Leukocyte Telomere Length as Potential Biomarker of HD Progression: A Follow-Up Study.},
journal = {International journal of molecular sciences},
volume = {23},
number = {21},
pages = {},
pmid = {36362235},
issn = {1422-0067},
support = {2018; 2019//Sapienza University of Rome/ ; grant 0942//EHDN seed fund/ ; 2020//AICH/ ; 2019-2021//Fondo Ordinario Enti (FOE D.M 865/2019) in the framework of a collaboration agreement between CNR and EBRI/ ; },
mesh = {Humans ; *Huntington Disease/diagnosis/genetics ; Follow-Up Studies ; Telomere/genetics ; Leukocytes, Mononuclear ; Leukocytes ; Biomarkers ; },
abstract = {The identification of biomarkers for neurodegenerative disorders such as Huntington's disease (HD) is crucial for monitoring disease progression and therapeutic trial outcomes, especially in the pre-manifest disease stage (pre-HD). In a previous study, we observed that leukocyte telomere length (LTL) was strongly correlated with the estimated time to clinical onset in pre-HD subjects. To validate this hypothesis, we designed a follow-up study in which we analyzed LTL in 45 pre-HD stage subjects at baseline (T0) and then again after clinical onset at follow-up (T1); the follow-up interval was about 3 years, and the CAG range was 39-51 repeats; 90 peripheral blood mononuclear cell samples (PBMCs) were obtained from the Enroll-HD biorepository. In pre-HD subjects at T0, LTL was significantly reduced by 22% compared to the controls and by 14% from T0 at T1. No relationship was observed between the LTL and CAG numbers in subjects carrying different CAG repeats at T0 and at T1, suggesting that LTL reduction occurs independently of CAG number in pre-HD subjects. ROC curve analysis was used to test the validity of LTL as a potential biomarker of HD progression and showed that LTL measurement is extremely accurate in discriminating pre-HD subjects from the controls and even pre-HD from manifest HD, thus yielding a robust prognostic value in pre-HD subjects.},
}
@article {pmid36362129,
year = {2022},
author = {Nonsa-Ard, R and Aneknan, P and Tong-Un, T and Honsawek, S and Leelayuwat, C and Leelayuwat, N},
title = {Telomere Length Is Correlated with Resting Metabolic Rate and Aerobic Capacity in Women: A Cross-Sectional Study.},
journal = {International journal of molecular sciences},
volume = {23},
number = {21},
pages = {},
pmid = {36362129},
issn = {1422-0067},
support = {PHD/0005/2559//The Royal Golden Jubilee (RGJ) Ph.D. Program/ ; },
mesh = {Humans ; Female ; *Basal Metabolism ; Cross-Sectional Studies ; *Obesity ; Energy Intake ; Telomere ; Body Composition ; },
abstract = {This study investigated the associations between relative telomere length (RTL) and resting metabolic rate (RMR), resting fat oxidation (RFO), and aerobic capacity and whether oxidative stress and inflammation are the underlying mechanisms in sedentary women. We also aimed to determine whether the correlations depend on age and obesity. Sixty-eight normal weight and 66 obese women participated in this study. After adjustment for age, energy expenditure, energy intake, and education level, the RTL of all participants was negatively correlated with absolute RMR (RMRAB) and serum high-sensitivity C-reactive protein (hsCRP) concentration, and positively correlated with maximum oxygen consumption (V˙O2max) (all p < 0.05). After additional adjustment for adiposity indices and fat-free mass (FFM), RTL was positively correlated with plasma vitamin C concentration (p < 0.05). Furthermore, after adjustment for fasting blood glucose concentration, RTL was negatively correlated with age and positively correlated with V˙O2max (mL/kg FFM/min). We found that normal weight women had longer RTL than obese women (p < 0.001). We suggest that RTL is negatively correlated with RMRAB and positively correlated with aerobic capacity, possibly via antioxidant and anti-inflammatory mechanisms. Furthermore, age and obesity influenced the associations. We provide useful information for the management of promotion strategies for health-related physical fitness in women.},
}
@article {pmid36359878,
year = {2022},
author = {Reddy, HM and Randall, TA and Cipressa, F and Porrazzo, A and Cenci, G and Frydrychova, RC and Mason, JM},
title = {Identification of the Telomere elongation Mutation in Drosophila.},
journal = {Cells},
volume = {11},
number = {21},
pages = {},
pmid = {36359878},
issn = {2073-4409},
mesh = {Animals ; *Drosophila/genetics ; *Drosophila melanogaster/genetics ; Gene Products, gag/genetics ; Telomere/genetics ; Mutation/genetics ; },
abstract = {Telomeres in Drosophila melanogaster, which have inspired a large part of Sergio Pimpinelli work, are similar to those of other eukaryotes in terms of their function. Yet, their length maintenance relies on the transposition of the specialized retrotransposons Het-A, TART, and TAHRE, rather than on the activity of the enzyme telomerase as it occurs in most other eukaryotic organisms. The length of the telomeres in Drosophila thus depends on the number of copies of these transposable elements. Our previous work has led to the isolation of a dominant mutation, Tel[1], that caused a several-fold elongation of telomeres. In this study, we molecularly identified the Tel[1] mutation by a combination of transposon-induced, site-specific recombination and next-generation sequencing. Recombination located Tel[1] to a 15 kb region in 92A. Comparison of the DNA sequence in this region with the Drosophila Genetic Reference Panel of wild-type genomic sequences delimited Tel[1] to a 3 bp deletion inside intron 8 of Ino80. Furthermore, CRISPR/Cas9-induced deletions surrounding the same region exhibited the Tel[1] telomere phenotype, confirming a strict requirement of this intron 8 gene sequence for a proper regulation of Drosophila telomere length.},
}
@article {pmid36359738,
year = {2022},
author = {Sung, JY and Cheong, JH},
title = {Single Cell Analysis of Gastric Cancer Reveals Non-Defined Telomere Maintenance Mechanism.},
journal = {Cells},
volume = {11},
number = {21},
pages = {},
pmid = {36359738},
issn = {2073-4409},
mesh = {Humans ; *Stomach Neoplasms/genetics ; Single-Cell Analysis ; Ubiquitin-Protein Ligases/metabolism ; Telomere/metabolism ; Tumor Necrosis Factor-alpha ; Homeostasis ; },
abstract = {Telomere maintenance mechanisms (TMMs) are important for cell survival and homeostasis. However, most related cancer research studies have used heterogenous bulk tumor tissue, which consists of various single cells, and the cell type properties cannot be precisely recognized. In particular, cells exhibiting non-defined TMM (NDTMM) indicate a poorer prognosis than those exhibiting alternative lengthening of telomere (ALT)-like mechanisms. In this study, we used bioinformatics to classify TMMs by cell type in gastric cancer (GC) in single cells and compared the biological processes of each TMM. We elucidated the pharmacological vulnerabilities of NDTMM type cells, which are associated with poor prognosis, based on molecular mechanisms. We analyzed differentially expressed genes in cells exhibiting different TMMs in two single-cell GC cohorts and the pathways enriched in single cells. NDTMM type cells showed high stemness, epithelial-mesenchymal transition, cancer hallmark activity, and metabolic reprogramming with mitochondrial abnormalities. Nuclear receptor subfamily 4 group A member 1 (NR4A1) activated parkin-dependent mitophagy in association with tumor necrosis factor-alpha (TNFA) to maintain cellular homeostasis without TMM. NR4A1 overexpression affected TNFA-induced GC cell apoptosis by inhibiting Jun N-terminal kinase/parkin-dependent mitophagy. Our findings also revealed that NR4A1 is involved in cell cycle mediation, inflammation, and apoptosis to maintain cell homeostasis, and is a novel potential therapeutic target in recalcitrant GC.},
}
@article {pmid36359275,
year = {2022},
author = {Macek, P and Poreba, R and Gac, P and Bogunia-Kubik, K and Dratwa, M and Wieckiewicz, M and Wojakowska, A and Michalek-Zrabkowska, M and Mazur, G and Martynowicz, H},
title = {Genetic Variants of the TERT Gene and Telomere Length in Obstructive Sleep Apnea.},
journal = {Biomedicines},
volume = {10},
number = {11},
pages = {},
pmid = {36359275},
issn = {2227-9059},
support = {STM.A210.20.006//Wroc&#x142;aw Medical University/ ; },
abstract = {Introduction: Obstructive sleep apnea (OSA) is a worldwide breathing disorder that has been diagnosed globally in almost 1 billion individuals aged 30−69 years. It is characterized by repeated upper airway collapses during sleep. Telomerase reverse transcriptase (TERT) is involved in the prevention of telomere shortening. This prospective, observational study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) of TERT and the severity of OSA, taking into account hypertension and diabetes prevalence. Methods: A total of 149 patients with OSA were diagnosed using one-night video-polysomnography based on the American Academy of Sleep Medicine guidelines. The TERT SNPs and telomere length (TL) were detected using real-time quantitative polymerase chain reaction. Results: Statistical analysis showed that there is no relationship between the rs2853669 and rs2736100 polymorphisms of TERT, and the severity of OSA (p > 0.05). Moreover, no relationship between TL and the severity of OSA was observed. The G allele in the locus of rs2736100 TERT was associated with hypertension prevalence and was more prevalent in hypertensives patients (46.00% vs. 24.49%, p = 0.011). The prevalence of hypertension was higher in patients with the C allele in the locus of rs2853669 than in patients without this allele (50.79% vs. 30.23%, p = 0.010). Moreover, a lower prevalence of diabetes was observed in homozygotes of rs2736100 TERT than in heterozygotes (5.63% vs. 15.38%, p = 0.039). Conclusion: This study showed no relationship between OSA and TERT SNPs. However, SNPs of the TERT gene (rs2736100 and rs2853669) were found to affect arterial hypertension and diabetes prevalence.},
}
@article {pmid36357941,
year = {2022},
author = {Shin, DY and Lim, KM and Park, HS and Kwon, S and Yoon, SS and Lee, DS},
title = {The importance of critically short telomere in myelodysplastic syndrome.},
journal = {Biomarker research},
volume = {10},
number = {1},
pages = {79},
pmid = {36357941},
issn = {2050-7771},
support = {NRF-2020R1A3B3079653//National Research Foundation of Korea/ ; },
abstract = {A few critically short telomeres trigger genomic instability regardless of average telomere length (TL). Recently, the telomere shortest length assay (TeSLA) was developed to detect critically short telomeres and measure absolute telomeres. Using TeSLA with the internally labeled biotin probe, we measured the TL of bone marrow (BM) aspirates from 52 patients with myelodysplastic syndrome (MDS). A percentage of shortest telomeres (< 1.0 kb (ShTL1.0)) were calculated. ShTL1.0 was correlated to IPSS-R risk (spearman's rho = 0.35 and p = 0.0196), and ShTL1.0 and BM blast (2.61% in < 5% blast, 4.15% in 5-10% blast, and 6.80% in 10-20% blast, respectively, p = 0.0332). Interestingly, MDS patients with a shortest TL ≥ 0.787 kb at the time of diagnosis showed better overall survival (OS) and progression-free survival (PFS) than patients with a shortest TL < 0.787 kb in the multivariate analyses (HR = 0.13 and 0.30, p = 0.011 and 0.048 for OS and PFS, respectively). Our results clearly show the presence and abundance of critically short telomeres in MDS patients. These pathologic telomeres are associated with IPSS-R which is a validated prognostic scoring system in MDS. Furthermore, they are independent prognostic factors for OS in MDS patients. Future prospective studies are needed to validate our results.},
}
@article {pmid36356143,
year = {2022},
author = {Chun-On, P and Hinchie, AM and Beale, HC and Gil Silva, AA and Rush, E and Sander, C and Connelly, CJ and Seynnaeve, BKN and Kirkwood, JM and Vaske, OM and Greider, CW and Alder, JK},
title = {TPP1 promoter mutations cooperate with TERT promoter mutations to lengthen telomeres in melanoma.},
journal = {Science (New York, N.Y.)},
volume = {378},
number = {6620},
pages = {664-668},
pmid = {36356143},
issn = {1095-9203},
support = {R01 HL135062/HL/NHLBI NIH HHS/United States ; R35 CA209974/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; *Melanoma/genetics ; Mutation ; *Promoter Regions, Genetic/genetics ; *Shelterin Complex/genetics ; *Skin Neoplasms/genetics ; *Telomerase/genetics ; Telomere/genetics/metabolism ; *Telomere Homeostasis/genetics ; *Telomere-Binding Proteins/genetics ; Transcriptional Activation ; },
abstract = {Overcoming replicative senescence is an essential step during oncogenesis, and the reactivation of TERT through promoter mutations is a common mechanism. TERT promoter mutations are acquired in about 75% of melanomas but are not sufficient to maintain telomeres, suggesting that additional mutations are required. We identified a cluster of variants in the promoter of ACD encoding the shelterin component TPP1. ACD promoter variants are present in about 5% of cutaneous melanoma and co-occur with TERT promoter mutations. The two most common somatic variants create or modify binding sites for E-twenty-six (ETS) transcription factors, similar to mutations in the TERT promoter. The variants increase the expression of TPP1 and function together with TERT to synergistically lengthen telomeres. Our findings suggest that TPP1 promoter variants collaborate with TERT activation to enhance telomere maintenance and immortalization in melanoma.},
}
@article {pmid36352846,
year = {2022},
author = {Deng, Y and Li, Q and Zhou, F and Li, G and Liu, J and Lv, J and Li, L and Chang, D},
title = {Telomere length and the risk of cardiovascular diseases: A Mendelian randomization study.},
journal = {Frontiers in cardiovascular medicine},
volume = {9},
number = {},
pages = {1012615},
pmid = {36352846},
issn = {2297-055X},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; },
abstract = {BACKGROUND: The causal direction and magnitude of the associations between telomere length (TL) and cardiovascular diseases (CVDs) remain uncertain due to susceptibility of reverse causation and confounding. This study aimed to investigate the associations between TL and CVDs using Mendelian randomization (MR).<br><br>MATERIALS AND METHODS: In this two-sample MR study, we identified 154 independent TL-associated genetic variants from a genome-wide association study (GWAS) consisting of 472,174 individuals (aged 40-69) in the UK Biobank. Summary level data of CVDs were obtained from different GWASs datasets. Methods of inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), Mendelian Randomization robust adjusted profile score (MR-RAPS), maximum likelihood estimation, weighted mode, penalized weighted mode methods, and Mendelian randomization pleiotropy residual sum and outlier test (MR-PRESSO) were conducted to investigate the associations between TL and CVDs.<br><br>RESULTS: Our findings indicated that longer TL was significantly associated with decreased risk of coronary atherosclerosis [odds ratio (OR), 0.85; 95% confidence interval (CI), 0.75-0.95; P = 4.36E-03], myocardial infarction (OR, 0.72; 95% CI, 0.63-0.83; P = 2.31E-06), ischemic heart disease (OR, 0.87; 95% CI, 0.78-0.97; P = 1.01E-02), stroke (OR, 0.87; 95% CI, 0.79-0.95; P = 1.60E-03), but an increased risk of hypertension (OR, 1.12; 95% CI, 1.02-1.23; P = 2.00E-02). However, there was no significant association between TL and heart failure (OR, 0.94; 95% CI, 0.87-1.01; P = 1.10E-01), atrial fibrillation (OR, 1.01; 95% CI, 0.93-1.11; P = 7.50E-01), or cardiac death (OR, 0.95; 95% CI, 0.82-1.10; P = 4.80E-01). Both raw and outlier corrected estimates from MR-PRESSO were consistent with those of IVW results. The sensitivity analyses showed no evidence of pleiotropy (MR-Egger intercept, P > 0.05), while Cochran's Q test and MR-Egger suggested different degrees of heterogeneity.<br><br>CONCLUSION: Our MR study suggested that longer telomeres were associated with decreased risk of several CVDs, including coronary atherosclerosis, myocardial infarction, ischemic heart disease, and stroke, as well as an increased risk of hypertension. Future studies are still warranted to validate the results and investigate the mechanisms underlying these associations.},
}
@article {pmid36350851,
year = {2022},
author = {Geiller, HEB and Harvey, A and Jones, RE and Grimstead, JW and Cleal, K and Hendrickson, EA and Baird, DM},
title = {ATRX modulates the escape from a telomere crisis.},
journal = {PLoS genetics},
volume = {18},
number = {11},
pages = {e1010485},
pmid = {36350851},
issn = {1553-7404},
support = {29202/CRUK_/Cancer Research UK/United Kingdom ; R01 CA266524/CA/NCI NIH HHS/United States ; A18246/A29202/CRUK_/Cancer Research UK/United Kingdom ; },
mesh = {Humans ; *Telomerase/genetics/metabolism ; Telomere Homeostasis/genetics ; X-linked Nuclear Protein/genetics ; *alpha-Thalassemia/genetics ; Telomere/genetics/metabolism ; *Neoplasms ; },
abstract = {Telomerase activity is the principal telomere maintenance mechanism in human cancers, however 15% of cancers utilise a recombination-based mechanism referred to as alternative lengthening of telomeres (ALT) that leads to long and heterogenous telomere length distributions. Loss-of-function mutations in the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) gene are frequently found in ALT cancers. Here, we demonstrate that the loss of ATRX, coupled with telomere dysfunction during crisis, is sufficient to initiate activation of the ALT pathway and that it confers replicative immortality in human fibroblasts. Additionally, loss of ATRX combined with a telomere-driven crisis in HCT116 epithelial cancer cells led to the initiation of an ALT-like pathway. In these cells, a rapid and precise telomeric elongation and the induction of C-circles was observed; however, this process was transient and the telomeres ultimately continued to erode such that the cells either died or the escape from crisis was associated with telomerase activation. In both of these instances, telomere sequencing revealed that all alleles, irrespective of whether they were elongated, were enriched in variant repeat types, that appeared to be cell-line specific. Thus, our data show that the loss of ATRX combined with telomere dysfunction during crisis induces the ALT pathway in fibroblasts and enables a transient activation of ALT in epithelial cells.},
}
@article {pmid36350415,
year = {2022},
author = {Bloom, SI and Tucker, JR and Lim, J and Thomas, TG and Stoddard, GJ and Lesniewski, LA and Donato, AJ},
title = {Aging results in DNA damage and telomere dysfunction that is greater in endothelial versus vascular smooth muscle cells and is exacerbated in atheroprone regions.},
journal = {GeroScience},
volume = {44},
number = {6},
pages = {2741-2755},
pmid = {36350415},
issn = {2509-2723},
support = {R01 AG060395/AG/NIA NIH HHS/United States ; F31 AG076312/AG/NIA NIH HHS/United States ; UL1 TR002538/TR/NCATS NIH HHS/United States ; UL1 TR001067/TR/NCATS NIH HHS/United States ; R01 AG050238/AG/NIA NIH HHS/United States ; R01 AG048366/AG/NIA NIH HHS/United States ; T32 HL007576/HL/NHLBI NIH HHS/United States ; UL1 RR025764/RR/NCRR NIH HHS/United States ; UL1 TR000105/TR/NCATS NIH HHS/United States ; R44 AG053131/AG/NIA NIH HHS/United States ; },
mesh = {*Muscle, Smooth, Vascular ; *Endothelial Cells ; Telomere/genetics ; DNA Damage ; },
abstract = {Aging increases the risk of atherosclerotic cardiovascular disease which is associated with arterial senescence; however, the mechanisms responsible for the development of cellular senescence in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) remain elusive. Here, we study the effect of aging on arterial DNA damage and telomere dysfunction. Aging resulted in greater DNA damage in ECs than VSMCs. Further, telomere dysfunction-associated DNA damage foci (TAF: DNA damage signaling at telomeres) were elevated with aging in ECs but not VMSCs. Telomere length was modestly reduced in ECs with aging and not sufficient to induce telomere dysfunction. DNA damage and telomere dysfunction were greatest in atheroprone regions (aortic minor arch) versus non-atheroprone regions (thoracic aorta). Collectively, these data demonstrate that aging results in DNA damage and telomere dysfunction that is greater in ECs than VSMCs and elevated in atheroprone aortic regions.},
}
@article {pmid36347948,
year = {2023},
author = {Bussa, RM and Mora-Plazas, M and Marín, C and Villamor, E},
title = {Vitamin D status and leukocyte telomere length in middle childhood.},
journal = {European journal of clinical nutrition},
volume = {77},
number = {2},
pages = {295-297},
pmid = {36347948},
issn = {1476-5640},
mesh = {Male ; Female ; Humans ; Child ; Child, Preschool ; Cross-Sectional Studies ; *Vitamin D ; *Vitamins ; Leukocytes ; Telomere ; },
abstract = {Short telomere length is associated with chronic diseases and decreased lifespan. Vitamin D and its binding protein (DBP) may maintain telomeres through anti-inflammatory actions, yet the role of vitamin D on telomere length is uncertain, especially in children. We assessed the cross-sectional associations of plasma 25-hydroxy vitamin D (25(OH)D) and DBP with leukocyte telomere length (LTL) in a group of 447 children ages 5-12 years from the Bogotá School Children Cohort. We compared the distribution of age-standardized LTL (z-score) between 25(OH)D categories and between DBP quartiles overall and by sex. Overall, 25(OH)D was not significantly associated with LTL. Nonetheless, among boys, 25(OH)D < 50 nmol/L was related to an adjusted 0.36 shorter LTL z-score (95% CI: -0.71, -0.01; P = 0.046) compared with 25(OH)D ≥ 75 nmol/L. There was no association among girls. DBP was not significantly related to LTL. Intervention studies are warranted to determine whether increasing vitamin D status enhances telomere length.},
}
@article {pmid36347559,
year = {2022},
author = {Glousker, G and Lingner, J},
title = {TFIIH moonlighting at telomeres.},
journal = {Genes &amp; development},
volume = {36},
number = {17-18},
pages = {951-953},
pmid = {36347559},
issn = {1549-5477},
mesh = {*Telomeric Repeat Binding Protein 1 ; Telomere/genetics/metabolism ; Telomere Shortening ; Telomere-Binding Proteins/metabolism ; *Telomerase/metabolism ; Shelterin Complex ; },
abstract = {Although telomeres are essential for chromosome stability, they represent fragile structures in our genome. Telomere shortening occurs during aging in cells lacking telomerase due to the end replication problem. In addition, recent work uncovered that the bulk of telomeric DNA poses severe hurdles for the semiconservative DNA replication machinery, requiring the assistance of an increasing number of specialized factors that prevent accidental telomere loss or damage events. In this issue of Genes &amp; Development, Yang and colleagues (pp. 956-969) discover that TFIIH, a basic component of the PolII transcription initiation and nucleotide excision repair machinery, facilitates telomere replication. TFIIH is recruited to telomeres by the shelterin component TRF1, taking on at telomeres a moonlighting function.},
}
@article {pmid36347449,
year = {2023},
author = {Wu, S and Wu, Y and Chen, J and Zhuang, P and Zhang, Y and Jiao, J},
title = {Lifelong docosahexaenoic acid intervention ameliorates aging in the telomere-DNA-mitochondria axis in telomerase-deficient mice.},
journal = {The Journal of nutritional biochemistry},
volume = {112},
number = {},
pages = {109202},
doi = {10.1016/j.jnutbio.2022.109202},
pmid = {36347449},
issn = {1873-4847},
mesh = {Female ; Animals ; Male ; Mice ; *Telomerase/genetics/metabolism ; Docosahexaenoic Acids/pharmacology/therapeutic use ; Cellular Senescence ; Aging/genetics ; *Fatty Acids, Omega-3 ; Inflammation ; DNA, Mitochondrial ; Mitochondria/metabolism ; Telomere/metabolism ; },
abstract = {The health benefits of n-3 polyunsaturated fatty acids (PUFAs) in multiple age-related diseases are associated with telomere length. Telomerase is intimately related to inflammation and oxidative stress, but whether the underlying function of n-3 PUFAs on telomere maintenance is based on telomerase activation or related mechanisms remains unclear. Herein, we utilized late-generation (G4) telomerase-deficient (Terc[-/-]) mice to perform a lifelong docosahexaenoic acid (DHA) intervention to determine the potential of DHA in telomere maintenance and health promotion. Unfortunately, DHA failed to prolong mouse longevity in either intrinsic or premature aging. However, intriguingly, lifelong dietary DHA intervention slowed the aging phenotypes and profoundly attenuated telomere attrition in blood leukocytes and multiple tissues, consistent with decreased β-galactosidase activity and other senescence hallmarks with no observed sex differences. Notably, DHA intervention alleviated telomere attrition-induced γ-H2AX accumulation dependent on poly (ADP-ribose) polymerase 1 (PARP1) recruitment, and further regulated mitochondrial dysfunction critically involved in the DNA damage response. Together with the improvement of mitochondria function, the blocked reactive oxygen species (ROS) accumulation and suppression of the nuclear factor-κB (NF-κB)/nucleotide-binding domain-like receptor protein 3 (NLRP3)/caspase-1 pathways partially indicated anti-oxidative and anti-inflammatory effects of DHA. These data revealed a regulatory paradigm involving DHA in the telomere-DNA-mitochondria feedback loop mediated by DNA damage response and inflammation in alleviating senescence, which may hold potential as a translatable intervention in telomere-related diseases during aging.},
}
@article {pmid36345036,
year = {2022},
author = {Rodríguez-Fernández, B and Vilor-Tejedor, N and Arenaza-Urquijo, EM and Sánchez-Benavides, G and Suárez-Calvet, M and Operto, G and Minguillón, C and Fauria, K and Kollmorgen, G and Suridjan, I and de Moura, MC and Piñeyro, D and Esteller, M and Blennow, K and Zetterberg, H and De Vivo, I and Molinuevo, JL and Navarro, A and Gispert, JD and Sala-Vila, A and Crous-Bou, M and , },
title = {Genetically predicted telomere length and Alzheimer's disease endophenotypes: a Mendelian randomization study.},
journal = {Alzheimer's research &amp; therapy},
volume = {14},
number = {1},
pages = {167},
pmid = {36345036},
issn = {1758-9193},
mesh = {Humans ; *Alzheimer Disease/cerebrospinal fluid ; Mendelian Randomization Analysis ; Endophenotypes ; Biomarkers/cerebrospinal fluid ; Apolipoproteins E/genetics ; Telomere ; tau Proteins/cerebrospinal fluid ; Amyloid beta-Peptides/cerebrospinal fluid ; },
abstract = {Telomere length (TL) is associated with biological aging, consequently influencing the risk of age-related diseases such as Alzheimer's disease (AD). We aimed to evaluate the potential causal role of TL in AD endophenotypes (i.e., cognitive performance, N = 2233; brain age and AD-related signatures, N = 1134; and cerebrospinal fluid biomarkers (CSF) of AD and neurodegeneration, N = 304) through a Mendelian randomization (MR) analysis. Our analysis was conducted in the context of the ALFA (ALzheimer and FAmilies) study, a population of cognitively healthy individuals at risk of AD. A total of 20 single nucleotide polymorphisms associated with TL were used to determine the effect of TL on AD endophenotypes. Analyses were adjusted by age, sex, and years of education. Stratified analyses by APOE-ɛ4 status and polygenic risk score of AD were conducted. MR analysis revealed significant associations between genetically predicted longer TL and lower levels of CSF Aβ and higher levels of CSF NfL only in APOE-ɛ4 non-carriers. Moreover, inheriting longer TL was associated with greater cortical thickness in age and AD-related brain signatures and lower levels of CSF p-tau among individuals at a high genetic predisposition to AD. Further observational analyses are warranted to better understand these associations.},
}
@article {pmid36342193,
year = {2023},
author = {Coutelier, H and Ilioaia, O and Le Peillet, J and Hamon, M and D'Amours, D and Teixeira, MT and Xu, Z},
title = {The Polo kinase Cdc5 is regulated at multiple levels in the adaptation response to telomere dysfunction.},
journal = {Genetics},
volume = {223},
number = {1},
pages = {},
pmid = {36342193},
issn = {1943-2631},
support = {FDN-167265//CIHR/Canada ; },
mesh = {*Protein Serine-Threonine Kinases/genetics/metabolism ; Cell Cycle Proteins/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; Protein Kinases/genetics ; Phosphorylation ; Saccharomyces cerevisiae/metabolism ; Checkpoint Kinase 2/genetics ; DNA Damage ; Telomere/genetics/metabolism ; },
abstract = {Telomere dysfunction activates the DNA damage checkpoint to induce a cell cycle arrest. After an extended period of time, however, cells can bypass the arrest and undergo cell division despite the persistence of the initial damage, a process called adaptation to DNA damage. The Polo kinase Cdc5 in Saccharomyces cerevisiae is essential for adaptation and for many other cell cycle processes. How the regulation of Cdc5 in response to telomere dysfunction relates to adaptation is not clear. Here, we report that Cdc5 protein level decreases after telomere dysfunction in a Mec1-, Rad53- and Ndd1-dependent manner. This regulation of Cdc5 is important to maintain long-term cell cycle arrest but not for the initial checkpoint arrest. We find that both Cdc5 and the adaptation-deficient mutant protein Cdc5-ad are heavily phosphorylated and several phosphorylation sites modulate adaptation efficiency. The PP2A phosphatases are involved in Cdc5-ad phosphorylation status and contribute to adaptation mechanisms. We finally propose that Cdc5 orchestrates multiple cell cycle pathways to promote adaptation.},
}
@article {pmid36341901,
year = {2022},
author = {Fan, G and Song, L and Liu, Q and Wu, M and Bi, J and Xu, L and Xiong, C and Cao, Z and Xu, S and Wang, Y},
title = {Association of maternal folic acid supplementation during pregnancy with newborn telomere length.},
journal = {Reproductive toxicology (Elmsford, N.Y.)},
volume = {114},
number = {},
pages = {52-56},
doi = {10.1016/j.reprotox.2022.10.006},
pmid = {36341901},
issn = {1873-1708},
mesh = {Humans ; Infant, Newborn ; Female ; Pregnancy ; Cohort Studies ; China ; *Dietary Supplements ; *Folic Acid ; Telomere ; },
abstract = {This study aimed to explore the associations between maternal folic acid (FA) supplementation during different trimesters of pregnancy and newborn telomere length (TL). Data were collected from a birth cohort study of 746 mother-newborn pairs conducted from November 2013 to March 2015 in Wuhan, China. After adjustment for potential confounders, maternal FA supplementation after the first trimester and throughout pregnancy were associated with longer newborn TL [β = 0.29, 95 % confidence interval (CI): 0.20, 0.38 and β = 0.24, 95 % CI: 0.16, 0.32, respectively]. No significant association was found between maternal FA supplementation in the first trimester and newborn TL. In conclusion, a possible association between maternal FA supplementation during pregnancy with longer newborn TL was suggested in the present study. This study provides insight into the benefit of newborn TL by maternal FA supplementation during pregnancy.},
}
@article {pmid36338739,
year = {2022},
author = {Li, Y and Ma, L},
title = {Relationship between telomere length and the prognosis of breast cancer based on estrogen receptor status: A Mendelian randomization study.},
journal = {Frontiers in oncology},
volume = {12},
number = {},
pages = {1024772},
pmid = {36338739},
issn = {2234-943X},
abstract = {OBJECTIVE: To identify the relationship between telomere length and the prognosis of breast cancer with different status of estrogen receptor (ER).<br><br>METHODS: We collected single nucleotide polymorphisms (SNPs) associated with telomere length and breast cancer prognosis from the MRCIEU GWAS database and the dataset of a large meta-analysis conducted by the Breast Cancer Association Consortium (BCAC), respectively. The relationship was identified using inverse-variance weighted (IVW), MR-Egger, weighted median, penalized weighted median, and maximum likelihood methods. IVW, MR-Egger, and MR-PRESSO methods were used to perform sensitivity analysis to assess the accuracy of the results.<br><br>RESULTS: Telomere length was negatively associated with the prognosis of total breast cancer (odds ratio [OR]=1.84, 95% confidence interval [CI]=1.08-3.14, IVW method), especially with ER- breast cancer (OR=1.89, 95% CI=1.11-3.22, IVW method). No similar relationship was found between telomere length and the prognosis of ER+ breast cancer (OR=0.99, 95% CI=0.62-1.58, IVW method). The findings from other methods were consistent with the results shown by the IVW method. The Mendelian randomization assumptions did not appear to be violated. Sensitivity analysis indicated that the result was robust, and no bias was observed in the study.<br><br>CONCLUSION: Telomere length is associated with the prognosis of total breast cancer, especially with ER- breast cancer. There is no significant correlation between telomere length and the prognosis of ER+ breast cancer. These findings add to the evidence that long telomere could predict a poor prognosis of ER- breast cancer.},
}
@article {pmid36334946,
year = {2022},
author = {Lansdorp, PM},
title = {Telomeres, Telomerase and Cancer.},
journal = {Archives of medical research},
volume = {53},
number = {8},
pages = {741-746},
doi = {10.1016/j.arcmed.2022.10.004},
pmid = {36334946},
issn = {1873-5487},
mesh = {Animals ; Humans ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; *Neoplasms/genetics ; Aging/genetics ; },
abstract = {Telomeres and telomerase play a crucial role in human aging and cancer. Three "drivers" of human aging can be identified. The developmental program encoded in DNA is the primary determinant of lifespan. Faithful execution of the developmental program requires stability of the (epi-)genome which is challenged throughout life by damage to DNA as well as epigenetic 'scars' from error-free DNA repair and stochastic errors made during the establishment and maintenance of the "epigenome". Over time (epi-)mutations accumulate, compromising cellular function and causing (pre-)malignant alterations. Damage to the genome and epigenome can be considered the second "driver" of aging. A third driver of the aging process, important to suppress tumors in long-lived animals, is caused by progressive loss of telomeric DNA. Telomere erosion protects against cancer early in life but limits cell renewal late in life, in agreement with the Antagonistic Pleiotropy theory on the evolutionary origin of aging. Malignant tumors arise when mutations and/or epimutations in cells (clock 2) corrupt the developmental program (clock 1) as well as tumor suppression by telomere erosion (clock 3). In cancer cells clock 3 is typically inactivated by loss of p53 as well as increased expression of telomerase. Taken together, aging in humans can be described by the ticking of three clocks: the clock that directs development, the accumulation of (epi-)mutations over time and the telomere clock that limits the number of cell divisions in normal stem and immune cells.},
}
@article {pmid36332602,
year = {2022},
author = {Decottignies, A},
title = {TERRA and RAD51AP1 at the R&amp;D-loop department of ALT telomeres.},
journal = {Molecular cell},
volume = {82},
number = {21},
pages = {3963-3965},
doi = {10.1016/j.molcel.2022.10.006},
pmid = {36332602},
issn = {1097-4164},
mesh = {*Telomere Homeostasis ; Telomere/genetics ; R-Loop Structures ; *RNA, Long Noncoding/genetics ; Chromatin ; },
abstract = {In this issue of Molecular Cell, Kaminski et al. and Yadav et al. demonstrate that RAD51AP1 and TERRA non-coding RNA positively regulate the alternative mechanism of telomere maintenance by promoting D-loop formation and chromatin-directed mechanisms to suppress transcription-collision events during ALT telomere synthesis.},
}
@article {pmid36330920,
year = {2022},
author = {Vaurs, M and Audry, J and Runge, KW and Géli, V and Coulon, S},
title = {A proto-telomere is elongated by telomerase in a shelterin-dependent manner in quiescent fission yeast cells.},
journal = {Nucleic acids research},
volume = {50},
number = {20},
pages = {11682-11695},
pmid = {36330920},
issn = {1362-4962},
support = {R01 HL158007/HL/NHLBI NIH HHS/United States ; R01 AG051601/AG/NIA NIH HHS/United States ; },
mesh = {*Schizosaccharomyces/genetics/metabolism ; *Schizosaccharomyces pombe Proteins/genetics/metabolism ; *Shelterin Complex ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; *Telomere-Binding Proteins/genetics/metabolism ; },
abstract = {Telomere elongation is coupled with genome replication, raising the question of the repair of short telomeres in post-mitotic cells. We investigated the fate of a telomere-repeat capped end that mimics a single short telomere in quiescent fission yeast cells. We show that telomerase is able to elongate this single short telomere during quiescence despite the binding of Ku to the proto-telomere. While Taz1 and Rap1 repress telomerase in vegetative cells, both shelterin proteins are required for efficient telomere extension in quiescent cells, underscoring a distinct mode of telomerase control. We further show that Rad3ATR and Tel1ATM are redundantly required for telomere elongation in quiescence through the phosphorylation of Ccq1 and that Rif1 and its associated-PP1 phosphatases negatively regulate telomerase activity by opposing Ccq1 phosphorylation. The distinct mode of telomerase regulation in quiescent fission yeast cells may be relevant to that in human stem and progenitor cells.},
}
@article {pmid36330807,
year = {2022},
author = {Wu, Y and Zhang, Y and Jiao, J},
title = {The relationship between n-3 polyunsaturated fatty acids and telomere: A review on proposed nutritional treatment against metabolic syndrome and potential signaling pathways.},
journal = {Critical reviews in food science and nutrition},
volume = {},
number = {},
pages = {1-20},
doi = {10.1080/10408398.2022.2142196},
pmid = {36330807},
issn = {1549-7852},
abstract = {Metabolic syndrome (MetS), a cluster of metabolic abnormalities composed of central obesity, elevated blood pressure, glucose disturbances, hypercholesterolemia and dyslipidaemia, has increasingly become a public health problem in the 21st century worldwide. The dysfunction of telomeres, the repetitive DNA with highly conserved sequences (5'-TTAGGG-3'), is remarkably correlated with organismal aging, even suggesting a causal relationship with metabolic disorders. The health benefits of n-3 polyunsaturated fatty acids (PUFAs) in multiple disorders are associated with telomere length in evidence, which have recently drawn wide attention. However, functional targets and pathways for the associations of n-3 PUFAs and telomere with MetS remain scare. Few studies have summarized the role of n-3 PUFAs in DNA damage repair pathways, anti-inflammatory pathways, and redox balance, linking with telomere biology, and other potential telomere-related signaling pathways. This review aims to (i) elucidate how n-3 PUFAs ameliorate telomere attrition in the context of anti-oxidation and anti-inflammation; (ii) unravel the role of n-3 PUFAs in modulating telomere-related neuron dysfunction and regulating the neuro-endocrine-immunological network in MetS; (iii) epidemiologically implicate the associations of metabolic disorders and n-3 PUFAs with telomere length; and (iv) suggest promising biochemical approaches and advancing methodologies to overcome the inter-variation problem helpful for future research.},
}
@article {pmid36330668,
year = {2022},
author = {Monaghan, P and Olsson, M and Richardson, DS and Verhulst, S and Rogers, SM},
title = {Integrating telomere biology into the ecology and evolution of natural populations: Progress and prospects.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {5909-5916},
doi = {10.1111/mec.16768},
pmid = {36330668},
issn = {1365-294X},
mesh = {*Ecology ; *Biological Evolution ; Telomere/genetics ; },
}
@article {pmid36319514,
year = {2023},
author = {Beranek, M and Borsky, P and Fiala, Z and Andrys, C and Hamakova, K and Chmelarova, M and Kovarikova, H and Karas, A and Kremlacek, J and Palicka, V and Borska, L},
title = {Telomere length, oxidative and epigenetic changes in blood DNA of patients with exacerbated psoriasis vulgaris.},
journal = {Anais brasileiros de dermatologia},
volume = {98},
number = {1},
pages = {68-74},
pmid = {36319514},
issn = {1806-4841},
mesh = {Female ; Humans ; *Metabolic Syndrome ; 5-Methylcytosine ; Epigenesis, Genetic ; Oxidative Stress/genetics ; RNA/metabolism ; Telomere/genetics/metabolism ; DNA/metabolism ; *Psoriasis/genetics ; },
abstract = {BACKGROUND: The pathogenesis of psoriasis vulgaris involves changes in DNA molecules, genomic instability, telomere attrition, and epigenetic alterations among them. These changes are also considered important mechanisms of aging in cells and tissues.<br><br>OBJECTIVE: This study dealt with oxidation damage, telomere length and methylation status in DNA originating from peripheral blood of 41 psoriatic patients and 30 healthy controls.<br><br>METHODS: Oxidative damage of serum DNA/RNA was determined immunochemically. Real-time PCR was used for the analysis of the telomere length. ELISA technique determined levels of 5-methylcytosine in blood cells' DNA.<br><br>RESULTS: Oxidative damage of serum DNA/RNA was higher in patients than in controls (median, 3758 vs. 2286pg/mL, p<0.001). A higher length of telomeres per chromosome was found in patients whole-cell DNA than in controls (3.57 vs. 3.04 kilobases, p=0.011). A negative correlation of the length of telomeres with an age of the control subjects was revealed (Spearman's rho=-0.420, p=0.028). Insignificantly different levels of 5-methylcytosine in patients and controls were observed (33.20 vs. 23.35%, p=0.234). No influences of sex, smoking, BMI, PASI score, and metabolic syndrome on the methylation status were found.<br><br>STUDY LIMITATIONS: i) A relatively small number of the participants, particularly for reliable subgroup analyses, ii) the Caucasian origin of the participants possibly influencing the results of the parameters determined, and iii) Telomerase activity was not directly measured in serum or blood cells.<br><br>CONCLUSION: The study demonstrated increased levels of oxidized DNA/RNA molecules in the serum of patients with exacerbated psoriasis vulgaris. The results were minimally influenced by sex, the presence of metabolic syndrome, or cigarette smoking. In the psoriatic blood cells' DNA, the authors observed longer telomeres compared to healthy controls, particularly in females. Insignificantly higher global DNA methylation in psoriasis cases compared to the controls indicated marginal clinical importance of this epigenetic test performed in the blood cells' DNA.},
}
@article {pmid36319501,
year = {2022},
author = {Ramírez-Sanabria, M and Martínez-Magaña, J and Nicolini-Sánchez, H and Guzmán-Sánchez, R and Genis-Mendoza, AD},
title = {[Association between telomere length and cognitive impairment in older adults].},
journal = {Revista espanola de geriatria y gerontologia},
volume = {57},
number = {6},
pages = {320-324},
doi = {10.1016/j.regg.2022.09.006},
pmid = {36319501},
issn = {1578-1747},
mesh = {Humans ; *Telomere Shortening ; Telomere ; *Cognitive Dysfunction/genetics ; Biomarkers ; },
abstract = {INTRODUCTION: Cognitive impairment is a transition stage between normal aging and dementia, the prevalence of last one increases with age; the damage of the functions and physical integrity, places the older adult in a greater susceptibility to get sick. Telomere length is a hallmark of aging to characterize this phenotype, as well as a biomarker that reflects the underlying state of the cell. In this work, the relative length of telomeres in older adults with cognitive impairment was correlated.<br><br>MATERIAL AND METHODS: Observational-analytical study, in samples of adult patients older than 65 years with and without cognitive impairment, in whom the relative length of telomeres was measured.<br><br>RESULTS: Ninety samples of older adults were included in the study and in the association analysis according to multivariate logistic models, cognitive impairment showed almost five times more risk for telomere shortening in relation to the presence of the diagnosis of cognitive impairment (Odds ratio 4.88, p=0.027).<br><br>CONCLUSIONS: When correlating the relative length of telomeres in older adults diagnosed with cognitive impairment, this association was confirmed for shorter.},
}
@article {pmid36311861,
year = {2022},
author = {de Mendonça Filho, EJ and Frechette, A and Pokhvisneva, I and Arcego, DM and Barth, B and Tejada, CV and Sassi, R and Wazana, A and Atkinson, L and Meaney, MJ and Silveira, PP},
title = {Examining attachment, cortisol secretion, and cognitive neurodevelopment in preschoolers and its predictive value for telomere length at age seven.},
journal = {Frontiers in behavioral neuroscience},
volume = {16},
number = {},
pages = {954977},
pmid = {36311861},
issn = {1662-5153},
abstract = {BACKGROUND: Secure attachment reflects caregiver-child relationship in which the caregiver is responsive when support and comforting are needed by the child. This pattern of bond has an important buffering role in the response to stress by the reduction of the negative experience and its associated physiological response. Disruption of the physiological stress system is thought to be a central mechanism by which early care impacts children. Early life stress causes cellular and molecular changes in brain regions associated with cognitive functions that are fundamental for early learning.<br><br>METHODS: The association between attachment, cortisol response before and after the Strange Situation Experiment, and neurodevelopment was examined in a sample of 107 preschoolers at age three. Also, the predictive effect of cortisol reactivity and attachment on telomere length at age seven was investigated in a followed-up sample of 77 children.<br><br>RESULTS: Children with insecure attachment had higher cortisol secretion and poorer neurodevelopmental skills at age three. A significant cortisol change was observed across the experiment with non-significant interaction with attachment. The attachment and neurodevelopment association was not mediated by cortisol secretion. Preschoolers' attachment and cortisol did not associate nor interacted to predict telomere length at age seven.<br><br>CONCLUSION: These findings add evidence to the detrimental effects of insecure attachment as an aggravator of the physiological response to stress and poorer neurodevelopment during the preschool period. Although attachment and cortisol were not predictive of telomere length, intervention policies that promote secure attachment are more likely to positively echo on several health domains.},
}
@article {pmid36311538,
year = {2022},
author = {Carvalho, VS and Gomes, WR and Calado, RT},
title = {Recent advances in understanding telomere diseases.},
journal = {Faculty reviews},
volume = {11},
number = {},
pages = {31},
pmid = {36311538},
issn = {2732-432X},
abstract = {Germline genetic defects impairing telomere length maintenance may result in severe medical conditions in humans, from aplastic anemia and myeloid neoplasms to interstitial lung disease and liver cirrhosis, from childhood (dyskeratosis congenita) to old age (pulmonary fibrosis). The molecular mechanisms underlying these clinically distinct disorders are pathologically excessive telomere erosion, limiting cell proliferation and differentiation, tissue regeneration, and increasing genomic instability. Recent findings also indicate that telomere shortening imbalances stem cell fate and is associated with an abnormal inflammatory response and the senescent-associated secretory phenotype. Bone marrow failure is the most common phenotype in patients with telomere diseases. Pulmonary fibrosis is a typical phenotype in older patients, and disease progression appears faster than in pulmonary fibrosis not associated with telomeropathies. Liver cirrhosis may present in isolation or in combination with other phenotypes. Diagnosis is based on clinical suspicion and may be confirmed by telomere length measurement and genetic testing. Next-generation sequencing (NGS) techniques have improved genetic testing; today, at least 16 genes have been implicated in telomeropathies. NGS also allows tracking of clonal hematopoiesis and malignant transformation. Patients with telomere diseases are at high risk of developing cancers, including myeloid neoplasms and head and neck cancer. However, treatment options are still limited. Transplant modalities (bone marrow, lung, and liver) may be definitive to the respective organ involvement but limited by donor availability, comorbidities, and impact on other affected organs. In clinical trials, androgens elongate telomeres of peripheral blood leukocytes and improve hematopoiesis. Further understanding of how telomere erosion impairs organ function and how somatic mutations evolve in the hematopoietic tissue may help develop new strategies to treat and prevent telomere diseases.},
}
@article {pmid36311389,
year = {2022},
author = {Dobson, FS and Schull, Q and Criscuolo, F},
title = {Two aspects of longevity are associated with rates of loss of telomeres in birds.},
journal = {Ecology and evolution},
volume = {12},
number = {10},
pages = {e9364},
pmid = {36311389},
issn = {2045-7758},
abstract = {Telomeres, the terminal repetitive DNA sequences at the ends of linear chromosomes, have strong associations with longevity in some major taxa. Longevity has been linked to rate of decline in telomere length in birds and mammals, and absolute telomere length seems to be associated with body mass in mammals. Using a phylogenetic comparative method and 30 species of birds, we examined longevity (reflected by maximum lifespan), absolute telomere length, the rate of change in telomere length (TROC), and body mass (often strongly associated with longevity) to ascertain their degree of association. We divided lifespan into two life-history components, one reflected by body size (measured as body mass) and a component that was statistically independent of body mass. While both lifespan and body mass were strongly associated with a family tree of the species (viz., the phylogeny of the species), telomere measures were not. Telomere length was not significantly associated with longevity or body mass or our measure of mass-independent lifespan. TROC, however, was strongly associated with mass-independent lifespan, but only to a much lesser degree at best with body mass-predicted lifespan. Our results supported an association of TROC and longevity, in particular longevity that was independent of body size and part of the pace-of-life syndrome of life histories.},
}
@article {pmid36304436,
year = {2022},
author = {Castro-Diehl, C and Smith, JA and Zhao, W and Wang, X and Mukherjee, B and Seeman, T and Needham, BL},
title = {Prediction of telomere length and telomere attrition using a genetic risk score: The multi-ethnic study of atherosclerosis (MESA).},
journal = {Frontiers in aging},
volume = {3},
number = {},
pages = {1021051},
pmid = {36304436},
issn = {2673-6217},
abstract = {Background: Short telomere length (TL) and telomere attrition (TA) have been associated with age-related diseases. Objective: We assessed whether a genetic risk score for short TL (GRS-TL) combining seven TL-associated genetic variants identified in a European-ancestry genome-wide association study (GWAS) was associated with TL and TA over 10 years. Methods: Relative TL (T/S ratio) was measured by the quantitative polymerase chain reaction method for a sample of white, African American, and Hispanic participants, who attended Exam 1 and/or 5 of the Multi-Ethnic Study of Atherosclerosis (MESA). Our final sample included 1,227 participants for the TL analysis and 1,138 for the TA analysis. Participants were 45-84 years at Exam 1. We used a linear mixed effects model and adjusted for age, sex, and population structure. Models were stratified by race/ethnicity. Results: In the TL analysis, higher GRS-TL significantly predicted shorter TL (estimates = -0.18 [S.E. = 0.08], p = 0.02 for white; -0.18 [0.07], p < 0.01 for African American; and -0.13 [0.05], p = 0.02 for Hispanic) in fully adjusted models. In the TA analysis, no association between GRS-TL and TA over 10 years was found. Conclusion: Although GRS-TL was developed in European-ancestry populations, it was significantly associated with TL (but not TA) in all three race/ethnic groups examined.},
}
@article {pmid36302456,
year = {2022},
author = {Katz, R and Gay, EL and Kuipers, AL and Lee, JH and Honig, LS and Christensen, K and Feitosa, MF and Wojczynski, MK and Glynn, NW and , },
title = {Association of leukocyte telomere length with perceived physical fatigability.},
journal = {Experimental gerontology},
volume = {170},
number = {},
pages = {111988},
doi = {10.1016/j.exger.2022.111988},
pmid = {36302456},
issn = {1873-6815},
support = {U19 AG063893/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; Female ; Aged ; Aged, 80 and over ; Male ; Longitudinal Studies ; *Telomere/genetics ; *Leukocytes ; Fatigue/genetics ; Aging/genetics ; },
abstract = {BACKGROUND: Leukocyte telomere length (LTL) is a potential genomic marker of biological aging, but its relation to fatigability, a prognostic indicator of phenotypic aging (e.g., functional decline) is unknown. We hypothesized shorter LTL would predict greater perceived physical fatigability, but that this association would be attenuated by adjusting for chronological age.<br><br>METHODS: Two generations of participants (N&#xa0;=&#xa0;1997; 309 probands, 1688 offspring) were from the Long Life Family Study (age&#xa0;=&#xa0;73.7&#xa0;&#xb1;&#xa0;10.4, range 60-108, 54.4&#xa0;% women), a longitudinal cohort study of aging. LTL was assayed at baseline. Perceived physical fatigability was measured 8.0&#xa0;&#xb1;&#xa0;1.1&#xa0;years later using the validated, self-administered 10-item Pittsburgh Fatigability Scale (PFS, 0-50, higher scores&#xa0;=&#xa0;greater fatigability). Generalized estimating equations were generated to model the association between LTL and PFS Physical scores.<br><br>RESULTS: Prevalence of greater physical fatigability (PFS scores&#x2265;15) was 41.9&#xa0;%. Using generalized estimating equations, a one kilobase pair shorter LTL was associated with higher PFS Physical scores (&#x3b2;&#xa0;=&#xa0;1.8, p&#xa0;<&#xa0;.0001), accounting for family structure, and adjusting for field center, follow-up time, sex, and follow-up body mass index, physical activity, and chronic health conditions. When age was included as a covariate, the association was fully attenuated (&#x3b2;&#xa0;=&#xa0;0.1, p&#xa0;=&#xa0;.78).<br><br>CONCLUSION: LTL may provide an alternative method for estimating an individual's lifetime exposure to chronic stressors, but does not appear to provide additional information not captured by chronological age. Further research is needed to characterize the interaction between age, LTL, and perceived fatigability, and develop a method of identifying individuals at risk for deleterious aging.},
}
@article {pmid36296977,
year = {2022},
author = {Cancello, R and Rey, F and Carelli, S and Cattaldo, S and Fontana, JM and Goitre, I and Ponzo, V and Merlo, FD and Zuccotti, G and Bertoli, S and Capodaglio, P and Bo, S and Brunani, A},
title = {Telomere Length and Mitochondrial DNA Copy Number Variations in Patients with Obesity: Effect of Diet-Induced Weight Loss-A Pilot Study.},
journal = {Nutrients},
volume = {14},
number = {20},
pages = {},
pmid = {36296977},
issn = {2072-6643},
mesh = {Humans ; *DNA Copy Number Variations ; Pilot Projects ; *Telomere/genetics ; Antioxidants ; Obesity/genetics ; DNA, Mitochondrial/genetics ; Weight Loss/genetics ; },
abstract = {Background: Telomere length (TL) and mitochondrial DNA (mtDNA) copy number shifts are linked to metabolic abnormalities, and possible modifications by diet-induced weight loss are poorly explored. We investigated the variations before (T0) and after a 1-year (T12) lifestyle intervention (diet + physical activity) in a group of outpatients with obesity. Methods: Patients aged 25−70 years with BMI ≥ 30 kg/m2 were enrolled. Clinical and biochemical assessments (including a blood sample for TL, mtDNA copy number and total antioxidant capacity, and TAC determinations) were performed at T0 and T12. Results: The change in TL and the mtDNA copy number was heterogeneous and not significantly different at T12. Patients were then divided by baseline TL values into lower than median TL (L-TL) and higher than median TL (H-TL) groups. The two groups did not differ at baseline for anthropometric, clinical, and laboratory characteristics. At T12, the L-TL group when compared to H-TL showed TL elongation (respectively, +0.57 ± 1.23 vs. −2.15 ± 1.13 kbp, p = 0.04), higher mtDNA copy number (+111.5 ± 478.5 vs. −2314.8 ± 724.2, respectively, p < 0.001), greater weight loss (−8.1 ± 2.7 vs. −6.1 ± 4.6 Kg, respectively, p = 0.03), fat mass reduction (−1.42 ± 1.3 vs. −1.22 ± 1.5%, respectively, p = 0.04), and increased fat-free mass (+57.8 ± 6.5 vs. +54.9 ± 5.3%, respectively, p = 0.04) and TAC levels (+58.5 ± 18.6 vs. +36.4 ± 24.1 µM/L, respectively, p = 0.04). Conclusions: TL and the mtDNA copy number significantly increased in patients with obesity and with lower baseline TL values after a 1-year lifestyle intervention. Larger longitudinal studies are needed to confirm the results of this pilot study.},
}
@article {pmid36294653,
year = {2022},
author = {Xu, F and Li, X and Ren, H and Zeng, R and Wang, Z and Hu, H and Bao, J and Que, Y},
title = {The First Telomere-to-Telomere Chromosome-Level Genome Assembly of Stagonospora tainanensis Causing Sugarcane Leaf Blight.},
journal = {Journal of fungi (Basel, Switzerland)},
volume = {8},
number = {10},
pages = {},
pmid = {36294653},
issn = {2309-608X},
support = {CARS-17//Modern Agriculture Technology of China/ ; CXZX2020083A//Special Fund for Science and Technology Innovation of Fujian Agriculture and Forestry University/ ; },
abstract = {The sexual morph Leptosphaeria taiwanensis Yen and Chi and its asexual morph Stagonospora tainanensis W. H. Hsieh is an important necrotrophic fungal phytopathogen, which causes sugarcane leaf blight, resulting in loss of cane tonnage and sucrose in susceptible sugarcane varieties. Decoding the genome and understanding of the basis of virulence is vitally important for devising effective disease control strategies. Here, we present a 38.25-Mb high-quality genome assembly of S. tainanensis strain StFZ01, denovo assembled with 10.19 Gb Nanopore sequencing long reads (~267×) and 3.82 Gb Illumina short reads (~100×). The genome assembly consists of 12 contigs with N50 of 2.86 Mb of which 5 belong to the telomere to telomere (T2T) chromosome. It contains 13.20% repeat sequences, 12,543 proteins, and 12,206 protein-coding genes with the BUSCO completeness 99.18% at fungi (n = 758) and 99.87% at ascomycota (n = 1706), indicating the high accuracy and completeness of our gene annotations. The virulence analysis in silico revealed the presence of 2379 PHIs, 599 CAZys, 248 membrane transport proteins, 191 cytochrome P450 enzymes, 609 putative secreted proteins, and 333 effectors in the StFZ01 genome. The genomic resources presented here will not only be helpful for development of specific molecular marker and diagnosis technique, population genetics, molecular taxonomy, and disease managements, it can also provide a significant precise genomic reference for investigating the ascomycetous genome, the necrotrophic lifestyle, and pathogenicity in the future.},
}
@article {pmid36292740,
year = {2022},
author = {Dlouha, D and Vymetalova, J and Novakova, S and Huckova, P and Lanska, V and Hubacek, JA},
title = {Posttransplant Complications and Genetic Loci Involved in Telomere Maintenance in Heart Transplant Patients.},
journal = {Genes},
volume = {13},
number = {10},
pages = {},
pmid = {36292740},
issn = {2073-4425},
mesh = {Humans ; Adult ; Middle Aged ; *Telomere/genetics ; Leukocytes/metabolism ; *Heart Transplantation/adverse effects ; Genetic Loci ; DNA/metabolism ; },
abstract = {Reaching critically short telomeres induces cellular senescence and ultimately cell death. Cellular senescence contributes to the loss of tissue function. We aimed to determine the association between variants within genes involved in telomere length maintenance, posttransplant events, and aortic telomere length in heart transplant patients. DNA was isolated from paired aortic samples of 383 heart recipients (age 50.7 ± 11.9 years) and corresponding donors (age 38.7 ± 12.0 years). Variants within the TERC (rs12696304), TERF2IP (rs3784929 and rs8053257), and OBCF1 (rs4387287) genes were genotyped, and telomere length was measured using qPCR. We identified similar frequencies of genotypes in heart donors and recipients. Antibody-mediated rejection (AMR) was more common (p < 0.05) in carriers of at least one G allele within the TERF2IP locus (rs3784929). Chronic graft dysfunction (CGD) was associated with the TERC (rs12696304) GG donor genotype (p = 0.05). The genetic risk score did not determine posttransplant complication risk prediction. No associations between the analyzed polymorphisms and telomere length were detected in either donor or recipient DNA. In conclusion, possible associations between donor TERF2IP (rs3784929) and AMR and between TERC (rs12696304) and CGD were found. SNPs within the examined genes were not associated with telomere length in transplanted patients.},
}
@article {pmid36292646,
year = {2022},
author = {M'Kacher, R and Miguet, M and Maillard, PY and Colicchio, B and Scheidecker, S and Najar, W and Arnoux, M and Oudrhiri, N and Borie, C and Biehler, M and Plesch, A and Heidingsfelder, L and Bennaceur-Griscelli, A and Dieterlen, A and Voisin, P and Junker, S and Carde, P and Jeandidier, E},
title = {A Central Role of Telomere Dysfunction in the Formation of a Unique Translocation within the Sub-Telomere Region Resulting in Duplication and Partial Trisomy.},
journal = {Genes},
volume = {13},
number = {10},
pages = {},
pmid = {36292646},
issn = {2073-4425},
mesh = {Humans ; *Trisomy/genetics ; In Situ Hybridization, Fluorescence ; Chromosome Banding ; *Translocation, Genetic/genetics ; Chromosome Aberrations ; Telomere/genetics ; },
abstract = {Telomeres play a major role in maintaining genome stability and integrity. Putative involvement of telomere dysfunction in the formation of various types of chromosomal aberrations is an area of active research. Here, we report a case of a six-month-old boy with a chromosomal gain encompassing the 11q22.3q25 region identified by SNP array analysis. The size of the duplication is 26.7 Mb and contains 170 genes (OMIM). The duplication results in partial trisomy of the region in question with clinical consequences, including bilateral renal dysplasia, delayed development, and a heart defect. Moreover, the karyotype determined by R-banding and chromosome painting as well as by hybridization with specific sub-telomere probes revealed the presence of an unbalanced t(9;11)(p24;q22.3) translocation with a unique breakpoint involving the sub-telomere region of the short arm of chromosome 9. The karyotypes of the parents were normal. Telomere integrity in circulating lymphocytes from the child and from his parents was assessed using an automated high-throughput method based on fluorescence in situ hybridization (FISH) with telomere- and centromere-specific PNA probes followed by M-FISH multicolor karyotyping. Very short telomeres, as well as an increased frequency of telomere loss and formation of telomere doublets, were detected in the child's cells. Interestingly, similar telomere profiles were found in the circulating lymphocytes of the father. Moreover, an assessment of clonal telomere aberrations identified chromosomes 9 and 11 with particularly high frequencies of such aberrations. These findings strongly suggest that telomere dysfunction plays a central role in the formation of this specific unbalanced chromosome rearrangement via chromosome end-to-end fusion and breakage-fusion-bridge cycles.},
}
@article {pmid36290385,
year = {2022},
author = {Dorador, AP and Dalikova, M and Cerbin, S and Stillman, CM and Zych, MG and Hawley, RS and Miller, DE and Ray, DA and Funikov, SY and Evgen'ev, MB and Blumenstiel, JP},
title = {Paramutation-like Epigenetic Conversion by piRNA at the Telomere of Drosophila virilis.},
journal = {Biology},
volume = {11},
number = {10},
pages = {},
pmid = {36290385},
issn = {2079-7737},
support = {1413532//National Science Foundation/ ; P20 GM103418/GM/NIGMS NIH HHS/United States ; 22-74-10050//Russian Science Foundation/ ; P20GM103418//National Institute of Health/ ; P20 GM103638/GM/NIGMS NIH HHS/United States ; NA//University of Kansas/ ; NA//Stowers Institute for Medical Research/ ; P30 GM145499/GM/NIGMS NIH HHS/United States ; 2025197//National Science Foundation/ ; P20GM103638//National Institute of Health/ ; },
abstract = {First discovered in maize, paramutation is a phenomenon in which one allele can trigger an epigenetic conversion of an alternate allele. This conversion causes a genetically heterozygous individual to transmit alleles that are functionally the same, in apparent violation of Mendelian segregation. Studies over the past several decades have revealed a strong connection between mechanisms of genome defense against transposable elements by small RNA and the phenomenon of paramutation. For example, a system of paramutation in Drosophila melanogaster has been shown to be mediated by piRNAs, whose primary function is to silence transposable elements in the germline. In this paper, we characterize a second system of piRNA-mediated paramutation-like behavior at the telomere of Drosophila virilis. In Drosophila, telomeres are maintained by arrays of retrotransposons that are regulated by piRNAs. As a result, the telomere and sub-telomeric regions of the chromosome have unique regulatory and chromatin properties. Previous studies have shown that maternally deposited piRNAs derived from a sub-telomeric piRNA cluster can silence the sub-telomeric center divider gene of Drosophila virilis in trans. In this paper, we show that this silencing can also be maintained in the absence of the original silencing allele in a subsequent generation. The precise mechanism of this paramutation-like behavior may be explained by either the production of retrotransposon piRNAs that differ across strains or structural differences in the telomere. Altogether, these results show that the capacity for piRNAs to mediate paramutation in trans may depend on the local chromatin environment and proximity to the uniquely structured telomere regulated by piRNAs. This system promises to provide significant insights into the mechanisms of paramutation.},
}
@article {pmid36289653,
year = {2022},
author = {Rangel-Pozzo, A and Wechsler, J and Groult, J and Da Meda, L and Lebbe, C and Mai, S},
title = {Telomere-Associated Changes in Nuclear Architecture of Cancer-Associated Macrophage-like Cells in Liquid Biopsies from Melanoma Patients.},
journal = {Biomedicines},
volume = {10},
number = {10},
pages = {},
pmid = {36289653},
issn = {2227-9059},
abstract = {During phagocytosis, tumor-associated macrophages (TAMs) can incorporate genetic material from tumor cells. The incorporation of extra genetic material may be responsible for advanced malignant behavior observed in some TAMs, making TAMs potentially important players in cancer progression. More recently, similar cells were described in the blood as cancer-associated macrophage-like cells (CAMLs). CAMLs may be equivalent to TAMs cells in the blood, and they express macrophage markers. However, their origin is still unclear. In a previous study, we showed for the first time the distinct telomere 3D structure of circulating tumor cells (CTCs) in melanoma and other cancers. In the present pilot study, we investigated, comparatively, the 3D telomere structure of CAMLs, CTCs and leucocytes from nine melanoma patients with metastatic cutaneous melanoma stage IV. CTC capture was performed by size-based filtration followed by cytological and immunocytological evaluation. Three-dimensional Quantitative Fluorescent in situ Hybridization was performed to measure differences in five 3D telomere parameters. Telomere parameters, such as number, length, telomere aggregates, nuclear volume, and a/c ratio, were compared among different cellular types (CTCs, CAMLs, and normal leucocytes). Three telomere parameters were significantly different between CAMLs and leucocytes. The combination of two telomere parameters (telomere length against the number of telomeres) resulted in the identification of two CAMLs subpopulations with different levels of genomic instability. Those populations were classified as profile 1 and 2. Profile 2, characterized by a high number of short telomeres, was observed in four of the nine melanoma patients. To our knowledge, this is the first pilot study to investigate 3D telomere parameters as hallmarks of nuclear architecture in CAMLs' population in comparison to leucocytes from the same patient. Further studies involving a larger patient sample size are necessary to validate these findings and explore their potential prognostic value.},
}
@article {pmid36289597,
year = {2022},
author = {Lupatov, AY and Yarygin, KN},
title = {Telomeres and Telomerase in the Control of Stem Cells.},
journal = {Biomedicines},
volume = {10},
number = {10},
pages = {},
pmid = {36289597},
issn = {2227-9059},
support = {122022800499-5//Program for Basic Research in the Russian Federation for a long-term period (2021-2030)/ ; },
abstract = {Stem cells serve as a source of cellular material in embryogenesis and postnatal growth and regeneration. This requires significant proliferative potential ensured by sufficient telomere length. Telomere attrition in the stem cells and their niche cells can result in the exhaustion of the regenerative potential of high-turnover organs, causing or contributing to the onset of age-related diseases. In this review, stem cells are examined in the context of the current telomere-centric theory of cell aging, which assumes that telomere shortening depends not just on the number of cell doublings (mitotic clock) but also on the influence of various internal and external factors. The influence of the telomerase and telomere length on the functional activity of different stem cell types, as well as on their aging and prospects of use in cell therapy applications, is discussed.},
}
@article {pmid36285820,
year = {2022},
author = {Iannarelli, NJ and Wade, TJ and Dempster, KS and Moore, J and MacNeil, AJ and O'Leary, DD},
title = {No Mediation Effect of Telomere Length or Mitochondrial DNA Copy Number on the Association Between Adverse Childhood Experiences (ACEs) and Central Arterial Stiffness.},
journal = {Journal of the American Heart Association},
volume = {11},
number = {21},
pages = {e026619},
pmid = {36285820},
issn = {2047-9980},
support = {363774//CIHR/Canada ; 399332//CIHR/Canada ; RFN 167014//CIHR/Canada ; },
mesh = {Young Adult ; Humans ; Female ; Adult ; DNA, Mitochondrial/genetics ; *Vascular Stiffness ; *Adverse Childhood Experiences ; DNA Copy Number Variations ; Pulse Wave Analysis ; Biomarkers/metabolism ; Telomere/genetics/metabolism ; *Cardiovascular Diseases/diagnosis/epidemiology/genetics ; },
abstract = {Background Adverse childhood experiences (ACEs) have been linked to increased cardiovascular disease (CVD) risk. Previous reports have suggested that accelerated biological aging-indexed by telomere length (TL) and mitochondrial DNA copy number (mtDNAcn)-may contribute to associations between ACEs and cardiovascular health outcomes. Here, we examine the potential mediating effects of TL and mtDNAcn on the association between ACEs and central arterial stiffness-an intermediate cardiovascular health outcome-as a novel pathway linking ACEs to CVD risk among young adults. Methods and Results One hundred and eighty-five (n=102 women; mean age, 22.5±1.5 years) individuals provided information on ACEs. TL (kb per diploid cell) and mtDNAcn (copies per diploid cell) were quantified using quantitative polymerase chain reaction techniques. Central arterial stiffness was measured as carotid-femoral pulse wave velocity (cfPWV; m/s). Multiple linear regression analyses were used to examine the associations between ACEs, TL, mtDNAcn, and cfPWV. ACEs were positively associated with cfPWV (β=0.147, P=0.035). TL (β=-0.170, P=0.011) and mtDNAcn (β=-0.159, P=0.019) were inversely associated with cfPWV. Neither TL (β=-0.027, P=0.726) nor mtDNAcn (β=0.038, P=0.620) was associated with ACEs. Neither marker mediated the association between ACEs and cfPWV. Conclusions An increasing number of ACEs were associated with a faster cfPWV and thus, a greater degree of central arterial stiffness. ACEs were not associated with either TL or mtDNAcn, suggesting that these markers do not represent a mediating pathway linking ACEs to central arterial stiffness.},
}
@article {pmid36283531,
year = {2023},
author = {Li, X and Liu, H and Wan, H and Li, Y and Xu, S and Xiao, H and Xia, W},
title = {Sex-specific associations between legacy and novel per- and polyfluoroalkyl substances and telomere length in newborns in Wuhan, China: Mixture and single pollutant associations.},
journal = {The Science of the total environment},
volume = {857},
number = {Pt 3},
pages = {159676},
doi = {10.1016/j.scitotenv.2022.159676},
pmid = {36283531},
issn = {1879-1026},
mesh = {Pregnancy ; Female ; Male ; Infant, Newborn ; Humans ; *Fluorocarbons/analysis ; *Environmental Pollutants/analysis ; *Alkanesulfonic Acids/analysis ; China ; Telomere ; },
abstract = {Telomere length (TL) at birth predicts later life TL and is related to health. Prenatal exposure to environmental pollutants might affect TL, but the associations between intrauterine per- and polyfluoroalkyl substances (PFASs) exposure and neonatal TL remained inconclusive. This study aimed to explore the single pollutant and mixture associations between legacy and novel PFASs and TL in newborns. In 908 mother-newborn pairs from Wuhan, China, thirteen PFASs were measured in cord serum, and TL was determined in cord leukocytes. Weighted quantile sum (WQS) regression and generalized linear model (GLM) were utilized to analyze the associations between PFASs mixture and single PFASs and TL in newborns. Furthermore, stratified and interaction analyses were performed to evaluate if there were sex-specific associations. The concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) ranked the highest (geometric mean, 4.12, 1.61, and 0.77 ng/mL, respectively) among the 13 measured PFASs. Each unit increase in WQS index of PFASs mixture was associated with -5.19 % change (95% CI, -9.44, -0.73) of neonatal TL, and 8:2 Cl-PFESA contributed most (32.59 %) to the mixture association. In stratified analyses by neonatal sex, PFOS (-4.73 % change, 95% CI, -8.40, -0.93 for per doubling concentration) and 8:2 Cl-PFESA (-4.52 % change, 95% CI, -8.20, -0.70) were negatively associated with neonatal TL in male newborns, but no significant association appeared in females. In summary, intrauterine exposure to PFASs in mixture was associated with shorter neonatal TL, and the negative associations of 8:2 Cl-PFESA and PFOS with neonatal TL were observed only in boys. Future risk assessments are needed to pay more attention to the health effects of novel PFASs.},
}
@article {pmid36282763,
year = {2022},
author = {Kertes, DA and Leri, J and Duan, K and Tarrence, J and Browning, C and Pickler, R and Ford, J},
title = {Demographic and health predictors of telomere length during adolescence.},
journal = {Developmental psychobiology},
volume = {64},
number = {7},
pages = {e22311},
pmid = {36282763},
issn = {1098-2302},
support = {R01 DA032371/DA/NIDA NIH HHS/United States ; P2C HD058484/HD/NICHD NIH HHS/United States ; R21 DA034960/DA/NIDA NIH HHS/United States ; R01 NR019008/NR/NINR NIH HHS/United States ; R01 MD011727/MD/NIMHD NIH HHS/United States ; },
mesh = {Adult ; Adolescent ; Humans ; *Telomere Shortening ; *Telomere ; Body Mass Index ; DNA ; Demography ; },
abstract = {Telomere length (TL) is proposed to play a mechanistic role in how the exposome affects health outcomes. Little is known about TL during adolescence, a developmental period during which precursors of adult-onset health problems often emerge. We examined health and demographic sources of variation in TL in 899 youth aged 11-17. Demographic and health information included age, sex, race, household income, caregiver age and marital status, youth tobacco exposure, body mass index, pubertal status, health problems, medication use, and season of data collection. Genomic DNA was extracted from saliva, and T/S ratios were computed following qPCR. Age, race, season of data collection, and household income were associated with the telomere to single copy (T/S) ratio. We found that T/S ratios were larger at younger ages, among Black youth, for saliva collected during autumn and winter, and among households with higher income. Analyses stratified by race revealed that the association between age and T/S ratio was present for Black youth, that season of collection was present across races, but that family demographic associations with T/S ratio varied by race. The results provide information for future telomere research and highlight adolescence as a potentially important developmental phase for racial disparities in telomere shortening and health.},
}
@article {pmid36276465,
year = {2022},
author = {Mishra, R and Haldar, S and Biondi, S and Bhari, VK and Singh, G and Bhowmick, NA},
title = {TGF-β controls stromal telomere length through epigenetic modifications.},
journal = {3 Biotech},
volume = {12},
number = {11},
pages = {290},
pmid = {36276465},
issn = {2190-572X},
support = {I01 BX001040/BX/BLRD VA/United States ; P01 CA233452/CA/NCI NIH HHS/United States ; },
abstract = {UNLABELLED: Telomere length is primarily controlled by the enzyme telomerase, but being chromatin structures, telomeres undergo epigenetic regulation for their maintenance and function. Altered telomere length among cancer cells combined with shorter telomere length in cancer-associated stromal cells, strongly implicated with progression to prostate cancer metastasis and cancer death and providing a novel target for therapeutics. Transforming growth factor-β (TGF-β) signaling pathways are well-recognized for their role in stromal-epithelial interactions responsible for prostate androgen responsiveness, promoting tumorigenesis. However, the underlying mechanism remains unclear. We sought to establish a role for TGF-β in the regulation of telomere length in mouse and human prostate fibroblast. Polymerase chain reaction (PCR)-based telomere length measuring methods are widely used due to their repeatability and reproducibility. Using real-time RT-PCR-based telomere length measuring method, we identified that TGF-beta regulates telomere length via increased expression of histone methyltransferase, Suv39h1, which in turn affected histone methylation levels at the telomeric ends. Moreover, treatment of DAPT and non-steroidal antiandrogen bicalutamide demonstrated that notch and androgen signaling co-operated with TGF-ß in regulating stromal telomere length. Telomere variation in tumor cells and non-tumor cells within the tumor microenvironment greatly facilitates the clinical assessment of prostate cancer; therefore, understanding stromal telomere length regulation mechanism will hold significant prospects for cancer treatment, diagnosis, and prognosis.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-022-03346-5.},
}
@article {pmid36270567,
year = {2022},
author = {Tang, P and He, W and Shao, Y and Liu, B and Huang, H and Liang, J and Liao, Q and Tang, Y and Mo, M and Zhou, Y and Li, H and Huang, D and Liu, S and Zeng, X and Qiu, X},
title = {Associations between prenatal multiple plasma metal exposure and newborn telomere length: Effect modification by maternal age and infant sex.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {315},
number = {},
pages = {120451},
doi = {10.1016/j.envpol.2022.120451},
pmid = {36270567},
issn = {1873-6424},
mesh = {Infant ; Infant, Newborn ; Humans ; Pregnancy ; Female ; *Arsenic ; Lead ; Maternal Age ; Prospective Studies ; Telomere ; Bayes Theorem ; Barium ; Cohort Studies ; China ; Maternal Exposure ; },
abstract = {Exposure to metals during pregnancy may affect maternal and infant health. However, studies on the combined effects of metals on the telomere length (TL) of newborns are limited. A prospective cohort study was conducted among 1313 mother-newborn pairs in the Guangxi Zhuang Birth Cohort. The concentrations of metals in maternal plasma during the first trimester were measured using inductively coupled plasma-mass spectrometry. We explored the associations between nine plasma metals and newborn TL using generalized linear models (GLMs), principal component analysis (PCA), quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR). The GLMs revealed the inverse association between plasma arsenic (percent change, -5.56%; 95% CI: -7.69%, -3.38%) and barium concentrations (-9.84%; 95% CI: -13.81%, -5.68%) and newborn TL. Lead levels were related to significant decreases in newborn TL only in females. The PCA revealed a negative association between the PC3 and newborn TL (-4.52%; 95% CI: -6.34%, -2.68%). In the BKMR, the joint effect of metals was negatively associated with newborn TL. Qgcomp indicated that each one-tertile increase in metal mixture levels was associated with shorter newborn TL (-9.39%; 95% CI: -14.32%, -4.18%). The single and joint effects of multiple metals were more pronounced among pregnant women carrying female fetuses and among pregnant women <28 years of age. The finding suggests that prenatal exposure to arsenic, barium, antimony, and lead and mixed metals may shorten newborn TLs. The relationship between metal exposures and newborn TL may exhibit heterogeneities according to infant sex and maternal age.},
}
@article {pmid36267401,
year = {2022},
author = {Wang, C and Alfano, R and Reimann, B and Hogervorst, J and Bustamante, M and De Vivo, I and Plusquin, M and Nawrot, TS and Martens, DS},
title = {Genetic regulation of newborn telomere length is mediated and modified by DNA methylation.},
journal = {Frontiers in genetics},
volume = {13},
number = {},
pages = {934277},
pmid = {36267401},
issn = {1664-8021},
abstract = {Telomere length at birth determines later life telomere length and potentially predicts ageing-related diseases. However, the genetic and epigenetic settings of telomere length in newborns have not been analyzed. In addition, no study yet has reported how the interplay between genetic variants and genome-wide cytosine methylation explains the variation in early-life telomere length. In this study based on 281 mother-newborn pairs from the ENVIRONAGE birth cohort, telomere length and whole-genome DNA methylation were assessed in cord blood and 26 candidate single nucleotide polymorphism related to ageing or telomere length were genotyped. We identified three genetic variants associated with cord blood telomere length and 57 cis methylation quantitative trait loci (cis-mQTLs) of which 22 mQTLs confirmed previous findings and 35 were newly identified. Five SNPs were found to have significant indirect effects on cord blood telomere length via the mediating CpGs. The association between rs911874 (SOD2) and newborn telomere length was modified by nearby DNA methylation indicated by a significant statistical interaction. Our results suggest that DNA methylation in cis might have a mediation or modification effect on the genetic difference in newborn telomere length. This novel approach warrants future follow-up studies that are needed to further confirm and extend these findings.},
}
@article {pmid36266468,
year = {2022},
author = {Asghar, M and Odeh, A and Fattahi, AJ and Henriksson, AE and Miglar, A and Khosousi, S and Svenningsson, P},
title = {Mitochondrial biogenesis, telomere length and cellular senescence in Parkinson's disease and Lewy body dementia.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {17578},
pmid = {36266468},
issn = {2045-2322},
mesh = {Humans ; *Parkinson Disease/genetics/complications ; *Lewy Body Disease/genetics ; *Dementia/etiology ; Organelle Biogenesis ; Levodopa ; Cellular Senescence/genetics ; DNA, Mitochondrial/genetics ; Telomere/genetics ; },
abstract = {Progressive age is the single major risk factor for neurodegenerative diseases. Cellular aging markers during Parkinson's disease (PD) have been implicated in previous studies, however the majority of studies have investigated the association of individual cellular aging hallmarks with PD but not jointly. Here, we have studied the association of PD with three aging hallmarks (telomere attrition, mitochondrial dysfunction, and cellular senescence) in blood and the brain tissue. Our results show that PD patients had 20% lower mitochondrial DNA copies but 26% longer telomeres in blood compared to controls. Moreover, telomere length in blood was positively correlated with medication (Levodopa Equivalent Daily Dose, LEDD) and disease duration. Similar results were found in brain tissue, where patients with Parkinson's disease (PD), Parkinson's disease dementia (PDD) and Dementia with Lewy Bodies (DLB) showed (46-95%) depleted mtDNA copies, but (7-9%) longer telomeres compared to controls. In addition, patients had lower mitochondrial biogenesis (PGC-1α and PGC-1β) and higher load of a cellular senescence marker in postmortem prefrontal cortex tissue, with DLB showing the highest effect among the patient groups. Our results suggest that mitochondrial dysfunction (copy number and biogenesis) in blood might be a valuable marker to assess the risk of PD. However, further studies with larger sample size are needed to evaluate these findings.},
}
@article {pmid36265486,
year = {2022},
author = {Yadav, T and Zhang, JM and Ouyang, J and Leung, W and Simoneau, A and Zou, L},
title = {TERRA and RAD51AP1 promote alternative lengthening of telomeres through an R- to D-loop switch.},
journal = {Molecular cell},
volume = {82},
number = {21},
pages = {3985-4000.e4},
pmid = {36265486},
issn = {1097-4164},
support = {R01 CA218856/CA/NCI NIH HHS/United States ; R35 CA263934/CA/NCI NIH HHS/United States ; },
mesh = {Telomere Homeostasis ; Telomere/genetics/metabolism ; *Telomerase/genetics/metabolism ; R-Loop Structures/genetics ; DNA Repair ; *RNA, Long Noncoding ; },
abstract = {Alternative lengthening of telomeres (ALT), a telomerase-independent process maintaining telomeres, is mediated by break-induced replication (BIR). RAD52 promotes ALT by facilitating D-loop formation, but ALT also occurs through a RAD52-independent BIR pathway. Here, we show that the telomere non-coding RNA TERRA forms dynamic telomeric R-loops and contributes to ALT activity in RAD52 knockout cells. TERRA forms R-loops in vitro and at telomeres in a RAD51AP1-dependent manner. The formation of R-loops by TERRA increases G-quadruplexes (G4s) at telomeres. G4 stabilization enhances ALT even when TERRA is depleted, suggesting that G4s act downstream of R-loops to promote BIR. In vitro, the telomeric R-loops assembled by TERRA and RAD51AP1 generate G4s, which persist after R-loop resolution and allow formation of telomeric D-loops without RAD52. Thus, the dynamic telomeric R-loops formed by TERRA and RAD51AP1 enable the RAD52-independent ALT pathway, and G4s orchestrate an R- to D-loop switch at telomeres to stimulate BIR.},
}
@article {pmid36263045,
year = {2022},
author = {Lai, TP and Verhulst, S and Dagnall, CL and Hutchinson, A and Spellman, SR and Howard, A and Katki, HA and Levine, JE and Saber, W and Aviv, A and Gadalla, SM},
title = {Decoupling blood telomere length from age in recipients of allogeneic hematopoietic cell transplant in the BMT-CTN 1202.},
journal = {Frontiers in immunology},
volume = {13},
number = {},
pages = {966301},
pmid = {36263045},
issn = {1664-3224},
support = {U01 AG066529/AG/NIA NIH HHS/United States ; KL2 TR003018/TR/NCATS NIH HHS/United States ; U01 AG066529/AG/NIA NIH HHS/United States ; U24 CA076518/CA/NCI NIH HHS/United States ; U10 HL069294/HL/NHLBI NIH HHS/United States ; U24 HL138660/HL/NHLBI NIH HHS/United States ; },
mesh = {Adult ; Aged ; Humans ; *Hematopoietic Stem Cell Transplantation ; Telomere/genetics ; Tissue Donors ; *Transplants ; },
abstract = {The age of allogeneic hematopoietic cell transplant (HCT) donors and their hematopoietic cell telomere length (TL) might affect recipients' outcomes. Our goals were to examine the possible effect of these donors' factors on the recipients' hematopoietic cell TL and quantify hematopoietic cell TL shortening in the critical first three-month post-HCT. We measured hematopoietic cell TL parameters in 75 recipient-donor pairs, from the Blood and Marrow Transplant Clinical Trials Network (protocol#1202), by Southern blotting (SB), the Telomeres Shortest Length Assay (TeSLA), and quantitative PCR (qPCR). Recipients' hematopoietic cell TL parameters post-HCT correlated with donors' age (p<0.001 for all methods), but not recipients' own age, and with donors' pre-HCT hematopoietic cell TL (p<0.0001 for all). Multivariate analyses showed that donors' hematopoietic cell TL pre-HCT, independent of donors' age, explained most of the variability in recipients' hematopoietic cell TL post-HCT (81% for SB, 56% for TeSLA, and 65% for qPCR; p>0.0001 for all). SB and TeSLA detected hematopoietic cell TL shortening in all recipients post-HCT (mean=0.52kb and 0.47kb, respectively; >15-fold the annual TL shortening in adults; p<0.00001 for both), but qPCR detected shortening only in 57.5% of recipients. TeSLA detected a buildup of post-HCT of telomeres <3 kb in 96% of recipients (p<0.0001). In conclusion, HCT decouples hematopoietic cell TL in the recipients from their own age to reflect the donors' age. The potential donors' age effect on outcomes of HCT might be partially mediated by short hematopoietic cell TL in older donors. qPCR-based TL measurement is suboptimal for detecting telomere shortening post-HCT.},
}
@article {pmid36254044,
year = {2022},
author = {Sung, MK and Koh, E and Kang, Y and Lee, JH and Park, JY and Kim, JY and Shin, SY and Kim, YH and Setou, N and Lee, US and Yang, HJ},
title = {Three months-longitudinal changes in relative telomere length, blood chemistries, and self-report questionnaires in meditation practitioners compared to novice individuals during midlife.},
journal = {Medicine},
volume = {101},
number = {41},
pages = {e30930},
pmid = {36254044},
issn = {1536-5964},
mesh = {Alanine Transaminase ; Aspartate Aminotransferases ; Glucose ; Humans ; Lipoproteins, HDL ; *Meditation/methods ; Self Report ; Surveys and Questionnaires ; Telomere ; Triglycerides ; },
abstract = {Aging accelerates during midlife. Researches have shown the health benefits of mind-body intervention (MBI). However, whether MBI is involved with aging process has not been well understood. In this study, we approach to examine the relations of MBI with this process by investigating an aging marker of the peripheral blood, blood chemistry, and self-report questionnaires. A quasi-experimental design was applied. Experienced MBI practitioners participated in a 3-month intensive meditation training, while the age, gender-matched MBI-naïve controls led a normal daily life. Measurements were taken at before and after the 3 months for relative telomere length (RTL), blood chemistry, and self-report questionnaires including items about sleep quality, somatic symptoms, depression, anxiety, stress, emotional intelligence (EI), and self-regulation. For RTL, the repeated measures analysis of variance showed a significant group*time interaction (P = .013) with a significant post hoc result (P = .030) within the control group: RTL was significantly reduced in the control while it was maintained in the meditation group. In repeated measures analysis of variance for blood chemistries, there were significant group differences between the groups in glucose and total protein. In the post hoc comparison analysis, at post measurements, the meditation group exhibited significantly lower values than the control group in both glucose and total protein. There were significant group-wise differences in the correlations of RTL with triglyceride (TG), high-density lipoprotein (HDL), glutamic oxaloacetic transaminase and glutamic pyruvic transaminase. Any of self-report results did not show significant changes in group*time interaction. However, there were group differences with significant (P < .05) or a tendency (.05 < P < .1) level. There were significant improvements in depression, stress and EI as well as tendencies of improvement in sleep quality and anxiety, in the meditation group compared to the control group. Our results suggest that meditation practice may have a potential to modify aging process in molecular cellular level combined with changes in psychological dimension.},
}
@article {pmid36253798,
year = {2022},
author = {Squassina, A and Meloni, A and Congiu, D and Bosganas, P and Patrinos, GP and Lin, R and Turecki, G and Severino, G and Ardau, R and Chillotti, C and Pisanu, C},
title = {Analysis on in vitro effect of lithium on telomere length in lymphoblastoid cell lines from bipolar disorder patients with different clinical response to long-term lithium treatment.},
journal = {Human genomics},
volume = {16},
number = {1},
pages = {45},
pmid = {36253798},
issn = {1479-7364},
mesh = {*Bipolar Disorder/diagnosis/drug therapy/genetics ; Cell Line ; Humans ; Lithium/pharmacology/therapeutic use ; Lithium Chloride/pharmacology/therapeutic use ; Lithium Compounds/pharmacology/therapeutic use ; *Neural Stem Cells/metabolism ; Telomere/genetics ; },
abstract = {BACKGROUND: It has been suggested that bipolar disorder (BD) is associated with clinical and biological features of accelerated aging. In our previous studies, we showed that long-term lithium treatment was correlated with longer leukocyte telomere length (LTL) in BD patients. A recent study explored the role of TL in BD using patients-derived lymphoblastoid cell lines (LCLs), showing that baseline TL was shorter in BD compared to controls and that lithium in vitro increased TL but only in BD. Here, we used the same cell system (LCLs) to explore if a 7-day treatment protocol with lithium chloride (LiCl) 1 mM was able to highlight differences in TL between BD patients clinically responders (Li-R; n = 15) or non-responders (Li-NR; n = 15) to lithium, and if BD differed from non-psychiatric controls (HC; n = 15).<br><br>RESULTS: There was no difference in TL between BD patients and HC. Moreover, LiCl did not influence TL in the overall sample, and there was no difference between diagnostic or clinical response groups. Likewise, LiCl did not affect TL in neural precursor cells from healthy donors.<br><br>CONCLUSIONS: Our findings suggest that a 7-day lithium treatment protocol and the use of LCLs might not represent a suitable approach to deepen our understanding on the role of altered telomere dynamics in BD as previously suggested by studies in vivo.},
}
@article {pmid36253342,
year = {2023},
author = {Hassani, MA and Murid, J and Yan, J},
title = {Regulator of telomere elongation helicase 1 gene and its association with malignancy.},
journal = {Cancer reports (Hoboken, N.J.)},
volume = {6},
number = {1},
pages = {e1735},
pmid = {36253342},
issn = {2573-8348},
mesh = {Humans ; DNA ; *Neoplasms/genetics ; *Telomere/genetics ; Tumor Microenvironment ; *DNA Helicases/genetics ; },
abstract = {BACKGROUND: With the progression of next-generation sequencing technologies, researchers have identified numerous variants of the regulator of telomere elongation helicase 1 (RTEL1) gene that are associated with a broad spectrum of phenotypic manifestations, including malignancies. At the molecular level, RTEL1 is involved in the regulation of the repair, replication, and transcription of deoxyribonucleic acid (DNA) and the maintenance of telomere length. RTEL1 can act both as a promotor and inhibitor of tumorigenesis. Here, we review the potential mechanisms implicated in the malignant transformation of tissues under conditions of RTEL1 deficiency or its aberrant overexpression.<br><br>RECENT FINDINGS: A major hemostatic challenge during RTEL1 dysfunction could arise from its unbalanced activity for unwinding guanine-rich quadruplex DNA (G4-DNA) structures. In contrast, RTEL1 deficiency leads to alterations in telomeric and genome-wide DNA maintenance mechanisms, ribonucleoprotein metabolism, and the creation of an inflammatory and immune-deficient microenvironment, all promoting malignancy. Additionally, we hypothesize that functionally similar molecules could act to compensate for the deteriorated functions of RTEL1, thereby facilitating the survival of malignant cells. On the contrary, RTEL1 over-expression was directed toward G4-unwinding, by promoting replication fork progression and maintaining intact telomeres, may facilitate malignant transformation and proliferation of various pre-malignant cellular compartments.<br><br>CONCLUSIONS: Therefore, restoring the equilibrium of RTEL1 functions could serve as a therapeutic approach for preventing and treating malignancies.},
}
@article {pmid36249518,
year = {2021},
author = {Albosale, AH and Mashkina, EV},
title = {Association of Relative Telomere Length and Risk of High Human Papillomavirus Load in Cervical Epithelial Cells.},
journal = {Balkan journal of medical genetics : BJMG},
volume = {24},
number = {2},
pages = {65-70},
pmid = {36249518},
issn = {1311-0160},
abstract = {Importunate high-risk HPV (HR-HPV) infection is the most common trigger for the cervical carcinogenesis process. In this respect, the presence of cancer can be imputed to telomere lengthening or shortening. This paper explores the possible correlation between relative telomere length and viral load in two groups of women, namely: those with high-risk HPV infection and those who do not have this infection. Thus, samples comprising of 50 women in each group were evaluated for this research. The Amplisens HPV HCR screen-titre-FRT PCR kite was employed for quantitative analysis. Relative telomere length was quantified by real-time PCR. In each of the two HPV load groups, there was no correlation between age and telomere length. Telomere shortening was found in the cervical cell samples of women with high HPV loads, compared with women in the control group. Telomere shortening is associated with elevated HPV loads.},
}
@article {pmid36248806,
year = {2022},
author = {Ye, M and Wang, Y and Zhan, Y},
title = {Genetic association of leukocyte telomere length with Graves' disease in Biobank Japan: A two-sample Mendelian randomization study.},
journal = {Frontiers in immunology},
volume = {13},
number = {},
pages = {998102},
pmid = {36248806},
issn = {1664-3224},
mesh = {Biological Specimen Banks ; Genome-Wide Association Study ; *Graves Disease/genetics ; Humans ; Japan/epidemiology ; Leukocytes ; *Mendelian Randomization Analysis ; Telomere ; },
abstract = {BACKGROUND: Telomere length (TL) has been recognized to be fundamental to the risk of autoimmune disorders. However, the role of leukocyte TL in Graves' disease has not yet been fully elucidated. In the study, we exploited the two-sample Mendelian randomization (MR) design to evaluate the causal effect of leukocyte TL on the risk of Graves' disease.<br><br>METHODS: Genome-wide association study (GWAS) data of leukocyte TL from the Singapore Chinese Health Study (SCHS) cohort and Graves' disease from Biobank Japan (BBJ, 2176 cases and 210,277 controls) were analyzed. Nine single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for TL. We used the inverse variance weighted (IVW) approach as the main estimator and MR-Egger regression, weighted median, simple mode, and weighed mode methods as complementary estimators. Horizontal pleiotropy was assessed using the intercept from MR-Egger.<br><br>RESULTS: The analysis demonstrated that genetically predicted longer leukocyte TL was causally associated with a lower risk of Graves' disease using the IVW method (odds ratio [OR]: 1.64, 95% confidence interval [CI]: 1.23-2.17, P=2.27e-04, and other complementary MR approaches&#xa0;achieved similar results. The intercept from the MR-Egger analysis provided no noticeable evidence of horizontal pleiotropy (&#x3b2;=0.02, P=0.641).&#xa0;MR-PRESSO method reported no outliers (P=0.266).<br><br>CONCLUSIONS: Our results provided evidence to support a genetic predisposition to shorter leukocyte TL with an increased risk of Graves' disease. Further studies are warranted to explore the mechanism underlying the association.},
}
@article {pmid36235538,
year = {2022},
author = {Valera-Gran, D and Prieto-Botella, D and Hurtado-Pomares, M and Baladia, E and Petermann-Rocha, F and Sánchez-Pérez, A and Navarrete-Muñoz, EM},
title = {The Impact of Foods, Nutrients, or Dietary Patterns on Telomere Length in Childhood and Adolescence: A Systematic Review.},
journal = {Nutrients},
volume = {14},
number = {19},
pages = {},
pmid = {36235538},
issn = {2072-6643},
support = {VIPROY21/8//Miguel Hernandez University/ ; GVA/2021/191//Generalitat Valenciana/ ; PI18/00825//Instituto de Salud Carlos III/ ; },
mesh = {Animals ; *Antioxidants ; *Diet ; Feeding Behavior ; Monosaccharides ; Nutrients ; Telomere ; Vegetables ; },
abstract = {Environmental factors such as diet can affect telomere length (TL) dynamics. However, the role that children's and adolescents' diets play in maintaining TL is not well understood. Thus, we conducted a systematic review to examine the association between the intake of nutrients, foods, food groups, and/or dietary patterns and TL in childhood and adolescence. Following the PRISMA guidelines, we searched MEDLINE via PubMed, Embase, and Cochrane databases and additional registers and methods. The five selected studies were cross-sectional and conducted in children and adolescents aged 2 to 18 years. The main results suggest that a higher consumption of fish, nuts and seeds, fruits and vegetables, green leafy and cruciferous vegetables, olives, legumes, polyunsaturated fatty acids, and an antioxidant-rich diet might positively affect TL. On the contrary, a higher intake of dairy products, simple sugar, sugar-sweetened beverages, cereals, especially white bread, and a diet high in glycaemic load were factors associated with TL shortening. To our knowledge, this is the first systematic review examining the impact of dietary intake factors on TL in childhood and adolescence. Although limited, these results are consistent with previous studies in different adult populations. Further research is needed to ascertain potential nutritional determinants of TL in childhood and adolescence.},
}
@article {pmid36233645,
year = {2022},
author = {Zia, S and Khan, N and Tehreem, K and Rehman, N and Sami, R and Baty, RS and Tayeb, FJ and Almashjary, MN and Alsubhi, NH and Alrefaei, GI and Shahid, R},
title = {Transcriptomic Analysis of Conserved Telomere Maintenance Component 1 (CTC1) and Its Association with Leukemia.},
journal = {Journal of clinical medicine},
volume = {11},
number = {19},
pages = {},
pmid = {36233645},
issn = {2077-0383},
abstract = {Telomere length (TEL) regulation is important for genome stability and is governed by the coordinated role of shelterin proteins, telomerase (TERT), and CST (CTC1/OBFC1/TEN1) complex. Previous studies have shown the association of telomerase expression with the risk of acute lymphoblastic leukemia (ALL). However, no data are available for CST association with the ALL. The current pilot study was designed to evaluate the CST expression levels in ALL. In total, 350 subjects were recruited, including 250 ALL cases and 100 controls. The subjects were stratified by age and categorized into pediatrics (1-18 years) and adults (19-54 years). TEL and expression patterns of CTC1, OBFC1, and TERT genes were determined by qPCR. The univariable logistic regression analysis was performed to determine the association of gene expression with ALL, and the results were adjusted for age and sex in multivariable analyses. Pediatric and adult cases did not reflect any change in telomere lengths relative to controls. However, expression of CTC1, OBFC1, and TERT genes were induced among ALL cases. Multivariable logistic regression analyses showed association of CTC1 with ALL in pediatric [β estimate (standard error (SE)= -0.013 (0.007), p = 0.049, and adults [0.053 (0.023), p = 0.025]. The association of CTC1 remained significant when taken together with OBFC1 and TERT in a multivariable model. Furthermore, CTC1 showed significant association with B-cell ALL [-0.057(0.017), p = 0.002) and T-cell ALL [-0.050 (0.018), p = 0.008] in pediatric group while no such association was noted in adults. Together, our findings demonstrated that telomere modulating genes, particularly CTC1, are strongly associated with ALL. Therefore, CTC1 can potentially be used as a risk biomarker for the identification of ALL in both pediatrics and adults.},
}
@article {pmid36231453,
year = {2022},
author = {Chen, XY and Lo, CKM and Chan, KL and Leung, WC and Ip, P},
title = {Association between Childhood Exposure to Family Violence and Telomere Length: A Meta-Analysis.},
journal = {International journal of environmental research and public health},
volume = {19},
number = {19},
pages = {},
pmid = {36231453},
issn = {1660-4601},
mesh = {Child ; *Domestic Violence ; Humans ; *Intimate Partner Violence ; Telomere ; },
abstract = {The aims of this meta-analysis were to examine the association between childhood exposure to family violence and telomere length and the moderating variables that influence this association. Relevant works published on or before 1st September 2022 were identified through a search in five major databases in English and 19 articles (N = 18,977) finally met the inclusion criteria. A meta-analysis was conducted to compute the pooled effect size (correlation; r), and moderator analyses were performed using a random effects meta-analytic model. The studies yielded a significant inverse association between childhood exposure to family violence and telomere length, with a small effect size (r = -0.038, 95% CI [-0.070, -0.005], p = 0.025). Furthermore, the strength of this association was stronger in studies examining the co-occurrence of multiple types of violence than in those examining just one type (Q = 8.143, p = 0.004). These findings suggested that victims' telomere length may be negatively influenced by childhood exposure to family violence and that such impairment appears to be stronger for those who are exposed to multiple types of violence. Future studies are necessary to examine the moderating and mediating factors underlying the association between childhood exposure to family violence and telomere length.},
}
@article {pmid36230999,
year = {2022},
author = {Shokr, H and Lush, V and Dias, IH and Ekárt, A and De Moraes, G and Gherghel, D},
title = {The Use of Retinal Microvascular Function and Telomere Length in Age and Blood Pressure Prediction in Individuals with Low Cardiovascular Risk.},
journal = {Cells},
volume = {11},
number = {19},
pages = {},
pmid = {36230999},
issn = {2073-4409},
mesh = {Adult ; Aged ; Biomarkers ; Blood Pressure/physiology ; *Cardiovascular Diseases ; Heart Disease Risk Factors ; Humans ; Middle Aged ; Risk Factors ; Telomere ; },
abstract = {Ageing represents a major risk factor for many pathologies that limit human lifespan, including cardiovascular diseases. Biological ageing is a good biomarker to assess early individual risk for CVD. However, finding good measurements of biological ageing is an ongoing quest. This study aims to assess the use retinal microvascular function, separate or in combination with telomere length, as a predictor for age and systemic blood pressure in individuals with low cardiovascular risk. In all, 123 healthy participants with low cardiovascular risk were recruited and divided into three groups: group 1 (less than 30 years old), group 2 (31-50 years old) and group 3 (over 50 years old). Relative telomere length (RTL), parameters of retinal microvascular function, CVD circulatory markers and blood pressure (BP) were measured in all individuals. Symbolic regression- analysis was used to infer chronological age and systemic BP measurements using either RTL or a combination of RTL and parameters for retinal microvascular function. RTL decreased significantly with age (p = 0.010). There were also age-related differences between the study groups in retinal arterial time to maximum dilation (p = 0.005), maximum constriction (p = 0.007) and maximum constriction percentage (p = 0.010). In the youngest participants, the error between predicted versus actual values for the chronological age were smallest in the case of using both retinal vascular functions only (p = 0.039) or the combination of this parameter with RTL (p = 0.0045). Systolic BP was better predicted by RTL also only in younger individuals (p = 0.043). The assessment of retinal arterial vascular function is a better predictor than RTL for non-modifiable variables such as age, and only in younger individuals. In the same age group, RTL is better than microvascular function when inferring modifiable risk factors for CVDs. In older individuals, the accumulation of physiological and structural biological changes makes such predictions unreliable.},
}
@article {pmid36229075,
year = {2022},
author = {Yang, Z and Sharma, K and de Lange, T},
title = {TRF1 uses a noncanonical function of TFIIH to promote telomere replication.},
journal = {Genes &amp; development},
volume = {36},
number = {17-18},
pages = {956-969},
pmid = {36229075},
issn = {1549-5477},
support = {R01 AG016642/AG/NIA NIH HHS/United States ; R35 CA210036/CA/NCI NIH HHS/United States ; R56 AG016642/AG/NIA NIH HHS/United States ; },
mesh = {*Telomeric Repeat Binding Protein 1 ; *Telomere/genetics/metabolism ; DNA Replication/genetics ; DNA Helicases/genetics/metabolism ; DNA/metabolism ; },
abstract = {Telomeric DNA challenges the replisome and requires TRF1 for efficient duplication. TRF1 recruits the BLM helicase, but BLM loss does not explain the extensive telomere fragility, ATR signaling, and sister telomere associations (STAs) induced by TRF1 deletion. Here, we document that Helix2 of the TRFH domain and Helix1 of the Myb domain of TRF1 are required for efficient telomere replication. Mutation of both helices generated a TRF1 separation-of-function mutant (TRF1-E83K/LW-TI) that induced severe telomere replication defects but no ATR signaling or STAs. We identified the transcription and nucleotide excision repair (NER) factor TFIIH as a critical effector of TRF1. Loss of TFIIH subunits, but no other NER factors, caused the same telomere replication phenotypes as the TRF1-E83K/LW-TI mutant independent of the effects on TRF1 expression. TFIIH subunits coimmunoprecipitated with wild-type TRF1 but not with TRF1-E83K/LW-TI. These results establish that the major mechanism by which TRF1 ensures telomere replication involves a noncanonical function of TFIIH.},
}
@article {pmid36222081,
year = {2023},
author = {Sheikh-Wu, SF and Liang, Z and Downs, CA},
title = {The Relationship Between Telomeres, Cognition, Mood, and Physical Function: A Systematic Review.},
journal = {Biological research for nursing},
volume = {25},
number = {2},
pages = {227-239},
doi = {10.1177/10998004221132287},
pmid = {36222081},
issn = {1552-4175},
mesh = {Humans ; *Oxidative Stress ; *Diet ; Risk Factors ; Cognition/physiology ; Telomere ; },
abstract = {Background and Purpose: Cognitive, affective, and physical symptoms and alterations in their function are seen across chronic illnesses. Data suggest that environmental, psychological, and physiological factors contribute to symptom experience, potentially through loss of telomeres (telomere attrition), structures at the ends of chromosomes. Telomere length is affected by many factors including environmental (e.g., exercise, diet, smoking) and physiological (e.g., response to stress), as well as from oxidative damage and inflammation that occurs in many disease processes. Moreover, telomere attrition is associated with chronic disease (cancer, cardiovascular disease, Alzheimer's disease) and predicts higher morbidity and mortality rates. However, findings are inconsistent among telomere roles and relationships with health outcomes. This article aims to synthesize the current state-of-the-science of telomeres and their relationship with cognitive, affective, and physical function and symptoms. Method: A comprehensive literature search was performed in two databases: CINAHL and PUBMED. A total of 33 articles published between 2000 and 2022 were included in the final analysis. Results: Telomere attrition is associated with various changes in cognitive, affective, and physical function and symptoms. However, findings are inconsistent. Interventional studies (e.g., meditation and exercise) may affect telomere attrition, potentially impacting health outcomes. Conclusion: Nursing research and practice are at the forefront of furthering the understanding of telomeres and their relationships with cognitive, affective, and physical function and symptoms. Future interventions targeting modifiable risk factors may be developed to improve health outcomes across populations.},
}
@article {pmid36221106,
year = {2022},
author = {Sanchez, M and Kannengiesser, C and Hoang, S and Potier, L and Fumeron, F and Venteclef, N and Scheen, A and Gautier, JF and Hadjadj, S and Marre, M and Roussel, R and Mohammedi, K and Velho, G},
title = {Leukocyte telomere length, allelic variations in related genes and risk of coronary heart disease in people with long-standing type 1 diabetes.},
journal = {Cardiovascular diabetology},
volume = {21},
number = {1},
pages = {206},
pmid = {36221106},
issn = {1475-2840},
mesh = {Adaptor Proteins, Signal Transducing/genetics ; Adult ; *Coronary Disease/diagnosis/epidemiology/genetics ; Cytoskeletal Proteins/genetics ; *Diabetes Mellitus, Type 1/diagnosis/epidemiology/genetics ; Humans ; Leukocytes ; *Myocardial Infarction/complications ; Prospective Studies ; Telomere/genetics ; },
abstract = {BACKGROUND: Type 1 diabetes is associated with accelerated vascular aging and advanced atherosclerosis resulting in increased rates of cardiovascular disease and premature death. We evaluated associations between Leukocyte telomere length (LTL), allelic variations (SNPs) in LTL-related genes and the incidence of coronary heart disease (CHD) in adults with long-standing type 1 diabetes.<br><br>METHODS: We assessed associations of LTL, measured at baseline by RT-PCR, and of SNPs in 11 LTL-related genes with the risk of coronary heart disease (CHD: myocardial infarction or coronary revascularization) and all-cause death during follow-up in two multicenter French-Belgian prospective cohorts of people with long-standing type 1 diabetes.<br><br>RESULTS: In logistic and Cox analyses, the lowest tertile of LTL distribution (short telomeres) at baseline was associated with the prevalence of myocardial infarction at baseline and with increased risk of CHD (Hazard ratio 3.14 (1.39-7.70), p&#x2009;=&#x2009;0.005, for shorter vs longer tertile of LTL) and all-cause death (Hazard ratio 1.63 (95% CI 1.04-2.55), p&#x2009;=&#x2009;0.03, for shorter vs combined intermediate and longer tertiles of LTL) during follow-up. Allelic variations in six genes related to telomere biology (TERC, NAF1, TERT, TNKS, MEN1 and BICD1) were also associated with the incidence of CHD during follow-up. The associations were independent of sex, age, duration of diabetes, and a range of relevant confounding factors at baseline.<br><br>CONCLUSIONS: Our results suggest that short LTL is an independent risk factor for CHD in people with type 1 diabetes.},
}
@article {pmid36219936,
year = {2022},
author = {Hatse, S and Serena, M and Vulsteke, C and Punie, K and Neven, P and Smeets, A and Laenen, A and Wildiers, H},
title = {Impact of baseline telomere length on survival and chemotherapy related toxicity in breast cancer patients receiving (neo)adjuvant anthracycline containing chemotherapy.},
journal = {Translational oncology},
volume = {26},
number = {},
pages = {101551},
pmid = {36219936},
issn = {1936-5233},
abstract = {PURPOSE: The aim of this study is to assess baseline mean leukocyte telomere length (TL) as a potential predictive factor for chemotherapy toxicity and a prognostic marker for long-term outcome in early breast cancer (BC) patients.<br><br>METHODS: 445 BC patients were selected, diagnosed between 2007 and 2010 with early BC and treated with (neo)adjuvant fluorouracil, epirubicin and cyclophosphamide (FEC) or with FEC and Docetaxel (FEC-D). RT-qPCR was performed on germline DNA samples collected at diagnosis before any treatment, to measure mean leukocyte TL. Uni- and multivariable logistic regression or Cox proportional hazard regression analyses were carried out to assess correlation between baseline TL and toxicity parameters (derived from the medical chart) or longer-term outcome.<br><br>RESULTS: Baseline TL correlated with age as expected (p&#xa0;=&#xa0;0.005), but not with febrile neutropenia (n&#xa0;=&#xa0;97), left ventricular ejection fraction >10% decrease (n&#xa0;=&#xa0;17) nor other toxicity endpoints measured (all p&#xa0;>&#xa0;0.05). TL was neither associated with overall survival, breast cancer specific survival or distant disease-free survival (all p&#xa0;>&#xa0;0.05).<br><br>CONCLUSIONS: Baseline TL is not associated with chemotherapy-related toxicity nor long-term outcome in BC patients.},
}
@article {pmid36218957,
year = {2023},
author = {Vaquero-Sedas, MI and Vega-Palas, MA},
title = {Epigenetic nature of Arabidopsis thaliana telomeres.},
journal = {Plant physiology},
volume = {191},
number = {1},
pages = {47-55},
pmid = {36218957},
issn = {1532-2548},
mesh = {*Arabidopsis/genetics ; Epigenesis, Genetic ; Telomere/genetics ; Heterochromatin/genetics ; },
abstract = {The epigenetic features of defined chromosomal domains condition their biochemical and functional properties. Therefore, there is considerable interest in studying the epigenetic marks present at relevant chromosomal loci. Telomeric regions, which include telomeres and subtelomeres, have been traditionally considered heterochromatic. However, whereas the heterochromatic nature of subtelomeres has been widely accepted, the epigenetic status of telomeres remains controversial. Here, we studied the epigenetic features of Arabidopsis (Arabidopsis thaliana) telomeres by analyzing multiple genome-wide ChIP-seq experiments. Our analyses revealed that Arabidopsis telomeres are not significantly enriched either in euchromatic marks like H3K4me2, H3K9ac, and H3K27me3 or in heterochromatic marks such as H3K27me1 and H3K9me2. Thus, telomeric regions in Arabidopsis have a bimodal chromatin organization with telomeres lacking significant levels of canonical euchromatic and heterochromatic marks followed by heterochromatic subtelomeres. Since heterochromatin is known to influence telomere function, the heterochromatic modifications present at Arabidopsis subtelomeres could play a relevant role in telomere biology.},
}
@article {pmid36216345,
year = {2023},
author = {Baser, E and Inandiklioglu, N and Aydogan Kırmızı, D and Ercan, F and Caniklioğlu, A and Kara, M and Onat, T and Yalvac, ES},
title = {Placental and Umbilical Cord Blood Oxidative Stress Level and Telomere Homeostasis in Early Onset Severe Preeclampsia.},
journal = {Zeitschrift fur Geburtshilfe und Neonatologie},
volume = {227},
number = {2},
pages = {112-119},
doi = {10.1055/a-1938-0010},
pmid = {36216345},
issn = {1439-1651},
mesh = {Infant, Newborn ; Pregnancy ; Humans ; Female ; *Placenta ; Telomere Homeostasis ; *Pre-Eclampsia/diagnosis ; Fetal Blood ; Oxidative Stress ; },
abstract = {OBJECTIVE: Although the etiopathogenesis of preeclampsia (PE) is unknown, evidence suggests that it may be associated with increased oxidative stress. Studies have shown that oxidative stress can affect DNA fragments called telomeres. However, the interactions of PE, oxidative stress, and telomere length are not clearly known. This study aims to evaluate the oxidative/anti-oxidative stress balance in the placenta and umbilical cord and examine the effect of oxidative stress on telomeres.<br><br>MATERIALS-METHOD: Cord blood and placental samples were collected from 27 pregnant women with severe PE (28[0/7]-33[6/7] gestational weeks) and 53 healthy pregnant women. Telomere length (TL) was measured by real-time PCR in the cord blood and placenta tissue. Total antioxidant status (TAS) and total oxidant status (TOS) levels were measured in the cord blood and placenta tissue using a colorimetric method.<br><br>RESULTS: No significant differences were found between groups regarding age, BMI, gravida, parity, and newborn gender (p>0.05). Cord blood and placental TL of PE patients were significantly shorter than the control group, while cord blood and placental TAS and TOS levels were higher (p<0.05). The results of a multivariate logistic regression analysis showed that the level of placental TOS in PE patients (OR=1.212, 95% CI=1.068-1.375) was an independent risk factor affecting PE.<br><br>CONCLUSION: This study found that oxidative stress is an independent risk factor in the development of PE and shortens TL in both placental and umbilical cord blood. Future research on telomere homeostasis may offer a new perspective for the treatment of PE.},
}
@article {pmid36214766,
year = {2023},
author = {Liang, Z and Saugar, EE and Alamian, A and Ferreira, T and Downs, CA},
title = {Changes in Telomere Length and Indicators of Oxidative Stress in Critically Ill Mechanically Ventilated Adults - A Pilot Study.},
journal = {Biological research for nursing},
volume = {25},
number = {2},
pages = {282-288},
doi = {10.1177/10998004221133395},
pmid = {36214766},
issn = {1552-4175},
mesh = {Humans ; Adult ; Male ; Middle Aged ; Aged ; Female ; Pilot Projects ; *Critical Illness ; *Respiration, Artificial ; Leukocytes, Mononuclear ; Glutathione Disulfide ; Intensive Care Units ; Telomere ; Oxidative Stress ; },
abstract = {BACKGROUND: Telomeres are structures at the end of chromosomes that shorten with each cell division. The purpose of this pilot project is to report changes in telomere length (T/S ratio), indicators of oxidative stress (serum protein carbonyl, vitamin C, GSH:GSSG, and total antioxidant capacity) from Intensive Care Unit (ICU) admission to ICU discharge, and to explore their association with ICU-related morbidities among critically ill mechanically ventilated adults.<br><br>METHODS: Blood was collected from mechanically ventilated patients (n = 25) at enrollment and within 48 hours of ICU discharge. Telomere length from peripheral blood mononuclear cells (PBMCs) was determined using RTqPCR. ELISAs were used to measure indicators of oxidative stress. Descriptive analysis, paired t-tests, and Pearson's correlations were performed.<br><br>RESULTS: Mean age was 62.0 &#xb1; 12.3&#xa0;years, 28.6% were male, and 76.2% were White with disease severity using APACHE III (74.6 &#xb1; 24.6) and SOFA (7.6 &#xb1; 3.2). Mean T/S ratios shortened (ICU: 0.712, post-ICU: 0.683, p < 0.001, n = 19) and serum protein carbonyl increased (ICU: 7437&#xa0;nmol/mg &#xb1; 3328, post-ICU: 10,254&#xa0;nmol/mg &#xb1; 3962, p < 0.005) as did the oxidative stress index (protein carbonyl/GSH:GSSG, ICU: 1049.972 &#xb1; 420.923, post-ICU: 1348.971 &#xb1; 417.175, p = 0.0104). T/S ratio was positively associated with APACHE III scores (ICU: r = 0.474, post-ICU: r = 0.628, p < 0.05).<br><br>CONCLUSIONS: Pilot findings suggest that critical illness significantly correlates with telomere attrition, perhaps due to increased oxidative stress. Future larger and longitudinal studies investigating mechanisms of telomere attrition and associations with clinical outcomes are needed to identify potential modifiable factors for subsequent intervention to improve outcomes for critically ill patients.},
}
@article {pmid36214364,
year = {2023},
author = {Hope, SF and Angelier, F and Ribout, C and Groffen, J and Kennamer, RA and Hopkins, WA},
title = {Warmer incubation temperatures and later lay-orders lead to shorter telomere lengths in wood duck (Aix sponsa) ducklings.},
journal = {Journal of experimental zoology. Part A, Ecological and integrative physiology},
volume = {339},
number = {1},
pages = {101-111},
doi = {10.1002/jez.2659},
pmid = {36214364},
issn = {2471-5646},
mesh = {Animals ; *Ducks/genetics ; Temperature ; *Embryonic Development/physiology ; Hot Temperature ; Telomere ; },
abstract = {The environment that animals experience during development shapes phenotypic expression. In birds, two important aspects of the early-developmental environment are lay-order sequence and incubation. Later-laid eggs tend to produce weaker offspring, sometimes with compensatory mechanisms to accelerate their growth rate to catch-up to their siblings. Further, small decreases in incubation temperature slow down embryonic growth rates and lead to wide-ranging negative effects on many posthatch traits. Recently, telomeres, noncoding DNA sequences at the end of chromosomes, have been recognized as a potential proxy for fitness because longer telomeres are positively related to lifespan and individual quality in many animals, including birds. Although telomeres appear to be mechanistically linked to growth rate, little is known about how incubation temperature and lay-order may influence telomere length. We incubated wood duck (Aix sponsa) eggs at two ecologically-relevant temperatures (34.9°C and 36.2°C) and measured telomere length at hatch and 1 week after. We found that ducklings incubated at the lower temperature had longer telomeres than those incubated at the higher temperature both at hatch and 1 week later. Further, we found that later-laid eggs produced ducklings with shorter telomeres than those laid early in the lay-sequence, although lay-order was not related to embryonic developmental rate. This study contributes to our broader understanding of how parental effects can affect telomere length early in life. More work is needed to determine if these effects on telomere length persist until adulthood, and if they are associated with effects on fitness in this precocial species.},
}
@article {pmid36213488,
year = {2022},
author = {Bürgin, D and Clemens, V and Varghese, N and Eckert, A and Huber, M and Bruttin, E and Boonmann, C and Unternährer, E and O'Donovan, A and Schmid, M},
title = {Adverse and traumatic exposures, posttraumatic stress disorder, telomere length, and hair cortisol - Exploring associations in a high-risk sample of young adult residential care leavers.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {26},
number = {},
pages = {100524},
pmid = {36213488},
issn = {2666-3546},
abstract = {BACKGROUND: Childhood adversities (CAs), potentially traumatic exposures (PTEs), and posttraumatic stress disorder (PTSD) are known to increase the risk for poor health outcomes, including diseases of aging and early mortality. Telomere length (TL) and hair cortisol concentrations (HCC) are biomarkers known to be associated with CA and PTEs, and PTSD, but there is considerable heterogeneity in findings.<br><br>OBJECTIVES: This study aims to investigate the association of CAs, PTEs, and PTSD with TL and HCC in a high-risk sample of young adults who were previously placed in youth residential care institutions throughout Switzerland.<br><br>METHOD: Our sample includes 130 participants (30.8% women, M Age&#xa0;=&#xa0;26.5&#xa0;&#xb1;&#xa0;3.7 years) with previous youth residential care placements (MPlacements=&#xa0;3.9). CAs and PTEs, as well as PTSD, were assessed with self-reported questionnaires and semi-structured clinical interviews. Immune cell TL was measured with quantitative polymerase chain reaction (qPCR) in whole blood. Hair samples were collected for HCC measurement and assayed with high-sensitivity ELISA. Multivariate regression models were fitted to describe the associations between CAs, PTEs, and PTSD with TL and HCC, adjusting for covariates.<br><br>RESULTS: In our high-risk sample, a higher burden of CAs, PTEs, Criterion A trauma, and PTSD was associated with longer TL. PTEs, Criterion A trauma, and PTSD were associated with lower HCC, however no significant associations between CAs and HCC were found. The magnitude of these effects varied depending on the dimensional or categorical nature of the stress-phenotype and the specific measure used.<br><br>CONCLUSIONS: Our findings are in contrast with many, but not all, previous studies of associations between adversity and both TL and HCC. For instance, our findings are in line with other studies that find a state of hypocortisolism in PTSD. Better measurement of adversities and trauma, multisystem biomarker approaches, and more research in larger high-risk samples at the upper end of the adversity-continuum is warranted.},
}
@article {pmid36210421,
year = {2022},
author = {Xu, L and Qiu, Z and Cong, YS},
title = {Comparison of Telomere Length between Buccal Cells and Blood Cells.},
journal = {Bulletin of experimental biology and medicine},
volume = {173},
number = {5},
pages = {677-679},
pmid = {36210421},
issn = {1573-8221},
mesh = {*Blood Cells ; DNA/genetics ; Humans ; *Mouth Mucosa ; Reproducibility of Results ; Telomere/genetics ; Telomere Homeostasis ; },
abstract = {Telomere length (TL) in blood cells is commonly used as a proxy for TL in other tissue types. The source of DNA of adequate quality and quantity is important for TL analysis. Compared to blood cells, buccal cells easy for genomic DNA preparation would facilitate the rapid and reliable TL analysis. However, the feasibility of buccal cells for TL analysis remains yet unestablished. We characterized TL of buccal cells and blood cells collected from 52 individuals using buccal cell swabs and fingertip sticks. Relative TL (RTL) determined by quantitative PCR showed that there is a strong correlation between buccal RTL and blood RTL (r=0.877, p<0.001), suggesting that buccal cells are adequate sources of DNA for TL analysis. The validity of sampling using buccal cell swabs provides simple operation and good reproducibility for TL analysis, that overcomes the discomfort and risk of infection caused by blood sampling.},
}
@article {pmid36208022,
year = {2022},
author = {Olsson, M and Bererhi, B and Miller, E and Schwartz, T and Rollings, N and Lindsay, W and Wapstra, E},
title = {Inbreeding effects on telomeres in hatchling sand lizards (Lacerta agilis): An optimal family affair?.},
journal = {Molecular ecology},
volume = {31},
number = {24},
pages = {6605-6616},
pmid = {36208022},
issn = {1365-294X},
mesh = {Pregnancy ; Animals ; Female ; Humans ; *Inbreeding ; *Lizards/genetics ; Telomere/genetics ; Telomere Shortening ; Genotype ; },
abstract = {Telomeres are nucleotide-protein caps, predominantly at the ends of Metazoan linear chromosomes, showing complex dynamics with regard to their lengthening and shortening through life. Their complexity has entertained the idea that net telomere length and attrition could be valuable biomarkers of phenotypic and genetic quality of their bearer. Intuitively, those individuals could be more heterozygous and, hence, less inbred. However, some inbred taxa have longer, not shorter, telomeres. To understand the role of inbreeding in this complex scenario we need large samples across a range of genotypes with known maternity and paternity in telomere-screened organisms under natural conditions. We assessed the effects of parental and hatchling inbreeding on telomere length in >1300 offspring from >500 sires and dams in a population of sand lizards (Lacerta agilis). Maternal and paternal ID and their interactions predict hatchling telomere length at substantial effect sizes (R[2] > .50). Deviation from mean maternal heterozygosity statistically predicts shorter offspring telomeres but this only when sibship is controlled for by paternal ID, and then is still limited (R[2] = .06). Raw maternal heterozygosity scores, ignoring absolute deviation from the mean, explained 0.07% of the variance in hatchling telomere length. In conclusion, inbreeding is not a driver of telomere dynamics in the sand lizard (Lacerta agilis) study system.},
}
@article {pmid36206470,
year = {2022},
author = {Miki, A and Matsuda, Y and Aida, J and Watanabe, J and Sanada, Y and Sakuma, Y and Lefor, AK and Fukushima, N and Sata, N and Arai, T and Takubo, K and Ishiwata, T},
title = {Telomere Attrition in Intraductal Papillary Mucinous Neoplasms of the Pancreas Associated With Carcinogenesis and Aging.},
journal = {Pancreas},
volume = {51},
number = {6},
pages = {678-683},
doi = {10.1097/MPA.0000000000002081},
pmid = {36206470},
issn = {1536-4828},
mesh = {*Adenocarcinoma, Mucinous/pathology ; Aging ; Carcinogenesis ; *Carcinoma, Pancreatic Ductal/pathology ; *Carcinoma, Papillary/pathology ; Humans ; In Situ Hybridization, Fluorescence ; Pancreas/pathology ; *Pancreatic Intraductal Neoplasms/pathology ; *Pancreatic Neoplasms/pathology ; Telomere/genetics ; },
abstract = {OBJECTIVES: It is challenging to preoperatively distinguish malignant and benign forms of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. The aims of this study were to investigate whether telomere length is associated with pathological grade of IPMNs and age and to clarify the utility of telomere length as a marker to identify malignant IPMNs.<br><br>METHODS: Pancreas tissue was obtained from 28 patients after resection. We measured the telomere lengths of tumor cells in IPMNs and normal duct cells by quantitative fluorescence in situ hybridization. The association of normalized telomere-centromere ratio (NTCR) to pathological grade of IPMNs and age were determined.<br><br>RESULTS: The NTCR showed a gradual decrease with increasing pathological grade of IPMNs. The NTCR in intermediate- and high-grade dysplasia and adenocarcinoma lesions was significantly shorter than in normal pancreatic ducts (P < 0.05). In multivariate analysis, telomere length was most associated with carcinogenesis. When the cutoff value of NTCR was set to 0.74, the sensitivity for detection of high-grade dysplasia and adenocarcinoma was 82.8%, with a specificity of 87.5%.<br><br>CONCLUSIONS: Telomere shortening occurs with carcinogenesis and aging. A significant reduction of telomere length in IPMNs may be useful for surgical decision making.},
}
@article {pmid36205590,
year = {2022},
author = {Madsen, T and Klaassen, M and Raven, N and Dujon, AM and Jennings, G and Thomas, F and Hamede, R and Ujvari, B},
title = {Transmissible cancer and longitudinal telomere dynamics in Tasmanian devils (Sarcophilus harrisii).},
journal = {Molecular ecology},
volume = {31},
number = {24},
pages = {6531-6540},
pmid = {36205590},
issn = {1365-294X},
mesh = {Animals ; Animals, Wild/genetics ; *Facial Neoplasms/epidemiology/genetics/pathology ; *Marsupialia/genetics ; Telomere/genetics ; },
abstract = {A plethora of intrinsic and environmental factors have been shown to influence the length of telomeres, the protector of chromosome ends. Despite the growing interest in infection-telomere interactions, there is very limited knowledge on how transmissible cancers influence telomere maintenance. An emblematic example of transmissible cancer occurs in the Tasmanian devil (Sarcophilus harrisii), whose populations have been dramatically reduced by infectious cancer cells. To investigate associations between telomere dynamics and the transmissible cancer, we used longitudinal data from a Tasmanian devil population that has been exposed to the disease for over 15 years. We detected substantial temporal variation in individual telomere length (TL), and a positive significant association between TL and age, as well as a marginally significant trend for devils with devil facial tumour disease (DFTD) having longer telomeres. A proportional hazard analysis yielded no significant effect of TL on the development of DFTD. Like previous studies, we show the complexity that TL dynamics may exhibit across the lifetime of organisms. Our work highlights the importance of long-term longitudinal sampling for understanding the effects of wildlife diseases on TL.},
}
@article {pmid36203452,
year = {2022},
author = {Tomasova, K and Kroupa, M and Zinkova, A and Korabecna, M and Vymetalkova, V and Skrobanek, P and Sojka, L and Levy, M and Hemminki, K and Liska, V and Hosek, P and Kumar, R and Vodickova, L and Vodicka, P},
title = {Monitoring of telomere dynamics in peripheral blood leukocytes in relation to colorectal cancer patients' outcomes.},
journal = {Frontiers in oncology},
volume = {12},
number = {},
pages = {962929},
pmid = {36203452},
issn = {2234-943X},
abstract = {We investigated the possible associations between leukocyte telomere length, therapy outcomes, and clinicopathological features in patients with colorectal cancer. Additionally, telomerase reverse transcriptase (TERT) expression was evaluated. Telomere length was measured using singleplex qPCR in 478 consecutive leukocyte DNA samples from 198 patients. Blood was drawn at diagnosis prior to any therapy and then at 6-month intervals for 18 months. Following diagnosis, the telomeres gradually shortened during the course of the treatment regardless of the patient's age. The most pronounced decrease was observed 12 months after the diagnosis (p < 0.0001). Based on tumor localization, the decrease in telomere length one year after the diagnosis followed different trajectories (p = 0.03). In patients treated with adjuvant therapy, telomere length correlated with the time elapsed after completion of therapy (p = 0.03). TERT expression did not correlate with the telomere length; however, it was higher in women than men (1.35-fold, 95% CI 1.11-1.65, p = 0.003) and in smokers than non-smokers (1.27-fold, 95% CI 1.01-1.61, p = 0.04). Leukocyte telomere length declines naturally during aging, but the accelerated shortening observed in our patients was age-independent. Telomere length manifestly reflected chemotherapy impact and could be linked to therapy toxicity.},
}
@article {pmid36202783,
year = {2022},
author = {Piñeiro-Hermida, S and Martínez, P and Bosso, G and Flores, JM and Saraswati, S and Connor, J and Lemaire, R and Blasco, MA},
title = {Consequences of telomere dysfunction in fibroblasts, club and basal cells for lung fibrosis development.},
journal = {Nature communications},
volume = {13},
number = {1},
pages = {5656},
pmid = {36202783},
issn = {2041-1723},
mesh = {Animals ; Bleomycin/toxicity ; Female ; Fibroblasts/metabolism ; Male ; Mice ; *Pulmonary Fibrosis/chemically induced/genetics/pathology ; Telomere/metabolism ; *Telomeric Repeat Binding Protein 1/genetics ; },
abstract = {TRF1 is an essential component of the telomeric protective complex or shelterin. We previously showed that dysfunctional telomeres in alveolar type II (ATII) cells lead to interstitial lung fibrosis. Here, we study the lung pathologies upon telomere dysfunction in fibroblasts, club and basal cells. TRF1 deficiency in lung fibroblasts, club and basal cells induced telomeric damage, proliferative defects, cell cycle arrest and apoptosis. While Trf1 deletion in fibroblasts does not spontaneously lead to lung pathologies, upon bleomycin challenge exacerbates lung fibrosis. Unlike in females, Trf1 deletion in club and basal cells from male mice resulted in lung inflammation and airway remodeling. Here, we show that depletion of TRF1 in fibroblasts, Club and basal cells does not lead to interstitial lung fibrosis, underscoring ATII cells as the relevant cell type for the origin of interstitial fibrosis. Our findings contribute to a better understanding of proper telomere protection in lung tissue homeostasis.},
}
@article {pmid36202131,
year = {2022},
author = {Aviv, A},
title = {The bullwhip effect, T-cell telomeres, and SARS-CoV-2.},
journal = {The lancet. Healthy longevity},
volume = {3},
number = {10},
pages = {e715-e721},
pmid = {36202131},
issn = {2666-7568},
support = {R01 HL134840/HL/NHLBI NIH HHS/United States ; R56 AG073226/AG/NIA NIH HHS/United States ; U01 AG066529/AG/NIA NIH HHS/United States ; },
mesh = {Adaptive Immunity ; Aged ; *COVID-19 ; Humans ; *SARS-CoV-2/genetics ; T-Lymphocytes ; Telomere/genetics ; },
abstract = {Both myeloid cells, which contribute to innate immunity, and lymphoid cells, which dominate adaptive immunity, partake in defending against SARS-CoV-2. In response to the virus, the otherwise slow haematopoietic production supply chain quickly unleashes its preconfigured myeloid element, which largely resists a bullwhip-like effect. By contrast, the lymphoid element risks a bullwhip-like effect when it produces T cells and B cells that are specifically designed to clear the virus. As T-cell production is telomere-length dependent and telomeres shorten with age, older adults are at higher risk of a T-cell shortfall when contracting SARS-CoV-2 than are younger adults. A poorly calibrated adaptive immune response, stemming from a bullwhip-like effect, compounded by a T-cell deficit, might thus contribute to the propensity of people with inherently short T-cell telomeres to develop severe COVID-19. The immune systems of these individuals might also generate an inadequate T-cell response to anti-SARS-CoV-2 vaccination.},
}
@article {pmid36196242,
year = {2022},
author = {Wilson, C and Murnane, JP},
title = {High-throughput screen to identify compounds that prevent or target telomere loss in human cancer cells.},
journal = {NAR cancer},
volume = {4},
number = {4},
pages = {zcac029},
pmid = {36196242},
issn = {2632-8674},
abstract = {Chromosome instability (CIN) is an early step in carcinogenesis that promotes tumor cell progression and resistance to therapy. Using plasmids integrated adjacent to telomeres, we have previously demonstrated that the sensitivity of subtelomeric regions to DNA double-strand breaks (DSBs) contributes to telomere loss and CIN in cancer. A high-throughput screen was created to identify compounds that affect telomere loss due to subtelomeric DSBs introduced by I-SceI endonuclease, as detected by cells expressing green fluorescent protein (GFP). A screen of a library of 1832 biologically-active compounds identified a variety of compounds that increase or decrease the number of GFP-positive cells following activation of I-SceI. A curated screen done in triplicate at various concentrations found that inhibition of classical nonhomologous end joining (C-NHEJ) increased DSB-induced telomere loss, demonstrating that C-NHEJ is functional in subtelomeric regions. Compounds that decreased DSB-induced telomere loss included inhibitors of mTOR, p38 and tankyrase, consistent with our earlier hypothesis that the sensitivity of subtelomeric regions to DSBs is a result of inappropriate resection during repair. Although this assay was also designed to identify compounds that selectively target cells experiencing telomere loss and/or chromosome instability, no compounds of this type were identified in the current screen.},
}
@article {pmid36193690,
year = {2023},
author = {Spano, L and Etain, B and Laplanche, JL and Leboyer, M and Gard, S and Bellivier, F and Marie-Claire, C},
title = {Telomere length and mitochondrial DNA copy number in bipolar disorder: A sibling study.},
journal = {The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry},
volume = {24},
number = {5},
pages = {449-456},
doi = {10.1080/15622975.2022.2131907},
pmid = {36193690},
issn = {1814-1412},
mesh = {Humans ; *DNA, Mitochondrial/genetics ; *Bipolar Disorder/genetics ; Siblings ; DNA Copy Number Variations ; Biomarkers ; Telomere/genetics ; },
abstract = {OBJECTIVES: An accelerated cellular ageing has been observed in bipolar disorder (BD) using biomarkers such as telomere length (TL) and mitochondrial DNA copy number (mtDNAcn). Several risk factors might drive premature ageing in individuals with BD, including a familial predisposition. This study compared TL and mtDNAcn between individuals with BD and their (un)-affected siblings, and explored factors that may explain proband-sibling differences.<br><br>METHODS: Sixty individuals with BD and seventy-four siblings (34 affected with BD or mood disorders and 40 unaffected) were included. Quantitative polymerase chain reaction (qPCR) was used to measure TL and mtDNAcn from peripheral blood genomic DNA.<br><br>RESULTS: TL and mtDNAcn did not significantly differ between probands and their siblings, whatever these latter were affected or not with mood disorders. However, the correlation plots of TL or mtDNAcn in proband-sibling pairs suggested that some pairs were discordant. The within proband-sibling pairs differences for TL and mtDNAcn were not explained by differences in all tested factors.<br><br>CONCLUSIONS: This study shows that probands with BD and their siblings are concordant for TL and mtDNAcn suggesting that they may share some environmental or genetic determinants of these two biomarkers of cellular ageing.},
}
@article {pmid36189312,
year = {2022},
author = {Li, SC and Jia, ZK and Yang, JJ and Ning, XH},
title = {Telomere-related gene risk model for prognosis and drug treatment efficiency prediction in kidney cancer.},
journal = {Frontiers in immunology},
volume = {13},
number = {},
pages = {975057},
pmid = {36189312},
issn = {1664-3224},
mesh = {*Carcinoma, Renal Cell/drug therapy/genetics/pathology ; Humans ; Immune Checkpoint Inhibitors ; *Kidney Neoplasms/drug therapy/genetics/pathology ; NIMA-Related Kinases/genetics ; Prognosis ; Protein Kinase C-theta/genetics ; Proteomics ; RNA ; Risk Factors ; Telomere/genetics ; },
abstract = {Kidney cancer is one of the most common urological cancers worldwide, and kidney renal clear cell cancer (KIRC) is the major histologic subtype. Our previous study found that von-Hippel Lindau (VHL) gene mutation, the dominant reason for sporadic KIRC and hereditary kidney cancer-VHL syndrome, could affect VHL disease-related cancers development by inducing telomere shortening. However, the prognosis role of telomere-related genes in kidney cancer has not been well discussed. In this study, we obtained the telomere-related genes (TRGs) from TelNet. We obtained the clinical information and TRGs expression status of kidney cancer patients in The Cancer Genome Atlas (TCGA) database, The International Cancer Genome Consortium (ICGC) database, and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Totally 353 TRGs were differential between tumor and normal tissues in the TCGA-KIRC dataset. The total TCGA cohort was divided into discovery and validation TCGA cohorts and then using univariate cox regression, lasso regression, and multivariate cox regression method to conduct data analysis sequentially, ten TRGs (ISG15, RFC2, TRIM15, NEK6, PRKCQ, ATP1A1, ELOVL3, TUBB2B, PLCL1, NR1H3) risk model had been constructed finally. The kidney patients in the high TRGs risk group represented a worse outcome in the discovery TCGA cohort (p<0.001), and the result was validated by these four cohorts (validation TCGA cohort, total TCGA cohort, ICGC cohort, and CPTAC cohort). In addition, the TRGs risk score is an independent risk factor for kidney cancer in all these five cohorts. And the high TRGs risk group correlated with worse immune subtypes and higher tumor mutation burden in cancer tissues. In addition, the high TRGs risk group might benefit from receiving immune checkpoint inhibitors and targeted therapy agents. Moreover, the proteins NEK6, RF2, and ISG15 were upregulated in tumors both at the RNA and protein levels, while PLCL1 and PRKCQ were downregulated. The other five genes may display the contrary expression status at the RNA and protein levels. In conclusion, we have constructed a telomere-related genes risk model for predicting the outcomes of kidney cancer patients, and the model may be helpful in selecting treatment agents for kidney cancer patients.},
}
@article {pmid36186140,
year = {2022},
author = {Liu, Y and Huang, Y and Liu, C and Liu, Q},
title = {Longer Leukocyte Telomere Length Increases the Risk of Atrial Fibrillation: A Mendelian Randomization Study.},
journal = {Aging and disease},
volume = {13},
number = {5},
pages = {1311-1313},
pmid = {36186140},
issn = {2152-5250},
}
@article {pmid36184605,
year = {2022},
author = {Guh, CY and Shen, HJ and Chen, LW and Chiu, PC and Liao, IH and Lo, CC and Chen, Y and Hsieh, YH and Chang, TC and Yen, CP and Chen, YY and Chen, TW and Chen, LY and Wu, CS and Egly, JM and Chu, HC},
title = {XPF activates break-induced telomere synthesis.},
journal = {Nature communications},
volume = {13},
number = {1},
pages = {5781},
pmid = {36184605},
issn = {2041-1723},
mesh = {DNA ; Endonucleases/metabolism ; RNA ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere Homeostasis ; },
abstract = {Alternative Lengthening of Telomeres (ALT) utilizes a recombination mechanism and break-induced DNA synthesis to maintain telomere length without telomerase, but it is unclear how cells initiate ALT. TERRA, telomeric repeat-containing RNA, forms RNA:DNA hybrids (R-loops) at ALT telomeres. We show that depleting TERRA using an RNA-targeting Cas9 system reduces ALT-associated PML bodies, telomere clustering, and telomere lengthening. TERRA interactome reveals that TERRA interacts with an extensive subset of DNA repair proteins in ALT cells. One of TERRA interacting proteins, the endonuclease XPF, is highly enriched at ALT telomeres and recruited by telomeric R-loops to induce DNA damage response (DDR) independent of CSB and SLX4, and thus triggers break-induced telomere synthesis and lengthening. The attraction of BRCA1 and RAD51 at telomeres requires XPF in FANCM-deficient cells that accumulate telomeric R-loops. Our results suggest that telomeric R-loops activate DDR via XPF to promote homologous recombination and telomere replication to drive ALT.},
}
@article {pmid36182724,
year = {2022},
author = {He, D and Meng, P and Li, C and Jia, Y and Wen, Y and Pan, C and Zhang, Z and Zhang, J and Zhang, H and Chen, Y and Zhao, Y and Qin, X and Cai, Q and Wei, W and Shi, S and Chu, X and Zhang, N and Zhang, F},
title = {Association between telomere length and insomnia: A mendelian randomization and colocalization study.},
journal = {Sleep medicine},
volume = {100},
number = {},
pages = {304-310},
doi = {10.1016/j.sleep.2022.09.002},
pmid = {36182724},
issn = {1878-5506},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Female ; Humans ; *Mendelian Randomization Analysis ; Genome-Wide Association Study/methods ; *Sleep Initiation and Maintenance Disorders/genetics ; Polymorphism, Single Nucleotide/genetics ; Telomere/genetics ; },
abstract = {BACKGROUND: Previous studies have suggested a potential association between sleep and telomere length (TL), but its genetic basis remains unclear. In this study, we aimed to explore the genetic correlation and potential causal association between TL and insomnia.<br><br>METHODS: The genome-wide association study (GWAS) datasets of TL and insomnia-related traits were used, including insomnia, snoring, daytime dozing and napping. Based on the polygenic risk scores (PRS) of TL, linear regression and linkage disequilibrium score (LDSC) regression were used to preliminarily explore the association between TL and insomnia parameters in the UK Biobank cohort. Then, we investigated the causal association between TL and insomnia by mendelian randomization (MR) analysis and colocalization analysis.<br><br>RESULTS: In the UK Biobank cohort, the association between TL and insomnia was observed in the female samples (t&#xa0;=&#xa0;2.968, P&#xa0;=&#xa0;3.00&#xa0;&#xd7;&#xa0;10[-3]). LDSC detected a genetic correlation between short TL and insomnia (Rg&#xa0;=&#xa0;-9.27&#xa0;&#xd7;&#xa0;10[-2], P&#xa0;=&#xa0;8.00&#xa0;&#xd7;&#xa0;10[-4]). We found no evidence supporting significant causal association between insomnia and TL in IVW method (b&#xa0;=&#xa0;-5.95&#xa0;&#xd7;&#xa0;10[-3], P&#xa0;=&#xa0;0.57), with horizontal pleiotropy and heterogeneity tests indicating the validity of our MR study. Finally, rs12638862 was classified as colocalized by COLOC (PP4&#xa0;=&#xa0;0.99), and TERC may be involved in regulating the association between insomnia and TL.<br><br>CONCLUSIONS: Our study found no evidence for causal association between insomnia and TL in individuals of European ancestry. We detected a candidate gene associated with both insomnia and TL, providing novel clues for understanding the roles of this association.},
}
@article {pmid36182046,
year = {2022},
author = {Hanis, F and Chung, ELT and Kamalludin, MH and Idrus, Z},
title = {Blood Profile, Hormones, and Telomere Responses: Potential Biomarkers in Horses Exhibiting Abnormal Oral Behavior.},
journal = {Journal of equine veterinary science},
volume = {118},
number = {},
pages = {104130},
doi = {10.1016/j.jevs.2022.104130},
pmid = {36182046},
issn = {0737-0806},
mesh = {Animals ; *Leptin ; *Ghrelin ; Hydrocortisone ; Creatine Kinase ; Biomarkers ; Telomere/genetics ; },
abstract = {The high prevalence of abnormal oral behavior (AOB) in working horses has been linked to management issues and the pathophysiology of this behavior remains unclear. Therefore, this study aims to elucidate the blood profile, hormones, and telomere length responses between low and high levels of AOB among different horse working groups. A total of 207 healthy horses from various breeds were initially selected from four working groups (leisure riding, equestrian, endurance, and patrolling) and observed for the time spent on AOB. Then, six horses each with higher and lower AOB than the population means were randomly selected from each of the working groups and categorized as high and low AOB horses, respectively. Blood samples were collected for hematology, biochemistry, cortisol, ghrelin, leptin, and relative telomere length analyzes. High AOB horses notably had higher values of glucose, alanine aminotransferase (ALT), alkaline phosphatase (ALP), and creatine kinase (CK) compared to low AOB horses. High AOB horses also recorded higher plasma cortisol and ghrelin, but lower leptin concentrations. Among working groups, both endurance and patrolling horses presented the highest values in sodium, potassium, chloride, phosphate, ALT, and CK. While patrolling horses had the lowest levels of urea, ALP, and albumin levels, equestrian and leisure horses recorded the highest and lowest plasma cortisol and leptin concentrations, respectively. Finally, the telomere length of endurance and patrolling horses were significantly greater than leisure and equestrian horses. The present findings suggest that AOB horses had distinctive physiological characteristics that could be linked to improper diet and a demanding workload, while ghrelin and leptin hormones could be potential biomarkers for this behavior.},
}
@article {pmid36181470,
year = {2023},
author = {Raftopoulou, C and Abawi, O and Sommer, G and Binou, M and Paltoglou, G and Flück, CE and van den Akker, ELT and Charmandari, E},
title = {Leukocyte Telomere Length in Children With Congenital Adrenal Hyperplasia.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {108},
number = {2},
pages = {443-452},
doi = {10.1210/clinem/dgac560},
pmid = {36181470},
issn = {1945-7197},
mesh = {Female ; Humans ; Child ; Adolescent ; Male ; *Adrenal Hyperplasia, Congenital/drug therapy/genetics/complications ; Hydrocortisone/therapeutic use ; Glucocorticoids/pharmacology/therapeutic use ; Prospective Studies ; Prednisolone/therapeutic use ; Telomere/genetics ; },
abstract = {CONTEXT: Exposure to chronic stress and hypercortisolism is associated with decreased leukocyte telomere length (LTL), a marker for biological aging and cardiovascular disease. Children with congenital adrenal hyperplasia (CAH) are treated with glucocorticoids.<br><br>OBJECTIVE: To investigate LTL in children with CAH.<br><br>METHODS: In this prospective observational cohort study, conducted at 4 academic pediatric endocrinology outpatient clinics, children with genetically confirmed CAH were assessed at 2 follow-up visits (mean 4.1 &#xb1; 0.7 months apart). At each visit, LTL was determined by quantitative real-time PCR. All subjects underwent detailed clinical and endocrinologic evaluation and were classified as undertreated, optimally treated, or overtreated, accordingly. The influence of clinical factors on LTL was investigated using linear mixed models adjusted for age, sex, and BMI-z.<br><br>RESULTS: We studied 76 patients, of whom 31 (41%) were girls, 63 (83%) had classic CAH, 67 (88%) received hydrocortisone, and 8 (11%) prednisolone. Median age at first visit was 12.0 years (IQR, 6.3-15.1), and median BMI-z was 0.51 (IQR, -0.12 to 1.43). LTL was shorter in patients with classic vs nonclassic CAH (-0.29, P = 0.012), in overtreated than in optimally treated patients (-0.07, P = 0.002), and patients receiving prednisolone compared with hydrocortisone (-0.34, P < 0.001). LTL was not associated with undertreatment or daily hydrocortisone-equivalent dose (P > 0.05).<br><br>CONCLUSION: LTL is shorter in patients with classic than nonclassic CAH, and in those who are overtreated with hydrocortisone or treated with long-acting glucocorticoids. These findings may be attributed to chronic exposure to supraphysiologic glucocorticoid concentrations and indicate that LTL may be used as a biomarker for monitoring glucocorticoid treatment.},
}
@article {pmid36177720,
year = {2022},
author = {Akinnibosun, OA and Maier, MC and Eales, J and Tomaszewski, M and Charchar, FJ},
title = {Telomere therapy for chronic kidney disease.},
journal = {Epigenomics},
volume = {14},
number = {17},
pages = {1039-1054},
doi = {10.2217/epi-2022-0073},
pmid = {36177720},
issn = {1750-192X},
mesh = {Animals ; Fibrosis ; Longitudinal Studies ; Nucleoproteins/genetics ; *Renal Insufficiency, Chronic/genetics/therapy ; *Telomere/genetics ; },
abstract = {Chronic kidney disease (CKD) is estimated to affect almost 10% of individuals worldwide and is one of the leading causes of morbidity and mortality. Renal fibrosis, a central pathway in CKD progression (irrespective of etiology), is associated with shortened or dysfunctional telomeres in animal studies. Telomeres are specialized nucleoprotein structures located at the chromosome end that maintain genomic integrity. The mechanisms of associations between telomere length and CKD have not yet been fully elucidated, however, CKD patients with shorter telomere length may have decreased renal function and a higher mortality rate. A plethora of ongoing research has focused on possible therapeutic applications of telomeres with the overall goal to preserve telomere length as a therapy to treat CKD.},
}
@article {pmid36175852,
year = {2022},
author = {de Oliveira, FM and Jamur, VR and Merfort, LW and Pozzo, AR and Mai, S},
title = {Three-dimensional nuclear telomere architecture and differential expression of aurora kinase genes in chronic myeloid leukemia to measure cell transformation.},
journal = {BMC cancer},
volume = {22},
number = {1},
pages = {1024},
pmid = {36175852},
issn = {1471-2407},
mesh = {Aurora Kinase A/genetics ; Blast Crisis ; Chromosome Aberrations ; *Graft vs Host Disease ; Humans ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; *Leukemia, Myeloid ; RNA, Messenger ; Telomere/genetics ; },
abstract = {BACKGROUND: Telomere dysfunction results in aneuploidy, and ongoing chromosomal abnormalities. The three-dimensional (3D) nuclear organization of telomeres allows for a distinction between normal and tumor cells. On the other hand, aurora kinase genes (AURKA and AURKB) play an important role regulating the cell cycle. A correlation between overexpression of aurora kinase genes and clinical aggressiveness has been demonstrated in different types of neoplasias. To better understand cellular and molecular mechanisms of CML evolution, it was examined telomere dysfunction (alterations in the 3D nuclear telomere architecture), and the expression levels of AURKA and AURKB genes in two clinical distinct subgroups of CML samples, from the same patient.<br><br>METHODS: Eighteen CML patients, in total, 36 bone marrow samples (18 patients, chronic vs. accelerated/blast phase) were eligible for 3D telomeric investigations. Quantitative 3D imaging, cytologic diagnosis and cytogenetic determination of additional chromosomal abnormalities were assessed according to standard protocols.<br><br>RESULTS: Using TeloView software, two CML subgroups were defined based on their 3D telomeric profiles, reflecting the different stages of the disease (chronic vs. accelerated/blast phase). Statistical analyses showed significant differences between the CML subgroups (p&#x2009;<&#x2009;0.001). We also found that AURKA and AURKB mRNA were expressed at significantly higher levels in both CML subgroups, when compared with healthy donors. Our findings suggest that the evolution of CML progresses from a low to a high level of telomere dysfunction, that is, from an early stage to a more aggressive stage, followed by disease transformation, as demonstrated by telomere, additional chromosomal abnormalities, and gene expression profile dynamics.<br><br>CONCLUSIONS: Thus, we demonstrated that 3D telomere organization, in accordance with the genomic instability observed in CML samples were able to distinguish subgroup CML patients. Classifying CML patients based on these characteristics might represent an important strategy to define better therapeutic strategies.},
}
@article {pmid36175503,
year = {2022},
author = {Bird, L},
title = {Gift of life: APC to T cell telomere transfer.},
journal = {Nature reviews. Immunology},
volume = {22},
number = {11},
pages = {653},
pmid = {36175503},
issn = {1474-1741},
mesh = {Humans ; *T-Lymphocytes ; *Telomere/genetics ; },
}
@article {pmid36175493,
year = {2022},
author = {Porrazzo, A and Cipressa, F and De Gregorio, A and De Pittà, C and Sales, G and Ciapponi, L and Morciano, P and Esposito, G and Tabocchini, MA and Cenci, G},
title = {Author Correction: Low dose rate γ-irradiation protects fruit fly chromosomes from double strand breaks and telomere fusions by reducing the esi-RNA biogenesis factor Loquacious.},
journal = {Communications biology},
volume = {5},
number = {1},
pages = {1033},
doi = {10.1038/s42003-022-03984-8},
pmid = {36175493},
issn = {2399-3642},
}
@article {pmid36174712,
year = {2022},
author = {Zhu, X and Fu, H and Sun, J and Di, Q and Xu, Q},
title = {N6-methyladenosine modification on Hmbox1 is related to telomere dysfunction in DEHP-induced male reproductive injury.},
journal = {Life sciences},
volume = {309},
number = {},
pages = {121005},
doi = {10.1016/j.lfs.2022.121005},
pmid = {36174712},
issn = {1879-0631},
mesh = {Animals ; Male ; Mice ; *Diethylhexyl Phthalate/toxicity ; *Telomerase/metabolism ; Telomere/genetics ; Adenosine ; Homeodomain Proteins/metabolism ; },
abstract = {AIMS: Di (2-ethylhexyl) phthalate (DEHP), as an environmental endocrine-disrupting chemical (EDC), can induce male reproductive injury. N6-methyladenosine (m6A) plays a vital role in environmental exposure-induced diseases by regulating gene expression. Therefore, we aim to investigate the role of m6A in DEHP-induced reproductive injury.<br><br>MAIN METHODS: We established an in vivo model of mice exposed to DEHP to explore the effect of DEHP on reproductive injury and m6A. To further explore the molecular mechanism of DEHP toxicity, we built a model of GC-2 cells exposed to mono-(2-ethylhexyl) phthalate (MEHP) in vitro and further silenced Mettl3 in GC-2cells. Besides, we also conducted MeRIP-qPCR and RIP assays to identify the target genes for m6A modification.<br><br>KEY FINDINGS: DEHP induced testicular injury and senescence. And telomeres shortening, reduced levels of telomere repeat-binding factor 1 (TRF1), TRF2, protection of telomeres 1 (POT1), and telomerase reverse transcriptase (TERT) can be observed in DEHP-treated testes. MEHP also induced GC-2 cellular senescence and telomere dysfunction. Besides, increased m6A mediated by METTL3 stabilized homeobox containing 1 (Hmbox1) in an m6A-dependent manner in MEHP-exposed GC-2 cells. Mettl3 knockdown led to lower m6A modification and reduced Hmbox1 stability, resulting in further shortening of telomere length.<br><br>SIGNIFICANCE: our work uncovered that DEHP led to male reproductive injury by telomere dysfunction and m6A modified Hmbox1 contributed to maintaining telomere homeostasis in this process, suggesting that accurate regulation of m6A modification level by drugs has potential value in the treatment of DEHP-induced male reproductive injury.},
}
@article {pmid36172207,
year = {2022},
author = {Xia, F and Li, Q and Luo, X and Wu, J},
title = {Association between urinary metals and leukocyte telomere length involving an artificial neural network prediction: Findings based on NHANES 1999-2002.},
journal = {Frontiers in public health},
volume = {10},
number = {},
pages = {963138},
pmid = {36172207},
issn = {2296-2565},
mesh = {Adult ; Aged ; *Cadmium ; Humans ; Leukocytes/physiology ; Molybdenum ; Neural Networks, Computer ; Nutrition Surveys ; *Telomere ; },
abstract = {OBJECTIVE: Leukocytes telomere length (LTL) was reported to be associated with cellular aging and aging related disease. Urine metal also might accelerate the development of aging related disease. We aimed to analyze the association between LTL and urinary metals.<br><br>METHODS: In this research, we screened all cycles of National Health and Nutrition Examination Survey (NHANES) dataset, and download the eligible dataset in NHANES 1999-2002 containing demographic, disease history, eight urine metal, and LTL. The analysis in this research had three steps including baseline difference comparison, multiple linear regression (MLR) for hazardous urine metals, and artificial neural network (ANN, based on Tensorflow framework) to make LTL prediction.<br><br>RESULTS: The MLR results showed that urinary cadmium (Cd) was negatively correlated with LTL in the USA population [third quantile: -9.36, 95% confidential interval (CI) = (-19.7, -2.32)], and in the elderly urinary molybdenum (Mo) was positively associated with LTL [third quantile: 24.37, 95%CI = (5.42, 63.55)]. An ANN model was constructed, which had 24 neurons, 0.375 exit rate in the first layer, 15 neurons with 0.53 exit rate in the second layer, and 7 neurons with 0.86 exit rate in the third layer. The squared error loss (LOSS) and mean absolute error (MAE) in the ANN model were 0.054 and 0.181, respectively, which showed a low error rate.<br><br>CONCLUSION: In conclusion, in adults especially the elderly, the relationships between urinary Cd and Mo might be worthy of further research. An accurate prediction model based on ANN could be further analyzed.},
}
@article {pmid36169361,
year = {2022},
author = {Maximov, VN and Orlov, PS and Gurazeva, AA and Melnikova, ES and Gafarov, VV and Chervova, OA and Voevoda, MI and Malyutina, SK},
title = {[The relationship between the relative length of leukocyte telomeres and mtDNA copy number and acute coronary syndrome in a 15-year follow-up.].},
journal = {Advances in gerontology = Uspekhi gerontologii},
volume = {35},
number = {3},
pages = {351-360},
pmid = {36169361},
issn = {1561-9125},
mesh = {*Acute Coronary Syndrome/diagnosis/genetics ; Aged ; Biomarkers ; DNA Copy Number Variations ; DNA, Mitochondrial/genetics ; Female ; Follow-Up Studies ; Humans ; Leukocytes ; Male ; Middle Aged ; *Myocardial Infarction ; Telomere/genetics ; },
abstract = {We studied the relationship between the leucocyte telomere length (LTL) and the copy number of mitochondrial DNA (CNmtDNA) and the development of acute coronary syndrome during 15 years of follow-up. A random population sample was examined at baseline in 2003-2005 (n=9 360, men and women 45-69 years old, Novosibirsk, the HAPIEE project) and followed-up for 15 years. In the frame of nested case-control design, we selected cases - incident myocardial infarction/acute coronary syndrome (MI/ACS) among those free from baseline CVD (n=256) and sex- and age-stratified control among those free from baseline CVD and cancer and alive by the end of follow-up (n=799). The relative LTL and CNmtDNA were assessed using quantitative real-time PCR. Results. The carriers of shorter telomeres had increased 15-year risk of MI/ACS with adjusted OR=1,87 (95% CI 1,70-2,06) per 1 LTL decile independent of other factors. Fewer CNmtDNA was associated with increased risk of MI/ACS with adjusted OR=1,19 (95% CI 1,12-1,26) per 1 CNmtDNA decile. The identified associations were confirmed in tertile analysis and in stepwise analysis with continuous variables of both biomarkers. All associations persisted after adjusting for gender, age, and traditional CVD risk factors. Conclusion. The LTL and CNmtDNA were independent predictors of the 15-year risk of MI/ACS in the middle- and elderly Siberian (Caucasoid) population cohort. These findings highlight the need for further research to elucidate the mechanisms by which LTL and mtDNA copy number may affect human health.},
}
@article {pmid36168042,
year = {2022},
author = {Carey, A and Niedernhofer, L and Camell, C},
title = {Telomeres are a life-extending gift.},
journal = {Nature cell biology},
volume = {24},
number = {10},
pages = {1449-1450},
pmid = {36168042},
issn = {1476-4679},
mesh = {*Telomere/genetics ; Cellular Senescence ; },
}
@article {pmid36160016,
year = {2022},
author = {Kahrizi, MS and Patra, I and Jalil, AT and Achmad, H and Alesaeidi, S and Al-Gazally, ME and Alesaeidi, S},
title = {Leukocyte telomere length and obesity in children and adolescents: A systematic review and meta-analysis.},
journal = {Frontiers in genetics},
volume = {13},
number = {},
pages = {861101},
pmid = {36160016},
issn = {1664-8021},
abstract = {Background: Several studies have revealed the negative effects of adiposity on telomere length shortening. However, the results of the studies assessing the negative relationship between obesity and leukocyte telomere length (LTL) are not consistent. This systematic review and meta-analysis are aimed to pool the results of articles assessing the relationship between obesity and LTL among children and adolescents. Methods: To retrieve the related studies, four online databases including PubMed, Embase, ProQuest, and Scopus were searched until May 2022. Observational studies evaluating the relationship between obesity and LTL among apparently healthy children and adolescents (aged ≤18 years) were included in the study. We considered the studies that had reported a mean ± standard deviation of LTL. The random-effects model was used to assess the pooled weighted mean difference (WMD) and a 95% confidence interval (CI). Results: The search yielded seven studies from an initial 3,403 records identified. According to the results of seven articles with 4,546 participants, obesity was associated with LTL shortening among children and adolescents (WMD = -0.081; 95% CI: -0.137 to -0.026; p = 0.004; I[2] = 99.9%). Also, no publication bias was observed. According to the results of subgrouping, significant results were only attributed to the studies conducted in Europe, with high quality scores, among overweight and obese adolescents, with a baseline LTL lower than 1, and performed in community-based school settings. Also, according to the subgrouping and meta-regression results, the obesity definition criteria and baseline LTL were the possible sources of between-study heterogeneity. Conclusion: We observed shorter LTL among overweight and obese children and adolescents. To obtain more reliable results, further longitudinal prospective studies with large sample sizes and more consistent and accurate definitions of obesity are required.},
}
@article {pmid36159052,
year = {2022},
author = {Krishna, M and Shetty, A and Manjappa, AB and Shetty, V and Hegde, MN and Kumar, BM},
title = {Comparative characterization and analysis of telomere length in stem cells derived from deciduous and permanent teeth.},
journal = {Dental research journal},
volume = {19},
number = {},
pages = {64},
pmid = {36159052},
issn = {1735-3327},
abstract = {BACKGROUND: Understanding the influence of age on growth kinetics and telomere length in dental stem cells is essential for the successful development of cell therapies. Hence, the present study compared the basic cellular and phenotypical characteristics of stem cells from human exfoliated deciduous teeth (SHEDs) and dental pulp stem cells (DPSCs) of permanent teeth and their telomere lengths using quantitative real-time polymerase chain reaction.<br><br>MATERIALS AND METHODS: The study is an in vitro original research article. Primary cultures of SHED and DPSCs (n = 6 each) were successfully established in vitro, and the parameters analyzed were the morphology, viability, proliferation rate, population doubling time (PDT), phenotypic markers expression, and the relative telomere lengths. Data were analyzed by analysis of variance and P < 0.05 was considered statistically significant.<br><br>RESULTS: SHED and DPSCs exhibited a small spindle-shaped fibroblast-like morphology with >90% viability. The proliferation assay showed that the cells had a typical growth pattern. The PDT values of SHED and DPSCs were 29.03 &#xb1; 9.71 h and 32.05 &#xb1; 9.76 h, respectively. Both cells were positive for surface markers CD29, CD44, and CD90. However, they were negative for CD45 and human leukocyte antigen DR. Although the differences in relative telomere lengths between the individual cell lines of SHED and DPSCs were observed, no significant (P > 0.05) variations were found for the mean T/S ratios of both the cells.<br><br>CONCLUSION: SHED and DPSCs displayed similar morphology, proliferation rates, and phenotypic features. The relative telomere lengths were slightly shorter in DPSCs than SHED, but the values were not significantly different. Thus, SHED and DPSCs can be considered as recognized sources for regenerative applications in dentistry.},
}
@article {pmid36153564,
year = {2022},
author = {Meeser, A and Bartenhagen, C and Werr, L and Hellmann, AM and Kahlert, Y and Hemstedt, N and Nürnberg, P and Altmüller, J and Ackermann, S and Hero, B and Simon, T and Peifer, M and Fischer, M and Rosswog, C},
title = {Reliable assessment of telomere maintenance mechanisms in neuroblastoma.},
journal = {Cell &amp; bioscience},
volume = {12},
number = {1},
pages = {160},
pmid = {36153564},
issn = {2045-3701},
support = {FI 1926/2-1//Deutsche Forschungsgemeinschaft/ ; as part of the SFB1399//Deutsche Forschungsgemeinschaft/ ; BA 6984/1-1//Deutsche Forschungsgemeinschaft/ ; 2016-Kolleg-19//Else Kr&#xf6;ner-Fresenius-Stiftung/ ; 01ZX1303//Bundesministerium f&#xfc;r Bildung und Forschung/ ; 01ZX1603//Bundesministerium f&#xfc;r Bildung und Forschung/ ; 01ZX1307//Bundesministerium f&#xfc;r Bildung und Forschung/ ; 01ZX1607//Bundesministerium f&#xfc;r Bildung und Forschung/ ; K&#xf6;ln Fortune Program/Faculty of Medicine//Universit&#xe4;t zu K&#xf6;ln/ ; },
abstract = {BACKGROUND: Telomere maintenance mechanisms (TMM) are a hallmark of high-risk neuroblastoma, and are conferred by activation of telomerase or alternative lengthening of telomeres (ALT). However, detection of TMM is not yet part of the clinical routine, and consensus on TMM detection, especially on ALT assessment, remains to be achieved.<br><br>METHODS: Whole genome sequencing (WGS) data of 68 primary neuroblastoma samples were analyzed. Telomere length was calculated from WGS data or by telomere restriction fragment analysis (n&#x2009;=&#x2009;39). ALT was assessed by C-circle assay (CCA, n&#x2009;=&#x2009;67) and detection of ALT-associated PML nuclear bodies (APB) by combined fluorescence in situ hybridization and immunofluorescence staining (n&#x2009;=&#x2009;68). RNA sequencing was performed (n&#x2009;=&#x2009;64) to determine expression of TERT and telomeric long non-coding RNA (TERRA). Telomerase activity was examined by telomerase repeat amplification protocol (TRAP, n&#x2009;=&#x2009;15).<br><br>RESULTS: Tumors were considered as telomerase-positive if they harbored a TERT rearrangement, MYCN amplification or high TERT expression (45.6%, 31/68), and ALT-positive if they were positive for APB and CCA (19.1%, 13/68). If all these markers were absent, tumors were considered TMM-negative (25.0%, 17/68). According to these criteria, the majority of samples were classified unambiguously (89.7%, 61/68). Assessment of additional ALT-associated parameters clarified the TMM status of the remaining seven cases with high likelihood: ALT-positive tumors had higher TERRA expression, longer telomeres, more telomere insertions, a characteristic pattern of telomere variant repeats, and were associated with ATRX mutations.<br><br>CONCLUSIONS: We here propose a workflow to reliably detect TMM in neuroblastoma. We show that unambiguous classification is feasible following a stepwise approach that determines both, activation of telomerase and ALT. The workflow proposed in this study can be used in clinical routine and provides a framework to systematically and reliably determine telomere maintenance mechanisms for risk stratification and treatment allocation of neuroblastoma patients.},
}
@article {pmid36151328,
year = {2023},
author = {Revy, P and Kannengiesser, C and Bertuch, AA},
title = {Genetics of human telomere biology disorders.},
journal = {Nature reviews. Genetics},
volume = {24},
number = {2},
pages = {86-108},
pmid = {36151328},
issn = {1471-0064},
support = {R01 HL131744/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Telomere/genetics/metabolism ; Aging/genetics ; Telomere Homeostasis ; Genomic Instability ; Biology ; *Telomerase/genetics ; },
abstract = {Telomeres are specialized nucleoprotein structures at the ends of linear chromosomes that prevent the activation of DNA damage response and repair pathways. Numerous factors localize at telomeres to regulate their length, structure and function, to avert replicative senescence or genome instability and cell death. In humans, Mendelian defects in several of these factors can result in abnormally short or dysfunctional telomeres, causing a group of rare heterogeneous premature-ageing diseases, termed telomeropathies, short-telomere syndromes or telomere biology disorders (TBDs). Here, we review the TBD-causing genes identified so far and describe their main functions associated with telomere biology. We present molecular aspects of TBDs, including genetic anticipation, phenocopy, incomplete penetrance and somatic genetic rescue, which underlie the complexity of these diseases. We also discuss the implications of phenotypic and genetic features of TBDs on fundamental aspects related to human telomere biology, ageing and cancer, as well as on diagnostic, therapeutic and clinical approaches.},
}
@article {pmid36146670,
year = {2022},
author = {Wight, DJ and Aimola, G and Beythien, G and Flamand, L and Kaufer, BB},
title = {Impact of Host Telomere Length on HHV-6 Integration.},
journal = {Viruses},
volume = {14},
number = {9},
pages = {},
pmid = {36146670},
issn = {1999-4915},
support = {Stg 677673/ERC_/European Research Council/International ; },
mesh = {Child ; HeLa Cells ; *Herpesvirus 6, Human/genetics ; Humans ; In Situ Hybridization, Fluorescence ; *Roseolovirus Infections/genetics ; Telomere ; Virus Integration ; },
abstract = {Human herpesvirus 6A and 6B are two closely related viruses that infect almost all humans. In contrast to most herpesviruses, HHV-6A/B can integrate their genomes into the telomeres during the infection process. Both viruses can also integrate in germ cells and subsequently be inherited in children. How HHV-6A/B integrate into host telomeres and the consequences of this remain a subject of active research. Here, we developed a method to measure telomere length by quantitative fluorescence in situ hybridization, confocal microscopy, and computational processing. This method was validated using a panel of HeLa cells having short or long telomeres. These cell lines were infected with HHV-6A, revealing that the virus could efficiently integrate into telomeres independent of their length. Furthermore, we assessed the telomere lengths after HHV-6A integration and found that the virus-containing telomeres display a variety of lengths, suggesting that either telomere length is restored after integration or telomeres are not shortened by integration. Our results highlight new aspects of HHV-6A/B biology and the role of telomere length on virus integration.},
}
@article {pmid36145097,
year = {2022},
author = {Ogłuszka, M and Lipiński, P and Starzyński, RR},
title = {Effect of Omega-3 Fatty Acids on Telomeres-Are They the Elixir of Youth?.},
journal = {Nutrients},
volume = {14},
number = {18},
pages = {},
pmid = {36145097},
issn = {2072-6643},
support = {2020/39/B/NZ5/02469//National Science Center/ ; 2015/17/N/NZ9/01105//National Science Center/ ; },
mesh = {Animals ; Cellular Senescence ; Cross-Sectional Studies ; *Fatty Acids, Omega-3/pharmacology ; Humans ; Inflammation ; Rats ; *Telomere ; Telomere Shortening ; },
abstract = {Telomeres are complexes consisting of tandem repeat DNA combined with associated proteins that play a key role in protecting the ends of chromosomes and maintaining genome stability. They are considered a biological clock, as they shorten in parallel with aging. Furthermore, short telomeres are associated with several age-related diseases. However, the variability in telomere shortening independent of chronological age suggests that it is a modifiable factor. In fact, it is regulated inter alia by genetic damage, cell division, aging, oxidative stress, and inflammation. A key question remains: how can we prevent accelerated telomere attrition and subsequent premature replicative senescence? A number of studies have explored the possible impact of omega-3 fatty acids on telomere shortening. This review summarizes published cross-sectional studies, randomized controlled trials, and rodent studies investigating the role of omega-3 fatty acids in telomere biology. It also covers a broad overview of the mechanism, currently favored in the field, that explains the impact of omega-3 fatty acids on telomeres-the food compound's ability to modulate oxidative stress and inflammation. Although the results of the studies performed to date are not consistent, the vast majority indicate a beneficial effect of omega-3 fatty acids on telomere length.},
}
@article {pmid36143917,
year = {2022},
author = {Liutkeviciene, R and Mikalauskaite, R and Gedvilaite, G and Glebauskiene, B and Kriauciuniene, L and Žemaitienė, R},
title = {Relative Leukocyte Telomere Length and Telomerase Complex Regulatory Markers Association with Leber's Hereditary Optic Neuropathy.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {58},
number = {9},
pages = {},
pmid = {36143917},
issn = {1648-9144},
mesh = {Adult ; Aged ; Case-Control Studies ; DNA, Mitochondrial/genetics ; Female ; Humans ; Leukocytes ; Male ; *Optic Atrophy, Hereditary, Leber/diagnosis/genetics/therapy ; *Telomerase/genetics ; Telomere/genetics ; },
abstract = {Background and Objectives: To evaluate the association of relative leukocyte telomere length (RLTL) and telomerase complex regulatory markers with Leber’s hereditary optic neuropathy (LHON). Material and Methods: A case-control study was performed in patients with LHON (≥18 years) and healthy subjects. The diagnosis of LHON was based on a genetic blood test (next-generation sequencing with Illumina MiSeq, computer analysis: BWA2.1 Illumina BaseSpace, Alamut, and mtDNA Variant analyzer 1000 were performed) and diagnostic criteria approved by the LHON disease protocol. Statistical analysis was performed using the standard statistical software package, IBM SPSS Statistics 27. Statistically significant results were considered when p < 0.05. Results: Significantly longer RLTL was observed in LHON patients than in healthy controls (p < 0.001). RLTL was significantly longer in women and men with LOHN than in healthy women and men in the control group (p < 0.001 and p = 0.003, respectively). In the elderly group (>32 years), RLTL was statistically significantly longer in LHON patients compared with healthy subjects (p < 0.001). The GG genotype of the TERC rs12696304 polymorphism was found to be statistically significantly higher in the LHON group (p = 0.041), and the C allele in the TERC rs12696304 polymorphism was found to be statistically significantly less common in the LHON group (p < 0.001). The RLTL of LHON patients was found to be statistically significantly longer in the TERC rs12696304 polymorphism in all tested genotypes (CC, p = 0.005; CG, p = 0.008; GG, p = 0.025), TEP1 rs1760904 polymorphism in the GA genotype (p < 0.001), and TEP1 gene rs1713418 in the AA and AG genotypes (p = 0.011 and p < 0.001, respectively). Conclusions: The RLTL in LHON patients was found to be longer than in healthy subjects regardless of treatment with idebenone. The TERC rs12696304 polymorphism, of all studied polymorphisms, was the most significantly associated with changes in LHON and telomere length.},
}
@article {pmid36140830,
year = {2022},
author = {Jenner, LP and Peska, V and Fulnečková, J and Sýkorová, E},
title = {Telomeres and Their Neighbors.},
journal = {Genes},
volume = {13},
number = {9},
pages = {},
pmid = {36140830},
issn = {2073-4425},
mesh = {Base Sequence ; DNA ; *DNA, Satellite ; Humans ; Repetitive Sequences, Nucleic Acid ; *Telomere/genetics ; },
abstract = {Telomeres are essential structures formed from satellite DNA repeats at the ends of chromosomes in most eukaryotes. Satellite DNA repeat sequences are useful markers for karyotyping, but have a more enigmatic role in the eukaryotic cell. Much work has been done to investigate the structure and arrangement of repetitive DNA elements in classical models with implications for species evolution. Still more is needed until there is a complete picture of the biological function of DNA satellite sequences, particularly when considering non-model organisms. Celebrating Gregor Mendel's anniversary by going to the roots, this review is designed to inspire and aid new research into telomeres and satellites with a particular focus on non-model organisms and accessible experimental and in silico methods that do not require specialized equipment or expensive materials. We describe how to identify telomere (and satellite) repeats giving many examples of published (and some unpublished) data from these techniques to illustrate the principles behind the experiments. We also present advice on how to perform and analyse such experiments, including details of common pitfalls. Our examples are a selection of recent developments and underexplored areas of research from the past. As a nod to Mendel's early work, we use many examples from plants and insects, especially as much recent work has expanded beyond the human and yeast models traditional in telomere research. We give a general introduction to the accepted knowledge of telomere and satellite systems and include references to specialized reviews for the interested reader.},
}
@article {pmid36139914,
year = {2022},
author = {Konstantinidou, F and Budani, MC and Marconi, GD and Gonnella, F and Sarra, A and Trubiani, O and Stuppia, L and Tiboni, GM and Gatta, V},
title = {The Aftermath of Long-Term Cigarette Smoking on Telomere Length and Mitochondrial DNA Copy Number in Human Cumulus Cells Prior to In Vitro Fertilization-A Pilot Study.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {11},
number = {9},
pages = {},
pmid = {36139914},
issn = {2076-3921},
abstract = {Cigarette smoking among women of reproductive age is known to take a toll on systemic health and fertility potential by severely impacting ovarian tissues and cells, such as granulosa and cumulus cells (CCs). The purpose of this study was to determine the potential damage caused by tobacco smoke at a molecular level in the CCs of females who had undergone in vitro fertilization. The level of intracellular damage was determined by estimating the average telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN), as well as the expression profile of telomere maintenance genes TERF1, TERF2, POT1 and microRNAs miR-155, miR-23a and miR-185. Western blotting analysis was performed to detect consequent protein levels of TERF1, TERF2 and POT1. Our results evidenced significantly lower relative TL and mtDNA-CN and a down-regulation pattern for all three described genes and corresponding proteins in the CCs of smokers compared with controls (p < 0.05). No significant differences were found in the miRNAs’ modulation. Combined, our data add another piece to the puzzle of the complex regulatory molecular networks controlling the general effects of tobacco smoke in CCs. This pilot study extends the until now modest number of studies simultaneously investigating the mtDNA-CN and TL pathways in the human CCs of smoking women.},
}
@article {pmid36138138,
year = {2023},
author = {Chandyo, RK and Schwinger, C and Kvestad, I and Ulak, M and Ranjitkar, S and Shrestha, M and Nguyen, LV and Corona-Perez, D and DeVivo, I and Shrestha, L and Strand, TA},
title = {The association between household biomass fuel use and leukocyte telomere length among toddlers in Bhaktapur, Nepal.},
journal = {Journal of exposure science &amp; environmental epidemiology},
volume = {33},
number = {3},
pages = {448-454},
pmid = {36138138},
issn = {1559-064X},
mesh = {Adult ; Humans ; Child, Preschool ; *Air Pollution, Indoor/adverse effects/analysis ; Nepal ; Prospective Studies ; *Petroleum ; Cooking ; Leukocytes ; Telomere ; },
abstract = {BACKGROUND: Biomass fuels are still in use for cooking by many households in resource poor countries such as Nepal and is a major source of household air pollution (HAP). Chronic exposure to HAP has been shown to be associated with shorter telomere length in adults.<br><br>OBJECTIVES: To measure the association between exposure related to household biomass fuel in infancy and leukocyte telomere length (LTL) at 18-23 months of age among 497 children from Bhaktapur, Nepal.<br><br>METHODS: In a prospective cohort study design, we have collected information on household cooking fuel use and several clinical, anthropometric, demographic, and socioeconomic variables. We estimated the association between biomass fuel use and the relative LTL in multiple linear regression models.<br><br>RESULTS: Most of the families (78%) reported liquified petroleum gas (LPG) as the primary cooking fuel, and 18.7% used biomass. The mean relative (SD) LTL was 1.03 (0.19). Children living in households using biomass fuel had on average 0.09 (95% CI: 0.05 to 0.13) units shorter LTL than children in households with no biomass fuel use. The observed association was unaltered after adjusting for relevant confounders. The association between LTL and biomass use was strongest among children from households with &#x2264;2 rooms and without separate kitchen.<br><br>SIGNIFICANCE: Exposure to biomass fuel use in early life might have consequences for longevity, and risk of chronic illnesses reflected in shortening of the telomeres. Our findings support the ongoing effort to reduce exposure to biomass fuel in low-resource settings.<br><br>IMPACT STATEMENTS: Biomass for cooking is a leading source of household air pollution in low and middle-income countries, contributing to many chronic diseases and premature deaths. Chronic exposure to biomass fuel through oxidative stress and inflammation has been associated with a shortening of the telomeres, a "biological marker" of longevity. This prospective cohort study describes the association between household biomass fuel use and leukocyte telomere length among 497 toddlers. Leukocyte telomere length was significantly shorter among children living in households with biomass fuel than in children from homes where mainly LPG was used for cooking.<br><br>CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT02272842, registered October 21, 2014, Universal Trial Number: U1111-1161-5187 (September 8, 2014).},
}
@article {pmid36137363,
year = {2022},
author = {Verma, AK and Singh, P and Al-Saeed, FA and Ahmed, AE and Kumar, S and Kumar, A and Dev, K and Dohare, R},
title = {Unravelling the role of telomere shortening with ageing and their potential association with diabetes, cancer, and related lifestyle factors.},
journal = {Tissue &amp; cell},
volume = {79},
number = {},
pages = {101925},
doi = {10.1016/j.tice.2022.101925},
pmid = {36137363},
issn = {1532-3072},
mesh = {Humans ; Telomere Shortening/genetics ; Telomere/genetics/metabolism ; *Telomerase/genetics/metabolism ; Aging/genetics ; *Neoplasms ; Life Style ; *Diabetes Mellitus ; RNA, Messenger ; },
abstract = {Telomeres are often considered as the 'ageing clock' that determines the lifespan at the cellular level, forming the ends of a chromosome, which shorten each time the cell divides itself to the point where they become so short the cell is unable to divide itself further. Telomere length alteration is often linked with lifestyle factors such as age, obesity, exposure to pesticides and pollution, depression, unhealthy diet, lack of exercise, and stress. The current review discusses the mechanism of telomere shortening in relation to ageing and lifestyle factors in general and its association with chronic diseases like diabetes which may influence the health and lifespan of an individual by increasing telomere shortening. Accelerated or excessive telomere shortening is also associated with the early onset of age-related disorders globally and, hence, reduced lifespan of individuals. Upregulated Telomerase activity and reactivation of telomeres is observed in > 70 % of cancer patients by TERT point mutations, rearrangements, DNA amplifications, and transcript fusions, making it a useful marker in diagnosis and prognosis of various cancers. The study presents a systematic review of the unregulated Telomere activity with progression of various cancer and extrapolation of suitable pathways and prognostic information correlated with mRNA levels of TERT, which are critical among thymic epithelial tumors (TETs). In most cancers, unlimited proliferation is due to the reactivation of reverse transcriptase gene TERT. All these observations are comprehensively presented in the paper and might be useful for researchers working in the field of telomere dynamics and finding the correlation of age shortening with mRNA expression profiling.},
}
@article {pmid36136831,
year = {2022},
author = {Chico-Sordo, L and Polonio, AM and Córdova-Oriz, I and Medrano, M and Herraiz, S and Bronet, F and García-Velasco, JA and Varela, E},
title = {Telomeres and oocyte maturation rate are not reduced by COVID-19 except in severe cases.},
journal = {Reproduction (Cambridge, England)},
volume = {164},
number = {5},
pages = {259-267},
doi = {10.1530/REP-22-0243},
pmid = {36136831},
issn = {1741-7899},
mesh = {*COVID-19 ; Female ; Humans ; Leukocytes, Mononuclear ; Male ; Oocytes ; Prospective Studies ; SARS-CoV-2 ; Telomere ; },
abstract = {IN BRIEF: COVID-19 does not affect the telomeres or fertility outcomes in mild cases. However, in women with severe symptoms, telomeres of granulosa cells are shorter, and the oocyte maturation rate is decreased.<br><br>ABSTRACT: The coronavirus SARS-CoV-2 causes COVID-19 disease and affects primarily the lungs and also other organs, causing accelerated cell aging. One of the main pathways involved in aging is telomere attrition, which ultimately leads to defective tissue regeneration and organ dysfunction. Indeed, short telomeres in aged people aggravate the COVID-19 symptoms, and COVID-19 survivors showed shorter telomeres in blood cells. The SARS-CoV-2 has been detected in testis, but the ovaries, which express the viral entry factors, have not been fully explored. Our objective was to analyze telomeres and reproductive outcomes in women who had COVID-19 and controls. In this prospective cohort study, granulosa cells (GCs) and blood were collected from 65 women. Telomere length (TL) was measured by high-throughput in situ hybridization. Mean TL of GCs and peripheral blood mononuclear cells (PBMCs) was alike in control and mild cases. However, mean TL of GCs was lower in severe cases compared to controls (P = 0.017). Control and COVID groups had similar ovarian reserve and number of total oocytes after puncture. However, the oocyte maturation rate was lower in severe cases (P = 0.018). Interestingly, a positive correlation between the oocyte maturation rate and TL of GCs was found in the control group (P = 0.024). Our findings point to a potential impact of the coronavirus infection on telomeres and reproductive outcomes in severe cases. This might be considered upon possible new SARS-CoV threats, to favor treatments that enhance oocyte maturation in women severely affected by coronavirus undergoing ART.},
}
@article {pmid36130485,
year = {2022},
author = {McKinney, AM and Mathur, R and Stevers, NO and Molinaro, AM and Chang, SM and Phillips, JJ and Costello, JF},
title = {GABP couples oncogene signaling to telomere regulation in TERT promoter mutant cancer.},
journal = {Cell reports},
volume = {40},
number = {12},
pages = {111344},
pmid = {36130485},
issn = {2211-1247},
support = {F31 CA243187/CA/NCI NIH HHS/United States ; P01 CA118816/CA/NCI NIH HHS/United States ; P50 CA097257/CA/NCI NIH HHS/United States ; R01 CA244838/CA/NCI NIH HHS/United States ; },
mesh = {AMP-Activated Protein Kinases/metabolism ; Adenosine Monophosphate ; ErbB Receptors/genetics/metabolism ; GA-Binding Protein Transcription Factor/metabolism ; *Glioblastoma/genetics ; Humans ; Mutation/genetics ; Oncogenes ; RNA, Messenger ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {Telomerase activation counteracts senescence and telomere erosion caused by uncontrolled proliferation. Epidermal growth factor receptor (EGFR) amplification drives proliferation while telomerase reverse transcriptase promoter (TERTp) mutations underlie telomerase reactivation through recruitment of GA-binding protein (GABP). EGFR amplification and TERTp mutations typically co-occur in glioblastoma, the most common and aggressive primary brain tumor. To determine if these two frequent alterations driving proliferation and immortality are functionally connected, we combine analyses of copy number, mRNA, and protein data from tumor tissue with pharmacologic and genetic perturbations. We demonstrate that proliferation arrest decreases TERT expression in a GABP-dependent manner and elucidate a critical proliferation-to-immortality pathway from EGFR to TERT expression selectively from the mutant TERTp through activation of AMP-mediated kinase (AMPK) and GABP upregulation. EGFR-AMPK signaling promotes telomerase activity and maintains telomere length. These results define how the tumor cell immortality mechanism keeps pace with persistent oncogene signaling and cell cycling.},
}
@article {pmid36130216,
year = {2022},
author = {Seo, B and Yang, K and Kahe, K and Qureshi, AA and Chan, AT and De Vivo, I and Cho, E and Giovannucci, EL and Nan, H},
title = {Association of omega-3 and omega-6 fatty acid intake with leukocyte telomere length in US males.},
journal = {The American journal of clinical nutrition},
volume = {116},
number = {6},
pages = {1759-1766},
pmid = {36130216},
issn = {1938-3207},
support = {U01 CA167552/CA/NCI NIH HHS/United States ; U01 CA167552/GF/NIH HHS/United States ; },
mesh = {Male ; Humans ; Cross-Sectional Studies ; *Telomere ; Case-Control Studies ; Follow-Up Studies ; Leukocytes ; *Fatty Acids, Omega-3/pharmacology ; Fatty Acids, Omega-6 ; Fatty Acids ; },
abstract = {BACKGROUND: Omega-3 (n-3) and omega-6 (n-6) fatty acids may contribute to oxidative stress and inflammation, which are related to telomere shortening. Evidence supporting an association between intake of n-3 or n-6 fatty acids and leukocyte telomere length (LTL) in males has been limited.<br><br>OBJECTIVES: We conducted a cross-sectional study to examine the associations of total or individual n-3 or total n-6 fatty acid intake with LTL in US males.<br><br>METHODS: We included 2,494 US males with LTL measurement from 4 nested case-control studies within the Health Professionals Follow-Up Study. Individuals with previous histories of cancers, diabetes, and cardiovascular diseases at or before blood collection were excluded. Blood collection was performed between 1993 and 1995, and relevant information including n-3 and n-6 intake was collected in 1994 by questionnaire. The LTL was log-transformed and Z scores of the LTL were calculated for statistical analyses by standardizing the LTL in comparison with the mean within each selected nested case-control study.<br><br>RESULTS: We found that consumption of DHA (22:6n-3) was positively associated with LTL. In the multivariable-adjusted model, compared with individuals who had the lowest intake of DHA (i.e., first quartile group), the percentage differences (95% CIs) of LTL were -3.7 (-13.7, 7.5), 7.0 (-4.3, 19.7), and 8.2 (-3.5, 21.3) for individuals in the second, third, and fourth quartiles of consumption, respectively (P-trend&#xa0;=&#xa0;0.0498). We did not find significant associations between total n-3 or total n-6 fatty acid intakes and LTL. In addition, we found that males who consumed canned tuna had longer LTL than those who did not; in the multivariable-adjusted model, the percentage difference of LTL was 10.5 (95% CI: 1.3, 20.4) (P&#xa0;=&#xa0;0.02).<br><br>CONCLUSIONS: Our results suggest that higher intakes of DHA and canned tuna consumption are associated with longer LTL.},
}
@article {pmid36126117,
year = {2022},
author = {Foley, JF},
title = {Telomeres to go.},
journal = {Science signaling},
volume = {15},
number = {752},
pages = {eade9136},
doi = {10.1126/scisignal.ade9136},
pmid = {36126117},
issn = {1937-9145},
mesh = {*Cellular Senescence/genetics ; *Telomere/genetics ; },
abstract = {By acquiring telomeres from antigen-presenting cells, some T cells are protected from senescence.},
}
@article {pmid36125668,
year = {2023},
author = {Tian, C and Heng, D and Zhao, N and Liu, L and Sheng, X and Chen, J and Liu, L},
title = {Short telomeres impede germ cell specification by upregulating MAPK and TGFβ signaling.},
journal = {Science China. Life sciences},
volume = {66},
number = {2},
pages = {324-339},
pmid = {36125668},
issn = {1869-1889},
mesh = {Animals ; Mice ; Chromatin/metabolism ; *Germ Cells/metabolism ; Telomerase/genetics/metabolism ; *Telomere/genetics/metabolism ; Transforming Growth Factor beta/metabolism ; MAP Kinase Signaling System/physiology ; },
abstract = {Functional telomeres protect chromosome ends and play important roles in stem cell maintenance and differentiation. Short telomeres negatively impact germ cell development and can contribute to age-associated infertility. Moreover, telomere syndrome resulting from mutations of telomerase or telomere-associated genes exhibits short telomeres and reduced fertility. It remains elusive whether and how telomere lengths affect germ cell specification. We report that functional telomere is required for the coordinated germ cell and somatic cell fate decisions. Using telomerase gene Terc deficient mice as a model, we show that short telomeres restrain germ cell specification of epiblast cells but promote differentiation towards somatic lineage. Short telomeres increase chromatin accessibility to elevate TGFβ and MAPK/ERK signaling for somatic cell differentiation. Notably, elevated Fst expression in TGFβ pathway represses the BMP4-pSmad signaling pathway, thus reducing germ cell formation. Re-elongation of telomeres by targeted knock-in of Terc restores normal chromatin accessibility to suppress TGFβ and MAPK signaling, thereby facilitating germ cell formation. Taken together, our data reveal that functional telomeres are required for germ cell specification by repressing TGFβ and MAPK signaling.},
}
@article {pmid36125233,
year = {2023},
author = {Park, HS and Son, BR and Kwon, J},
title = {Usefulness of Genetic Aberration and Shorter Telomere Length in Myelodysplastic Syndrome: A Pilot Study.},
journal = {Laboratory medicine},
volume = {54},
number = {2},
pages = {199-205},
doi = {10.1093/labmed/lmac100},
pmid = {36125233},
issn = {1943-7730},
support = {//Chonbuk National University Hospital/ ; },
mesh = {Humans ; Pilot Projects ; *Myelodysplastic Syndromes/diagnosis/genetics ; Prognosis ; Real-Time Polymerase Chain Reaction ; Telomere/genetics ; },
abstract = {OBJECTIVE: We aimed to evaluate the clinical usefulness of genetic aberration and shorter telomere length (TL) in individuals with myelodysplastic syndrome (MDS).<br><br>METHODS: A targeted sequencing panel with 49 genes and TL measurement by quantitative real-time polymerase chain reaction were performed for 46 subjects.<br><br>RESULTS: According to the revised International Prognostic Scoring System (IPSS-R) subtypes, the mutation frequency was 33.3%, 57.9%, and 100% in the very low/low, intermediate, and very high/high risk groups, respectively. A shorter telomere was detected in 43.5%. We defined group 1 as IPSS-R-high or -very high risk, group 2 as having 1 or more genetic aberrations, group 3 as having a shorter TL, and group 4 as having a longer TL than the age-matched reference. Group 1 and group 2 showed an adverse prognosis. The TL was not strongly correlated with MDS prognosis. However, it may be related to a poor long-term prognosis.<br><br>CONCLUSION: Genetic variation and shorter TL may be helpful in reclassifying non-high-risk groups.},
}
@article {pmid36122232,
year = {2022},
author = {Silva, B and Arora, R and Azzalin, CM},
title = {The alternative lengthening of telomeres mechanism jeopardizes telomere integrity if not properly restricted.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {119},
number = {39},
pages = {e2208669119},
pmid = {36122232},
issn = {1091-6490},
mesh = {DNA ; Endonucleases/metabolism ; Humans ; *RNA, Long Noncoding ; *Telomerase/genetics ; Telomere/genetics/metabolism ; },
abstract = {A substantial number of human cancers are telomerase-negative and elongate physiologically damaged telomeres through a break-induced replication (BIR)-based mechanism known as alternative lengthening of telomeres (ALT). We recently demonstrated that inhibiting the transcription of the telomeric long noncoding RNA TERRA suppresses telomere damage and ALT features, indicating that telomere transcription is a main trigger of ALT activity. Here we show that experimentally increased TERRA transcription not only increases ALT features, as expected, but also causes rapid loss of telomeric DNA through a pathway that requires the endonuclease Mus81. Our data indicate that the ALT mechanism can endanger telomere integrity if not properly controlled and point to TERRA transcription as a uniquely versatile target for therapy.},
}
@article {pmid36121249,
year = {2022},
author = {Sharqawi, M and Hantisteanu, S and Bilgory, A and Aslih, N and Shibli Abu Raya, Y and Atzmon, Y and Estrada, D and Limonad, O and Meisel-Sharon, S and Shalom-Paz, E},
title = {The Impact of Lifestyle on Sperm Function, Telomere Length, and IVF Outcomes.},
journal = {American journal of men's health},
volume = {16},
number = {5},
pages = {15579883221119931},
pmid = {36121249},
issn = {1557-9891},
mesh = {Female ; Fertilization in Vitro ; Humans ; Life Style ; Male ; Pregnancy ; *Semen ; *Sperm Motility ; Spermatozoa ; Telomere ; },
abstract = {Many risk factors can potentially influence sperm quality. Telomeres confer stability on the chromosome and their dysfunction has been implicated in conditions such as cancer, aging, and lifestyle. The impact of lifestyle on sperm cell telomeres is unclear. The objectives of this study were to evaluate the impact of lifestyle behaviors on telomere length in sperm and to follow the correlation with pregnancy outcomes in patients undergoing in vitro fertilization (IVF). In this prospective observational study, sperm was analyzed for telomere length (TL). Men were asked to report lifestyle behaviors including occupation (physical or sedentary), smoking duration and amount, physical activity, dietary habits, and where they keep their cellular phone (bag, pants, or shirt pocket). Correlations among semen analysis, TL, men's habits, and embryo quality and pregnancy outcomes were evaluated. Among 34 patients recruited, 12 had longer TL and 13 shorter TL. Sperm motility was negatively correlated with TL (Pearson correlation = -.588, p = .002). Smoking adversely affected native sperm motility (53% motility in nonsmokers vs. 37% in smokers; p = .006). However, there was no significant impact on TL. The group with longer telomeres demonstrated significant association with healthy diet (10/12 vs. 6/13; p = .05) and a trend toward more sports activity, weekly (16/84 vs. 7/91; p = .04) compared with the shorter telomeres group. This study suggests that lifestyle, healthy diet, and sports activity are associated with long telomeres in sperm. Sperm quality is also influenced by patients' habits. The study strongly recommends maintaining a healthy lifestyle to preserve general health and fertility.},
}
@article {pmid36119151,
year = {2022},
author = {Kazantseva, AV and Davydova, YD and Enikeeva, RF and Mustafin, RN and Lobaskova, MM and Malykh, SB and Khusnutdinova, EK},
title = {Individual Differences in Relative Telomere Length in Mentally Healthy Subjects: The Effect of TERT Gene Polymorphism and Urban Residency.},
journal = {Russian journal of genetics},
volume = {58},
number = {9},
pages = {1135-1144},
pmid = {36119151},
issn = {1022-7954},
abstract = {The changes in the telomere length caused by the terminal underreplication in the existing literature are related to depressive disorders. However, the use of the telomere length as a biomarker of depressive states is ambiguous, which is due to the effect of various environmental factors on both the psychoemotional state and cellular aging of an organism. In order to identify the possible use of the relative telomere length (RTL) measured in peripheral blood leukocytes as a biomarker of enhanced liability to depression prior to the clinical symptoms, as well as to determine the link between telomere length, sociodemographic factors, allelic variants of the genes involved in the regulation of telomere elongation, and depression level, the association analysis of reverse transcriptase (TERT rs7726159), telomerase RNA component (TERC rs1317082), and the CST complex encoding protein (OBFC1 rs2487999) gene polymorphisms was performed with RTL and depression level in mentally healthy individuals (N = 1065) aged 18-25 years. Together with genetic variants, the examined regression models included various sociodemographic parameters as predictors. As a result of statistical analysis, we failed to observe the association between RTL and individual differences in depression level in the studied sample. Nevertheless, multiple regression analysis allowed us to construct a statistically significant model of individual variance in RTL (P = 4.3е-4; r [2] = 0.018), which included rs7726159 in the TERT gene (P = 0.020; β = 0.078) and such environmental predictors as age (P = 0.001; β = -0.027) and place of residence in childhood (urban/rural area) (P = 0.048; β = 0.063). The data obtained confirm the involvement of TERT gene variants and age in telomere length in mentally healthy individuals aged 18-25 years and indicate a negative effect of urban residency on telomere length shortening, which reflects the cellular aging of an organism.},
}
@article {pmid36116241,
year = {2022},
author = {Saini, D and Jain, V and Das, B},
title = {Evaluation of natural chronic low dose radiation exposure on telomere length and transcriptional response of shelterin complex in individuals residing in Kerala coast, India.},
journal = {Mutation research},
volume = {825},
number = {},
pages = {111797},
doi = {10.1016/j.mrfmmm.2022.111797},
pmid = {36116241},
issn = {1873-135X},
mesh = {Humans ; Male ; Shelterin Complex ; Leukocytes, Mononuclear/radiation effects ; Background Radiation ; Telomere/genetics/metabolism ; *Radiation Exposure/adverse effects ; X-ray Repair Cross Complementing Protein 1/metabolism ; Cell Cycle Proteins/metabolism ; *DNA Glycosylases/metabolism ; },
abstract = {The high level natural radiation areas (HLNRA) of Kerala coast provide unique opportunity to study the biological effect of chronic low dose ionizing radiation (LDIR) on human population below 100 mSv. The radiation level in this area varies from < 1.0-45 mGy /year due to patchy distribution of monazite in the sand, which contains [232]Th (8-10%), [238]U (0.3%), and their decay products. Telomere length attrition has been correlated to DNA damage due to genotoxic agents. The objective of the present study is to evaluate the effect of natural chronic LDIR exposure on telomere length and transcriptional response of telomere specific and DNA damage repair genes in peripheral blood mononuclear cells (PBMCs) of individuals from normal level natural radiation areas (NLNRA) and HLNRA of Kerala coast, southwest India. Blood samples were collected from 71 random male donors (24-80 years) from NLNRA (≤1.50 mGy/year; N = 19) and two HLNRA dose groups [1.51-10 mGy/year (N = 17); > 10 mGy/year, (N = 35)]. Genomic DNA was isolated from PBMCs and relative telomere length (RTL) was determined using real time q-PCR. Radio-adaptive response (RAR) study was carried out in PBMCs of 40 random males from NLNRA (N = 20) and HLNRA (>10 mGy/year; N = 20), where PBMCs were given a challenged dose of 2.0 Gy gamma radiation at 4 h. Transcriptional profile of telomere specific (TRF1, TRF2, POT1, TIN2, TPP1, RAP1), DNA damage response (RAD17, ATM, CHEK1) and base excision repair pathway (BER) (OGG1, XRCC1, NTH1, NEIL1, MUTYH, MBD4) genes were analysed at basal level and after a challenge dose of 2.0 Gy at 4 h. Our results did not show any significant effect of chronic LDR on RTL among the individuals from NLNRA and two HLNRA groups (p = 0.195). However, influence of age on RTL was clearly evident among NLNRA and HLNRA individuals. At basal level, TRF1, TRF2, TIN2, MBD4, NEIL1 and RAD17 showed significant up-regulation, whereas XRCC1 was significantly down regulated in HLNRA individuals. After a challenge dose of 2.0 Gy, significant transcriptional up-regulation was observed at telomere specific (TRF2, POT1) and BER (MBD4, NEIL1) genes in HLNRA individuals as compared to NLNRA suggesting their role in RAR. In conclusion, elevated level of natural chronic LDR exposure did not have any adverse effect on telomere length in Kerala coast. Significant transcriptional response at TRF2, MBD4 and NEIL1 at basal level and with a challenge dose of 2.0 Gy suggested their active involvement in efficient repair and telomere maintenance in individuals from HLNRA of Kerala coast.},
}
@article {pmid36110146,
year = {2022},
author = {Panelli, DM and Diwan, M and Cruz, GI and Leonard, SA and Chueh, J and Gotlib, IH and Bianco, K},
title = {An exploratory analysis of leukocyte telomere length among pregnant and non-pregnant people.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {25},
number = {},
pages = {100506},
pmid = {36110146},
issn = {2666-3546},
abstract = {BACKGROUND: Leukocyte telomere length (LTL) is a biomarker that is affected by older age, psychosocial stress, and medical comorbidities. Despite the relevance of these factors to obstetric practice, little is known about LTL in pregnancy. Our study explored longitudinal LTL dynamics in pregnant and non-pregnant people.<br><br>OBJECTIVE: This pilot study compares changes in LTL between pregnant and non-pregnant people over time, explores potential correlations between LTL and mental health measures, and investigates associations between short first-trimester LTL and adverse pregnancy outcomes.<br><br>STUDY DESIGN: This was a prospective pilot cohort study of nulliparous pregnant and non-pregnant people between ages 18 and 50 who presented for care at a single institution from January to November 2020. Pregnant people were enrolled between 10 and 14 weeks gestation. Participants had two blood samples drawn for LTL; the first on the day of enrollment and the second on postpartum day 1 (pregnant cohort) or 7 months later (non-pregnant cohort). LTL was measured using quantitative PCR. The primary outcome was the difference between pregnant and non-pregnant people in LTL change between the two timepoints (basepair difference per 30-day period). Secondary outcomes included differences in responses to the Patient Health Questionnaire-9 (PHQ-9) and a survey about stress related to COVID-19. Differences in LTL were tested using t-tests and linear regression models, both crude and adjusted for age. A subgroup analysis was conducted within the pregnant cohort to examine whether shorter first-trimester LTL was associated with adverse pregnancy outcomes. We conducted t-tests to compare LTL between people with and without each categorical outcome and computed Pearson correlation coefficients between LTL and continuous outcomes such as gestational age at delivery.<br><br>RESULTS: 46 pregnant and 30 non-pregnant people were enrolled; 44 pregnant and 18 non-pregnant people completed all LTL assessments. There were no between-group differences in LTL change (-4.2&#xa0;&#xb1;&#xa0;22.2 bp per 30 days pregnant versus -6.4&#xa0;&#xb1;&#xa0;11.2 bp per 30 days non-pregnant, adjusted beta 2.1, 95% CI -9.0-13.2, p&#xa0;=&#xa0;0.60). The prevalence of depression and pandemic-related stress were both low overall. The two groups did not differ in PHQ-9 scores, and no correlations were significant between LTL and PHQ-9 scores. Among the 44 pregnant people, shorter first-trimester LTL was significantly correlated with earlier gestational age at delivery (r&#xa0;=&#xa0;0.35, p&#xa0;=&#xa0;0.02).<br><br>CONCLUSION: In this exploratory pilot cohort of reproductive-aged people with low levels of psychological stress, we described baseline changes in LTL over time in pregnant and non-pregnant participants. We found a correlation between shorter first-trimester LTL and earlier gestational age at delivery, which warrants further investigation in a larger cohort.},
}
@article {pmid36109671,
year = {2022},
author = {Lanna, A and Vaz, B and D'Ambra, C and Valvo, S and Vuotto, C and Chiurchiù, V and Devine, O and Sanchez, M and Borsellino, G and Akbar, AN and De Bardi, M and Gilroy, DW and Dustin, ML and Blumer, B and Karin, M},
title = {An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory.},
journal = {Nature cell biology},
volume = {24},
number = {10},
pages = {1461-1474},
pmid = {36109671},
issn = {1476-4679},
support = {100262Z/12/Z/WT_/Wellcome Trust/United Kingdom ; 110229/WT_/Wellcome Trust/United Kingdom ; MR/P00184X/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/M003833/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {*Telomerase/genetics/metabolism ; Immunologic Memory ; T-Lymphocytes/metabolism ; Telomere/genetics/metabolism ; Cellular Senescence/genetics ; },
abstract = {The common view is that T lymphocytes activate telomerase to delay senescence. Here we show that some T cells (primarily naïve and central memory cells) elongated telomeres by acquiring telomere vesicles from antigen-presenting cells (APCs) independently of telomerase action. Upon contact with these T cells, APCs degraded shelterin to donate telomeres, which were cleaved by the telomere trimming factor TZAP, and then transferred in extracellular vesicles at the immunological synapse. Telomere vesicles retained the Rad51 recombination factor that enabled telomere fusion with T-cell chromosome ends lengthening them by an average of ~3,000 base pairs. Thus, there are antigen-specific populations of T cells whose ageing fate decisions are based on telomere vesicle transfer upon initial contact with APCs. These telomere-acquiring T cells are protected from senescence before clonal division begins, conferring long-lasting immune protection.},
}
@article {pmid36104328,
year = {2022},
author = {Bowyer, P and Currin, A and Delneri, D and Fraczek, MG},
title = {Telomere-to-telomere genome sequence of the model mould pathogen Aspergillus fumigatus.},
journal = {Nature communications},
volume = {13},
number = {1},
pages = {5394},
pmid = {36104328},
issn = {2041-1723},
support = {208396/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; /DH_/Department of Health/United Kingdom ; },
mesh = {*Aspergillus fumigatus/genetics ; DNA Transposable Elements/genetics ; *Fungi ; Humans ; Sequence Analysis, DNA ; Telomere/genetics ; },
abstract = {The pathogenic fungus Aspergillus fumigatus is a major etiological agent of fungal invasive and chronic diseases affecting tens of millions of individuals worldwide. Draft genome sequences of two clinical isolates (Af293 and A1163) are commonly used as reference genomes for analyses of clinical and environmental strains. However, the reference sequences lack coverage of centromeres, an accurate sequence for ribosomal repeats, and a comprehensive annotation of chromosomal rearrangements such as translocations and inversions. Here, we used PacBio Single Molecule Real-Time (SMRT), Oxford Nanopore and Illumina HiSeq sequencing for de novo genome assembly and polishing of two laboratory reference strains of A. fumigatus, CEA10 (parental isolate of A1163) and its descendant A1160. We generated full length chromosome assemblies and a comprehensive telomere-to-telomere coverage for CEA10 and near complete assembly of A1160 including ribosomal repeats and the sequences of centromeres, which we discovered to be composed of long transposon elements. We envision these high-quality reference genomes will become fundamental resources to study A. fumigatus biology, pathogenicity and virulence, and to discover more effective treatments against diseases caused by this fungus.},
}
@article {pmid36103374,
year = {2022},
author = {Barbosa, ARC and Nunes, DP and Lima, DB and Colombo, FA and Nunes, JB and Santos Orlandi, AAD and Rocha, GDS and Pereira, DS and Corona, LP and Brito, TRP},
title = {Association of Social Support Network with Telomere Length: A Cross-Sectional Study with Community-Dwelling Older Adults.},
journal = {Rejuvenation research},
volume = {25},
number = {6},
pages = {253-259},
doi = {10.1089/rej.2022.0037},
pmid = {36103374},
issn = {1557-8577},
mesh = {Humans ; Aged ; *Independent Living ; Cross-Sectional Studies ; *Activities of Daily Living ; Social Support ; Telomere ; },
abstract = {Considering that telomere length can be determined not only by issues related to cell biology but also by aspects related to social factors and environmental exposures, studies on the relationship between social aspects and telomere length can help to better understand the still scarcely known aspects of the human aging process. Thus, this research seeks to verify whether social support networks are associated with telomere length in older adults. This is a cross-sectional study conducted with 448 individuals aged at least 60 years living in the urban area of an inland Brazilian municipality. Relative quantification of telomere length was obtained through real-time qPCR. Social support was assessed through the Medical Outcomes Study Social Support Scale. Descriptive statistics and multiple logistic regression were used in data analysis. The evaluated social support networks for older adults consist in a mean of 16.4 people, and the percentage of older adults who reported up to five members in their network was 27.75%. Shorter telomere length was identified in 25% of the participants, and the older adults who reported having up to five members in their support network were more likely to have a shorter telomere length than those who reported more numerous networks (odds ratio: 1.89, p = 0.011) regardless of gender, age, household arrangement, cognitive decline, and dependence for basic and instrumental activities of daily living, which suggests that measures that stimulate the creation and maintenance of social support networks should be implemented to improve older adults' health.},
}
@article {pmid36098743,
year = {2022},
author = {Liu, Z and Wei, X and Gao, Y and Gao, X and Li, X and Zhong, Y and Wang, X and Liu, C and Shi, T and Lv, J and Liu, T},
title = {Zbtb34 promotes embryonic stem cell proliferation by elongating telomere length.},
journal = {Aging},
volume = {14},
number = {17},
pages = {7126-7136},
pmid = {36098743},
issn = {1945-4589},
mesh = {Animals ; Mice ; Alanine/genetics ; Cell Proliferation ; DNA ; DNA, Complementary ; *DNA, Single-Stranded ; DNA-Binding Proteins/genetics ; Embryonic Stem Cells/metabolism ; *Repressor Proteins/metabolism ; Shelterin Complex ; Telomere/genetics/metabolism ; *Telomere-Binding Proteins/genetics/metabolism ; },
abstract = {Zbtb34 is a novel zinc finger protein, which is revealed by biological software analysis to have 3 zinc fingers, but its functions remain unknown. In this study, mouse Zbtb34 cDNA was amplified by PCR and inserted into the plasmid pEGFP-N1 to generate Zbtb34-EGFP fusion protein. The upregulation of Zbtb34 in mouse embryonic stem cells promoted telomere elongation and increased cell proliferation. In order to understand the above phenomena, the telomere co-immunoprecipitation technique was employed to investigate the relationship between Zbtb34 and telomeres. The results indicated that Zbtb34 could bind to the DNA sequences of the telomeres. Alanine substitution of the third zinc finger abolished such binding. Since Pot1 is the only protein binding to the single-stranded DNA at the end of the telomeres, we further investigated the relationship between Zbtb34 and Pot1. The results revealed that the upregulation of Zbtb34 decreased the binding of Pot1b to the telomeres. Through the upregulation of Pot1b, the binding of Zbtb34 to the telomeres was also reduced. In conclusion, we showed that the main biological function of Zbtb34 was to bind telomere DNA via its third ZnF, competing with Pot1b for the binding sites, resulting in telomere elongation and cell proliferation.},
}
@article {pmid36091172,
year = {2022},
author = {Fiesco-Roa, M&#xd3; and García-de Teresa, B and Leal-Anaya, P and van 't Hek, R and Wegman-Ostrosky, T and Frías, S and Rodríguez, A},
title = {Fanconi anemia and dyskeratosis congenita/telomere biology disorders: Two inherited bone marrow failure syndromes with genomic instability.},
journal = {Frontiers in oncology},
volume = {12},
number = {},
pages = {949435},
pmid = {36091172},
issn = {2234-943X},
abstract = {Inherited bone marrow failure syndromes (IBMFS) are a complex and heterogeneous group of genetic diseases. To date, at least 13 IBMFS have been characterized. Their pathophysiology is associated with germline pathogenic variants in genes that affect hematopoiesis. A couple of these diseases also have genomic instability, Fanconi anemia due to DNA damage repair deficiency and dyskeratosis congenita/telomere biology disorders as a result of an alteration in telomere maintenance. Patients can have extramedullary manifestations, including cancer and functional or structural physical abnormalities. Furthermore, the phenotypic spectrum varies from cryptic features to patients with significantly evident manifestations. These diseases require a high index of suspicion and should be considered in any patient with abnormal hematopoiesis, even if extramedullary manifestations are not evident. This review describes the disrupted cellular processes that lead to the affected maintenance of the genome structure, contrasting the dysmorphological and oncological phenotypes of Fanconi anemia and dyskeratosis congenita/telomere biology disorders. Through a dysmorphological analysis, we describe the phenotypic features that allow to make the differential diagnosis and the early identification of patients, even before the onset of hematological or oncological manifestations. From the oncological perspective, we analyzed the spectrum and risks of cancers in patients and carriers.},
}
@article {pmid36087937,
year = {2022},
author = {Svyryd, Y and Pascual-Ramos, V and Contreras-Yañez, I and Muñoz-Tellez, LA and Luna-Muñoz, L and López-Hernández, MA and Aguayo-Gómez, A and Mutchinick, OM},
title = {Telomeres Length Variations in a Rheumatoid Arthritis Patients Cohort at Early Disease Onset and after Follow-Up.},
journal = {Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion},
volume = {74},
number = {4},
pages = {202-211},
doi = {10.24875/RIC.22000048},
pmid = {36087937},
issn = {0034-8376},
mesh = {Humans ; *Arthritis, Rheumatoid/genetics ; Follow-Up Studies ; Telomere/genetics ; Telomere Shortening ; },
abstract = {BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial joint inflammation, progressive disability, premature immune aging, and telomere length (TL) shortening.<br><br>OBJECTIVES: The objective of the study was to study TL changes in patients at early disease onset and after follow-up.<br><br>METHODS: Relative leukocyte TL (rLTL) was measured by quantitative polymerase chain reaction (qPCR) in 88 at-admission patients (AAP) with < 1 year of symptoms onset, self-compared after follow-up, and a reference group of sex- and age-matched healthy individuals. Correlations between rLTL percentage change after variable disease exposure time (DET) and clinical laboratory disease activity markers and treatments were assessed. Non-parametrical statistics were applied, considering < 0.05 p-value significant.<br><br>RESULTS: The median (p25, p75) rLTL was lower in patients after DET (0.61, 0.49-0.70) than in AAP (0.64, 0.50-0.77), p = 0.017. Furthermore, telomeres at early stages of RA were shorter than in the reference group (0.77, 0.59-0.92; p = 0.003). HLA-DRB1*04 allele carrier status did not significantly affect rLTL at an early stage and after follow-up. The patients' rLTL shortening was mainly associated with longer at-admission telomeres (OR 16.2, 95%CI: 3.5-74.4; p < 0.0001).<br><br>CONCLUSIONS: At follow-up, RA patients showed significantly shorter rLTL than AAP, particularly in those AAP with longer telomeres, disregarding disease activity and treatments, denoting an rLTL shortening effect influenced by age, DET, and native rLTL.},
}
@article {pmid36085441,
year = {2023},
author = {Qureshi, F and Aris, IM and Rifas-Shiman, SL and Perng, W and Oken, E and Rich-Edwards, J and Cardenas, A and Baccarelli, AA and Enlow, MB and Belfort, MB and Tiemeier, H},
title = {Associations of cord blood leukocyte telomere length with adiposity growth from infancy to adolescence.},
journal = {Pediatric obesity},
volume = {18},
number = {1},
pages = {e12977},
pmid = {36085441},
issn = {2047-6310},
support = {R03 AG067064/AG/NIA NIH HHS/United States ; T32 CA009001/CA/NCI NIH HHS/United States ; R24 ES030894/ES/NIEHS NIH HHS/United States ; R01 HD034568/HD/NICHD NIH HHS/United States ; P30 DK048520/DK/NIDDK NIH HHS/United States ; R01 HD082078/HD/NICHD NIH HHS/United States ; R01 ES031259/ES/NIEHS NIH HHS/United States ; UH3 OD023286/OD/NIH HHS/United States ; },
mesh = {Child ; Infant, Newborn ; Male ; Infant ; Adolescent ; Female ; Humans ; *Adiposity ; *Fetal Blood ; Obesity ; Body Mass Index ; Leukocytes ; Telomere ; Biomarkers ; },
abstract = {OBJECTIVE: Leukocyte telomere length (LTL) may be a biomarker for chronic disease susceptibility, but no work has tested this hypothesis directly. Our study investigated associations of LTL at birth with markers of adiposity growth that are linked with cardiometabolic health later in life.<br><br>METHODS: Participants were 375 children in Project Viva (48% female, 71% White). Body mass index (BMI) trajectories from birth to 18&#x2009;years were tracked using repeated measures of BMI collected in physical examinations and via medical records, then used to predict age (months) and magnitude (kg/m[2]) of BMI peak and rebound. LTL was measured from cord blood via duplex quantitative PCR. A binary variable indicating LTL shorter than the reference population average was the primary exposure.<br><br>RESULTS: LTL was unrelated to BMI at peak or rebound, but associations were apparent with the timing of BMI growth milestones. Short LTL was related to a later age of peak for females (&#x3b2;&#xa0;=&#xa0;0.99, 95% CI&#xa0;=&#xa0;0.16, 1.82; psex interaction &#xa0;=&#xa0;0.015) and an earlier age of rebound for both males and females (&#x3b2;combined &#xa0;=&#xa0;-5.26, 95% CI&#xa0;=&#xa0;-9.44, -1.08).<br><br>CONCLUSION: LTL at birth may be an early biomarker of altered adiposity growth. Newborn telomere biology may shed new insight into the developmental origins of health and disease.},
}
@article {pmid36078786,
year = {2022},
author = {Montiel Ishino, FA and Rowan, CE and Villalobos, K and Rajbhandari-Thapa, J and Williams, F},
title = {A Time-Varying Effect Model (TVEM) of the Complex Association of Tobacco Use and Smoke Exposure on Mean Telomere Length: Differences between Racial and Ethnic Groups Assessed in the National Health and Nutrition Examination Survey.},
journal = {International journal of environmental research and public health},
volume = {19},
number = {17},
pages = {},
pmid = {36078786},
issn = {1660-4601},
mesh = {Adult ; Aged ; *Cotinine ; Ethnicity ; Humans ; Middle Aged ; Nutrition Surveys ; Telomere ; *Tobacco Smoke Pollution ; Tobacco Use ; },
abstract = {Telomere length is affected by lifestyle and environmental factors and varies between racial and ethnic groups; however, studies are limited, with mixed findings. This study examined the effects of tobacco use and smoke exposure on mean telomere length to identify critical age periods by race/ethnicity. We used time-varying effect modeling on the National Health and Nutrition Examination Survey for continuous years 1999-2002 to observe the effects of active tobacco use and environmental tobacco smoke-measured through serum cotinine-and mean telomere length for adults 19 to 85 and older (N = 7826). Models were run for Mexican American, other Hispanic, non-Hispanic White, non-Hispanic Black, and other/multi-race categories to allow for time-varying group differences, and controlled for biological sex, socioeconomic status, education, and ever-smoker status. Serum cotinine was found to have an increasing effect on telomere length from age 37 to approximately age 74 among Mexican Americans. Among other/multi-race individuals serum cotinine was found to have a decreasing effect at approximately age 42, and among Blacks, it had an overall decreasing effect from age 61 to 78. Findings reveal a further need to focus additional support and resources to intervene regarding disparate health effects from tobacco use and environmental smoke exposure for already vulnerable groups at particular ages.},
}
@article {pmid36077523,
year = {2022},
author = {Jitjumnong, M and Chalermkitpanit, P and Suantawee, T and Dechsupa, S and Vajarintarangoon, L and Honsawek, S},
title = {Telomere Shortening and Increased Oxidative Stress in Lumbar Disc Degeneration.},
journal = {International journal of molecular sciences},
volume = {23},
number = {17},
pages = {},
pmid = {36077523},
issn = {1422-0067},
support = {CUGR 63953002//Fundamental Fund, Ratchadapiseksompotch Fund/ ; },
mesh = {8-Hydroxy-2'-Deoxyguanosine ; Antioxidants ; Case-Control Studies ; Humans ; *Intervertebral Disc Degeneration/genetics ; Oxidative Stress/genetics ; Telomere/genetics ; *Telomere Shortening ; },
abstract = {Lumbar disc degeneration (LDD) contributes to low back pain. This study aimed to determine relative telomere length (RTL), oxidative stress status, and antioxidant levels and examine the relationships between RTL, oxidative stress, and the severity in LDD patients. A total of 100 subjects, 50 LDD patients and 50 healthy controls, were enrolled in the case−control study. Blood leukocyte RTL was analyzed using quantitative real-time polymerase chain reaction. Lipid peroxidation was determined by malondialdehyde (MDA) assay. Plasma 8-hydroxy 2′-deoxyguanosine (8-OHdG) values were determined using enzyme-linked immunosorbent assay. Total antioxidant capacity (TAC) and ferric reducing antioxidant power (FRAP) in plasma were also measured. The LDD patients had significantly shorter telomeres than the healthy controls (p = 0.04). Blood leukocyte RTL was inversely correlated with the LDD severity (r = −0.41, p = 0.005). Additionally, plasma MDA and 8-OHdG levels were markedly greater in LDD patients than in the controls (p = 0.01 and p = 0.002, respectively). Furthermore, the plasma MDA level showed a positive correlation with the radiographic severity (r = 0.49, p = 0.001). There was a positive correlation between plasma 8-OHdG and the severity (r = 0.60, p < 0.001). Moreover, plasma TAC and FRAP levels were significantly lower in LDD patients than in the controls (p = 0.04). No significant differences in plasma TAC and FRAP were observed among the three groups of LDD severity. We found that RTL was negatively correlated with the severity while plasma MDA and 8-OHdG levels were positively correlated with the severity. These findings suggest that blood leukocyte RTL, plasma MDA, and 8-OHdG may have potential as noninvasive biomarkers for the assessment of severity in LDD.},
}
@article {pmid36074986,
year = {2022},
author = {Andrés, V and Díez, J},
title = {Failing Hypertensive Heart: a Question of Altered Telomere Biology?.},
journal = {Hypertension (Dallas, Tex. : 1979)},
volume = {79},
number = {10},
pages = {2185-2187},
doi = {10.1161/HYPERTENSIONAHA.122.19937},
pmid = {36074986},
issn = {1524-4563},
mesh = {Biology ; Heart ; *Heart Failure/genetics ; Humans ; *Hypertension/genetics ; Telomere/genetics ; },
}
@article {pmid36074951,
year = {2022},
author = {Pölönen, J and Pinola, P and Ronkainen, J and Blakemore, AI and Buxton, JL and Tapanainen, JS and Franks, S and Piltonen, TT and Sebert, S and Morin-Papunen, L},
title = {Polycystic ovary syndrome and leukocyte telomere length: cross-sectional and longitudinal changes.},
journal = {European journal of endocrinology},
volume = {187},
number = {5},
pages = {651-661},
pmid = {36074951},
issn = {1479-683X},
mesh = {Adult ; Biomarkers ; Cohort Studies ; Cross-Sectional Studies ; DNA ; Female ; Humans ; Leukocytes ; Longitudinal Studies ; Middle Aged ; *Polycystic Ovary Syndrome/epidemiology/genetics ; Telomere ; },
abstract = {OBJECTIVE: Telomeres are DNA-protein complexes that protect chromosome ends from DNA damage and are surrogate biomarkers of cellular aging. Current evidence, almost entirely from cross-sectional observations, supports negative associations between leukocyte telomere length (LTL) and adverse lifestyle factors and cardiometabolic risk factors. Polycystic ovary syndrome (PCOS), the most common gynecological endocrine disorder, is associated with inflammation and oxidative stress, both factors associated with accelerated telomere attrition. We therefore hypothesized that LTL would be shorter and decrease more rapidly in women with PCOS in comparison to a control population.<br><br>DESIGN: This is a population-based cohort study comprising women of Northern Finland Birth Cohort 1966, with clinical examinations at ages 31 and 46. The sample included self-reported PCOS (age 31, n = 190; age 46, n = 207) and referent women (age 31, n = 1054; age 46, n = 1324) with data on LTL.<br><br>METHODS: The association between LTL and PCOS at ages 31 and 46 was analyzed by linear regression models adjusted for BMI, smoking, alcohol consumption and socioeconomic status at the corresponding age.<br><br>RESULTS: Women with PCOS had similar mean LTL at ages 31 and 46 (P > 0.4 for both). The mean LTL change between ages 31 and 46 did not differ between groups (P = 0.19). However, we observed a significant LTL attrition between ages 31 and 46 in the reference population (P < 0.001), but not in women with PCOS (P = 0.96).<br><br>CONCLUSIONS: This finding may suggest a difference in the LTL attrition rate in women with PCOS, an unexpected finding that might affect their risk of age-related disease. Further research is needed to clarify the underlying mechanisms.},
}
@article {pmid36070080,
year = {2022},
author = {Faingelernt, Y and Nassar, R and Ling, G and Kodman, Y and Feuerstein, T and Yerushalmi, B},
title = {Early-life liver cirrhosis and variable clinical presentation in telomere disease.},
journal = {Acta paediatrica (Oslo, Norway : 1992)},
volume = {111},
number = {12},
pages = {2416-2421},
doi = {10.1111/apa.16539},
pmid = {36070080},
issn = {1651-2227},
mesh = {Child, Preschool ; Humans ; *Telomerase/genetics/metabolism ; Telomere/genetics ; Liver Cirrhosis/genetics ; Mutation ; Phenotype ; },
abstract = {AIM: Telomeres are DNA sequences of tandem TTAGGG repeats that protect chromosome ends from degradation and instability. Constitutional loss-of-function telomerase mutations result in rapid telomere shortening, premature senescence and cell death. Liver cirrhosis is rare and has only been reported in adults. We present five family members of Bedouin-Muslim origin, all of which carry the same mutation, and yet demonstrate an extremely variable phenotypical presentation, including liver cirrhosis during early childhood.<br><br>METHODS: A multidisciplinary long-term follow-up of two healthy and three affected patients was analysed. The mutation (r.95G>C) was identified in all patients using Sanger sequencing. Telomere length samples were obtained and analysed.<br><br>RESULTS: Clinical phenotypes were extremely variable, including age at first symptoms, organ involvement, disease severity and patient prognosis. The most prominent clinical phenotype is liver involvement, including end-stage liver disease early in life, which affects three members of the family. Affected patients had markedly shorter telomeres.<br><br>CONCLUSION: We describe an unusual presentation of early liver failure in telomere disease patients. Little, if any, is known about the association between the genotype and phenotype among children with telomere disease and whether the mutation we have described (r.95G>C) is predisposed to early severe hepatic involvement.},
}
@article {pmid36069016,
year = {2022},
author = {Young, RC and Westneat, DF and Vangorder-Braid, J and Sirman, AE and Siller, SJ and Kittilson, J and Ghimire, A and Heidinger, BJ},
title = {Stressors interact across generations to influence offspring telomeres and survival.},
journal = {Proceedings. Biological sciences},
volume = {289},
number = {1982},
pages = {20220868},
pmid = {36069016},
issn = {1471-2954},
mesh = {Animals ; Longevity ; *Sparrows/physiology ; Telomere ; },
abstract = {Parental stress often has long-term consequences for offspring. However, the mechanisms underlying these effects and how they are shaped by conditions offspring subsequently experience are poorly understood. Telomeres, which often shorten in response to stress and predict longevity, may contribute to, and/or reflect these cross-generational effects. Traditionally, parental stress is expected to have negative effects on offspring telomeres, but experimental studies in captive animals suggest that these effects may depend on the subsequent conditions that offspring experience. Yet, the degree to which parental stress influences and interacts with stress experienced by offspring to affect offspring telomeres and survival in free-living organisms is unknown. To assess this, we experimentally manipulated the stress exposure of free-living parent and offspring house sparrows (Passer domesticus). We found a weak, initial, negative effect of parental stress on offspring telomeres, but this effect was no longer evident at the end of post-natal development. Instead, the effects of parental stress depended on the natural sources of stress that offspring experienced during post-natal development whereby some outcomes were improved under more stressful rearing conditions. Thus, the effects of parental stress on offspring telomeres and survival are context-dependent and may involve compensatory mechanisms of potential benefit under some circumstances.},
}
@article {pmid36067971,
year = {2022},
author = {Assavanopakun, P and Sapbamrer, R and Kumfu, S and Chattipakorn, N and Chattipakorn, SC},
title = {Effects of air pollution on telomere length: Evidence from in vitro to clinical studies.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {312},
number = {},
pages = {120096},
doi = {10.1016/j.envpol.2022.120096},
pmid = {36067971},
issn = {1873-6424},
mesh = {*Air Pollutants/analysis/toxicity ; *Air Pollution/adverse effects/analysis ; Cellular Senescence ; Environmental Exposure/adverse effects/analysis ; Humans ; *Occupational Exposure ; Particulate Matter/analysis ; Telomere ; },
abstract = {Air pollution remains the major environmental problem globally. There is extensive evidence showing that the variety of air pollutants from environmental and occupational exposures cause adverse effects to our health. The clinical symptoms of those effects may present at a late stage, so surveillance is difficult to manage. Several biomarkers have been used for the early detection of health issues following exposure to air pollution, including the use of telomere length which indicates cellular senescence in response to oxidative stress. Oxidative stress is one of the most plausible mechanisms associated with exposure to air pollutants. Some specific contexts including age groups, gender, ethnicity, occupations, and health conditions, showed significant alterations in telomere length after exposure to air pollutants. Several reports demonstrated both negative and positive associations between telomere length and air pollution, the studies using different concentrations and exposure times to air pollution on the study of telomere lengths. Surprisingly, some studies reported that low levels of exposure to air pollutants (lower than regulated levels) caused the alterations in telomere length. Those findings suggest that telomere length could be one of most practical biomarkers in air pollution surveillance. Therefore, this review aimed to summarize and discuss the relationship between telomere length and exposure to air pollution. The knowledge from this review will be beneficial for the planning of public health to reduce health problems in the general population, particularly in vulnerable people, who still live in areas with high air pollution.},
}
@article {pmid36066716,
year = {2023},
author = {Kato, TA},
title = {Nontraditional Method for Telomere Staining by PNA Probes.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2519},
number = {},
pages = {111-116},
pmid = {36066716},
issn = {1940-6029},
mesh = {DNA Probes/genetics ; In Situ Hybridization, Fluorescence/methods ; *Peptide Nucleic Acids/chemistry ; Telomere/genetics ; },
abstract = {The standard FISH uses DNA probes to hybridize to the designated complementary strands. This is DNA-DNA interaction, and it usually takes much longer time to obtain detectable signals compared to other reactions such as immunochemical reactions and simple chemical reactions. Certain proteins bind to specific DNA sequences and regulate the biological function of DNA. These DNA-binding proteins have specific domains to interact with single- or double-stranded DNA. Some of telomere proteins apparently bind to telomere sequence and form nucleoprotein complex to protect chromosome ends. Using telomere PNA probes, probes can be accumulated at the telomere sites in a non-hybridization manner. This chapter introduces nontraditional PNA telomere staining protocol without DNA-DNA hybridization to visualize telomere locations on metaphase chromosomes.},
}
@article {pmid36066715,
year = {2023},
author = {Kato, TA},
title = {Telomere Aberration Detection by PNA FISH Probe.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2519},
number = {},
pages = {105-110},
pmid = {36066715},
issn = {1940-6029},
mesh = {DNA Probes ; In Situ Hybridization, Fluorescence/methods ; *Repetitive Sequences, Nucleic Acid ; *Telomere/genetics ; },
abstract = {Telomere is a structure of the end cap of chromosomes. Telomere gets shorter as cell aging and progressing cell division. Shorter telomere may cause telomere fusion, thus inducing genomic instability. Telomere dysfunction can be visualized by PNA FISH probe against telomere repeat sequence (TTAGGG)n. PNA probes have higher hybridization affinity than DNA probes. The traditional FISH or modified FISH protocol can stain telomere relatively easier than whole-chromosome painting probes. This chapter introduces PNA telomere FISH protocol to visualize telomere signals on metaphase chromosomes.},
}
@article {pmid37881560,
year = {2023},
author = {Mutz, J and Lewis, CM},
title = {Telomere Length Associations With Clinical Diagnosis, Age, and Polygenic Risk Scores for Anxiety Disorder, Depression, and Bipolar Disorder.},
journal = {Biological psychiatry global open science},
volume = {3},
number = {4},
pages = {1012-1020},
pmid = {37881560},
issn = {2667-1743},
abstract = {BACKGROUND: Accelerated biological aging might contribute to the lower life expectancy of individuals with mental disorders. The aim of this study was to characterize telomere length, a biological hallmark of aging, in individuals with mental disorders.<br><br>METHODS: The UK Biobank is a multicenter community-based observational study that recruited >500,000 middle-aged and older adults. Average leukocyte telomere length (telomere repeat copy number/single-copy gene ratio) was measured using quantitative polymerase chain reaction. Polygenic risk scores (PRSs) were calculated for individuals of European ancestry. We estimated differences in telomere length between individuals with anxiety disorder, depression, or bipolar disorder and people without mental disorders and examined associations with psychotropic medication use, age, and PRSs for these 3 disorders.<br><br>RESULTS: The analyses included up to 308,725 participants. Individuals with depression had shorter telomeres than people without mental disorders (&#x3b2;&#xa0;=&#xa0;-0.011, 95% CI,&#xa0;-0.019 to&#xa0;-0.004, Bonferroni-corrected&#xa0;p&#xa0;= .027). Associations between bipolar disorder and telomere length differed by lithium use. There was limited evidence that individuals with an anxiety disorder had shorter telomeres. There was no evidence that associations between age and telomere length differed between individuals with and without these disorders. PRSs for depression, but not anxiety disorder or bipolar disorder, were associated with shorter telomeres (&#x3b2;&#xa0;=&#xa0;-0.006, 95% CI,&#xa0;-0.010 to&#xa0;-0.003, Bonferroni-corrected&#xa0;p&#xa0;= .001).<br><br>CONCLUSIONS: Differences in telomere length were observed primarily for individuals with depression or bipolar disorder and in individuals with a higher PRS for depression. There was no evidence that the association between age and telomere length differed between individuals with and without an anxiety disorder, depression, or bipolar disorder.},
}
@article {pmid36060975,
year = {2022},
author = {Ghoussaini, R and Tamim, H and Elbejjani, M and Makki, M and Nasreddine, L and Ismaeel, H and Nasrallah, MP and Zgheib, NK},
title = {C-peptide is a predictor of telomere shortening: A five-year longitudinal study.},
journal = {Frontiers in endocrinology},
volume = {13},
number = {},
pages = {978747},
pmid = {36060975},
issn = {1664-2392},
mesh = {C-Peptide ; Humans ; Longitudinal Studies ; Risk Factors ; *Telomere/genetics ; *Telomere Shortening ; },
abstract = {AIM: Relative telomere length (RTL) predicts the development of many age-related diseases. Yet, few studies have evaluated their longitudinal effect on RTL. We investigated longitudinally the association between cardiometabolic risk factors and RTL.<br><br>METHODS: This was a longitudinal study with a 5-year follow-up period, based on data collected in 2014 and 2019. Of 478 participants in 2014, 198 consented to be followed-up in 2019. The associations between RTL and risk factors were analyzed using t-test, ANOVA or simple linear regression as applicable.<br><br>RESULTS: RTL was significantly shortened after 5 years (P<0.001). Older age (P=0.018) and gender (P=0.05) were significantly associated with shorter RTL at follow-up. Higher baseline C-peptide correlated with shorter RTL (P=0.04) and shortening of RTL (P=0.03) after 5 years. Multivariate linear regression including both age and gender revealed a significant trend for C-peptide and change in RTL after 5 years (P=0.04). Interestingly, there was a trend of shorter RTL at follow-up with diabetes, though the findings were not statistically significant.<br><br>CONCLUSIONS: Higher C-peptide level contributes to telomere shortening over time, suggesting that metabolic dysregulation may play a role in early aging. Further understanding of this relationship and addressing high C-peptide levels can be important to prevent premature aging.},
}
@article {pmid36059259,
year = {2022},
author = {Pan, L and Tormey, D and Bobon, N and Baumann, P},
title = {Rap1 prevents fusions between long telomeres in fission yeast.},
journal = {The EMBO journal},
volume = {41},
number = {20},
pages = {e110458},
pmid = {36059259},
issn = {1460-2075},
support = {//Howard Hughes Medical Institute (HHMI)/ ; },
mesh = {Amino Acids/metabolism ; *Schizosaccharomyces/genetics/metabolism ; *Schizosaccharomyces pombe Proteins/genetics/metabolism ; Shelterin Complex ; Telomere/genetics/metabolism ; Telomere Homeostasis ; Telomere-Binding Proteins/genetics/metabolism ; },
abstract = {The conserved Rap1 protein is part of the shelterin complex that plays critical roles in chromosome end protection and telomere length regulation. Previous studies have addressed how fission yeast Rap1 contributes to telomere length maintenance, but the mechanism by which the protein inhibits end fusions has remained elusive. Here, we use a mutagenesis screen in combination with high-throughput sequencing to identify several amino acid positions in Rap1 that have key roles in end protection. Interestingly, mutations at these sites render cells susceptible to genome instability in a conditional manner, whereby longer telomeres are prone to undergoing end fusions, while telomeres within the normal length range are sufficiently protected. The protection of long telomeres is in part dependent on their nuclear envelope attachment mediated by the Rap1-Bqt4 interaction. Our data demonstrate that long telomeres represent a challenge for the maintenance of genome integrity, thereby providing an explanation for species-specific upper limits on telomere length.},
}
@article {pmid36057868,
year = {2022},
author = {Schellnegger, M and Lin, AC and Hammer, N and Kamolz, LP},
title = {Physical Activity on Telomere Length as a Biomarker for Aging: A Systematic Review.},
journal = {Sports medicine - open},
volume = {8},
number = {1},
pages = {111},
pmid = {36057868},
issn = {2199-1170},
abstract = {BACKGROUND: Overall life expectancy continues to rise, approaching 80 years of age in several developed countries. However, healthy life expectancy lags far behind, which has, in turn, contributed to increasing costs in healthcare. One way to improve health and attenuate the socio-economic impact of an aging population is to increase overall fitness through physical activity. Telomere attrition or shortening is a well-known molecular marker in aging. As such, several studies have focused on whether exercise influences health and aging through telomere biology. This systematic review examines the recent literature on the effect of physical activity on telomere length (TL) and/or telomerase activity as molecular markers of aging.<br><br>METHODS: A focused search was performed in the databases PubMed and Web of Science for retrieving relevant articles over the past ten years. The search contained the following keywords: exercise, sport, physical activity, fitness, sedentary, physical inactivity, telomere, telomere length, t/s ratio, and telomerase. PRISMA guidelines for systematic reviews were observed.<br><br>RESULTS: A total of 43 articles were identified and categorized into randomized controlled trials (RCT), observational or interventional studies. RCTs (n&#x2009;=&#x2009;8) showed inconsistent findings of increased TL length with physical activity in, e.g. obese, post-menopausal women. In comparison with a predominantly sedentary lifestyle, observational studies (n&#x2009;=&#x2009;27) showed significantly longer TL with exercise of moderate to vigorous intensity; however, there was no consensus on the duration and type of physical activity and training modality. Interventional studies (n&#x2009;=&#x2009;8) also showed similar findings of significantly longer TL prior to exercise intervention; however, these studies had smaller numbers of enrolled participants (mostly of high-performance athletes), and the physical activities covered a range of exercise intensities and duration. Amongst the selected studies, aerobic training of moderate to vigorous intensity is most prevalent. For telomere biology analysis, TL was determined mainly from leukocytes using qPCR. In some cases, especially in RCT and interventional studies, different sample types such as saliva, sperm, and muscle biopsies were analyzed; different leukocyte cell types and potential genetic markers in regulating telomere biology were also investigated.<br><br>CONCLUSIONS: Taken together, physical activity with regular aerobic training of moderate to vigorous intensity appears to help preserve TL. However, the optimal intensity, duration of physical activity, as well as type of exercise still need to be further elucidated. Along with TL or telomerase activity, participants' fitness level, the type of physical activity, and training modality should be assessed at different time points in future studies, with the plan for long-term follow-up. Reducing the amount of sedentary behavior may have a positive effect of preserving and increasing TL. Further molecular characterization of telomere biology in different cell types and tissues is required in order to draw definitive causal conclusions on how physical activity affects TL and aging.},
}
@article {pmid36057690,
year = {2022},
author = {Porrazzo, A and Cipressa, F and De Gregorio, A and De Pittà, C and Sales, G and Ciapponi, L and Morciano, P and Esposito, G and Tabocchini, MA and Cenci, G},
title = {Low dose rate γ-irradiation protects fruit fly chromosomes from double strand breaks and telomere fusions by reducing the esi-RNA biogenesis factor Loquacious.},
journal = {Communications biology},
volume = {5},
number = {1},
pages = {905},
pmid = {36057690},
issn = {2399-3642},
mesh = {Animals ; Dose-Response Relationship, Radiation ; *Drosophila melanogaster/genetics/radiation effects ; Gamma Rays ; Humans ; RNA ; *Telomere/genetics ; },
abstract = {It is still continuously debated whether the low-dose/dose-rate (LDR) of ionizing radiation represents a hazard for humans. Model organisms, such as fruit flies, are considered valuable systems to reveal insights into this issue. We found that, in wild-type Drosophila melanogaster larval neuroblasts, the frequency of Chromosome Breaks (CBs), induced by acute γ-irradiation, is considerably reduced when flies are previously exposed to a protracted dose of 0.4 Gy delivered at a dose rate of 2.5 mGy/h. This indicates that this exposure, which is associated with an increased expression of DNA damage response proteins, induces a radioadaptive response (RAR) that protects Drosophila from extensive DNA damage. Interestingly, the same exposure reduces the frequency of telomere fusions (TFs) from Drosophila telomere capping mutants suggesting that the LDR can generally promote a protective response on chromatin sites that are recognized as DNA breaks. Deep RNA sequencing revealed that RAR is associated with a reduced expression of Loquacious D (Loqs-RD) gene that encodes a well-conserved dsRNA binding protein required for esiRNAs biogenesis. Remarkably, loss of Loqs mimics the LDR-mediated chromosome protection as it decreases the IR-induced CBs and TFs frequency. Thus, our molecular characterization of RAR identifies Loqs as a key factor in the cellular response to LDR and in the epigenetic routes involved in radioresistance.},
}
@article {pmid36057525,
year = {2022},
author = {Batista, LFZ and Dokal, I and Parker, R},
title = {Telomere biology disorders: time for moving towards the clinic?.},
journal = {Trends in molecular medicine},
volume = {28},
number = {10},
pages = {882-891},
pmid = {36057525},
issn = {1471-499X},
support = {MR/P018440/1/MRC_/Medical Research Council/United Kingdom ; R01 CA258386/CA/NCI NIH HHS/United States ; R01 HL137793/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; },
mesh = {Biology ; Cell Cycle Proteins/genetics/metabolism ; *Dyskeratosis Congenita/genetics/metabolism ; Humans ; Mutation ; Nuclear Proteins/genetics ; RNA/metabolism ; RNA-Binding Proteins/genetics ; *Telomerase/genetics/metabolism ; Telomere/genetics ; },
abstract = {Telomere biology disorders (TBDs) are a group of rare diseases caused by mutations that impair telomere maintenance. Mutations that cause reduced levels of TERC/hTR, the telomerase RNA component, are found in most TBD patients and include loss-of-function mutations in hTR itself, in hTR-binding proteins [NOP10, NHP2, NAF1, ZCCHC8, and dyskerin (DKC1)], and in proteins required for hTR processing (PARN). These patients show diverse clinical presentations that most commonly include bone marrow failure (BMF)/aplastic anemia (AA), pulmonary fibrosis, and liver cirrhosis. There are no curative therapies for TBD patients. An understanding of hTR biogenesis, maturation, and degradation has identified pathways and pharmacological agents targeting the poly(A) polymerase PAPD5, which adds 3'-oligoadenosine tails to hTR to promote hTR degradation, and TGS1, which modifies the 5'-cap structure of hTR to enhance degradation, as possible therapeutic approaches. Critical next steps will be clinical trials to establish the effectiveness and potential side effects of these compounds in TBD patients.},
}
@article {pmid36055854,
year = {2022},
author = {Seibt, KD and Ghaffari, MH and Scheu, T and Koch, C and Sauerwein, H},
title = {Effects of different feeding levels during a 14-week preweaning phase in dairy heifer calves on telomere length and mitochondrial DNA copy number in blood.},
journal = {Journal of dairy science},
volume = {105},
number = {10},
pages = {8509-8522},
doi = {10.3168/jds.2022-21891},
pmid = {36055854},
issn = {1525-3198},
mesh = {*Animal Feed/analysis ; Animals ; Cattle ; DNA Copy Number Variations ; DNA, Mitochondrial ; *Diet/veterinary ; Female ; Milk/metabolism ; Mitochondria ; Reactive Oxygen Species/metabolism ; Telomere ; Weaning ; },
abstract = {Telomeres cap the ends of eukaryotic chromosomes, and the telomere length (TL) is related to cellular age. The mitochondrial DNA copy number (mtDNAcn) reflects the abundance of mitochondria in a cell. In addition to generating energy, mitochondria are also the main producers of reactive oxygen species, which in turn can accelerate TL attrition and impair mitochondrial function. Nutrition in early life could influence mtDNAcn and TL in later life. In the present study, we investigated the effects of feeding different levels of milk replacer (MR) on TL shortening and energetic status by examining mtDNAcn of heifers during their first year of life. In this study, whole blood samples were obtained from German Holstein heifer calves 36 to 48 h after birth (wk 1) and at wk 12 and wk 16 of life (n = 37), as well as from 31 calves when reaching 1 yr of age. Calves were fed either a high level of MR (14% solids) at 10 L/d (1.4 kg of MR/d; n = 18) or a restrictive low level at 5.7 L/d (0.8 kg of MR/d; n = 19) until linear weaning in wk 13 to 14 of life. Additional whole blood samples were taken from their respective dams 36 to 48 h after calving. Relative TL (qT) and mtDNAcn in cells from whole blood were measured by multiplex quantitative PCR. The greatest qT values were observed in neonates (36-48 h after birth), with decreasing qT values thereafter. Delta qT values were calculated as ΔqT = qT (first year of life) - initial qT (36-48 h after birth). We found no effect of the feeding regimen on qT values, but qT decreased with age. The mtDNAcn was lowest in neonates, increased until wk 12 of life, and then remained at a constant level until after weaning (wk 16). After the first year of life, mtDNAcn was decreased and returned to levels comparable to those of the neonatal stage. No differences in mtDNAcn were detectable between feeding groups within each time point. When comparing the values of qT and mtDNAcn between the calves and their dams after calving (36-48 h after birth and after calving), greater values were observed in calves than in dams. Delta qT values were negative in all but 2 calves (on the restricted diet), indicating that the change in TL with age was not uniform among individual animals, whereas no difference in mean ΔqT values occurred between the feeding groups. Additional analyses of the correlation between qT, mtDNAcn, and various indicators of oxidative status from birth until wk 16 of life did not indicate major interactions between oxidative status, qT and mtDNAcn. The results of this study support an age-dependent decrease of TL in calves independent of the MR feeding level and show the dynamic changes of mtDNAcn in early life.},
}
@article {pmid36054116,
year = {2022},
author = {Chen, L and Dickerhoff, J and Sakai, S and Yang, D},
title = {DNA G-Quadruplex in Human Telomeres and Oncogene Promoters: Structures, Functions, and Small Molecule Targeting.},
journal = {Accounts of chemical research},
volume = {55},
number = {18},
pages = {2628-2646},
pmid = {36054116},
issn = {1520-4898},
support = {U01 CA240346/CA/NCI NIH HHS/United States ; R01 CA122952/CA/NCI NIH HHS/United States ; R01 CA177585/CA/NCI NIH HHS/United States ; S10 RR016649/RR/NCRR NIH HHS/United States ; R01 CA153821/CA/NCI NIH HHS/United States ; P30 CA023168/CA/NCI NIH HHS/United States ; K01 CA083886/CA/NCI NIH HHS/United States ; R01 GM083117/GM/NIGMS NIH HHS/United States ; },
mesh = {Chromatin ; DNA/chemistry ; *G-Quadruplexes ; Guanine/chemistry ; Humans ; Ligands ; Oncogenes ; Proto-Oncogene Proteins c-bcl-2/genetics ; Receptors, Drug/genetics ; Telomere/genetics ; Vascular Endothelial Growth Factor A ; },
abstract = {DNA G-quadruplex secondary structures formed in guanine-rich human telomeres and oncogene promoters are functionally important and have emerged as a promising new class of cancer-specific drug targets. These globular intramolecular structures are stabilized by K[+] or Na[+] and form readily under physiological solution conditions. Moreover, G-quadruplexes are epigenetic features and can alter chromatin structure and function together with interactive proteins. Here, we discuss our efforts over the last two decades to understand the structures and functions of DNA G-quadruplexes formed in key oncogene promoters and human telomeres and their interactions with small molecules. Using high-field NMR spectroscopy, we determined the high-resolution structures of physiologically relevant telomeric G-quadruplexes in K[+] solution with a major form (hybrid-2) and a minor form (hybrid-1), as well as a two-tetrad intermediate. The intrinsic structural polymorphism of telomeric DNA may be important for the biology of human telomeres, and we proposed a model for the interconversion. More recently, we have worked on G-quadruplexes of MYC, BCL2, PDGFR-β, VEGF, and k-RAS oncogene promoters. We determined the structure of the major G-quadruplex formed in the MYC promoter, a prototype for parallel G-quadruplexes. It is the first example of the parallel-stranded G3NG3 structure motif with a 1-nt loop, which is prevalent in promoter sequences and likely evolutionarily selected to initiate folding. Remarkably, the parallel MYC promoter G-quadruplexes are highly stable. Additionally, we determined the molecular structures of G-quadruplexes formed in human BCL2, VEGF, and PDGFR-β promoters, each adopting a unique structure. For example, the BCL2 promoter contains distinct interchangeable G-quadruplexes in two adjacent regions, suggesting precise regulation by different proteins. The PDGFR-β promoter adopts unique "broken-strand" and vacancy G-quadruplexes, which can be recognized by cellular guanine metabolites for a potential regulatory role.Structural information on G-quadruplexes in complex with small-molecules is critical for understanding specific recognition and structure-based rational drug design. Our studies show that many G-quadruplexes contain unique structural features such as capping and loop structures, allowing specific recognition by drugs and protein. This represents a paradigm shift in understanding DNA as a drug target: Rather than a uniform, nonselective binding site in duplex DNA, the G-quadruplex is being pursued as a new class of selectively targetable drug receptors. We focus on targeting the biologically relevant MYC promoter G-quadruplex (MycG4) with small molecules and have determined its first and additional drug complex structures. Very recently, we have discovered clinically tested indenoisoquinolines as strong MycG4 binders and potent MYC inhibitors. We have also discovered drugs targeting the unique dGMP-bound-vG4 formed in the PDGFR-β promoter. Moreover, we determined the complex structures of the first small molecules that specifically recognize the physiologically relevant human telomeric G-quadruplexes. Unlike the previously recognized dogma that the optimal G-quadruplex ligands are large aromatic or cyclic compounds, our results suggest that smaller asymmetric compounds with appropriate functional groups are better choices to specifically bind G-quadruplexes. This body of work lays a strong foundation for future work aimed at understanding the cellular functions of G-quadruplexes and G-quadruplex-targeted drug design.},
}
@article {pmid36051868,
year = {2022},
author = {Rodríguez-Fernández, B and Gispert, JD and Guigo, R and Navarro, A and Vilor-Tejedor, N and Crous-Bou, M},
title = {Genetically predicted telomere length and its relationship with neurodegenerative diseases and life expectancy.},
journal = {Computational and structural biotechnology journal},
volume = {20},
number = {},
pages = {4251-4256},
pmid = {36051868},
issn = {2001-0370},
abstract = {Telomere length (TL) is a biomarker of biological aging. Shorter telomeres have been associated with mortality and increased rates of age-related diseases. However, observational studies are unable to conclude whether TL is causally associated with those outcomes. Mendelian randomization (MR) was developed for assessing causality using genetic variants in epidemiological research. The objective of this study was to test the potential causal role of TL in neurodegenerative disorders and life expectancy through MR analysis. Summary level data were extracted from the most recent genome-wide association studies for TL, Alzheimer's disease (AD), Parkinson's disease, Frontotemporal dementia, Amyotrophic Lateral Sclerosis, Progressive Supranuclear Palsy and life expectancy. MR estimates revealed that longer telomeres inferred a protective effect on risk of AD (OR = 0.964; adjusted p-value = 0.039). Moreover, longer telomeres were significantly associated with increased life expectancy (βIVW = 0.011; adjusted p-value = 0.039). Sensitivity analyses suggested evidence for directional pleiotropy in AD analyses. Our results showed that genetically predicted longer TL may increase life expectancy and play a protective causal effect on AD. We did not observe significant causal relationships between longer TL and other neurodegenerative diseases. This suggests that the involvement of TL on specific biological mechanisms might differ between AD and life expectancy, with respect to that in other neurodegenerative diseases. Moreover, the presence of pleiotropy may reflect the complex interplay between TL homeostasis and AD pathophysiology. Further observational studies are needed to confirm these results.},
}
@article {pmid36047552,
year = {2022},
author = {Coukos, A and Daccord, C and Lazor, R and Blum, S and Naveiras, O and Unger, S and Vionnet, J and Gaide, O and Koutsokera, A and Moschouri, E and Sempoux, C and Good, JM and Moradpour, D and Baerlocher, GM and Fraga, M},
title = {[Short telomere syndrome in adults: a rare entity that should be evoked].},
journal = {Revue medicale suisse},
volume = {18},
number = {793},
pages = {1606-1613},
doi = {10.53738/REVMED.2022.18.793.1606},
pmid = {36047552},
issn = {1660-9379},
mesh = {Adult ; *Bone Marrow Diseases/genetics/pathology ; Child ; Growth Disorders ; Humans ; Hypercalcemia ; Metabolic Diseases ; *Nephrocalcinosis ; Syndrome ; Telomere/genetics/pathology ; },
abstract = {Short telomere syndrome (STS) is a group of rare, often underrecognized, diseases caused by defects in telomere-maintenance genes, leading to abnormal telomere shortening and associated with diverse multi-organ manifestations. In pediatric patients, STS typically presents with mucocutaneous or gastrointestinal lesions, bone marrow failure and neoplasia. In adulthood, aplastic bone marrow disease, liver disease and pulmonary fibrosis are classic clinical manifestations. At present, medical treatment options for STS remain limited. Danazol, a synthetic androgenic hormone, can slow down telomere shortening and thus limit the progression of the disease. Finally, hematopoietic, hepatic and pulmonary transplantation, sometimes combined, may be discussed in a multidisciplinary setting in certain situations.},
}
@article {pmid36041576,
year = {2022},
author = {Dey, A and Pandav, K and Nath, M and Barthwal, R and Prasad, R},
title = {Molecular rec§ognition of telomere DNA sequence by 2, 6 anthraquinone derivatives leads to thermal stabilization and induces apoptosis in cancer cells.},
journal = {International journal of biological macromolecules},
volume = {221},
number = {},
pages = {355-370},
doi = {10.1016/j.ijbiomac.2022.08.156},
pmid = {36041576},
issn = {1879-0003},
mesh = {Base Sequence ; Telomere/genetics/metabolism ; *G-Quadruplexes ; Anthraquinones/pharmacology ; *Telomerase/genetics ; DNA/chemistry ; Apoptosis ; Anthracenes ; *Neoplasms/drug therapy/genetics ; },
abstract = {According to current research, anti-cancer anthraquinones impact telomere disruption and may interact with G-quadruplex DNA that triggers signaling to apoptosis. The present study represents the biophysical investigation of oxidative stress, late apoptosis, and induced senescence among cancer cells after binding laboratory synthesized piperidine-based anthraquinone derivatives, 2, 6- Bis [(3-piperidino)acetamido)]anthracene-9,10-dione (N1P) and 2, 6-Bis [piperidino)propionamido]anthracene-9,10-dione (N2P), with G-quadruplex DNA. We employed biophysical approaches to explore the interaction of synthetic anthraquinone derivatives with quadruplex DNA sequences to influence biological activities in the presence of K[+] and Na[+] cations. The binding affinity for N2P and N1P are Kb = 5.8 × 10[6] M[-1] and Kb = 1.0 × 10[6] M[-1], respectively, leading to hypo-/hyper-chromism with 5-7 nm red shift and significant fluorescence quenching and changes in ellipticity resulting in external binding of both the ligands to G-quadruplex DNA. Ligand binding induced enhancement of thermostability of G4 DNA is greater in Na[+] environment (ΔTm = 34 °C) as compared to that in K[+] environment (ΔTm = 21 °C), thereby restricting telomerase binding access to telomeres. Microscopic images of treated cells indicated cellular shape, nuclear condensation, and fragmentation alterations. The findings pave the path for therapeutic research, given the great potential of modifying anthraquinone substituent groups towards improved efficacy, ROS generation, and G-quadruplex DNA selectivity.},
}
@article {pmid36038949,
year = {2022},
author = {Kille, B and Balaji, A and Sedlazeck, FJ and Nute, M and Treangen, TJ},
title = {Multiple genome alignment in the telomere-to-telomere assembly era.},
journal = {Genome biology},
volume = {23},
number = {1},
pages = {182},
pmid = {36038949},
issn = {1474-760X},
support = {P01 AI152999/AI/NIAID NIH HHS/United States ; T15 LM007093/LM/NLM NIH HHS/United States ; },
mesh = {*Genome, Human ; *Genomics/methods ; Humans ; Nucleotides ; Telomere/genetics ; },
abstract = {With the arrival of telomere-to-telomere (T2T) assemblies of the human genome comes the computational challenge of efficiently and accurately constructing multiple genome alignments at an unprecedented scale. By identifying nucleotides across genomes which share a common ancestor, multiple genome alignments commonly serve as the bedrock for comparative genomics studies. In this review, we provide an overview of the algorithmic template that most multiple genome alignment methods follow. We also discuss prospective areas of improvement of multiple genome alignment for keeping up with continuously arriving high-quality T2T assembled genomes and for unlocking clinically-relevant insights.},
}
@article {pmid36038827,
year = {2022},
author = {Fohringer, C and Hoelzl, F and Allen, AM and Cayol, C and Ericsson, G and Spong, G and Smith, S and Singh, NJ},
title = {Large mammal telomere length variation across ecoregions.},
journal = {BMC ecology and evolution},
volume = {22},
number = {1},
pages = {105},
pmid = {36038827},
issn = {2730-7182},
mesh = {Animals ; Animals, Wild/genetics ; *Deer/genetics ; *Ecosystem ; Female ; Humans ; Male ; Seasons ; Telomere/genetics ; },
abstract = {BACKGROUND: Telomere length provides a physiological proxy for accumulated stress in animals. While there is a growing consensus over how telomere dynamics and their patterns are linked to life history variation and individual experience, knowledge on the impact of exposure to different stressors at a large spatial scale on telomere length is still lacking. How exposure to different stressors at a regional scale interacts with individual differences in life history is also poorly understood. To better understand large-scale regional influences, we investigated telomere length variation in moose (Alces alces) distributed across three ecoregions. We analyzed 153 samples of 106 moose representing moose of both sexes and range of ages to measure relative telomere lengths (RTL) in white blood cells.<br><br>RESULTS: We found that average RTL was significantly shorter in a northern (montane) and southern (sarmatic) ecoregion where moose experience chronic stress related to severe summer and winter temperatures as well as high anthropogenic land-use compared to the boreal region. Our study suggests that animals in the northern boreal forests, with relatively homogenous land use, are less disturbed by environmental and anthropogenic stressors. In contrast, animals in areas experiencing a higher rate of anthropogenic and environmental change experience increased stress.<br><br>CONCLUSION: Although animals can often adapt to predictable stressors, our data suggest that some environmental conditions, even though predictable and ubiquitous, can generate population level differences of long-term stress. By measuring RTL in moose for the first time, we provide valuable insights towards our current understanding of telomere biology in free-ranging wildlife in human-modified ecosystems.},
}
@article {pmid36037299,
year = {2022},
author = {Jentsch, A and Hoferichter, F and Raufelder, D and Hageman, G and Maas, L},
title = {The relation between sensory processing sensitivity and telomere length in adolescents.},
journal = {Brain and behavior},
volume = {12},
number = {9},
pages = {e2751},
pmid = {36037299},
issn = {2162-3279},
mesh = {Adolescent ; Biomarkers ; Body Mass Index ; Humans ; Perception ; *Telomere ; *Telomere Shortening ; },
abstract = {BACKGROUND: In the present study, we investigated the association between sensory processing sensitivity (SPS) and telomere length (TL), which is considered a biomarker of cellular aging. SPS is an individual characteristic describing increased perception and procession of inner or outer stimuli, and is positively related to self-perceived stress.<br><br>METHODS: We recruited 82 healthy adolescents aged 13-16 from secondary schools in Germany. SPS was measured with the Highly Sensitive Person Scale, and TL was determined by a multiplex quantitative PCR method.<br><br>RESULTS: Our results show that students with higher values of SPS are likely to have shorter telomeres (&#x3b2;&#xa0;=&#xa0;0.337, p&#xa0;=&#xa0;.001), when adjusting for sex, socioeconomic status, age, and body mass index. These findings are also independent of the negative impact of stress students might have perceived shortly before data collection.<br><br>CONCLUSIONS: Our analysis suggests that students who struggle with low sensory threshold are likely to have shorter telomeres.},
}
@article {pmid36036734,
year = {2023},
author = {Salisbury, ML and Markin, CR and Wu, P and Cogan, JD and Mitchell, DB and Liu, Q and Loyd, JE and Lancaster, LH and Kropski, JA and Blackwell, TS},
title = {Peripheral Blood Telomere Attrition in Persons at Risk for Familial Pulmonary Fibrosis.},
journal = {American journal of respiratory and critical care medicine},
volume = {207},
number = {2},
pages = {208-211},
pmid = {36036734},
issn = {1535-4970},
support = {P01 HL092870/HL/NHLBI NIH HHS/United States ; K23 HL141539/HL/NHLBI NIH HHS/United States ; K08HL130595/HL/NHLBI NIH HHS/United States ; P01HL092870/HL/NHLBI NIH HHS/United States ; R01 HL151016/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Idiopathic Pulmonary Fibrosis ; Mutation ; Telomere/genetics ; },
}
@article {pmid36036284,
year = {2023},
author = {Khalil, D and Giurgescu, C and Misra, DP and Templin, T and Jenuwine, E and Drury, SS},
title = {Psychosocial Factors and Telomere Length Among Parents and Infants of Immigrant Arab American Families.},
journal = {Biological research for nursing},
volume = {25},
number = {1},
pages = {137-149},
pmid = {36036284},
issn = {1552-4175},
support = {U24 AG066528/AG/NIA NIH HHS/United States ; },
mesh = {Infant ; Female ; Humans ; Child, Preschool ; Cross-Sectional Studies ; Pilot Projects ; *Mothers/psychology ; *Emigrants and Immigrants ; Arabs ; Telomere ; },
abstract = {Background: Immigrant Arab American families face multiple stressors related to migration and resettlement. Telomere length (TL) is an established biomarker of aging and psychosocial stress. No published studies have concurrently examined the association between maternal and paternal psychosocial factors and infants' TL. The purpose of this study was to: (1) compare mother, father, and infant TLs; (2) explore the association of maternal and paternal psychosocial factors (acculturative stress and depressive symptoms) with maternal and paternal TL; and (3) explore the association of maternal and paternal psychosocial factors with infants' TL among Arab American immigrants. Method: Using a cross-sectional exploratory design, a sample of 52 immigrant Arab American mother-father-infant triads were recruited from community centers. Data were collected in a single home visit when the infant was 6-24 months old. Each parent completed the study questionnaires addressing their psychosocial factors (acculturative stress, and depressive symptoms), then parents and infants provided buccal cell for TL measurement. Results: Maternal TL was positively correlated to infants' TL (r = .31, p = .04) and significantly shorter (p < .001). Paternal TL was not correlated with infant TL but was significantly shorter than infant's TL (p < .001). Maternal depression was significantly correlated with mothers' TL (r = .4, p = .007). Higher levels of maternal depressive symptoms were significantly associated with shorter infant TL when controlling for background characteristics. Conclusions: Our pilot study is the first study to examine maternal and paternal psychosocial factors related to migration and infants' TL. More research is needed to advance our understanding of the effects of immigration on the intergenerational transfer of stress and trauma.},
}
@article {pmid36035793,
year = {2022},
author = {Wang, Y and Ferrucci, L and Seidman, MM and Liu, Y},
title = {An optimized proximity ligation assay to detect telomere dysfunction induced foci in human and mouse cells.},
journal = {STAR protocols},
volume = {3},
number = {3},
pages = {101610},
pmid = {36035793},
issn = {2666-1667},
mesh = {Animals ; Fluorescent Antibody Technique ; Humans ; In Situ Hybridization, Fluorescence ; Mice ; *Telomere ; },
abstract = {Telomere dysfunction-induced foci (TIF) can be measured by immunofluorescence, combined with telomere-fluorescent in situ hybridization. We modified this approach by combining the proximity ligation assay (PLA), which detects colocalization of two molecules in proximity through a signal amplification step and improves the fidelity and sensitivity of TIF detection in human and mouse cells. The protocol includes cell preparation, permeabilization, fixation, and blocking PLA detection of DNA damage response proteins within proximity with telomeres and optional PLA verification by immunofluorescence-based technique.},
}
@article {pmid36031719,
year = {2022},
author = {Maher, TM},
title = {A clinical short-cut to identifying short telomeres in idiopathic pulmonary fibrosis?.},
journal = {Respirology (Carlton, Vic.)},
volume = {27},
number = {11},
pages = {916-917},
doi = {10.1111/resp.14355},
pmid = {36031719},
issn = {1440-1843},
mesh = {Humans ; *Idiopathic Pulmonary Fibrosis/diagnosis/genetics ; *Telomerase/genetics ; Telomere/genetics/metabolism ; Telomere Shortening ; },
}
@article {pmid36030273,
year = {2022},
author = {Yu, EY and Cheung, NV and Lue, NF},
title = {Connecting telomere maintenance and regulation to the developmental origin and differentiation states of neuroblastoma tumor cells.},
journal = {Journal of hematology &amp; oncology},
volume = {15},
number = {1},
pages = {117},
pmid = {36030273},
issn = {1756-8722},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Cell Differentiation ; Cell Proliferation ; Child ; Humans ; *Neuroblastoma ; *Telomerase ; Telomere ; Telomere Homeostasis ; },
abstract = {A cardinal feature that distinguishes clinically high-risk neuroblastoma from low-risk tumors is telomere maintenance. Specifically, neuroblastoma tumors with either active telomerase or alternative lengthening of telomeres exhibit aggressive growth characteristics that lead to poor outcomes, whereas tumors without telomere maintenance can be managed with observation or minimal treatment. Even though the need for cancer cells to maintain telomere DNA-in order to sustain cell proliferation-is well established, recent studies suggest that the neural crest origin of neuroblastoma may enforce unique relationships between telomeres and tumor malignancy. Specifically in neuroblastoma, telomere structure and telomerase activity are correlated with the adrenergic/mesenchymal differentiation states, and manipulating telomerase activity can trigger tumor cell differentiation. Both findings may reflect features of normal neural crest development. This review summarizes recent advances in the characterization of telomere structure and telomere maintenance mechanisms in neuroblastoma and discusses the findings in the context of relevant literature on telomeres during embryonic and neural development. Understanding the canonical and non-canonical roles of telomere maintenance in neuroblastoma could reveal vulnerabilities for telomere-directed therapies with potential applications to other pediatric malignancies.},
}
@article {pmid36028900,
year = {2022},
author = {Tan, KT and Slevin, MK and Meyerson, M and Li, H},
title = {Identifying and correcting repeat-calling errors in nanopore sequencing of telomeres.},
journal = {Genome biology},
volume = {23},
number = {1},
pages = {180},
pmid = {36028900},
issn = {1474-760X},
support = {U41 HG010972/HG/NHGRI NIH HHS/United States ; U01 HG010961/HG/NHGRI NIH HHS/United States ; R01 HG010040/HG/NHGRI NIH HHS/United States ; U01 HG010971/HG/NHGRI NIH HHS/United States ; R35 CA197568/CA/NCI NIH HHS/United States ; },
mesh = {Genomics ; High-Throughput Nucleotide Sequencing ; *Nanopore Sequencing ; *Nanopores ; Repetitive Sequences, Nucleic Acid ; Sequence Analysis, DNA ; Telomere ; },
abstract = {Nanopore long-read sequencing is an emerging approach for studying genomes, including long repetitive elements like telomeres. Here, we report extensive basecalling induced errors at telomere repeats across nanopore datasets, sequencing platforms, basecallers, and basecalling models. We find that telomeres in many organisms are frequently miscalled. We demonstrate that tuning of nanopore basecalling models leads to improved recovery and analysis of telomeric regions, with minimal negative impact on other genomic regions. We highlight the importance of verifying nanopore basecalls in long, repetitive, and poorly defined regions, and showcase how artefacts can be resolved by improvements in nanopore basecalling models.},
}
@article {pmid36014852,
year = {2022},
author = {Opstad, TB and Alexander, J and Aaseth, JO and Larsson, A and Seljeflot, I and Alehagen, U},
title = {Selenium and Coenzyme Q10 Intervention Prevents Telomere Attrition, with Association to Reduced Cardiovascular Mortality-Sub-Study of a Randomized Clinical Trial.},
journal = {Nutrients},
volume = {14},
number = {16},
pages = {},
pmid = {36014852},
issn = {2072-6643},
support = {N/A//Stein Erik Hagen Foundation for Clinical Heart Research, Oslo, Norway and County Council of &#xd6;sterg&#xf6;tland, Link&#xf6;ping University, Sweden./ ; },
mesh = {Aged ; Aged, 80 and over ; *Cardiovascular Diseases/mortality/physiopathology/prevention &amp; control ; Dietary Supplements ; Humans ; Leukocytes ; Prospective Studies ; *Selenium/pharmacology/therapeutic use ; *Telomere/drug effects/physiology ; *Ubiquinone/pharmacology/therapeutic use ; },
abstract = {Short telomeres have been associated with ageing and cardiovascular disease. The influence on leukocyte telomere length (LTL) of long-term intervention with combined selenium and coenzyme Q10 is unknown. Our aim was to determine whether 42 months of selenium and coenzyme Q10 supplementation prevented telomere attrition and further cardiovascular mortality. The investigation is an explorative sub-study of a double-blind, placebo-controlled, randomized trial. Swedish citizens low in selenium (n = 118), aged 70−80 years, were included. Intervention time was 4 years, with 10 years’ follow-up time. LTL was relatively quantified with PCR at baseline and after 42 months. At baseline, LTL (SD) was 0.954 (0.260) in the active treatment group and 1.018 (0.317) in the placebo group (p = 0.23). At 42 months, less shortening of LTL was observed after active treatment compared with placebo (+0.019 vs. −0.129, respectively, p = 0.02), with a significant difference in change basing the analysis on individual changes in LTL (p < 0.001). Subjects suffering future death presented with significantly shorter LTL at 42 months than survivors [0.791 (0.190) vs. 0.941 (0.279), p = 0.01], with a significant difference in change of LTL according to cardiovascular mortality and survival (p = 0.03). To conclude, preservation of LTL after selenium and coenzyme Q10 supplementation associated with reduced cardiovascular mortality.},
}
@article {pmid36011306,
year = {2022},
author = {Oudrhiri, N and M'kacher, R and Chaker, D and Colicchio, B and Borie, C and Jeandidier, E and Dieterlen, A and Griscelli, F and Bennaceur-Griscelli, A and Turhan, AG},
title = {Patient-Derived iPSCs Reveal Evidence of Telomere Instability and DNA Repair Deficiency in Coats Plus Syndrome.},
journal = {Genes},
volume = {13},
number = {8},
pages = {},
pmid = {36011306},
issn = {2073-4425},
mesh = {Ataxia ; Brain Neoplasms ; Calcinosis ; Central Nervous System Cysts ; *DNA Repair-Deficiency Disorders ; Humans ; *Induced Pluripotent Stem Cells/metabolism ; Leukoencephalopathies ; Muscle Spasticity ; Retinal Diseases ; Seizures ; *Telomerase/genetics ; Telomere/genetics/metabolism ; Telomere Homeostasis/genetics ; },
abstract = {Coats plus (CP) syndrome is an inherited autosomal recessive condition that results from mutations in the conserved telomere maintenance component 1 gene (CTC1). The CTC1 protein functions as a part of the CST protein complex, a protein heterotrimer consisting of CTC1-STN1-TEN1 which promotes telomere DNA synthesis and inhibits telomerase-mediated telomere elongation. However, it is unclear how CTC1 mutations may have an effect on telomere structure and function. For that purpose, we established the very first induced pluripotent stem cell lines (iPSCs) from a compound heterozygous patient with CP carrying deleterious mutations in both alleles of CTC1. Telomere dysfunction and chromosomal instability were assessed in both circulating lymphocytes and iPSCs from the patient and from healthy controls of similar age. The circulating lymphocytes and iPSCs from the CP patient were characterized by their higher telomere length heterogeneity and telomere aberrations compared to those in control cells from healthy donors. Moreover, in contrast to iPSCs from healthy controls, the high levels of telomerase were associated with activation of the alternative lengthening of telomere (ALT) pathway in CP-iPSCs. This was accompanied by inappropriate activation of the DNA repair proteins γH2AX, 53BP1, and ATM, as well as with accumulation of DNA damage, micronuclei, and anaphase bridges. CP-iPSCs presented features of cellular senescence and increased radiation sensitivity. Clonal dicentric chromosomes were identified only in CP-iPSCs after exposure to radiation, thus mirroring the role of telomere dysfunction in their formation. These data demonstrate that iPSCs derived from CP patients can be used as a model system for molecular studies of the CP syndrome and underscores the complexity of telomere dysfunction associated with the defect of DNA repair machinery in the CP syndrome.},
}
@article {pmid36010691,
year = {2022},
author = {Derevyanko, A and Skowronska, A and Skowronski, MT and Kordowitzki, P},
title = {The Interplay between Telomeres, Mitochondria, and Chronic Stress Exposure in the Aging Egg.},
journal = {Cells},
volume = {11},
number = {16},
pages = {},
pmid = {36010691},
issn = {2073-4409},
mesh = {*Aging/genetics ; Female ; Humans ; Mitochondria/genetics/metabolism ; Oocytes/metabolism ; Pregnancy ; *Telomere ; Telomere Shortening ; },
abstract = {While at the organismal level, biological aging can be estimated by telomere length and DNA methylation signatures, reliable biomarkers that can predict reproductive age are much needed to gauge the quality of an oocyte. Reproductive medicine and fertility centers often merely quantitate the ovarian reserve to predict the likelihood of fertilization and pregnancy in women of advanced reproductive age. It is highly important to address the level of age-related decline in oocyte quality since it leads to an increased risk of miscarriages and aneuploidy. Conversely, the pathways behind oocyte aging remain, in large part, elusive. Telomere shortening upon chronic stress exposure regulates mitochondria function and biogenesis by various pathways; therefore, establishing a link between these two important players and extrapolating them for the aging of oocytes will be the purpose of our commentary.},
}
@article {pmid36009574,
year = {2022},
author = {Opstad, TB and Solheim, S and Pettersen, AR and Kalstad, AA and Arnesen, H and Seljeflot, I},
title = {TERT and TET2 Genetic Variants Affect Leukocyte Telomere Length and Clinical Outcome in Coronary Artery Disease Patients-A Possible Link to Clonal Hematopoiesis.},
journal = {Biomedicines},
volume = {10},
number = {8},
pages = {},
pmid = {36009574},
issn = {2227-9059},
abstract = {Inherited and acquired mutations in hematopoietic stem cells can cause clonal expansion with increased risk of cardiovascular disease (CVD), a condition known for the clonal hematopoiesis of indeterminate potential (CHIP). Inherited genetic variants in two CHIP-associated genome loci, the telomerase gene telomerase enzyme reverse transcriptase (TERT) (rs7705526) and the epigenetic regulator ten−eleven translocation 2 (TET2) (rs2454206), were investigated in 1001 patients with stable coronary artery disease (CAD) (mean age 62 years, 22% women), with regards to cardiovascular outcome, comorbidities, and leukocyte telomere length. Over 2 years, mutated TERT increased the risk two-fold for major clinical events (MACEs) in all patients (p = 0.004), acute myocardial infarction (AMI) in male patients (p = 0.011), and stroke in female patients (p < 0.001). Mutated TET2 correlated with type 2 diabetes (p < 0.001), the metabolic syndrome (p = 0.002), as well as fasting glucose, HbA1c, and shorter telomeres (p = 0.032, p = 0.003, and p = 0.016, respectively). In conclusion, our results from stable CAD patients highlight TERTs’ role in CVD, and underline TET2s’ role in the epigenetic regulation of lifestyle-related diseases.},
}
@article {pmid36006930,
year = {2022},
author = {Sharaf, R and Frampton, GM and Albacker, LA},
title = {Mutations in the TERC template sequence can be incorporated into the telomeres of human tumors.},
journal = {PloS one},
volume = {17},
number = {8},
pages = {e0272707},
pmid = {36006930},
issn = {1932-6203},
mesh = {Humans ; Mutation ; *Neoplasms/genetics ; RNA/genetics/metabolism ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {Telomerase-mediated lengthening is a mechanism by which some cancer cells avoid senescence-mediated cell cycle arrest due to shortened telomeres. By reverse transcribing an RNA template, encoded by TERC, the enzyme telomerase synthesizes the elongation of telomeric DNA using the 3' end of the chromosome as a primer. TERC harbors a highly conserved template region consisting of 11 nucleotides spanning hg19 coordinates chr3:169482793-169482803. In human cell lines, when TERC was mutated to alter its template region, telomerase generated the predicted mutant telomeric repeats. However, it is unknown if this can occur in human clinical samples. Here, we report on the rare occurrence of two tumor samples where TERC template mutations were reflected in telomeric repeats.},
}
@article {pmid36005153,
year = {2022},
author = {Tacheva, T and Zienolddiny-Narui, S and Dimov, D and Vlaykova, D and Miteva, I and Vlaykova, T},
title = {The Leucocyte Telomere Length, GSTM1 and GSTT1 Null Genotypes and the Risk of Chronic Obstructive Pulmonary Disease.},
journal = {Current issues in molecular biology},
volume = {44},
number = {8},
pages = {3757-3769},
pmid = {36005153},
issn = {1467-3045},
support = {3/2019//Medical Faculty, Trakia University, Stara Zagora, Bulgaria/ ; },
abstract = {Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and oxidative stress both in the airways and blood and other organs. Elevated oxidative stress and inflammation have been reported to affect leucocyte telomere length (LTL). Glutathione S-transferase (GST) enzymes are a large family of xenobiotic-metabolizing enzymes that utilize different ROS products. We aimed to explore the link between GSTM1 and GSTT1 gene polymorphisms, LTL and COPD risk. For GSTM1, we genotyped 152 COPD patients and 131 non-affected controls; for GSTT1, we genotyped 149 COPD patients and 130 controls. We were able to assess TL for 91 patients and 88 controls. There was a significant difference in the GSTM1 null genotype frequency between the patients and controls (0.59 vs. 0.38, p ≤ 0.000), but such was not found for GSTT1 (p = 0.192). When combining both polymorphisms, we obtained a significantly greater presence of at least one null genotype among patients (0.12 vs. 0.05, p = 0.027). An association between GSTT1 and LTL was not found. COPD patients carrying the GSTM1 null genotype had shorter telomeres compared to those carrying the non-null genotype (15,720 bp vs. 22,442 bp, p = 0.008); as for the controls, it was the opposite (31,354 bp vs. 17,800 bp, p = 0.020). The significance in both groups remained when combining GSTM1 and GSTT1 (COPD (at least one null) 16,409 bp vs. COPD (non-null) 22,092 bp, p = 0.029; control (at least one null) 29,666 bp vs. control (non-null) 16,370 bp, p = 0.027). The total glutathione level in GSTM1 non-null controls was higher compared to the null genotype (15.39 ng/mL vs. 5.53 ng/mL, p = 0.002). In COPD patients, we found no association (p = 0.301). In conclusion, according to our results, GSTM1, but not GSTT1, null genotypes might play a role in leucocyte telomere shortening, and thus be involved in the pathogenesis of COPD.},
}
@article {pmid35996190,
year = {2022},
author = {Retuerto, M and Lledó, A and Fernandez-Varas, B and Guerrero-López, R and Usategui, A and Lalueza, A and García-García, R and Mancebo, E and Paz-Artal, E and Sastre, L and Perona, R and Pablos, JL},
title = {Shorter telomere length is associated with COVID-19 hospitalization and with persistence of radiographic lung abnormalities.},
journal = {Immunity &amp; ageing : I &amp; A},
volume = {19},
number = {1},
pages = {38},
pmid = {35996190},
issn = {1742-4933},
abstract = {BACKGROUND: Age and comorbidity are the main determinants of COVID-19 outcome. Shorter leukocyte telomere length (TL), a hallmark of biological aging, has been associated with worse COVID-19 outcomes. We sought to determine TL in patients with severe COVID-19 requiring hospitalization to analyze whether clinical outcomes and post-COVID-19 manifestations are associated with shorter TL.<br><br>RESULTS: We analyzed 251 patients with PCR-confirmed COVID-19, hospitalized in the first months of the pandemics. We determined TL in PBL at admission by quantitative-PCR (qPCR) analysis in patients. A healthy cohort from the same area with a similar age range (n&#x2009;=&#x2009;169) was used to calculate TL Z-scores. After hospital discharge, 144 COVID-19 survivors were followed-up for persistent COVID-19 manifestations. A second TL determination was performed in a smaller group of 63 patients 1&#x2009;year later and compared with baseline TL. Hospitalized COVID-19 patients had a decreased baseline age-adjusted TL Z-score compared to the reference group. No differences in Z-scores were observed in patients with different COVID-19 outcomes, classified as WHO ordinal scores. In 144 patients, followed for a median of 8&#x2009;months, post-COVID manifestations were not associated to differences in TL. Persistence of lung radiographic abnormalities was associated with shorter baseline TL. In patients with a second TL determination, further telomere shortening (TS) was observed in 35% and telomere lengthening in 49%. Patients with further TS had suffered a more severe disease.<br><br>CONCLUSION: Shorter TL is associated with COVID-19 hospitalization but not with hospital clinical outcomes nor with persistent post-COVID-19 manifestations. Delayed resolution of radiographic lung abnormalities was also associated with shorter TL.},
}
@article {pmid35992857,
year = {2022},
author = {Li, JH and Tao, YF and Shen, CH and Li, RD and Wang, Z and Xing, H and Ma, ES and Xue, HY and Zhang, QB and Ma, ZY and Wang, ZX},
title = {Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma.},
journal = {Frontiers in oncology},
volume = {12},
number = {},
pages = {939948},
pmid = {35992857},
issn = {2234-943X},
abstract = {Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a high recurrence rate. Accurate prediction of recurrence risk is urgently required for tailoring personalized treatment programs for individual HCC patients in advance. In this study, we analyzed a gene expression dataset from an HCC cohort with 247 samples and identified five genes including ENY2, GPAA1, NDUFA4L2, NEDD9, and NRP1 as the variables for the prediction of HCC recurrence, especially the early recurrence. The Cox model and risks score were validated in two public HCC cohorts (GSE76427 and The Cancer Genome Atlas (TCGA)) and one cohort from Huashan Hospital, which included a total of 641 samples. Moreover, the multivariate Cox regression analysis revealed that the risk score could serve as an independent prognostic factor in the prediction of HCC recurrence. In addition, we found that ENY2, GPAA1, and NDUFA4L2 were significantly upregulated in HCC of the two validation cohorts, and ENY2 had significantly higher expression levels than another four genes in malignant cells, suggesting that ENY2 might play key roles in malignant cells. The cell line analysis revealed that ENY2 could promote cell cycle progression, cell proliferation, migration, and invasion. The functional analysis of the genes correlated with ENY2 revealed that ENY2 might be involved in telomere maintenance, one of the fundamental hallmarks of cancer. In conclusion, our data indicate that ENY2 may regulate the malignant phenotypes of HCC via activating telomere maintenance.},
}
@article {pmid35988638,
year = {2022},
author = {Lynn, SE and Kern, MD and Serrurier, B and Sirman, A and Heidinger, BJ},
title = {Chill out: Environmentally relevant cooling challenge does not increase telomere loss during early life.},
journal = {General and comparative endocrinology},
volume = {329},
number = {},
pages = {114108},
doi = {10.1016/j.ygcen.2022.114108},
pmid = {35988638},
issn = {1095-6840},
mesh = {Animals ; Female ; *Corticosterone ; Stress, Physiological ; Telomere ; Telomere Shortening ; *Songbirds/physiology ; },
abstract = {In vertebrates, exposure to diverse stressors during early life activates a stress response that can initiate compensatory mechanisms or promote cellular damage with long-term fitness consequences. A growing number of studies associate exposure to stressors during early life with increased damage to telomeres (i.e., promoting the shortening of these highly conserved, repeating sequences of non-coding DNA at chromosome ends). However, some studies show no such relationship, suggesting that the nature, timing, and context of these challenges may determine the degree to which physiological mediators of the stress response act in a damage-mitigating or damage promoting way in relation to telomere dynamics. In free-living eastern bluebirds (Sialia sialis), we have previously demonstrated that bouts of offspring cooling that occur when brooding females leave the nest increase at least one such physiological mediator of the stress response (circulating glucocorticoids), suggesting that variation in patterns of maternal brooding may result in different impacts on telomere dynamics at a young age. Here we experimentally tested whether repeated bouts of ecologically relevant offspring cooling affected telomere dynamics during post-natal development. Rates of telomere shortening during the nestling stage were not affected by experimental cooling, but they were affected by brood size and the rate of growth during the nestling stage. Our data suggest that the effects of developmental stress exposure on offspring telomeres are often context-dependent and that not all challenges that increase physiological mediators of stress result in damage to telomeres. Under some conditions, physiological mediators of stress may instead act as protective regulators, allowing for optimization of fitness outcomes in the face of environmental challenges.},
}
@article {pmid35987624,
year = {2022},
author = {Wang, T and Jia, Z and Li, S and Li, Y and Yu, T and Lu, T and Shi, Y},
title = {The association between leukocyte telomere length and chronic obstructive pulmonary disease is partially mediated by inflammation: a meta-analysis and population-based mediation study.},
journal = {BMC pulmonary medicine},
volume = {22},
number = {1},
pages = {320},
pmid = {35987624},
issn = {1471-2466},
mesh = {Aging ; Humans ; Inflammation/genetics ; Leukocytes ; Nutrition Surveys ; *Pulmonary Disease, Chronic Obstructive ; *Smoking ; Telomere ; },
abstract = {BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the major health issues worldwide. Pathophysiological changes in COPD are mainly reflected in the deterioration of lung function with aging.<br><br>METHODS: Considering that telomere length is a hallmark of biological aging, we first performed a meta-analysis to summarize the current knowledge about the relationship between telomere length and COPD and then employed individual-level data from the continuous National Health and Nutrition Examination Survey (NHANES) to investigate whether telomere length could reflect accelerated aging in COPD and serve as an independent predictor. A mediation study was further performed to examine whether the association between telomeres and COPD could be mediated by inflammation, as one of the most important etiologies and characteristics of COPD.<br><br>RESULTS: The four studies included in our meta-analysis were with high heterogeneity (I[2]&#x2009;=&#x2009;95.7%, Phet&#x2009;<&#x2009;0.001), and the pooled relative risk for COPD comparing the shortest tertile versus the longest tertile was 4.06 (95% CI&#x2009;=&#x2009;1.38 to 11.96). Of the 6,378 subjects in the individual-level data analyses using NHANES, 455 were diagnosed with COPD, and multivariable-adjusted logistic regression also indicated that short telomere length was associated with COPD. Consistently, cubic regression spline analyses showed that long telomeres exhibited a significant association with a decreased risk of COPD. In the subsequent mediation analyses, C-reactive protein concentration, white blood cells count and blood neutrophil count, as inflammatory biomarkers, showed a significant indirect effect on the relationship between telomere length and COPD.<br><br>CONCLUSION: Accelerated aging in COPD could be characterized by excessive telomere shortening, and inflammatory response might be involved in the underlying mechanisms of COPD pathogenesis promoted by short telomere length. Telomere length measurement may facilitate clinical translational research and targeted therapy of COPD.},
}
@article {pmid37519465,
year = {2023},
author = {Ratanatharathorn, A and Roberts, AL and Chibnik, LB and Choi, KW and De Vivo, I and Kim, Y and Nishimi, K and Rimm, EB and Sumner, JA and Kubzansky, LD and Koenen, KC},
title = {Posttraumatic Stress Disorder, Depression, and Accelerated Aging: Leukocyte Telomere Length in the Nurses' Health Study II.},
journal = {Biological psychiatry global open science},
volume = {3},
number = {3},
pages = {510-518},
pmid = {37519465},
issn = {2667-1743},
abstract = {BACKGROUND: Exposure to trauma, posttraumatic stress disorder (PTSD), and depression have been independently associated with leukocyte telomere length (LTL), a cellular marker of aging associated with mortality and age-related diseases. However, the joint contributions of trauma and its psychological sequelae on LTL have not been examined.<br><br>METHODS: We conducted an analysis of LTL in a subset of women from the Nurses' Health Study II (N = 1868). Lifetime exposure to traumatic events, PTSD, and depression was assessed with validated measures. DNA was extracted from peripheral blood leukocytes and telomere repeat copy number to single gene copy number was determined by quantitative real-time polymerase chain reaction telomere assay. Linear regression models assessed the association of trauma, PTSD, and depression with LTL after adjustment for health behaviors and medical conditions.<br><br>RESULTS: Trauma, PTSD, and depression were not independently associated with LTL in mutually adjusted models. However, individuals with severe psychological distress-characterized by comorbid PTSD and depression-had shorter LTL equivalent to being 7.62 years older (95% CI, 0.02 to 17.97) than participants who had never experienced a traumatic event and were not depressed. Further examination found only an association among individuals with the highest number of PTSD symptoms and comorbid depression equivalent to 9.71 additional years of aging (95% CI, 1.36 to 20.49). No effect was found among individuals meeting the minimum threshold for probable PTSD with comorbid depression.<br><br>CONCLUSIONS: Severe psychological distress, as indicated by the presence of comorbid PTSD and depression, may be associated with shorter LTL.},
}
@article {pmid37117760,
year = {2022},
author = {Codd, V and Denniff, M and Swinfield, C and Warner, SC and Papakonstantinou, M and Sheth, S and Nanus, DE and Budgeon, CA and Musicha, C and Bountziouka, V and Wang, Q and Bramley, R and Allara, E and Kaptoge, S and Stoma, S and Jiang, T and Butterworth, AS and Wood, AM and Di Angelantonio, E and Thompson, JR and Danesh, JN and Nelson, CP and Samani, NJ},
title = {Measurement and initial characterization of leukocyte telomere length in 474,074 participants in UK Biobank.},
journal = {Nature aging},
volume = {2},
number = {2},
pages = {170-179},
pmid = {37117760},
issn = {2662-8465},
support = {MR/L003120/1/MRC_/Medical Research Council/United Kingdom ; RG/13/13/30194/BHF_/British Heart Foundation/United Kingdom ; SP/16/4/32697/BHF_/British Heart Foundation/United Kingdom ; RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; MR/M012816/1/MRC_/Medical Research Council/United Kingdom ; CH/12/2/29428/BHF_/British Heart Foundation/United Kingdom ; },
mesh = {Infant, Newborn ; Humans ; Male ; Female ; *Biological Specimen Banks ; *Ethnicity ; Leukocytes ; Telomere/genetics ; United Kingdom ; },
abstract = {Leukocyte telomere length (LTL) is a proposed marker of biological age. Here we report the measurement and initial characterization of LTL in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ~7 years younger in 'biological age' than men. Compared to white Europeans, LTL is markedly longer in African and Chinese ancestries. Older paternal age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes show weaker associations. Age, ethnicity, sex and white cell count explain ~5.5% of LTL variance. Using paired samples from 1,351 participants taken ~5 years apart, we estimate the within-individual variability in LTL and provide a correction factor for this. This resource provides opportunities to investigate determinants and biomedical consequences of variation in LTL.},
}
@article {pmid37117759,
year = {2022},
author = {Hägg, S and Zhan, Y},
title = {Telomere research entering the big data era.},
journal = {Nature aging},
volume = {2},
number = {2},
pages = {102-104},
pmid = {37117759},
issn = {2662-8465},
support = {U24 AG066528/AG/NIA NIH HHS/United States ; },
mesh = {*Big Data ; *Telomere/genetics ; Databases, Factual ; },
}
@article {pmid36324603,
year = {2022},
author = {Ridout, KK and Syed, SA and Kao, HT and Porton, B and Rozenboym, AV and Tang, J and Fulton, S and Perera, T and Jackowski, AP and Kral, JG and Tyrka, AR and Coplan, J},
title = {Relationships Between Telomere Length, Plasma Glucagon-like Peptide 1, and Insulin in Early-Life Stress-Exposed Nonhuman Primates.},
journal = {Biological psychiatry global open science},
volume = {2},
number = {1},
pages = {54-60},
pmid = {36324603},
issn = {2667-1743},
abstract = {BACKGROUND: Early-life stress is associated with alterations in telomere length, a marker of accumulated stress and aging, and a risk factor for psychiatric disorders. Nonhuman primate maternal variable foraging demand (VFD) is a validated early-life stress model, resulting in anxiety- and depressive-like symptoms in offspring. Previous studies reported increased plasma glucagon-like peptide 1 (pGLP-1) along with insulin resistance in this model. We investigated whether VFD rearing related to adult telomere length and to these neuroendocrine markers.<br><br>METHODS: Adult leukocyte telomere length was measured in VFD-reared (12 males, 13 females) and non-VFD-reared (9 males, 26 females) bonnet macaques. Associations between adult telomere length and adolescent fasting pGLP-1 or insulin resistance in VFD-reared versus non-VFD-reared groups were examined using regression modeling, controlling for sex, weight, and age.<br><br>RESULTS: VFD subjects had relatively longer telomeres than non-VFD subjects (p&#xa0;= .017), and females relatively longer than males (p&#xa0;= .0004). Telomere length was positively associated with pGLP-1 (p&#xa0;= .0009) and with reduced insulin sensitivity (p < .0001) in both sexes, but not as a function of rearing group.<br><br>CONCLUSIONS: Unexpectedly, VFD was associated with longer adult telomere length. Insulin resistance may lead to higher pGLP-1 levels in adolescence, which could protect telomere length in VFD offspring as adults. Associations between adult telomere length and adolescent insulin resistance and high pGLP-1 may reflect an adaptive, compensatory response after early-life stress exposure.},
}
@article {pmid37034531,
year = {2023},
author = {Vukašinović, A and Ostanek, B and Klisic, A and Kafedžić, S and Zdravković, M and Ilić, I and Sopić, M and Hinić, S and Stefanović, M and Memon, L and Gaković, B and Bogavac-Stanojević, N and Spasojević-Kalimanovska, V and Marc, J and Nešković, AN and Kotur-Stevuljević, J},
title = {Telomere-telomerase system status in patients with acute myocardial infarction with ST-segment elevation - relationship with oxidative stress.},
journal = {Archives of medical science : AMS},
volume = {19},
number = {2},
pages = {313-323},
pmid = {37034531},
issn = {1734-1922},
abstract = {INTRODUCTION: Telomeres are protective chromosomal ends. Short telomeres are a proven biomarker of biological aging. We aimed to find an association of telomere length and telomerase activity in circulating leukocytes and thromboaspirates of patients with acute myocardial infarction. Furthermore, association of the telomere-telomerase system with oxidative stress markers (as common risk factors for coronary artery disease (CAD)) was tested.<br><br>MATERIAL AND METHODS: Patients were selected from the patients admitted to the intensive care unit with acute myocardial infarction with ST-segment elevation (STEMI), with the following inclusion criteria - STEMI patients between 18 and 80 years old of both genders and candidates for primary percutaneous coronary intervention, with infarction pain present for a maximum of 12 h. In all the patients leukocyte telomere length, telomerase activity and scores related to oxidative-stress status (Protective, Damage and OXY) were evaluated.<br><br>RESULTS: Patients were divided into different groups: with stable angina pectoris (AP) (n = 22), acute myocardial infarction with: STEMI (n = 93), non-obstructive coronary arteries (MINOCA) (n = 7), blood vessel rupture (n = 6) at three time points, and compared to the group of 84 healthy subjects. Telomerase activity was significantly higher in all CAD sub-groups compared to the control group (AP = 0.373 (0.355-0.386), STEMI = 0.375 (0.349-0.395), MINOCA = 0.391 (0.366-0.401), blood vessel rupture = 0.360 (0.352-0.385) vs. CG = 0.069 (0.061-0.081), p < 0.001), while telomeres were significantly shorter in STEMI, MINOCA and blood vessel rupture groups compared to the control group (STEMI = 1.179 (0.931-1.376), MINOCA = 1.026 (0.951-1.070), blood vessel rupture = 1.089 (0.842-1.173) vs. CG = 1.329 (1.096-1.624), p = 0.030]. Values of OXY score were significantly higher in STEMI and MINOCA patients compared to the control group and AP patients (5.83 (4.55-7.54) and 10.28 (9.19-10.72) vs. 4.94 (3.29-6.18) and 4.18 (2.58-4.86), p < 0.001). Longer telomeres and higher telomerase activity were found in thromboaspirates, compared to the peripheral blood leukocytes in the same patients (1.25 (1.01-1.84) vs. 1.18 (0.909-1.516), p = 0.036; and 0.366 (0.367-0.379) vs. 0.366 (0.367-0.379), p < 0.001, respectively). In addition, telomere length and telomerase activity had good diagnostic ability to separate STEMI patients from healthy persons.<br><br>CONCLUSIONS: Leukocyte telomere length and telomerase activity can differentiate CAD patients from healthy persons, and relate CAD to oxidative stress.},
}
@article {pmid37118410,
year = {2021},
author = {Saraswati, S and Martínez, P and Graña-Castro, O and Blasco, MA},
title = {Short and dysfunctional telomeres sensitize the kidneys to develop fibrosis.},
journal = {Nature aging},
volume = {1},
number = {3},
pages = {269-283},
pmid = {37118410},
issn = {2662-8465},
mesh = {Mice ; Animals ; Humans ; *Telomerase/genetics ; Telomere/genetics ; Shelterin Complex ; Fibrosis ; Kidney/metabolism ; Folic Acid ; },
abstract = {Accumulation of short telomeres is a hallmark of aging. Mutations in telomerase or telomere-binding proteins lead to telomere shortening or dysfunction and are at the origin of human pathologies known as 'telomere syndromes', which are characterized by loss of the regenerative capacity of tissues and fibrotic pathologies. Here, we generated two mouse models of kidney fibrosis, either by combining telomerase deficiency to induce telomere shortening and a low dose of folic acid, or by conditionally deleting Trf1, a component of the shelterin telomere protective complex, from the kidneys. We find that short telomeres sensitize the kidneys to develop fibrosis in response to folic acid and exacerbate the epithelial-to-mesenchymal transition (EMT) program. Trf1 deletion in kidneys led to fibrosis and EMT activation. Our findings suggest that telomere shortening or dysfunction may contribute to pathological, age-associated renal fibrosis by influencing the EMT program.},
}
@article {pmid35986545,
year = {2022},
author = {Zafirovic, S and Macvanin, M and Stanimirovic, J and Obradovic, M and Radovanovic, J and Melih, I and Isenovic, E},
title = {Association Between Telomere Length and Cardiovascular Risk: Pharmacological Treatments Affecting Telomeres and Telomerase Activity.},
journal = {Current vascular pharmacology},
volume = {20},
number = {6},
pages = {465-474},
doi = {10.2174/1570161120666220819164240},
pmid = {35986545},
issn = {1875-6212},
mesh = {Humans ; *Telomerase/genetics/metabolism ; *Cardiovascular Diseases/diagnosis/drug therapy/genetics ; Risk Factors ; Telomere/genetics/metabolism ; Heart Disease Risk Factors ; },
abstract = {Telomeres represent the ends of chromosomes, and they are composed of an extensive number of - TTAGGG nucleotide sequence repeats in humans. Telomeres prevent chromosome degradation, participate in stabilization, and regulate the DNA repair system. Inflammation and oxidative stress have been identified as important processes causing cardiovascular disease and accelerating telomere shortening rate. This review investigates the link between telomere length and pathological vascular conditions from experimental and human studies. Also, we discuss pharmacological treatments affecting telomeres and telomerase activity.},
}
@article {pmid35983406,
year = {2022},
author = {Hoffmann, J and Tabata, N and Mas-Peiro, S and Spyridopoulos, I and Sinning, JM and Berkowitsch, A and Martin-Ruiz, C and Al-Kassou, B and Herrmann, E and Dimmeler, S and Zeiher, AM and Vasa-Nicotera, M},
title = {Longer leukocyte telomere length is associated with myeloid inflammation and increased mortality after transcatheter aortic valve replacement.},
journal = {European heart journal open},
volume = {2},
number = {4},
pages = {oeac045},
pmid = {35983406},
issn = {2752-4191},
abstract = {AIMS: Inflammatory activation of leukocytes may limit prognosis of patients (pts) with severe aortic valve stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Leukocyte telomere length (LTL) is a marker of proliferative capacity and inflammatory responsiveness but the impact of LTL on the prognosis in AS remains elusive. The aim of this study was to analyse the association of LTL with inflammatory markers and prognosis of pts undergoing TAVR.<br><br>METHODS AND RESULTS: LTL was analysed using quantitative real-time PCR in 285 consecutive pts (median age 82 years) undergoing TAVR and correlated with 18-month all-cause mortality. C-reactive protein was significantly elevated in pts with the longest LTL (P&#x2009;=&#x2009;0.017), paralleled by increased procalcitonin (PCT) serum levels (P&#x2009;=&#x2009;0.0006). This inflammatory reaction was accompanied by increased myeloid cells in the highest LTL tertile, mainly a rise in circulating neutrophils (P&#x2009;=&#x2009;0.0025) and monocytes (P&#x2009;=&#x2009;0.01). Multivariate analysis revealed LTL (HR 2.6, 95%CI 1.4-5.1, &#x2009;P=&#x2009;0.004) and PCT levels (HR 4.3, 95%CI 1.7-11.0, P&#x2009;=&#x2009;0.003) as independent predictors of mortality.<br><br>CONCLUSIONS: Longer LTL is associated with increased mortality after TAVR. This might be explained by enhanced proliferative capacity of cells resulting in myeloid and systemic inflammation. Our findings suggest that targeting the specific inflammation pathways could present a novel strategy to augment survival in selected patients with degenerative aortic stenosis.},
}
@article {pmid35977791,
year = {2022},
author = {Romero-Haro, A&#xc1; and Morger, J and Haussmann, MF and Tschirren, B},
title = {Reproductive Strategies Affect Telomere Dynamics across the Life Course.},
journal = {The American naturalist},
volume = {200},
number = {3},
pages = {373-382},
doi = {10.1086/720440},
pmid = {35977791},
issn = {1537-5323},
mesh = {Adult ; Aging/genetics ; Animals ; *Coturnix/genetics ; Humans ; Infant, Newborn ; *Life Change Events ; Male ; Reproduction ; Telomere ; },
abstract = {AbstractBecause parental care has a heritable basis, the benefits of receiving increased parental provisioning early in life are genetically linked to the costs of providing increased parental provisioning at adulthood. Reproductive strategies thus result in distinct cost-benefit syndromes across the life course that may shape individual health and aging trajectories. Here we used an artificial selection approach in Japanese quail (Coturnix japonica) to test how reproductive strategies affect telomere length, a biomarker of somatic state, at different life stages. We show that males but not females from lines selected for low maternal investment (i.e., developing in a relatively small egg) had shorter telomeres at birth. These patterns were still weakly present at the end of the juvenile growth period. In contrast, significantly shorter telomeres were found in reproductively active adult birds from the high-investment lines, suggesting that telomere attrition was accelerated in these individuals once they had become reproductively active. Our study shows that reproductive strategies differentially affect telomere dynamics across the life course, highlighting the role of cross-generational constraints in shaping individual aging trajectories.},
}
@article {pmid35974160,
year = {2023},
author = {Petermann-Rocha, F and Valera-Gran, D and Fernández-Pires, P and Martens, DS and Júlvez, J and Rodríguez-Dehli, C and Andiarena, A and Lozano, M and Fernández-Somoano, A and Lertxundi, A and Llop, S and Guxens, M and Nawrot, TS and Navarrete-Muñoz, EM},
title = {Children who sleep more may have longer telomeres: evidence from a longitudinal population study in Spain.},
journal = {Pediatric research},
volume = {93},
number = {5},
pages = {1419-1424},
pmid = {35974160},
issn = {1530-0447},
mesh = {Humans ; Child ; Child, Preschool ; Cohort Studies ; Spain ; Cross-Sectional Studies ; *Sleep ; *Telomere ; },
abstract = {BACKGROUND: Inadequate sleep duration has been suggested as a chronic stressor associated with changes in telomere length (TL). This study aimed to explore the association between sleep duration and TL using the INMA birth cohort study data.<br><br>METHODS: A total of 1014 children were included in this study (cross-sectional: 686; longitudinal: 872). Sleep duration (h/day) was reported by caregivers at 4 years and classified into tertiles (7-10&#x2009;h/day; >10-11&#x2009;h/day; >11-14&#x2009;h/day). Leucocyte TL at 4 and 7-9 years were measured using quantitative PCR methods. Multiple robust linear regression models, through log-level regression models, were used to report the % of difference among tertiles of sleep duration.<br><br>RESULTS: In comparison to children who slept between >10 and 11&#x2009;h/day, those in the highest category (more than 11&#x2009;h/day) had 8.5% (95% CI: 3.56-13.6) longer telomeres at 4 years. Longitudinal analysis showed no significant association between sleep duration at 4 years and TL at 7-9 years.<br><br>CONCLUSION: Children who slept more hours per day had longer TL at 4 years independently of a wide range of confounder factors. Environmental conditions, such as sleep duration, might have a major impact on TL during the first years of life.<br><br>IMPACT: Telomere length was longer in children with longer sleep duration (>11&#x2009;h/day) independently of a wide range of confounder factors at age 4 and remained consistent by sex. Sleep routines are encouraged to promote positive child development, like the number of hours of sleep duration. Considering the complex biology of telomere length, future studies still need to elucidate which biological pathways might explain the association between sleep duration and telomere length.},
}
@article {pmid35968296,
year = {2022},
author = {Maroon, JC},
title = {The effect of hyperbaric oxygen therapy on cognition, performance, proteomics, and telomere length-The difference between zero and one: A case report.},
journal = {Frontiers in neurology},
volume = {13},
number = {},
pages = {949536},
pmid = {35968296},
issn = {1664-2295},
abstract = {INTRODUCTION: Hyperbaric oxygen (HBO2) therapy has recently been suggested for the treatment of different brain injuries as well as for physical and cognitive enhancement. The author recently carried out a self-experiment to obtain objective information on the effects of HBO2 therapy on neurocognition, cardiopulmonary function, neuroimaging and its effect on novel biomarkers such as telomere length and proteomics. In the following case report, the author will present and discuss the results and the differences between zero and one.<br><br>METHODS: This is a personal case report on a single subject, myself, who underwent a protocol of 60 daily HBO2 therapy sessions within 3 months. Pre- and post-therapy objective evaluation measured included computerized cognitive assessment, brain imaging, cardiopulmonary exercise test, physical assessments and blood tests including telomere length and proteomics.<br><br>RESULTS: Neurocognitive results showed a 3.1-3.8% improvements in global cognitive function as well as all other cognitive function domains. In the perfusion MRI, there was a relative increase ranging from 43.3 to 52.3% in cerebral perfusion in various areas subserving memory, coordination, and visual motor cortex function. Similar improvements in cerebral perfusion were seen in the SPECT scans, which ranged from 8.79 to 16.12% increased perfusion in the temporal pole and entorhinal cortex subserving memory, as well as in the subcallosal area and lingual gyrus. MRI-DTI showed prominent increases in fractional anisotropy in several white matter areas including 9% in the body of the corpus callosum, 16.85% in for the fornix and 22.06% in the tapetum. In the physical domains, there were improvements in both anaerobic threshold, exercise endurance, muscle strength, gait speed and grip strength in the 7-15% range. The telomeres length was doubled and clusters of inflammatory proteins dropped around the 40th session and remained low at the 60th session.<br><br>CONCLUSION: The difference between zero and one in this single case study of HBO2 therapy confirmed improvement in objective biomarkers which measured cognition, memory, brain processing speed, athletic performance and neuroimaging modalities measuring cerebral perfusion, blood flow and tractography. Additional studies with larger sample size and randomized clinical trials using similar biomarkers are needed to confirm the results and to delineate the longevity of these improvements.},
}
@article {pmid35959813,
year = {2022},
author = {Byrjalsen, A and Bygum, A and Lautrup, CK and Frederiksen, AL and Fialla, AD and Raaschou-Jensen, K and Bendstrup, E and Madsen, TN and Klarskov, M and Jelsig, AM},
title = {[Telomere biology disorders].},
journal = {Ugeskrift for laeger},
volume = {184},
number = {28},
pages = {},
pmid = {35959813},
issn = {1603-6824},
mesh = {Adult ; Biology ; Child ; *Diet, Ketogenic ; *Epilepsy/therapy ; Humans ; Telomere ; *Vagus Nerve Stimulation ; },
abstract = {The end of the chromosomes consists of DNA referred to as telomeres. The telomeres protect chromosomal DNA against shortening when cells divide. Patients with telomere biology disorders carry pathogenic germline variants in a gene involved in telomere function. New technologic advances have enabled us to identify more patients with telomere biology disorders, which in turn have increased our understanding of the phenotypic spectrum. The latter have proved wider than previously thought, and now we know that e.g. patients with isolated lung fibrosis can have an underlying telomere biology disorder.},
}
@article {pmid35953846,
year = {2022},
author = {Kim, S and Chowdhury, T and Yu, HJ and Kahng, JY and Lee, CE and Choi, SA and Kim, KM and Kang, H and Lee, JH and Lee, ST and Won, JK and Kim, KH and Kim, MS and Lee, JY and Kim, JW and Kim, YH and Kim, TM and Choi, SH and Phi, JH and Shin, YK and Ku, JL and Lee, S and Yun, H and Lee, H and Kim, D and Kim, K and Hur, JK and Park, SH and Kim, SK and Park, CK},
title = {The telomere maintenance mechanism spectrum and its dynamics in gliomas.},
journal = {Genome medicine},
volume = {14},
number = {1},
pages = {88},
pmid = {35953846},
issn = {1756-994X},
mesh = {*Glioma/genetics ; Humans ; Mutation ; *Telomerase/genetics ; Telomere/genetics ; Telomere Homeostasis ; },
abstract = {BACKGROUND: The activation of the telomere maintenance mechanism (TMM) is one of the critical drivers of cancer cell immortality. In gliomas, TERT expression and TERT promoter mutation are considered to reliably indicate telomerase activation, while ATRX mutation and/or loss indicates an alternative lengthening of telomeres (ALT). However, these relationships have not been extensively validated in tumor tissues.<br><br>METHODS: Telomerase repeated amplification protocol (TRAP) and C-circle assays were used to profile and characterize the TMM cross-sectionally (n = 412) and temporally (n = 133) across glioma samples. WES, RNA-seq, and NanoString analyses were performed to identify and validate the genetic characteristics of the TMM groups.<br><br>RESULTS: We show through the direct measurement of telomerase activity and ALT in a large set of glioma samples that the TMM in glioma cannot be defined solely by the combination of telomerase activity and ALT, regardless of TERT expression, TERT promoter mutation, and ATRX loss. Moreover, we observed that a considerable proportion of gliomas lacked both telomerase activity and ALT. This telomerase activation-negative and ALT negative group exhibited evidence of slow growth potential. By analyzing a set of longitudinal samples from a separate cohort of glioma patients, we discovered that the TMM is not fixed and can change with glioma progression.<br><br>CONCLUSIONS: This study suggests that the TMM is dynamic and reflects the plasticity and oncogenicity of tumor cells. Direct measurement of telomerase enzyme activity and evidence of ALT should be considered when defining TMM. An accurate understanding of the TMM in glioma is expected to provide important information for establishing cancer management strategies.},
}
@article {pmid35950364,
year = {2022},
author = {Lundsgaard, NU and Cramp, RL and Franklin, CE},
title = {Early exposure to UV radiation causes telomere shortening and poorer condition later in life.},
journal = {The Journal of experimental biology},
volume = {225},
number = {17},
pages = {},
pmid = {35950364},
issn = {1477-9145},
support = {DP190102152//Australian Research Council/ ; //Australian Government/ ; //The University of Queensland/ ; },
mesh = {Animals ; Anura/genetics ; Australia ; Larva/genetics ; Metamorphosis, Biological ; *Telomere Shortening ; *Ultraviolet Rays/adverse effects ; },
abstract = {Determining the contribution of elevated ultraviolet-B radiation (UVBR; 280-315 nm) to amphibian population declines is being hindered by a lack of knowledge about how different acute UVBR exposure regimes during early life-history stages might affect post-metamorphic stages via long-term carryover effects. We acutely exposed tadpoles of the Australian green tree frog (Litoria caerulea) to a combination of different UVBR irradiances and doses in a multi-factorial laboratory experiment, and then reared them to metamorphosis in the absence of UVBR to assess carryover effects in subsequent juvenile frogs. Dose and irradiance of acute UVBR exposure influenced carryover effects into metamorphosis in somewhat opposing manners. Higher doses of UVBR exposure in larvae yielded improved rates of metamorphosis. However, exposure at a high irradiance resulted in frogs metamorphosing smaller in size and in poorer condition than frogs exposed to low and medium irradiance UVBR as larvae. We also demonstrate some of the first empirical evidence of UVBR-induced telomere shortening in vivo, which is one possible mechanism for life-history trade-offs impacting condition post-metamorphosis. These findings contribute to our understanding of how acute UVBR exposure regimes in early life affect later life-history stages, which has implications for how this stressor may shape population dynamics.},
}
@article {pmid35949423,
year = {2022},
author = {Yu, HJ and Koh, SH},
title = {Is Telomere Length Shortening a Risk Factor for Neurodegenerative Disorders?.},
journal = {Dementia and neurocognitive disorders},
volume = {21},
number = {3},
pages = {83-92},
pmid = {35949423},
issn = {2384-0757},
abstract = {Telomeres are located at the end of chromosomes. They are known to protect chromosomes and prevent cellular senescence. Telomere length shortening has been considered an important marker of aging. Many studies have reported this concept in connection with neurodegenerative disorders. Considering the role of telomeres, it seems that longer telomeres are beneficial while shorter telomeres are detrimental in preventing neurodegenerative disorders. However, several studies have shown that people with longer telomeres might also be vulnerable to neurodegenerative disorders. Before these conflicting results can be explained through large-scale longitudinal clinical studies on the role of telomere length in neurodegenerative disorders, it would be beneficial to simultaneously review these opposing results. Understanding these conflicting results might help us plan future studies to reveal the role of telomere length in neurodegenerative disorders. In this review, these contradictory findings are thoroughly discussed, with the aim to better understand the role of telomere length in neurodegenerative disorders.},
}
@article {pmid35948770,
year = {2022},
author = {Olson, CL and Barbour, AT and Wuttke, DS},
title = {Filling in the blanks: how the C-strand catches up to the G-strand at replicating telomeres using CST.},
journal = {Nature structural &amp; molecular biology},
volume = {29},
number = {8},
pages = {730-733},
pmid = {35948770},
issn = {1545-9985},
support = {R24 OD033699/OD/NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; },
mesh = {*Telomerase/genetics/metabolism ; *Telomere/genetics/metabolism ; Telomere-Binding Proteins/metabolism ; },
}
@article {pmid35947933,
year = {2022},
author = {Natalini, JG and England, BR and Baker, JF and Chen, Q and Singh, N and Mahajan, TD and Roul, P and Thiele, GM and Sauer, BC and Mikuls, TR and Johnson, FB and Kawut, SM},
title = {Associations between shortened telomeres and rheumatoid arthritis-associated interstitial lung disease among U.S. Veterans.},
journal = {Respiratory medicine},
volume = {201},
number = {},
pages = {106943},
pmid = {35947933},
issn = {1532-3064},
support = {IK2 CX002203/CX/CSRD VA/United States ; I01 CX001703/CX/CSRD VA/United States ; IK6 BX004600/BX/BLRD VA/United States ; T32 HL007891/HL/NHLBI NIH HHS/United States ; K24 HL103844/HL/NHLBI NIH HHS/United States ; U54 GM115458/GM/NIGMS NIH HHS/United States ; I01 BX004660/BX/BLRD VA/United States ; },
mesh = {*Arthritis, Rheumatoid/complications/epidemiology/genetics ; Cross-Sectional Studies ; Female ; Humans ; *Lung Diseases, Interstitial/etiology/genetics ; Male ; Telomere/genetics ; Telomere Shortening ; *Veterans ; },
abstract = {BACKGROUND: Shortened telomeres are associated with several different subtypes of interstitial lung disease (ILD), although studies of telomere length and ILD in rheumatoid arthritis (RA) are lacking.<br><br>METHODS: Within the Veterans Affairs Rheumatoid Arthritis (VARA) registry, we performed cross-sectional and case-control studies of prevalent and incident ILD, respectively. We randomly selected a subset of RA patients with ILD and individually matched them to RA patients without ILD according to age, sex, and VARA enrollment date. Telomere length was measured on peripheral blood leukocytes collected at registry enrollment using quantitative PCR (T/S ratio). Short telomeres were defined as a T/S ratio in the lowest 10th percentile of the cohort.<br><br>RESULTS: Our cross-sectional study cohort was comprised of 54 RA-ILD patients and 92 RA-non-ILD patients. T/S ratios significantly differed between patients with and without prevalent ILD (1.56 [IQR 1.30, 1.78] vs. 1.96 [IQR 1.65, 2.27], p <&#xa0;0.001). Similarly, prevalence of ILD was significantly higher in patients with short vs. normal-length telomeres (73.3% vs. 32.8%, p&#xa0;=&#xa0;0.002). Short telomeres were independently associated with an increased odds of prevalent ILD compared to normal-length telomeres (adjusted OR 6.60, 95% CI 1.78-24.51, p&#xa0;=&#xa0;0.005). In our case-control analysis, comprised of 22 incident RA-ILD cases and 36 RA-non-ILD controls, short telomeres were not associated with incident RA-ILD (adjusted OR 0.90, 95% CI 0.06-13.4, p&#xa0;=&#xa0;0.94).<br><br>CONCLUSION: Short telomeres were strongly associated with prevalent but not incident ILD among patients with RA. Additional studies are needed to better understand telomere length dynamics among RA patients with and without ILD.},
}
@article {pmid35947641,
year = {2022},
author = {Macha, SJ and Koneru, B and Burrow, TA and Zhu, C and Savitski, D and Rahman, RL and Ronaghan, CA and Nance, J and McCoy, K and Eslinger, C and Reynolds, CP},
title = {Alternative Lengthening of Telomeres in Cancer Confers a Vulnerability to Reactivation of p53 Function.},
journal = {Cancer research},
volume = {82},
number = {18},
pages = {3345-3358},
pmid = {35947641},
issn = {1538-7445},
support = {R01 CA264949/CA/NCI NIH HHS/United States ; R01 CA217251/CA/NCI NIH HHS/United States ; R01 CA221957/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; *Carcinoma ; Humans ; Irinotecan ; Mice ; *Neuroblastoma/drug therapy/genetics ; *Sarcoma/genetics ; *Telomerase/genetics ; Telomere/genetics/metabolism ; Telomere Homeostasis/genetics ; Tumor Suppressor Protein p53/genetics/metabolism ; },
abstract = {UNLABELLED: A subset of cancers across multiple histologies with predominantly poor outcomes use the alternative lengthening of telomeres (ALT) mechanism to maintain telomere length, which can be identified with robust biomarkers. ALT has been reported to be prevalent in high-risk neuroblastoma and certain sarcomas, and ALT cancers are a major clinical challenge that lack targeted therapeutic approaches. Here, we found ALT in a variety of pediatric and adult cancer histologies, including carcinomas. Patient-derived ALT cancer cell lines from neuroblastomas, sarcomas, and carcinomas were hypersensitive to the p53 reactivator eprenetapopt (APR-246) relative to telomerase-positive (TA+) models. Constitutive telomere damage signaling in ALT cells activated ataxia-telangiectasia mutated (ATM) kinase to phosphorylate p53, which resulted in selective ALT sensitivity to APR-246. Treatment with APR-246 combined with irinotecan achieved complete responses in mice xenografted with ALT neuroblastoma, rhabdomyosarcoma, and breast cancer and delayed tumor growth in ALT colon cancer xenografts, while the combination had limited efficacy in TA+ tumor models. A large number of adult and pediatric cancers present with the ALT phenotype, which confers a uniquely high sensitivity to reactivation of p53. These data support clinical evaluation of a combinatorial approach using APR-246 and irinotecan in ALT patients with cancer.<br><br>SIGNIFICANCE: This work demonstrates that constitutive activation of ATM in chemotherapy-refractory ALT cancer cells renders them hypersensitive to reactivation of p53 function by APR-246, indicating a potential strategy to overcome therapeutic resistance.},
}
@article {pmid35947638,
year = {2022},
author = {Lemaître, JF and Gaillard, JM and Gilson, E},
title = {Telomeres as a sentinel of population decline in the context of global warming.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {119},
number = {35},
pages = {e2211349119},
pmid = {35947638},
issn = {1091-6490},
mesh = {Animals ; *Extinction, Biological ; *Global Warming ; *Lizards/genetics ; Population Dynamics ; Sentinel Species ; *Telomere/genetics ; },
}
@article {pmid35942347,
year = {2022},
author = {Zhang, JM and Zou, L},
title = {Protocol to stimulate and delineate alternative lengthening of telomeres in human U2OS cells.},
journal = {STAR protocols},
volume = {3},
number = {3},
pages = {101594},
pmid = {35942347},
issn = {2666-1667},
mesh = {DNA Replication ; Humans ; *Telomerase/genetics ; *Telomere/genetics ; },
abstract = {Alternative lengthening of telomeres (ALT) is a telomerase-independent but recombination-dependent pathway that maintains telomeres. Here, we describe a protocol to stimulate the formation of ALT-associated PML bodies (APBs) and ALT activity by tethering PML-IV to telomeres in human U2OS cells. Through immunofluorescence, in situ hybridization, and microscopy, we analyze dynamics of telomere clustering, visualize recruitment of DNA repair proteins to APBs, and measure telomere DNA synthesis during ALT. This protocol provides a unique approach to delineate the ALT pathway. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2021).},
}
@article {pmid35939862,
year = {2022},
author = {Woo, JMP and Parks, CG and Hyde, EE and Auer, PL and Simanek, AM and Konkel, RH and Taylor, J and Sandler, DP and Meier, HCS},
title = {Early life trauma and adult leucocyte telomere length.},
journal = {Psychoneuroendocrinology},
volume = {144},
number = {},
pages = {105876},
pmid = {35939862},
issn = {1873-3360},
support = {Z01 ES044005/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Adult ; Child ; Female ; Humans ; Leukocytes ; Life Change Events ; Prospective Studies ; *Telomere ; *Telomere Shortening ; },
abstract = {BACKGROUND: Telomere length, a biomarker of cell division and cellular aging, has been associated with multiple chronic disease endpoints. Experienced trauma over the life course may contribute to telomere shortening via mechanisms of stress embodiment. However, it is unclear how patterns of co-occurring trauma during sensitive periods (e.g., early life) throughout the life course may influence telomere shortening. We examine the relationship between co-occurring early life trauma on adult telomere length and the extent to which adulthood trauma, socioeconomic position, and health and lifestyle factors may mediate this relationship.<br><br>METHODS: We use data from a sample of participants in the Sister Study (N&#xa0;=&#xa0;740, analytic sample: n&#xa0;=&#xa0;602), a prospective cohort of U.S. self-identified females aged 35-74 years at enrollment (2003-2009) for whom leukocyte telomere length was measured in baseline blood samples. Participants reported their experience of 20 different types of trauma, from which we identified patterns of co-occurring early life trauma (before age 18) using latent class analysis. We estimated the direct and indirect effects of early life trauma on leukocyte telomere length using structural equation modeling, allowing for mediating adult pathways.<br><br>RESULTS: Approximately 47 % of participants reported early life trauma. High early life trauma was associated with shorter telomere length compared to low early life trauma (&#x3b2;&#xa0;=&#xa0;-0.11; 95 % CI: -0.22, -0.004) after adjusting for age and childhood socioeconomic position. The inverse association between early life trauma and adult leukocyte telomere length was largely attributable to the direct effect of early life trauma on telomere length (&#x3b2;&#xa0;=&#xa0;-0.12; 95 %CI: -0.23, -0.01). Mediating indirect pathways via adult trauma, socioeconomic position, and health metrics did not substantively contribute the overall association.<br><br>CONCLUSIONS: These findings highlight the role of patterns of co-occurring early life trauma on shortened telomere length independent of adult pathways.},
}
@article {pmid35939680,
year = {2022},
author = {Dupoué, A and Blaimont, P and Angelier, F and Ribout, C and Rozen-Rechels, D and Richard, M and Miles, D and de Villemereuil, P and Rutschmann, A and Badiane, A and Aubret, F and Lourdais, O and Meylan, S and Cote, J and Clobert, J and Le Galliard, JF},
title = {Lizards from warm and declining populations are born with extremely short telomeres.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {119},
number = {33},
pages = {e2201371119},
pmid = {35939680},
issn = {1091-6490},
mesh = {*Aging/genetics ; Animals ; *Extinction, Biological ; Female ; *Global Warming ; *Lizards/genetics ; Population Dynamics ; Reproduction ; Risk ; *Telomere/genetics ; *Telomere Shortening ; },
abstract = {Aging is the price to pay for acquiring and processing energy through cellular activity and life history productivity. Climate warming can exacerbate the inherent pace of aging, as illustrated by a faster erosion of protective telomere DNA sequences. This biomarker integrates individual pace of life and parental effects through the germline, but whether intra- and intergenerational telomere dynamics underlies population trends remains an open question. Here, we investigated the covariation between life history, telomere length (TL), and extinction risk among three age classes in a cold-adapted ectotherm (Zootoca vivipara) facing warming-induced extirpations in its distribution limits. TL followed the same threshold relationships with population extinction risk at birth, maturity, and adulthood, suggesting intergenerational accumulation of accelerated aging rate in declining populations. In dwindling populations, most neonates inherited already short telomeres, suggesting they were born physiologically old and unlikely to reach recruitment. At adulthood, TL further explained females' reproductive performance, switching from an index of individual quality in stable populations to a biomarker of reproductive costs in those close to extirpation. We compiled these results to propose the aging loop hypothesis and conceptualize how climate-driven telomere shortening in ectotherms may accumulate across generations and generate tipping points before local extirpation.},
}
@article {pmid35939618,
year = {2022},
author = {Quque, M and Ferreira, C and Sosa, S and Schull, Q and Zahn, S and Criscuolo, F and Bleu, J and Viblanc, VA},
title = {Cascading Effects of Conspecific Aggression on Oxidative Status and Telomere Length in Zebra Finches.},
journal = {Physiological and biochemical zoology : PBZ},
volume = {95},
number = {5},
pages = {416-429},
doi = {10.1086/721252},
pmid = {35939618},
issn = {1537-5293},
mesh = {Aggression/physiology ; Animals ; *Finches/physiology ; Oxidative Stress ; *Physical Conditioning, Animal ; Telomere ; },
abstract = {Living in social groups may exacerbate interindividual competition for territory, food, and mates, leading to stress and possible health consequences. Unfavorable social contexts have been shown to elevate glucocorticoid levels (often used as biomarkers of individual stress), but the downstream consequences of socially stressful environments are rarely explored. Our study experimentally tests the mechanistic links between social aggression, oxidative stress, and somatic maintenance in captive zebra finches (Taeniopygia guttata). Over 64 d, we measured the effects of aggression (received or emitted) on the individual oxidative status, body condition, and changes in relative telomere length (rTL) of birds living in high- and low-social-density conditions. Using path analyses, we found that birds living at high social density increased their aggressive behavior. Birds receiving the highest number of aggressions exhibited the strongest activation of antioxidant defenses and highest plasmatic levels of reactive oxygen metabolites. In turn, this prevented birds from maintaining or restoring telomere length between the beginning and the end of the experiment. Received aggression also had a direct negative effect on changes in rTL, unrelated to oxidative stress. In contrast, emitted aggression had no significant effect on individual oxidative stress or changes in rTL. Body condition did not appear to affect the physiological response to aggression or oxidative stress. At low density, we found trends that were similar to those at high density but nonsignificant. Our study sheds light on the causal chain linking the social environment and aggressive behavior to individual oxidative stress and telomere length. The long-term consequences of socially induced stress on fitness remain to be characterized.},
}
@article {pmid35938805,
year = {2022},
author = {Moazamian, A and Gharagozloo, P and Aitken, RJ and Drevet, JR},
title = {OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: Sperm telomeres, oxidative stress, and infertility.},
journal = {Reproduction (Cambridge, England)},
volume = {164},
number = {6},
pages = {F125-F133},
doi = {10.1530/REP-22-0189},
pmid = {35938805},
issn = {1741-7899},
mesh = {Male ; Humans ; Reactive Oxygen Species/metabolism ; *Antioxidants/metabolism ; *Infertility, Male/metabolism ; Semen/metabolism ; Spermatozoa/metabolism ; Oxidative Stress ; Telomere/metabolism ; Guanine/metabolism ; DNA ; Deoxyguanosine/metabolism ; Biomarkers/metabolism ; },
abstract = {IN BRIEF: Oxidative stress is recognized as an underlying driving factor of both telomere dysfunction and human subfertility/infertility. This review briefly reassesses telomere integrity as a fertility biomarker before proposing a novel, mechanistic rationale for the role of oxidative stress in the seemingly paradoxical lengthening of sperm telomeres with aging.<br><br>ABSTRACT: The maintenance of redox balance in the male reproductive tract is critical to sperm health and function. Physiological levels of reactive oxygen species (ROS) promote sperm capacitation, while excess ROS exposure, or depleted antioxidant defenses, yields a state of oxidative stress which disrupts their fertilizing capacity and DNA structural integrity. The guanine moiety is the most readily oxidized of the four DNA bases and gets converted to the mutagenic lesion 8-hydroxy-deoxyguanosine (8-OHdG). Numerous studies have also confirmed oxidative stress as a driving factor behind accelerated telomere shortening and dysfunction. Although a clear consensus has not been reached, clinical studies also appear to associate telomere integrity with fertility outcomes in the assisted reproductive technology setting. Intriguingly, while sperm cellular and molecular characteristics make them more susceptible to oxidative insult than any other cell type, they are also the only cell type in which telomere lengthening accompanies aging. This article focuses on the oxidative stress response pathways to propose a mechanism for the explanation of this apparent paradox.},
}
@article {pmid35934479,
year = {2022},
author = {Paul, T and Myong, S},
title = {Helicase mediated vectorial folding of telomere G-quadruplex.},
journal = {Methods in enzymology},
volume = {672},
number = {},
pages = {283-297},
doi = {10.1016/bs.mie.2022.03.065},
pmid = {35934479},
issn = {1557-7988},
support = {R01 GM115631/GM/NIGMS NIH HHS/United States ; R01 CA207342/CA/NCI NIH HHS/United States ; RF1 NS113636/NS/NINDS NIH HHS/United States ; },
mesh = {DNA Helicases/metabolism ; *G-Quadruplexes ; Shelterin Complex ; *Telomerase/metabolism ; Telomere/genetics/metabolism ; Telomere-Binding Proteins/chemistry/genetics/metabolism ; },
abstract = {The G-rich single-stranded telomere overhang can self-fold into G-quadruplex (G4) structure both in vivo and in vitro. In somatic cells, telomeres shorten progressively due to the end-replication. In stem cells, however, telomeres are replenished by a special enzyme, telomerase which synthesizes single-stranded telomere overhang. The active extension by the telomerase releases G-rich overhang segmentally in 5' to 3' direction as the overhang folds into G4 structure after successive elongation. To replicate such vectorial G4 folding process, we employed a superhelicase, Rep-X to release the G-rich sequence gradually. Using single-molecule assay we demonstrated that the folded conformation achieved by the vectorial folding is inherently different from the post-folding where the entire overhang is allowed to fold at once. In addition, the vectorially folded overhangs are less stable and more accessible to a complementary C-rich strand and the telomere binding protein, POT1 compared to the post-folded state. The higher accessibility may have implications for the facile loading of shelterin proteins after DNA replication.},
}
@article {pmid35934145,
year = {2022},
author = {Lai, X and Yuan, Y and Liu, M and Xiao, Y and Ma, L and Guo, W and Fang, Q and Yang, H and Hou, J and Yang, L and Yang, H and He, MA and Guo, H and Zhang, X},
title = {Individual and joint associations of co-exposure to multiple plasma metals with telomere length among middle-aged and older Chinese in the Dongfeng-Tongji cohort.},
journal = {Environmental research},
volume = {214},
number = {Pt 3},
pages = {114031},
doi = {10.1016/j.envres.2022.114031},
pmid = {35934145},
issn = {1096-0953},
mesh = {Aged ; *Aluminum ; Bayes Theorem ; China ; Humans ; *Manganese ; Middle Aged ; Telomere ; Vanadium/toxicity ; },
abstract = {Studies on associations of metals with leucocyte telomere length (LTL) were mainly limited to several most common toxic metals and single-metal effect, but the impact of other common metals and especially the overall joint associations and interactions of metal mixture with LTL are largely unknown. We included 15 plasma metals and LTL among 4906 participants from Dongfeng-Tongji cohort. Multivariable linear regression was used to estimate associations of individual metals with LTL. We also applied Bayesian kernel machine regression (BKMR) and quantile g-computation regression (Q-g) to evaluate the overall association and interactions, and identified the major contributors as well as the potential modifications by major characteristics. Multivariable linear regression found vanadium, copper, arsenic, aluminum and nickel were negatively associated with LTL, and a 2-fold change was related to 1.9%-5.1% shorter LTL; while manganese and zinc showed 3.7% and 4.0% longer LTL (all P < 0.05) in multiple-metal models. BKMR confirmed above metals and revealed a linearly inverse joint association between 15 metals and LTL. Q-g regression further indicated each quantile increase in mixture was associated with 5.2% shorter LTL (95% CI: -8.1%, -2.3%). Furthermore, manganese counteracted against aluminum and vanadium respectively (Pint<0.05). In addition, associations of vanadium, aluminum and metal mixture with LTL were more prominent in overweight participants. Our results are among the first to provide a new comprehensive view of metal mixture exposure on LTL attrition in the general population, including identifying the major components, metals interactions and the overall effects.},
}
@article {pmid35933575,
year = {2022},
author = {Fan, Y and Guo, Y and Zhong, J and Chi, H and Zhao, X and Su, P and Gao, J and Chen, M},
title = {The association between visceral adiposity index and leukocyte telomere length in adults: results from National Health and Nutrition Examination Survey.},
journal = {Aging clinical and experimental research},
volume = {34},
number = {9},
pages = {2177-2183},
pmid = {35933575},
issn = {1720-8319},
support = {81870310//National Natural Science Foundation of China/ ; 81200194//National Natural Science Foundation of China/ ; },
mesh = {*Adiposity/genetics ; Humans ; *Leukocytes ; Nutrition Surveys ; Obesity, Abdominal ; Risk Factors ; Telomere/genetics ; United States ; },
abstract = {BACKGROUND: Leukocyte telomere length (LTL) is a robust marker of biological aging, which is associated with obesity. Recently, the visceral adiposity index (VAI) has been proposed as an indicator of adipose distribution and function.<br><br>OBJECTIVE: To evaluated the association between VAI and LTL in adult Americans.<br><br>METHODS: There were 3193 participants in U.S. National Health and Nutrition Examination Surveys (1999-2002) included in this analysis. LTL was measured using quantitative PCR (qPCR) and expressed as telomere to single-gene copy ratio (T/S ratio). We performed multiple logistic regression models to explore the association between VAI and LTL by adjusting for potential confounders.<br><br>RESULTS: Among all participants, VAI was associated with the shorter LTL (&#x3b2;: &#x2009;-&#x2009;14.81, 95% CI &#x2009;-&#x2009;22.28 to &#x2009;-&#x2009;7.34, p&#x2009;<&#x2009;0.001). There were significant differences of LTL in VAI tertiles (p&#x2009;<&#x2009;0.001). Participants in the higher VAI tertile had the shorter LTL (1.26&#x2009;&#x2264;&#x2009;VAI&#x2009;<&#x2009;2.46: &#x3b2;&#x2009;=&#x2009;&#x2009;-&#x2009;130.16, 95% CI [&#x2009;-&#x2009;183.44, &#x2009;-&#x2009;76.87]; VAI&#x2009;&#x2265;&#x2009;2.46: &#x3b2;&#x2009;=&#x2009;&#x2009;-&#x2009;216.12, 95% CI [&#x2009;-&#x2009;216.12, &#x2009;-&#x2009;81.42], p for trend:&#x2009;<&#x2009;0.001) comparing with the lower VAI tertile. We also found a non-linear relationship between VAI and LTL. VAI was negatively correlated with LTL when VAI was less than 2.84.<br><br>CONCLUSIONS: The present study demonstrates that VAI is independently associated with telomere length. A higher VAI is associated with shorter LTL. The results suggest that VAI may provide prediction for LTL and account for accelerating the biological aging.},
}
@article {pmid35932977,
year = {2022},
author = {Zheng, Y and Zhang, N and Wang, Y and Wang, F and Li, G and Tse, G and Liu, T},
title = {Association between leucocyte telomere length and the risk of atrial fibrillation: An updated systematic review and meta-analysis.},
journal = {Ageing research reviews},
volume = {81},
number = {},
pages = {101707},
doi = {10.1016/j.arr.2022.101707},
pmid = {35932977},
issn = {1872-9649},
mesh = {*Atrial Fibrillation/epidemiology/genetics ; *Biological Products ; Female ; Humans ; Leukocytes ; Male ; Telomere/genetics ; Telomere Shortening ; },
abstract = {BACKGROUND AND AIMS: Advancing age is the most important risk factor of atrial fibrillation (AF). The shortening of telomere length is a biomarker of biologic aging. There is an increasing body of evidence that leucocyte telomere length (LTL) is associated with the risk of AF development. However, the results in these studies were controversial. The current systematic review and meta-analysis was conducted to examine the role of LTL in predicting the incidence of AF.<br><br>METHODS AND RESULTS: Observational studies reporting the association between LTL and the risk of AF were retrieved through 25th June, 2022 from PubMed and Embase. A total of twelve studies including 18,293 patients were included in the present analysis. Leucocyte telomere shortening was found to be an independent predictor of AF as a continuous variable in both univariate [OR:2.14; 95%CI(1.48,3.10); P&#xa0;<&#xa0;0.0001] and multivariate analyses [OR:1.41;95%CI(1.11,1.79); P&#xa0;=&#xa0;0.005], as well as categorical variable in multivariate analysis [OR:1.53; 95%CI(1.04,2.27); P&#xa0;=&#xa0;0.03]. Furthermore, leucocyte telomere shortening was significantly associated with recurrent AF [OR:4.32;95%CI(2.42,7.69); P&#xa0;<&#xa0;0.00001] but not new-onset AF [OR:1.14; 95%CI(0.90,1.45); P&#xa0;=&#xa0;0.29]. Leucocyte telomere shortening was also associated with an increased risk of persistent AF [OR:14.73;95%CI (3.16,68.67); P&#xa0;=&#xa0;0.0006] and paroxysmal AF [OR:2.74;95%CI(1.45,5.18); P&#xa0;=&#xa0;0.002]. Besides, LTL was an independent predictor for progression from paroxysmal AF to persistent AF [OR:3.2;95%CI(1.66,6.18); P&#xa0;=&#xa0;0.0005]. Differences between males [OR:1.99; 95%CI(1.29,3.06); P&#xa0;=&#xa0;0.002] and females [OR:0.86; 95%CI (0.29,2.56);P&#xa0;=&#xa0;0.79] were observed.<br><br>CONCLUSIONS: Leucocyte telomere shortening predicts the risk of AF, especially recurrent AF. The predictive value is more prominent in males than in females. Shortening in LTL can predict the progression from paroxysmal to persistent AF.},
}
@article {pmid35932478,
year = {2022},
author = {Chik, HYJ and Sparks, AM and Schroeder, J and Dugdale, HL},
title = {A meta-analysis on the heritability of vertebrate telomere length.},
journal = {Journal of evolutionary biology},
volume = {35},
number = {10},
pages = {1283-1295},
pmid = {35932478},
issn = {1420-9101},
support = {NE/P011284/1//Natural Environment Research Council/ ; },
mesh = {Animals ; Phylogeny ; *Telomere/genetics ; *Vertebrates/genetics ; },
abstract = {Telomere dynamics are linked with both cellular and organismal senescence, and life history, individual quality and health. Telomere dynamics, particularly telomere length, have therefore garnered much research interest in evolutionary biology. To examine the evolution of telomere length, it is important to quantify its heritability, the proportion of total variation explained by additive genetic effects. Many studies have quantified telomere length heritability, but estimates are varied, and no general conclusion has been drawn. Additionally, it is unclear whether biological and methodological factors influence telomere length heritability estimates. We present the first meta-analysis of telomere length heritability, using 104 estimates from 43 studies over 18 vertebrate species. We calculated an overall mean heritability and examined how estimates varied by study, phylogeny, species-specific ecology, environmental setting, age at sampling, laboratory methods, statistical methods, sex and repeated measurements. Overall heritability was moderate (44.9%, 95% CI: 25.2-64.7%), and there was considerable heterogeneity in heritability estimates, in particular among studies and estimates. Laboratory method influenced heritability estimates, with in-gel hybridization TRF yielding higher heritabilities than qPCR and Southern blot TRF. There was also an effect from statistical method, with twin-based and SNP-based estimates lower than correlation-based or pedigree-based estimates. Our results highlight an overall heritable basis of telomere length, and we recommend future research on a wider range of taxa, and the use of variance-partitioning methods with relatedness or SNP data over correlation methods to minimize heritability estimation bias.},
}
@article {pmid35931358,
year = {2022},
author = {Guo, Z and Zou, K and Li, X and Duan, X and Fan, Y and Liu, X and Wang, W},
title = {Relationship between miRNAs polymorphisms and peripheral blood leukocyte DNA telomere length in coke oven workers: A cross-sectional study.},
journal = {Environmental toxicology and pharmacology},
volume = {95},
number = {},
pages = {103941},
doi = {10.1016/j.etap.2022.103941},
pmid = {35931358},
issn = {1872-7077},
mesh = {*Coke/analysis ; Cross-Sectional Studies ; DNA ; DNA Damage ; Humans ; Leukocytes ; *MicroRNAs/genetics ; *Occupational Exposure/adverse effects/analysis ; *Polycyclic Aromatic Hydrocarbons/analysis ; Telomere/genetics ; },
abstract = {OBJECTIVE: The purpose of this study was to investigate the factors affecting telomere length (TL) in coke oven workers by analyzing the interaction between miRNAs polymorphisms and coke oven emissions (COEs) exposure.<br><br>METHODS: A total of 544 coke oven workers and 238 healthy controls were recruited. Peripheral blood was collected from the subjects, genomic DNA was extracted, leukocyte TL was detected by real-time quantitative polymerase chain reaction, and fifteen polymorphisms of eight miRNAs were genotyped by flight mass spectrometry.<br><br>RESULTS: Statistical analysis showed that the peripheral blood DNA TL in the exposure group was shorter than that in the control group (P&#xa0;<&#xa0;0.001). Generalized linear model found that COEs-exposure [&#x3b2; (95%CI) =&#xa0;-0.427 (-0.556, -0.299), P&#xa0;<&#xa0;0.001], genotype CC+CT for miR-612 rs1144925 [&#x3b2; (95%CI) =&#xa0;-0.367 (-0.630, -0.104), P&#xa0;=&#xa0;0.006], and the interaction of miR-181B1 rs12039395 TT genotype and COEs-exposure [&#x3b2; (95% CI) =&#xa0;0.564 (0.108, 1.020), P&#xa0;=&#xa0;0.015] were associated with the shortened TL.<br><br>CONCLUSION: COEs-exposure and miR-612 rs1144925 TT could promote telomere shortening in coke oven workers. The interaction of miR-181B1 rs12039395 TT genotype and COEs-exposure could protect telomere. This provides clues for further mechanistic studies between miRNA and telomere damage.},
}
@article {pmid35930283,
year = {2022},
author = {Martens, DS and Sleurs, H and Dockx, Y and Rasking, L and Plusquin, M and Nawrot, TS},
title = {Association of Newborn Telomere Length With Blood Pressure in Childhood.},
journal = {JAMA network open},
volume = {5},
number = {8},
pages = {e2225521},
pmid = {35930283},
issn = {2574-3805},
mesh = {Adult ; Blood Pressure ; Child ; Child, Preschool ; Cohort Studies ; Female ; Humans ; *Hypertension ; Infant, Newborn ; Male ; *Placenta ; Pregnancy ; Prospective Studies ; Telomere ; United States ; },
abstract = {IMPORTANCE: Adult telomere length (TL) is a biological marker of aging associated with vascular health. TL at birth is associated with later life TL and may contain early biological information of later life cardiovascular health and disease.<br><br>OBJECTIVE: To evaluate whether newborn TL is associated with early life blood pressure differences in childhood.<br><br>This cohort study was part of the ENVIRONAGE (Environmental Influence on Aging in Early Life) study, a birth cohort of Belgian mother-child pairs with recruitment at birth and a median follow-up of 4.5 years conducted between October 2014 and July 2021. Participants included for analysis provided full data for evaluation at follow-up visit. Data analysis was conducted between August and September 2021.<br><br>MAIN OUTCOMES AND MEASURES: Cord blood and placental average relative TL were measured at birth using quantitative polymerase chain reaction (qPCR). Systolic, diastolic, and mean arterial pressure (MAP) were evaluated at follow-up. High childhood blood pressure (standardized for child age, sex, and height) was defined following the 2017 American Academy of Pediatrics guidelines. Multivariable adjusted linear and logistic regression models were used to associate newborn TL and blood pressure indicators in childhood.<br><br>RESULTS: This study included 485 newborn children (52.8% girls) with a mean (SD) age of 4.6 (0.4) years at the follow-up visit. Newborn TL was associated with lower blood pressure in childhood. A 1-IQR increase in cord blood TL was associated with a -1.54 mm Hg (95% CI, -2.36 to -0.72 mm Hg) lower diastolic blood pressure and -1.18 mm Hg (95% CI, -1.89 to -0.46 mm Hg) lower MAP. No association was observed with systolic blood pressure. Furthermore, a 1-IQR increase in cord blood TL was associated with lower odds of having high blood pressure at the age of 4 to 6 years (adjusted OR, 0.72; 95% CI, 0.53 to 0.98). In placenta, a 1-IQR increase in TL was associated with a -0.96 mm Hg (95% CI, -1.72 to -0.21 mm Hg) lower diastolic, -0.88 mm Hg (95% CI, -1.54 to -0.22 mm Hg) lower MAP, and a lower adjusted OR of 0.69 (95% CI, 0.52 to 0.92) for having a high blood pressure in childhood.<br><br>CONCLUSIONS AND RELEVANCE: In this prospective birth cohort study, variation in early life blood pressure at school-age was associated with TL at birth. Cardiovascular health may to some extent be programmed at birth, and these results suggest that TL entails a biological mechanism in this programming.},
}
@article {pmid35929966,
year = {2022},
author = {Tummala, H and Walne, A and Dokal, I},
title = {The biology and management of dyskeratosis congenita and related disorders of telomeres.},
journal = {Expert review of hematology},
volume = {15},
number = {8},
pages = {685-696},
doi = {10.1080/17474086.2022.2108784},
pmid = {35929966},
issn = {1747-4094},
support = {14032/LLR_/Blood Cancer UK/United Kingdom ; MR/P018440/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Biology ; Danazol ; *Dyskeratosis Congenita/diagnosis/genetics/therapy ; Humans ; Mutation ; Oxymetholone ; *Telomerase ; Telomere/genetics/metabolism ; },
abstract = {BACKGROUND: Dyskeratosis congenita (DC) is a multisystem syndrome characterized by mucocutaneous abnormalities, bone marrow failure, and predisposition to cancer. Studies over the last 25 years have led to the identification of 18 disease genes. These have a principal role in telomere maintenance, and patients usually have very short/abnormal telomeres. The advances have also led to the unification of DC with a number of other diseases, now collectively referred to as the telomeropathies or telomere biology disorders.<br><br>WHAT IS COVERED: Clinical features, genetics, and biology of the different subtypes. Expert view on diagnosis, treatment of the hematological complications and future.<br><br>EXPERT VIEW: As these are very pleotropic disorders affecting multiple organs, a high index of suspicion is necessary to make the diagnosis. Telomere length measurement and genetic analysis of the disease genes have become useful diagnostic tools. Although hematological defects can respond to danazol/oxymetholone, the only current curative treatment for these is hematopoietic stem cell transplantation (HSCT) using fludarabine-based conditioning protocols. New therapies are needed where danazol/oxymetholone is ineffective and HSCT is not feasible.},
}
@article {pmid35923948,
year = {2022},
author = {Pepke, ML and Kvalnes, T and Ranke, PS and Araya-Ajoy, YG and Wright, J and Sæther, BE and Jensen, H and Ringsby, TH},
title = {Causes and consequences of variation in early-life telomere length in a bird metapopulation.},
journal = {Ecology and evolution},
volume = {12},
number = {8},
pages = {e9144},
pmid = {35923948},
issn = {2045-7758},
abstract = {Environmental conditions during early-life development can have lasting effects shaping individual heterogeneity in fitness and fitness-related traits. The length of telomeres, the DNA sequences protecting chromosome ends, may be affected by early-life conditions, and telomere length (TL) has been associated with individual performance within some wild animal populations. Thus, knowledge of the mechanisms that generate variation in TL, and the relationship between TL and fitness, is important in understanding the role of telomeres in ecology and life-history evolution. Here, we investigate how environmental conditions and morphological traits are associated with early-life blood TL and if TL predicts natal dispersal probability or components of fitness in 2746 wild house sparrow (Passer domesticus) nestlings from two populations sampled across 20 years (1994-2013). We retrieved weather data and we monitored population fluctuations, individual survival, and reproductive output using field observations and genetic pedigrees. We found a negative effect of population density on TL, but only in one of the populations. There was a curvilinear association between TL and the maximum daily North Atlantic Oscillation index during incubation, suggesting that there are optimal weather conditions that result in the longest TL. Dispersers tended to have shorter telomeres than non-dispersers. TL did not predict survival, but we found a tendency for individuals with short telomeres to have higher annual reproductive success. Our study showed how early-life TL is shaped by effects of growth, weather conditions, and population density, supporting that environmental stressors negatively affect TL in wild populations. In addition, shorter telomeres may be associated with a faster pace-of-life, as individuals with higher dispersal rates and annual reproduction tended to have shorter early-life TL.},
}
@article {pmid35920280,
year = {2022},
author = {Borges, G and Criqui, M and Harrington, L},
title = {Tieing together loose ends: telomere instability in cancer and aging.},
journal = {Molecular oncology},
volume = {16},
number = {18},
pages = {3380-3396},
pmid = {35920280},
issn = {1878-0261},
support = {148936//CIHR/Canada ; },
mesh = {Aging/genetics ; Cellular Senescence/genetics ; Genomic Instability ; Humans ; *Neoplasms/genetics ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {Telomere maintenance is essential for maintaining genome integrity in both normal and cancer cells. Without functional telomeres, chromosomes lose their protective structure and undergo fusion and breakage events that drive further genome instability, including cell arrest or death. One means by which this loss can be overcome in stem cells and cancer cells is via re-addition of G-rich telomeric repeats by the telomerase reverse transcriptase (TERT). During aging of somatic tissues, however, insufficient telomerase expression leads to a proliferative arrest called replicative senescence, which is triggered when telomeres reach a critically short threshold that induces a DNA damage response. Cancer cells express telomerase but do not entirely escape telomere instability as they often possess short telomeres; hence there is often selection for genetic alterations in the TERT promoter that result in increased telomerase expression. In this review, we discuss our current understanding of the consequences of telomere instability in cancer and aging, and outline the opportunities and challenges that lie ahead in exploiting the reliance of cells on telomere maintenance for preserving genome stability.},
}
@article {pmid35920237,
year = {2023},
author = {Gurvich, C and Thomas, N and Hudaib, AR and Van Rheenen, TE and Thomas, EHX and Tan, EJ and Neill, E and Carruthers, SP and Sumner, PJ and Romano-Silva, M and Bozaoglu, K and Kulkarni, J and Rossell, SL},
title = {The relationship between cognitive clusters and telomere length in bipolar-schizophrenia spectrum disorders.},
journal = {Psychological medicine},
volume = {53},
number = {11},
pages = {5119-5126},
doi = {10.1017/S0033291722002148},
pmid = {35920237},
issn = {1469-8978},
mesh = {Humans ; *Bipolar Disorder/genetics/complications ; *Schizophrenia/genetics/complications ; *Psychotic Disorders/genetics/complications ; Cognition ; Telomere ; },
abstract = {BACKGROUND: Schizophrenia and bipolar disorder are complex mental illnesses that are associated with cognitive deficits. There is considerable cognitive heterogeneity that exists within both disorders. Studies that cluster schizophrenia and bipolar patients into subgroups based on their cognitive profile increasingly demonstrate that, relative to healthy controls, there is a severely compromised subgroup and a relatively intact subgroup. There is emerging evidence that telomere shortening, a marker of cellular senescence, may be associated with cognitive impairments. The aim of this study was to explore the relationship between cognitive subgroups in bipolar-schizophrenia spectrum disorders and telomere length against a healthy control sample.<br><br>METHODS: Participants included a transdiagnostic group diagnosed with bipolar, schizophrenia or schizoaffective disorder (n = 73) and healthy controls (n = 113). Cognitive clusters within the transdiagnostic patient group, were determined using K-means cluster analysis based on current cognitive functioning (MATRICS Consensus Cognitive Battery scores). Telomere length was determined using quantitative PCRs genomic DNA extracted from whole blood. Emergent clusters were then compared to the healthy control group on telomere length.<br><br>RESULTS: Two clusters emerged within the patient group that were deemed to reflect a relatively intact cognitive group and a cognitively impaired subgroup. Telomere length was significantly shorter in the severely impaired cognitive subgroup compared to the healthy control group.<br><br>CONCLUSIONS: This study replicates previous findings of transdiagnostic cognitive subgroups and associates shorter telomere length with the severely impaired cognitive subgroup. These findings support emerging literature associating cognitive impairments in psychiatric disorders to accelerated cellular aging as indexed by telomere length.},
}
@article {pmid35920029,
year = {2022},
author = {Vernasco, BJ and Watts, HE},
title = {Telomere length predicts timing and intensity of migratory behaviour in a nomadic songbird.},
journal = {Biology letters},
volume = {18},
number = {8},
pages = {20220176},
pmid = {35920029},
issn = {1744-957X},
mesh = {Animal Migration/physiology ; Animals ; *Finches ; Psychomotor Agitation ; Seasons ; *Songbirds/genetics ; Telomere ; Telomere Shortening ; },
abstract = {Our understanding of state-dependent behaviour is reliant on identifying physiological indicators of condition. Telomeres are of growing interest for understanding behaviour as they capture differences in biological state and residual lifespan. To understand the significance of variable telomere lengths for behaviour and test two hypotheses describing the relationship between telomeres and behaviour (i.e. the causation and the selective adoption hypotheses), we assessed if telomere lengths are longitudinally repeatable traits related to spring migratory behaviour in captive pine siskins (Spinus pinus). Pine siskins are nomadic songbirds that exhibit highly flexible, facultative migrations, including a period of spring nomadism. Captive individuals exhibit extensive variation in spring migratory restlessness and are an excellent system for mechanistic studies of migratory behaviour. Telomere lengths were found to be significantly repeatable (R = 0.51) over four months, and shorter pre-migratory telomeres were associated with earlier and more intense expression of spring nocturnal migratory restlessness. Telomere dynamics did not vary with migratory behaviour. Our results describe the relationship between telomere length and migratory behaviour and provide support for the selective adoption hypothesis. More broadly, we provide a novel perspective on the significance of variable telomere lengths for animal behaviour and the timing of annual cycle events.},
}
@article {pmid35918419,
year = {2022},
author = {Huang, MY and Madhani, HD},
title = {Telomere transposon takeover in Cryptococcus.},
journal = {Nature microbiology},
volume = {7},
number = {8},
pages = {1108-1109},
pmid = {35918419},
issn = {2058-5276},
support = {T32 AI060537/AI/NIAID NIH HHS/United States ; },
mesh = {Automation ; *Cryptococcus/genetics ; Telomere ; },
}
@article {pmid35914599,
year = {2022},
author = {Passos, JDC and Felisbino, K and Laureano, HA and Guiloski, IC},
title = {Occupational exposure to pesticides and its association with telomere length - A systematic review and meta-analysis.},
journal = {The Science of the total environment},
volume = {849},
number = {},
pages = {157715},
doi = {10.1016/j.scitotenv.2022.157715},
pmid = {35914599},
issn = {1879-1026},
mesh = {Biomarkers ; Humans ; *Occupational Exposure/adverse effects/analysis ; *Pesticides/toxicity ; Telomere ; },
abstract = {BACKGROUND: Telomere length is a common biomarker for the cumulative effect of environmental factors on aging-related diseases, therefore an association has been hypothesized between occupational exposure to pesticides and shorter telomere length.<br><br>OBJECTIVE: This study is a systematic review and meta-analysis aiming to examine the association between telomere length and occupational exposure to pesticides.<br><br>METHODS: We systematically searched in SciELO, PubMed, Scopus, Embase, Cochrane, Lilacs, Science Direct, and Web of Science databases for all observational studies containing measurements of telomere length on groups occupationally exposed to pesticides. Data were synthesized through qualitative synthesis and meta-analysis. We estimated the associations between exposed and non-exposed groups by using the natural log of the response ratio (lnRR). Heterogeneity was quantified using the Cochran Q test and I[2] statistics.<br><br>RESULTS: Six studies were included in the qualitative synthesis and meta-analysis, with a total of 480 participants exposed to pesticides. The time of exposure evaluated 391 participants that had a range of 5 to >30 years of occupational exposure. Most studies presented shorter telomere length in the occupationally exposed group. From the six studies included in the meta-analysis, three presented telomere length measurement as a single copy gene (T/S), and three presented telomere length measurement as base pairs (bp). The statistical analysis pooled estimates (log ratio of means) of the telomere length in both measurements (T/S and bp) showed a shortening of telomere length in the exposed group when compared with the non-exposed (control) group. Two of six studies reported longer telomere length in the group exposed to pesticides.<br><br>DISCUSSION: Our findings suggest an association between occupational exposure to pesticides and shorter telomere length. However, we found a small number of studies to include in our meta-analysis, being required more high-quality studies to strengthen our findings and conclusions.},
}
@article {pmid35912187,
year = {2022},
author = {Mushtaq, I and Bhat, GR and Rah, B and Besina, S and Zahoor, S and Wani, MA and Shah, MA and Bashir, S and Farooq, M and Rather, RA and Afroze, D},
title = {Telomere Attrition With Concomitant hTERT Overexpression Involved in the Progression of Gastric Cancer May Have Prognostic and Clinical Implications in High-Risk Population Group From North India.},
journal = {Frontiers in oncology},
volume = {12},
number = {},
pages = {919351},
pmid = {35912187},
issn = {2234-943X},
abstract = {Genetic instabilities exacerbated by the dysfunction of telomeres can lead to the development of cancer. Nearly 90% of all human malignancies are linked with telomere dysregulation and overexpression of telomerase, an enzyme that catalyzes the synthesis of telomeric DNA repeats at the ends of chromosomes. The burden of gastric cancer continues to inflict a deterring impact on the global health scenario, accounting for over one million new cases in 2020. The disease is asymptomatic in its early stages of progression, which is attributed to the poor prognosis and overall surge in mortality rate worldwide. Exploiting telomere physiology can provide extensive mechanistic insight into telomere-associated gastric cancer progression and its use as a target in a variety of therapeutic interventions. In this study, we aimed to evaluate the clinical implications of c-Myc, human telomerase reverse transcriptase (hTERT) expression, and telomere length in patients with gastric cancer. A total of 57 gastric cancer cases and adjacent controls were included in the study. RT-PCR and immunohistochemistry were used to assess the expression levels of c-Myc and hTERT. The relative telomere length was measured by MMQPCR using the Cawthon method. Our results indicated that the shorter telomere and increased hTERT expression were associated with gastric cancer progression. The study also highlighted the role of short telomeres and increased expression of hTERT in gastric cancer progression and its association with various etiological risk factors, transcriptional activators, and overall survival among the ethnic Kashmiri population of North India.},
}
@article {pmid35911771,
year = {2022},
author = {Liao, Q and He, J and Tian, FF and Bi, FF and Huang, K},
title = {A causal relationship between leukocyte telomere length and multiple sclerosis: A Mendelian randomization study.},
journal = {Frontiers in immunology},
volume = {13},
number = {},
pages = {922922},
pmid = {35911771},
issn = {1664-3224},
mesh = {Genome-Wide Association Study ; Humans ; Leukocytes ; *Mendelian Randomization Analysis ; *Multiple Sclerosis/genetics ; Polymorphism, Single Nucleotide ; Telomere/genetics ; },
abstract = {OBJECTIVES: Multiple sclerosis (MS) is a chronic inflammatory autoimmune and degenerative disorder of the central nervous system. Telomeres are protective structures located at the ends of linear chromosomes, and leukocyte telomere length (LTL) is closely connected with cell aging and senescence. However, the relationship between LTL and the risk of MS remains unknown.<br><br>METHODS: We performed a two-sample Mendelian randomization (MR) to evaluate whether LTL was causally associated with MS risk.<br><br>RESULTS: In our MR analysis, 12 LTL-related variants were selected as valid instrumental variables, and a causal relationship between LTL and MS was suggested. The risk of MS nearly doubled as the genetically predicted LTL shortened by one standard deviation (SD) under the inverse variance weighted (IVW) fixed effect model (odds ratio (OR) = 2.00, 95% confidence interval (CI): 1.52-2.62, p = 6.01e-07). Similar estimated causal effects were also observed under different MR models. The MR-Egger regression test did not reveal any evidence of directional pleiotropy (intercept = -0.005, stand error (SE) = 0.03, p = 0.87). The Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) analysis also indicated no directional pleiotropy or outliers for any LTL-related IVs (p-global test = 0.13). In addition, a leave-one-out sensitivity analysis showed similar findings, which further emphasized the validity and stability of the causal relationship.<br><br>CONCLUSIONS: Our results suggest a potential causal effect of LTL on the risk of MS. Genetically predicted shorter LTL could increase the risk of MS in the European population. LTL should be noted and emphasized in the pathogenesis and treatment of MS.},
}
@article {pmid35910300,
year = {2022},
author = {Aviv, A},
title = {The telomere tumult: meaning and metrics in population studies.},
journal = {The lancet. Healthy longevity},
volume = {3},
number = {5},
pages = {e308-e309},
pmid = {35910300},
issn = {2666-7568},
support = {R01 HL134840/HL/NHLBI NIH HHS/United States ; U01 AG066529/AG/NIA NIH HHS/United States ; },
mesh = {*Benchmarking ; *Biological Specimen Banks ; Health Behavior ; Leukocytes ; Telomere/genetics ; United Kingdom ; },
}
@article {pmid35903361,
year = {2022},
author = {Son, N and Cui, Y and Xi, W},
title = {Association Between Telomere Length and Skin Cancer and Aging: A Mendelian Randomization Analysis.},
journal = {Frontiers in genetics},
volume = {13},
number = {},
pages = {931785},
pmid = {35903361},
issn = {1664-8021},
abstract = {Background: Telomere shortening is a hallmark of cellular senescence. However, telomere length (TL)-related cellular senescence has varying effects in different cancers, resulting in a paradoxical relationship between senescence and cancer. Therefore, we used observational epidemiological studies to investigate the association between TL and skin cancer and aging, and to explore whether such a paradoxical relationship exists in skin tissue. Methods: This study employed two-sample Mendelian randomization (MR) to analyze the causal relationship between TL and skin cancer [melanoma and non-melanoma skin cancers (NMSCs)] and aging. We studied single nucleotide polymorphisms (SNPs) obtained from pooled data belonging to genome-wide association studies (GWAS) in the literature and biobanks. Quality control was performed using pleiotropy, heterogeneity, and sensitivity analyses. Results: We used five algorithms to analyze the causal relationship between TL and skin aging, melanoma, and NMSCs, and obtained consistent results. TL shortening reduced NMSC and melanoma susceptibility risk with specific odds ratios (ORs) of 1.0344 [95% confidence interval (CI): 1.0168-1.0524, p = 0.01] and 1.0127 (95% CI: 1.0046-1.0209, p = 6.36E-07), respectively. Conversely, TL shortening was validated to increase the odds of skin aging (OR = 0.96, 95% CI: 0.9332-0.9956, p = 0.03). Moreover, the MR-Egger, maximum likelihood, and inverse variance weighted (IVW) methods found significant heterogeneity among instrumental variable (IV) estimates (identified as MR-Egger skin aging Q = 76.72, p = 1.36E-04; melanoma Q = 97.10, p = 1.62E-07; NMSCsQ = 82.02, p = 1.90E-05). The leave-one-out analysis also showed that the SNP sensitivity was robust to each result. Conclusion: This study found that TL shortening may promote skin aging development and reduce the risk of cutaneous melanoma and NMSCs. The results provide a reference for future research on the causal relationship between skin aging and cancer in clinical practice.},
}
@article {pmid35902621,
year = {2022},
author = {Bae, JS and Lee, JW and Joung, JG and Cho, HW and Ju, HY and Yoo, KH and Koo, HH and Sung, KW},
title = {Clinical significance of germline telomere length and associated genetic factors in patients with neuroblastoma.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {12954},
pmid = {35902621},
issn = {2045-2322},
mesh = {Genetic Markers ; *Genome-Wide Association Study ; Humans ; Leukocytes, Mononuclear ; *Neuroblastoma/genetics ; Polymorphism, Single Nucleotide ; Telomere/genetics ; },
abstract = {Studies investigating the relationship between germline telomere length and the clinical characteristics of tumors are very limited. This study evaluated the relationship between germline telomere length and the clinical characteristics of neuroblastoma. In addition, a genome-wide association study (GWAS) was performed to investigate the genetic factors associated with germline telomere length. The germline telomere length of peripheral blood mononuclear cells from 186 patients with neuroblastoma was measured by quantitative polymerase chain reaction. The association between germline telomere length and clinical characteristics, including long-term survival, was investigated. For the GWAS, genotyping was performed with a high-density bead chip (Illumina, San Diego, CA, USA). After strict quality-control checks of the samples, an association analysis was conducted. The result showed that longer germline telomeres were significantly associated with longer event-free survival (P = 0.032). To identify significantly assocated genetic markers for germline telomere length, genome wide association analysis was performed. As a result, several single nucleotide polymorphisms located in HIVEP3, LRRTM4, ADGRV1, RAB30, and CHRNA4 genes were discovered. During gene-based analysis (VEGAS2 tool), the CNTN4 gene had the most significant association with germline telomere length (P = 1.0E-06). During gene ontology analysis, susceptible genes associated with germline telomere length were mainly distributed in neurite morphogenesis and neuron development. A longer germline telomere length is associated with favorable prognostic factors at diagnosis and eventually better event-free survival in patients with neuroblastoma. In addition, the GWAS demonstrated that genetic markers and genes related to germline telomere length are associated with neurite morphogenesis and neuron development. Further research with larger cohorts of patients and functional investigations are needed.},
}
@article {pmid35897312,
year = {2022},
author = {Liu, Y and Liu, S and Xin, J and Qian, P and Guo, S and Xu, X and Wang, D and Yang, L},
title = {Telomere Length and Hearing Loss: A Two-Sample Mendelian Randomization.},
journal = {International journal of environmental research and public health},
volume = {19},
number = {15},
pages = {},
pmid = {35897312},
issn = {1660-4601},
mesh = {Genome-Wide Association Study ; *Hearing Loss/epidemiology/genetics ; Humans ; *Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Telomere ; },
abstract = {BACKGROUND: Observational studies have suggested that there may be an association between telomere length (TL) and hearing loss (HL). However, inferring causality from observational studies is subject to residual confounding effects, reverse causation, and bias. This study adopted a two-sample Mendelian randomization (MR) approach to evaluate the causal relationship between TL and increased risk of HL.<br><br>METHODS: A total of 16 single nucleotide polymorphisms (SNPs) associated with TL were identified from a genome-wide association study (GWAS) meta-analysis of 78,592 European participants and applied to our modeling as instrumental variables. Summary-level data for hearing loss (HL), age-related hearing loss (ARHL), and noise-induced hearing loss (NIHL) were obtained from the recent largest available GWAS and five MR analyses were used to investigate the potential causal association of genetically predicted TL with increased risk for HL, including the inverse-variance-weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode. In addition, sensitivity analysis, pleiotropy, and heterogeneity tests were also used to evaluate the robustness of our findings.<br><br>RESULTS: There was no causal association between genetically predicted TL and HL or its subtypes (by the IVW method, HL: odds ratio (OR) = 1.216, p = 0.382; ARHL: OR = 0.934, p = 0.928; NIHL: OR = 1.003, p = 0.776). Although heterogenous sites rs2736176, rs3219104, rs8105767, and rs2302588 were excluded for NIHL, the second MR analysis was consistent with the first analysis (OR = 1.003, p = 0.572).<br><br>CONCLUSION: There was no clear causal relationship between shorter TLs and increased risk of HL or its subtypes in this dataset.},
}
@article {pmid35892638,
year = {2022},
author = {Scarabino, D and Veneziano, L and Fiore, A and Nethisinghe, S and Mantuano, E and Garcia-Moreno, H and Bellucci, G and Solanky, N and Morello, M and Zanni, G and Corbo, RM and Giunti, P},
title = {Leukocyte Telomere Length Variability as a Potential Biomarker in Patients with PolyQ Diseases.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {11},
number = {8},
pages = {},
pmid = {35892638},
issn = {2076-3921},
abstract = {SCA1, SCA2, and SCA3 are the most common forms of SCAs among the polyglutamine disorders, which include Huntington's Disease (HD). We investigated the relationship between leukocyte telomere length (LTL) and the phenotype of SCA1, SCA2, and SCA3, comparing them with HD. The results showed that LTL was significantly reduced in SCA1 and SCA3 patients, while LTL was significantly longer in SCA2 patients. A significant negative relationship between LTL and age was observed in SCA1 but not in SCA2 subjects. LTL of SCA3 patients depend on both patient's age and disease duration. The number of CAG repeats did not affect LTL in the three SCAs. Since LTL is considered an indirect marker of an inflammatory response and oxidative damage, our data suggest that in SCA1 inflammation is present already at an early stage of disease similar to in HD, while in SCA3 inflammation and impaired antioxidative processes are associated with disease progression. Interestingly, in SCA2, contrary to SCA1 and SCA3, the length of leukocyte telomeres does not reduce with age. We have observed that SCAs and HD show a differing behavior in LTL for each subtype, which could constitute relevant biomarkers if confirmed in larger cohorts and longitudinal studies.},
}
@article {pmid35887427,
year = {2022},
author = {Quenu, M and Treindl, AD and Lee, K and Takemoto, D and Thünen, T and Ashrafi, S and Winter, D and Ganley, ARD and Leuchtmann, A and Young, CA and Cox, MP},
title = {Telomere-to-Telomere Genome Sequences across a Single Genus Reveal Highly Variable Chromosome Rearrangement Rates but Absolute Stasis of Chromosome Number.},
journal = {Journal of fungi (Basel, Switzerland)},
volume = {8},
number = {7},
pages = {},
pmid = {35887427},
issn = {2309-608X},
abstract = {Genome rearrangements in filamentous fungi are prevalent but little is known about the modalities of their evolution, in part because few complete genomes are available within a single genus. To address this, we have generated and compared 15 complete telomere-to-telomere genomes across the phylogeny of a single genus of filamentous fungi, Epichloë. We find that the striking distinction between gene-rich and repeat-rich regions previously reported for isolated species is ubiquitous across the Epichloë genus. We built a species phylogeny from single-copy gene orthologs to provide a comparative framing to study chromosome composition and structural change through evolutionary time. All Epichloë genomes have exactly seven nuclear chromosomes, but despite this conserved ploidy, analyses reveal low synteny and substantial rearrangement of gene content across the genus. These rearrangements are highly lineage-dependent, with most occurring over short evolutionary distances, with long periods of structural stasis. Quantification of chromosomal rearrangements shows they are uncorrelated with numbers of substitutions and evolutionary distances, suggesting that different modes of evolution are acting to create nucleotide and chromosome-scale changes.},
}
@article {pmid35886017,
year = {2022},
author = {Zimnitskaya, OV and Petrova, MM and Lareva, NV and Cherniaeva, MS and Al-Zamil, M and Ivanova, AE and Shnayder, NA},
title = {Leukocyte Telomere Length as a Molecular Biomarker of Coronary Heart Disease.},
journal = {Genes},
volume = {13},
number = {7},
pages = {},
pmid = {35886017},
issn = {2073-4425},
mesh = {Adult ; Biomarkers ; *Cardiovascular Diseases ; *Coronary Disease/genetics ; Humans ; Leukocytes ; Telomere/genetics ; },
abstract = {BACKGROUND: This work is a review of preclinical and clinical studies of the role of telomeres and telomerase in the development and progression of coronary heart disease (CHD).<br><br>MATERIALS AND METHODS: A search for full-text publications (articles, reviews, meta-analyses, Cochrane reviews, and clinical cases) in English and Russian was carried out in the databases PubMed, Oxford University Press, Scopus, Web of Science, Springer, and E-library electronic library using keywords and their combinations. The search depth is 11 years (2010-2021).<br><br>RESULTS: The review suggests that the relative leukocyte telomere length (LTL) is associated with the development of socially significant and widespread cardiovascular diseases such as CHD and essential hypertension. At the same time, the interests of researchers are mainly focused on the study of the relative LTL in CHD.<br><br>CONCLUSIONS: Despite the scientific and clinical significance of the analyzed studies of the relative length of human LTL as a biological marker of cardiovascular diseases, their implementation in real clinical practice is difficult due to differences in the design and methodology of the analyzed studies, as well as differences in the samples by gender, age, race, and ethnicity. The authors believe that clinical studies of the role of the relative length of leukocyte telomeres in adult patients with coronary heart disease are the most promising and require large multicenter studies with a unified design and methodology.},
}
@article {pmid35884905,
year = {2022},
author = {Lauriola, A and Davalli, P and Marverti, G and Caporali, A and Mai, S and D'Arca, D},
title = {Telomere Dysfunction Is Associated with Altered DNA Organization in Trichoplein/Tchp/Mitostatin (TpMs) Depleted Cells.},
journal = {Biomedicines},
volume = {10},
number = {7},
pages = {},
pmid = {35884905},
issn = {2227-9059},
support = {MR/R014353/1/MRC_/Medical Research Council/United Kingdom ; MR/R014353/1//MRC-IMPC Pump Priming Award/ ; },
abstract = {Recently, we highlighted a novel role for the protein Trichoplein/TCHP/Mitostatin (TpMs), both as mitotic checkpoint regulator and guardian of chromosomal stability. TpMs-depleted cells show numerical and structural chromosome alterations that lead to genomic instability. This condition is a major driving force in malignant transformation as it allows for the cells acquiring new functional capabilities to proliferate and disseminate. Here, the effect of TpMs depletion was investigated in different TpMs-depleted cell lines by means of 3D imaging and 3D Structured illumination Microscopy. We show that TpMs depletion causes alterations in the 3D architecture of telomeres in colon cancer HCT116 cells. These findings are consistent with chromosome alterations that lead to genomic instability. Furthermore, TpMs depletion changes the spatial arrangement of chromosomes and other nuclear components. Modified nuclear architecture and organization potentially induce variations that precede the onset of genomic instability and are considered as markers of malignant transformation. Our present observations connect the tumor suppression ability of TpMs with its novel functions in maintaining the proper chromosomal segregation as well as the proper telomere and nuclear architecture. Further investigations will investigate the connection between alterations in telomeres and nuclear architecture with the progression of human tumors with the aim of developing personalized therapeutic interventions.},
}
@article {pmid35880304,
year = {2022},
author = {Curtis, EM and Codd, V and Nelson, C and D'Angelo, S and Wang, Q and Allara, E and Kaptoge, S and Matthews, PM and Tobias, JH and Danesh, J and Cooper, C and Samani, NJ and Harvey, NC},
title = {Telomere Length and Risk of Incident Fracture and Arthroplasty: Findings From UK Biobank.},
journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research},
volume = {37},
number = {10},
pages = {1997-2004},
pmid = {35880304},
issn = {1523-4681},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; 209233/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; MC_PC_15015/MRC_/Medical Research Council/United Kingdom ; MC_PC_21002/MRC_/Medical Research Council/United Kingdom ; MC_PC_21001/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MC_PC_21003/MRC_/Medical Research Council/United Kingdom ; MR/M012816/1/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; MC_PC_21022/MRC_/Medical Research Council/United Kingdom ; 201268/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /BHF_/British Heart Foundation/United Kingdom ; },
mesh = {Female ; Male ; Humans ; Middle Aged ; Hand Strength ; *Arthroplasty, Replacement, Hip ; Biological Specimen Banks ; *Arthroplasty, Replacement, Knee ; *Fractures, Bone/epidemiology/genetics ; Bone Density ; Telomere ; United Kingdom/epidemiology ; Risk Factors ; *Osteoporotic Fractures/epidemiology ; *Hip Fractures/epidemiology ; },
abstract = {We investigated independent associations between telomere length and risk of fracture and arthroplasty in UK Biobank participants. Leukocyte telomere length (LTL) was measured in baseline samples using a validated polymerase chain reaction (PCR) method. We used, in men and women separately, Cox proportional hazards models to calculate the hazard ratio (HR) for incident fracture (any, osteoporotic) or arthroplasty (hip or knee) over 1,186,410 person-years of follow-up. Covariates included age, white cell count, ethnicity, smoking, alcohol, physical activity, and menopause (women). In further analyses we adjusted for either estimated bone mineral density (eBMD) from heel quantitative ultrasound, handgrip strength, gait speed, total fat mass (bioimpedance), or blood biomarkers, all measured at baseline (2006-2010). We studied 59,500 women and 51,895 men, mean ± standard deviation (SD) age 56.4 ± 8.0 and 57.0 ± 8.3 years, respectively. During follow-up there were 5619 fractures; 5285 hip and 4261 knee arthroplasties. In confounder-adjusted models, longer LTL was associated with reduced risk of incident knee arthroplasty in both men (HR/SD 0.93; 95% confidence interval [CI], 0.88-0.97) and women (0.92; 95% CI, 0.88-0.96), and hip arthroplasty in men (0.91; 95% CI, 0.87-0.95), but not women (0.98; 95% CI, 0.94-1.01). Longer LTL was weakly associated with reduced risk of any incident fracture in women (HR/SD 0.96; 95% CI, 0.93-1.00) with less evidence in men (0.98; 95% CI, 0.93-1.02). Associations with incident outcomes were not materially altered by adjustment for heel eBMD, grip strength, gait speed, fat mass, or blood biomarker measures. In this, the largest study to date, longer LTL was associated with lower risk of incident knee or hip arthroplasty, but only weakly associated with lower risk of fracture. The relative risks were low at a population level, but our findings suggest that common factors acting on the myeloid and musculoskeletal systems might influence later life musculoskeletal outcomes. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).},
}
@article {pmid35879401,
year = {2022},
author = {Topiwala, A and Taschler, B and Ebmeier, KP and Smith, S and Zhou, H and Levey, DF and Codd, V and Samani, NJ and Gelernter, J and Nichols, TE and Burgess, S},
title = {Alcohol consumption and telomere length: Mendelian randomization clarifies alcohol's effects.},
journal = {Molecular psychiatry},
volume = {27},
number = {10},
pages = {4001-4008},
pmid = {35879401},
issn = {1476-5578},
support = {204623/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; RG/13/13/30194/BHF_/British Heart Foundation/United Kingdom ; UL1 TR001863/TR/NCATS NIH HHS/United States ; MR/K013351/1/MRC_/Medical Research Council/United Kingdom ; BRC-1215-20010/DH_/Department of Health/United Kingdom ; I01 CX001849/CX/CSRD VA/United States ; MC_UU_00002/7/MRC_/Medical Research Council/United Kingdom ; MR/M012816/1/MRC_/Medical Research Council/United Kingdom ; 216462/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; R21 CA252916/CA/NCI NIH HHS/United States ; CH/12/2/29428/BHF_/British Heart Foundation/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; G1001354/MRC_/Medical Research Council/United Kingdom ; BRC-1215-20014/DH_/Department of Health/United Kingdom ; 100309/Z/12/Z/WT_/Wellcome Trust/United Kingdom ; R01 EB026859/EB/NIBIB NIH HHS/United States ; RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; },
mesh = {Humans ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; Alcohol Drinking/genetics ; Ethanol ; Telomere/genetics ; },
abstract = {Alcohol's impact on telomere length, a proposed marker of biological aging, is unclear. We performed the largest observational study to date (in n = 245,354 UK Biobank participants) and compared findings with Mendelian randomization (MR) estimates. Two-sample MR used data from 472,174 participants in a recent genome-wide association study (GWAS) of telomere length. Genetic variants were selected on the basis of associations with alcohol consumption (n = 941,280) and alcohol use disorder (AUD) (n = 57,564 cases). Non-linear MR employed UK Biobank individual data. MR analyses suggested a causal relationship between alcohol traits, more strongly for AUD, and telomere length. Higher genetically-predicted AUD (inverse variance-weighted (IVW) β = -0.06, 95% confidence interval (CI): -0.10 to -0.02, p = 0.001) was associated with shorter telomere length. There was a weaker association with genetically-predicted alcoholic drinks weekly (IVW β = -0.07, CI: -0.14 to -0.01, p = 0.03). Results were consistent across methods and independent from smoking. Non-linear analyses indicated a potential threshold relationship between alcohol and telomere length. Our findings indicate that alcohol consumption may shorten telomere length. There are implications for age-related diseases.},
}
@article {pmid35878015,
year = {2022},
author = {Zhan, Y and Kang, X},
title = {Disentangling the Causal Effect of Telomere Length in Systemic Lupus Erythematosus Using Genetic Variants as Instruments.},
journal = {Arthritis &amp; rheumatology (Hoboken, N.J.)},
volume = {74},
number = {12},
pages = {1890-1892},
doi = {10.1002/art.42313},
pmid = {35878015},
issn = {2326-5205},
mesh = {Humans ; *Lupus Erythematosus, Systemic/genetics ; Telomere/genetics ; Causality ; },
}
@article {pmid35876482,
year = {2022},
author = {},
title = {Corrigendum to: TERT promoter C228T mutation in neural progenitors confers growth advantage following telomere shortening in vivo.},
journal = {Neuro-oncology},
volume = {24},
number = {11},
pages = {2008},
doi = {10.1093/neuonc/noac178},
pmid = {35876482},
issn = {1523-5866},
}
@article {pmid35872157,
year = {2022},
author = {Heaphy, CM and Singhi, AD},
title = {The diagnostic and prognostic utility of incorporating DAXX, ATRX, and alternative lengthening of telomeres to the evaluation of pancreatic neuroendocrine tumors.},
journal = {Human pathology},
volume = {129},
number = {},
pages = {11-20},
doi = {10.1016/j.humpath.2022.07.015},
pmid = {35872157},
issn = {1532-8392},
support = {R37 CA263622/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Adaptor Proteins, Signal Transducing/genetics/metabolism ; Biomarkers, Tumor/genetics ; Co-Repressor Proteins/metabolism ; In Situ Hybridization, Fluorescence ; Molecular Chaperones/metabolism ; *Neuroendocrine Tumors/diagnosis/genetics/pathology ; Nuclear Proteins/genetics/metabolism ; *Pancreatic Neoplasms/diagnosis/genetics/metabolism ; Prognosis ; *Telomere/pathology ; X-linked Nuclear Protein/genetics ; },
abstract = {Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and an ill-defined pathobiology. Although many PanNETs are indolent and remain stable for years, a subset may behave aggressively and metastasize widely. Thus, the increasing and frequent detection of PanNETs presents a treatment dilemma. Current prognostic systems are susceptible to interpretation errors, sampling issues, and do not accurately reflect the clinical behavior of these neoplasms. Hence, additional biomarkers are needed to improve the prognostic stratification of patients diagnosed with a PanNET. Recent studies have identified alterations in death domain-associated protein 6 (DAXX) and alpha-thalassemia/mental retardation X-linked (ATRX), as well as alternative lengthening of telomeres (ALT), as promising prognostic biomarkers. This review summarizes the identification, clinical utility, and specific nuances in testing for DAXX/ATRX by immunohistochemistry and ALT by telomere-specific fluorescence in situ hybridization in PanNETs. Furthermore, a discussion on diagnostic indications for DAXX, ATRX, and ALT status is provided to include the distinction between PanNETs and pancreatic neuroendocrine carcinomas (PanNECs), and determining pancreatic origin for metastatic neuroendocrine tumors in the setting of an unknown primary.},
}
@article {pmid35862346,
year = {2022},
author = {Nadri, P and Ansari-Mahyari, S and Jafarpour, F and Mahdavi, AH and Tanhaei Vash, N and Lachinani, L and Dormiani, K and Nasr-Esfahani, MH},
title = {Melatonin accelerates the developmental competence and telomere elongation in ovine SCNT embryos.},
journal = {PloS one},
volume = {17},
number = {7},
pages = {e0267598},
pmid = {35862346},
issn = {1932-6203},
mesh = {Animals ; Blastocyst/metabolism ; Culture Media/metabolism ; Embryonic Development/genetics ; *Melatonin/metabolism/pharmacology ; *Nuclear Transfer Techniques/veterinary ; RNA, Messenger/metabolism ; Sheep/genetics ; Telomere ; },
abstract = {SCNT embryos suffer from poor developmental competence (both in vitro and in vivo) due to various defects such as oxidative stress, incomplete epigenetic reprogramming, and flaws in telomere rejuvenation. It is very promising to ameliorate all these defects in SCNT embryos by supplementing the culture medium with a single compound. It has been demonstrated that melatonin, as a multitasking molecule, can improve the development of SCNT embryos, but its function during ovine SCNT embryos is unclear. We observed that supplementation of embryonic culture medium with 10 nM melatonin for 7 days accelerated the rate of blastocyst formation in ovine SCNT embryos. In addition, the quality of blastocysts increased in the melatonin-treated group compared with the SCNT control groups in terms of ICM, TE, total cell number, and mRNA expression of NANOG. Mechanistic studies in this study revealed that the melatonin-treated group had significantly lower ROS level, apoptotic cell ratio, and mRNA expression of CASPASE-3 and BAX/BCL2 ratio. In addition, melatonin promotes mitochondrial membrane potential and autophagy status (higher number of LC3B dots). Our results indicate that melatonin decreased the global level of 5mC and increased the level of H3K9ac in the treated blastocyst group compared with the blastocysts in the control group. More importantly, we demonstrated for the first time that melatonin treatment promoted telomere elongation in ovine SCNT embryos. This result offers the possibility of better development of ovine SCNT embryos after implantation. We concluded that melatonin can accelerate the reprogramming of telomere length in sheep SCNT embryos, in addition to its various beneficial effects such as increasing antioxidant capacity, reducing DNA damage, and improving the quality of derived blastocysts, all of which led to a higher in vitro development rate.},
}
@article {pmid35862118,
year = {2022},
author = {Brandt, M and Dörschmann, H and Khraisat, S and Knopp, T and Ringen, J and Kalinovic, S and Garlapati, V and Siemer, S and Molitor, M and Göbel, S and Stauber, R and Karbach, SH and Münzel, T and Daiber, A and Wenzel, P},
title = {Telomere Shortening in Hypertensive Heart Disease Depends on Oxidative DNA Damage and Predicts Impaired Recovery of Cardiac Function in Heart Failure.},
journal = {Hypertension (Dallas, Tex. : 1979)},
volume = {79},
number = {10},
pages = {2173-2184},
doi = {10.1161/HYPERTENSIONAHA.121.18935},
pmid = {35862118},
issn = {1524-4563},
mesh = {Animals ; DNA ; *Heart Failure ; *Hypertension ; Mice ; NADPH Oxidases/metabolism ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Superoxides/metabolism ; Telomere Shortening ; },
abstract = {BACKGROUND: Heart failure (HF) coincides with cardiomyocyte telomere shortening. Arterial hypertension is the most prominent risk factor for HF. Both HF and arterial hypertension are associated with dysregulation of the neurohormonal axis. How neurohormonal activation is linked to telomere shortening in the pathogenesis of HF is incompletely understood.<br><br>METHODS: Cardiomyocyte telomere length was assessed in a mouse model of hypertensive HF induced by excess neurohormonal activation (AngII [angiotensin II] infusion, high salt diet, and uninephrectomy), in AngII-stimulated cardiomyocytes and in endomyocardial biopsies from patients with HF. Superoxide production, expression of NOX2 (NADPH oxidase 2) and PRDX1 (peroxiredoxin 1) and HDAC6 (histone deacetylase 6) activity were assessed.<br><br>RESULTS: Telomere shortening occurred in vitro and in vivo, correlating with both left ventricular (LV) dilatation and LV systolic function impairment. Telomere shortening coincided with increased superoxide production, increased NOX2 expression, increased HDAC6 activity, loss of the telomere-specific antioxidant PRDX1, and increased oxidative DNA-damage. NOX2 knockout prevented PRDX1 depletion, DNA-damage and telomere shortening confirming this enzyme as a critical source of reactive oxygen species. Cotreatment with the NOX inhibitor apocynin ameliorated hypertensive HF and telomere shortening. Similarly, treatment with the HDAC6 inhibitor tubastatin A, which increases PRDX1 bioavailability, prevented telomere shortening in adult cardiomyocytes. To explore the clinical relevance of our findings, we examined endomyocardial biopsies from an all-comer population of patients with HF with reduced ejection fraction. Here, cardiomyocyte telomere length predicted the recovery of cardiac function.<br><br>CONCLUSIONS: Cardiomyocyte telomere shortening and oxidative damage in heart failure with reduced ejection fraction induced by excess neurohormonal activation depends on NOX2-derived superoxide and may help to stratify HF therapy.},
}
@article {pmid35861921,
year = {2022},
author = {Kayacık Günday, &#xd6; and Özdemir Erdoğan, M and Pehlivan, A and Yılmazer, M},
title = {The effect of metformin treatment on leukocyte telomere length in patients with polycystic ovary syndrome: a prospective case-control study.},
journal = {Journal of assisted reproduction and genetics},
volume = {39},
number = {9},
pages = {2153-2161},
pmid = {35861921},
issn = {1573-7330},
mesh = {Body Mass Index ; C-Reactive Protein/genetics/metabolism ; Case-Control Studies ; Female ; Humans ; Leukocytes/metabolism ; *Metformin/therapeutic use ; *Polycystic Ovary Syndrome/drug therapy/genetics ; Telomere/genetics ; },
abstract = {PURPOSE: The study aimed to investigate the effect of metformin treatment on leukocyte telomere length (LTL) and the relationship of LTL with C-reactive protein (CRP), homocysteine, albumin, complete blood count, and HOMA-IR values in patients with polycystic ovary syndrome (PCOS).<br><br>MATERIAL AND METHOD: A prospective case-control study consisting of 30 women with PCOS and 30 healthy women without PCOS was performed. The relationship between clinical and laboratory parameters and LTL was analyzed. PCOS patients were treated with metformin (850&#xa0;mg/day) for three months. Before treatment (BT) and after treatment (AT), each patient's LTL was evaluated and compared with the control group.<br><br>RESULTS: In the comparison between PCOS and control groups, the difference was significant for LTL, age, body mass index (BMI), and CRP (p&#x2009;=&#x2009;0.002; p&#x2009;<&#x2009;0.001; p&#x2009;=&#x2009;0.001; p&#x2009;=&#x2009;0.01, respectively). In PCOS patients, the difference between BT and AT, LTL was not statistically significant (BT: 6.06&#x2009;&#xb1;&#x2009;2.12; AT: 6.30&#x2009;&#xb1;&#x2009;1.93; p&#x2009;=&#x2009;0.623; 95% C.I:&#x2009;-&#x2009;1.22-0.74); however, the difference for weight was significant (BT: 83.78&#x2009;&#xb1;&#x2009;15.31; AT: 80.62&#x2009;&#xb1;&#x2009;15.40; p&#x2009;=&#x2009;0.02; 95% CI: 1.34-4.99). The logistic regression model established by BMI (group 1: 21-24, group 2: 24-29, group 3: 29-34, group 4:&#x2009;>&#x2009;34), age, and RDW, which predicted the PCOS group by affecting the LTL level, was statistically significant (p&#x2009;<&#x2009;0.001/PPV&#x2009;=&#x2009;96.3%; NPV&#x2009;=&#x2009;88.5%). Each unit reduction in telomere length increased women's probability of PCOS by 0.4 times (p&#x2009;=&#x2009;0.013; OR&#x2009;=&#x2009;0.419, 95% CI: 0.211-0.835).<br><br>CONCLUSION: Although statistically insignificant, LTL increased after metformin use in PCOS patients, and the mean weight loss reduction was statistically significant. Telomere shortening increased the likelihood of PCOS 0.4 times.},
}
@article {pmid35860550,
year = {2022},
author = {Lansdorp, P},
title = {Telomere Length Regulation.},
journal = {Frontiers in oncology},
volume = {12},
number = {},
pages = {943622},
pmid = {35860550},
issn = {2234-943X},
abstract = {The number of (TTAGGG)n repeats at the ends of chromosomes is highly variable between individual chromosomes, between different cells and between species. Progressive loss of telomere repeats limits the proliferation of pre-malignant human cells but also contributes to aging by inducing apoptosis and senescence in normal cells. Despite enormous progress in understanding distinct pathways that result in loss and gain of telomeric DNA in different cell types, many questions remain. Further studies are needed to delineate the role of damage to telomeric DNA, replication errors, chromatin structure, liquid-liquid phase transition, telomeric transcripts (TERRA) and secondary DNA structures such as guanine quadruplex structures, R-loops and T-loops in inducing gains and losses of telomere repeats in different cell types. Limitations of current telomere length measurements techniques and differences in telomere biology between species and different cell types complicate generalizations about the role of telomeres in aging and cancer. Here some of the factors regulating the telomere length in embryonic and adult cells in mammals are discussed from a mechanistic and evolutionary perspective.},
}
@article {pmid35858061,
year = {2022},
author = {Benowitz-Fredericks, ZM and Lacey, LM and Whelan, S and Will, AP and Hatch, SA and Kitaysky, AS},
title = {Telomere length correlates with physiological and behavioural responses of a long-lived seabird to an ecologically relevant challenge.},
journal = {Proceedings. Biological sciences},
volume = {289},
number = {1978},
pages = {20220139},
pmid = {35858061},
issn = {1471-2954},
mesh = {Animals ; *Charadriiformes/physiology ; *Corticosterone ; Food ; Male ; Reproduction/physiology ; Telomere ; },
abstract = {Determinants of individual variation in reallocation of limited resources towards self-maintenance versus reproduction are not well known. We tested the hypothesis that individual heterogeneity in long-term 'somatic state' (i) explains variation in endocrine and behavioural responses to environmental challenges, and (ii) is associated with variation in strategies for allocating to self-maintenance versus reproduction. We used relative telomere length as an indicator of somatic state and experimentally generated an abrupt short-term reduction of food availability (withdrawal of food supplementation) for free-living seabirds (black-legged kittiwakes, Rissa tridactyla). Incubating male kittiwakes responded to withdrawal by increasing circulating corticosterone and losing more weight compared to continuously supplemented controls. Males with longer telomeres increased time in directed travel regardless of treatment, while experiencing smaller increases in corticosterone. Males with longer telomeres fledged more chicks in the control group and tended to be more likely to return regardless of treatment. This study supports the hypothesis that somatic state can explain variation in short-term physiological and behavioural responses to challenges, and longer-term consequences for fitness. Male kittiwakes with longer telomeres appear to have prioritized investment in self over investment in offspring under challenging conditions.},
}
@article {pmid35854470,
year = {2022},
author = {Huang, D and Lin, S and He, J and Wang, Q and Zhan, Y},
title = {Association between COVID-19 and telomere length: A bidirectional Mendelian randomization study.},
journal = {Journal of medical virology},
volume = {94},
number = {11},
pages = {5345-5353},
pmid = {35854470},
issn = {1096-9071},
mesh = {*COVID-19/genetics ; Critical Illness ; *Genome-Wide Association Study ; Humans ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Telomere/genetics ; },
abstract = {Several traditional observational studies suggested an association between COVID-19 and leukocyte telomere length (LTL), a biomarker for biological age. However, whether there was a causal association between them remained unclear. We aimed to investigate whether genetically predicted COVID-19 is related to the risk of LTL, and vice versa. We performed bidirectional Mendelian randomization (MR) study using summary statistics from the genome-wide association studies of critically ill COVID-19 (n = 1 388 342) and LTL (n = 472 174) of European ancestry. The random-effects inverse-variance weighted estimation method was applied as the primary method with several other estimators as complementary methods. Using six single-nucleotide polymorphisms (SNPs) of genome-wide significance as instrumental variables for critically ill COVID-19, we did not find a significant association of COVID-19 on LTL (β = 0.0075, 95% confidence interval [CI]: -0.018 to 0.021, p = 0.733). Likewise, using 97 SNPs of genome-wide significance as instrumental variables for LTL, we did not find a significant association of LTL on COVID-19 (odds ratio = 1.00, 95% CI: 0.79-1.28, p = 0.973). Comparable results were obtained using MR-Egger regression, weighted median, and weighted mode approaches. We did not find evidence to support a causal association between COVID-19 and LTL in either direction.},
}
@article {pmid35853584,
year = {2022},
author = {Hawks, RM and Kahn, LG and Fang, W and Keefe, D and Mehta-Lee, SS and Brubaker, S and Trasande, L},
title = {Prenatal phthalate exposure and placental telomere length.},
journal = {American journal of obstetrics &amp; gynecology MFM},
volume = {4},
number = {6},
pages = {100694},
pmid = {35853584},
issn = {2589-9333},
support = {R00 ES030403/ES/NIEHS NIH HHS/United States ; },
mesh = {Pregnancy ; Humans ; Female ; *Placenta ; *Phthalic Acids/toxicity ; Telomere/genetics ; },
}
@article {pmid35852986,
year = {2022},
author = {Chang, TR and Long, X and Shastry, S and Parks, JW and Stone, MD},
title = {Single-Molecule Mechanical Analysis of Strand Invasion in Human Telomere DNA.},
journal = {Biochemistry},
volume = {61},
number = {15},
pages = {1554-1560},
pmid = {35852986},
issn = {1520-4995},
support = {R01 GM095850/GM/NIGMS NIH HHS/United States ; },
mesh = {DNA/chemistry ; DNA Replication ; *DNA, Single-Stranded ; *G-Quadruplexes ; Guanine ; Humans ; Telomere/genetics ; },
abstract = {Telomeres are essential chromosome end capping structures that safeguard the genome from dangerous DNA processing events. DNA strand invasion occurs during vital transactions at telomeres, including telomere length maintenance by the alternative lengthening of telomeres (ALT) pathway. During telomeric strand invasion, a single-stranded guanine-rich (G-rich) DNA invades at a complementary duplex telomere repeat sequence, forming a displacement loop (D-loop) in which the displaced DNA consists of the same G-rich sequence as the invading single-stranded DNA. Single-stranded G-rich telomeric DNA readily folds into stable, compact, structures called G-quadruplexes (GQs) in vitro and is anticipated to form within the context of a D-loop; however, evidence supporting this hypothesis is lacking. Here, we report a magnetic tweezers assay that permits the controlled formation of telomeric D-loops (TDLs) within uninterrupted duplex human telomere DNA molecules of physiologically relevant lengths. Our results are consistent with a model wherein the displaced single-stranded DNA of a TDL fold into a GQ. This study provides new insight into telomere structure and establishes a framework for the development of novel therapeutics designed to target GQs at telomeres in cancer cells.},
}
@article {pmid35841174,
year = {2022},
author = {Grigoryan, OR and Frolova, TM and Mikheev, RK and Sheremetyeva, EV and Absatarova, YS and Uzhegova, ZA and Andreeva, EN and Mokrysheva, NG},
title = {[The dual role of the menopausal hormonal therapy as the enhancer of pleiotropic telomere rejuvenation and the silencer of cellular aging (literature review)].},
journal = {Problemy endokrinologii},
volume = {68},
number = {3},
pages = {105-112},
pmid = {35841174},
issn = {2308-1430},
mesh = {Cellular Senescence/genetics ; Female ; Humans ; Menopause ; *Quality of Life ; *Rejuvenation ; Telomere/genetics ; },
abstract = {Present worldwide healthcare researches prove that female patients are more sensitive to the population aging. Menopause or climacteria (climax) - is not as ageing itself, but a physiological unstoppable process. The main task for a physician is to improve life quality for female despite of ageing problems. Menopausal hormone therapy (MHT) due to the estrogen component has an anti-inflammatory, antioxidant effect and promotes the expression of telomerase, which together changes the homeostasis and integrity of telomeres. The use of MHT for five years or more can not only significantly change the quality of life, but also increase its duration. Literature search was carried out in national (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases in Russian and English. The priority was free access to the full text of articles. The choice of sources was prioritized for the period from 2019 to 2021. However, taking into account the insufficient knowledge of the chosen topic, the choice of sources dates back to 1989.},
}
@article {pmid35838223,
year = {2022},
author = {Daios, S and Anogeianaki, A and Kaiafa, G and Kontana, A and Veneti, S and Gogou, C and Karlafti, E and Pilalas, D and Kanellos, I and Savopoulos, C},
title = {Telomere Length as a Marker of Biological Aging: A Critical Review of Recent Literature.},
journal = {Current medicinal chemistry},
volume = {29},
number = {34},
pages = {5478-5495},
doi = {10.2174/0929867329666220713123750},
pmid = {35838223},
issn = {1875-533X},
mesh = {Aging/genetics/metabolism ; Biomarkers ; *Cardiovascular Diseases/genetics ; *Heart Diseases ; Humans ; *Stroke ; Telomere/genetics ; },
abstract = {INTRODUCTION: Aging is characterized as a syndrome of deleterious, progressive, universal, and irreversible function changes affecting every structural and functional aspect of the organism and accompanied by a generalized increase in mortality. Although a substantial number of candidates for biomarkers of aging have been proposed, none has been validated or universally accepted. Human telomeres constitute hexameric repetitive DNA sequence nucleoprotein complexes that cap chromosome ends, regulating gene expression and modulating stress-related pathways. Telomere length (TL) shortening is observed both in cellular senescence and advanced age, leading to the investigation of TL as a biomarker for aging and a risk factor indicator for the development and progression of the most common age-related diseases.<br><br>OBJECTIVE: The present review underlines the connection between TL and the pathophysiology of the diseases associated with telomere attrition.<br><br>METHODS: We performed a structured search of the PubMed database for peer-reviewed research of the literature regarding leukocyte TL and cardiovascular diseases (CVD), more specifically stroke and heart disease, and focused on the relevant articles published during the last 5 years. We also applied Hill's criteria of causation to strengthen this association.<br><br>RESULTS: We analyzed the recent literature regarding TL length, stroke, and CVD. Although approximately one-third of the available studies support the connection, the results of different studies seem to be rather conflicting as a result of different study designs, divergent methods of TL determination, small study samples, and patient population heterogeneity. After applying Hill's criteria, we can observe that the literature conforms to them weakly, with chronology being the only Hill criterion of causality that probably cannot be contested.<br><br>CONCLUSION: The present review attempted to examine the purported relation between leukocyte TL and age-related diseases such as CVD and more specific stroke and heart disease in view of the best established, comprehensive, medical and epidemiological criteria that have characterized the focused recent relevant research. Although several recommendations have been made that may contribute significantly to the field, a call for novel technical approaches and studies is mandatory to further elucidate the possible association.},
}
@article {pmid35836303,
year = {2022},
author = {Heaphy, CM and Joshu, CE and Barber, JR and Davis, C and Lu, J and Zarinshenas, R and Giovannucci, E and Mucci, LA and Stampfer, MJ and Han, M and De Marzo, AM and Lotan, TL and Platz, EA and Meeker, AK},
title = {The prostate tissue-based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy.},
journal = {The journal of pathology. Clinical research},
volume = {8},
number = {5},
pages = {481-491},
pmid = {35836303},
issn = {2056-4538},
support = {P50 CA058236/CA/NCI NIH HHS/United States ; P30 CA006973/CA/NCI NIH HHS/United States ; U01 CA167552/CA/NCI NIH HHS/United States ; P30 CA006516/CA/NCI NIH HHS/United States ; P50 CA090381/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Male ; Prognosis ; *Prostate/pathology/surgery ; Prostatectomy/methods ; *Prostatic Neoplasms/pathology/surgery ; Risk Factors ; Telomere/pathology ; },
abstract = {Current biomarkers are inadequate prognostic predictors in localized prostate cancer making treatment decision-making challenging. Previously, we observed that the combination of more variable telomere length among prostate cancer cells and shorter telomere length in prostate cancer-associated stromal cells - the telomere biomarker - is strongly associated with progression to metastasis and prostate cancer death after prostatectomy independent of currently used pathologic indicators. Here, we optimized our method allowing for semi-automated telomere length determination in single cells in fixed tissue, and tested the telomere biomarker in five cohort studies of men surgically treated for clinically localized disease (N = 2,255). We estimated the relative risk (RR) of progression to metastasis (N = 311) and prostate cancer death (N = 85) using models appropriate to each study's design adjusting for age, prostatectomy stage, and tumor grade, which then we meta-analyzed using inverse variance weights. Compared with men who had less variable telomere length among prostate cancer cells and longer telomere length in prostate cancer-associated stromal cells, men with the combination of more variable and shorter telomere length had 3.76 times the risk of prostate cancer death (95% confidence interval [CI] 1.37-10.3, p = 0.01) and had 2.23 times the risk of progression to metastasis (95% CI 0.99-5.02, p = 0.05). The telomere biomarker was associated with prostate cancer death in men with intermediate risk disease (grade groups 2/3: RR = 9.18, 95% CI 1.14-74.0, p = 0.037) and with PTEN protein intact tumors (RR = 6.74, 95% CI 1.46-37.6, p = 0.015). In summary, the telomere biomarker is robust and associated with poor outcome independent of current pathologic indicators in surgically treated men.},
}
@article {pmid35835478,
year = {2022},
author = {Bhatt, SP and Misra, A and Pandey, RM and Upadhyay, AD},
title = {Shortening of leucocyte telomere length is independently correlated with high body mass index and subcutaneous obesity (predominantly truncal), in Asian Indian women with abnormal fasting glycemia.},
journal = {BMJ open diabetes research &amp; care},
volume = {10},
number = {4},
pages = {},
pmid = {35835478},
issn = {2052-4897},
mesh = {Body Mass Index ; *Fasting ; Female ; Glucose ; Humans ; *Obesity/epidemiology/genetics ; Telomere/genetics ; },
abstract = {INTRODUCTION: Leucocyte telomere length (LTL) is linked to accelerate aging and premature mortality. In this research, we aimed to explore the relations between biochemical and anthropometry markers and LTL in Asian Indian women with abnormal fasting glycemia (impaired fasting glucose).<br><br>RESEARCH DESIGN AND METHODS: In this study, 797 pre-diabetic women (obese, 492; non-obese, 305) were recruited. Demographic and clinical profiles, anthropometry, and fasting blood glucose were evaluated. LTL was quantified by a quantitative PCR. LTL was expressed as the relative telomere length or telomere repeat:single copy gene (T:S) ratio. The subjects were separated into quartiles according to the LTL.<br><br>RESULTS: The average LTL was significantly decreased with increasing age. The average LTL was significantly shorter in obese women with abnormal fasting glycemia (p<0.05). R-squared (R[2]) statistic for multivariable linear model after adjusted for age, family income, education and hypertension showed that LTL was inversely correlated with body mass index (BMI), waist and hip circumference, waist-hip and waist-to-height ratio, truncal skinfolds (subscapular, and subscapular/triceps ratio, central and total skinfolds), fat mass (kg) and % body fat. The relationship between obesity measures and LTL (using the LTL quartile 1 as reference) identified central skinfolds (R[2]=0.92, p<0.0001), &#x3a3;4SF (R[2]=0.90, p<0.0001), BMI (R[2]=0.93, p<0.0001) and % body fat (R[2]=0.91, p<0.0001) as independent predictors of LTL.<br><br>CONCLUSIONS: Besides age, obesity and subcutaneous adiposity (predominantly truncal) are major contributors to telomere shortening in Asian Indian women with abnormal fasting glycemia (impaired fasting glucose).},
}
@article {pmid35830881,
year = {2022},
author = {He, Q and Lin, X and Chavez, BL and Agrawal, S and Lusk, BL and Lim, CJ},
title = {Structures of the human CST-Polα-primase complex bound to telomere templates.},
journal = {Nature},
volume = {608},
number = {7924},
pages = {826-832},
pmid = {35830881},
issn = {1476-4687},
support = {75N91019D00024/CA/NCI NIH HHS/United States ; R00 GM131023/GM/NIGMS NIH HHS/United States ; },
mesh = {DNA/metabolism ; *DNA Primase/chemistry/metabolism ; DNA Primers/biosynthesis ; DNA Replication ; Humans ; Protein Domains ; RNA/biosynthesis/metabolism ; *Shelterin Complex/chemistry/metabolism ; Substrate Specificity ; *Telomere/chemistry/genetics/metabolism ; *Templates, Genetic ; },
abstract = {The mammalian DNA polymerase-α-primase (Polα-primase) complex is essential for DNA metabolism, providing the de novo RNA-DNA primer for several DNA replication pathways[1-4] such as lagging-strand synthesis and telomere C-strand fill-in. The physical mechanism underlying how Polα-primase, alone or in partnership with accessory proteins, performs its complicated multistep primer synthesis function is unknown. Here we show that CST, a single-stranded DNA-binding accessory protein complex for Polα-primase, physically organizes the enzyme for efficient primer synthesis. Cryogenic electron microscopy structures of the CST-Polα-primase preinitiation complex (PIC) bound to various types of telomere overhang reveal that template-bound CST partitions the DNA and RNA catalytic centres of Polα-primase into two separate domains and effectively arranges them in RNA-DNA synthesis order. The architecture of the PIC provides a single solution for the multiple structural requirements for the synthesis of RNA-DNA primers by Polα-primase. Several insights into the template-binding specificity of CST, template requirement for assembly of the CST-Polα-primase PIC and activation are also revealed in this study.},
}
@article {pmid35830513,
year = {2022},
author = {Wang, XF and Xu, WJ and Wang, FF and Leng, R and Yang, XK and Ling, HZ and Fan, YG and Tao, JH and Shuai, ZW and Zhang, L and Ye, DQ and Leng, RX},
title = {Telomere Length and Development of Systemic Lupus Erythematosus: A Mendelian Randomization Study.},
journal = {Arthritis &amp; rheumatology (Hoboken, N.J.)},
volume = {74},
number = {12},
pages = {1984-1990},
doi = {10.1002/art.42304},
pmid = {35830513},
issn = {2326-5205},
mesh = {Humans ; *Mendelian Randomization Analysis ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide ; *Lupus Erythematosus, Systemic/epidemiology ; Telomere/genetics ; Autoantibodies/genetics ; },
abstract = {OBJECTIVE: Previous observational studies demonstrated that a subset of patients with systemic lupus erythematosus (SLE) have markedly short telomere length in leukocytes. This study was undertaken to test whether leukocyte telomere length is causally associated with risk of SLE.<br><br>METHODS: A 2-sample Mendelian randomization (MR) analysis was conducted to estimate causality of telomere length on SLE in European populations. A replication 2-sample MR study using Asian genetic data was also conducted. A reverse MR analysis was then performed to test the effects of SLE on telomere length. The autoantibodies targeting telomere-associated protein (telomeric repeat-binding factor 1 [TERF1] autoantibodies) were detected in patients with SLE, healthy controls, and patients with rheumatoid arthritis.<br><br>RESULTS: The results of the inverse variance-weighted method (odds ratio [OR] 2.96 [95% confidence interval (95% CI) 1.58-5.55], P&#x2009;<&#x2009;0.001) showed strong evidence for a causal relationship between longer telomere length and risk of SLE in people with European ancestry. The outcomes of MR-Egger regression analysis (OR 29.46 [95% CI 3.02-287.60], P&#xa0;=&#xa0;0.033) and MR pleiotropy residual sum and outlier analysis (OR 3.62 [95% CI 2.03-6.46], P&#xa0;=&#xa0;0.002) also showed that longer telomere length was significantly associated with increased risk of SLE in a European population. Sensitivity analyses using different methods and summary data sets showed that the results were still broadly consistent. A replication MR study using Asian genetic data yielded similar findings. However, the reverse MR analysis showed that genetically predicted SLE was not causally associated with telomere length. In addition, we found that TERF1 autoantibodies were present in 2 of 40 SLE patients (5.0%).<br><br>CONCLUSION: In contrast with previous observational studies, MR analyses show that longer telomere length is significantly associated with increased risk of SLE.},
}
@article {pmid35830448,
year = {2022},
author = {Edelson, PK and Sawyer, MR and Gray, KJ and Cantonwine, DE and McElrath, TF and Phillippe, M},
title = {Increase in short telomeres during the third trimester in human placenta.},
journal = {PloS one},
volume = {17},
number = {7},
pages = {e0271415},
pmid = {35830448},
issn = {1932-6203},
support = {K08 HL146963/HL/NHLBI NIH HHS/United States ; },
mesh = {Animals ; Female ; Gestational Age ; Humans ; Infant ; Mice ; *Placenta ; Pregnancy ; Pregnancy Trimester, Third ; Telomere/genetics ; *Telomere Shortening ; },
abstract = {An increase in telomere shortening in gestational tissues has been proposed as a mechanism involved in the timing for the initiation of parturition. An increase in very short telomeres with increasing gestational age has been observed in mice; this study sought to explore this phenomenon in human pregnancies. Specifically, this study addressed the hypothesis that prior to labor, the quantity of very short telomeres (<3 kilobase (kb) lengths) increases in human placental tissue as term gestation approaches. The primary outcome was the quantity of very short telomeres present in placental tissue. Quantitative measurements of very short telomeres were performed using real-time polymerase chain reaction (qPCR) adaptation of the telomere restriction fragment technique. Placental tissue from 69 pregnant individuals were included. Mean gestational age was 39.1 weeks (term) and 36.2 weeks (preterm). For term versus preterm placentas, the observed increase in very short telomeres were as follows: 500 bp telomeres increased by 1.67-fold (p < 0.03); 1 kb telomeres increased 1.67-fold (p < 0.08); and 3 kb telomeres increased 5.20-fold (p < 0.001). This study confirms a significant increase in very short telomeres in human placental tissue at term; thereby supporting the hypothesis that telomere shortening at term contributes to the mechanism that determine the length of pregnancy thereby leading to onset of parturition.},
}
@article {pmid35822010,
year = {2021},
author = {Stock, AJ and Liu, Y},
title = {NAD-Linked Metabolism and Intervention in Short Telomere Syndromes and Murine Models of Telomere Dysfunction.},
journal = {Frontiers in aging},
volume = {2},
number = {},
pages = {785171},
pmid = {35822010},
issn = {2673-6217},
abstract = {Telomeres are specialized nucleoprotein structures that form protective caps at the ends of chromosomes. Short telomeres are a hallmark of aging and a principal defining feature of short telomere syndromes, including dyskeratosis congenita (DC). Emerging evidence suggests a crucial role for critically short telomere-induced DNA damage signaling and mitochondrial dysfunction in cellular dysfunction in DC. A prominent factor linking nuclear DNA damage and mitochondrial homeostasis is the nicotinamide adenine dinucleotide (NAD) metabolite. Recent studies have demonstrated that patients with DC and murine models with critically short telomeres exhibit lower NAD levels, and an imbalance in the NAD metabolome, including elevated CD38 NADase and reduced poly (ADP-ribose) polymerase and SIRT1 activities. CD38 inhibition and/or supplementation with NAD precursors reequilibrate imbalanced NAD metabolism and alleviate mitochondrial impairment, telomere DNA damage, telomere dysfunction-induced DNA damage signaling, and cellular growth retardation in primary fibroblasts derived from DC patients. Boosting NAD levels also ameliorate chemical-induced liver fibrosis in murine models of telomere dysfunction. These findings underscore the relevance of NAD dysregulation to telomeropathies and demonstrate how NAD interventions may prove to be effective in combating cellular and organismal defects that occur in short telomere syndromes.},
}
@article {pmid35821228,
year = {2022},
author = {Bürgin, D and Varghese, N and Eckert, A and Clemens, V and Unternährer, E and Boonmann, C and O'Donovan, A and Schmid, M},
title = {Higher hair cortisol concentrations associated with shorter leukocyte telomere length in high-risk young adults.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {11730},
pmid = {35821228},
issn = {2045-2322},
support = {K01 MH109871/MH/NIMH NIH HHS/United States ; },
mesh = {Adult ; Female ; Hair ; Humans ; *Hydrocortisone ; *Leukocytes/physiology ; Male ; Pituitary-Adrenal System ; Telomere/genetics ; Young Adult ; },
abstract = {Chronic stress is associated with accelerated biological aging as indexed by short age-adjusted leukocyte telomere length (LTL). Exploring links of biological stress responses with LTL has proved challenging due to the lack of biological measures of chronic psychological stress. Hair cortisol concentration (HCC) has emerged as a measure of chronic hypothalamic pituitary adrenal (HPA) axis activation, allowing the examination of relationships between aggregate cortisol concentrations over time and LTL. Our sample includes 92 participants (38% women, Mage = 26 ± 3.7 years) from a high-risk sample of young adults with previous residential care placements. Two cm hair was collected for HCC, reflecting approximately eight weeks of cortisol secretion. LTL was measured with quantitative polymerase chain reaction (qPCR) in whole blood samples. All samples for LTL were run in triplicate and assayed twice. Linear and polynomial regression models were used to describe the association between HCC and LTL, adjusting for age and sex. HCC and LTL showed negative associations (std. ß = - 0.67, 95% CI [- 0.83, - 0.52], p < .001) in age- and sex-adjusted analyses, indicating that higher HCCs are associated with shorter LTL. Using polynomial regression, we found a curvilinear relationship indicating a stronger negative association at lower cortisol concentrations. Higher HCCs were associated with shorter LTL, supporting the hypothesized involvement of prolonged cortisol secretion in telomere attrition. Thus, HCC may prove useful as a biological indicator of chronic stress associated with aging-related processes in samples exposed to high levels of stress.},
}
@article {pmid35820929,
year = {2022},
author = {Ellis, PS and Martins, RR and Thompson, EJ and Farhat, A and Renshaw, SA and Henriques, CM},
title = {A subset of gut leukocytes has telomerase-dependent "hyper-long" telomeres and require telomerase for function in zebrafish.},
journal = {Immunity &amp; ageing : I &amp; A},
volume = {19},
number = {1},
pages = {31},
pmid = {35820929},
issn = {1742-4933},
support = {MR/M004864/1/MRC_/Medical Research Council/United Kingdom ; MR/M004864/1/MRC/MRC_/Medical Research Council/United Kingdom ; 206224/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; Vice Chancellor's Fellowship//University of Sheffield/ ; MR/P020941/1/MRC_/Medical Research Council/United Kingdom ; PhD Studentship//The University of Sheffield/ ; },
abstract = {BACKGROUND: Telomerase, the enzyme capable of elongating telomeres, is usually restricted in human somatic cells, which contributes to progressive telomere shortening with cell-division and ageing. T and B-cells cells are somatic cells that can break this rule and can modulate telomerase expression in a homeostatic manner. Whereas it seems intuitive that an immune cell type that depends on regular proliferation outbursts for function may have evolved to modulate telomerase expression it is less obvious why others may also do so, as has been suggested for macrophages and neutrophils in some chronic inflammation disease settings. The gut has been highlighted as a key modulator of systemic ageing and is a key tissue where inflammation must be carefully controlled to prevent dysfunction. How telomerase may play a role in innate immune subtypes in the context of natural ageing in the gut, however, remains to be determined.<br><br>RESULTS: Using the zebrafish model, we show that subsets of gut immune cells have telomerase-dependent"hyper-long" telomeres, which we identified as being predominantly macrophages and dendritics (mpeg1.1[+] and cd45[+]mhcII[+]). Notably, mpeg1.1[+] macrophages have much longer telomeres in the gut than in their haematopoietic tissue of origin, suggesting that there is modulation of telomerase in these cells, in the gut. Moreover, we show that a subset of gut mpeg1.1[+] cells express telomerase (tert) in young WT zebrafish, but that the relative proportion of these cells decreases with ageing. Importantly, this is accompanied by telomere shortening and DNA damage responses with ageing and a telomerase-dependent decrease in expression of autophagy and immune activation markers. Finally, these telomerase-dependent molecular alterations are accompanied by impaired phagocytosis of E. coli and increased gut permeability in vivo.<br><br>CONCLUSIONS: Our data show that limiting levels of telomerase lead to alterations in gut immunity, impacting on the ability to clear pathogens in vivo. These are accompanied by increased gut permeability, which, together, are likely contributors to local and systemic tissue degeneration and increased susceptibility to infection with ageing.},
}
@article {pmid35820392,
year = {2022},
author = {Olaya, I and Burgess, SM},
title = {When the anchor's away, meiotic telomeres go astray.},
journal = {Developmental cell},
volume = {57},
number = {13},
pages = {1563-1565},
doi = {10.1016/j.devcel.2022.06.014},
pmid = {35820392},
issn = {1878-1551},
support = {R25 GM116690/GM/NIGMS NIH HHS/United States ; R35 GM145244/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Chromosome Pairing ; Meiosis/genetics ; Microtubules ; *Telomere/genetics ; *Zebrafish/genetics ; },
abstract = {During meiosis, microtubules emanate from the centrosome to cluster telomeres in the bouquet configuration and facilitate chromosome pairing. In a recent issue of Science, Mytlis et al. establish that a cilium in zebrafish anchors the centrosome and is important for telomere clustering and germ cell development.},
}
@article {pmid35818177,
year = {2022},
author = {Inandiklioglu, N and Demir, V and Celik, Y and Demirtas, M},
title = {Leukocyte telomere length and lipid parameters in patients with myocardial infarction with non-obstructive coronary arteries.},
journal = {Cellular and molecular biology (Noisy-le-Grand, France)},
volume = {67},
number = {6},
pages = {346-352},
doi = {10.14715/cmb/2021.67.6.45},
pmid = {35818177},
issn = {1165-158X},
mesh = {Cholesterol, HDL ; *Coronary Artery Disease/diagnosis ; Coronary Vessels ; Humans ; Leukocytes ; MINOCA ; *Myocardial Infarction/genetics ; Risk Factors ; Telomere/genetics ; },
abstract = {Myocardial infarction with non-obstructive coronary arteries (MINOCA) is defined as stenosis of less than 50% or no stenosis on coronary angiography in a patient diagnosed with myocardial infarction. Telomere length is expressed by studies that it acts as a biomarker, especially for biological aging and cardiovascular diseases. In this study, we aimed to investigate whether there is a relationship between circulating leukocyte telomere length (LTL) and serum lipid values in MINOCA patients. Forty-five newly diagnosed patients with MINOCA were included in the study, along with 45 healthy controls who matched the patients in terms of age and gender. We determined the LTL value using the RT-PCR method. As a result of the study, we found LTL (p< 0.001) and serum lipid values (HDL-cholesterol (p< 0.001), LDL-cholesterol (p< 0.001), triglycerides (p< 0.05), and total cholesterol (p< 0.05)) to be significantly higher in the MINOCA group than in the control group. When the correlation relationship between LTL and lipid values in the MINOCA group was evaluated, a negative correlation was determined only between LTL and HDL (p=0.014, r=-0.362). This is the first study to evaluate telomere length in MINOCA patients in Turkey. Our results support the existence of short telomere length in MINOCA patients.},
}
@article {pmid35816887,
year = {2022},
author = {Ribas-Maynou, J and Llavanera, M and Mateo-Otero, Y and Ruiz, N and Muiño, R and Bonet, S and Yeste, M},
title = {Telomere length in bovine sperm is related to the production of reactive oxygen species, but not to reproductive performance.},
journal = {Theriogenology},
volume = {189},
number = {},
pages = {290-300},
doi = {10.1016/j.theriogenology.2022.06.025},
pmid = {35816887},
issn = {1879-3231},
mesh = {Animals ; Cattle ; Female ; Humans ; In Situ Hybridization, Fluorescence/veterinary ; Insemination, Artificial/veterinary ; Male ; Reactive Oxygen Species ; *Semen ; *Spermatozoa ; Telomere ; },
abstract = {Over the last decades, selection in cattle has mainly been based on milk production rather than on reproductive efficiency. While, when applied, focus on reproduction has involved females, attention has barely been paid to males and, if so, it has only looked at classical sperm quality parameters. In effect, variables such as telomere length have been missed, despite the fact that longer telomeres have been suggested to be linked to male fertility in humans. For this reason, the present study aimed to determine the length of telomeres in bovine sperm and their relationship with a) sperm quality evaluated through the conventional spermiogram and flow cytometry, and b) bull reproductive performance. For this purpose, 29 bulls were involved in this study. Sperm telomere length was evaluated through quantitative Fluorescent In Situ Hybridization (qFISH), and sperm quality was determined at 0 h and 4 h post-thaw. Bull fertility was assessed as non-return to estrus rates after 90 days of artificial insemination. Although the mean telomere length in bovine sperm was 12.06 ± 2.75 kb, the intra-individual variability in length led us to observe three different groups of telomeres in each sperm cell: short telomeres (7.14% ± 5.79% of telomeres; 8.29 ± 2.34 kb), medium telomeres (31.03% ± 12.92% of telomeres; 16.00 ± 2.72 kb) and long telomeres (61.93% ± 18.11% of telomeres; 30.13 ± 11.35 kb). Moreover, whereas reactive oxygen species (ROS) were found to be correlated to sperm telomere length (Rs = -0.492; P= 0.007), no correlation with other sperm quality parameters was found (P > 0.05). Reproductive performance after artificial insemination was not seen to be correlated to sperm telomere length (Rs = 0.123; P= 0.520). In conclusion, this study determined, for the first time, the mean telomere length in bovine sperm and also reported that there is a high variability within each sperm cell. Yet, while telomere length was found to be correlated to ROS generation, it was not related to bull reproductive performance.},
}
@article {pmid35812693,
year = {2022},
author = {Gupta, A and Hwang, BJ and Benyamien-Roufaeil, D and Jain, S and Liu, S and Gonzales, R and Brown, RA and Zalzman, M and Lu, AL},
title = {Mammalian MutY Homolog (MYH or MUTYH) is Critical for Telomere Integrity under Oxidative Stress.},
journal = {OBM geriatrics},
volume = {6},
number = {2},
pages = {},
pmid = {35812693},
issn = {2638-1311},
support = {R01 AR070819/AR/NIAMS NIH HHS/United States ; R01 GM118837/GM/NIGMS NIH HHS/United States ; },
abstract = {Telomeres consist of special features and proteins to protect the ends of each chromosome from deterioration and fusion. The telomeric DNA repeats are highly susceptible to oxidative damage that can accelerate telomere shortening and affect telomere integrity. Several DNA repair factors including MYH/MUTYH DNA glycosylase, its interacting partners Rad9/Rad1/Hus1 checkpoint clamp, and SIRT6 aging regulator, are associated with the telomeres. MYH prevents C:G to A:T mutation by removing adenine mispaired with a frequent oxidative DNA lesion, 8-oxoguanine. Here, we show that hMYH knockout (KO) human HEK-293T cells are more sensitive to H2O2 treatment, have higher levels of DNA strand breaks and shorter telomeres than the control hMYH [+/+] cells. SIRT6 foci increase at both the global genome and at telomeric regions in H2O2-treated hMYH [+/+] cells. However, in untreated hMYH KO HEK-293T cells, SIRT6 foci only increase at the global genome, but not at the telomeric regions. In addition, the hMYH KO HEK-293T cells have increased extra-chromosomal and intra-chromosomal telomeres compared to the control cells, even in the absence of H2O2 treatment. After H2O2 treatment, the frequency of extra-chromosomal telomeres increased in control HEK-293T cells. Remarkably, in H2O2-treated hMYH KO cells, the frequencies of extra-chromosomal telomeres, intra-chromosomal telomeres, and telomere fusions are further increased. We further found that the sensitivity to H2O2 and shortened telomeres of hMYH KO cells, are restored by expressing wild-type hMYH, and partially rescued by expressing hMYH[Q324H] mutant (defective in Hus1 interaction only), but not by expressing hMYH[V315A] mutant (defective in both SIRT6 and Hus1 interactions). Thus, MYH interactions with SIRT6 and Hus1 are critical for maintaining cell viability and telomeric stability. Therefore, the failure to coordinate 8-oxoG repair is detrimental to telomere integrity.},
}
@article {pmid35811822,
year = {2022},
author = {Giguere, DJ and Bahcheli, AT and Slattery, SS and Patel, RR and Browne, TS and Flatley, M and Karas, BJ and Edgell, DR and Gloor, GB},
title = {Telomere-to-telomere genome assembly of Phaeodactylum tricornutum.},
journal = {PeerJ},
volume = {10},
number = {},
pages = {e13607},
pmid = {35811822},
issn = {2167-8359},
mesh = {*Diatoms/genetics ; *Genome, Mitochondrial/genetics ; Telomere/genetics ; },
abstract = {Phaeodactylum tricornutum is a marine diatom with a growing genetic toolbox available and is being used in many synthetic biology applications. While most of the genome has been assembled, the currently available genome assembly is not a completed telomere-to-telomere assembly. Here, we used Oxford Nanopore long reads to build a telomere-to-telomere genome for Phaeodactylum tricornutum. We developed a graph-based approach to extract all unique telomeres, and used this information to manually correct assembly errors. In total, we found 25 nuclear chromosomes that comprise all previously assembled fragments, in addition to the chloroplast and mitochondrial genomes. We found that chromosome 19 has filtered long-read coverage and a quality estimate that suggests significantly less haplotype sequence variation than the other chromosomes. This work improves upon the previous genome assembly and provides new opportunities for genetic engineering of this species, including creating designer synthetic chromosomes.},
}
@article {pmid35810694,
year = {2022},
author = {Seo, SH and Shin, JH and Ham, DW and Shin, EH},
title = {PTEN/AKT signaling pathway related to hTERT downregulation and telomere shortening induced in Toxoplasma GRA16-expressing colorectal cancer cells.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {153},
number = {},
pages = {113366},
doi = {10.1016/j.biopha.2022.113366},
pmid = {35810694},
issn = {1950-6007},
mesh = {*Colorectal Neoplasms/genetics ; Down-Regulation/genetics ; Humans ; PTEN Phosphohydrolase/genetics/metabolism ; Protein Phosphatase 2/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; *Telomerase/metabolism ; Telomere/genetics/metabolism ; Telomere Shortening ; *Toxoplasma ; },
abstract = {This study investigated whether the molecular mechanism of granule protein 16 (GRA16), a dense granule protein of Toxoplasma gondii (T. gondii) that induces cancer cell apoptosis, results in telomere shortening in cancer cells. The molecular mechanism of GRA16 responsible for regulating telomerase reverse transcriptase (hTERT) activity and telomere shortening was investigated using GRA16-transferred HCT116 human colorectal cancer cells (GRA16-stable cells). GRA16 directly decreased hTERT expression by downregulating the expression and phosphorylation of hTERT transcriptional factors accompanied by decreased expression of shelterin complex molecules. Moreover, GRA16 resulted in cancer cell death through reduction of telomerase activity which leads to telomere shortening (decreased relative ratio of telomeric repeat-amplified sequence to that of a single-copy gene) (T/S ratio)), and at the same time gamma-H2A histone family member X (γ-H2A.X) stained nucleus was increased in the cells. The molecular mechanism between GRA16 and hTERT inactivation was revealed using inhibitors for phosphatase and tensin homolog (PTEN) and protein phosphatase 2A (PP2A) as well as siRNAs against PTEN and PP2A. hTERT dephosphorylation was induced effectively by the signaling pathway of HAUSP/PTEN/p-AKT(S473) but not by PP2A-B55/p-AKT(T308). Inhibition of the PTEN signaling pathway increased mRNA expressions in hTERT transcriptional factors, cell cycle activating factors, and apoptosis-inhibiting factors. When HCT116 cells were infected with T. gondii, the number of γ-H2A.X-stained nuclei also increased and p-hTERT/hTERT decreased as in GRA16-stable cells. Altogether, our results emphasize that GRA16 is a novel promising telomerase inhibitor that causes telomere shortening through telomerase inactivation by inducing the activation of the tumor suppressor PTEN.},
}
@article {pmid35807292,
year = {2022},
author = {Zou, T and Sato, Y and Kaneyoshi, S and Mano, K and Yasukawa, R and Nakano, Y and Fujii, S and Sato, S and Takenaka, S},
title = {Naphthalene Diimides Carrying Two β-Cyclodextrins Prefer Telomere RNA G-Quadruplex Recognition.},
journal = {Molecules (Basel, Switzerland)},
volume = {27},
number = {13},
pages = {},
pmid = {35807292},
issn = {1420-3049},
support = {19H02748//Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology,/ ; S.T.//Nakatani Foundation for advancement of measuring technologies in biomedical engineering/ ; },
mesh = {*G-Quadruplexes ; Imides/chemistry ; Ligands ; Naphthalenes ; RNA ; Telomere/genetics ; *beta-Cyclodextrins ; },
abstract = {Newly synthesized naphthalene diimide carrying two β-cyclodextrins (NDI-β-CyDs) showed improved specificity for the parallel G-quadruplex structure alongside the hybrid G-quadruplex structure. Specifically, the highest binding affinity of NDI-β-CyDs for the telomere RNA G-quadruplex was observed. The binding simulation indicated that β-cyclodextrins might be available for loop nucleobase inclusion under its complex.},
}
@article {pmid35805953,
year = {2022},
author = {Zhou, D and Li, Z and Sun, Y and Yan, J and Huang, G and Li, W},
title = {Early Life Stage Folic Acid Deficiency Delays the Neurobehavioral Development and Cognitive Function of Rat Offspring by Hindering De Novo Telomere Synthesis.},
journal = {International journal of molecular sciences},
volume = {23},
number = {13},
pages = {},
pmid = {35805953},
issn = {1422-0067},
support = {81602849//National Natural Science Foundation of China/ ; 81730091//National Natural Science Foundation of China/ ; 82003439//National Natural Science Foundation of China/ ; 19JCQNJC11700//Natural Science Foundation of Tianjin City/ ; },
mesh = {Animals ; Cognition ; Dietary Supplements ; Female ; Folic Acid/metabolism ; *Folic Acid Deficiency/complications/metabolism ; Rats ; Telomere/metabolism ; Uracil ; },
abstract = {Early life stage folate status may influence neurodevelopment in offspring. The developmental origin of health and disease highlights the importance of the period of the first 1000 days (from conception to 2 years) of life. This study aimed to evaluate the effect of early life stage folic acid deficiency on de novo telomere synthesis, neurobehavioral development, and the cognitive function of offspring rats. The rats were divided into three diet treatment groups: folate-deficient, folate-normal, and folate-supplemented. They were fed the corresponding diet from 5 weeks of age to the end of the lactation period. After weaning, the offspring rats were still fed with the corresponding diet for up to 100 days. Neurobehavioral tests, folic acid and homocysteine (Hcy) levels, relative telomere length in brain tissue, and uracil incorporation in telomere in offspring were measured at different time points. The results showed that folic acid deficiency decreased the level of folic acid, increased the level of Hcy of brain tissue in offspring, increased the wrong incorporation of uracil into telomeres, and hindered de novo telomere synthesis. However, folic acid supplementation increased the level of folic acid, reduced the level of Hcy of brain tissue in offspring, reduced the wrong incorporation of uracil into telomeres, and protected de novo telomere synthesis of offspring, which was beneficial to the development of early sensory-motor function, spatial learning, and memory in adolescence and adulthood. In conclusion, early life stage folic acid deficiency had long-term inhibiting effects on neurodevelopment and cognitive function in offspring.},
}
@article {pmid35805470,
year = {2022},
author = {Assis, V and de Sousa Neto, IV and Ribeiro, FM and de Cassia Marqueti, R and Franco, OL and da Silva Aguiar, S and Petriz, B},
title = {The Emerging Role of the Aging Process and Exercise Training on the Crosstalk between Gut Microbiota and Telomere Length.},
journal = {International journal of environmental research and public health},
volume = {19},
number = {13},
pages = {},
pmid = {35805470},
issn = {1660-4601},
mesh = {Dysbiosis ; Exercise ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; Telomere ; },
abstract = {Aging is a natural process of organism deterioration, which possibly impairs multiple physiological functions. These harmful effects are linked to an accumulation of somatic mutations, oxidative stress, low-grade inflammation, protein damage, and mitochondrial dysfunction. It is known that these factors are capable of inducing telomere shortening, as well as intestinal dysbiosis. Otherwise, among the biological mechanisms triggered by physical exercise, the attenuation of pro-inflammatory mediators accompanied by redox state improvement can be the main mediators for microbiota homeostasis and telomere wear prevention. Thus, this review highlights how oxidative stress, inflammation, telomere attrition, and gut microbiota (GM) dysbiosis are interconnected. Above all, we provide a logical foundation for unraveling the role of physical exercise in this process. Based on the studies summarized in this article, exercise training can increase the biodiversity of beneficial microbial species, decrease low-grade inflammation and improve oxidative metabolism, these factors together possibly reduce telomeric shortening.},
}
@article {pmid35805162,
year = {2022},
author = {Min, S and Kwon, SM and Hong, J and Lee, YK and Park, TJ and Lim, SB and Yoon, G},
title = {Mitoribosomal Deregulation Drives Senescence via TPP1-Mediated Telomere Deprotection.},
journal = {Cells},
volume = {11},
number = {13},
pages = {},
pmid = {35805162},
issn = {2073-4409},
mesh = {Animals ; *Cellular Senescence/physiology ; Mice ; *Mitochondria/metabolism ; Rats ; *Ribosomes/metabolism ; *Shelterin Complex ; Telomere/metabolism ; *Telomere-Binding Proteins/genetics/metabolism ; },
abstract = {While mitochondrial bioenergetic deregulation has long been implicated in cellular senescence, its mechanistic involvement remains unclear. By leveraging diverse mitochondria-related gene expression profiles derived from two different cellular senescence models of human diploid fibroblasts, we found that the expression of mitoribosomal proteins (MRPs) was generally decreased during the early-to-middle transition prior to the exhibition of noticeable SA-β-gal activity. Suppressed expression patterns of the identified senescence-associated MRP signatures (SA-MRPs) were validated in aged human cells and rat and mouse skin tissues and in aging mouse fibroblasts at single-cell resolution. TIN2- and POT1-interaction protein (TPP1) was concurrently suppressed, which induced senescence, accompanied by telomere DNA damage. Lastly, we show that SA-MRP deregulation could be a potential upstream regulator of TPP1 suppression. Our results indicate that mitoribosomal deregulation could represent an early event initiating mitochondrial dysfunction and serve as a primary driver of cellular senescence and an upstream regulator of shelterin-mediated telomere deprotection.},
}
@article {pmid35804173,
year = {2022},
author = {Magnano San Lio, R and Maugeri, A and La Rosa, MC and Giunta, G and Panella, M and Cianci, A and Caruso, MAT and Agodi, A and Barchitta, M},
title = {Nutrient intakes and telomere length of cell-free circulating DNA from amniotic fluid: findings from the Mamma &amp; Bambino cohort.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {11671},
pmid = {35804173},
issn = {2045-2322},
mesh = {*Amniotic Fluid ; *Cell-Free Nucleic Acids/genetics ; Diet ; Eating ; Female ; Humans ; Magnesium ; Pregnancy ; Prospective Studies ; Telomere/genetics ; },
abstract = {Pregnancy represents a crucial period in which several exposures-and especially maternal diet-might shape children's health. Thus, identifying how maternal dietary intakes early affect biological aging in children represents a public health mission. We aimed to assess the relationship between maternal intake of nutrients in early pregnancy and telomere length of cell-free circulating DNA (cfDNA) from amniotic fluid. We used data and samples from the ongoing prospective "Mamma &amp; Bambino" study, which recruits mother-child pairs from Catania at the first prenatal visit. Maternal nutrient intakes were assessed using a Food Frequency Questionnaire, while relative telomere length of cfDNA was assessed by real-time polymerase chain reaction. Our analysis included 174 mother-child pairs. The intakes of iron, vitamin B1, and magnesium were positively correlated with relative telomere length (p-values < 0.05). However, only the intake of magnesium was positively associated with relative telomere length, after applying a linear regression model (β = 0.002; SE = 0.001; p = 0.024). Magnesium deficiency was negatively associated with relative telomere length after adjusting for the same covariates (β = -0.467; SE = 0.176; p = 0.009). To our knowledge, this is the first evidence of a positive relationship between maternal nutrient intake and telomere length of cfDNA. Further efforts are needed for deeply investigating the effect of maternal dietary intakes on telomere length, in order to develop effective public health strategies.},
}
@article {pmid35802889,
year = {2022},
author = {Zhou, J and Chen, F and Yan, A and Xia, X},
title = {Explore the molecular mechanism of angle-closure glaucoma in elderly patients induced telomere shortening of retinal ganglion cells through oxidative stress.},
journal = {Nucleosides, nucleotides &amp; nucleic acids},
volume = {41},
number = {10},
pages = {1024-1035},
doi = {10.1080/15257770.2022.2094947},
pmid = {35802889},
issn = {1532-2335},
mesh = {Animals ; Disease Models, Animal ; Fluorescent Dyes/metabolism ; *Glaucoma/metabolism/pathology ; *Glaucoma, Angle-Closure/metabolism/pathology ; Intraocular Pressure ; *Ketamine/metabolism ; Mice ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Retinal Ganglion Cells/metabolism/pathology ; *Telomerase ; Telomere Shortening ; Xylazine/metabolism ; beta-Galactosidase/metabolism ; },
abstract = {Senile glaucoma is a common ophthalmological disease in the elderly. It is a disease of visual papillary perfusion caused by elevated intraocular pressure, complicated by visual dysfunction. Glaucoma can cause serious damage to the normal vision of the elderly. Therefore, exploring the related molecular mechanisms of glaucoma is of great significance to the diagnosis and treatment of glaucoma. This is an exploratory study. Establish a mouse model and conduct experimental groupings. After one week of adaptive feeding, the mice were intraperitoneally injected with an anesthetic mixture: ketamine + xylazine. Then the mice were sacrificed by neck dissection, and the eyeball tissues were immediately dissected. HE staining was used to analyze the histopathological characteristics of the retina of each group of mice. MitoSOX fluorescent probe was used to analyze the content of ROS in retinal tissue. The ELISA analysis was used to detect the activation of β-galactosidase for the aging characteristics of retinal ganglion cells in retinal tissues. Immunohistochemistry experiments were used to analyze the expression of telomerase TERT in retinal tissues. Western blot analysis was used to determine the expression of proteins POT1, TERF1, TERF2, and TINF2 in retinal tissues. The HE staining experiment showed that the damage of retinal tissue decreased from group Glaucoma to group Old, group Old to group Young. The experimental results of MitoSOX fluorescent probe show that ROS content is positively correlated with the degree of tissue damage. ELISA analysis results showed that the expression trend of β-galactosidase was the same as the ROS content. The protein expression levels related to telomere protection (TRET, POT1, TREF1, TREF2 and TINF2) all increased from group Glaucoma to group Old, group Old to group Young. The increase in ROS content, the decrease in telomere protection-related protein expression (telomere shortening) induced by ROS, and the increase of the expression of β-galactosidase, are all potential molecular mechanisms for the occurrence of angle-closure glaucoma in elderly patients.},
}
@article {pmid35801658,
year = {2022},
author = {Tsai, LK and Ou-Yang, H and Xu, J and Chen, CM and Chang, WF and Sung, LY},
title = {Effects of Recloning on the Telomere Lengths of Mouse Terc[+/-] Nuclear Transfer-Derived Embryonic Stem Cells.},
journal = {Stem cells and development},
volume = {31},
number = {21-22},
pages = {720-729},
doi = {10.1089/scd.2022.0115},
pmid = {35801658},
issn = {1557-8534},
mesh = {Mice ; Animals ; *Telomerase/genetics/metabolism ; RNA/genetics ; Telomere/genetics ; Embryonic Stem Cells/metabolism ; },
abstract = {Haploinsufficiency of genes that participate in telomere elongation and maintenance processes, such as telomerase RNA component (Terc) and telomere reverse transcriptase (Tert), often leads to premature aging-related diseases such as dyskeratosis congenita and aplastic anemia. Previously, we reported that when mouse Terc[+/-] tail tip fibroblasts (TTFs) were used as donor cells for somatic cell nuclear transfer (SCNT, also known as cloning), the derivative embryonic stem cells (ntESCs) had elongated telomeres. In the present work, we are interested to know if an additional round of SCNT, or recloning, could lead to further elongation of telomeres. Terc[+/-] TTFs were used to derive the first-generation (G1) ntESCs, followed by a second round of SCNT using G1-Terc[+/-] ntESCs as donor cells to derive G2-Terc[+/-] ntESCs. Multiple lines of G1- and G2-Terc[+/-] ntESCs were efficiently established, and all expressed major pluripotent markers and supported efficient chondrocyte differentiation in vitro. Compared with donor TTFs, telomere lengths of G1 ntESCs were elongated to the level comparable with that in wild-type ntESCs. Interestingly, recloning did not further elongate the telomere lengths of Terc[+/-] ntESCs. Together, our work demonstrates that while a single round of SCNT is a viable means to reprogram Terc haploinsufficient cells to the ESC state, and to elongate these cells' telomere lengths, a second round of SCNT does not necessarily further elongate the telomeres.},
}
@article {pmid35795254,
year = {2022},
author = {Stinus, S and Bringas, FRR and Wanders, L and Chang, M},
title = {Investigating the role of G-quadruplexes at Saccharomyces cerevisiae telomeres.},
journal = {Microbial cell (Graz, Austria)},
volume = {9},
number = {6},
pages = {126-132},
pmid = {35795254},
issn = {2311-2638},
abstract = {The G-quadruplex consensus motif G≥3NxG≥3NxG≥3NxG≥3 is found at telomeres of many species, ranging from yeast to plants to humans, but the biological significance of this fact remains largely unknown. In this study, we examine the in vivo relevance of telomeric G-quadruplexes in the budding yeast Saccharomyces cerevisiae by expressing a mutant telomerase RNA subunit (tlc1-tm) that introduces mutant [(TG)0-4TGG]xATTTGG telomeric repeats instead of wild-type (TG)0-6TGGGTGTG(G)0-1 repeats to the distal ends of telomeres. The tlc1-tm telomere sequences lack the GGG motif present in every wild-type repeat and, therefore, are expected to be impaired in the formation of G-quadruplexes. Circular dichroism analysis of oligonucleotides consisting of tlc1-tm telomeric sequence is consistent with this hypothesis. We have previously shown that tlc1-tm cells grow similarly to wild-type cells, suggesting that the ability to form telomeric G-quadruplexes is not essential for telomere capping in S. cerevisiae cells.},
}
@article {pmid35791675,
year = {2024},
author = {Ma, Y and Wang, M and Chen, X and Ruan, W and Yao, J and Lian, X},
title = {Telomere length and multiple sclerosis: a Mendelian randomization study.},
journal = {The International journal of neuroscience},
volume = {134},
number = {3},
pages = {229-233},
doi = {10.1080/00207454.2022.2098737},
pmid = {35791675},
issn = {1563-5279},
mesh = {Humans ; *Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Multiple Sclerosis/genetics ; Odds Ratio ; Telomere/genetics ; },
abstract = {PURPOSE OF THE STUDY: Previous studies have established that telomere length is associated with multiple sclerosis (MS). However, confounding factors and reverse causality bias can impair observational research. Here, we conducted a two-sample MR study to see if telomere length is causally linked to MS using publically available GWAS summary statistics.<br><br>MATERIALS AND METHODS: We screened 13 independent single-nucleotide polymorphisms (SNPs) related to leukocyte telomere length in a recent genome-wide association meta-analysis, which was available for 78,592 samples of European ancestry. The summary statistics for MS were from the latest meta-analyses conducted by the International Multiple Sclerosis Genetics Consortium (IMSGC), which included 115,803 European participants (47,429&#x2009;MS, 68,374 controls).<br><br>RESULTS: We found that leukocyte telomere length and MS are correlated (IVW estimate of odds ratio (OR): 2.13 per 1-SD increase in genetically determined telomere length, 95% confidence interval (CI): 1.55-2.92, p&#x2009;=&#x2009;3.18&#x2009;&#xd7;&#x2009;10[-6]).<br><br>CONCLUSION: Our MR study supported that leukocyte telomere length and MS have a positive causal relationship. Further researches are warranted to elucidate the physiological mechanism.},
}
@article {pmid35790854,
year = {2022},
author = {Gao, J and Pickett, HA},
title = {Targeting telomeres: advances in telomere maintenance mechanism-specific cancer therapies.},
journal = {Nature reviews. Cancer},
volume = {22},
number = {9},
pages = {515-532},
pmid = {35790854},
issn = {1474-1768},
mesh = {DNA Replication ; Humans ; *Neoplasms/drug therapy/genetics ; *Telomerase/genetics ; Telomere/genetics/metabolism ; Telomere Homeostasis ; },
abstract = {Cancer cells establish replicative immortality by activating a telomere-maintenance mechanism (TMM), be it telomerase or the alternative lengthening of telomeres (ALT) pathway. Targeting telomere maintenance represents an intriguing opportunity to treat the vast majority of all cancer types. Whilst telomerase inhibitors have historically been heralded as promising anticancer agents, the reality has been more challenging, and there are currently no therapeutic options for cancer types that use ALT despite their aggressive nature and poor prognosis. In this Review, we discuss the mechanistic differences between telomere maintenance by telomerase and ALT, the current methods used to detect each mechanism, the utility of these tests for clinical diagnosis, and recent developments in the therapeutic strategies being employed to target both telomerase and ALT. We present notable developments in repurposing established therapeutic agents and new avenues that are emerging to target cancer types according to which TMM they employ. These opportunities extend beyond inhibition of telomere maintenance, by finding and exploiting inherent weaknesses in the telomeres themselves to trigger rapid cellular effects that lead to cell death.},
}
@article {pmid35789082,
year = {2022},
author = {Elam, KK and Johnson, SL and Ruof, A and Eisenberg, DTA and Rej, PH and Sandler, I and Wolchik, S},
title = {Examining the influence of adversity, family contexts, and a family-based intervention on parent and child telomere length.},
journal = {European journal of psychotraumatology},
volume = {13},
number = {1},
pages = {2088935},
pmid = {35789082},
issn = {2000-8066},
mesh = {Adolescent ; Child ; Divorce ; Family Conflict/psychology ; Humans ; *Parenting/psychology ; *Parents/psychology ; Telomere/genetics ; },
abstract = {UNLABELLED: Background: Exposure to adversity, trauma, and negative family environments can prematurely shorten telomeres, the protective caps at the ends of chromosomes. Conversely, some evidence indicates that positive environments and psychosocial interventions can buffer the shortening of telomere length (TL). However, most work has examined individual aspects of the family environment as predictive of TL with little work investigating multiple risk and protective factors. Further, most research has not examined parent TL relative to child TL despite its heritability. Objective: In the current study, we examined interparental conflict, positive parenting, alcohol use, adverse childhood experiences (ACEs), and a family-based intervention as predictive of parent TL. We also examined interparental conflict, positive parenting, ACEs, and a family-based intervention as predictive of child TL. Method: Parents and adolescents from a sample of divorced families participated in either a 10-session family-based intervention, the New Beginnings Programme (NBP), or a 2-week active control condition. Approximately six years after the intervention, a subsample of parents (n = 45) and adolescents (n = 41) were assessed for TL. Parents reported on interparental conflict, ACEs, and alcohol use. Children reported on interparental conflict, positive parenting, and ACEs. In separate models, these constructs and the NBP intervention condition were examined as predictors of parent TL and child TL. Results: Findings indicated that the family-based intervention was associated with longer TL in parents. Also, positive parenting was associated with longer TL in children. Conclusions: These findings have important implications for the role of the family and family-based preventive interventions in buffering parent and child biological stress.<br><br>HIGHLIGHTS: Across multiple indices of psychosocial functioning, we found a family-based intervention associated with longer telomere length in parents and positive parenting associated with longer telomere length in children.},
}
@article {pmid35787517,
year = {2022},
author = {von Falkenhausen, AS and Freudling, R and Waldenberger, M and Gieger, C and Peters, A and Müller-Nurasyid, M and Kääb, S and Sinner, MF},
title = {Common electrocardiogram measures are not associated with telomere length.},
journal = {Aging},
volume = {14},
number = {14},
pages = {5620-5627},
pmid = {35787517},
issn = {1945-4589},
mesh = {Aged ; Aging/genetics ; *Atrial Fibrillation/diagnosis/genetics ; Electrocardiography ; Female ; Humans ; Leukocytes ; Male ; Telomere/genetics ; *Telomere Shortening ; },
abstract = {AIMS: Aging is accompanied by telomere shortening. Increased telomere shortening is considered a marker of premature aging. Cardiac aging results in the development of cardiac pathologies. Electrocardiogram (ECG) measures reflect cardiac excitation, conduction, and repolarization. ECG measures also prolong with aging and are associated with cardiac pathologies including atrial fibrillation. As premature prolongation of ECG measures is observed, we hypothesized that such prolongation may be associated with telomere length.<br><br>METHODS AND RESULTS: We studied the large, community-based KORA F4 Study. Of 3,080 participants enrolled between 2006 and 2007 with detailed information on demographic, anthropometric, clinical, and ECG characteristics, 2,575 presented with available data on leukocyte telomere length. Telomere length was determined by real-time quantitative PCR and expressed relative to a single copy gene. We fitted multivariable adjusted linear regression models to associate the ECG measures RR-interval, PR-interval, QRS-duration, and heart rate corrected QTc with telomere length. In our cohort, the mean age was 54.9&#xb1;12.9 years and 46.6% were men. Increased age was associated with shorter telomere length (p<0.01), and men had shorter telomere length than women (p<0.05). In unadjusted models, heart rate (p=0.023), PR-interval (p<0.01), and QTc-interval (p<0.01) were significantly associated with shorter telomere length. However, no significant associations remained after accounting for age, sex, and covariates.<br><br>CONCLUSIONS: ECG measures are age-dependent, but not associated with shortened telomere length as a marker of biological aging. Further research is warranted to clarify if shortened telomeres are associated with clinical cardiac pathologies including atrial fibrillation.},
}
@article {pmid35784039,
year = {2022},
author = {van de Crommenacker, J and Hammers, M and Dugdale, HL and Burke, TA and Komdeur, J and Richardson, DS},
title = {Early-life conditions impact juvenile telomere length, but do not predict later life-history strategies or fitness in a wild vertebrate.},
journal = {Ecology and evolution},
volume = {12},
number = {6},
pages = {e8971},
pmid = {35784039},
issn = {2045-7758},
abstract = {Environmental conditions experienced during early life may have long-lasting effects on later-life phenotypes and fitness. Individuals experiencing poor early-life conditions may suffer subsequent fitness constraints. Alternatively, individuals may use a strategic "Predictive Adaptive Response" (PAR), whereby they respond-in terms of physiology or life-history strategy-to the conditions experienced in early life to maximize later-life fitness. Particularly, the Future Lifespan Expectation (FLE) PAR hypothesis predicts that when poor early-life conditions negatively impact an individual's physiological state, it will accelerate its reproductive schedule to maximize fitness during its shorter predicted life span. We aimed to measure the impact of early-life conditions and resulting fitness across individual lifetimes to test predictions of the FLE hypothesis in a wild, long-lived model species. Using a long-term individual-based dataset, we investigated how early-life conditions are linked with subsequent fitness in an isolated population of the Seychelles warbler Acrocephalus sechellensis. How individuals experience early-life environmental conditions may vary greatly, so we also tested whether telomere length-shorter telomers are a biomarker of an individual's exposure to stress-can provide an effective measure of the individual-specific impact of early-life conditions. Specifically, under the FLE hypothesis, we would expect shorter telomeres to be associated with accelerated reproduction. Contrary to expectations, shorter juvenile telomere length was not associated with poor early-life conditions, but instead with better conditions, probably as a result of faster juvenile growth. Furthermore, neither juvenile telomere length, nor other measures of early-life conditions, were associated with age of first reproduction or the number of offspring produced during early life in either sex. We found no support for the FLE hypothesis. However, for males, poor early-life body condition was associated with lower first-year survival and reduced longevity, indicating that poor early-life conditions pose subsequent fitness constraints. Our results also showed that using juvenile telomere length as a measure of early-life conditions requires caution, as it is likely to not only reflect environmental stress but also other processes such as growth.},
}
@article {pmid35782414,
year = {2022},
author = {Durand, M and Nagot, N and Michel, L and Le, SM and Duong, HT and Vallo, R and Vizeneux, A and Rapoud, D and Giang, HT and Quillet, C and Thanh, NTT and Hai Oanh, KT and Vinh, VH and Feelemyer, J and Vande Perre, P and Minh, KP and Laureillard, D and Des Jarlais, D and Molès, JP},
title = {Mental Disorders Are Associated With Leukocytes Telomere Shortening Among People Who Inject Drugs.},
journal = {Frontiers in psychiatry},
volume = {13},
number = {},
pages = {846844},
pmid = {35782414},
issn = {1664-0640},
abstract = {Premature biological aging, assessed by shorter telomere length (TL) and mitochondrial DNA (mtDNA) alterations, has been reported among people with major depressive disorders or psychotic disorders. However, these markers have never been assessed together among people who inject drugs (PWIDs), although mental disorders are highly prevalent in this population, which, in addition, is subject to other aggravating exposures. Diagnosis of mental disorders was performed by a psychiatrist using the Mini International Neuropsychiatric Interview test among active PWIDs in Haiphong, Vietnam. mtDNA copy number (MCN), mtDNA deletion, and TL were assessed by quantitative PCR and compared to those without any mental disorder. We next performed a multivariate analysis to identify risk factors associated with being diagnosed with a major depressive episode (MDE) or a psychotic syndrome (PS). In total, 130 and 136 PWIDs with and without psychiatric conditions were analyzed. Among PWIDs with mental disorders, 110 and 74 were diagnosed with MDE and PS, respectively. TL attrition was significantly associated with hepatitis C virus-infected PWIDs with MDE or PS (adjusted odds ratio [OR]: 0.53 [0.36; 0.80] and 0.59 [0.39; 0.88], respectively). TL attrition was even stronger when PWIDs cumulated at least two episodes of major depressive disorders. On the other hand, no difference was observed in mtDNA alterations between groups. The telomeric age difference with drug users without a diagnosis of psychiatric condition was estimated during 4.2-12.8 years according to the number of MDEs, making this group more prone to age-related diseases.},
}
@article {pmid35777725,
year = {2022},
author = {Gampawar, P and Schmidt, R and Schmidt, H},
title = {Telomere length and brain aging: A systematic review and meta-analysis.},
journal = {Ageing research reviews},
volume = {80},
number = {},
pages = {101679},
doi = {10.1016/j.arr.2022.101679},
pmid = {35777725},
issn = {1872-9649},
mesh = {Aged ; *Aging/genetics/psychology ; Brain ; Cognition ; Female ; Humans ; Leukocytes/chemistry ; *Telomere ; Telomere Shortening ; },
abstract = {The current evidence on the association of leukocyte telomere length (LTL) with age-related structural and cognitive changes in the brain is mixed. Herein conforming to PRISMA 2020 guidelines, we performed a systematic review and meta-analysis using data from 27 observational studies in non-demented individuals. We used effect size and p-value based meta-analysis methods considering marked heterogeneity among studies. We found that the longer LTL was associated with higher brain volume (β = 0.43, 95%CI: 0.36-0.50%, p = 0.008, N = 1102) and with higher global cognition (β = 0.01; 95%CI: 0.00-0.02, p = 0.03, N = 19609) by effect size based meta-analysis and with brain volume, hippocampal volume, global cognition, cognitive domains of attention/speed as well as executive functions by p-value based meta-analysis. No significant association of LTL with brain white matter hyperintensities was detected. Furthermore, the evidence strongly suggests a subgroup-specific canonical effect of telomeres, notably in older individuals and females. In conclusion, we provide meta-analytic evidence on the beneficial effect of telomeres on brain structure as well as cognition and advocate for a beneficial subgroup-specific effect that warrants further attention.},
}
@article {pmid35775462,
year = {2022},
author = {Iannuzzi, A and Albarella, S and Parma, P and Galdiero, G and D'Anza, E and Pistucci, R and Peretti, V and Ciotola, F},
title = {Characterization of telomere length in Agerolese cattle breed, correlating blood and milk samples.},
journal = {Animal genetics},
volume = {53},
number = {5},
pages = {676-679},
pmid = {35775462},
issn = {1365-2052},
mesh = {Aging ; Animals ; Cattle/genetics ; Dairying/methods ; Female ; Lactation ; *Longevity ; *Milk ; Telomere/genetics ; },
abstract = {Studies into telomere length in cattle are relatively recent and have focused mainly on the Holstein Friesian cattle breed, making it arduous to evaluate the correlation with ageing due to the early age of culling in this breed. Telomere length provides information about the productive lifespan and the quality of farm management, complying with the 'One Health' approach. This study evaluated telomere length in Agerolese cattle, an autochthonous dairy breed characterized by a long productive lifespan (13 years). Multiplex quantitative PCR estimated telomere length in DNA extracted from blood and milk matrices. Interestingly, the results showed longer telomeres in Agerolese (compared to the Holstein Friesian cattle control group), with a negative correlation between telomere length and increasing age and a synchronous trend between blood and milk samples, with a positive correlation between them.},
}
@article {pmid35773409,
year = {2022},
author = {Barnes, RP and de Rosa, M and Thosar, SA and Detwiler, AC and Roginskaya, V and Van Houten, B and Bruchez, MP and Stewart-Ornstein, J and Opresko, PL},
title = {Telomeric 8-oxo-guanine drives rapid premature senescence in the absence of telomere shortening.},
journal = {Nature structural &amp; molecular biology},
volume = {29},
number = {7},
pages = {639-652},
pmid = {35773409},
issn = {1545-9985},
support = {P30 CA047904/CA/NCI NIH HHS/United States ; R01 CA207342/CA/NCI NIH HHS/United States ; K99 ES033771/ES/NIEHS NIH HHS/United States ; R01 EB017268/EB/NIBIB NIH HHS/United States ; R35 ES030396/ES/NIEHS NIH HHS/United States ; F32 AG067710/AG/NIA NIH HHS/United States ; R35 ES031638/ES/NIEHS NIH HHS/United States ; },
mesh = {Cellular Senescence/genetics ; DNA/metabolism ; DNA Damage ; *Guanine ; Humans ; Oxidative Stress ; Telomere/metabolism ; *Telomere Shortening ; },
abstract = {Oxidative stress is a primary cause of cellular senescence and contributes to the etiology of numerous human diseases. Oxidative damage to telomeric DNA has been proposed to cause premature senescence by accelerating telomere shortening. Here, we tested this model directly using a precision chemoptogenetic tool to produce the common lesion 8-oxo-guanine (8oxoG) exclusively at telomeres in human fibroblasts and epithelial cells. A single induction of telomeric 8oxoG is sufficient to trigger multiple hallmarks of p53-dependent senescence. Telomeric 8oxoG activates ATM and ATR signaling, and enriches for markers of telomere dysfunction in replicating, but not quiescent cells. Acute 8oxoG production fails to shorten telomeres, but rather generates fragile sites and mitotic DNA synthesis at telomeres, indicative of impaired replication. Based on our results, we propose that oxidative stress promotes rapid senescence by producing oxidative base lesions that drive replication-dependent telomere fragility and dysfunction in the absence of shortening and shelterin loss.},
}
@article {pmid35769259,
year = {2022},
author = {Robinson, H and Ali, SI and Diaz-Hernandez, ME and Lopez-Gonzalez, R},
title = {Telomere Attrition in Induced Pluripotent Stem Cell-Derived Neurons From ALS/FTD-Related C9ORF72 Repeat Expansion Carriers.},
journal = {Frontiers in cell and developmental biology},
volume = {10},
number = {},
pages = {874323},
pmid = {35769259},
issn = {2296-634X},
abstract = {The GGGGCC (G4C2) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dysregulated DNA damage response and the generation of reactive oxygen species (ROS) have been postulated as major drivers of toxicity in C9ORF72 pathogenesis. Telomeres are tandem-repeated nucleotide sequences that are located at the end of chromosomes and protect them from degradation. Interestingly, it has been established that telomeres are sensitive to ROS. Here, we analyzed telomere length in neurons and neural progenitor cells from several induced pluripotent stem cell (iPSC) lines from control subjects and C9ORF72 repeat expansion carriers. We found an age-dependent decrease in telomere length in two-month-old iPSC-derived motor neurons from C9ORF72 carriers as compared to control subjects and a dysregulation in the protein levels of shelterin complex members TRF2 and POT1.},
}
@article {pmid35769005,
year = {2022},
author = {Choi, BE and Lee, HT},
title = {DNA-RNA hybrid G-quadruplex tends to form near the 3' end of telomere overhang.},
journal = {Biophysical journal},
volume = {121},
number = {15},
pages = {2962-2980},
pmid = {35769005},
issn = {1542-0086},
mesh = {DNA/chemistry/genetics ; DNA, Single-Stranded ; *G-Quadruplexes ; *RNA/chemistry ; Telomere/genetics/metabolism ; },
abstract = {Telomeric repeat-containing RNA (TERRA) has been suggested to participate in telomere maintenance. TERRA consisting of UUAGGG repeats is capable of forming an intermolecular G-quadruplex (GQ) with single-stranded TTAGGG-repeat DNA in the telomere 3' overhang. To explore the structural features and potential functions of this DNA-RNA hybrid GQ (HGQ), we used single-molecule FRET to study the folding patterns of DNA with four to seven telomeric tandem repeats annealed with a short RNA consisting of two or five telomeric repeats. Our data highlight that RNA prefers to form DNA-RNA HGQ near the 3' end of telomeric DNA. Furthermore, the unfolding of secondary structures by a complementary C-rich sequence was observed for DNA GQ but not for DNA-RNA HGQ, which demonstrated the enhanced stability of the telomere 3' end via hybridization with RNA. These conformational and physical properties of telomeric DNA-RNA HGQ suggest that TERRA might limit access to the 3' end of the telomeric DNA overhang, which is known to be critical for the interaction with telomerase and other telomere-associated proteins.},
}
@article {pmid35760212,
year = {2022},
author = {Buttet, M and Bagheri, R and Ugbolue, UC and Laporte, C and Trousselard, M and Benson, A and Bouillon-Minois, JB and Dutheil, F},
title = {Effect of a lifestyle intervention on telomere length: A systematic review and meta-analysis.},
journal = {Mechanisms of ageing and development},
volume = {206},
number = {},
pages = {111694},
doi = {10.1016/j.mad.2022.111694},
pmid = {35760212},
issn = {1872-6216},
mesh = {Exercise ; Female ; Humans ; *Life Style ; Male ; Nutritional Status ; *Telomere ; },
abstract = {BACKGROUND: We conducted a systematic review and meta-analysis to assess the effects of lifestyle intervention on telomere length (TL).<br><br>METHOD: Four databases were searched for studies reporting TL in leukocytes, before and after a lifestyle intervention. We computed random-effects meta-analysis on TL within intervention and control group after versus before intervention, and on changes in TL between groups. Sensitivity analyses and Meta-regression were conducted.<br><br>RESULTS: We included 20 studies in the systematic review (2995 participants, mean 50.3 years old, 77% women, 2045 following an intervention and 950 controls) and 19 in the meta-analysis. TL were similar at baseline between intervention and control groups. The physical activity &#xb1;&#xa0;diet group had an increase in TL (Effect size 0.17, 95%CI 0.03-0.31, p&#xa0;=&#xa0;0.020) using changes within the intervention group, whereas TL shortened in the control group (-0.32, -0.61 to -0.02, p&#xa0;=&#xa0;0.037). TL was longer in the physical activity &#xb1;&#xa0;diet intervention group (0.24, 0.08-0.40, p&#xa0;=&#xa0;0.004) compared to controls after the intervention. Sensitivity analysis gave similar results. Meta-regressions demonstrated that combining strength and endurance exercise increased TL more than endurance alone or strength alone.<br><br>CONCLUSION: A lifestyle intervention with physical activity &#xb1;&#xa0;diet can increase telomere length, independently of population characteristics or baseline TL.},
}
@article {pmid35760210,
year = {2022},
author = {Llorente, H and Perez-Rivera, JA and Perez-Nieto, M and Cieza-Borrella, C and Pastor, I and Novo-Veleiro, I and Fernández-Mateos, J and Chamorro, AJ and Crecente-Otero, P and Laso, FJ and González-Sarmiento, R and Marcos, M},
title = {Genetic susceptibility to telomere shortening through the rs2293607 polymorphism is associated with a greater risk of alcohol use disorder.},
journal = {Mechanisms of ageing and development},
volume = {206},
number = {},
pages = {111693},
doi = {10.1016/j.mad.2022.111693},
pmid = {35760210},
issn = {1872-6216},
mesh = {*Alcoholism/genetics ; Genetic Predisposition to Disease ; Humans ; Male ; Polymorphism, Single Nucleotide ; RNA/genetics ; Telomerase/*genetics ; Telomere/genetics ; Telomere Shortening ; },
abstract = {Telomere shortening is usually considered a biomarker of ageing. Harmful alcohol use promotes accelerated biological ageing and alcohol use disorders (AUDs) are associated with short telomere length (TL). This study was conducted to examine the relationship of TL to AUD and determine whether single nucleotide polymorphisms (SNPs) in TERC and TERT modulate this association. For this purpose, we genotyped TERC SNPs rs2293607, rs12696304, and rs16847897 and TERT SNPs rs2735940, rs2736100, and rs2736098 in 308 male patients with AUD and 255 sex-matched healthy controls and measured TL in a subset of 99 patients and 99 controls paired by age and smoking status. Our results showed that the mean TL was shorter in patients with AUD than in controls. The area under the ROC curve was 0.70 (P < 0.001). The GG genotype of TERC rs2293607 was more common among patients with AUD than among controls (9.8% vs. 5.1%; P = 0.038). No difference was found for the other SNPs. Carriers of the GG genotype of rs2293607 had shorter telomeres than did allele A carriers. In conclusion, patients with AUD had shorter telomeres. Genetic susceptibility to telomere shortening through the rs2293607 SNP is associated with a greater risk of AUD.},
}
@article {pmid35759567,
year = {2022},
author = {Madaeva, IM and Kurashova, NA and Ukhinov, EB and Berdina, ON and Semenova, NV and Madaev, VV and Kolesnikova, LI and Kolesnikov, SI},
title = {[Changes in the telomeres length in patients with obstructive sleep apnea after continuous positive airway pressure therapy: a pilot study].},
journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova},
volume = {122},
number = {5. Vyp. 2},
pages = {52-57},
doi = {10.17116/jnevro202212205252},
pmid = {35759567},
issn = {1997-7298},
mesh = {*Continuous Positive Airway Pressure ; Humans ; Hypoxia ; Male ; Middle Aged ; Pilot Projects ; *Sleep Apnea, Obstructive/diagnosis/genetics/therapy ; Telomere/genetics ; },
abstract = {OBJECTIVE: To evaluate a relative telomere length in patients with obstructive sleep apnea (OSA) before and after a 6-month course of continuous positive airway pressure (CPAP) therapy.<br><br>MATERIAL AND METHODS: Seventy-five men participated in the study, including 50 men with OSA (the main group 1) and 25 men without OSA (the control group). The average age in the total group was 53.4&#xb1;3.6 years. Thirty-five men completed the study (the main group 2). According to the design, night polysomnography (PSG) was performed for all the subjects, blood sampling to assess the length of telomeres was carried out in the morning according to the standard method. The values of the relative telomere length were obtained using the difference between the values of the threshold cycles for telomeric DNA and the reference gene albumin (&#x2206;CCt). After clarifying the diagnosis, CPAP was applied for 6 months.<br><br>RESULTS: Statistically significant indicators of PSG were revealed: a decrease in NREM 3 in patients with OSA compared to controls (89.3&#xb1;15.8 versus 150&#xb1;23.4 minutes), an increase in NREM1-2 in OSA (296.2&#xb1;31.1 and 170.1&#xb1;24.5, respectively), REM was 84.6&#xb1;15.4 in the main group and 118.5&#xb1;19.5 in the control group. CPAP therapy conducted for 6 months (at least 4-5 nights a week, lasting at least 5-6 hours of night sleep) demonstrated a significant improvement in the qualitative and quantitative parameters of sleep. In patients of the main group 1, there is a shortening of the telomere length compared with the control group (p<0.001). With the elimination of hypoxia and improvement of the structure of sleep after CPAP, there was an increase in the telomere lengths in the main group 1 from 0.28 [0.24-0.29] to 0.32 [0.30-0.34] in the main group 2 (p=0.03). The telomers length in the control group was 0.53 [0.50-0.55].<br><br>CONCLUSION: Intermittent hypoxia and fragmentation of sleep in OSA leads to shortening of telomeres. CPAP, by eliminating the pathophysiological triggers of OSA, contributes to an increase in telomeres lengths and can slow down the premature aging in OSA.},
}
@article {pmid35748695,
year = {2022},
author = {Zhang, Y and Fu, J and Wang, K and Han, X and Yan, T and Su, Y and Li, Y and Lin, Z and Qin, P and Fu, C and Deng, XW and Zhou, D and Yang, Y and He, H},
title = {The telomere-to-telomere gap-free genome of four rice parents reveals SV and PAV patterns in hybrid rice breeding.},
journal = {Plant biotechnology journal},
volume = {20},
number = {9},
pages = {1642-1644},
pmid = {35748695},
issn = {1467-7652},
mesh = {Genome, Plant/genetics ; Hybrid Vigor ; Hybridization, Genetic ; *Oryza/genetics ; Plant Breeding ; Telomere/genetics ; },
}
@article {pmid35747346,
year = {2022},
author = {Isehunwa, OO and Warner, ET and Spiegelman, D and Zhang, Y and Palmer, JR and Kanaya, AM and Cole, SA and Tworoger, SS and Shields, LO and Gu, Y and Kent, BV and De Vivo, I and Shields, AE},
title = {Depression, religiosity, and telomere length in the Study on Stress, Spirituality, and Health (SSSH).},
journal = {International journal of mental health and addiction},
volume = {20},
number = {3},
pages = {1465-1484},
pmid = {35747346},
issn = {1557-1874},
support = {U01 HL041642/HL/NHLBI NIH HHS/United States ; R01 HL093009/HL/NHLBI NIH HHS/United States ; U01 CA176726/CA/NCI NIH HHS/United States ; U01 CA167552/CA/NCI NIH HHS/United States ; UL1 RR024131/RR/NCRR NIH HHS/United States ; U01 HL041652/HL/NHLBI NIH HHS/United States ; P30 DK098722/DK/NIDDK NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; R01 HL109319/HL/NHLBI NIH HHS/United States ; P30 DK092924/DK/NIDDK NIH HHS/United States ; R01 HL109284/HL/NHLBI NIH HHS/United States ; U01 HL065521/HL/NHLBI NIH HHS/United States ; R01 HL109301/HL/NHLBI NIH HHS/United States ; R01 HL109282/HL/NHLBI NIH HHS/United States ; P30 DK063720/DK/NIDDK NIH HHS/United States ; U01 HL041654/HL/NHLBI NIH HHS/United States ; U01 CA164974/CA/NCI NIH HHS/United States ; R01 CA067262/CA/NCI NIH HHS/United States ; R01 CA098663/CA/NCI NIH HHS/United States ; R01 CA163451/CA/NCI NIH HHS/United States ; UL1 TR001872/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; UM1 CA176726/CA/NCI NIH HHS/United States ; R01 CA058420/CA/NCI NIH HHS/United States ; R01 HL109315/HL/NHLBI NIH HHS/United States ; R01 HL120725/HL/NHLBI NIH HHS/United States ; U01 HL065520/HL/NHLBI NIH HHS/United States ; },
abstract = {Prospective studies on the association between depression and telomere length have produced mixed results and have been largely limited to European ancestry populations. We examined the associations between depression and telomere length, and the modifying influence of religion and spirituality, in four cohorts, each representing a different race/ethnic population. Relative leukocyte telomere length (RTL) was measured by a quantitative polymerase chain reaction. Our result showed that depression was not associated with RTL (percent difference: 3.0 95% CI: -3.9, 10.5; p = 0.41; p-heterogeneity across studies = 0.67) overall or in cohort-specific analyses. However, in cohort-specific analyses, there was some evidence of effect modification by the extent of religiosity or spirituality, religious congregation membership, and group prayer. Further research is needed to investigate prospective associations between depression and telomere length, and the resources of resilience including dimensions of religion and spirituality that may impact such dynamics in diverse racial/ethnic populations.},
}
@article {pmid35746868,
year = {2022},
author = {Deng, Y and Liu, S and Zhang, Y and Tan, J and Li, X and Chu, X and Xu, B and Tian, Y and Sun, Y and Li, B and Xu, Y and Deng, XW and He, H and Zhang, X},
title = {A telomere-to-telomere gap-free reference genome of watermelon and its mutation library provide important resources for gene discovery and breeding.},
journal = {Molecular plant},
volume = {15},
number = {8},
pages = {1268-1284},
doi = {10.1016/j.molp.2022.06.010},
pmid = {35746868},
issn = {1752-9867},
mesh = {Chromosome Mapping ; *Citrullus/genetics ; Genetic Association Studies ; Genome, Plant/genetics ; INDEL Mutation ; Plant Breeding ; Telomere ; },
abstract = {Watermelon, Citrullus lanatus, is the world's third largest fruit crop. Reference genomes with gaps and a narrow genetic base hinder functional genomics and genetic improvement of watermelon. Here, we report the assembly of a telomere-to-telomere gap-free genome of the elite watermelon inbred line G42 by incorporating high-coverage and accurate long-read sequencing data with multiple assembly strategies. All 11 chromosomes have been assembled into single-contig pseudomolecules without gaps, representing the highest completeness and assembly quality to date. The G42 reference genome is 369 321 829 bp in length and contains 24 205 predicted protein-coding genes, with all 22 telomeres and 11 centromeres characterized. Furthermore, we established a pollen-EMS mutagenesis protocol and obtained over 200 000 M1 seeds from G42 . In a sampling pool, 48 monogenic phenotypic mutations, selected from 223 M1 and 78 M2 mutants with morphological changes, were confirmed. The average mutation density was 1 SNP/1.69 Mb and 1 indel/4.55 Mb per M1 plant and 1 SNP/1.08 Mb and 1 indel/6.25 Mb per M2 plant. Taking advantage of the gap-free G42 genome, 8039 mutations from 32 plants sampled from M1 and M2 families were identified with 100% accuracy, whereas only 25% of the randomly selected mutations identified using the 97103v2 reference genome could be confirmed. Using this library and the gap-free genome, two genes responsible for elongated fruit shape and male sterility (ClMS1) were identified, both caused by a single base change from G to A. The validated gap-free genome and its EMS mutation library provide invaluable resources for functional genomics and genetic improvement of watermelon.},
}
@article {pmid35741087,
year = {2022},
author = {Ebata, H and Loo, TM and Takahashi, A},
title = {Telomere Maintenance and the cGAS-STING Pathway in Cancer.},
journal = {Cells},
volume = {11},
number = {12},
pages = {},
pmid = {35741087},
issn = {2073-4409},
mesh = {Humans ; Membrane Proteins/metabolism ; *Neoplasms/metabolism ; Nucleotidyltransferases/metabolism ; *Telomerase/metabolism ; Telomere/metabolism ; Tumor Microenvironment ; },
abstract = {Cancer cells exhibit the unique characteristics of high proliferation and aberrant DNA damage response, which prevents cancer therapy from effectively eliminating them. The machinery required for telomere maintenance, such as telomerase and the alternative lengthening of telomeres (ALT), enables cancer cells to proliferate indefinitely. In addition, the molecules in this system are involved in noncanonical pro-tumorigenic functions. Of these, the function of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which contains telomere-related molecules, is a well-known contributor to the tumor microenvironment (TME). This review summarizes the current knowledge of the role of telomerase and ALT in cancer regulation, with emphasis on their noncanonical roles beyond telomere maintenance. The components of the cGAS-STING pathway are summarized with respect to intercell communication in the TME. Elucidating the underlying functional connection between telomere-related molecules and TME regulation is important for the development of cancer therapeutics that target cancer-specific pathways in different contexts. Finally, strategies for designing new cancer therapies that target cancer cells and the TME are discussed.},
}
@article {pmid35738556,
year = {2022},
author = {Miller, JG and Buthmann, JL and Gotlib, IH},
title = {Hippocampal volume indexes neurobiological sensitivity to the effect of pollution burden on telomere length in adolescents.},
journal = {New directions for child and adolescent development},
volume = {2022},
number = {181-182},
pages = {155-172},
pmid = {35738556},
issn = {1534-8687},
support = {R37 MH101495/MH/NIMH NIH HHS/United States ; Young Investigator Award 23819//Brain and Behavior Research Foundation/ ; R37MH1014945/NH/NIH HHS/United States ; //Klingenstein Third Generation Foundation/ ; },
mesh = {Adolescent ; Child ; Environmental Exposure/adverse effects ; *Environmental Pollutants ; Environmental Pollution ; Hippocampus ; Humans ; *Telomere/genetics ; },
abstract = {Exposure to environmental pollutants has been associated with cellular aging in children and adolescents. Individuals may vary, however, in their sensitivity or vulnerability to the effects of environmental pollutants. Larger hippocampal volume has emerged as a potential index of increased sensitivity to social contexts. In exploratory analyses (N = 214), we extend work in this area by providing evidence that larger hippocampal volume in early adolescence reflects increased sensitivity to the effect of neighborhood pollution burden on telomere length (standardized β = -0.40, 95% CI[-0.65, -0.15]). In contrast, smaller hippocampal volume appears to buffer this association (standardized β = 0.02). In youth with larger hippocampal volume, pollution burden was indirectly associated with shorter telomere length approximately 2 years later through shorter telomere length at baseline (indirect standardized β = -0.25, 95% CI[-0.40, 0.10]). For these youth, living in high or low pollution-burdened neighborhoods may predispose them to develop shorter or longer telomeres, respectively, later in adolescence.},
}
@article {pmid35736788,
year = {2022},
author = {Xiong, K and Ouyang, C and Liu, J and Karges, J and Lin, X and Chen, X and Chen, Y and Wan, J and Ji, L and Chao, H},
title = {Chiral Ru[II] -Pt[II] Complexes Inducing Telomere Dysfunction against Cisplatin-Resistant Cancer Cells.},
journal = {Angewandte Chemie (International ed. in English)},
volume = {61},
number = {33},
pages = {e202204866},
doi = {10.1002/anie.202204866},
pmid = {35736788},
issn = {1521-3773},
mesh = {Animals ; *Antineoplastic Agents/pharmacology/therapeutic use ; Cisplatin/metabolism/pharmacology ; *Coordination Complexes/metabolism/pharmacology/therapeutic use ; DNA ; *G-Quadruplexes ; Mice ; *Neoplasms ; *Ruthenium/metabolism/pharmacology ; *Telomerase/genetics ; Telomere ; },
abstract = {The application of G-quadruplex stabilizers presents a promising anticancer strategy. However, the molecular crowding conditions within cells diminish the potency of current G-quadruplex stabilizers. Herein, chiral Ru[II] -Pt[II] dinuclear complexes were developed as highly potent G-quadruplex stabilizers even under challenging molecular crowding conditions. The compounds were encapsulated with biotin-functionalized DNA cages to enhance sub-cellular localization and provide cancer selectivity. The nanoparticles were able to efficiently inhibit the endogenous activities of telomerase in cisplatin-resistant cancer cells and cause cell death by apoptosis. The nanomaterials demonstrated high antitumor activity towards cisplatin-resistant tumor cells as well as tumor-bearing mice. To the best of our knowledge, this study presents the first example of a Ru[II] -Pt[II] dinuclear complex as a G-quadruplex stabilizer with an anti-cancer effect towards drug-resistant tumors inside an animal model.},
}
@article {pmid35733342,
year = {2022},
author = {Benelli, R and Weiss, M},
title = {Probing local chromatin dynamics by tracking telomeres.},
journal = {Biophysical journal},
volume = {121},
number = {14},
pages = {2684-2692},
pmid = {35733342},
issn = {1542-0086},
mesh = {*Chromatin ; Interphase ; Motion ; Polymers ; *Telomere ; },
abstract = {Chromatin dynamics is key for cell viability and replication. In interphase, chromatin is decondensed, allowing the transcription machinery to access a plethora of DNA loci. Yet, decondensed chromatin occupies almost the entire nucleus, suggesting that DNA molecules can hardly move. Recent reports have even indicated that interphase chromatin behaves like a solid body on mesoscopic scales. To explore the local chromatin dynamics, we have performed single-particle tracking on telomeres under varying conditions. We find that mobile telomeres feature, under all conditions, a strongly subdiffusive, antipersistent motion that is consistent with the monomer motion of a Rouse polymer in viscoelastic media. In addition, telomere trajectories show intermittent accumulations in local niches at physiological conditions, suggesting that the surrounding chromatin reorganizes on these timescales. Reducing the temperature or exposing cells to osmotic stress resulted in a significant reduction of mobile telomeres and the number of visited niches. Altogether, our data indicate a vivid local chromatin dynamics, akin to a semidilute polymer solution, unless perturbations enforce a more rigid or entangled state of chromatin.},
}
@article {pmid35732925,
year = {2022},
author = {Mao, Y and Zhang, G},
title = {Publisher Correction: A complete, telomere-to-telomere human genome sequence presents new opportunities for evolutionary genomics.},
journal = {Nature methods},
volume = {19},
number = {7},
pages = {899},
doi = {10.1038/s41592-022-01551-x},
pmid = {35732925},
issn = {1548-7105},
}
@article {pmid35730364,
year = {2022},
author = {Cozzolino, M and Seli, E},
title = {Mitochondrial dysfunction caused by targeted deletion of Mfn1 does not result in telomere shortening in oocytes.},
journal = {Zygote (Cambridge, England)},
volume = {30},
number = {5},
pages = {735-737},
doi = {10.1017/S0967199422000089},
pmid = {35730364},
issn = {1469-8730},
mesh = {Animals ; GTP Phosphohydrolases/genetics/metabolism ; *Infertility ; Mice ; Mitochondria/metabolism ; Oocytes/physiology ; Reactive Oxygen Species/metabolism ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere Shortening ; },
abstract = {Telomere shortening during oocyte growth and development is related to reproductive ageing and infertility. The main mechanism involved in the maintenance of telomeres is based on telomerase activity, a specialized enzyme complex, which is capable of adding TTAGGG repeats at the ends of the chromosomes. Mitochondrial dysfunction may cause progressive shortening of telomeres by promoting the generation of reactive oxygen species. Mitofusin-1 is a protein required for mitochondrial fusion. Mice with the mitofusin-1 (Mfn1) deletion in the oocyte are characterized by accelerated follicular depletion and infertility, associated with defective oocyte maturation and follicular development. We hypothesized whether mitochondrial dysfunction in oocytes with targeted deletion of Mfn1 causes telomere shortening. We analyzed telomere length in oocyte and somatic cells in 3-, 6- and 9-month-old Mfn1[-/-] and wild-type mice. Immunofluorescence in oocyte mice of TRF1 and H2A.X was assessed to evaluate the interplay between the end-protection functions and the response to DNA damage occurring inside the telomeric repeats. Mitochondrial dysfunction due to the deletion of Mfn1 does not seem to affect telomere length in mouse oocytes.},
}
@article {pmid35725832,
year = {2022},
author = {Qin, S and Chen, X and Xu, Z and Li, T and Zhao, S and Hu, R and Zhu, J and Li, Y and Yang, Y and Liu, M},
title = {Telomere G-triplex lights up Thioflavin T for RNA detection: new wine in an old bottle.},
journal = {Analytical and bioanalytical chemistry},
volume = {414},
number = {20},
pages = {6149-6156},
pmid = {35725832},
issn = {1618-2650},
support = {22174150//National Natural Science Foundation of China/ ; },
mesh = {Benzothiazoles ; *Biosensing Techniques/methods ; *COVID-19 ; DNA/genetics ; Fluorescent Dyes ; *G-Quadruplexes ; Humans ; Limit of Detection ; RNA ; SARS-CoV-2 ; Spectrometry, Fluorescence/methods ; Telomere ; },
abstract = {Few reports are found working on the features and functions of the human telomere G-triplex (ht-G3) though the telomere G-quadruplex has been intensely studied and widely implemented to develop various biosensors. We herein report that ht-G3 lights up Thioflavin T (ThT) and establish a sensitive biosensing platform for RNA detection by introducing a target recycling strategy. An optimal condition was selected out for ht-G3 to promote ThT to generate a strong fluorescence. Accordingly, an ht-G3-based molecular beacon was successfully designed against the corresponding RNA sequence of the SARS-CoV-2 N-gene. The sensitivity for the non-amplified RNA target achieves 0.01 nM, improved 100 times over the conventional ThT-based method. We believe this ht-G3/ThT-based label-free strategy could be widely applied for RNA detection.},
}
@article {pmid35721750,
year = {2022},
author = {Hu, L and Zhang, Q and Bai, Y and Hu, G and Li, J},
title = {Triglyceride-Glucose Index Correlate With Telomere Length in Healthy Adults From the National Health and Nutrition Examination Survey.},
journal = {Frontiers in endocrinology},
volume = {13},
number = {},
pages = {844073},
pmid = {35721750},
issn = {1664-2392},
mesh = {Adult ; Blood Glucose/analysis ; Glucose ; Humans ; *Insulin Resistance/genetics ; Nutrition Surveys ; Telomere/chemistry/genetics ; Triglycerides ; },
abstract = {AIM: The present investigation was designed to test the association between leukocyte telomere length (LTL) and two simple markers of insulin resistance, that is, homeostatic model assessment of insulin resistance (HOMA-IR) and triglyceride-glucose (TyG) index in U.S. adults without metabolic diseases.<br><br>METHODS: A total of 6489 U.S. adults without diabetes from NHANES 1999-2002 were analyzed. TyG index was calculated as ln [fasting triglycerides (mg/dL) &#xd7; fasting glucose (mg/dL)/2]. HOMA-Index was calculated as fasting plasma glucose (mmol/L) &#xd7; fasting serum insulin (mU/mL)/22.5. LTL was obtained using the quantitative polymerase chain reaction method. Multivariate linear regression analysis was assessed to evaluate the association of TyG index HOMA-IR with LTL. We further conducted a generalized additive model (GAM) and a fitted smoothing curve with penalized spline method.<br><br>RESULTS: It was found that the mean LTL was 5796.1 bp in the measured healthy adults. Overall, TyG index was significantly associated with LTL, while HOMA-IR was not. Compared with participants in tertile 1 of the TyG index, the &#x3b2; (95% CI) for those in the second (8.27 to 8.77) and third (&#x2265; 8.77) were -4.31 (95% CI: -48.12~39.49) and -95.98 (95% CI: -145.08~-46.89), respectively. Subjects with TyG index &#x2265; 8.77 had statistically significant shorter LTL (&#x3b2; = -93.33, 95%CI: -134.33~-52.32), compared with TyG index < 8.77. We further explored a dose-response relation between TyG index by a decile approach [&#x2264; 7.81 (reference), 7.81-8.04, 8.04-8.21, 8.21-8.37, 8.37-8.52, 8.52-8.68, 8.68-8.83, 8.83-9.03, 9.03-9.33, and >9.33] and LTL. Five subgroups (TyG index 7.81-8.04, 8.04-8.21, 8.21-8.37, 8.37-8.52, and 8.52-8.68) did not show significant effect on LTL; while there was a significantly shorter LTL for participants with the TyG index > 8.68, supporting a threshold effect of TyG index on LTL.<br><br>CONCLUSIONS: The results suggested that higher TyG index (> 8.68) was closely related to shorter LTL and the TyG index was better associated with LTL than HOMA-IR.},
}
@article {pmid35721024,
year = {2022},
author = {Long, L and Meng, Z and Jia, Z and Tang, X},
title = {Exploring the Association of Leukocyte Telomere Length and Hearing Threshold Shifts of Adults in the United States.},
journal = {Frontiers in aging neuroscience},
volume = {14},
number = {},
pages = {770159},
pmid = {35721024},
issn = {1663-4365},
abstract = {BACKGROUND: Although telomere length has a significant relationship with various age-related diseases, studies on its relationship with hearing status in adults are limited and equivocal. This study investigated the associations between mean telomere length (MTL) and low-, speech-, and high-frequency hearing threshold shifts of adults in the United States.<br><br>METHODS: A total of 2,027 adults, aged 20-69 years, from the National Health and Nutrition Examination Surveys (NHANES, 1999-2002) were included in the analytic sample. The quantitative polymerase chain reaction method was used for the MTL assay, and MTL was expressed using the telomere-to-single copy gene (T/S) ratio. Hearing loss was defined as a pure-tone average (PTA) for the better ear at &#x2265; 20 dB HL at frequencies 500, 1,000, 2,000, and 4,000 Hz. Univariate and multivariate linear regression analyses and smooth curve fittings were conducted to evaluate the correlation between MTL and low-, speech-, and high-frequency hearing levels.<br><br>RESULTS: The mean age of the participants was 40.60 &#xb1; 12.76 years, including 952 men (weighted, 48.67%) and 303 (weighted, 12.88%) participants with hearing loss. After adjusting for potential confounders in the multivariate linear regression model, the relationship between MTL and hearing thresholds was not statistically significant. Smooth curve fittings indicated a non-linear relationship between MTL and high-frequency PTA hearing threshold shifts. MTL was inversely related to high-frequency PTA to the turning point (T/S ratio = 0.82) (adjusted &#x3b2;-21.45, 95% CI -37.28, -5.62; P = 0.008). When the T/S ratio exceeded0.82, MTL was not associated with high-frequency PTA (adjusted &#x3b2;0.18, 95% CI -2.21, 2.57; P = 0.8809).<br><br>CONCLUSION: Our findings revealed that MTL was associated with high-frequency PTA hearing threshold shifts of adults in the United States in a non-linear manner.},
}
@article {pmid35719148,
year = {2022},
author = {Khosravaniardakani, S and Bokov, DO and Mahmudiono, T and Hashemi, SS and Nikrad, N and Rabieemotmaen, S and Abbasalizad-Farhangi, M},
title = {Obesity Accelerates Leukocyte Telomere Length Shortening in Apparently Healthy Adults: A Meta-Analysis.},
journal = {Frontiers in nutrition},
volume = {9},
number = {},
pages = {812846},
pmid = {35719148},
issn = {2296-861X},
abstract = {BACKGROUND: Shorter telomere length is associated with numerous comorbidities. Several studies have investigated the role of obesity in telomere shortening. In the current systematic review and meta-analysis, we summarized the results of studies that evaluated the association between obesity and telomere length.<br><br>METHODS: A systematic search from Scopus, PubMed, Embase, and ProQuest electronic databases up to 19 March 2021 without language restriction was performed and after data extraction and screening, 19 manuscripts were eligible to be included in the final meta-synthesis.<br><br>RESULTS: The highest category of telomere length was associated with an approximate 0.75 kg/m[2] reduction in body mass index (BMI; WMD = -0.75 kg/m[2]; CI = -1.19, -0.31; p < 0.001; I [2] = 99.4%). Moreover, overweight/obese individuals had 0.036 kbp shorter telomere length compared with non-overweight/obese adults (WMD = -0.036; CI = -0.05, -0.02; p = 0.030; I [2] = 100%). According to the results of subgroupings, continent, age, and sample size could be possible sources of heterogeneity.<br><br>CONCLUSION: From the results, it was clear that obesity was associated with shorter telomere length. Because of the observational design of included studies, the causality inference of results should be done with caution; thus, further longitudinal studies are warranted for better inference of causal association.},
}
@article {pmid35715571,
year = {2022},
author = {Courtney, MG and Roberts, J and Godde, K},
title = {Author Correction: How social/environmental determinants and inflammation affect salivary telomere length among middle-older adults in the health and retirement study.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {10195},
doi = {10.1038/s41598-022-14839-x},
pmid = {35715571},
issn = {2045-2322},
}
@article {pmid35715316,
year = {2022},
author = {Guérin, C and Crestani, B and Dupin, C and Kawano-Dourado, L and Ba, I and Kannengiesser, C and Borie, R},
title = {[Telomeres and lung].},
journal = {Revue des maladies respiratoires},
volume = {39},
number = {7},
pages = {595-606},
doi = {10.1016/j.rmr.2022.03.011},
pmid = {35715316},
issn = {1776-2588},
mesh = {Cell Cycle Proteins/genetics ; Humans ; *Idiopathic Pulmonary Fibrosis/diagnosis/epidemiology/genetics ; Lung ; *Lung Diseases, Interstitial/diagnosis/epidemiology/genetics ; Nuclear Proteins/genetics ; Telomere ; Vital Capacity ; },
abstract = {Genetic studies of familial forms of interstitial lung disease (ILD) have led to the discovery of telomere-related gene (TRG) mutations (TERT, TERC, RTEL1, PARN, DKC1, TINF2, NAF1, NOP10, NHP2, ACD, ZCCH8) in approximately 30% of familial ILD forms. ILD patients with TRG mutation are also subject to extra-pulmonary (immune-hematological, hepatic and/or mucosal-cutaneous) manifestations. TRG mutations may be associated not only with idiopathic pulmonary fibrosis (IPF), but also with non-IPF ILDs, including idiopathic and secondary ILDs, such as hypersensitivity pneumonitis (HP). The presence of TRG mutation may also be associated with an accelerated decline of forced vital capacity (FVC) or poorer prognosis after lung transplantation, notwithstanding which, usual ILD treatments may be proposed. Lastly, patients and their relatives are called upon to reduce their exposure to environmental lung toxicity, and are likely to derive benefit from specific genetic counseling and pre-symptomatic genetic testing.},
}
@article {pmid35713713,
year = {2022},
author = {Viblanc, VA and Criscuolo, F and Sosa, S and Schull, Q and Boonstra, R and Saraux, C and Lejeune, M and Roth, JD and Uhlrich, P and Zahn, S and Dobson, FS},
title = {Telomere dynamics in female Columbian ground squirrels: recovery after emergence and loss after reproduction.},
journal = {Oecologia},
volume = {199},
number = {2},
pages = {301-312},
pmid = {35713713},
issn = {1432-1939},
support = {The present study was supported by a USIAS fellowship//University of Strasbourg/ ; by a Gutenberg Chair awarded to F.S. Dobson.//University of Strasbourg/ ; },
mesh = {Animals ; Female ; Longitudinal Studies ; Male ; Reproduction/physiology ; Sciuridae/genetics ; *Telomere ; *Telomere Homeostasis ; },
abstract = {Telomeres are specialized non-coding DNA sequences located at the end of chromosomes and that protect genetic information. Telomere loss over lifespan is generally viewed as a phenomenon associated with aging in animals. Recently, telomere elongation after hibernation has been described in several mammals. Whether this pattern is an adaptation to repair DNA damage caused during rewarming from torpor or if it coevolved as a mechanism to promote somatic maintenance in preparation for the upcoming reproductive effort remains unclear. In a longitudinal study measuring telomere length using buccal swabs, we tested if telomere elongation was related to reproductive success in wild adult female Columbian ground squirrels (Urocitellus columbianus) that were monitored from emergence from hibernation to the end of the reproductive season. We found three key results. First, female telomere length increased at the start of the breeding season, both in breeding and non-breeding individuals. Second, post-emergence telomere lengthening was unrelated to female future reproductive output. Third, telomere length decreased in breeding females during lactation, but remained stable in non-breeding females over a similar period. Within breeders, telomeres shortened more in females producing larger and heavier litters. We concluded that telomere lengthening after hibernation did not constrain immediate female reproductive capacities. It was more likely to be part of the body recovery process that takes place after hibernation. Telomere erosion that occurs after birth may constitute a physiological cost of female reproduction.},
}
@article {pmid35710461,
year = {2023},
author = {Liu, W and Wang, N and Zhu, J and Zhang, M and Lu, L and Pan, H and He, X and Yi, H and Tang, S},
title = {The relationship between relative telomere length and anti-tuberculosis drug-induced hepatitis : A case-control study.},
journal = {Therapie},
volume = {78},
number = {3},
pages = {259-266},
doi = {10.1016/j.therap.2022.05.007},
pmid = {35710461},
issn = {1958-5578},
mesh = {Humans ; Case-Control Studies ; *Antitubercular Agents/adverse effects ; Risk Factors ; *Hepatitis ; Telomere ; },
abstract = {AIM: Anti-tuberculosis drug-induced hepatitis (AT-DIH) is a common and serious adverse drug reaction of tuberculosis treatment. Evidence demonstrated that many factors could affect the occurrence of AT-DIH, such as ageing, smoking, alcohol, oxidative stress, etc., while these factors could also promote telomere shortening. Therefore, relative telomere length (RTL) is indirectly related to the occurrence of AT-DIH. The present study aimed to explore and validate this relationship in Chinese tuberculosis patients.<br><br>METHODS: A 1:4 matched case-control study was undertaken using 202 AT-DIH cases and 808 controls. Logistic regression models were used to estimate the association between RTL and AT-DIH with odds ratios (ORs) and 95% confidence intervals (CIs). The area under receiver operating characteristic curve (AUC) was calculated to estimate the discriminative performance for distinguishing AT-DIH cases from controls.<br><br>RESULTS: The average RTL in AT-DIH cases was significantly shorter than that in controls (1.24 vs. 1.46, P=0.002). Patients with longer RTL were at a reduced risk of AT-DIH (OR=0.79, 95% CI: 0.66-0.94, P=0.009), and a dose-response relationship also existed between RTL and lower AT-DIH risk (P for trend=0.012). Under the optimal RTL cut-off value of 1.22, the corresponding AUCs were 0.57 (95% CI: 0.53-0.62, P=0.001) in the univariate model and 0.62 (95% CI: 0.57-0.66, P<0.001) in the multivariate model.<br><br>CONCLUSION: This study showed that the shorter the RTL, the higher the risk of AT-DIH during an anti-tuberculosis treatment. The short RTL could potentially serve as a risk factor or a predictive test of the hepatotoxic risk associated with anti-tuberculosis treatments.},
}
@article {pmid35707279,
year = {2022},
author = {Gu, W and Lin, Z and Zhao, S and Wang, G and Shen, Z and Liu, W and Cai, Y and Wang, K and Wan, CC and Yan, T},
title = {Research Progress on G-Quadruplexes in Human Telomeres and Human Telomerase Reverse Transcriptase (hTERT) Promoter.},
journal = {Oxidative medicine and cellular longevity},
volume = {2022},
number = {},
pages = {2905663},
pmid = {35707279},
issn = {1942-0994},
mesh = {Animals ; *G-Quadruplexes ; Humans ; Ligands ; Mice ; Promoter Regions, Genetic/genetics ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {The upregulation telomerase activity is observed in over 85-90% of human cancers and provides an attractive target for cancer therapies. The high guanine content in the telomere DNA sequences and the hTERT promoter can form G-quadruplexes (G4s). Small molecules targeting G4s in telomeres and hTERT promoter could stabilize the G4s and inhibit hTERT expression and telomere extension. Several G4 ligands have shown inhibitory effects in cancer cells and xenograft mouse models, indicating these ligands have a potential for cancer therapies. The current review article describes the concept of the telomere, telomerase, and G4s. Moreover, the regulation of telomerase and G4s in telomeres and hTERT promoter is discussed as well. The summary of the small molecules targeting G4s in telomeric DNA sequences and the hTERT promoter will also be shown.},
}
@article {pmid35706406,
year = {2022},
author = {Zhang, Y and Fu, F and Zhang, L and Zhang, W and Chen, L and Zhang, Y and Chen, W and Du, Y and Chen, S and Zhan, Q and Feng, Z and Xu, H and Nie, Y},
title = {Telomere is shortened in patients with irritable bowel syndrome in the Chinese population.},
journal = {Journal of gastroenterology and hepatology},
volume = {37},
number = {9},
pages = {1749-1755},
doi = {10.1111/jgh.15912},
pmid = {35706406},
issn = {1440-1746},
support = {202002020012//Guangzhou Planned Project of Science and Technology/ ; //Guangzhou Postdoctoral Sciences Foundation/ ; },
mesh = {China ; Humans ; *Irritable Bowel Syndrome/genetics ; Leukocytes ; Telomere/genetics ; Telomere Shortening/genetics ; },
abstract = {BACKGROUND AND AIM: Telomere shortening is an accepted indicator of aging. Many studies have investigated an association between leukocyte telomere length (LTL) and psychiatric disorders. Mental or psychological factors could be an important cause of irritable bowel syndrome (IBS). However, there are currently few research evaluating correlations between LTL and IBS.<br><br>METHODS: We examined associations between LTL and IBS using quantitative polymerase chain reaction in independent cohorts, including 205 patients with IBS and 189 healthy controls. Furthermore, we examined whether mental or psychological factors, types of IBS, duration of IBS and antidepressants had an association with LTL in patients with IBS.<br><br>RESULTS: Among total samples, patients with IBS presented shorter LTL when compared to healthy controls (P&#xa0;<&#xa0;0.0001). Moreover, in subgroup analyses of patients with IBS, not only the LTL in patients with IBS caused by mental or psychological factors was shorter (P&#xa0;<&#xa0;0.0001), but also in patients with IBS that were caused by other factors (P&#xa0;=&#xa0;0.0082). Furthermore, LTL in patients with IBS who had taken antidepressants for more than 1&#xa0;month was longer than that in patients with IBS who did not take antidepressants or took for less than 1&#xa0;month (P&#xa0;<&#xa0;0.0001).<br><br>CONCLUSIONS: This is the first study to describe the relationship between LTL and IBS. This study showed significantly shorter telomeres in patients with IBS. Our findings suggest that LTL may hold the potential to serve as a predictor of IBS diagnosis.},
}
@article {pmid35705636,
year = {2022},
author = {Jung, J and McCartney, DL and Wagner, J and Rosoff, DB and Schwandt, M and Sun, H and Wiers, CE and de Carvalho, LM and Volkow, ND and Walker, RM and Campbell, A and Porteous, DJ and McIntosh, AM and Marioni, RE and Horvath, S and Evans, KL and Lohoff, FW},
title = {Alcohol use disorder is associated with DNA methylation-based shortening of telomere length and regulated by TESPA1: implications for aging.},
journal = {Molecular psychiatry},
volume = {27},
number = {9},
pages = {3875-3884},
pmid = {35705636},
issn = {1476-5578},
support = {ZIA AA000242/ImNIH/Intramural NIH HHS/United States ; 220857/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; 104036/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; Alcohol Drinking/genetics ; *Alcoholism/genetics ; DNA Methylation/genetics ; Genome-Wide Association Study ; Telomere/genetics ; *Telomere Shortening ; *Aging ; *Adaptor Proteins, Signal Transducing/genetics ; },
abstract = {Chronic heavy alcohol consumption is associated with increased mortality and morbidity and often leads to premature aging; however, the mechanisms of alcohol-associated cellular aging are not well understood. In this study, we used DNA methylation derived telomere length (DNAmTL) as a novel approach to investigate the role of alcohol use on the aging process. DNAmTL was estimated by 140 cytosine phosphate guanines (CpG) sites in 372 individuals with alcohol use disorder (AUD) and 243 healthy controls (HC) and assessed using various endophenotypes and clinical biomarkers. Validation in an independent sample of DNAmTL on alcohol consumption was performed (N = 4219). Exploratory genome-wide association studies (GWAS) on DNAmTL were also performed to identify genetic variants contributing to DNAmTL shortening. Top GWAS findings were analyzed using in-silico expression quantitative trait loci analyses and related to structural MRI hippocampus volumes of individuals with AUD. DNAmTL was 0.11-kilobases shorter per year in AUD compared to HC after adjustment for age, sex, race, and blood cell composition (p = 4.0 × 10[-12]). This association was partially attenuated but remained significant after additionally adjusting for BMI, and smoking status (0.06 kilobases shorter per year, p = 0.002). DNAmTL shortening was strongly associated with chronic heavy alcohol use (ps < 0.001), elevated gamma-glutamyl transferase (GGT), and aspartate aminotransferase (AST) (ps < 0.004). Comparison of DNAmTL with PCR-based methods of assessing TL revealed positive correlations (R = 0.3, p = 2.2 × 10[-5]), highlighting the accuracy of DNAmTL as a biomarker. The GWAS meta-analysis identified a single nucleotide polymorphism (SNP), rs4374022 and 18 imputed ones in Thymocyte Expressed, Positive Selection Associated 1(TESPA1), at the genome-wide level (p = 3.75 × 10[-8]). The allele C of rs4374022 was associated with DNAmTL shortening, lower hippocampus volume (p < 0.01), and decreased mRNA expression in hippocampus tissue (p = 0.04). Our study demonstrates DNAmTL-related aging acceleration in AUD and suggests a functional role for TESPA1 in regulating DNAmTL length, possibly via the immune system with subsequent biological effects on brain regions negatively affected by alcohol and implicated in aging.},
}
@article {pmid35704191,
year = {2022},
author = {Glousker, G and Fernandes, RV and Feretzaki, M and Lingner, J},
title = {Detection of TERRA R-Loops at Human Telomeres.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2528},
number = {},
pages = {159-171},
pmid = {35704191},
issn = {1940-6029},
mesh = {DNA/chemistry ; Humans ; Nucleic Acid Hybridization ; *R-Loop Structures ; *RNA, Long Noncoding/genetics ; Telomere/genetics ; },
abstract = {R-loops are three-stranded nucleic acid structures composed of a DNA-RNA hybrid and a displaced DNA strand. The long noncoding RNA TERRA forms R-loops at telomeres influencing the telomeric chromatin composition and impacting on telomere maintenance mechanisms by semiconservative DNA replication, homology directed DNA repair and telomerase. Here, we describe a method to detect R-loops at telomeres, which involves immunoprecipitation with the R-loop recognizing S9.6 antibody, followed by detection of telomeric DNA by either dot-blot hybridization with a radiolabeled telomeric probe, or qPCR using DNA primers that are specific for subtelomeric sequences.},
}
@article {pmid35704190,
year = {2022},
author = {Wagner, CB and Luke, B},
title = {DNA-RNA Hybrids at Telomeres in Budding Yeast.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2528},
number = {},
pages = {145-157},
pmid = {35704190},
issn = {1940-6029},
mesh = {DNA/genetics ; *RNA/genetics/metabolism ; Ribonuclease H/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomycetales/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {It has recently been demonstrated that budding yeast telomeres are transcribed into TERRA, a long noncoding RNA. Due to the G-rich nature of the coding strand, TERRA has a tendency to form DNA-RNA hybrids and potentially R-loops, which in turn, promote repair at short telomeres. Here, we report two methods to detect DNA-RNA hybrids at yeast telomeres, namely, DRIP, which employs the S9.6 hybrid-recognizing antibody, and R-ChIP, which takes advantage of a catalytic dead form of RNase H1 (Rnh1-cd). We use cross-linked material for both protocols as we have found that this does not negatively affect recovered material, and furthermore allows the precipitation of other proteins from the identical cross-linked material. Although both methods are successful in terms of detecting DNA-RNA hybrids at telomeres, the R-ChIP method yields an approximately ten-fold increased enrichment.},
}
@article {pmid35698093,
year = {2022},
author = {Zhang, R and Du, J and Xiao, Z and Jiang, Y and Jin, L and Weng, Q},
title = {Association between the peripartum maternal and fetal telomere lengths and mitochondrial DNA copy numbers and preeclampsia: a prospective case-control study.},
journal = {BMC pregnancy and childbirth},
volume = {22},
number = {1},
pages = {483},
pmid = {35698093},
issn = {1471-2393},
support = {81701475//National Natural Science Foundation of China/ ; 81701475//National Natural Science Foundation of China/ ; BK20211006//Natural Science Foundation of Jiangsu Province/ ; },
mesh = {Case-Control Studies ; DNA Copy Number Variations ; *DNA, Mitochondrial/genetics ; Female ; Humans ; Infant ; Peripartum Period ; *Pre-Eclampsia/genetics ; Pregnancy ; Telomere ; },
abstract = {PURPOSE: To explore changes in telomere length (TL) and mitochondrial copy number (mtDNA-CN) in preeclampsia (PE) and to evaluate the combined effect of maternal TL and mtDNA-CN on PE risk.<br><br>METHODS: A case-control study of 471 subjects (130 PE cases and 341 age frequency matched controls with gestational age rank from 24 to 42&#xa0;weeks) was conducted in Nanjing Drum Tower Hospital, Jiangsu Province of China. Relative telomere length (RTL) and mtDNA-CN were measured using quantitative polymerase chain reaction (qPCR), and PE risk was compared between groups by logistic regression analyses.<br><br>RESULTS: PE patients displayed longer RTL (0.48 versus 0.30) and higher mtDNA-CN (3.02 versus 2.00) in maternal blood as well as longer RTL (0.61 versus 0.35) but lower mtDNA-CN (1.69 versus 5.49) in cord blood (all p&#x2009;<&#x2009;0.001). Exercise during pregnancy exerted an obvious effect of maternal telomere length prolongation. Multiparous women with folic acid intake during early pregnancy and those who delivered vaginally showed longer telomere length, while those factors imposed no or opposite effect on RTL in PE cases. Furthermore, RTL and mtDNA-CN were positively correlated in controls (in maternal blood r&#x2009;=&#x2009;0.18, p&#x2009;<&#x2009;0.01; in cord blood r&#x2009;=&#x2009;0.19, p&#x2009;<&#x2009;0.001), but this correlation was disrupted in PE patients in both maternal blood and cord blood. Longer maternal RTL and higher mtDNA-CN were associated with a higher risk of PE, and the ROC curve of RTL and mtDNA-CN for predicting PE risk presented an AUC of 0.755 (95% CI: 0.698-0.812).<br><br>CONCLUSIONS: The interaction of TL and mtDNA-CN may play an important role in the pathogenesis of PE and could be a potential biomarker of PE risk.},
}
@article {pmid35697743,
year = {2022},
author = {Lee, J and Sung, K and Joo, SY and Jeong, JH and Kim, SK and Lee, H},
title = {Dynamic interaction of BRCA2 with telomeric G-quadruplexes underlies telomere replication homeostasis.},
journal = {Nature communications},
volume = {13},
number = {1},
pages = {3396},
pmid = {35697743},
issn = {2041-1723},
mesh = {DNA Replication ; *G-Quadruplexes ; Homeostasis ; Telomere/genetics ; Telomere Homeostasis ; },
abstract = {BRCA2-deficient cells precipitate telomere shortening upon collapse of stalled replication forks. Here, we report that the dynamic interaction between BRCA2 and telomeric G-quadruplex (G4), the non-canonical four-stranded secondary structure, underlies telomere replication homeostasis. We find that the OB-folds of BRCA2 binds to telomeric G4, which can be an obstacle during replication. We further demonstrate that BRCA2 associates with G-triplex (G3)-derived intermediates, which are likely to form during direct interconversion between parallel and non-parallel G4. Intriguingly, BRCA2 binding to G3 intermediates promoted RAD51 recruitment to the telomere G4. Furthermore, MRE11 resected G4-telomere, which was inhibited by BRCA2. Pathogenic mutations at the OB-folds abrogated the binding with telomere G4, indicating that the way BRCA2 associates with telomere is innate to its tumor suppressor activity. Collectively, we propose that BRCA2 binding to telomeric G4 remodels it and allows RAD51-mediated restart of the G4-driven replication fork stalling, simultaneously preventing MRE11-mediated breakdown of telomere.},
}
@article {pmid35697164,
year = {2022},
author = {Shen, Z and Zheng, R and Yang, H and Xing, S and Jin, X and Yan, H and Zhu, J and Mei, Y and Lin, F and Zheng, X},
title = {G-quadruplex stabilizer Tetra-Pt(bpy) disrupts telomere maintenance and impairs FAK-mediated migration of telomerase-positive cells.},
journal = {International journal of biological macromolecules},
volume = {213},
number = {},
pages = {858-870},
doi = {10.1016/j.ijbiomac.2022.06.015},
pmid = {35697164},
issn = {1879-0003},
mesh = {Animals ; *Antineoplastic Agents/pharmacology/therapeutic use ; *G-Quadruplexes ; Humans ; In Situ Hybridization, Fluorescence ; Mice ; *Neoplasms/drug therapy ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {G-quadruplex regulates a wide spectrum of biological processes, including telomere maintenance, DNA replication and transcription. The development of small molecules to selectively target G-quadruplex and their application remain hotspots in cancer therapy. Here, we explored the biological effect of G-quadruplexes stabilizer Tetra-Pt(bpy) in telomerase-positive cancer cells. Telomere maintenance was evaluated by telomerase repeat amplification protocol, chromosome orientation fluorescence in situ hybridization and telomere restriction fragment assays. We found that Tetra-Pt(bpy) accelerates telomere shortening through dual inhibition of telomerase activity and telomere sister chromatin exchanges mediated by telomeric G-quadruplexes. Consequently, Tetra-Pt(bpy)-treated cancer cells became enriched with extremely short telomeres and produced a strong telomeric DNA damage response following long-term treatment, leading to cell proliferation inhibition and senescence. Experimental evidence from RNA seq and cell migration-related assays showed that Tetra-Pt(bpy) decreased cell-matrix adhesion and inhibited the migration of non-senescent tumor cells. Mechanistically, Tetra-Pt(bpy) induced the formation of G-quadruplexes in focal adhesion kinase (FAK)-encoding gene PTK2, resulting in FAK transcription inhibition. Tetra-Pt(bpy) reduced xenograft tumor formation and inhibited tumor cell growth and migration in mice. This study further elucidates the function of G-quadruplexes in the human genome and reveals the potential of Tetra-Pt(bpy) as a novel chemotherapeutic agent for targeting telomerase-positive cancer cells.},
}
@article {pmid35696588,
year = {2022},
author = {Eastwood, JR and Connallon, T and Delhey, K and Hall, ML and Teunissen, N and Kingma, SA and La Porte, AM and Verhulst, S and Peters, A},
title = {Hot and dry conditions predict shorter nestling telomeres in an endangered songbird: Implications for population persistence.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {119},
number = {25},
pages = {e2122944119},
pmid = {35696588},
issn = {1091-6490},
mesh = {Animals ; *Climate Change ; *Endangered Species ; *Extinction, Biological ; Hot Temperature ; *Longevity/genetics ; *Songbirds/genetics/growth &amp; development ; Telomere/genetics ; *Telomere Shortening ; Water ; },
abstract = {Climate warming is increasingly exposing wildlife to sublethal high temperatures, which may lead to chronic impacts and reduced fitness. Telomere length (TL) may link heat exposure to fitness, particularly at early-life stages, because developing organisms are especially vulnerable to adverse conditions, adversity can shorten telomeres, and TL predicts fitness. Here, we quantify how climatic and environmental conditions during early life are associated with TL in nestlings of wild purple-crowned fairy-wrens (Malurus coronatus), endangered songbirds of the monsoonal tropics. We found that higher average maximum air temperature (range 31 to 45 °C) during the nestling period was associated with shorter early-life TL. This effect was mitigated by water availability (i.e., during the wet season, with rainfall), but independent of other pertinent environmental conditions, implicating a direct effect of heat exposure. Models incorporating existing information that shorter early-life TL predicts shorter lifespan and reduced fitness showed that shorter TL under projected warming scenarios could lead to population decline across plausible future water availability scenarios. However, if TL is assumed to be an adaptive trait, population viability could be maintained through evolution. These results are concerning because the capacity to change breeding phenology to coincide with increased water availability appears limited, and the evolutionary potential of TL is unknown. Thus, sublethal climate warming effects early in life may have repercussions beyond individual fitness, extending to population persistence. Incorporating the delayed reproductive costs associated with sublethal heat exposure early in life is necessary for understanding future population dynamics with climate change.},
}
@article {pmid35691385,
year = {2022},
author = {De Ruyter, T and Martens, DS and Bijnens, EM and Nawrot, TS and De Henauw, S and Michels, N},
title = {A multi-exposure approach to study telomere dynamics in childhood: A role for residential green space and waist circumference.},
journal = {Environmental research},
volume = {213},
number = {},
pages = {113656},
doi = {10.1016/j.envres.2022.113656},
pmid = {35691385},
issn = {1096-0953},
mesh = {Child ; Cross-Sectional Studies ; Female ; Humans ; Longitudinal Studies ; Male ; *Parks, Recreational ; *Telomere ; Waist Circumference ; },
abstract = {BACKGROUND: Telomeres are vulnerable to various environmental exposures and lifestyle factors, encompassed in the exposome. Recent research shows that telomere length is substantially determined early in life and that exposures in childhood may have important consequences in setting later life telomere length.<br><br>OBJECTIVES: We explore in a child population the associations of 17 exposures with telomere length and longitudinal telomere change.<br><br>METHODS: Children (2.8-10.3y at baseline, 51.3% boys) were followed-up for five to seven years. Relative telomere length was measured at baseline and follow-up using quantitative real-time PCR. Exposures and lifestyle factors included: body composition (body mass index and waist circumference), dietary habits (sugar- and fat-rich food intake, vegetables and fruit intake), psychosocial stress (events, emotions, behaviour), sleep duration, physical activity, and residential environmental quality (longterm black carbon, particulate matter exposure, and residential green space). Cross-sectional (n=182) and longitudinal (n=150) analyses were assessed using linear regression models, adjusting for age, sex, socioeconomic status and multiple testing.<br><br>RESULTS: Our longitudinal analyses showed that higher residential green space at baseline was associated with (&#x3b2;=0.261, p=0.002) lower telomere attrition and that children with a higher waist circumference at baseline showed a higher telomere attrition (&#x3b2;=-0.287, p=0.001). These two predictors were confirmed via LASSO variable selection and correction for multiple testing. In addition, children with more unhealthy exposures at baseline had a significantly higher telomere attrition over the follow-up period compared to children with more healthy exposures (&#x3b2;=-0.200, p=0.017).<br><br>DISCUSSION: Waist circumference and residential green space were identified as predictors associated with telomere attrition in childhood. These results further support the advantages of a healthy lifestyle from early age onwards and the importance of a green environment to promote molecular longevity from childhood onwards.},
}
@article {pmid35689027,
year = {2022},
author = {Mao, Y and Zhang, G},
title = {A complete, telomere-to-telomere human genome sequence presents new opportunities for evolutionary genomics.},
journal = {Nature methods},
volume = {19},
number = {6},
pages = {635-638},
pmid = {35689027},
issn = {1548-7105},
mesh = {Base Sequence ; *Genome, Human ; *Genomics ; Humans ; Telomere/genetics ; },
}
@article {pmid35688856,
year = {2022},
author = {Massey, DJ and Koren, A},
title = {Telomere-to-telomere human DNA replication timing profiles.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {9560},
pmid = {35688856},
issn = {2045-2322},
support = {DP2 GM123495/GM/NIGMS NIH HHS/United States ; DP2-GM123495/NH/NIH HHS/United States ; },
mesh = {*Centromere/genetics ; DNA Replication/genetics ; *DNA Replication Timing ; Genome, Human ; Humans ; Telomere/genetics ; },
abstract = {The spatiotemporal organization of DNA replication produces a highly robust and reproducible replication timing profile. Sequencing-based methods for assaying replication timing genome-wide have become commonplace, but regions of high repeat content in the human genome have remained refractory to analysis. Here, we report the first nearly-gapless telomere-to-telomere replication timing profiles in human, using the T2T-CHM13 genome assembly and sequencing data for five cell lines. We find that replication timing can be successfully assayed in centromeres and large blocks of heterochromatin. Centromeric regions replicate in mid-to-late S-phase and contain replication-timing peaks at a similar density to other genomic regions, while distinct families of heterochromatic satellite DNA differ in their bias for replicating in late S-phase. The high degree of consistency in centromeric replication timing across chromosomes within each cell line prompts further investigation into the mechanisms dictating that some cell lines replicate their centromeres earlier than others, and what the consequences of this variation are.},
}
@article {pmid35687934,
year = {2022},
author = {Sengupta, D and Sengupta, K},
title = {Lamin A and telomere maintenance in aging: Two to Tango.},
journal = {Mutation research},
volume = {825},
number = {},
pages = {111788},
doi = {10.1016/j.mrfmmm.2022.111788},
pmid = {35687934},
issn = {1873-135X},
mesh = {Humans ; Lamin Type A/genetics/metabolism ; *Progeria/genetics/metabolism ; Aging/genetics ; *Aging, Premature/genetics ; Telomere/genetics/metabolism ; Mutation ; },
abstract = {Lamin proteins which constitute the nuclear lamina in almost all higher eukaryotes, are mainly of two types A &amp; B encoded by LMNA and LMNB1/B2 genes respectively. While lamin A remains the principal product of LMNA gene, variants like lamin C, C2 and A∆10 are also formed as alternate splice products. Role of lamin A in aging has been highlighted in recent times due to its association with progeroid or premature aging syndromes which is classified as a type of laminopathy. Progeria caused by accelerated accumulation of lamin A Δ50 or progerin occurs due to a mutation in this LMNA gene leading to defects in post translational modification of lamin A. One of the most common and severe symptoms of progeroid laminopathy is accelerated cellular senescence or aging along with bone resorption, muscle weakness, lipodystrophy and cardiovascular disorders. On the other hand, progerin accumulation and telomere dysfunction merge as common traits in the process of chronological aging. Two major hallmarks of physiological aging in humans include loss of genomic integrity and telomere attrition which can result from defective laminar organization leading to deformed nuclear architecture and culminates into replicative senescence. This also adversely affects epigenetic landscape, mitochondrial dysfunction and several signalling pathways like DNA repair, mTOR, MAPK, TGFβ. In this review, we discuss the telomere-lamina interplay in the context of physiological aging and progeria.},
}
@article {pmid35687089,
year = {2022},
author = {Paul, T and Opresko, PL and Ha, T and Myong, S},
title = {Vectorial folding of telomere overhang promotes higher accessibility.},
journal = {Nucleic acids research},
volume = {50},
number = {11},
pages = {6271-6283},
pmid = {35687089},
issn = {1362-4962},
support = {R01 CA207342/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; RF1 NS113636/NS/NINDS NIH HHS/United States ; R35 GM122569/GM/NIGMS NIH HHS/United States ; R01 GM115631/GM/NIGMS NIH HHS/United States ; },
mesh = {DNA/chemistry ; *G-Quadruplexes ; Humans ; Nucleic Acid Conformation ; Shelterin Complex ; Telomerase/metabolism ; *Telomere/chemistry/genetics ; Telomere-Binding Proteins/metabolism ; },
abstract = {Human telomere overhang composed of tandem repeats of TTAGGG folds into G-quadruplex (G4). Unlike in an experimental setting in the test tube in which the entire length is allowed to fold at once, inside the cell, the overhang is expected to fold as it is synthesized directionally (5' to 3') and released segmentally by a specialized enzyme, the telomerase. To mimic such vectorial G4 folding process, we employed a superhelicase, Rep-X which can unwind DNA to release the TTAGGG repeats in 5' to 3' direction. We demonstrate that the folded conformation achieved by the refolding of full sequence is significantly different from that of the vectorial folding for two to eight TTAGGG repeats. Strikingly, the vectorially folded state leads to a remarkably higher accessibility to complementary C-rich strand and the telomere binding protein POT1, reflecting a less stably folded state resulting from the vectorial folding. Importantly, our study points to an inherent difference between the co-polymerizing and post-polymerized folding of telomere overhang that can impact telomere architecture and downstream processes.},
}
@article {pmid35686443,
year = {2022},
author = {Gong, H and Yu, Q and Guo, D and Wang, Y and Duan, L and Huang, W and Zhou, J and Wang, J and Huang, P},
title = {The relationship between dietary selenium intake and telomere length among diabetes.},
journal = {The British journal of nutrition},
volume = {},
number = {},
pages = {1-7},
doi = {10.1017/S000711452200174X},
pmid = {35686443},
issn = {1475-2662},
abstract = {Se is an indispensable trace element for the human body, and telomere length is considered a marker of biological ageing. Previous studies have shown that dietary Se intake is associated with telomere length. However, the relationship between Se intake and telomere length in patients with diabetes has not been well studied. Therefore, this study aimed to investigate the relationship between dietary Se intake and telomere length in patients with diabetes. We extracted 878 participants with diabetes from the National Health and Nutrition Examination Survey database for 1990-2002. Dietary Se intake was assessed using the 24 h dietary recall method, and telomere length was measured using quantitative PCR. Generalised linear models were constructed to assess the relationship between dietary Se intake and telomere length. After controlling for the confounders, 1 μg increase in dietary Se intake in female patients with diabetes, and telomere length increased by 1·84 base pairs (β = 1·84 (95 % CI: 0·15, 3·53)), there was a line relationship between dietary Se intake and telomere length in female patients with diabetes and telomere length increased with increasing dietary Se intake within the range of 0-250 μg. The study demonstrates that dietary Se intake is significantly associated with telomere length only in the female population with diabetes in the USA. However, further prospective studies are required to confirm this finding.},
}
@article {pmid35685390,
year = {2022},
author = {Bountziouka, V and Musicha, C and Allara, E and Kaptoge, S and Wang, Q and Angelantonio, ED and Butterworth, AS and Thompson, JR and Danesh, JN and Wood, AM and Nelson, CP and Codd, V and Samani, NJ},
title = {Modifiable traits, healthy behaviours, and leukocyte telomere length: a population-based study in UK Biobank.},
journal = {The lancet. Healthy longevity},
volume = {3},
number = {5},
pages = {e321-e331},
pmid = {35685390},
issn = {2666-7568},
support = {MR/L003120/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; SP/16/4/32697/BHF_/British Heart Foundation/United Kingdom ; MR/M012816/1/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; RG/13/13/30194/BHF_/British Heart Foundation/United Kingdom ; CH/12/2/29428/BHF_/British Heart Foundation/United Kingdom ; },
mesh = {Biological Specimen Banks ; *Coronary Artery Disease ; Female ; Health Behavior ; Health Status ; Humans ; Leukocytes ; Male ; Mendelian Randomization Analysis ; *Telomere ; United Kingdom ; },
abstract = {BACKGROUND: Telomere length is associated with risk of several age-related diseases and cancers. We aimed to investigate the extent to which telomere length might be modifiable through lifestyle and behaviour, and whether such modification has any clinical consequences.<br><br>METHODS: In this population-based study, we included participants from UK Biobank who had leukocyte telomere length (LTL) measurement, ethnicity, and white blood cell count data. We investigated associations of LTL with 117 potentially modifiable traits, as well as two indices of healthy behaviours incorporating between them smoking, physical activity, diet, maintenance of a healthy bodyweight, and alcohol intake, using both available and imputed data. To help interpretation, associations were summarised as the number of equivalent years of age-related change in LTL by dividing the trait &#x3b2; coefficients with the age &#x3b2; coefficient. We used mendelian randomisation to test causality of selected associations. We investigated whether the associations of LTL with 22 diseases were modified by the number of healthy behaviours and the extent to which the associations of more healthy behaviours with greater life expectancy and lower risk of coronary artery disease might be mediated through LTL.<br><br>FINDINGS: 422&#x2008;797 participants were available for the analysis (227&#x2008;620 [53&#xb7;8%] were women and 400&#x2008;036 [94&#xb7;6%] were White). 71 traits showed significant (p<4&#xb7;27&#x2008;&#xd7;&#x2008;10[-4]) associations with LTL but most were modest, equivalent to less than 1 year of age-related change in LTL. In multivariable analyses of 17 traits with stronger associations (equivalent to &#x2265;2 years of age-related change in LTL), oily fish intake, educational attainment, and general health status retained a significant association of this magnitude, with walking pace and current smoking being additionally significant at this level of association in the imputed models. Mendelian randomisation analysis suggested that educational attainment and smoking behaviour causally affect LTL. Both indices of healthy behaviour were positively and linearly associated with LTL, with those with the most healthy behaviours having longer LTL equivalent to about 3&#xb7;5 years of age-related change in LTL than those with the least heathy behaviours (p<0&#xb7;001). However, healthy behaviours explained less than 0&#xb7;2% of the total variation in LTL and did not significantly modify the association of LTL with risk of any of the diseases studied. Neither the association of more healthy behaviours on greater life expectancy or lower risk of coronary artery disease were substantially mediated through LTL.<br><br>INTERPRETATION: Although several potentially modifiable traits and healthy behaviours have a quantifiable association with LTL, at least some of which are likely to be causal, these effects are not of a sufficient magnitude to substantially alter the association between LTL and various diseases or life expectancy. Attempts to change telomere length through lifestyle or behavioural changes might not confer substantial clinical benefit.<br><br>FUNDING: UK Medical Research Council, UK Biotechnology and Biological Sciences Research Council, and British Heart Foundation.},
}
@article {pmid35682685,
year = {2022},
author = {Alswady-Hoff, M and Erdem, JS and Aleksandersen, M and Anmarkrud, KH and Skare, &#xd8; and Lin, FC and Simensen, V and Arnoldussen, YJ and Skaug, V and Ropstad, E and Zienolddiny-Narui, S},
title = {Multiwalled Carbon Nanotubes Induce Fibrosis and Telomere Length Alterations.},
journal = {International journal of molecular sciences},
volume = {23},
number = {11},
pages = {},
pmid = {35682685},
issn = {1422-0067},
support = {19/00274//National Institute of Occupational Health, Norway/ ; NFR 204341/H10, fellowship Y.J.A.//Research Council of Norway/ ; FP7/2007-2013//EU Seventh Framework Programme, NANoREG project/ ; },
mesh = {Animals ; Epithelial Cells/metabolism ; Fibrosis ; Lung/pathology ; Mice ; *Nanotubes, Carbon/toxicity ; Telomere/genetics ; },
abstract = {Telomere shortening can result in cellular senescence and in increased level of genome instability, which are key events in numerous of cancer types. Despite this, few studies have focused on the effect of nanomaterial exposure on telomere length as a possible mechanism involved in nanomaterial-induced carcinogenesis. In this study, effects of exposure to multiwalled carbon nanotubes (MWCNT) on telomere length were investigated in mice exposed by intrapleural injection, as well as in human lung epithelial and mesothelial cell lines. In addition, cell cycle, apoptosis, and regulation of genes involved in DNA damage repair were assessed. Exposure to MWCNT led to severe fibrosis, infiltration of inflammatory cells in pleura, and mesothelial cell hyperplasia. These histological alterations were accompanied by deregulation of genes involved in fibrosis and immune cell recruitment, as well as a significant shortening of telomeres in the pleura and the lung. Assessment of key carcinogenic mechanisms in vitro confirmed that long-term exposure to the long MWCNT led to a prominent telomere shortening in epithelial cells, which coincided with G1-phase arrest and enhanced apoptosis. Altogether, our data show that telomere shortening resulting in cell cycle arrest and apoptosis may be an important mechanism in long MWCNT-induced inflammation and fibrosis.},
}
@article {pmid35681604,
year = {2022},
author = {Alessandrini, I and Percio, S and Naghshineh, E and Zuco, V and Stacchiotti, S and Gronchi, A and Pasquali, S and Zaffaroni, N and Folini, M},
title = {Telomere as a Therapeutic Target in Dedifferentiated Liposarcoma.},
journal = {Cancers},
volume = {14},
number = {11},
pages = {},
pmid = {35681604},
issn = {2072-6694},
support = {C56167/A29363/CRUK_/Cancer Research UK/United Kingdom ; 29363/CRUK_/Cancer Research UK/United Kingdom ; },
abstract = {BACKGROUND: Well-differentiated (WD)/dedifferentiated (DD) liposarcoma (LPS) accounts for ~60% of retroperitoneal sarcomas. WDLPS and DDLPS divergently evolve from a common precursor and are both marked by the amplification of the 12q13-q15 region, leading to the abnormal expression of MDM2, CDK4, and HMGA2 genes. DDLPS is a non-lipogenic disease associated with aggressive clinical behavior. Patients have limited therapeutic options, especially for advanced disease, and their outcome remains largely unsatisfactory. This evidence underlines the need for identifying and validating DDLPS-specific actionable targets to design novel biology-driven therapies.<br><br>METHODS: Following gene expression profiling of DDLPS clinical specimens, we observed the up-regulation of "telomere maintenance" (TMM) pathways in paired DD and WD components of DDLPS. Considering the relevance of TMM for LPS onset and progression, the activity of a telomeric G-quadruplex binder (RHPS4) was assessed in DDLPS patient-derived cell lines.<br><br>RESULTS: Equitoxic concentrations of RHPS4 in DDLPS cells altered telomeric c-circle levels, induced DNA damage, and resulted in the accumulation of &#x3b3;-H2AX-stained micronuclei. This evidence was paralleled by an RHPS4-mediated reduction of in vitro cell migration and induction of apoptosis/autophagy.<br><br>CONCLUSIONS: Our findings support telomere as an intriguing therapeutic target in DDLPS and suggest G-quadruplex binders as innovative therapeutic agents.},
}
@article {pmid35681050,
year = {2022},
author = {Andreu-Sánchez, S and Aubert, G and Ripoll-Cladellas, A and Henkelman, S and Zhernakova, DV and Sinha, T and Kurilshikov, A and Cenit, MC and Jan Bonder, M and Franke, L and Wijmenga, C and Fu, J and van der Wijst, MGP and Melé, M and Lansdorp, P and Zhernakova, A},
title = {Genetic, parental and lifestyle factors influence telomere length.},
journal = {Communications biology},
volume = {5},
number = {1},
pages = {565},
pmid = {35681050},
issn = {2399-3642},
mesh = {*Aging/genetics ; Epigenesis, Genetic ; Female ; Humans ; Life Style ; Parents ; Pregnancy ; *Telomere/genetics ; },
abstract = {The average length of telomere repeats (TL) declines with age and is considered to be a marker of biological ageing. Here, we measured TL in six blood cell types from 1046 individuals using the clinically validated Flow-FISH method. We identified remarkable cell-type-specific variations in TL. Host genetics, environmental, parental and intrinsic factors such as sex, parental age, and smoking are associated to variations in TL. By analysing the genome-wide methylation patterns, we identified that the association of maternal, but not paternal, age to TL is mediated by epigenetics. Single-cell RNA-sequencing data for 62 participants revealed differential gene expression in T-cells. Genes negatively associated with TL were enriched for pathways related to translation and nonsense-mediated decay. Altogether, this study addresses cell-type-specific differences in telomere biology and its relation to cell-type-specific gene expression and highlights how perinatal factors play a role in determining TL, on top of genetics and lifestyle.},
}
@article {pmid35679773,
year = {2022},
author = {Kuehl, LK and de Punder, K and Deuter, CE and Martens, DS and Heim, C and Otte, C and Wingenfeld, K and Entringer, S},
title = {Telomere length in individuals with and without major depression and adverse childhood experiences.},
journal = {Psychoneuroendocrinology},
volume = {142},
number = {},
pages = {105762},
doi = {10.1016/j.psyneuen.2022.105762},
pmid = {35679773},
issn = {1873-3360},
support = {R01 HD065825/HD/NICHD NIH HHS/United States ; R01 HD060628/HD/NICHD NIH HHS/United States ; R01 AG050455/AG/NIA NIH HHS/United States ; },
mesh = {Adult ; *Adverse Childhood Experiences ; Depression ; *Depressive Disorder, Major/genetics ; Humans ; Leukocytes ; Male ; Telomere ; Telomere Shortening ; },
abstract = {Major depressive disorder (MDD) and adverse childhood experiences (ACE) are associated with poor physical and mental health in adulthood. One underlying mechanism might be accelerated cellular aging. For example, both conditions, MDD and ACE, have been related to a biological marker of cellular aging, accelerated shortening of telomere length (TL). Since MDD and ACE are confounded in many studies, we aimed with the current study to further disentangle the effects of MDD and ACE on TL using a full-factorial design including four carefully diagnosed groups of healthy participants and MDD patients with and without ACE (total N = 90, all without use of antidepressants). As dependent variable, TL was assessed in leukocytes. We found no group differences based on MDD and ACE exposure in TL. While TL was negatively associated with age and male sex, TL was not associated with any measure of severity of MDD, ACE or current stress. One possible explanation for our null result may be the comparatively good physical health status of our sample. Future research is needed to elucidate the relation of TL, MDD and ACE, taking potential effect modification by medication intake and physical health status into account.},
}
@article {pmid35677559,
year = {2022},
author = {Jiang, L and Tang, BS and Guo, JF and Li, JC},
title = {Telomere Length and COVID-19 Outcomes: A Two-Sample Bidirectional Mendelian Randomization Study.},
journal = {Frontiers in genetics},
volume = {13},
number = {},
pages = {805903},
pmid = {35677559},
issn = {1664-8021},
abstract = {Observational studies have found a relationship between directly measured short leukocyte telomere length (LTL) and severe coronavirus disease 19 (COVID-19). We investigated the causal association between genetically predicted LTL and COVID-19 susceptibility or severity. A previous genome-wide association study (GWAS) of 78,592 European-ancestry participants identified single nucleotidepolymorphisms (SNPs) that can be utilized to genetically predict LTL. Summary-level data for COVID-19 outcomes were analyzed from the COVID-19 Host Genetics Initiative. A two-sample bidirectional Mendelian randomization (MR) study was designed to evaluate these causal relationships. Using an inverse-weighted MR analysis and population-based controls, genetically predicted LTL did not reveal any significant association with COVID-19 susceptibility (odds ratio (OR): 0.94; 95% CI: 0.85-1.04; p = 0.202) or severity (OR: 0.85; 95% CI: 0.70-1.03; p = 0.099). Similar results were found for five other definitions of cases/controls and/or COVID-19 outcomes. Six additional MR methods and sensitivity analyses were conducted after removing variants with potential horizontal pleiotropy and including variants at a liberal significance level, which produced similar results. Using SNPs identified for the prediction of LTL from another GWAS study, we found a non-significant association for COVID-19 susceptibility or severity with narrower CIs toward the null hypothesis. No proof of genetically predicted COVID-19 phenotypes remained causally associated with genetically predicted LTL, and the null association was consistent with a lack of significant genetic correlation. Genetic evidence does not support shorter LTL as a causal risk factor for COVID-19 susceptibility or severity.},
}
@article {pmid35676815,
year = {2022},
author = {Fan, YH and Li, XL and Liu, XH and Guo, ZF and Yan, MQ and Duan, XR and Miao, WB and Wang, W},
title = {Association between Polymorphisms in Telomere-Associated Protein Genes and the Cholinesterase Activity of Omethoate-Exposed Workers.},
journal = {Biomedical and environmental sciences : BES},
volume = {35},
number = {5},
pages = {448-452},
doi = {10.3967/bes2022.060},
pmid = {35676815},
issn = {2214-0190},
mesh = {Cholinesterases/genetics ; *Dimethoate/analogs &amp; derivatives ; Humans ; *Occupational Exposure/adverse effects ; Polymorphism, Genetic ; Telomere ; },
}
@article {pmid35675759,
year = {2022},
author = {Giaccherini, M and Gentiluomo, M and Arcidiacono, PG and Falconi, M and Testoni, SGG and Apadula, L and Lauri, G and Di Franco, G and Fatucchi, LM and Petrone, MC and Corradi, C and Crippa, S and Morelli, L and Capurso, G and Campa, D},
title = {A polymorphic variant in telomere maintenance is associated with worrisome features and high-risk stigmata development in IPMNs.},
journal = {Carcinogenesis},
volume = {43},
number = {8},
pages = {728-735},
doi = {10.1093/carcin/bgac051},
pmid = {35675759},
issn = {1460-2180},
mesh = {*Carcinoma, Pancreatic Ductal/genetics/pathology ; Humans ; *Pancreatic Intraductal Neoplasms ; *Pancreatic Neoplasms/genetics/pathology ; Retrospective Studies ; Telomere/genetics ; },
abstract = {Intraductal papillary mucinous neoplasms (IPMNs) are nonobligatory precursor lesions of pancreatic ductal adenocarcinoma (PDAC). The identification of molecular biomarkers able to predict the risk of progression of IPMNs toward malignancy is largely lacking and sorely needed. Telomere length (TL) is associated with the susceptibility of developing cancers, including PDAC. Moreover, several PDAC risk factors have been shown to be associated with IPMN transition to malignancy. TL is genetically determined, and the aim of this study was to use 11 SNPs, alone or combined in a score (teloscore), to estimate the causal relation between genetically determined TL and IPMNs progression. For this purpose, 173 IPMN patients under surveillance were investigated. The teloscore did not show any correlation, however, we observed an association between PXK-rs6772228-A and an increased risk of IPMN transition to malignancy (HR = 3.17; 95%CI 1.47-6.84; P = 3.24 × 10-3). This effect was also observed in a validation cohort of 142 IPMNs even though the association was not statistically significant. The combined analysis was consistent showing an association between PXK-rs6772228-A and increased risk of progression. The A allele of this SNP is strongly associated with shorter LTL that in turn have been reported to be associated with increased risk of developing PDAC. These results clearly highlight the importance of looking for genetic variants as potential biomarkers in this setting in order to further our understanding the etiopathogenesis of PDAC and suggest that genetically determined TL might be an additional marker of IPMN prognosis.},
}
@article {pmid35670038,
year = {2022},
author = {Carroll, JE and Olmstead, R and Haque, R and Irwin, MR},
title = {Accelerated mononuclear cell telomere attrition in breast cancer survivors with depression history: A 2-year longitudinal cohort study.},
journal = {Cancer},
volume = {128},
number = {16},
pages = {3109-3119},
doi = {10.1002/cncr.34329},
pmid = {35670038},
issn = {1097-0142},
support = {R01 CA160245/CA/NCI NIH HHS/United States ; R01 CA207130/CA/NCI NIH HHS/United States ; },
mesh = {*Breast Neoplasms/genetics ; *Cancer Survivors ; Cohort Studies ; Depression/epidemiology ; *Depressive Disorder, Major ; Female ; Humans ; Leukocytes, Mononuclear ; Longitudinal Studies ; Prospective Studies ; Telomere ; },
abstract = {BACKGROUND: Cancer treatments are thought to accelerate biological aging, although this trajectory is highly variable. Depression is more prevalent in breast cancer survivors and is thought to be a vulnerability factor for biological aging. A lifetime history of depression and cumulative lifetime number of depression episodes could hypothetically be associated with an accelerated rate of biological aging as indexed by attrition of telomere length in a prospective cohort of breast cancer survivors who were not currently depressed.<br><br>METHODS: Breast cancer survivors (n&#xa0;=&#xa0;206) without current depression were recruited from a large community-based health plan and were assessed for depression history by a structured diagnostic interview. Blood specimens were provided at baseline and every 8&#x2009;months over 24&#x2009;months to measure peripheral blood mononuclear cell (PBMC) telomere length. Mixed linear models examined associations of depression history and number of depression episodes with change in telomere length, adjusting for demographic, comorbidity, and cancer-specific factors.<br><br>RESULTS: In the fully adjusted model, depression history predicted attrition of PBMC telomere length over 24&#x2009;months (Beta [SE]&#xa0;=&#xa0;-.006 [.002], p&#xa0;=&#xa0;.001). Greater number of depressive episodes over the lifetime was also associated with accelerated attrition of PBMC telomere length over 24&#x2009;months (Beta [SE]&#xa0;=&#xa0;-.004 [.001], p&#xa0;=&#xa0;.001).<br><br>CONCLUSIONS: In breast cancer survivors without current depression, telomere attrition over 24&#x2009;months was greatest in those with a lifetime depression history, particularly those with the greatest number of episodes of major depressive disorder over their lifetime. Depression history and its cumulative burden may contribute to accelerated biological aging, with implications for risk of morbidity and mortality in breast cancer survivors.},
}
@article {pmid35666175,
year = {2022},
author = {Memaran, N and Wilke, H and Sugianto, RI and Baumann, U and Bauer, E and Swallow, M and Beuke, E and Junge, N and Pfister, ED and Grabitz, C and Richter, N and Goldschmidt, I and Schmidt, BMW and Melk, A},
title = {Telomere length is associated with intima-media thickness in pediatric liver transplant patients: A prospective cohort study.},
journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society},
volume = {28},
number = {11},
pages = {1766-1775},
doi = {10.1002/lt.26524},
pmid = {35666175},
issn = {1527-6473},
mesh = {Aspartate Aminotransferases ; *Atherosclerosis/epidemiology/etiology ; Carotid Intima-Media Thickness ; Child ; Humans ; Leukocytes ; *Liver Transplantation/adverse effects ; Prospective Studies ; Tacrolimus ; Telomere ; },
abstract = {Leukocyte telomere length (LTL) is a marker for biological age. Pediatric liver transplant recipients show a high rate of subclinical atherosclerosis, indicated by elevated intima-media thickness (IMT). We hypothesized that atherosclerosis is associated with biological age in these patients and investigated the course of LTL over time. We measured LTL from peripheral blood leukocytes by quantitative polymerase chain reaction and IMT from 97 pediatric patients after liver transplantation in a prospective cohort study. Of the patients, 71% (n = 69) had two or more assessments (total, 228 observations; median follow-up, 1.1 years). Lower LTL was associated with higher IMT (β = -0.701, p = 0.01) and higher aspartate aminotransferase (β = -0.001, p = 0.02), adjusted for age, sex, and age at transplantation. Of the patients, 45% showed decreasing LTL over time, whereas 55% exhibited stable LTL. Patients with stable LTL showed a decrease in IMT (median, -0.02 mm/year) and a decrease of tacrolimus trough levels (median, -0.08 μg/L/year). LTL is associated with IMT independent of age in pediatric liver transplant patients, suggesting that early aging contributes to the high burden of subclinical cardiovascular damage and may furthermore negatively affect the graft.},
}
@article {pmid35664481,
year = {2022},
author = {Carvalho, CM and Coimbra, BM and Xavier, G and Bugiga, AVG and Fonseca, T and Olff, M and Polimanti, R and Mello, AF and Ota, VK and Mello, MF and Belangero, SI},
title = {Shorter Telomeres Related to Posttraumatic Stress Disorder Re-experiencing Symptoms in Sexually Assaulted Civilian Women.},
journal = {Frontiers in psychiatry},
volume = {13},
number = {},
pages = {835783},
pmid = {35664481},
issn = {1664-0640},
abstract = {Telomeres are short tandem repeats of "TTAGGG" that protect the chromosome ends from deterioration or fusion of chromosomes. Their repeat length shortens with cell division acting as a biomarker of cellular aging. Traumatic stress events during adulthood or childhood have been associated with posttraumatic stress disorder (PTSD) and short leukocyte telomere length (LTL). This study investigated whether LTL was associated with PTSD in a Brazilian sample of sexually assaulted civilian women at two time points: baseline and 1-year follow-up. At baseline, we assessed 64 women with PTSD following sexual assault (cases) and 60 women with no previous history of sexual trauma or mental disorders (healthy controls - HC). At follow-up visit, 13 persistent PTSD cases, 11 HCs, and 11 PTSD remitters patients were evaluated. PTSD diagnosis and severity were assessed using Mini International Neuropsychiatric Interview (Diagnostic and Statistical Manual of Mental Disorders III/IV criteria) and Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), respectively. LTL was measured using multiplex real-time polymerase chain reaction (PCR). In the baseline analysis, we observed that LTL was associated with re-experiencing symptoms (B = -0.16; confidence interval (CI) 95% = -0.027--0.005; Bonferroni-adjusted p-value = 0.02), but no association was observed between other PTSD symptoms and LTL. In the longitudinal analysis, telomere shortening was no longer observed in patients with PTSD and PTSD remitters. In conclusion, our findings indicate that shorter baseline LTL is associated with early stage of PTSD re-experiencing symptoms in recently sexually assaulted women.},
}
@article {pmid35662923,
year = {2022},
author = {Hu, L and Bai, Y and Hu, G and Zhang, Y and Han, X and Li, J},
title = {Association of Dietary Magnesium Intake With Leukocyte Telomere Length in United States Middle-Aged and Elderly Adults.},
journal = {Frontiers in nutrition},
volume = {9},
number = {},
pages = {840804},
pmid = {35662923},
issn = {2296-861X},
abstract = {AIM: Magnesium supplementation may extend the life span; however, the biological mechanism is still unknown. Leukocyte telomere length (LTL) is a marker of cell aging and biological health in humans. Data concerning whether magnesium supplementation can maintain telomere length, thus prolonging life are limited. We aimed to investigate the association between dietary magnesium intake and LTL in United States middle-aged and elderly adults.<br><br>METHODS: A total of 4,039 United States adults aged &#x2265; 45 years from National Health and Nutrition Examination Survey (1999-2002). Dietary magnesium intake was collected by a trained interviewer using 24-h dietary recall method and LTL was obtained using the quantitative polymerase chain reaction method. Multiple linear regression analysis was performed to evaluate the crude and adjusted association of dietary magnesium intake with LTL.<br><br>RESULTS: The overall mean (SD) of LTL was 5.6 (0.6) kp. After adjusting potential confounders, every 1 mg increase in log-transformed dietary magnesium intake was associated with 0.20 kp (95% confidence intervals: 0.05-0.34) longer LTL. Participants with the highest tertile (&#x2265;299 mg) of dietary magnesium intake had statistically significant longer LTL (&#x3b2; = 0.07, P = 0.038) compared with the lowest tertile (<198 mg), with significant linear trends across tertiles. Moreover, the association between dietary magnesium intake and LTL was significantly stronger in participants with higher levels of education (&#x2265;high school compared with < high school, P for interaction = 0.002). E-value analysis suggested robustness to unmeasured confounding.<br><br>CONCLUSION: Our findings showed that increased dietary magnesium intake was associated with longer LTL, which suggested that magnesium was conducive to a longer life expectancy.},
}
@article {pmid35661999,
year = {2022},
author = {da Silva, A and Silveira, BKS and Hermsdorff, HHM and da Silva, W and Bressan, J},
title = {Effect of omega-3 fatty acid supplementation on telomere length and telomerase activity: A systematic review of clinical trials.},
journal = {Prostaglandins, leukotrienes, and essential fatty acids},
volume = {181},
number = {},
pages = {102451},
doi = {10.1016/j.plefa.2022.102451},
pmid = {35661999},
issn = {1532-2823},
mesh = {Clinical Trials as Topic ; *Diabetes Mellitus, Type 2/drug therapy ; Dietary Supplements ; *Fatty Acids, Omega-3/pharmacology/therapeutic use ; Humans ; *Telomerase/genetics/metabolism ; Telomere ; },
abstract = {Evidence suggests antioxidant and anti-inflammatory properties of omega-3 polyunsaturated fatty acids (n-3 PUFA). However, the effect of supplementation of this fatty acid profile on the telomere length and the telomerase enzyme activity was not revised yet. The PubMed and Embase® databases were used to search for clinical trials. A total of six clinical trials were revised. Omega-3 PUFA supplementation did not statistically affect telomere length in three out of three studies but affected telomerase activity in two out of four studies. The supplementation increased telomerase enzyme activity in subjects with first-episode schizophrenia. Besides, it decreased telomerase enzyme activity without modulating the effects of Pro12Ala polymorphism on the PPARγ gene in type 2 diabetes subjects. The methodological differences between the studies and the limited number of studies on the theme suggest that further studies are needed to elucidate the effects of n-3 PUFA supplementation on telomere length and telomerase enzyme activity in humans.},
}
@article {pmid35660961,
year = {2022},
author = {Lim, HF and Tan, NS and Dehghan, R and Shen, M and Liew, MF and Bee, SWL and Sia, YY and Liu, J and Khor, CC and Kwok, I and Ng, LG and Angeli, V and Dorajoo, R},
title = {Shortened Telomere Length in Sputum Cells of Bronchiectasis Patients is Associated with Dysfunctional Inflammatory Pathways.},
journal = {Lung},
volume = {200},
number = {3},
pages = {401-407},
pmid = {35660961},
issn = {1432-1750},
mesh = {*Bronchiectasis ; Humans ; Respiratory System ; *Sputum ; Telomere ; Telomere Shortening ; },
abstract = {Telomere attrition is an established ageing biomarker and shorter peripheral blood leukocyte telomere length has been associated with increased risks of respiratory diseases. However, whether telomere length in disease-relevant sputum immune cells of chronic respiratory disease patients is shortened and which pathways are dysfunctional are not clear. Here we measured telomere length from sputum samples of bronchiectasis and asthmatic subjects and determined that telomere length in sputum of bronchiectasis subjects was significantly shorter (Beta = - 1.167, PAdj = 2.75 × 10[-4]). We further performed global gene expression analysis and identified genes involved in processes such as NLRP3 inflammasome activation and regulation of adaptive immune cells when bronchiectasis sputum telomere length was shortened. Our study provides insights on dysfunctions related to shortened telomere length in sputum immune cells of bronchiectasis patients.},
}
@article {pmid35659559,
year = {2022},
author = {Morosinotto, C and Bensch, S and Tarka, M and Karell, P},
title = {Heritability and Parental Effects in Telomere Length in a Color Polymorphic Long-Lived Bird.},
journal = {Physiological and biochemical zoology : PBZ},
volume = {95},
number = {4},
pages = {350-364},
doi = {10.1086/720161},
pmid = {35659559},
issn = {1537-5293},
mesh = {Animals ; Birds ; Melanins/genetics ; *Physical Conditioning, Animal ; Telomere/genetics ; Telomere Shortening ; },
abstract = {AbstractRelative telomere length (RTL), an indicator of senescence, has been shown to be heritable but can also be affected by environmental factors, such as parental effects. Investigating heritability as well as parental effects and rearing environment can help us to understand the factors affecting offspring telomeres. Moreover, how phenotypic parental traits linked with fitness can impact offspring RTL is still unclear. A phenotypic marker closely associated with physiological traits and fitness is melanin-based color polymorphism, which in tawny owl (Strix aluco) is highly heritable and strongly associated with adult telomere shortening and survival. We studied narrow-sense heritability (h[2]) of RTL, as well as the impact of parental age and color morph and their interaction on offspring RTL. Offspring RTL at fledging was strongly positively correlated with both mother RTL and father RTL at breeding. Offspring RTL was also negatively associated with father age, suggesting that older fathers sired offspring with shorter telomeres. Parental color morph did not explain offspring RTL, and there were no interactive effects of parental morph and age, despite previously documented morph-specific senescence patterns. Our results suggest that RTL is highly heritable and affected by paternal age but not related to color polymorphism. This suggests that either morph-specific telomere shortening as an adult does not result in significantly shorter telomeres in their gametes, or that parents compensate morph-specific senescence via parental care. Morph-specific patterns of telomere dynamics in polymorphic species may thus emerge from different life history strategies adopted in adulthood.},
}
@article {pmid35657918,
year = {2022},
author = {Armstrong, ND and Irvin, MR and Haley, WE and Blinka, MD and Kamin Mukaz, D and Patki, A and Rutherford Siegel, S and Shalev, I and Durda, P and Mathias, RA and Walston, JD and Roth, DL},
title = {Telomere shortening and the transition to family caregiving in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.},
journal = {PloS one},
volume = {17},
number = {6},
pages = {e0268689},
pmid = {35657918},
issn = {1932-6203},
support = {U01 NS041588/NS/NINDS NIH HHS/United States ; RF1 AG050609/AG/NIA NIH HHS/United States ; P30 AG021334/AG/NIA NIH HHS/United States ; },
mesh = {Cross-Sectional Studies ; Humans ; Race Factors ; Stress, Psychological/genetics ; *Stroke/genetics ; Telomere/genetics ; *Telomere Shortening ; },
abstract = {Telomere length (TL) is widely studied as a possible biomarker for stress-related cellular aging and decreased longevity. There have been conflicting findings about the relationship between family caregiving stress and TL. Several initial cross-sectional studies have found associations between longer duration of caregiving or perceived stressfulness of caregiving and shortened TL, suggesting that caregiving poses grave risks to health. Previous reviews have suggested the need for longitudinal methods to investigate this topic. This study examined the association between the transition to family caregiving and change in TL across ~9 years. Data was utilized from the Caregiving Transitions Study, an ancillary study to the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. TL was assayed using qPCR and analyzed as the telomere-to-single copy gene ratio for each participant at baseline and follow-up. General linear models examined the association between caregiving status and the change in TL for 208 incident caregivers and 205 controls, as well as associations between perceived stress and TL among caregivers. No association was found between TL change and caregiving (p = 0.494), and fully adjusted models controlling for health and socioeconomic factors did not change the null relationship (p = 0.305). Among caregivers, no association was found between perceived caregiving stress and change in TL (p = 0.336). In contrast to earlier cross-sectional studies, this longitudinal, population-based study did not detect a significant relationship between the transition into a family caregiving role and changes in TL over time. Given the widespread citation of previous findings suggesting that caregiving shortens telomeres and places caregivers at risk of early mortality, these results demonstrate the potential need of a more balanced narrative about caregiving.},
}
@article {pmid35656320,
year = {2022},
author = {Bennett, S and Girndt, A and Sánchez-Tójar, A and Burke, T and Simons, M and Schroeder, J},
title = {Evidence of Paternal Effects on Telomere Length Increases in Early Life.},
journal = {Frontiers in genetics},
volume = {13},
number = {},
pages = {880455},
pmid = {35656320},
issn = {1664-8021},
abstract = {Offspring of older parents in many species have decreased longevity, a faster ageing rate and lower fecundity than offspring born to younger parents. Biomarkers of ageing, such as telomeres, that tend to shorten as individuals age, may provide insight into the mechanisms of such parental age effects. Parental age may be associated with offspring telomere length either directly through inheritance of shortened telomeres or indirectly, for example, through changes in parental care in older parents affecting offspring telomere length. Across the literature there is considerable variation in estimates of the heritability of telomere length, and in the direction and extent of parental age effects on telomere length. To address this, we experimentally tested how parental age is associated with the early-life telomere dynamics of chicks at two time points in a captive population of house sparrows Passer domesticus. We experimentally separated parental age from sex effects, and removed effects of age-assortative mating, by allowing the parent birds to only mate with young, or old partners. The effect of parental age was dependent on the sex of the parent and the chicks, and was found in the father-daughter relationship only; older fathers produced daughters with longer telomere lengths post-fledging. Overall we found that chick telomere length increased between the age of 0.5 and 3 months at the population and individual level. This finding is unusual in birds with such increases more commonly associated with non-avian taxa. Our results suggest parental age effects on telomere length are sex-specific either through indirect or direct inheritance. The study of similar patterns in different species and taxa will help us further understand variation in telomere length and its evolution.},
}
@article {pmid35654175,
year = {2022},
author = {Bauch, C and Gatt, MC and Verhulst, S and Granadeiro, JP and Catry, P},
title = {Higher mercury contamination is associated with shorter telomeres in a long-lived seabird - A direct effect or a consequence of among-individual variation in phenotypic quality?.},
journal = {The Science of the total environment},
volume = {839},
number = {},
pages = {156359},
doi = {10.1016/j.scitotenv.2022.156359},
pmid = {35654175},
issn = {1879-1026},
mesh = {Aging/genetics ; Animals ; Birds ; Female ; Humans ; Male ; *Mercury/toxicity ; Telomere ; *Telomere Shortening ; },
abstract = {Mercury is a heavy metal, which is pervasive and persistent in the marine environment. It bioaccumulates within organisms and biomagnifies in the marine food chain. Due to its high toxicity, mercury contamination is a major concern for wildlife and human health. Telomere length is a biomarker of aging and health, because it predicts survival, making it a potential tool to investigate sublethal effects of mercury contamination. However, the relationship between telomeres and mercury contamination is unclear. We measured feather mercury concentration in Cory's Shearwaters Calonectris borealis, long-lived seabirds and top predators, between 9 and 35 years of age and related it to telomere length in erythrocytes. Cory's Shearwaters with higher mercury concentrations had shorter telomeres and the effect was sex-dependent, reaching significance in males only. This may be explained by the fact that males have longer telomeres and higher and more variable mercury concentrations than females in this population. The mercury effect on telomere length was stronger on longer telomeres in the genome within individuals. We discuss the hypotheses that the negative correlation could either be a direct effect of mercury on telomere shortening and/or a consequence of variation in phenotypic quality among individuals that results in a covariation between mercury contamination and telomere length.},
}
@article {pmid35649672,
year = {2022},
author = {Dos Santos, IC and da Silva, JT and Rohr, P and Lengert, AVH and de Lima, MA and Kahl, VFS and da Silva, J and Reis, RM and Silveira, HCS},
title = {Genomic instability evaluation by BMCyt and telomere length in Brazilian family farmers exposed to pesticides.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {878},
number = {},
pages = {503479},
doi = {10.1016/j.mrgentox.2022.503479},
pmid = {35649672},
issn = {1879-3592},
mesh = {Adult ; Brazil ; DNA Damage ; *Farmers ; Female ; Genomic Instability ; Humans ; Male ; Middle Aged ; *Pesticides/toxicity ; Telomere/genetics ; },
abstract = {Brazil is one of the largest consumers of pesticides in the world. This high consumption has resulted in higher potential health risk to agricultural farm workers due to occupational exposure. Hence, the aim of this study is to evaluate genomic instability, using Buccal Micronucleus Cytome (BMCyt) and telomere length (TL) measurement as biomarkers of occupational exposure to pesticides in rural workers living in the State of São Paulo, Brazil. Genomic instability was evaluated in 81 pesticide-exposed farm workers (69 males and 12 females) with a mean age of 49.16 ± 10.06 years and a mean time job of 30.00 ± 14.00 years,81 non-exposed individuals (62 males and 15 females) with a mean age of 47.87 ± 10.66 years. BMCyt results showed significantly higher levels of cell damage (micronuclei and binucleated cells) and cell death (karyorrhectic and condensed chromatin cells) in subjects exposed to pesticide when compared to those non-exposed (p < 0.05). Although our results did not show significant differences in TL among exposed and non-exposed groups, effects in TL due to pesticide exposure was found in a multivariable linear regression model when we stratified the groups by age (≤ 49 years and ≥ 50 years old; β = 11.21, p = 0.006). In addition, TL reduction on was identified in relation to an increase in cigarette pack consumption (β = -0.633, p = 0.045). Furthermore, exposure to specific pesticides presented different effects in TL. Cypermethrin exposure resulted in a reduction in TL (β = -18.039, p = 0.018), while abamectin exposure led to an increase in TL (β = 23.990, p = 0.007). Thus, our findings substantiate genomic instability due to pesticides exposure.},
}
@article {pmid35646972,
year = {2022},
author = {Shull, JG and Planas-Cerezales, L and Lara Compte, C and Perona, R and Molina-Molina, M},
title = {Harnessing PM2.5 Exposure Data to Predict Progression of Fibrotic Interstitial Lung Diseases Based on Telomere Length.},
journal = {Frontiers in medicine},
volume = {9},
number = {},
pages = {871898},
pmid = {35646972},
issn = {2296-858X},
abstract = {Cross-analysis of clinical and pollution factors could help calculate the risk of fibrotic interstitial lung disease (ILD) development and progression. The intent of this study is to build a body of knowledge around early detection and diagnosis of lung disease, harnessing new data sets generated for other purposes. We cross-referenced exposure levels to particulate matter 2.5 (PM2.5) with telomere length of a cohort of 280 patients with fibrotic ILD to weigh impact and associations. There was no linear correlation between PM2.5 and telomere length in our data sets, as the value of the correlation coefficient was 0.08. This exploratory study offers additional insights into methodologies for investigating the development and prognosis of pulmonary fibrosis.},
}
@article {pmid35645014,
year = {2022},
author = {Córdova-Oriz, I and Chico-Sordo, L and Varela, E},
title = {Telomeres, aging and reproduction.},
journal = {Current opinion in obstetrics &amp; gynecology},
volume = {34},
number = {3},
pages = {151-158},
doi = {10.1097/GCO.0000000000000779},
pmid = {35645014},
issn = {1473-656X},
mesh = {Aging/genetics ; Female ; Humans ; Infant, Newborn ; *Infertility, Female ; Pregnancy ; *Premature Birth ; Reproduction ; Telomere ; },
abstract = {PURPOSE OF REVIEW: Women's fertility decay starts at the mid 30 s. However, the current delay of childbearing leads to ovarian aging and the need of assisted reproduction technologies (ART). Telomere biology is one of the main pathways involved in organismal aging. Thus, this review will focus on the knowledge acquired during the last 2 years about the telomere pathway and its influence on female fertility and the consequences for the newborn.<br><br>RECENT FINDINGS: New research on telomere biology reaffirms the relationship of telomere attrition and female infertility. Shorter maternal telomeres, which could be aggravated by external factors, underly premature ovarian aging and other complications including preeclampsia, preterm birth and idiopathic pregnancy loss. Finally, the telomere length of the fetus or the newborn is also affected by external factors, such as stress and nutrition.<br><br>SUMMARY: Recent evidence shows that telomeres are implicated in most processes related to female fertility, embryo development and the newborn's health. Thus, telomere length and telomerase activity may be good biomarkers for early detection of ovarian and pregnancy failures, opening the possibility to use telomere therapies to try to solve the infertility situation.},
}
@article {pmid35628895,
year = {2022},
author = {Svikle, Z and Pahirko, L and Zariņa, L and Baumane, K and Kardonaite, D and Radzeviciene, L and Daugintyte-Petrusiene, L and Balciuniene, VJ and Verkauskiene, R and Tiščuka, A and Rovite, V and Sjakste, N and Sokolovska, J},
title = {Telomere Lengths and Serum Proteasome Concentrations in Patients with Type 1 Diabetes and Different Severities of Diabetic Retinopathy in Latvia and Lithuania.},
journal = {Journal of clinical medicine},
volume = {11},
number = {10},
pages = {},
pmid = {35628895},
issn = {2077-0383},
support = {"Novel biomarkers of diabetic retinopathy: epigenetic modifications of genes of ubiquitin-proteasome system, telomere length and proteasome concentration"//Mutual funds Taiwan - Latvia - Lithuania/ ; "Research of biomarkers and natural substances for acute and chronic diseases' diagnostics and personalized treatment"//University of Latvia/ ; },
abstract = {The aim of the study was to compare telomere lengths and circulating proteasome concentrations in patients with different stages of diabetic retinopathy and type 1 diabetes in Latvia and Lithuania. Methods. Patients with no diabetic retinopathy and with non-proliferative diabetic retinopathy were included in the NDR/NPDR group (n = 187). Patients with proliferative diabetic retinopathy and status post laser-photocoagulation were included int the PDR/LPC group (n = 119). Telomeres were evaluated by real-time quantitative polymerase chain reaction. Proteasome concentration was measured by ELISA. Results. Telomeres were longer in PDR/LPC (ΔCT 0.21 (0.12−0.28)) vs. NDR/NPDR (ΔCT 0.18 (0.1−0.28)), p = 0.036. In NDR/NPDR, telomeres were correlated negatively with age (R = −0.17, p = 0.019), BMI (R = −0.21, p = 0.004), waist/hip ratio (R = −0.21, p = 0.005), total cholesterol (R = −0.18, p = 0.021), and low-density cholesterol (R = −0.20, p = 0.010), and positively with estimated glomerular filtration rate (eGFR) (R = 0.28, p < 0.001). None of the above correlations were observed in PRD/LPC. Proteasome concentrations were lower in PDR/LPC (130 (90−210) ng/mL) vs. NDR/NPDR (150 (100−240) ng/mL), p = 0.024. This correlated negatively with eGFR (R = −0.17, p = 0.025) in the NDR/NPDR group and positively with age (R = 0.23, p = 0.014) and systolic blood pressure (R = 0.20, p = 0.032) in the PRD/LPC group. Telomere lengths did not correlate with proteasome concentrations. Conclusion. Longer telomeres and lower circulating proteasome concentrations are observed in patients with type 1 diabetes and advanced diabetic retinopathy.},
}
@article {pmid35627106,
year = {2022},
author = {Tung, KTS and Wong, RS and Tsang, HW and Wong, WHS and Tso, WWY and Yam, JC and Lum, TYS and Chan, GCF and Wong, ICK and Ip, P},
title = {Family Financial Pressure in Childhood and Telomere Length in Early Adolescence: A Prospective Study.},
journal = {Genes},
volume = {13},
number = {5},
pages = {},
pmid = {35627106},
issn = {2073-4425},
mesh = {Adolescent ; Female ; *Financial Stress ; Humans ; Male ; Prospective Studies ; Stress, Psychological/genetics ; *Telomere/genetics ; Telomere Shortening/genetics ; },
abstract = {Much research on children in high-risk environments has focused on the biological consequences of maltreatment, adversity, and trauma. Whether other early-life stress sources such as family financial hardship are implicated in the cellular mechanism of disease development remains unclear. This study investigated the long-term effect of childhood exposure to family financial pressure on telomere length. It involved two waves of data collection occurring when participants reached Grade 3 (W1) and 7 (W2), respectively. In W1, parents reported family demographics and perceived financial stressors and pressure. In W2, participants provided buccal swab samples for measurement of their telomere length. Data from 92 participants (Mage in W2 = 13.2 years; 56.5% male) were analyzed. The main type of stressors reported by parents who perceived high family financial pressure in W1 were child-level stressors including affordability of their medical and educational expenses. Participants exposed to high parent-perceived family financial pressure in W1 had shorter telomeres in W2 when compared to those exposed to low parent-perceived family financial pressure (β = -0.61, p = 0.042). Subgroup analyses revealed stronger associations in girls than boys. These findings reveal an important spillover effect between parental financial perceptions and stress and children's health at the cellular level.},
}
@article {pmid35626642,
year = {2022},
author = {Semeraro, MD and Almer, G and Renner, W and Gruber, HJ and Herrmann, M},
title = {Influences of Long-Term Exercise and High-Fat Diet on Age-Related Telomere Shortening in Rats.},
journal = {Cells},
volume = {11},
number = {10},
pages = {},
pmid = {35626642},
issn = {2073-4409},
mesh = {Animals ; Diet, High-Fat ; Female ; Leukocytes, Mononuclear ; Rats ; Rats, Sprague-Dawley ; *Telomerase/genetics ; *Telomere Shortening ; },
abstract = {(1) Obesity and exercise are believed to modify age-related telomere shortening by regulating telomerase and shelterins. Existing studies are inconsistent and limited to peripheral blood mononuclear cells (PBMCs) and selected solid tissues. (2) Female Sprague Dawley (SD) rats received either standard diet (ND) or high-fat diet (HFD). For 10 months, half of the animals from both diet groups performed 30 min running at 30 cm/s on five consecutive days followed by two days of rest (exeND, exeHFD). The remaining animals served as sedentary controls (coND, coHFD). Relative telomere length (RTL) and mRNA expression of telomerase (TERT) and the shelterins TERF-1 and TERF-2 were mapped in PBMCs and nine solid tissues. (3) At study end, coND and coHFD animals showed comparable RTL in most tissues with no systematic differences in TERT, TERF-1 and TERF-2 expression. Only visceral fat of coHFD animals showed reduced RTL and lower expression of TERT, TERF-1 and TERF-2. Exercise had heterogeneous effects on RTL in exeND and exeHFD animals with longer telomeres in aorta and large intestine, but shorter telomeres in PBMCs and liver. Telomere-regulating genes showed inconsistent expression patterns. (4) In conclusion, regular exercise or HFD cannot systematically modify RTL by regulating the expression of telomerase and shelterins.},
}
@article {pmid35622501,
year = {2022},
author = {Lee, BY and Kim, J and Lee, J},
title = {Long-read sequencing infers a mechanism for copy number variation of template for alternative lengthening of telomeres in a wild C. elegans strain.},
journal = {microPublication biology},
volume = {2022},
number = {},
pages = {},
pmid = {35622501},
issn = {2578-9430},
abstract = {Template for alternative lengthening of telomeres 1 (TALT1) is a specific sequence used to protect chromosomal ends from telomere damage first identified in the CB4856 strain of Caenorhabditis elegans . Here we assembled the genome of DL226, a wild strain with one more copy of TALT1-like sequences in its genome compared to those of CB4856, using long-read DNA sequencing. We found that a five-copy array of short telomeric repeats and TALT1s present in CB4856 were changed to a six-copy array due to the duplication of the third copy; there was an additional damage-repair trace in the new short telomeric repeat near the newly replicated TALT1.},
}
@article {pmid35619042,
year = {2022},
author = {Spano, L and Hennion, V and Marie-Claire, C and Bellivier, F and Scott, J and Etain, B},
title = {Associations between circadian misalignment and telomere length in BD: an actigraphy study.},
journal = {International journal of bipolar disorders},
volume = {10},
number = {1},
pages = {14},
pmid = {35619042},
issn = {2194-7511},
support = {Prix Face//Fondation FondaMental/ ; Prix Marcel Dassault//Fondation FondaMental/ ; C0829//Institut National de la Sant&#xe9; et de la Recherche M&#xe9;dicale/ ; GAN12//Assistance Publique - H&#xf4;pitaux de Paris/ ; },
abstract = {BACKGROUND: Life expectancy is significantly decreased in bipolar disorder (BD). This is associated with accelerated cellular aging which can be estimated by telomere length (TL). However, specific determinants of shorter TL in BD are under-explored. This study examines whether circadian misalignment (i.e. mismatch between preferred and actual phase of circadian activity rhythms) is associated with shorter TL in BD.<br><br>METHODS: Euthymic individuals with BD (n&#x2009;=&#x2009;101) undertook 21 consecutive days of actigraphy recording and completed the Composite Scale of Morningness (CSM) to assess phase preference for activities (chronotype). Polymerase chain reaction was used to measure TL in blood. Cluster analysis identified circadian aligned/misaligned subgroups as defined by preferred (CSM score) and actual phases of activity (actigraphically determined onset of active and inactive periods). We tested for any associations between TL and clusters, with adjustments for between-cluster differences in socio-demographic and illness factors.<br><br>RESULTS: We identified three clusters: an "Aligned Morning" cluster (n&#x2009;=&#x2009;31) with preferred and actual timing of activity in the morning, an "Aligned Evening" cluster (n&#x2009;=&#x2009;37) with preferred and actual timing of activity in the evening and a "Misaligned" cluster (n&#x2009;=&#x2009;32) with an evening chronotype, but an earlier objective onset of active periods. After adjustment for confounders, we found that TL was significantly associated with circadian misalignment and older age.<br><br>CONCLUSIONS: Circadian misalignment may partly explain shorter TL in BD and could contribute to accelerated aging in these individuals.},
}
@article {pmid35614304,
year = {2022},
author = {Courtney, MG and Roberts, J and Godde, K},
title = {How social/environmental determinants and inflammation affect salivary telomere length among middle-older adults in the health and retirement study.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {8882},
pmid = {35614304},
issn = {2045-2322},
support = {R15 AG063330/AG/NIA NIH HHS/United States ; U01 AG009740/AG/NIA NIH HHS/United States ; R21 AG045625/AG/NIA NIH HHS/United States ; R15AG063330/AG/NIA NIH HHS/United States ; UL1 TR001086/TR/NCATS NIH HHS/United States ; P01 AG017625/AG/NIA NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Aging ; *C-Reactive Protein/metabolism ; Humans ; *Inflammation/metabolism ; Middle Aged ; Retirement/statistics &amp; numerical data ; *Social Determinants of Health ; *Telomere/genetics/metabolism ; *Telomere Shortening/genetics/physiology ; },
abstract = {Social epidemiology posits that chronic stress from social determinants will lead to a prolonged inflammatory response that may induce accelerated aging as measured, for example, through telomere length (TL). In this paper, we hypothesize variables across demographic, health-related, and contextual/environmental domains influence the body's stress response, increase inflammation (as measured through high-sensitivity C-reactive protein (hs-CRP)), and thereby lead to shortening of telomeres. This population-based research uses data from the 2008 Health and Retirement Study on participants ages ≤ 54-95 + years, estimating logistic regression and Cox proportional hazards models of variables (with and without confounders) across the domains on shortened TL. A mediation analysis is also conducted. Contrary to expectations, hs-CRP is not associated with risk of shortened TL. Rather, factors related to accessing health care, underlying conditions of frailty, and social inequality appear to predict risk of shorter TL, and models demonstrate considerable confounding. Further, hs-CRP is not a mediator for TL. Therefore, the social determinants of health examined do not appear to follow an inflammatory pathway for shortened TL. The finding of a relationship to social determinants affecting access to health care and medical conditions underscores the need to address social determinants alongside primary care when examining health inequities.},
}
@article {pmid35612837,
year = {2022},
author = {Koller, A and Brandl, C and Lamina, C and Zimmermann, ME and Summerer, M and Stark, KJ and Würzner, R and Heid, IM and Kronenberg, F},
title = {Relative Telomere Length Is Associated With Age-Related Macular Degeneration in Women.},
journal = {Investigative ophthalmology &amp; visual science},
volume = {63},
number = {5},
pages = {30},
pmid = {35612837},
issn = {1552-5783},
support = {W 1253/FWF_/Austrian Science Fund FWF/Austria ; },
mesh = {Aged ; Aged, 80 and over ; Aging/physiology ; Cholesterol, HDL ; Female ; Humans ; *Macular Degeneration/genetics ; Male ; Odds Ratio ; Risk Factors ; *Telomere/genetics ; },
abstract = {PURPOSE: Relative telomere length (RTL) is a biomarker for physiological aging. Premature shortening of telomeres is associated with oxidative stress, which is one possible pathway that might contribute to age-related macular degeneration (AMD). We therefore aimed to investigate the association between RTL and AMD in a well-characterized group of elderly individuals.<br><br>METHODS: We measured RTL in participants of the AugUR study using a multiplex quantitative PCR-based assay determining the ratio between the telomere product and a single-copy gene product (T/S ratio). AMD was assessed by manual grading of color fundus images using the Three Continent AMD Consortium Severity Scale.<br><br>RESULTS: Among the 2262 individuals 70 to 95 years old (627 with AMD and 1635 without AMD), RTL was significantly shorter in individuals with AMD compared to AMD-free participants. In age- and sex-adjusted logistic regression analyses, we observed an 8% higher odds for AMD per 0.1 unit shorter RTL (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.02-1.14; P = 0.005). The estimates remained stable when adjusted for smoking, high-density lipoprotein cholesterol, cardiovascular disease, diabetes, and hypertension. Interestingly, this association was only present in women (OR = 1.14; 95% CI, 1.06-1.23; P < 0.001), but not in men (OR = 1.01; 95% CI, 0.93-1.10; P = 0.76). A significant sex-by-RTL interaction on AMD was detected (P = 0.043).<br><br>CONCLUSIONS: Our results show an association of RTL with AMD that was restricted to women. This is in line with altered reactive oxygen species levels and higher telomerase activity in women and provides an indication for a sex-differential pathway for oxidative stress and AMD.},
}
@article {pmid35609925,
year = {2022},
author = {Armanios, M},
title = {The Role of Telomeres in Human Disease.},
journal = {Annual review of genomics and human genetics},
volume = {23},
number = {},
pages = {363-381},
pmid = {35609925},
issn = {1545-293X},
support = {R01 CA225027/CA/NCI NIH HHS/United States ; R01 HL119476/HL/NHLBI NIH HHS/United States ; },
mesh = {Animals ; Genomic Instability ; Growth Disorders ; Humans ; Hypercalcemia ; Metabolic Diseases ; Mice ; *Neoplasms/genetics/pathology ; Nephrocalcinosis ; Syndrome ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism/pathology ; },
abstract = {Telomere biology was first studied in maize, ciliates, yeast, and mice, and in recent decades, it has informed understanding of common disease mechanisms with broad implications for patient care. Short telomere syndromes are the most prevalent premature aging disorders, with prominent phenotypes affecting the lung and hematopoietic system. Less understood are a newly recognized group of cancer-prone syndromes that are associated with mutations that lengthen telomeres. A large body of new data from Mendelian genetics and epidemiology now provides an opportunity to reconsider paradigms related to the role of telomeres in human aging and cancer, and in some cases, the findings diverge from what was interpreted from model systems. For example, short telomeres have been considered potent drivers of genome instability, but age-associated solid tumors are rare in individuals with short telomere syndromes, and T cell immunodeficiency explains their spectrum. More commonly, short telomeres promote clonal hematopoiesis, including somatic reversion, providing a new leukemogenesis paradigm that is independent of genome instability. Long telomeres, on the other hand, which extend the cellular life span in vitro, are now appreciated to be the most common shared germline risk factor for cancer in population studies. Through this contemporary lens, I revisit here the role of telomeres in human aging, focusing on how short and long telomeres drive cancer evolution but through distinct mechanisms.},
}
@article {pmid35608796,
year = {2023},
author = {Farladansky-Gershnabel, S and Dekel, N and Biron-Shental, T and Shechter-Maor, G and Amiel, A and Weisz, A and Benchetrit, S and Zitman-Gal, T},
title = {Spontaneous Preterm Birth: Elevated Galectin-3 and Telomere Shortening May Reflect a Common Pathway of Enhanced Inflammation and Senescence.},
journal = {Reproductive sciences (Thousand Oaks, Calif.)},
volume = {30},
number = {2},
pages = {487-493},
pmid = {35608796},
issn = {1933-7205},
mesh = {Pregnancy ; Female ; Infant, Newborn ; Humans ; *Premature Birth/metabolism ; Placenta/metabolism ; Telomere Shortening ; Galectin 3/metabolism ; *Obstetric Labor, Premature/metabolism ; Inflammation/metabolism ; },
abstract = {Preterm delivery complicates 5-12% of pregnancies and is the primary cause of neonatal morbidity and mortality. The pathophysiology of preterm labor and parturition is not fully known, although it is probably related to inflammation and placental senescence. Telomere shortening is related to senescence and galectin-3 (Gal-3) protein is involved in cell growth, differentiation, inflammation, and fibrosis. This study examined changes in Gal-3 expression and telomere homeostasis (which represent inflammatory and stress markers) in maternal blood and placental tissue of spontaneous preterm births (SPTB) and uncomplicated, spontaneous term pregnancies (NTP) during labor. Participants included 19 women with NTP and 11 with SPTB who were enrolled during admission for delivery. Maternal blood samples were obtained along with placental tissue for Gal-3 analysis and telomere length evaluation. Gal-3 protein expression in placental tissue was increased in SPTB compared to NTP (fold change: 1.89 ± 0.36, P < 0.05). Gal-3 immunohistochemistry demonstrated strong staining in placental extravillous trophoblast tissue from SPTB. Maternal blood levels of Gal-3 protein were elevated in SPTB compared to NTP (19.3 ± 1.3 ng/ml vs. 13.6 ± 1.07 ng/ml, P = 0.001). Placental samples from SPTB had a higher percentage of trophoblasts with short telomeres (47.6%) compared to NTP (15.6%, P < 0.0001). Aggregate formation was enhanced in SPTB (7.8%) compared to NTP (1.98%, P < 0.0001). Maternal blood and placental samples from SPTB had shorter telomeres and increased Gal-3 expression compared to NTP. These findings suggest that increased senescence and inflammation might be factors in the abnormal physiology of spontaneous preterm labor.},
}
@article {pmid35601455,
year = {2022},
author = {Roast, MJ and Eastwood, JR and Aranzamendi, NH and Fan, M and Teunissen, N and Verhulst, S and Peters, A},
title = {Telomere length declines with age, but relates to immune function independent of age in a wild passerine.},
journal = {Royal Society open science},
volume = {9},
number = {4},
pages = {212012},
pmid = {35601455},
issn = {2054-5703},
abstract = {Telomere length (TL) shortens with age but telomere dynamics can relate to fitness components independent of age. Immune function often relates to such fitness components and can also interact with telomeres. Studying the link between TL and immune function may therefore help us understand telomere-fitness associations. We assessed the relationships between erythrocyte TL and four immune indices (haptoglobin, natural antibodies (NAbs), complement activity (CA) and heterophil-lymphocyte (HL) ratio; n = 477-589), from known-aged individuals of a wild passerine (Malurus coronatus). As expected, we find that TL significantly declined with age. To verify whether associations between TL and immune function were independent of parallel age-related changes (e.g. immunosenescence), we statistically controlled for sampling age and used within-subject centring of TL to separate relationships within or between individuals. We found that TL positively predicted CA at the between-individual level (individuals with longer average TL had higher CA), but no other immune indices. By contrast, age predicted the levels of NAbs and HL ratio, allowing inference that respective associations between TL and age with immune indices are independent. Any links existing between TL and fitness are therefore unlikely to be strongly mediated by innate immune function, while TL and immune indices appear independent expressions of individual heterogeneity.},
}
@article {pmid35597826,
year = {2022},
author = {Zhang, JC and Li, SJ and Guo, JY and Zhang, GY and Kang, H and Shi, XJ and Zhou, H and Liang, YF and Shen, WT and Lei, LJ},
title = {Urinary cadmium and peripheral blood telomere length predict the risk of renal function impairment: a study of 547 community residents of Shanxi, China.},
journal = {Environmental science and pollution research international},
volume = {29},
number = {47},
pages = {71427-71438},
pmid = {35597826},
issn = {1614-7499},
support = {81872701//National Natural Science Foundation of China/ ; 81273040//National Natural Science Foundation of China/ ; },
mesh = {Acetylglucosaminidase/urine ; *Cadmium/toxicity/urine ; China ; Creatinine ; Cross-Sectional Studies ; Female ; Humans ; Kidney/physiology ; Male ; *Renal Insufficiency/chemically induced ; Telomere ; },
abstract = {Few reports have investigated the predictive value of urinary cadmium (UCd) and telomere length on renal function impairment. Therefore, we constructed nomogram models, using a cross-sectional survey to analyze the potential function of UCd and telomere length in renal function impairment risk. We randomly selected two community populations in Shanxi, China, and general information of the subjects was collected through face-to-face questionnaire surveys. Venous blood of subjects was collected to detect absolute telomere length (ATL) by real-time quantitative chain reaction (RT-PCR). Collecting urinary samples detected UCd and urinary N-acetyl-β-d-glucosaminidase (UNAG). Estimated glomerular filtration rate (eGFR) was obtained based on serum creatinine (SCr). Nomogram models on risk prediction analysis of renal function impairment was constructed. After adjusting for other confounding factors, UCd (β = 0.853, 95% confidence interval (CI): 0.739 ~ 0.986) and ATL (β = 1.803, 95%CI: 1.017 ~ 1.154) were independent risk influencing factors for increased UNAG levels, and the risk factors for eGFR reduction were UCd (β = 1.011, 95%CI: 1.187 ~ 1.471), age (β = 1.630, 95%CI: 1.303 ~ 2.038), and sex (β = 0.181, 95%CI: 0.105 ~ 0.310). Using UCd, ATL, sex, and age to construct the nomogram, and the C-statistics 0.584 (95%CI: 0.536 ~ 0.632) and 0.816 (95%CI: 0.781 ~ 0.851) were obtained by internal verification of the calibration curve, C-statistics revealed nomogram model validation was good and using decision curve analysis (DCA) confirmed a good predictive value of the nomogram models. In a nomogram model, ATL, UCd, sex, and age were detected as independent risk factors for renal function impairment, with UCd being the strongest predictor.},
}
@article {pmid35590036,
year = {2022},
author = {Dempsey, PC and Musicha, C and Rowlands, AV and Davies, M and Khunti, K and Razieh, C and Timmins, I and Zaccardi, F and Codd, V and Nelson, CP and Yates, T and Samani, NJ},
title = {Author Correction: Investigation of a UK biobank cohort reveals causal associations of self-reported walking pace with telomere length.},
journal = {Communications biology},
volume = {5},
number = {1},
pages = {498},
doi = {10.1038/s42003-022-03459-w},
pmid = {35590036},
issn = {2399-3642},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; },
}
@article {pmid35588569,
year = {2022},
author = {Bhargava, R and Lynskey, ML and O'Sullivan, RJ},
title = {New twists to the ALTernative endings at telomeres.},
journal = {DNA repair},
volume = {115},
number = {},
pages = {103342},
pmid = {35588569},
issn = {1568-7856},
support = {P30 CA047904/CA/NCI NIH HHS/United States ; R01 CA207209/CA/NCI NIH HHS/United States ; R01 CA262316/CA/NCI NIH HHS/United States ; R37 CA263622/CA/NCI NIH HHS/United States ; },
mesh = {Chromatin ; Histones/genetics ; *Telomerase/metabolism ; Telomere/metabolism ; *Telomere Homeostasis ; },
abstract = {Activation of a telomere maintenance mechanism is key to achieving replicative immortality. Alternative Lengthening of Telomeres (ALT) is a telomerase-independent pathway that hijacks the homologous recombination pathways to elongate telomeres. Commitment to ALT is often associated with several hallmarks including long telomeres of heterogenous lengths, mutations in histone H3.3 or the ATRX/DAXX histone chaperone complex, and incorporation of non-canonical telomere sequences. The consequences of these genetic and epigenetic changes include enhanced replication stress and the presence of transcriptionally permissive chromatin, which can result in replication-associated DNA damage. Here, we detail the molecular mechanisms that are critical to repairing DNA damage at ALT telomeres, including the BLM Helicase, which acts at several steps in the ALT process. Furthermore, we discuss the emerging findings related to the telomere-associated RNA, TERRA, and its roles in maintaining telomeric integrity. Finally, we review new evidence for therapeutic interventions for ALT-positive cancers which are rooted in understanding the molecular underpinnings of this process.},
}
@article {pmid35588001,
year = {2022},
author = {Wong, KK and Cheng, F and Mao, D and Lim, CKP and Tam, CHT and Wang, CC and Yuen, LY and Chan, MHM and Ho, CS and Joglekar, MV and Hardikar, AA and Jenkins, AJ and Metzger, BE and Lowe, WL and Tam, WH and Ma, RCW},
title = {Vitamin D Levels During Pregnancy Are Associated With Offspring Telomere Length: A Longitudinal Mother-Child Study.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {107},
number = {9},
pages = {e3901-e3909},
pmid = {35588001},
issn = {1945-7197},
support = {R01 HD034242/HD/NICHD NIH HHS/United States ; },
mesh = {Calcifediol ; Child ; Cohort Studies ; *Diabetes Mellitus, Type 2 ; Female ; Humans ; Male ; Mother-Child Relations ; Pregnancy ; Telomere ; Vitamin D ; *Vitamin D Deficiency/complications/epidemiology ; Vitamins ; },
abstract = {CONTEXT: Leukocyte telomere length (LTL) is a biomarker of biological aging and is associated with metabolic diseases such as type 2 diabetes. Insufficient maternal vitamin D was associated with increased risk for many diseases and adverse later life outcomes.<br><br>OBJECTIVE: This study investigates the relationship between vitamin D levels and offspring LTL at early life.<br><br>METHODS: This observational, longitudinal, hospital-based cohort study included eligible mother-child pairs from the HAPO Hong Kong Field Centre, with 853 offspring at age 6.96&#x2005;&#xb1;&#x2005;0.44 (mean&#x2005;&#xb1;&#x2005;SD) years. LTL was measured using real-time polymerase chain reaction while serum vitamin D metabolites 25(OH)D2, 25(OH)D3, and 3-epi-25(OH)D3 were measured in maternal blood (at gestation 24-32 weeks) and cord blood by liquid chromatography-mass spectrometry.<br><br>RESULTS: LTL at follow-up was significantly shorter in boys compared with girls (P&#x2005;<&#x2005;0.001) at age 7. Childhood LTL was negatively associated with childhood BMI (&#x3b2;&#x2005;&#xb1;&#x2005;SE&#x2005;=&#x2005;-0.016&#x2005;&#xb1;&#x2005;0.007)(P&#x2005;=&#x2005;0.02) and HOMA-IR (&#x3b2;&#x2005;&#xb1;&#x2005;SE&#x2005;=&#x2005;-0.065&#x2005;&#xb1;&#x2005;0.021)(P&#x2005;=&#x2005;0.002). Multiple linear regression was used to evaluate the relationship between 25(OH)D and LTL, with covariate adjustments. Childhood LTL was positively correlated with total maternal 25(OH)D (0.048&#x2005;&#xb1;&#x2005;0.017) (P&#x2005;=&#x2005;0.004) and maternal 3-epi-25(OH)D3 (0.05&#x2005;&#xb1;&#x2005;0.017) (P&#x2005;=&#x2005;0.003), even after adjustment for covariates. A similar association was also noted for cord 3-epi-25(OH)D3 (0.037&#x2005;&#xb1;&#x2005;0.018) (P&#x2005;=&#x2005;0.035) after adjustment for offspring sex and age.<br><br>CONCLUSION: Our findings suggest 25(OH)D3 and 3-epi-25(OH)D3 in utero may impact on childhood LTLs, highlighting a potential link between maternal vitamin D and biological aging.},
}
@article {pmid35587917,
year = {2022},
author = {Zahid, S and Aloe, S and Sutherland, JH and Holloman, WK and Lue, NF},
title = {Ustilago maydis telomere protein Pot1 harbors an extra N-terminal OB fold and regulates homology-directed DNA repair factors in a dichotomous and context-dependent manner.},
journal = {PLoS genetics},
volume = {18},
number = {5},
pages = {e1010182},
pmid = {35587917},
issn = {1553-7404},
support = {R01 GM107287/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Basidiomycota ; DNA/genetics ; DNA Repair/genetics ; Mammals/genetics ; Protein Binding ; *Telomere/genetics/metabolism ; Telomere-Binding Proteins/genetics/metabolism ; *Ustilago/genetics ; },
abstract = {The telomere G-strand binding protein Pot1 plays multifaceted roles in telomere maintenance and protection. We examined the structure and activities of Pot1 in Ustilago maydis, a fungal model that recapitulates key features of mammalian telomere regulation. Compared to the well-characterized primate and fission yeast Pot1 orthologs, UmPot1 harbors an extra N-terminal OB-fold domain (OB-N), which was recently shown to be present in most metazoans. UmPot1 binds directly to Rad51 and regulates the latter's strand exchange activity. Deleting the OB-N domain, which is implicated in Rad51-binding, caused telomere shortening, suggesting that Pot1-Rad51 interaction facilitates telomere maintenance. Depleting Pot1 through transcriptional repression triggered growth arrest as well as rampant recombination, leading to multiple telomere aberrations. In addition, telomere repeat RNAs transcribed from both the G- and C-strand were dramatically up-regulated, and this was accompanied by elevated levels of telomere RNA-DNA hybrids. Telomere abnormalities of pot1-deficient cells were suppressed, and cell viability was restored by the deletion of genes encoding Rad51 or Brh2 (the BRCA2 ortholog), indicating that homology-directed repair (HDR) proteins are key mediators of telomere aberrations and cellular toxicity. Together, these observations underscore the complex physical and functional interactions between Pot1 and DNA repair factors, leading to context-dependent and dichotomous effects of HDR proteins on telomere maintenance and protection.},
}
@article {pmid35587764,
year = {2022},
author = {Gong, H and Yu, Q and Yuan, M and Jiang, Y and Wang, J and Huang, P and Zhou, J},
title = {The Relationship between Dietary Copper intake and Telomere Length in Hypertension.},
journal = {The journal of nutrition, health &amp; aging},
volume = {26},
number = {5},
pages = {510-514},
doi = {10.1007/s12603-022-1787-7},
pmid = {35587764},
issn = {1760-4788},
mesh = {Copper ; Humans ; *Hypertension/genetics ; Leukocytes ; Nutrition Surveys ; Prospective Studies ; *Telomere ; },
abstract = {BACKGROUND: More indications proved that diet might be involved in the telomere length, a marker of biological aging and chronic diseases. Copper is widely viewed as one of the essential elements in the diet. Therefore, this study aimed to evaluate the relationship between telomere length and dietary copper intake in hypertension and provide a basis for guiding dietary copper intake in patients with hypertension.<br><br>METHODS: The data was collected from the National Health and Nutrition Examination Survey (NHANES) in 1999-2000 and 2001-2002. The relevance between telomere length and dietary copper intake in hypertension is assessed using a multivariable linear regression model.<br><br>RESULTS: We gathered 1,867 participants with hypertension with assessed telomere length and dietary copper intake. We found that one unit increasing log-transformed dietary copper intake in hypertension was significantly associated with longer telomere length base pair (bp) (&#x3b2; = 112.20, 95% confidence interval [CI]: 5.48, 218.92), after controlling for covariates, including age, sex, ethnicity, body mass index (BMI), physical activity, and taking medication for hypertension. For the age group, we found that one unit increasing log-transformed dietary copper in hypertension was associated with longer telomere length (&#x3b2; = 237.95, 95% CI: 114.39, 361.51) in the age group >45 years. The grouping was based on whether the participants take medication for hypertension. We found that one unit increasing log-transformed dietary copper in hypertension was associated with longer telomere length (&#x3b2; = 116.47, 95% CI: 0.72, 232.21) in the group that takes medication for hypertension.<br><br>CONCLUSIONS: This study demonstrates that dietary copper intake was associated with longer telomere length in patients with hypertension, which provides evidence for guiding dietary copper intake in patients with hypertension. However, further studies are needed to evaluate the effect of copper supplementation on telomere length in patients with hypertension in well-designed random control studies and prospective studies.},
}
@article {pmid35585300,
year = {2022},
author = {Pearce, EE and Alsaggaf, R and Katta, S and Dagnall, C and Aubert, G and Hicks, BD and Spellman, SR and Savage, SA and Horvath, S and Gadalla, SM},
title = {Telomere length and epigenetic clocks as markers of cellular aging: a comparative study.},
journal = {GeroScience},
volume = {44},
number = {3},
pages = {1861-1869},
pmid = {35585300},
issn = {2509-2723},
mesh = {Biomarkers ; Cellular Senescence ; *DNA Methylation ; Epigenesis, Genetic ; *Epigenomics ; Humans ; Telomere/genetics ; },
abstract = {Telomere length (TL) and DNA methylation-based epigenetic clocks are markers of biological age, but the relationship between the two is not fully understood. Here, we used multivariable regression models to evaluate the relationships between leukocyte TL (LTL; measured by qPCR [n = 635] or flow FISH [n = 144]) and five epigenetic clocks (Hannum, DNAmAge pan-tissue, PhenoAge, SkinBlood, or GrimAge clocks), or their epigenetic age acceleration measures in healthy adults (age 19-61 years). LTL showed statistically significant negative correlations with all clocks (qPCR: r = - 0.26 to - 0.32; flow FISH: r = - 0.34 to - 0.49; p < 0.001 for all). Yet, models adjusted for age, sex, and race revealed significant associations between three of five clocks (PhenoAge, GrimAge, and Hannum clocks) and LTL by flow FISH (p < 0.01 for all) or qPCR (p < 0.001 for all). Significant associations between age acceleration measures for the same three clocks and qPCR or flow FISH TL were also found (p < 0.01 for all). Additionally, LTL (by qPCR or flow FISH) showed significant associations with extrinsic epigenetic age acceleration (EEAA: p < 0.0001 for both), but not intrinsic epigenetic age acceleration (IEAA; p > 0.05 for both). In conclusion, the relationships between LTL and epigenetic clocks were limited to clocks reflecting phenotypic age. The observed association between LTL and EEAA reflects the ability of both measures to detect immunosenescence. The observed modest correlations between LTL and epigenetic clocks highlight a possible benefit from incorporating both measures in understanding disease etiology and prognosis.},
}
@article {pmid35584004,
year = {2022},
author = {Mota, JIS and Silva-Júnior, RMP and Martins, CS and Bueno, AC and Wildemberg, LE and Antunes, XLDS and Ozaki, JGO and Coeli-Lacchini, FB and Garcia-Peral, C and Oliveira, AER and Santos, AC and Moreira, AC and Machado, HR and Dos Santos, MV and Colli, LM and Gadelha, MR and Antonini, SRR and de Castro, M},
title = {Telomere length and Wnt/β-catenin pathway in adamantinomatous craniopharyngiomas.},
journal = {European journal of endocrinology},
volume = {187},
number = {2},
pages = {219-230},
doi = {10.1530/EJE-21-1269},
pmid = {35584004},
issn = {1479-683X},
mesh = {Adolescent ; Child ; *Craniopharyngioma/genetics ; Cross-Sectional Studies ; Humans ; Mutation ; Retrospective Studies ; *Telomere/ultrastructure ; Wnt Signaling Pathway ; *beta Catenin/genetics ; },
abstract = {OBJECTIVES: To evaluate how telomere length behaves in adamantinomtous craniopharyngioma (aCP) and if it contributes to the pathogenesis of aCPs with and without CTNNB1 mutations.<br><br>DESIGN: Retrospective cross-sectional study enrolling 42 aCP patients from 2 tertiary institutions.<br><br>METHODS: Clinicopathological features were retrieved from the patient's charts. Fresh frozen tumors were used for RNA and DNA analyses. Telomere length was evaluated by qPCR (T/S ratio). Somatic mutations in TERT promoter (TERTp) and CTNNB1 were detected by Sanger and/or whole-exome sequencing. We performed RNA-Seq to identify differentially expressed genes in aCPs presenting with shorter or longer telomere lengths.<br><br>RESULTS: Mutations in CTNNB1 were detected in 29 (69%) tumors. There was higher frequency of CTNNB1 mutations in aCPs from patients diagnosed under the age of 15 years (85% vs 15%; P = 0.04) and a trend to recurrent disease (76% vs 24%; P = 0.1). No mutation was detected in the TERTp region. The telomeres were shorter in CTNNB1-mutated aCPs (0.441, IQR: 0.297-0.597vs 0.607, IQR: 0.445-0.778; P = 0.04), but it was neither associated with clinicopathological features nor with recurrence. RNAseq identified a total of 387 differentially expressed genes, generating two clusters, being one enriched for short telomeres and CTNNB1-mutated aCPs.<br><br>CONCLUSIONS: CTNNB1: mutations are more frequent in children and adolescents and appear to associate with progressive disease. CTNNB1-mutated aCPs have shorter telomeres, demonstrating a relationship between the Wnt/&#x3b2;-catenin pathway and telomere biology in the pathogenesis of aCPs.},
}
@article {pmid35580703,
year = {2022},
author = {Syreeni, A and Carroll, LM and Mutter, S and Januszewski, AS and Forsblom, C and Lehto, M and Groop, PH and Jenkins, AJ and , },
title = {Telomeres do not always shorten over time in individuals with type 1 diabetes.},
journal = {Diabetes research and clinical practice},
volume = {188},
number = {},
pages = {109926},
doi = {10.1016/j.diabres.2022.109926},
pmid = {35580703},
issn = {1872-8227},
mesh = {Cholesterol, HDL/genetics ; *Diabetes Mellitus, Type 1/drug therapy/genetics ; Humans ; Leukocytes ; Male ; Telomere/genetics ; Telomere Homeostasis ; },
abstract = {AIMS: We aimed to determine how white blood cell (WBC) telomeres and telomere length change over time are associated with health status in type 1 diabetes.<br><br>METHODS: Relative telomere length (rTL) was measured in WBC DNA from two time-points (median 6.8&#xa0;years apart) in 618 individuals from the Finnish Diabetic Nephropathy Study by quantitative PCR, with interassay CV&#xa0;&#x2264;&#xa0;4%.<br><br>RESULTS: Baseline rTL correlated inversely with age and was shorter in men. Individuals in the shortest vs. longest rTL tertile had adverse cardiometabolic profiles, worse renal function, and were prescribed more antihypertensive and lipid-lowering drugs. While overall rTL tended to decrease during the median 6.8-years of follow-up, telomeres shortened in 55.3% of subjects, lengthened in 40.0%, and did not change in 4.7%. Baseline rTL correlated inversely with rTL change. Telomere lengthening was associated with higher HDL-Cholesterol (HDL-C), HDL-C/ApoA1, and with antihypertensive drug and (inversely) with lipid-lowering drug commencement during follow-up. Correlates of rTL percentage change per-annum (adjusted model) were baseline BMI, eGFR, previous retinal laser treatment, HDL-C, and HDL-C/ApoA1.<br><br>CONCLUSIONS: Telomere length measurements may facilitate the treatment and monitoring of the health status of individuals with type 1 diabetes.},
}
@article {pmid35575903,
year = {2022},
author = {Tissier, ML and Bergeron, P and Garant, D and Zahn, S and Criscuolo, F and Réale, D},
title = {Telomere length positively correlates with pace-of-life in a sex- and cohort-specific way and elongates with age in a wild mammal.},
journal = {Molecular ecology},
volume = {31},
number = {14},
pages = {3812-3826},
doi = {10.1111/mec.16533},
pmid = {35575903},
issn = {1365-294X},
mesh = {Adult ; Aging/genetics ; Animals ; Female ; Humans ; *Longevity/genetics ; Male ; Mammals/genetics ; Telomere/genetics ; *Telomere Shortening ; },
abstract = {Understanding ageing and the diversity of life histories is a cornerstone in biology. Telomeres, the protecting caps of chromosomes, are thought to be involved in ageing, cancer risks and life-history strategies. They shorten with cell division and age in somatic tissues of most species, possibly limiting lifespan. The resource allocation trade-off hypothesis predicts that short telomeres have thus coevolved with early reproduction, proactive behaviour and reduced lifespan, that is, a fast pace-of-life syndrome (POLS). Conversely, since short telomeres may also reduce the risks of cancer, the anticancer hypothesis advances that they should be associated with slow POLS. Conclusion on which hypothesis best supports the role of telomeres as mediators of life-history strategies is hampered by a lack of study on wild short-lived vertebrates, apart from birds. Using seven years of data on wild Eastern chipmunks Tamias striatus, we highlighted that telomeres elongate with age (n = 204 and n = 20) and do not limit lifespan in this species (n = 51). Furthermore, short telomeres correlated with a slow POLS in a sex-specific way (n = 37). Females with short telomeres had a delayed age at first breeding and a lower fecundity rate than females with long telomeres, while we found no differences in males. Our findings support most predictions adapted from the anticancer hypothesis, but none of those from the resource allocation trade-off hypothesis. Results are in line with an increasing body of evidence suggesting that other evolutionary forces than resource allocation trade-offs shape the diversity of telomere length in adult somatic cells and the relationships between telomere length and life-histories.},
}
@article {pmid35567940,
year = {2022},
author = {Tang, L and Li, T and Chang, Y and Wang, Z and Li, Y and Wang, F and Sui, L},
title = {Diabetic oxidative stress-induced telomere damage aggravates periodontal bone loss in periodontitis.},
journal = {Biochemical and biophysical research communications},
volume = {614},
number = {},
pages = {22-28},
doi = {10.1016/j.bbrc.2022.04.039},
pmid = {35567940},
issn = {1090-2104},
mesh = {*Alveolar Bone Loss ; Animals ; *Diabetes Mellitus, Experimental/complications ; Mice ; Oxidative Stress ; Periodontal Ligament ; *Periodontitis/complications ; Reactive Oxygen Species ; Telomere ; },
abstract = {Periodontitis, one of the most common oral complications of diabetes mellitus (DM), causes a reduction in alveolar bone height and loss of alveolar bone mass. It has been shown that DM aggravates the progression of periodontitis, but the mechanism remains inconclusive. The hyperglycemic environment of DM has been proven to generate reactive oxygen species (ROS). Since telomeres, guanine-rich repeats, are highly susceptible to oxidative attack, we speculate that the excessive accumulation of ROS in DM could induce telomere damage resulting in dysfunction of periodontal ligament cells, especially periodontal ligament stem cells (PDLSCs), which reduces the ability of tissue repair and reconstruction in diabetic periodontitis. In this study, our current data revealed that oxidative telomere damage occurred in the periodontal ligaments of diabetic mice. And Micro-CT scans showed reduced alveolar bone height and impaired alveolar bone mass in a diabetic periodontitis model. Next, cultured mouse PDLSCs (mPDLSCs) were treated with the oxidant tert-butyl hydroperoxide (t-BHP) in vitro, as we expected telomere damage was observed and resulted in cellular senescence and dysfunction. Taken together, oxidative stress in DM causes telomere dysfunction and PDLSCs senescence, which influences periodontal bone tissue regeneration and reconstruction and ultimately exacerbates bone loss in periodontitis.},
}
@article {pmid35566652,
year = {2022},
author = {Min, J and Kim, JY and Choi, JY and Kong, ID},
title = {Association between Physical Activity and Telomere Length in Women with Breast Cancer: A Systematic Review.},
journal = {Journal of clinical medicine},
volume = {11},
number = {9},
pages = {},
pmid = {35566652},
issn = {2077-0383},
support = {NRF-2020R1I1A3070520//the National Research Foundation of Korea (NRF) grant/ ; },
abstract = {The association between physical activity and telomere length (TL) has been continuously reported. However, the interplay of physical activity and TL among women with breast cancer has not been elucidated. Thus, the purpose of this systematic review was to synthesize the evidence for the association of physical activity with TL in women with breast cancer. Systematic searches were conducted to identify quantified studies using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and Clinical Trials.gov. Five studies were included in this systematic review. Three of the five studies reported that physical activity has a significant relationship in delaying TL shortening, but others observed no association between physical activity and TL in breast cancer survivors. Although the heterogeneous studies acted as limitations in drawing clear conclusions, physical activity strategies show encouraging impacts in delaying TL shortening. To understand the effects of physical activity on TL shortening in breast cancer survivors, further studies are needed considering the tissue site, treatments for breast cancer, DNA extraction methods, and tools for measuring physical activity.},
}
@article {pmid35565445,
year = {2022},
author = {Kjeldsen, E},
title = {Congenital Aneuploidy in Klinefelter Syndrome with B-Cell Acute Lymphoblastic Leukemia Might Be Associated with Chromosomal Instability and Reduced Telomere Length.},
journal = {Cancers},
volume = {14},
number = {9},
pages = {},
pmid = {35565445},
issn = {2072-6694},
abstract = {Rare congenital aneuploid conditions such as trisomy 13, trisomy 18, trisomy 21 and Klinefelter syndrome (KS, 47,XXY) are associated with higher susceptibility to developing cancer compared with euploid genomes. Aneuploidy frequently co-exists with chromosomal instability, which can be viewed as a "vicious cycle" where aneuploidy potentiates chromosomal instability, leading to further karyotype diversity, and in turn, paving the adaptive evolution of cancer. However, the relationship between congenital aneuploidy per se and tumor initiation and/or progression is not well understood. We used G-banding analysis, array comparative genomic hybridization analysis and quantitative fluorescence in situ hybridization for telomere length analysis to characterize the leukemic blasts of a three-year-old boy with KS and B-cell acute lymphoblastic leukemia (B-ALL), to gain insight into genomic evolution mechanisms in congenital aneuploidy and leukemic development. We found chromosomal instability and a significant reduction in telomere length in leukemic blasts when compared with the non-leukemic aneuploid cells. Reviewing published cases with KS and B-ALL revealed 20 additional cases with B-ALL diagnostic cytogenetics. Including our present case, 67.7% (14/21) had acquired two or more additional chromosomal aberrations at B-ALL diagnosis. The presented data indicate that congenital aneuploidy in B-ALL might be associated with chromosomal instability, which may be fueled by enhanced telomere attrition.},
}
@article {pmid35565379,
year = {2022},
author = {Kibriya, MG and Raza, M and Kamal, M and Haq, Z and Paul, R and Mareczko, A and Pierce, BL and Ahsan, H and Jasmine, F},
title = {Relative Telomere Length Change in Colorectal Carcinoma and Its Association with Tumor Characteristics, Gene Expression and Microsatellite Instability.},
journal = {Cancers},
volume = {14},
number = {9},
pages = {},
pmid = {35565379},
issn = {2072-6694},
support = {R24 ES028532/ES/NIEHS NIH HHS/United States ; P30 ES027792/ES/NIEHS NIH HHS/United States ; R35 ES028379/ES/NIEHS NIH HHS/United States ; },
abstract = {We compared tumor and adjacent normal tissue samples from 165 colorectal carcinoma (CRC) patients to study change in relative telomere length (RTL) and its association with different histological and molecular features. To measure RTL, we used a Luminex-based assay. We observed shorter RTL in the CRC tissue compared to paired normal tissue (RTL 0.722 ± SD 0.277 vs. 0.809 ± SD 0.242, p = 0.00012). This magnitude of RTL shortening (by ~0.08) in tumor tissue is equivalent to RTL shortening seen in human leukocytes over 10 years of aging measured by the same assay. RTL was shorter in cancer tissue, irrespective of age group, gender, tumor pathology, location and microsatellite instability (MSI) status. RTL shortening was more prominent in low-grade CRC and in the presence of microsatellite instability (MSI). In a subset of patients, we also examined differential gene expression of (a) telomere-related genes, (b) genes in selected cancer-related pathways and (c) genes at the genome-wide level in CRC tissues to determine the association between gene expression and RTL changes. RTL shortening in CRC was associated with (a) upregulation of DNA replication genes, cyclin dependent-kinase genes (anti-tumor suppressor) and (b) downregulation of "caspase executor", reducing apoptosis.},
}
@article {pmid35565323,
year = {2022},
author = {Hou, K and Yu, Y and Li, D and Zhang, Y and Zhang, K and Tong, J and Yang, K and Jia, S},
title = {Alternative Lengthening of Telomeres and Mediated Telomere Synthesis.},
journal = {Cancers},
volume = {14},
number = {9},
pages = {},
pmid = {35565323},
issn = {2072-6694},
support = {YNWRQNBJ-2019-240//Yunnan "Ten Thousand Talents Plan" Young Top Talent Project/ ; 202201AS070074//Yunnan Fundamental Research Project/ ; },
abstract = {Telomeres are DNA-protein complexes that protect eukaryotic chromosome ends from being erroneously repaired by the DNA damage repair system, and the length of telomeres indicates the replicative potential of the cell. Telomeres shorten during each division of the cell, resulting in telomeric damage and replicative senescence. Tumor cells tend to ensure cell proliferation potential and genomic stability by activating telomere maintenance mechanisms (TMMs) for telomere lengthening. The alternative lengthening of telomeres (ALT) pathway is the most frequently activated TMM in tumors of mesenchymal and neuroepithelial origin, and ALT also frequently occurs during experimental cellular immortalization of mesenchymal cells. ALT is a process that relies on homologous recombination (HR) to elongate telomeres. However, some processes in the ALT mechanism remain poorly understood. Here, we review the most recent understanding of ALT mechanisms and processes, which may help us to better understand how the ALT pathway is activated in cancer cells and determine the potential therapeutic targets in ALT pathway-stabilized tumors.},
}
@article {pmid35563554,
year = {2022},
author = {Dratwa, M and Wysoczanska, B and Brankiewicz, W and Stachowicz-Suhs, M and Wietrzyk, J and Matkowski, R and Ekiert, M and Szelachowska, J and Maciejczyk, A and Szajewski, M and Baginski, M and Bogunia-Kubik, K},
title = {Relationship between Telomere Length, TERT Genetic Variability and TERT, TP53, SP1, MYC Gene Co-Expression in the Clinicopathological Profile of Breast Cancer.},
journal = {International journal of molecular sciences},
volume = {23},
number = {9},
pages = {},
pmid = {35563554},
issn = {1422-0067},
support = {STRATEGMED3/306853//National Centre for Research and Development/ ; 2017/27/B/NZ5/01167//National Science Center/ ; },
mesh = {*Breast Neoplasms/genetics/pathology ; Female ; Genes, myc ; Humans ; Polymorphism, Single Nucleotide ; Sp1 Transcription Factor/genetics ; *Telomerase/genetics ; Telomere/pathology ; Tumor Suppressor Protein p53/genetics ; },
abstract = {The molecular mechanisms of telomerase reverse transcriptase (TERT) upregulation in breast cancer (BC) are complex. We compared genetic variability within TERT and telomere length with the clinical data of patients with BC. Additionally, we assessed the expression of the TERT, MYC, TP53 and SP1 genes in BC patients and in BC organoids (3D cell cultures obtained from breast cancer tissues). We observed the same correlation in the blood of BC patients and in BC organoids between the expression of TERT and TP53. Only in BC patients was a correlation found between the expression of the TERT and MYC genes and between TP53 and MYC. We found associations between TERT genotypes (rs2735940 and rs10069690) and TP53 expression and telomere length. BC patients with the TT genotype rs2735940 have a shorter telomere length, but patients with A allele rs10069690 have a longer telomere length. BC patients with a short allele VNTR-MNS16A showed higher expression of the SP1 and had a longer telomere. Our results bring new insight into the regulation of TERT, MYC, TP53 and SP1 gene expression related to TERT genetic variability and telomere length. Our study also showed for the first time a similar relationship in the expression of the above genes in BC patients and in BC organoids. These findings suggest that TERT genetic variability, expression and telomere length might be useful biomarkers for BC, but their prognostic value may vary depending on the clinical parameters of BC patients and tumor aggressiveness.},
}
@article {pmid35563512,
year = {2022},
author = {Libera, V and Bianchi, F and Rossi, B and D'Amico, F and Masciovecchio, C and Petrillo, C and Sacchetti, F and Paciaroni, A and Comez, L},
title = {Solvent Vibrations as a Proxy of the Telomere G-Quadruplex Rearrangements across Thermal Unfolding.},
journal = {International journal of molecular sciences},
volume = {23},
number = {9},
pages = {},
pmid = {35563512},
issn = {1422-0067},
support = {COAN:07.70.01.06.01 UA.PG.DFIG//PETCARESS/ ; },
mesh = {Circular Dichroism ; *G-Quadruplexes ; Gene Rearrangement ; Humans ; Solvents ; Telomere/genetics ; Vibration ; Water ; },
abstract = {G-quadruplexes (G4s) are noncanonical forms of DNA involved in many key genome functions. Here, we exploited UV Resonance Raman scattering to simultaneously explore the vibrational behavior of a human telomeric G4 (Tel22) and its aqueous solvent as the biomolecule underwent thermal melting. We found that the OH stretching band, related to the local hydrogen-bonded network of a water molecule, was in strict relation with the vibrational features of the G4 structure as a function of temperature. In particular, the modifications to the tetrahedral ordering of the water network were strongly coupled to the DNA rearrangements, showing changes in temperature that mirrored the multi-step melting process of Tel22. The comparison between circular dichroism and Raman results supported this view. The present findings provide novel insights into the impact of the molecular environment on G4 conformation. Improving current knowledge on the solvent structural properties will also contribute to a better understanding of the role played by water arrangement in the complexation of G4s with ligands.},
}
@article {pmid35563379,
year = {2022},
author = {Castillo-González, C and Barbero Barcenilla, B and Young, PG and Hall, E and Shippen, DE},
title = {Quantification of 8-oxoG in Plant Telomeres.},
journal = {International journal of molecular sciences},
volume = {23},
number = {9},
pages = {},
pmid = {35563379},
issn = {1422-0067},
support = {R01 GM065383/GM/NIGMS NIH HHS/United States ; GM065383/NH/NIH HHS/United States ; },
mesh = {DNA/chemistry ; DNA Damage ; Guanine/analogs &amp; derivatives/chemistry ; *Telomerase/genetics/metabolism ; *Telomere/genetics/metabolism ; },
abstract = {Chemical modifications in DNA impact gene regulation and chromatin structure. DNA oxidation, for example, alters gene expression, DNA synthesis and cell cycle progression. Modification of telomeric DNA by oxidation is emerging as a marker of genotoxic damage and is associated with reduced genome integrity and changes in telomere length and telomerase activity. 8-oxoguanine (8-oxoG) is the most studied and common outcome of oxidative damage in DNA. The G-rich nature of telomeric DNA is proposed to make it a hotspot for oxidation, but because telomeres make up only a tiny fraction of the genome, it has been difficult to directly test this hypothesis by studying dynamic DNA modifications specific to this region in vivo. Here, we present a new, robust method to differentially enrich telomeric DNA in solution, coupled with downstream methods for determination of chemical modification. Specifically, we measure 8-oxoG in Arabidopsis thaliana telomeres under normal and oxidative stress conditions. We show that telomere length is unchanged in response to oxidative stress in three different wild-type accessions. Furthermore, we report that while telomeric DNA comprises only 0.02-0.07% of the total genome, telomeres contribute between 0.2 and 15% of the total 8-oxoG. That is, plant telomeres accumulate 8-oxoG at levels approximately 100-fold higher than the rest of the genome under standard growth conditions. Moreover, they are the primary targets of further damage upon oxidative stress. Interestingly, the accumulation of 8-oxoG in the chromosome body seems to be inversely proportional to telomere length. These findings support the hypothesis that telomeres are hotspots of 8-oxoG and may function as sentinels of oxidative stress in plants.},
}
@article {pmid35562991,
year = {2022},
author = {Pham, C and Vryer, R and O'Hely, M and Mansell, T and Burgner, D and Collier, F and Symeonides, C and Tang, MLK and Vuillermin, P and Gray, L and Saffery, R and Ponsonby, AL and On Behalf Of The Barwon Infant Study Investigator Group, },
title = {Shortened Infant Telomere Length Is Associated with Attention Deficit/Hyperactivity Disorder Symptoms in Children at Age Two Years: A Birth Cohort Study.},
journal = {International journal of molecular sciences},
volume = {23},
number = {9},
pages = {},
pmid = {35562991},
issn = {1422-0067},
support = {N/A//Murdoch Children's Research Institute/ ; N/A//Deakin University/ ; N/A//Barwon Health/ ; N/A//National Health and Medical Research Council of Australia/ ; N/A//The Jack Brockhoff Foundation/ ; N/A//Scobie Trust/ ; N/A//Shane O'Brien Memorial Asthma Foundation/ ; N/A//Our Women's Our Children's FundRaising Committee Barwon Health/ ; N/A//The Shepherd Foundation/ ; N/A//Rotary Club of Geelong/ ; N/A//Ilhan Food Allergy Foundation/ ; N/A//GMHBA Limited/ ; N/A//Percy Baxter Charitable Trust/ ; N/A//Perpetual Trustees/ ; N/A//Minderoo Foundation/ ; N/A//Cotton On Foundation/ ; N/A//CreativeForce/ ; N/A//Victorian Government's Operational Infrastructure Support Program/ ; APP1197234 to AL Ponsonby//NHMRC Investigator Grant/ ; 2018-984 to C Pham//Melbourne Children's Campus LifeCourse PhD Support Program/ ; },
mesh = {*Attention Deficit Disorder with Hyperactivity/genetics ; Birth Cohort ; Child ; Child, Preschool ; Cohort Studies ; Humans ; Infant ; Schools ; Telomere/genetics ; },
abstract = {Environmental factors can accelerate telomere length (TL) attrition. Shortened TL is linked to attention deficit/hyperactivity disorder (ADHD) symptoms in school-aged children. The onset of ADHD occurs as early as preschool-age, but the TL-ADHD association in younger children is unknown. We investigated associations between infant TL and ADHD symptoms in children and assessed environmental factors as potential confounders and/or mediators of this association. Relative TL was measured by quantitative polymerase chain reaction in cord and 12-month blood in the birth cohort study, the Barwon Infant Study. Early life environmental factors collected antenatally to two years were used to measure confounding. ADHD symptoms at age two years were evaluated by the Child Behavior Checklist Attention Problems (AP) and the Attention Deficit/Hyperactivity Problems (ADHP). Associations between early life environmental factors on TL or ADHD symptoms were assessed using multivariable regression models adjusted for relevant factors. Telomere length at 12 months (TL12), but not at birth, was inversely associated with AP (β = -0.56; 95% CI (-1.13, 0.006); p = 0.05) and ADHP (β = -0.66; 95% CI (-1.11, -0.21); p = 0.004). Infant secondhand smoke exposure at one month was independently associated with shorter TL12 and also higher ADHD symptoms. Further work is needed to elucidate the mechanisms that influence TL attrition and early neurodevelopment.},
}
@article {pmid35559731,
year = {2022},
author = {Fernandez, RJ and Gardner, ZJG and Slovik, KJ and Liberti, DC and Estep, KN and Yang, W and Chen, Q and Santini, GT and Perez, JV and Root, S and Bhatia, R and Tobias, JW and Babu, A and Morley, MP and Frank, DB and Morrisey, EE and Lengner, CJ and Johnson, FB},
title = {GSK3 inhibition rescues growth and telomere dysfunction in dyskeratosis congenita iPSC-derived type II alveolar epithelial cells.},
journal = {eLife},
volume = {11},
number = {},
pages = {},
pmid = {35559731},
issn = {2050-084X},
support = {R21 AG054209/AG/NIA NIH HHS/United States ; R01 HL148821/HL/NHLBI NIH HHS/United States ; T32 AG000255/AG/NIA NIH HHS/United States ; P30 DK050306/DK/NIDDK NIH HHS/United States ; P30 CA016520/CA/NCI NIH HHS/United States ; },
mesh = {Alveolar Epithelial Cells/metabolism ; *Dyskeratosis Congenita/genetics/pathology ; Glycogen Synthase Kinase 3 ; Humans ; *Induced Pluripotent Stem Cells/metabolism ; Mutation ; *Telomerase/genetics/metabolism ; Telomere/metabolism ; },
abstract = {Dyskeratosis congenita (DC) is a rare genetic disorder characterized by deficiencies in telomere maintenance leading to very short telomeres and the premature onset of certain age-related diseases, including pulmonary fibrosis (PF). PF is thought to derive from epithelial failure, particularly that of type II alveolar epithelial (AT2) cells, which are highly dependent on Wnt signaling during development and adult regeneration. We use human induced pluripotent stem cell-derived AT2 (iAT2) cells to model how short telomeres affect AT2 cells. Cultured DC mutant iAT2 cells accumulate shortened, uncapped telomeres and manifest defects in the growth of alveolospheres, hallmarks of senescence, and apparent defects in Wnt signaling. The GSK3 inhibitor, CHIR99021, which mimics the output of canonical Wnt signaling, enhances telomerase activity and rescues the defects. These findings support further investigation of Wnt agonists as potential therapies for DC-related pathologies.},
}
@article {pmid35546751,
year = {2023},
author = {Fathi, E and Montazersaheb, S and Sanaat, Z and Nakhlband, A and Vandghanooni, S and Farahzadi, R and Vietor, I},
title = {L-Carnitine Reduced Cellular Aging of Bone Marrow Resident C-Kit+ Hematopoietic Progenitor Cells Through Telomere Dependent Pathways.},
journal = {Current stem cell research &amp; therapy},
volume = {18},
number = {2},
pages = {231-236},
doi = {10.2174/1574888X17666220511141123},
pmid = {35546751},
issn = {2212-3946},
support = {63634//Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran/ ; },
mesh = {Humans ; *Bone Marrow ; *Carnitine/pharmacology/metabolism ; Cellular Senescence/genetics ; Hematopoietic Stem Cells ; Telomere/genetics ; Bone Marrow Cells ; },
abstract = {BACKGROUND: Increased oxygen species levels can induce mitochondrial DNA damage and chromosomal aberrations and cause defective stem cell differentiation, leading finally to senescence of stem cells. In recent years, several studies have reported that antioxidants can improve stem cell survival and subsequently affect the potency and differentiation of these cells. Finding factors, which reduce the senescence tendency of stem cells upon expansion, has great potential for cellular therapy in regenerative medicine. This study aimed to evaluate the effects of L-carnitine (LC) on the aging of C-kit+ hematopoietic progenitor cells (HPCs) via examining the expression of some signaling pathway components.<br><br>METHODS: For this purpose, bone marrow resident C-kit+ HPCs were enriched by the magnetic-activated cell sorting (MACS) method and were characterized using flow cytometry as well as immunocytochemistry. Cells were treated with LC, and at the end of the treatment period, the cells were subjected to the realtime PCR technique along with a western blotting assay for measurement of the telomere length and assessment of protein expression, respectively.<br><br>RESULTS: The results showed that 0.2 mM LC caused the elongation of the telomere length and increased the TERT protein expression. In addition, a significant increase was observed in the protein expression of p38, p53, BCL2, and p16 as key components of the telomere-dependent pathway.<br><br>CONCLUSION: It can be concluded that LC can increase the telomere length as an effective factor in increasing the cell survival and maintenance of the C-kit+ HPCs via these signaling pathway components.},
}
@article {pmid35534619,
year = {2023},
author = {Yang, Q and Liu, R and Gao, Y and Kang, H and Zhang, Z and Han, Z and Zhang, Y and Li, Y and Mu, L and Lei, L},
title = {Mediating effect of telomere length in a hypertension population exposed to cadmium: a case-control study.},
journal = {Journal of human hypertension},
volume = {37},
number = {5},
pages = {386-393},
pmid = {35534619},
issn = {1476-5527},
mesh = {Humans ; *Cadmium/adverse effects/urine ; Case-Control Studies ; *Hypertension ; Blood Pressure ; Telomere ; },
abstract = {Cadmium (Cd) is associated with telomere length and hypertension, respectively, but the mechanism behind its relationship is unclear. Our study aimed to clarify the role of telomere length in the relationship between Cd and hypertension. A 1:1 matched case-control study was conducted with 213 hypertensive patients and 213 normotensive controls in Taiyuan, Shanxi Province, China, from February and June 2016. General demographic characteristics information and lifestyle were collected using a structured questionnaire. Urine samples were collected to test urinary Cd (UCd) levels and corrected by urinary creatinine (UCr) levels. Peripheral leukocyte absolute telomere length (ATL) was measured using quantitative polymerase chain reaction. Logistic regression was used to screen the influencing factors of hypertension. A mediation effect analysis was used to explore the role of telomere length between Cd exposure and the risk of hypertension. We found that the hypertension group had a significantly higher UCd level compared to the control group (0.91 vs 0.80 μg/g Cr, P < 0.01), while ATL showed the opposite relationship (2.36 vs 2.65 kb, P < 0.01). The Regression analysis of hypertension identified these significant predictors: family history of hypertension (OR = 3.129, 95% confidence interval (95% CI): 1.767-5.540), Body mass index (BMI, OR = 1.088, 95% CI: 1.023-1.157), total cholesterol (TC, OR = 1.277, 95% CI: 1.024-1.592), UCd (OR = 2.092, 95% CI: 1.179-3.710), ATL (OR = 0.105, 95% CI: 0.025-0.453) and 8-hydroxy-2-deoxyguanosine (8-OHdG, OR = 7.864, 95% CI: 3.516-17.589). Mediating effect analysis revealed that ATL was a potential partial mediating factor between Cd and hypertension. Cd may induce hypertension by affecting telomere length, but this requires further exploration.},
}
@article {pmid35533552,
year = {2022},
author = {Nasiri, L and Vaez-Mahdavi, MR and Hassanpour, H and Askari, N and Ardestani, SK and Ghazanfari, T},
title = {Concomitant use of relative telomere length, biological health score and physical/social statuses in the biological aging evaluation of mustard-chemical veterans.},
journal = {International immunopharmacology},
volume = {109},
number = {},
pages = {108785},
doi = {10.1016/j.intimp.2022.108785},
pmid = {35533552},
issn = {1878-1705},
mesh = {Aging ; Humans ; *Mustard Gas/toxicity ; Mustard Plant ; Telomere ; Telomere Shortening ; *Veterans ; },
abstract = {Sulfur mustard (SM) is a toxic gas that has been used as a chemical weapon in wars. After many years, SM-exposed people are still suffering from its side effects such as biological and premature aging. This study was aimed to evaluate biological aging rate via involving biological health scoring (BHS), relative telomere length (TL) and different physical/social variables i.e. marital and smoking statuses, body mass index, salary and educational levels. BHS was calculated according to measurement of 18 biomarkers related to function of four physiological systems (endocrine, inflammatory, cardiovascular and metabolic systems) and two organs (liver and kidney). The volunteers were 442 individuals exposed to SM gas in 1987 and 119 healthy individuals as non-exposed group. Each group was divided based on leukocyte relative TL (short, intermediate and long). Our data showed an inverse correlation between BHS and relative TL in two groups. The BHS was significantly higher in SM-exposed group than non-exposed group, especially in the participants with short and intermediate TL. The BHS had also a positive correlation with smoking and BMI parameters, and a negative correlation with salary and educational levels in the participants with shorter telomeres; and SM strengthened these correlations in the shorter telomeres. It is concluded that the higher BHS along with shorter relative TL that are indices for lower health quality and biological aging, could be used in the health evaluation of non- and SM-exposed people; and involving of BHS, TL and physical/social covariates could be useful to make this evaluation more accurate.},
}
@article {pmid35532056,
year = {2022},
author = {Alder, JK and Armanios, M},
title = {Telomere-mediated lung disease.},
journal = {Physiological reviews},
volume = {102},
number = {4},
pages = {1703-1720},
pmid = {35532056},
issn = {1522-1210},
support = {R01 HL135062/HL/NHLBI NIH HHS/United States ; R01 CA225027/CA/NCI NIH HHS/United States ; R01 HL119476/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Idiopathic Pulmonary Fibrosis/genetics ; Lung/metabolism ; *Lung Diseases/genetics ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism/pathology ; },
abstract = {Parenchymal lung disease is the fourth leading cause of death in the United States; among the top causes, it continues on the rise. Telomeres and telomerase have historically been linked to cellular processes related to aging and cancer, but surprisingly, in the recent decade genetic discoveries have linked the most apparent manifestations of telomere and telomerase dysfunction in humans to the etiology of lung disease: both idiopathic pulmonary fibrosis (IPF) and emphysema. The short telomere defect is pervasive in a subset of IPF patients, and human IPF is the phenotype most intimately tied to germline defects in telomere maintenance. One-third of families with pulmonary fibrosis carry germline mutations in telomerase or other telomere maintenance genes, and one-half of patients with apparently sporadic IPF have short telomere length. Beyond explaining genetic susceptibility, short telomere length uncovers clinically relevant syndromic extrapulmonary disease, including a T-cell immunodeficiency and a propensity to myeloid malignancies. Recognition of this subset of patients who share a unifying molecular defect has provided a precision medicine paradigm wherein the telomere-mediated lung disease diagnosis provides more prognostic value than histopathology or multidisciplinary evaluation. Here, we critically evaluate this progress, emphasizing how the genetic findings put forth a new pathogenesis paradigm of age-related lung disease that links telomere abnormalities to alveolar stem senescence, remodeling, and defective gas exchange.},
}
@article {pmid35530816,
year = {2022},
author = {Taub, MA and Conomos, MP and Keener, R and Iyer, KR and Weinstock, JS and Yanek, LR and Lane, J and Miller-Fleming, TW and Brody, JA and Raffield, LM and McHugh, CP and Jain, D and Gogarten, SM and Laurie, CA and Keramati, A and Arvanitis, M and Smith, AV and Heavner, B and Barwick, L and Becker, LC and Bis, JC and Blangero, J and Bleecker, ER and Burchard, EG and Celedón, JC and Chang, YPC and Custer, B and Darbar, D and de Las Fuentes, L and DeMeo, DL and Freedman, BI and Garrett, ME and Gladwin, MT and Heckbert, SR and Hidalgo, BA and Irvin, MR and Islam, T and Johnson, WC and Kaab, S and Launer, L and Lee, J and Liu, S and Moscati, A and North, KE and Peyser, PA and Rafaels, N and Seidman, C and Weeks, DE and Wen, F and Wheeler, MM and Williams, LK and Yang, IV and Zhao, W and Aslibekyan, S and Auer, PL and Bowden, DW and Cade, BE and Chen, Z and Cho, MH and Cupples, LA and Curran, JE and Daya, M and Deka, R and Eng, C and Fingerlin, TE and Guo, X and Hou, L and Hwang, SJ and Johnsen, JM and Kenny, EE and Levin, AM and Liu, C and Minster, RL and Naseri, T and Nouraie, M and Reupena, MS and Sabino, EC and Smith, JA and Smith, NL and Su, JL and Taylor, JG and Telen, MJ and Tiwari, HK and Tracy, RP and White, MJ and Zhang, Y and Wiggins, KL and Weiss, ST and Vasan, RS and Taylor, KD and Sinner, MF and Silverman, EK and Shoemaker, MB and Sheu, WH and Sciurba, F and Schwartz, DA and Rotter, JI and Roden, D and Redline, S and Raby, BA and Psaty, BM and Peralta, JM and Palmer, ND and Nekhai, S and Montgomery, CG and Mitchell, BD and Meyers, DA and McGarvey, ST and , and Mak, AC and Loos, RJ and Kumar, R and Kooperberg, C and Konkle, BA and Kelly, S and Kardia, SL and Kaplan, R and He, J and Gui, H and Gilliland, FD and Gelb, BD and Fornage, M and Ellinor, PT and de Andrade, M and Correa, A and Chen, YI and Boerwinkle, E and Barnes, KC and Ashley-Koch, AE and Arnett, DK and , and , and , and Laurie, CC and Abecasis, G and Nickerson, DA and Wilson, JG and Rich, SS and Levy, D and Ruczinski, I and Aviv, A and Blackwell, TW and Thornton, T and O'Connell, J and Cox, NJ and Perry, JA and Armanios, M and Battle, A and Pankratz, N and Reiner, AP and Mathias, RA},
title = {Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed.},
journal = {Cell genomics},
volume = {2},
number = {1},
pages = {},
pmid = {35530816},
issn = {2666-979X},
support = {R01 HL104135/HL/NHLBI NIH HHS/United States ; U10 HL054472/HL/NHLBI NIH HHS/United States ; U01 HL054472/HL/NHLBI NIH HHS/United States ; R01 HL113264/HL/NHLBI NIH HHS/United States ; S10 OD017985/OD/NIH HHS/United States ; R01 HL080083/HL/NHLBI NIH HHS/United States ; OT3 HL142478/HL/NHLBI NIH HHS/United States ; UM1 HL098162/HL/NHLBI NIH HHS/United States ; R01 HL112064/HL/NHLBI NIH HHS/United States ; R01 ES021801/ES/NIEHS NIH HHS/United States ; UL1 TR000445/TR/NCATS NIH HHS/United States ; R01 HL095080/HL/NHLBI NIH HHS/United States ; U01 HL072496/HL/NHLBI NIH HHS/United States ; UM1 HL098123/HL/NHLBI NIH HHS/United States ; R01 HL133040/HL/NHLBI NIH HHS/United States ; R01 HL120393/HL/NHLBI NIH HHS/United States ; R01 HL087698/HL/NHLBI NIH HHS/United States ; R01 HL046380/HL/NHLBI NIH HHS/United States ; R01 HL092217/HL/NHLBI NIH HHS/United States ; R01 HL121007/HL/NHLBI NIH HHS/United States ; R01 HL111249/HL/NHLBI NIH HHS/United States ; R01 HL071259/HL/NHLBI NIH HHS/United States ; U01 HL054527/HL/NHLBI NIH HHS/United States ; U01 HL080295/HL/NHLBI NIH HHS/United States ; R01 HL069234/HL/NHLBI NIH HHS/United States ; UM1 HG008895/HG/NHGRI NIH HHS/United States ; R01 HL068986/HL/NHLBI NIH HHS/United States ; U01 HL130114/HL/NHLBI NIH HHS/United States ; R01 HL087660/HL/NHLBI NIH HHS/United States ; R01 AR048797/AR/NIAMS NIH HHS/United States ; R01 HL092577/HL/NHLBI NIH HHS/United States ; HHSN268200800007C/HL/NHLBI NIH HHS/United States ; R01 HL085251/HL/NHLBI NIH HHS/United States ; U19 HL065962/HL/NHLBI NIH HHS/United States ; R01 HL066216/HL/NHLBI NIH HHS/United States ; U01 HL089897/HL/NHLBI NIH HHS/United States ; R01 HL113338/HL/NHLBI NIH HHS/United States ; U10 HL064307/HL/NHLBI NIH HHS/United States ; UH3 HL151865/HL/NHLBI NIH HHS/United States ; R01 AG058921/AG/NIA NIH HHS/United States ; R01 HL071250/HL/NHLBI NIH HHS/United States ; P30 AG028747/AG/NIA NIH HHS/United States ; S10 RR025141/RR/NCRR NIH HHS/United States ; R01 NS058700/NS/NINDS NIH HHS/United States ; U01 HL130045/HL/NHLBI NIH HHS/United States ; T32 HG000040/HG/NHGRI NIH HHS/United States ; UH3 OD023282/OD/NIH HHS/United States ; R01 HL141845/HL/NHLBI NIH HHS/United States ; R01 HL089856/HL/NHLBI NIH HHS/United States ; U10 HL064295/HL/NHLBI NIH HHS/United States ; OT3 HL142481/HL/NHLBI NIH HHS/United States ; U01 HL065962/HL/NHLBI NIH HHS/United States ; U10 HL064288/HL/NHLBI NIH HHS/United States ; U01 AI126614/AI/NIAID NIH HHS/United States ; U01 HL054464/HL/NHLBI NIH HHS/United States ; N01HC85086/HL/NHLBI NIH HHS/United States ; OT3 HL147154/HL/NHLBI NIH HHS/United States ; U10 HL064287/HL/NHLBI NIH HHS/United States ; R01 HL119443/HL/NHLBI NIH HHS/United States ; R37 HL066289/HL/NHLBI NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; R01 HL067348/HL/NHLBI NIH HHS/United States ; R35 HL135818/HL/NHLBI NIH HHS/United States ; R25 GM062459/GM/NIGMS NIH HHS/United States ; I01 BX005295/BX/BLRD VA/United States ; R01 HL113326/HL/NHLBI NIH HHS/United States ; R01 HL071051/HL/NHLBI NIH HHS/United States ; U01 HL072524/HL/NHLBI NIH HHS/United States ; P01 ES011627/ES/NIEHS NIH HHS/United States ; HHSN268201200036C/HL/NHLBI NIH HHS/United States ; HHSN268201800001C/HL/NHLBI NIH HHS/United States ; U10 HL064305/HL/NHLBI NIH HHS/United States ; U01 HL054457/HL/NHLBI NIH HHS/United States ; N01HC95159/HL/NHLBI NIH HHS/United States ; R01 HD074711/HD/NICHD NIH HHS/United States ; R01 HL104608/HL/NHLBI NIH HHS/United States ; RC2 GM092618/GM/NIGMS NIH HHS/United States ; UG3 OD023282/OD/NIH HHS/United States ; P01 HL045522/HL/NHLBI NIH HHS/United States ; OT3 HL142480/HL/NHLBI NIH HHS/United States ; UM1 HL128761/HL/NHLBI NIH HHS/United States ; U01 HL072518/HL/NHLBI NIH HHS/United States ; P50 GM115305/GM/NIGMS NIH HHS/United States ; U10 HL109164/HL/NHLBI NIH HHS/United States ; HHSN268201500014C/HL/NHLBI NIH HHS/United States ; R01 HL133221/HL/NHLBI NIH HHS/United States ; 75N92021D00006/HL/NHLBI NIH HHS/United States ; R01 HL080467/HL/NHLBI NIH HHS/United States ; N01HC85082/HL/NHLBI NIH HHS/United States ; R01 HL068959/HL/NHLBI NIH HHS/United States ; U01 HL072507/HL/NHLBI NIH HHS/United States ; R01 HL132523/HL/NHLBI NIH HHS/United States ; R01 DK071891/DK/NIDDK NIH HHS/United States ; U01 HG006378/HG/NHGRI NIH HHS/United States ; R01 HL093093/HL/NHLBI NIH HHS/United States ; R01 HL087263/HL/NHLBI NIH HHS/United States ; R01 HL097163/HL/NHLBI NIH HHS/United States ; N01HC85083/HL/NHLBI NIH HHS/United States ; N01HC25195/HL/NHLBI NIH HHS/United States ; R01 HL117004/HL/NHLBI NIH HHS/United States ; R01 HL071205/HL/NHLBI NIH HHS/United States ; U01 HL054481/HL/NHLBI NIH HHS/United States ; R03 HL154284/HL/NHLBI NIH HHS/United States ; OT3 HL142479/HL/NHLBI NIH HHS/United States ; UL1 RR024975/RR/NCRR NIH HHS/United States ; UM1 HL128711/HL/NHLBI NIH HHS/United States ; R01 NS032830/NS/NINDS NIH HHS/United States ; UG1 HL139054/HL/NHLBI NIH HHS/United States ; U01 HG004798/HG/NHGRI NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; U01 HL117721/HL/NHLBI NIH HHS/United States ; UM1 HL098147/HL/NHLBI NIH HHS/United States ; R01 HL117626/HL/NHLBI NIH HHS/United States ; N01HC85079/HL/NHLBI NIH HHS/United States ; U10 HL098112/HL/NHLBI NIH HHS/United States ; R01 HL090682/HL/NHLBI NIH HHS/United States ; R01 HL073410/HL/NHLBI NIH HHS/United States ; RC1 HL099355/HL/NHLBI NIH HHS/United States ; N01HC85080/HL/NHLBI NIH HHS/United States ; R01 HL118267/HL/NHLBI NIH HHS/United States ; R01 HL071258/HL/NHLBI NIH HHS/United States ; R01 HL055673/HL/NHLBI NIH HHS/United States ; R01 HL079915/HL/NHLBI NIH HHS/United States ; R01 HL056177/HL/NHLBI NIH HHS/United States ; R01 HL092301/HL/NHLBI NIH HHS/United States ; K01 HL135405/HL/NHLBI NIH HHS/United States ; N01HC85081/HL/NHLBI NIH HHS/United States ; U10 HL064313/HL/NHLBI NIH HHS/United States ; R01 HL091889/HL/NHLBI NIH HHS/United States ; },
abstract = {Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value <5×10[-9]) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes.},
}
@article {pmid35524933,
year = {2022},
author = {Ferrer, A and Mangaonkar, AA and Patnaik, MM},
title = {Clonal Hematopoiesis and Myeloid Neoplasms in the Context of Telomere Biology Disorders.},
journal = {Current hematologic malignancy reports},
volume = {17},
number = {3},
pages = {61-68},
pmid = {35524933},
issn = {1558-822X},
mesh = {Biology ; Clonal Hematopoiesis/genetics ; Humans ; *Leukemia, Myeloid, Acute ; Mutation ; *Myeloproliferative Disorders/genetics/therapy ; Telomere/genetics ; },
abstract = {PURPOSE OF REVIEW: Telomere biology disorders (TBDs) are cancer-predisposing multisystemic diseases that portend a higher risk of transforming into myeloid neoplasms (MNs). Due to the rarity and high variability of clinical presentations, TBD-specific characteristics of MN and the mechanisms behind this predisposition are not well defined. Herein, we review recent studies on TBD patient cohorts describing myeloid transformation events and summarize efforts to develop screening and treatment guidelines for these patients.<br><br>RECENT FINDINGS: Preliminary studies have indicated that TBD patients have a higher prevalence of somatic genetic alterations in hematopoietic cells, an age-related phenomenon, also known as clonal hematopoiesis; increasing predisposition to MN. The CH mutational landscape in TBD differs from that observed in non-TBD patients and preliminary data suggest a higher frequency of somatic mutations in the DNA repair mechanism pathway. Although initial studies did not observe specific features of MN in TBD patients, certain events are common in TBD, such as hypocellular bone marrows. The mechanisms of MN development need further elucidation. Current management options for MN-TBD patients need to be individualized and tailored as per the clinical context. Because of the high sensitivity to alkylator chemotherapy and radiation conferred by short telomeres, non-cytotoxic targeted therapies and immunotherapy are ideal therapeutic options, but these therapies are still being tested in clinical trials. Defining the mechanisms of CH evolution in TBD and identifying risk factors leading to MN evolution will allow for the development of screening and treatment guidelines for these patients.},
}
@article {pmid35511166,
year = {2022},
author = {Shakirov, EV and Chen, JJ and Shippen, DE},
title = {Plant telomere biology: The green solution to the end-replication problem.},
journal = {The Plant cell},
volume = {34},
number = {7},
pages = {2492-2504},
pmid = {35511166},
issn = {1532-298X},
support = {R01 GM065383/GM/NIGMS NIH HHS/United States ; R01 GM127402/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; *Arabidopsis/genetics/metabolism ; Biology ; Plants/genetics/metabolism ; *Telomerase/genetics ; Telomere/genetics/metabolism ; },
abstract = {Telomere maintenance is a fundamental cellular process conserved across all eukaryotic lineages. Although plants and animals diverged over 1.5 billion years ago, lessons learned from plants continue to push the boundaries of science, revealing detailed molecular mechanisms in telomere biology with broad implications for human health, aging biology, and stress responses. Recent studies of plant telomeres have unveiled unexpected divergence in telomere sequence and architecture, and the proteins that engage telomeric DNA and telomerase. The discovery of telomerase RNA components in the plant kingdom and some algae groups revealed new insight into the divergent evolution and the universal core of telomerase across major eukaryotic kingdoms. In addition, resources cataloging the abundant natural variation in Arabidopsis thaliana, maize (Zea mays), and other plants are providing unparalleled opportunities to understand the genetic networks that govern telomere length polymorphism and, as a result, are uncovering unanticipated crosstalk between telomeres, environmental factors, organismal fitness, and plant physiology. Here we recap current advances in plant telomere biology and put this field in perspective relative to telomere and telomerase research in other eukaryotic lineages.},
}
@article {pmid35510763,
year = {2022},
author = {Ujvari, B and Raven, N and Madsen, T and Klaassen, M and Dujon, AM and Schultz, AG and Nunney, L and Lemaître, JF and Giraudeau, M and Thomas, F},
title = {Telomeres, the loop tying cancer to organismal life-histories.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6273-6285},
pmid = {35510763},
issn = {1365-294X},
mesh = {Humans ; *Ecosystem ; Telomere Shortening/genetics ; *Neoplasms/genetics ; Biological Evolution ; Telomere/genetics ; },
abstract = {Recent developments in telomere and cancer evolutionary ecology demonstrate a very complex relationship between the need of tissue repair and controlling the emergence of abnormally proliferating cells. The trade-off is balanced by natural and sexual selection and mediated via both intrinsic and environmental factors. Here, we explore the effects of telomere-cancer dynamics on life history traits and strategies as well as on the cumulative effects of genetic and environmental factors. We show that telomere-cancer dynamics constitute an incredibly complex and multifaceted process. From research to date, it appears that the relationship between telomere length and cancer risk is likely nonlinear with good evidence that both (too) long and (too) short telomeres can be associated with increased cancer risk. The ability and propensity of organisms to respond to the interplay of telomere dynamics and oncogenic processes, depends on the combination of its tissue environments, life history strategies, environmental challenges (i.e., extreme climatic conditions), pressure by predators and pollution, as well as its evolutionary history. Consequently, precise interpretation of telomere-cancer dynamics requires integrative and multidisciplinary approaches. Finally, incorporating information on telomere dynamics and the expression of tumour suppressor genes and oncogenes could potentially provide the synergistic overview that could lay the foundations to study telomere-cancer dynamics at ecosystem levels.},
}
@article {pmid35501726,
year = {2022},
author = {Panelli, DM and Leonard, SA and Wong, RJ and Becker, M and Mayo, JA and Wu, E and Girsen, AI and Gotlib, IH and Aghaeepour, N and Druzin, ML and Shaw, GM and Stevenson, DK and Bianco, K},
title = {Leukocyte telomere dynamics across gestation in uncomplicated pregnancies and associations with stress.},
journal = {BMC pregnancy and childbirth},
volume = {22},
number = {1},
pages = {381},
pmid = {35501726},
issn = {1471-2393},
support = {R35 GM138353/GM/NIGMS NIH HHS/United States ; },
mesh = {Adult ; Cohort Studies ; Female ; Humans ; Leukocytes ; Pilot Projects ; Pregnancy ; *Telomere ; *Telomere Shortening ; },
abstract = {BACKGROUND: Short leukocyte telomere length is a biomarker associated with stress and morbidity in non-pregnant adults. Little is known, however, about maternal telomere dynamics in pregnancy. To address this, we examined changes in maternal leukocyte telomere length (LTL) during uncomplicated pregnancies and explored correlations with perceived stress.<br><br>METHODS: In this pilot study, maternal LTL was measured in blood collected from nulliparas who delivered live, term, singleton infants between 2012 and 2018 at a single institution. Participants were excluded if they had diabetes or hypertensive disease. Samples were collected over the course of pregnancy and divided into three time periods: <&#x2009;20[0/7] weeks (Timepoint 1); 20[1/7] to 36[6/7] weeks (Timepoint 2); and 37[0/7] to 9-weeks postpartum (Timepoint 3). All participants also completed a survey assessing a multivariate profile of perceived stress at the time of enrollment in the first trimester. LTL was measured using quantitative polymerase chain reaction (PCR). Wilcoxon signed-rank tests were used to compare LTL differences within participants across all timepoint intervals. To determine whether mode of delivery affected LTL, we compared postpartum Timepoint 3 LTLs between participants who had vaginal versus cesarean birth. Secondarily, we evaluated the association of the assessed multivariate stress profile and LTL using machine learning analysis.<br><br>RESULTS: A total of 115 samples from 46 patients were analyzed. LTL (mean&#x2009;&#xb1;&#x2009;SD), expressed as telomere to single copy gene (T/S) ratios, were: 1.15&#x2009;&#xb1;&#x2009;0.26, 1.13&#x2009;&#xb1;&#x2009;0.23, and 1.07&#x2009;&#xb1;&#x2009;0.21 for Timepoints 1, 2, and 3, respectively. There were no significant differences in LTL between Timepoints 1 and 2 (LTL T/S change -&#x2009;0.03&#x2009;&#xb1;&#x2009;0.26, p&#x2009;=&#x2009;0.39); 2 and 3 (-&#x2009;0.07&#x2009;&#xb1;&#x2009;0.29, p&#x2009;=&#x2009;0.38) or Timepoints 1 and 3 (-&#x2009;0.07&#x2009;&#xb1;&#x2009;0.21, p&#x2009;=&#x2009;0.06). Participants who underwent cesareans had significantly shorter postpartum LTLs than those who delivered vaginally (T/S ratio: 0.94&#x2009;&#xb1;&#x2009;0.12 cesarean versus 1.12&#x2009;&#xb1;&#x2009;0.21 vaginal, p&#x2009;=&#x2009;0.01). In secondary analysis, poor sleep quality was the main stress construct associated with shorter Timepoint 1 LTLs (p&#x2009;=&#x2009;0.02) and shorter mean LTLs (p&#x2009;=&#x2009;0.03).<br><br>CONCLUSIONS: In this cohort of healthy pregnancies, maternal LTLs did not significantly change across gestation and postpartum LTLs were shorter after cesarean than after vaginal birth. Significant associations between sleep quality and short LTLs warrant further investigation.},
}
@article {pmid35500959,
year = {2022},
author = {Nickels, M and Mastana, S and Denniff, M and Codd, V and Akam, E},
title = {Pilates and telomere dynamics: A 12-month longitudinal study.},
journal = {Journal of bodywork and movement therapies},
volume = {30},
number = {},
pages = {118-124},
doi = {10.1016/j.jbmt.2022.02.013},
pmid = {35500959},
issn = {1532-9283},
mesh = {*Antioxidants ; *Body Composition/physiology ; Female ; Humans ; Longitudinal Studies ; RNA, Messenger ; Telomere ; },
abstract = {Telomeres are dynamic structures that appear to be positively influenced by healthy lifestyle factors such as exercise. Pilates is an increasingly popular exercise modality that is reported to exert beneficial physiological effects in the body, although the cellular mechanisms are poorly understood. The aim of the present study was to investigate the influence of Pilates exercise on telomere length. This longitudinal study followed experienced female Pilates practitioners (n = 11, 50.8 ± 7.5 years) and healthy age- and sex-matched sedentary controls (n = 11, 49.3 ± 6.1 years) over a 12-month period. Leukocyte telomere length was quantified using qPCR. Circulatory inflammatory markers, mRNA gene expression, body composition, physical performance, and mental well-being were also assessed. Telomere length was comparable between Pilates practitioners and controls at baseline (Pre) and 12-months (Post) (p > 0.0125). Pilates practitioners displayed enhanced mRNA gene expression of antioxidant enzymes (SOD2 and GPX1), and lower body fat percentage and visceral fat rating, compared with sedentary controls (p < 0.0125). Over the 12-month longitudinal period, Pilates participants significantly increased dynamic balance (p < 0.05). In conclusion, long-term Pilates participation does not appear to influence telomere length. Nonetheless, Pilates exercise appears to increase antioxidant enzyme gene expression, effectively manage body composition, and improve dynamic balance.},
}
@article {pmid35493096,
year = {2022},
author = {de Oliveira, BCD and Shiburah, ME and Paiva, SC and Vieira, MR and Morea, EGO and da Silva, MS and Alves, CS and Segatto, M and Gutierrez-Rodrigues, F and Borges, JC and Calado, RT and Cano, MIN},
title = {Corrigendum: Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania Amazonensis Developmental Cycle and Population Proliferation.},
journal = {Frontiers in cell and developmental biology},
volume = {10},
number = {},
pages = {894949},
doi = {10.3389/fcell.2022.894949},
pmid = {35493096},
issn = {2296-634X},
abstract = {[This corrects the article DOI: 10.3389/fcell.2021.713415.].},
}
@article {pmid35489708,
year = {2022},
author = {Kirk, B and Kuo, CL and Xiang, M and Duque, G},
title = {Associations between leukocyte telomere length and osteosarcopenia in 20,400 adults aged 60 years and over: Data from the UK Biobank.},
journal = {Bone},
volume = {161},
number = {},
pages = {116425},
doi = {10.1016/j.bone.2022.116425},
pmid = {35489708},
issn = {1873-2763},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; R21 NR018963/NR/NINR NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Biological Specimen Banks ; Bone Density/physiology ; *Bone Diseases, Metabolic/complications ; Female ; Hand Strength/physiology ; Humans ; Leukocytes ; Male ; Middle Aged ; *Osteoporosis/complications ; *Sarcopenia/complications/epidemiology/genetics ; Telomere/genetics ; United Kingdom/epidemiology ; },
abstract = {PURPOSE: Two mechanisms implicated in telomere shortening are oxidative stress and inflammation, both of which are linked to bone and muscle loss suggesting a pathological link between telomere attrition and osteosarcopenia. Using older adults aged 60 years and over in the UK Biobank, we examined the association between leukocyte telomere length and osteosarcopenia.<br><br>METHODS: Baseline leukocyte telomere length was measured using a multiplex qPCR technique and expressed as the amount of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Osteosarcopenia data was from the first imaging visit and defined by WHO criteria (femoral neck bone density T score&#xa0;&#x2264;&#xa0;-1) for osteopenia/osteoporosis plus either the EWGSOP2 (low appendicular lean mass/height[2] and low grip strength) or SDOC (low grip strength and slow walking pace) criteria for sarcopenia. Binary or multinomial logistic regression models were used to associate telomere length and osteosarcopenia or its components, adjusting for the covariates: age, sex, race, education, Townsend deprivation index, alcohol, smoking, BMI/weight, physical activity levels.<br><br>RESULTS: Among 20,400 older adults (mean age: 67.79&#xa0;&#xb1;&#xa0;4.9&#xa0;years, 53% men), the prevalence of osteosarcopenia by EWGSOP2 (n&#xa0;=&#xa0;96, 0.47%) or SDOC (n&#xa0;=&#xa0;205, 1%) criteria was low at the first imaging visit (mean 8.82&#xa0;years after baseline). Baseline telomere length was not associated with osteosarcopenia by EWGSOP2 (Relative Risk (RR): 1.00, 95% CI: 0.82-1.23 comparing osteosarcopenia to normal (non-osteopenic, non-osteoporotic, and non-sarcopenic) per Standard Deviation (SD) increase in telomere length) or SDOC (RR: 0.95, 95% CI: 0.83-1.09) criteria. Longer telomere length was associated with a lower risk of slow walking pace (Odds Ratio: 0.92, 95% CI: 0.87-0.99 per SD increase in telomere length, p&#xa0;=&#xa0;0.021). Telomere length, however, was not associated with low grip strength, low bone density or low appendicular lean mass/height[2] (p&#xa0;>&#xa0;0.05).<br><br>CONCLUSIONS: In this population-based study, telomere length was not associated with osteosarcopenia; however, slow walking pace was. Further studies are needed to reexamine this relationship, including a greater number of the oldest-old (&#x2265;75&#xa0;years) where osteosarcopenia is more prevalent.},
}
@article {pmid35488763,
year = {2022},
author = {Mikheev, RK and Grigoryan, OR and Pankratova, MS and Andreeva, EN and Sheremetyeva, EV and Absatarova, YS and Mokrysheva, NG},
title = {[Telomere pathology in ontogenesis in patients with Turner syndrome].},
journal = {Problemy endokrinologii},
volume = {68},
number = {2},
pages = {128-132},
pmid = {35488763},
issn = {2308-1430},
mesh = {*Cardiovascular Abnormalities ; Female ; Humans ; Male ; Prospective Studies ; Proteomics ; Telomere/genetics/pathology ; *Turner Syndrome/complications/genetics/pathology ; },
abstract = {According to present medical databases there many trials to provide in vivo researches in vivo to confirm/refute shortening process of telomeres among patients with Turner syndrome. Despite the successful clinical experience of providing such patients with Turner syndrome, a lot of omics (proteomic and metabolomic) aspects still stay unclear. Main disadvantages of most researches are small volume and minimized mathematical correlation with chronic disease (coronary heart disease, essential hypertension, cardiovascular malformations). Finally, organization of international prospective multi-centered researches in vivo including patients with mosaic cariotype and co-operation between physicians and biologists are optimal solutions for this present problem.},
}
@article {pmid35484160,
year = {2022},
author = {Buemi, V and Schillaci, O and Santorsola, M and Bonazza, D and Broccia, PV and Zappone, A and Bottin, C and Dell'Omo, G and Kengne, S and Cacchione, S and Raffa, GD and Piazza, S and di Fagagna, FD and Benetti, R and Cortale, M and Zanconati, F and Del Sal, G and Schoeftner, S},
title = {TGS1 mediates 2,2,7-trimethyl guanosine capping of the human telomerase RNA to direct telomerase dependent telomere maintenance.},
journal = {Nature communications},
volume = {13},
number = {1},
pages = {2302},
pmid = {35484160},
issn = {2041-1723},
mesh = {Guanosine ; Humans ; RNA/genetics ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {Pathways that direct the selection of the telomerase-dependent or recombination-based, alternative lengthening of telomere (ALT) maintenance pathway in cancer cells are poorly understood. Using human lung cancer cells and tumor organoids we show that formation of the 2,2,7-trimethylguanosine (TMG) cap structure at the human telomerase RNA 5' end by the Trimethylguanosine Synthase 1 (TGS1) is central for recruiting telomerase to telomeres and engaging Cajal bodies in telomere maintenance. TGS1 depletion or inhibition by the natural nucleoside sinefungin impairs telomerase recruitment to telomeres leading to Exonuclease 1 mediated generation of telomere 3' end protrusions that engage in RAD51-dependent, homology directed recombination and the activation of key features of the ALT pathway. This indicates a critical role for 2,2,7-TMG capping of the RNA component of human telomerase (hTR) in enforcing telomerase-dependent telomere maintenance to restrict the formation of telomeric substrates conductive to ALT. Our work introduces a targetable pathway of telomere maintenance that holds relevance for telomere-related diseases such as cancer and aging.},
}
@article {pmid35483787,
year = {2022},
author = {Ng, GY and Hande, V and Ong, MH and Wong, BW and Loh, ZW and Ho, WD and Handison, LB and Tan, IMP and Fann, DY and Arumugam, TV and Hande, MP},
title = {Effects of dietary interventions on telomere dynamics.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {876-877},
number = {},
pages = {503472},
doi = {10.1016/j.mrgentox.2022.503472},
pmid = {35483787},
issn = {1879-3592},
mesh = {*DNA Damage ; Diet ; Humans ; Prospective Studies ; *Telomere/genetics ; },
abstract = {Telomeres play a critical role in maintaining cellular fate through tight regulation of cell division and DNA damage or repair. Over the years, it is established that biological ageing is defined by a gradual derangement in functionality, productivity, and robustness of biological processes. The link between telomeres and ageing is highlighted when derangement in telomere biology often leads to premature ageing and concomitant accompaniment of numerous age-associated diseases. Unfortunately, given that ageing is a biologically complicated intricacy, measures to reduce morbidity and improve longevity are still largely in the infancy stage. Recently, it was discovered that dietary habits and interventions might play a role in promoting successful healthy ageing. The intricate relationship between dietary components and its potential to protect the integrity of telomeres may provide unprecedented health benefits and protection against age-related pathologies. However, more focused prospective and follow-up studies with and without interventions are needed to unequivocally link dietary interventions with telomere maintenance in humans. This review aims to summarise recent findings that investigate the roles of nutrition on telomere biology and provide enough evidence for further studies to consider the topic of nutrigenomics and its contributions toward healthy ageing and concomitant strategy against age-associated diseases.},
}
@article {pmid35477473,
year = {2022},
author = {Howell, MP and Jones, CW and Herman, CA and Mayne, CV and Fernandez, C and Theall, KP and Esteves, KC and Drury, SS},
title = {Impact of prenatal tobacco smoking on infant telomere length trajectory and ADHD symptoms at 18 months: a longitudinal cohort study.},
journal = {BMC medicine},
volume = {20},
number = {1},
pages = {153},
pmid = {35477473},
issn = {1741-7015},
support = {R01 MH101533/MH/NIMH NIH HHS/United States ; T32 HL007713/HL/NHLBI NIH HHS/United States ; },
mesh = {*Attention Deficit Disorder with Hyperactivity/epidemiology/etiology ; Child ; Child, Preschool ; Cohort Studies ; Female ; Humans ; Infant ; Longitudinal Studies ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Telomere ; Tobacco Smoking ; },
abstract = {BACKGROUND: Prenatal maternal tobacco smoking is a predictor of child attention-deficit/hyperactivity disorder (ADHD) and is associated with offspring telomere length (TL). In this study, we examine the relationship between maternal prenatal smoking, infant TL, and maternal report of early childhood symptoms of ADHD.<br><br>METHODS: One-hundred and eighty-one mother-infant dyads were followed prospectively for the infant's first 18&#x2009;months of life. Prenatal smoking was assessed from maternal report and medical records. TL was measured from infant buccal swab DNA obtained across the first 18&#x2009;months of life. ADHD symptoms were obtained from maternal report on the Child Behavior Check List. Multiple regression models tested the relation between prenatal smoking and both ADHD symptoms and infant TL. Additional analyses tested whether the change in infant TL influenced the relation between prenatal smoking and ADHD symptoms.<br><br>RESULTS: Sixteen percent of mothers reported prenatal smoking. Infant TL at 4, 12, and 18&#x2009;months of age were correlated. Consistent with previous cross-sectional studies linking shorter offspring TL to maternal prenatal smoking, maternal prenatal smoking predicted greater telomere shortening from four to 18&#x2009;months of infant age (&#x3b2;&#x2009;=&#x2009;-&#x2009;5.797, 95% CI [-10.207, -1.386]; p&#x2009;=&#x2009;0.010). Maternal depression was positively associated with both prenatal smoking (odds ratio (OR): 4.614, 95% CI [1.733, 12.282]; p&#x2009;=&#x2009;0.002) and child ADHD symptoms (&#x3b2;&#x2009;=&#x2009;4.713, 95% CI [2.073, 7.354]; p&#x2009;=&#x2009;0.0006). To prevent confounding, analyses examined the relation between TL, ADHD symptoms, and prenatal smoking only in non-depressed mothers. In non-depressed mothers, infant TL attrition across the first 18&#x2009;months moderated the relation between smoking and child ADHD.<br><br>CONCLUSIONS: The findings extend previous studies linking prenatal smoking to shorter infant TL by providing data demonstrating the effect on TL trajectory. The relation between prenatal smoking and early infant ADHD symptoms was moderated by the change in TL. The findings provide novel initial evidence suggesting that TL dynamics are one mechanistic pathway influencing the relation between maternal prenatal smoking and ADHD.},
}
@article {pmid35477117,
year = {2022},
author = {Niaz, A and Truong, J and Manoleras, A and Fox, LC and Blombery, P and Vasireddy, RS and Pickett, HA and Curtin, JA and Barbaro, PM and Rodgers, J and Roy, J and Riley, LG and Holien, JK and Cohen, SB and Bryan, TM},
title = {Functional interaction between compound heterozygous TERT mutations causes severe telomere biology disorder.},
journal = {Blood advances},
volume = {6},
number = {12},
pages = {3779-3791},
pmid = {35477117},
issn = {2473-9537},
mesh = {Biology ; Humans ; Mutation ; RNA/genetics ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {Telomere biology disorders (TBDs) are a spectrum of multisystem inherited disorders characterized by bone marrow failure, resulting from mutations in the genes encoding telomerase or other proteins involved in maintaining telomere length and integrity. Pathogenicity of variants in these genes can be hard to evaluate, because TBD mutations show highly variable penetrance and genetic anticipation related to inheritance of shorter telomeres with each generation. Thus, detailed functional analysis of newly identified variants is often essential. Herein, we describe a patient with compound heterozygous variants in the TERT gene, which encodes the catalytic subunit of telomerase, hTERT. This patient had the extremely severe Hoyeraal-Hreidarsson form of TBD, although his heterozygous parents were clinically unaffected. Molecular dynamic modeling and detailed biochemical analyses demonstrate that one allele (L557P) affects association of hTERT with its cognate RNA component hTR, whereas the other (K1050E) affects the binding of telomerase to its DNA substrate and enzyme processivity. Unexpectedly, the data demonstrate a functional interaction between the proteins encoded by the two alleles, with wild-type hTERT rescuing the effect of K1050E on processivity, whereas L557P hTERT does not. These data contribute to the mechanistic understanding of telomerase, indicating that RNA binding in one hTERT molecule affects the processivity of telomere addition by the other molecule. This work emphasizes the importance of functional characterization of TERT variants to reach a definitive molecular diagnosis for patients with TBD, and, in particular, it illustrates the importance of analyzing the effects of compound heterozygous variants in combination, to reveal interallelic effects.},
}
@article {pmid35472852,
year = {2022},
author = {Gentiluomo, M and Capurso, G and Morelli, L and Ermini, S and Pasquali, C and Latiano, A and Tavano, F and Greenhalf, W and Milanetto, AC and Landi, S and Roth, S and Malecka-Wojciesko, E and Costello, E and Jamroziak, K and Perri, F and Boggi, U and Basso, D and Farinati, F and Kaaks, R and Vanella, G and Gais Zurcher, AJ and Archibugi, L and Lawlor, RT and Canzian, F and Campa, D},
title = {Genetically Determined Telomere Length Is Associated with Pancreatic Neuroendocrine Neoplasms Onset.},
journal = {Neuroendocrinology},
volume = {112},
number = {12},
pages = {1168-1176},
doi = {10.1159/000524659},
pmid = {35472852},
issn = {1423-0194},
support = {MR/N003284/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Humans ; Genome-Wide Association Study ; Case-Control Studies ; Telomere/genetics ; Polymorphism, Single Nucleotide/genetics ; *Neoplasms ; *Pancreatic Neoplasms/genetics ; Acid Anhydride Hydrolases/genetics ; },
abstract = {INTRODUCTION: Telomere length (TL) is a potential indicator of cancer predisposition; however, the multitude of techniques used to measure it causes the results to be heterogeneous and, in some cases, controversial. In the last years, several studies adopted a strategy based on TL-associated genetic variants to generate a polygenic score, often referred as teloscore, used in lieu of direct TL measurement. For pancreatic neuroendocrine neoplasms (PanNEN), this strategy has not been attempted yet.<br><br>METHODS: A teloscore was generated using 11 SNPs (NAF1-rs7675998, ZNF676-rs409627, TERC-rs10936599, CTC1-rs3027234, PXK-rs6772228, DHX35-rs6028466, OBFC1-rs9420907, ZNF208-rs8105767, ACYP2-rs11125529, TERT-rs2736100, and ZBTB46-rs755017), and 291 PanNEN cases and 1,686 controls collected by the PANcreatic Disease ReseArch (PANDoRA) consortium were genotyped to analyse the association of the teloscore and its individual SNPs with the risk of developing PanNEN.<br><br>RESULTS: An association between genetically determined long telomeres and the risk of developing PanNEN (OR = 1.99, CI: 1.33-2.98, p = 0.0008) for highest versus median (third) quintile was observed. In addition, two novel SNPs associated with PanNEN risk were identified: ZNF676-rs409627 (ORC/C_vs_G/G = 2.27, CI: 1.58-3.27, p = 8.80 &#xd7; 10-6) and TERT-rs2736100 (ORC/A_vs_C/C = 2.03, CI: 1.42-2.91, p = 1.06 &#xd7; 10-4).<br><br>CONCLUSION: In conclusion, this study provides for the first time a clear indication of the association between long genetically determined telomeres and increased risk of developing PanNEN.},
}
@article {pmid35472831,
year = {2022},
author = {Yu, J and Mathi Kanchi, M and Rawtaer, I and Feng, L and Kumar, AP and Kua, EH and Mahendran, R and , },
title = {Differences between multimodal brain-age and chronological-age are linked to telomere shortening.},
journal = {Neurobiology of aging},
volume = {115},
number = {},
pages = {60-69},
pmid = {35472831},
issn = {1558-1497},
support = {U01 AG024904/AG/NIA NIH HHS/United States ; U19 AG024904/AG/NIA NIH HHS/United States ; //CIHR/Canada ; },
mesh = {Aging/genetics/psychology ; Brain ; *Cognitive Dysfunction ; Humans ; Machine Learning ; Telomere/genetics ; *Telomere Shortening ; },
abstract = {Telomere shortening is theorized to accelerate biological aging, however, this has not been tested in the brain and cognitive contexts. We used machine learning age-prediction models to determine brain/cognitive age and quantified the degree of accelerated aging as the discrepancy between brain and/or cognitive and chronological ages (i.e., age gap). We hypothesized these age gaps are associated with telomere length (TL). Using healthy participants from the ADNI-3 cohort (N = 196, Agemean=70.7), we trained age-prediction models using 4 modalities of brain features and cognitive scores, as well as a 'stacked' model combining all brain modalities. Then, these 6 age-prediction models were applied to an independent sample diagnosed with mild cognitive impairment (N = 91, Agemean=71.3) to determine, for each subject, the model-specific predicted age and age gap. TL was most strongly associated with age gaps from the resting-state functional connectivity model after controlling for confounding variables. Overall, telomere shortening was significantly related to older brain but not cognitive age gaps. In particular, functional relative to structural brain-age gaps, were more strongly implicated in telomere shortening.},
}
@article {pmid35469505,
year = {2023},
author = {Yan, M and Cheng, S and Wang, S and Duan, X and Mensah, AR and Li, L and Zhang, Y and Li, G and Zhao, J and Feng, F and Zhou, X and Wu, Y and Yang, Y and Wang, W},
title = {Association of Genetic Polymorphisms of TERT with Telomere Length in Coke Oven Emissions-Exposed Workers.},
journal = {International journal of environmental health research},
volume = {33},
number = {11},
pages = {1059-1069},
doi = {10.1080/09603123.2022.2069687},
pmid = {35469505},
issn = {1369-1619},
mesh = {Humans ; *Coke/adverse effects ; Genotype ; *Occupational Exposure/adverse effects/analysis ; *Polycyclic Aromatic Hydrocarbons/analysis ; Polymorphism, Genetic ; *Telomerase/genetics ; Telomere/chemistry ; },
abstract = {We explored the association between variations in the telomere maintenance genes and change in telomere length (TL) in workers. The TL of peripheral blood leukocytes from 544 coke oven workers and 238 controls were detected using the Real-time PCR method. Variations in four genes were then detected using the PCR based restriction fragment length polymorphism. The effects of environmental and genetic factors on TL were subsequently analyzed through covariance analysis and a generalized linear model .The TL of subjects with GG genotypes were longer than those with AG genotype in the TERT rs2736098 locus amongst the controls (P = .032). The combined effect of COEs exposure and AG+AA genotypes had a significant effect on TL (P < .001). The interaction between the COEs exposure factor and the rs2736098AG+AA genotypes had a significant effect on the TL (P < .05). The TL in coke oven workers is associated with the interactions between TERT rs2736098 AG+AA and COEs exposure.},
}
@article {pmid35466826,
year = {2023},
author = {Rohr, P and Campanelli Dos Santos, I and van Helvoort Lengert, A and Alves de Lima, M and Manuel Reis, R and Barbosa, F and Cesar Santejo Silveira, H},
title = {Absolute telomere length in peripheral blood lymphocytes of workers exposed to construction environment.},
journal = {International journal of environmental health research},
volume = {33},
number = {10},
pages = {949-957},
doi = {10.1080/09603123.2022.2066069},
pmid = {35466826},
issn = {1369-1619},
mesh = {Male ; Humans ; *Arsenic/toxicity ; Lead/toxicity ; Environmental Exposure ; Lymphocytes ; Telomere ; },
abstract = {Construction environment is composed of various substances classified as carcinogens. Thus, workers exposed in this environment can be susceptible to genomic instability that can be evaluated by absolute telomere length (TL). In this work, we evaluated TL in construction workers compared to a non-exposed group performed by qPCR assay. The TL was evaluated in 59 men exposed to the construction environment (10 years of exposure) and 49 men non-exposed. Our data showed that individuals exposed to the construction environment exhibited a significantly lower TL in relation to non-exposed group (p = 0.009). Also, on the multiple linear regression model, we observed that TL was significantly influenced by the construction environment exposure (p ≤ 0.001). Additionally, the arsenic exposure is associated to a shortening telomere (p ≤ 0.001), and the lead exposure caused an increase in TL (p ≤ 0.001). Thus, our findings suggest a modulation in TL by construction environment exposure, mainly by arsenic and lead exposure.},
}
@article {pmid35464834,
year = {2022},
author = {Pérez-Martínez, L and Wagner, T and Luke, B},
title = {Telomere Interacting Proteins and TERRA Regulation.},
journal = {Frontiers in genetics},
volume = {13},
number = {},
pages = {872636},
pmid = {35464834},
issn = {1664-8021},
abstract = {Telomere shortening rates inversely correlate with life expectancy and hence it is critical to understand how telomere shortening is regulated. Recently, the telomeric non-coding RNA, TERRA has been implicated in the regulation of replicative senescence. To better understand how TERRA is regulated we employed a proteomics approach to look for potential RNA regulators that associate with telomeric sequences. Based on the results, we have identified proteins that may regulate TERRA in both a positive and negative manner, depending on the state of the telomere. In this mini-review, we discuss and speculate about these data to expand our understanding of TERRA and telomere interactors with respect to telomere shortening dynamics.},
}
@article {pmid35460626,
year = {2022},
author = {Phillippe, M},
title = {Telomeres, oxidative stress, and timing for spontaneous term and preterm labor.},
journal = {American journal of obstetrics and gynecology},
volume = {227},
number = {2},
pages = {148-162},
doi = {10.1016/j.ajog.2022.04.024},
pmid = {35460626},
issn = {1097-6868},
mesh = {Adult ; Female ; Humans ; Infant, Newborn ; *Obstetric Labor, Premature ; Oxidative Stress ; Pregnancy ; *Premature Birth/epidemiology ; Telomere ; Vitamins ; },
abstract = {Telomeres are nucleoprotein complexes located at the distal ends of chromosomes. In adults, progressive telomere shortening occurs throughout the lifetime and is thought to contribute to progressive aging, physiological senescence, multiorgan dysfunction, and ultimately, death. As discussed in this review, multiple lines of evidence provide support for the biological plausibility that a telomere-based clock mechanism also determines the length of gestation, leading to the onset of labor (parturition). After telomere expansion at the beginning of pregnancy, the telomere lengths in the gestational tissues (ie, the placenta and fetal membranes) progressively shorten throughout the remainder of pregnancy. The rate of telomere shortening can be accelerated by conditions that affect the mother and result in oxidative stress. Preterm births in the United States are associated with multiple risk factors that are linked with increased oxidative stress. Antioxidant vitamins (ie, vitamins E and C) mitigate the effects of oxidative stress and delay or prevent telomere shortening. Clinical trials with vitamins E and C and with multivitamins started during the periconception period have been associated with reduced rates of preterm births. In the United States, African-American women have a 2-3-fold higher rate of preterm birth. African-American women have multiple risk factors for premature birth, all of which are distinct and potentially additive with regard to epigenetic telomere shortening. The "weathering effect" is the hypothesis to explain the increased rates of chronic illness, disabilities, and early death observed in African-Americans. With regard to pregnancy, accelerated weathering with the associated telomere shortening in the gestational tissues would not only explain the preterm birth disparity but could also explain why highly educated, affluent African-American women continue to have an increased rate of preterm birth. These studies suggest that the racial disparities in preterm birth are potentially mediated by telomere shortening produced by lifetime or even generational exposure to the effects of systemic racism and socioeconomic marginalization. In conclusion, this review presents multiple lines of evidence supporting a novel hypothesis regarding the biological clock mechanism that determines the length of pregnancy, and it opens the possibility of new approaches to prevent or reduce the rate of spontaneous preterm birth.},
}
@article {pmid35460064,
year = {2022},
author = {Gao, X and Yu, X and Zhang, C and Wang, Y and Sun, Y and Sun, H and Zhang, H and Shi, Y and He, X},
title = {Telomeres and Mitochondrial Metabolism: Implications for Cellular Senescence and Age-related Diseases.},
journal = {Stem cell reviews and reports},
volume = {18},
number = {7},
pages = {2315-2327},
pmid = {35460064},
issn = {2629-3277},
mesh = {Adenosine Triphosphate/metabolism ; Aged ; Aging/genetics ; Animals ; Cellular Senescence/genetics ; Humans ; Mice ; Mitochondria/genetics/metabolism ; Reactive Oxygen Species/metabolism ; *Telomerase/metabolism ; Telomere/genetics/metabolism ; },
abstract = {Cellular senescence is an irreversible cell arrest process, which is determined by a variety of complicated mechanisms, including telomere attrition, mitochondrial dysfunction, metabolic disorders, loss of protein homeostasis, epigenetic changes, etc. Cellular senescence is causally related to the occurrence and development of age-related disease. The elderly is liable to suffer from disorders such as neurodegenerative diseases, cancer, and diabetes. Therefore, it is increasingly imperative to explore specific countermeasures for the treatment of age-related diseases. Numerous studies on humans and mice emphasize the significance of metabolic imbalance caused by short telomeres and mitochondrial damages in the onset of age-related diseases. Although the experimental data are relatively independent, more and more evidences have shown that there is mutual crosstalk between telomeres and mitochondrial metabolism in the process of cellular senescence. This review systematically discusses the relationship between telomere length, mitochondrial metabolic disorder, as well as their underlying mechanisms for cellular senescence and age-related diseases. Future studies on telomere and mitochondrial metabolism may shed light on potential therapeutic strategies for age-related diseases. Graphical Abstract The characteristics of cellular senescence mainly include mitochondrial dysfunction and telomere attrition. Mitochondrial dysfunction will cause mitochondrial metabolic disorders, including decreased ATP production, increased ROS production, as well as enhanced cellular apoptosis. While oxidative stress reaction to produce ROS, leads to DNA damage, and eventually influences telomere length. Under the stimulation of oxidative stress, telomerase catalytic subunit TERT mainly plays an inhibitory role on oxidative stress, reduces the production of ROS and protects telomere function. Concurrently, mitochondrial dysfunction and telomere attrition eventually induce a range of age-related diseases, such as T2DM, osteoporosis, AD, etc. :increase; :reduce;⟝:inhibition.},
}
@article {pmid35456510,
year = {2022},
author = {Boniewska-Bernacka, E and Pańczyszyn, A and Hobot, J and Donizy, P and Ziembik, Z and Goc, A and Klinger, M},
title = {The Length of Leukocyte and Femoral Artery Telomeres in Patients with Peripheral Atherosclerosis.},
journal = {Genes},
volume = {13},
number = {4},
pages = {},
pmid = {35456510},
issn = {2073-4425},
mesh = {*Atherosclerosis/genetics ; *Femoral Artery ; Humans ; Leukocytes ; Telomere/genetics ; },
abstract = {The length of telomeres (TLs) that protect chromosome ends may reflect the age of cells as well as the degree of genetic material damage caused by external factors. Since leukocyte telomere length is associated with cardiovascular diseases, the aim of this study was to evaluate whether leukocyte TL reflects femoral artery wall telomeres of patients with atherosclerosis and lower limb ischemia. Samples of femoral artery wall and blood were collected from 32 patients qualified to surgical revascularization. The analysis included blood and artery wall telomere length measurement and biochemical parameters. The study indicated that there was a moderate correlation between artery wall TL and leukocyte TL. Leukocyte TL was, on average, two times shorter than artery wall TL and correlated with the number of white blood cells. In turn, artery TL was impacted by total cholesterol level. The results suggest that the length of leukocyte telomeres may reflect artery wall TL and indirectly reflect the processes taking place in the artery wall in patients with atherosclerosis.},
}
@article {pmid35455044,
year = {2022},
author = {Takahashi, S and Bhowmik, S and Sato, S and Takenaka, S and Sugimoto, N},
title = {Replication Control of Human Telomere G-Quadruplex DNA by G-Quadruplex Ligands Dependent on Solution Environment.},
journal = {Life (Basel, Switzerland)},
volume = {12},
number = {4},
pages = {},
pmid = {35455044},
issn = {2075-1729},
support = {JP17H06351, 18KK0164, and 19K05723//Japan Society for the Promotion of Science/ ; },
abstract = {The human telomere region is known to contain guanine-rich repeats and form a guanine-quadruplex (G4) structure. As telomeres play a role in the regulation of cancer progression, ligands that specifically bind and stabilize G4 have potential therapeutic applications. However, as the human telomere sequence can form G4 with various topologies due to direct interaction by ligands and indirect interaction by the solution environment, it is of great interest to study the topology-dependent control of replication by ligands. In the present study, a DNA replication assay of a template with a human telomere G4 sequence in the presence of various ligands was performed. Cyclic naphthalene diimides (cNDI1 and cNDI2) efficiently increased the replication stall of the template DNA at G4 with an anti-parallel topology. This inhibition was stability-dependent and topology-selective, as the replication of templates with hybrid or parallel G4 structures was not affected by the cNDI and cNDI2. Moreover, the G4 ligand fisetin repressed replication with selectivity for anti-parallel and hybrid G4 structures without stabilization. Finally, the method used, referred to as quantitative study of topology-dependent replication (QSTR), was adopted to evaluate the correlation between the replication kinetics and the stability of G4. Compared to previous results obtained using a modified human telomere sequence, the relationship between the stability of G4 and the effect on the topology-dependent replication varied. Our results suggest that native human telomere G4 is more flexible than the modified sequence for interacting with ligands. These findings indicate that the modification of the human telomeric sequence forces G4 to rigidly form a specific structure of G4, which can restrict the change in topology-dependent replication by some ligands.},
}
@article {pmid35447111,
year = {2022},
author = {McGrath, SL and Huang, SH and Kobryn, K},
title = {The N-terminal domain of the Agrobacterium tumefaciens telomere resolvase, TelA, regulates its DNA cleavage and rejoining activities.},
journal = {The Journal of biological chemistry},
volume = {298},
number = {5},
pages = {101951},
pmid = {35447111},
issn = {1083-351X},
mesh = {*Agrobacterium tumefaciens/enzymology/genetics ; Bacterial Proteins/genetics/metabolism ; DNA/metabolism ; DNA Cleavage ; *Recombinases/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {Linear replicons can be found in a minority of prokaryotic organisms, including Borrelia species and Agrobacterium tumefaciens. The problem with replicating the lagging strand end of linear DNAs is circumvented in these organisms by the presence of covalently closed DNA hairpin telomeres at the DNA termini. Telomere resolvases are enzymes responsible for generating these hairpin telomeres from a dimeric replication intermediate through a two-step DNA cleavage and rejoining reaction referred to as telomere resolution. It was previously shown that the agrobacterial telomere resolvase, TelA, possesses ssDNA annealing activity in addition to telomere resolution activity. The annealing activity derives, chiefly, from the N-terminal domain. This domain is dispensable for telomere resolution. In this study, we used activity analyses of an N-terminal domain deletion mutant, domain add back experiments, and protein-protein interaction studies and we report that the N-terminal domain of TelA is involved in inhibitory interactions with the remainder of TelA that are relieved by the binding of divalent metal ions. We also found that the regulation of telomere resolution by the N-terminal domain of TelA extends to suppression of inappropriate enzymatic activity, including hairpin telomere fusion (reaction reversal) and recombination between replicated telomeres to form a Holliday junction.},
}
@article {pmid35446515,
year = {2022},
author = {Giha, HA and Joatar, FE and AlDehaini, DMB and Malalla, ZHA and Ali, ME and Al Qarni, AA},
title = {Association of obesity in T2DM with differential polymorphism of ghrelin, growth hormone secretagogue receptor-1 and telomeres maintenance genes.},
journal = {Hormone molecular biology and clinical investigation},
volume = {43},
number = {3},
pages = {297-306},
doi = {10.1515/hmbci-2021-0063},
pmid = {35446515},
issn = {1868-1891},
mesh = {Acid Anhydride Hydrolases/genetics ; Carrier Proteins ; Cross-Sectional Studies ; *Diabetes Mellitus, Type 2/complications/genetics ; Ghrelin/genetics ; Humans ; Obesity/complications/genetics ; Polymorphism, Single Nucleotide ; *Receptors, Ghrelin/genetics ; Telomere/genetics ; },
abstract = {BACKGROUND: Although obesity and T2DM comorbidity is too frequent, the molecular basis of diabetic obesity is largely unexplained and barely investigated.<br><br>MATERIALS: Cross-sectional studies were conducted in Kingdom of Saudi Arabia (KSA) in 2013 and Kuwait in 2019. Fasting blood samples were obtained from a total of 216 T2DM patients (104 from KSA) and 193 nondiabetic subjects (93 from KSA) after their consents. Eight SNPs in 5 genes known to be associated with both obesity and T2DM, ghrelin (GHRL) and growth hormone secretagogue receptor -GHSR (KSA) and telomeres maintenance genes (Kuwait) were genotyped by rtPCR. Both patients and controls were grouped into obese and non-obese and sub-grouped into 4-BMI- grades: normal, overweight (OW), obese (OBS) and severely obese (SOBS).<br><br>RESULTS: Showed that the only SNP which was distinguished between all groups/subgroups in all study subjects was the ACYP2 rs6713088G/C, where the common CC genotype was under-expressed in the obese compared to non-obese diabetics (17.8% vs. 40.4%, p 0.01) and between the 4-BMI-grade (p 0.025). Interestingly the same genotype was over-expressed in obese compared to non-obese non-diabetics (50% vs. 27.6%, p 0.04). Furthermore, the GHRL (rs27647C/T), GHSR (rs509030G/C) and TERC (rs12696304G/C) MAFs were significantly low in normal BMI patients; p=0.034, 0.008 and 0.011, respectively.<br><br>CONCLUSIONS: This is the first report about the molecular distinction between the obese and non-obese diabetics, it showed the association of rs6713088G/C mutant allele with diabetic obesity, while the GHRL, GHSR and TERC SNPs were differentially expressed based on the BMI-grades.},
}
@article {pmid35446379,
year = {2022},
author = {Wlodarski, MW},
title = {The rise of Apollo, protector of telomeres.},
journal = {Blood},
volume = {139},
number = {16},
pages = {2415-2416},
doi = {10.1182/blood.2021015199},
pmid = {35446379},
issn = {1528-0020},
mesh = {*Telomere/genetics ; *Telomere-Binding Proteins/genetics ; },
}
@article {pmid35444173,
year = {2022},
author = {Dempsey, PC and Musicha, C and Rowlands, AV and Davies, M and Khunti, K and Razieh, C and Timmins, I and Zaccardi, F and Codd, V and Nelson, CP and Yates, T and Samani, NJ},
title = {Investigation of a UK biobank cohort reveals causal associations of self-reported walking pace with telomere length.},
journal = {Communications biology},
volume = {5},
number = {1},
pages = {381},
pmid = {35444173},
issn = {2399-3642},
support = {MC_UU_12015/3/MRC_/Medical Research Council/United Kingdom ; /BHF_/British Heart Foundation/United Kingdom ; MC_UU_00006/4/MRC_/Medical Research Council/United Kingdom ; MR/M012816/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {*Biological Specimen Banks ; Humans ; Self Report ; Telomere/genetics ; United Kingdom ; *Walking Speed ; },
abstract = {Walking pace is a simple and functional form of movement and a strong predictor of health status, but the nature of its association with leucocyte telomere length (LTL) is unclear. Here we investigate whether walking pace is associated with LTL, which is causally associated with several chronic diseases and has been proposed as a marker of biological age. Analyses were conducted in 405,981 UK Biobank participants. We show that steady/average and brisk walkers had significantly longer LTL compared with slow walkers, with accelerometer-assessed measures of physical activity further supporting this through an association between LTL and habitual activity intensity, but not with total amount of activity. Bi-directional mendelian randomisation analyses suggest a causal link between walking pace and LTL, but not the other way around. A faster walking pace may be causally associated with longer LTL, which could help explain some of the beneficial effects of brisk walking on health status. Given its simple measurement and low heritability, self-reported walking pace may be a pragmatic target for interventions.},
}
@article {pmid35443468,
year = {2022},
author = {KrishnaKuchipudi, GS and Prabhu, M},
title = {Study of Association of Leptin and Leucocyte Telomere Length with Body Mass Index in Adult Indian Population a One Year Cross Sectional Study.},
journal = {The Journal of the Association of Physicians of India},
volume = {70},
number = {4},
pages = {11-12},
pmid = {35443468},
issn = {0004-5772},
mesh = {Adult ; Aged ; Body Mass Index ; Cross-Sectional Studies ; Humans ; *Leptin ; Middle Aged ; *Obesity/epidemiology ; Telomere ; Waist Circumference ; Waist-Hip Ratio ; },
abstract = {UNLABELLED: Obesity is a leading preventable cause of death and a growing health problem worldwide with increasing rate in both adults and children. Obesity is an important factor causing accelerated aging and various metabolic syndromes. Leptin role as proinflammatory adipokine in obesity is well established. Telomere length acts as a biological clock and a marker for cellular senescence. This study is aimed to quantify leucocyte telomere length &amp; its association with biochemical and anthropometric surrogates of obesity.<br><br>MATERIAL: This cross-sectional study was conducted for a duration of 1yr on patients admitted in the wards or attending OPD, fulfilling the inclusion criteria. After a written informed consent and a thorough history, patient's anthropometric measurements were taken following all guidelines. Based on the values obtained the participants were divided into categories based on age and BMI. Blood samples are collected for the assessment of Leucocyte Telomere length through qPCR technique, Leptin through ELIZA method and HBA1c through HPLC method.<br><br>OBSERVATION: In our present study, a total of 90 patients were included. These patients are equally divided in age groups of 25-39yrs, 40-54yrs and >=55yrs of age. The mean age of the patients was 48.84&#xb1;16.84yrs. The patients were further categorized equally in each age group into normal, overweight and obese. The mean BMI of the study subjects was 24.20&#xb1;3.32 kg/m2. Age is found to have a negative correlation with telomere length (r=-0.205). A significant negative correlation of BMI with telomere length is observed (r=-0.20, p<0.05). No significant correlation between leptin with telomere length (r=0.092, p=0.386) or other anthropometric variables is observed. Waist circumference has a positive correlation with waist/hip ratio (r=0.281) (p=0.007), BMI (r=0.640), weight (r=0.677) and neck circumference(r=0.687). Whereas Telomere length has a negative correlation with waist circumference (r= -0.171), neck circumference (r=--0.2266) (p=0.0318) and positive correlation with waist/hip ratio (r=0.043). In our study a negative correlation was observed between waist/ height ratio and telomere length. Waist hip ratio had a positive correlation with BMI (r= 0.138) and telomere length (r=0.232).<br><br>CONCLUSION: Telomere length showed a negative correlation with all anthropometric measures except WHR which showed a positive correlation. Leptin did not show any association with telomere length or anthropometric measures in our study. Our study shows that WHR is a better marker of central obesity than BMI. The notion of metabolically healthy obese also holds true in our study results.},
}
@article {pmid35441417,
year = {2022},
author = {Lansdorp, PM},
title = {Sex differences in telomere length, lifespan, and embryonic dyskerin levels.},
journal = {Aging cell},
volume = {21},
number = {5},
pages = {e13614},
pmid = {35441417},
issn = {1474-9726},
support = {PJT-159787//CIHR/Canada ; },
mesh = {Cell Cycle Proteins/metabolism ; *Dyskeratosis Congenita/genetics/pathology ; Female ; Humans ; Infant, Newborn ; Longevity/genetics ; Male ; Nuclear Proteins/genetics/metabolism ; Sex Characteristics ; *Telomerase/genetics/metabolism ; Telomere/metabolism ; },
abstract = {Telomerase levels in most human cells are insufficient to prevent loss of telomeric DNA with each replication cycle. The resulting "Hayflick" limit may have allowed lifespan to increase by suppressing the development of tumors early in life be it at the expense of compromised cellular responses late in life. At any given age, the average telomere length in leukocytes shows considerably variation between individuals with females having, on average, longer telomeres than males. Sex differences in average telomere length are already present at birth and correspond to reported differences in the average life expectancy between the sexes. Levels of telomerase RNA and dyskerin, encoded by DKC1, are known to limit telomerase activity in embryonic stem cells. X-linked DKC1 is expressed from both alleles in female embryo cells and higher levels of dyskerin and telomerase could elongate telomeres prior to embryo implantation. The hypothesis that embryonic telomerase levels set the stage for the sex differences in telomere length and lifespan deserves further study.},
}
@article {pmid35440402,
year = {2022},
author = {Brenner, KA and Nandakumar, J},
title = {Consequences of telomere replication failure: the other end-replication problem.},
journal = {Trends in biochemical sciences},
volume = {47},
number = {6},
pages = {506-517},
pmid = {35440402},
issn = {0968-0004},
support = {R01 GM120094/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; DNA Repair ; DNA Replication ; Genomic Instability ; Mammals ; *Telomerase/genetics/metabolism ; *Telomere/genetics/metabolism ; Telomere Homeostasis ; },
abstract = {Telomeres are chromosome-capping structures that protect ends of the linear genome from DNA damage sensors. However, these structures present obstacles during DNA replication. Incomplete telomere replication accelerates telomere shortening and limits replicative lifespan. Therefore, continued proliferation under conditions of replication stress requires a means of telomere repair, particularly in the absence of telomerase. It was recently revealed that replication stress triggers break-induced replication (BIR) and mitotic DNA synthesis (MiDAS) at mammalian telomeres; however, these mechanisms are error prone and primarily utilized in tumorigenic contexts. In this review article, we discuss the consequences of replication stress at telomeres and how use of available repair pathways contributes to genomic instability. Current research suggests that fragile telomeres are ultimately tumor-suppressive and thus may be better left unrepaired.},
}
@article {pmid35433791,
year = {2022},
author = {Chen, W and Shi, S and Jiang, Y and Chen, L and Liao, Y and Chen, K and Huang, K},
title = {Association Between Riboflavin Intake and Telomere Length: A Cross-Sectional Study From National Health and Nutrition Examination Survey 1999-2002.},
journal = {Frontiers in nutrition},
volume = {9},
number = {},
pages = {744397},
pmid = {35433791},
issn = {2296-861X},
abstract = {BACKGROUND: Dietary habits and dietary intake affect telomere length, a reliable marker of biological aging and a predictor of chronic disease. Riboflavin (RF) is known as a water-soluble antioxidant vitamin, but its role in telomere length maintenance has yet to be elucidated.<br><br>OBJECTIVE: The purpose of this study was to examine the relationship between dietary RF intake and telomere length in a nationally representative sample of adults.<br><br>METHODS: Using the NHANES (1999-2002), telomere data of 4,298 participants aged &#x2265;45 years were analyzed in a cross-sectional manner. Leukocyte telomere length was measured using the quantitative real-time polymerase chain reaction (qPCR). Dietary RF intake was assessed by a trained interviewer using 24-h dietary recall method. Generalized linear regressions were performed to evaluate the association between dietary RF intake and telomere length. Subgroup analyses were performed to further explore this relationship in sex and body mass index (BMI) subgroups.<br><br>RESULTS: Among the 3,788 participants included, the average telomere length was longer in females (P = 0.014), while they had a lower average RF intake compared to males (P < 0.001). There was a weak positive correlation between RF intake and telomere length both when unadjusted (&#x3b2; = 0.011; P = 0.037) and adjusted for age, sex, and ethnicity (&#x3b2; = 0.013; P = 0.033). Subgroup analyses showed a positive association between RF intake and the telomere length in female after adjusting for confounding factors (&#x3b2; = 0.029; P = 0.046). In the female subgroup, there were significant positive relationships between telomere length and RF intake in the obese group (&#x3b2; = 0.086, P = 0.022).<br><br>CONCLUSION: Increased dietary RF intake was significantly associated with longer telomere length in middle-aged and older American females, especially in low RF intake obese female.},
}
@article {pmid35427669,
year = {2022},
author = {Takahashi, T and Eguchi, A and Watanabe, M and Todaka, E and Sakurai, K and Mori, C},
title = {Association between telomere length in human umbilical cord tissues and polychlorinated biphenyls in maternal and cord serum.},
journal = {Chemosphere},
volume = {300},
number = {},
pages = {134560},
doi = {10.1016/j.chemosphere.2022.134560},
pmid = {35427669},
issn = {1879-1298},
mesh = {Cohort Studies ; *Environmental Pollutants/analysis ; Female ; Fetal Blood/chemistry ; Humans ; Infant, Newborn ; Male ; Maternal Exposure/adverse effects ; *Polychlorinated Biphenyls/analysis ; Pregnancy ; Telomere ; Umbilical Cord ; },
abstract = {Environmental exposure to persistent organic pollutants during pregnancy has potential adverse health effects on the fetus. One of the environmental pollutants is polychlorinated biphenyl (PCB). Earlier, we reported the presence of PCBs in fetal tissues such as the umbilical cord. Telomere length (TL) is a biomarker of aging because it shortens with each cell division. According to the Developmental Origins of Health and Disease hypothesis, fetal exposure to environmental pollutants during pregnancy affects the occurrence of non-communicable diseases in later life. In the current study, we investigated the association between cord tissue TL and serum levels of PCBs. The subjects were 114 mother-child pairs participating in a birth cohort study, the Chiba Study of Mother and Child Health (C-MACH). Maternal serum was collected during pregnancy, and cord serum and tissue were obtained at birth. TL was assessed by qPCR using genomic DNA extracted from the cord tissue. Maternal and cord serum PCB congener levels were assessed using gas chromatography and negative ion chemical ionization qMS. In male fetuses, serum levels of PCB74 in the cord blood were significantly associated with TL following covariate adjustment, but no significant association was found in female fetuses. These data suggest that the TL of the umbilical cord is affected by fetal exposure to PCBs.},
}
@article {pmid35426375,
year = {2022},
author = {Muralidharan, A and Sotocinal, SG and Yousefpour, N and Akkurt, N and Lima, LV and Tansley, S and Parisien, M and Wang, C and Austin, JS and Ham, B and Dutra, GM and Rousseau, P and Maldonado-Bouchard, S and Clark, T and Rosen, SF and Majeed, MR and Silva, O and Nejade, R and Li, X and Donayre Pimentel, S and Nielsen, CS and Neely, GG and Autexier, C and Diatchenko, L and Ribeiro-da-Silva, A and Mogil, JS},
title = {Long-term male-specific chronic pain via telomere- and p53‑mediated spinal cord cellular senescence.},
journal = {The Journal of clinical investigation},
volume = {132},
number = {8},
pages = {},
pmid = {35426375},
issn = {1558-8238},
support = {//CIHR/Canada ; },
mesh = {Animals ; Cellular Senescence ; *Chronic Pain/genetics/metabolism ; Female ; Hyperalgesia/metabolism ; Male ; Mice ; Microglia/metabolism ; *Neuralgia/genetics/metabolism ; Spinal Cord/metabolism ; Telomere/genetics/metabolism ; Tumor Suppressor Protein p53/genetics/metabolism ; },
abstract = {Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53‑specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male‑specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.},
}
@article {pmid35425228,
year = {2022},
author = {S M N Mydin, RB and Sreekantan, S and Widera, D and Saharudin, KA and Hazan, R and Farid Wajidi, MF},
title = {Genome-nanosurface interaction of titania nanotube arrays: evaluation of telomere, telomerase and NF-κB activities on an epithelial cell model.},
journal = {RSC advances},
volume = {12},
number = {4},
pages = {2237-2245},
pmid = {35425228},
issn = {2046-2069},
abstract = {Titanium dioxide nanotube arrays (TNAs) provide a promising platform for medical implants and nanomedicine applications. The present cell-TNA study has provided profound understanding on protection of genome integrity via telomere, telomerase and NF-κB activities using an epithelial cell model. It has been revealed in this study that cell-TNA interaction triggers the telomere shortening activity and inhibition of telomerase activity at the mRNA and protein level. The present work supported that the cell-TNA stimulus might involve controlled transcription and proliferative activities via NBN and TERF21P mechanisms. Moreover, inhibition of NF-κB may promote molecular sensitivity via senescence-associated secretory phenotype activities and might result in reduced inflammatory response which would be good for cell and nanosurface adaptation activities. Thus, this nanomaterial-molecular knowledge is beneficial for further nanomaterial characterization and advanced medical application.},
}
@article {pmid35422196,
year = {2023},
author = {Zhang, X and Cheng, S and Li, Z and Gu, H and Jiang, Y and Li, H and Meng, X and Wang, Y},
title = {Telomere length and stroke recurrence after ischemic stroke and TIA.},
journal = {International journal of stroke : official journal of the International Stroke Society},
volume = {18},
number = {2},
pages = {208-214},
doi = {10.1177/17474930221096552},
pmid = {35422196},
issn = {1747-4949},
mesh = {Humans ; Aged ; *Stroke/epidemiology/genetics/complications ; *Ischemic Attack, Transient/epidemiology/genetics/complications ; *Ischemic Stroke/complications ; Risk Factors ; Telomere ; Recurrence ; },
abstract = {BACKGROUND AND OBJECTIVE: Shortening telomere length (TL), as an indicator of aging, has been associated with increased risk of cardiovascular disease and incident stroke. However, there are limited data relating to the association between TL and recurrent stroke.<br><br>METHODS: Patients from the Third China National Stroke Registry who had whole genome sequencing (WGS) were selected. TL was estimated using TelSeq based on binary sequence alignment/map files derived from WGS data. Cox proportional hazards regression models were performed to assess the association of TL with recurrent stroke.<br><br>RESULTS: A total of 8041 patients with ischemic stroke (IS) or transient ischemic attack (TIA) were included. Mean TL was 2.14&#x2009;&#xb1;&#x2009;0.82&#x2009;kb. Patients in the lowest tertile of TL had higher incidence of stroke recurrence compared to those in the middle and highest tertile (6.4% vs 5.9% vs 5.2%), but the difference was not longer significant after adjusting for age, sex, cardiovascular risk factors and stroke severity. Similarly, when analyzing TL as a continuous variable, the HR per 1000&#x2009;bp increase in TL was significant 0.88 (0.79-0.98), but after adjusting for co-variates, was no longer significant (0.91; 95% confidence interval (CI), 0.81-1.02). In patients aged&#x2009;>&#x2009;65&#x2009;years, but not in younger patients, after adjusting for co-variates, TL was significantly associated with stroke recurrence. Compared to the lowest tertile, HRs (95% CI) after adjustment for all co-variates for the middle and highest tertiles were 0.78 (0.55-1.10) and 0.67 (0.46-0.98), respectively, with p for trend of 0.03. In analyses using TL as a continuous variable, adjusted HR (95% CI) per 1000&#x2009;bp increase in TL was 0.80 (0.66-0.96). However, there was no significant interaction between TL and age on risk of stroke recurrence (p for interaction&#x2009;=&#x2009;0.09).<br><br>CONCLUSIONS: In Chinese IS or TIA patients, no independent association was found between TL and risk of stroke recurrence after adjusting for co-variates. We found a possible association in older patients but this needs replicating.},
}
@article {pmid35421215,
year = {2022},
author = {Choo, S and Lorbeer, FK and Regalado, SG and Short, SB and Wu, S and Rieser, G and Bertuch, AA and Hockemeyer, D},
title = {Editing TINF2 as a potential therapeutic approach to restore telomere length in dyskeratosis congenita.},
journal = {Blood},
volume = {140},
number = {6},
pages = {608-618},
pmid = {35421215},
issn = {1528-0020},
support = {R01 CA196884/CA/NCI NIH HHS/United States ; R01 HL131744/HL/NHLBI NIH HHS/United States ; },
mesh = {*Dyskeratosis Congenita/genetics/therapy ; Humans ; Mutation ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere Shortening/genetics ; Telomere-Binding Proteins/genetics/metabolism ; },
abstract = {Mutations in the TINF2 gene, encoding the shelterin protein TIN2, cause telomere shortening and the inherited bone marrow (BM) failure syndrome dyskeratosis congenita (DC). A lack of suitable model systems limits the mechanistic understanding of telomere shortening in the stem cells and thus hinders the development of treatment options for BM failure. Here, we endogenously introduced TIN2-DC mutations in human embryonic stem cells (hESCs) and human hematopoietic stem and progenitor cells (HSPCs) to dissect the disease mechanism and identify a gene-editing strategy that rescued the disease phenotypes. The hESCs with the T284R disease mutation exhibited the short telomere phenotype observed in DC patients. Yet, telomeres in mutant hESCs did not trigger DNA damage responses at telomeres or show exacerbated telomere shortening when differentiated into telomerase-negative cells. Disruption of the mutant TINF2 allele by introducing a frameshift mutation in exon 2 restored telomere length in stem cells and the replicative potential of differentiated cells. Similarly, we introduced TIN2-DC disease variants in human HSPCs to assess the changes in telomere length and proliferative capacity. Lastly, we showed that editing at exon 2 of TINF2 that restored telomere length in hESCs could be generated in TINF2-DC patient HSPCs. Our study demonstrates a simple genetic intervention that rescues the TIN2-DC disease phenotype in stem cells and provides a versatile platform to assess the efficacy of potential therapeutic approaches in vivo.},
}
@article {pmid35420632,
year = {2022},
author = {Kelich, J and Aramburu, T and van der Vis, JJ and Showe, L and Kossenkov, A and van der Smagt, J and Massink, M and Schoemaker, A and Hennekam, E and Veltkamp, M and van Moorsel, CHM and Skordalakes, E},
title = {Telomere dysfunction implicates POT1 in patients with idiopathic pulmonary fibrosis.},
journal = {The Journal of experimental medicine},
volume = {219},
number = {5},
pages = {},
pmid = {35420632},
issn = {1540-9538},
support = {R01 CA201312/CA/NCI NIH HHS/United States ; P30 CA010815/CA/NCI NIH HHS/United States ; R50 CA211199/CA/NCI NIH HHS/United States ; T32 CA009171/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; *Idiopathic Pulmonary Fibrosis/genetics ; Shelterin Complex ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere-Binding Proteins/genetics ; },
abstract = {Exonic sequencing identified a family with idiopathic pulmonary fibrosis (IPF) containing a previously unreported heterozygous mutation in POT1 p.(L259S). The family displays short telomeres and genetic anticipation. We found that POT1(L259S) is defective in binding the telomeric overhang, nuclear accumulation, negative regulation of telomerase, and lagging strand maintenance. Patient cells containing the mutation display telomere loss, lagging strand defects, telomere-induced DNA damage, and premature senescence with G1 arrest. Our data suggest POT1(L259S) is a pathogenic driver of IPF and provide insights into gene therapy options.},
}
@article {pmid35419815,
year = {2022},
author = {Hoffman, TW and van der Vis, JJ and Biesma, DH and Grutters, JC and van Moorsel, CHM},
title = {Extrapulmonary manifestations of a telomere syndrome in patients with idiopathic pulmonary fibrosis are associated with decreased survival.},
journal = {Respirology (Carlton, Vic.)},
volume = {27},
number = {11},
pages = {959-965},
doi = {10.1111/resp.14264},
pmid = {35419815},
issn = {1440-1843},
mesh = {Cohort Studies ; Humans ; *Idiopathic Pulmonary Fibrosis/genetics ; Retrospective Studies ; Telomere/genetics ; Telomere Shortening/genetics ; },
abstract = {BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a heterogenous disease with a median survival of 3-4 years. Patients with mutations in telomere-related genes exhibit extrapulmonary signs and symptoms. These patients represent a distinct phenotype of IPF with worse survival. As genetic analyses are not available for most patients with IPF, we sought to determine the predictive value of extrapulmonary signs and symptoms of a telomere syndrome in patients with IPF.<br><br>METHODS: We retrospectively studied 409 patients with IPF. Clinical characteristics, laboratory results and family history suggestive of a telomere syndrome were related to leukocyte telomere length measured by quantitative PCR and patient outcomes.<br><br>RESULTS: The cohort included 293 patients with sporadic IPF and 116 patients with a background of familial pulmonary fibrosis. Any or a combination of a clinical history (haematological disease, liver disease, early greying of hair, nail dystrophy, skin abnormalities), a family history or haematological laboratory abnormalities (macrocytosis, anaemia, thrombopenia or leukopenia) suggestive of a telomere syndrome was present in 27% of IPF patients and associated with shorter leukocyte telomere length and shorter survival (p&#x2009;=&#x2009;0.002 in a multivariate model). In sporadic IPF, having either a clinical history, family history or haematological laboratory abnormalities was not significantly associated with decreased survival (p&#x2009;=&#x2009;0.07 in a multivariate model).<br><br>CONCLUSION: Taking a careful clinical and family history focused on extrapulmonary manifestations of a telomere syndrome can provide important prognostic information in patients with IPF, as this is associated with shorter survival.},
}
@article {pmid35418675,
year = {2022},
author = {Liu, B and He, Y and Wang, Y and Song, H and Zhou, ZH and Feigon, J},
title = {Structure of active human telomerase with telomere shelterin protein TPP1.},
journal = {Nature},
volume = {604},
number = {7906},
pages = {578-583},
pmid = {35418675},
issn = {1476-4687},
support = {1S10 OD018111/NH/NIH HHS/United States ; 1S10 RR23057/NH/NIH HHS/United States ; R35 GM131901/GM/NIGMS NIH HHS/United States ; S10 OD018111/OD/NIH HHS/United States ; S10 RR023057/RR/NCRR NIH HHS/United States ; U24 GM116792/GM/NIGMS NIH HHS/United States ; R01 GM071940/GM/NIGMS NIH HHS/United States ; },
mesh = {Binding Sites ; Cryoelectron Microscopy ; Humans ; Protein Binding ; *Shelterin Complex/ultrastructure ; Tartrate-Resistant Acid Phosphatase ; *Telomerase/ultrastructure ; Telomere/genetics/metabolism ; *Telomere-Binding Proteins/metabolism/ultrastructure ; },
abstract = {Human telomerase is a RNA-protein complex that extends the 3' end of linear chromosomes by synthesizing multiple copies of the telomeric repeat TTAGGG[1]. Its activity is a determinant of cancer progression, stem cell renewal and cellular aging[2-5]. Telomerase is recruited to telomeres and activated for telomere repeat synthesis by the telomere shelterin protein TPP1[6,7]. Human telomerase has a bilobal structure with a catalytic core ribonuclear protein and a H and ACA box ribonuclear protein[8,9]. Here we report cryo-electron microscopy structures of human telomerase catalytic core of telomerase reverse transcriptase (TERT) and telomerase RNA (TER (also known as hTR)), and of telomerase with the shelterin protein TPP1. TPP1 forms a structured interface with the TERT-unique telomerase essential N-terminal domain (TEN) and the telomerase RAP motif (TRAP) that are unique to TERT, and conformational dynamics of TEN-TRAP are damped upon TPP1 binding, defining the requirements for recruitment and activation. The structures further reveal that the elements of TERT and TER that are involved in template and telomeric DNA handling-including the TEN domain and the TRAP-thumb helix channel-are largely structurally homologous to those in Tetrahymena telomerase[10], and provide unique insights into the mechanism of telomerase activity. The binding site of the telomerase inhibitor BIBR1532[11,12] overlaps a critical interaction between the TER pseudoknot and the TERT thumb domain. Numerous mutations leading to telomeropathies[13,14] are located at the TERT-TER and TEN-TRAP-TPP1 interfaces, highlighting the importance of TER-TERT and TPP1 interactions for telomerase activity, recruitment and as drug targets.},
}
@article {pmid35418123,
year = {2022},
author = {Sehl, ME and Henry, JE and Storniolo, AM and Horvath, S and Ganz, PA},
title = {The impact of reproductive factors on DNA methylation-based telomere length in healthy breast tissue.},
journal = {NPJ breast cancer},
volume = {8},
number = {1},
pages = {48},
pmid = {35418123},
issn = {2374-4677},
abstract = {Estrogen promotes breast tissue proliferation and telomerase activation. We investigated the effects of reproductive history on cell cycling and telomere length using a DNA methylation-based estimate of telomere length (DNAmTL) in breast and blood from healthy women donors. We demonstrate that DNAmTL is shorter in breast than in blood, and that nulliparous women have longer age-adjusted DNAmTL in both breast and blood, potentially explaining their higher risk of breast cancer.},
}
@article {pmid35416741,
year = {2022},
author = {Korkiakoski, A and Käräjämäki, AJ and Ronkainen, J and Auvinen, J and Hannuksela, J and Kesäniemi, YA and Ukkola, O},
title = {Nonalcoholic fatty liver disease and its prognosis associates with shorter leucocyte telomeres in a 21-year follow-up study.},
journal = {Scandinavian journal of clinical and laboratory investigation},
volume = {82},
number = {3},
pages = {173-180},
doi = {10.1080/00365513.2022.2059698},
pmid = {35416741},
issn = {1502-7686},
mesh = {Follow-Up Studies ; Humans ; Leukocytes ; Middle Aged ; *Non-alcoholic Fatty Liver Disease/diagnosis/genetics ; Prognosis ; Telomere/genetics ; },
abstract = {Leucocyte telomere length (LTL) has been associated with nonalcoholic fatty liver disease (NAFLD), but the evidence is imperfect. Furthermore, liver fibrosis has been shown to correlate with mortality and recent studies have also found associations with LTL and fibrosis suggesting that LTL may have additional prognostic value in liver diseases. Our objective was to study the association of LTL and NAFLD and evaluate the association of LTL in prognosis of NAFLD subjects. Study subjects (n = 847) were middle-aged hypertensive patients. All participants were evaluated for NAFLD and their LTL was measured at baseline. Outcomes were obtained from Finnish Causes-of-Death Register and the Care Register for Health Care in Statistics Finland to the end of 2014. An inverse association with NAFLD prevalence and LTL length was observed (p < .001 for trend). Shortest telomere tertile possessed statistically significantly more NAFLD subjects even with multivariate analysis (shortest vs. middle tertile HR 1.98 p = .006 and shortest vs. longest tertile HR 2.03 p = .007). For the study period, mortality of the study group showed statistically significant relation with telomere length in univariate but not for multivariate analysis. In subgroup analysis, LTL did not associate with prognosis of non-NAFLD subjects. However, LTL was inversely associated with overall mortality in the subjects with NAFLD in both univariate (HR 0.16 p = .007) and multivariate analysis (HR 0.20 p = .045). In middle-aged Caucasian cohort, shorter leucocyte telomeres associated independently with increased prevalence of NAFLD. Shorter LTL was not associated with mortality in non-NAFLD patients whereas it predicted mortality of NAFLD patients independently.},
}
@article {pmid35414715,
year = {2022},
author = {Yamakawa, K and Mukai, Y and Ye, J and Muto-Ishizuka, M and Ito, M and Tanimoto, M and Suizu, F and Asano, K and Kurose, A and Matsuda, Y},
title = {Telomere length was associated with grade and pathological features of meningioma.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {6143},
pmid = {35414715},
issn = {2045-2322},
mesh = {Chromosomal Instability ; Humans ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/genetics ; *Meningeal Neoplasms/genetics/pathology ; *Meningioma/genetics/pathology ; Telomere/genetics/pathology ; },
abstract = {Telomeres are tandem repeats of the TTAGGG sequence at chromosomal ends and afford protection against chromosomal instability. To investigate the contribution of telomere dysfunction in meningiomas, here we estimate the associations between telomere length, tumor grade, and proliferation index in a series of 14 archived samples, using quantitative-fluorescence in situ hybridization, Ki67 immunostaining, and pathological analysis. The number of mitoses per 10 high-power fields (HPF) and Ki67 index was higher in grade III cases than in grade I or grade II cases. Telomere length was negatively associated with both the number of mitoses/10HPF and Ki67 index. Meningioma cases with atypical mitosis, a morphological marker of chromosomal instability, exhibited shortened telomeres. Among telomere-shortened meningioma cases, 40% were grade I, 20% were grade II, and 100% were grade III. In grade I or II meningiomas, shortened telomeres lacked high proliferation activity and atypical mitosis. In conclusion, telomere shortening might be pivotal in the development of high-grade meningioma. Analysis of telomere length might be a selective marker for meningiomas with high-grade malignant potential.},
}
@article {pmid35411811,
year = {2022},
author = {Ito, T and Saeki, H and Guo, X and Sysa-Shah, P and Tamashiro, KL and Lee, RS and Ishiyama, S and Orita, H and Sato, K and Brock, MV and Gabrielson, K},
title = {Prenatal stress enhances atherosclerosis and telomere shortening in ApoE knockout mouse offspring.},
journal = {American journal of physiology. Regulatory, integrative and comparative physiology},
volume = {323},
number = {1},
pages = {R68-R80},
doi = {10.1152/ajpregu.00201.2021},
pmid = {35411811},
issn = {1522-1490},
mesh = {Animals ; Aorta ; Apolipoproteins E/genetics ; *Atherosclerosis/genetics/pathology ; Female ; Humans ; Mice ; Mice, Knockout ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Stress, Psychological ; Telomere Shortening ; },
abstract = {Children born to women who experience stress during pregnancy have an increased risk of atherosclerosis in later life, but few animal models have explored mechanisms. To study this phenomenon, timed-bred ApoE knockout mice were determined pregnant with ultrasound and randomly assigned on gestation day 8.5 to either a control (no stress) or prenatal stress (PS) group using 2 h of restraint for five consecutive days. PS significantly increased plasma corticosterone levels in pregnant mice. The litters from PS mice showed increased neonatal mortality within the first week of life. Body weights (at euthanasia) of adult offspring at 25 wk from the PS group were significantly increased compared with weights of controls. Adult offspring from these pregnancies were serially imaged with ultrasound to measure plaque thickness and were compared with plaque macroscopic and microscopic pathology. PS groups had increased plaque thickness determined by ultrasound, gross, histological evaluation and increased aortic root and valve macrophage infiltration at 25 wk. Five-week-old mice from PS group had significant decrease in mean arterial pressure, yet blood pressure normalized by 10 wk. As prenatal stress induced increased atherosclerosis, and telomeres are susceptible to stress, aortas from 10-wk-old mice were compared for telomere lengths and were found to be significantly shorter in PS mice compared with control mice. These studies support future investigation of how stress impacts telomere shortening in animal models and human aortas. This model could be further used to investigate the role of prenatal stress, telomere biology, and atherosclerosis pathogenesis in adults.},
}
@article {pmid35411518,
year = {2022},
author = {Song, L and Wu, M and Wang, L and Bi, J and Cao, Z and Xu, S and Tian, Y and Xiong, C and Wang, Y},
title = {Ambient ozone exposure during pregnancy and telomere length in newborns: a prospective investigation in Wuhan, China.},
journal = {Environmental science and pollution research international},
volume = {29},
number = {41},
pages = {62662-62668},
pmid = {35411518},
issn = {1614-7499},
support = {82003479//National Natural Science Foundation of China/ ; 82073660//National Natural Science Foundation of China/ ; 2019M662646//China Postdoctoral Science Foundation/ ; 2020T130220//China Postdoctoral Science Foundation/ ; },
mesh = {China ; Cohort Studies ; Female ; Humans ; Infant, Newborn ; *Maternal Exposure ; *Ozone ; Pregnancy ; Prospective Studies ; Telomere ; },
abstract = {Recent studies suggest that environmental exposures, including air pollution, may influence initial (newborn) telomere length (TL), which has important implications for lifetime health. However, the effect of prenatal ozone exposure on newborn TL is unclear. This study aimed to examine the association of ozone exposure during pregnancy with newborn TL. We used data from a birth cohort study of 762 mother-newborn pairs performed in Wuhan, China, during 2013-2015. Land-use regression models were used to assess prenatal ozone exposure. Newborn TL was quantified in cord blood by qPCR assay. We applied multiple informant model to explore the relationship of prenatal ozone exposure with newborn TL. After adjustment for potential confounders, an interquartile range (IQR) increase in ozone exposure during the 2nd trimester, 3rd trimester, and whole pregnancy were associated with 6.00% (95% confidence interval [CI]: 1.59%, 10.62%), 12.64% (95% CI: 7.52%, 18.00%), and 7.10% (95% CI: 4.09%, 10.20%) longer cord blood TL, respectively. In contrast, an IQR increase in ozone exposure during the 1st trimester was associated with a 8.39% (95% CI: - 12.90%, - 3.65%) shorter cord blood TL. In multipollutant models, consistent associations were observed between ozone exposures during the 2nd trimester and whole pregnancy and cord blood TL, but not significant for the 1st and 3rd trimesters. In conclusion, our findings suggest positive associations of ozone exposure during the 2nd trimester, 3rd trimester, and whole pregnancy with newborn TL and a negative association during the 1st trimester. This study provides new evidence in humans for a potential "programming" mechanism linking maternal ozone exposure to the initial (newborn) setting of offspring's telomere biology.},
}
@article {pmid35410445,
year = {2022},
author = {Franzoni, LT and Garcia, EL and Motta, SB and Ahner, MM and Bertoletti, OA and Saffi, MAL and da Silveira, AD and Pereira, AA and Pereira, AH and Danzmann, LC and Stein, R},
title = {Aerobic exercise and telomere length in patients with systolic heart failure: protocol study for a randomized controlled trial.},
journal = {Trials},
volume = {23},
number = {1},
pages = {283},
pmid = {35410445},
issn = {1745-6215},
support = {180651//Hospital de Cl&#xed;nicas de Porto Alegre/ ; },
mesh = {Aged ; Aged, 80 and over ; Exercise/physiology ; Exercise Therapy/methods ; Female ; *Heart Failure/diagnosis/genetics/therapy ; *Heart Failure, Systolic ; Humans ; Male ; Middle Aged ; Quality of Life ; Randomized Controlled Trials as Topic ; Stroke Volume/physiology ; Telomere ; },
abstract = {BACKGROUND: Heart failure (HF) with reduced ejection fraction (HFrEF) is a syndrome that leads to fatigue and reduced functional capacity due to disease-related pathophysiological mechanisms. Aerobic exercise (AERO) plays a key role in improving HF outcomes, such as an increase in peak oxygen uptake (VO2peak). In addition, HF promotes cell senescence, which involves reducing telomere length. Several studies have shown that patients with a worse prognosis (i.e., reduced VO2 peak) also have shorter telomeres. However, the effects of AERO on telomere length in patients with HFrEF are still unknown. In an attempt to fill this gap, we designed a study to determine the effects of 16 weeks of aerobic training (32 sessions) on telomere length in HFrEF patients.<br><br>METHODS: In this single-center randomized controlled trial, men and women between 50 and 80&#x2009;years old will be allocated into two different groups: a moderate-intensity aerobic training and a control grouTelomere length, functional capacity, echocardiographic variables, endothelial function, and walking ability will be assessed before and after the 16-week intervention period.<br><br>DISCUSSION: Understanding the role of physical exercise in biological aging in HFrEF patients is relevant. Due to cell senescence, these individuals have shown a shorter telomere length. AERO can delay biological aging according to a balance in oxidative stress through antioxidant action. Positive telomere length results are expected for the aerobic training group.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT03856736 . Registered on February 27, 2019.},
}
@article {pmid35409143,
year = {2022},
author = {Vertecchi, E and Rizzo, A and Salvati, E},
title = {Telomere Targeting Approaches in Cancer: Beyond Length Maintenance.},
journal = {International journal of molecular sciences},
volume = {23},
number = {7},
pages = {},
pmid = {35409143},
issn = {1422-0067},
support = {17121//Italian Association for Cancer Research/ ; },
mesh = {Cellular Senescence ; DNA/metabolism ; DNA Damage ; Humans ; *Neoplasms/drug therapy/genetics ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere Homeostasis ; },
abstract = {Telomeres are crucial structures that preserve genome stability. Their progressive erosion over numerous DNA duplications determines the senescence of cells and organisms. As telomere length homeostasis is critical for cancer development, nowadays, telomere maintenance mechanisms are established targets in cancer treatment. Besides telomere elongation, telomere dysfunction impinges on intracellular signaling pathways, in particular DNA damage signaling and repair, affecting cancer cell survival and proliferation. This review summarizes and discusses recent findings in anticancer drug development targeting different "telosome" components.},
}
@article {pmid35407431,
year = {2022},
author = {Yu, TN and Cheng, EH and Tsai, HN and Lin, PY and Chen, CH and Huang, CC and Lee, TH and Lee, MS},
title = {Assessment of Telomere Length and Mitochondrial DNA Copy Number in Granulosa Cells as Predictors of Aneuploidy Rate in Young Patients.},
journal = {Journal of clinical medicine},
volume = {11},
number = {7},
pages = {},
pmid = {35407431},
issn = {2077-0383},
abstract = {Background: To identify the correlation among female age, cellular aging markers, and aneuploidy rate in in vitro fertilization (IVF) and the preimplantation genetic test for aneuploidy (PGT-A) cycles. Methods: This is a prospective cohort study recruiting 110 infertile women between August 2017 and July 2018. They were divided into young-age (<38 years, n = 60) and advanced-age (≥38 years, n = 50) groups. Peripheral leukocytes were assessed, and the granulosa cells were pooled during oocyte pickup. Mitochondrial DNA (mtDNA) copy number and telomere length (TL) were measured using real-time polymerase chain reaction. PGT-A was performed on the NGS platform. Results: mtDNA copy number and TL were positively correlated in both leukocytes (rho = 0.477, p < 0.001) and granulosa cells (rho = 0.361, p < 0.001), but the two parameters in leukocytes were not correlated with those in granulosa cells. In the young-age group, TL in the granulosa cells was the only factor correlated with the aneuploidy rate (rho = −0.283, p = 0.044), whereas in the advanced-age group, age was the main factor (rho = 0.358, p = 0.018). Conclusions: TL in the granulosa cells was negatively correlated with the aneuploidy rate in the young-age group, supporting the application of PGT-A in younger women.},
}
@article {pmid35402460,
year = {2022},
author = {Pavanello, S and Campisi, M and Rigotti, P and Bello, MD and Nuzzolese, E and Neri, F and Furian, L},
title = {DNA Methylation - and Telomere - Based Biological Age Estimation as Markers of Biological Aging in Donors Kidneys.},
journal = {Frontiers in medicine},
volume = {9},
number = {},
pages = {832411},
pmid = {35402460},
issn = {2296-858X},
abstract = {The biological age of an organ may represent a valuable tool for assessing its quality, especially in the elder. We examined the biological age of the kidneys [right (RK) and left kidney (LK)] and blood leukocytes in the same subject and compared these to assess whether blood mirrors kidney biological aging. Biological age was studied in n = 36 donors (median age: 72 years, range: 19-92; male: 42%) by exploring mitotic and non-mitotic pathways, using telomere length (TL) and age-methylation changes (DNAmAge) and its acceleration (AgeAcc). RK and LK DNAmAge are older than blood DNAmAge (RK vs. Blood, p = 0.0271 and LK vs. Blood, p = 0.0245) and RK and LK AgeAcc present higher score (this mean the AgeAcc is faster) than that of blood leukocytes (p = 0.0271 and p = 0.0245) in the same donor. TL of RK and LK are instead longer than that of blood (p = 0.0011 and p = 0.0098) and the increase in Remuzzi-Karpinski score is strongly correlated with kidney TL attrition (p = 0.0046). Finally, blood and kidney TL (p < 0.01) and DNAmAge (p < 0.001) were correlated. These markers can be evaluated in further studies as indicators of biological age of donor organ quality and increase the usage of organs from donors of advanced age therefore offering a potential translational research inkidney transplantation.},
}
@article {pmid35397997,
year = {2022},
author = {Balmori, C and Cordova-Oriz, I and De Alba, G and Medrano, M and Jiménez-Tormo, L and Polonio, AM and Chico-Sordo, L and Pacheco, A and García-Velasco, JA and Varela, E},
title = {Effects of age and oligoasthenozoospermia on telomeres of sperm and blood cells.},
journal = {Reproductive biomedicine online},
volume = {44},
number = {6},
pages = {1090-1100},
doi = {10.1016/j.rbmo.2021.10.010},
pmid = {35397997},
issn = {1472-6491},
mesh = {Adult ; Humans ; Leukocytes, Mononuclear/metabolism ; Male ; Middle Aged ; RNA, Messenger/genetics ; Spermatozoa/metabolism ; *Telomerase/genetics/metabolism ; Telomere ; *Telomeric Repeat Binding Protein 1/genetics/metabolism ; },
abstract = {RESEARCH QUESTION: How do age and normo- or oligoasthenozoospermia affect telomere length dynamics in spermatozoa and blood?<br><br>DESIGN: Sperm and blood samples were collected from a cohort of 37 men aged 25 and under and 40 men aged 40 and over, with either normozoospermia (NZ) or oligoasthenozoospermia (OAZ). Telomere length was evaluated using quantitative fluorescence in-situ hybridization. Telomerase mRNA (TERC and TERT) and shelterin (TRF1) gene expression were analysed using quantitative real-time polymerase chain reaction. TRF1 protein immunoreactivity was also evaluated using immunofluorescence.<br><br>RESULTS: Mean sperm telomere length (STL) increased with age in the NZ group; older NZ men accumulated the longest telomeres (P < 0.001). In peripheral blood mononuclear cells (PBMC), mean telomere length decreased with age in NZ groups, although not reaching statistical significance. Interestingly, the younger OAZ group had the shortest mean telomere length (versus young NZ, P&#x202f;=&#x202f;0.0081; versus old NZ, P&#x202f;=&#x202f;0.0116; versus old OAZ, P&#x202f;=&#x202f;0.0009) and accumulated the highest percentage of short telomeres compared with the other groups (overall P&#x202f;=&#x202f;0.0017). Analysis of TERC and TERT mRNA expression in spermatozoa and PBMC did not show significant differences among groups. Statistically significant positive correlations were found between STL and seminal parameters in younger NZ men (P&#x202f;=&#x202f;0.009 for sperm count and P&#x202f;=&#x202f;0.007 for total progressive motility). Protein immunoreactivity of TRF1 in blood was not significantly different in all groups analysed.<br><br>CONCLUSIONS: The OAZ group did not show the increase of STL with age that is seen in NZ individuals, suggesting that telomere length elongation mechanisms fail in OAZ patients. In PBMC, younger OAZ individuals showed significantly shorter mean telomere length, suggesting that this parameter could be a good biomarker of OAZ in younger OAZ patients. Telomerase gene and TRF1 mRNA expression and TRF1 protein immunoreactivity did not differ significantly between groups, and so these factors cannot be used as OAZ biomarkers.},
}
@article {pmid35393557,
year = {2022},
author = {Ayora, M and Fraguas, D and Abregú-Crespo, R and Recio, S and Blasco, MA and Moises, A and Derevyanko, A and Arango, C and Díaz-Caneja, CM},
title = {Leukocyte telomere length in patients with schizophrenia and related disorders: a meta-analysis of case-control studies.},
journal = {Molecular psychiatry},
volume = {27},
number = {7},
pages = {2968-2975},
pmid = {35393557},
issn = {1476-5578},
mesh = {Case-Control Studies ; Humans ; Leukocytes ; *Psychotic Disorders ; *Schizophrenia/genetics ; Telomere/genetics ; Telomere Shortening/genetics ; },
abstract = {CONTEXT: Telomere length may serve as a biomarker of cellular aging. The literature assessing telomere length in schizophrenia contains conflicting results.<br><br>OBJECTIVE: To assess differences in leukocyte telomere length (LTL) in peripheral blood in patients with schizophrenia and related disorders and healthy controls and to explore the effect of potential confounding variables.<br><br>DATA SOURCES: A search of Ovid MEDLINE, and Proquest databases was conducted to identify appropriate studies published from database inception through December 2020. The review protocol was registered with PROSPERO-ID: CRD42021233280.<br><br>STUDY SELECTION: The initial literature search yielded 192 studies. After study selection in 3 phases, we included 29 samples from 22 studies in the meta-analysis database.<br><br>DATA EXTRACTION: We used random effects and meta-regression models to derive Cohen d values with pooled 95% confidence intervals (CI) as estimates of effect size (ES) and to test effects of potential moderators.<br><br>RESULTS: The overall meta-analysis included 4145 patients with schizophrenia and related disorders and 4184 healthy controls and showed that LTL was significantly shorter in patients, with a small to medium effect size (ES, -0.388; 95% CI, -0.492 to -0.283; p&#x2009;<&#x2009;0.001). Subgroup meta-analyses did not find a significant effect of age or illness duration on differences in LTL in patients with psychosis relative to controls. Meta-regression analyses showed that none of the putative moderators had a significant effect on effect size estimates.<br><br>CONCLUSIONS: This meta-analysis find further support for the hypothesis of accelerated cellular aging in schizophrenia and related disorders and highlights the need for large longitudinal studies with repeated LTL measurements over time and appropriate assessments of associated factors.},
}
@article {pmid35391893,
year = {2022},
author = {Córdoba-Lanús, E and Falfán-Valencia, R},
title = {Editorial: Telomere Dysfunction and Lung Diseases.},
journal = {Frontiers in medicine},
volume = {9},
number = {},
pages = {861228},
pmid = {35391893},
issn = {2296-858X},
}
@article {pmid35390241,
year = {2022},
author = {Tričković, JF and Šobot, AV and Joksić, I and Joksić, G},
title = {Telomere fragility in radiology workers occupationally exposed to low doses of ionising radiation.},
journal = {Arhiv za higijenu rada i toksikologiju},
volume = {73},
number = {1},
pages = {23-30},
pmid = {35390241},
issn = {1848-6312},
mesh = {8-Hydroxy-2'-Deoxyguanosine ; Chromosome Aberrations ; Humans ; *Occupational Exposure/adverse effects ; Radiation, Ionizing ; *Radiology ; Telomere ; },
abstract = {Ionising radiation damages DNA directly and indirectly through increased production of reactive oxygen species. Although telomeres have been reported as indicators of radiosensitivity, their maintenance in response to occupational exposure to low radiation doses is still a matter of debate. In this work we aimed to investigate telomere length and structure in hospital workers occupationally exposed to X-rays and to relate these findings to oxidation of biomolecules and chromosome aberrations. Blood samples of exposed participants and matching controls were taken during periodical check-ups. Chromosome aberrations and telomere length and structure were analysed in peripheral blood lymphocytes using Q-FISH, whereas oxidative stress parameters [pro/antioxidant balance (PAB), lipid peroxidation, and 8-oxo-dG] were measured in plasma samples. Based on the CA findings we divided the exposed group into two subgroups, of which one had chromosome aberrations in the first division metaphases and the other did not. There was no significant difference in telomere length between any of the groups. However, both subgroups showed significantly higher rate of fragile telomeres and higher lipid peroxidation product and 8-oxo-dG levels than controls. The rate of fragile telomeres significantly correlated with plasma levels of 8-oxo-dG, which suggests that continuous exposure to low radiation doses induces oxidative base damage of guanine resulting in telomere fragility.},
}
@article {pmid35385755,
year = {2022},
author = {Sakellariou, D and Bak, ST and Isik, E and Barroso, SI and Porro, A and Aguilera, A and Bartek, J and Janscak, P and Peña-Diaz, J},
title = {MutSβ regulates G4-associated telomeric R-loops to maintain telomere integrity in ALT cancer cells.},
journal = {Cell reports},
volume = {39},
number = {1},
pages = {110602},
doi = {10.1016/j.celrep.2022.110602},
pmid = {35385755},
issn = {2211-1247},
mesh = {DNA/metabolism ; Humans ; *Neoplasms/genetics ; R-Loop Structures ; *RNA, Long Noncoding/metabolism ; Telomere/metabolism ; Telomere Homeostasis ; },
abstract = {Up to 15% of human cancers maintain their telomeres through a telomerase-independent mechanism, termed "alternative lengthening of telomeres" (ALT) that relies on homologous recombination between telomeric sequences. Emerging evidence suggests that the recombinogenic nature of ALT telomeres results from the formation of RNA:DNA hybrids (R-loops) between telomeric DNA and the long-noncoding telomeric repeat-containing RNA (TERRA). Here, we show that the mismatch repair protein MutSβ, a heterodimer of MSH2 and MSH3 subunits, is enriched at telomeres in ALT cancer cells, where it prevents the accumulation of telomeric G-quadruplex (G4) structures and R-loops. Cells depleted of MSH3 display increased incidence of R-loop-dependent telomere fragility and accumulation of telomeric C-circles. We also demonstrate that purified MutSβ recognizes and destabilizes G4 structures in vitro. These data suggest that MutSβ destabilizes G4 structures in ALT telomeres to regulate TERRA R-loops, which is a prerequisite for maintenance of telomere integrity during ALT.},
}
@article {pmid35385311,
year = {2022},
author = {Nakao, T and Bick, AG and Taub, MA and Zekavat, SM and Uddin, MM and Niroula, A and Carty, CL and Lane, J and Honigberg, MC and Weinstock, JS and Pampana, A and Gibson, CJ and Griffin, GK and Clarke, SL and Bhattacharya, R and Assimes, TL and Emery, LS and Stilp, AM and Wong, Q and Broome, J and Laurie, CA and Khan, AT and Smith, AV and Blackwell, TW and Codd, V and Nelson, CP and Yoneda, ZT and Peralta, JM and Bowden, DW and Irvin, MR and Boorgula, M and Zhao, W and Yanek, LR and Wiggins, KL and Hixson, JE and Gu, CC and Peloso, GM and Roden, DM and Reupena, MS and Hwu, CM and DeMeo, DL and North, KE and Kelly, S and Musani, SK and Bis, JC and Lloyd-Jones, DM and Johnsen, JM and Preuss, M and Tracy, RP and Peyser, PA and Qiao, D and Desai, P and Curran, JE and Freedman, BI and Tiwari, HK and Chavan, S and Smith, JA and Smith, NL and Kelly, TN and Hidalgo, B and Cupples, LA and Weeks, DE and Hawley, NL and Minster, RL and , and Deka, R and Naseri, TT and de Las Fuentes, L and Raffield, LM and Morrison, AC and Vries, PS and Ballantyne, CM and Kenny, EE and Rich, SS and Whitsel, EA and Cho, MH and Shoemaker, MB and Pace, BS and Blangero, J and Palmer, ND and Mitchell, BD and Shuldiner, AR and Barnes, KC and Redline, S and Kardia, SLR and Abecasis, GR and Becker, LC and Heckbert, SR and He, J and Post, W and Arnett, DK and Vasan, RS and Darbar, D and Weiss, ST and McGarvey, ST and de Andrade, M and Chen, YI and Kaplan, RC and Meyers, DA and Custer, BS and Correa, A and Psaty, BM and Fornage, M and Manson, JE and Boerwinkle, E and Konkle, BA and Loos, RJF and Rotter, JI and Silverman, EK and Kooperberg, C and Danesh, J and Samani, NJ and Jaiswal, S and Libby, P and Ellinor, PT and Pankratz, N and Ebert, BL and Reiner, AP and Mathias, RA and Do, R and , and Natarajan, P},
title = {Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of indeterminate potential.},
journal = {Science advances},
volume = {8},
number = {14},
pages = {eabl6579},
pmid = {35385311},
issn = {2375-2548},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; R35 HL135818/HL/NHLBI NIH HHS/United States ; R01 HL146860/HL/NHLBI NIH HHS/United States ; HHSN268201800001C/HL/NHLBI NIH HHS/United States ; DP2 HL157540/HL/NHLBI NIH HHS/United States ; KL2 TR002490/TR/NCATS NIH HHS/United States ; R01 DK124097/DK/NIDDK NIH HHS/United States ; R01 HL117626/HL/NHLBI NIH HHS/United States ; RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; DP5 OD029586/OD/NIH HHS/United States ; R01 HL120393/HL/NHLBI NIH HHS/United States ; R01 HL046380/HL/NHLBI NIH HHS/United States ; R01 EB015611/EB/NIBIB NIH HHS/United States ; RG/13/13/30194/BHF_/British Heart Foundation/United Kingdom ; U01 HL120393/HL/NHLBI NIH HHS/United States ; R01 HL148565/HL/NHLBI NIH HHS/United States ; R01 HL113338/HL/NHLBI NIH HHS/United States ; R01 HL134892/HL/NHLBI NIH HHS/United States ; R01 HL142302/HL/NHLBI NIH HHS/United States ; R01 DK110113/DK/NIDDK NIH HHS/United States ; T32 HG000040/HG/NHGRI NIH HHS/United States ; R01 DK107786/DK/NIDDK NIH HHS/United States ; P01 HL132825/HL/NHLBI NIH HHS/United States ; R01 HL148050/HL/NHLBI NIH HHS/United States ; CH/12/2/29428/BHF_/British Heart Foundation/United Kingdom ; },
abstract = {Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.},
}
@article {pmid35368045,
year = {2022},
author = {Cigan, SS and Meredith, JJ and Kelley, AC and Yang, T and Langer, EK and Hooten, AJ and Lane, JA and Cole, BR and Krailo, M and Frazier, AL and Pankratz, N and Poynter, JN},
title = {Predicted leukocyte telomere length and risk of germ cell tumours.},
journal = {British journal of cancer},
volume = {127},
number = {2},
pages = {301-312},
pmid = {35368045},
issn = {1532-1827},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; R01 CA151284/CA/NCI NIH HHS/United States ; U10 CA180899/CA/NCI NIH HHS/United States ; U10 CA180886/CA/NCI NIH HHS/United States ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Adult ; Child ; Female ; Humans ; Leukocytes ; *Neoplasms, Germ Cell and Embryonal/genetics ; *Telomere/genetics ; Telomere Homeostasis/genetics ; },
abstract = {BACKGROUND: Genetically predicted leukocyte telomere length (LTL) has been evaluated in several studies of childhood and adult cancer. We test whether genetically predicted longer LTL is associated with germ cell tumours (GCT) in children and adults.<br><br>METHODS: Paediatric GCT samples were obtained from a Children's Oncology Group study and state biobank programs in California and Michigan (N&#x2009;=&#x2009;1413 cases, 1220 biological parents and 1022 unrelated controls). Replication analysis included 396 adult testicular GCTs (TGCT) and 1589 matched controls from the UK Biobank. Mendelian randomisation was used to look at the association between genetically predicted LTL and GCTs and TERT variants were evaluated within GCT subgroups.<br><br>RESULTS: We identified significant associations between TERT variants reported in previous adult TGCT GWAS in paediatric GCT: TERT/rs2736100-C (OR&#x2009;=&#x2009;0.82; P&#x2009;=&#x2009;0.0003), TERT/rs2853677-G (OR&#x2009;=&#x2009;0.80; P&#x2009;=&#x2009;0.001), and TERT/rs7705526-A (OR&#x2009;=&#x2009;0.81; P&#x2009;=&#x2009;0.003). We also extended these findings to females and tumours outside the testes. In contrast, we did not observe strong evidence for an association between genetically predicted LTL by other variants and GCT risk in children or adults.<br><br>CONCLUSION: While TERT is a known susceptibility locus for GCT, our results suggest that LTL predicted by other variants is not strongly associated with risk in either children or adults.},
}
@article {pmid35367774,
year = {2022},
author = {Anderson, JJ and Susser, E and Arbeev, KG and Yashin, AI and Levy, D and Verhulst, S and Aviv, A},
title = {Telomere-length dependent T-cell clonal expansion: A model linking ageing to COVID-19 T-cell lymphopenia and mortality.},
journal = {EBioMedicine},
volume = {78},
number = {},
pages = {103978},
pmid = {35367774},
issn = {2352-3964},
support = {P2C HD042828/HD/NICHD NIH HHS/United States ; R56 AG073226/AG/NIA NIH HHS/United States ; U24 AG066528/AG/NIA NIH HHS/United States ; U01 AG066529/AG/NIA NIH HHS/United States ; RF1 AG046860/AG/NIA NIH HHS/United States ; },
mesh = {Adult ; Aged ; Aging ; *COVID-19 ; Humans ; *Lymphopenia ; T-Lymphocytes ; Telomere/genetics ; Young Adult ; },
abstract = {BACKGROUND: Severe COVID-19 T-cell lymphopenia is more common among older adults and entails poor prognosis. Offsetting the decline in T-cell count during COVID-19 demands fast and massive T-cell clonal expansion, which is telomere length (TL)-dependent.<br><br>METHODS: We developed a model of TL-dependent T-cell clonal expansion capacity with age and virtually examined the relation of T-cell clonal expansion with COVID-19 mortality in the general population.<br><br>FINDINGS: The model shows that an individual with average hematopoietic cell TL (HCTL) at age twenty years maintains maximal T-cell clonal expansion capacity until the 6th decade of life when this capacity rapidly declines by more than 90% over the next ten years. The collapse in the T-cell clonal expansion capacity coincides with the steep increase in COVID-19 mortality with age.<br><br>INTERPRETATION: Short HCTL might increase vulnerability of many older adults, and some younger individuals with inherently short HCTL, to COVID-19 T-cell lymphopenia and severe disease.<br><br>FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.},
}
@article {pmid35366243,
year = {2022},
author = {Jin, JH and Kwon, HS and Choi, SH and Koh, SH and Lee, EH and Jeong, JH and Jang, JW and Park, KW and Kim, EJ and Kim, HJ and Hong, JY and Yoon, SJ and Yoon, B and Park, HH and Ha, J and Park, JE and Han, MH},
title = {Association between sleep parameters and longitudinal shortening of telomere length.},
journal = {Aging},
volume = {14},
number = {7},
pages = {2930-2944},
pmid = {35366243},
issn = {1945-4589},
support = {27398C0007/ES/NIEHS NIH HHS/United States ; },
mesh = {Aging/genetics ; Humans ; Leukocytes ; Longitudinal Studies ; Sleep ; *Telomere ; *Telomere Shortening ; },
abstract = {BACKGROUND: The relationship between sleep parameters and longitudinal shortening of telomere length is unclear. This study aimed to investigate the relationship between sleep parameters and the shortening of leukocyte telomere length (LTL) over a year.<br><br>METHODS: Among the participants in the validation cohort of the Korea Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, participants who measured both baseline and follow-up (two years later) of LTL were analyzed. They were dichotomized according to the degree of LTL attrition over two years. Clinical characteristics were compared between the faster and slower LTL shortening groups (cut-off points: -0.710 kbp, n = 119 each). Multivariable logistic regression analyses were performed to determine independent relationships between faster shortening of LTL length and sleep parameters.<br><br>RESULTS: A total of 238 participants, aged 55-88 years, were included. Participants with faster LTL shortening had a shorter duration of sleep (P = 0.013) and longer sleep latency (P = 0.007). Among the components of the PSQI, subjective measures of sleep quality, sleep latency, sleep duration, and sleep efficiency were significantly worse in participants with faster LTL shortening. Multivariate logistic regression analysis showed that sleep duration (per hour, OR = 0.831, 95% CI = 0.698-0.989), sleep latency (per minute, OR = 1.013, 95% CI = 1.002-1.024), global PSQI score (OR = 1.134, 95% CI = 1.040-1.236), shortest sleep duration (OR = 5.173, 95% CI = 1.563-17.126), and lowest sleep efficiency (OR = 7.351, 95% CI = 1.943-27.946) were independently associated with faster LTL shortening.<br><br>CONCLUSIONS: Poor sleep quality, specifically short sleep duration, long sleep latency, and low sleep efficiency were associated with faster longitudinal shortening of LTL.},
}
@article {pmid35365597,
year = {2022},
author = {Spano, L and Etain, B and Meyrel, M and Hennion, V and Gross, G and Laplanche, JL and Bellivier, F and Marie-Claire, C},
title = {Telomere length and mitochondrial DNA copy number in bipolar disorder: identification of a subgroup of young individuals with accelerated cellular aging.},
journal = {Translational psychiatry},
volume = {12},
number = {1},
pages = {135},
pmid = {35365597},
issn = {2158-3188},
mesh = {Adult ; *Bipolar Disorder/genetics ; Cellular Senescence ; DNA Copy Number Variations ; *DNA, Mitochondrial/genetics ; Humans ; Telomere/genetics ; },
abstract = {The 10-15-years decrease in life expectancy observed in individuals with bipolar disorder (BD) has been linked to the concept of accelerated cellular aging. Telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) have been proposed as markers of cellular aging and comparisons between individuals with BD and healthy controls (HC) sometimes led to conflicting results. Previous studies had moderate sample sizes and studies combining these two markers into a single analysis are scarce. Using quantitative polymerase chain reaction, we measured both TL and mtDNAcn in DNA (peripheral blood) in a sample of 130 individuals with BD and 78 HC. Regression analyses, receiver operating characteristic (ROC), and clustering analyses were performed. We observed significantly lower TL and mtDNAcn in individuals with BD as compared to HC (respective decrease of 26.5 and 35.8%). ROC analyses showed that TL and mtDNAcn highly discriminated groups (AUC = 0.904 for TL and AUC = 0.931 for mtDNAcn). In the whole population, clustering analyses identified a group of young individuals (age around 36 years), with accelerated cellular aging (both shorter TL and lower mtDNAcn), which consisted mostly of individuals with BD (85.5%). The subgroup of patients with young age but accelerated aging was not characterized by specific clinical variables related to the course of BD or childhood maltreatment. However, patients in this subgroup were more frequently treated with anticonvulsants. Further characterization of this subgroup is required to better understand the molecular mechanisms and the risk factors of accelerated cellular aging in BD.},
}
@article {pmid35361931,
year = {2022},
author = {Mc Cartney, AM and Shafin, K and Alonge, M and Bzikadze, AV and Formenti, G and Fungtammasan, A and Howe, K and Jain, C and Koren, S and Logsdon, GA and Miga, KH and Mikheenko, A and Paten, B and Shumate, A and Soto, DC and Sović, I and Wood, JMD and Zook, JM and Phillippy, AM and Rhie, A},
title = {Chasing perfection: validation and polishing strategies for telomere-to-telomere genome assemblies.},
journal = {Nature methods},
volume = {19},
number = {6},
pages = {687-695},
pmid = {35361931},
issn = {1548-7105},
support = {R01 HG006677/HG/NHGRI NIH HHS/United States ; U01 HG010961/HG/NHGRI NIH HHS/United States ; WT206194/WT_/Wellcome Trust/United Kingdom ; U41 HG010972/HG/NHGRI NIH HHS/United States ; F32 GM134558/GM/NIGMS NIH HHS/United States ; OT2 OD026682/OD/NIH HHS/United States ; Z99 HG999999/ImNIH/Intramural NIH HHS/United States ; R01 HG011274/HG/NHGRI NIH HHS/United States ; R21 HG010548/HG/NHGRI NIH HHS/United States ; U01 HG010971/HG/NHGRI NIH HHS/United States ; U24 HG011853/HG/NHGRI NIH HHS/United States ; R01 HG010485/HG/NHGRI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; ZIA HG200398/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Female ; Genome, Human ; *High-Throughput Nucleotide Sequencing/methods ; Humans ; *Nanopores ; Pregnancy ; Sequence Analysis, DNA/methods ; Telomere/genetics ; },
abstract = {Advances in long-read sequencing technologies and genome assembly methods have enabled the recent completion of the first telomere-to-telomere human genome assembly, which resolves complex segmental duplications and large tandem repeats, including centromeric satellite arrays in a complete hydatidiform mole (CHM13). Although derived from highly accurate sequences, evaluation revealed evidence of small errors and structural misassemblies in the initial draft assembly. To correct these errors, we designed a new repeat-aware polishing strategy that made accurate assembly corrections in large repeats without overcorrection, ultimately fixing 51% of the existing errors and improving the assembly quality value from 70.2 to 73.9 measured from PacBio high-fidelity and Illumina k-mers. By comparing our results to standard automated polishing tools, we outline common polishing errors and offer practical suggestions for genome projects with limited resources. We also show how sequencing biases in both high-fidelity and Oxford Nanopore Technologies reads cause signature assembly errors that can be corrected with a diverse panel of sequencing technologies.},
}
@article {pmid35359435,
year = {2022},
author = {da Silva, MS and McCulloch, R and Cano, MIN},
title = {Editorial: Nuclear Genome Stability: DNA Replication, Telomere Maintenance, and DNA Repair.},
journal = {Frontiers in cell and developmental biology},
volume = {10},
number = {},
pages = {875749},
doi = {10.3389/fcell.2022.875749},
pmid = {35359435},
issn = {2296-634X},
}
@article {pmid35359323,
year = {2022},
author = {Joseph, NA and Chen, CF and Chen, JH and Chen, LY},
title = {Monitoring Telomere Maintenance During Regeneration of Annelids.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2450},
number = {},
pages = {467-478},
pmid = {35359323},
issn = {1940-6029},
mesh = {Animals ; *Annelida ; In Situ Hybridization, Fluorescence ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere Homeostasis ; },
abstract = {Telomere shortening is a hallmark of aging and eventually constrains the proliferative capacity of cells. The protocols discussed here are used for monitoring telomeres comprehensively in Aeolosoma viride, a model system for regeneration studies. We present methods for analyzing the activity of telomerase enzyme in regenerating tissue by telomeric repeat amplification protocol (TRAP) assay, for comparing telomere length between existing tissue and newly regenerated tissue by telomere restriction fragment (TRF) assay, as well as for visualizing telomeres by fluorescence in situ hybridization (FISH).},
}
@article {pmid35357925,
year = {2022},
author = {Hoyt, SJ and Storer, JM and Hartley, GA and Grady, PGS and Gershman, A and de Lima, LG and Limouse, C and Halabian, R and Wojenski, L and Rodriguez, M and Altemose, N and Rhie, A and Core, LJ and Gerton, JL and Makalowski, W and Olson, D and Rosen, J and Smit, AFA and Straight, AF and Vollger, MR and Wheeler, TJ and Schatz, MC and Eichler, EE and Phillippy, AM and Timp, W and Miga, KH and O'Neill, RJ},
title = {From telomere to telomere: The transcriptional and epigenetic state of human repeat elements.},
journal = {Science (New York, N.Y.)},
volume = {376},
number = {6588},
pages = {eabk3112},
pmid = {35357925},
issn = {1095-9203},
support = {U24 HG010263/HG/NHGRI NIH HHS/United States ; R35 GM128857/GM/NIGMS NIH HHS/United States ; T32 GM007445/GM/NIGMS NIH HHS/United States ; R21 CA240199/CA/NCI NIH HHS/United States ; R01 HG010169/HG/NHGRI NIH HHS/United States ; U01 CA253481/CA/NCI NIH HHS/United States ; R01 HG002939/HG/NHGRI NIH HHS/United States ; U01 HG010971/HG/NHGRI NIH HHS/United States ; P20 GM103546/GM/NIGMS NIH HHS/United States ; R01 HG002385/HG/NHGRI NIH HHS/United States ; R01 HG011274/HG/NHGRI NIH HHS/United States ; U24 HG006620/HG/NHGRI NIH HHS/United States ; U24 HG010136/HG/NHGRI NIH HHS/United States ; R21 HG010548/HG/NHGRI NIH HHS/United States ; R01 HG009909/HG/NHGRI NIH HHS/United States ; R01 GM123312/GM/NIGMS NIH HHS/United States ; R01 HG009190/HG/NHGRI NIH HHS/United States ; R24 DK106766/DK/NIDDK NIH HHS/United States ; R01 GM132600/GM/NIGMS NIH HHS/United States ; ZIA HG200398/ImNIH/Intramural NIH HHS/United States ; },
mesh = {*Epigenesis, Genetic ; *Genome, Human ; Humans ; *Repetitive Sequences, Nucleic Acid ; Telomere/*genetics ; *Transcription, Genetic ; },
abstract = {Mobile elements and repetitive genomic regions are sources of lineage-specific genomic innovation and uniquely fingerprint individual genomes. Comprehensive analyses of such repeat elements, including those found in more complex regions of the genome, require a complete, linear genome assembly. We present a de novo repeat discovery and annotation of the T2T-CHM13 human reference genome. We identified previously unknown satellite arrays, expanded the catalog of variants and families for repeats and mobile elements, characterized classes of complex composite repeats, and located retroelement transduction events. We detected nascent transcription and delineated CpG methylation profiles to define the structure of transcriptionally active retroelements in humans, including those in centromeres. These data expand our insight into the diversity, distribution, and evolution of repetitive regions that have shaped the human genome.},
}
@article {pmid35351386,
year = {2022},
author = {Nandavaram, S and Chandrashekaran, S and Gelman, AE},
title = {Short telomeres in lung transplantation: Known unknowns.},
journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation},
volume = {41},
number = {5},
pages = {664-666},
doi = {10.1016/j.healun.2022.02.001},
pmid = {35351386},
issn = {1557-3117},
mesh = {Humans ; *Lung Transplantation ; *Telomerase/genetics ; Telomere/genetics ; },
}
@article {pmid35348914,
year = {2022},
author = {Muoio, D and Laspata, N and Fouquerel, E},
title = {Functions of ADP-ribose transferases in the maintenance of telomere integrity.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {79},
number = {4},
pages = {215},
pmid = {35348914},
issn = {1420-9071},
support = {R00 ES027028/ES/NIEHS NIH HHS/United States ; R35 GM142982/GM/NIGMS NIH HHS/United States ; R35GM142982/GM/NIGMS NIH HHS/United States ; R00ES027028/ES/NIEHS NIH HHS/United States ; },
mesh = {*ADP Ribose Transferases/metabolism ; Adenosine Diphosphate Ribose/metabolism ; DNA Repair ; Genomic Instability ; Humans ; *Telomere/genetics/metabolism ; },
abstract = {The ADP-ribose transferase (ART) family comprises 17 enzymes that catalyze mono- or poly-ADP-ribosylation, a post-translational modification of proteins. Present in all subcellular compartments, ARTs are implicated in a growing number of biological processes including DNA repair, replication, transcription regulation, intra- and extra-cellular signaling, viral infection and cell death. Five members of the family, PARP1, PARP2, PARP3, tankyrase 1 and tankyrase 2 are mainly described for their crucial functions in the maintenance of genome stability. It is well established that the most describedrole of PARP1, 2 and 3 is the repair of DNA lesions while tankyrases 1 and 2 are crucial for maintaining the integrity of telomeres. Telomeres, nucleoprotein complexes located at the ends of eukaryotic chromosomes, utilize their unique structure and associated set of proteins to orchestrate the mechanisms necessary for their own protection and replication. While the functions of tankyrases 1 and 2 at telomeres are well known, several studies have also brought PARP1, 2 and 3 to the forefront of telomere protection. The singular quality of the telomeric environment has highlighted protein interactions and molecular pathways distinct from those described throughout the genome. The aim of this review is to provide an overview of the current knowledge on the multiple roles of PARP1, PARP2, PARP3, tankyrase 1 and tankyrase 2 in the maintenance and preservation of telomere integrity.},
}
@article {pmid35347712,
year = {2022},
author = {Aoulad Fares, D and Wiegel, RE and Eggink, AJ and Willemsen, SP and van Meurs, JBJ and Steegers-Theunissen, RPM},
title = {Shorter periconception maternal telomere length and the risk of congenital cardiac outflow defects in the offspring.},
journal = {European journal of clinical investigation},
volume = {52},
number = {8},
pages = {e13784},
pmid = {35347712},
issn = {1365-2362},
support = {//The Bo Hjelt Foundation for Spina Bifida in memory of Madeleine Hjelt/ ; },
mesh = {Female ; *Heart Defects, Congenital ; *Heart Septal Defects, Ventricular/genetics ; Humans ; Mothers ; Odds Ratio ; Telomere/genetics ; Telomere Shortening ; },
abstract = {BACKGROUND: Congenital cardiac outflow defects (COD) are the largest group of congenital heart defects, with ventricular septal defect (VSD) as the most prevalent phenotype. Increased maternal age, excessive oxidative stress and inflammation are involved in the pathophysiology of COD and enhance telomere length (TL) shortening. We investigated the association between periconception maternal TL and the risk of having a child with COD.<br><br>METHODS: From a multicentre case-control trial, 306 case mothers of a child with COD and 424 control mothers of a child without a congenital malformation were selected. Relative TL was measured by qPCR. Multivariable logistic regression was used to compute crude and adjusted odds ratios, per standard deviation decrease, between maternal T/S ratio and COD and VSD risk. Adjustments were made for maternal age. Additional adjustments were made in a second model.<br><br>RESULTS: Shorter maternal relative TL was significantly associated with an OR of 1.29 (95% CI 1.04-1.61), p&#xa0;=&#xa0;.02, for the risk of VSD in offspring, which remained significant after an adjustment for maternal age (adjOR 1.25(95% CI 1.01-1.55), p&#xa0;=&#xa0;.04). No association between maternal TL and the risk of overall COD in offspring was observed.<br><br>CONCLUSION: Shorter maternal relative TL is associated with an approximately 1.3-OR for the risk, per SD in relative TL shortening, of VSD in the offspring. These findings need further confirmation in other studies on the predictive value of maternal TL.},
}
@article {pmid35346819,
year = {2022},
author = {Gordon, CA and Madamanchi, NR and Runge, MS and Jarstfer, MB},
title = {Effect of oxidative stress on telomere maintenance in aortic smooth muscle cells.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {1868},
number = {7},
pages = {166397},
doi = {10.1016/j.bbadis.2022.166397},
pmid = {35346819},
issn = {1879-260X},
mesh = {Animals ; *Cardiovascular Diseases/pathology ; Mice ; Myocytes, Smooth Muscle/metabolism ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase-1/genetics ; *Telomerase/genetics/metabolism ; Telomere/genetics ; },
abstract = {Reactive oxygen species (ROS) and telomere dysfunction are both associated with aging and the development of age-related diseases. Although there is evidence for a direct relationship between ROS and telomere dysfunction as well as an independent association of oxidative stress and telomere attrition with age-related disorders, there has not been sufficient exploration of how the interaction between oxidative stress and telomere function may contribute to the pathophysiology of cardiovascular diseases (CVD). To better understand the complex relationships between oxidative stress, telomerase biology and pathophysiology, we examined the telomere biology of aortic smooth muscle cells (ASMCs) isolated from mutant mouse models of oxidative stress. We discovered that telomere lengths were significantly shorter in ASMCs isolated from superoxide dismutase 2 heterozygous (Sod2[+/-]) mice, which exhibit increased arterial stiffness with aging, and the observed telomere attrition occurred over time. Furthermore, the telomere erosion occurred even though telomerase activity increased. In contrast, telomeres remained stable in wild-type and superoxide dismutase 1 heterozygous (Sod1[+/-]) mice, which do not exhibit CVD phenotypes. The data indicate that mitochondrial oxidative stress, in particular elevated superoxide levels and decreased hydrogen peroxide levels, induces telomere erosion in the ASMCs of the Sod2[+/-] mice. This reduction in telomere length occurs despite an increase in telomerase activity and correlates with the onset of disease phenotype. Our results suggest that the oxidative stress caused by imbalance in mitochondrial ROS, from deficient SOD2 activity as a model for mitochondrial dysfunction results in telomere dysfunction, which may contribute to pathogenesis of CVD.},
}
@article {pmid35342938,
year = {2022},
author = {Zhang, Y and Luo, S and Jia, Y and Zhang, X},
title = {Telomere maintenance mechanism dysregulation serves as an early predictor of adjuvant therapy response and a potential therapeutic target in human cancers.},
journal = {International journal of cancer},
volume = {151},
number = {2},
pages = {313-327},
doi = {10.1002/ijc.34007},
pmid = {35342938},
issn = {1097-0215},
mesh = {Genomic Instability ; Humans ; *Neoplasms/drug therapy/genetics ; Prognosis ; Telomere/metabolism ; Telomere Homeostasis ; },
abstract = {Telomere maintenance mechanisms (TMMs) rescue cells from telomere crisis, endow cells immortal property, stabilize genomic integrity. However, TMM-associated molecular profiles and their clinical outcomes in cancer remain elusive. Here, we performed a pan-cancer and integrated analysis of TMM gene expression profiles from 10 107 unique samples with clinicopathological, molecular and outcome features across seven malignancies from the same microarray platform (Affymetrix GPL570 platform). This resource was divided into case-control datasets for obtaining dysregulated TMM genes and survival datasets for evaluating clinical outcomes. Multidimensional data from The Cancer Genome Atlas (TCGA) were used to elucidate associations between TMM dysregulation and survival, genomic instability. Our results demonstrated that TMMs had a consistent dysregulation spectrum across cancers, based on which we developed the TMM-dysregulation signature TMS score (TMScore) that was positively associated with various tumor adverse features. Two opposite prognostic patterns of TMScore independent of clinicopathological and molecular characteristics were identified, which might be explained by genomic instability: breast and lung cancer patients with elevated TMScore had inferior outcomes, suggesting TMScore-related genes as potential therapeutic targets, on the contrary, colon and stomach cancer patients had superior outcomes. Most important, the prognostic value of TMScore was still significant regardless of whether patients had received adjuvant therapy, which was valuable for discriminating nonresponders from responders, and could predict the effectiveness of adjuvant therapy. In summary, our resources delineate TMMs dysregulated landscape across cancers, shed light on the impact of TMMs dysregulation on patient outcomes and adjuvant therapy, and provide novel therapeutic opportunities for cancer treatment.},
}
@article {pmid35339005,
year = {2022},
author = {Shu, MJ and Li, J and Zhu, YC},
title = {Genetically predicted telomere length and multiple sclerosis.},
journal = {Multiple sclerosis and related disorders},
volume = {60},
number = {},
pages = {103731},
doi = {10.1016/j.msard.2022.103731},
pmid = {35339005},
issn = {2211-0356},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; },
mesh = {*Genome-Wide Association Study ; Humans ; Mendelian Randomization Analysis ; *Multiple Sclerosis/genetics ; Polymorphism, Single Nucleotide ; Telomere/genetics ; },
abstract = {BACKGROUND: Previous epidemiological studies have indicated a role for telomere length in multiple sclerosis (MS) severity and phenotype. However, these studies failed to establish the causality between telomere length and MS susceptibility. Hence, we performed two-sample Mendelian randomization (MR) analysis to explore the causal relationship between telomere length and MS susceptibility.<br><br>METHODS: We used data of genetic variants associated with leukocyte telomere length as instrumental variables (IVs), which was identified from the largest and latest genome-wide association study (GWAS) from UK Biobank (UKB) with 472,174 participants. Summary data of MS was obtained from the International Multiple Sclerosis Genetics Consortium. We performed two-sample MR analyses using the inverse-variance weighted method as the primary approach. Other MR approaches, including the MR-Egger, the inverse variance weighted (multiplicative random effects), weighted median, simple median, weighted mode-based methods, and Causal Analysis Using Summary Effect estimates (CAUSE), were also conducted to detect the result robustness.<br><br>RESULTS: The genetic liability to longer telomere length was associated with a higher risk of MS susceptibility (odds ratio [OR] per one-SD telomere length, 1.91; 95% confidence interval [CI], 1.48-2.47; P&#xa0;=&#xa0;8.04&#xa0;&#xd7;&#xa0;10[-7]). The results remained consistent across multiple sensitivity analyses.<br><br>CONCLUSIONS: Our study supports the causal relationship between longer telomere length and increased risk of MS susceptibility.},
}
@article {pmid35338946,
year = {2022},
author = {Murkey, JA and Watkins, BX and Vieira, D and Boden-Albala, B},
title = {Disparities in allostatic load, telomere length and chronic stress burden among African American adults: A systematic review.},
journal = {Psychoneuroendocrinology},
volume = {140},
number = {},
pages = {105730},
doi = {10.1016/j.psyneuen.2022.105730},
pmid = {35338946},
issn = {1873-3360},
mesh = {Adult ; Black or African American ; *Allostasis/physiology ; Biomarkers ; Health Status Disparities ; Humans ; Stress, Psychological/complications ; Telomere ; },
abstract = {BACKGROUND: The chronic disease burden among African Americans has continued to rise. Although racial disparities in chronic disease risk are well documented, the role of chronic stress in risk disparities among racial and ethnic minorities is not well understood. This systematic review of studies reporting on the relationship between chronic stress, education, and/or income, and biomarkers of chronic stress (allostatic load and telomere length) longitudinally among African Americans, seeks to contribute to this knowledge gap.<br><br>OBJECTIVE: To use the existing literature to both examine the strength of two objective biomarkers--telomere length and allostatic load--as measures of the overactivation of physiological stress processes in African American adults; and determine if existing studies used these two biomarkers to assess the relationship between chronic stress, income and level of educational attainment among African Americans longitudinally.<br><br>METHODS: In order to identify English-language articles published prior to October 11, 2021, a comprehensive search strategy was developed using five databases: PubMed/Medline, EMBASE, Web of Science Plus, Global Health (Ovid), and PsycINFO. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was used to record progress on the comprehensive search for studies reporting on allostatic load and/or telomere length biomarkers longitudinally within all bodily fluids and chronic stress among African American adults.<br><br>RESULTS: In total, 7 studies met the search criteria; 902 were excluded. Thus, less than 1% of all studies reporting on biomarkers of chronic stress longitudinally included African Americans. Each of the 7 studies described the relationship between telomere length and/or allostatic load among African Americans and chronic stress, education, and/or income. Higher chronic stress levels and experiences of racial discrimination were associated with telomere shortening while lower income and higher chronic stress levels were associated with an increase in allostatic load among African Americans.<br><br>DISCUSSION: Given the limited number of studies reporting on the association between allostatic load, telomere length, and/or the relationship between both in assessing chronic stress severity longitudinally among African American populations, it is impossible to determine whether one biomarker has greater predictive value than the other. However, based on the literature included in this review, higher chronic stress levels and experiences of racial discrimination were associated with shorter telomere length, while lower income and higher chronic stress levels are associated with an increase in allostatic load among African Americans.<br><br>CONCLUSION: These data illustrate a gap in the literature on the relationship between the biomarkers of telomere length and allostatic load combined as a potential measure for chronic stress among African Americans. To our knowledge, none the current literature describes the relationship between telomere length and allostatic load longitudinally among African American adults. As the field strives to develop a "gold standard" for measuring chronic stress, the combination of these biomarkers needs to be the subject of scientific inquiry and thus, fully examined. Future longitudinal studies among African Americans are needed to better understand which biomarker, or combination of biomarkers will provide the most accurate measure of physiological stress processes.},
}
@article {pmid35338551,
year = {2022},
author = {Navrátilová, P and Toegelová, H and Tulpová, Z and Kuo, YT and Stein, N and Doležel, J and Houben, A and Šimková, H and Mascher, M},
title = {Prospects of telomere-to-telomere assembly in barley: Analysis of sequence gaps in the MorexV3 reference genome.},
journal = {Plant biotechnology journal},
volume = {20},
number = {7},
pages = {1373-1386},
pmid = {35338551},
issn = {1467-7652},
mesh = {Chromosomes, Plant/genetics ; DNA, Ribosomal/genetics ; Genome, Plant/genetics ; *Hordeum/genetics ; Sequence Analysis, DNA ; Telomere/genetics ; },
abstract = {The first gapless, telomere-to-telomere (T2T) sequence assemblies of plant chromosomes were reported recently. However, sequence assemblies of most plant genomes remain fragmented. Only recent breakthroughs in accurate long-read sequencing have made it possible to achieve highly contiguous sequence assemblies with a few tens of contigs per chromosome, that is a number small enough to allow for a systematic inquiry into the causes of the remaining sequence gaps and the approaches and resources needed to close them. Here, we analyse sequence gaps in the current reference genome sequence of barley cv. Morex (MorexV3). Optical map and sequence raw data, complemented by ChIP-seq data for centromeric histone variant CENH3, were used to estimate the abundance of centromeric, ribosomal DNA, and subtelomeric repeats in the barley genome. These estimates were compared with copy numbers in the MorexV3 pseudomolecule sequence. We found that almost all centromeric sequences and 45S ribosomal DNA repeat arrays were absent from the MorexV3 pseudomolecules and that the majority of sequence gaps can be attributed to assembly breakdown in long stretches of satellite repeats. However, missing sequences cannot fully account for the difference between assembly size and flow cytometric genome size estimates. We discuss the prospects of gap closure with ultra-long sequence reads.},
}
@article {pmid35337624,
year = {2022},
author = {Praveen, G and Sivaprasad, M and Reddy, GB},
title = {Telomere length and vitamin B12.},
journal = {Vitamins and hormones},
volume = {119},
number = {},
pages = {299-324},
doi = {10.1016/bs.vh.2022.01.014},
pmid = {35337624},
issn = {0083-6729},
mesh = {Aging/genetics ; Cellular Senescence ; Humans ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; *Vitamin B 12 ; },
abstract = {Telomeres are non-coding nucleoprotein structures consisting of a highly conserved tandem repeat DNA sequence that caps the ends of chromosomes in eukaryotes. Telomeres confer chromosomal stability, protect the genome from nucleolytic degradation, avoid aberrant recombination and improper repair, and prevent random fusion of chromosomes. The end-replication problem results in telomere shortening with every cell division, eventually leading to cellular senescence and aging. Telomere length (TL) is thereby an ideal candidate for "biological aging." Telomeres possess guanine-rich repeats, which are highly susceptible to oxidative stress. Epidemiological studies have indicated the association of telomere attrition with mortality and various age-related diseases. Micronutrients comprising vitamins and minerals act as potential modulators of stress and can influence TL. Research has indicated that vitamin B12 (B12) regulates oxidative stress and maintains genomic stability, thereby influencing telomere integrity and cellular aging. The deficiency of B12 leads to elevated levels of homocysteine, which reduces the methylation potential and increases oxidative stress, thereby compromising the TL. Telomere shortening and mitochondrial dysfunction are independently linked to aging. However, they are connected through telomerase reverse transcriptase activity, which regulates mitochondrial biogenesis. Further, experimental evidence indicated the positive association of B12 with relative TL and mitochondrial DNA copy number, an indirect index of mitochondrial biogenesis. The present chapter provides some insights into the role of B12 in influencing TL. Exploring their association might open new avenues to understand the pathophysiology of aging and age-related diseases.},
}
@article {pmid35337612,
year = {2022},
author = {Wan, S and Zhao, X and Pei, J and Han, Z and Che, R and Qin, S and Hua, X},
title = {Association of age at benign hysterectomy with leukocyte telomere length in a nationally representative population.},
journal = {Maturitas},
volume = {159},
number = {},
pages = {46-51},
doi = {10.1016/j.maturitas.2022.01.002},
pmid = {35337612},
issn = {1873-4111},
mesh = {Cross-Sectional Studies ; Female ; Humans ; Hysterectomy/adverse effects ; *Leukocytes ; Nutrition Surveys ; *Telomere ; },
abstract = {OBJECTIVES: Hysterectomy is one of the most common gynecological surgical procedures, and most hysterectomies are performed for benign indications. Despite the frequency and known benefits of the procedure, it remains unclear whether it has potential adverse effects on long-term health and longevity. The aim of this study was to evaluate the association of age at benign hysterectomy with leukocyte telomere length, in data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002.<br><br>STUDY DESIGN: In total, 811 women who had a hysterectomy were included in this cross-sectional study.<br><br>MAIN OUTCOME MEASURES: To estimate the association of age at benign hysterectomy with telomere length, multivariate regression analyses adjusted for age, race/ ethnicity, education, marital status, income poverty ratio, body mass index (BMI), physical activity, smoking behavior, alcohol consumption, history of chronic disease and history of oophorectomy were conducted. Fitted smoothing curves were also evaluated.<br><br>RESULTS: We found leukocyte telomere length was positively correlated with age at benign hysterectomy after adjusting for other confounders in both a minimally adjusted model [&#x3b2;&#xa0;=&#xa0;4.18, 95%CI: (0.17,8.20)] and a fully adjusted model [&#x3b2;&#xa0;=&#xa0;4.63, 95% CI:(0.56,8.70)].<br><br>CONCLUSIONS: Earlier age at benign hysterectomy was associated with shorter telomere length in a nationally representative population of women. These data provide new information in pre-surgical counseling and decision-making.},
}
@article {pmid35334902,
year = {2022},
author = {Raftopoulou, C and Paltoglou, G and Charmandari, E},
title = {Association between Telomere Length and Pediatric Obesity: A Systematic Review.},
journal = {Nutrients},
volume = {14},
number = {6},
pages = {},
pmid = {35334902},
issn = {2072-6643},
support = {project code: T1EDK-01386, MIS: 5030543, Acronym: PEDOBESITY//This research was co-financed by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH-CREATE-INNOVATE/ ; },
mesh = {Adult ; Aging ; Child ; Humans ; *Pediatric Obesity ; Prospective Studies ; Telomere ; Telomere Homeostasis ; },
abstract = {OBJECTIVE: Telomere length (TL) is a robust marker of biological aging, and increased telomere attrition is noted in adults with obesity. The primary objective of this systematic review was to summarize current knowledge on the effects of childhood obesity in TL. The secondary objective was to assess the effect of weight management interventions in TL.<br><br>METHODS: The following databases were searched: PubMed, Scopus, Web of Science and Heal-link.gr from inception to September 2021. The search was performed using the following combinations of terms: "telomer*" [All Fields] AND ("length" [All Fields] OR "lengths" [All Fields]) AND "obes*" [All Fields] AND ("child*" [All Fields] OR "adolescen*" [All Fields]).<br><br>RESULTS: A total of 16 original articles were included in this systematic review. Eleven of them were cross-sectional and five were lifestyle interventions.<br><br>CONCLUSIONS: There was a tendency towards a negative association between childhood obesity and TL. Life-style interventions in children have been associated with increased TL peripherally, indicating a possible association of the redistribution of younger cells in the periphery with the favorable effect of these interventions. Further prospective studies with larger sample sizes that employ other markers of cell aging would potentially elucidate this important mechanistic relation.},
}
@article {pmid35334391,
year = {2022},
author = {Li, X and Cai, J and Yang, L and Zhang, X and Deng, W and Ni, P and Zhao, L and Du, XD and Li, T},
title = {Correlation between reduced telomere length and behavioural and emotional problems in left-behind children in a rural area in China.},
journal = {Psychoneuroendocrinology},
volume = {140},
number = {},
pages = {105732},
doi = {10.1016/j.psyneuen.2022.105732},
pmid = {35334391},
issn = {1873-3360},
mesh = {Adolescent ; Child ; China ; Humans ; *Mental Health ; *Self Concept ; Surveys and Questionnaires ; Telomere ; },
abstract = {Evidence shows that being left behind experience (LBE) during childhood may increase the risks of poor psychopathological outcomes. However, it is unclear to what extent the mental health is affected by the LBE. Telomere length (TL), one of the most extensively studied biological markers of cellular ageing, provides a valuable tool for exploring the potential effects of parent-child separation on psychological problems by integrating genetic and environmental factors. In this study, a total of 613 children (mean age = 10.77, SD = 1.92) were recruited from the rural area of Deyang, Sichuan Province, China. We used a self-designed questionnaire to assess LBE, and collected psychopathological outcomes by using the Piers-Harris Children's Self-concept Scale, the Teacher's Report Form 6/18 and the Youth Self-Report 11/18. Terminal restriction fragment analysis was used to measure TL in peripheral blood leukocytes. Analyses revealed that 342 out of 613 participants (55.79%) were Left-behind children. LBE was observed to associated with shorter TL, lower self-esteem, and increased behavioural and emotional problems. The cumulative effects of LBE may be reflected by greater altered telomere homeostasis, decreased self-esteem, and worsened behavioural and emotional problems. The association of the total time of being left behind with self-esteem and behavioural and emotional problems was significantly mediated by altered telomere homeostasis, with estimated effects of 14.19%, 47.95% and 45.13%, respectively. The LBE in childhood, especially prolonged parent-child separation, increases the risk of mental health problems in childhood and adolescence.},
}
@article {pmid35330058,
year = {2022},
author = {Sánchez-González, JL and Sánchez-Rodríguez, JL and Juárez-Vela, R and Ruiz de Viñaspre-Hernandez, R and González-Sarmiento, R and Martin-Vallejo, FJ},
title = {Analysis of Telomere Length and Its Implication in Neurocognitive Functions in Elderly Women.},
journal = {Journal of clinical medicine},
volume = {11},
number = {6},
pages = {},
pmid = {35330058},
issn = {2077-0383},
abstract = {During the normal aging process, a series of events occur, such as a decrease in telomere length and a decrease in various cognitive functions, such as attention, memory, or perceptual-motor speed. Several studies have attempted to establish a correlation between both variables; however, there is considerable controversy in the scientific literature. The aim of our study was to establish a correlation between the scores obtained in the following different cognitive tests: the Mini-Mental State Examination, the Benton Visual Retention Test, the Trail Making Test, the Rey Auditory Verbal Learning Test, the Stroop Test, and the measurement of telomere length. The sample consisted of a total of 41 physically active, healthy women, with a mean age of 71.21 (±4.32) and of 33 physically inactive, healthy women, with a mean age of 72.70 (±4.13). Our results indicate that there is no correlation between the scores obtained by the women in either group and their telomere length. Therefore, it is not possible to conclude that telomere length can be correlated with cognitive performance.},
}
@article {pmid35328692,
year = {2022},
author = {Oliva-Rico, D and Fabian-Morales, E and Cáceres-Gutiérrez, RE and Gudiño, A and Cisneros-Soberanis, F and Dominguez, J and Almaraz-Rojas, O and Arriaga-Canon, C and Castro-Hernández, C and De la Rosa, C and Reyes, JL and Herrera, LA},
title = {Methylation of Subtelomeric Chromatin Modifies the Expression of the lncRNA TERRA, Disturbing Telomere Homeostasis.},
journal = {International journal of molecular sciences},
volume = {23},
number = {6},
pages = {},
pmid = {35328692},
issn = {1422-0067},
support = {513107//Consejo Nacional de Ciencia y Tecnolog&#xed;a/ ; },
mesh = {Chromatin/genetics ; Heterochromatin ; Methylation ; *RNA, Long Noncoding/genetics/metabolism ; Telomere/genetics/metabolism ; *Telomere Homeostasis ; },
abstract = {The long noncoding RNA (lncRNA) telomeric repeat-containing RNA (TERRA) has been associated with telomeric homeostasis, telomerase recruitment, and the process of chromosome healing; nevertheless, the impact of this association has not been investigated during the carcinogenic process. Determining whether changes in TERRA expression are a cause or a consequence of cell transformation is a complex task because studies are usually carried out using either cancerous cells or tumor samples. To determine the role of this lncRNA in cellular aging and chromosome healing, we evaluated telomeric integrity and TERRA expression during the establishment of a clone of untransformed myeloid cells. We found that reduced expression of TERRA disturbed the telomeric homeostasis of certain loci, but the expression of the lncRNA was affected only when the methylation of subtelomeric bivalent chromatin domains was compromised. We conclude that the disruption in TERRA homeostasis is a consequence of cellular transformation and that changes in its expression profile can lead to telomeric and genomic instability.},
}
@article {pmid35328421,
year = {2022},
author = {Porika, M and Tippani, R and Saretzki, GC},
title = {CRISPR/Cas: A New Tool in the Research of Telomeres and Telomerase as Well as a Novel Form of Cancer Therapy.},
journal = {International journal of molecular sciences},
volume = {23},
number = {6},
pages = {},
pmid = {35328421},
issn = {1422-0067},
mesh = {CRISPR-Cas Systems/genetics ; Gene Editing/methods ; *Neoplasms/genetics/therapy ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {Due to their close connection with senescence, aging, and disease, telomeres and telomerase provide a unique and vital research route for boosting longevity and health span. Despite significant advances during the last three decades, earlier studies into these two biological players were impeded by the difficulty of achieving real-time changes inside living cells. As a result of the clustered regularly interspaced short palindromic repeats (CRISPR)-associated system's (Cas) method, targeted genetic studies are now underway to change telomerase, the genes that govern it as well as telomeres. This review will discuss studies that have utilized CRISPR-related technologies to target and modify genes relevant to telomeres and telomerase as well as to develop targeted anti-cancer therapies. These studies greatly improve our knowledge and understanding of cellular and molecular mechanisms that underlie cancer development and aging.},
}
@article {pmid35325218,
year = {2022},
author = {Miki, S and Koga, T and Mckinney, AM and Parisian, AD and Tadokoro, T and Vadla, R and Marsala, M and Hevner, RF and Costello, JF and Furnari, F},
title = {TERT promoter C228T mutation in neural progenitors confers growth advantage following telomere shortening in vivo.},
journal = {Neuro-oncology},
volume = {24},
number = {12},
pages = {2063-2075},
pmid = {35325218},
issn = {1523-5866},
support = {F31 CA243187/CA/NCI NIH HHS/United States ; R01 CA258248/CA/NCI NIH HHS/United States ; P50 CA097257/CA/NCI NIH HHS/United States ; T32 GM008666/GM/NIGMS NIH HHS/United States ; R01 NS080939/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; Mice ; Animals ; Telomere Shortening/genetics ; *Induced Pluripotent Stem Cells ; *Telomerase/genetics ; Telomere/genetics ; *Glioblastoma/genetics ; Mutation ; Carcinogenesis ; },
abstract = {BACKGROUND: Heterozygous TERT (telomerase reverse transcriptase) promoter mutations (TPMs) facilitate TERT expression and are the most frequent mutation in glioblastoma (GBM). A recent analysis revealed this mutation is one of the earliest events in gliomagenesis. However, no appropriate human models have been engineered to study the role of this mutation in the initiation of these tumors.<br><br>METHOD: We established GBM models by introducing the heterozygous TPM in human induced pluripotent stem cells (hiPSCs) using a two-step targeting approach in the context of GBM genetic alterations, CDKN2A/B and PTEN deletion, and EGFRvIII overexpression. The impact of the mutation was evaluated through the in vivo passage and in vitro experiment and analysis.<br><br>RESULTS: Orthotopic injection of neuronal precursor cells (NPCs) derived from hiPSCs with the TPM into immunodeficient mice did not enhance tumorigenesis compared to TERT promoter wild type NPCs at initial in vivo passage presumably due to relatively long telomeres. However, the mutation recruited GA-Binding Protein and engendered low-level TERT expression resulting in enhanced tumorigenesis and maintenance of short telomeres upon secondary passage as observed in human GBM. These results provide the first insights regarding increased tumorigenesis upon introducing a TPM compared to isogenic controls without TPMs.<br><br>CONCLUSION: Our novel GBM models presented the growth advantage of heterozygous TPMs for the first time in the context of GBM driver mutations relative to isogenic controls, thereby allowing for the identification and validation of TERT promoter-specific vulnerabilities in a genetically accurate background.},
}
@article {pmid35323880,
year = {2022},
author = {Shimamura, A},
title = {Telomere biology disorders: ends and (genetic) means.},
journal = {Blood},
volume = {139},
number = {12},
pages = {1776-1777},
doi = {10.1182/blood.2021014855},
pmid = {35323880},
issn = {1528-0020},
mesh = {Biology ; *Telomerase/genetics/metabolism ; *Telomere/genetics/metabolism ; },
}
@article {pmid35323213,
year = {2022},
author = {Lister-Shimauchi, EH and McCarthy, B and Lippincott, M and Ahmed, S},
title = {Genetic and Epigenetic Inheritance at Telomeres.},
journal = {Epigenomes},
volume = {6},
number = {1},
pages = {},
pmid = {35323213},
issn = {2075-4655},
support = {R01 GM135470/GM/NIGMS NIH HHS/United States ; },
abstract = {Transgenerational inheritance can occur at telomeres in distinct contexts. Deficiency for telomerase or telomere-binding proteins in germ cells can result in shortened or lengthened chromosome termini that are transmitted to progeny. In human families, altered telomere lengths can result in stem cell dysfunction or tumor development. Genetic inheritance of altered telomeres as well as mutations that alter telomeres can result in progressive telomere length changes over multiple generations. Telomeres of yeast can modulate the epigenetic state of subtelomeric genes in a manner that is mitotically heritable, and the effects of telomeres on subtelomeric gene expression may be relevant to senescence or other human adult-onset disorders. Recently, two novel epigenetic states were shown to occur at C. elegans telomeres, where very low or high levels of telomeric protein foci can be inherited for multiple generations through a process that is regulated by histone methylation.Together, these observations illustrate that information relevant to telomere biology can be inherited via genetic and epigenetic mechanisms, although the broad impact of epigenetic inheritance to human biology remains unclear.},
}
@article {pmid35317118,
year = {2021},
author = {Fathi, E and Vandghanooni, S and Montazersaheb, S and Farahzadi, R},
title = {Mesenchymal stem cells promote caspase-3 expression of SH-SY5Y neuroblastoma cells via reducing telomerase activity and telomere length.},
journal = {Iranian journal of basic medical sciences},
volume = {24},
number = {11},
pages = {1583-1589},
pmid = {35317118},
issn = {2008-3866},
abstract = {OBJECTIVES: The use of mesenchymal stem cells in malignancies has attracted much attention due to their ability to deliver anticancer agents to tumors, including cytokines, chemokines, etc. This study aimed to investigate the effect of MSCs on the neuroblastoma SH-SY5Y cells through proliferation/apoptosis, senescence assessment, telomere length, and telomerase activity in vitro. BAX and BCL2 were also examined as potential signaling pathways in this process.<br><br>MATERIALS AND METHODS: For this reason, two cell populations (MSCs and SH-SY5Y cells) were co-cultured on trans-well plates for 7 days. In a subsequent step, SH-SY5Y cells were harvested from both control and experimental groups and subjected to flow cytometry, ELISA, real-time PCR, PCR-ELISA TRAP assay, and Western blotting assay for Ki67/Caspase3 investigation, &#x3b2;-Galactosidase assessment, telomere length, and telomerase activity assay. Also, expression of genes and proteins through real-time PCR and Western blotting demonstrated the involvement of the aforementioned signaling pathways in this process.<br><br>RESULTS: It was found that MSCs contributed significantly to decrease and increase of Ki-67 and Caspase-3, respectively. Also, MSCs dramatically reduced the length of telomere and telomerase activity and increased the &#x3b2;-Galactosidase activity in a significant manner. In addition, significant increase and decrease were also seen in BAX and BCL2 gene and protein expressions, respectively.<br><br>CONCLUSION: These findings revealed that close interaction between MSCs and neuroblastoma cells causes inhibition of the SH-SY5Y cell proliferation and promotes cell senescence via BAX and caspase-3 cascade pathways.},
}
@article {pmid35316424,
year = {2022},
author = {Berteli, TS and Wang, F and Kohlrausch, FB and Da Luz, CM and Oliveira, FV and Keefe, DL and Navarro, PA},
title = {Impact of superovulation and in vitro fertilization on LINE-1 copy number and telomere length in C57BL/6 J mice blastocysts.},
journal = {Molecular biology reports},
volume = {49},
number = {6},
pages = {4909-4917},
pmid = {35316424},
issn = {1573-4978},
support = {88887.371487/2019-00//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 204747/2018-0//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; },
mesh = {Animals ; Blastocyst ; *DNA Copy Number Variations/genetics ; Female ; Fertilization in Vitro ; Mice ; Mice, Inbred C57BL ; *Superovulation ; Telomere/genetics ; },
abstract = {OBJECTIVE: Millions of babies have been conceived by IVF, yet debate about its safety to offspring continues. We hypothesized that superovulation and in vitro fertilization (IVF) promote genomic changes, including altered telomere length (TL) and activation of the retrotransposon LINE-1 (L1), and tested this hypothesis in a mouse model.<br><br>MATERIAL AND METHODS: Experimental study analyzing TL and L1 copy number in C57BL/6&#xa0;J mouse blastocysts in vivo produced from natural mating cycles (N), in vivo produced following superovulation (S), or in vitro produced following superovulation (IVF). We also examined the effects of prolonged culture on TL and L1 copy number in the IVF group comparing blastocysts cultured 96&#xa0;h versus blastocysts cultured 120&#xa0;h. TL and L1 copy number were measured by Real Time PCR.<br><br>RESULTS: TL in S (n&#x2009;=&#x2009;77; Mean: 1.50&#x2009;&#xb1;&#x2009;1.15; p&#x2009;=&#x2009;0.0007) and IVF (n&#x2009;=&#x2009;82; Mean: 1.72&#x2009;&#xb1;&#x2009;1.44; p&#x2009;<&#x2009;0.0001) exceeded that in N (n&#x2009;=&#x2009;16; Mean: 0.61&#x2009;&#xb1;&#x2009;0.27). TL of blastocysts cultured 120&#xa0;h (n&#x2009;=&#x2009;15, Mean: 2.14&#x2009;&#xb1;&#x2009;1.05) was significantly longer than that of embryos cultured for 96&#xa0;h (n&#x2009;=&#x2009;67, Mean: 1.63&#x2009;&#xb1;&#x2009;1.50; p&#x2009;=&#x2009;0.0414). L1 copy number of blastocysts cultured for 120&#xa0;h (n&#x2009;=&#x2009;15, Mean: 1.71&#x2009;&#xb1;&#x2009;1.49) exceeded that of embryos cultured for 96&#xa0;h (n&#x2009;=&#x2009;67, Mean: 0.95&#x2009;&#xb1;&#x2009;1.03; p&#x2009;=&#x2009;0.0162).<br><br>CONCLUSIONS: Intriguingly ovarian stimulation, alone or followed by IVF, produced embryos with significantly longer telomeres compared to in vivo, natural cycle-produced embryos. The significance of this enriched telomere endowment for the health and longevity of offspring born from IVF merit future studies.},
}
@article {pmid35313074,
year = {2022},
author = {Lv, N and Zhao, Y and Liu, X and Ye, L and Liang, Z and Kang, Y and Dong, Y and Wang, W and Kolliputi, N and Shi, L},
title = {Dysfunctional telomeres through mitostress-induced cGAS/STING activation to aggravate immune senescence and viral pneumonia.},
journal = {Aging cell},
volume = {21},
number = {4},
pages = {e13594},
pmid = {35313074},
issn = {1474-9726},
mesh = {Animals ; *COVID-19 ; *Immunity, Innate ; Inflammation ; Membrane Proteins/genetics/metabolism ; Mice ; Nucleotidyltransferases/genetics/metabolism ; SARS-CoV-2 ; Signal Transduction ; Telomere/metabolism ; },
abstract = {Disproportionately high incidence and mortality of respiratory infection such as influenza A virus (IAV) and SARS-CoV-2 have been evidenced in the elderly, but the role and the mechanism of age-associated immune deregulation in disease exacerbation are not well defined. Using a late generation of mice deficient in telomerase RNA (Terc[-/-]), we herein demonstrated that aged mice were exquisitely susceptible to respiratory viral infection, with excessive inflammation and increased mortality. Furthermore, we identified the cGAS/STING pathway, which was essentially induced by the leaked mitochondrial DNA, as a biologically relevant mechanism contributing to exaggerated inflammation in Terc[-/-] mice following viral infection. Innate immune cells, mainly, macrophages with shortened telomeres, exhibited hallmarks of cellular senescence, mitochondrial distress, and aberrant activation of STING and NLRP3 inflammasome pathways, which predisposed mice to severe viral pneumonia during commonly mild infections. Application of STING inhibitor and, more importantly, senolytic agent, reduced the burden of stressed macrophages, improved mitochondrial integrity, and suppressed STING activation, thereby conferring the protection for Terc[-/-] mice against respiratory infection. Together, the findings expand our understanding of innate immune senescence and reveal the potential of the senolytics as a promising treatment to alleviate the symptom of viral pneumonia, particularly for the older population.},
}
@article {pmid35312207,
year = {2022},
author = {Wu, W and Du, Z and Wu, L},
title = {Dexmedetomidine attenuates hypoxia-induced cardiomyocyte injury by promoting telomere/telomerase activity: Possible involvement of ERK1/2-Nrf2 signaling pathway.},
journal = {Cell biology international},
volume = {46},
number = {7},
pages = {1036-1046},
doi = {10.1002/cbin.11799},
pmid = {35312207},
issn = {1095-8355},
mesh = {Apoptosis ; Cardiomegaly/metabolism ; *Dexmedetomidine/metabolism/pharmacology ; Humans ; Hypoxia/metabolism ; MAP Kinase Signaling System ; Myocytes, Cardiac/metabolism ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress ; RNA, Messenger/metabolism ; Signal Transduction ; *Telomerase/genetics ; Telomere/metabolism ; },
abstract = {Dexmedetomidine (Dex), an α2-adrenergic receptor (α2-AR) agonist, possesses cardioprotection against ischemic/hypoxic injury, but the exact mechanism is not fully elucidated. Since telomere/telomerase dysfunction is involved in myocardial ischemic damage, the present study aimed to investigate whether Dex ameliorates cobalt chloride (CoCl2; a hypoxia mimic agent in vitro)-induced the damage of H9c2 cardiomyocytes by improving telomere/telomerase dysfunction and further explored the underlying mechanism focusing on extracellular signal-regulated kinase (ERK1/2)-NF-E2-related factor 2 (Nrf2) signaling pathway. The result showed that Dex increased cell viability, decreased apoptosis, and reduced cardiomyocyte hypertrophy as illustrated by the decreases in cell surface area and the biomarker levels for cardiac hypertrophy including atrial natriuretic peptide, brain natriuretic peptide, and myosin heavy chain β messenger RNA (mRNA) and protein in CoCl2 -exposed H9c2 cells. Intriguingly, Dex increased the telomere length and telomerase activity as well as telomere reverse transcriptase protein and mRNA levels in H9c2 cells exposed to CoCl2 , indicating that Dex promotes telomere/telomerase function under hypoxia. In addition, Dex remarkably diminished the reactive oxygen species generation, reduced malondialdehyde content, and increased antioxidative signaling as evidenced by the increases in superoxide dismutase and plasma glutathione peroxidase activities. Furthermore, Dex increased the ratio of P-ERK1/2/T-ERK1/2 and P-Nrf2/T-Nrf2 and enhanced Nrf2 nuclear translocation in CoCl2 -subjected H9c2 cells, suggesting that Dex promotes the activation of the ERK1/2-Nrf2 signaling pathway. These novel findings indicated that Dex attenuates myocardial ischemic damage and reduces myocardial hypertrophy by promoting telomere/telomerase function, which may be associated with the activation of the ERK1/2-Nrf2 signaling pathway in vitro.},
}
@article {pmid35297226,
year = {2022},
author = {Bountziouka, V and Nelson, CP and Codd, V and Wang, Q and Musicha, C and Allara, E and Kaptoge, S and Di Angelantonio, E and Butterworth, AS and Thompson, JR and Curtis, EM and Wood, AM and Danesh, JN and Harvey, NC and Cooper, C and Samani, NJ},
title = {Association of shorter leucocyte telomere length with risk of frailty.},
journal = {Journal of cachexia, sarcopenia and muscle},
volume = {13},
number = {3},
pages = {1741-1751},
pmid = {35297226},
issn = {2190-6009},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MR/M012816/1//UK Medical Research Council (MRC)/ ; MR/L003120/1/MRC_/Medical Research Council/United Kingdom ; /BHF_/British Heart Foundation/United Kingdom ; MC_PC_21022/MRC_/Medical Research Council/United Kingdom ; MR/M012816/1/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Adult ; Cross-Sectional Studies ; Female ; *Frailty/epidemiology/genetics ; Humans ; Leukocytes ; Male ; Risk Factors ; Telomere/genetics ; },
abstract = {BACKGROUND: Frailty is a multidimensional syndrome of decline that affects multiple systems and predisposes to adverse health outcomes. Although chronological age is the major risk factor, inter-individual variation in risk is not fully understood. Leucocyte telomere length (LTL), a proposed marker of biological age, has been associated with risk of many diseases. We sought to determine whether LTL is associated with risk of frailty.<br><br>METHODS: We utilized cross-sectional data from 441&#xa0;781 UK Biobank participants (aged 40-69&#xa0;years), with complete data on frailty indicators and LTL. Frailty was defined as the presence of at least three of five indicators: weaker grip strength, slower walking pace, weight loss in the past year, lower physical activity, and exhaustion in the past 2&#xa0;weeks. LTL was measured using a validated qPCR method and reported as a ratio of the telomere repeat number (T) to a single-copy gene (S) (T/S ratio). Association of LTL with frailty was evaluated using adjusted (chronological age, sex, deprivation, smoking, alcohol intake, body mass index, and multimorbidity) multinomial and ordinal regression models, and results are presented as relative risk (RRR) or odds ratios (OR), respectively, alongside the 95% confidence interval (CI). Mendelian randomization (MR), using 131 genetic variants associated with LTL, was used to assess if the association of LTL with frailty was causal.<br><br>RESULTS: Frail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years, P&#xa0;=&#xa0;2.73&#xa0;&#xd7;&#xa0;10[-33]), more likely to be female (61%, P&#xa0;=&#xa0;1.97&#xa0;&#xd7;&#xa0;10[-129]), and had shorter LTL (-0.13SD vs. 0.03SD, P&#xa0;=&#xa0;5.43&#xa0;&#xd7;&#xa0;10[-111]) than non-frail. In adjusted analyses, both age and LTL were associated with frailty (RRR&#xa0;=&#xa0;1.03 (95% CI: 1.02; 1.04) per year of older chronological age, P&#xa0;=&#xa0;3.99&#xa0;&#xd7;&#xa0;10[-12] ; 1.10 (1.08; 1.11) per SD shorter LTL, P&#xa0;=&#xa0;1.46&#xa0;&#xd7;&#xa0;10[-30]). Within each age group (40-49, 50-59, 60-69&#xa0;years), the prevalence of frailty was about 33% higher in participants with shorter (-2SD) versus longer telomeres (+2SD). MR analysis showed an association of LTL with frailty that was directionally consistent with the observational association, but not statistically significant (MR-Median: OR (95% CI): 1.08 (0.98; 1.19) per SD shorter LTL, P&#xa0;=&#xa0;0.13).<br><br>CONCLUSIONS: Inter-individual variation in LTL is associated with the risk of frailty independently of chronological age and other risk factors. Our findings provide evidence for an additional biological determinant of frailty.},
}
@article {pmid35296692,
year = {2022},
author = {Törn, C and Liu, X and Onengut-Gumuscu, S and Counts, KM and Moreno, JL and Remedios, CL and Chen, WM and LeFaive, J and Butterworth, MD and Akolkar, B and Krischer, JP and Lernmark, &#xc5; and Rewers, M and She, JX and Toppari, J and Ziegler, AG and Ratan, A and Smith, AV and Hagopian, WA and Rich, SS and Parikh, HM and , },
title = {Telomere length is not a main factor for the development of islet autoimmunity and type 1 diabetes in the TEDDY study.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {4516},
pmid = {35296692},
issn = {2045-2322},
support = {UC4 DK063836/DK/NIDDK NIH HHS/United States ; UC4 DK112243/DK/NIDDK NIH HHS/United States ; U01 DK063865/DK/NIDDK NIH HHS/United States ; U01 DK063821/DK/NIDDK NIH HHS/United States ; UC4 DK063821/DK/NIDDK NIH HHS/United States ; UC4 DK117483/DK/NIDDK NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; U01 DK063836/DK/NIDDK NIH HHS/United States ; /JDRF/Juvenile Diabetes Research Foundation/United States ; U01 DK124166/DK/NIDDK NIH HHS/United States ; U01 DK128847/DK/NIDDK NIH HHS/United States ; U01 DK063861/DK/NIDDK NIH HHS/United States ; UC4 DK095300/DK/NIDDK NIH HHS/United States ; UC4 DK063865/DK/NIDDK NIH HHS/United States ; UC4 DK063863/DK/NIDDK NIH HHS/United States ; UC4 DK100238/DK/NIDDK NIH HHS/United States ; HHSN267200700014C/LM/NLM NIH HHS/United States ; U01 DK063790/DK/NIDDK NIH HHS/United States ; U01 DK063863/DK/NIDDK NIH HHS/United States ; UC4 DK063829/DK/NIDDK NIH HHS/United States ; UL1 TR000064/TR/NCATS NIH HHS/United States ; UC4 DK063861/DK/NIDDK NIH HHS/United States ; UC4 DK106955/DK/NIDDK NIH HHS/United States ; },
mesh = {Autoantibodies ; Autoimmunity/genetics ; Case-Control Studies ; Child ; *Diabetes Mellitus, Type 1 ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; *Islets of Langerhans ; Telomere/genetics ; },
abstract = {The Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8676 children, 3-4 months of age, born with HLA-susceptibility genotypes for islet autoimmunity (IA) and type 1 diabetes (T1D). Whole-genome sequencing (WGS) was performed in 1119 children in a nested case-control study design. Telomere length was estimated from WGS data using five tools: Computel, Telseq, Telomerecat, qMotif and Motif_counter. The estimated median telomere length was 5.10 kb (IQR 4.52-5.68 kb) using Computel. The age when the blood sample was drawn had a significant negative correlation with telomere length (P = 0.003). European children, particularly those from Finland (P = 0.041) and from Sweden (P = 0.001), had shorter telomeres than children from the U.S.A. Paternal age (P = 0.019) was positively associated with telomere length. First-degree relative status, presence of gestational diabetes in the mother, and maternal age did not have a significant impact on estimated telomere length. HLA-DR4/4 or HLA-DR4/X children had significantly longer telomeres compared to children with HLA-DR3/3 or HLA-DR3/9 haplogenotypes (P = 0.008). Estimated telomere length was not significantly different with respect to any IA (P = 0.377), IAA-first (P = 0.248), GADA-first (P = 0.248) or T1D (P = 0.861). These results suggest that telomere length has no major impact on the risk for IA, the first step to develop T1D. Nevertheless, telomere length was shorter in the T1D high prevalence populations, Finland and Sweden.},
}
@article {pmid35295138,
year = {2021},
author = {Mandakh, Y and Oudin, A and Erlandsson, L and Isaxon, C and Hansson, SR and Broberg, K and Malmqvist, E},
title = {Association of Prenatal Ambient Air Pollution Exposure With Placental Mitochondrial DNA Copy Number, Telomere Length and Preeclampsia.},
journal = {Frontiers in toxicology},
volume = {3},
number = {},
pages = {659407},
pmid = {35295138},
issn = {2673-3080},
abstract = {Background: Studies have shown that ambient air pollution is linked to preeclampsia (PE), possibly via generation of oxidative stress in the placenta. Telomere length and mitochondrial DNA copy number (mtDNAcn) are sensitive to oxidative stress damage. Objective: To study the association between prenatal exposure to ambient nitrogen oxides (NOx, a marker for traffic-related air pollution), and PE, as well as potential mediation effects by placental telomere length and mtDNAcn. Methods: This is a cross-sectional study of 42 preeclamptic and 95 arbitrarily selected normotensive pregnant women with gestational ambient NOx exposure assessment in southern Scania, Sweden. Hourly concentrations of NOx were estimated at the residential addresses by a Gaussian-plume dispersion model with 100 × 100 m spatial resolutions and aggregated into trimester-specific mean concentrations. Placental relative mtDNAcn and telomere length were measured using qPCR. Linear and logistic regression models were used to investigate associations, adjusted for perinatal and seasonal characteristics. Results: Exposure was categorized into low and high exposures by median cut-offs during first [11.9 μg/m[3]; interquartile range (IQR) 7.9, 17.9], second (11.6 μg/m[3]; IQR: 7.1, 21.1), third trimesters (11.9 μg/m[3]; IQR: 7.7, 19.5) and entire pregnancy (12.0 μg/m[3]; IQR: 7.6, 20.1). Increased risk of PE was found for high prenatal NOx exposure during the first trimester (OR 4.0; 95% CI: 1.4, 11.1; p = 0.008), and entire pregnancy (OR 3.7; 95% CI: 1.3, 10.4; p = 0.012). High exposed group during the first trimester had lower placental relative mtDNAcn compared with low exposed group (-0.20; 95% CI: -0.36, -0.04; p = 0.01). Changes in relative mtDNAcn did not mediate the association between prenatal NOx exposure and PE. No statistically significant association was found between placental relative telomere length, prenatal NOx exposure and PE. Conclusion: In this region with relatively low levels of air pollution, ambient NOx exposure during the first trimester was associated with reduced placental relative mtDNAcn and an increased risk of PE. However, we did not find any evidence that mtDNAcn or TL mediated the association between air pollution and PE. Future research should further investigate the role of mtDNAcn for pregnancy complications in relation to exposure to ambient air pollution during pregnancy.},
}
@article {pmid35294438,
year = {2022},
author = {Wei, H and Aucoin, J and Kuntapay, GR and Justice, A and Jones, A and Zhang, C and Santos, HP and Hall, LA},
title = {The prevalence of nurse burnout and its association with telomere length pre and during the COVID-19 pandemic.},
journal = {PloS one},
volume = {17},
number = {3},
pages = {e0263603},
pmid = {35294438},
issn = {1932-6203},
mesh = {Adult ; Burnout, Professional/*epidemiology/genetics/psychology ; COVID-19/complications/*epidemiology/psychology ; Clinical Competence ; Cross-Sectional Studies ; Female ; Humans ; Job Satisfaction ; Male ; Middle Aged ; Nursing Staff, Hospital/*psychology ; Prevalence ; Quality of Health Care ; Regression Analysis ; Telomere/*genetics ; Telomere Homeostasis ; Young Adult ; },
abstract = {BACKGROUND: Burnout is a work-related stress syndrome characterized by emotional exhaustion, depersonalization, and reduced personal accomplishment. Nurse burnout is related to nurses' deteriorating mental health and poorer patient care quality and thus, is a significant concern in healthcare. The Coronavirus Disease 2019 (COVID-19) pandemic has swept the world and distressed the healthcare systems. Because of the body's stress mechanism, it is vital to examine the current prevalence of nurse burnout and understand it at a biological level, using an epigenetic biomarker, telomere length.<br><br>PURPOSE: To determine the prevalence of burnout among nurses in the Peri-Operative and Labor &amp; Delivery settings pre and during the COVID-19 pandemic and to examine the effects of burnout on absolute telomere length.<br><br>METHODS: This is a cross-sectional study assessing the prevalence of nurses' burnout and the relationships between nurses' burnout and telomere length. Due to the COVID-19 pandemic, we had to stop the study during the mid of data collection. Even though the study was not designed to capture changes before and during the pandemic, we analyzed two groups' data before and during the pandemic. The study took place in a US hospital. Nurses in the hospital's Operating Room, Post-Anesthesia Care Unit, and Labor &amp; Delivery Unit participated in the study. Maslach Burnout Inventory survey and nurses' demographics were administered online. Telomere length was measured via finger-prick blood.<br><br>RESULTS: 146 nurses participated in the study, with 120 participants' blood samples collected. The high-level burnout rate was 70.5%. Correlation analysis did not reveal a direct correlation between nurse burnout and telomere length. However, in a multiple regression analysis, the final model contained the burnout subscale of emotional exhaustion, years as an RN, and work unit's nursing care quality. There was a low degree of departure from normality of the mean absolute telomere length in the pre-pandemic group and a substantial degree of departure in the during-pandemic group.<br><br>CONCLUSIONS: Nurse burnout is a prevalent phenomenon in healthcare, and this study indicates that nurses currently experience high levels of burnout. Nurses' cellular biomarker, telomere length, is shorter in the group of nurses during the COVID-19 pandemic than before. Appropriate measures should be implemented to decrease nurses' burnout symptoms and improve nurses' psychological and physical health. Nurses, especially those younger than 60, report higher burnout symptoms, particularly emotional exhaustion. This study indicates the need for intervention to promote nurses' health during the pandemic and beyond. If not appropriately managed, nurse burnout may continue to be a significant issue facing the healthcare system.},
}
@article {pmid35290636,
year = {2022},
author = {Barnes, RP and Thosar, SA and Fouquerel, E and Opresko, PL},
title = {Targeted Formation of 8-Oxoguanine in Telomeres.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2444},
number = {},
pages = {141-159},
pmid = {35290636},
issn = {1940-6029},
mesh = {Animals ; *DNA Damage ; Guanine/analogs &amp; derivatives/metabolism ; Mammals/genetics ; Oxidative Stress/genetics ; *Telomere/genetics/metabolism ; },
abstract = {Mammalian telomeres are guanine-rich sequences which cap the ends of linear chromosomes. While recognized as sites sensitive to oxidative stress, studies on the consequences of oxidative damage to telomeres have been primarily limited to experimental conditions which cause oxidative damage throughout the whole genome and cell. We developed a chemoptogenetic tool (FAP-mCER-TRF1) to specifically induce singlet oxygen at telomeres, resulting in the formation of the common oxidative lesion 8-oxo-guanine. Here, we describe this tool and detail how to generate cell lines which express FAP-mCER-TRF1 at telomeres and verify the formation of 8-oxo-guanine.},
}
@article {pmid35290406,
year = {2022},
author = {Shenouda, MM and Noyce, RS and Lee, SZ and Wang, JL and Lin, YC and Favis, NA and Desaulniers, MA and Evans, DH},
title = {The mismatched nucleotides encoded in vaccinia virus flip-and-flop hairpin telomeres serve an essential role in virion maturation.},
journal = {PLoS pathogens},
volume = {18},
number = {3},
pages = {e1010392},
pmid = {35290406},
issn = {1553-7374},
support = {PJT 159614//CIHR/Canada ; },
mesh = {Animals ; DNA ; Mice ; Mice, SCID ; *Nucleotides ; Telomere ; *Vaccinia virus/genetics ; Virion/genetics ; Virus Replication/genetics ; },
abstract = {Poxvirus genomes consist of a linear duplex DNA that ends in short inverted and complementary hairpin structures. These elements also encode loops and mismatches that likely serve a role in genome packaging and perhaps replication. We constructed mutant vaccinia viruses (VACV) where the native hairpins were replaced by altered forms and tested effects on replication, assembly, and virulence. Our studies showed that structure, not sequence, likely determines function as one can replace an Orthopoxvirus (VACV) hairpin with one copied from a Leporipoxvirus with no effect on growth. Some loops can be deleted from VACV hairpins with little effect, but VACV bearing too few mismatches grew poorly and we couldn't recover viruses lacking all mismatches. Further studies were conducted using a mutant bearing only one of six mismatches found in wild-type hairpins (SΔ1Δ3-6). This virus grew to ~20-fold lower titers, but neither DNA synthesis nor telomere resolution was affected. However, the mutant exhibited a particle-to-PFU ratio 10-20-fold higher than wild-type viruses and p4b/4b core protein processing was compromised, indicating an assembly defect. Electron microscopy showed that SΔ1Δ3-6 mutant development was blocked at the immature virus (IV) stage, which phenocopies known effects of I1L mutants. Competitive DNA binding assays showed that recombinant I1 protein had less affinity for the SΔ1Δ3-6 hairpin than the wild-type hairpin. The SΔ1Δ3-6 mutant was also attenuated when administered to SCID-NCR mice by tail scarification. Mice inoculated with viruses bearing wild-type hairpins exhibited a median survival of 30-37 days, while mice infected with SΔ1Δ3-6 virus survived >70 days. Persistent infections favor genetic reversion and genome sequencing detected one example where a small duplication near the hairpin tip likely created a new loop. These observations show that mismatches serve a critical role in genome packaging and provide new insights into how VACV "flip and flop" telomeres are arranged.},
}
@article {pmid35282254,
year = {2022},
author = {Méndez-Chacón, E},
title = {Gender Differences in Perceived Stress and Its Relationship to Telomere Length in Costa Rican Adults.},
journal = {Frontiers in psychology},
volume = {13},
number = {},
pages = {712660},
pmid = {35282254},
issn = {1664-1078},
support = {R01 AG031716/AG/NIA NIH HHS/United States ; },
abstract = {INTRODUCTION: Stress is associated with disease and reduced leukocyte telomere length (LTL). The objective of this research is to determine if self-perceived stress is associated with telomere length in Costa Rican adults and the gender differences in this association. Findings may help explain how some populations in apparent socioeconomic disadvantage and with limited access to specialized medical services have a remarkably high life expectancy.<br><br>METHODOLOGY: Data come from the pre-retirement cohort of the Costa Rican Longevity and Healthy Aging Study (CRELES), a population based survey conducted in the households to 2,327 adults aged 53 to 66 years. The DNA to measure LTL was extracted from blood cells in laboratories of the University of Costa Rica whereas the Blackburn laboratory at the University of California performed the telomere length measurement applying the quantitative polymerase chain reaction (Q-PCR). The relationship between telomere length and perceived stress was measured using least-squares multiple regression. Perceived stress was measured by a set of questions about family, job, finances and, health reasons to be stressed. Models included the control variables: (1) age and sex of the participant, (2) whether he or she resides in the Nicoya area, a "blue zone" known for its high longevity, and (3) the aforementioned sociodemographic, health and lifestyles characteristics.<br><br>RESULTS: Stress perception and LTL are significantly different by sex. Women perceived higher stress levels than men in almost all aspects studied, except work. Women have significantly longer telomeres. Shorter telomeres are significantly associated with caregiving stress in men and with parental health concerns in women. Counter-intuitive telomere lengthenings were observed among women who feel stressed about caring for family members; and among men who feel stressed due to their family relationships as well as concerns about their own health.<br><br>DISCUSSION: Results confirm that people with self-perceived stress due to caregiving or health issues have shorter telomeres. The relationship between stress and telomere length differs between men and women. Gender relations exert a strong modifier effect on the relationship between stress and LTL: gender is related to perceived stress, telomere length, and apparently also to the way stress and LTL are related.},
}
@article {pmid35279598,
year = {2022},
author = {Yuan, H and Wu, Y and Wang, J and Qin, X and Huang, Y and Yan, L and Fana, Y and Zedenius, J and Juhlin, CC and Larsson, C and Lui, WO and Xu, D},
title = {Synergistic effects of telomerase reverse transcriptase and regulator of telomere elongation helicase 1 on aggressiveness and outcomes in adrenocortical carcinoma.},
journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie},
volume = {149},
number = {},
pages = {112796},
doi = {10.1016/j.biopha.2022.112796},
pmid = {35279598},
issn = {1950-6007},
mesh = {*Adrenal Cortex Neoplasms/genetics ; *Adrenocortical Carcinoma/genetics ; Humans ; RNA, Messenger/genetics ; *Telomerase/genetics ; Telomere/genetics ; },
abstract = {Adrenocortical carcinoma (ACC) is one of the deadliest endocrine malignancies and telomere maintenance by activated telomerase is critically required for ACC development and progression. Because telomerase reverse transcriptase (TERT) and regulator of telomere elongation helicase 1 (RTEL1) play key roles in telomere homeostasis, we determined their effect on ACC pathogenesis and outcomes. Analyses of TCGA and GEO datasets showed significantly higher expression of RTEL1 but not TERT in ACC tumors, compared to their benign or normal counterparts. Furthermore, gains/amplifications of both TERT and RTEL1 genes were widespread in ACC tumors and their expression correlated with their gene copy numbers. Higher expression of either TERT or RTEL1 was associated with shorter overall and progression-free survival (OS and PFS) in the TCGA ACC patient cohort, and higher levels of both TERT and RTEL1 mRNA predicted the shortest patient OS and PFS. However, multivariate analyses showed that only RTEL1 independently predicted patient OS and PFS. Gene set enrichment analysis further showed enrichments of wnt/β-catenin, MYC, glycolysis, MTOR, and DNA repair signaling pathways in ACC tumors expressing high TERT and RTEL1 mRNA levels. Taken together, TERT and RTEL1 promote ACC aggressiveness synergistically and may serve as prognostic factors and therapeutic targets for ACC.},
}
@article {pmid35278080,
year = {2022},
author = {Chen, SS and Liao, XM and Wei, QZ and Zhou, YY and Su, MY and Hu, Y and Song, YY and Zhang, ZQ and Liang, JJ},
title = {Associations of the Gut Microbiota Composition and Fecal Short-Chain Fatty Acids with Leukocyte Telomere Length in Children Aged 6 to 9 Years in Guangzhou, China: A Cross-sectional Study.},
journal = {The Journal of nutrition},
volume = {152},
number = {6},
pages = {1549-1559},
doi = {10.1093/jn/nxac063},
pmid = {35278080},
issn = {1541-6100},
mesh = {Adult ; Child ; Cross-Sectional Studies ; Fatty Acids, Volatile/analysis ; Feces/chemistry ; *Gastrointestinal Microbiome/genetics ; Humans ; Leukocytes/chemistry ; RNA, Ribosomal, 16S/analysis/genetics ; Telomere ; Young Adult ; },
abstract = {BACKGROUND: Telomere length (TL) serves as a marker of cellular senescence and appears to plateau between the age of 4 y and young adulthood, after which the gut microbiota are supposed to be established. However, scarce data are available regarding the correlation between gut microbiota composition and TL in the pediatric population.<br><br>OBJECTIVES: We aimed to investigate whether the gut microbiota and the concentrations of SCFAs in feces are associated with leukocyte TL in children.<br><br>METHODS: In total, 401 children aged 6-9 y from Guangzhou were enrolled in this cross-sectional study. qPCR was used to determine relative TL in peripheral blood leukocytes. The gut microbiota was characterized by 16S ribosomal RNA amplicon sequencing and the fecal concentrations of total SCFAs and SCFA subtypes were determined using HPLC. The multivariate methods with an unbiased variable selection (MUVR) algorithm and partial least square models were used to select predictable operational taxonomic units (OTUs). Further correlation analyses were performed based on multiple linear regression models with adjustment for covariates and false discovery rate.<br><br>RESULTS: With the use of MUVR, 35 relevant and minimal optimal OTUs were finally selected. Multiple linear regression analysis showed that the abundance of several OTUs, including OTU334 (belonging to the genus Family XIII AD3011 group), OTU726 (belonging to the species Lachnoclostridium phocaeense), OTU1441 (belonging to the genus Ruminococcus torques group), OTU2553 (belonging to the genus Lachnospiraceae UCG-010), and OTU3375 (belonging to the family Lachnospiraceae), was negatively associated with leukocyte TL (&#x3b2;: -0.187 to -0.142; false discovery rate (FDR)-corrected P value (PFDR)&#xa0;=&#xa0;0.009-0.035]. However, neither SCFA subtype nor total SCFA content in feces exhibited significant associations with TL (&#x3b2;: -0.032 to 0.048; PFDR&#xa0;=&#xa0;0.915-0.969).<br><br>CONCLUSIONS: The gut microbiota, but not fecal SCFA concentration, was significantly associated with TL in this pediatric population.},
}
@article {pmid35274784,
year = {2022},
author = {Zhang, X and Shi, M and Zhao, X and Bin, E and Hu, Y and Tang, N and Dai, H and Wang, C},
title = {Telomere shortening impairs alveolar regeneration.},
journal = {Cell proliferation},
volume = {55},
number = {4},
pages = {e13211},
pmid = {35274784},
issn = {1365-2184},
support = {92068108//National Natural Science Foundation of China/ ; },
mesh = {Alveolar Epithelial Cells/metabolism ; Animals ; Cell Differentiation/physiology ; *Lung Injury/metabolism ; Mice ; Telomere/genetics ; Telomere Shortening ; },
abstract = {OBJECTIVES: Short telomeres in alveolar type 2 (AT2) cells have been associated with many lung diseases. The study aimed to investigate the regeneration capacity of AT2 cells with short telomeres by knocking out Tert in mice (G4 Tert[-/-]) from the whole to the cellular level.<br><br>MATERIALS AND METHODS: The lung injury model of mice was established by left pneumonectomy (PNX). The proliferation and differentiation of AT2 cells were observed by immunofluorescence staining in vivo and in vitro. The difference of the gene expression between control and G4 Tert[-/-] group during the regeneration of AT2 cells was compared by RNA sequencing. The expression of tubulin polymerization promoting protein 3 (TPPP3) was reduced by adeno-associated virus delivery.<br><br>RESULTS: The alveolar regeneration in G4 Tert[-/-] mice was impaired after PNX-induced lung injury. The regulation of cytoskeleton remodelling was defective in G4 Tert[-/-] AT2 cells. The expression of TPPP3 was gradually increased during AT2 cell differentiation. The expression level of TPPP3 was reduced in G4 Tert[-/-] AT2 cells. Reducing TPPP3 expression in AT2 cells limits the microtubule remodelling and differentiation of AT2 cells.<br><br>CONCLUSION: Short telomeres in AT2 cells result in the reduced expression level of TPPP3, leading to impaired regeneration capacity of AT2 cells.},
}
@article {pmid35273922,
year = {2022},
author = {Edwards-Smallbone, J and Jensen, AL and Roberts, LE and Totañes, FIG and Hart, SR and Merrick, CJ},
title = {Plasmodium falciparum GBP2 Is a Telomere-Associated Protein That Binds to G-Quadruplex DNA and RNA.},
journal = {Frontiers in cellular and infection microbiology},
volume = {12},
number = {},
pages = {782537},
pmid = {35273922},
issn = {2235-2988},
support = {MR/P010873/2/MRC_/Medical Research Council/United Kingdom ; BB/K009206/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/L008823/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {DNA/metabolism ; *G-Quadruplexes ; Plasmodium falciparum/genetics ; RNA ; Telomere/metabolism ; },
abstract = {In the early-diverging protozoan parasite Plasmodium, few telomere-binding proteins have been identified and several are unique. Plasmodium telomeres, like those of most eukaryotes, contain guanine-rich repeats that can form G-quadruplex structures. In model systems, quadruplex-binding drugs can disrupt telomere maintenance and some quadruplex-binding drugs are potent anti-plasmodial agents. Therefore, telomere-interacting and quadruplex-interacting proteins may offer new targets for anti-malarial therapy. Here, we report that P. falciparum GBP2 is such a protein. It was identified via 'Proteomics of Isolated Chromatin fragments', applied here for the first time in Plasmodium. In vitro, PfGBP2 binds specifically to G-rich telomere repeats in quadruplex form and it can also bind to G-rich RNA. In vivo, PfGBP2 partially colocalises with the known telomeric protein HP1 but is also found in the cytoplasm, probably due to its affinity for RNA. Consistently, its interactome includes numerous RNA-associated proteins. PfGBP2 is evidently a multifunctional DNA/RNA-binding factor in Plasmodium.},
}
@article {pmid35272158,
year = {2022},
author = {Li, P and Wang, ZY and Yueying Li, and Liu, LZ and Qiu, JG and Zhang, CY},
title = {Bsu polymerase-mediated fluorescence coding for rapid and sensitive detection of 8-oxo-7,8-dihydroguanine in telomeres of cancer cells.},
journal = {Talanta},
volume = {243},
number = {},
pages = {123340},
doi = {10.1016/j.talanta.2022.123340},
pmid = {35272158},
issn = {1873-3573},
mesh = {DNA Damage ; Fluorescence ; Guanine/analogs &amp; derivatives ; HeLa Cells ; Humans ; *Hydrogen Peroxide ; *Neoplasms/diagnosis/genetics ; Oxidation-Reduction ; Telomere/genetics ; },
abstract = {Guanine is the most susceptible to oxidation among all the DNA bases, and 8-oxo-7,8-dihydroguanine (OG) is one of main oxidation products that can occur in any part of chromosomal DNA. OG in the telomere sequence is associated with telomere shortening, cell aging, and dysfunction, and it may induce cancers. The accurate detection of OG in telomeres is important to early clinical diagnosis and molecular research. Herein, we develop a simple and rapid method to sensitively measure 8-oxo-7,8-dihydroguanine (OG) in telomeres of cancer cells by using Bsu polymerase-mediated fluorescence coding. This method is very simple without the requirement for any nucleic acid amplification or specific restriction enzyme recognition reaction, and Bsu polymerase can selectively incorporate Cy5-dATP into the opposite site of OG, endowing this method with good specificity. Moreover, the introduction of single-molecule detection significantly improves the sensitivity. This method can detect OG within 70 min with a limit of detection (LOD) of 2.45 × 10[-18] M, and it can detect OG in genomic DNA extracted from H2O2-treated HeLa cells with a LOD of 0.0094 ng, holding great potential in disease-specific gene damage research and early clinic diagnosis.},
}
@article {pmid35265860,
year = {2022},
author = {Lu, R and Allen, JAM and Galaviz, P and Pickett, HA},
title = {A DNA-fiber protocol for single molecule analysis of telomere (SMAT) length and extension events in cancer cells.},
journal = {STAR protocols},
volume = {3},
number = {1},
pages = {101212},
pmid = {35265860},
issn = {2666-1667},
mesh = {DNA/genetics ; In Situ Hybridization, Fluorescence/methods ; *Neoplasms/genetics ; *Single Molecule Imaging ; Telomere/genetics ; Telomere Homeostasis/genetics ; },
abstract = {Alternative lengthening of telomeres (ALT) is a homologous recombination-based telomere maintenance mechanism. It is active in approximately 10-15% of cancers. We present a DNA-fiber protocol, combining YOYO-1 staining of genomic DNA, telomere fluorescence in situ hybridization (FISH), and EdU labeling of nascent DNA, to measure telomere extension events in ALT cancer cells. The protocol can be used to delineate ALT-mediated telomere extension. For complete details on the use and execution of this protocol, please refer to Barroso-Gonzalez et al. (2021).},
}
@article {pmid35260310,
year = {2022},
author = {Vecoli, C and Basta, G and Borghini, A and Gaggini, M and Del Turco, S and Mercuri, A and Gastaldelli, A and Andreassi, MG},
title = {Advanced glycation end products, leukocyte telomere length, and mitochondrial DNA copy number in patients with coronary artery disease and alterations of glucose homeostasis: From the GENOCOR study.},
journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD},
volume = {32},
number = {5},
pages = {1236-1244},
doi = {10.1016/j.numecd.2022.01.021},
pmid = {35260310},
issn = {1590-3729},
mesh = {Biomarkers ; Blood Glucose ; *Coronary Artery Disease/diagnosis/genetics ; DNA Copy Number Variations ; DNA, Mitochondrial/genetics ; *Diabetes Mellitus, Type 2 ; Glycation End Products, Advanced ; Homeostasis ; Humans ; Leukocytes ; Receptor for Advanced Glycation End Products/genetics ; Telomere/genetics ; },
abstract = {BACKGROUND AND AIM: Alterations of glucose homeostasis can increase advanced glycation end products (AGEs) that exacerbate vascular inflammatory disease and may increase vascular senescence and aging. This study examined the relationships between carboxymethyl-lysine (CML) and soluble receptor for AGEs (sRAGE) with leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn), as cell aging biomarkers, in patients with established coronary artery disease (CAD).<br><br>METHODS AND RESULTS: We studied 459 patients with CAD further categorized as having normal glucose homeostasis (NG, n&#xa0;=&#xa0;253), pre-diabetes (preT2D, n&#xa0;=&#xa0;85), or diabetes (T2D, n&#xa0;=&#xa0;121). All patients were followed up for the occurrence of major adverse cardiovascular events (MACEs). Plasma concentrations of sRAGE and CML were measured by ELISA. mtDNAcn and LTL were measured by qRT-PCR. CML levels were significantly higher in patients with preT2D (p&#xa0;<&#xa0;0.007) or T2D (p&#xa0;<&#xa0;0.003) compared with those with NG. mtDNAcn resulted lower in T2D vs preT2D (p&#xa0;=&#xa0;0.04). At multivariate Cox proportional hazard analysis, short LTL (HR: 2.89; 95% CI: 1.11-10.1; p&#xa0;=&#xa0;0.04) and high levels of sRAGE (HR: 2.20; 95% CI: 1.01-5.14; p&#xa0;=&#xa0;0.04) were associated with an increased risk for MACEs in patients with preT2D and T2D, respectively. T2D patients with both short LTL and high sRAGE levels had the highest risk of MACEs (HR: 3.11; 95% CI: 1.11-9.92; p&#xa0;=&#xa0;0.04).<br><br>CONCLUSIONS: High levels of sRAGE and short LTL were associated with an increased risk of MACEs, especially in patients with diabetes, supporting the usefulness of both biomarkers of glycemic impairment and aging in predicting cardiovascular outcomes in patients with CAD.},
}
@article {pmid35259951,
year = {2022},
author = {Lu, R and Pickett, HA},
title = {Telomeric replication stress: the beginning and the end for alternative lengthening of telomeres cancers.},
journal = {Open biology},
volume = {12},
number = {3},
pages = {220011},
pmid = {35259951},
issn = {2046-2441},
mesh = {DNA Repair ; DNA Replication ; Humans ; *Neoplasms/genetics ; Telomere/genetics ; *Telomere Homeostasis ; },
abstract = {Telomeres are nucleoprotein structures that cap the ends of linear chromosomes. Telomeric DNA comprises terminal tracts of G-rich tandem repeats, which are inherently difficult for the replication machinery to navigate. Structural aberrations that promote activation of the alternative lengthening of telomeres (ALT) pathway of telomere maintenance exacerbate replication stress at ALT telomeres, driving fork stalling and fork collapse. This form of telomeric DNA damage perpetuates recombination-mediated repair pathways and break-induced telomere synthesis. The relationship between replication stress and DNA repair is tightly coordinated for the purpose of regulating telomere length in ALT cells, but has been shown to be experimentally manipulatable. This raises the intriguing possibility that induction of replication stress can be used as a means to cause toxic levels of DNA damage at ALT telomeres, thereby selectively disrupting the viability of ALT cancers.},
}
@article {pmid35254177,
year = {2022},
author = {Tajada, M and Dieste-Pérez, P and Sanz-Arenal, A and Pérez-Roncero, G and López-Baena, MT and Pérez-López, FR},
title = {Leukocyte telomere length in women with and without polycystic ovary syndrome: a systematic review and meta-analysis.},
journal = {Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology},
volume = {38},
number = {5},
pages = {391-397},
doi = {10.1080/09513590.2022.2047922},
pmid = {35254177},
issn = {1473-0766},
mesh = {Body Mass Index ; Female ; Humans ; Leukocytes/metabolism ; *Polycystic Ovary Syndrome/metabolism ; Telomere/metabolism ; Testosterone ; },
abstract = {AIM: To study the telomere length and the telomerase activity in women with and without polycystic ovary syndrome (PCOS).<br><br>METHODS: Relevant studies were searched from PubMed, Embase, and LILACS online databases and manual screening. The mean differences (MDs) or standardized MDs (SMDs) with their 95% confidence intervals (CIs) were calculated. The methodological quality of included studies was evaluated with the Newcastle-Ottawa Scale (NOS), and heterogeneity with the I[2] and Tau[2] statistics.<br><br>RESULTS: Six studies including 2109 non-pregnant women with (n&#x2009;=&#x2009;1155) or without (n&#x2009;=&#x2009;954) PCOS assessed leukocyte telomere length. There was a non-significant leukocyte telomere length difference (SMD = 0.25, 95% CI: -0.01, 0.51, p&#x2009;=&#x2009;.06, I[2] = 81%, Tau[2] = 0.08) comparing PCOS patients with the control group. Studied PCOS women were younger (MD&#x2009;=&#x2009;-1.39, 95% CI: -2.47, -0.31&#x2009;years, I[2] = 83%), and had higher body mass index (BMI; MD = 3.66, 95% CI: 2.11, 5.20&#x2009;kg/m[2], I[2] = 94%). There were significantly higher testosterone (SMD = 0.88, 95% CI: 0.65, 1.10) and luteinizing hormone levels (SMD = 0.60, 95% CI: 0.12, 1.08) in women with PCOS as compared to controls. There was a low risk of bias and there were not sufficient studies to meta-analyze other cell types.<br><br>CONCLUSIONS: Leukocyte telomere length did not differ between women with and without PCOS. Further studies with large sample sizes and including other outcomes are warranted to further substantiate the reported evidence.},
}
@article {pmid35253187,
year = {2022},
author = {Liu, XG and Li, M and Mai, SJ and Cai, RJ},
title = {Telomere length-related signature as a novel biomarker of prognosis and immune response in non-small cell lung cancer.},
journal = {European review for medical and pharmacological sciences},
volume = {26},
number = {4},
pages = {1304-1319},
doi = {10.26355/eurrev_202202_28124},
pmid = {35253187},
issn = {2284-0729},
mesh = {Biomarkers, Tumor/genetics ; *Carcinoma, Non-Small-Cell Lung/diagnosis/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Immunity ; *Lung Neoplasms/diagnosis/genetics ; Prognosis ; Telomere/genetics ; },
abstract = {OBJECTIVE: Telomere length-related genes (TLRGs) play an important role in multiple tumors; however, there is a lack of systematic reporting about their relevance in non-small cell lung cancer (NSCLC). This study investigated the relation between TLRG gene expression and the immunotherapeutic response of patients with NSCLC.<br><br>MATERIALS AND METHODS: Differentially expressed TLRGs in tumor tissues and normal tissues were screened using Gene Expression Omnibus (GEO) datasets. A univariate Cox regression analysis was performed to identify the optimal prognosis-related genes. A prognostic risk model was constructed by using least absolute shrinkage, selection operator, and multivariate Cox regression analysis results. The model was then evaluated by a Kaplan-Meier analysis, functional enrichment annotation, and a receiver operating characteristic curve analysis; after which, it was validated in the TCGA dataset. The model was used to predict immunotherapeutic response and drug sensitivity.<br><br>RESULTS: An 18-gene prognostic signature was developed and used to stratify NSCLC patients into a low- or high-risk group in GEO cohorts. Patients in the low-risk group had better survival possibilities than those in the high-risk group, and showed significantly higher overall survival times in the TCGA cohort. The risk score was identified as an independent prognostic factor, when compared with other clinical factors. ssGSEA scores showed that the risk model was mainly linked to cancer- and immune-related pathways. Importantly, the candidate risk model was linked to tumor immunity and predicted a patient's response to PDL-1 blockade immune therapy. Several potential drugs that might target this model were identified.<br><br>CONCLUSIONS: This study provides broad molecular signatures that can be used in further functional and therapeutic studies of the telomere system, and also represents an integrated approach for characterizing key protein complexes when creating a prognosis and identifying new targets for cancer immunotherapy.},
}
@article {pmid35247880,
year = {2022},
author = {Rybicki, BA and Sadasivan, SM and Chen, Y and Loveless, I and Gupta, NS and Chitale, DA and Williamson, SR and Rundle, AG and Tang, DL},
title = {Race Differences in Telomere Length in Benign Prostate Biopsies and Subsequent Risk of Prostate Cancer.},
journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {31},
number = {5},
pages = {991-998},
pmid = {35247880},
issn = {1538-7755},
support = {R01 ES011126/ES/NIEHS NIH HHS/United States ; },
mesh = {Biopsy ; Case-Control Studies ; Humans ; Leukocytes ; Male ; *Prostate ; *Prostatic Neoplasms/genetics ; Race Factors ; Risk Factors ; Telomere/genetics ; },
abstract = {BACKGROUND: Telomere shortening is linked to aging and may be associated with increased risk for cancer. Most cancer studies have used telomere length in leukocytes rather than in the target tissue of cancer origin.<br><br>METHODS: A case-control study of 524 case-control pairs with a benign prostate biopsy nested within a historical cohort of 10,478 men was conducted to determine whether premalignant prostate telomere length (assessed using a modified qRT-PCR) is associated with prostate cancer risk.<br><br>RESULTS: Telomere lengths in benign prostate biopsies of cases versus controls were similar (1.46 &#xb1; 0.38 vs. 1.45 &#xb1; 0.42; P = 0.49). African American (AA) men had significantly shorter telomeres compared with White men (1.51 &#xb1; 0.38 vs. 1.63 &#xb1; 0.39; P < 0.0001). In race-stratified analyses, increasing telomere length was more strongly associated with prostate cancer risk in White men, wherein those with telomere length in the highest quartile had 1.9-fold greater adjusted risk of prostate cancer compared with men with prostate telomere lengths in the lowest quartile [OR = 1.90; 95% confidence interval (CI) = 1.08-3.36]. Men in the highest telomere length quartile also had a greater risk of aggressive prostate cancer compared with men with telomere lengths in the lowest quartile (OR = 2.78; 95% CI = 1.25-6.19).<br><br>CONCLUSIONS: White men have longer telomeres in benign prostate tissue compared with AA men, and those with the longest telomeres may be at increased risk for prostate cancer, particularly the more aggressive form of the disease.<br><br>IMPACT: Race-specific telomere length measures may be an early biomarker of aggressive prostate cancer.},
}
@article {pmid35246468,
year = {2022},
author = {Huda, N and Kusumanchi, P and Perez, K and Jiang, Y and Skill, NJ and Sun, Z and Ma, J and Yang, Z and Liangpunsakul, S},
title = {Telomere length in patients with alcohol-associated liver disease: a brief report.},
journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research},
volume = {70},
number = {6},
pages = {1438-1441},
pmid = {35246468},
issn = {1708-8267},
support = {UH2 AA026903/AA/NIAAA NIH HHS/United States ; R01 AA025208/AA/NIAAA NIH HHS/United States ; I01 CX000361/CX/CSRD VA/United States ; U01 AA026917/AA/NIAAA NIH HHS/United States ; K01 AA026385/AA/NIAAA NIH HHS/United States ; R24 AA025017/AA/NIAAA NIH HHS/United States ; UH3 AA026903/AA/NIAAA NIH HHS/United States ; },
mesh = {*Hepatitis, Alcoholic ; Humans ; Liver Cirrhosis, Alcoholic/genetics ; *Liver Diseases, Alcoholic/genetics ; *Telomerase/genetics/metabolism ; Telomere/metabolism ; Telomere Shortening ; },
abstract = {The intact telomere structure is essential for the prevention of the chromosome end-to-end fusions and maintaining genomic integrity. The maintenance of telomere length is critical for cellular homeostasis. The shortening of telomeres has been reported in patients with chronic liver diseases. The telomere length has not been systemically studied in patients with alcohol-associated liver disease (ALD) at different stages, such as alcoholic hepatitis and alcoholic cirrhosis. In this brief report, we observed evidence of telomere shortening without changes in the telomerase activity in the liver of patients with alcoholic hepatitis and alcoholic cirrhosis when compared with controls. The alterations in the genes associated with telomere binding proteins were only observed in patients with alcoholic cirrhosis. Future studies are required to determine the mechanism of how alcohol affects the length of the telomere and if the shortening impacts the disease progression in ALD.},
}
@article {pmid35246364,
year = {2022},
author = {Schürhoff, F and Corfdir, C and Pignon, B and Lajnef, M and Richard, JR and Marcos, E and Leboyer, M and Adnot, S and Jamain, S and Szöke, A},
title = {Shortening telomere is associated with psychotic dimensions in the general population.},
journal = {Schizophrenia research},
volume = {243},
number = {},
pages = {470-471},
doi = {10.1016/j.schres.2022.02.030},
pmid = {35246364},
issn = {1573-2509},
mesh = {Humans ; *Mental Disorders ; *Telomere/genetics ; Telomere Shortening ; },
}
@article {pmid35244708,
year = {2022},
author = {Goumy, C and Veronese, L and Stamm, R and Domas, Q and Hadjab, K and Gallot, D and Laurichesse, H and Delabaere, A and Gouas, L and Salaun, G and Perbel-Richard, C and Vago, P and Tchirkov, A},
title = {Reduced telomere length in amniocytes: an early biomarker of abnormal fetal development?.},
journal = {Human molecular genetics},
volume = {31},
number = {16},
pages = {2669-2677},
doi = {10.1093/hmg/ddac054},
pmid = {35244708},
issn = {1460-2083},
mesh = {Biomarkers ; Female ; *Fetal Development ; Fetal Growth Retardation/diagnosis/genetics ; Humans ; Pregnancy ; Telomere/genetics ; *Telomere Shortening/genetics ; },
abstract = {Telomeres protect chromosome ends and control cell division and senescence. During organogenesis, telomeres need to be long enough to ensure the cell proliferation necessary at this stage of development. Previous studies have shown that telomere shortening is associated with growth retardation and congenital malformations. However, these studies were performed in newborns or postnatally, and data on telomere length (TL) during the prenatal period are still very limited. We measured TL using quantitative PCR in amniotic fluid (AF) and chorionic villi (CV) samples from 69 control fetuses with normal ultrasound (52 AF and 17 CV) and 213 fetuses (165 AF and 48 CV) with intrauterine growth retardation (IUGR) or congenital malformations diagnosed by ultrasound. The samples were collected by amniocentesis at the gestational age (GA) of 25.0 ± 5.4 weeks and by CV biopsy at 18.1 ± 6.3 weeks. In neither sample type was TL influenced by GA or fetal sex. In AF, a comparison of abnormal versus normal fetuses showed a significant telomere shortening in cases of IUGR (reduction of 34%, P < 10-6), single (29%, P < 10-6) and multiple (44%, P < 10-6) malformations. Similar TL shortening was also observed in CV from abnormal fetuses but to a lesser extent (25%, P = 0.0002; 18%, P = 0.016; 20%, P = 0.004, respectively). Telomere shortening was more pronounced in cases of multiple congenital anomalies than in fetuses with a single malformation, suggesting a correlation between TL and the severity of fetal phenotype. Thus, TL measurement in fetal samples during pregnancy could provide a novel predictive marker of pathological development.},
}
@article {pmid35243342,
year = {2022},
author = {Machan, M and Tabor, JB and Wang, M and Sutter, B and Wiley, JP and Mychasiuk, R and Debert, CT},
title = {The Impact of Concussion, Sport, and Time in Season on Saliva Telomere Length in Healthy Athletes.},
journal = {Frontiers in sports and active living},
volume = {4},
number = {},
pages = {816607},
pmid = {35243342},
issn = {2624-9367},
abstract = {To date, sport-related concussion diagnosis and management is primarily based on subjective clinical tests in the absence of validated biomarkers. A major obstacle to clinical validation and application is a lack of studies exploring potential biomarkers in non-injured populations. This cross-sectional study examined the associations between saliva telomere length (TL) and multiple confounding variables in a healthy university athlete population. One hundred eighty-three (108 male and 75 female) uninjured varsity athletes were recruited to the study and provided saliva samples at either pre- or mid-season, for TL analysis. Multiple linear regression was used to determine the associations between saliva TL and history of concussion, sport contact type, time in season (pre vs. mid-season collection), age, and sex. Results showed no significant associations between TL and history of concussion, age, or sport contact type. However, TL from samples collected mid-season were longer than those collected pre-season [β = 231.4, 95% CI (61.9, 401.0), p = 0.008], and males had longer TL than females [β = 284.8, 95% CI (111.5, 458.2), p = 0.001] when adjusting for all other variables in the model. These findings population suggest that multiple variables may influence TL. Future studies should consider these confounders when evaluating saliva TL as a plausible fluid biomarker for SRC.},
}
@article {pmid35240880,
year = {2023},
author = {Siwik, CJ and Cash, E and Sephton, SE},
title = {Depressive symptoms and shorter survival in lung cancer: the role of leukocyte telomere length.},
journal = {Psychology &amp; health},
volume = {38},
number = {12},
pages = {1649-1664},
pmid = {35240880},
issn = {1476-8321},
support = {L30 AT011624/AT/NCCIH NIH HHS/United States ; T32 AT003997/AT/NCCIH NIH HHS/United States ; },
abstract = {OBJECTIVE: To examine the association between depressive symptoms, leukocyte telomere length-a marker of cellular ageing, and survival amongst lung cancer patients.<br><br>DESIGN: Patients with non-small cell lung cancer were recruited from a university-affiliated cancer center clinic.<br><br>MAIN OUTCOME: Patients (N&#x2009;=&#x2009;67) reported on depressive symptoms and provided a blood sample for leukocyte telomere length assessment at baseline and at a 3-month follow-up. Survival status was tracked over 3&#xa0;years.<br><br>RESULTS: Age at diagnosis and depressive symptoms, as measured by the CES-D, were associated with shorter leukocyte telomere length (p < .05), although only age at diagnosis contributed statistical significance to the model. Depressive symptoms predicted shorter survival from date of diagnosis (p < .01). Patients who reported experiencing clinically meaningful levels of depressive symptoms (CES-D scores &#x2265; 16) demonstrated shorter survival than those who reported sub-clinical levels of depressive symptoms (p < .05). Leukocyte telomere length did not emerge as a predictor of shorter survival.<br><br>CONCLUSION: Clinically meaningful levels of depressive symptoms are associated with shorter survival amongst lung cancer patients. These findings support the on-going efforts to screen all cancer patients for low mood and to investigate mechanisms linking depressive symptoms and shorter survival in cancer contexts.},
}
@article {pmid35234973,
year = {2021},
author = {Osnato, M},
title = {Searching for the link between telomere length and life history traits in plants.},
journal = {The Plant cell},
volume = {33},
number = {4},
pages = {1087-1088},
pmid = {35234973},
issn = {1532-298X},
mesh = {*Life History Traits ; Telomere/genetics ; Telomere Homeostasis ; },
}
@article {pmid35228641,
year = {2022},
author = {Ngwa, NE and Matsha, TE and Lombard, C and Levitt, N and Sobngwi, E and Kengne, AP and Peer, N},
title = {Cardiometabolic profile and leukocyte telomere length in a Black South African population.},
journal = {Scientific reports},
volume = {12},
number = {1},
pages = {3323},
pmid = {35228641},
issn = {2045-2322},
mesh = {Cholesterol, LDL ; Cross-Sectional Studies ; Female ; Humans ; *Hypertension/epidemiology/genetics ; *Leukocytes ; Male ; South Africa/epidemiology ; Telomere/genetics ; },
abstract = {Several studies have reported a possible association between leucocyte telomere length (LTL) and cardio-metabolic diseases (CMDs). However, studies investigating such association are lacking in South Africa despite having a very high prevalence of CMDs. We investigated the association between LTL and CMD risk profile in a black South African population. This was a cross-sectional study with participants > 21 years of age and residing in five townships in Cape Town. CMD markers were compared between men and women and across quartiles of LTL. Linear and logistic regressions relate increasing quartile and Log10LTL with CMD risk profile, with appropriate adjustment. Among 676-participants, diabetes, obesity and hypertension prevalence were 11.5%, 23.1% and 47.5%. Waist-circumference, hip-circumference and highly sensitive c-reactive protein values were significantly higher in women (all p < 0.001), while HDL-C (p = 0.023), creatinine (p = 0.005) and gamma glutamyl transferase (p < 0.001) values were higher in men. In age, sex and BMI adjusted linear regression model, Log10 of LTL was associated with low HDL-C (beta = 0.221; p = 0.041) while logistic regression showed a significant association between Log10LTL and prevalent dyslipidaemia characterised by high LDL-C. In this population, the relationship between LTL and CMD is weak given its association with only HDL-C and LDL-C.},
}
@article {pmid35227290,
year = {2022},
author = {Sharaf, R and Montesion, M and Hopkins, JF and Song, J and Frampton, GM and Albacker, LA},
title = {A pan-cancer landscape of telomeric content shows that RAD21 and HGF alterations are associated with longer telomeres.},
journal = {Genome medicine},
volume = {14},
number = {1},
pages = {25},
pmid = {35227290},
issn = {1756-994X},
mesh = {Cell Cycle Proteins/genetics ; DNA-Binding Proteins/genetics ; Hepatocyte Growth Factor/genetics/metabolism ; Humans ; *Neoplasms/genetics ; *Telomerase/genetics ; Telomere/genetics ; Telomere Homeostasis ; X-linked Nuclear Protein/genetics ; },
abstract = {BACKGROUND: Cancer cells can proliferate indefinitely through telomere maintenance mechanisms. These mechanisms include telomerase-dependent elongation, mediated by TERT activation, and alternative lengthening of telomeres (ALT), linked to loss of ATRX or DAXX.<br><br>METHODS: We analyzed the telomeric content of 89,959 tumor samples within the Foundation Medicine dataset and investigated the genomic determinants of high telomeric content, linking them to clinical outcomes, when available.<br><br>RESULTS: Telomeric content varied widely by disease type with leiomyosarcoma having the highest and Merkel cell carcinoma having the lowest telomeric content. In agreement with previous studies, telomeric content was significantly higher in samples with alterations in TERC, ATRX, and DAXX. We further identified that amplifications in two genes, RAD21 and HGF, were enriched in samples with high telomeric content, which was confirmed using the PCAWG/ICGC dataset. We identified the minimal amplified region associated with high telomeric content for RAD21 (8q23.1-8q24.12), which excludes MYC, and for HGF (7q21.11). Our results demonstrated that RAD21 and HGF exerted an additive telomere lengthening effect on samples with existing alterations in canonical genes previously associated with telomere elongation. Furthermore, patients with breast cancer who harbor RAD21 alterations had poor median overall survival and trended towards higher levels of Ki-67 staining.<br><br>CONCLUSIONS: This study highlights the importance of the role played by RAD21 (8q23.1-8q24.12) and HGF (7q21.11) in the lengthening of telomeres, supporting unlimited replication in tumors. These findings open avenues for work aimed at targeting this crucial pathway in tumorigenesis.},
}
@article {pmid35226812,
year = {2022},
author = {Fletcher, K and Shin, OH and Clark, KJ and Feng, C and Putman, AI and Correll, JC and Klosterman, SJ and Van Deynze, A and Michelmore, RW},
title = {Ancestral Chromosomes for Family Peronosporaceae Inferred from a Telomere-to-Telomere Genome Assembly of Peronospora effusa.},
journal = {Molecular plant-microbe interactions : MPMI},
volume = {35},
number = {6},
pages = {450-463},
doi = {10.1094/MPMI-09-21-0227-R},
pmid = {35226812},
issn = {0894-0282},
mesh = {*Oomycetes/genetics ; *Peronospora/genetics ; Plant Diseases/microbiology ; Spinacia oleracea ; Telomere/genetics ; },
abstract = {Downy mildew disease of spinach, caused by the oomycete Peronospora effusa, causes major losses to spinach production. In this study, the 17 chromosomes of P. effusa were assembled telomere-to-telomere, using Pacific Biosciences high-fidelity reads. Of these, 16 chromosomes are complete and gapless; chromosome 15 contains one gap bridging the nucleolus organizer region. This is the first telomere-to-telomere genome assembly for an oomycete. Putative centromeric regions were identified on all chromosomes. This new assembly enables a reevaluation of the genomic composition of Peronospora spp.; the assembly was almost double the size and contained more repeat sequences than previously reported for any Peronospora species. Genome fragments consistently underrepresented in six previously reported assemblies of P. effusa typically encoded repeats. Some genes annotated as encoding effectors were organized into multigene clusters on several chromosomes. Putative effectors were annotated on 16 of the 17 chromosomes. The intergenic distances between annotated genes were consistent with compartmentalization of the genome into gene-dense and gene-sparse regions. Genes encoding putative effectors were enriched in gene-sparse regions. The near-gapless assembly revealed apparent horizontal gene transfer from Ascomycete fungi. Gene order was highly conserved between P. effusa and the genetically oriented assembly of the oomycete Bremia lactucae; high levels of synteny were also detected with Phytophthora sojae. Extensive synteny between phylogenetically distant species suggests that many other oomycete species may have similar chromosome organization. Therefore, this assembly provides the foundation for genomic analyses of diverse oomycetes.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.},
}
@article {pmid35222015,
year = {2021},
author = {Xu, X and Chen, Z and Wu, W and Tian, X},
title = {Polyadenylated Telomeric Noncoding RNA Functions as a Pivotal Therapeutic Target of Anti-Ageing to Stabilize Telomere Length of Chromosomes Via Collaborating With Zscan4c.},
journal = {Frontiers in pharmacology},
volume = {12},
number = {},
pages = {822779},
pmid = {35222015},
issn = {1663-9812},
abstract = {Telomeres are closely associated with the development of cell aging. Shortening or erosion of telomeres will cause cell mortality, suggesting that the maintenance of telomere integrity facilitates cell anti-senescence. However, the mechanism of how to keep the telomere length remains fragmentary. Here, we found that polyadenylated telomeric noncoding RNA (TERRA) can promote the self-renewal when overexpressed in mouse embryonic stem cells (mESCs), implying that TERRA with polyadenylation is critical for mESC maintenance. Further studies revealed that TERRA with a polyadenylated tail plays an important role in the sustenance of telomere length. High-throughput sequencing and quantitative real-time PCR show that zinc finger and SCAN domain containing 4C (Zscan4c) may be a potential target of TERRA. Zscan4c is negatively regulated by TERRA and collaborates with TERRA to stabilize the telomere length of chromosomes in mESCs. Our study not only identifies TERRA as a potential novel factor of telomere length regulation and uncovers the new molecular mechanism of cell anti-aging, but also indicates that Zscan4c could be a key therapeutic target candidate for therapy in dysfunctional chromosome diseases. These data will expand our understanding of the cell fate regulatory network and will be beneficial to drug discovery and theragnostics for antiaging and anticancer therapy in the future.},
}
@article {pmid35221117,
year = {2022},
author = {Ningarhari, M and Caruso, S and Hirsch, TZ and Bayard, Q and Franconi, A and Védie, AL and Noblet, B and Blanc, JF and Amaddeo, G and Ganne, N and Ziol, M and Paradis, V and Guettier, C and Calderaro, J and Morcrette, G and Kim, Y and MacLeod, AR and Nault, JC and Rebouissou, S and Zucman-Rossi, J},
title = {Corrigendum to: 'Telomere length is key to hepatocellular carcinoma diversity and telomerase addiction is an actionable therapeutic target' [J Hepatol 2021 (74) 1155-1166].},
journal = {Journal of hepatology},
volume = {76},
number = {5},
pages = {1242-1243},
doi = {10.1016/j.jhep.2022.01.019},
pmid = {35221117},
issn = {1600-0641},
}
@article {pmid35220523,
year = {2023},
author = {Panahi, Y and Salasar Moghaddam, F and Babaei, K and Eftekhar, M and Shervin Badv, R and Eskandari, MR and Vafaee-Shahi, M and Pezeshk, H and Pedram, M},
title = {Sexual Dimorphism in Telomere Length in Childhood Autism.},
journal = {Journal of autism and developmental disorders},
volume = {53},
number = {5},
pages = {2050-2061},
pmid = {35220523},
issn = {1573-3432},
support = {A-12-534/1-4//Zanjan University of Medical Sciences/ ; A-12-534/6-8//Zanjan University of Medical Sciences/ ; },
mesh = {Child ; Humans ; Male ; Female ; *Autistic Disorder/genetics ; *Autism Spectrum Disorder/genetics ; Sex Characteristics ; Biomarkers ; Telomere ; },
abstract = {Autism spectrum disorders (ASD) are strikingly more prevalent in males, but the molecular mechanisms responsible for ASD sex-differential risk are poorly understood. Abnormally shorter telomeres have been associated with autism. Examination of relative telomere lengths (RTL) among non-syndromic male (N = 14) and female (N = 10) children with autism revealed that only autistic male children had significantly shorter RTL than typically-developing controls (N = 24) and paired siblings (N = 10). While average RTL of autistic girls did not differ significantly from controls, it was substantially longer than autistic boys. Our findings indicate a sexually-dimorphic pattern of RTL in childhood autism and could have important implications for RTL as a potential biomarker and the role/s of telomeres in the molecular mechanisms responsible for ASD sex-biased prevalence and etiology.},
}
@article {pmid35220278,
year = {2022},
author = {Semeraro, MD and Almer, G and Renner, W and Gruber, HJ and Herrmann, M},
title = {Telomere length in leucocytes and solid tissues of young and aged rats.},
journal = {Aging},
volume = {14},
number = {4},
pages = {1713-1728},
pmid = {35220278},
issn = {1945-4589},
mesh = {Animals ; *Leukocytes, Mononuclear/metabolism ; RNA, Messenger/genetics ; Rats ; Rats, Sprague-Dawley ; *Telomerase/genetics/metabolism ; Telomere/metabolism ; },
abstract = {BACKGROUND: Telomeres are protective nucleoprotein structures at the end of chromosomes that shorten with age. Telomere length (TL) in peripheral blood mononuclear cells (PBMCs) has been proposed as surrogate marker for TL in the entire organism. Solid evidence that supports this concept is lacking.<br><br>METHODS: Relative TL (RTL) was measured in PBMCS and multiple solid tissues from 24 young (4 months) and 24 aged (14 months) Sprague-Dawley (SD) rats. The mRNA expression of telomerase (TERT) and shelterin proteins TERF-1 and TERF-2 was also measured.<br><br>RESULTS: Mean RTL in PBMCs and solid tissues of young rats ranged from 0.64 &#xb1; 0.26 in large intestine to 1.07 &#xb1; 0.22 in skeletal muscle. RTL in PBMCs correlated with that in kidney (r = 0.315, p = 0.008), skeletal muscle (r = 0.276, p = 0.022), liver (r = 0.269, p = 0.033), large intestine (r = -0.463, p = 7.035E-5) and aorta (r = -0.273, p = 0.028). A significant difference of RTL between young and aged animals was only observed in aorta (0.98 &#xb1; 0.15 vs. 0.76 &#xb1; 0.11, p = 1.987E-6), lung (0.76 &#xb1; 0.14 vs. 0.85 &#xb1; 0.14, p = 0.024) and visceral fat (0.83 &#xb1; 0.14 vs. 0.92 &#xb1; 0.15, p = 0.44). The expression of TERT significantly differed between the tested organs with highest levels in liver and kidney. Age-related differences in TERT expression were found in PBMCs, skeletal muscle, and visceral fat. mRNA expression of TERF-1 and TERF-2 was tissue-specific with the highest levels in liver. Age-related differences in TERF-1 and TERF-2 expression were inconsistent.<br><br>CONCLUSIONS: The present study questions the utility of RTL in PBMCs as a biomarker for the individual assessment of aging.},
}
@article {pmid35217318,
year = {2022},
author = {Almuwaqqat, Z and Wittbrodt, MT and Moazzami, K and Nye, JA and Lima, BB and Shah, AJ and Alkhalaf, J and Pearce, B and Sun, YV and Quyyumi, AA and Vaccarino, V and Bremner, JD},
title = {Neural correlates of stress and leucocyte telomere length in patients with coronary artery disease.},
journal = {Journal of psychosomatic research},
volume = {155},
number = {},
pages = {110760},
pmid = {35217318},
issn = {1879-1360},
support = {S10 RR016917/RR/NCRR NIH HHS/United States ; I01 RX003418/RX/RRD VA/United States ; R01 MH056120/MH/NIMH NIH HHS/United States ; K24 HL077506/HL/NHLBI NIH HHS/United States ; R01 HL125246/HL/NHLBI NIH HHS/United States ; T32 MH067547/MH/NIMH NIH HHS/United States ; TL1 TR002382/TR/NCATS NIH HHS/United States ; R01 MH120262/MH/NIMH NIH HHS/United States ; T32 HL130025/HL/NHLBI NIH HHS/United States ; K23 HL127251/HL/NHLBI NIH HHS/United States ; UL1 TR000454/TR/NCATS NIH HHS/United States ; P01 HL101398/HL/NHLBI NIH HHS/United States ; UG3 DA048502/DA/NIDA NIH HHS/United States ; KL2 TR000455/TR/NCATS NIH HHS/United States ; R01 HL109413/HL/NHLBI NIH HHS/United States ; K24 MH076955/MH/NIMH NIH HHS/United States ; R01 HL088726/HL/NHLBI NIH HHS/United States ; },
mesh = {*Coronary Artery Disease/genetics ; Cross-Sectional Studies ; Female ; Humans ; Leukocytes ; Male ; Middle Aged ; Telomere ; Telomere Shortening ; },
abstract = {BACKGROUND: Accelerated biological aging, as indicated by telomere shortening, is associated with CAD pathogenesis. In a cross-sectional study, we investigated neural correlates of acute psychological stress and short telomeres in patients with CAD.<br><br>METHODS: Individuals with CAD (N&#xa0;=&#xa0;168) underwent a validated mental stress protocol including public speaking and mental arithmetic. Imaging of the brain with [O-15] water and high-resolution positron emission tomography (HR-PET) was performed during mental stress and control conditions. Blood flow during stressful tasks (average of speech and arithmetic) and control tasks were assessed. Telomere length in peripheral leucocytes was measured by quantitative polymerase chain reaction and expressed as Telomere/Single Copy Gene (T/S) ratio. Voxel-wise regression models were constructed to assess the association between brain areas and activity during rest and mental stress after adjustments for demographic factors and clinical characteristics.<br><br>RESULTS: The mean (SD) age of the sample was 62 (8) years, and 69% were men. Increased activation with mental stress in the lingual gyrus, cerebellum and superior and inferior frontal gyri were associated with reduced telomere length; 1.6 higher voxel activation of these areas was associated with 0.1&#xa0;T/S-units reduction in telomere length (P&#xa0;<&#xa0;0.005). Additionally, during neutral counting and speaking tasks, brain activity in the precentral, middle and superior frontal and middle temporal gyri was inversely associated with telomere length. Results remained consistent after adjustment for demographic and clinical risk factors.<br><br>CONCLUSION: Increased stress-induced activity in brain areas mediating the stress response was associated with shortened telomere length in CAD patients.},
}
@article {pmid35210806,
year = {2022},
author = {Zhang, J},
title = {Mendelian Randomization Study Implies Causal Linkage Between Telomere Length and Juvenile Idiopathic Arthritis in a European Population.},
journal = {Journal of inflammation research},
volume = {15},
number = {},
pages = {977-986},
pmid = {35210806},
issn = {1178-7031},
abstract = {BACKGROUND: Telomere maintenance is increasingly being considered as fundamental to the progression of immune-mediated inflammatory diseases. However, the causality underlying the purported relationship has not been fully elucidated. In the present work, we applied Mendelian randomization (MR) analysis to obtain estimates of the causal effect of telomere length (TL) on the risk of juvenile idiopathic arthritis (JIA) and JIA-associated iridocyclitis.<br><br>METHODS: Two-sample MR analysis was conducted using summary-level data from the largest genome-wide association studies concerning TL (78,592 individuals), JIA (6056 cases and 25,086 controls), and JIA-associated iridocyclitis (1430 cases and 9,2767 controls). All the participants were of European ancestry. The inverse variance weighted (IVW) method was applied to estimate the causal effects. Sensitivity analyses incorporating multiple complementary MR approaches were implemented to test the robustness of the association and examine potential bias from pleiotropy.<br><br>RESULTS: In our MR analysis, genetically predicted shorter TL was associated with an increased risk of JIA (IVW: odds ratio=1.68, 95% CI: 1.13-2.48, P=0.009), but not with the risk of JIA-associated iridocyclitis (IVW: odds ratio=1.75, 95% CI: 0.81-3.79, P=0.155). The other MR methods produced consistent results. Besides, a leave-one-out sensitivity analysis yielded similar findings and validated the robustness of the causal relationship. MR-Egger regression revealed no notable horizontal pleiotropy (intercept=0.046, P=0.175).<br><br>CONCLUSION: This work provides evidence of a negative association between TL and JIA risk, but not for the association between TL and the risk of JIA-associated iridocyclitis, in a European population. Future studies with larger sample sizes are warranted to elucidate the underlying role of TL in these diseases.},
}
@article {pmid35208566,
year = {2022},
author = {Song, S and Lee, E and Kim, H},
title = {Does Exercise Affect Telomere Length? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {58},
number = {2},
pages = {},
pmid = {35208566},
issn = {1648-9144},
mesh = {*Exercise ; Humans ; *Life Style ; Randomized Controlled Trials as Topic ; Telomere/genetics ; },
abstract = {Background and objectives: Telomere length is an indicator of biological aging, and it shortens during cell division. A short telomere length is associated with various age-related diseases and mortality. It is suggested that physical activity has a positive effect on the rate of telomere length shortening. Materials and Methods: Related studies, published in electronic databases, were searched with keywords, including exercise, telomere length, and randomized controlled trial. The data were weighted and pooled through a fixed-effect model. Results: Of the total 49 studies searched, 7 studies with 939 participants were considered suitable, and were analyzed qualitatively and quantitatively. Exercise is beneficial to telomere length. Aerobic exercise was effective as the type of exercise (MD, -0.03; 95% CI, -0.04 to -0.01). In addition, exercise for more than 6 months, with a change in lifestyle, is beneficial for telomere length (MD, -0.02; 95% CI, -0.04 to -0.01). Conclusions: The type and duration of exercise for positive improvement in telomere length is aerobic exercise for more than 6 months.},
}
@article {pmid35205387,
year = {2022},
author = {Umriukhin, PE and Ershova, ES and Filev, AD and Agafonova, ON and Martynov, AV and Zakharova, NV and Veiko, RV and Porokhovnik, LN and Kostyuk, GP and Kutsev, SI and Veiko, NN and Kostyuk, SV},
title = {The Psychoemotional Stress-Induced Changes in the Abundance of SatIII (1q12) and Telomere Repeats, but Not Ribosomal DNA, in Human Leukocytes.},
journal = {Genes},
volume = {13},
number = {2},
pages = {},
pmid = {35205387},
issn = {2073-4425},
mesh = {*DNA Copy Number Variations ; DNA, Ribosomal/genetics ; Humans ; Leukocytes ; *Schizophrenia/genetics ; Telomere/genetics ; },
abstract = {INTRODUCTION: As shown earlier, copy number variations (CNV) in the human satellite III (1q12) fragment (f-SatIII) and the telomere repeat (TR) reflects the cell's response to oxidative stress. The contents of f-SatIII and TR in schizophrenic (SZ) patients were found to be lower than in healthy controls (HC) in previous studies. The major question of this study was: 'What are the f-SatIII and TR CNV dynamic changes in human leukocytes, depending on psychoemotional stress?'<br><br>MATERIALS AND METHODS: We chose a model of psychoemotional stress experienced by second-year medical students during their exams. Blood samples were taken in stressful conditions (exams) and in a control non-stressful period. Biotinylated probes were used for f-SatIII, rDNA, and TR quantitation in leukocyte DNA by non-radioactive quantitative hybridization in SZ patients (n = 97), HC (n = 97), and medical students (n = 17, n = 42). A flow cytometry analysis was used for the oxidative stress marker (NOX4, 8-oxodG, and &#x3b3;H2AX) detection in the lymphocytes of the three groups.<br><br>RESULTS: Oxidative stress markers increased significantly in the students' lymphocytes during psychoemotional stress. The TR and f-SatIII, but not the rDNA, contents significantly changed in the DNA isolated from human blood leukocytes. After a restoration period (post-examinational vacations), the f-SatIII content decreased, and the TR content increased. Changes in the blood cells of students during examinational stress were similar to those in SZ patients during an exacerbation of the disease.<br><br>CONCLUSIONS: Psychoemotional stress in students during exams triggers a universal mechanism of oxidative stress. The oxidative stress causes significant changes in the f-SatIII and TR contents, while the ribosomal repeat content remains stable. A hypothesis is proposed to explain the quantitative polymorphisms of f-SatIII and TR contents under transient (e.g., students' exams) or chronic (in SZ patients) stress. The changes in the f-SatIII and TR copy numbers are non-specific events, irrespective of the source of stress. Thus, our findings suggest that the psychoemotional stress, common in SZ patients and healthy students during exams, but not in a schizophrenia-specific event, was responsible for the changes in the repeat contents that we observed earlier in SZ patients.},
}
@article {pmid35205225,
year = {2022},
author = {Li, D and Hou, K and Zhang, K and Jia, S},
title = {Regulation of Replication Stress in Alternative Lengthening of Telomeres by Fanconi Anaemia Protein.},
journal = {Genes},
volume = {13},
number = {2},
pages = {},
pmid = {35205225},
issn = {2073-4425},
mesh = {DNA Repair/genetics ; Fanconi Anemia Complementation Group A Protein/genetics ; Fanconi Anemia Complementation Group Proteins/genetics ; *Telomere/genetics/metabolism ; *Telomere Homeostasis/genetics ; },
abstract = {Fanconi anaemia (FA)-related proteins function in interstrand crosslink (ICL) repair pathways and multiple damage repair pathways. Recent studies have found that FA proteins are involved in the regulation of replication stress (RS) in alternative lengthening of telomeres (ALT). Since ALT cells often exhibit high-frequency ATRX mutations and high levels of telomeric secondary structure, high levels of DNA damage and replicative stress exist in ALT cells. Persistent replication stress is required to maintain the activity of ALT mechanistically, while excessive replication stress causes ALT cell death. FA proteins such as FANCD2 and FANCM are involved in the regulation of this balance by resolving or inhibiting the formation of telomere secondary structures to stabilize stalled replication forks and promote break-induced repair (BIR) to maintain the survival of ALT tumour cells. Therefore, we review the role of FA proteins in replication stress in ALT cells, providing a rationale and direction for the targeted treatment of ALT tumours.},
}
@article {pmid35205052,
year = {2022},
author = {Armendáriz-Castillo, I and Hidalgo-Fernández, K and Pérez-Villa, A and García-Cárdenas, JM and López-Cortés, A and Guerrero, S},
title = {Identification of Key Proteins from the Alternative Lengthening of Telomeres-Associated Promyelocytic Leukemia Nuclear Bodies Pathway.},
journal = {Biology},
volume = {11},
number = {2},
pages = {},
pmid = {35205052},
issn = {2079-7737},
abstract = {Alternative lengthening of telomeres-associated promyelocytic leukemia nuclear bodies (APBs) are a hallmark of telomere maintenance. In the last few years, APBs have been described as the main place where telomeric extension occurs in ALT-positive cancer cell lines. A different set of proteins have been associated with APBs function, however, the molecular mechanisms behind their assembly, colocalization, and clustering of telomeres, among others, remain unclear. To improve the understanding of APBs in the ALT pathway, we integrated multiomics analyses to evaluate genomic, transcriptomic and proteomic alterations, and functional interactions of 71 APBs-related genes/proteins in 32 Pan-Cancer Atlas studies from The Cancer Genome Atlas Consortium (TCGA). As a result, we identified 13 key proteins which showed distinctive mutations, interactions, and functional enrichment patterns across all the cancer types and proposed this set of proteins as candidates for future ex vivo and in vivo analyses that will validate these proteins to improve the understanding of the ALT pathway, fill the current research gap about APBs function and their role in ALT, and be considered as potential therapeutic targets for the diagnosis and treatment of ALT-positive cancers in the future.},
}
@article {pmid35203522,
year = {2022},
author = {M'Kacher, R and Jaillet, M and Colicchio, B and Vasarmidi, E and Mailleux, A and Dieterlen, A and Kannengiesser, C and Borie, C and Oudrhiri, N and Junker, S and Voisin, P and Jeandidier, E and Carde, P and Fenech, M and Bennaceur-Griscelli, A and Crestani, B and Borie, R},
title = {Lung Fibroblasts from Idiopathic Pulmonary Fibrosis Patients Harbor Short and Unstable Telomeres Leading to Chromosomal Instability.},
journal = {Biomedicines},
volume = {10},
number = {2},
pages = {},
pmid = {35203522},
issn = {2227-9059},
abstract = {Idiopathic pulmonary fibrosis (IPF) is associated with several hallmarks of aging including telomere shortening, which can result from germline mutations in telomere related genes (TRGs). Here, we assessed the length and stability of telomeres as well as the integrity of chromosomes in primary lung fibroblasts from 13 IPF patients (including seven patients with pathogenic variants in TRGs) and seven controls. Automatized high-throughput detection of telomeric FISH signals highlighted lower signal intensity in lung fibroblasts from IPF patients, suggesting a telomere length defect in these cells. The increased detection of telomere loss and terminal deletion in IPF cells, particularly in TRG-mutated cells (IPF-TRG), supports the notion that these cells have unstable telomeres. Furthermore, fibroblasts from IPF patients with TRGs mutations exhibited dicentric chromosomes and anaphase bridges. Collectively, our study indicates that fibroblasts from IPF patients exhibit telomere and chromosome instability that likely contribute to the physiopathology.},
}
@article {pmid35202418,
year = {2022},
author = {Agirbasli, D and Kalyoncu, M and Muftuoglu, M and Aksungar, FB and Agirbasli, M},
title = {Leukocyte telomere length as a compensatory mechanism in vitamin D metabolism.},
journal = {PloS one},
volume = {17},
number = {2},
pages = {e0264337},
pmid = {35202418},
issn = {1932-6203},
mesh = {Aged ; Cohort Studies ; Female ; Humans ; Leukocytes, Mononuclear/*drug effects/ultrastructure ; Middle Aged ; Postmenopause ; Receptors, Calcitriol/blood ; Telomere/*drug effects ; Telomere Homeostasis/*drug effects ; Transcriptome ; Vitamin D/administration &amp; dosage/blood/*pharmacology ; Vitamin D Deficiency/*drug therapy/pathology ; },
abstract = {Vitamin D deficiency is common among postmenopausal women. Telomere length can be a potential protective mechanism for age-related diseases. The objective of our study is to examine the association of vitamin D supplementation on leukocyte telomere length (LTL) in healthy postmenopausal women with vitamin D deficiency. The study was designed as a placebo-controlled study to investigate the short-term effects of vitamin D supplementation and seasonal changes on vitamin D related parameters, including 25(OH)D, 1,25(OH)2D parathormone (PTH), Vitamin D binding protein (VDBP), vitamin D receptor (VDR), and telomere length in a cohort of postmenopausal women (n = 102). The group was divided as supplementation (n = 52) and placebo groups (n = 50). All parameters were measured before and after treatment. Serum VDBP levels were measured by ELISA method and VDR, GC (VDBP) gene expressions and relative telomere lengths were measured in peripheral blood mononuclear cells (PBMC) using a quantitative real-time PCR method. The results demonstrate that baseline levels were similar between the groups. After vitamin D supplementation 25(OH)D, 1,25(OH)2D, PTH and VDBP levels were changed significantly compared to the placebo group. At the end of the study period, LTL levels were significantly increased in both groups and this change was more prominent in placebo group. The change in GC expression was significant between treatment and placebo groups but VDR expression remained unchanged. Even though the study was designed to solely assess the effects of vitamin D supplementation, LTL was significantly increased in the whole study group in summer months suggesting that LTL levels are affected by sun exposure and seasonal changes rather than supplementation. The study displayed the short-term effect of Vitamin D supplementation on vitamin D, PTH levels, LTL and vitamin D associated gene expressions. The relation between Vitamin D and LTL is not linear and could be confounded by several factors such as the population differences, regional and seasonal changes in sun exposure.},
}
@article {pmid35189049,
year = {2022},
author = {Ali, S and Scapagnini, G and Davinelli, S},
title = {Effect of omega-3 fatty acids on the telomere length: A mini meta-analysis of clinical trials.},
journal = {Biomolecular concepts},
volume = {13},
number = {1},
pages = {25-33},
doi = {10.1515/bmc-2021-0024},
pmid = {35189049},
issn = {1868-503X},
mesh = {Antioxidants/pharmacology ; *Fatty Acids, Omega-3/pharmacology/therapeutic use ; Humans ; Inflammation ; Oxidative Stress ; Telomere ; },
abstract = {Telomeres are protective caps at the end of eukaryotic chromosomes, whose length is correlated with health and lifespan. Telomere attrition is a common feature of the aging process and can be accelerated by oxidative stress and chronic inflammation. Various nutrients influence the telomere length, partially due to their antioxidant and anti-inflammatory properties. The aim of this review was to meta-analytically assess the effect of omega-3 fatty acids on the telomere length. We searched four databases (PubMed, Web of Sciences, Scopus, and the Cochrane Library) from inception until November 2021. Of 573 records, a total of 5 clinical trials were included for the quantitative meta-analysis, comprising a total of 337 participants. The results revealed an overall beneficial effect of omega-3 fatty acids on the telomere length (mean difference = 0.16; 95% CI, 0.02, 0.30; p = 0.02). Despite a limited number of studies, the available evidence suggests that omega-3 fatty acids may positively affect the telomere length. However, larger clinical trials are needed to confirm our findings, along with studies aimed to clarify the underlying molecular mechanisms.},
}
@article {pmid35188570,
year = {2022},
author = {Frank, L and Rademacher, A and Mücke, N and Tirier, SM and Koeleman, E and Knotz, C and Schumacher, S and Stainczyk, SA and Westermann, F and Fröhling, S and Chudasama, P and Rippe, K},
title = {ALT-FISH quantifies alternative lengthening of telomeres activity by imaging of single-stranded repeats.},
journal = {Nucleic acids research},
volume = {50},
number = {11},
pages = {e61},
pmid = {35188570},
issn = {1362-4962},
mesh = {Cell Line ; DNA, Single-Stranded/genetics ; Humans ; In Situ Hybridization, Fluorescence ; Neoplasms/genetics ; Telomerase/genetics ; Telomere/genetics/*metabolism ; Telomere Homeostasis ; },
abstract = {Alternative lengthening of telomeres (ALT) occurs in ∼10% of cancer entities. However, little is known about the heterogeneity of ALT activity since robust ALT detection assays with high-throughput in situ readouts are lacking. Here, we introduce ALT-FISH, a method to quantitate ALT activity in single cells from the accumulation of single-stranded telomeric DNA and RNA. It involves a one-step fluorescent in situ hybridization approach followed by fluorescence microscopy imaging. Our method reliably identified ALT in cancer cell lines from different tumor entities and was validated in three established models of ALT induction and suppression. Furthermore, we successfully applied ALT-FISH to spatially resolve ALT activity in primary tissue sections from leiomyosarcoma and neuroblastoma tumors. Thus, our assay provides insights into the heterogeneity of ALT tumors and is suited for high-throughput applications, which will facilitate screening for ALT-specific drugs.},
}
@article {pmid35186180,
year = {2022},
author = {Zhang, W and Peng, SF and Chen, L and Chen, HM and Cheng, XE and Tang, YH},
title = {Association between the Oxidative Balance Score and Telomere Length from the National Health and Nutrition Examination Survey 1999-2002.},
journal = {Oxidative medicine and cellular longevity},
volume = {2022},
number = {},
pages = {1345071},
pmid = {35186180},
issn = {1942-0994},
mesh = {Adult ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Female ; History, 20th Century ; History, 21st Century ; Humans ; Male ; Middle Aged ; Nutrition Surveys/*methods ; *Oxidation-Reduction ; Risk Factors ; Telomere Homeostasis/*immunology ; United States ; Young Adult ; },
abstract = {PURPOSE: Leukocyte telomere length (LTL) is an important biomarker of aging. The oxidative balance score (OBS) is used to assess the oxidative stress-related exposures of diet and lifestyle. This study is aimed at exploring if the OBS was associated with LTL.<br><br>METHODS: 3220 adults were included in this study from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. LTL was assayed from leukocyte DNA. Twenty dietary and lifestyle factors were selected to score the OBS. Survey-based multivariable linear regression was conducted to assess the association between the OBS and log-transformed LTL.<br><br>RESULTS: The association between the OBS and log-transformed LTL was positive in females but not males. For females, compared with the lowest OBS category as a reference, the multivariable-adjusted beta estimate (95% confidence interval, CI) for the highest OBS category was 0.0701 (0.0205-0.1197) (p for trend < 0.01), and the multivariable-adjusted beta estimate (95% CI) of the continuous OBS was 0.0039 (0.0014-0.0065). There was also the gender difference in the correlations of the dietary OBS and the lifestyle OBS with log-transformed LTL.<br><br>CONCLUSION: There was a positive association between the OBS and LTL in females. This result suggested that diet and lifestyle might affect LTL by regulating oxidative balance.},
}
@article {pmid35183942,
year = {2022},
author = {Pan, D and Shao, Y and Song, Y and Huang, D and Liu, S and Zeng, X and Liang, J and Juan Jennifer Tan, H and Qiu, X},
title = {Association between maternal per- and polyfluoroalkyl substance exposure and newborn telomere length: Effect modification by birth seasons.},
journal = {Environment international},
volume = {161},
number = {},
pages = {107125},
doi = {10.1016/j.envint.2022.107125},
pmid = {35183942},
issn = {1873-6750},
mesh = {*Alkanesulfonic Acids ; Bayes Theorem ; China ; Cohort Studies ; *Environmental Pollutants ; Female ; *Fluorocarbons/toxicity ; Humans ; Infant ; Infant, Newborn ; Maternal Exposure/adverse effects ; Pregnancy ; Seasons ; Telomere ; },
abstract = {BACKGROUND: Telomere length (TL) is an important biomarker of biological aging and disease that may be affected by prenatal exposure to environmental pollutants. Birth seasons have been linked to reproductive and immune-related diseases. Prenatal exposure to per- and polyfluoroalkyl substance (PFAS) has been associated with adverse birth outcomes, but the effects of PFAS and birth seasons on newborn TL are poorly understood.<br><br>OBJECTIVES: To explore the individual and combined effects of maternal PFAS exposure on newborn TL, with exploration of the interaction between PFAS and birth seasons on newborn TL.<br><br>METHODS: Between June 2015 and May 2018, a total of 499 mother-newborn pairs were recruited for a birth cohort study in Guangxi, China. Maternal blood samples were collected during pregnancy. Nine PFASs were measured by ultraperformance liquid chromatography-mass spectrometry. Newborn TL was assessed using quantitative real-time polymerase chain reaction. Modeling newborn TL as the outcome, multivariable linear regressions were performed for individual PFAS exposures, and Bayesian Kernel Machine Regressions were performed for PFAS mixtures. Furthermore, interaction analyses were conducted to evaluate the effect modification by birth seasons in these relationships.<br><br>RESULTS: For both single and multipollutant models, PFASs exposure were inversely associated with newborn TL, although none of the relationships were significant. The mixture of PFASs showed a potential positive trend of combined effect on newborn TL but non-statistically significant. Each ln-transformed unit concentration increase in PFOA was related to a 20.41% (95% CI: -30.44%, -8.93%) shorter TL in spring-born infants but not in those born in other birth seasons. Mothers in the middle and highest tertiles of PFOA exposure had 11.69% and 10.71% shorter TLs in spring-born infants, respectively.<br><br>CONCLUSION: Maternal PFAS exposure showed little association with newborn TL. The results suggested potential effect modification by birth season on the association between PFOA exposure and newborn TL.},
}
@article {pmid35179471,
year = {2022},
author = {Collin, V and Flamand, L},
title = {[The importance of telomeres in human herpesvirus-6A/B infections].},
journal = {Medecine sciences : M/S},
volume = {38},
number = {2},
pages = {168-176},
doi = {10.1051/medsci/2022008},
pmid = {35179471},
issn = {1958-5381},
mesh = {Genome, Viral ; *Herpesvirus 6, Human/genetics ; Humans ; *Roseolovirus Infections/genetics ; Telomere/genetics ; Virus Integration/genetics ; },
abstract = {Herpesviruses are undisputed masters of disguise. The ability to become invisible to the immune system effectors is a complex process resting on a variety of stealth approaches. Among these, human herpesviruses-6A and -6B (HHV-6A/B) have developed the unique ability to integrate their genome within the ends of chromosomes allowing viral persistence in the absence of viral protein expression. This aptitude, unique to HHV-6A/B among human herpesviruses, requires close interactions between the telomeric regions of chromosomes and the viral genome. In this review article, the biology of telomeres and the mechanisms responsible for viral integration are discussed. In closing, the possible biological consequences of HHV-6A/B integration into chromosomal DNA are discussed.},
}
@article {pmid35178897,
year = {2022},
author = {Bridges, J and Chung, KW and Martz, CD and Smitherman, EA and Drenkard, C and Wu, C and Lin, J and Lim, SS and Chae, DH},
title = {Leukocyte Telomere Length and Childhood Onset of Systemic Lupus Erythematosus in the Black Women's Experiences Living with Lupus Study.},
journal = {ACR open rheumatology},
volume = {4},
number = {5},
pages = {426-431},
pmid = {35178897},
issn = {2578-5745},
support = {U01DP005119/CC/CDC HHS/United States ; U01DP006488/CC/CDC HHS/United States ; U01DP005119/CC/CDC HHS/United States ; U01DP006488/CC/CDC HHS/United States ; },
abstract = {OBJECTIVE: The study objective was to compare leukocyte telomere length (LTL) among patients with systemic lupus erythematosus (SLE) diagnosed in childhood versus adulthood.<br><br>METHODS: Data are from the Black Women's Experiences Living with Lupus (BeWELL) study. Multivariable linear regression analyses that examined childhood diagnosis of SLE (diagnosed before 18&#x2009;years of age), age, and their interaction in relationship to LTL were conducted, adjusting for a range of demographic, socioeconomic, and health-related covariates.<br><br>RESULTS: The total analytic sample size was 415. Forty participants (9.6%) were diagnosed in childhood. There was no main effect of childhood diagnosis on LTL (b&#xa0;=&#x2009;0.007; 95% confidence interval [CI]: -0.089 to 0.103). However, the interaction between age and childhood diagnosis was significant (b&#xa0;=&#xa0;-0.008; 95% CI: -0.016 to -0.001), indicating a steeper inverse association between age and LTL among those diagnosed in childhood compared with those diagnosed in adulthood. This interaction remained statistically significant (P&#xa0;=&#x2009;0.024) after controlling for disease duration measured dichotomously (less than 10&#x2009;years vs. 10&#x2009;years or more); it was marginally significant (P&#xa0;=&#x2009;0.083) when controlling for disease duration measured continuously.<br><br>CONCLUSION: This cross-sectional analysis suggests that Black women with childhood-onset SLE may undergo accelerated LTL shortening compared with their adult-onset counterparts. This relationship persisted even after controlling for differences in SLE damage and disease duration. These findings inform research on immunosenescence mechanisms of SLE.},
}
@article {pmid35178191,
year = {2022},
author = {Sahm, V and Maurer, C and Baumeister, T and Anand, A and Strangmann, J and Schmid, RM and Wang, TC and Quante, M},
title = {Telomere shortening accelerates tumor initiation in the L2-IL1B mouse model of Barrett esophagus and emerges as a possible biomarker.},
journal = {Oncotarget},
volume = {13},
number = {},
pages = {347-359},
pmid = {35178191},
issn = {1949-2553},
mesh = {Adenocarcinoma ; Animals ; *Barrett Esophagus/genetics/pathology ; Biomarkers ; Cell Transformation, Neoplastic ; Disease Models, Animal ; *Esophageal Neoplasms/pathology ; Humans ; Interleukin-1beta ; Metaplasia ; Mice ; Telomere Shortening ; },
abstract = {Barrett's esophagus (BE) is a precursor of the esophageal adenocarcinoma (EAC). BE- development and its progression to cancer is associated with gastroesophageal reflux disease. However, there is currently no molecular risk prediction model that accurately identifies patients at high risk for EAC. Here, we investigated the impact of shortened telomeres in a mouse model for Barrett esophagus (L2-IL1B). The L2-IL1B mouse model is characterized by IL-1β-mediated inflammation, which leads to a Barrett-like metaplasia in the transition zone between the squamous forestomach and glandular cardia/stomach. Telomere shortening was achieved by mTERC knockout. In the second generation (G2) of mTERC knockout L2-IL1B.mTERC[-/-] G2 mice exhibited telomere dysfunction with significantly shorter telomeres as measured by qFISH compared to L2-IL1B mice, correlating with stronger DNA damage in the form of phosphorylation of H2AX (γH2AX). Macroscopically, tumor area along the squamocolumnar junction (SCJ) was increased in L2-IL1B.mTERC[-/-] G2 mice, along with increased histopathological dysplasia. In vitro studies indicated increased organoid formation capacity in BE tissue from L2-IL1B.mTERC[-/-] G2 mice. In addition, pilot studies of human BE-, dysplasia- and EAC tissue samples confirmed that BE epithelial cells with or without dysplasia (LGD) had shorter telomeres compared to gastric cardia tissue. Of note, differentiated goblet cells retained longer telomeres than columnar lined BE epithelium. In conclusion, our studies suggest that shortened telomeres are functionally important for tumor development in a mouse model of BE and are associated with proliferating columnar epithelium in human BE. We propose that shortened telomeres should be evaluated further as a possible biomarker of cancer risk in BE patients.},
}
@article {pmid35175322,
year = {2022},
author = {Savage, SA},
title = {Telomere biology disorders gain a family member.},
journal = {Blood},
volume = {139},
number = {7},
pages = {957-959},
pmid = {35175322},
issn = {1528-0020},
mesh = {Biology ; *Dyskeratosis Congenita ; Family ; Humans ; *Telomere/genetics ; },
}
@article {pmid35169632,
year = {2022},
author = {Costanzo, A and Ambrosini, R and Parolini, M and Caprioli, M and Secomandi, S and Rubolini, D and Fusani, L and Canoine, V},
title = {Telomere shortening is associated with corticosterone stress response in adult barn swallows.},
journal = {Current zoology},
volume = {68},
number = {1},
pages = {93-101},
pmid = {35169632},
issn = {1674-5507},
abstract = {When vertebrates face stressful events, the hypothalamic-pituitary-adrenal (HPA) axis is activated, generating a rapid increase in circulating glucocorticoid (GC) stress hormones followed by a return to baseline levels. However, repeated activation of HPA axis may lead to increase in oxidative stress. One target of oxidative stress is telomeres, nucleoprotein complexes at the end of chromosomes that shorten at each cell division. The susceptibility of telomeres to oxidizing molecules has led to the hypothesis that increased GC levels boost telomere shortening, but studies on this link are scanty. We studied if, in barn swallows Hirundo rustica, changes in adult erythrocyte telomere length between 2 consecutive breeding seasons are related to corticosterone (CORT) (the main avian GC) stress response induced by a standard capture-restraint protocol. Within-individual telomere length did not significantly change between consecutive breeding seasons. Second-year individuals showed the highest increase in circulating CORT concentrations following restraint. Moreover, we found a decline in female stress response along the breeding season. In addition, telomere shortening covaried with the stress response: a delayed activation of the negative feedback loop terminating the stress response was associated with greater telomere attrition. Hence, among-individual variation in stress response may affect telomere dynamics.},
}
@article {pmid35169104,
year = {2022},
author = {Van Der Stukken, C and Nawrot, TS and Alfano, R and Wang, C and Langie, SAS and Plusquin, M and Janssen, BG and Martens, DS},
title = {The telomere-mitochondrial axis of aging in newborns.},
journal = {Aging},
volume = {14},
number = {4},
pages = {1627-1650},
pmid = {35169104},
issn = {1945-4589},
mesh = {Aging/genetics ; DNA, Mitochondrial/genetics ; Female ; Fetal Blood ; Humans ; *Placenta ; Pregnancy ; Telomere/genetics ; *Tumor Suppressor Protein p53/genetics ; },
abstract = {Aging starts at the beginning of life as evidenced by high variability in telomere length (TL) and mitochondrial DNA content (mtDNAc) at birth. Whether p53 and PGC-1α are connected to these age-related markers in early life is unclear. In this study, we hypothesized that these hallmarks of aging are associated at birth. In 613 newborns from the ENVIRONAGE birth cohort, p53 and PGC-1α protein levels were measured in cord plasma, while TL and mtDNAc were measured in both cord blood and placental tissue. Cord blood methylation data of genes corresponding to the measured protein levels were available from the Human MethylationEPIC 850K BeadChip array. Pearson correlations and linear regression models were applied while accounting for selected covariates. In cord, a 10% increase in TL was associated with 5.22% (95% CI: 3.26 to 7.22; p < 0.0001) higher mtDNAc and -2.66% (95% CI: -5.04 to -0.23%; p = 0.032) lower p53 plasma level. In placenta, a 10% increase in TL was associated with 5.46% (95% CI: 3.82 to 7.13%; p < 0.0001) higher mtDNAc and -2.42% (95% CI: -4.29 to -0.52; p = 0.0098) lower p53 plasma level. Methylation level of TP53 was correlated with TL and mtDNAc in cord blood and with cord plasma p53 level. Our study suggests that p53 may be an important factor both at the protein and methylation level for the telomere-mitochondrial axis of aging at birth.},
}
@article {pmid35166828,
year = {2022},
author = {Long, W and Zheng, BX and Li, Y and Huang, XH and Lin, DM and Chen, CC and Hou, JQ and Ou, TM and Wong, WL and Zhang, K and Lu, YJ},
title = {Rational design of small-molecules to recognize G-quadruplexes of c-MYC promoter and telomere and the evaluation of their in vivo antitumor activity against breast cancer.},
journal = {Nucleic acids research},
volume = {50},
number = {4},
pages = {1829-1848},
pmid = {35166828},
issn = {1362-4962},
mesh = {Animals ; Antineoplastic Agents/*chemistry ; *Breast Neoplasms/drug therapy/genetics ; Drug Design ; Female ; *G-Quadruplexes ; Genes, myc ; Humans ; Ligands ; MCF-7 Cells ; Mice ; Promoter Regions, Genetic ; Telomere ; },
abstract = {DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket. This structural feature may render the molecules higher selectivity toward c-MYC G4s than other structures. The ligand-G4 interaction studied with 1H NMR may suggest a stacking interaction with the terminal G-tetrad. Moreover, the intracellular co-localization study with BG4 and cellular competition experiments with BRACO-19 may suggest that the binding targets of the ligands in cells are most probably G4-structures. Furthermore, the ligands that either preferentially bind to c-MYC promoter or telomeric G4s are able to downregulate markedly the c-MYC and hTERT gene expression in MCF-7 cells, and induce senescence and DNA damage to cancer cells. The in vivo antitumor activity of the ligands in MCF-7 tumor-bearing mice is also demonstrated.},
}
@article {pmid35165420,
year = {2022},
author = {Rossiello, F and Jurk, D and Passos, JF and d'Adda di Fagagna, F},
title = {Telomere dysfunction in ageing and age-related diseases.},
journal = {Nature cell biology},
volume = {24},
number = {2},
pages = {135-147},
pmid = {35165420},
issn = {1476-4679},
support = {P01 AG062413/AG/NIA NIH HHS/United States ; R01 AG068182/AG/NIA NIH HHS/United States ; UG3 CA268103/CA/NCI NIH HHS/United States ; UL1 TR002377/TR/NCATS NIH HHS/United States ; R01 AG068048/AG/NIA NIH HHS/United States ; P30 DK084567/DK/NIDDK NIH HHS/United States ; },
mesh = {Age Factors ; Aging/genetics/*metabolism/pathology ; Animals ; *Cellular Senescence ; DNA Damage ; Humans ; *Noncommunicable Diseases ; Telomere/genetics/*metabolism/pathology ; *Telomere Homeostasis ; *Telomere Shortening ; },
abstract = {Ageing organisms accumulate senescent cells that are thought to contribute to body dysfunction. Telomere shortening and damage are recognized causes of cellular senescence and ageing. Several human conditions associated with normal ageing are precipitated by accelerated telomere dysfunction. Here, we systematize a large body of evidence and propose a coherent perspective to recognize the broad contribution of telomeric dysfunction to human pathologies.},
}
@article {pmid35159322,
year = {2022},
author = {Michaeli, J and Smoom, R and Serruya, N and El Ayoubi, H and Rotshenker-Olshinka, K and Srebnik, N and Michaeli, O and Eldar-Geva, T and Tzfati, Y},
title = {Leukocyte Telomere Length Correlates with Extended Female Fertility.},
journal = {Cells},
volume = {11},
number = {3},
pages = {},
pmid = {35159322},
issn = {2073-4409},
support = {2107/18//Israel Science Foundation/ ; Mirsky fund SZMC//Mirsky fund SZMC/ ; Kamla fund, HUJI//Kamla fund, HUJI/ ; Israel-UK-Palestine GROWTH Fellowship Scheme, the British Council//Israel-UK-Palestine GROWTH Fellowship Scheme, the British Council/ ; },
mesh = {Aging/genetics ; Female ; Fertility/genetics ; Humans ; *Leukocytes ; Longevity/genetics ; Pregnancy ; *Telomere/genetics ; },
abstract = {Current social trends of delayed reproduction to the fourth and fifth decade of life call for a better understanding of reproductive aging. Demographic studies correlated late reproduction with general health and longevity. Telomeres, the protective ends of eukaryotic chromosomes, were implicated in various aging-associated pathologies and longevity. To examine whether telomeres are also associated with reproductive aging, we measured by Southern analysis the terminal restriction fragments (TRF) in leukocytes of women delivering a healthy infant following a spontaneous pregnancy at 43-48 years of age. We compared them to age-matched previously fertile women who failed to conceive above age 41. The average TRF length in the extended fertility group (9350 bp) was significantly longer than in the normal fertility group (8850 bp; p-value = 0.03). Strikingly, excluding women with nine or more children increased the difference between the groups to over 1000 bp (9920 and 8880 bp; p-value = 0.0009). Nevertheless, we observed no apparent effects of pregnancy, delivery, or parity on telomere length. We propose that longer leukocyte telomere length reflects higher oocyte quality, which can compensate for other limiting physiological and behavioral factors and enable successful reproduction. Leukocyte telomere length should be further explored as a novel biomarker of oocyte quality for assessing reproductive potential and integrating family planning with demanding women's careers.},
}
@article {pmid35159266,
year = {2022},
author = {Dan, J and Zhou, Z and Wang, F and Wang, H and Guo, R and Keefe, DL and Liu, L},
title = {Zscan4 Contributes to Telomere Maintenance in Telomerase-Deficient Late Generation Mouse ESCs and Human ALT Cancer Cells.},
journal = {Cells},
volume = {11},
number = {3},
pages = {},
pmid = {35159266},
issn = {2073-4409},
support = {202001BC070001, 202102AA100053//Natural Science Foundation of Yunnan Province/ ; 2018YFA0107000//China National Key R&amp;D Program/ ; 31571546, 91749129//National Natural Science Foundation of China/ ; },
mesh = {Animals ; DNA Methylation/genetics ; DNA-Binding Proteins/metabolism ; Humans ; Mice ; Mouse Embryonic Stem Cells ; *Neoplasms/genetics/metabolism ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere Homeostasis ; Transcription Factors/metabolism ; },
abstract = {Proper telomere length is essential for indefinite self-renewal of embryonic stem (ES) cells and cancer cells. Telomerase-deficient late generation mouse ES cells and human ALT cancer cells are able to propagate for numerous passages, suggesting telomerase-independent mechanisms responding for telomere maintenance. However, the underlying mechanisms ensuring the telomere length maintenance are unclear. Here, using late generation telomerase KO (G4 Terc[-/-]) ESCs as a model, we show that Zscan4, highly upregulated in G4 Terc[-/-] ESCs, is responsible for the prolonged culture of these cells with stably short telomeres. Mechanistically, G4 Terc[-/-] ESCs showed reduced levels of DNA methylation and H3K9me3 at Zscan4 promoter and subtelomeres, which relieved the expression of Zscan4. Similarly, human ZSCAN4 was also derepressed by reduced H3K9me3 at its promoter in ALT U2 OS cells, and depletion of ZSCAN4 significantly shortened telomeres. Our results define a similar conserved pathway contributing to the telomere maintenance in telomerase-deficient late generation mESCs and human ALT U2OS cancer cells.},
}
@article {pmid35155512,
year = {2021},
author = {Liu, X and Shi, Q and Fan, X and Chen, H and Chen, N and Zhao, Y and Qi, K},
title = {Associations of Maternal Polyunsaturated Fatty Acids With Telomere Length in the Cord Blood and Placenta in Chinese Population.},
journal = {Frontiers in nutrition},
volume = {8},
number = {},
pages = {779306},
pmid = {35155512},
issn = {2296-861X},
abstract = {Few studies have investigated the correlation between maternal polyunsaturated fatty acids (PUFAs) and telomeres in offspring, and the underlying influential mechanisms. In this study, we assessed the associations of maternal PUFAs with telomere length (TL) and DNA methylation of the telomerase reverse transcriptase (TERT) promoter in the cord blood and the placenta. A total of 274 pregnant women and their newborn babies were enrolled in this study. Maternal blood before delivery, the cord blood, and the placenta at birth were collected. Fatty acids in maternal erythrocytes and cord blood cells were measured by gas chromatography (GC). TL in the cord blood and the placenta was determined using real-time quantitative PCR (qPCR) by calculating the product ratio of telomeric DNA to the single-copy gene β-globin. The TERT promoter methylation was analyzed by DNA bisulfite sequencing. The associations of maternal fatty acids with TL were analyzed by univariate and multivariate regression. We found that low concentrations of docosapentaenoci acid (DPA, C22: 5n-3) and total n-3 PUFAs, adrenic acid (ADA, C22: 4n-6), and osbond acid (OA, C22: 5n-6) and high concentrations of linoleic acid (LA, C18: 2n-6) in maternal erythrocytes were associated with the shortened TL in cord blood cells (estimated difference in univariate analysis -0.36 to -0.46 for extreme quintile compared with middle quintile), and that low concentrations of cord blood docosahexaenoic acid (DHA, C22: 6n-3) were related to the shortened TL in cord blood cells. Differently, high concentrations of α-linolenic acid (LNA, C18: 3n-3), eicosatrienoic acid (EA, C20: 3n-3), DHA, and γ-linoleic acid (GLA, C18:3n-6) in maternal erythrocytes were associated with the shortened TL in the placenta (estimated difference in univariate analysis -0.36 to -0.45 for higher quintiles compared with the middle quintile). Further examination demonstrated that the concentrations of DHA and total n-3 PUFAs in maternal erythrocytes had positive associations with DNA methylation of the TERT promoter in the cord blood instead of the placenta. These data suggest that maternal PUFAs are closely correlated to infant TL and the TERT promoter methylation, which are differently affected by maternal n-3 PUFAs between the cord blood and the placenta. Therefore, keeping higher levels of maternal n-3 PUFAs during pregnancy may help to maintain TL in the offspring, which is beneficial to long-term health.},
}
@article {pmid35155172,
year = {2021},
author = {Arjmand, B and Safari-Alighiarloo, N and Razzaghi, M and Rezaei Tavirani, M and Rostami Nejad, M and Rezaei Tavirani, M and Mansouri, V and Vafaee, R},
title = {Effect of UV Laser Radiation on "Positive Regulation of Telomere Maintenance" in Saccharomyces cerevisiae.},
journal = {Journal of lasers in medical sciences},
volume = {12},
number = {},
pages = {e87},
pmid = {35155172},
issn = {2008-9783},
abstract = {Introduction: Excessive exposure to ultraviolet (UV) radiation may cause a variety of skin cancers and damage to the eye lens. The assessment of different aspects of UV damage has attracted researchers' interest. UV radiation to simple biological models such as Saccharomyces cerevisiae of yeast family could help to find out different molecular changes resulting from radiation. The assessment and network analysis of gene expression data about yeast cells radiated by the UV laser was the aim of this study. Methods: The gene expression profiles of S. cerevisiae samples in the presence of the UV laser at 30 seconds radiation and 15 minutes' post-radiation time are compared with the control profiles. The significant expressed genes interacted and the central nodes and related biological terms were identified. Results: The main connected component of the network including 427 nodes was analyzed and 11 central differentially expressed genes (DEGs) were determined. RPN11, UBI4, HSP82, and HSC82 as critical DEGs and "positive regulation of telomere maintenance" as a related biological term were introduced. Conclusion: The finding has provided a new perspective on laser application in the rejuvenation process. It seems that the laser can be used as a suitable agent against the aging process which is a limiting factor in human life.},
}
@article {pmid35152597,
year = {2021},
author = {Fursova, AZ and Derbeneva, AS and Tarasov, MS and Nikulich, IF and Devyatkin, VA and Telegina, DV and Kolosova, NG and Kozhevnikova, OS},
title = {[Leukocyte telomere length and response to antiangiogenic therapy in patients with neovascular age-related macular degeneration.].},
journal = {Advances in gerontology = Uspekhi gerontologii},
volume = {34},
number = {6},
pages = {823-830},
pmid = {35152597},
issn = {1561-9125},
mesh = {Aged ; Angiogenesis Inhibitors ; Humans ; Leukocytes ; *Macular Degeneration/diagnosis/drug therapy/genetics ; Middle Aged ; Ranibizumab/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Retrospective Studies ; Telomere ; Treatment Outcome ; *Vascular Endothelial Growth Factor A ; Visual Acuity ; },
abstract = {Age-related macular degeneration (AMD) is becoming the leading cause of vision loss in people over 60 years of age. The neovascular form of AMD (nVMD) is characterized by choroidal neovascularization (CNV), the main trigger of which is vascular endothelial growth factor (VEGF), the inhibition of which is the current standard of treatment. Significant variability of response to anti-VEGF therapy determines the relevance of the search for biological markers - prognostic criteria of treatment response. We analyzed the response of 110 nVMD patients to anti-VEGF therapy depending on the functional and anatomical parameters of the retina (according to optical coherence tomography, OCT) and leukocyte telomere length (LTL, was assessed by quantitative PCR). Positive dynamics of best corrected visual acuity (BCVA) was observed in 100% of eyes. The central retinal thickness (CRT) decreased after the 3rd injection to 265 [234-306] µm, by the end of the observation period - to 211 [190-262] µm. The retention of activity of the subretinal neovascular membrane (SNM) at the end of the observation period correlated with lower values of the initial BCVA and high values of the initial CRT. An association of LTL with response to treatment was revealed: in patients with higher LTL the active form of SNM was more often switched to inactive after three injections, while with lower LTL, the activity of SNM was more often preserved, which determined the need for more intravitreal injections.},
}
@article {pmid35151422,
year = {2022},
author = {Rai, S and Badarinath, ARS and George, A and Sitaraman, S and Bronson, SC and Anandt, S and Babu, KT and Moses, A and Saraswathy, R and Hande, MP},
title = {Association of telomere length with diabetes mellitus and idiopathic dilated cardiomyopathy in a South Indian population: A pilot study.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {874-875},
number = {},
pages = {503439},
doi = {10.1016/j.mrgentox.2021.503439},
pmid = {35151422},
issn = {1879-3592},
mesh = {*Cardiomyopathy, Dilated/genetics ; *Diabetes Mellitus, Type 2/genetics ; Humans ; India ; Pilot Projects ; Stroke Volume ; *Telomere/genetics ; Ventricular Function, Left ; },
abstract = {Telomere shortening has been associated with ageing and with many age-related diseases including cancer, coronary artery disease, heart failure and diabetes. We sought to investigate the link between telomere shortening and age-related diseases like type 2 diabetes mellitus (DM) (without any complications: DM; with neuropathic complication: DN) and idiopathic dilated cardiomyopathy (IDCM) in south Indian population. We compared telomere lengths of blood lymphocytes taken from patients with associated age-related diseases, namely DM (n = 47), DN (n = 52) and IDCM (n = 34) and controls (n = 46). In addition, we evaluated the relationship between echocardiographic left ventricular ejection fraction (LVEF), left ventricular end diastolic and systolic diameters (LVEDd and LVESd) and telomere length in IDCM patients. Telomere length negatively correlated with age in the cohorts with diabetes and IDCM, and in controls. Average telomere length in diabetes and IDCM patients was significantly shorter than that of controls either before or after adjustments for age and sex. Duration of diabetes in patients with type 2 diabetes did not correlate with telomere length. No correlation was found between the length of telomeres and echocardiography parameters like LVEF, LVEDd and LVESd in IDCM patients. Though echocardiographic characteristics of IDCM did not correlate with telomere length, telomere shortening was found to be accelerated in diabetes (both DM and DN) and IDCM in a south Indian population. Neuropathic complication in diabetes had no effect on telomere shortening. While telomere shortening is a cause or a consequence of diabetic and cardiac pathology remains further investigation, the current study substantiates the usefulness of telomere length measurements as a marker in conjunction with other biochemical markers of age-related diseases.},
}
@article {pmid35150467,
year = {2022},
author = {Kauzálová, T and Tomášek, O and Mulder, E and Verhulst, S and Albrecht, T},
title = {Telomere length is highly repeatable and shorter in individuals with more elaborate sexual ornamentation in a short-lived passerine.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6172-6183},
doi = {10.1111/mec.16397},
pmid = {35150467},
issn = {1365-294X},
mesh = {Humans ; Male ; Animals ; Female ; *Sex Characteristics ; Sex ; *Swallows/genetics ; Feathers ; Telomere/genetics ; },
abstract = {Quantifying an individual's state as a fitness proxy has proven challenging, but accumulating evidence suggests that telomere length and attrition may indicate individual somatic state and success at self-maintenance, respectively. Sexual ornamentation is also thought to signal phenotypic quality, but links between telomeres and sexual ornamentation have been little explored. To address this issue, we examined whether telomere length and dynamics are predicted by the expression of a sexually selected ornament, the length of the outermost tail feathers (streamers), using longitudinal data from a population of European barn swallows (Hirundo rustica). In 139 adult individuals, each measured twice, we further assessed associations of telomere length with age, sex, breeding status and survival. Telomere length showed high individual repeatability (R = .97) across years while shortening with age in both sexes. Telomere length and dynamics were not significantly associated with survival to the next year, remaining lifespan or reproduction status (comparing breeding and nonbreeding yearlings). Tail streamer length, a sexually selected trait in barn swallows, was negatively associated with telomere length, independent of sex. Thus, telomere length may reflect the costs of carrying an elaborated sexual ornament, although ornament size did not significantly predict telomere shortening. In conclusion, telomere length in adult barn swallows is a highly consistent trait that shows a negative relationship with sexual ornamentation, suggesting a trade-off between sexual ornamentation and telomere length.},
}
@article {pmid35142846,
year = {2022},
author = {Lansdorp, PM},
title = {Telomeres, aging, and cancer: the big picture.},
journal = {Blood},
volume = {139},
number = {6},
pages = {813-821},
pmid = {35142846},
issn = {1528-0020},
support = {PJT-159787//CIHR/Canada ; },
mesh = {*Aging ; Animals ; DNA/genetics/metabolism ; DNA Damage ; Disease Models, Animal ; Humans ; Mutation ; Neoplasms/*genetics/metabolism ; Telomerase/genetics/metabolism ; Telomere/*genetics/metabolism ; *Telomere Shortening ; },
abstract = {The role of telomeres in human health and disease is yet to be fully understood. The limitations of mouse models for the study of human telomere biology and difficulties in accurately measuring the length of telomere repeats in chromosomes and cells have diverted attention from many important and relevant observations. The goal of this perspective is to summarize some of these observations and to discuss the antagonistic role of telomere loss in aging and cancer in the context of developmental biology, cell turnover, and evolution. It is proposed that both damage to DNA and replicative loss of telomeric DNA contribute to aging in humans, with the differences in leukocyte telomere length between humans being linked to the risk of developing specific diseases. These ideas are captured in the Telomere Erosion in Disposable Soma theory of aging proposed herein.},
}
@article {pmid35141296,
year = {2021},
author = {Wang, Q and Liu, Z and Dong, Y and Yang, X and Chen, M and Gao, Y},
title = {Leukocyte Telomere Length Predicts Progression From Paroxysmal to Persistent Atrial Fibrillation in the Long Term After Catheter Ablation.},
journal = {Frontiers in cardiovascular medicine},
volume = {8},
number = {},
pages = {813390},
pmid = {35141296},
issn = {2297-055X},
abstract = {BACKGROUND: Aging is significantly associated with the incidence and progression of atrial fibrillation (AF) incidence. This study aimed to evaluate the potential predictive value of leukocyte telomere length (LTL) for progression from paroxysmal AF (PAF) to persistent AF (PsAF) after catheter ablation.<br><br>METHODS AND RESULTS: A total of 269 patients with AF (154 patients with PAF and 115 patients with PsAF, respectively) were prospectively enrolled, and all patients with PAF at baseline were regularly followed up to determine whether and when they should progress to PsAF after catheter ablation therapy. Baseline relative LTL was measured by quantitative real-time PCR (rt-PCT). There was a significant negative association between LTL and age (r = -0.23, p < 0.001). Patients with PsAF had significantly shorter LTL than those with PAF. After a mean follow-up of 854.9 &#xb1; 18.7 d, progression events occurred in 35 out of the 154 patients with PAF. Those progressed patients with PAF were older (70.9 &#xb1; 8.0 vs. 62.3 &#xb1; 10.3, p < 0.001) and had shorter LTL (1.2 &#xb1; 0.3 vs. 1.5 &#xb1; 0.3, p < 0.001) than those who did not. The receiver operating characteristic (ROC) curve analysis showed a significant value of LTL in distinguishing patients with PAF from patients with PsAF, with an area under the ROC curve (AUC) of 0.63 (95% CI 0.56-0.70, p < 0.001), and the optimal cut-off value of LTL was 1.175, with a sensitivity and specificity of 56.03 and 82.04%, respectively. All patients with PAF were divided into two subgroups according to the optimal cut-off point of LTL calculated by the ROC curve analysis: high LTL group (&#x2265;1.175) and low LTL group (<1.175). Kaplan-Meier curve analysis showed that PAF patients with shorter LTL had a significantly higher rate of progression after catheter ablation (40.5% vs. 18.8%, log-rank test p < 0.001). Multivariate Cox proportional-hazards model indicated that LTL [hazard ratio (HR): 2.71, 95% CI 1.36-5.42, p = 0.005] was an independent predictor for progression from PAF to PsAF after catheter ablation therapy, but HATCH score was not (HR: 1.02, 95% CI: 0.68-1.52, p = 0.923).<br><br>CONCLUSION: Leukocyte telomere length was significantly associated with AF types. LTL was independently associated with progression from PAF to PsAF after catheter ablation therapy.Chinese Clinical Trial Registry, Registration Number: ChiCTR1900021341.},
}
@article {pmid35140887,
year = {2022},
author = {Aramburu, T and Kelich, J and Rice, C and Skordalakes, E},
title = {POT1-TPP1 binding stabilizes POT1, promoting efficient telomere maintenance.},
journal = {Computational and structural biotechnology journal},
volume = {20},
number = {},
pages = {675-684},
pmid = {35140887},
issn = {2001-0370},
support = {P30 CA010815/CA/NCI NIH HHS/United States ; },
abstract = {Telomeric POT1-TPP1 binding is critical to telomere maintenance and disruption of this complex may lead to cancer. Current data suggests a reduction of intracellular POT1 levels in the absence of TPP1. Here we provide evidence of POT1 plasticity that contributes to its lack of stability in the absence of TPP1 binding. Structural data reveals inter- and intramolecular POT1C domain flexibility in the absence of TPP1. Thermostability and proteolytic resistance assays show that POT1C and the mutant complex POT1C(Q623H)-TPP1(PBD) are less stable than the wild type POT1C-TPP1(PBD), suggesting that TPP1 binding to POT1 stabilizes POT1C and makes it less accessible to proteasomal degradation in the cell. Disruption of the POT1-TPP1 complex such as through cancer-associated mutations leads to a reduction of intracellular POT1, telomere uncapping, and telomere associated DNA damage response (DDR). DDR in turn leads to senescence or genomic instability and oncogenesis.},
}
@article {pmid35129114,
year = {2022},
author = {Malyavko, AN and Petrova, OA and Zvereva, MI and Polshakov, VI and Dontsova, OA},
title = {Telomere length regulation by Rif1 protein from Hansenula polymorpha.},
journal = {eLife},
volume = {11},
number = {},
pages = {},
pmid = {35129114},
issn = {2050-084X},
mesh = {Cell Cycle Proteins/genetics/*metabolism ; DNA Replication ; Repressor Proteins/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Saccharomycetales/genetics/*metabolism ; Telomere/*ultrastructure ; Telomere Homeostasis ; Telomere-Binding Proteins/genetics/*metabolism ; },
abstract = {Rif1 is a large multifaceted protein involved in various processes of DNA metabolism - from telomere length regulation and replication to double-strand break repair. The mechanistic details of its action, however, are often poorly understood. Here, we report functional characterization of the Rif1 homologue from methylotrophic thermotolerant budding yeast Hansenula polymorpha DL-1. We show that, similar to other yeast species, H. polymorpha Rif1 suppresses telomerase-dependent telomere elongation. We uncover two novel modes of Rif1 recruitment at H. polymorpha telomeres: via direct DNA binding and through the association with the Ku heterodimer. Both of these modes (at least partially) require the intrinsically disordered N-terminal extension - a region of the protein present exclusively in yeast species. We also demonstrate that Rif1 binds Stn1 and promotes its accumulation at telomeres in H. polymorpha.},
}
@article {pmid35127871,
year = {2021},
author = {Zhang, A and Fan, L and Bao, X and Xu, Z and Yin, Z and Zhuo, Y and Zhang, J and Gu, J and Chang, ACY and Fan, Y and Wang, C},
title = {Leukocyte Telomere Length Shortening Implies Plaque Instability and Major Adverse Cardiovascular Events in Patients With Angiographically Intermediate Lesions.},
journal = {Frontiers in cardiovascular medicine},
volume = {8},
number = {},
pages = {812363},
pmid = {35127871},
issn = {2297-055X},
abstract = {BACKGROUND: Telomere shortening, an indicator of aging, is associated with age-related diseases. This study aims to investigate the association between leukocyte telomere length (LTL) and thin-capped fibroatheromata (TCFA) and the impact of using LTL cutoff to determine the incidence of major adverse cardiovascular events (MACEs) in patients with angiographically intermediate coronary lesions.<br><br>METHODS: This was a signal-center retrospective study focusing on patients who underwent coronary angiography and optical coherence tomography (OCT). The degree of coronary stenosis was assessed by angiography. The presence of TCFA was determined by OCT imaging. A total of 156 patients with angiographically intermediate coronary lesions were enrolled.<br><br>RESULTS: Leukocyte telomere lengths were significantly shorter in the TCFA group compared with non-TCFA group [11.95 (10.56, 15.21) kb vs. 13.81 (12.06, 16.11) kb, p = 0.003]. The short-LTL group and long-LTL group were divided according to the optimal cut-off value which was determined by the receiver operating characteristic (ROC) curve analysis. Logistic regression model revealed that short-LTL was independently associated with TCFA incidence (odds ratio [OR] 4.387, 95% CI: 1.902-10.120, p = 0.001) after adjusting for confounding factors. Over a 24-months follow-up, the MACE incidence among patients with short-LTL was significantly higher than those in the long-LTL group (12.5 vs. 2.0%, p = 0.006 by log-rank test). Multivariable cox regression analysis indicated that short-LTL (hazard ratio [HR] 9.716, 95% CI: 1.995-47.319, p = 0.005) was an independent prognostic factor of MACE incidence in angiographically intermediate coronary lesions patients.<br><br>CONCLUSIONS: Short-LTL was independently associated with the incidence of TCFA and may serve as a prognostic factor for MACE risk on top of conventional risk factors.},
}
@article {pmid35123384,
year = {2022},
author = {Coimbra, BM and Carvalho, CM and van Zuiden, M and Williamson, RE and Ota, VK and Mello, AF and Belangero, SI and Olff, M and Mello, MF},
title = {The impact of neighborhood context on telomere length: A systematic review.},
journal = {Health &amp; place},
volume = {74},
number = {},
pages = {102746},
doi = {10.1016/j.healthplace.2022.102746},
pmid = {35123384},
issn = {1873-2054},
mesh = {Humans ; Residence Characteristics ; *Telomere ; *Telomere Shortening ; },
abstract = {A growing body of research demonstrates the association between neighborhood context and health. The underlying biological mechanisms of this association are not fully understood. We conducted a systematic review of studies that investigated the association between neighborhood context and telomere length (TL), a DNA-protein complex that shortens after cell division. Short TL is linked to age-related diseases and may be impacted by chronic stress. Nineteen eligible articles identified through PubMed and Scopus met inclusion criteria. Results demonstrated inconsistent support for the relationship between neighborhood disadvantage and short TL. However, findings across several studies provide evidence for an inverse association between perceived neighborhood problems and TL, suggesting that TL may be an important factor in understanding health vulnerabilities associated specifically with negative perceptions of the neighborhood context.},
}
@article {pmid35123339,
year = {2022},
author = {Incollingo Rodriguez, AC and Polcari, JJ and Nephew, BC and Harris, R and Zhang, C and Murgatroyd, C and Santos, HP},
title = {Acculturative stress, telomere length, and postpartum depression in Latinx mothers.},
journal = {Journal of psychiatric research},
volume = {147},
number = {},
pages = {301-306},
pmid = {35123339},
issn = {1879-1379},
support = {K23 NR017898/NR/NINR NIH HHS/United States ; UL1 TR001111/TR/NCATS NIH HHS/United States ; },
mesh = {Acculturation ; Adult ; Depression/psychology ; *Depression, Postpartum/epidemiology/genetics ; Female ; Hispanic or Latino ; Humans ; Mothers/psychology ; Pregnancy ; Stress, Psychological ; Telomere ; Telomere Shortening ; United States/epidemiology ; },
abstract = {Latinx mothers in the United States are highly vulnerable to psychosocial stressors, including discrimination and acculturative stress, which increase maternal health risks. Previous work in Latinx mothers indicates that prenatal discrimination influences epigenetic immune markers that may increase risk for postpartum depression. Discrimination and acculturative stress have also been linked to cellular aging, including telomere degradation, in Hispanic populations broadly, but not in this particularly vulnerable population. The present work addressed this gap in a sample of 150 Latinx mothers living in the United States (mean age 27.6 years). Psychosocial measures (including discrimination, stress, and mental health) and blood were collected at 24-32 weeks gestation. Psychosocial measures were re-evaluated at 4-6 weeks postpartum. First, we examined the relationship between maternal prenatal cultural stress (i.e., discrimination and acculturative stress) and telomere length (TL). Second, we tested whether TL predicted postpartum depression. Acculturative stress - but not discrimination - predicted shorter TL, especially among participants with high methylation of the FOXP3 promoter region. Further, shorter telomere measures during pregnancy predicted greater postpartum depression symptom severity. TL was not related to any sociodemographic characteristics such as age, income, country of origin, or years in the United States. These results highlight the uniquely impactful role of acculturative stress on Latinx maternal health and the potential interactive role of telomere length and epigenetic immune alterations in risk for maternal mental health concerns.},
}
@article {pmid35122449,
year = {2022},
author = {Marasco, V and Smith, S and Angelier, F},
title = {How does early-life adversity shape telomere dynamics during adulthood? Problems and paradigms.},
journal = {BioEssays : news and reviews in molecular, cellular and developmental biology},
volume = {44},
number = {4},
pages = {e2100184},
doi = {10.1002/bies.202100184},
pmid = {35122449},
issn = {1521-1878},
support = {M 2520/FWF_/Austrian Science Fund FWF/Austria ; },
mesh = {*Adverse Childhood Experiences ; Longevity ; Telomere/genetics ; *Telomere Shortening ; Humans ; Animals ; *Stress, Physiological ; },
abstract = {Although early-life adversity has been associated with negative consequences during adulthood, growing evidence shows that such adversity can also lead to subsequent stress resilience and positive fitness outcomes. Telomere dynamics are relevant in this context because of the link with developmental conditions and longevity. However, few studies have assessed whether the effects of early-life adversity on developmental telomere dynamics may relate to adult telomere dynamics. We propose that the potential links between early-life adversity and adult telomere dynamics could be driven by developmental constraints (the Constraint hypothesis), by the nature/severity of developmental adversity (the Resilience hypothesis), or by developmental-mediated changes in individual life-history strategies (the Pace of Life hypothesis). We discuss these non-mutually exclusive hypotheses, explore future research directions, and propose specific studies to test these hypotheses. Our article aims to expand our understanding of the evolutionary role of developmental conditions on adult telomere dynamics, stress resilience and ageing.},
}
@article {pmid35119008,
year = {2022},
author = {Ngwa, NE and Peer, N and Matsha, TE and de Villiers, A and Sobngwi, E and Kengne, AP},
title = {Associations of leucocyte telomere length with cardio-metabolic risk profile in a South African HIV-infected population.},
journal = {Medicine},
volume = {101},
number = {5},
pages = {e28642},
pmid = {35119008},
issn = {1536-5964},
support = {Hypertension Grant #0169-04//Grand Challenges Canada/ ; Hypertension Grant #0169-04//South African Medical Research Council/ ; },
mesh = {Adult ; Cholesterol ; Cross-Sectional Studies ; *Diabetes Mellitus/epidemiology/genetics ; Female ; *HIV Infections/epidemiology ; Heart Disease Risk Factors ; Humans ; *Hypertension/epidemiology/genetics ; Leukocytes ; Male ; *Obesity/epidemiology/genetics ; Prospective Studies ; South Africa/epidemiology ; *Telomere/genetics ; Telomere Shortening ; },
abstract = {Leukocyte Telomere length (LTL) is an independent predictor of cardio-metabolic diseases (CMDs) and Human Immuno Virus (HIV) infection. However, studies are lacking on the association between LTL with CMD profile in people with HIV. Accordingly, we investigated the association between LTL and CMD profile in HIV-infected adult South Africans.This cross-sectional study included 728 HIV patients (20.6% men; median age 38 years) recruited across 17 public healthcare facilities in Cape Town. CMD markers were compared across quartiles of LTL, and spearman correlations assessed the continuous association of LTL with CMD markers. Linear and logistic regressions were then used to relate LTL with CMD risk profile, with appropriate adjustment for confounders.The prevalence of obesity, hypertension and diabetes were 34.8%, 36.8%, and 8.4%, respectively. In age, sex and body mass index adjusted models, increasing Log10LTL was associated with decreasing systolic (β = -10.52) and diastolic (β = -6.74) blood pressures, HOMA-β (β = -70.72), increasing total cholesterol (β = 0.544), non-high-density lipoprotein cholesterol (β = 0.472), and waist-to-height-ratio > 0.5 (odds ratio [OR] = 5.67), all P < .05. Compared to those in the bottom quarter, those in the top LTL quarter had lower prevalence of hypertension (OR = 0.65), and higher prevalence of total cholesterol > 5 mmol/L (OR = 1.94), and low-density lipoprotein-cholesterol > 3 mmol/L (OR = 1.62), all P < .05. LTL was not associated with diabetes nor general obesity. It was associated with Alanine Transaminase (ALT) and heart rate in univariable analyses.LTL shortening was associated with some CMD risk factors in HIV-infected adults on anti-retroviral therapy in South Africa. Prospective research is needed to explore the direction and implications of these associations.},
}
@article {pmid35116600,
year = {2021},
author = {Ye, X and Li, J and Song, C and Chen, W},
title = {Telomere in colorectal cancer associated with distant metastases and predicted a poor prognosis.},
journal = {Translational cancer research},
volume = {10},
number = {6},
pages = {2906-2917},
pmid = {35116600},
issn = {2219-6803},
abstract = {BACKGROUND: Telomere is essential for chromosomal stability and its length has been proven to be related to prognosis in many malignant tumors. This study aims to investigate the relevance of telomere length with clinical and pathologic features and its prognostic value in colorectal cancer (CRC).<br><br>METHODS: Telomere status of CRC and adenoma cells were measured by telomere-specific quantitative fluorescent in situ hybridization (Q-FISH). The relative telomere length (RTL) was calculated as the mean telomere fluorescent intensity units (TFUs) in carcinoma cell divided by the TFU in cancer-associated fibroblast cell (CAF).<br><br>RESULTS: One hundred CRC patients, who were received surgery treatment during 2013 to 2014 and fifty-seven patients who underwent the examination of colonoscope and were confirmed as adenoma were enrolled. TFUs of carcinoma cell and CAF were statistically significantly lower than in adjacent mucosa cell (P=0.0079). Although there was no difference between the three kinds of adenoma cells (P=0.5457), TFU in adenoma cells was significantly lower than in CAF (P<0.0001) and independent with age. TFU and the RTL were statistically significantly lower in adenoma cells than in carcinoma (all P<0.0001). TFU of carcinoma cell in distant metastases patients were significantly lower than that without distant metastases patients (P=0.002). When cut by the median value of TFU of carcinoma cell and RTL, patients with a lower TFU or RTL had statistically significantly poorer overall survival (OS) (P=0.0027, HR: 4.6, 95% CI: 1.9-11.0; P=0.0163, HR: 2.95, 95% CI: 1.22-7.12) and disease-free survival (DFS) (P=0.0057, HR: 3.14, 95% CI: 1.40-7.06; P=0.0271, HR: 2.49, 95% CI: 1.11-5.59, respectively) than those patients with higher TFU or RTL. On multivariate analysis, the TFU of carcinoma cell was proved to be an independent prognostic value both for OS and DFS (P=0.0005, HR: 4.975, 95% CI: 1.616-15.385; P=0.007, HR: 3.57, 95% CI: 1.410-9.010).<br><br>CONCLUSIONS: The length of telomere in carcinoma and adenoma cells were consistently shorter and the telomere changes were early carcinogenesis event, even the epithelial cells were morphologically not malignant. The length of telomere was associated with tumor metastases and prognosis, suggesting telomere probably was an important cue of the biological behavior of CRC.},
}
@article {pmid35115918,
year = {2021},
author = {Gao, X and Kong, Y and Li, S and Dong, S and Huang, X and Qi, D and Zhang, T and Yan, Y and Chen, W},
title = {Intermediate Effects of Body Mass Index and C-Reactive Protein on the Serum Cotinine- Leukocyte Telomere Length Association.},
journal = {Frontiers in aging neuroscience},
volume = {13},
number = {},
pages = {827465},
pmid = {35115918},
issn = {1663-4365},
abstract = {We aimed to examine the association between serum cotinine and leukocyte telomere length (LTL) and the intermediate effects of body mass index (BMI) and C-reactive protein (CRP) on modulating the association. This study included 4,047 adults from the 1999 to 2002 National Health and Nutrition Examination Survey. In the combined sample, after adjusting for age, race, sex, physical activity, and alcohol use, the total effect of serum cotinine on LTL was significant (standardized regression coefficient, β = -0.049, p = 0.001) without BMI and CRP included in the model. With inclusion of BMI but without CRP in the model, the direct effect of cotinine on LTL in its absolute value increased to β = -0.053 (p < 0.001), and the suppression effect of BMI was estimated at 8.8%. With inclusion of CRP but without BMI in the model, the direct effect of cotinine on LTL in its absolute value decreased to β = -0.040 (p = 0.008), and the mediation effect of CRP was estimated at 16.9%. With inclusion of both BMI and CRP in the model, BMI and CRP still had significant suppression and mediation effects, respectively, on the cotinine-LTL association. These findings suggest that weight and inflammation have different roles in the inverse association between serum cotinine and LTL.},
}
@article {pmid35115336,
year = {2022},
author = {Putman, RK and Axelsson, GT and Ash, SY and Sanders, JL and Menon, AA and Araki, T and Nishino, M and Yanagawa, M and Gudmundsson, EF and Qiao, D and San José Estépar, R and Dupuis, J and O'Connor, GT and Rosas, IO and Washko, GR and El-Chemaly, S and Raby, BA and Gudnason, V and DeMeo, DL and Silverman, EK and Hatabu, H and De Vivo, I and Cho, MH and Gudmundsson, G and Hunninghake, GM},
title = {Interstitial lung abnormalities are associated with decreased mean telomere length.},
journal = {The European respiratory journal},
volume = {60},
number = {2},
pages = {},
pmid = {35115336},
issn = {1399-3003},
support = {R01 HL122464/HL/NHLBI NIH HHS/United States ; R01 HL149877/HL/NHLBI NIH HHS/United States ; T32 HL007633/HL/NHLBI NIH HHS/United States ; R01 HL130974/HL/NHLBI NIH HHS/United States ; R21 HL140422/HL/NHLBI NIH HHS/United States ; R01 HL147148/HL/NHLBI NIH HHS/United States ; R01 HL116473/HL/NHLBI NIH HHS/United States ; R01 HL135142/HL/NHLBI NIH HHS/United States ; R01 HL137927/HL/NHLBI NIH HHS/United States ; K01 HL129039/HL/NHLBI NIH HHS/United States ; 75N92019D00031/HL/NHLBI NIH HHS/United States ; U01 HL089897/HL/NHLBI NIH HHS/United States ; U01 HL133232/HL/NHLBI NIH HHS/United States ; K08 HL140087/HL/NHLBI NIH HHS/United States ; R01 HL111024/HL/NHLBI NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; N01HC25195/HL/NHLBI NIH HHS/United States ; K08 HL145118/HL/NHLBI NIH HHS/United States ; R01 CA203636/CA/NCI NIH HHS/United States ; U01 CA209414/CA/NCI NIH HHS/United States ; P01 HL132825/HL/NHLBI NIH HHS/United States ; R01 HL149861/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; Lung ; *Lung Diseases, Interstitial/epidemiology/genetics ; *Pulmonary Disease, Chronic Obstructive ; Telomere/genetics ; Tomography, X-Ray Computed ; },
abstract = {BACKGROUND: Interstitial lung abnormalities (ILA) share many features with idiopathic pulmonary fibrosis; however, it is not known if ILA are associated with decreased mean telomere length (MTL).<br><br>METHODS: Telomere length was measured with quantitative PCR in the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) and Age Gene/Environment Susceptibility Reykjavik (AGES-Reykjavik) cohorts and Southern blot analysis was used in the Framingham Heart Study (FHS). Logistic and linear regression were used to assess the association between ILA and MTL; Cox proportional hazards models were used to assess the association between MTL and mortality.<br><br>RESULTS: In all three cohorts, ILA were associated with decreased MTL. In the COPDGene and AGES-Reykjavik cohorts, after adjustment there was greater than twofold increase in the odds of ILA when comparing the shortest quartile of telomere length to the longest quartile (OR 2.2, 95% CI 1.5-3.4, p=0.0001, and OR 2.6, 95% CI 1.4-4.9, p=0.003, respectively). In the FHS, those with ILA had shorter telomeres than those without ILA (-767&#x2005;bp, 95% CI 76-1584&#x2005;bp, p=0.03). Although decreased MTL was associated with chronic obstructive pulmonary disease (OR 1.3, 95% CI 1.1-1.6, p=0.01) in COPDGene, the effect estimate was less than that noted with ILA. There was no consistent association between MTL and risk of death when comparing the shortest quartile of telomere length in COPDGene and AGES-Reykjavik (HR 0.82, 95% CI 0.4-1.7, p=0.6, and HR 1.2, 95% CI 0.6-2.2, p=0.5, respectively).<br><br>CONCLUSION: ILA are associated with decreased MTL.},
}
@article {pmid35114947,
year = {2022},
author = {Olbertova, H and Plevova, K and Pavlova, S and Malcikova, J and Kotaskova, J and Stranska, K and Spunarova, M and Trbusek, M and Navrkalova, V and Dvorackova, B and Tom, N and Pal, K and Jarosova, M and Brychtova, Y and Panovska, A and Doubek, M and Pospisilova, S},
title = {Evolution of TP53 abnormalities during CLL disease course is associated with telomere length changes.},
journal = {BMC cancer},
volume = {22},
number = {1},
pages = {137},
pmid = {35114947},
issn = {1471-2407},
support = {MH-CZ RVO 65269705//Ministerstvo Zdravotnictv&#xed; Cesk&#xe9; Republiky/ ; AZV NU21-08-00237//Ministerstvo Zdravotnictv&#xed; Cesk&#xe9; Republiky/ ; AZV NV19-03-00091//Ministerstvo Zdravotnictv&#xed; Cesk&#xe9; Republiky/ ; GACR 19-15737S//Grantov&#xe1; Agentura &#x10c;esk&#xe9; Republiky/ ; GACR 19-11299S//Grantov&#xe1; Agentura &#x10c;esk&#xe9; Republiky/ ; LM2018132//Technologick&#xe1; Agentura &#x10c;esk&#xe9; Republiky/ ; LM2018133//Technologick&#xe1; Agentura &#x10c;esk&#xe9; Republiky/ ; CZ.02.1.01/0.0/0.0/18_046/0015515//Ministerstvo &#x160;kolstv&#xed;, Ml&#xe1;de&#x17e;e a T&#x11b;lov&#xfd;chovy/ ; },
mesh = {Clonal Evolution/*genetics ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/*genetics ; Male ; Middle Aged ; Mutation ; Proto-Oncogene Proteins c-bcr/metabolism ; Signal Transduction ; Telomerase/genetics ; Telomere/*ultrastructure ; Tumor Suppressor Protein p53/*genetics ; },
abstract = {BACKGROUND: Telomeres are protective structures at chromosome ends which shorten gradually with increasing age. In chronic lymphocytic leukemia (CLL), short telomeres have been associated with unfavorable disease outcome, but the link between clonal evolution and telomere shortening remains unresolved.<br><br>METHODS: We investigated relative telomere length (RTL) in a well-characterized cohort of 198 CLL patients by qPCR and focused in detail on a subgroup 26 patients who underwent clonal evolution of TP53 mutations (evolTP53). In the evolTP53 subgroup we explored factors influencing clonal evolution and corresponding changes in telomere length through measurements of telomerase expression, lymphocyte doubling time, and BCR signaling activity.<br><br>RESULTS: At baseline, RTL of the evolTP53 patients was scattered across the entire RTL spectrum observed in our CLL cohort. RTL changed in the follow-up samples of 16/26 (62%) evolTP53 cases, inclining to reach intermediate RTL values, i.e., longer telomeres shortened compared to baseline while shorter ones prolonged. For the first time we show that TP53 clonal shifts are linked to RTL change, including unexpected RTL prolongation. We further investigated parameters associated with RTL changes. Unstable telomeres were significantly more frequent among younger patients (P&#x2009;=&#x2009;0.032). Shorter telomeres were associated with decreased activity of the B-cell receptor signaling components p-ERK1/2, p-ZAP-70/SYK, and p-NF&#x3ba;B (P&#x2009;=&#x2009;0.04, P&#x2009;=&#x2009;0.01, and P&#x2009;=&#x2009;0.02, respectively).<br><br>CONCLUSIONS: Our study revealed that changes of telomere length reflect evolution in leukemic subclone proportion, and are associated with specific clinico-biological features of the explored cohort.},
}
@article {pmid35101395,
year = {2022},
author = {Niu, Z and Wen, X and Wang, M and Tian, L and Mu, L},
title = {Personal exposure to benzene, toluene, ethylbenzene, and xylenes (BTEXs) mixture and telomere length: a cross-sectional study of the general US adult population.},
journal = {Environmental research},
volume = {209},
number = {},
pages = {112810},
doi = {10.1016/j.envres.2022.112810},
pmid = {35101395},
issn = {1096-0953},
support = {UL1 TR001412/TR/NCATS NIH HHS/United States ; R21 HD091515/HD/NICHD NIH HHS/United States ; },
mesh = {Adult ; Bayes Theorem ; *Benzene/analysis/toxicity ; Benzene Derivatives/toxicity ; Cross-Sectional Studies ; Humans ; Middle Aged ; Nutrition Surveys ; Telomere ; Toluene/analysis ; *Xylenes/analysis/toxicity ; Young Adult ; },
abstract = {BACKGROUND: Benzene, Toluene, Ethylbenzene, and Xylenes (BTEXs) are a group of aromatic air pollutants from fossil fuels. There is no research on associations of the BTEXs mixture with telomere length (TL), a marker of cellular aging, in the general population.<br><br>METHODS: We analyzed a subsample of 549 US adults aged 20-59 years from the National Health and Nutrition Examination Survey 1999-2000. BTEXs samples were collected by passive exposure badges worn by participants for 48-72&#xa0;h. Levels of BTEXs were measured with gas chromatography/mass spectrometry. Leukocyte TL was measured with qPCR. We used Bayesian Kernel Machine Regression (BKMR) to examine the effect of the BTEXs mixture on TL adjusting for potential confounders. Analyses were stratified by tobacco smoking status (serum cotinine&#x2265;10&#xa0;ng/mL vs. <10&#xa0;ng/mL).<br><br>RESULTS: Levels of personal exposure to BTEXs were detectable in most participants and were relatively higher in the 150 smokers than in the 399 nonsmokers. The BTEXs were moderately or strongly intercorrelated (0.5&#xa0;<&#xa0;r&#xa0;&#x2264;&#xa0;0.9, P&#xa0;<&#xa0;0.05). All chemicals had weak, inverse correlations with TL (-0.1<r&#xa0;<&#xa0;0, P&#xa0;>&#xa0;0.05). In BKMR models among the nonsmokers, the BTEXs mixture was significantly inversely associated with TL at a low range of the BTEXs (20th-65th percentile) but was not associated with TL at a higher range (>65th percentile). Also, we found a U-shape association of benzene and a positive association of ethylbenzene with TL independent of other BTEXs. Among smokers, neither the BTEXs mixture nor any individual BTEXs were significantly associated with TL.<br><br>CONCLUSION: Within a low-to-middle range, exposure to the BTEXs mixture may be associated with shorter telomere length in the general nonsmoking population.},
}
@article {pmid35100428,
year = {2022},
author = {Ceschi, S and Berselli, M and Cozzaglio, M and Giantin, M and Toppo, S and Spolaore, B and Sissi, C},
title = {Vimentin binds to G-quadruplex repeats found at telomeres and gene promoters.},
journal = {Nucleic acids research},
volume = {50},
number = {3},
pages = {1370-1381},
pmid = {35100428},
issn = {1362-4962},
mesh = {*G-Quadruplexes ; Guanine/chemistry ; Intermediate Filaments ; *Promoter Regions, Genetic ; Telomere/*metabolism ; Vimentin/*metabolism ; },
abstract = {G-quadruplex (G4) structures that can form at guanine-rich genomic sites, including telomeres and gene promoters, are actively involved in genome maintenance, replication, and transcription, through finely tuned interactions with protein networks. In the present study, we identified the intermediate filament protein Vimentin as a binder with nanomolar affinity for those G-rich sequences that give rise to at least two adjacent G4 units, named G4 repeats. This interaction is supported by the N-terminal domains of soluble Vimentin tetramers. The selectivity of Vimentin for G4 repeats versus individual G4s provides an unprecedented result. Based on GO enrichment analysis performed on genes having putative G4 repeats within their core promoters, we suggest that Vimentin recruitment at these sites may contribute to the regulation of gene expression during cell development and migration, possibly by reshaping the local higher-order genome topology, as already reported for lamin B.},
}
@article {pmid35098380,
year = {2022},
author = {Wang, LN and Wang, L and Cheng, G and Dai, M and Yu, Y and Teng, G and Zhao, J and Xu, D},
title = {The association of telomere maintenance and TERT expression with susceptibility to human papillomavirus infection in cervical epithelium.},
journal = {Cellular and molecular life sciences : CMLS},
volume = {79},
number = {2},
pages = {110},
pmid = {35098380},
issn = {1420-9071},
support = {ZR201702160271//Natural Science Foundation of Shandong Province/ ; },
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Epithelium/metabolism/virology ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease/*genetics ; HeLa Cells ; Humans ; Middle Aged ; Papillomavirus Infections/complications/*genetics/virology ; Polymorphism, Single Nucleotide ; Telomerase/*genetics/metabolism ; Telomere/enzymology/*genetics ; Uterine Cervical Neoplasms/complications/*genetics/metabolism ; Young Adult ; },
abstract = {The role of telomerase reverse transcriptase (TERT) induction and telomere maintenance in carcinogenesis including cervical cancer (CC) pathogenesis has been well established. However, it remains unclear whether they affect infection of high-risk human papillomavirus (hrHPV), an initiating event for CC development. Similarly, genetic variants at the TERT locus are shown to be associated with susceptibility to CC, but it is unclear whether these SNPs modify the risk for cervical HPV infection. Here we show that in CC-derived HeLa cells, TERT overexpression inhibits, while its depletion upregulates expression of Syndecan-1 (SDC-1), a key component for HPV entry receptors. The TCGA cohort of CC analyses reveals an inverse correlation between TERT and SDC-1 expression (R = -0.23, P = 0.001). We further recruited 1330 females (520 non-HPV and 810 hrHPV-infected) without CC or high-grade cervical intraepithelial neoplasia to analyze telomeres in cervical epithelial cells and SNPs at rs2736098, rs2736100 and rs2736108, previously identified TERT SNPs for CC risk. Non-infected females exhibited age-related telomere shortening in cervical epithelial cells and their telomeres were significantly longer than those in hrHPV-infected group (1.31 ± 0.62 vs 1.19 ± 0.48, P < 0.001). There were no differences in rs2736098 and rs2736100 genotypes, but non-infected individuals had significantly a higher C-allele frequency (associated with higher TERT expression) while lower T-allele levels at rs2736108 compared with those in the hrHPV group (P = 0.020). Collectively, appropriate telomere maintenance and TERT expression in normal cervical cells may prevent CC by modulating hrHPV infection predisposition, although they are required for CC development and progression.},
}
@article {pmid35097237,
year = {2022},
author = {Dorgaleleh, S and Naghipoor, K and Hajimohammadi, Z and Dastaviz, F and Oladnabi, M},
title = {Molecular insight of dyskeratosis congenita: Defects in telomere length homeostasis.},
journal = {Journal of clinical and translational research},
volume = {8},
number = {1},
pages = {20-30},
pmid = {35097237},
issn = {2424-810X},
abstract = {BACKGROUND: Dyskeratosis congenita (DC) is a rare disease and is a heterogenous disorder, with its inheritance patterns as autosomal dominant, autosomal recessive, and X-linked recessive. This disorder occurs due to faulty maintenance of telomeres in stem cells. This congenital condition is diagnosed with three symptoms: oral leukoplakia, nail dystrophy, and abnormal skin pigmentation. However, because it has a wide range of symptoms, it may have phenotypes similar to other diseases. For this reason, it is necessary to use methods of measuring the Telomere Length (TL) and determining the shortness of the telomere in these patients so that it can be distinguished from other diseases. Today, the Next Generation Sequencing technique accurately detects mutations in the target genes.<br><br>AIM: This work aims to review and summarize how each of the DC genes is involved in TL, and how to diagnose and differentiate the disease using clinical signs and methods to measure TL. It also offers treatments for DC patients, such as Hematopoietic Stem Cell Transplantation and Androgen therapy.<br><br>RELEVANCE FOR PATIENTS: In DC patients, the genes involved in telomere homeostasis are mutated. Because these patients may have an overlapping phenotype with other diseases, it is best to perform whole-exome sequencing after genetics counseling to find the relevant mutation. As DC is a multi-systemic disease, we need to monitor patients frequently through annual lung function tests, ultrasounds, gynecological examinations, and skin examinations.},
}
@article {pmid35092358,
year = {2022},
author = {Shinko, Y and Okazaki, S and Otsuka, I and Horai, T and Kim, S and Tanifuji, T and Hishimoto, A},
title = {Accelerated epigenetic age and shortened telomere length based on DNA methylation in Nicolaides-Baraitser syndrome.},
journal = {Molecular genetics &amp; genomic medicine},
volume = {10},
number = {3},
pages = {e1876},
pmid = {35092358},
issn = {2324-9269},
mesh = {*DNA Methylation ; Epigenesis, Genetic ; Facies ; Foot Deformities, Congenital ; Humans ; Hypotrichosis ; Intellectual Disability ; Telomere/genetics ; *Telomere Shortening ; },
abstract = {BACKGROUND: Nicolaides-Baraitser syndrome (NCBRS) is a rare disorder characterized by neurodevelopmental delays, seizures, and diverse physical characteristics. The DNA methylation (DNAm) profile in NCBRS is significantly different. DNAm is linked to the biological aging of cells and the health risks associated with biological aging. In this study, we examined changes in biological ages in NCBRS to provide insights into the prognosis and health risks of NCBRS.<br><br>METHODS: We used a publicly available dataset to examine biological aging in NCBRS using DNAm-based epigenetic ages, such as PhenoAge and GrimAge, as well as DNAm-based estimator of telomere length (DNAmTL). We investigated 12 cases, clinically diagnosed as NCBRS, and 27 controls.<br><br>RESULTS: Compared to controls, NCBRS cases exhibited significantly accelerated PhenoAge and GrimAge as well as significantly shortened DNAmTL.<br><br>CONCLUSION: These results suggest an acceleration of biological aging in NCBRS and provide insights into the prognosis and health risks of NCBRS.},
}
@article {pmid35088059,
year = {2021},
author = {Heard, E and Johnson, AD and Korbel, JO and Lee, C and Snyder, MP and Sturgill, D},
title = {The X chromosome from telomere to telomere: key achievements and future opportunities.},
journal = {Faculty reviews},
volume = {10},
number = {},
pages = {63},
pmid = {35088059},
issn = {2732-432X},
abstract = {While the human genome represents the most accurate vertebrate reference assembly to date, it still contains numerous gaps, including centromeric and other large repeat-containing regions - often termed the "dark side" of the genome - many of which are of fundamental biological importance. Miga et al.[1,2] present the first gapless assembly of the human X chromosome, with the help of ultra-long-read nanopore reads generated for the haploid complete hydatidiform mole (CHM13) genome. They reconstruct the ~3.1 megabase centromeric satellite DNA array and map DNA methylation patterns across complex tandem repeats and satellite arrays. This Telomere-to-Telomere assembly provides a superior human X chromosome reference enabling future sex-determination and X-linked disease research, and provides a path towards finishing the entire human genome sequence.},
}
@article {pmid35086525,
year = {2022},
author = {Usategui, A and Municio, C and Arias-Salgado, EG and Martín, M and Fernández-Varas, B and Del Rey, MJ and Carreira, P and González, A and Criado, G and Perona, R and Pablos, JL},
title = {Evidence of telomere attrition and a potential role for DNA damage in systemic sclerosis.},
journal = {Immunity &amp; ageing : I &amp; A},
volume = {19},
number = {1},
pages = {7},
pmid = {35086525},
issn = {1742-4933},
support = {PI19/01129//Instituto de Salud Carlos III/ ; RD16/0012 RETICS program//Instituto de Salud Carlos III/ ; },
abstract = {BACKGROUND: To investigate the role of cell senescence in systemic sclerosis (SSc), we analyzed telomere shortening (TS) in SSc patients and the effect of targeting DNA damage in the bleomycin model of skin fibrosis.<br><br>RESULTS: Telomere length (TL) in blood leukocytes of 174 SSc patients and 68 healthy controls was measured by Southern blot, and we found shorter age-standardized TL in SSc patients compared to healthy controls. TL was shorter in SSc patients with ILD compared to those without ILD and in anti-topoisomerase I positive compared to anti-centromere positive patients. To analyze the potential role of DNA damage in skin fibrosis, we evaluated the effects of the DNA protective GSE4 peptide in the bleomycin mouse model of scleroderma and the fibrotic response of cultured human dermal fibroblasts. Administration of GSE4-nanoparticles attenuated bleomycin-induced skin fibrosis as measured by Masson's staining of collagen and reduced Acta2 and Ctgf mRNA expression, whereas transduction of dermal fibroblasts with a lentiviral GSE4 expression vector reduced COL1A1, ACTA2 and CTGF gene expression after stimulation with bleomycin or TGF-&#x3b2;, in parallel to a reduction of the phospho-histone H2A.X marker of DNA damage.<br><br>CONCLUSIONS: SSc is associated with TS, particularly in patients with lung disease or anti-topoisomerase I antibodies. Administration of GSE4 peptide attenuated experimental skin fibrosis and reduced fibroblast expression of profibrotic factors, supporting a role for oxidative DNA damage in scleroderma.},
}
@article {pmid35085380,
year = {2022},
author = {Cheng, F and Luk, AO and Shi, M and Huang, C and Jiang, G and Yang, A and Wu, H and Lim, CKP and Tam, CHT and Fan, B and Lau, ESH and Ng, ACW and Wong, KK and Carroll, L and Lee, HM and Kong, AP and Keech, AC and Chow, E and Joglekar, MV and Tsui, SKW and So, WY and So, HC and Hardikar, AA and Jenkins, AJ and Chan, JCN and Ma, RCW},
title = {Shortened Leukocyte Telomere Length Is Associated With Glycemic Progression in Type 2 Diabetes: A Prospective and Mendelian Randomization Analysis.},
journal = {Diabetes care},
volume = {45},
number = {3},
pages = {701-709},
pmid = {35085380},
issn = {1935-5548},
mesh = {Cohort Studies ; *Diabetes Mellitus, Type 2/genetics ; Humans ; Leukocytes ; Mendelian Randomization Analysis ; Middle Aged ; Prospective Studies ; Telomere/genetics ; Telomere Shortening ; },
abstract = {OBJECTIVE: Several studies support associations between relative leukocyte telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates the relationship between rLTL and the risk of glycemic progression in patients with type 2 diabetes.<br><br>RESEARCH DESIGN AND METHODS: In this cohort study, consecutive Chinese patients with type 2 diabetes (N = 5,506) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using quantitative PCR. Glycemic progression was defined as the new need for exogenous insulin.<br><br>RESULTS: The mean (SD) age of the 5,349 subjects was 57.0 (13.3) years, and mean (SD) follow-up was 8.8 (5.4) years. Baseline rLTL was significantly shorter in the 1,803 subjects who progressed to insulin requirement compared with the remaining subjects (4.43 &#xb1; 1.16 vs. 4.69 &#xb1; 1.20). Shorter rLTL was associated with a higher risk of glycemic progression (hazard ratio [95% CI] for each unit decrease [to &#x223c;0.2 kilobases]: 1.10 [1.06-1.14]), which remained significant after adjusting for confounders. Baseline rLTL was independently associated with glycemic exposure during follow-up (&#x3b2; = -0.05 [-0.06 to -0.04]). Each 1-kilobase decrease in absolute LTL was on average associated with a 1.69-fold higher risk of diabetes progression (95% CI 1.35-2.11). Two-sample Mendelian randomization analysis showed per 1-unit genetically decreased rLTL was associated with a 1.38-fold higher risk of diabetes progression (95% CI 1.12-1.70).<br><br>CONCLUSIONS: Shorter rLTL was significantly associated with an increased risk of glycemic progression in individuals with type 2 diabetes, independent of established risk factors. Telomere length may be a useful biomarker for glycemic progression in people with type 2 diabetes.},
}
@article {pmid35081355,
year = {2022},
author = {Zhang, K and Tarczykowska, A and Gupta, DK and Pendlebury, DF and Zuckerman, C and Nandakumar, J and Shibuya, H},
title = {The TERB1 MYB domain suppresses telomere erosion in meiotic prophase I.},
journal = {Cell reports},
volume = {38},
number = {4},
pages = {110289},
pmid = {35081355},
issn = {2211-1247},
support = {R01 GM120094/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Female ; Humans ; Male ; Meiotic Prophase I/*physiology ; Mice ; Mice, Inbred C57BL ; Protein Domains ; Telomere/*metabolism ; Telomere-Binding Proteins/*chemistry/*metabolism ; },
abstract = {The meiosis-specific telomere-binding protein TERB1 anchors telomeres to the nuclear envelope and drives chromosome movements for the pairing of homologous chromosomes. TERB1 has an MYB-like DNA-binding (MYB) domain, which is a hallmark of telomeric DNA-binding proteins. Here, we demonstrate that the TERB1 MYB domain has lost its canonical DNA-binding activity. The analysis of Terb1 point mutant mice expressing TERB1 lacking its MYB domain showed that the MYB domain is dispensable for telomere localization of TERB1 and the downstream TERB2-MAJIN complex, the promotion of homologous pairing, and even fertility. Instead, the TERB1 MYB domain regulates the enrichment of cohesin and promotes the remodeling of axial elements in the early-to-late pachytene transition, which suppresses telomere erosion. Considering its conservation across metazoan phyla, the TERB1 MYB domain is likely to be important for the maintenance of telomeric DNA and thus for genomic integrity by suppressing meiotic telomere erosion over long evolutionary timescales.},
}
@article {pmid35080073,
year = {2022},
author = {Salmón, P and Burraco, P},
title = {Telomeres and anthropogenic disturbances in wildlife: A systematic review and meta-analysis.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6018-6039},
pmid = {35080073},
issn = {1365-294X},
mesh = {Animals ; Humans ; *Animals, Wild/genetics ; *Telomere Shortening ; Anthropogenic Effects ; Telomere/genetics ; Biological Evolution ; },
abstract = {Human-driven environmental changes are affecting wildlife across the globe. These challenges do not influence species or populations to the same extent and therefore a comprehensive evaluation of organismal health is needed to determine their ultimate impact. Evidence suggests that telomeres (the terminal chromosomal regions) are sensitive to environmental conditions and have been posited as a surrogate for animal health and fitness. Evaluation of their use in an applied ecological context is still scarce. Here, using information from molecular and occupational biomedical studies, we aim to provide ecologists and evolutionary biologists with an accessible synthesis of the links between human disturbances and telomere length. In addition, we perform a systematic review and meta-analysis on studies measuring telomere length in wild/wild-derived animals facing anthropogenic disturbances. Despite the relatively small number of studies to date, our meta-analysis revealed a significant small negative association between disturbances and telomere length (-0.092 [-0.153, -0.031]; n = 28; k = 159). Yet, our systematic review suggests that the use of telomeres as a biomarker to understand the anthropogenic impact on wildlife is limited. We propose some research avenues that will help to broadly evaluate their suitability: (i) further causal studies on the link between human disturbances and telomeres; (ii) investigating the organismal implications, in terms of fitness and performance, of a given telomere length in anthropogenically disturbed scenarios; and (iii) better understanding of the underlying mechanisms of telomere dynamics. Future studies in these facets will help to ultimately determine their role as markers of health and fitness in wildlife facing anthropogenic disturbances.},
}
@article {pmid35079641,
year = {2022},
author = {Karlsen, TR and Olsen, MB and Kong, XY and Yang, K and Quiles-Jiménez, A and Kroustallaki, P and Holm, S and Lines, GT and Aukrust, P and Skarpengland, T and Bjørås, M and Dahl, TB and Nilsen, H and Gregersen, I and Halvorsen, B},
title = {NEIL3-deficient bone marrow displays decreased hematopoietic capacity and reduced telomere length.},
journal = {Biochemistry and biophysics reports},
volume = {29},
number = {},
pages = {101211},
pmid = {35079641},
issn = {2405-5808},
abstract = {Deficiency of NEIL3, a DNA repair enzyme, has significant impact on mouse physiology, including vascular biology and gut health, processes related to aging. Leukocyte telomere length (LTL) is suggested as a marker of biological aging, and shortened LTL is associated with increased risk of cardiovascular disease. NEIL3 has been shown to repair DNA damage in telomere regions in vitro. Herein, we explored the role of NEIL3 in telomere maintenance in vivo by studying bone marrow cells from atherosclerosis-prone NEIL3-deficient mice. We found shortened telomeres and decreased activity of the telomerase enzyme in bone marrow cells derived from Apoe [-/-] Neil3 [-/-] as compared to Apoe [-/-] mice. Furthermore, Apoe [-/-] Neil3 [-/-] mice had decreased leukocyte levels as compared to Apoe [-/-] mice, both in bone marrow and in peripheral blood. Finally, RNA sequencing of bone marrow cells from Apoe [-/-] Neil3 [-/-] and Apoe [-/-] mice revealed different expression levels of genes involved in cell cycle regulation, cellular senescence and telomere protection. This study points to NEIL3 as a telomere-protecting protein in murine bone marrow in vivo.},
}
@article {pmid35077681,
year = {2022},
author = {Jack, A and Kim, Y and Strom, AR and Lee, DSW and Williams, B and Schaub, JM and Kellogg, EH and Finkelstein, IJ and Ferro, LS and Yildiz, A and Brangwynne, CP},
title = {Compartmentalization of telomeres through DNA-scaffolded phase separation.},
journal = {Developmental cell},
volume = {57},
number = {2},
pages = {277-290.e9},
pmid = {35077681},
issn = {1878-1551},
support = {R35 GM136414/GM/NIGMS NIH HHS/United States ; T32 GM007388/GM/NIGMS NIH HHS/United States ; R01 GM120554/GM/NIGMS NIH HHS/United States ; U01 DA040601/DA/NIDA NIH HHS/United States ; F31 GM123655/GM/NIGMS NIH HHS/United States ; T32 GM008295/GM/NIGMS NIH HHS/United States ; K99 GM124463/GM/NIGMS NIH HHS/United States ; R00 GM124463/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 GM118773/GM/NIGMS NIH HHS/United States ; },
mesh = {Cell Line ; Chromatin/genetics ; DNA/metabolism ; DNA Damage/physiology ; DNA Repair/genetics/physiology ; Humans ; Optogenetics/methods ; Protein Binding/genetics/physiology ; Shelterin Complex/genetics/*metabolism/physiology ; Telomere/*metabolism/physiology ; Telomere-Binding Proteins/genetics/*metabolism ; Telomeric Repeat Binding Protein 1/metabolism ; Telomeric Repeat Binding Protein 2/genetics/*metabolism ; },
abstract = {Telomeres form unique nuclear compartments that prevent degradation and fusion of chromosome ends by recruiting shelterin proteins and regulating access of DNA damage repair factors. To understand how these dynamic components protect chromosome ends, we combine in vivo biophysical interrogation and in vitro reconstitution of human shelterin. We show that shelterin components form multicomponent liquid condensates with selective biomolecular partitioning on telomeric DNA. Tethering and anomalous diffusion prevent multiple telomeres from coalescing into a single condensate in mammalian cells. However, telomeres coalesce when brought into contact via an optogenetic approach. TRF1 and TRF2 subunits of shelterin drive phase separation, and their N-terminal domains specify interactions with telomeric DNA in vitro. Telomeric condensates selectively recruit telomere-associated factors and regulate access of DNA damage repair factors. We propose that shelterin mediates phase separation of telomeric chromatin, which underlies the dynamic yet persistent nature of the end-protection mechanism.},
}
@article {pmid35077392,
year = {2022},
author = {Hastings, WJ and Etzel, L and Heim, CM and Noll, JG and Rose, EJ and Schreier, HMC and Shenk, CE and Tang, X and Shalev, I},
title = {Comparing qPCR and DNA methylation-based measurements of telomere length in a high-risk pediatric cohort.},
journal = {Aging},
volume = {14},
number = {2},
pages = {660-677},
pmid = {35077392},
issn = {1945-4589},
support = {P50 HD089922/HD/NICHD NIH HHS/United States ; T32 AG049676/AG/NIA NIH HHS/United States ; U01 ES030949/ES/NIEHS NIH HHS/United States ; },
mesh = {Aged ; Aging/genetics ; Cohort Studies ; *DNA Methylation ; Humans ; Male ; Reproducibility of Results ; *Telomere/genetics ; },
abstract = {Various approaches exist to assess population differences in biological aging. Telomere length (TL) is one such measure, and is associated with disease, disability and early mortality. Yet, issues surrounding precision and reproducibility are a concern for TL measurement. An alternative method to estimate TL using DNA methylation (DNAmTL) was recently developed. Although DNAmTL has been characterized in adult and elderly cohorts, its utility in pediatric populations remains unknown. We examined the comparability of leukocyte TL measurements generated using qPCR (absolute TL; aTL) to those estimated using DNAmTL in a high-risk pediatric cohort (N = 269; age: 8-13 years, 83% investigated for maltreatment). aTL and DNAmTL measurements were correlated with one another (r = 0.20, p = 0.001), but exhibited poor measurement agreement and were significantly different in paired-sample t-tests (Cohen's d = 0.77, p < 0.001). Shorter DNAmTL was associated with older age (r = -0.25, p < 0.001), male sex (β = -0.27, p = 0.029), and White race (β = -0.74, p = 0.008). By contrast, aTL was less strongly associated with age (r = -0.13, p = 0.040), was longer in males (β = 0.31, p = 0.012), and was not associated with race (p = 0.820). These findings highlight strengths and limitations of high-throughput measures of TL; although DNAmTL replicated hypothesized associations, aTL measurements were positively skewed and did not replicate associations with external validity measures. These results also extend previous research in adults and suggest that DNAmTL is a sensitive TL measure for use in pediatric populations.},
}
@article {pmid35073935,
year = {2022},
author = {Chen, L and Tan, KML and Gong, M and Chong, MFF and Tan, KH and Chong, YS and Meaney, MJ and Gluckman, PD and Eriksson, JG and Karnani, N},
title = {Variability in newborn telomere length is explained by inheritance and intrauterine environment.},
journal = {BMC medicine},
volume = {20},
number = {1},
pages = {20},
pmid = {35073935},
issn = {1741-7015},
mesh = {Cohort Studies ; Female ; *Genome-Wide Association Study ; Humans ; Infant, Newborn ; Male ; Mothers ; Pregnancy ; *Telomere/genetics ; Telomere Homeostasis ; },
abstract = {BACKGROUND: Telomere length (TL) and its attrition are important indicators of physiological stress and biological aging and hence may vary among individuals of the same age. This variation is apparent even in newborns, suggesting potential effects of parental factors and the intrauterine environment on TL of the growing fetus.<br><br>METHODS: Average relative TLs of newborns (cord tissue, N = 950) and mothers (buffy coat collected at 26-28&#x2009;weeks of gestation, N = 892) were measured in a birth cohort. This study provides a comprehensive analysis of the effects of heritable factors, socioeconomic status, and in utero exposures linked with maternal nutrition, cardiometabolic health, and mental well-being on the newborn TL. The association between maternal TL and antenatal maternal health was also studied.<br><br>RESULTS: Longer maternal TL (&#x3b2; = 0.14, P = 1.99E-05) and higher paternal age (&#x3b2; = 0.10, P = 3.73E-03) were positively associated with newborn TL. Genome-wide association studies on newborn and maternal TLs identified 6 genetic variants in a strong linkage disequilibrium on chromosome 3q26.2 (Tag SNP-LRRC34-rs10936600: Pmeta = 5.95E-08). Mothers with higher anxiety scores, elevated fasting blood glucose, lower plasma insulin-like growth factor-binding protein 3 and vitamin B12 levels, and active smoking status during pregnancy showed a higher risk of giving birth to offspring with shorter TL. There were sex-related differences in the factors explaining newborn TL variation. Variation in female newborn TL was best explained by maternal TL, mental health, and plasma vitamin B12 levels, while that in male newborn TL was best explained by paternal age, maternal education, and metabolic health. Mother's TL was associated with her own metabolic health and nutrient status, which may have transgenerational effects on offspring TL.<br><br>CONCLUSIONS: Our findings provide a comprehensive understanding of the heritable and environmental factors and their relative contributions to the initial setting of TL and programing of longevity in early life. This study provides valuable insights for preventing in utero telomere attrition by improving the antenatal health of mothers via targeting the modifiable factors.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov , NCT01174875. Registered on 1 July 2010.},
}
@article {pmid35073322,
year = {2022},
author = {Li Piani, L and Reschini, M and Somigliana, E and Ferrari, S and Busnelli, A and Viganò, P and Favero, C and Albetti, B and Hoxha, M and Bollati, V},
title = {Peripheral mitochondrial DNA, telomere length and DNA methylation as predictors of live birth in in vitro fertilization cycles.},
journal = {PloS one},
volume = {17},
number = {1},
pages = {e0261591},
pmid = {35073322},
issn = {1932-6203},
mesh = {Adult ; Birth Rate ; *DNA Methylation ; DNA, Mitochondrial/*genetics ; Epigenesis, Genetic ; Female ; Fertilization in Vitro ; Humans ; Italy ; Long Interspersed Nucleotide Elements ; Maternal Age ; Mitochondria/*genetics ; Pregnancy ; Pregnancy Rate ; Prospective Studies ; *Telomere Homeostasis ; },
abstract = {OBJECTIVE: To evaluate whether telomere length (TL), mitochondrial-DNA (mt-DNA) or epigenetic age estimators based on DNA methylation (DNAm) pattern could be considered reliable predictors of in-vitro-fertilization (IVF) success in terms of live birth rate.<br><br>DESIGN: Prospective cohort study.<br><br>SETTING: Infertility Unit of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico.<br><br>PATIENTS: 181 women aged 37-39 years who underwent IVF at a single-centre between January 2017 and December 2018.<br><br>INTERVENTIONS: On the day of recruitment, blood samples were collected, and genomic DNA was isolated from white blood cells. TL, mt-DNA and DNAm assessment was performed using quantitative real-time polymerase chain reaction (qPCR). Biological age (DNAm age) was computed as the algorithm based on methylation pattern of five genes. Epigenetic age acceleration was estimated from the residuals of the linear model of epigenetic age regressed on chronological age. Long Interspersed Nuclear Elements (LINE)-1 methylation pattern was used as a surrogate for global DNA methylation.<br><br>MAIN OUTCOME MEASURES: This study investigated whether peripheral TL, mt-DNA and DNAm could predict live birth in IVF cycles.<br><br>RESULTS: TL, mt-DNA and LINE-1 methylation were not associated with IVF success. Conversely, DNAm age resulted significantly lower in women who had a live birth compared to women who did not (36.1 &#xb1; 4.2 and 37.3 &#xb1; 3.3 years, respectively, p = 0.04). For DNAm age, odds ratio (OR) for live birth per year of age was 0.90 (95%CI: 0.82-0.99, p = 0.036) after adjusting for FSH and antral follicle count (AFC) and 0.90 (95%CI: 0.82-0.99, p = 0.028) after adjusting also for number of oocytes retrieved. A significant association also emerged for epigenetic age acceleration after adjustments (OR = 0.91, 95%CI: 0.83-1.00, p = 0.048).<br><br>CONCLUSION: DNAm age is associated with IVF success but the magnitude of this association is insufficient to claim a clinical use. However, our findings are promising and warrant further investigation. Assessment of biological age using different epigenetic clocks or focusing on different tissues may reveal new predictors of IVF success.},
}
@article {pmid35063426,
year = {2022},
author = {Isaevska, E and Fiano, V and Asta, F and Stafoggia, M and Moirano, G and Popovic, M and Pizzi, C and Trevisan, M and De Marco, L and Polidoro, S and Gagliardi, L and Rusconi, F and Brescianini, S and Nisticò, L and Stazi, MA and Ronfani, L and Porta, D and Richiardi, L},
title = {Prenatal exposure to PM10 and changes in DNA methylation and telomere length in cord blood.},
journal = {Environmental research},
volume = {209},
number = {},
pages = {112717},
doi = {10.1016/j.envres.2022.112717},
pmid = {35063426},
issn = {1096-0953},
support = {MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Child ; DNA Methylation ; Female ; *Fetal Blood ; Humans ; Infant, Newborn ; Maternal Exposure/adverse effects ; Pregnancy ; *Prenatal Exposure Delayed Effects/chemically induced/genetics ; Telomere ; },
abstract = {BACKGROUND: Air pollution exposure in pregnancy can cause molecular level alterations that might influence later disease susceptibility.<br><br>OBJECTIVES: We investigated DNA methylation (DNAm) and telomere length (TL) in the cord blood in relation to gestational PM10 exposure and explored potential gestational windows of susceptibility.<br><br>METHODS: Cord blood epigenome-wide DNAm (N&#xa0;=&#xa0;384) and TL (N&#xa0;=&#xa0;500) were measured in children of the Italian birth cohort Piccolipi&#xf9;, using the Infinium Methylation EPIC BeadChip and qPCR, respectively. PM10 daily exposure levels, based on maternal residential address, were estimated for different gestational periods using models based on satellite data. Epigenome-wide analysis to identify differentially methylated probes (DMPs) and regions (DMRs) was conducted, followed by a pathway analysis and replication analysis in an second Piccolipi&#xf9; dataset. Distributed lag models (DLMs) using weekly exposures were used to study the association of PM10 exposure across pregnancy with telomere length, as well as with the DMPs that showed robust associations.<br><br>RESULTS: Gestational PM10 exposure was associated with the DNA methylation of more than 250 unique DMPs, most of them identified in early gestation, and 1 DMR. Out of 151 DMPs available in the replication dataset, ten DMPs showed robust associations: eight were associated with exposure during early gestation and 2 with exposure during the whole pregnancy. These exposure windows were supported by the DLM analysis. The PM10 exposure between 15th and 20th gestational week seem to be associated with shorter telomeres at birth, while exposure between 24th and 29th was associated with longer telomeres.<br><br>DISCUSSION: The early pregnancy period is a potential critical window during which PM10 exposure can influence cord blood DNA methylation. The results from the TL analysis were consistent with previous findings and merit further exploration in future studies. The study underlines the importance of considering gestational windows outside of the predefined trimesters that may not always overlap with biologically relevant windows of exposure.},
}
@article {pmid35063336,
year = {2022},
author = {Penev, A and Markiewicz-Potoczny, M and Sfeir, A and Lazzerini Denchi, E},
title = {Stem cells at odds with telomere maintenance and protection.},
journal = {Trends in cell biology},
volume = {32},
number = {6},
pages = {527-536},
pmid = {35063336},
issn = {1879-3088},
support = {F30 CA221285/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; U01 CA231019/CA/NCI NIH HHS/United States ; },
mesh = {Embryonic Stem Cells ; Genomic Instability ; Humans ; Shelterin Complex ; *Telomerase/chemistry/genetics/metabolism ; Telomere/metabolism ; },
abstract = {Telomeres are distinctive structures that protect the ends of linear chromosomes and ensure genome stability. They are composed of long tracks of repetitive and G-rich DNA that is bound by shelterin, a dedicated six-subunit protein complex. In somatic cells, shelterin protects telomeres from the DNA damage response and regulates telomere length. Telomere repeats are replenished by telomerase, a specialized ribonucleoprotein composed of telomerase reverse transcriptase and an integral RNA component. Telomere protection and telomerase regulation have been primarily studied in somatic cells. However, recent evidence points out striking differences in the context of embryonic stem cells (ESCs). In this review, we discuss insights into telomere protection in ESCs versus somatic cells and summarize findings on telomerase regulation as a function of pluripotency.},
}
@article {pmid35061898,
year = {2022},
author = {Rabbani, MAG and Tonini, ML and Afrin, M and Li, B},
title = {POLIE suppresses telomerase-mediated telomere G-strand extension and helps ensure proper telomere C-strand synthesis in trypanosomes.},
journal = {Nucleic acids research},
volume = {50},
number = {4},
pages = {2036-2050},
pmid = {35061898},
issn = {1362-4962},
support = {R01 AI127562/AI/NIAID NIH HHS/United States ; S10 OD025252/OD/NIH HHS/United States ; },
mesh = {DNA/metabolism ; Humans ; *Telomerase/genetics/metabolism ; *Telomere/genetics/metabolism ; Trypanosoma/genetics/*metabolism ; Variant Surface Glycoproteins, Trypanosoma/genetics ; },
abstract = {Trypanosoma brucei causes human African trypanosomiasis and sequentially expresses distinct VSGs, its major surface antigen, to achieve host immune evasion. VSGs are monoallelically expressed from subtelomeric loci, and telomere proteins regulate VSG monoallelic expression and VSG switching. T. brucei telomerase is essential for telomere maintenance, but no regulators of telomerase have been identified. T. brucei appears to lack OB fold-containing telomere-specific ssDNA binding factors that are critical for coordinating telomere G- and C-strand syntheses in higher eukaryotes. We identify POLIE as a telomere protein essential for telomere integrity. POLIE-depleted cells have more frequent VSG gene conversion-mediated VSG switching and an increased amount of telomeric circles (T-circles), indicating that POLIE suppresses DNA recombination at the telomere/subtelomere. POLIE-depletion elongates telomere 3' overhangs dramatically, indicating that POLIE is essential for coordinating DNA syntheses of the two telomere strands. POLIE depletion increases the level of telomerase-dependent telomere G-strand extension, identifying POLIE as the first T. brucei telomere protein that suppresses telomerase. Furthermore, depletion of POLIE results in an elevated telomeric C-circle level, suggesting that the telomere C-strand experiences replication stress and that POLIE may promote telomere C-strand synthesis. Therefore, T. brucei uses a novel mechanism to coordinate the telomere G- and C-strand DNA syntheses.},
}
@article {pmid35057533,
year = {2022},
author = {Alonso-Pedrero, L and Donat-Vargas, C and Bes-Rastrollo, M and Ojeda-Rodríguez, A and Zalba, G and Razquin, C and Martínez-González, MA and Marti, A},
title = {Dietary Exposure to Polychlorinated Biphenyls and Dioxins and Its Relationship to Telomere Length in Subjects Older Than 55 Years from the SUN Project.},
journal = {Nutrients},
volume = {14},
number = {2},
pages = {},
pmid = {35057533},
issn = {2072-6643},
support = {(27/2011, 45/2011, 122/2014)//University of Navarra and Navarra Regional Government/ ; (RD 06/0045, CIBER-OBN, and Fondo de Investigaciones sanitarias, Grants PI10/02658, PI10/02293, PI13/00615, PI14/01668, PI14/01798, PI14/01764, PI17/01795, PI20/00564 and G03/140)//Spanish Government-Instituto de Salud Carlos III and the European Regional Development Fund (FEDER)/ ; (2020/021)//PNDS (Plan Nacional sobre Drogas)/ ; },
mesh = {Cross-Sectional Studies ; Diet/*adverse effects/statistics &amp; numerical data ; Diet Surveys ; Dietary Exposure/*adverse effects ; Dioxins/*toxicity ; Female ; Humans ; Linear Models ; Male ; Middle Aged ; Polychlorinated Biphenyls/*toxicity ; Spain ; Telomere Homeostasis/drug effects ; Telomere Shortening/*drug effects ; },
abstract = {Exposure to persistent organic pollutants (POPs) may influence telomere length (TL), which is considered as a marker of biological age associated with the risk of chronic disease. We hypothesized that dietary exposure to polychlorinated biphenyls (PCBs) and dioxins could affect TL. Our aim was to evaluate the association of dietary exposure to PCBs and dioxins with TL. In this cross-sectional study of 886 subjects older than 55 y (mean age: 67.7; standard deviation (SD): 6.1; 27% women) from the "Seguimiento Universidad de Navarra" (SUN) project. TL was determined by real-time quantitative polymerase chain reaction and dietary PCBs and dioxins exposure was collected using a validated 136-item Food Frequency Questionnaire. Multivariable linear regression models were used to control for potential confounding factors. Shorter TL was associated with dietary total PCBs (SD of T/S ratio/(ng/day) = -0.30 × 10[-7]; 95% CI, -0.55 × 10[-7] to -0.06 × 10[-7]), dioxin-like PCBs (DL-PCBs) (SD of T/S ratio/(pg WHO TEQ (Toxic Equivalents)/day) = -6.17 × 10[-7]; 95% CI, -11.30 × 10[-7] to -1.03 × 10[-7]), and total TEQ exposure (SD of T/S ratio/(pg WHO TEQ/day) = -5.02 × 10[-7]; 95% CI, -9.44 × 10[-7] to -0.61 × 10[-7]), but not with dioxins (SD of T/S ratio/(pg WHO TEQ/day) = -13.90 × 10[-7]; 95% CI, -37.70 × 10[-7] to 9.79 × 10[-7]). In this sample of middle-aged and older Spanish adults, dietary exposure to total PCBs and DL-PCBs alone and together with dioxins was associated with shorter TL. Further longitudinal studies, preferably with POPs measured in biological samples, are needed to confirm this finding.},
}
@article {pmid35054812,
year = {2022},
author = {Button, L and Rogers, B and Thomas, E and Bradfield, A and Alnafakh, R and Drury, J and Hapangama, DK},
title = {Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival.},
journal = {International journal of molecular sciences},
volume = {23},
number = {2},
pages = {},
pmid = {35054812},
issn = {1422-0067},
support = {NO//University of Liverpool (MRes studentships L.B, E.T., A.B.)/ ; N/A//Liverpool Women's Hospital NHS Trust (Research and development J.D.)/ ; N/A//Higher Committee for Education Development in Iraq (R.A.)/ ; grants RG1487 and RG2137//Wellbeing of Women's/ ; RDG2021.18//Northwest Cancer Research/ ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Carcinogenesis/*metabolism/*pathology ; Endometrial Neoplasms/genetics/*metabolism/*pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Ki-67 Antigen/metabolism ; Middle Aged ; Neoplasm Proteins/genetics/*metabolism ; Receptors, Steroid ; Survival Analysis ; Telomerase/*metabolism ; Telomere/*metabolism ; },
abstract = {Risk of relapse of endometrial cancer (EC) after surgical treatment is 13% and recurrent disease carries a poor prognosis. Research into prognostic indicators is essential to improve EC management and outcome. "Immortality" of most cancer cells is dependent on telomerase, but the role of associated proteins in the endometrium is poorly understood. The Cancer Genome Atlas data highlighted telomere/telomerase associated genes (TTAGs) with prognostic relevance in the endometrium, and a recent in silico study identified a group of TTAGs and proteins as key regulators within a network of dysregulated genes in EC. We characterise relevant telomere/telomerase associated proteins (TTAPs) NOP10, NHP2, NOP56, TERF1, TERF2 and TERF2IP in the endometrium using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). qPCR data demonstrated altered expression of multiple TTAPs; specifically, increased NOP10 (p = 0.03) and reduced NHP2 (p = 0.01), TERF2 (p = 0.01) and TERF2IP (p < 0.003) in EC relative to post-menopausal endometrium. Notably, we report reduced NHP2 in EC compared to post-menopausal endometrium in qPCR and IHC (p = 0.0001) data; with survival analysis indicating high immunoscore is favourable in EC (p = 0.0006). Our findings indicate a potential prognostic role for TTAPs in EC, particularly NHP2. Further evaluation of the prognostic and functional role of the examined TTAPs is warranted to develop novel treatment strategies.},
}
@article {pmid35052747,
year = {2021},
author = {Maugeri, A and Magnano San Lio, R and La Rosa, MC and Giunta, G and Panella, M and Cianci, A and Caruso, MAT and Agodi, A and Barchitta, M},
title = {The Relationship between Telomere Length and Gestational Weight Gain: Findings from the Mamma &amp; Bambino Cohort.},
journal = {Biomedicines},
volume = {10},
number = {1},
pages = {},
pmid = {35052747},
issn = {2227-9059},
support = {Programma ricerca di ateneo UNICT 2020-22 linea 2, PIAno di inCEntivi per la RIcerca di Ateneo 2020/2022//University of Catania/ ; },
abstract = {Inadequate gestational weight gain (GWG) affects a growing number of pregnancies, influencing intrauterine environment and long-term health. Uncovering molecular mechanisms associated with GWG could be helpful to develop public health strategies for tackling this issue. Here, our study aimed to understand the relationship of DNA telomere length with weigh gain during pregnancy, using data and samples from the ongoing prospective "Mamma &amp; Bambino" study (Catania, Italy). GWG was calculated according to the Institute of Medicine (IOM) guidelines. Relative telomere length was assessed by real-time quantitative polymerase chain reaction in 252 samples of maternal leucocyte DNA (mlDNA) and 150 samples of cell-free DNA (cfDNA) from amniotic fluid. We observed that relative telomere length of mlDNA seemed to weakly increase with GWG. In contrast, telomere length of cfDNA exhibited a U-shaped relationship with GWG. Women with adequate GWG showed longer telomere length than those who gained weight inadequately. Accordingly, the logistic regression model confirmed the association between telomere length of cfDNA and adequate GWG, after adjusting for potential confounders. Our findings suggest an early effect of GWG on telomere length of cfDNA, which could represent a molecular mechanism underpinning the effects of maternal behaviours on foetal well-being.},
}
@article {pmid35052422,
year = {2021},
author = {Gunnarsdottir, SR and Bjarnason, H and Thorvaldsdottir, B and Paland, F and Steinarsdottir, M and Eyfjörd, JE and Bödvarsdottir, SK},
title = {BRCA2 Haploinsufficiency in Telomere Maintenance.},
journal = {Genes},
volume = {13},
number = {1},
pages = {},
pmid = {35052422},
issn = {2073-4425},
mesh = {BRCA2 Protein/*genetics ; Breast Neoplasms/genetics/*pathology ; Female ; *Genetic Predisposition to Disease ; *Haploinsufficiency ; *Heterozygote ; Humans ; *Mutation ; *Telomere Shortening ; },
abstract = {Our previous studies showed an association between monoallelic BRCA2 germline mutations and dysfunctional telomeres in epithelial mammary cell lines and increased risk of breast cancer diagnosis for women with BRCA2 999del5 germline mutation and short telomeres in blood cells. In the current study, we analyzed telomere dysfunction in lymphoid cell lines from five BRCA2 999del5 mutation carriers and three Fanconi Anemia D1 patients by fluorescence in situ hybridization (FISH). Metaphase chromosomes were harvested from ten lymphoid cell lines of different BRCA2 genotype origin and analyzed for telomere loss (TL), multitelomeric signals (MTS), interstitial telomere signals (ITS) and extra chromosomal telomere signals (ECTS). TL, ITS and ECTS were separately found to be significantly increased gradually between the BRCA2[+/+], BRCA2[+/-] and BRCA2[-/-] lymphoid cell lines. MTS were found to be significantly increased between the BRCA2[+/+] and the BRCA2[+/-] heterozygous (p < 0.0001) and the BRCA2[-/-] lymphoid cell lines (p < 0.0001) but not between the BRCA2 mutated genotypes. Dysfunctional telomeres were found to be significantly increased in a stepwise manner between the BRCA2 genotypes indicating an effect of BRCA2 haploinsufficiency on telomere maintenance.},
}
@article {pmid35051766,
year = {2022},
author = {De Loma, J and Krais, AM and Lindh, CH and Mamani, J and Tirado, N and Gardon, J and Broberg, K},
title = {Arsenic exposure and biomarkers for oxidative stress and telomere length in indigenous populations in Bolivia.},
journal = {Ecotoxicology and environmental safety},
volume = {231},
number = {},
pages = {113194},
doi = {10.1016/j.ecoenv.2022.113194},
pmid = {35051766},
issn = {1090-2414},
mesh = {*Arsenic ; Biomarkers ; Bolivia ; Chromatography, Liquid ; Female ; Humans ; Indigenous Peoples ; Methyltransferases ; Oxidative Stress/genetics ; Tandem Mass Spectrometry ; Telomere/genetics ; },
abstract = {BACKGROUND: Women living in the Bolivian Andes are environmentally exposed to arsenic, yet there is scarce information about arsenic-related effects in this region. Several biomarkers for telomere length and oxidative stress (mitochondrial DNA copy number, mtDNAcn; 8-Oxo-2'-deoxyguanosine, 8-oxo-dG; and 4-hydroxy nonenal mercapturic acid, 4-HNE-MA) have been previously linked to arsenic, and some of which are prospective biomarkers for cancer risk.<br><br>OBJECTIVE AND HYPOTHESIS: To evaluate associations between arsenic exposure and telomere length, mtDNAcn, 8-oxo-dG, and 4-HNE-MA in Bolivians. Arsenic exposure was hypothesized to be positively associated with all four toxicity biomarkers, particularly in individuals with a less efficient arsenic metabolism.<br><br>METHODS: The study encompassed 193 indigenous women. Arsenic exposure was assessed in urine as the sum of inorganic arsenic metabolite concentrations (U-As) measured by HPLC-HG-ICP-MS, and in whole blood as total arsenic (B-As) measured by ICP-MS. Efficiency of arsenic metabolism was evaluated by a polymorphism (rs3740393) in the main arsenic methylating gene AS3MT measured by TaqMan allelic discrimination, and by the relative fractions of urinary inorganic arsenic metabolites. Telomere length and mtDNAcn were determined in peripheral blood leukocytes by quantitative PCR, and urinary 8-oxo-dG and 4-HNE-MA by LC-MS/MS.<br><br>RESULTS: U-As and B-As were associated with longer telomeres and higher mtDNAcn, particularly in women with a less efficient arsenic metabolism. Urinary 8-oxo-dG and 4-HNE-MA were positively associated with U-As, but only 4-HNE-MA was associated with B-As. Arsenic metabolism efficiency did not have a clear effect on the concentrations of either of these biomarkers.<br><br>CONCLUSION: Bolivian women showed indications of arsenic toxicity, measured by four different biomarkers. Telomere length, mtDNAcn, and 4-HNE-MA were positively associated with both U-As and B-As. The association of arsenic exposure with telomere length and mtDNAcn was only present in Bolivian women with a less efficient metabolism. These findings call for additional efforts to evaluate and reduce arsenic exposure in Bolivia.},
}
@article {pmid35051055,
year = {2022},
author = {Durham, T and Guo, J and Cowell, W and Riley, KW and Wang, S and Tang, D and Perera, F and Herbstman, JB},
title = {Prenatal PM2.5 Exposure in Relation to Maternal and Newborn Telomere Length at Delivery.},
journal = {Toxics},
volume = {10},
number = {1},
pages = {},
pmid = {35051055},
issn = {2305-6304},
support = {UG3OD023290/NH/NIH HHS/United States ; R01ES13163/ES/NIEHS NIH HHS/United States ; P50ES09600/ES/NIEHS NIH HHS/United States ; RD82702701/EPA/EPA/United States ; RD832141/EPA/EPA/United States ; R01ES014393/ES/NIEHS NIH HHS/United States ; P30 ES009089/ES/NIEHS NIH HHS/United States ; P01ES09600/ES/NIEHS NIH HHS/United States ; Environmental Protection Agency/EPA/EPA/United States ; R01ES08977/ES/NIEHS NIH HHS/United States ; R03ES026416/NH/NIH HHS/United States ; P30ES009089/NH/NIH HHS/United States ; RD834509/EPA/EPA/United States ; },
abstract = {Particulate matter with an aerodynamic diameter of 2.5 μm or less (PM2.5) is a ubiquitous air pollutant that is increasingly threatening the health of adults and children worldwide. One health impact of elevated PM2.5 exposure is alterations in telomere length (TL)-protective caps on chromosome ends that shorten with each cell division. Few analyses involve prenatal PM2.5 exposure, and paired maternal and cord TL measurements. Here, we analyzed the association between average and trimester-specific prenatal PM2.5 exposure, and maternal and newborn relative leukocyte TL measured at birth among 193 mothers and their newborns enrolled in a New-York-City-based birth cohort. Results indicated an overall negative relationship between prenatal PM2.5 and maternal TL at delivery, with a significant association observed in the second trimester (β = -0.039, 95% CI: -0.074, -0.003). PM2.5 exposure in trimester two was also inversely related to cord TL; however, this result did not reach statistical significance (β = -0.037, 95% CI: -0.114, 0.039), and no clear pattern emerged between PM2.5 and cord TL across the different exposure periods. Our analysis contributes to a limited body of research on ambient air pollution and human telomeres, and emphasizes the need for continued investigation into how PM2.5 exposure during pregnancy influences maternal and newborn health.},
}
@article {pmid35050506,
year = {2022},
author = {Stout-Oswald, SA and Glynn, LM and Bisoffi, M and Demers, CH and Davis, EP},
title = {Prenatal exposure to maternal psychological distress and telomere length in childhood.},
journal = {Developmental psychobiology},
volume = {64},
number = {1},
pages = {e22238},
doi = {10.1002/dev.22238},
pmid = {35050506},
issn = {1098-2302},
support = {R01 MH109662/MH/NIMH NIH HHS/United States ; T32 MH015442/MH/NIMH NIH HHS/United States ; },
mesh = {Adult ; Child ; Female ; Humans ; Infant, Newborn ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Prospective Studies ; *Psychological Distress ; Telomere ; Telomere Shortening ; },
abstract = {Telomere length (TL) is a biological marker of cellular aging, and shorter TL in adulthood is associated with increased morbidity and mortality risk. It is likely that these differences in TL are established long before adulthood, and there is growing evidence that TL can reflect prenatal experiences. Although maternal prenatal distress predicts newborn TL, it is unknown whether the relation between prenatal exposure to maternal distress and child TL persists through childhood. The purpose of the current longitudinal, prospective study is to examine the relation between prenatal exposure to maternal distress (perceived stress, depressive symptoms, pregnancy-related anxiety) and TL in childhood. Participants included 102 children (54 girls) and their mothers. Mothers' distress was assessed five times during pregnancy, at 12 weeks postpartum, and at the time of child telomere measurement between 6 and 16 years of age. Maternal distress during pregnancy predicted shorter offspring TL in childhood, even after accounting for postnatal exposure to maternal distress and other covariates. These findings indicate that maternal mental health predicts offspring TL biology later in childhood than previously observed. This study bolsters claims that telomere biology is subject to fetal programming and highlights the importance of supporting maternal mental health during pregnancy.},
}
@article {pmid35049825,
year = {2022},
author = {Ribas-Maynou, J and Mateo-Otero, Y and Sanchez-Quijada, M and Recuero, S and Delgado-Bermúdez, A and Llavanera, M and Yeste, M},
title = {Telomere Length in Pig Sperm Is Related to In Vitro Embryo Development Outcomes.},
journal = {Animals : an open access journal from MDPI},
volume = {12},
number = {2},
pages = {},
pmid = {35049825},
issn = {2076-2615},
support = {AGL2017-88329-R//Ministry of science and innovation, Spain/ ; 2017-SGR-1229//Generalitat de Catalunya/ ; 214/857-202039//La marat&#xf3; de TV3/ ; Tecniospring INDUSTRY; TECSPR-19-1-0003//European Union's Horizon 2020 research and innovation programme under the Marie Sk&#x142;odowska-Curie grant agreement No 801342/ ; },
abstract = {Telomere length has attracted much interest as a topic of study in human reproduction; furthermore, the link between sperm telomere length and fertility outcomes has been investigated in other species. This biomarker, however, has not been much explored in other animals, such as pigs, and whether it is related to sperm quality and fertility outcomes remains unknown. The present work aimed to determine the absolute value of telomere length in pig sperm, as well as its relationship to sperm quality parameters and embryo development. Telomere length was determined through quantitative fluorescence in situ hybridization (qFISH) in 23 pig sperm samples and data were correlated to quality parameters (motility, morphology, and viability) and in vitro fertilization outcomes. We found that the mean telomere length in pig sperm was 22.1 ± 3.6 kb, which is longer than that previously described in humans. Whilst telomere length was not observed to be correlated to sperm quality variables (p > 0.05), a significant correlation between telomere length and the percentage of morulae 6 days after in vitro fertilization was observed (rs = 0.559; 95% C.I. = (-0.007 to 0.854); p = 0.047). Interestingly, this correlation was not found when percentages of early blastocysts/blastocysts (rs = 0.410; 95% C.I. = (-0.200 to 0.791); p = 0.164) and of hatching/hatched blastocysts (rs = 0.356; 95% C.I. = (- 0.260 to 0.766); p = 0.233) were considered. Through the separation of the samples into two groups by the median value, statistically significant differences between samples with shorter telomeres than the median and samples with longer telomeres than the median were found regarding development to morula (11.5 ± 3.6 vs. 21.8 ± 6.9, respectively) and to early blastocyst/blastocysts (7.6 ± 1.4 vs. 17.9 ± 12.2, respectively) (p < 0.05). In the light of these results, sperm telomere length may be a useful biomarker for embryo development in pigs, as sperm with longer telomeres lead to higher rates of morulae and blastocysts.},
}
@article {pmid35045162,
year = {2022},
author = {Rodríguez-Centeno, J and Esteban-Cantos, A and Montejano, R and Stella-Ascariz, N and De Miguel, R and Mena-Garay, B and Saiz-Medrano, G and Alejos, B and Jiménez-González, M and Bernardino, JI and Cadiñanos, J and Castro-Alvarez, JM and Rodés, B and Arribas, JR},
title = {Effects of tenofovir on telomeres, telomerase and T cell maturational subset distribution in long-term aviraemic HIV-infected adults.},
journal = {The Journal of antimicrobial chemotherapy},
volume = {77},
number = {4},
pages = {1125-1132},
doi = {10.1093/jac/dkab492},
pmid = {35045162},
issn = {1460-2091},
support = {FI17/00194//Instituto de Salud Carlos III-Fondo Social Europeo/ ; CM17/00064//Instituto de Salud Carlos III-Fondo Social Europeo/ ; },
mesh = {Adult ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes ; *HIV Infections ; Humans ; *Telomerase/metabolism ; Telomere/metabolism ; Tenofovir/therapeutic use ; },
abstract = {OBJECTIVES: To evaluate whether the negative impact of tenofovir on telomere length (TL) is due to immune reconstitution interference or inhibition of telomerase.<br><br>METHODS: One hundred and twenty-eight long-term aviraemic HIV adults treated with tenofovir-containing (n = 79) or tenofovir-sparing regimens (n = 49) were recruited to compare the following: TL in whole blood, PBMCs, CD4+ T cells and CD8+ T cells by quantitative PCR (qPCR); telomerase activity in PBMCs, CD4+ cells and CD8+ T cells using the TRAPeze RT Telomerase Detection Kit; and T cell maturational subset distribution by flow cytometry.<br><br>RESULTS: In an adjusted analysis, participants treated with tenofovir for at least 4 years had shorter TL in CD8+ T cells (P = 0.04) and lower telomerase activity in CD4+ (P = 0.012) and CD8+ T cells (P = 0.023). Tenofovir treatment was also associated with lower proportions of recent thymic emigrant (RTE) CD4+ cells (P = 0.031) and PD1 marker expression (P = 0.013).<br><br>CONCLUSIONS: In long-term aviraemic HIV adults, the inhibition of telomerase by tenofovir could explain telomere shortening in CD8+ T cells. There is no telomere shortening in the CD4+ compartment and the decrease in telomerase activity could be explained both by the inhibition by tenofovir and by the lower proportion of RTE CD4+cells.},
}
@article {pmid35044907,
year = {2022},
author = {Rosas Bringas, FR and Stinus, S and de Zoeten, P and Cohn, M and Chang, M},
title = {Rif2 protects Rap1-depleted telomeres from MRX-mediated degradation in Saccharomyces cerevisiae.},
journal = {eLife},
volume = {11},
number = {},
pages = {},
pmid = {35044907},
issn = {2050-084X},
mesh = {Multiprotein Complexes/*metabolism ; RNA/*metabolism ; RNA, Fungal/*metabolism ; Saccharomyces cerevisiae/*genetics/metabolism ; Saccharomyces cerevisiae Proteins/*genetics/*metabolism ; Shelterin Complex/*metabolism ; Telomerase/*metabolism ; Telomere/*metabolism ; Telomere-Binding Proteins/*genetics/*metabolism ; Transcription Factors/*metabolism ; },
abstract = {Rap1 is the main protein that binds double-stranded telomeric DNA in Saccharomyces cerevisiae. Examination of the telomere functions of Rap1 is complicated by the fact that it also acts as a transcriptional regulator of hundreds of genes and is encoded by an essential gene. In this study, we disrupt Rap1 telomere association by expressing a mutant telomerase RNA subunit (tlc1-tm) that introduces mutant telomeric repeats. tlc1-tm cells grow similar to wild-type cells, although depletion of Rap1 at telomeres causes defects in telomere length regulation and telomere capping. Rif2 is a protein normally recruited to telomeres by Rap1, but we show that Rif2 can still associate with Rap1-depleted tlc1-tm telomeres, and that this association is required to inhibit telomere degradation by the MRX complex. Rif2 and the Ku complex work in parallel to prevent tlc1-tm telomere degradation; tlc1-tm cells lacking Rif2 and the Ku complex are inviable. The partially redundant mechanisms may explain the rapid evolution of telomere components in budding yeast species.},
}
@article {pmid35044242,
year = {2022},
author = {Yadav, S and Maurya, PK},
title = {Correlation Between Telomere Length and Biomarkers of Oxidative Stress in Human Aging.},
journal = {Rejuvenation research},
volume = {25},
number = {1},
pages = {25-29},
doi = {10.1089/rej.2021.0045},
pmid = {35044242},
issn = {1557-8577},
mesh = {Aged ; *Aging ; Biomarkers ; Female ; Humans ; Male ; Oxidative Stress ; *Telomere ; Telomere Shortening ; },
abstract = {The telomere length (TL) has increasingly been used as a biomarker of human aging because it has been shown to predict the chances of survival and longevity. Oxidative stress is presumed to be a major cause of telomere shortening, but the importance of oxidative stress as a determinant of telomere shortening remains less clear and has recently been questioned. We analyzed 105 healthy subjects of both sexes between the ages of 20-77 years. The TL and biomarkers of oxidative stress were estimated as per standard protocols. A significant (p < 0.001) age-dependent decline in TL was observed. TL was positively correlated with the ferric reducing ability of plasma value (r = 0.8811) and reduced glutathione (r = 0.8209), whereas negatively correlated with malondialdehyde (r = -0.7191). Our findings supported the idea of a possible correlation between the TL and biomarkers of oxidative stress in aging. The study has remarkable scope in medical science as the findings on correlation of TL with biomarkers of oxidative stress in aging are novel and they will help in further research against oxidative stress.},
}
@article {pmid35040871,
year = {2022},
author = {Schneider, CV and Schneider, KM and Teumer, A and Rudolph, KL and Hartmann, D and Rader, DJ and Strnad, P},
title = {Association of Telomere Length With Risk of Disease and Mortality.},
journal = {JAMA internal medicine},
volume = {182},
number = {3},
pages = {291-300},
pmid = {35040871},
issn = {2168-6114},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Leukocytes/*physiology ; Longitudinal Studies ; Male ; Middle Aged ; Mortality/*trends ; Risk ; Telomere/*physiology ; United Kingdom ; },
abstract = {IMPORTANCE: Telomeres protect DNA from damage. Because they shorten with each mitotic cycle, leukocyte telomere length (LTL) serves as a mitotic clock. Reduced LTL has been associated with multiple human disorders.<br><br>OBJECTIVE: To determine the association between LTL and overall as well as disease-specific mortality and morbidity.<br><br>This multicenter, community-based cohort study conducted from March 2006 to December 2010 included longitudinal follow-up (mean [SD], 12 [2] years) for 472 432 English participants from the United Kingdom Biobank (UK Biobank) and analyzed morbidity and mortality. The data were analyzed in 2021.<br><br>MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) and odds ratios for mortality and morbidity associated with a standard deviation change in LTL, adjusted for age, sex, body mass index (calculated as weight in kilograms divided by height in meters squared), and ethnicity.<br><br>RESULTS: This study included a total of 472&#x202f;432 English participants, of whom 54% were women (mean age, 57 years). Reduced LTL was associated with increased overall (HR, 1.08; 95% CI, 1.07-1.09), cardiovascular (HR, 1.09; 95% CI, 1.06-1.12), respiratory (HR, 1.40; 95% CI, 1.34-1.45), digestive (HR, 1.26; 95% CI, 1.19-1.33), musculoskeletal (HR, 1.51; 95% CI, 1.35-1.92), and COVID-19 (HR, 1.15; 95% CI, 1.07-1.23) mortality, but not cancer-related mortality. A total of 214 disorders were significantly overrepresented and 37 underrepresented in participants with shorter LTL. Respiratory (11%), digestive/liver-related (14%), circulatory (18%), and musculoskeletal conditions (6%), together with infections (5%), accounted for most positive associations, whereas (benign) neoplasms and endocrinologic/metabolic disorders were the most underrepresented entities. Malignant tumors, esophageal cancer, and lymphoid and myeloid leukemia were significantly more common in participants with shorter LTL, whereas brain cancer and melanoma were less prevalent. While smoking and alcohol consumption were associated with shorter LTL, additional adjustment for both factors, as well as cognitive function/major comorbid conditions, did not significantly alter the results.<br><br>CONCLUSIONS AND RELEVANCE: This cohort study found that shorter LTL was associated with a small risk increase of overall mortality, but a higher risk of mortality was associated with specific organs and diseases.},
}
@article {pmid35038777,
year = {2022},
author = {Cuadrado, &#xc1; and Figueroa, RI and Sixto, M and Bravo, I and De Bustos, A},
title = {First record of the spatial organization of the nucleosome-less chromatin of dinoflagellates: The nonrandom distribution of microsatellites and bipolar arrangement of telomeres in the nucleus of Gambierdiscus australes (Dinophyceae).},
journal = {Journal of phycology},
volume = {58},
number = {2},
pages = {297-307},
doi = {10.1111/jpy.13236},
pmid = {35038777},
issn = {1529-8817},
mesh = {Cell Nucleus/genetics ; Chromatin/metabolism ; DNA/metabolism ; *Dinoflagellida/genetics/metabolism ; In Situ Hybridization, Fluorescence ; Microsatellite Repeats ; Nucleosomes/metabolism ; Telomere ; },
abstract = {Dinoflagellates are a group of protists whose exceptionally large genome is organized in permanently condensed nucleosome-less chromosomes. In this study, we examined the potential role of repetitive DNAs in both the structure of dinoflagellate chromosomes and the architecture of the dinoflagellate nucleus. Non-denaturing fluorescent in situ hybridization (ND-FSH) was used to determine the abundance and physical distribution of telomeric DNA and 16 microsatellites (1- to 4-bp repeats) in the nucleus of Gambierdiscus australes. The results showed an increased relative abundance of the different microsatellite motifs with increasing GC content. Two ND-FISH probes, (A)20 and (AAT)5 , did not yield signals whereas the remainder revealed a dispersed but nonrandom distribution of the microsatellites, mostly in clusters. The bean-shaped interphase nucleus of G. australes contained a region with a high density of trinucleotides. This nuclear compartment was located between the nucleolar organizer region (NOR), located on the concave side of the nucleus, and the convex side. Telomeric DNA was grouped in multiple foci and distributed in two polarized compartments: one associated with the NOR and the other peripherally located along the convex side of the nucleus. Changes in the position of the telomeres during cell division evidenced their dynamic distribution and thus that of the chromosomes during dinomitosis. These insights into the spatial organization of microsatellites and telomeres and thus into the nuclear architecture of G. australes will open up new lines of research into the structure and function of the nucleosome-less chromatin of dinoflagellates.},
}
@article {pmid35033923,
year = {2022},
author = {Yang, K and Prescott, J and Hazra, A and Meyerhardt, JA and Zhang, X and De Vivo, I and Chan, AT and Du, M and Giovannucci, EL and Nan, H},
title = {Pre-diagnostic telomere length and colorectal cancer risk.},
journal = {Cancer epidemiology},
volume = {77},
number = {},
pages = {102100},
pmid = {35033923},
issn = {1877-783X},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; U01 CA167552/CA/NCI NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; R35 CA253185/CA/NCI NIH HHS/United States ; },
mesh = {Case-Control Studies ; *Colorectal Neoplasms/diagnosis/epidemiology/genetics ; Follow-Up Studies ; Humans ; Leukocytes ; Risk Factors ; *Telomere/genetics ; },
abstract = {BACKGROUND: Progressive telomere shortening may be related to genomic instability and carcinogenesis. Prospective evidence relating telomere length (TL) with colorectal cancer (CRC) risk has been limited and inconsistent.<br><br>METHODS: We examined the association between pre-diagnostic peripheral blood leukocyte TL and CRC risk in two matched case-control studies nested within the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). Relative leukocyte TL was measured using qPCR among 356 incident CRC cases and 801 controls (NHS: 186/465, HPFS: 170/336).<br><br>RESULTS: We did not find a significant association between pre-diagnostic TL and CRC risk [in all participants, multivariable-adjusted odds ratio (OR) (95% CI) for TL Quartile 1 (shortest) vs. Quartile 4 (longest)&#xa0;=&#xa0;1.36 (0.85, 2.17), P-trend&#xa0;=&#xa0;0.27; OR (95% CI) per 1 SD decrease in TL&#xa0;=&#xa0;1.12 (0.92, 1.36)].<br><br>CONCLUSIONS: Our prospective analysis did not support a significant association between pre-diagnostic leukocyte TL and CRC risk.},
}
@article {pmid35032170,
year = {2022},
author = {Vetter, VM and Kalies, CH and Sommerer, Y and Spira, D and Drewelies, J and Regitz-Zagrosek, V and Bertram, L and Gerstorf, D and Demuth, I},
title = {Relationship Between 5 Epigenetic Clocks, Telomere Length, and Functional Capacity Assessed in Older Adults: Cross-Sectional and Longitudinal Analyses.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {77},
number = {9},
pages = {1724-1733},
doi = {10.1093/gerona/glab381},
pmid = {35032170},
issn = {1758-535X},
support = {DE 842/7-1//Deutsche Forschungsgemeinschaft/ ; #01UW0808//German Federal Ministry of Education and Research/ ; },
mesh = {*Activities of Daily Living ; Aged ; Aging/genetics ; Biomarkers ; Cross-Sectional Studies ; *DNA Methylation ; Epigenesis, Genetic ; Humans ; Telomere/genetics ; },
abstract = {DNA methylation age acceleration (DNAmAA, derived from an epigenetic clock) and relative leukocyte telomere length (rLTL) are widely accepted biomarkers of aging. Nevertheless, it is still unclear which aspects of aging they represent best. Here we evaluated longitudinal associations between baseline rLTL and DNAmAA (estimated with 7-CpG clock) and functional assessments covering different domains of aging. Additionally, we made use of cross-sectional data on these assessments and examined their association with DNAmAA estimated by 5 different DNAm age measures. Two-wave longitudinal data were available for 1 083 participants of the Berlin Aging Study II who were reexamined on average 7.4 years after baseline as part of the GendAge study. Functional outcomes were assessed with Fried's frailty score, Tinetti mobility test, falls in the past 12 months (yes/no), finger-floor distance, Mini-Mental State Examination, Center for Epidemiologic Studies-Depression scale, activities of daily living, instrumented ADL, and mini nutritional assessment. Overall, we found no evidence for an association between the molecular biomarkers measured at baseline, rLTL, and DNAmAA (7-CpG clock), and functional assessments assessed at follow-up. Similarly, a cross-sectional analysis of follow-up data did also not show evidence for associations of the various DNAmAA measures (7-CpG clock, Horvath's clock, Hannum's clock PhenoAge, and GrimAge) with functional assessments. In conclusion, neither rLTL nor 7-CpG DNAmAA was able to predict impairment in the analyzed assessments over a ~7-year time course. Similarly, DNAmAA estimated from 5 epigenetic clocks was not a good cross-sectional marker of health deterioration either.},
}
@article {pmid35024423,
year = {2022},
author = {Amin, V and Fletcher, JM and Sun, Z and Lu, Q},
title = {Higher educational attainment is associated with longer telomeres in midlife: Evidence from sibling comparisons in the UK Biobank.},
journal = {SSM - population health},
volume = {17},
number = {},
pages = {101018},
pmid = {35024423},
issn = {2352-8273},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; P30 AG017266/AG/NIA NIH HHS/United States ; R01 AG060109/AG/NIA NIH HHS/United States ; },
abstract = {Prior studies have established that higher educational attainment is associated with a longer telomere length (TL), a marker of cellular aging. However, it is unclear whether extant associations are causal, since they are likely confounded by unobserved genetic, early-life and family background factors that are correlated with education and TL. We leverage sibling differences in TL, education and measured genetics (polygenic scores for educational attainment and TL) to estimate associations between educational attainment and TL in midlife for European ancestry individuals in the UK Biobank, while controlling for unobserved confounders shared by siblings. After controlling for genetics and shared background between siblings, we find suggestive evidence that high school graduates have longer telomeres than high school dropouts, but we find no differences in TL between high school dropouts and college graduates.},
}
@article {pmid35022670,
year = {2022},
author = {Stephens, Z and Ferrer, A and Boardman, L and Iyer, RK and Kocher, JA},
title = {Telogator: a method for reporting chromosome-specific telomere lengths from long reads.},
journal = {Bioinformatics (Oxford, England)},
volume = {38},
number = {7},
pages = {1788-1793},
pmid = {35022670},
issn = {1367-4811},
support = {R01 CA204013/CA/NCI NIH HHS/United States ; },
mesh = {*Telomere/genetics ; *Repetitive Sequences, Nucleic Acid ; Haplotypes ; },
abstract = {MOTIVATION: Telomeres are the repetitive sequences found at the ends of eukaryotic chromosomes and are often thought of as a 'biological clock,' with their average length shortening during division in most cells. In addition to their association with senescence, abnormal telomere lengths are well known to be associated with multiple cancers, short telomere syndromes and as risk factors for a broad range of diseases. While a majority of methods for measuring telomere length will report average lengths across all chromosomes, it is known that aberrations in specific chromosome arms are biomarkers for certain diseases. Due to their repetitive nature, characterizing telomeres at this resolution is prohibitive for short read sequencing approaches, and is challenging still even with longer reads.<br><br>RESULTS: We present Telogator: a method for reporting chromosome-specific telomere length from long read sequencing data. We demonstrate Telogator's sensitivity in detecting chromosome-specific telomere length in simulated data across a range of read lengths and error rates. Telogator is then applied to 10 germline samples, yielding a high correlation with short read methods in reporting average telomere length. In addition, we investigate common subtelomere rearrangements and identify the minimum read length required to anchor telomere/subtelomere boundaries in samples with these haplotypes.<br><br>Telogator is written in Python3 and is available at github.com/zstephens/telogator.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
}
@article {pmid35018411,
year = {2022},
author = {Westbrook, A and Zhang, R and Shi, M and Razavi, AC and Huang, Z and Chen, J and He, J and Kelly, T and Shen, Y and Li, C},
title = {Association Between Baseline Buccal Telomere Length and Progression of Kidney Function: The Health and Retirement Study.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {77},
number = {3},
pages = {471-476},
pmid = {35018411},
issn = {1758-535X},
support = {P20 GM109036/GM/NIGMS NIH HHS/United States ; U01 AG009740/AG/NIA NIH HHS/United States ; U01AG009740/AG/NIA NIH HHS/United States ; },
mesh = {Female ; Glomerular Filtration Rate ; Glycated Hemoglobin ; Humans ; *Kidney ; Male ; *Retirement ; Risk Factors ; Telomere/genetics ; },
abstract = {We aimed to evaluate associations of baseline telomere length with overall and annual change in estimated glomerular filtration rate (eGFR) and trajectory of kidney function during an 8-year follow-up. A total of 3 964 participants of the Health and Retirement Study were included. We identified 3 trajectory groups of kidney function: consistently normal (n = 1 163 or 29.3%), normal to impaired (n = 2 306 or 58.2%), and consistently impaired groups (n = 495 or 12.5%). After controlling for age, sex, race, education, smoking, drinking, diabetes, heart disease, blood pressure, body mass index, total cholesterol, and hemoglobin A1c, participants with longer telomere length were 20% less likely (odds ratio = 0.80, 95% confidence interval: 0.69-0.93, p = .003) to have a normal to impaired kidney function trajectory than a consistently normal function trajectory. Telomere length was not associated with changing rate of eGFR over 8 years (p = .45). Participants with longer telomere length were more likely to have consistently normal kidney function.},
}
@article {pmid35016866,
year = {2022},
author = {Hansen, E and Skotnes, T and Bustnes, JO and Helander, B and Eulaers, I and Sun, J and Covaci, A and Bårdsen, BJ and Zahn, S and Criscuolo, F and Bourgeon, S},
title = {Telomere length in relation to persistent organic pollutant exposure in white-tailed eagle (Haliaeetus albicilla) nestlings from Sweden sampled in 1995-2013.},
journal = {Environmental research},
volume = {208},
number = {},
pages = {112712},
doi = {10.1016/j.envres.2022.112712},
pmid = {35016866},
issn = {1096-0953},
mesh = {Animals ; *Eagles ; Environmental Monitoring ; *Environmental Pollutants ; Persistent Organic Pollutants ; Sweden ; Telomere ; },
abstract = {Telomeres are used as biomarkers of vertebrate health because of the link between their length, lifespan, and survival. Exposure to environmental stressors appears to alter telomere dynamics, but little is known about telomere length and persistent organic pollutant (POP) exposure in wildlife. The white-tailed eagle (WTE; Haliaeetus albicilla) is an avian top predator that accumulates high levels of POPs and may subsequently suffer adverse health effects. Here we study the Baltic WTE population that is well documented to have been exposed to large contaminant burdens, thereby making it a promising candidate species for analyzing pollutant-mediated effects on telomeres. We investigated telomere lengths in WTE nestlings (n = 168) over 19 years and examined legacy POP concentrations (organochlorines and polybrominated diphenyl ethers) in whole blood and serum as potential drivers of differences in telomere length. Although we detected significant year-to-year variations in telomere lengths among the WTE nestlings, telomere lengths did not correlate with any of the investigated POP concentrations of several classes. Given that telomere lengths did not associate with POP contamination in the Baltic WTE nestlings, we propose that other environmental and biological factors, which likely fluctuate on a year-to-year basis, could be more important drivers of telomere lengths in this population.},
}
@article {pmid35011817,
year = {2021},
author = {Barragán, R and Ortega-Azorín, C and Sorlí, JV and Asensio, EM and Coltell, O and St-Onge, MP and Portolés, O and Corella, D},
title = {Effect of Physical Activity, Smoking, and Sleep on Telomere Length: A Systematic Review of Observational and Intervention Studies.},
journal = {Journal of clinical medicine},
volume = {11},
number = {1},
pages = {},
pmid = {35011817},
issn = {2077-0383},
support = {PROMETEO 17/2017//Conselleria de Innovaci&#xf3;n, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana/ ; APOSTD/2019/136//Conselleria de Innovaci&#xf3;n, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana/ ; PI19/00781//Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Econom&#xed;a y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER)/ ; SAF2016-80532-R//Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Econom&#xed;a y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER)/ ; PID2019-108858RB-I00//Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Econom&#xed;a y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER)/ ; UJI-B2018-69//Universitat Jaume I/ ; PROMETEO 21/2021//Generalitat Valenciana Conselleria de Innovaci&#xf3;n, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana/ ; PID2019-108858RB-I00//AEI 10.13039/501100011033 and, by "ERDF A way of making Europe"/ ; },
abstract = {Aging is a risk factor for several pathologies, restricting one's health span, and promoting chronic diseases (e.g., cardiovascular and neurodegenerative diseases), as well as cancer. Telomeres are regions of repetitive DNA located at chromosomal ends. Telomere length has been inversely associated with chronological age and has been considered, for a long time, a good biomarker of aging. Several lifestyle factors have been linked with telomere shortening or maintenance. However, the consistency of results is hampered by some methodological issues, including study design, sample size, measurement approaches, and population characteristics, among others. Therefore, we aimed to systematically review the current literature on the effects of three relevant lifestyle factors on telomere length in human adults: physical activity, smoking, and sleep. We conducted a qualitative systematic review of observational and intervention studies using the Preferred Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The systematic literature search covered articles published in MEDLINE and EMBASE databases (from 2010 to 2020). A total of 1400 studies were identified; 83 were included after quality control. Although fewer sedentary activities, optimal sleep habits, and non- or ex-smoker status have been associated with less telomere shortening, several methodological issues were detected, including the need for more targeted interventions and standardized protocols to better understand how physical activity and sleep can impact telomere length and aging. We discuss the main findings and current limitations to gain more insights into the influence of these lifestyle factors on the healthy aging process.},
}
@article {pmid35011715,
year = {2022},
author = {Haupt, S and Niedrist, T and Sourij, H and Schwarzinger, S and Moser, O},
title = {The Impact of Exercise on Telomere Length, DNA Methylation and Metabolic Footprints.},
journal = {Cells},
volume = {11},
number = {1},
pages = {},
pmid = {35011715},
issn = {2073-4409},
mesh = {Aged ; Aging/*genetics ; Cellular Senescence/*genetics ; DNA Methylation/*genetics ; Exercise/*genetics ; Humans ; Telomere Homeostasis/*physiology ; },
abstract = {Aging as a major risk factor influences the probability of developing cancer, cardiovascular disease and diabetes, amongst others. The underlying mechanisms of disease are still not fully understood, but research suggests that delaying the aging process could ameliorate these pathologies. A key biological process in aging is cellular senescence which is associated with several stressors such as telomere shortening or enhanced DNA methylation. Telomere length as well as DNA methylation levels can be used as biological age predictors which are able to detect excessive acceleration or deceleration of aging. Analytical methods examining aging are often not suitable, expensive, time-consuming or require a high level of technical expertise. Therefore, research focusses on combining analytical methods which have the potential to simultaneously analyse epigenetic, genomic as well as metabolic changes.},
}
@article {pmid35008850,
year = {2021},
author = {Ruiz, A and Flores-Gonzalez, J and Buendia-Roldan, I and Chavez-Galan, L},
title = {Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases.},
journal = {International journal of molecular sciences},
volume = {23},
number = {1},
pages = {},
pmid = {35008850},
issn = {1422-0067},
mesh = {Animals ; COVID-19/genetics/immunology ; Cellular Senescence/genetics ; Genetic Therapy/methods ; Humans ; Immunotherapy/methods ; Lung Diseases/drug therapy/*genetics/*immunology ; Telomere Shortening/*immunology ; },
abstract = {Telomeres are localized at the end of chromosomes to provide genome stability; however, the telomere length tends to be shortened with each cell division inducing a progressive telomere shortening (TS). In addition to age, other factors, such as exposure to pollutants, diet, stress, and disruptions in the shelterin protein complex or genes associated with telomerase induce TS. This phenomenon favors cellular senescence and genotoxic stress, which increases the risk of the development and progression of lung diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, SARS-CoV-2 infection, and lung cancer. In an infectious environment, immune cells that exhibit TS are associated with severe lymphopenia and death, whereas in a noninfectious context, naïve T cells that exhibit TS are related to cancer progression and enhanced inflammatory processes. In this review, we discuss how TS modifies the function of the immune system cells, making them inefficient in maintaining homeostasis in the lung. Finally, we discuss the advances in drug and gene therapy for lung diseases where TS could be used as a target for future treatments.},
}
@article {pmid35006465,
year = {2021},
author = {Claude, E and de Lhoneux, G and Pierreux, CE and Marbaix, E and de Ville de Goyet, M and Boulanger, C and Van Damme, A and Brichard, B and Decottignies, A},
title = {Detection of alternative lengthening of telomeres mechanism on tumor sections.},
journal = {Molecular biomedicine},
volume = {2},
number = {1},
pages = {32},
pmid = {35006465},
issn = {2662-8651},
support = {7.6519.20//fonds de la recherche scientifique - fnrs/ ; 2018-072-project # FAF-F/208/1208//fondation contre le cancer (be)/ ; 2016-J1151710-206515//king baudouin foundation (be)/ ; },
abstract = {The vast majority of adult cancer cells achieve cellular immortality by activating a telomere maintenance mechanism (TMM). While this is mostly achieved by the de-silencing of hTERT telomerase gene expression, an alternative homologous recombination-based and telomerase-independent mechanism, known as ALT (Alternative Lengthening of Telomeres), is frequently activated in a subset of tumors, including paediatric cancers. Being absent from normal cells, the ALT mechanism offers interesting perspectives for new targeted cancer therapies. To date, however, the development of better translationally applicable tools for ALT detection in tumor sections is still needed. Here, using a newly derived ALT-positive cancer cell mouse xenograft model, we extensively examined how the previously known ALT markers could be used as reliable tools for ALT diagnosis in tumor sections. We found that, together with the detection of ultra-bright telomeric signals (UBS), an ALT hallmark, native telomeric FISH, that detects single-stranded C-rich telomeric DNA, provides a very sensitive and robust tool for ALT diagnosis in tissues. We applied these assays to paediatric tumor samples and readily identified three ALT-positive tumors for which the TMM was confirmed by the gold-standard C-circle amplification assay. Although the latter offers a robust assay for ALT detection in the context of research laboratories, it is more difficult to set up in histopathological laboratories and could therefore be conveniently replaced by the combination of UBS detection and native telomeric FISH.},
}
@article {pmid34998722,
year = {2022},
author = {Pauleck, S and Gigic, B and Cawthon, RM and Ose, J and Peoples, AR and Warby, CA and Sinnott, JA and Lin, T and Boehm, J and Schrotz-King, P and Li, CI and Shibata, D and Siegel, EM and Figueiredo, JC and Toriola, AT and Schneider, M and Ulrich, AB and Hoffmeister, A and Ulrich, CM and Hardikar, S},
title = {Association of circulating leukocyte telomere length with survival in patients with colorectal cancer.},
journal = {Journal of geriatric oncology},
volume = {13},
number = {4},
pages = {480-485},
pmid = {34998722},
issn = {1879-4076},
support = {R01 CA189184/CA/NCI NIH HHS/United States ; U01 CA206110/CA/NCI NIH HHS/United States ; R01 NR018762/NR/NINR NIH HHS/United States ; P30 CA042014/CA/NCI NIH HHS/United States ; R01 CA207371/CA/NCI NIH HHS/United States ; K07 CA222060/CA/NCI NIH HHS/United States ; },
mesh = {*Colorectal Neoplasms/genetics ; Disease-Free Survival ; Humans ; Kaplan-Meier Estimate ; Leukocytes ; *Telomere/genetics ; },
abstract = {INTRODUCTION: Telomere shortening, as seen with aging, can cause chromosomal instability and promote cancer progression. We investigated the association between circulating telomere length and overall and disease-free survival in a sub-cohort of patients with colorectal cancer.<br><br>METHODS: Baseline genomic DNA from blood leukocytes was extracted from N&#xa0;=&#xa0;92 newly diagnosed stage I-IV patients with colorectal cancer enrolled at the ColoCare Study site in Heidelberg, Germany. Detailed information on clinicodemographic (including age) and lifestyle risk factors, and clinical outcomes (including recurrence and survival) was collected. Telomere length was measured in DNA using multiplex quantitative polymerase chain reaction. Kaplan Meier survival curves were generated comparing shorter to longer telomere lengths with log-rank testing.<br><br>RESULTS: The mean T/S ratio for study patients was 0.5 (range: 0.3-0.9). Shorter telomeres were associated with older age at baseline. Patients with shorter telomeres experienced a worse overall and disease-free survival, although this association did not reach statistical significance. Kaplan-Meier survival curves for those with circulating telomere length below vs. above the median showed poorer overall (log-rank p&#xa0;=&#xa0;0.31) and disease-free survival (long-rank p&#xa0;=&#xa0;0.23).<br><br>CONCLUSIONS: Our results suggest that individuals with shorter telomeres, as seen with aging, may experience a worse overall and disease-free survival after colorectal cancer diagnosis. Larger sample sizes with longer follow-up are needed to further evaluate telomere length as a prognostic biomarker in colorectal cancer progression.},
}
@article {pmid34997994,
year = {2022},
author = {Pepke, ML and Kvalnes, T and Rønning, B and Jensen, H and Boner, W and Saether, BE and Monaghan, P and Ringsby, TH},
title = {Artificial size selection experiment reveals telomere length dynamics and fitness consequences in a wild passerine.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6224-6238},
doi = {10.1111/mec.16340},
pmid = {34997994},
issn = {1365-294X},
mesh = {Humans ; Male ; Female ; Animals ; *Longevity/genetics ; Selection, Genetic ; Telomere ; *Passeriformes/genetics ; Telomere Shortening/genetics ; },
abstract = {Telomere dynamics could underlie life-history trade-offs among growth, size and longevity, but our ability to quantify such processes in natural, unmanipulated populations is limited. We investigated how 4 years of artificial selection for either larger or smaller tarsus length, a proxy for body size, affected early-life telomere length (TL) and several components of fitness in two insular populations of wild house sparrows over a study period of 11 years. The artificial selection was expected to shift the populations away from their optimal body size and increase the phenotypic variance in body size. Artificial selection for larger individuals caused TL to decrease, but there was little evidence that TL increased when selecting for smaller individuals. There was a negative correlation between nestling TL and tarsus length under both selection regimes. Males had longer telomeres than females and there was a negative effect of harsh weather on TL. We then investigated whether changes in TL might underpin fitness effects due to the deviation from the optimal body size. Mortality analyses indicated disruptive selection on TL because both short and long early-life telomeres tended to be associated with the lowest mortality rates. In addition, there was a tendency for a negative association between TL and annual reproductive success, but only in the population where body size was increased experimentally. Our results suggest that natural selection for optimal body size in the wild may be associated with changes in TL during growth, which is known to be linked to longevity in some bird species.},
}
@article {pmid34995210,
year = {2022},
author = {Guo, L and Chen, Y and Li, H and Yin, F and Ge, M and Hu, L and Zi, M and Qin, Z and He, Y},
title = {Telomere length is maternally inherited and associated with lipid metabolism in Chinese population.},
journal = {Aging},
volume = {14},
number = {1},
pages = {354-367},
pmid = {34995210},
issn = {1945-4589},
mesh = {Aged ; Aged, 80 and over ; Aging ; Asian People/*genetics ; China ; Female ; Humans ; Lipid Metabolism/*genetics ; Male ; Middle Aged ; Telomere/*genetics/*physiology ; Young Adult ; },
abstract = {Telomere is a unique DNA-protein complex which covers the ends of chromosomes to avoid end fusion and maintain the stability and integrity of chromosomes. Telomere length (TL) shortening has been linked to aging and various age-related diseases in humans. Here we recruited a total of 1031 Chinese individuals aged between 12 and 111 years, including 108 families with parents and their offspring. DNA was extracted from peripheral white blood cells and TL was measured by quantitative PCR (qPCR). We explored the associations of TL with age, gender and clinical variables, and tested the parental effects on TL variation. First, we found that TL was shortened with age, however, TL was better maintained in females than males. Second, there was a robust association of TL between mother and offspring, but not between father and their offspring. In addition, TL was inversely associated with visceral fat index in females, and positively associated with apolipoprotein A levels. Knockdown of the key genes for lipid metabolism (PNPLA2 and CPT1) shortened the TL in HepG2 cells. These findings indicate that TL is maternally inherited, and impairment of lipid metabolism may contribute to the TL shortening in the Chinese population.},
}
@article {pmid34993885,
year = {2022},
author = {Alzoubi, H and Minasi, S and Gianno, F and Antonelli, M and Belardinilli, F and Giangaspero, F and Jaffrain-Rea, ML and Buttarelli, FR},
title = {Alternative Lengthening of Telomeres (ALT) and Telomerase Reverse Transcriptase Promoter Methylation in Recurrent Adult and Primary Pediatric Pituitary Neuroendocrine Tumors.},
journal = {Endocrine pathology},
volume = {33},
number = {4},
pages = {494-505},
pmid = {34993885},
issn = {1559-0097},
mesh = {Adult ; Child ; Humans ; In Situ Hybridization, Fluorescence ; Neoplasm Recurrence, Local/genetics ; *Neuroendocrine Tumors/genetics/pathology ; *Pituitary Neoplasms/genetics ; *Telomerase/genetics ; *Telomere/genetics/pathology ; Telomere Homeostasis/genetics ; X-linked Nuclear Protein/genetics ; DNA Methylation ; Promoter Regions, Genetic ; },
abstract = {Neoplastic cells acquire the ability to proliferate endlessly by maintaining telomeres via telomerase, or alternative lengthening of telomeres (ALT). The role of telomere maintenance in pituitary neuroendocrine tumors (PitNETs) has yet to be thoroughly investigated. We analyzed surgical samples of 24 adult recurrent PitNETs (including onset and relapses for 14 of them) and 12 pediatric primary PitNETs. The presence of ALT was assessed using telomere-specific fluorescence in situ hybridization, methylation of telomerase reverse transcriptase promoter (TERTp) by methylation-specific PCR, and ATRX expression by immunohistochemistry. Among the adult recurrent PitNETs, we identified 3/24 (12.5%) ALT-positive cases. ALT was present from the onset and maintained in subsequent relapses, suggesting that this mechanism occurs early in tumorigenesis and is stable during progression. ATRX loss was only seen in one ALT-positive case. Noteworthy, ALT was observed in 3 out of 5 aggressive PitNETs, including two aggressive corticotroph tumors, eventually leading to patient's death. ALT-negative tumors (87.5%) were classified according to their low (29.2%), medium (50%), and high (8.3%) telomere fluorescence intensity, with no significant differences emerging in their molecular, clinical, or pathological characteristics. TERTp methylation was found in 6/24 cases (25%), with a total concordance in methylation status between onset and recurrences, suggesting that this mechanism remains stable throughout disease progression. TERTp methylation did not influence telomere length. In the pediatric cohort of PitNETs, TERTp methylation was also observed in 4/12 cases (33.3%), but no case of ALT activation was observed. In conclusion, ALT is triggered at onset and maintained during tumor progression in a subset of adult PitNETs, suggesting that it could be used for clinical purposes, as a potential predictor of aggressive behavior.},
}
@article {pmid34988401,
year = {2022},
author = {Song, S and Ma, D and Xu, L and Wang, Q and Liu, L and Tong, X and Yan, H},
title = {Low-intensity pulsed ultrasound-generated singlet oxygen induces telomere damage leading to glioma stem cell awakening from quiescence.},
journal = {iScience},
volume = {25},
number = {1},
pages = {103558},
pmid = {34988401},
issn = {2589-0042},
abstract = {Cancer stem cells, quiescent and drug resistant, have become a therapeutic target. Unlike high-intensity focused ultrasound directly killing tumor, low-intensity pulsed ultrasound (LIPUS), a new noninvasive physical device, promotes pluripotent stem cell differentiation and is primarily applied in tissue engineering but rarely in oncotherapy. We explored the effect and mechanism of LIPUS on glioma stem cell (GSC) expulsion from quiescence. Here, we observed that LIPUS led to attenuated expression of GSC biomarkers, promoted GSC escape from G0 quiescence, and significantly weakened the Wnt and Hh pathways. Of note, LIPUS transferred sonomechanical energy into cytochrome c and B5 proteins, which converted oxygen molecules into singlet oxygen, triggering telomere crisis. The in vivo and in vitro results confirmed that LIPUS enhanced the GSC sensitivity to temozolomide. These results demonstrated that LIPUS "waked up" GSCs to improve their sensitivity to chemotherapy, and importantly, we confirmed the direct targeted proteins of LIPUS in GSCs.},
}
@article {pmid34988044,
year = {2021},
author = {Montiel Ishino, FA and McNab, P and Villalobos, K and Cohen, JH and Nápoles, AM and Williams, F},
title = {Hispanic/Latino Acculturation Profiles and Telomere Length: Latent Class Analysis on a Nationally Representative Sample.},
journal = {Frontiers in public health},
volume = {9},
number = {},
pages = {640226},
pmid = {34988044},
issn = {2296-2565},
mesh = {*Acculturation ; Child ; Hispanic or Latino ; Humans ; Latent Class Analysis ; Nutrition Surveys ; Telomere ; Telomere Shortening ; United States ; },
abstract = {Background: Acculturation profiles and their impact on telomere length among foreign-born Hispanics/Latinos living in the United States (US) are relatively unknown. The limited research available has linked acculturation with shortened telomere length. Objectives: To identify acculturation profiles among a US representative sample of Hispanics/Latinos and to then examine telomere length differences between profiles. Methods: We conducted a latent class analysis among a non-institutionalized US-representative sample of Hispanics/Latinos using the 1999-2002 National Health and Nutrition Examination Survey (N = 2,292). The latent variable of acculturation was assessed by length of time in the US and language used as a child, read and spoken, usually spoken at home, used to think, and used with friends (i.e., Spanish and/or English). Telomere length assessed from leukocytes was used as the distal continuous outcome. Results: We identified five profiles: (1) low acculturated [33.2% of sample]; (2) partially integrated [18.6% of sample]; (3) integrated [19.4% of sample]; (4) partially assimilated [15.1% of sample]; and (5) assimilated [13.7% of sample]. Acculturation profiles revealed nuanced differences in conditional probabilities with language use despite the length of time spent in the US. While telomere length did vary, there were no significant differences between profiles. Conclusion: Profiles identified revealed that possible life-course and generational effects may be at play in the partially assimilated and assimilated profiles. Our findings expand public health research using complex survey data to identify and assess the dynamic relationship of acculturation profiles and health biomarkers, while being among the first to examine this context using a person-centered approach.},
}
@article {pmid34977149,
year = {2021},
author = {Al-Muraikhy, S and Sellami, M and Domling, AS and Rizwana, N and Agouni, A and Al-Khelaifi, F and Donati, F and Botre, F and Diboun, I and Elrayess, MA},
title = {Metabolic Signature of Leukocyte Telomere Length in Elite Male Soccer Players.},
journal = {Frontiers in molecular biosciences},
volume = {8},
number = {},
pages = {727144},
pmid = {34977149},
issn = {2296-889X},
abstract = {Introduction: Biological aging is associated with changes in the metabolic pathways. Leukocyte telomere length (LTL) is a predictive marker of biological aging; however, the underlying metabolic pathways remain largely unknown. The aim of this study was to investigate the metabolic alterations and identify the metabolic predictors of LTL in elite male soccer players. Methods: Levels of 837 blood metabolites and LTL were measured in 126 young elite male soccer players who tested negative for doping abuse at anti-doping laboratory in Italy. Multivariate analysis using orthogonal partial least squares (OPLS), univariate linear models and enrichment analyses were conducted to identify metabolites and metabolic pathways associated with LTL. Generalized linear model followed by receiver operating characteristic (ROC) analysis were conducted to identify top metabolites predictive of LTL. Results: Sixty-seven metabolites and seven metabolic pathways showed significant associations with LTL. Among enriched pathways, lysophospholipids, benzoate metabolites, and glycine/serine/threonine metabolites were elevated with longer LTL. Conversely, monoacylglycerols, sphingolipid metabolites, long chain fatty acids and polyunsaturated fatty acids were enriched with shorter telomeres. ROC analysis revealed eight metabolites that best predict LTL, including glutamine, N-acetylglutamine, xanthine, beta-sitosterol, N2-acetyllysine, stearoyl-arachidonoyl-glycerol (18:0/20:4), N-acetylserine and 3-7-dimethylurate with AUC of 0.75 (0.64-0.87, p < 0.0001). Conclusion: This study characterized the metabolic activity in relation to telomere length in elite soccer players. Investigating the functional relevance of these associations could provide a better understanding of exercise physiology and pathophysiology of elite athletes.},
}
@article {pmid34976365,
year = {2021},
author = {Akash, C and Prabhu, M and Maldar, A and Akash, P and Mishra, S and Madhura, TK and Kumar, S and Patil, RS and Piplani, S and Smitha, KS},
title = {Association of Telomere Length and Serum Vitamin D Levels with Type 2 Diabetes Mellitus and its Related Complications: A Possible Future Perspective.},
journal = {Genome integrity},
volume = {12},
number = {},
pages = {2},
pmid = {34976365},
issn = {2041-9414},
abstract = {Evidence show that shortened telomere length (TL) and low Vitamin D levels can increase the risk of type 2 diabetes mellitus (T2DM) and its associated complications. T2DM has been considered as an age-related disease, it may be associated with TL. The study aimed to evaluate the association of TL and Vitamin D levels with complications of T2DM and the impact of Vitamin D on TL in patients with T2DM. This 1-year cross-sectional study was conducted at a tertiary care hospital on 90 patients. Height, weight, body mass index, waist-hip ratio was calculated. Fasting blood sugars, postprandial blood sugar, and glycated hemoglobin (HbA1c) were analyzed. Absolute TL was obtained from quantitative real-time polymerase chain reaction (qPCR). Vitamin D estimation was done by chemiluminescent immunoassay. Descriptive analysis of the data was done using R i386 3.6.3. The study found a positive correlation between TL and Vitamin D levels (r = 0.64; P < 0.0001). The interaction with high HbA1c levels and lower levels of Vitamin D led to the shortening of TL (P = 0.0001). The median of TL and mean of Vitamin D levels were significantly less in the diabetic group (P < 0.0001). Vitamin D levels positively affected the TL and its levels had an inverse relation with the HbA1c levels. This association had a significant effect on the shortening of TL. Vitamin D also had a significant association with other diabetic complications that instigated the shortening of TL. Therefore, assessing the role of Vitamin D levels on the shortening of TL can prove to be crucial biomarkers in managing optimal glycemic levels in T2DM patients.},
}
@article {pmid34965558,
year = {2021},
author = {Belyi, DO and Ilyenko, I and Nastina, O and Sydorenko, G and Gabulavichene, Z and Kursina, N and Bazyka, O and Bilaya, V and Kovaliov, O and Bazyka, D},
title = {RELATIVE TELOMERE LENGTH OF PERIPHERAL BLOOD LYMPHOCYTES AND STRUCTURAL AND FUNCTIONAL STATE OF THE LEFT VENTRICLE MYOCARDIUM IN CLEAN-UP WORKERS OF THE CHORNOBYL ACCIDENT WHO SUFFERED FROM STENOTIC CORONARY ATHEROSCLEROSIS.},
journal = {Problemy radiatsiinoi medytsyny ta radiobiolohii},
volume = {26},
number = {},
pages = {319-338},
doi = {10.33145/2304-8336-2021-26-319-338},
pmid = {34965558},
issn = {2313-4607},
mesh = {Abnormalities, Radiation-Induced/epidemiology/*physiopathology ; Adult ; Case-Control Studies ; Chernobyl Nuclear Accident ; Coronary Artery Disease/epidemiology/*physiopathology ; Emergency Responders/*statistics &amp; numerical data ; Heart Ventricles/*physiopathology/*radiation effects ; Humans ; Lymphocytes/*pathology ; Male ; Middle Aged ; Radiation Exposure/adverse effects ; Radiation Injuries/epidemiology ; Radioactive Hazard Release/statistics &amp; numerical data ; Telomere Shortening/*radiation effects ; Ukraine/epidemiology ; },
abstract = {UNLABELLED: The objective was to analyze the relative telomere length (RTL) of peripheral blood lymphocytes depending onmyocardium structural and functional state in emergency workers (EW) of the Chornobyl accident who suffered fromcoronary arteries stenotic atherosclerosis.<br><br>MATERIALS AND METHODS: There were examined 60 male EW who operated at the Chornobyl nuclear power plant at1986 and 25 male non-irradiated persons (control group - CG) with coronary heart disease (CHD). Everyone EW andCG patients were almost healthy before the accident. During the period 2016-2021, they underwent a comprehen-sive clinical and laboratory examination, echodopplercardiographic examination and determination of RTL by fluo-rescent hybridization in situ using laser flow cytometry.<br><br>RESULTS: EW almost did not differ from CG according to its clinical characteristics, the presence of risk factors,indices of systolic and diastolic heart functions, as well as RTL. The analysis of variance showed that RTL was influ-enced by the fact of irradiation in combination with obesity (p = 0.020). At normal body weight, RTL average valuein CG was significantly higher than in EW (p = 0.023). According to the results of hierarchical cluster analysis of twovariables as RTL and end-diastolic volume normalized by body surface area (EDV/BSA), EW and CG patients togeth-er were divided into two subgroups. The first subgroup (1st cluster) differed from the second (2nd cluster) by signi-ficantly larger average values of left ventricle (LV) EDV and end-systolic volume (ESV) as well as EDV/BSA andESV/BSA, LV myocardial mass (MM) and MM/BSA, reduced ejection fraction (EF). In patients of the 1st cluster telom-eres were significantly shorter than in the 2nd one (10,3 &#xb1; 1.7 vs. 14.3 &#xb1; 2.0 at p = 0.000). The increase of myocar-dial mass and LV wall thickness caused the development of its hypertrophy. The number of people with hypertrophyLV was significantly higher among patients of the 1st cluster (91.6 vs. 67.2 %, p < 0.001) due to eccentric hypertro-phy LV. Accordingly, concentric hypertrophy LV was more common among patients in the 2nd cluster (24.6 vs. 4.2 %at p < 0.01). Patients of the 1st cluster was characterized by a more severe course of heart failure.<br><br>CONCLUSIONS: In patients who suffered from CHD with stenotic atherosclerosis of the coronary arteries and wereexposed to radiation 30-35 years earlier, having normal body weight, there was a reduction in telomere. Hierarchicalcluster analysis proved to be a good tool that allows by the value of RTL and EDV/BSA to separate the group ofpatients with the most severe clinical course of CHD and LV systolic dysfunction among patients with the samepathology.},
}
@article {pmid34965251,
year = {2021},
author = {Poláková, E and Albanaz, ATS and Zakharova, A and Novozhilova, TS and Gerasimov, ES and Yurchenko, V},
title = {Ku80 is involved in telomere maintenance but dispensable for genomic stability in Leishmania mexicana.},
journal = {PLoS neglected tropical diseases},
volume = {15},
number = {12},
pages = {e0010041},
pmid = {34965251},
issn = {1935-2735},
mesh = {Genome, Protozoan ; *Genomic Instability ; Humans ; Ku Autoantigen/genetics/*metabolism ; Leishmania mexicana/*genetics/*metabolism ; Leishmaniasis, Cutaneous/parasitology ; Protozoan Proteins/genetics/*metabolism ; Telomere/genetics/*metabolism ; Trypanosoma brucei brucei/genetics/metabolism ; },
abstract = {BACKGROUND: Telomeres are indispensable for genome stability maintenance. They are maintained by the telomere-associated protein complex, which include Ku proteins and a telomerase among others. Here, we investigated a role of Ku80 in Leishmania mexicana. Leishmania is a genus of parasitic protists of the family Trypanosomatidae causing a vector-born disease called leishmaniasis.<br><br>We used the previously established CRISPR/Cas9 system to mediate ablation of Ku80- and Ku70-encoding genes in L. mexicana. Complete knock-outs of both genes were confirmed by Southern blotting, whole-genome Illumina sequencing, and RT-qPCR. Resulting telomeric phenotypes were subsequently investigated using Southern blotting detection of terminal restriction fragments. The genome integrity in the Ku80- deficient cells was further investigated by whole-genome sequencing. Our work revealed that telomeres in the &#x394;Ku80 L. mexicana are elongated compared to those of the wild type. This is a surprising finding considering that in another model trypanosomatid, Trypanosoma brucei, they are shortened upon ablation of the same gene. A telomere elongation phenotype has been documented in other species and associated with a presence of telomerase-independent alternative telomere lengthening pathway. Our results also showed that Ku80 appears to be not involved in genome stability maintenance in L. mexicana.<br><br>CONCLUSION/SIGNIFICANCE: Ablation of the Ku proteins in L. mexicana triggers telomere elongation, but does not have an adverse impact on genome integrity.},
}
@article {pmid34964306,
year = {2022},
author = {Wolf, SE and Rosvall, KA},
title = {A multi-tissue view on telomere dynamics and postnatal growth.},
journal = {Journal of experimental zoology. Part A, Ecological and integrative physiology},
volume = {337},
number = {4},
pages = {346-355},
pmid = {34964306},
issn = {2471-5646},
support = {IOS-1656109//National Science Foundation/ ; //Indiana Academy of Science/ ; T32 HD049336/HD/NICHD NIH HHS/United States ; //The Society for Integrative &amp; Comparative Biology/ ; },
mesh = {Animals ; Biomarkers ; Longevity ; *Telomere ; Telomere Homeostasis ; *Telomere Shortening ; },
abstract = {Trade-offs between growth and self-maintenance are common in nature, such that early-life effects on growth can generate lasting consequences on survival and longevity. Telomeres-putative biomarkers of self-maintenance-may link early growth with these later phenotypic effects, but evidence for growth-telomere trade-offs is mixed. Null or even positive relationships between growth and telomeres may be driven by heterogeneity in resource availability or invariable allocation towards telomere maintenance within a population. We used nestling tree swallows (Tachycineta bicolor) to assess the directionality and timing of relationships between growth and telomere length in several tissues. We focused on two important phases of growth: first, the peak of postnatal growth occurring around 6 days old when nestlings grow by ~33% in a single day, and subsequently, the later phase of growth occurring as body mass plateaus near adult size at 12 days old. We quantified telomere attrition in blood during postnatal growth, as well as telomere length in the blood, brain, adrenals, and liver at 12 days old. Growth was unrelated to telomere length in the liver and telomere dynamics in blood. However, brain telomere length was positively correlated with peak growth, and adrenal telomere length was positively related to later growth, particularly for chicks that had experienced a temporary stressor. These observations suggest that variation in resource availability may mask trade-offs, generating positive correlations between growth and telomere length at the population level. They also provide insights into complex relationships between growth and self-maintenance that can be revealed by looking in multiple tissues.},
}
@article {pmid34959893,
year = {2021},
author = {Hakeem, S and Mendonça, N and Aspray, T and Kingston, A and Martin-Ruiz, C and Robinson, L and Hill, TR},
title = {The Association between 25-Hydroxyvitamin D Concentration and Telomere Length in the Very-Old: The Newcastle 85+ Study.},
journal = {Nutrients},
volume = {13},
number = {12},
pages = {},
pmid = {34959893},
issn = {2072-6643},
support = {MR/J50001X/1/MRC_/Medical Research Council/United Kingdom ; grant reference R124/0509//Dunhill Medical Trust/ ; grant reference G0500997/MRC_/Medical Research Council/United Kingdom ; grant reference G0500997/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {Age Factors ; Aged, 80 and over ; Aging/blood/*genetics/*physiology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Prospective Studies ; *Telomere Homeostasis ; Vitamin D/*analogs &amp; derivatives/blood ; },
abstract = {(1) Introduction: vitamin D may maintain the telomere length, either directly or via the inflammation effect and/or modulating the rate of cell proliferation. Whilst results from cross-sectional studies investigating the association between 25(OH)D concentration and telomere length have been mixed, there is a dearth of data from prospective studies which have assessed these associations. This study aimed to examine the association between 25(OH)D concentration in plasma and telomere length in blood cells in very-old adults (≥85 years old) at baseline, 18 months and 36 months by controlling for related lifestyle factors. (2) Methodology: our prospective cohort study comprised 775 participants from the Newcastle 85+ Study who had 25(OH)D measurements at baseline. Plasma 25(OH)D was stratified as <25 nmol/L (low), 25-50 nmol/L (moderate) and >50 nmol/L (high). Peripheral blood mononuclear cell telomere length was measured by quantitative real-time polymerase chain reaction at baseline, 18 and 36 months from baseline. (3) Results: a positive significant association was found between 25(OH)D concentration and telomere length amongst very-old participants at baseline (95% CI = 12.0-110.3, B = 61.2 ± 5.0, p = 0.015). This association was negative at 18 months (95% CI = -59.9--7.5, B = -33.7 ± 13.3, p = 0.012) but was non-significant at 36 months. (4) Conclusion: Circulating 25(OH)D concentration shows inconsistent relationships with telomere length over time in very-old (85+ year old) adults.},
}
@article {pmid34957928,
year = {2023},
author = {Liu, Q and Zhou, D and Duan, H and Zhu, Y and Du, Y and Sun, C and Lin, H and Jin, M and Fu, J and Gao, Y and Ma, F and Chen, Y and Zhang, M and Huang, G},
title = {Association of dietary inflammatory index and leukocyte telomere length with mild cognitive impairment in Chinese older adults.},
journal = {Nutritional neuroscience},
volume = {26},
number = {1},
pages = {50-59},
doi = {10.1080/1028415X.2021.2017660},
pmid = {34957928},
issn = {1476-8305},
mesh = {Aged ; Humans ; Middle Aged ; Cohort Studies ; Cross-Sectional Studies ; *East Asian People ; *Cognitive Dysfunction ; Leukocytes ; Telomere ; },
abstract = {BACKGROUND: There are minimal data on the relationship between DII and MCI in an elderly Chinese population and no research has assessed the potential effect of LTL.<br><br>OBJECTIVE: We investigated the association between DII and MCI while taking into account the potential effect of LTL.<br><br>METHODS: This cross-sectional study included 3,386 participants aged &#x2265; 60 years of age from the Tianjin Elderly Nutrition and Cognition Cohort study. DII score was constructed based on a validated self-administered food frequency questionnaire was calculated based on the method developed by Shivappa et al. LTL was measured by quantitative real-time polymerase chain reaction. Multivariable logistic regression analysis was used to analyze the association between DII, LTL and MCI. Moreover, mediation analysis was employed to test the mediation effect of LTL on the total effect of DII on MCI.<br><br>RESULTS: Compared with the participants in the lowest tertiles of LTL and DII score, the odds ratios (ORs) of MCI in the highest tertiles were 0.386(95% CI: 0.281-0.529) and 1.650 (95% CI: 1.232-2.209), respectively. The significant association between DII score and MCI persisted after further adjusting for LTL (OR: 1.595; 95% CI: 1.189-2.140). The link between DII score and MCI was mediated partially by LTL (&#x3b2;indirect effect= -0.008, P<0.05).<br><br>CONCLUSION: High DII score was positively associated with MCI prevalence in an elderly Chinese population and the link between DII scores and MCI seemed to be mediated partially by LTL.},
}
@article {pmid34955515,
year = {2022},
author = {Darvishi, FZ and Saadat, M},
title = {Morphine may have a role in telomere shortening.},
journal = {Psychiatric genetics},
volume = {32},
number = {2},
pages = {87-89},
pmid = {34955515},
issn = {1473-5873},
mesh = {Heroin/adverse effects ; Humans ; Leukocytes ; *Morphine/adverse effects ; Telomere/genetics ; *Telomere Shortening ; },
abstract = {Morphine/heroin may increase oxidative stress in drug-dependent persons. The imbalance between oxidative stress and antioxidant defense mechanisms can accelerate the shortening of telomere length. This article reports two sets of data; comparison of relative telomere length between heroin-dependent patients and healthy control group, as well as, investigation of the effect of morphine on the relative telomere length of human SH-SY5Y cells treated by morphine. Study participants were composed of 163 heroin-dependent patients and 166 unrelated healthy controls. SH-SY5Y cells were treated with (5 μM) morphine hydrochloride and incubated for 40 and 60 days. The relative telomere length was calculated as the T/S (telomere/single-copy gene) ratio using 36B4 as a reference for each sample, using quantitative real-time PCR. The mean (± SE) value of relative telomere length was 4.81 ± 0.21 and 6.38 ± 0.23 in leukocytes of heroin-dependent and control groups, respectively. The telomere length was significantly decreased in heroin-dependent participants (t = 4.97; df = 327; P < 0.0001). The relative telomere length in cells treated with morphine for 60 days was 4.50 ± 0.14 and in untreated cells was 5.75 ± 0.08. The difference was highly significant (t = 7.68; df = 4; P = 0.002). Our present findings indicate that morphine and dependency on heroin are significantly associated with shorter telomeres. The present findings may help to explain some of the adverse effects of drug dependency on health such as accelerating biologic processes related to aging.},
}
@article {pmid34949741,
year = {2022},
author = {Lim, YS and Nguyen, MTN and Pham, TX and Huynh, TTX and Park, EM and Choi, DH and Kang, SM and Tark, D and Hwang, SB},
title = {Hepatitis C Virus Nonstructural 5A Protein Interacts with Telomere Length Regulation Protein: Implications for Telomere Shortening in Patients Infected with HCV.},
journal = {Molecules and cells},
volume = {45},
number = {3},
pages = {148-157},
pmid = {34949741},
issn = {0219-1032},
mesh = {*Hepacivirus/physiology ; *Hepatitis C/genetics ; Humans ; RNA, Viral ; Telomere/genetics ; Telomere Shortening ; },
abstract = {Hepatitis C virus (HCV) is a major cause of chronic liver disease and is highly dependent on cellular proteins for viral propagation. Using protein microarray analysis, we identified 90 cellular proteins as HCV nonstructural 5A (NS5A) interacting partners, and selected telomere length regulation protein (TEN1) for further study. TEN1 forms a heterotrimeric complex with CTC and STN1, which is essential for telomere protection and maintenance. Telomere length decreases in patients with active HCV, chronic liver disease, and hepatocellular carcinoma. However, the molecular mechanism of telomere length shortening in HCV-associated disease is largely unknown. In the present study, protein interactions between NS5A and TEN1 were confirmed by immunoprecipitation assays. Silencing of TEN1 reduced both viral RNA and protein expression levels of HCV, while ectopic expression of the siRNA-resistant TEN1 recovered the viral protein level, suggesting that TEN1 was specifically required for HCV propagation. Importantly, we found that TEN1 is re-localized from the nucleus to the cytoplasm in HCV-infected cells. These data suggest that HCV exploits TEN1 to promote viral propagation and that telomere protection is compromised in HCV-infected cells. Overall, our findings provide mechanistic insight into the telomere shortening in HCV-infected cells.},
}
@article {pmid34947936,
year = {2021},
author = {Fan, HC and Chang, FW and Tsai, JD and Lin, KM and Chen, CM and Lin, SZ and Liu, CA and Harn, HJ},
title = {Telomeres and Cancer.},
journal = {Life (Basel, Switzerland)},
volume = {11},
number = {12},
pages = {},
pmid = {34947936},
issn = {2075-1729},
support = {TTMHH-R1100003 and TTMHH-R1100004.//Tungs' Taichung MetroHarbor Hospital/ ; },
abstract = {Telomeres cap the ends of eukaryotic chromosomes and are indispensable chromatin structures for genome protection and replication. Telomere length maintenance has been attributed to several functional modulators, including telomerase, the shelterin complex, and the CST complex, synergizing with DNA replication, repair, and the RNA metabolism pathway components. As dysfunctional telomere maintenance and telomerase activation are associated with several human diseases, including cancer, the molecular mechanisms behind telomere length regulation and protection need particular emphasis. Cancer cells exhibit telomerase activation, enabling replicative immortality. Telomerase reverse transcriptase (TERT) activation is involved in cancer development through diverse activities other than mediating telomere elongation. This review describes the telomere functions, the role of functional modulators, the implications in cancer development, and the future therapeutic opportunities.},
}
@article {pmid34945752,
year = {2021},
author = {Wai, KM and Kaori, S and Itoh, K and Shinya, O and Uchikawa, Y and Hayashi, S and Shiraki, A and Murashita, K and Nakaji, S and Ihara, K},
title = {Telomere Length and Arterial Stiffness Reflected by Brachial-Ankle Pulse Wave Velocity: A Population-Based Cross-Sectional Study.},
journal = {Journal of personalized medicine},
volume = {11},
number = {12},
pages = {},
pmid = {34945752},
issn = {2075-4426},
support = {JMPJCE1302//Japan Science and Technology Agency/ ; },
abstract = {Telomere (TL) is a biomarker of biological aging, and its shortening is associated with major risk factors for cardiovascular diseases (CVD). This study aimed to identify whether TL is associated with arterial stiffness as reflected by brachial-ankle pulse wave velocity (baPWV). This population-based cross-sectional study involved 1065 individuals in the Iwaki area, Japan. Total TL length and TL G-tail length were measured by hybridization protection assay. The baPWV was measured on the right and left sides using a non-invasive vascular screening device. The associations between TL and baPWV were assessed by multivariate linear regression. Compared with the shortest total TL tertile, the longest total TL group showed a significant decrease in baPWV (lowest vs. highest tertile: adjusted beta: -41.24, 95% confidence interval (CI): -76.81, -5.68). The mean baPWV decreased with a longer TL (TL G-tail length: p trend < 0.001, total TL: p trend < 0.001). TL G-tail and total TL lengths were inversely associated with baPWV, implicating TL shortening in the development of CVD. This study provides evidence of the factors influencing CVD risks at a very early stage when individuals can still take necessary precautions before CVD gives rise to a symptomatic health outcome.},
}
@article {pmid34944968,
year = {2021},
author = {Roy Choudhury, S and Ashby, C and Zhan, F and van Rhee, F},
title = {Epigenetic Deregulation of Telomere-Related Genes in Newly Diagnosed Multiple Myeloma Patients.},
journal = {Cancers},
volume = {13},
number = {24},
pages = {},
pmid = {34944968},
issn = {2072-6694},
support = {R01 CA236814/CA/NCI NIH HHS/United States ; },
abstract = {High-risk Multiple Myeloma (MM) patients were found to maintain telomere length (TL), below the margin of short critical length, consistent with proactive overexpression of telomerase. Previously, DNA methylation has been shown as a determinant of telomere-related gene (TRG) expression and TL to assess risk in different types of cancer. We mapped genome-wide DNA methylation in a cohort of newly diagnosed MM (NDMM; n = 53) patients of major molecular subgroups, compared to age-matched healthy donors (n = 4). Differential methylation and expression at TRG-loci were analyzed in combination with overlapping chromatin marks and underlying DNA-sequences. We observed a strong correlation (R[2] ≥ 0.5) between DNA methylation and expression amongst selective TRGs, such that demethylation at the promoters of DDX1 and TERF1 were associated to their oncogenic upregulation, while demethylation at the bodies of two key tumor suppressors ZNF208 and RAP1A led to downregulation of the genes. We demonstrated that TRG expression may be controlled by DNA methylation alone or in cooperation with chromatin modifications or CCCTC-binding factor at the regulatory regions. Additionally, we showed that hypomethylated DMRs of TRGs in NDMM are stabilized with G-quadruplex forming sequences, suggesting a crucial role of these epigenetically vulnerable loci in MM pathogenesis. We have identified a panel of five TRGs, which are epigenetically deregulated in NDMM patients and may serve as early detection biomarkers or therapeutic targets in the disease.},
}
@article {pmid34943011,
year = {2021},
author = {Hassler, E and Almer, G and Reishofer, G and Marsche, G and Mangge, H and Deutschmann, H and Herrmann, M and Leber, S and Gunzer, F and Renner, W},
title = {Sex-Specific Association of Serum Anti-Oxidative Capacity and Leukocyte Telomere Length.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {10},
number = {12},
pages = {},
pmid = {34943011},
issn = {2076-3921},
abstract = {Telomeres are a crucial factor in the preservation of genomic integrity, and an elevated risk for diseases such as cancer and cardiovascular events is related to shortened telomeres. However, telomere deterioration could be caused by factors such as chronic oxidative stress and inflammation, which are promoted by an imbalance among reactive oxygen species (ROS) and antioxidants. In this cross-sectional study, we investigated the relationship between telomeres and oxidative stress. The serum leucocyte telomer length (LTL), serum total antioxidant capacity (TAC) and the total serum lipid panel of 180 healthy athletic volunteers (90 males, 90 females) were measured Additionally, a questionnaire about sports behaviour and the type of training was completed. We observed a positive significant relation between serum LTL and TAC in the male group (cc = 3.4/p = 0.001) but not in females. There was no statistically significant correlation between age and physical activity and LTL in both groups. This is the first cross sectional study demonstrating an association between total serum TAC and LTL in healthy males, but interestingly, not in the females. Nevertheless, these results should be interpreted as preliminary, and further studies in independent cohorts are needed to investigate the sex-specific effects of oxidative stress on telomere length and telomerase activity.},
}
@article {pmid34941841,
year = {2021},
author = {Quimby, J and Erickson, A and Mcleland, S and Cianciolo, R and Maranon, D and Lunn, K and Elliott, J and Lawson, J and Hess, A and Paschall, R and Bailey, S},
title = {Renal Senescence, Telomere Shortening and Nitrosative Stress in Feline Chronic Kidney Disease.},
journal = {Veterinary sciences},
volume = {8},
number = {12},
pages = {},
pmid = {34941841},
issn = {2306-7381},
abstract = {Kidney tissues from cats with naturally occurring chronic kidney disease (CKD) and adult and senior cats without CKD were assessed to determine whether telomere shortening and nitrosative stress are associated with senescence in feline CKD. The histopathologic assessment of percent global glomerulosclerosis, inflammatory infiltrate, and fibrosis was performed. Senescence and nitrosative stress were evaluated utilizing p16 and iNOS immunohistochemistry, respectively. Renal telomere length was evaluated using telomere fluorescent in situ hybridization combined with immunohistochemistry. CKD cats were found to have significantly increased p16 staining in both the renal cortex and corticomedullary junction compared to adult and senior cats. Senior cats had significantly increased p16 staining in the corticomedullary junction compared to adult cats. p16 staining in both the renal cortex and corticomedullary junction were found to be significantly correlated with percent global glomerulosclerosis, cortical inflammatory infiltrate, and fibrosis scores. p16 staining also correlated with age in non-CKD cats. Average telomere length was significantly decreased in CKD cats compared to adult and senior cats. CKD cats had significantly increased iNOS staining compared to adult cats. Our results demonstrate increased renal senescence, telomere shortening, and nitrosative stress in feline CKD, identifying these patients as potential candidates for senolytic therapy with translational potential.},
}
@article {pmid34937532,
year = {2021},
author = {Libertini, G and Shubernetskaya, O and Corbi, G and Ferrara, N},
title = {Is Evidence Supporting the Subtelomere-Telomere Theory of Aging?.},
journal = {Biochemistry. Biokhimiia},
volume = {86},
number = {12},
pages = {1526-1539},
doi = {10.1134/S0006297921120026},
pmid = {34937532},
issn = {1608-3040},
mesh = {Aging/*genetics/metabolism ; Animals ; Cellular Senescence/*genetics ; *Epigenesis, Genetic ; Humans ; Inflammation/genetics/metabolism ; *Models, Genetic ; Oxidation-Reduction ; Telomere/*genetics/metabolism ; Telomere Homeostasis/*genetics ; },
abstract = {The telomere theory tries to explain cellular mechanisms of aging as mainly caused by telomere shortening at each duplication. The subtelomere-telomere theory overcomes various shortcomings of telomere theory by highlighting the essential role of subtelomeric DNA in aging mechanisms. The present work illustrates and deepens the correspondence between assumptions and implications of subtelomere-telomere theory and experimental results. In particular, it is investigated the evidence regarding the relationships between aging and (i) epigenetic modifications; (ii) oxidation and inflammation; (iii) telomere protection; (iv) telomeric heterochromatin hood; (v) gradual cell senescence; (vi) cell senescence; and (vii) organism decline with telomere shortening. The evidence appears broadly in accordance or at least compatible with the description and implications of the subtelomere-telomere theory. In short, phenomena of cellular aging, by which the senescence of the whole organism is determined in various ways, appear substantially dependent on epigenetic modifications regulated by the subtelomere-telomere-telomeric hood-telomerase system. These phenomena appear to be not random, inevitable, and irreversible but rather induced and regulated by genetically determined mechanisms, and modifiable and reversible by appropriate methods. All this supports the thesis that aging is a genetically programmed and regulated phenoptotic phenomenon and is against the opposite thesis of aging as caused by random and inevitable degenerative factors.},
}
@article {pmid34933911,
year = {2022},
author = {Sui, JD and Tang, Z and Chen, BPC and Huang, P and Yang, MQ and Wang, NH and Yang, HN and Tu, HL and Jiang, QM and Zhang, J and Wang, Y and Wu, YZ},
title = {Protein Phosphatase 2A-Dependent Mitotic hnRNPA1 Dephosphorylation and TERRA Formation Facilitate Telomere Capping.},
journal = {Molecular cancer research : MCR},
volume = {20},
number = {4},
pages = {583-595},
doi = {10.1158/1541-7786.MCR-21-0581},
pmid = {34933911},
issn = {1557-3125},
mesh = {DNA-Binding Proteins ; Heterogeneous Nuclear Ribonucleoprotein A1/genetics/metabolism ; Humans ; *Protein Phosphatase 2/genetics/metabolism ; Replication Protein A/genetics/metabolism ; Telomere/genetics/metabolism ; *Telomere-Binding Proteins/genetics ; Transcription Factors ; },
abstract = {UNLABELLED: The heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), telomeric repeat-containing RNA (TERRA), and protection of telomeres 1 (POT1) have been reported to orchestrate to displace replication protein A (RPA) from telomeric overhangs, ensuring orderly telomere replication and capping. Our previous studies further demonstrated that DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-dependent hnRNPA1 phosphorylation plays a crucial role in the promotion of hnRNPA1 binding to telomeric overhangs and RPA displacement during G2-M phases. However, it is unclear that how the subsequent exchange between hnRNPA1 and POT1 is orchestrated. Here we report that the protein phosphatase 2A (PP2A) depends on its scaffold subunit, which is called PPP2R1A, to interact with and dephosphorylate hnRNPA1 in the late M phase. Furthermore, PP2A-mediated hnRNPA1 dephosphorylation and TERRA accumulation act in concert to promote the hnRNPA1-to-POT1 switch on telomeric single-stranded DNA. Consequently, defective PPP2R1A results in ataxia telangiectasia and Rad3-related (ATR)-mediated DNA damage response at telomeres as well as induction of fragile telomeres. Combined inhibition of ATR and PP2A induces entry into a catastrophic mitosis and leads to synthetic lethality of tumor cells. In addition, PPP2R1A levels correlate with clinical stages and prognosis of multiple types of cancers. Taken together, our results indicate that PP2A is critical for telomere maintenance.<br><br>IMPLICATIONS: This study demonstrates that the PP2A-dependent hnRNPA1 dephosphorylation and TERRA accumulation facilitates the formation of the protective capping structure of newly replicated telomeres, thus exerting essential oncogenic role in tumorigenesis.},
}
@article {pmid34933798,
year = {2022},
author = {Alder, JK and Sutton, RM and Iasella, CJ and Nouraie, M and Koshy, R and Hannan, SJ and Chan, EG and Chen, X and Zhang, Y and Brown, M and Popescu, I and Veatch, M and Saul, M and Berndt, A and Methé, BA and Morris, A and Pilewski, JM and Sanchez, PG and Morrell, MR and Shapiro, SD and Lindell, KO and Gibson, KF and Kass, DJ and McDyer, JF},
title = {Lung transplantation for idiopathic pulmonary fibrosis enriches for individuals with telomere-mediated disease.},
journal = {The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation},
volume = {41},
number = {5},
pages = {654-663},
pmid = {34933798},
issn = {1557-3117},
support = {R01 HL133184/HL/NHLBI NIH HHS/United States ; R01 HL135062/HL/NHLBI NIH HHS/United States ; R35 HL139860/HL/NHLBI NIH HHS/United States ; },
mesh = {Humans ; *Idiopathic Pulmonary Fibrosis/genetics/surgery ; *Lung Diseases, Interstitial ; *Lung Transplantation ; Middle Aged ; Telomere/genetics ; Telomere Shortening/genetics ; },
abstract = {BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common indication for lung transplantation in North America and variants in telomere-maintenance genes are the most common identifiable cause of IPF. We reasoned that younger IPF patients are more likely to undergo lung transplantation and we hypothesized that lung transplant recipients would be enriched for individuals with telomere-mediated disease due to the earlier onset and more severe disease in these patients.<br><br>METHODS: Individuals with IPF who underwent lung transplantation or were evaluated in an interstitial lung disease specialty clinic who did not undergo lung transplantation were examined. Genetic evaluation was completed via whole genome sequencing (WGS) of 426 individuals and targeted sequencing for 5 individuals. Rare variants in genes previously associated with IPF were classified using the American College of Medical Genetics guidelines. Telomere length from WGS data was measured using TelSeq software. Patient characteristics were collected via medical record review.<br><br>RESULTS: Of 431 individuals, 149 underwent lung transplantation for IPF. The median age of diagnosis of transplanted vs non-transplanted individuals was significantly younger (60 years vs 70 years, respectively, p<0.0001). IPF lung transplant recipients (IPF-LTRs) were twice as likely to have telomere-related rare variants compared to non-transplanted individuals (24% vs 12%, respectively, p=0.0013). IPF-LTRs had shorter telomeres than non-transplanted IPF patients (p=0.0028) and >85% had telomeres below the age-adjusted mean. Post-transplant survival and CLAD were similar amongst IPF-LTRs with rare variants in telomere-maintenance genes compared to those without, as well as in those with short telomeres versus longer telomeres.<br><br>CONCLUSIONS: There is an enrichment for telomere-maintenance gene variants and short telomeres among IPF-LTRs. However, transplant outcomes of survival and CLAD do not differ by gene variants or telomere length within IPF-LTRs. Our findings support individual with telomere-mediated disease should not be excluded from lung transplantation and focusing research efforts on therapies directed toward individuals with short-telomere mediated disease.},
}
@article {pmid34928768,
year = {2022},
author = {Abramson, DH and Cruz-Abrams, R and Francis, JH},
title = {Coats Disease and Premature Telomere Shortening.},
journal = {Journal of pediatric ophthalmology and strabismus},
volume = {59},
number = {4},
pages = {280},
doi = {10.3928/01913913-20211115-01},
pmid = {34928768},
issn = {1938-2405},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; },
mesh = {Female ; Humans ; *Premature Birth ; *Retinal Telangiectasis/diagnosis/genetics ; Telomere Shortening ; },
}
@article {pmid34924765,
year = {2021},
author = {Xie, Y and Lou, D and Zhang, D},
title = {Melatonin Alleviates Age-Associated Endothelial Injury of Atherosclerosis via Regulating Telomere Function.},
journal = {Journal of inflammation research},
volume = {14},
number = {},
pages = {6799-6812},
pmid = {34924765},
issn = {1178-7031},
abstract = {BACKGROUND: Atherosclerosis is an aging-related disease, partly attributed to telomerase dysfunction. This study aims to investigate whether telomere dysfunction-related vascular aging is involved in the protection mechanism of melatonin (MLT) in atherosclerosis.<br><br>METHODS: Young and aged ApoE[-/-] mice were used to establish atherosclerotic mice model. H&amp;E staining and immunofluorescence assay were performed to detect endothelial cell injury and apoptosis. Inflammatory cytokines and oxidative stress-related factors were determined using corresponding commercial assay kits. Telomerase activity was detected by TRAP assay, and SA-&#x3b2;-gal staining was conducted to evaluate cellular senescence. HUVECs were treated with H2O2 for 1 h to induce senescence. Western blot was performed to measure protein expression.<br><br>RESULTS: An obvious vascular endothelial injury, reflected by excessive production of inflammatory cytokines, elevated ROS, MDA and SOD levels, and more apoptotic endothelial cells, was found in atherosclerotic mice, especially in aged mice, which were then greatly suppressed by MLT. In addition, telomere dysfunction and senescence occurred in atherosclerosis, especially in aged mice, while MLT significantly alleviated the conditions. CYP1A1, one of the targeted genes of MLT, was verified to be upregulated in atherosclerotic mice but downregulated by MLT. Furthermore, H2O2 induced a senescence model in HUVECs, which was accompanied with a remarkably increased cell viability loss and apoptosis rate, and a downregulated telomerase activity of HUVECs, and this phenomenon was strengthened by RHPS4, an inhibitor of telomerase activity. However, MLT could partly abolish these changes in H2O2- and RHPS4-treated HUVECs, demonstrating that MLT alleviated vascular endothelial injury by regulating senescence and telomerase activity.<br><br>CONCLUSIONS: Collectively, this study provided evidence for the protective role of MLT in atherosclerosis through regulating telomere dysfunction-related vascular aging.},
}
@article {pmid34921825,
year = {2022},
author = {Herrera-Moreno, JF and Estrada-Gutierrez, G and Wu, H and Bloomquist, TR and Rosa, MJ and Just, AC and Lamadrid-Figueroa, H and Téllez-Rojo, MM and Wright, RO and Baccarelli, AA},
title = {Prenatal lead exposure, telomere length in cord blood, and DNA methylation age in the PROGRESS prenatal cohort.},
journal = {Environmental research},
volume = {205},
number = {},
pages = {112577},
doi = {10.1016/j.envres.2021.112577},
pmid = {34921825},
issn = {1096-0953},
support = {R00 ES027496/ES/NIEHS NIH HHS/United States ; R01 ES021357/ES/NIEHS NIH HHS/United States ; R01 ES032242/ES/NIEHS NIH HHS/United States ; },
mesh = {Adult ; DNA Methylation ; Female ; *Fetal Blood ; Humans ; Infant, Newborn ; *Lead/toxicity ; Maternal Exposure/adverse effects ; Obesity ; Pregnancy ; Telomere ; Young Adult ; },
abstract = {BACKGROUND: Lead is a ubiquitous pollutant with deleterious effects on human health and remains a major current public health concern in developing countries. This heavy metal may interfere with nucleic acids via oxidative stress or epigenetic changes that affect biological markers of aging, e.g., telomere length and DNA methylation (DNAm). Telomere shortening associates with biological age in newborns, and DNA methylation at specific CpG sites can be used to calculate "epigenetic clocks".<br><br>OBJECTIVE: The aim of this study was to examine the associations of prenatal lead exposures with telomere length and DNA-methylation-based predictors of age in cord blood.<br><br>DESIGN: The study included 507 mother-child pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a birth cohort in Mexico City. Maternal blood (second trimester, third trimester and at delivery) and bone lead levels (one month postpartum) were measured using inductively coupled plasma-mass spectrometry and X-ray fluorescence, respectively. Cord blood leukocyte telomere length was measured using quantitative PCR and apparent age by DNA methylation biomarkers, i.e., Horvath's DNA methylation age and the Knight's predictor of gestational age.<br><br>RESULTS: Average maternal age was 28.5&#xa0;&#xb1;&#xa0;5.5 years, and 51.5% reported low socioeconomic status. Children's mean telomere length was 1.2&#xa0;&#xb1;&#xa0;1.3 relative units, and mean DNA methylation ages using the Horvath's and Knight's clocks were -2.6&#xa0;&#xb1;&#xa0;0.1 years and 37.9&#xa0;&#xb1;&#xa0;1.4 weeks (mean&#xa0;&#xb1;&#xa0;SD), respectively. No significant associations were found between maternal blood and bone lead concentrations with telomere length and DNAm age in newborns.<br><br>CONCLUSION: We found no associations of prenatal lead exposure with telomere length and DNA methylation age biomarkers.},
}
@article {pmid34919564,
year = {2021},
author = {Rahimi Mehdi Abad, F and Khalili, P and Jalali, F and Pirsadeghi, A and Esmaeili Nadimi, A and Manshoori, A and Jalali, Z},
title = {Maternal opioid use is reflected on leukocyte telomere length of male newborns.},
journal = {PloS one},
volume = {16},
number = {12},
pages = {e0261013},
pmid = {34919564},
issn = {1932-6203},
mesh = {Adolescent ; Adult ; Case-Control Studies ; Female ; Fetal Blood ; Humans ; Infant, Newborn ; Male ; Maternal Age ; Maternal Exposure ; Opioid-Related Disorders/complications/*genetics ; Pregnancy ; Pregnancy Complications/*genetics ; Prenatal Exposure Delayed Effects/*genetics ; *Telomere Shortening ; Young Adult ; },
abstract = {Opioid use accelerates normal aging in adults that raises a question on whether it may trans-generationally affect aging and aging biomarkers in the offspring of users as well? In the present research, we investigated the relative telomere length in umbilical cord blood of newborns born to opioid consuming mothers compared to normal controls. Telomere length shortening is a known biomarker of aging and aging related diseases. Its measure at birth or early in life is considered as a predictor of individual health in adulthood. Here, we performed a case-control study to investigate whether maternal opioid use affects newborns relative telomere length (RTL). 57 mother-newborn dyads were included in this study, 30 neonates with opioid using mothers (OM), and 27 with not-opioid using mothers (NOM)). RTL was measured in leukocyte cells genomic DNA using real-time PCR. The correlation of maternal opioid use with neonates telomer length was assessed using logistic regression analysis. The results displayed a significant association between odds ratio of long RTL and maternal opioid use when sensitivity analysis was performed by neonate sex; where the data indicates significantly increased odds ratio of long leukocyte RTL in association with maternal opioid use in male neonates only. Further work is necessary to assess this association in larger samples and test the potential underlying mechanisms for this observation.},
}
@article {pmid34915934,
year = {2021},
author = {Lu, Y and Liu, X and Zhao, Z and Ou, X and Yang, Y and Wei, Q and Chen, J and Jiang, J and Sun, Y and Zhao, H and Wu, S and He, Y},
title = {Telomere length in peripheral leukocytes is a sensitive marker for assessing genetic damage among workers exposed to isopropanol, lead and noise: the case of an electronics manufacturer.},
journal = {Genes and environment : the official journal of the Japanese Environmental Mutagen Society},
volume = {43},
number = {1},
pages = {57},
pmid = {34915934},
issn = {1880-7046},
support = {81472998//national natural science foundation of china/ ; 81872661//national natural science foundation of china/ ; },
abstract = {BACKGROUND: Workers in electronics manufacturers may be exposed to various occupational hazards such as isopropanol, lead, and noise. Telomeres are special segments of cap-like DNA protein complex at end of liner chromosomes in eukaryotic cells. Telomere length is a potential marker of genetic damage. The aim of this study is to evaluate the effect of occupational hazards on the relative telomere length (rTL) of peripheral blood cells of workers in an electronics manufacturer, and to explore whether relative telomere length could be a biomarker for assessing genetic damage in the electronics manufacturing industry.<br><br>METHODS: We investigated a large-scale electronics manufacturer in the Pearl River Delta Region. We ultimately collected 699 qualified workers (248 with isopropanol exposure, 182 with lead exposure, 157 with noise exposure, and 112 controls). During physical examination of the workers, we gave them questionnaires to understand their health statuses and living habits. We also collected peripheral blood samples from these workers to test exposure levels and rTL in the leucocytes.<br><br>RESULTS: The concentrations of air isopropanol in all monitored workshops was 25.3&#xa0;mg/m[3] and air lead smoke was 0.020&#xa0;mg/m[3]. The maximum equivalent continuous A sound level noise exposure position was 82.2dB (A). All were lower than those in the Occupational Exposure Limits in Workplaces in China. Urinary acetone in the isopropanol exposed group was 1.04 (0, 1.50) mg/L, and cumulative urinary acetone was 1.48 (0, 5.09) mg-years/L. Blood lead levels (BLLs) were 28.57 (22.77, 37.06) &#xb5;g/dL, and cumulative blood lead levels (CBLLs) were 92.75 (55.47, 165.13) &#xb5;g-years/dL. rTL was different between occupational exposed workers and controls: rTL was 0.140 units (95&#x2009;% CI: 0.022, 0.259) shorter in lead exposed workers and 0.467 units (95&#x2009;% CI: 0.276-0.658) shorter in noise exposed workers compared to the controls. There is no statistical difference in rTL between isopropanol exposure workers and the controls. In order to elucidate the relationship between rTL and occupational hazards exposure, we divided the isopropanol exposure workers into three groups (0, ~1.43&#xa0;mg/L, and >1.43&#xa0;mg/L). None of the rTL difference was statistically significant among exposed workers at different uroacetone levels (P>0.05). The groups with &#x2265;100&#xa0;&#xb5;g/dL blood lead had shorter rTL than the group with blood lead below 100&#xa0;&#xb5;g/dL (F=4.422, P=0.013). We incorporated age, gender, birthplace, race, education level, smoking, and alcohol consumption into the linear regression equation. Only blood lead concentration (X) was entered into the regression equation, yielding a multivariate linear regression equation of Y=0.397-0.124X (F=8.091, P=0.005). Workers with different hearing loss also had statistically significant differences in rTL (F=5.731, P=0.004). rTL was a protective factor for the occurrence of noise-induced hearing loss (NIHL). The longer the rTL, the lower the risk of NIHL [OR=0.64 (0.42, 0.98)].<br><br>CONCLUSIONS: rTL was shorter in lead exposed workers and noise exposed workers, and it was a protective factor for the occurrence of the noise-induced hearing loss. Thus, rTL of peripheral blood may be a sensitive marker of genetic damage among workers in environments with lead and noise exposure.},
}
@article {pmid34912838,
year = {2021},
author = {Niu, KM and Bao, T and Gao, L and Ru, M and Li, Y and Jiang, L and Ye, C and Wang, S and Wu, X},
title = {The Impacts of Short-Term NMN Supplementation on Serum Metabolism, Fecal Microbiota, and Telomere Length in Pre-Aging Phase.},
journal = {Frontiers in nutrition},
volume = {8},
number = {},
pages = {756243},
pmid = {34912838},
issn = {2296-861X},
abstract = {Aging is a natural process with concomitant changes in the gut microbiota and associate metabolomes. Beta-nicotinamide mononucleotide, an important NAD[+] intermediate, has drawn increasing attention to retard the aging process. We probed the changes in the fecal microbiota and metabolomes of pre-aging male mice (C57BL/6, age: 16 months) following the oral short-term administration of nicotinamide mononucleotide (NMN). Considering the telomere length as a molecular gauge for aging, we measured this in the peripheral blood mononuclear cells (PBMC) of pre-aging mice and human volunteers (age: 45-60 years old). Notably, the NMN administration did not influence the body weight and feed intake significantly during the 40 days in pre-aging mice. Metabolomics suggested 266 upregulated and 58 downregulated serum metabolites. We identified 34 potential biomarkers linked with the nicotinamide, purine, and proline metabolism pathways. Nicotinamide mononucleotide significantly reduced the fecal bacterial diversity (p < 0.05) with the increased abundance of Helicobacter, Mucispirillum, and Faecalibacterium, and lowered Akkermansia abundance associated with nicotinamide metabolism. We propose that this reshaped microbiota considerably lowered the predicated functions of aging with improved immune and cofactors/vitamin metabolism. Most notably, the telomere length of PBMC was significantly elongated in the NMN-administered mice and humans. Taken together, these findings suggest that oral NMN supplementation in the pre-aging stage might be an effective strategy to retard aging. We recommend further studies to unravel the underlying molecular mechanisms and comprehensive clinical trials to validate the effects of NMN on aging.},
}
@article {pmid34910909,
year = {2021},
author = {Liu, R and Kasowitz, SD and Homolka, D and Leu, NA and Shaked, JT and Ruthel, G and Jain, D and Lin, H and Keeney, S and Luo, M and Pillai, RS and Wang, PJ},
title = {YTHDC2 is essential for pachytene progression and prevents aberrant microtubule-driven telomere clustering in male meiosis.},
journal = {Cell reports},
volume = {37},
number = {11},
pages = {110110},
pmid = {34910909},
issn = {2211-1247},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; P50 HD068157/HD/NICHD NIH HHS/United States ; R01 HD069592/HD/NICHD NIH HHS/United States ; R35 GM118052/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Female ; Male ; *Meiosis ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microtubules/*physiology ; *Pachytene Stage ; RNA Helicases/*physiology ; Spermatocytes/*cytology/metabolism ; *Telomere ; *Transcriptome ; },
abstract = {Mechanisms driving the prolonged meiotic prophase I in mammals are poorly understood. RNA helicase YTHDC2 is critical for mitosis to meiosis transition. However, YTHDC2 is highly expressed in pachytene cells. Here we identify an essential role for YTHDC2 in meiotic progression. Specifically, YTHDC2 deficiency causes microtubule-dependent telomere clustering and apoptosis at the pachytene stage of prophase I. Depletion of YTHDC2 results in a massively dysregulated transcriptome in pachytene cells, with a tendency toward upregulation of genes normally expressed in mitotic germ cells and downregulation of meiotic transcripts. Dysregulation does not correlate with m[6]A status, and YTHDC2-bound mRNAs are enriched in genes upregulated in mutant germ cells, revealing that YTHDC2 primarily targets mRNAs for degradation. Furthermore, altered transcripts in mutant pachytene cells encode microtubule network proteins. Our results demonstrate that YTHDC2 regulates the pachytene stage by perpetuating a meiotic transcriptome and preventing microtubule network changes that could lead to telomere clustering.},
}
@article {pmid34910812,
year = {2022},
author = {Schoepf, IC and Thorball, CW and Ledergerber, B and Kootstra, NA and Reiss, P and Raffenberg, M and Engel, T and Braun, DL and Hasse, B and Thurnheer, C and Marzolini, C and Seneghini, M and Bernasconi, E and Cavassini, M and Buvelot, H and Arribas, JR and Kouyos, RD and Fellay, J and Günthard, HF and Tarr, PE},
title = {Telomere Length Declines in Persons With Human Immunodeficiency Virus Before Antiretroviral Therapy Start but Not After Viral Suppression: A Longitudinal Study Over &gt;17 Years.},
journal = {The Journal of infectious diseases},
volume = {225},
number = {9},
pages = {1581-1591},
doi = {10.1093/infdis/jiab603},
pmid = {34910812},
issn = {1537-6613},
support = {177499/SNSF_/Swiss National Science Foundation/Switzerland ; },
mesh = {Anti-Retroviral Agents/therapeutic use ; Cohort Studies ; HIV/genetics ; *HIV Infections ; Humans ; Leukocytes, Mononuclear ; Longitudinal Studies ; Telomere/genetics ; },
abstract = {BACKGROUND: In people with human immunodeficiency virus (PWH), long-term telomere length (TL) change without/with suppressive antiretroviral therapy (ART) and the contribution of genetic background to TL are incompletely understood.<br><br>METHODS: We measured TL change in peripheral blood mononuclear cells by quantitative polymerase chain reaction in 107 Swiss HIV Cohort Study participants with longitudinal samples available both before and during suppressive ART. We applied mixed-effects multilevel regression to obtain uni-/multivariable estimates for longitudinal TL dynamics including age, sex, and CD4/CD8 ratio. We assessed the effect of (1) individual antiretrovirals and (2) an individual TL-polygenic risk score ([TL-PRS] based on 239 single-nucleotide polymorphisms) on TL in 798 additional participants from our previous longitudinal studies.<br><br>RESULTS: During untreated human immunodeficiency virus (HIV) infection (median observation, 7.7; interquartile range [IQR], 4.7-11] years), TL declined significantly (median -2.12%/year; IQR, -3.48% to -0.76%/year; P&#x2005;=&#x2005;.002). During suppressive ART (median observation, 9.8; IQR, 7.1-11.1 years), there was no evidence of TL decline or increase (median&#x2005;+&#x2005;0.54%/year; IQR, -0.55% to&#x2005;+&#x2005;1.63%/year; P&#x2005;=&#x2005;.329). The TL-PRS contributed to TL change (global P&#x2005;=&#x2005;.019) but particular antiretrovirals did not (all P&#x2005;>&#x2005;.15).<br><br>CONCLUSIONS: In PWH, TL is associated with an individual PRS. Telomere length declined significantly during untreated chronic HIV infection, but no TL change occurred during suppressive ART.},
}
@article {pmid34906191,
year = {2021},
author = {Xia, K and Zhang, L and Zhang, G and Wang, Y and Huang, T and Fan, D},
title = {Leukocyte telomere length and amyotrophic lateral sclerosis: a Mendelian randomization study.},
journal = {Orphanet journal of rare diseases},
volume = {16},
number = {1},
pages = {508},
pmid = {34906191},
issn = {1750-1172},
mesh = {*Amyotrophic Lateral Sclerosis/genetics ; Genome-Wide Association Study ; Humans ; Leukocytes ; Mendelian Randomization Analysis/methods ; Polymorphism, Single Nucleotide/genetics ; Telomere/genetics ; },
abstract = {BACKGROUND: Observational studies have suggested that telomere length is associated with amyotrophic lateral sclerosis (ALS). However, whether this association is causal remains unclear. In this study, we aimed to explore the causal relationship between leukocyte telomere length (LTL) and ALS by a two-sample Mendelian randomization (MR) approach. Single-nucleotide polymorphisms (SNPs) for LTL were identified through high-quality genome-wide association studies (GWASs). The ALS GWAS summary data (20,806 cases; 59,804 controls) with largest sample size to date was obtained. We adopted the inverse variance weighted (IVW) method to examine the effect of LTL on ALS and used the weighted median method, simple median method, MR Egger method and MR-PRESSO method to perform sensitivity analyses.<br><br>RESULTS: We found that genetically determined increased LTL was inversely associated with the risk of ALS (odds ratio (OR)&#x2009;=&#x2009;0.846, 95% confidence interval (CI): 0.744-0.962, P&#x2009;=&#x2009;0.011), which was mainly driven by rs940209 in the OBFC1 gene, suggesting a potential effect of OBFC1 on ALS. The results were further confirmed by sensitivity analysis with the MR Egger method (OR&#x2009;=&#x2009;0.647, 95% CI&#x2009;=&#x2009;0.447-0.936, P&#x2009;=&#x2009;0.050). Analyses by the weighted median method (OR&#x2009;=&#x2009;0.893, P&#x2009;=&#x2009;0.201) and simple median method (OR&#x2009;=&#x2009;0.935, P&#x2009;=&#x2009;0.535) also showed a similar trend. The MR Egger analysis did not suggest directional pleiotropy, with an intercept of 0.025 (P&#x2009;=&#x2009;0.168). Neither the influence of instrumental outliers nor heterogeneity was found.<br><br>CONCLUSIONS: Our results suggest that genetically predicted increased LTL has a causal relationship with a lower risk of ALS. Protecting against telomere loss may be of great importance in the prevention and treatment of ALS.},
}
@article {pmid34902558,
year = {2022},
author = {Engin, AB and Coleman, MD},
title = {Telomere attrition may be a more realistic toxicity test for both low and high dose exposure.},
journal = {Environmental toxicology and pharmacology},
volume = {90},
number = {},
pages = {103788},
doi = {10.1016/j.etap.2021.103788},
pmid = {34902558},
issn = {1872-7077},
mesh = {Aging ; Environmental Exposure/*adverse effects/analysis ; Environmental Pollutants/toxicity ; Humans ; Risk Assessment ; Telomerase/analysis/metabolism ; Telomere Shortening/*drug effects ; Toxicity Tests/*methods ; },
}
@article {pmid34901077,
year = {2021},
author = {Casas-Recasens, S and Mendoza, N and López-Giraldo, A and Garcia, T and Cosio, BG and Pascual-Guardia, S and Acosta-Castro, A and Borras-Santos, A and Gea, J and Garrabou, G and Agusti, A and Faner, R},
title = {Telomere Length but Not Mitochondrial DNA Copy Number Is Altered in Both Young and Old COPD.},
journal = {Frontiers in medicine},
volume = {8},
number = {},
pages = {761767},
pmid = {34901077},
issn = {2296-858X},
abstract = {Accelerated ageing is implicated in the pathogenesis of respiratory diseases as chronic obstructive pulmonary disease (COPD), but recent evidence indicates that the COPD can have roots early in life. Here we hypothesise that the accelerated ageing markers might have a role in the pathobiology of young COPD. The objective of this study was to compare two hallmarks of ageing, telomere length (TL), and mitochondrial DNA copy number (mtDNA-CN, as a surrogate marker of mitochondrial dysfunction) in young (≤ 50 years) and old (>50 years) smokers, with and without COPD. Both, TL and mtDNA-CN were measured in whole blood DNA by quantitative PCR [qPCR] in: (1) young ever smokers with (n = 81) or without (n = 166) COPD; and (2) old ever smokers with (n = 159) or without (n = 29) COPD. A multivariable linear regression was used to assess the association of TL and mtDNA-CN with lung function. We observed that in the entire study population, TL and mtDNA-CN decreased with age, and the former but not the latter related to FEV1/FVC (%), FEV1 (% ref.), and DLCO (% ref.). The short telomeres were found both in the young and old patients with severe COPD (FEV1 <50% ref.). In addition, we found that TL and mtDNA-CN were significantly correlated, but their relationship was positive in younger while negative in the older patients with COPD, suggesting a mitochondrial dysfunction. We conclude that TL, but not mtDNA-CN, is associated with the lung function impairment. Both young and old patients with severe COPD have evidence of accelerated ageing (shorter TL) but differ in the direction of the correlation between TL and mtDNA-CN in relation to age.},
}
@article {pmid34900979,
year = {2021},
author = {Nozaki, T and Chang, F and Weiner, B and Kleckner, N},
title = {High Temporal Resolution 3D Live-Cell Imaging of Budding Yeast Meiosis Defines Discontinuous Actin/Telomere-Mediated Chromosome Motion, Correlated Nuclear Envelope Deformation and Actin Filament Dynamics.},
journal = {Frontiers in cell and developmental biology},
volume = {9},
number = {},
pages = {687132},
pmid = {34900979},
issn = {2296-634X},
support = {R35 GM136322/GM/NIGMS NIH HHS/United States ; },
abstract = {Chromosome movement is prominent at mid-meiotic prophase and is proposed to enhance the efficiency and/or stringency of homolog pairing and/or to help prevent or resolve topological entanglements. Here, we combine fluorescent repressor operator system (FROS) labeling with three-dimensional (3D) live-cell imaging at high spatio-temporal resolution to define the detailed kinetics of mid-meiotic prophase motion for a single telomere-proximal locus in budding yeast. Telomere motions can be grouped into three general categories: (i) pauses, in which the telomere "jiggles in place"; (ii) rapid, straight/curvilinear motion which reflects Myo2/actin-mediated transport of the monitored telomere; and (iii) slower directional motions, most of which likely reflect indirectly promoted motion of the monitored telomere in coordination with actin-mediated motion of an unmarked telomere. These and other findings highlight the importance of dynamic assembly/disassembly of telomere/LINC/actin ensembles and also suggest important roles for nuclear envelope deformations promoted by actin-mediated telomere/LINC movement. The presented low-SNR (signal-to-noise ratio) imaging methodology provides opportunities for future exploration of homolog pairing and related phenomena.},
}
@article {pmid34900769,
year = {2021},
author = {Al-Thuwaini, TM},
title = {Association of antidiabetic therapy with shortened telomere length in middle-aged Type 2 diabetic patients.},
journal = {Journal of diabetes and metabolic disorders},
volume = {20},
number = {2},
pages = {1161-1168},
pmid = {34900769},
issn = {2251-6581},
abstract = {INTRODUCTION: A wide range of antidiabetic therapies have been developed to manage diabetes and limit its lifespan but each of them have adverse long-term drug reactions. This study was performed for the investigation of the possible association of antidiabetic therapy with shortened telomere length in middle-aged Type 2 diabetic patients.<br><br>MATERIALS AND METHODS: The subjects in this case-control study included 100 non-diabetic patients and 300 patients with Type 2 diabetes with ages in the range of 30-50&#xa0;years. The treated patients were further subdivided into diabetic patients using Doanil, those using insulin and those using both the therapies. The mean telomere length was determined using the southern-blotting technique. A logistic regression analysis was performed to predict the relationship between antidiabetic therapy and shortened telomere length.<br><br>RESULTS: The results revealed a significant increase (P&#x2009;<&#x2009;0.01) in the fasting blood glucose and lipid profile in non-treatment diabetic patients compared to diabetic patients with treatment, and also in diabetic patients with insulin therapy, compared to diabetic patients with Doanil or both therapies. The results showed that non-treatment diabetic patients had shorter telomere length, compared to the diabetic patients with treatment, and patients treated with insulin therapy had shorter telomere length, compared to the diabetic patients with Doanil or both therapies. The logistic regression analysis confirmed that insulin therapy was closely related to diabetic risk factors and shortened telomere length.<br><br>CONCLUSIONS: The results revealed that Doanil therapy was more effective in managing diabetic risk and limiting the shortening telomere length than insulin therapy.},
}
@article {pmid34895035,
year = {2022},
author = {Rungnirundorn, T and Krusong, K and Kalayasiri, R and Maes, M},
title = {Leukocyte telomere length is not shortened in methamphetamine dependence or methamphetamine-induced psychosis but is increased following traumatic events.},
journal = {The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry},
volume = {23},
number = {8},
pages = {613-621},
pmid = {34895035},
issn = {1814-1412},
support = {D43 TW006166/TW/FIC NIH HHS/United States ; K24 DA017899/DA/NIDA NIH HHS/United States ; },
mesh = {Humans ; *Methamphetamine/adverse effects ; *Tobacco Use Disorder/complications ; *Amphetamine-Related Disorders/complications ; *Substance Withdrawal Syndrome ; *Alcoholism/genetics/complications ; *Psychotic Disorders/genetics/complications ; Leukocytes ; Telomere/genetics ; },
abstract = {OBJECTIVE: This study aims to examine the effects of methamphetamine (MA) use and dependence and MA withdrawal symptoms on the telomere length and whether shortening of the latter is associated with MA-induced psychosis (MIP).<br><br>METHODS: This study included 185&#x2009;MA-abuse, 118&#x2009;MA-dependent, and 67 MIP patients, diagnosed using DSM-IV criteria. The Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA) questionnaire was employed to collect MA-related data. MIP was confirmed using the Methamphetamine Experience Questionnaire (MEQ). The leukocyte telomere length was measured using real-time polymerase chain reaction measuring the Telomere/Single gene ratio (T/S ratio). Data were analysed using multivariate statistical analyses.<br><br>RESULTS: There were no significant associations between the T/S ratio and severity of MA-use, MIP, and MA withdrawal symptoms. MIP was significantly predicted by alcohol dependence, antisocial personality disorder, and MA-use severity. There were significantly positive associations between the T/S ratio and previous traumatic and life-threatening events. The T/S ratio was not affected by alcohol and nicotine dependence. Alcohol and nicotine dependence, antisocial personality disorder, and severity of MA use increased risk of MA withdrawal symptoms.<br><br>CONCLUSION: MIP and MA-use severity are not associated with leukocyte telomere length, but previous traumatic and life-threatening events are associated with increased telomere length.},
}
@article {pmid34894710,
year = {2022},
author = {Zhang, A and Fan, L and Sun, T and Fan, Y and Xu, Z and Yin, Z and Zhuo, Y and Zhang, J and Gu, J and Chang, ACY and Wang, C},
title = {The association of leukocyte telomere length and intermediate coronary lesions-a retrospective study.},
journal = {Annals of palliative medicine},
volume = {11},
number = {4},
pages = {1210-1221},
doi = {10.21037/apm-21-2295},
pmid = {34894710},
issn = {2224-5839},
mesh = {Humans ; Leukocytes ; Lipids ; *Percutaneous Coronary Intervention/methods ; *Plaque, Atherosclerotic/diagnostic imaging/genetics ; Retrospective Studies ; Telomere/genetics ; Telomere Shortening ; },
abstract = {BACKGROUND: Intermediate coronary lesions (40-70% stenosis) present a higher risk for future cardiovascular events for instability of plaques. Shortened telomere is an indicator of cellular senescence, which is associated with age-related diseases. However, the relationship between telomere length and severity of intermediate coronary lesions remains largely unknown.<br><br>METHODS: A total of 121 lesions of 121 patients with intermediate coronary disease that underwent intravascular optical coherence tomography were enrolled. These patients were retrospectively divided into two groups according to whether accept percutaneous coronary intervention (PCI) treatment: non-PCI group and PCI group.<br><br>RESULTS: Leukocyte telomere length (LTL) in patients of PCI group were significantly shorter (12.54&#xb1;2.70 vs. 15.32&#xb1;3.72 kb, P<0.001) than non-PCI group. The PCI group had longer lipid length (17.17&#xb1;9.94 vs. 12.21&#xb1;10.15 mm, P=0.01) and greater lipid index (4,286.82&#xb1;3,012.54 vs. 2,444.87&#xb1;2,677.59 &#xb0;*mm, P<0.001). There was a significant difference in the prevalence of thin-cap fibroatheroma (36.6% vs. 16.0%, P=0.013), macrophages (56.3% vs. 38.0%, P=0.047), plaque rupture (23.9% vs. 6.0%, P=0.009), cholesterol crystal (49.3% vs. 30.0%, P=0.034), dissection (23.9% vs. 4.0%, P=0.003) between PCI and non-PCI group. Logistic regression revealed that LTL was independently associated with PCI after adjusting for confounding factors (OR 0.952, CI: 0.930-0.974, per 1unit increase, P<0.001). Receiver operating characteristic (ROC) analysis revealed a LTL area under the ROC curve (AUC) of 0.714 (95% CI: 0.619-0.808, P<0.001) in the study population. Furthermore, LTL was inversely correlated with lipid length (r =-0.190, P=0.037), lipid arc (r =-0.301, P=0.001), lipid index (r =-0.182, P=0.046), and positive correlation with FCT (r =0.213, P=0.034).<br><br>CONCLUSIONS: LTL was independently associated with possibility of receiving PCI in intermediate coronary lesion patients and LTL is also significantly related to plaque instability features that evaluated by optical coherence tomography. LTL may be as an indicator to assess the necessity of PCI in intermediate coronary lesion patients.},
}
@article {pmid34890718,
year = {2022},
author = {Womersley, JS and Xulu, KR and Sommer, J and Hinsberger, M and Kidd, M and Elbert, T and Weierstall, R and Kaminer, D and Malan-Müller, S and Seedat, S and M J Hemmings, S},
title = {Associations between telomere length and symptoms of posttraumatic stress disorder and appetitive aggression in trauma-exposed men.},
journal = {Neuroscience letters},
volume = {769},
number = {},
pages = {136388},
doi = {10.1016/j.neulet.2021.136388},
pmid = {34890718},
issn = {1872-7972},
mesh = {Adolescent ; Adult ; *Aggression ; *Appetitive Behavior ; Humans ; Male ; South Africa ; Stress Disorders, Post-Traumatic/epidemiology/*genetics/physiopathology ; *Telomere Homeostasis ; Violence/psychology/statistics &amp; numerical data ; },
abstract = {Exposure to community violence is common in South Africa and negatively impacts on biopsychosocial health. Posttraumatic stress disorder (PTSD) is characterised by symptoms of intrusion, avoidance, hypervigilance and negative alterations in cognition and mood, and can develop consequent to trauma exposure. Individuals who repeatedly experience and witness violence may also come to view it as appealing and rewarding. This appetitive aggression (AA) increases the likelihood of perpetrating violence. Telomeres are repetitive nucleotide sequences that protect the ends of chromosomes. Telomere length (TL) attrition is a stress-sensitive marker of biological aging that has been associated with a range of psychiatric disorders. This study investigated the cross-sectional relationship between TL and symptoms of PTSD and AA in South African men residing in areas with high community violence. PTSD and AA symptom severity was assessed in 290 men using the Posttraumatic Stress Disorder Symptom Scale - Interview (PSS-I) and Appetitive Aggression Scale (AAS), respectively. Quantitative polymerase chain reaction was performed on DNA extracted from saliva and used to calculate relative TL (rTL). Regression models were used to assess the relationships between rTL and PSS-I and AAS scores. Network analyses using EBIC glasso methods were performed using rTL and items from each of the AAS and PSS-I measures. Both PSS-I (p = 0.023) and AAS (p = 0.016) scores were positively associated with rTL. Network analyses indicated that rTL was weakly related to two PSS-I and five AAS items but performed poorly on indicators of centrality and was not strongly associated with measure items either directly or indirectly. The positive association between rTL and measures of AA and PTSD may be due to the induction of protective homeostatic mechanisms, which reduce TL attrition, following early life trauma exposure.},
}
@article {pmid34887119,
year = {2022},
author = {Kardeh, S and Saber, A and Mazloomrezaei, M and Hosseini, A},
title = {Telomere targeting is insufficient to ameliorate multifaceted hallmarks of aging in cultured keratinocytes.},
journal = {Burns : journal of the International Society for Burn Injuries},
volume = {48},
number = {2},
pages = {470-471},
doi = {10.1016/j.burns.2021.07.012},
pmid = {34887119},
issn = {1879-1409},
mesh = {Aging ; *Burns ; Cells, Cultured ; Humans ; Keratinocytes ; Telomere/genetics ; },
}
@article {pmid34884608,
year = {2021},
author = {Lee, KH and Kim, DY and Kim, W},
title = {Regulation of Gene Expression by Telomere Position Effect.},
journal = {International journal of molecular sciences},
volume = {22},
number = {23},
pages = {},
pmid = {34884608},
issn = {1422-0067},
support = {2021R1F1A1062392//National Research Foundation of Korea/ ; },
mesh = {*Aging ; Animals ; *Epigenesis, Genetic ; *Gene Expression Regulation ; Humans ; Neoplasms/genetics/*pathology ; Telomere/*chemistry/*genetics ; },
abstract = {Many diseases that involve malignant tumors in the elderly affect the quality of human life; therefore, the relationship between aging and pathogenesis in geriatric diseases must be under-stood to develop appropriate treatments for these diseases. Recent reports have shown that epigenetic regulation caused by changes in the local chromatin structure plays an essential role in aging. This review provides an overview of the roles of telomere shortening on genomic structural changes during an age-dependent shift in gene expression. Telomere shortening is one of the most prominent events that is involved in cellular aging and it affects global gene expression through genome rearrangement. This review provides novel insights into the roles of telomere shortening in disease-affected cells during pathogenesis and suggests novel therapeutic approaches.},
}
@article {pmid34882527,
year = {2022},
author = {Rangel-Pozzo, A and Dettori, T and Virginia Frau, D and Etzi, F and Gartner, J and Fisher, G and Vanni, R and Mai, S and Caria, P},
title = {Three-dimensional telomere profiles in papillary thyroid cancer variants: A pilot study.},
journal = {Bosnian journal of basic medical sciences},
volume = {22},
number = {3},
pages = {481-487},
pmid = {34882527},
issn = {1840-4812},
mesh = {*Adenocarcinoma, Follicular/metabolism/pathology ; Humans ; Pilot Projects ; Telomere/genetics ; Thyroid Cancer, Papillary/genetics/pathology ; *Thyroid Neoplasms/genetics/pathology ; },
abstract = {Besides the two main histologic types of papillary thyroid carcinoma (PTC), the classical PTC (CL-PTC) and the follicular variant PTC (FV-PTC), several other variants are described. The encapsulated FV-PTC variant was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to its similarities to benign lesions. Specific molecular signatures, however, are still unavailable. It is well known that improper DNA repair of dysfunctional telomeres may cause telomere-related genome instability. The mechanisms involved in the damaged telomere repair processing may lead to detrimental outcomes, altering the three-dimensional (3D) nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether a specific 3D nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples, and the telomere length of NIFTP overlaps with that of the FTA histotype. In contrast, there was no association between BRAF expression and telomere length in all tested samples. These preliminary findings reinforce the view that NIFTP is closer to non-malignant thyroid nodules and confirm that PTC features short telomeres.},
}
@article {pmid34881184,
year = {2021},
author = {Tang, Y and Mukherjee, J and Pieper, RO},
title = {MRE11 and UBR5 Co-Operate to Suppress RNF168-Mediated Fusion of Dysfunctional Telomeres.},
journal = {Frontiers in oncology},
volume = {11},
number = {},
pages = {772233},
pmid = {34881184},
issn = {2234-943X},
support = {R01 CA265983/CA/NCI NIH HHS/United States ; },
abstract = {TRF2 is part of the shelterin complex that hides telomeric DNA ends and prevents the activation of the cNHEJ pathway that can lead to chromosomal fusion. TRF2, however, also actively suppresses the cNHEJ pathway by recruiting two proteins, MRE11 and UBR5. MRE11 binds BRCC3, which in turn deubiquitinates γH2AX deposited at exposed telomeric DNA ends and limits RNF168 recruitment to the telomere. UBR5, in contrast directly ubiquitinates and destroys RNF168. The loss of telomeric RNF168 in turn blocks the subsequent recruitment of 53BP1 and prevents the cNHEJ-mediated fusion of chromosomes with exposed telomeric DNA ends. Although MRE11 and UBR5 are both involved in the control of telomeric RNF168 levels and the chromosome fusion process, their relative contributions have not been directly addressed. To do so we genetically suppressed MRE11 and UBR5 alone or in combination in glioma cell lines which we previously showed contained dysfunctional telomeres that were dependent on TRF2 for suppression of telomeric fusion and monitored the effects on events associated with telomere fusion. We here show that while suppression of either MRE11 or UBR5 alone had minimal effects on RNF168 telomeric accumulation, 53BP1 recruitment, and telomeric fusion, their combined suppression led to significant increases in RNF168 and 53BP1 telomeric recruitment and telomeric fusion and eventually cell death, all of which were reversible by suppression of RNF168 itself. These results show that MRE11 and UBR5 co-operate to suppress fusion at dysfunctional telomeres.},
}
@article {pmid34879271,
year = {2021},
author = {Barroso-González, J and García-Expósito, L and Galaviz, P and Lynskey, ML and Allen, JAM and Hoang, S and Watkins, SC and Pickett, HA and O'Sullivan, RJ},
title = {Anti-recombination function of MutSα restricts telomere extension by ALT-associated homology-directed repair.},
journal = {Cell reports},
volume = {37},
number = {10},
pages = {110088},
pmid = {34879271},
issn = {2211-1247},
support = {P30 CA047904/CA/NCI NIH HHS/United States ; R01 CA207209/CA/NCI NIH HHS/United States ; R37 CA263622/CA/NCI NIH HHS/United States ; S10 OD019973/OD/NIH HHS/United States ; },
mesh = {Cell Line, Tumor ; DNA Mismatch Repair ; DNA, Neoplasm/genetics/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Genomic Instability ; HeLa Cells ; Humans ; Models, Genetic ; MutS Homolog 2 Protein/genetics/*metabolism ; Neoplasms/*enzymology/genetics/pathology ; Nucleic Acid Conformation ; Nucleic Acid Heteroduplexes/genetics/*metabolism ; RecQ Helicases/genetics/metabolism ; Telomere/genetics/*metabolism ; *Telomere Homeostasis ; },
abstract = {Alternative lengthening of telomeres (ALT) is a telomere-elongation mechanism observed in ∼15% of cancer subtypes. Current models indicate that ALT is mediated by homology-directed repair mechanisms. By disrupting MSH6 gene expression, we show that the deficiency of MutSα (MSH2/MSH6) DNA mismatch repair complex causes striking telomere hyperextension. Mechanistically, we show MutSα is specifically recruited to telomeres in ALT cells by associating with the proliferating-cell nuclear antigen (PCNA) subunit of the ALT telomere replisome. We also provide evidence that MutSα counteracts Bloom (BLM) helicase, which adopts a crucial role in stabilizing hyper-extended telomeres and maintaining the survival of MutSα-deficient ALT cancer cells. Lastly, we propose a model in which MutSα deficiency impairs heteroduplex rejection, leading to premature initiation of telomere DNA synthesis that coincides with an accumulation of telomere variant repeats (TVRs). These findings provide evidence that the MutSα DNA mismatch repair complex acts to restrain unwarranted ALT.},
}
@article {pmid34875134,
year = {2022},
author = {Kärkkäinen, T and Laaksonen, T and Burgess, M and Cantarero, A and Martínez-Padilla, J and Potti, J and Moreno, J and Thomson, RL and Tilgar, V and Stier, A},
title = {Population differences in the length and early-life dynamics of telomeres among European pied flycatchers.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {5966-5978},
pmid = {34875134},
issn = {1365-294X},
mesh = {Animals ; *Songbirds/genetics ; Telomere Shortening/genetics ; Telomere/genetics ; Estonia ; Finland ; },
abstract = {Telomere length and shortening rate are increasingly being used as biomarkers for long-term costs in ecological and evolutionary studies because of their relationships with survival and fitness. Both early-life conditions and growth, and later-life stressors can create variation in telomere shortening rate. Studies on between-population telomere length and dynamics are scarce, despite the expectation that populations exposed to varying environmental constraints would present divergent telomere length patterns. The pied flycatcher (Ficedula hypoleuca) is a passerine bird breeding across Eurasia (from Spain to western Siberia) and migrating through the Iberian Peninsula to spend the nonbreeding period in sub-Saharan Africa. Thus, different populations show marked differences in migration distance. We studied the large-scale variation of telomere length and early-life dynamics in the pied flycatcher by comparing six European populations across a north-south gradient (Finland, Estonia, England and Spain) predicting a negative effect of migration distance on adult telomere length, and of nestling growth on nestling telomere dynamics. There were clear population differences in telomere length, with English birds from midlatitudes having the longest telomeres. Telomere length did not thus show consistent latitudinal variation and was not linearly linked to differences in migration distance. Early-life telomere shortening rate tended to vary between populations. Fast growth was associated with shorter telomeres in the early life, but faster nestling growth affected telomeres more negatively in northern than southern populations. While the sources of between-population differences in telomere-related biology remain to be more intensively studied, our study illustrates the need to expand telomere studies at the between-population level.},
}
@article {pmid34875050,
year = {2022},
author = {van der Spek, A and Karamujić-Čomić, H and Pool, R and Bot, M and Beekman, M and Garmaeva, S and Arp, PP and Henkelman, S and Liu, J and Alves, AC and Willemsen, G and van Grootheest, G and Aubert, G and , and Ikram, MA and Jarvelin, MR and Lansdorp, P and Uitterlinden, AG and Zhernakova, A and Slagboom, PE and Penninx, BWJH and Boomsma, DI and Amin, N and van Duijn, CM},
title = {Fat metabolism is associated with telomere length in six population-based studies.},
journal = {Human molecular genetics},
volume = {31},
number = {7},
pages = {1159-1170},
doi = {10.1093/hmg/ddab281},
pmid = {34875050},
issn = {1460-2083},
mesh = {Biomarkers/metabolism ; Cross-Sectional Studies ; Fatty Acids/metabolism ; Humans ; *Leukocytes/metabolism ; Lipids ; Telomere/genetics ; *Telomere Shortening ; },
abstract = {Telomeres are repetitive DNA sequences located at the end of chromosomes, which are associated to biological aging, cardiovascular disease, cancer and mortality. Lipid and fatty acid metabolism have been associated with telomere shortening. We have conducted an in-depth study investigating the association of metabolic biomarkers with telomere length (LTL). We performed an association analysis of 226 metabolic biomarkers with LTL using data from 11 775 individuals from six independent population-based cohorts (BBMRI-NL consortium). Metabolic biomarkers include lipoprotein lipids and subclasses, fatty acids, amino acids, glycolysis measures and ketone bodies. LTL was measured by quantitative polymerase chain reaction or FlowFISH. Linear regression analysis was performed adjusting for age, sex, lipid-lowering medication and cohort-specific covariates (model 1) and additionally for body mass index (BMI) and smoking (model 2), followed by inverse variance-weighted meta-analyses (significance threshold Pmeta = 6.5 × 10-4). We identified four metabolic biomarkers positively associated with LTL, including two cholesterol to lipid ratios in small VLDL (S-VLDL-C % and S-VLDL-CE %) and two omega-6 fatty acid ratios (FAw6/FA and LA/FA). After additionally adjusting for BMI and smoking, these metabolic biomarkers remained associated with LTL with similar effect estimates. In addition, cholesterol esters in very small VLDL (XS-VLDL-CE) became significantly associated with LTL (P = 3.6 × 10-4). We replicated the association of FAw6/FA with LTL in an independent dataset of 7845 individuals (P = 1.9 × 10-4). To conclude, we identified multiple metabolic biomarkers involved in lipid and fatty acid metabolism that may be involved in LTL biology. Longitudinal studies are needed to exclude reversed causation.},
}
@article {pmid34874050,
year = {2021},
author = {Hahn, MC and Werlang, ICR and Rechenmacher, C and Morais, RV and Barbé-Tuana, FM and Grun, LK and Guma, FTCR and Silva, CHD and Bernardi, JR and Michalowski, MB and Goldani, MZ},
title = {Telomere length in healthy newborns is not affected by adverse intrauterine environments.},
journal = {Genetics and molecular biology},
volume = {44},
number = {4},
pages = {e20200411},
pmid = {34874050},
issn = {1415-4757},
abstract = {Different intrauterine exposures are associated with different metabolic profiles leading to growth and development characteristics in children and also relate to health and disease patterns in adult life. The objective of this work was to evaluate the impact of four different intrauterine environments on the telomere length of newborns. This is a longitudinal observational study using a convenience sample of 222 mothers and their term newborns (>37 weeks of gestational age) from hospitals in Porto Alegre, Rio Grande do Sul (Brazil), from September 2011 to January 2016. Sample was divided into four groups: pregnant women with Gestational Diabetes Mellitus (DM) (n=38), smoking pregnant women (TOBACCO) (n=52), mothers with small-for-gestational age (SGA) children due to idiopathic intrauterine growth restriction (n=33), and a control group (n=99). Maternal and newborn genomic DNA were obtained from epithelial mucosal cells. Telomere length was assessed by qPCR, with the calculation of the telomere and single copy gene (T/S ratio). In this sample, there was no significant difference in telomere length between groups (p>0.05). There was also no association between childbirth weight and telomere length in children (p>0.05). For term newborns different intrauterine environments seems not to influence telomere length at birth.},
}
@article {pmid34873130,
year = {2022},
author = {da Silva, RS and de Moraes, LS and da Rocha, CAM and Ferreira-Fernandes, H and Yoshioka, FKN and Rey, JA and Pinto, GR and Burbano, RR},
title = {Telomere length and telomerase activity of leukocytes as biomarkers of selective serotonin reuptake inhibitor responses in patients with major depressive disorder.},
journal = {Psychiatric genetics},
volume = {32},
number = {1},
pages = {34-36},
doi = {10.1097/YPG.0000000000000305},
pmid = {34873130},
issn = {1473-5873},
mesh = {Biomarkers ; *Depressive Disorder, Major/drug therapy/genetics ; Humans ; Leukocytes/metabolism ; Selective Serotonin Reuptake Inhibitors/therapeutic use ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {We analyze the leukocyte telomere length (LTL) and telomerase activity in patients with major depressive disorder (MDD) before and after treatment with selective serotonin reuptake inhibitors (SSRIs). Before treatment, there was a reduction in the LTLs and expression levels of the human telomerase reverse transcriptase (hTERT) in the patients with MDD compared with controls. However, after 24 weeks of treatment with SSRIs, there was a significant increase in the LTLs and the expression levels of hTERT, with values approaching those observed in the controls. We conclude that SSRI antidepressant therapy can directly influence the increased expression levels of hTERT in patients.},
}
@article {pmid34869348,
year = {2021},
author = {De Rosa, M and Johnson, SA and Opresko, PL},
title = {Roles for the 8-Oxoguanine DNA Repair System in Protecting Telomeres From Oxidative Stress.},
journal = {Frontiers in cell and developmental biology},
volume = {9},
number = {},
pages = {758402},
pmid = {34869348},
issn = {2296-634X},
abstract = {Telomeres are protective nucleoprotein structures that cap linear chromosome ends and safeguard genome stability. Progressive telomere shortening at each somatic cell division eventually leads to critically short and dysfunctional telomeres, which can contribute to either cellular senescence and aging, or tumorigenesis. Human reproductive cells, some stem cells, and most cancer cells, express the enzyme telomerase to restore telomeric DNA. Numerous studies have shown that oxidative stress caused by excess reactive oxygen species is associated with accelerated telomere shortening and dysfunction. Telomeric repeat sequences are remarkably susceptible to oxidative damage and are preferred sites for the production of the mutagenic base lesion 8-oxoguanine, which can alter telomere length homeostasis and integrity. Therefore, knowledge of the repair pathways involved in the processing of 8-oxoguanine at telomeres is important for advancing understanding of the pathogenesis of degenerative diseases and cancer associated with telomere instability. The highly conserved guanine oxidation (GO) system involves three specialized enzymes that initiate distinct pathways to specifically mitigate the adverse effects of 8-oxoguanine. Here we introduce the GO system and review the studies focused on investigating how telomeric 8-oxoguanine processing affects telomere integrity and overall genome stability. We also discuss newly developed technologies that target oxidative damage selectively to telomeres to investigate roles for the GO system in telomere stability.},
}
@article {pmid34865259,
year = {2022},
author = {Tobler, M and Gómez-Blanco, D and Hegemann, A and Lapa, M and Neto, JM and Tarka, M and Xiong, Y and Hasselquist, D},
title = {Telomeres in ecology and evolution: A review and classification of hypotheses.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {5946-5965},
doi = {10.1111/mec.16308},
pmid = {34865259},
issn = {1365-294X},
mesh = {*Telomere Shortening/genetics ; Ecology ; Telomere/genetics ; *Life History Traits ; },
abstract = {Research on telomeres in the fields of ecology and evolution has been rapidly expanding over the last two decades. This has resulted in the formulation of a multitude of, often name-given, hypotheses related to the associations between telomeres and life-history traits or fitness-facilitating processes (and the mechanisms underlying them). However, the differences (or similarities) between the various hypotheses, which can originate from different research fields, are often not obvious. Our aim here is therefore to give an overview of the hypotheses that are of interest in ecology and evolution and to provide two frameworks that help discriminate among them. We group the hypotheses (i) based on their association with different research questions, and (ii) using a hierarchical approach that builds on the assumptions they make, such as about causality of telomere length/shortening and/or the proposed functional consequences of telomere shortening on organism performance. Both our frameworks show that there exist parallel lines of thoughts in different research fields. Moreover, they also clearly illustrate that there are in many cases competing hypotheses within clusters, and that some of these even have contradictory assumptions and/or predictions. We also touch upon two topics in telomere research that would benefit from further conceptualization. This review should help researchers, both those familiar with and those new to the subject, to identify future avenues of research.},
}
@article {pmid34859008,
year = {2021},
author = {Zhang, K and Xu, L and Cong, YS},
title = {Telomere Dysfunction in Idiopathic Pulmonary Fibrosis.},
journal = {Frontiers in medicine},
volume = {8},
number = {},
pages = {739810},
pmid = {34859008},
issn = {2296-858X},
abstract = {Idiopathic pulmonary fibrosis is an age-dependent progressive and fatal lung disease of unknown etiology, which is characterized by the excessive accumulation of extracellular matrix inside the interstitial layer of the lung parenchyma that leads to abnormal scar architecture and compromised lung function capacity. Recent genetic studies have attributed the pathological genes or genetic mutations associated with familial idiopathic pulmonary fibrosis (IPF) and sporadic IPF to telomere-related components, suggesting that telomere dysfunction is an important determinant of this disease. In this study, we summarized recent advances in our understanding of how telomere dysfunction drives IPF genesis. We highlighted the key role of alveolar stem cell dysfunction caused by telomere shortening or telomere uncapping, which bridged the gap between telomere abnormalities and fibrotic lung pathology. We emphasized that senescence-associated secretory phenotypes, innate immune cell infiltration, and/or inflammation downstream of lung stem cell dysfunction influenced the native microenvironment and local cell signals, including increased transforming growth factor-beta (TGF-β) signaling in the lung, to induce pro-fibrotic conditions. In addition, the failed regeneration of new alveoli due to alveolar stem cell dysfunction might expose lung cells to elevated mechanical tension, which could activate the TGF-β signaling loop to promote the fibrotic process, especially in a periphery-to-center pattern as seen in IPF patients. Understanding the telomere-related molecular and pathophysiological mechanisms of IPF would provide new insights into IPF etiology and therapeutic strategies for this fatal disease.},
}
@article {pmid34857839,
year = {2021},
author = {Dratwa, M and Wysoczańska, B and Butrym, A and Łacina, P and Mazur, G and Bogunia-Kubik, K},
title = {TERT genetic variability and telomere length as factors affecting survival and risk in acute myeloid leukaemia.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {23301},
pmid = {34857839},
issn = {2045-2322},
mesh = {Age Factors ; Female ; *Genetic Association Studies ; Humans ; Leukemia, Myeloid, Acute/*genetics/mortality ; Leukocyte Count ; Male ; Middle Aged ; Nucleophosmin/genetics ; Polymorphism, Genetic/*genetics ; Risk ; Survival Rate ; Telomerase/*genetics ; Telomere Homeostasis/*genetics ; fms-Like Tyrosine Kinase 3/genetics ; },
abstract = {Acute myeloid leukaemia (AML) is a neoplasm of immature myeloid cells characterized by various cytogenetic alterations. The present study showed that in addition to the FLT3-ITD and NPM1 mutation status, telomere length (TL) and telomerase reverse transcriptase (TERT) gene polymorphisms may affect risk and overall survival (OS) in AML. TL was longer in healthy controls than in AML patients and positively correlated with age in the patients, but not in healthy subjects. TL was found to be independently affected by the presence of the FLT3-ITD mutation. As for the TERT gene polymorphism, AML patients with the TERT rs2853669 CC genotype were characterized by significantly shorter OS than patients carrying the T allele. Another observation in our study is the difference in TL and OS in patients belonging to various risk stratification groups related to the FLT3-ITD and NPM1 mutation status. Patients with adverse risk classification (mutation in FLT3-ITD and lack of mutation in NPM1) presented with the shortest telomeres and significantly worse OS. In conclusion, OS of AML patients appears to be affected by TERT gene variability and TL in addition to other well-established factors such as age, WBC count, or FLT3-ITD and NPM1 mutation status.},
}
@article {pmid34857525,
year = {2021},
author = {Mackintosh, JA and Pietsch, M and Lutzky, V and Enever, D and Bancroft, S and Apte, SH and Tan, M and Yerkovich, ST and Dickinson, JL and Pickett, HA and Selvadurai, H and Grainge, C and Goh, NS and Hopkins, P and Glaspole, I and Reynolds, PN and Wrobel, J and Jaffe, A and Corte, TJ and Chambers, DC},
title = {TELO-SCOPE study: a randomised, double-blind, placebo-controlled, phase 2 trial of danazol for short telomere related pulmonary fibrosis.},
journal = {BMJ open respiratory research},
volume = {8},
number = {1},
pages = {},
pmid = {34857525},
issn = {2052-4439},
mesh = {Australia ; *COVID-19 ; Child ; Danazol/therapeutic use ; Humans ; *Pulmonary Fibrosis ; Telomere/genetics ; Treatment Outcome ; },
abstract = {INTRODUCTION: Recent discoveries have identified shortened telomeres and related mutations in people with pulmonary fibrosis (PF). There is evidence to suggest that androgens, including danazol, may be effective in lengthening telomeres in peripheral blood cells. This study aims to assess the safety and efficacy of danazol in adults and children with PF associated with telomere shortening.<br><br>METHODS AND ANALYSIS: A multi-centre, double-blind, placebo-controlled, randomised trial of danazol will be conducted in subjects aged >5 years with PF associated with age-adjusted telomere length &#x2264;10th centile measured by flow fluorescence in situ hybridisation; or in children, a diagnosis of dyskeratosis congenita. Adult participants will receive danazol 800&#x2009;mg daily in two divided doses or identical placebo capsules orally for 12 months, in addition to standard of care (including pirfenidone or nintedanib). Paediatric participants will receive danazol 2&#x2009;mg/kg/day orally in two divided doses or identical placebo for 6 months. If no side effects are encountered, the dose will be escalated to 4&#x2009;mg/kg/day (maximum 800&#x2009;mg daily) orally in two divided doses for a further 6 months. The primary outcome is change in absolute telomere length in base pairs, measured using the telomere shortest length assay (TeSLA), at 12 months in the intention to treat population.<br><br>ETHICS AND DISSEMINATION: Ethics approval has been granted in Australia by the Metro South Human Research Ethics Committee (HREC/2020/QMS/66385). The study will be conducted and reported according to Standard Protocol Items: Recommendations for Interventional Trials guidelines. Results will be published in peer-reviewed journals and presented at international and national conferences.<br><br>TRIAL REGISTRATION NUMBERS: NCT04638517; Australian New Zealand Clinical Trials Registry (ACTRN12620001363976p).},
}
@article {pmid34856024,
year = {2022},
author = {Choi, B and Messika, J and Courtwright, A and Mornex, JF and Hirschi, S and Roux, A and Le Pavec, J and Quêtant, S and Froidure, A and Lazor, R and Reynaud-Gaubert, M and Borgne, AL and Houlbracq, MP and Goldberg, H and El-Chemaly, S and Borie, R and , },
title = {Airway complications in lung transplant recipients with telomere-related interstitial lung disease.},
journal = {Clinical transplantation},
volume = {36},
number = {3},
pages = {e14552},
doi = {10.1111/ctr.14552},
pmid = {34856024},
issn = {1399-0012},
support = {R01-HL130272/NH/NIH HHS/United States ; },
mesh = {Constriction, Pathologic/complications ; Female ; Humans ; Lung ; *Lung Diseases, Interstitial/genetics/surgery ; *Lung Transplantation/adverse effects ; Retrospective Studies ; Telomere/genetics ; Transplant Recipients ; },
abstract = {INTRODUCTION: Patients with short telomere-related interstitial lung disease (ILD) have worse outcomes after lung transplantation. We hypothesized that post-transplant airway complications, including dehiscence and bronchial stenosis, would be more common in the short telomere ILD lung transplant population.<br><br>METHODS: We conducted a multi-institutional (Brigham and Women's Hospital, Groupe de Transplantation de la SPLF) retrospective cohort study of 63 recipients between 2009 and 2019 with ILD and short telomeres, compared to 4359 recipients from the Scientific Registry of Transplant Recipients with ILD and no known telomeropathy.<br><br>RESULTS: In the short telomere cohort, six recipients (9.5%) developed dehiscence and nine recipients (14.3%) developed stenosis, compared to 60 (1.4%) and 149 (3.4%) in the control, respectively. After adjusting for age, sex, and bilaterality, the presence of short telomeres was associated with higher odds of dehiscence (odds ratio (OR)&#xa0;=&#xa0;8.24, 95% confidence interval (CI)&#xa0;=&#xa0;3.34 20.29, p&#xa0;<&#xa0;.001) and stenosis (OR&#xa0;=&#xa0;4.63, 95% CI 2.21 9.69, p&#xa0;<&#xa0;.001).<br><br>CONCLUSION: The association between the presence of short telomeres and post-transplant dehiscence and stenosis suggest that airway complications may be a contributor to increased morbidity and mortality in patients with telomere-related ILD.},
}
@article {pmid34854526,
year = {2022},
author = {Sepe, S and Rossiello, F and Cancila, V and Iannelli, F and Matti, V and Cicio, G and Cabrini, M and Marinelli, E and Alabi, BR and di Lillo, A and Di Napoli, A and Shay, JW and Tripodo, C and d'Adda di Fagagna, F},
title = {DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging.},
journal = {EMBO reports},
volume = {23},
number = {2},
pages = {e53658},
pmid = {34854526},
issn = {1469-3178},
support = {//Fondazione Umberto Veronesi (Umberto Veronesi Foundation)/ ; 835103//EC|H2020|H2020 Priority Excellent Science|H2020 European Research Council (ERC)/ ; 875139//EC|H2020|H2020 Priority Excellent Science|H2020 European Research Council (ERC)/ ; 21091//Associazione Italiana per la Ricerca sul Cancro (AIRC)/ ; P50 CA070907/CA/NCI NIH HHS/United States ; //Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica (AriSLA)/ ; GGP17111//Fondazione Telethon (Telethon Foundation)/ ; 21762//Associazione Italiana per la Ricerca sul Cancro (AIRC)/ ; },
mesh = {Aged ; *Aging/genetics ; Angiotensin-Converting Enzyme 2/*genetics ; Animals ; *COVID-19 ; *DNA Damage ; Humans ; Mice ; SARS-CoV-2 ; *Telomere/genetics ; },
abstract = {The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), known to be more common in the elderly, who also show more severe symptoms and are at higher risk of hospitalization and death. Here, we show that the expression of the angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 cell receptor, increases during aging in mouse and human lungs. ACE2 expression increases upon telomere shortening or dysfunction in both cultured mammalian cells and in vivo in mice. This increase is controlled at the transcriptional level, and Ace2 promoter activity is DNA damage response (DDR)-dependent. Both pharmacological global DDR inhibition of ATM kinase activity and selective telomeric DDR inhibition by the use of antisense oligonucleotides prevent Ace2 upregulation following telomere damage in cultured cells and in mice. We propose that during aging telomere dysfunction due to telomeric shortening or damage triggers DDR activation and this causes the upregulation of ACE2, the SARS-CoV-2 cell receptor, thus contributing to make the elderly more susceptible to the infection.},
}
@article {pmid34854357,
year = {2022},
author = {Huang, YC and Lin, PY and Lee, Y and Lee, CY and Lo, YC and Hung, CF and Chen, CS},
title = {Metabolic syndrome components and leukocyte telomere length in patients with major depressive disorder.},
journal = {The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry},
volume = {23},
number = {6},
pages = {483-492},
doi = {10.1080/15622975.2021.2013091},
pmid = {34854357},
issn = {1814-1412},
mesh = {Humans ; Female ; Adult ; Male ; *Metabolic Syndrome/genetics/epidemiology ; *Depressive Disorder, Major/genetics/metabolism ; Prospective Studies ; Leukocytes/metabolism ; Telomere ; },
abstract = {OBJECTIVES: The relationship between metabolic syndrome (MetS) components and leukocyte telomere length (LTL) attrition in major depressive disorder (MDD) remains unclear.<br><br>METHODS: We recruited 70 MDD patients (mean age: 44.6&#x2009;years, 60.0% female) and 51 age- and sex-matched controls (mean age: 41.2&#x2009;years, 68.6% female) to examine the associations of MetS components and LTL. Five MetS components-waist circumference, systolic/diastolic blood pressure, serum levels of fasting glucose, high-density lipoprotein cholesterol (HDL-C), and triglycerides-were assessed. LTL was measured through quantitative polymerase chain reaction.<br><br>RESULTS: MDD had higher prevalence of MetS (34.3 vs. 17.6%, p=.042), low HDL-C (25.7 vs. 7.8%, p=.009) and shorter LTL (-0.038&#x2009;&#xb1;&#x2009;0.169 vs. 0.033&#x2009;&#xb1;&#x2009;0.213, p=.042). Regression analysis revealed that MDD (p=.046) and age (p=.003) associated with LTL, while a significant interaction effect of group (MDD vs. controls) &#xd7; HDL-C (p=.037) was observed. Post-hoc analysis showed MDD with low HDL-C had greater LTL attrition than controls without low HDL-C (p=.020). In MDD, HDL-C dysregulation negatively correlated with LTL (p=.010); but no significance after Bonferroni correction.<br><br>CONCLUSIONS: HDL-C may be involved in accelerated ageing process regarding metabolic disturbance in MDD only. The relationship merits prospective investigations with larger sample size for clarification.},
}
@article {pmid34853825,
year = {2021},
author = {Estrada, N and Xicoy, B and Beier, F and Garcia, O and Morales, C and Boqué, C and Sagüés, M and Ventura Ferreira, MS and Vallansot, R and Marcé, S and Cabezón, M and Brümmendorf, TH and Zamora, L},
title = {Influence of Telomere Length on the Achievement of Deep Molecular Response With Imatinib in Chronic Myeloid Leukemia Patients.},
journal = {HemaSphere},
volume = {5},
number = {12},
pages = {e657},
pmid = {34853825},
issn = {2572-9241},
abstract = {Tyrosine kinase inhibitors have dramatically changed the outcome of chronic myeloid leukemia (CML), and nowadays, one of the main treatment goals is the achievement of deep molecular responses (DMRs), which can eventually lead to therapy discontinuation approaches. Few biological factors at diagnosis have been associated with this level of response. Telomere length (TL) in peripheral blood cells of patients with CML has been related to disease stage, response to therapy and disease progression, but little is known about its role on DMR. In this study, we analyzed if age-adjusted TL (referred as "delta-TL") at diagnosis of chronic phase (CP)-CML might correlate with the achievement of DMR under first-line imatinib treatment. TL from 96 CP-CML patients had been retrospectively analyzed at diagnosis by monochrome multiplex quantitative PCR. We observed that patients with longer age-adjusted telomeres at diagnosis had higher probabilities to achieve DMR with imatinib than those with shortened telomeres (P = 0.035 when delta-TL was studied as a continuous variable and P = 0.047 when categorized by the median). Moreover, patients carrying long telomeres also achieved major molecular response significantly earlier (P = 0.012). This study provides proof of concept that TL has a role in CML biology and when measured at diagnosis of CP-CML could help to identify patients likely to achieve DMR to first-line imatinib treatment.},
}
@article {pmid34852175,
year = {2022},
author = {Niewisch, MR and Giri, N and McReynolds, LJ and Alsaggaf, R and Bhala, S and Alter, BP and Savage, SA},
title = {Disease progression and clinical outcomes in telomere biology disorders.},
journal = {Blood},
volume = {139},
number = {12},
pages = {1807-1819},
pmid = {34852175},
issn = {1528-0020},
support = {ZIA CP010190/ImNIH/Intramural NIH HHS/United States ; },
mesh = {Biology ; Disease Progression ; *Dyskeratosis Congenita/genetics/therapy ; Humans ; Male ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere Shortening ; },
abstract = {Dyskeratosis congenita related telomere biology disorders (DC/TBDs) are characterized by very short telomeres caused by germline pathogenic variants in telomere biology genes. Clinical presentations can affect all organs, and inheritance patterns include autosomal dominant (AD), autosomal recessive (AR), X-linked (XLR), or de novo. This study examined the associations between mode of inheritance with phenotypes and long-term clinical outcomes. Two hundred thirty-one individuals with DC/TBDs (144 male, 86.6% known genotype, median age at diagnosis 19.4 years [range 0 to 71.6]), enrolled in the National Cancer Institute's Inherited Bone Marrow Failure Syndrome Study, underwent detailed clinical assessments and longitudinal follow-up (median follow-up 5.2 years [range 0 to 36.7]). Patients were grouped by inheritance pattern, considering AD-nonTINF2, AR/XLR, and TINF2 variants separately. Severe bone marrow failure (BMF), severe liver disease, and gastrointestinal telangiectasias were more prevalent in AR/XLR or TINF2 disease, whereas pulmonary fibrosis developed predominantly in adults with AD disease. After adjusting for age at DC/TBD diagnosis, we observed the highest cancer risk in AR/XLR individuals. At last follow-up, 42% of patients were deceased with a median overall survival (OS) of 52.8 years (95% confidence interval [CI] 45.5-57.6), and the hematopoietic cell or solid organ transplant-free median survival was 45.3 years (95% CI 37.4-52.1). Significantly better OS was present in AD vs AR/XLR/TINF2 disease (P < .01), while patients with AR/XLR and TINF2 disease had similar survival probabilities. This long-term study of the clinical manifestations of DC/TBDs creates a foundation for incorporating the mode of inheritance into evidence-based clinical care guidelines and risk stratification in patients with DC/TBDs. This trial was registered at www.clinicaltrials.gov as #NCT00027274.},
}
@article {pmid34850488,
year = {2022},
author = {Sheldon, EL and Eastwood, JR and Teunissen, N and Roast, MJ and Aranzamendi, NH and Fan, M and Louise Hall, M and Kingma, SA and Verhulst, S and Peters, A},
title = {Telomere dynamics in the first year of life, but not later in life, predict lifespan in a wild bird.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6008-6017},
doi = {10.1111/mec.16296},
pmid = {34850488},
issn = {1365-294X},
mesh = {Animals ; Animals, Wild/genetics ; *Longevity/genetics ; Longitudinal Studies ; *Songbirds/genetics ; Telomere/genetics ; Telomere Shortening/genetics ; },
abstract = {Telomeres are protective, nucleoprotein structures at the end of chromosomes that have been associated with lifespan across taxa. However, the extent to which these associations can be attributed to absolute length vs. the rate of telomere shortening prior to sampling remains unresolved. In a longitudinal study, we examined the relationship between lifespan, telomere length and the rate of telomere shortening in wild, purple-crowned fairy-wrens (Malurus coronatus coronatus). To this end, we measured telomere length using quantitative polymerase chain reaction in the blood of 59 individuals sampled as nestlings and 4-14 months thereafter, and in 141 known-age individuals sampled on average three times across adulthood. We applied within-subject centring analyses to simultaneously test for associations between lifespan and average telomere length and telomere shortening. We reveal that the rate of telomere shortening and to a lesser extent telomere length in the first year of life independently predicted lifespan, with individuals with faster shortening rates and/or shorter telomeres living less long. In contrast, in adulthood neither telomere shortening nor telomere length predicted lifespan, despite a considerably larger data set. Our results suggest that telomere length measured very early in life (during development) and longitudinal assessments of telomere shortening during the first year of life constitute more useful biomarkers of total life expectancy than either telomere length measured after development, or telomere shortening later in adulthood.},
}
@article {pmid34849882,
year = {2021},
author = {Watson, JM and Trieb, J and Troestl, M and Renfrew, K and Mandakova, T and Fulnecek, J and Shippen, DE and Riha, K},
title = {A hypomorphic allele of telomerase uncovers the minimal functional length of telomeres in Arabidopsis.},
journal = {Genetics},
volume = {219},
number = {2},
pages = {},
pmid = {34849882},
issn = {1943-2631},
support = {R01 GM065383/GM/NIGMS NIH HHS/United States ; R01-GM065383/NH/NIH HHS/United States ; },
mesh = {Arabidopsis ; Arabidopsis Proteins/genetics/*metabolism ; Mutation ; Telomerase/genetics/*metabolism ; Telomere/genetics ; *Telomere Homeostasis ; },
abstract = {Despite the essential requirement of telomeric DNA for genome stability, the length of telomere tracts between species substantially differs, raising the question of the minimal length of telomeric DNA necessary for proper function. Here, we address this question using a hypomorphic allele of the telomerase catalytic subunit, TERT. We show that although this construct partially restored telomerase activity to a tert mutant, telomeres continued to shorten over several generations, ultimately stabilizing at a bimodal size distribution. Telomeres on two chromosome arms were maintained at a length of 1 kb, while the remaining telomeres were maintained at 400 bp. The longest telomeres identified in this background were also significantly longer in wild-type populations, suggesting cis-acting elements on these arms either promote telomerase processivity or recruitment. Genetically disrupting telomerase processivity in this background resulted in immediate lethality. Thus, telomeres of 400 bp are both necessary and sufficient for Arabidopsis viability. As this length is the estimated minimal length for t-loop formation, our data suggest that telomeres long enough to form a t-loop constitute the minimal functional length.},
}
@article {pmid34848322,
year = {2022},
author = {Mahmoodpoor, A and Sanaie, S and Roudbari, F and Sabzevari, T and Sohrabifar, N and Kazeminasab, S},
title = {Understanding the role of telomere attrition and epigenetic signatures in COVID-19 severity.},
journal = {Gene},
volume = {811},
number = {},
pages = {146069},
pmid = {34848322},
issn = {1879-0038},
mesh = {COVID-19/*genetics/*immunology/*metabolism/virology ; DNA Methylation ; *Epigenesis, Genetic ; *Epigenomics ; Genetic Predisposition to Disease ; Humans ; Immunity ; MicroRNAs/metabolism ; SARS-CoV-2/immunology ; *Severity of Illness Index ; Telomere/*genetics ; },
abstract = {Within the past several decades, the emergence and spread of infectious diseases with pandemic potential have endangered human lives. Coronavirus disease 2019 (COVID-19) outbreak represents an unprecedented threat for all health systems worldwide. The clinical spectrum of COVID-19 is highly heterogeneous, ranging from asymptomatic and mild upper respiratory tract illness to severe interstitial pneumonia with respiratory failure and even death. Highly age-dependent patterns of immune response potentially explain the higher rates of the severe forms of COVID-19 in elderly patients. However, genetic and epigenetic architecture can influence multiple biological processes during the lifespan, therefore as far as our knowledge shows, vulnerability to viral infection concerning telomere length and epigenetic signature is not a new idea. This review aims is to summarize the current understanding of the role of telomere length and epigenetic mechanisms on the severity of COVID-19. The current knowledge highlights the significant association between the shorter telomere length and the higher risk of developing severe COVID-19. Differential DNA methylation patterns and miRNA expression profiles imply that these hallmarks can play a pivotal role in COVID- 19 pathogenesis. Understanding the causes of inter-individual variations in COVID-19 outcomes could provide clues to the development of the personalized therapeutic intervention.},
}
@article {pmid34845136,
year = {2022},
author = {Panelli, DM and Bianco, K},
title = {Cellular aging and telomere dynamics in pregnancy.},
journal = {Current opinion in obstetrics &amp; gynecology},
volume = {34},
number = {2},
pages = {57-61},
doi = {10.1097/GCO.0000000000000765},
pmid = {34845136},
issn = {1473-656X},
support = {K12 HD103084/HD/NICHD NIH HHS/United States ; },
mesh = {Cellular Senescence/genetics ; Female ; Humans ; Infant, Newborn ; Parturition ; *Placenta ; Pregnancy ; *Telomere ; Telomere Shortening ; },
abstract = {PURPOSE OF REVIEW: Telomere biology is an emerging area of scientific interest. Telomeres are deoxynucleic acid caps at the ends of chromosomes that naturally shorten over one's lifespan; because of this, short telomeres have been studied as a marker of cellular aging. Given the association between short telomeres and genetic and environmental factors, their role in pregnancy has become an intriguing area of research.<br><br>RECENT FINDINGS: This review describes recent data on telomeres in pregnancy. Specifically, we discuss the association between short maternal leukocyte telomeres and poor nutritional status, between short neonatal telomeres and greater maternal psychosocial stress, and between shorter fetal amniotic membrane telomeres and the spontaneous onset of parturition. We also review recent studies suggesting that events during pregnancy can impact telomeres in the offspring years into the future.<br><br>SUMMARY: Telomere length varies in maternal, placental, and neonatal cells, but within each of these compartments telomeres may play their own distinct role during pregnancy. Whether telomeres are reflective of the cumulative impact of stressors, or part of an as-yet unknown fetal programming mechanism is an area of interest. With future research, we may work toward a better understanding of gestational biology which could have far reaching intergenerational impacts.},
}
@article {pmid34845112,
year = {2021},
author = {Guerrero, EN and Vega, S and Fu, C and De León, R and Beltran, D and Solis, MA},
title = {Increased proliferation and differentiation capacity of placenta-derived mesenchymal stem cells from women of median maternal age correlates with telomere shortening.},
journal = {Aging},
volume = {13},
number = {22},
pages = {24542-24559},
pmid = {34845112},
issn = {1945-4589},
mesh = {Adolescent ; Adult ; Cell Differentiation/*physiology ; Cell Proliferation/physiology ; Female ; Humans ; *Maternal Age ; Mesenchymal Stem Cells/*physiology ; Placenta/*cytology ; Pregnancy ; Telomere Shortening/*physiology ; Young Adult ; },
abstract = {Mesenchymal stem cells (MSCs) experience functional decline with systemic aging, resulting in reduced proliferation, increased senescence, and lower differentiation potential. The placenta represents a valuable source of MSCs, but the possible effect of donor age on the properties of placenta-derived mesenchymal stem cells (PDMSCs) has not been thoroughly studied. Thus, the aim of this study was to underscore the effect of maternal age on the biological characteristics and stemness properties of PDMSCs. PDMSCs were isolated from 5 donor age groups (A: 18-21, B: 22-25, C: 26-30, D:31-35 and E: ≥36 years) for comparison of morphological, proliferative and differentiation properties. The pluripotency markers NANOG, OCT4, and SSEA4, as well as multipotency and differentiation markers, showed higher expression in PDMSCs from mothers aged 22-35 years, with up to a 7-fold increase in adipogenesis. Cumulative population doubling, cell growth curves, and colony-forming unit-fibroblast assays revealed higher self-renewal ability in donors 26-30 years old. An increase in the proliferative characteristics of PDMSCs correlated with increased telomere shortening, suggesting that shorter telomere lengths could be related to cellular division rather than aging. A clear understanding of the effect of maternal age on MSC regenerative potential will assist in increasing the effectiveness of future cell therapies.},
}
@article {pmid34842724,
year = {2021},
author = {Anifandis, G and Samara, M and Simopoulou, M and Messini, CI and Chatzimeletiou, K and Thodou, E and Daponte, A and Georgiou, I},
title = {Insights into the Role of Telomeres in Human Embryological Parameters. Opinions Regarding IVF.},
journal = {Journal of developmental biology},
volume = {9},
number = {4},
pages = {},
pmid = {34842724},
issn = {2221-3759},
abstract = {Telomeres promote genome integrity by protecting chromosome ends from the activation of the DNA damage response and protecting chromosomes from the loss of coding sequences due to the end replication problem. Telomere length (TL) is progressively shortened as age progresses, thus resulting in cellular senescence. Therefore, TL is in strong adverse linear correlation with aging. Mounting evidence supports the notion that telomeres and male/female infertility are in a close relationship, posing the biology of telomeres as a hot topic in the era of human-assisted reproduction. Specifically, the length of sperm telomeres is gradually increasing as men get older, while the telomere length of the oocytes seems not to follow similar patterns with that of sperm. Nonetheless, the telomere length of the embryos during the cleavage stages seems to have a paternal origin, but the telomere length can be further extended by telomerase activity during the blastocyst stage. The latter has been proposed as a new molecular biomarker with strong predictive value regarding male infertility. As far as the role of telomeres in assisted reproduction, the data is limited but the length of telomeres in both gametes seems to be affected mainly by the cause of infertility rather than the assisted reproductive therapy (ART) procedure itself. The present review aims to shed more light into the role of telomeres in human embryological parameters, including gametes and embryos and also presents opinions regarding the association between telomeres and in vitro fertilization (IVF).},
}
@article {pmid34834452,
year = {2021},
author = {Pisanu, C and Vitali, E and Meloni, A and Congiu, D and Severino, G and Ardau, R and Chillotti, C and Trabucchi, L and Bortolomasi, M and Gennarelli, M and Minelli, A and Squassina, A},
title = {Investigating the Role of Leukocyte Telomere Length in Treatment-Resistant Depression and in Response to Electroconvulsive Therapy.},
journal = {Journal of personalized medicine},
volume = {11},
number = {11},
pages = {},
pmid = {34834452},
issn = {2075-4426},
support = {Year 2019 and 2020//Fondo integrativo per la ricerca (Fir)/ ; RASSR57271//Autonomous Region of Sardinia ("Legge Regionale 7 agosto 2007, n. 7 - call 2017")/ ; P.O.R. Sardegna F.S.E. - Operational Programme of the Autonomous Region of Sardinia, European Social Fund 2014-2020//Sardinian Regional Government/ ; },
abstract = {Psychiatric disorders seem to be characterized by premature cell senescence. However, controversial results have also been reported. In addition, the relationship between accelerated aging and treatment-resistance has scarcely been investigated. In the current study, we measured leukocyte telomere length (LTL) in 148 patients with treatment-resistant depression (TRD, 125 with major depressive disorder, MDD, and 23 with bipolar disorder, BD) treated with electroconvulsive therapy (ECT) and analyzed whether LTL was associated with different response profiles. We also compared LTL between patients with TRD and 335 non-psychiatric controls. For 107 patients for which genome-wide association data were available, we evaluated whether a significant overlap among genetic variants or genes associated with LTL and with response to ECT could be observed. LTL was negatively correlated with age (Spearman's correlation coefficient = -0.25, p < 0.0001) and significantly shorter in patients with treatment-resistant MDD (Quade's F = 35.18, p < 0.0001) or BD (Quade's F = 20.84, p < 0.0001) compared to controls. Conversely, baseline LTL was not associated with response to ECT or remission. We did not detect any significant overlap between genetic variants or genes associated with LTL and response to ECT. Our results support previous findings suggesting premature cell senescence in patients with severe psychiatric disorders and suggest that LTL could not be a predictive biomarker of response to ECT.},
}
@article {pmid34831418,
year = {2021},
author = {Assis, LHC and Andrade-Silva, D and Shiburah, ME and de Oliveira, BCD and Paiva, SC and Abuchery, BE and Ferri, YG and Fontes, VS and de Oliveira, LS and da Silva, MS and Cano, MIN},
title = {Cell Cycle, Telomeres, and Telomerase in Leishmania spp.: What Do We Know So Far?.},
journal = {Cells},
volume = {10},
number = {11},
pages = {},
pmid = {34831418},
issn = {2073-4409},
support = {2018/04375-2 (MICANO) and 2019/10753-2 and 2020/10277-3 (MSdS)//S&#xe3;o Paulo Research Foundation/ ; 2021/04253-7 (LHCA), 2021/05523-8 (DAS), 2019/25985-6 (BCDO), 2020/00316-1 (MES), 2020/16480-5 (BEA), 2020/16465-6 (YGF), 2020/08162-3 (VSF)//S&#xe3;o Paulo Research Foundation/ ; SCP//Coordena&#xe7;&#xe3;o de Aperfeicoamento de Pessoal de N&#xed;vel Superior/ ; },
mesh = {*Cell Cycle ; Humans ; Leishmania/*cytology/*enzymology ; Models, Biological ; Phylogeny ; Telomerase/*metabolism ; Telomere/*metabolism ; },
abstract = {Leishmaniases belong to the inglorious group of neglected tropical diseases, presenting different degrees of manifestations severity. It is caused by the transmission of more than 20 species of parasites of the Leishmania genus. Nevertheless, the disease remains on the priority list for developing new treatments, since it affects millions in a vast geographical area, especially low-income people. Molecular biology studies are pioneers in parasitic research with the aim of discovering potential targets for drug development. Among them are the telomeres, DNA-protein structures that play an important role in the long term in cell cycle/survival. Telomeres are the physical ends of eukaryotic chromosomes. Due to their multiple interactions with different proteins that confer a likewise complex dynamic, they have emerged as objects of interest in many medical studies, including studies on leishmaniases. This review aims to gather information and elucidate what we know about the phenomena behind Leishmania spp. telomere maintenance and how it impacts the parasite's cell cycle.},
}
@article {pmid34830418,
year = {2021},
author = {Turkiewicz, S and Ditmer, M and Sochal, M and Białasiewicz, P and Strzelecki, D and Gabryelska, A},
title = {Obstructive Sleep Apnea as an Acceleration Trigger of Cellular Senescence Processes through Telomere Shortening.},
journal = {International journal of molecular sciences},
volume = {22},
number = {22},
pages = {},
pmid = {34830418},
issn = {1422-0067},
support = {564/5-000-00/564-20-054//Medical University of Lodz/ ; },
mesh = {Aging/genetics ; Cellular Senescence/*genetics/physiology ; Humans ; Leukocytes/metabolism ; Oxidative Stress/genetics ; Sleep Apnea, Obstructive/*genetics/pathology ; Telomere/*genetics ; Telomere Shortening/*genetics ; },
abstract = {Obstructive sleep apnea (OSA) is chronic disorder which is characterized by recurrent pauses of breathing during sleep which leads to hypoxia and its two main pathological sequelae: oxidative stress and chronic inflammation. Both are also associated with cellular senescence. As OSA patients present with higher prevalence of age-related disorders, such as atrial hypertension or diabetes mellitus type 2, a relationship between OSA and accelerated aging is observable. Furthermore, it has been established that these OSA are associated with telomere shortening. This process in OSA is likely caused by increased oxidative DNA damage due to increased reactive oxygen species levels, DNA repair disruptions, hypoxia, chronic inflammation, and circadian clock disturbances. The aim of the review is to summarize study outcomes on changes in leukocyte telomere length (LTL) in OSA patients and describe possible molecular mechanisms which connect cellular senescence and the pathophysiology of OSA. The majority of OSA patients are characterized by LTL attrition due to oxidative stress, hypoxia and inflammation, which make a kind of positive feedback loop, and circadian clock disturbance.},
}
@article {pmid34829621,
year = {2021},
author = {Tarazón, E and Pérez-Carrillo, L and Giménez-Escamilla, I and Ramos-Castellanos, P and Martínez-Dolz, L and Portolés, M and Roselló-Lletí, E},
title = {Relationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {10},
number = {11},
pages = {},
pmid = {34829621},
issn = {2076-3921},
support = {PI20/01469, PI20/00071, CP18/00145//Instituto de Salud Carlos III/ ; CB16/11/00261//Centro de Investigaci&#xf3;n en Red en Enfermedades Cardiovasculares/ ; ERDF, "A way to make Europe"//European Union/ ; },
abstract = {Although the roles of telomeres and oxidative stress in ischaemic cardiomyopathy (ICM) are known, mechanisms of telomere homeostasis and their relationship with oxidative stress are incompletely understood. We performed two RNA-seq analyses (mRNA n = 23; ncRNA n = 30) and protein validation on left ventricles of explanted hearts from ICM and control subjects. We observed dysregulation of the shelterin and cohesin complexes, which was related to an increase in the response to cellular oxidative stress. Moreover, we found alterations at mRNA level in the mechanisms of telomeric DNA repair. Specifically, increased RAD51D mRNA levels were correlated with left ventricular diameters. RAD51D protein levels were unaltered, however, and were inversely corelated with the miR-103a-3p upregulation. We also observed the overexpression of lncRNAs (TERRA and GUARDIN) involved in telomere protection in response to stress and alterations in their regulatory molecules. Expression of the TERRA transcription factor ATF7 was correlated with superoxide dismutase 1 expression and left ventricular diameters. The levels of GUARDIN and its transcription factor FOSL2 were correlated with those of catalase. Therefore, we showed specific alterations in the mechanisms of telomeric DNA repair and protection, and these alterations are related to an increase in the response mechanisms to oxidative stress and cardiac dysfunction in ICM.},
}
@article {pmid34828344,
year = {2021},
author = {Kent, T and Clynes, D},
title = {Alternative Lengthening of Telomeres: Lessons to Be Learned from Telomeric DNA Double-Strand Break Repair.},
journal = {Genes},
volume = {12},
number = {11},
pages = {},
pmid = {34828344},
issn = {2073-4425},
support = {MC_UU_12009/3/MRC_/Medical Research Council/United Kingdom ; MC_UU_12025/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Cell Cycle ; DNA/metabolism ; *DNA Breaks, Double-Stranded ; *DNA Repair ; *DNA Replication ; Telomere/*metabolism ; *Telomere Homeostasis ; },
abstract = {The study of the molecular pathways underlying cancer has given us important insights into how breaks in our DNA are repaired and the dire consequences that can occur when these processes are perturbed. Extensive research over the past 20 years has shown that the key molecular event underpinning a subset of cancers involves the deregulated repair of DNA double-strand breaks (DSBs) at telomeres, which in turn leads to telomere lengthening and the potential for replicative immortality. Here we discuss, in-depth, recent major breakthroughs in our understanding of the mechanisms underpinning this pathway known as the alternative lengthening of telomeres (ALT). We explore how this gives us important insights into how DSB repair at telomeres is regulated, with relevance to the cell-cycle-dependent regulation of repair, repair of stalled replication forks and the spatial regulation of DSB repair.},
}
@article {pmid34828008,
year = {2021},
author = {Badmus, KA and Idrus, Z and Meng, GY and Mamat-Hamidi, K},
title = {Telomere Length, Apoptotic, and Inflammatory Genes: Novel Biomarkers of Gastrointestinal Tract Pathology and Meat Quality Traits in Chickens under Chronic Stress (Gallus gallus domesticus).},
journal = {Animals : an open access journal from MDPI},
volume = {11},
number = {11},
pages = {},
pmid = {34828008},
issn = {2076-2615},
support = {9629100//Universiti Putra Malaysia/ ; },
abstract = {This study was designed to examine the potentials of telomere length, mitochondria, and acute phase protein genes as novel biomarkers of gastrointestinal (GI) tract pathologies and meat quality traits. Chickens were fed a diet containing corticosterone (CORT) for 4 weeks and records on body weight, telomere length, GI tract and muscle histopathological test, meat quality traits, mitochondria, and acute phase protein genes were obtained at weeks 4 and 6 of age. The body weight of CORT-fed chickens was significantly suppressed (p < 0.05). CORT significantly altered the GI tract and meat quality traits. The interaction effect of CORT and age on body weight, duodenum and ileum crypt depth, pH, and meat color was significant (p < 0.05). CORT significantly (p < 0.05) shortened buffy coat telomere length. UCP3 and COX6A1 were diversely and significantly expressed in the muscle, liver, and heart of the CORT-fed chicken. Significant expression of SAAL1 and CRP in the liver and hypothalamus of the CORT-fed chickens was observed at week 4 and 6. Therefore, telomere lengths, mitochondria, and acute phase protein genes could be used as novel biomarkers for GI tract pathologies and meat quality traits.},
}
@article {pmid34827691,
year = {2021},
author = {Al-Daghri, NM and Abdi, S and Sabico, S and Alnaami, AM and Wani, KA and Ansari, MGA and Khattak, MNK and Khan, N and Tripathi, G and Chrousos, GP and McTernan, PG},
title = {Gut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes.},
journal = {Biomolecules},
volume = {11},
number = {11},
pages = {},
pmid = {34827691},
issn = {2218-273X},
mesh = {Aging ; *Diabetes Mellitus, Type 2 ; Endotoxins ; Humans ; Middle Aged ; Telomere ; },
abstract = {Premature aging, as denoted by a reduced telomere length (TL), has been observed in several chronic inflammatory diseases, such as obesity and type 2 diabetes mellitus (T2DM). However, no study to date has addressed the potential inflammatory influence of the gut-derived Gram-negative bacterial fragments lipopolysaccharide, also referred to as endotoxin, and its influence on TL in low-grade inflammatory states such as type 2 diabetes mellitus (T2DM). The current study therefore investigated the influence of endotoxin and inflammatory factors on telomere length (TL) in adults with (T2DM: n = 387) and without (non-diabetic (ND) controls: n = 417) obesity and T2DM. Anthropometric characteristics were taken, and fasted blood samples were used to measure biomarkers, TL, and endotoxin. The findings from this study highlighted across all participants that circulating endotoxin (r = -0.17, p = 0.01) was inversely associated with TL, noting that endotoxin and triglycerides predicted 18% of the variance perceived in TL (p < 0.001). Further stratification of the participants according to T2DM status and sex highlighted that endotoxin significantly predicted 19% of the variance denoted in TL among male T2DM participants (p = 0.007), where TL was notably influenced. The influence on TL was not observed to be impacted by anti-T2DM medications, statins, or anti-hypertensive therapies. Taken together, these results show that TL attrition was inversely associated with circulating endotoxin levels independent of the presence of T2DM and other cardiometabolic factors, suggesting that low-grade chronic inflammation may trigger premature biological aging. The findings further highlight the clinical relevance of mitigating the levels of circulating endotoxin (e.g., manipulation of gut microbiome) not only for the prevention of chronic diseases but also to promote healthy aging.},
}
@article {pmid34827416,
year = {2021},
author = {Sánchez-González, JL and Sánchez-Rodríguez, JL and Martín-Vallejo, J and Martel-Martel, A and González-Sarmiento, R},
title = {Effects of Physical Exercise on Cognition and Telomere Length in Healthy Older Women.},
journal = {Brain sciences},
volume = {11},
number = {11},
pages = {},
pmid = {34827416},
issn = {2076-3425},
abstract = {BACKGROUND: Physical exercise is an effective measure for preventing the onset of cognitive decline and has a direct influence on the aging process. The purpose of this study was to assess the effect of a 6-month physical exercise program on cognition and telomere length in adults over 65 years of age.<br><br>METHOD: Seventy-four healthy women were separated into two groups: 41 were included in the intervention group (IG) (72.70 &#xb1; 4.127 years and 8.18 &#xb1; 1.551 years of education) and 33 in the control group (CG) (71.21 &#xb1; 4.127 years and 8.42 &#xb1; 2.562). The participants included within the IG carried out three sessions of physical exercise per week for six months. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), the Stroop test and the Trail Making Test (TMT). Saliva samples were taken and analyzed and relative telomere length was calculated. Those conducting the analysis were blind to the group to which the participants had been assigned.<br><br>RESULTS: An improvement was observed in global cognitive function, in both attentional and executive functions, in the group of adults doing physical exercise as compared to the control group. Six months after the physical exercise program had finished, relative telomere length was found to have increased in the participants in the intervention group.<br><br>CONCLUSION: Physical exercise programs can lead to an improvement in both cognitive functions and telomere length.},
}
@article {pmid34826177,
year = {2022},
author = {Reichard, M and Giannetti, K and Ferreira, T and Maouche, A and Vrtílek, M and Polačik, M and Blažek, R and Ferreira, MG},
title = {Lifespan and telomere length variation across populations of wild-derived African killifish.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {5979-5992},
doi = {10.1111/mec.16287},
pmid = {34826177},
issn = {1365-294X},
mesh = {Animals ; Female ; Male ; Longevity/genetics ; *Fundulidae/genetics ; Telomere Shortening/genetics ; *Cyprinodontiformes/genetics ; Telomere/genetics ; },
abstract = {Telomeres and telomerase prevent the continuous erosion of chromosome-ends caused by lifelong cell division. Shortened telomeres are associated with age-related pathologies. While short telomere length is positively correlated with increased lethality at the individual level, in comparisons across species short telomeres are associated with long (and not short) lifespans. Here, we tested this contradiction between individual and evolutionary patterns in telomere length using African annual killifish. We analysed lifespan and telomere length in a set of captive strains derived from well-defined wild populations of Nothobranchius furzeri and its sister species, N. kadleci, from sites along a strong gradient of aridity which ultimately determines maximum natural lifespan. Overall, males were shorter-lived than females, and also had shorter telomeres. Male lifespan (measured in controlled laboratory conditions) was positively associated with the amount of annual rainfall in the site of strain origin. However, fish from wetter climates had shorter telomeres. In addition, individual fish which grew largest over the juvenile period possessed shorter telomeres at the onset of adulthood. This demonstrates that individual condition and environmentally-driven selection indeed modulate the relationship between telomere length and lifespan in opposite directions, validating the existence of inverse trends within a single taxon. Intraindividual heterogeneity of telomere length (capable to detect very short telomeres) was not associated with mean telomere length, suggesting that the shortest telomeres are controlled by regulatory pathways other than those that determine mean telomere length. The substantial variation in telomere length between strains from different environments identifies killifish as a powerful system in understanding the adaptive value of telomere length.},
}
@article {pmid34826163,
year = {2022},
author = {Campitelli, BE and Razzaque, S and Barbero, B and Abdulkina, LR and Hall, MH and Shippen, DE and Juenger, TE and Shakirov, EV},
title = {Plasticity, pleiotropy and fitness trade-offs in Arabidopsis genotypes with different telomere lengths.},
journal = {The New phytologist},
volume = {233},
number = {4},
pages = {1939-1952},
pmid = {34826163},
issn = {1469-8137},
support = {R01 GM065383/GM/NIGMS NIH HHS/United States ; R01 GM127402/GM/NIGMS NIH HHS/United States ; },
mesh = {*Arabidopsis ; Genetic Fitness ; Genotype ; Selection, Genetic ; Telomere/genetics ; },
abstract = {Telomere length has been implicated in the organismal response to stress, but the underlying mechanisms are unknown. Here we examine the impact of telomere length changes on the responses to three contrasting abiotic environments in Arabidopsis, and measure 32 fitness, developmental, physiological and leaf-level anatomical traits. We report that telomere length in wild-type and short-telomere mutants is resistant to abiotic stress, while the elongated telomeres in ku70 mutants are more plastic. We detected significant pleiotropic effects of telomere length on flowering time and key leaf physiological and anatomical traits. Furthermore, our data reveal a significant genotype by environment (G × E) interaction for reproductive fitness, with the benefits and costs to performance depending on the growth conditions. These results imply that life-history trade-offs between flowering time and reproductive fitness are impacted by telomere length variation. We postulate that telomere length in plants is subject to natural selection imposed by different environments.},
}
@article {pmid34825754,
year = {2022},
author = {Pepke, ML and Kvalnes, T and Lundregan, S and Boner, W and Monaghan, P and Saether, BE and Jensen, H and Ringsby, TH},
title = {Genetic architecture and heritability of early-life telomere length in a wild passerine.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6360-6381},
doi = {10.1111/mec.16288},
pmid = {34825754},
issn = {1365-294X},
mesh = {Animals ; *Genome-Wide Association Study ; Longevity/genetics ; Telomere/genetics ; *Passeriformes/genetics ; },
abstract = {Early-life telomere length (TL) is associated with fitness in a range of organisms. Little is known about the genetic basis of variation in TL in wild animal populations, but to understand the evolutionary and ecological significance of TL it is important to quantify the relative importance of genetic and environmental variation in TL. In this study, we measured TL in 2746 house sparrow nestlings sampled across 20 years and used an animal model to show that there is a small heritable component of early-life TL (h[2] = 0.04). Variation in TL among individuals was mainly driven by environmental (annual) variance, but also brood and parental effects. Parent-offspring regressions showed a large maternal inheritance component in TL (h maternal 2 = 0.44), but no paternal inheritance. We did not find evidence for a negative genetic correlation underlying the observed negative phenotypic correlation between TL and structural body size. Thus, TL may evolve independently of body size and the negative phenotypic correlation is likely to be caused by nongenetic environmental effects. We further used genome-wide association analysis to identify genomic regions associated with TL variation. We identified several putative genes underlying TL variation; these have been inferred to be involved in oxidative stress, cellular growth, skeletal development, cell differentiation and tumorigenesis in other species. Together, our results show that TL has a low heritability and is a polygenic trait strongly affected by environmental conditions in a free-living bird.},
}
@article {pmid34824901,
year = {2021},
author = {Tacheva, T and Zienolddiny, S and Dimov, D and Vlaykova, D and Vlaykova, T},
title = {The leukocyte telomere length, single nucleotide polymorphisms near TERC gene and risk of COPD.},
journal = {PeerJ},
volume = {9},
number = {},
pages = {e12190},
pmid = {34824901},
issn = {2167-8359},
abstract = {Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and is associated with chronic local and systemic inflammation and oxidative stress. The enhanced oxidative stress and inflammation have been reported to affect telomere length (TL). Furthermore, a number of SNPs at loci encoding the main components of the telomerase genes, TERT and TERC have been shown to correlate with TL. We aimed to explore the leukocyte TL and genotypes for single nucleotide polymorphisms, rs12696304 (C > G) and rs10936599 (C > T) near TERC in COPD cases and matched healthy controls using q-PCR technologies. Successful assessment of TL was performed for 91 patients and 88 controls. The patients had shorter TL (17919.36 ± 1203.01 bp) compared to controls (21 271.48 ± 1891.36 bp) although not significant (p = 0.137). The TL did not associate with the gender, age, spirometric indexes, smoking habits but tended to correlate negatively with BMI (Rho = - 0.215, p = 0.076) in the controls, but not in COPD patients. The genotype frequencies of the SNPs rs12696304 and rs10936599 were compared between patients and controls and the odds ratios (OR) for developing COPD were calculated. The carriers of the common homozygous (CC) genotypes of the SNPs had higher risk for COPD, compared to carriers of the variants alleles (rs12696304 CG+GG vs. CC; OR: 0.615, 95% CI [0.424-0.894], p = 0.011 and for rs10936599 CT+TT vs. CC OR = 0.668, 95% CI [0.457-0.976], p = 0.044). Analysis on the combined effects of the TERC rs12696304 (C > G) and rs10936599 (C > T) genotypes, CC/CC genotype combination was associated with higher risk for COPD (p < 0.0001) and marginally lower FEV1% pr. in patients with GOLD II (p = 0.052). There was no association between the SNP genotypes and TL. In summary, our results suggest that COPD patients may have shorter TL, and rs12696304 and rs10936599 near TERC may affect the risk of COPD independently of TL.},
}
@article {pmid34824250,
year = {2021},
author = {Livingstone, J and Shiah, YJ and Yamaguchi, TN and Heisler, LE and Huang, V and Lesurf, R and Gebo, T and Carlin, B and Eng, S and Drysdale, E and Green, J and van der Kwast, T and Bristow, RG and Fraser, M and Boutros, PC},
title = {The telomere length landscape of prostate cancer.},
journal = {Nature communications},
volume = {12},
number = {1},
pages = {6893},
pmid = {34824250},
issn = {2041-1723},
support = {U24 CA248265/CA/NCI NIH HHS/United States ; U01 CA214194/CA/NCI NIH HHS/United States ; P50 CA092131/CA/NCI NIH HHS/United States ; P30 CA016042/CA/NCI NIH HHS/United States ; },
mesh = {DNA Copy Number Variations ; Epigenome ; Gene Fusion ; Genomics ; Humans ; Male ; Prostatic Neoplasms/*genetics/metabolism/pathology ; Proteome ; Telomerase/genetics/metabolism ; Telomere/*genetics ; Transcriptome ; },
abstract = {Replicative immortality is a hallmark of cancer, and can be achieved through telomere lengthening and maintenance. Although the role of telomere length in cancer has been well studied, its association to genomic features is less well known. Here, we report the telomere lengths of 392 localized prostate cancer tumours and characterize their relationship to genomic, transcriptomic and proteomic features. Shorter tumour telomere lengths are associated with elevated genomic instability, including single-nucleotide variants, indels and structural variants. Genes involved in cell proliferation and signaling are correlated with tumour telomere length at all levels of the central dogma. Telomere length is also associated with multiple clinical features of a tumour. Longer telomere lengths in non-tumour samples are associated with a lower rate of biochemical relapse. In summary, we describe the multi-level integration of telomere length, genomics, transcriptomics and proteomics in localized prostate cancer.},
}
@article {pmid34824242,
year = {2021},
author = {Thongon, N and Ma, F and Santoni, A and Marchesini, M and Fiorini, E and Rose, A and Adema, V and Ganan-Gomez, I and Groarke, EM and Gutierrez-Rodrigues, F and Chen, S and Lockyer, P and Schneider, S and Bueso-Ramos, C and Montalban-Bravo, G and Class, CA and Soltysiak, KA and Pellegrini, M and Sahin, E and Bertuch, AA and DiNardo, CD and Garcia-Manero, G and Young, NS and Dwyer, K and Colla, S},
title = {Hematopoiesis under telomere attrition at the single-cell resolution.},
journal = {Nature communications},
volume = {12},
number = {1},
pages = {6850},
pmid = {34824242},
issn = {2041-1723},
support = {P30 CA016672/CA/NCI NIH HHS/United States ; P50 CA100632/CA/NCI NIH HHS/United States ; P50 CA211015/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Bone Marrow Failure Disorders/genetics/metabolism/pathology ; Cell Self Renewal ; Cellular Reprogramming ; Hematopoiesis/genetics/*physiology ; Hematopoietic Stem Cells/cytology/metabolism ; Humans ; Interferons/metabolism ; Megakaryocytes/cytology/metabolism ; Mice ; Nuclear Proteins/metabolism ; Oligodeoxyribonucleotides/metabolism ; Phosphoproteins/metabolism ; Signal Transduction ; Single-Cell Analysis ; Telomere/chemistry/physiology ; Telomere Shortening/genetics/*physiology ; },
abstract = {The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light of recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematopoietic stem cells under telomere attrition, as induced by pathogenic germline variants in telomerase complex genes. Here, we show that telomere attrition maintains hematopoietic stem cells under persistent metabolic activation and differentiation towards the megakaryocytic lineage through the cell-intrinsic upregulation of the innate immune signaling response, which directly compromises hematopoietic stem cells' self-renewal capabilities and eventually leads to their exhaustion. Mechanistically, we demonstrate that targeting members of the Ifi20x/IFI16 family of cytosolic DNA sensors using the oligodeoxynucleotide A151, which comprises four repeats of the TTAGGG motif of the telomeric DNA, overcomes interferon signaling activation in telomere-dysfunctional hematopoietic stem cells and these cells' skewed differentiation towards the megakaryocytic lineage. This study challenges the historical hypothesis that telomere attrition limits the proliferative potential of hematopoietic stem cells by inducing apoptosis, autophagy, or senescence, and suggests that targeting IFI16 signaling axis might prevent hematopoietic stem cell functional decline in conditions affecting telomere maintenance.},
}
@article {pmid34817067,
year = {2022},
author = {Galati, A and Scatolini, L and Micheli, E and Bavasso, F and Cicconi, A and Maccallini, P and Chen, L and Roake, CM and Schoeftner, S and Artandi, SE and Gatti, M and Cacchione, S and Raffa, GD},
title = {The S-adenosylmethionine analog sinefungin inhibits the trimethylguanosine synthase TGS1 to promote telomerase activity and telomere lengthening.},
journal = {FEBS letters},
volume = {596},
number = {1},
pages = {42-52},
doi = {10.1002/1873-3468.14240},
pmid = {34817067},
issn = {1873-3468},
mesh = {*Methyltransferases ; },
abstract = {Mutations in many genes that control the expression, the function, or the stability of telomerase cause telomere biology disorders (TBDs), such as dyskeratosis congenita, pulmonary fibrosis, and aplastic anemia. Mutations in a subset of the genes associated with TBDs cause reductions of the telomerase RNA moiety hTR, thus limiting telomerase activity. We have recently found that loss of the trimethylguanosine synthase TGS1 increases both hTR abundance and telomerase activity and leads to telomere elongation. Here, we show that treatment with the S-adenosylmethionine analog sinefungin inhibits TGS1 activity, increases the hTR levels, and promotes telomere lengthening in different cell types. Our results hold promise for restoring telomere length in stem and progenitor cells from TBD patients with reduced hTR levels.},
}
@article {pmid34813587,
year = {2021},
author = {Cui, M and Bai, Y and Li, K and Rong, YS},
title = {Taming active transposons at Drosophila telomeres: The interconnection between HipHop's roles in capping and transcriptional silencing.},
journal = {PLoS genetics},
volume = {17},
number = {11},
pages = {e1009925},
pmid = {34813587},
issn = {1553-7404},
mesh = {Animals ; Chromatin/genetics ; Chromosomal Proteins, Non-Histone/genetics ; DNA Transposable Elements/*genetics ; Drosophila Proteins/*genetics ; Drosophila melanogaster/genetics ; Female ; Genomic Instability/genetics ; Germ Cells/metabolism ; Heterochromatin/genetics ; Mutation ; RNA, Small Interfering/genetics ; Retroelements/*genetics ; Silencer Elements, Transcriptional/*genetics ; Telomere/*genetics ; },
abstract = {Drosophila chromosomes are elongated by retrotransposon attachment, a process poorly understood. Here we characterized a mutation affecting the HipHop telomere-capping protein. In mutant ovaries and the embryos that they produce, telomere retrotransposons are activated and transposon RNP accumulates. Genetic results are consistent with that this hiphop mutation weakens the efficacy of HP1-mediated silencing while leaving piRNA-based mechanisms largely intact. Remarkably, mutant females display normal fecundity suggesting that telomere de-silencing is compatible with germline development. Moreover, unlike prior mutants with overactive telomeres, the hiphop stock does not over-accumulate transposons for hundreds of generations. This is likely due to the loss of HipHop's abilities both to silence transcription and to recruit transposons to telomeres in the mutant. Furthermore, embryos produced by mutant mothers experience a checkpoint activation, and a further loss of maternal HipHop leads to end-to-end fusion and embryonic arrest. Telomeric retroelements fulfill an essential function yet maintain a potentially conflicting relationship with their Drosophila host. Our study thus showcases a possible intermediate in this arm race in which the host is adapting to over-activated transposons while maintaining genome stability. Our results suggest that the collapse of such a relationship might only occur when the selfish element acquires the ability to target non-telomeric regions of the genome. HipHop is likely part of this machinery restricting the elements to the gene-poor region of telomeres. Lastly, our hiphop mutation behaves as a recessive suppressor of PEV that is mediated by centric heterochromatin, suggesting its broader effect on chromatin not limited to telomeres.},
}
@article {pmid34813074,
year = {2022},
author = {Panasiak, L and Szubert, K and Polonis, M and Ocalewicz, K},
title = {Correction to: Telomere length variation does not correspond with the growth disturbances in the rainbow trout (Oncorhynchus mykiss).},
journal = {Journal of applied genetics},
volume = {63},
number = {1},
pages = {183},
doi = {10.1007/s13353-021-00671-y},
pmid = {34813074},
issn = {2190-3883},
}
@article {pmid34807303,
year = {2022},
author = {Cheng, F and Luk, AO and Wu, H and Tam, CHT and Lim, CKP and Fan, B and Jiang, G and Carroll, L and Yang, A and Lau, ESH and Ng, ACW and Lee, HM and Chow, E and Kong, APS and Keech, AC and Joglekar, MV and So, WY and Hardikar, AA and Chan, JCN and Jenkins, AJ and Ma, RCW},
title = {Relative leucocyte telomere length is associated with incident end-stage kidney disease and rapid decline of kidney function in type 2 diabetes: analysis from the Hong Kong Diabetes Register.},
journal = {Diabetologia},
volume = {65},
number = {2},
pages = {375-386},
pmid = {34807303},
issn = {1432-0428},
mesh = {Aged ; Diabetes Mellitus, Type 2/*physiopathology ; Female ; Glomerular Filtration Rate ; Hong Kong ; Humans ; Incidence ; Kidney/*physiopathology ; Kidney Failure, Chronic/*epidemiology/physiopathology ; Leukocytes/*metabolism ; Male ; Middle Aged ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Registries ; Telomere/metabolism ; Telomere Shortening/*physiology ; },
abstract = {AIMS/HYPOTHESIS: Few large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in individuals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese individuals with type 2 diabetes.<br><br>METHODS: We studied 4085 Chinese individuals with type 2 diabetes observed between 1995 and 2007 in the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data. rLTL was measured using quantitative PCR. ESKD was diagnosed based on the ICD-9 code and eGFR.<br><br>RESULTS: In this cohort (mean&#x2009;&#xb1;&#x2009;SD age 54.3&#x2009;&#xb1;&#x2009;12.6&#xa0;years) followed up for 14.1&#x2009;&#xb1;&#x2009;5.3&#xa0;years, 564 individuals developed incident ESKD and had shorter rLTL at baseline (4.2&#x2009;&#xb1;&#x2009;1.2 vs 4.7&#x2009;&#xb1;&#x2009;1.2, p&#xa0;<&#x2009;0.001) than the non-progressors (n&#x2009;=&#x2009;3521). On Cox regression analysis, each &#x2206;&#x2206;Ct decrease in rLTL was associated with an increased risk of incident ESKD (HR 1.21 [95% CI 1.13, 1.30], p&#xa0;<&#x2009;0.001); the association remained significant after adjusting for baseline age, sex, HbA1c, lipids, renal function and other risk factors (HR 1.11 [95% CI 1.03, 1.19], p&#x2009;=&#x2009;0.007). Shorter rLTL at baseline was associated with rapid decline in eGFR (>4% per year) during follow-up (unadjusted OR 1.22 [95% CI 1.15, 1.30], p&#xa0;<&#x2009;0.001; adjusted OR 1.09 [95% CI 1.01, 1.17], p&#x2009;=&#x2009;0.024).<br><br>CONCLUSIONS/INTERPRETATION: rLTL is independently associated with incident ESKD and rapid eGFR loss in individuals with type 2 diabetes. Telomere length may be a useful biomarker for the progression of kidney function and ESKD in type 2 diabetes.},
}
@article {pmid34803652,
year = {2021},
author = {Wang, Y and Jiao, F and Zheng, H and Kong, Q and Li, R and Zhang, X and Yan, L and Hao, Y and Wu, Y},
title = {Gender Difference in Associations Between Telomere Length and Risk Factors in Patients With Stroke.},
journal = {Frontiers in aging neuroscience},
volume = {13},
number = {},
pages = {719538},
pmid = {34803652},
issn = {1663-4365},
abstract = {Multiple risk factors of stroke are associated with telomere length shortening. Although leukocyte telomere length (LTL) is shorter in patients with stroke, the heterogeneity is high. Risk factors may be differentially associated with LTL in male and female patients contributing to the heterogeneity. However, the gender difference in associations between LTL and risk factors in stroke patients has not been investigated. In this study, we investigated the gender difference in associations between LTL and risk factors in 312 stroke patients. Real-time quantitative PCR was used to determine relative LTL, and multiple linear regression analysis was applied for association analyses. We found that LTL was negatively associated with triglyceride (TG) in all patients [β(95% CI) = -0.69 (-1.26, -0.11), P < 0.05] after adjusting confounders. Importantly, LTL was negatively associated with lack of exercise [β(95% CI) = -1.80 (-3.12, -0.49), P < 0.05] and LDL levels [β(95% CI) = -3.22 (-6.05, -0.390), P < 0.05] in male patients, while LTL was negatively associated with dyssomnia [β(95%CI) = -2.00 (-3.96, -0.07), P < 0.05] and diabetes [β(95%CI) = -2.13 (-4.10, -0.27), P < 0.01] in female patients. Our study showed that LTL is differently associated with risk factors in male and female patients with stroke, indicating that gender difference should be considered when LTL is potentially applied as an index of risk and prognosis for stroke. Our study also provides an insight into that gender differences should be considered when developing intervention strategies for stroke prevention and treatment.},
}
@article {pmid34798938,
year = {2021},
author = {Kahl, VFS and da Silva, J},
title = {Inorganic elements in occupational settings: A review on the effects on telomere length and biology.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {872},
number = {},
pages = {503418},
doi = {10.1016/j.mrgentox.2021.503418},
pmid = {34798938},
issn = {1879-3592},
mesh = {Humans ; Lead/toxicity ; *Occupational Exposure/adverse effects/analysis ; Particulate Matter ; *Telomere/genetics ; *Welding ; Xenobiotics ; },
abstract = {The past decades have shown that telomere crisis is highly affected by external factors. Effects of human exposure to xenobiotics on telomere length (TL), particularly in their workplace, have been largely studied. TL has been shown to be an efficient biomarker in occupational risk assessment. This is the first review focusing on studies about the effects on TL from occupational exposures to metals (lead [Pb] and mixtures), and particulate matter (PM) related to inorganic elements. Data from 15 studies were evaluated regarding occupational exposure to metals and PM-associated inorganic elements and impact on TL. Potential complementary analyses and subjects' background (age, length of employment and gender) were also assessed. There was limited information on the correlations between work length and TL dynamics, and that was also true for the correlation between age and TL. Results indicated that TL is affected differently across the types of occupational exposure investigated in this review, and even within the same exposure, a variety of effects can be observed. Fifty-three percent of the studies observed decreased TL in occupational exposure among welding fumes, open-cast coal mine, Pb and PM industries workers. Two studies focused particularly on the levels of metals and association with TL, and both linear and non-linear associations were found. Interestingly, TL modifications were accompanied by increase in DNA damage in 7 out of 8 studies that investigated it, measured either by Cytokinesis-block Micronucleus Assay or Comet assay. Five studies also investigated oxidative stress parameters, and 4 of them found increased levels of oxidative damage along with TL impairment. Oxidative stress is one of the main mechanisms by which telomeres are affected due to their high guanine content. Our review highlights the need of further studies accessing TL in simultaneous occupational exposure to mixtures of xenobiotics.},
}
@article {pmid34797948,
year = {2021},
author = {Dalzini, A and Ballin, G and Dominguez-Rodriguez, S and Rojo, P and Petrara, MR and Foster, C and Cotugno, N and Ruggiero, A and Nastouli, E and Klein, N and Rinaldi, S and Pahwa, S and Rossi, P and Giaquinto, C and Palma, P and De Rossi, A and , },
title = {Size of HIV-1 reservoir is associated with telomere shortening and immunosenescence in early-treated European children with perinatally acquired HIV-1.},
journal = {Journal of the International AIDS Society},
volume = {24},
number = {11},
pages = {e25847},
pmid = {34797948},
issn = {1758-2652},
mesh = {Adolescent ; CD4-Positive T-Lymphocytes ; Cross-Sectional Studies ; *HIV Infections/drug therapy ; *HIV-1/genetics ; Humans ; *Immunosenescence ; Telomere Shortening ; },
abstract = {INTRODUCTION: Persistence of HIV-1, causing chronic immune activation, is a key determinant of premature senescence. Early antiretroviral therapy (ART) has been associated with a reduced HIV-1 reservoir in children with perinatally acquired HIV-1 (PHIV), but its impact on the senescence process is an open question. We investigated the association between HIV-1 reservoir and biological and immune ageing profile in PHIV enrolled in the multicentre cross-sectional study CARMA (Child and Adolescent Reservoir Measurements on early suppressive ART) conducted within the EPIICAL (Early treated Perinatally HIV Infected individuals: Improving Children's Actual Life) consortium.<br><br>METHODS: Between September 2017 and June 2018, CARMA enrolled 40 PHIV who started ART before 2 years of age and had undetectable viremia for at least 5 years before sampling date. Samples from 37 children with a median age of 13.8 years were available for this study. HIV-1 DNA copies on CD4 cells, relative telomere length (marker of cellular senescence) and levels of T-cell receptor rearrangement excision circle (TREC, marker of thymic output) on CD4 and CD8 cells were quantified by qPCR. Immunological profile was assessed by flow cytometry. Associations between molecular and phenotypic markers, HIV-1 reservoir and age at ART initiation were explored using a multivariable Poisson regression.<br><br>RESULTS: Higher HIV-1 reservoir was associated (p<0.001) with telomere shortening (incidence rate ratio [IRR] = 0.15 [0.13-0.17]), immunosenescence (CD28[-] CD57[+] , IRR = 1.23 [1.21-1.26]) and immunoactivation (CD38[+] HLADR[+] , IRR = 7.29 [6.58-8.09]) of CD4 cells. Late ART initiation (after 6 months of age) correlated with higher HIV-1 reservoir levels (552 [303-1001] vs. 89 [56-365] copies/10[6] CD4 cells, p = 0.003) and percentage of CD4 senescent cells (2.89 [1.95-6.31] vs. 1.02 [0.45-2.69, p = 0.047). TREC levels in CD8 cells were inversely associated with HIV-1 reservoir (IRR = 0.77 [0.76-0.79]) and were significantly lower in late treated PHIV (1128 [486-1671] vs. 2278 [1425-3314], p = 0.042).<br><br>CONCLUSIONS: Later ART initiation is associated with higher HIV-1 reservoir size, which correlates with increased telomere shortening and senescence of CD4 cells. Timing of ART initiation in infancy has long-term consequences on the immune and biological ageing profile of children with perinatally acquired HIV-1.},
}
@article {pmid34797165,
year = {2021},
author = {Smith, AR and Lin, PD and Rifas-Shiman, SL and Rahman, ML and Gold, DR and Baccarelli, AA and Claus Henn, B and Amarasiriwardena, C and Wright, RO and Coull, B and Hivert, MF and Oken, E and Cardenas, A},
title = {Prospective Associations of Early Pregnancy Metal Mixtures with Mitochondria DNA Copy Number and Telomere Length in Maternal and Cord Blood.},
journal = {Environmental health perspectives},
volume = {129},
number = {11},
pages = {117007},
pmid = {34797165},
issn = {1552-9924},
support = {U2C ES026555/ES/NIEHS NIH HHS/United States ; U2C ES026561/ES/NIEHS NIH HHS/United States ; R01 HD034568/HD/NICHD NIH HHS/United States ; R01 ES031259/ES/NIEHS NIH HHS/United States ; UH3 OD023286/OD/NIH HHS/United States ; },
mesh = {Bayes Theorem ; Child ; DNA Copy Number Variations ; DNA, Mitochondrial/genetics ; Female ; *Fetal Blood ; Humans ; *Metals, Heavy ; Mitochondria ; Pregnancy ; Telomere ; },
abstract = {BACKGROUND: Metal exposure during pregnancy influences maternal and child health. Oxidative stress and inflammation may mediate adverse effects of heavy metals, whereas essential metals may act as antioxidants. Mitochondrial DNA is a prime target for metal-induced oxidative damage. Telomere dysfunction is attributed to imbalances between reactive oxidant species and antioxidants.<br><br>OBJECTIVES: We evaluated individual and joint associations of prenatal metals with mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) in maternal and cord blood as biomarkers of inflammation and oxidative stress.<br><br>METHODS: We measured six nonessential metals (arsenic, barium, cadmium, cesium, lead, mercury) and four essential metals (magnesium, manganese, selenium, zinc) in first-trimester maternal red blood cells in Project Viva, a U.S. prebirth cohort. We measured relative mtDNAcn (n=898) and TL (n=893) in second-trimester maternal blood and mtDNAcn (n=419) and TL (n=408) in cord blood. We used multivariable linear regression and quantile g-computation to estimate associations between prenatal metals and the biomarkers. We used generalized additive models and Bayesian kernel machine regression to examine nonlinearity and interactions.<br><br>RESULTS: A 2-fold increase in maternal magnesium was associated with lower maternal [&#x3b2;=-0.07, 95% confidence interval (CI): -0.10, -0.01] and cord blood (&#x3b2;=-0.08, 95% CI: -0.20, -0.01) mtDNAcn. Lead was associated with higher maternal mtDNAcn (&#x3b2;=0.04, 95% CI: 0.01, 0.06). Selenium was associated with longer cord blood TL (&#x3b2;=0.30, 95% CI: 0.01 0.50). An association was observed between the nonessential metal mixture and higher maternal mtDNAcn (&#x3b2;=0.04, 95% CI: 0.01, 0.07). There was a nonlinear relationship between cord blood mtDNAcn and magnesium; maternal mtDNAcn and barium, lead, and mercury; and maternal TL and barium.<br><br>DISCUSSION: Maternal exposure to metals such as lead, magnesium, and selenium was associated with mtDNAcn and TL in maternal second trimester and cord blood. Future work will evaluate whether these biomarkers are associated with child health. https://doi.org/10.1289/EHP9294.},
}
@article {pmid34794487,
year = {2021},
author = {Razazi, K and Marcos, E and Hüe, S and Boyer, L and Adnot, S and Mekontso Dessap, A},
title = {Telomere shortening during human septic shock: influence of sepsis mediators, role in organ failures, and septic myocardial dysfunction.},
journal = {Critical care (London, England)},
volume = {25},
number = {1},
pages = {401},
pmid = {34794487},
issn = {1466-609X},
mesh = {Cardiomyopathies ; Humans ; Multiple Organ Failure ; Sepsis ; *Shock, Septic/genetics/physiopathology ; *Telomere Shortening ; },
}
@article {pmid34789157,
year = {2021},
author = {Chung, D and Kwon, YM and Yang, Y},
title = {Telomere-to-telomere genome assembly of asparaginase-producing Trichoderma simmonsii.},
journal = {BMC genomics},
volume = {22},
number = {1},
pages = {830},
pmid = {34789157},
issn = {1471-2164},
mesh = {Asparaginase ; Genome ; Hypocreales ; Telomere ; *Trichoderma/genetics ; },
abstract = {BACKGROUND: Trichoderma is a genus of fungi in the family Hypocreaceae and includes species known to produce enzymes with commercial use. They are largely found in soil and terrestrial plants. Recently, Trichoderma simmonsii isolated from decaying bark and decorticated wood was newly identified in the Harzianum clade of Trichoderma. Due to a wide range of applications in agriculture and other industries, genomes of at least 12 Trichoderma spp. have been studied. Moreover, antifungal and enzymatic activities have been extensively characterized in Trichoderma spp. However, the genomic information and bioactivities of T. simmonsii from a particular marine-derived isolate remain largely unknown. While we screened for asparaginase-producing fungi, we observed that T. simmonsii GH-Sj1 strain isolated from edible kelp produced asparaginase. In this study, we report a draft genome of T. simmonsii GH-Sj1 using Illumina and Oxford Nanopore technologies. Furthermore, to facilitate biotechnological applications of this species, RNA-sequencing was performed to elucidate the transcriptional profile of T. simmonsii GH-Sj1 in response to asparaginase-rich conditions.<br><br>RESULTS: We generated ~&#x2009;14 Gb of sequencing data assembled in a&#x2009;~&#x2009;40&#x2009;Mb genome. The T. simmonsii GH-Sj1 genome consisted of seven telomere-to-telomere scaffolds with no sequencing gaps, where the N50 length was 6.4&#x2009;Mb. The total number of protein-coding genes was 13,120, constituting ~&#x2009;99% of the genome. The genome harbored 176 tRNAs, which encode a full set of 20 amino acids. In addition, it had an rRNA repeat region consisting of seven repeats of the 18S-ITS1-5.8S-ITS2-26S cluster. The T. simmonsii genome also harbored 7 putative asparaginase-encoding genes with potential medical applications. Using RNA-sequencing analysis, we found that 3 genes among the 7 putative genes were significantly upregulated under asparaginase-rich conditions.<br><br>CONCLUSIONS: The genome and transcriptome of T. simmonsii GH-Sj1 established in the current work represent valuable resources for future comparative studies on fungal genomes and asparaginase production.},
}
@article {pmid34786545,
year = {2021},
author = {Wang, Y and Chen, S and Feng, S and Wang, C and Jiang, H and Rong, S and Hermann, H and Chen, J and Zhang, P},
title = {Telomere shortening in patients on long-term hemodialysis.},
journal = {Chronic diseases and translational medicine},
volume = {7},
number = {4},
pages = {266-275},
pmid = {34786545},
issn = {2589-0514},
abstract = {BACKGROUND: Leukocyte telomere length shortening is a characteristic of premature senescence, a process that can be accelerated by oxidative stress. In general, patients with end-stage renal disease undergoing regular hemodialysis (HD) are repeatedly exposed to oxidative stress. Patients undergoing HD tend to have cardiovascular diseases associated with oxidative stress and inflammation. Therefore, we assumed that telomere length is associated with HD vintage and the degree of vascular calcification.<br><br>METHODS: A total of 144 patients undergoing regular HD before kidney transplantation and 62 patients on hemodialysis, but not undergoing kidney transplantation, were enrolled. We measured common laboratory values, such as calcium, phosphate, and hemoglobin levels, and assessed the degree of vascular calcification in the patients. The leukocyte telomere length was measured using reverse transcription polymerase chain reaction, and Spearman correlation was used for correlation analysis.<br><br>RESULTS: The leukocyte telomere length was negatively associated with age (rho&#xa0;=&#xa0;-0.306, P&#xff1c;0.01); it was shorter in middle-aged patients than in young patients (13.48&#xa0;&#xb1;&#xa0;4.80 vs. 15.86&#xa0;&#xb1;&#xa0;4.51, P&#xa0;<&#xa0;0.01). The telomere length was significantly different among patients aged 52-74 years in groups with different HD vintages. Additionally, the telomere length was positively associated with serum hemoglobin (Hb) levels in all patients (rho&#xa0;=&#xa0;0.290, P&#xa0;<&#xa0;0.01). There was a significant difference among patients divided into three groups according to the degree of anemia (17.09&#xa0;&#xb1;&#xa0;5.64 vs. 14.40&#xa0;&#xb1;&#xa0;4.07 vs. 13.99&#xa0;&#xb1;&#xa0;3.95, P&#xa0;<&#xa0;0.01). Further, a significant difference was observed in the telomere length among patients with different degrees of vascular calcification (16.79&#xa0;&#xb1;&#xa0;4.91 vs. 13.61&#xa0;&#xb1;&#xa0;2.82 vs. 14.62&#xa0;&#xb1;&#xa0;3.63 vs. 10.71&#xa0;&#xb1;&#xa0;3.74, P&#xa0;<&#xa0;0.01). The telomere length was shorter in the patients on hemodialysis who did not receive a kidney transplant than in the surgical patients (8.12&#xa0;&#xb1;&#xa0;1.83 vs. 14.33&#xa0;&#xb1;&#xa0;4.63, P&#xa0;<&#xa0;0.01).<br><br>CONCLUSION: This study demonstrated that the telomere length was significantly correlated with HD vintage in patients of a certain age group. The telomere length was shorter in patients on hemodialysis who matched for age and dialysis vintage with kidney transplant patients. It was also associated with vascular calcification and serum Hb levels in all patients undergoing HD.},
}
@article {pmid34784790,
year = {2021},
author = {Vedelek, B and Kovács, &#xc1; and Boros, IM},
title = {Evolutionary mode for the functional preservation of fast-evolving Drosophila telomere capping proteins.},
journal = {Open biology},
volume = {11},
number = {11},
pages = {210261},
pmid = {34784790},
issn = {2046-2441},
mesh = {Animals ; Chromosomal Proteins, Non-Histone/chemistry/genetics/*metabolism ; DNA Replication ; DNA, Single-Stranded/*metabolism ; Drosophila Proteins/chemistry/genetics/*metabolism ; Drosophila melanogaster/*genetics/metabolism ; Evolution, Molecular ; Models, Molecular ; Mutation ; Protein Conformation ; Structural Homology, Protein ; Telomere-Binding Proteins/chemistry/genetics/*metabolism ; },
abstract = {DNA end protection is fundamental for the long-term preservation of the genome. In vertebrates the Shelterin protein complex protects telomeric DNA ends, thereby contributing to the maintenance of genome integrity. In the Drosophila genus, this function is thought to be performed by the Terminin complex, an assembly of fast-evolving subunits. Considering that DNA end protection is fundamental for successful genome replication, the accelerated evolution of Terminin subunits is counterintuitive, as conservation is supposed to maintain the assembly and concerted function of the interacting partners. This problem extends over Drosophila telomere biology and provides insight into the evolution of protein assemblies. In order to learn more about the mechanistic details of this phenomenon we have investigated the intra- and interspecies assemblies of Verrocchio and Modigliani, two Terminin subunits using in vitro assays. Based on our results and on homology-based three-dimensional models for Ver and Moi, we conclude that both proteins contain Ob-fold and contribute to the ssDNA binding of the Terminin complex. We propose that the preservation of Ver function is achieved by conservation of specific amino acids responsible for folding or localized in interacting surfaces. We also provide here the first evidence on Moi DNA binding.},
}
@article {pmid34782750,
year = {2021},
author = {Wan, F and Ding, Y and Zhang, Y and Wu, Z and Li, S and Yang, L and Yan, X and Lan, P and Li, G and Wu, J and Lei, M},
title = {Zipper head mechanism of telomere synthesis by human telomerase.},
journal = {Cell research},
volume = {31},
number = {12},
pages = {1275-1290},
pmid = {34782750},
issn = {1748-7838},
mesh = {DNA ; Holoenzymes/genetics ; Humans ; RNA ; Repetitive Sequences, Nucleic Acid ; *Telomerase/metabolism ; Telomere/genetics/metabolism ; },
abstract = {Telomerase, a multi-subunit ribonucleoprotein complex, is a unique reverse transcriptase that catalyzes the processive addition of a repeat sequence to extend the telomere end using a short fragment of its own RNA component as the template. Despite recent structural characterizations of human and Tetrahymena telomerase, it is still a mystery how telomerase repeatedly uses its RNA template to synthesize telomeric DNA. Here, we report the cryo-EM structure of human telomerase holoenzyme bound with telomeric DNA at resolutions of 3.5 Å and 3.9 Å for the catalytic core and biogenesis module, respectively. The structure reveals that a leucine residue Leu980 in telomerase reverse transcriptase (TERT) catalytic subunit functions as a zipper head to limit the length of the short primer-template duplex in the active center. Moreover, our structural and computational analyses suggest that TERT and telomerase RNA (hTR) are organized to harbor a preformed active site that can accommodate short primer-template duplex substrates for catalysis. Furthermore, our findings unveil a double-fingers architecture in TERT that ensures nucleotide addition processivity of human telomerase. We propose that the zipper head Leu980 is a structural determinant for the sequence-based pausing signal of DNA synthesis that coincides with the RNA element-based physical template boundary. Functional analyses unveil that the non-glycine zipper head plays an essential role in both telomerase repeat addition processivity and telomere length homeostasis. In addition, we also demonstrate that this zipper head mechanism is conserved in all eukaryotic telomerases. Together, our study provides an integrated model for telomerase-mediated telomere synthesis.},
}
@article {pmid34782395,
year = {2022},
author = {Man, TK and Aubert, G and Richard, MA and LeJeune, W and Hariri, E and Goltsova, T and Gaikwad, A and Chen, Y and Whitton, J and Leisenring, WM and Arnold, MA and Neglia, JP and Yasui, Y and Robison, LL and Armstrong, GT and Bhatia, S and Gramatges, MM},
title = {Short NK- and Naïve T-Cell Telomere Length Is Associated with Thyroid Cancer in Childhood Cancer Survivors: A Report from the Childhood Cancer Survivor Study.},
journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {31},
number = {2},
pages = {453-460},
pmid = {34782395},
issn = {1538-7755},
support = {P30 CA021765/CA/NCI NIH HHS/United States ; R01 CA194473/CA/NCI NIH HHS/United States ; U24 CA055727/CA/NCI NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Cancer Survivors/*statistics &amp; numerical data ; Case-Control Studies ; Child ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Neoplasms, Second Primary/blood/*genetics ; Radiotherapy/adverse effects ; Surveys and Questionnaires ; T-Lymphocytes ; Telomere Shortening/*genetics ; Thyroid Neoplasms/blood/*genetics ; },
abstract = {BACKGROUND: Survivors of childhood cancer are at risk for therapy-related subsequent malignant neoplasms (SMN), including thyroid SMN. Telomere length (TL) is associated with cancer risk, but the relationship between TL and SMN risk among survivors is less clear.<br><br>METHODS: We conducted a nested, matched case-control study of radiation-exposed 15-year+ adult survivors of childhood cancer with thyroid SMN (cases) and without SMN (controls). Forty-six cases were matched to 46 controls by primary diagnosis, chemotherapy (yes/no), radiation field, and follow-up duration. Lymphocyte TL (LTL) was measured by telomere flow-FISH cytometry using blood samples banked at a mean of 38.9 years (cases), 39.2 years (controls). Genetic variation in telomere genes was assessed by whole genome sequencing. Point estimates for LTL <10th percentile were determined for cases and controls.<br><br>RESULTS: Cases had shorter median LTL than controls in three out of four leukocyte subsets. Cases were more likely to have NK cell LTL <10th percentile (P = 0.01), and 2.8-fold more likely to have na&#xef;ve T-cell LTL <10th percentile than controls (CI, 1.07-8.78). Five out of 15 cases with a rare indel or missense variant had na&#xef;ve T-cell LTL <10th percentile, compared with one out of eight controls.<br><br>CONCLUSIONS: Long-term survivors have shorter than expected LTL, a finding that is more pronounced among survivors with thyroid SMN.<br><br>IMPACT: The long-term impact of childhood cancer treatment on immune function is poorly understood. Our findings support immune function studies in larger survivor cohorts to assess long-term deficits in adaptive and innate immunity that may underlie SMN risk.},
}
@article {pmid34782052,
year = {2021},
author = {Cheng, S and Liu, B and Guo, ZF and Duan, XR and Liu, SX and Li, L and Yao, W and Yang, YL and Wang, W},
title = {Relationship between TERT Polymorphism and Telomere Length in Workers Exposed to Omethoate.},
journal = {Biomedical and environmental sciences : BES},
volume = {34},
number = {10},
pages = {838-841},
doi = {10.3967/bes2021.115},
pmid = {34782052},
issn = {2214-0190},
mesh = {Adult ; China ; Dimethoate/adverse effects/*analogs &amp; derivatives ; Farmers/statistics &amp; numerical data ; Female ; Humans ; Male ; Middle Aged ; *Occupational Exposure ; Pesticides/*adverse effects ; *Polymorphism, Single Nucleotide ; Telomerase/*genetics ; Telomere/*drug effects/physiology ; },
}
@article {pmid34781413,
year = {2022},
author = {Connelly, CJ and Vidal-Cardenas, S and Goldsmith, S and Greider, CW},
title = {The Bur1 cyclin-dependent kinase regulates telomere length in Saccharomyces cerevisiae.},
journal = {Yeast (Chichester, England)},
volume = {39},
number = {3},
pages = {177-192},
pmid = {34781413},
issn = {1097-0061},
mesh = {Cyclin-Dependent Kinases/genetics/*metabolism ; *Saccharomyces cerevisiae/genetics/metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; Telomere/genetics/metabolism ; Transcription, Genetic ; },
abstract = {Telomere length regulation is essential for cell viability in eukaryotes. While many pathways that affect telomere length are known, we do not yet have a complete understanding of the mechanism of length regulation. To identify new pathways that might regulate telomere length, we carried out a genetic screen in yeast and identified the cyclin-dependent kinase complex Bur1/2 as a regulator of telomere length. Mutations in either BUR1 cyclin-dependent kinase or the associated BUR2 cyclin resulted in short telomeres. This regulation did not function through the known role of BUR1 in regulating histone modification as bur1∆ set2∆ and bur2∆ set2∆ double mutants rescued cell growth but did not rescue the telomere shortening effects. We found that both bur1∆ and bur2∆ set2∆ were also defective in de novo telomere addition, and deletion of SET2 did also not rescue this elongation defect. The Bur1/2 cyclin-dependent kinase regulates transcription of many genes. We found that TLC1 RNA levels were reduced in bur2∆ set2∆ mutants; however, overexpression of TLC1 restored the transcript levels but did not restore de novo telomere elongation or telomere length. These data suggest that the Bur1/2 kinase plays a role in telomere elongation separate from its role in transcription of telomerase components. Dissecting the role of the Bur1/2 kinase pathway at telomeres will help complete our understanding of the complex network of telomere length regulation.},
}
@article {pmid34781086,
year = {2021},
author = {Freimane, L and Barkane, L and Igumnova, V and Kivrane, A and Zole, E and Ranka, R},
title = {Telomere length and mitochondrial DNA copy number in multidrug-resistant tuberculosis.},
journal = {Tuberculosis (Edinburgh, Scotland)},
volume = {131},
number = {},
pages = {102144},
doi = {10.1016/j.tube.2021.102144},
pmid = {34781086},
issn = {1873-281X},
mesh = {Adult ; Aged ; Antitubercular Agents/therapeutic use ; *DNA Copy Number Variations ; DNA, Mitochondrial/*genetics/immunology ; Female ; Humans ; Male ; Middle Aged ; Risk Factors ; Telomere Homeostasis/*genetics/immunology ; Tuberculosis, Multidrug-Resistant/drug therapy/*genetics ; },
abstract = {Multidrug resistant tuberculosis (MDR-TB) is a severe disease that requires prolonged chemotherapy and is associated with an increased probability of treatment failure and death. MDR-TB is a state of heightened oxidative stress and inflammation, which could be related to the aging-related processes and immunosenescence. We, therefore, tested the hypothesis that MDR-TB is associated with alterations in aging biomarkers in peripheral blood cells. We investigated 51 MDR-TB patients and 57 healthy individuals and carried out an analysis of covariance to assess the possible impact of different variables on biomarker perturbations. The results showed that MDR-TB patients had significantly reduced telomere length (TL) and increased mitochondrial DNA copy number (mtDNA CN) (P < 0.05) in comparison to the controls, and MDR-TB infection was the main influencing factor. Male sex and extrapulmonary TB strongly influenced mtDNA CN increment, and MDR-TB patients with normal weight had longer telomeres than those who were underweight (P < 0.05). In conclusion, the evidence for shorter telomeres and higher mtDNA CN in the peripheral blood cells of MDR-TB patients was obtained indicating the connection between MDR-TB and aging biomarkers. The observed associations highlight a complicated interplay between MDR-TB and immunosenescence, thus further studies are required to achieve full understanding.},
}
@article {pmid34780645,
year = {2021},
author = {Brown, HA and Williams, CAC and Zhou, H and Rios-Szwed, D and Fernandez-Alonso, R and Mansoor, S and McMulkin, L and Toth, R and Gourlay, R and Peltier, J and Dieguez-Martinez, N and Trost, M and Lizcano, JM and Stavridis, MP and Findlay, GM},
title = {An ERK5-KLF2 signalling module regulates early embryonic gene expression and telomere rejuvenation in stem cells.},
journal = {The Biochemical journal},
volume = {478},
number = {23},
pages = {4119-4136},
pmid = {34780645},
issn = {1470-8728},
support = {211209/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; MR/N000609/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Animals ; Kruppel-Like Transcription Factors/*metabolism ; Mice ; Mitogen-Activated Protein Kinase 7/*metabolism ; *Mouse Embryonic Stem Cells/cytology/metabolism ; },
abstract = {The ERK5 MAP kinase signalling pathway drives transcription of naïve pluripotency genes in mouse Embryonic Stem Cells (mESCs). However, how ERK5 impacts on other aspects of mESC biology has not been investigated. Here, we employ quantitative proteomic profiling to identify proteins whose expression is regulated by the ERK5 pathway in mESCs. This reveals a function for ERK5 signalling in regulating dynamically expressed early embryonic 2-cell stage (2C) genes including the mESC rejuvenation factor ZSCAN4. ERK5 signalling and ZSCAN4 induction in mESCs increases telomere length, a key rejuvenative process required for prolonged culture. Mechanistically, ERK5 promotes ZSCAN4 and 2C gene expression via transcription of the KLF2 pluripotency transcription factor. Surprisingly, ERK5 also directly phosphorylates KLF2 to drive ubiquitin-dependent degradation, encoding negative feedback regulation of 2C gene expression. In summary, our data identify a regulatory module whereby ERK5 kinase and transcriptional activities bi-directionally control KLF2 levels to pattern 2C gene transcription and a key mESC rejuvenation process.},
}
@article {pmid34778247,
year = {2021},
author = {de Oliveira, BCD and Shiburah, ME and Paiva, SC and Vieira, MR and Morea, EGO and da Silva, MS and Alves, CS and Segatto, M and Gutierrez-Rodrigues, F and Borges, JC and Calado, RT and Cano, MIN},
title = {Possible Involvement of Hsp90 in the Regulation of Telomere Length and Telomerase Activity During the Leishmania amazonensis Developmental Cycle and Population Proliferation.},
journal = {Frontiers in cell and developmental biology},
volume = {9},
number = {},
pages = {713415},
pmid = {34778247},
issn = {2296-634X},
abstract = {The Leishmania developmental cycle comprises three main life forms in two hosts, indicating that the parasite is continually challenged due to drastic environmental changes. The disruption of this cycle is critical for discovering new therapies to eradicate leishmaniasis, a neglected disease that affects millions worldwide. Telomeres, the physical ends of chromosomes, maintain genome stability and cell proliferation and are potential antiparasitic drug targets. Therefore, understanding how telomere length is regulated during parasite development is vital. Here, we show that telomeres form clusters spread in the nucleoplasm of the three parasite life forms. We also observed that amastigotes telomeres are shorter than metacyclic and procyclic promastigotes and that in parasites with continuous in vitro passages, telomere length increases over time. These observed differences in telomere length among parasite's life stages were not due to lack/inhibition of telomerase since enzyme activity was detected in all parasite life stages, although the catalysis was temperature-dependent. These data led us to test if, similar to other eukaryotes, parasite telomere length maintenance could be regulated by Hsp83, the ortholog of Hsp90 in trypanosomatids, and Leishmania (LHsp90). Parasites were then treated with the Hsp90 inhibitor 17AAG. The results showed that 17AAG disturbed parasite growth, induced accumulation into G2/M phases, and telomere shortening in a time-dependent manner. It has also inhibited procyclic promastigote's telomerase activity. Besides, LHsp90 interacts with the telomerase TERT component as shown by immunoprecipitation, strongly suggesting a new role for LHsp90 as a parasite telomerase component involved in controlling telomere length maintenance and parasite life span.},
}
@article {pmid34775545,
year = {2022},
author = {Panasiak, L and Szubert, K and Polonis, M and Ocalewicz, K},
title = {Telomere length variation does not correspond with the growth disturbances in the rainbow trout (Oncorhynchus mykiss).},
journal = {Journal of applied genetics},
volume = {63},
number = {1},
pages = {133-139},
pmid = {34775545},
issn = {2190-3883},
support = {2017/27/B/NZ9/00113//Narodowe Centrum Nauki/ ; },
mesh = {Animals ; Diploidy ; Female ; Haploidy ; Humans ; Infant ; Male ; *Oncorhynchus mykiss/genetics ; *Telomerase ; Telomere/genetics ; },
abstract = {Somatic growth is considered to affect pace of the telomere attrition in vertebrates. As normally developed and dwarf fish differ in the body size we have decided to compare telomere length in the rainbow trout (Oncorhynchus mykiss) with normal growth and with growth reduced due to the dwarf condition. Examined 1-year-old fish with normal and dwarf appearance were siblings originated from androgenetic fully homozygous doubled haploid (DH) line of rainbow trout. Particular dwarf individuals had body deformities such as humpback, kyphosis, and lordosis. Somatic cells of examined rainbow trout had an average telomere length between 17 and 20 kb, comparable in females and males. Dwarf rainbow trout exhibited significantly lower body length and weight than their normally developed siblings even though no differences in the telomere length were found between these fishes. Statistical analysis did not exhibit any correlation between body size and the telomere length. Equal length of telomeres observed in the studied normal and dwarf rainbow trout suggests morphological and physiological differences in fish with different growth rates do not affect dynamics of telomeric DNA. Or any variation in the telomere length might have been levelled by telomerase that in rainbow trout is active in all tissues irrespective of the individual developmental stage.},
}
@article {pmid34774607,
year = {2022},
author = {Kosmopoulos, M and Chiriacò, M and Stamatelopoulos, K and Tsioufis, C and Masci, PG and Kontogiannis, C and Mengozzi, A and Pugliese, NR and Taddei, S and Virdis, A and Masi, S and Georgiopoulos, G},
title = {The relationship between telomere length and putative markers of vascular ageing: A systematic review and meta-analysis.},
journal = {Mechanisms of ageing and development},
volume = {201},
number = {},
pages = {111604},
doi = {10.1016/j.mad.2021.111604},
pmid = {34774607},
issn = {1872-6216},
mesh = {Aging/*physiology ; *Blood Vessels/pathology/physiopathology ; Cardiovascular Physiological Phenomena ; Cellular Senescence/*physiology ; Humans ; Telomere Homeostasis/*physiology ; *Vascular Remodeling ; },
abstract = {Accelerated biological aging contributes to the evolution of cardiovascular disease. However, its influence on subclinical organ damage remains unclear. Leukocyte telomere length (LTL) is emerging as a marker of biological cardiovascular aging. We performed a systematic review and meta-analysis to assess the association between LTL and measures of end-organ damage. PubMed, Medline, Embase, Cinahl Plus, ClinicalTrials.gov, and grey literature databases were searched for studies that assessed the association of LTL with arterial pulse wave velocity (aPWV), carotid intima-media thickness (cIMT), left ventricular mass (LVM or LVMI), renal outcomes, coronary artery calcium (CAC) and presence of carotid plaques. In a sample of 7256 patients, we found that cIMT (pooled correlation coefficient (r) = -0.249; 95 %CI -0.37, -0.128) and aPWV (pooled r = -0.194; 95 % CI -0.290, -0.100) inversely correlate with LTL. Compared to aPWV, cIMT had a stronger correlation with LTL. Patients without carotid plaques had longer telomeres than patients with carotid plaques. Quantitative analyses documented LTL association with renal outcomes and CAC, but not with LVM/LVMI. Among measures of end-organ damage, cIMT and aPWV provide the most accurate information on the contribution of biological aging to the process of vascular remodeling/damage.},
}
@article {pmid34771533,
year = {2021},
author = {Chen, YY and Dagg, R and Zhang, Y and Lee, JHY and Lu, R and Martin La Rotta, N and Sampl, S and Korkut-Demirbaş, M and Holzmann, K and Lau, LMS and Reddel, RR and Henson, JD},
title = {The C-Circle Biomarker Is Secreted by Alternative-Lengthening-of-Telomeres Positive Cancer Cells inside Exosomes and Provides a Blood-Based Diagnostic for ALT Activity.},
journal = {Cancers},
volume = {13},
number = {21},
pages = {},
pmid = {34771533},
issn = {2072-6694},
support = {09CDF225//Cancer Institute NSW/ ; RG14-04//Cancer Council NSW/ ; },
abstract = {C-Circles, self-primed telomeric C-strand templates for rolling circle amplification, are the only known alternative-lengthening-of-telomeres (ALT)-specific molecule. However, little is known about the biology of C-Circles and if they may be clinically useful. Here we show that C-Circles are secreted by ALT+ cancer cells inside exosomes, and that a blood-based C-Circle Assay (CCA) can provide an accurate diagnostic for ALT activity. Extracellular vesicles were isolated by differential centrifugation from the growth media of lung adenocarcinoma, glioblastoma, neuroblastoma, osteosarcoma, and soft tissue sarcoma cell lines, and C-Circles were detected in the exosome fraction from all eleven ALT+ cancer cell lines and not in any extracellular fraction from the eight matching telomerase positive cancer cell lines or the normal fibroblast strain. The existence of C-Circles in ALT+ exosomes was confirmed with exosomes isolated by iodixanol gradient separation and CD81-immunoprecipitation, and C-Circles in the exosomes were protected from nucleases. On average, 0.4% of the total ALT+ intracellular C-Circles were secreted in the exosomes every 24 h. Comparing the serum-based and tumor-based CCAs in 35 high risk neuroblastoma patients divided randomly into ALT+ threshold derivation and validation groups, we found the serum-based CCA to have 100% sensitivity (6/6), 70% specificity (7/10), and 81% concordance (13/16). We conclude that the secretion of C-Circles by ALT+ cancer cells in the exosomes provides a stable blood-based biomarker and a potential clinical diagnostic for ALT activity.},
}
@article {pmid34769797,
year = {2021},
author = {Ribeiro, VB and Pedroso, DCC and Kogure, GS and Lopes, IP and Santana, BA and Dutra de Souza, HC and Ferriani, RA and Calado, RT and Furtado, CLM and Reis, RMD},
title = {Short-Term Aerobic Exercise Did Not Change Telomere Length While It Reduced Testosterone Levels and Obesity Indexes in PCOS: A Randomized Controlled Clinical Trial Study.},
journal = {International journal of environmental research and public health},
volume = {18},
number = {21},
pages = {},
pmid = {34769797},
issn = {1660-4601},
mesh = {Body Mass Index ; Exercise ; Female ; Humans ; *Insulin Resistance ; Obesity ; *Polycystic Ovary Syndrome ; Telomere ; Testosterone ; },
abstract = {Metabolic and hormonal outcomes of polycystic ovary syndrome (PCOS) have implications on telomere biology and physical activity may prevent telomere erosion. We sought to observe the effects of continuous (CAT) and intermittent (IAT) aerobic training on telomere length, inflammatory biomarkers, and its correlation with metabolic, hormonal, and anthropometric parameters of PCOS. This randomized controlled clinical trial study included 87 PCOS randomly stratified according to body mass index (BMI) in CAT (n = 28), IAT (n = 29) and non-training control group (CG, n = 30). The exercises were carried out on a treadmill, three times per week for 16 weeks. The participants' anthropometric characteristics and biochemical and hormonal concentrations were measured before and after aerobic training or observation period, as the telomere length that was evaluated using quantitative real-time PCR. Four months of aerobic exercises (CAT or IAT) did not alter telomere length and inflammatory biomarkers in PCOS women. Obesity index as BMI and waist circumference (WC), and inflammatory biomarkers negatively affect telomeres. The hyper-andro-genism measured by testosterone levels was reduced after both exercises (CAT, p ≤ 0.001; IAT, p = 0.019). In particular, the CAT reduced WC (p = 0.045), hip circumference (p = 0.032), serum cholesterol (p ≤ 0.001), and low-density lipoprotein (p = 0.030). Whereas, the IAT decreased WC (p = 0.014), waist-to-hip ratio (p = 0.012), free androgen index (FAI) (p = 0.037). WC (p = 0.049) and body fat (p = 0.015) increased in the non-training group while total cholesterol was reduced (p = 0.010). Booth exercises reduced obesity indices and hyperandrogenism on PCOS women without changes in telomere length or inflammatory biomarkers.},
}
@article {pmid34767620,
year = {2022},
author = {Sharma, R and Sahoo, SS and Honda, M and Granger, SL and Goodings, C and Sanchez, L and Künstner, A and Busch, H and Beier, F and Pruett-Miller, SM and Valentine, MB and Fernandez, AG and Chang, TC and Géli, V and Churikov, D and Hirschi, S and Pastor, VB and Boerries, M and Lauten, M and Kelaidi, C and Cooper, MA and Nicholas, S and Rosenfeld, JA and Polychronopoulou, S and Kannengiesser, C and Saintomé, C and Niemeyer, CM and Revy, P and Wold, MS and Spies, M and Erlacher, M and Coulon, S and Wlodarski, MW},
title = {Gain-of-function mutations in RPA1 cause a syndrome with short telomeres and somatic genetic rescue.},
journal = {Blood},
volume = {139},
number = {7},
pages = {1039-1051},
pmid = {34767620},
issn = {1528-0020},
support = {P30 CA021765/CA/NCI NIH HHS/United States ; P30 CA086862/CA/NCI NIH HHS/United States ; R35 GM131704/GM/NIGMS NIH HHS/United States ; U01 HG007709/HG/NHGRI NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Bone Marrow Failure Disorders/etiology/metabolism/*pathology ; Cell Differentiation ; Child ; Female ; *Gain of Function Mutation ; *Heterozygote ; Humans ; Infant, Newborn ; Male ; Middle Aged ; Myelodysplastic Syndromes/etiology/metabolism/*pathology ; Replication Protein A/*genetics ; Telomere/*genetics ; *Telomere Shortening ; Young Adult ; },
abstract = {Human telomere biology disorders (TBD)/short telomere syndromes (STS) are heterogeneous disorders caused by inherited loss-of-function mutations in telomere-associated genes. Here, we identify 3 germline heterozygous missense variants in the RPA1 gene in 4 unrelated probands presenting with short telomeres and varying clinical features of TBD/STS, including bone marrow failure, myelodysplastic syndrome, T- and B-cell lymphopenia, pulmonary fibrosis, or skin manifestations. All variants cluster to DNA-binding domain A of RPA1 protein. RPA1 is a single-strand DNA-binding protein required for DNA replication and repair and involved in telomere maintenance. We showed that RPA1E240K and RPA1V227A proteins exhibit increased binding to single-strand and telomeric DNA, implying a gain in DNA-binding function, whereas RPA1T270A has binding properties similar to wild-type protein. To study the mutational effect in a cellular system, CRISPR/Cas9 was used to knock-in the RPA1E240K mutation into healthy inducible pluripotent stem cells. This resulted in severe telomere shortening and impaired hematopoietic differentiation. Furthermore, in patients with RPA1E240K, we discovered somatic genetic rescue in hematopoietic cells due to an acquired truncating cis RPA1 mutation or a uniparental isodisomy 17p with loss of mutant allele, coinciding with stabilized blood counts. Using single-cell sequencing, the 2 somatic genetic rescue events were proven to be independently acquired in hematopoietic stem cells. In summary, we describe the first human disease caused by germline RPA1 variants in individuals with TBD/STS.},
}
@article {pmid34764923,
year = {2021},
author = {Bhatt, SP and Guleria, R and Vikram, NK},
title = {The Effect of the Severity of Obstructive Sleep Apnea on Leukocyte Telomere Length, 25 Hydroxy Vitamin D, and Parathyroid Hormonal Concentrations in Asian Indians.},
journal = {Frontiers in neurology},
volume = {12},
number = {},
pages = {682739},
pmid = {34764923},
issn = {1664-2295},
abstract = {Background: Obstructive sleep apnea (OSA) is a common disorder in which breathing repeatedly stops during sleep. Leukocyte telomere length (LTL) and OSA are linked with an increased risk of oxidative stress and inflammation. The possible link between LTL and OSA in Asian Indians has not been evaluated. Thus, the present study aims to compare the link between LTL and OSA in Asian Indians. Methods: In this study, 300 subjects (120 obese with OSA, 110 obese without OSA, and 70 non-obese without OSA) were included after overnight polysomnography and a fasting blood sample. Clinical, anthropometry, metabolic markers, insulin, 25-hydroxyvitamin D [25(OH) D], and parathyroid hormones (PTH) levels were investigated. LTL was investigated by a QPCR. Univariate and stepwise multivariate linear regression analyses adjusting for age, gender, BMI, and % body fat were conducted while treating LTL as a dependent variable in relation to AHI and other covariates. Results: Obese subjects with OSA had significantly decreased 25(OH)D and increased PTH levels. The mean telomere length (T/S) ratio was significantly shorter in patients with OSA. The adjusted correlation analysis showed that shortening of telomere length correlated with increasing age, apnea-hypopnea index (AHI), oxygen desaturation index, and RDI. Univariate analysis showed that LTL revealed a trend toward a negative correlation with a mean age (β + SE, -0.015 + 0.0006; p = 0.01) and positive correlation with AHI [β +slandered error (SE), 0.042 + 0.017; p = 0.008]. In the multiple regression analysis, LTL was positively associated with AHI (β + SE, 0.281 + 0.04; p = 0.001) after adjusting for age, sex, BMI, and % body fat. Even when adjusted for confounding factors, 25(OH)D, and PTH levels, LTL still was related to AHI (β + SE, 0.446 + 0.02; p = 0.05). Conclusion: Our study indicates the presence of an association between LTL and OSA and a significant impact of OSA severity and telomeres shortening in Asian Indians.},
}
@article {pmid34761561,
year = {2022},
author = {Garfein, J and Flannagan, KSJ and Mora-Plazas, M and Oliveros, H and Marín, C and Villamor, E},
title = {Prospective associations between leukocyte telomere length and adiposity in childhood.},
journal = {Pediatric obesity},
volume = {17},
number = {4},
pages = {e12868},
doi = {10.1111/ijpo.12868},
pmid = {34761561},
issn = {2047-6310},
mesh = {*Adiposity/genetics ; Adolescent ; Child ; Child, Preschool ; Colombia ; Cross-Sectional Studies ; Female ; Humans ; Leukocytes ; Male ; Models, Biological ; *Obesity/genetics ; Prospective Studies ; Sex Factors ; *Telomere/genetics ; Waist Circumference/genetics ; },
abstract = {Leukocyte telomere length (LTL) is associated with obesity and may be involved in its aetiology, but few studies have focused on children and most have been cross-sectional. We assessed the relation of LTL with adiposity development in a prospective study of Colombian children. We quantified LTL at enrollment in 722 children aged 5-12 years and measured anthropometry annually for a median 6 years. Using mixed effects models, we estimated changes in adiposity measures including BMI and waist circumference (WC)-for-age z-scores in relation to baseline LTL z-score. In girls, longer LTL was linearly related to a lower increase in WC z-score from age 6 to 16 years. Every 1 SD LTL was associated with an adjusted 0.13 units lower increase in WC (95% CI: -0.23, -0.03; p = 0.01). In conclusion, longer LTL among girls in middle childhood is associated with smaller increases in WC, an indicator of abdominal adiposity.},
}
@article {pmid34761263,
year = {2021},
author = {Higa, M and Matsuda, Y and Fujii, J and Sugimoto, N and Yoshida, K and Fujita, M},
title = {TRF2-mediated ORC recruitment underlies telomere stability upon DNA replication stress.},
journal = {Nucleic acids research},
volume = {49},
number = {21},
pages = {12234-12251},
pmid = {34761263},
issn = {1362-4962},
mesh = {Cell Line, Tumor ; DNA Damage ; DNA Replication/*genetics ; Gene Expression Regulation ; HCT116 Cells ; HEK293 Cells ; HeLa Cells ; Humans ; Microscopy, Fluorescence ; *Mutation ; Origin Recognition Complex/*genetics ; Protein Binding ; Reverse Transcriptase Polymerase Chain Reaction ; Telomere/*genetics/metabolism ; Telomeric Repeat Binding Protein 2/*genetics/metabolism ; },
abstract = {Telomeres are intrinsically difficult-to-replicate region of eukaryotic chromosomes. Telomeric repeat binding factor 2 (TRF2) binds to origin recognition complex (ORC) to facilitate the loading of ORC and the replicative helicase MCM complex onto DNA at telomeres. However, the biological significance of the TRF2-ORC interaction for telomere maintenance remains largely elusive. Here, we employed a TRF2 mutant with mutations in two acidic acid residues (E111A and E112A) that inhibited the TRF2-ORC interaction in human cells. The TRF2 mutant was impaired in ORC recruitment to telomeres and showed increased replication stress-associated telomeric DNA damage and telomere instability. Furthermore, overexpression of an ORC1 fragment (amino acids 244-511), which competitively inhibited the TRF2-ORC interaction, increased telomeric DNA damage under replication stress conditions. Taken together, these findings suggest that TRF2-mediated ORC recruitment contributes to the suppression of telomere instability.},
}
@article {pmid34758087,
year = {2022},
author = {Kachuri, L and Walsh, KM},
title = {Long telomeres in need of a SNP: Germline contributions of telomere maintenance to glioma.},
journal = {Neuro-oncology},
volume = {24},
number = {2},
pages = {182-183},
pmid = {34758087},
issn = {1523-5866},
support = {P30 CA014236/CA/NCI NIH HHS/United States ; },
mesh = {*Glioma/genetics ; Humans ; *Telomere/genetics ; },
}
@article {pmid34754432,
year = {2021},
author = {Gurung, RL and Dorajoo, R and M, Y and Wang, L and Liu, S and Liu, JJ and Shao, YM and Chen, Y and Sim, X and Ang, K and Subramaniam, T and Tang, WE and Sum, CF and Liu, JJ and Lim, SC},
title = {Association of leukocyte telomere length with chronic kidney disease in East Asians with type 2 diabetes: a Mendelian randomization study.},
journal = {Clinical kidney journal},
volume = {14},
number = {11},
pages = {2371-2376},
pmid = {34754432},
issn = {2048-8505},
abstract = {BACKGROUND: Chronic kidney disease (CKD) is common among people with type 2 diabetes (T2D), and increases the risk of kidney failure and cardiovascular diseases. Shorter leukocyte telomere length (LTL) is associated with CKD in patients with T2D. We previously reported single-nucleotide polymorphisms (SNPs) associated with LTL in an Asian population. In this study, we elucidated the association of these SNPs with CKD in patients with T2D using the Mendelian randomization (MR) approach.<br><br>METHODS: The cross-sectional association of 16 LTL SNPs with CKD, defined as an estimated glomerular filtration rate of <60&#x2009;mL/min/1.73&#x2009;m[2], was assessed among 4768 (1628 cases and 3140 controls) participants in the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in T2D and Diabetic Nephropathy cohorts. MR analysis was performed using the random-effect inverse-variance weighted (IVW) method, the weighted median, MR-Egger and Radial MR adjusted for age and sex-stratified by cohorts and ethnicity (Chinese and Malays), then meta-analyzed.<br><br>RESULTS: Genetically determined shorter LTL was associated with increased risk of CKD in patients with T2D (meta-IVW adjusted odds ratio&#x2009;= 1.51, 95% confidence interval 1.12-2.12, P&#x2009;=&#x2009;0.007, Phet &#x2009;=&#x2009;0.547). Similar results were obtained following sensitivity analysis. MR-Egger analysis (intercept) suggested no evidence of horizontal pleiotropy (&#x3b2;&#x2009;=&#x2009;0.010, P&#x2009;=&#x2009;0.751).<br><br>CONCLUSIONS: Our findings suggest that genetically determined LTL is associated with CKD in patients with T2D. Further studies are warranted to elucidate the causal role of telomere length in CKD progression.},
}
@article {pmid34752684,
year = {2021},
author = {Wang, L and Lu, Z and Zhao, J and Schank, M and Cao, D and Dang, X and Nguyen, LN and Nguyen, LNT and Khanal, S and Zhang, J and Wu, XY and El Gazzar, M and Ning, S and Moorman, JP and Yao, ZQ},
title = {Selective oxidative stress induces dual damage to telomeres and mitochondria in human T cells.},
journal = {Aging cell},
volume = {20},
number = {12},
pages = {e13513},
pmid = {34752684},
issn = {1474-9726},
support = {S10 OD021572/OD/NIH HHS/United States ; I01 BX004281/BX/BLRD VA/United States ; R01 AI114748/AI/NIAID NIH HHS/United States ; R21 AI157909/AI/NIAID NIH HHS/United States ; I01 BX002670/BX/BLRD VA/United States ; R21 AI138598/AI/NIAID NIH HHS/United States ; R15 AG069544/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; Mitochondria/*metabolism ; Oxidative Stress/*genetics ; T-Lymphocytes/*metabolism ; Telomere/*metabolism ; },
abstract = {Oxidative stress caused by excess reactive oxygen species (ROS) accelerates telomere erosion and mitochondrial injury, leading to impaired cellular functions and cell death. Whether oxidative stress-mediated telomere erosion induces mitochondrial injury, or vice versa, in human T cells-the major effectors of host adaptive immunity against infection and malignancy-is poorly understood due to the pleiotropic effects of ROS. Here we employed a novel chemoptogenetic tool that selectively produces a single oxygen ([1] O2) only at telomeres or mitochondria in Jurkat T cells. We found that targeted [1] O2 production at telomeres triggered not only telomeric DNA damage but also mitochondrial dysfunction, resulting in T cell apoptotic death. Conversely, targeted [1] O2 formation at mitochondria induced not only mitochondrial injury but also telomeric DNA damage, leading to cellular crisis and apoptosis. Targeted oxidative stress at either telomeres or mitochondria increased ROS production, whereas blocking ROS formation during oxidative stress reversed the telomeric injury, mitochondrial dysfunction, and cellular apoptosis. Notably, the X-ray repair cross-complementing protein 1 (XRCC1) in the base excision repair (BER) pathway and multiple mitochondrial proteins in other cellular pathways were dysregulated by the targeted oxidative stress. By confining singlet [1] O2 formation to a single organelle, this study suggests that oxidative stress induces dual injury in T cells via crosstalk between telomeres and mitochondria. Further identification of these oxidation pathways may offer a novel approach to preserve mitochondrial functions, protect telomere integrity, and maintain T cell survival, which can be exploited to combat various immune aging-associated diseases.},
}
@article {pmid34747482,
year = {2021},
author = {Lin, CG and Näger, AC and Lunardi, T and Vančevska, A and Lossaint, G and Lingner, J},
title = {The human telomeric proteome during telomere replication.},
journal = {Nucleic acids research},
volume = {49},
number = {21},
pages = {12119-12135},
pmid = {34747482},
issn = {1362-4962},
mesh = {*DNA Replication ; HEK293 Cells ; HeLa Cells ; Histones/metabolism ; Humans ; Shelterin Complex/metabolism ; Telomerase/*metabolism ; Telomere/*metabolism ; Telomere Shortening ; Telomere-Binding Proteins/metabolism ; },
abstract = {Telomere shortening can cause detrimental diseases and contribute to aging. It occurs due to the end replication problem in cells lacking telomerase. Furthermore, recent studies revealed that telomere shortening can be attributed to difficulties of the semi-conservative DNA replication machinery to replicate the bulk of telomeric DNA repeats. To investigate telomere replication in a comprehensive manner, we develop QTIP-iPOND - Quantitative Telomeric chromatin Isolation Protocol followed by isolation of Proteins On Nascent DNA - which enables purification of proteins that associate with telomeres specifically during replication. In addition to the core replisome, we identify a large number of proteins that specifically associate with telomere replication forks. Depletion of several of these proteins induces telomere fragility validating their importance for telomere replication. We also find that at telomere replication forks the single strand telomere binding protein POT1 is depleted, whereas histone H1 is enriched. Our work reveals the dynamic changes of the telomeric proteome during replication, providing a valuable resource of telomere replication proteins. To our knowledge, this is the first study that examines the replisome at a specific region of the genome.},
}
@article {pmid34745087,
year = {2021},
author = {Chuenwisad, K and More-Krong, P and Tubsaeng, P and Chotechuang, N and Srisa-Art, M and Storer, RJ and Boonla, C},
title = {Premature Senescence and Telomere Shortening Induced by Oxidative Stress From Oxalate, Calcium Oxalate Monohydrate, and Urine From Patients With Calcium Oxalate Nephrolithiasis.},
journal = {Frontiers in immunology},
volume = {12},
number = {},
pages = {696486},
pmid = {34745087},
issn = {1664-3224},
mesh = {Aged ; Aging, Premature/*etiology ; Calcium Oxalate/*pharmacology ; Cell Line ; Cyclin-Dependent Kinase Inhibitor p16/analysis ; DNA Damage ; Female ; Humans ; Hydrogen Peroxide/pharmacology ; Male ; Middle Aged ; Nephrolithiasis/etiology/*urine ; Oxalates/*pharmacology ; Oxidative Stress/*drug effects ; *Telomere Shortening ; Telomeric Repeat Binding Protein 1/genetics ; },
abstract = {Oxidative stress, a well-known cause of stress-induced premature senescence (SIPS), is increased in patients with calcium oxalate (CaOx) kidney stones (KS). Oxalate and calcium oxalate monohydrate (COM) induce oxidative stress in renal tubular cells, but to our knowledge, their effect on SIPS has not yet been examined. Here, we examined whether oxalate, COM, or urine from patients with CaOx KS could induce SIPS and telomere shortening in human kidney (HK)-2 cells, a proximal tubular renal cell line. Urine from age- and sex-matched individuals without stones was used as a control. In sublethal amounts, H2O2, oxalate, COM, and urine from those with KS evoked oxidative stress in HK-2 cells, indicated by increased protein carbonyl content and decreased total antioxidant capacity, but urine from those without stones did not. The proportion of senescent HK-2 cells, as indicated by SA-βgal staining, increased after treatment with H2O2, oxalate, COM, and urine from those with KS. Expression of p16 was higher in HK-2 cells treated with H2O2, oxalate, COM, and urine from those with KS than it was in cells treated with urine from those without stones and untreated controls. p16 was upregulated in the SA-βgal positive cells. Relative telomere length was shorter in HK-2 cells treated with H2O2, oxalate, COM, and urine from those with KS than that in cells treated with urine from those without stones and untreated controls. Transcript expression of shelterin components (TRF1, TRF2 and POT1) was decreased in HK-2 cells treated with H2O2, oxalate, COM, and urine from those with KS, in which case the expression was highest. Urine from those without KS did not significantly alter TRF1, TRF2, and POT1 mRNA expression in HK-2 cells relative to untreated controls. In conclusion, oxalate, COM, and urine from patients with CaOx KS induced SIPS and telomere shortening in renal tubular cells. SIPS induced by a lithogenic milieu may result from upregulation of p16 and downregulation of shelterin components, specifically POT1, and might contribute, at least in part, to the development of CaOx KS.},
}
@article {pmid34741234,
year = {2022},
author = {Li, Z and Li, W and Zhou, D and Zhao, J and Ma, Y and Huang, L and Dong, C and Wilson, JX and Huang, G},
title = {Alleviating Oxidative Damage-Induced Telomere Attrition: a Potential Mechanism for Inhibition by Folic Acid of Apoptosis in Neural Stem Cells.},
journal = {Molecular neurobiology},
volume = {59},
number = {1},
pages = {590-602},
pmid = {34741234},
issn = {1559-1182},
support = {81730091//National Natural Science Foundation of China/ ; 19JCQNJC11700//Natural Science Foundation of Tianjin City/ ; },
mesh = {Animals ; Antioxidants/*pharmacology ; Apoptosis/*drug effects ; Cell Proliferation/drug effects ; Corpus Striatum/drug effects/metabolism ; Folic Acid/*pharmacology ; Hippocampus/drug effects/metabolism ; Hydrogen Peroxide/pharmacology ; Neural Stem Cells/*drug effects/metabolism ; Oxidative Stress/*drug effects ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Telomere/*drug effects/metabolism ; },
abstract = {DNA oxidative damage can cause telomere attrition or dysfunction that triggers cell senescence and apoptosis. The hypothesis of this study is that folic acid decreases apoptosis in neural stem cells (NSCs) by preventing oxidative stress-induced telomere attrition. Primary cultures of NSCs were incubated for 9 days with various concentrations of folic acid (0-40 µM) and then incubated for 24 h with a combination of folic acid and an oxidant (100-µM hydrogen peroxide, H2O2), antioxidant (10-mM N-acetyl-L-cysteine, NAC), or vehicle. Intracellular folate concentration, apoptosis rate, cell proliferative capacity, telomere length, telomeric DNA oxidative damage, telomerase activity, intracellular reactive oxygen species (ROS) levels, cellular oxidative damage, and intracellular antioxidant enzyme activities were determined. The results showed that folic acid deficiency in NSCs decreased intracellular folate concentration, cell proliferation, telomere length, and telomerase activity but increased apoptosis, telomeric DNA oxidative damage, and intracellular ROS levels. In contrast, folic acid supplementation dose-dependently increased intracellular folate concentration, cell proliferative capacity, telomere length, and telomerase activity but decreased apoptosis, telomeric DNA oxidative damage, and intracellular ROS levels. Exposure to H2O2 aggravated telomere attrition and oxidative damage, whereas NAC alleviated the latter. High doses of folic acid prevented telomere attrition and telomeric DNA oxidative damage by H2O2. In conclusion, inhibition of telomeric DNA oxidative damage and telomere attrition in NSCs may be potential mechanisms of inhibiting NSC apoptosis by folic acid.},
}
@article {pmid34737398,
year = {2022},
author = {Goddard, T and Tsintzas, K and Stephan, BCM and Prado, CM and Mazidi, M and Siervo, M},
title = {Sarcopenic obesity is associated with telomere shortening: findings from the NHANES 1999-2002.},
journal = {International journal of obesity (2005)},
volume = {46},
number = {2},
pages = {437-440},
pmid = {34737398},
issn = {1476-5497},
mesh = {Absorptiometry, Photon/methods/statistics &amp; numerical data ; Adult ; Body Mass Index ; Female ; Humans ; Male ; Middle Aged ; Obesity/epidemiology/*etiology/physiopathology ; Risk Factors ; Sarcopenia/*complications/epidemiology/physiopathology ; Surveys and Questionnaires ; Telomere Shortening/*physiology ; },
abstract = {Sarcopenic obesity (SO) is characterised by the concurrent presence of sarcopenia and excess adiposity. Telomere shortening has been associated with sarcopenia and obesity alone but the association between SO and telomere length (TL) has not been investigated. This study aimed to investigate SO and TL in an adult population. Data were from 5397 individuals (mean age = 44.7 years, 51.3% male) enrolled in the National Health and Nutrition Examination Survey. Body composition (BC) was assessed by Dual Energy X-Ray Absorptiometry. Two models were used to assess SO: a BC model including four phenotypes derived from the combination of high or low adiposity and muscle mass; and, a truncal fat mass to appendicular skeletal mass ratio (TrFM/ASM). TL was assessed using quantitative polymerase chain reaction and expressed as base pairs. The mean TL, relative to the reference DNA, was calculated and expressed as the mean T/S ratio. A General Linear Model was applied to determine associations between TL for SO. In adjusted analysis, only individuals with SO, defined as the presence of high adiposity-low muscle mass (four-phenotype model), had significantly shorter telomeres (p = 0.05) than the reference group (i.e. low adiposity-high muscle mass), with a mean T/S ratio of 1.02 (95%CI: 0.98-1.05) compared to 1.05 (95%CI: 1.01-1.09), respectively. TrFM/ASM was not associated with TL. Preliminary findings suggest that sarcopenia and obesity may act synergistically to shorten telomeres.},
}
@article {pmid34737002,
year = {2022},
author = {Brázda, V and Bohálová, N and Bowater, RP},
title = {New telomere to telomere assembly of human chromosome 8 reveals a previous underestimation of G-quadruplex forming sequences and inverted repeats.},
journal = {Gene},
volume = {810},
number = {},
pages = {146058},
doi = {10.1016/j.gene.2021.146058},
pmid = {34737002},
issn = {1879-0038},
mesh = {*Chromosomes, Human, Pair 8 ; *G-Quadruplexes ; Genome, Human ; Humans ; Sequence Analysis, DNA ; *Sequence Inversion ; *Telomere ; },
abstract = {Taking advantage of evolving and improving sequencing methods, human chromosome 8 is now available as a gapless, end-to-end assembly. Thanks to advances in long-read sequencing technologies, its centromere, telomeres, duplicated gene families and repeat-rich regions are now fully sequenced. We were interested to assess if the new assembly altered our understanding of the potential impact of non-B DNA structures within this completed chromosome sequence. It has been shown that non-B secondary structures, such as G-quadruplexes, hairpins and cruciforms, have important regulatory functions and potential as targeted therapeutics. Therefore, we analysed the presence of putative G-quadruplex forming sequences and inverted repeats in the current human reference genome (GRCh38) and in the new end-to-end assembly of chromosome 8. The comparison revealed that the new assembly contains significantly more inverted repeats and G-quadruplex forming sequences compared to the current reference sequence. This observation can be explained by improved accuracy of the new sequencing methods, particularly in regions that contain extensive repeats of bases, as is preferred by many non-B DNA structures. These results show a significant underestimation of the prevalence of non-B DNA secondary structure in previous assembly versions of the human genome and point to their importance being not fully appreciated. We anticipate that similar observations will occur as the improved sequencing technologies fill in gaps across the genomes of humans and other organisms.},
}
@article {pmid34736994,
year = {2022},
author = {Lin, J and Epel, E},
title = {Stress and telomere shortening: Insights from cellular mechanisms.},
journal = {Ageing research reviews},
volume = {73},
number = {},
pages = {101507},
pmid = {34736994},
issn = {1872-9649},
support = {R01 HL128156/HL/NHLBI NIH HHS/United States ; R24 AG048024/AG/NIA NIH HHS/United States ; U01 AG064785/AG/NIA NIH HHS/United States ; U24 AG066528/AG/NIA NIH HHS/United States ; },
mesh = {Aging/genetics ; Cellular Senescence ; Female ; Humans ; Mitochondria/metabolism ; Pregnancy ; Reactive Oxygen Species ; *Telomerase/metabolism ; Telomere/metabolism ; *Telomere Shortening ; },
abstract = {Short telomeres confer risk of degenerative diseases. Chronic psychological stress can lead to disease through many pathways, and research from in vitro studies to human longitudinal studies has pointed to stress-induced telomere damage as an important pathway. However, there has not been a comprehensive model to describe how changes in stress physiology and neuroendocrine pathways can lead to changes in telomere biology. Critically short telomeres or the collapse of the telomere structure caused by displacement of telomere binding protein complex shelterin elicit a DNA damage response and lead to senescence or apoptosis. In this narrative review, we summarize the key roles glucocorticoids, reactive oxygen species (ROS) and mitochondria, and inflammation play in mediating the relationship between psychological stress and telomere maintenance. We emphasis that these mediators are interconnected and reinforce each other in positive feedback loops. Telomere length has not been studied across the lifespan yet, but the initial setting point at birth appears to be the most influential point, as it sets the lifetime trajectory, and is influenced by stress. We describe two types of intergenerational stress effects on telomeres - prenatal stress effects on telomeres during fetal development, and 'telotype transmission" -the directly inherited transmission of short telomeres from parental germline. It is clear that the initial simplistic view of telomere length as a mitotic clock has evolved into a far more complex picture of both transgenerational telomere influences, and of interconnected molecular and cellular pathways and networks, as hallmarks of aging where telomere maintenance is a key player interacting with mitochondria. Further mechanistic investigations testing this comprehensive model of stress mediators shaping telomere biology and the telomere-mitochondrial nexus will lead to better understanding from cell to human lifespan aging, and could lead to anti-aging interventions.},
}
@article {pmid34736527,
year = {2021},
author = {Torres-Montaner, A},
title = {The telomere complex and the origin of the cancer stem cell.},
journal = {Biomarker research},
volume = {9},
number = {1},
pages = {81},
pmid = {34736527},
issn = {2050-7771},
abstract = {Exquisite regulation of telomere length is essential for the preservation of the lifetime function and self-renewal of stem cells. However, multiple oncogenic pathways converge on induction of telomere attrition or telomerase overexpression and these events can by themselves trigger malignant transformation. Activation of NFκB, the outcome of telomere complex damage, is present in leukemia stem cells but absent in normal stem cells and can activate DOT1L which has been linked to MLL-fusion leukemias. Tumors that arise from cells of early and late developmental stages appear to follow two different oncogenic routes in which the role of telomere and telomerase signaling might be differentially involved. In contrast, direct malignant transformation of stem cells appears to be extremely rare. This suggests an inherent resistance of stem cells to cancer transformation which could be linked to a stem cell'specific mechanism of telomere maintenance. However, tumor protection of normal stem cells could also be conferred by cell extrinsic mechanisms.},
}
@article {pmid34727279,
year = {2023},
author = {Daoust, AR and Thakur, A and Kotelnikova, Y and Kleiber, ML and Singh, SM and Hayden, EP},
title = {Associations Between Children's Telomere Length, Parental Intrusiveness, and the Development of Early Externalizing Behaviors.},
journal = {Child psychiatry and human development},
volume = {54},
number = {3},
pages = {672-682},
pmid = {34727279},
issn = {1573-3327},
mesh = {*Telomere/metabolism ; *Parents/psychology ; *Child Behavior/psychology ; *Parenting/psychology ; Humans ; Male ; Female ; Child, Preschool ; Child ; *Acting Out ; Adverse Childhood Experiences/psychology ; Sex Characteristics ; Stress, Psychological/psychology ; Adult ; Attention ; Aggression ; Child Behavior Disorders/psychology ; },
abstract = {Shorter telomeres mark cellular aging and are linked to chronic stress exposure as well as negative physical and psychological outcomes. However, it is unclear whether telomere length mediates associations between early stress exposure and later externalizing problems, or whether boys and girls differ in pathways to these concerns. We therefore examined associations between telomere length, early stress via negative caregiving, and children's externalizing symptom development over time in 409 three-year-old children and their parents. Telomere length mediated the association between early parental intrusiveness and later rule-breaking behavior; however, this association was moderated by children's biological sex such that parent intrusiveness was related only to boys' rule-breaking. Findings support the notion that children's telomere length may mark individual differences in responses to negative early caregiving, and highlight a potential mechanism contributing to the development of rule-breaking problems in boys.},
}
@article {pmid34725903,
year = {2022},
author = {Pal, J and Rajput, Y and Shrivastava, S and Gahine, R and Mungutwar, V and Barardiya, T and Chandrakar, A and Ramakrishna, PP and Mishra, SS and Banjara, H and Choudhary, V and Patra, PK and Shammas, MA},
title = {A standalone approach to utilize telomere length measurement as a surveillance tool in oral leukoplakia.},
journal = {Molecular oncology},
volume = {16},
number = {8},
pages = {1650-1660},
pmid = {34725903},
issn = {1878-0261},
support = {I01 BX001584/BX/BLRD VA/United States ; P50 CA100707/CA/NCI NIH HHS/United States ; },
mesh = {*Carcinoma, Squamous Cell/diagnosis/genetics/metabolism ; Female ; *Head and Neck Neoplasms ; Humans ; Leukocytes, Mononuclear/metabolism ; Leukoplakia, Oral/diagnosis/genetics/metabolism ; Male ; *Mouth Neoplasms/genetics ; Telomere/metabolism/pathology ; },
abstract = {Oral squamous cell carcinoma (OSCC) is often preceded by a white patch on a surface of the mouth, called oral leukoplakia (OL). As accelerated telomere length (TL) shortening in dividing epithelial cells may lead to oncogenic transformation, telomere length measurement could serve as a predictive biomarker in OL. However, due to high variability and lack of a universal reference, there has been a limited translational application. Here, we describe an approach of evaluating TL using paired peripheral blood mononuclear cells (PBMC) as an internal reference and demonstrate its translational relevance. Oral brush biopsy and paired venous blood were collected from 50 male OL patients and 44 male healthy controls (HC). Relative TL was measured by quantitative PCR. TL of each OL or healthy sample was normalized to the paired PBMC sample (TL ratio). In OL patients, the mean TL ratio was significantly smaller not only in the patch but also in distal normal oral tissue, relative to healthy controls without a high-risk oral habit. Dysplasia was frequently associated with a subgroup that showed a normal TL ratio at the patch but significantly smaller TL ratio at a paired normal distal site. Our data suggest that evaluation of TL attrition using a paired PBMC sample eliminates the requirement of external reference DNA, makes data universally comparable and provides a useful marker to define high-risk OL groups for follow-up programs. Larger studies will further validate the approach and its broader application in other premalignant conditions.},
}
@article {pmid34725692,
year = {2021},
author = {Ghadaouia, S and Olivier, MA and Martinez, A and Kientega, T and Qin, J and Lambert-Lanteigne, P and Cardin, GB and Autexier, C and Malaquin, N and Rodier, F},
title = {Homologous recombination-mediated irreversible genome damage underlies telomere-induced senescence.},
journal = {Nucleic acids research},
volume = {49},
number = {20},
pages = {11690-11707},
pmid = {34725692},
issn = {1362-4962},
support = {MOP114962//CIHR/Canada ; },
mesh = {Cells, Cultured ; DNA Damage ; DNA End-Joining Repair ; *Genomic Instability ; *Homologous Recombination ; Humans ; Rad51 Recombinase/metabolism ; Telomere Shortening/*genetics ; },
abstract = {Loss of telomeric DNA leads to telomere uncapping, which triggers a persistent, p53-centric DNA damage response that sustains a stable senescence-associated proliferation arrest. Here, we show that in normal cells telomere uncapping triggers a focal telomeric DNA damage response accompanied by a transient cell cycle arrest. Subsequent cell division with dysfunctional telomeres resulted in sporadic telomeric sister chromatid fusions that gave rise to next-mitosis genome instability, including non-telomeric DNA lesions responsible for a stable, p53-mediated, senescence-associated proliferation arrest. Unexpectedly, the blocking of Rad51/RPA-mediated homologous recombination, but not non-homologous end joining (NHEJ), prevented senescence despite multiple dysfunctional telomeres. When cells approached natural replicative senescence, interphase senescent cells displayed genome instability, whereas near-senescent cells that underwent mitosis despite the presence of uncapped telomeres did not. This suggests that these near-senescent cells had not yet acquired irreversible telomeric fusions. We propose a new model for telomere-initiated senescence where tolerance of telomere uncapping eventually results in irreversible non-telomeric DNA lesions leading to stable senescence. Paradoxically, our work reveals that senescence-associated tumor suppression from telomere shortening requires irreversible genome instability at the single-cell level, which suggests that interventions to repair telomeres in the pre-senescent state could prevent senescence and genome instability.},
}
@article {pmid34725130,
year = {2021},
author = {Lazzerini Denchi, E and Celli, G and de Lange, T},
title = {Corrigendum: Hepatocytes with extensive telomere deprotection and fusion remain viable and regenerate liver mass through endoreduplication.},
journal = {Genes &amp; development},
volume = {35},
number = {21-22},
pages = {1548-1549},
doi = {10.1101/gad.349030.121},
pmid = {34725130},
issn = {1549-5477},
}
@article {pmid34718547,
year = {2021},
author = {Holland, CL and Sanderson, BA and Titus, JK and Weis, MF and Riojas, AM and Malczewskyj, E and Wasko, BM and Lewis, LK},
title = {Suppression of telomere capping defects of Saccharomyces cerevisiae yku70 and yku80 mutants by telomerase.},
journal = {G3 (Bethesda, Md.)},
volume = {11},
number = {12},
pages = {},
pmid = {34718547},
issn = {2160-1836},
support = {R25 GM102783/GM/NIGMS NIH HHS/United States ; R15 GM139093/GM/NIGMS NIH HHS/United States ; },
mesh = {DNA-Binding Proteins/genetics/metabolism ; Repressor Proteins ; Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; Silent Information Regulator Proteins, Saccharomyces cerevisiae ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere-Binding Proteins/genetics ; },
abstract = {The Ku complex performs multiple functions inside eukaryotic cells, including protection of chromosomal DNA ends from degradation and fusion events, recruitment of telomerase, and repair of double-strand breaks (DSBs). Inactivation of Ku complex genes YKU70 or YKU80 in cells of the yeast Saccharomyces cerevisiae gives rise to mutants that exhibit shortened telomeres and temperature-sensitive growth. In this study, we have investigated the mechanism by which overexpression of telomerase suppresses the temperature sensitivity of yku mutants. Viability of yku cells was restored by overexpression of the Est2 reverse transcriptase and TLC1 RNA template subunits of telomerase, but not the Est1 or Est3 proteins. Overexpression of other telomerase- and telomere-associated proteins (Cdc13, Stn1, Ten1, Rif1, Rif2, Sir3, and Sir4) did not suppress the growth defects of yku70 cells. Mechanistic features of suppression were assessed using several TLC1 RNA deletion derivatives and Est2 enzyme mutants. Supraphysiological levels of three catalytically inactive reverse transcriptase mutants (Est2-D530A, Est2-D670A, and Est2-D671A) suppressed the loss of viability as efficiently as the wild-type Est2 protein, without inducing cell senescence. Roles of proteins regulating telomere length were also determined. The results support a model in which chromosomes in yku mutants are stabilized via a replication-independent mechanism involving structural reinforcement of protective telomere cap structures.},
}
@article {pmid34717997,
year = {2022},
author = {He, J and Ge, X and Cheng, H and Bao, Y and Feng, X and Zan, G and Wang, F and Zou, Y and Yang, X},
title = {Sex-specific associations of exposure to metal mixtures with telomere length change: Results from an 8-year longitudinal study.},
journal = {The Science of the total environment},
volume = {811},
number = {},
pages = {151327},
doi = {10.1016/j.scitotenv.2021.151327},
pmid = {34717997},
issn = {1879-1026},
mesh = {Bayes Theorem ; *Cadmium ; Female ; Humans ; Longitudinal Studies ; Male ; *Metals/toxicity ; Telomere ; },
abstract = {Studies on the relationships between exposure to metal mixtures and telomere length (TL) are limited, particularly longitudinal studies. Few studies are available on the potential sex-specific associations between metal exposures and TL change. We examined blood metal concentrations and TL at baseline (August 2012) and follow-up (June 2020) among 316 participants in a ferro-manganese refinery. The least absolute shrinkage and selection operator (LASSO) followed by the generalized linear model (GLM) was applied to evaluate the associations between multiple-metal exposures and TL change (TL in 2012 minus TL in 2020). Bayesian kernel machine regression (BKMR) was applied to cope with metal mixtures and evaluate their joint effects on TL change. Among men, three statistical methods consistently showed rubidium was negatively associated with TL change (β [95% CI] = -2.755 [-5.119, -0.391] in the GLM) and dominated the negative overall effects of 10 metal mixtures (magnesium, manganese, iron, cobalt, copper, zinc, selenium, rubidium, cadmium, and lead) on TL change (posterior inclusion probabilities = 0.816). Among women, the GLM (β [95% CI] = 4.463 [0.943, 7.983]) and LASSO (β = 4.289) showed rubidium was positively associated with TL change. Interestingly, no significant association was observed between exposure to metal mixtures and TL change in overall participants (P > 0.05). Furthermore, stratified analysis showed significant relationships between rubidium and TL change in men (β = -2.744), women (β = 3.624), and current smokers (β = -3.266) (both P interaction <0.05). In summary, our findings underlined the steady and negative association between rubidium and TL change among men with potential sex-dependent heterogeneities. Further experimental studies are required to expound the underlying mechanisms.},
}
@article {pmid34715000,
year = {2022},
author = {Pippal, N and Halder, S and Srivastava, S and Kar, R and Gupta, R and Anthonio, AE},
title = {Correlation between telomere length and efficacy of oral and long-acting injectable antipsychotics on severity and cognitive impairment of schizophrenia.},
journal = {International journal of psychiatry in clinical practice},
volume = {26},
number = {2},
pages = {157-164},
doi = {10.1080/13651501.2021.1994613},
pmid = {34715000},
issn = {1471-1788},
mesh = {*Antipsychotic Agents ; *Cognitive Dysfunction ; Delayed-Action Preparations ; Humans ; *Schizophrenia ; Telomere ; },
abstract = {OBJECTIVE: To study the correlation between telomere length (TL) and long-acting injectable (LAI) and oral atypical antipsychotic (OAA) efficacy on schizophrenia (SCZ) severity and cognitive impairment.<br><br>METHODS: Sixty Schizophrenia patients of 18-50&#x2009;years and of either sex were included in a 12-week study. Thirty patients were recruited in each group, LAI and OAA. Positive and Negative Syndrome Scale (PANSS) and National Institute of Mental Health and Neuro-Sciences (NIMHANS) neuropsychological battery tests were evaluated at baseline and 12&#x2009;weeks. TL was estimated at baseline.<br><br>RESULTS: Both groups showed a significant improvement in PANSS and NIMHANS battery test scores after treatment (p&#x2009;<&#x2009;0.001) within the group, though not between the groups. Mean TL at baseline was 407.58&#x2009;&#xb1;&#x2009;143.93 and 443.40&#x2009;&#xb1;&#x2009;178.46 in LAI and OAA groups respectively. A significant negative correlation (r = -0.28, p&#x2009;=&#x2009;0.03) of TL was seen with the mean change in negative PANSS score after treatment.<br><br>CONCLUSIONS: LAI antipsychotics are similar to OAA in decreasing the disorder severity and improving the cognitive impairment in schizophrenia. Also, patients who have shorter TL show greater improvement in the negative PANSS score. Hence, TL holds the potential of predicting antipsychotic drug response in schizophrenia patients.KEY POINTSLong-acting injectable antipsychotic was comparable to oral atypical antipsychotics in bringing out improvement in disorder severity, cognitive functions over 12 weeks.Shorter telomere length has been found to be associated with a greater response in negative symptoms of schizophrenia.},
}
@article {pmid34714693,
year = {2022},
author = {Bai, L and Rohrer, C and Liu, Y},
title = {Liver Histology in Short Telomere Syndrome: A Case Report and Review of the Literature.},
journal = {International journal of surgical pathology},
volume = {30},
number = {3},
pages = {350-355},
doi = {10.1177/10668969211054102},
pmid = {34714693},
issn = {1940-2465},
mesh = {Adult ; *Dyskeratosis Congenita/diagnosis/genetics/pathology ; Growth Disorders ; Humans ; Hypercalcemia ; Inflammation ; *Liver Diseases/diagnosis/genetics ; Male ; Metabolic Diseases ; Middle Aged ; Mutation ; Nephrocalcinosis ; Telomere/genetics/pathology ; },
abstract = {Short telomere syndrome (STS) encompasses a broad family of genetically inherited conditions caused by various mutations in telomerase and other telomere maintenance genes, resulting in premature telomere shortening. STS involves a variety of clinical manifestations, including dyskeratosis congenita, premature achromotrichia, bone marrow failure, immunodeficiency, pulmonary fibrosis and liver disease. Liver histopathologic features in STS patients have not been well characterized. We report a 46-year-old male patient who presented for dyspnea. The patient had a complicated medical history significant for immune thrombocytopenic purpura and splenectomy, recurrent respiratory tract infections, pneumonia, primary immunodeficiency, and severe hepatopulmonary syndrome. He and his brother both developed gray hair by their late 20s. He had a long history of intermittently elevated liver enzymes starting at age 33. These clinical manifestations prompted an evaluation for a possible telomere biology disorder, which revealed the telomere length was critically short and fell at or below the first percentile for age, supporting the diagnosis. The liver biopsy showed marked portal inflammation with interface hepatitis, ductular reaction and frequent foci of lobular inflammation with focal hepatocyte dropout. Hepatocytes around the portal tracts demonstrated ballooning degeneration and occasional Mallory-Denk bodies. A trichrome stain highlighted bridging fibrosis. A literature review shows liver histology is available in only a small number of STS patients, demonstrating a variety of morphologic features. Our case and others suggest liver disease associated with STS exhibits a spectrum of histopathology. Being aware of these features is important for establishing the correct diagnosis of STS which is under recognized.},
}
@article {pmid34708049,
year = {2021},
author = {Panner Selvam, MK and Baskaran, S and Sikka, SC},
title = {Telomere Signaling and Maintenance Pathways in Spermatozoa of Infertile Men Treated With Antioxidants: An in silico Approach Using Bioinformatic Analysis.},
journal = {Frontiers in cell and developmental biology},
volume = {9},
number = {},
pages = {768510},
pmid = {34708049},
issn = {2296-634X},
abstract = {Telomere shortening is considered as a marker of cellular senescence and it is regulated by various signaling pathways. Sperm telomere appears to play important role in its longevity and function. Antioxidant intake has been known to prevent the shortening of telomere. In the management of male infertility, antioxidants are commonly used to counterbalance the seminal oxidative stress. It is important to understand how antioxidants treatment may modulate telomere signaling in sperm. In the current study, we have identified 377 sperm proteins regulated by antioxidants based on data mining of published literature. Bioinformatic analysis revealed involvement of 399 upstream regulators and 806 master regulators associated with differentially expressed sperm proteins. Furthermore, upstream regulator analysis indicated activation of kinases (EGFR and MAPK3) and transcription factors (CCNE1, H2AX, MYC, RB1, and TP53). Hence, it is evident that antioxidant supplementation activates molecules associated with telomere function in sperm. The outcome of this in silico study suggests that antioxidant therapy has beneficial effects on certain transcription factors and kinases associated with sperm telomere maintenance and associated signaling pathways that may play an important role in the management of male factor infertility.},
}
@article {pmid34706411,
year = {2021},
author = {Birkenæs, V and Elvsåshagen, T and Westlye, LT and Høegh, MC and Haram, M and Werner, MCF and Quintana, DS and Lunding, SH and Martin-Ruiz, C and Agartz, I and Djurovic, S and Steen, NE and Andreassen, OA and Aas, M},
title = {Telomeres are shorter and associated with number of suicide attempts in affective disorders.},
journal = {Journal of affective disorders},
volume = {295},
number = {},
pages = {1032-1039},
doi = {10.1016/j.jad.2021.08.135},
pmid = {34706411},
issn = {1573-2517},
mesh = {*Depressive Disorder, Major/epidemiology/genetics ; Humans ; Mood Disorders/epidemiology/genetics ; Suicide, Attempted ; *Telomere/genetics ; Telomere Shortening/genetics ; },
abstract = {BACKGROUND: Shorter telomere length is a putative biomarker of accelerated aging and has been associated with affective disorders and mortality. Psychological factors and behaviors associated with telomere shortening are yet to be clarified. Here, we investigate the association between history of suicide attempts and telomere length in patients with affective disorders.<br><br>METHODS: Leucocyte telomere length was determined by quantitative real-time Polymerase Chain Reaction (qPCR) in patients with affective disorders (n&#xa0;=&#xa0;248) including bipolar disorders type I (n&#xa0;=&#xa0;159), type II (n&#xa0;=&#xa0;67), major depressive disorder (n&#xa0;=&#xa0;22), and healthy controls (n&#xa0;=&#xa0;401). Diagnosis, duration of illness, and age at onset were assessed using the Structural Clinical Interview for DSM-IV (SCID-I). Number of lifetime suicide attempts were based on self-reports. Effect size was calculated using Cohen's d.<br><br>RESULTS: Telomere length was reduced in patients with affective disorders relative to healthy controls (d&#xa0;=&#xa0;0.18, F&#xa0;=&#xa0;5.26, p&#xa0;=&#xa0;0.02). Among patients, a higher number of suicide attempts was associated with shorter telomere length (&#x3b2;&#xa0;=&#xa0;-0.24, t&#xa0;=&#xa0;-3.83, CI&#xa0;=&#xa0;-0.44 to -0.14, p&#xa0;<&#xa0;0.001), also when controlling for duration of illness and age at onset (&#x3b2;&#xa0;=&#xa0;-.23, CI&#xa0;=&#xa0;-.42 to -.12, p&#xa0;=&#xa0;0.001). Multiple suicide attempts were associated with telomere length reduction comparable to eight years lifespan, adjusted for demographic and clinical characteristics.<br><br>CONCLUSIONS: While longitudinal data are needed to clarify the temporal course, previous suicide attempts and related distress may accelerate telomere shortening and aging in patients with affective disorders.},
}
@article {pmid34703795,
year = {2021},
author = {Heidari, HR and Fathi, E and Montazersaheb, S and Mamandi, A and Farahzadi, R and Zalavi, S and Nozad Charoudeh, H},
title = {Mesenchymal Stem Cells cause Telomere Length Reduction of Molt-4 Cells via Caspase-3, BAD and P53 Apoptotic Pathway.},
journal = {International journal of molecular and cellular medicine},
volume = {10},
number = {2},
pages = {113-122},
pmid = {34703795},
issn = {2251-9637},
abstract = {Mesenchymal stem cells (MSCs) as undifferentiated cells are specially considered in cell-based cancer therapy due to unique features such as multi-potency, pluripotency, and self-renewal. A multitude of cytokines secreted from MSCs are known to give such multifunctional attributes, but details of their role are yet to be unknown. In the present study, MSCs were cultured, characterized and co-cultured with Molt-4 cells as acute lymphoblastic leukemia cell line in a trans-well plate. Then, cultured Molt-4 alone and Molt-4 co-cultured with MSCs (10:1) were collected on day 7 and subjected to real time-PCR and Western blotting for gene and protein expression assessment, respectively. Ki-67/caspase-3 as well as telomere length were investigated by flow cytometry and real time-PCR, respectively. The results showed that MSCs caused significant decrease in telomere length as well as hTERT gene expression of Molt-4 cells. Also, gene and protein expression of BAD and P53 were significantly increased. Furthermore, the flow cytometry analysis indicated the decrease and increase of the Ki-67 and caspaspase-3 expression, respectively. It was concluded that MSCs co-cultured with Molt-4 cells could be involved in the promotion of Molt-4 cell apoptosis via caspase-3, BAD, and P53 expression. In addition, the decrease of telomere length is another effect of MSCs on Molt-4 leukemic cells.},
}
@article {pmid34702734,
year = {2022},
author = {Sholes, SL and Karimian, K and Gershman, A and Kelly, TJ and Timp, W and Greider, CW},
title = {Chromosome-specific telomere lengths and the minimal functional telomere revealed by nanopore sequencing.},
journal = {Genome research},
volume = {32},
number = {4},
pages = {616-628},
pmid = {34702734},
issn = {1549-5469},
support = {R35 CA209974/CA/NCI NIH HHS/United States ; T32 GM007445/GM/NIGMS NIH HHS/United States ; U01 CA253481/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 CA013106/CA/NCI NIH HHS/United States ; },
mesh = {Intracellular Signaling Peptides and Proteins/genetics ; *Nanopore Sequencing ; Protein Serine-Threonine Kinases ; Repressor Proteins/genetics ; Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere-Binding Proteins/genetics/metabolism ; },
abstract = {We developed a method to tag telomeres and measure telomere length by nanopore sequencing in the yeast S. cerevisiae Nanopore allows long-read sequencing through the telomere, through the subtelomere, and into unique chromosomal sequence, enabling assignment of telomere length to a specific chromosome end. We observed chromosome end-specific telomere lengths that were stable over 120 cell divisions. These stable chromosome-specific telomere lengths may be explained by slow clonal variation or may represent a new biological mechanism that maintains equilibrium unique to each chromosome end. We examined the role of RIF1 and TEL1 in telomere length regulation and found that TEL1 is epistatic to RIF1 at most telomeres, consistent with the literature. However, at telomeres that lack subtelomeric Y' sequences, tel1Δ rif1Δ double mutants had a very small, but significant, increase in telomere length compared with the tel1Δ single mutant, suggesting an influence of Y' elements on telomere length regulation. We sequenced telomeres in a telomerase-null mutant (est2Δ) and found the minimal telomere length to be ∼75 bp. In these est2Δ mutants, there were apparent telomere recombination events at individual telomeres before the generation of survivors, and these events were significantly reduced in est2Δ rad52Δ double mutants. The rate of telomere shortening in the absence of telomerase was similar across all chromosome ends at ∼5 bp per generation. This new method gives quantitative, high-resolution telomere length measurement at each individual chromosome end and suggests possible new biological mechanisms regulating telomere length.},
}
@article {pmid34700072,
year = {2022},
author = {Wani, NA and Praveen Kumar, K and Hong, S and Umer, MA},
title = {Telomere length in dromedary camels (Camelus dromedarius) produced by somatic cell nuclear transfer (SCNT) and their age-matched naturally produced counterparts.},
journal = {Theriogenology},
volume = {177},
number = {},
pages = {151-156},
doi = {10.1016/j.theriogenology.2021.10.012},
pmid = {34700072},
issn = {1879-3231},
mesh = {Animals ; *Camelus ; *Cloning, Organism/veterinary ; Embryo Transfer/veterinary ; Nuclear Transfer Techniques/veterinary ; Telomere/genetics ; },
abstract = {There are controversial reports on the restoration of eroded telomere length in offspring produced by somatic cell nuclear transfer (SCNT) in different animal species. To the best of our knowledge, no earlier studies report the telomere length in naturally produced or cloned animals in any of the camelid species. Therefore, the present study was conducted to estimate the telomere length in dromedary camels produced by SCNT, the donor cells, and their age-matched naturally produced counterparts by Terminal Restriction Fragment (TRF) length analysis and real-time Q PCR T/S ratio methods. Genomic DNA was extracted from venous blood collected from 6 cloned animals and their age-matched counterparts. Using the southern blot technique, digested DNA was blotted onto a positively charged nylon membrane, and its hybridization was carried out using telomere (TTAGGG)n specific, DIG-labeled hybridization probe (Roche Diagnostics, Germany) at 42 °C for 4 h. Stringent washes were carried out at the same temperature, followed by a chemiluminescence reaction. The signals were captured using the Azure Biosystems C600 gel documentation system. A TeloTool program from MATLAB software with a built-in probe intensity correction algorithm was used for TRF analysis. The experiment was replicated three times, and the data, presented as mean ± SEM, were analyzed using a two-sample t-test (MINITAB statistical software, Minitab ltd, CV3 2 TE, UK). No difference was found in the mean telomere length of cloned camels when compared to their naturally produced age-matched counterparts. However, the telomere length was more (P < 0.05) than that of the somatic cells used for producing the SCNT embryos. A moderate positive Pearson correlation coefficient (r = 0.6446) was observed between the telomere lengths estimated by TRF and Q PCR T/S ratio method. In conclusion, this is the first study wherein we are reporting telomere length in naturally produced and cloned dromedary camels produced by somatic cell nuclear transfer. We found that telomere lengths in cloned camels were similar to their age-matched naturally produced counterparts, suggesting that the camel cytoplast reprograms the somatic cell nucleus and restores the telomere length to its totipotency stage.},
}
@article {pmid34697054,
year = {2022},
author = {Zhang, X and Wolff, MS and Shen, J and Parada, H and Santella, RM and Neugut, AI and Chen, J and Teitelbaum, SL},
title = {Phthalates and Phenols, Leukocyte Telomere Length, and Breast Cancer Risk and Mortality in the Long Island Breast Cancer Study Project.},
journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
volume = {31},
number = {1},
pages = {117-123},
pmid = {34697054},
issn = {1538-7755},
support = {UG3 OD023320/OD/NIH HHS/United States ; K01 ES012645/ES/NIEHS NIH HHS/United States ; U01 CA066572/CA/NCI NIH HHS/United States ; P30 ES023515/ES/NIEHS NIH HHS/United States ; U01 ES019459/ES/NIEHS NIH HHS/United States ; U54 CA132379/CA/NCI NIH HHS/United States ; K01 CA234317/CA/NCI NIH HHS/United States ; UH3 OD023337/OD/NIH HHS/United States ; P30 ES009089/ES/NIEHS NIH HHS/United States ; P30 AG059299/AG/NIA NIH HHS/United States ; U54 CA132384/CA/NCI NIH HHS/United States ; },
mesh = {Biomarkers, Tumor/*analysis ; Breast Neoplasms/*chemically induced/*genetics/mortality ; Case-Control Studies ; Environmental Exposure/*adverse effects ; Female ; Humans ; Leukocytes ; Middle Aged ; New York ; Phenols/urine ; Phthalic Acids/urine ; Risk Factors ; Telomere/*genetics ; },
abstract = {BACKGROUND: Phthalates and phenols from the environment have been inconsistently associated with breast cancer risk or mortality. Studies on the potential modifying role of leukocyte telomere length (LTL), a biomarker of biological aging, on these associations are lacking.<br><br>METHODS: We included 1,268 women from the Long Island Breast Cancer Study Project with available data on phthalate and phenol analytes and LTL measurements. Twenty-two phthalate and phenol analytes were measured in spot urines and LTL was measured in blood. The modifying effect of LTL on the associations of individual analyte with breast cancer risk as well as mortalities was estimated using interaction terms between LTL and urinary concentrations of analyte in logistic regression and Cox regression models, respectively. ORs, HRs, and corresponding 95% confidence intervals for a one-unit (ln &#x3bc;g/g creatinine) increase of urinary phthalate/phenol level were estimated at 10th, 50th, and 90th percentiles of LTL.<br><br>RESULTS: LTL significantly (P < 0.05) modified associations between 11 of 22 of urinary phthalate/phenols analytes and breast cancer risk. An inverse association between phthalate/phenols analytes and breast cancer risk at shorter LTL and a positive association at longer LTL was generally suggested. No modifying effect was found for LTL on the association between these phthalate/phenols analytes and breast cancer mortalities.<br><br>CONCLUSIONS: LTL may modify the associations between phthalate and phenol exposures and breast cancer risk.<br><br>IMPACT: This study is the first study that determined the modifying effect of biological aging in the association between environmental chemical exposure and breast cancer risk.},
}
@article {pmid34695574,
year = {2021},
author = {Giaccherini, M and Gentiluomo, M and Fornili, M and Lucenteforte, E and Baglietto, L and Campa, D},
title = {Association between telomere length and mitochondrial copy number and cancer risk in humans: A meta-analysis on more than 300,000 individuals.},
journal = {Critical reviews in oncology/hematology},
volume = {167},
number = {},
pages = {103510},
doi = {10.1016/j.critrevonc.2021.103510},
pmid = {34695574},
issn = {1879-0461},
mesh = {DNA Copy Number Variations ; DNA, Mitochondrial/genetics ; Humans ; Leukocytes/metabolism ; Mitochondria/genetics ; *Neoplasms/epidemiology/genetics/metabolism ; *Telomere/genetics ; },
abstract = {In the last decades the association of leukocyte telomere length (LTL) and mitochondrial copy number (mtDNAcn) with cancer risk has been the focus of many reports, however the relation is not yet completely understood. A meta-analysis of 112 studies including 64,184 cancer cases and 278,641 controls that analysed LTL and mtDNAcn in relation to cancer risk has been conducted to further our understanding of the topic. Stratified analyses for tumor type were also performed. Overall, no association was observed for all cancer combined neither for LTL nor mtDNAcn. Significant associations were detected for these biomarkers and specific cancer type; however, a large degree of heterogeneity was present, even within the same tumor type. Alternatives approaches based on polymorphic variants, such as polygenic risk scores and mendelian randomization, could be adopted to unravel the causal correlation of telomere length and mitochondrial copy number with cancer risk.},
}
@article {pmid34688387,
year = {2021},
author = {Kronenberg, F},
title = {Telomere length and chronic kidney disease: cause or consequence?.},
journal = {Kidney international},
volume = {100},
number = {5},
pages = {980-983},
doi = {10.1016/j.kint.2021.08.013},
pmid = {34688387},
issn = {1523-1755},
mesh = {Aging/genetics ; Humans ; Mendelian Randomization Analysis ; *Renal Insufficiency, Chronic/genetics ; *Telomere/genetics ; Telomere Shortening ; },
abstract = {Telomere length is considered as a clock mirroring aging and is influenced by oxidative stress and inflammation. Both conditions are highly prevalent in patients with chronic kidney disease and other degenerative disorders, such as cardiovascular disease. However, it is discussed controversially whether short telomeres are causally associated with chronic kidney disease or whether chronic kidney disease is contributing to an attrition of telomere length. Park et al., in this issue of Kidney International, use an extended 2-sample Mendelian randomization analysis with large data sets to shed new light on this research question.},
}
@article {pmid34687577,
year = {2022},
author = {Spießberger, M and Hoelzl, F and Smith, S and Vetter, S and Ruf, T and Nowack, J},
title = {The tarnished silver spoon? Trade-off between prenatal growth and telomere length in wild boar.},
journal = {Journal of evolutionary biology},
volume = {35},
number = {1},
pages = {81-90},
pmid = {34687577},
issn = {1420-9101},
mesh = {Animals ; *Silver ; Sus scrofa/genetics ; Swine ; Telomere ; Telomere Homeostasis ; *Telomere Shortening ; },
abstract = {Life-history theory predicts a trade-off between growth rates and lifespan, which is reflected by telomere length, a biomarker of somatic state. We investigated the correlation between telomere length and early-life growth of wild boar piglets, Sus scrofa, kept under semi-natural conditions with high food availability to examine our hypothesis that increased pre- and postnatal growth will lead to telomere length attrition, but that a high supply of nutrient may provide the possibility to compensate telomere loss via telomere repair mechanisms. As predicted, our data showed a clear negative correlation between birth body mass and initial telomere length: heavier neonates had shorter telomeres at birth, and we did not find an influence of the mother on initial telomere length. Body mass at birth correlated with body mass later in life and postnatal growth rate did not affect telomere length. We observed an increase in telomere length during postnatal development, suggesting that high food availability allowed piglets to invest into both, growth and telomere restoration. The increase in telomere length over the duration of the study was not accompanied by telomerase activity; thus, telomere elongation was caused either by alternative mechanisms or by short pulses of telomerase activity that we missed. Taken together, this study suggests a trade-off between investment into growth and telomere maintenance even before birth and the possibility to compensate telomere attrition during growth under high amounts of available energy.},
}
@article {pmid34687313,
year = {2022},
author = {Gao, X and Li, S and Dong, S and Li, J and Yan, Y and Zhang, T and Chen, W},
title = {Response to Letter to the Editor from Bin Zhou et al: "Association Between Body Weight and Telomere Length Is Predominantly Mediated Through C-reactive Protein".},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {107},
number = {3},
pages = {e1329-e1330},
doi = {10.1210/clinem/dgab765},
pmid = {34687313},
issn = {1945-7197},
mesh = {Body Weight ; *C-Reactive Protein ; Humans ; *Telomere/genetics ; },
}
@article {pmid34687310,
year = {2022},
author = {Lahav, Y and Avidor, S and Levy, D and Ohry, A and Zeilig, G and Lahav, M and Golander, H and Guber, AC and Uziel, O and Defrin, R},
title = {Shorter Telomeres Among Individuals With Physical Disability: The Moderating Role of Perceived Stress.},
journal = {The journals of gerontology. Series B, Psychological sciences and social sciences},
volume = {77},
number = {8},
pages = {1384-1393},
doi = {10.1093/geronb/gbab200},
pmid = {34687310},
issn = {1758-5368},
mesh = {Aged ; Cellular Senescence ; Humans ; Male ; Stress, Psychological/psychology ; Surveys and Questionnaires ; *Telomere ; *Telomere Shortening ; },
abstract = {OBJECTIVES: Evidence suggests that individuals with physical disability may suffer from psychological distress and accelerated cellular aging, manifested by shortened telomere length (TL), compared with healthy individuals. Studies indicate that high levels of perceived stress and depression may increase the physiological susceptibility and, thus, may contribute to a short TL. However, the moderating role of perceived stress and depression within the relationship between physical disability and TL remains unknown.<br><br>METHOD: The participants consisted of 119 male subjects (mean age 54.36 years, range 35-70). Of them, 30 were able-bodied and 89 had a physical disability: 34 were due to poliomyelitis (polio) and 55 were due to spinal cord injury. Blood samples for TL analysis were collected; the participants completed questionnaires and underwent disability evaluation.<br><br>RESULTS: Participants with disability had a shorter TL as well as elevated levels of perceived stress and depression compared with able-bodied controls. Both the perceived stress and depression were correlated with a shorter TL. Nonetheless, perceived stress, rather than depression, moderated the relationship between disability and TL; among participants with higher perceived stress levels, in particular, individuals with physical disability had a shorter TL than the able-bodied controls.<br><br>DISCUSSION: The present findings suggest that individuals with physical disability and who exhibit high levels of perceived stress may be particularly vulnerable for accelerated cellular aging, suggesting that perceived stress can be used as a valuable target for intervention.},
}
@article {pmid34687297,
year = {2022},
author = {Zhou, B and Sun, X and Yu, N and Zhang, S},
title = {Letter to the Editor From Zhou et al.: "Association Between Body Weight and Telomere Length Is Predominantly Mediated Through C-Reactive Protein".},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {107},
number = {3},
pages = {e1319-e1320},
doi = {10.1210/clinem/dgab764},
pmid = {34687297},
issn = {1945-7197},
mesh = {Body Weight ; *C-Reactive Protein ; Humans ; *Telomere/genetics ; },
}
@article {pmid34686653,
year = {2021},
author = {Mangaonkar, AA and Ferrer, A and Vairo, FPE and Hammel, CW and Prochnow, C and Gangat, N and Hogan, WJ and Litzow, MR and Peters, SG and Scott, JP and Utz, JP and Baqir, M and Carmona-Porquera, EM and Kalra, S and Sekiguchi, H and Khan, SP and Simonetto, DA and Klee, EW and Kamath, PS and Roden, AC and Joshi, AY and Kennedy, CC and Wylam, ME and Patnaik, MM},
title = {Clinical and molecular correlates from a predominantly adult cohort of patients with short telomere lengths.},
journal = {Blood cancer journal},
volume = {11},
number = {10},
pages = {170},
pmid = {34686653},
issn = {2044-5385},
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; RNA/*genetics ; Retrospective Studies ; Telomerase/*genetics ; Telomere/*genetics ; *Telomere Homeostasis ; },
}
@article {pmid34685641,
year = {2021},
author = {Kordowitzki, P and Merle, R and Hass, PK and Plendl, J and Rieger, J and Kaessmeyer, S},
title = {Influence of Age and Breed on Bovine Ovarian Capillary Blood Supply, Ovarian Mitochondria and Telomere Length.},
journal = {Cells},
volume = {10},
number = {10},
pages = {},
pmid = {34685641},
issn = {2073-4409},
mesh = {Aging/*physiology ; Animals ; *Breeding ; Capillaries/*physiology ; Cattle ; Female ; Leukocytes, Mononuclear/metabolism ; Mitochondria/*metabolism/ultrastructure ; Organ Size ; Ovarian Follicle/blood supply/ultrastructure ; Ovary/*blood supply/ultrastructure ; *Telomere Homeostasis ; },
abstract = {Worldwide, dairy cows of the type of high-producing cattle (HPC) suffer from health and fertility problems at a young age and therefore lose productivity after an average of only three lactations. It is still contentious whether these problems are primarily due to genetics, management, feeding or other factors. Vascularization plays a fundamental role in the cyclic processes of reproductive organs, as well as in the regeneration of tissues. In a previous study, HPC were shown to have a greater ovarian corpus luteum vascularization compared to dual-purpose breeds. We hypothesize that this activated angiogenesis could likely lead to an early exhaustion of HPC's regenerative capacity and thus to premature reproductive senescence. The objective of this study was to investigate if a HPC breed (Holstein-Friesian, HF) exhibits higher ovarian angiogenesis than a dual-purpose breed (Polish Red cow, PR) and if this is related to early ovarian aging and finally reproductive failure. For this purpose, we assessed the degree of vascularization by means of ovarian blood vessel characterization using light microscopy. As indicators for aging, we measured ovarian mitochondrial size and telomere length in peripheral leukocytes. We report in this study that in both breeds the distance between capillaries became smaller with increasing age and that the mean telomere length decreased with increasing age. The only difference between the two breeds was that PR developed larger capillaries than HF. Neither a relationship between telomere length, nor the morphology of the mitochondrial apparatus and nor angiogenesis in HF was proven. Although the data trends indicated that the proportion of shortened telomeres in HF was higher than in the PR, no significant difference between the two breeds was detected.},
}
@article {pmid34685603,
year = {2021},
author = {Zeid, D and Mooney-Leber, S and Seemiller, LR and Goldberg, LR and Gould, TJ},
title = {Terc Gene Cluster Variants Predict Liver Telomere Length in Mice.},
journal = {Cells},
volume = {10},
number = {10},
pages = {},
pmid = {34685603},
issn = {2073-4409},
support = {1U01DA041632/DA/NIDA NIH HHS/United States ; 1F31DA049395/DA/NIDA NIH HHS/United States ; T32 GM108563/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Genetic Variation ; Genotype ; Liver/*metabolism ; Male ; Mice, Inbred C57BL ; *Multigene Family ; RNA/*genetics/metabolism ; Telomerase/*genetics/metabolism ; Telomere/*genetics ; Telomere Homeostasis/*genetics ; Mice ; },
abstract = {Variants in a gene cluster upstream-adjacent to TERC on human chromosome 3, which includes genes APRM, LRRC31, LRRC34 and MYNN, have been associated with telomere length in several human populations. Currently, the mechanism by which variants in the TERC gene cluster influence telomere length in humans is unknown. Given the proximity between the TERC gene cluster and TERC (~0.05 Mb) in humans, it is speculated that cluster variants are in linkage disequilibrium with a TERC causal variant. In mice, the Terc gene/Terc gene cluster are also located on chromosome 3; however, the Terc gene cluster is located distantly downstream of Terc (~60 Mb). Here, we initially aim to investigate the interactions between genotype and nicotine exposure on absolute liver telomere length (aTL) in a panel of eight inbred mouse strains. Although we found no significant impact of nicotine on liver aTL, this first experiment identified candidate single nucleotide polymorphisms (SNPs) in the murine Terc gene cluster (within genes Lrrc31, Lrriq4 and Mynn) co-varying with aTL in our panel. In a second experiment, we tested the association of these Terc gene cluster variants with liver aTL in an independent panel of eight inbred mice selected based on candidate SNP genotype. This supported our initial finding that Terc gene cluster polymorphisms impact aTL in mice, consistent with data in human populations. This provides support for mice as a model for telomere dynamics, especially for studying mechanisms underlying the association between Terc cluster variants and telomere length. Finally, these data suggest that mechanisms independent of linkage disequilibrium between the Terc/TERC gene cluster and the Terc/TERC gene mediate the cluster's regulation of telomere length.},
}
@article {pmid34681758,
year = {2021},
author = {Sung, JY and Cheong, JH},
title = {Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism.},
journal = {International journal of molecular sciences},
volume = {22},
number = {20},
pages = {},
pmid = {34681758},
issn = {1422-0067},
mesh = {Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics/mortality ; Head and Neck Neoplasms/genetics/metabolism ; Humans ; Neoplasms/*genetics/*mortality/pathology ; Pancreatic Neoplasms/genetics/mortality ; Prognosis ; Squamous Cell Carcinoma of Head and Neck/genetics/mortality ; Telomere/genetics/*physiology ; Telomere Homeostasis/physiology ; },
abstract = {Understanding the telomere maintenance mechanism (TMM) in immortal cancer cells is vital for TMM-targeted therapies in clinical settings. In this study, we classified four telomere maintenance mechanisms into telomerase, ALT, telomerase + ALT, and non-defined telomere maintenance mechanism (NDTMM) across 31 cancer types using 10,704 transcriptomic datasets from The Cancer Genome Atlas. Our results demonstrated that approximately 50% of the total cohort displayed ALT activity with high telomerase activity in most cancer types. We confirmed significant patient prognoses according to distinct TMMs in six cancer types: adrenocortical carcinoma (ACC), PAAD, HNSC, SARC, GBM, and metastatic cancer. Patients with metastasis had a poor prognosis in the ALT group (p < 0.006) subjected to RAS protein signal transduction. Glioblastoma patients had poor prognosis in NDTMM (p < 0.0043) and showed high levels of myeloid leukocyte activation. Pancreatic adenocarcinoma (p < 0.04) and head and neck squamous cell carcinoma (p < 0.046) patients had a good prognosis in the ALT group with high immune cell activation. Furthermore, we showed that master transcriptional regulators might affect the selection of the TMM pathway and explained why different telomere maintenance mechanisms exist. Furthermore, they can be used to segregate patients and predict responders to different TMM-targeted therapeutics.},
}
@article {pmid34680452,
year = {2021},
author = {Gruber, HJ and Semeraro, MD and Renner, W and Herrmann, M},
title = {Telomeres and Age-Related Diseases.},
journal = {Biomedicines},
volume = {9},
number = {10},
pages = {},
pmid = {34680452},
issn = {2227-9059},
abstract = {Telomeres are at the non-coding ends of linear chromosomes. Through a complex 3-dimensional structure, they protect the coding DNA and ensure appropriate separation of chromosomes. Aging is characterized by a progressive shortening of telomeres, which compromises their structure and function. Because of their protective function for genomic DNA, telomeres appear to play an important role in the development and progression of many age-related diseases, such as cardiovascular disease (CVD), malignancies, dementia, and osteoporosis. Despite substantial evidence that links telomere length with these conditions, the nature of these observations remains insufficiently understood. Therefore, future studies should address the question of causality. Furthermore, analytical methods should be further improved with the aim to provide informative and comparable results. This review summarize the actual knowledge of telomere biology and the possible implications of telomere dysfunction for the development and progression of age-related diseases. Furthermore, we provide an overview of analytical techniques for the measurement of telomere length and telomerase activity.},
}
@article {pmid34680268,
year = {2021},
author = {Forsyth, RG and Krenács, T and Athanasou, N and Hogendoorn, PCW},
title = {Cell Biology of Giant Cell Tumour of Bone: Crosstalk between m/wt Nucleosome H3.3, Telomeres and Osteoclastogenesis.},
journal = {Cancers},
volume = {13},
number = {20},
pages = {},
pmid = {34680268},
issn = {2072-6694},
abstract = {Giant cell tumour of bone (GCTB) is a rare and intriguing primary bone neoplasm. Worrisome clinical features are its local destructive behaviour, its high tendency to recur after surgical therapy and its ability to create so-called benign lung metastases (lung 'plugs'). GCTB displays a complex and difficult-to-understand cell biological behaviour because of its heterogenous morphology. Recently, a driver mutation in histone H3.3 was found. This mutation is highly conserved in GCTB but can also be detected in glioblastoma. Denosumab was recently introduced as an extra option of medical treatment next to traditional surgical and in rare cases, radiotherapy. Despite these new insights, many 'old' questions about the key features of GCTB remain unanswered, such as the presence of telomeric associations (TAs), the reactivation of hTERT, and its slight genomic instability. This review summarises the recent relevant literature of histone H3.3 in relation to the GCTB-specific G34W mutation and pays specific attention to the G34W mutation in relation to the development of TAs, genomic instability, and the characteristic morphology of GCTB. As pieces of an etiogenetic puzzle, this review tries fitting all these molecular features and the unique H3.3 G34W mutation together in GCTB.},
}
@article {pmid34680143,
year = {2021},
author = {Hecker, M and Bühring, J and Fitzner, B and Rommer, PS and Zettl, UK},
title = {Genetic, Environmental and Lifestyle Determinants of Accelerated Telomere Attrition as Contributors to Risk and Severity of Multiple Sclerosis.},
journal = {Biomolecules},
volume = {11},
number = {10},
pages = {},
pmid = {34680143},
issn = {2218-273X},
mesh = {Aging/*genetics ; Cellular Senescence/genetics ; Chromosomes/genetics ; Humans ; Inflammation/*genetics/pathology ; Life Style ; Multiple Sclerosis/*genetics/pathology ; Oxidative Stress/genetics ; Telomere/genetics ; Telomere Shortening/*genetics ; },
abstract = {Telomeres are protective structures at the ends of linear chromosomes. Shortened telomere lengths (TL) are an indicator of premature biological aging and have been associated with a wide spectrum of disorders, including multiple sclerosis (MS). MS is a chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system. The exact cause of MS is still unclear. Here, we provide an overview of genetic, environmental and lifestyle factors that have been described to influence TL and to contribute to susceptibility to MS and possibly disease severity. We show that several early-life factors are linked to both reduced TL and higher risk of MS, e.g., adolescent obesity, lack of physical activity, smoking and vitamin D deficiency. This suggests that the mechanisms underlying the disease are connected to cellular aging and senescence promoted by increased inflammation and oxidative stress. Additional prospective research is needed to clearly define the extent to which lifestyle changes can slow down disease progression and prevent accelerated telomere loss in individual patients. It is also important to further elucidate the interactions between shared determinants of TL and MS. In future, cell type-specific studies and advanced TL measurement methods could help to better understand how telomeres may be causally involved in disease processes and to uncover novel opportunities for improved biomarkers and therapeutic interventions in MS.},
}
@article {pmid34679783,
year = {2021},
author = {Badmus, KA and Idrus, Z and Meng, GY and Sazili, AQ and Mamat-Hamidi, K},
title = {Telomere Length and Regulatory Genes as Novel Stress Biomarkers and Their Diversities in Broiler Chickens (Gallus gallus domesticus) Subjected to Corticosterone Feeding.},
journal = {Animals : an open access journal from MDPI},
volume = {11},
number = {10},
pages = {},
pmid = {34679783},
issn = {2076-2615},
support = {9629100//Universiti Putra Malaysia/ ; },
abstract = {This study was designed to characterize telomere length and its regulatory genes and to evaluate their potential as well-being biomarkers. Chickens were fed a diet containing corticosterone (CORT) for 4 weeks and performances, organ weight, plasma CORT levels, telomere lengths and regulatory genes were measured and recorded. Body weights of CORT-fed chickens were significantly suppressed (p < 0.05), and organ weights and circulating CORT plasma levels (p < 0.05) were altered. Interaction effect of CORT and duration was significant (p < 0.05) on heart and liver telomere length. CORT significantly (p < 0.05) shortened the telomere length of the whole blood, muscle, liver and heart. The TRF1, chTERT, TELO2 and HSF1 were significantly (p < 0.05) upregulated in the liver and heart at week 4 although these genes and TERRA were downregulated in the muscles at weeks 2 and 4. Therefore, telomere lengths and their regulators are associated and diverse, so they can be used as novel biomarkers of stress in broiler chickens fed with CORT.},
}
@article {pmid34679731,
year = {2021},
author = {Fernández de la Puente, M and Hernández-Alonso, P and Canudas, S and Marti, A and Fitó, M and Razquin, C and Salas-Salvadó, J},
title = {Modulation of Telomere Length by Mediterranean Diet, Caloric Restriction, and Exercise: Results from PREDIMED-Plus Study.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {10},
number = {10},
pages = {},
pmid = {34679731},
issn = {2076-3921},
support = {021/CB07/03/2004//Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition/ ; },
abstract = {Telomere length (TL) has been associated with aging and is determined by lifestyle. However, the mechanisms by which a dietary pattern such as the Mediterranean diet (MedDiet) affects TL homeostasis are still unknown. Our aim was to analyse the effect of an energy-restricted MedDiet with physical activity promotion (intervention group) versus an unrestricted-caloric MedDiet with no weight-loss advice (control group) on TL and 8-hydroxydeoxyguanosine (8-OHdG) plasma levels. In total, 80 non-diabetic participants with metabolic syndrome were randomly selected from the PREDIMED (PREvención con DIeta MEDiterránea)-Plus-Reus study. TL was measured by a hybridisation method and 8-OHdG levels by ELISA at baseline and after one year of intervention. Linear mixed models (LMM)-raw and after adjusting for potential confounders-were used to examine the associations between TL or 8-OHdG plasma levels by intervention group and/or time. A total of 69 subjects with available DNA samples were included in the analyses. A significant β-coefficient was found for time towards increasing values through the year of follow-up for TL (unadjusted β of 0.740 (95% CI: 0.529 to 0.951), and multivariable model β of 0.700 (95% CI: 0.477 to 0.922)). No significant βs were found, neither for the intervention group nor for the interaction between the intervention group and time. Regarding 8-OHdG plasma levels, no significant βs were found for the intervention group, time, and its interaction. Our results suggest that MedDiet could have an important role in preventing telomere shortening, but calorie restriction and exercise promotion did not provide an additional advantage concerning telomere length after one year of MedDiet intervention.},
}
@article {pmid34675961,
year = {2021},
author = {Yang, J and Xu, H and Cai, B and Wei, J and Sun, L and Li, Y and Wang, T and Li, Y},
title = {Genetically Predicted Longer Telomere Length May Reduce Risk of Hip Osteoarthritis.},
journal = {Frontiers in genetics},
volume = {12},
number = {},
pages = {718890},
pmid = {34675961},
issn = {1664-8021},
abstract = {Objective: This two-sample Mendelian randomization (MR) study aimed to examine the potential causal association of telomere length (TL) with the risk of osteoarthritis (OA). Method: The summary-level data for OA was derived from the United Kingdom Biobank cohort, including 50,508 individuals of European descent. Eighteen single nucleotide polymorphisms associated with TL were identified as instrumental variables from the most up-to-date TL genome-wide association study (GWAS) involving over 78,592 individuals of European descent. Based on the GWASs data, MR was performed using established statistical analysis methods including the inverse variance weighted, weighted median, MR-Egger, and MR pleiotropy residual sum and outlier. Results: Genetically determined TL was not associated with the risk of total OA (IVW odds ratio [OR] = 1.00, 95% confidence interval [CI] = 0.83, 1.21). In subgroup analyses stratified by OA site, no evidence in favor of association between genetically determined TL and knee OA was found (IVW OR = 1.18, 95% CI = 0.89, 1.58). However, using WM method, we observed a limited protective effect of longer TL on the risk of hip OA (OR = 0.60, 95% CI = 0.36-0.99), whereas the results of the IVW (p = 0.931) and MR-PRESSO (p = 0.932) showed that TL had no effect on hip OA. Conclusions: This study does not support a causal association between TL and total OA. A potential protective association between longer TL and hip OA, though possible, remains less certain.},
}
@article {pmid34674335,
year = {2022},
author = {Wolf, SE and Sanders, TL and Beltran, SE and Rosvall, KA},
title = {The telomere regulatory gene POT1 responds to stress and predicts performance in nature: Implications for telomeres and life history evolution.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6155-6171},
doi = {10.1111/mec.16237},
pmid = {34674335},
issn = {1365-294X},
support = {T32HD049336/NH/NIH HHS/United States ; },
mesh = {Female ; Genes, Regulator ; Shelterin Complex ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; *Telomere-Binding Proteins/genetics/metabolism ; *Swallows/genetics ; Animals ; },
abstract = {Telomeres are emerging as correlates of fitness-related traits and may be important mediators of ecologically relevant variation in life history strategies. Growing evidence suggests that telomere dynamics can be more predictive of performance than length itself, but very little work considers how telomere regulatory mechanisms respond to environmental challenges or influence performance in nature. Here, we combine observational and experimental data sets from free-living tree swallows (Tachycineta bicolor) to assess how performance is predicted by the telomere regulatory gene POT1, which encodes a shelterin protein that sterically blocks telomerase from repairing the telomere. First, we show that lower POT1 gene expression in the blood was associated with higher female quality, that is, earlier breeding and heavier body mass. We next challenged mothers with an immune stressor (lipopolysaccharide injection) that led to "sickness" in mothers and 24 h of food restriction in their offspring. While POT1 did not respond to maternal injection, females with lower constitutive POT1 gene expression were better able to maintain feeding rates following treatment. Maternal injection also generated a 1-day stressor for chicks, which responded with lower POT1 gene expression and elongated telomeres. Other putatively stress-responsive mechanisms (i.e., glucocorticoids, antioxidants) showed marginal responses in stress-exposed chicks. Model comparisons indicated that POT1 mRNA abundance was a largely better predictor of performance than telomere dynamics, indicating that telomere regulators may be powerful modulators of variation in life history strategies.},
}
@article {pmid34673443,
year = {2021},
author = {Martinez-Verbo, L and Estrada, N and Cabezón, M and Palomo, L and García, O and Arnan, M and Coll, R and Xicoy, B and Zamora, L},
title = {Mutational profile and relative telomere length in Chronic Myelomonocytic Leukemia subgroups according to the 2016 World Health Organization classification.},
journal = {Leukemia research},
volume = {111},
number = {},
pages = {106726},
doi = {10.1016/j.leukres.2021.106726},
pmid = {34673443},
issn = {1873-5835},
mesh = {Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; Case-Control Studies ; Female ; Follow-Up Studies ; Humans ; Leukemia, Myelomonocytic, Chronic/classification/genetics/*pathology ; Male ; Middle Aged ; *Mutation ; Prognosis ; Retrospective Studies ; *Telomere Homeostasis ; World Health Organization ; },
}
@article {pmid34672915,
year = {2021},
author = {Mizuno, Y and Konishi, S and Imai, H and Fujimori, E and Kojima, N and Kajiwara, C and Yoshinaga, J},
title = {Telomere length and urinary 8-hydroxy-2'-deoxyguanosine and essential trace element concentrations in female Japanese university students.},
journal = {Journal of environmental science and health. Part A, Toxic/hazardous substances &amp; environmental engineering},
volume = {56},
number = {12},
pages = {1328-1334},
doi = {10.1080/10934529.2021.1991741},
pmid = {34672915},
issn = {1532-4117},
mesh = {8-Hydroxy-2'-Deoxyguanosine ; Adolescent ; Adult ; Biomarkers ; Deoxyguanosine ; Female ; Humans ; Japan ; Oxidative Stress ; Students ; Telomere ; *Trace Elements ; Universities ; Young Adult ; },
abstract = {Telomere length is thought to be a biomarker of biological aging. This study examined whether telomere length was associated with urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative stress, and antioxidative trace elements in 73 female Japanese university students (age: 19.2 ± 0.7 years). We quantified 8-OHdG and selenium in urine by liquid chromatography-mass spectrometry and inductively coupled plasma-mass spectrometry, respectively. Telomere length and urinary concentrations of other essential trace elements (molybdenum, cobalt, and chromium) that were previously measured in the same study participants, were used in this study. We used multiple linear regression analysis to examine the associations of telomere length with urinary 8-OHdG and essential trace element concentrations (covariates: urinary cotinine concentration, age, BMI, and drinking status). The geometric means (geometric standard deviation) of 8-OHdG and selenium were 3.4 (1.5) and 31 (1.3) µg/g creatinine, respectively. Telomere length was not associated with urinary 8-OHdG concentration, but was negatively associated with urinary selenium concentration. In conclusion, telomere length was not associated with urinary 8-OHdG concentration in the young women in this study. Longitudinal studies should be conducted to clarify the association between telomere shortening rate and oxidative stress level.},
}
@article {pmid34671387,
year = {2021},
author = {Čapková Frydrychová, R and Mason, JM and Peska, V},
title = {Editorial: Telomere Flexibility and Versatility: A Role of Telomeres in Adaptive Potential.},
journal = {Frontiers in genetics},
volume = {12},
number = {},
pages = {771938},
pmid = {34671387},
issn = {1664-8021},
}
@article {pmid34671377,
year = {2021},
author = {Yin, X and Zhang, Y and Chen, Y and Wang, J and Wang, RR and Fan, C and Hu, Z},
title = {Precise Characterization and Tracking of Stably Inherited Artificial Minichromosomes Made by Telomere-Mediated Chromosome Truncation in Brassica napus.},
journal = {Frontiers in plant science},
volume = {12},
number = {},
pages = {743792},
pmid = {34671377},
issn = {1664-462X},
abstract = {Plant artificial minichromosomes are the next-generation technology for plant genetic engineering and represent an independent platform for expressing foreign genes and the tools for studying the structure and function of chromosomes. Minichromosomes have been successfully produced by telomere-mediated chromosome truncation in several plants. However, previous studies have primarily focused on the construction and rough characterization of minichromosomes, while the development of stably inherited minichromosomes and their precise characterization and tracking over different generations have rarely been demonstrated. In this study, a 0.35-kb direct repeat of the Arabidopsis telomeric sequence was transformed into Brassica napus to produce artificial minichromosomes, which were analyzed by multifluorescence in situ hybridization (multi-FISH), Southern hybridization, and primer extension telomere rapid amplification (PETRA). The stably inherited minichromosomes C2 and C4 were developed by crossing transgenic plants with wild-type plants and then selfing the hybrids. Notably, two truncation sites on chromosomes C2 and C4, respectively, were identified by resequencing; thus, the artificial minichromosomes were tracked over different generations with insertion site-specific PCR. This study provided two stably inherited minichromosomes in oilseed rape and describes approaches to precisely characterize the truncation position and track the minichromosomes in offspring through multi-FISH, genome resequencing, and insertion site-specific PCR.},
}
@article {pmid34669125,
year = {2021},
author = {Navarro, PA and Wang, F and Pimentel, R and Robinson, LG and Berteli, TS and Keefe, DL},
title = {Zidovudine inhibits telomere elongation, increases the transposable element LINE-1 copy number and compromises mouse embryo development.},
journal = {Molecular biology reports},
volume = {48},
number = {12},
pages = {7767-7773},
pmid = {34669125},
issn = {1573-4978},
support = {Process 2015/21907-0//FAPESP/ ; process n. 88887.371487/2019-00//CAPES/ ; },
mesh = {Animals ; Anti-HIV Agents/pharmacology ; Blastocyst/drug effects ; DNA Transposable Elements/genetics ; Embryonic Development/drug effects ; Female ; HIV Infections/drug therapy/genetics ; Long Interspersed Nucleotide Elements/genetics/physiology ; Mice/embryology ; Models, Animal ; Oocytes/drug effects ; Pregnancy ; RNA-Binding Proteins/*genetics/metabolism ; Reverse Transcriptase Inhibitors/pharmacology ; Telomere/drug effects/*metabolism ; Zidovudine/adverse effects/metabolism/*pharmacology ; Zygote/drug effects ; },
abstract = {PURPOSE: Millions of pregnant, HIV-infected women take reverse transcriptase inhibitors, such as zidovudine (azidothymidine or AZT), during pregnancy. Reverse transcription plays important roles in early development, including regulation of telomere length (TL) and activity of transposable elements (TE). So we evaluated the effects of AZT on embryo development, TL, and copy number of an active TE, Long Interspersed Nuclear Element 1 (LINE-1), during early development in a murine model.<br><br>DESIGN: Experimental study.<br><br>METHODS: In vivo fertilized mouse zygotes from B6C3F1/B6D2F1 mice were cultured for 48&#xa0;h in KSOM with no AZT (n&#x2009;=&#x2009;45), AZT 1&#xa0;&#x3bc;M (n&#x2009;=&#x2009;46) or AZT 10&#xa0;&#x3bc;M (n&#x2009;=&#x2009;48). TL was measured by single-cell quantitative PCR (SC-pqPCR) and LINE-1 copy number by qPCR. The percentage of morulas at 48&#xa0;h, TL and LINE-1 copy number were compared among groups.<br><br>RESULTS: Exposure to AZT 1&#xa0;&#x3bc;M or 10&#xa0;&#x3bc;M significantly impairs early embryo development. TL elongates from oocyte to control embryos. TL in AZT 1&#xa0;&#x3bc;M embryos is shorter than in control embryos. LINE-1 copy number is significantly lower in oocytes than control embryos. AZT 1&#xa0;&#x3bc;M increases LINE-1 copy number compared to oocytes controls, and AZT 10&#xa0;&#x3bc;M embryos.<br><br>CONCLUSION: AZT at concentrations approaching those used to prevent perinatal HIV transmission compromises mouse embryo development, prevents telomere elongation and increases LINE-1 copy number after 48&#xa0;h treatment. The impact of these effects on the trajectory of aging of children exposed to AZT early during development deserves further investigation.},
}
@article {pmid34665991,
year = {2021},
author = {Brown, AM and Wood, EM and Capilla-Lasheras, P and Harrison, XA and Young, AJ},
title = {Longitudinal evidence that older parents produce offspring with longer telomeres in a wild social bird.},
journal = {Biology letters},
volume = {17},
number = {10},
pages = {20210409},
pmid = {34665991},
issn = {1744-957X},
support = {BB/H022716/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M009122/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J014400/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {Animals ; Animals, Wild ; Longevity ; *Sparrows ; *Telomere/genetics ; Telomere Shortening ; },
abstract = {As telomere length (TL) often predicts survival and lifespan, there is considerable interest in the origins of inter-individual variation in TL. Cross-generational effects of parental age on offspring TL are thought to be a key source of variation, but the rarity of longitudinal studies that examine the telomeres of successive offspring born throughout the lives of parents leaves such effects poorly understood. Here, we exploit TL measures of successive offspring produced throughout the long breeding tenures of parents in wild white-browed sparrow weaver (Plocepasser mahali) societies, to isolate the effects of within-parent changes in age on offspring TLs. Our analyses reveal the first evidence to date of a positive within-parent effect of advancing age on offspring TL: as individual parents age, they produce offspring with longer telomeres (a modest effect that persists into offspring adulthood). We consider the potential for pre- and post-natal mechanisms to explain our findings. As telomere attrition predicts offspring survival to adulthood in this species, this positive parental age effect could impact parent and offspring fitness if it arose via differential telomere attrition during offspring development. Our findings support the view that cross-generational effects of parental age can be a source of inter-individual variation in TL.},
}
@article {pmid34661551,
year = {2021},
author = {Gorenjak, V and Petrelis, AM and Stathopoulou, MG and Toupance, S and Kumar, S and Labat, C and Masson, C and Murray, H and Lamont, J and Fitzgerald, P and Benetos, A and Visvikis-Siest, S and , },
title = {A genetic determinant of VEGF-A levels is associated with telomere attrition.},
journal = {Aging},
volume = {13},
number = {20},
pages = {23517-23526},
pmid = {34661551},
issn = {1945-4589},
mesh = {Hematopoiesis/genetics ; Humans ; Polymorphism, Single Nucleotide/genetics ; Telomere/*genetics ; Telomere Shortening/*genetics ; Vascular Endothelial Growth Factor A/*genetics ; },
abstract = {Telomere length (TL) is a hallmark of cellular aging and is associated with chronic diseases development. The vascular endothelial growth factor A (VEGF-A), a potent angiogenesis factor, is implicated in the pathophysiology of many chronic diseases. The aim of the present study was to investigate the associations between VEGF-A and TL. TL in leukocytes (LTL) and skeletal muscle (MTL) were measured, 10 VEGF-related polymorphisms genotyped, and VEGF-A plasma concentrations determined in 402 individuals from the TELARTA cohort. LTL/MTL ratio was calculated as an estimate of lifelong TL attrition. Associations between VEGF-A variants and levels, and TL parameters were investigated. We identified one significant association between the minor allele (T) of rs6993770 variant and LTL/MTL ratio (P=0.001143, β=0.0148, SE=0.004516). The rs6993770 is an intronic variant of the ZFPM2 gene, which is involved in haematopoiesis and the identified association with increased telomere attrition could be due to increased haematopoiesis. No significant epistatic interaction was identified, and no association was found between levels of VEGF-A and any of assessed phenotypes. We identified a potential common genetic regulation between VEGF-A and telomere length attrition that could be explained by mechanisms of increased hematopoiesis and production of platelets. VEGF-A and TL could play an important role in personalized medicine of chronic diseases and identification of molecular links between them can promote the understanding of their complex implications.},
}
@article {pmid34661200,
year = {2021},
author = {Chakravarti, D and DePinho, RA},
title = {Telomere Dysfunction as an Initiator of Inflammation: Clues to an Age-Old Mystery.},
journal = {Journal of inflammatory bowel diseases &amp; disorders},
volume = {6},
number = {2},
pages = {},
pmid = {34661200},
support = {R01 CA084628/CA/NCI NIH HHS/United States ; },
abstract = {Inflammatory Bowel Disease (IBD) is a challenging medical condition that is driven by various genetic and environmental factors. Therapeutic opportunities for this disease remain limited due to the lack of in-depth understanding of the pathogenetic mechanisms and actionable targets driving the disease. Analysis of telomere dysfunctional mice and patients with genetic defects in telomere maintenance unexpectedly revealed phenotypes mirroring those observed in IBD. Molecular characterization of this model identified a pathway driven by telomere DNA damage-mediated activation of the ATM/cABL/YAP1 pathway, which directly regulates genes central to IBD pathogenesis and amenable to therapeutic intervention. This review summarizes the evidence correlating telomere dysfunction with IBD and colitis-associated cancer and proposes therapeutic opportunities for such inflammatory conditions targeting this newly identified pathway.},
}
@article {pmid34661101,
year = {2021},
author = {Luttermann, T and Rückert, C and Wibberg, D and Busche, T and Schwarzhans, JP and Friehs, K and Kalinowski, J},
title = {Establishment of a near-contiguous genome sequence of the citric acid producing yeast Yarrowia lipolytica DSM 3286 with resolution of rDNA clusters and telomeres.},
journal = {NAR genomics and bioinformatics},
volume = {3},
number = {4},
pages = {lqab085},
pmid = {34661101},
issn = {2631-9268},
abstract = {Yarrowia lipolytica is an oleaginous yeast that is particularly suitable for the sustainable production of secondary metabolites. The genome of this yeast is characterized by its relatively large size and its high number of different rDNA clusters located in its telomeric regions. However, due to the presence of long repetitive elements in the sub-telomeric regions, rDNA clusters and telomeres are missing in current genome assemblies of Y. lipolytica. Here, we present the near-contiguous genome sequence of the biotechnologically relevant strain DSM 3286. We employed a hybrid assembly strategy combining Illumina and nanopore sequencing reads to integrate all six rDNA clusters as well as telomeric repeats into the genome sequence. By fine-tuning of DNA isolation and library preparation protocols, we were able to create ultra-long reads that not only contained multiples of mitochondrial genomes but also shed light on the inter- and intra-chromosomal diversity of rDNA cluster types. We show that there are ten different rDNA units present in this strain that additionally appear in a predefined order in a cluster. Based on single reads, we also demonstrate that the number of rDNA repeats in a specific cluster varies from cell to cell within a population.},
}
@article {pmid34659314,
year = {2021},
author = {Barakate, A and Arrieta, M and Macaulay, M and Vivera, S and Davidson, D and Stephens, J and Orr, J and Schreiber, M and Ramsay, L and Halpin, C and Waugh, R},
title = {Downregulation of Barley Regulator of Telomere Elongation Helicase 1 Alters the Distribution of Meiotic Crossovers.},
journal = {Frontiers in plant science},
volume = {12},
number = {},
pages = {745070},
pmid = {34659314},
issn = {1664-462X},
support = {BB/F020872/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
abstract = {Programmed meiotic DNA double-strand breaks (DSBs), necessary for proper chromosomal segregation and viable gamete formation, are repaired by homologous recombination (HR) as crossovers (COs) or non-crossovers (NCOs). The mechanisms regulating the number and distribution of COs are still poorly understood. The regulator of telomere elongation helicase 1 (RTEL1) DNA helicase was previously shown to enforce the number of meiotic COs in Caenorhabditis elegans but its function in plants has been studied only in the vegetative phase. Here, we characterised barley RTEL1 gene structure and expression using RNA-seq data previously obtained from vegetative and reproductive organs and tissues. Using RNAi, we downregulated RTEL1 expression specifically in reproductive tissues and analysed its impact on recombination using a barley 50k iSelect SNP Array. Unlike in C. elegans, in a population segregating for RTEL1 downregulated by RNAi, high resolution genome-wide genetic analysis revealed a significant increase of COs at distal chromosomal regions of barley without a change in their total number. Our data reveal the important role of RTEL1 helicase in plant meiosis and control of recombination.},
}
@article {pmid34656614,
year = {2022},
author = {Ingold, N and Dusingize, JC and Neale, RE and Olsen, CM and Whiteman, DC and Duffy, DL and MacGregor, S and Law, MH},
title = {Examining Evidence for a Causal Association between Telomere Length and Nevus Count.},
journal = {The Journal of investigative dermatology},
volume = {142},
number = {5},
pages = {1502-1505.e6},
doi = {10.1016/j.jid.2021.09.021},
pmid = {34656614},
issn = {1523-1747},
mesh = {Humans ; *Nevus/genetics ; *Nevus, Pigmented ; *Skin Neoplasms/genetics ; Telomere/genetics ; },
}
@article {pmid34654043,
year = {2022},
author = {Fu, J and Ji, X and Liu, J and Chen, X and Shang, H},
title = {Meta-analysis of the Connection Between Alzheimer Disease and Telomeres.},
journal = {Alzheimer disease and associated disorders},
volume = {36},
number = {1},
pages = {73-79},
doi = {10.1097/WAD.0000000000000468},
pmid = {34654043},
issn = {1546-4156},
mesh = {*Alzheimer Disease/genetics ; China ; Humans ; *Neurodegenerative Diseases ; Telomere ; },
abstract = {BACKGROUND: Alzheimer disease (AD) is the most common neurodegenerative disease of the central nervous system. The stability of the telomere-telomerase system is closely related to AD. A previous meta-analysis indicated that AD patients had shorter telomere length (TL) than control subjects. However, there are no consistent telomerase activity findings in AD patients, and the published telomerase studies were not meta-analyzed yet.<br><br>METHODS: We searched all the related studies that probed into TL and/or telomerase activity in AD patients based on PubMed and Embase database from the establishment to September 2020. The Chinese National Knowledge Infrastructure, Wanfang and China Science and Technology Journal Database were also utilized. The quality of the included studies was evaluated by using Newcastle-Ottawa Scale. All the statistical analyses of this meta-analysis were performed using Stata version 15.0.<br><br>RESULTS: Analyzing 30 TL data from 2248 AD patients and 4865 controls, AD patients had a significantly shorter TL than the controls, with a standardized mean difference of -0.70 (confidence interval: -0.95 to -0.46; P<0.05). The meta-analysis included 3 primary studies and did not find a significant difference in the telomerase activity between 233 AD patients and 132 controls, but AD patients had a trend of increased telomerase activity compared with controls (standardized mean difference: 0.47; confidence interval: -0.29 to 1.23; P>0.05).<br><br>CONCLUSION: Our results showed that compared with the control group, the AD group had a shorter TL and may have higher telomerase activity.},
}
@article {pmid34646443,
year = {2021},
author = {Criscuolo, F and Dobson, FS and Schull, Q},
title = {The influence of phylogeny and life history on telomere lengths and telomere rate of change among bird species: A meta-analysis.},
journal = {Ecology and evolution},
volume = {11},
number = {19},
pages = {12908-12922},
pmid = {34646443},
issn = {2045-7758},
abstract = {Longevity is highly variable among animal species and has coevolved with other life-history traits, such as body size and rates of reproduction. Telomeres, through their erosion over time, are one of the cell mechanisms that produce senescence at the cell level and might even have an influence on the rate of aging in whole organisms. However, uneroded telomeres are also risk factors of cell immortalization. The associations of telomere lengths, their rate of change, and life-history traits independent of body size are largely underexplored for birds. To test associations of life-history traits and telomere dynamics, we conducted a phylogenetic meta-analysis using studies of 53 species of birds. We restricted analyses to studies that applied the telomere restriction fragment length (TRF) method, and examined relationships between mean telomere length at the chick (Chick TL) and adult (Adult TL) stages, the mean rate of change in telomere length during life (TROC), and life-history traits. We examined 3 principal components of 12 life-history variables that represented: body size (PC1), the slow-fast continuum of pace of life (PC2), and postfledging parental care (PC3). Phylogeny had at best a small-to-medium influence on Adult and Chick TL (r [2] = .190 and .138, respectively), but a substantial influence on TROC (r [2] = .688). Phylogeny strongly influenced life histories: PC1 (r [2] = .828), PC2 (.838), and PC3 (.613). Adult TL and Chick TL were poorly associated with the life-history variables. TROC, however, was negatively and moderate-to-strongly associated with PC2 (unadjusted r = -.340; with phylogenetic correction, r = -.490). Independent of body size, long-lived species with smaller clutches, and slower embryonic rate of growth may exhibit less change in telomere length over their lifetimes. We suggest that telomere lengths may have diverged, even among closely avian-related species, yet telomere dynamics are strongly linked to the pace of life.},
}
@article {pmid34638246,
year = {2021},
author = {Monteagudo, M and Martínez, P and Leandro-García, LJ and Martínez-Montes, &#xc1;M and Calsina, B and Pulgarín-Alfaro, M and Díaz-Talavera, A and Mellid, S and Letón, R and Gil, E and Pérez-Martínez, M and Megías, D and Torres-Ruiz, R and Rodriguez-Perales, S and González, P and Caleiras, E and Jiménez-Villa, S and Roncador, G and Álvarez-Escolá, C and Regojo, RM and Calatayud, M and Guadalix, S and Currás-Freixes, M and Rapizzi, E and Canu, L and Nölting, S and Remde, H and Fassnacht, M and Bechmann, N and Eisenhofer, G and Mannelli, M and Beuschlein, F and Quinkler, M and Rodríguez-Antona, C and Cascón, A and Blasco, MA and Montero-Conde, C and Robledo, M},
title = {Analysis of Telomere Maintenance Related Genes Reveals NOP10 as a New Metastatic-Risk Marker in Pheochromocytoma/Paraganglioma.},
journal = {Cancers},
volume = {13},
number = {19},
pages = {},
pmid = {34638246},
issn = {2072-6694},
support = {LCF/BQ/PI20/11760011//"la Caixa" Foundation/ ; 16-1177/AICR_/Worldwide Cancer Research/United Kingdom ; no grant number applicable to M.R.//Pheipas Association/ ; S2017/BMD-3724; TIRONET2-CM//Comunidad de Madrid/ ; ERC-AvG Shelterines GA882385/ERC_/European Research Council/International ; no grant number applicable//Centro de Investigacion Biom&#xe9;dica en Red de Enfermedades Raras/ ; no grant number applicable//Immuno-TargET project under the umbrella of University Medicine Zurich/ ; Becas de Excelencia Rafael del Pino 2017//Fundaci&#xf3;n Rafael del Pino/ ; 205/1//Deutsche Forschungsgemeinschaft (DFG) within the CRC/Transregio/ ; AIO15152858 MONT//Fundaci&#xf3;n Cient&#xed;fica Asociaci&#xf3;n Espa&#xf1;ola Contra el C&#xe1;ncer/ ; no grant number applicable//Fundaci&#xf3;n Bot&#xed;n/ ; PI17/01796//Instituto de Salud Carlos III/ ; no grant number applicable to M.R.//Paradifference Foundation/ ; SAF2017-82623-R, SAF2015-72455-EXP//Spanish State Research Agency (AEI), Ministry of Science and Innovation, cofounded by the European Regional Development Fund (ERDF)/ ; S2017/BMD-3770//Comunidad de Madrid/ ; FPU18/00064//Spanish Ministry of Science, Innovation and Universities/ ; PI17/01796, PI20/01169//Instituto de Salud Carlos III (ISCIII), Acci&#xf3;n Estrat&#xe9;gica en Salud, cofinanciado a trav&#xe9;s del Fondo Europeo de Desarrollo Regional (FEDER)/ ; },
abstract = {One of the main problems we face with PPGL is the lack of molecular markers capable of predicting the development of metastases in patients. Telomere-related genes, such as TERT and ATRX, have been recently described in PPGL, supporting the association between the activation of immortalization mechanisms and disease progression. However, the contribution of other genes involving telomere preservation machinery has not been previously investigated. In this work, we aimed to analyze the prognostic value of a comprehensive set of genes involved in telomere maintenance. For this study, we collected 165 PPGL samples (97 non-metastatic/63 metastatic), genetically characterized, in which the expression of 29 genes of interest was studied by NGS. Three of the 29 genes studied, TERT, ATRX and NOP10, showed differential expression between metastatic and non-metastatic cases, and alterations in these genes were associated with a shorter time to progression, independent of SDHB-status. We studied telomere length by Q-FISH in patient samples and in an in vitro model. NOP10 overexpressing tumors displayed an intermediate-length telomere phenotype without ALT, and in vitro results suggest that NOP10 has a role in telomerase-dependent telomere maintenance. We also propose the implementation of NOP10 IHC to better stratify PPGL patients.},
}
@article {pmid34637637,
year = {2021},
author = {Velando, A and Noguera, JC and Aira, M and Domínguez, J},
title = {Gut microbiome and telomere length in gull hatchlings.},
journal = {Biology letters},
volume = {17},
number = {10},
pages = {20210398},
pmid = {34637637},
issn = {1744-957X},
mesh = {Animals ; *Charadriiformes ; Corticosterone ; *Gastrointestinal Microbiome ; Telomere ; Telomere Shortening ; },
abstract = {In many animals, recent evidence indicates that the gut microbiome may be acquired during early development, with possible consequences on newborns' health. Thus, it has been hypothesized that a healthy microbiome protects telomeres and genomic integrity against cellular stress. However, the link between the early acquired microbiome and telomere dynamics has not hitherto been investigated. In birds, this link may also be potentially modulated by the transfer of maternal glucocorticoids, since these substances dysregulate microbiome composition during postnatal development. Here, we examined the effect of the interplay between the microbiome and stress hormones on the telomere length of yellow-legged gull hatchlings by using a field experiment in which we manipulated the corticosterone content in eggs. We found that the hatchling telomere length was related to microbiome composition, but this relationship was not affected by the corticosterone treatment. Hatchlings with a microbiome dominated by potential commensal bacteria (i.e. Catellicoccus and Cetobacterium) had larger telomeres, suggesting that an early establishment of the species-specific microbiome during development may have important consequences on offspring health and survival.},
}
@article {pmid34636058,
year = {2022},
author = {Stainczyk, SA and Westermann, F},
title = {Neuroblastoma-Telomere maintenance, deregulated signaling transduction and beyond.},
journal = {International journal of cancer},
volume = {150},
number = {6},
pages = {903-915},
doi = {10.1002/ijc.33839},
pmid = {34636058},
issn = {1097-0215},
mesh = {Anaplastic Lymphoma Kinase/antagonists &amp; inhibitors/genetics ; Animals ; Aurora Kinase A/antagonists &amp; inhibitors ; Chromosome Aberrations ; Genes, p53 ; Genes, ras ; Humans ; Mutation ; Neuroblastoma/drug therapy/*genetics ; Signal Transduction ; Telomere Homeostasis/drug effects/*physiology ; },
abstract = {The childhood malignancy neuroblastoma belongs to the group of embryonal tumors and originates from progenitor cells of the sympathoadrenal lineage. Treatment options for children with high-risk and relapsed disease are still very limited. In recent years, an ever-growing molecular diversity was identified using (epi)-genetic profiling of neuroblastoma tumors, indicating that molecularly targeted therapies could be a promising therapeutic option. In this review article, we summarize the various molecular subtypes and genetic events associated with neuroblastoma and describe recent advances in targeted therapies. We lay a strong emphasis on the importance of telomere maintenance mechanisms for understanding tumor progression and risk classification of neuroblastoma.},
}
@article {pmid34631753,
year = {2021},
author = {van Batenburg, AA and van Oosterhout, MFM and Knoppert, SN and Kazemier, KM and van der Vis, JJ and Grutters, JC and Goldschmeding, R and van Moorsel, CHM},
title = {The Extent of Inflammatory Cell Infiltrate and Fibrosis in Lungs of Telomere- and Surfactant-Related Familial Pulmonary Fibrosis.},
journal = {Frontiers in medicine},
volume = {8},
number = {},
pages = {736485},
pmid = {34631753},
issn = {2296-858X},
abstract = {Familial pulmonary fibrosis (FPF) is a monogenic disease most commonly involving telomere- (TERT) or surfactant- (SFTP) related mutations. These mutations have been shown to alter lymphocytic inflammatory responses, and FPF biopsies with histological lymphocytic infiltrates have been reported. Recently, a model of a surfactant mutation in mice showed that the disease initially started with an inflammatory response followed by fibrogenesis. Since inflammation and fibrogenesis are targeted by different drugs, we investigated whether the degree of these two features co-localize or occur independently in different entities of FPF, and whether they influence survival. We quantified the number of lymphocyte aggregates per surface area, the extent of diffuse lymphocyte cell infiltrate, the number of fibroblast foci per surface area, and the percentage of fibrotic lung surface area in digitally scanned hematoxylin and eosin (H&amp;E) sections of diagnostic surgical biopsies of patients with TERT-related FPF (TERT-PF; n = 17), SFTP-related FPF (SFTP-PF; n = 7), and sporadic idiopathic pulmonary fibrosis (sIPF; n = 10). For comparison, we included biopsies of patients with cellular non-specific interstitial pneumonia (cNSIP; n = 10), an inflammatory interstitial lung disease with high lymphocyte influx and usually responsive to immunosuppressive therapy. The degree of inflammatory cell infiltrate and fibrosis in TERT-PF and SFTP-PF was not significantly different from that in sIPF. In comparison with cNSIP, the extent of lymphocyte infiltrates was significantly lower in sIPF and TERT-PF, but not in SFTP-PF. However, in contrast with cNSIP, in sIPF, TERT-PF, and SFTP-PF, diffuse lymphocyte cell infiltrates were predominantly present and lymphocyte aggregates were only present in fibrotic areas (p < 0.0001). Furthermore, fibroblast foci and percentage of fibrotic lung surface were associated with survival (p = 0.022 and p = 0.018, respectively), while this association was not observed for lymphocyte aggregates or diffuse lymphocytic infiltration. Inflammatory cells in diagnostic lung biopsies of TERT-PF, SFTP-PF, and sIPF were largely confined to fibrotic areas. However, based on inflammation and fibrosis, no differences were found between FPF and sIPF, substantiating the histological similarities between monogenic familial and sporadic disease. Furthermore, the degree of fibrosis, rather than inflammation, correlates with survival, supporting that fibrogenesis is the key feature for therapeutic targeting of FPF.},
}
@article {pmid34630527,
year = {2021},
author = {Buddhachat, K and Brown, JL and Kaewkool, M and Poommouang, A and Kaewmong, P and Kittiwattanawong, K and Nganvongpanit, K},
title = {Life Expectancy in Marine Mammals Is Unrelated to Telomere Length but Is Associated With Body Size.},
journal = {Frontiers in genetics},
volume = {12},
number = {},
pages = {737860},
pmid = {34630527},
issn = {1664-8021},
abstract = {Marine mammals vary greatly in size and lifespan across species. This study determined whether measures of adult body weight, length and relative telomere length were related to lifespan. Skin tissue samples (n = 338) were obtained from 23 marine mammal species, including four Mysticeti, 19 Odontoceti and one dugong species, and the DNA extracted to measure relative telomere length using real-time PCR. Life span, adult body weight, and adult body length of each species were retrieved from existing databases. The phylogenetic signal analysis revealed that body length might be a significant factor for shaping evolutionary processes of cetacean species through time, especially for genus Balaenoptera that have an enormous size. Further, our study found correlations between lifespan and adult body weight (R [2] = 0.6465, p < 0.001) and adult body length (R [2] = 0.6142, p ≤0.001), but no correlations with relative telomere length (R [2] = -0.0476, p = 0.9826). While data support our hypothesis that larger marine mammals live longer, relative telomere length is not a good predictor of species longevity.},
}
@article {pmid34628468,
year = {2021},
author = {Lin, YF and Chen, PY and Liu, HC and Chen, YL and Chou, WH and Huang, MC},
title = {Shortened leukocyte telomere length in young adults who use methamphetamine.},
journal = {Translational psychiatry},
volume = {11},
number = {1},
pages = {519},
pmid = {34628468},
issn = {2158-3188},
mesh = {Adult ; Aging ; Humans ; Leukocytes ; *Methamphetamine/adverse effects ; *Telomere/genetics ; Telomere Shortening ; Young Adult ; },
abstract = {Methamphetamine (METH) use, most prevalent in young adults, has been associated with high rates of morbidity and mortality. The relationship between METH use and accelerated biological aging, which can be measured using leukocyte telomere length (LTL), remains unclear. We examined whether young adult METH users have shorter LTL and explored the relationship between characteristics of METH use and LTL by using Mendelian randomization (MR) analysis. We compared the LTL for 187 METH users and 159 healthy individuals aged between 25 and 34 years and examined the relationship of LTL with METH use variables (onset age, duration, and maximum frequency of METH use) by using regression analyses. In addition, 2-stage-least-squares (2SLS) MR was also performed to possibly avoid uncontrolled confounding between characteristics of METH use and LTL. We found METH users had significantly shorter LTL compared to controls. Multivariate regression analysis showed METH use was negatively associated with LTL (β = -0.36, P < .001). Among METH users, duration of METH use was negatively associated with LTL after adjustment (β = -0.002, P = .01). We identified a single nucleotide polymorphism (SNP) rs6585206 genome-wide associated with duration of METH use. This SNP was used as an instrumental variable to avoid uncontrolled confounding for the relationship between the use duration and LTL shortening. In conclusion, we show that young adult METH users may have shorter LTL compared with controls and longer duration of METH use was significantly associated with telomere shortening. These observations suggest that METH use may accelerate biological senescence.},
}
@article {pmid34627377,
year = {2021},
author = {Martin, H and Doumic, M and Teixeira, MT and Xu, Z},
title = {Telomere shortening causes distinct cell division regimes during replicative senescence in Saccharomyces cerevisiae.},
journal = {Cell &amp; bioscience},
volume = {11},
number = {1},
pages = {180},
pmid = {34627377},
issn = {2045-3701},
support = {ANR-17-CE20-0002-01//agence nationale de la recherche/ ; LabEx Dynamo ANR-11-LABX-0011-01//agence nationale de la recherche/ ; ANR-16-CE12-0026//agence nationale de la recherche/ ; Programme &#xc9;mergence(s)//ville de paris/ ; &#xc9;quipe FRM EQU202003010428//fondation pour la recherche m&#xe9;dicale/ ; INCa_15192//institut national du cancer/ ; },
abstract = {BACKGROUND: Telomerase-negative cells have limited proliferation potential. In these cells, telomeres shorten until they reach a critical length and induce a permanently arrested state. This process called replicative senescence is associated with genomic instability and participates in tissue and organismal ageing. Experimental data using single-cell approaches in the budding yeast model organism show that telomerase-negative cells often experience abnormally long cell cycles, which can be followed by cell cycles of normal duration, before reaching the terminal senescent state. These series of non-terminal cell cycle arrests contribute to the heterogeneity of senescence and likely magnify its genomic instability. Due to their apparent stochastic nature, investigating the dynamics and the molecular origins of these arrests has been difficult. In particular, whether the non-terminal arrests series stem from a mechanism similar to the one that triggers terminal senescence is not known.<br><br>RESULTS: Here, we provide a mathematical description of sequences of non-terminal arrests to understand how they appear. We take advantage of an experimental data set of cell cycle duration measurements performed in individual telomerase-negative yeast cells that keep track of the number of generations since telomerase inactivation. Using numerical simulations, we show that the occurrence of non-terminal arrests is a generation-dependent process that can be explained by the shortest telomere reaching a probabilistic threshold length. While the onset of senescence is also triggered by telomere shortening, we highlight differences in the laws that describe the number of consecutive arrests in non-terminal arrests compared to senescence arrests, suggesting distinct underlying mechanisms and cellular states.<br><br>CONCLUSIONS: Replicative senescence is a complex process that affects cell divisions earlier than anticipated, as exemplified by the frequent occurrence of non-terminal arrests early after telomerase inactivation. The present work unravels two kinetically and mechanistically distinct generation-dependent processes underlying non-terminal and terminal senescence arrests. We suggest that these two processes are responsible for two consequences of senescence at the population level, the increase of genome instability on the one hand, and the limitation of proliferation capacity on the other hand.},
}
@article {pmid34627342,
year = {2021},
author = {Ide, S and Sasaki, A and Kawamoto, Y and Bando, T and Sugiyama, H and Maeshima, K},
title = {Telomere-specific chromatin capture using a pyrrole-imidazole polyamide probe for the identification of proteins and non-coding RNAs.},
journal = {Epigenetics &amp; chromatin},
volume = {14},
number = {1},
pages = {46},
pmid = {34627342},
issn = {1756-8935},
mesh = {Animals ; *Chromatin ; Imidazoles ; Mice ; *Nylons ; Pyrroles ; Telomere ; },
abstract = {BACKGROUND: Knowing chromatin components at a DNA regulatory element at any given time is essential for understanding how the element works during cellular proliferation, differentiation and development. A region-specific chromatin purification is an invaluable approach to dissecting the comprehensive chromatin composition at a particular region. Several methods (e.g., PICh, enChIP, CAPTURE and CLASP) have been developed for isolating and analyzing chromatin components. However, all of them have some shortcomings in identifying non-coding RNA associated with DNA regulatory elements.<br><br>RESULTS: We have developed a new approach for affinity purification of specific chromatin segments employing an N-methyl pyrrole (P)-N-methylimidazole (I) (PI) polyamide probe, which binds to a specific sequence in double-stranded DNA via Watson-Crick base pairing as a minor groove binder. This new technique is called proteomics and RNA-omics of isolated chromatin segments (PI-PRICh). Using PI-PRICh to isolate mouse and human telomeric components, we found enrichments of shelterin proteins, the well-known telomerase RNA component (TERC) and telomeric repeat-containing RNA (TERRA). When PI-PRICh was performed for alternative lengthening of telomere (ALT) cells with highly recombinogenic telomeres, in addition to the conventional telomeric chromatin, we obtained chromatin regions containing telomeric repeat insertions scattered in the genome and their associated RNAs.<br><br>CONCLUSION: PI-PRICh reproducibly identified both the protein and RNA components of telomeric chromatin when targeting telomere repeats. PI polyamide is a promising alternative to simultaneously isolate associated proteins and RNAs of sequence-specific chromatin regions under native conditions, allowing better understanding of chromatin organization and functions within the cell.},
}
@article {pmid34624827,
year = {2021},
author = {Cavalcante, SG and Pereira, BJA and Lerario, AM and Sola, PR and Oba-Shinjo, SM and Marie, SKN},
title = {The chromatin remodeler complex ATRX-DAXX-H3.3 and telomere length in meningiomas.},
journal = {Clinical neurology and neurosurgery},
volume = {210},
number = {},
pages = {106962},
doi = {10.1016/j.clineuro.2021.106962},
pmid = {34624827},
issn = {1872-6968},
mesh = {Adult ; Aged ; Aged, 80 and over ; Co-Repressor Proteins/genetics/*metabolism ; Female ; Histones/genetics/*metabolism ; Humans ; Male ; Meningeal Neoplasms/genetics/*metabolism/pathology ; Meningioma/genetics/*metabolism/pathology ; Middle Aged ; Molecular Chaperones/genetics/*metabolism ; Telomere/genetics/*metabolism ; X-linked Nuclear Protein/genetics/*metabolism ; },
abstract = {ATRX-DAXX-H3.3 chromatin remodeler complex is a well known epigenetic factor responsible for the heterochromatin maintenance and control. ATRX is an important nucleosome controller, especially in tandem repeat regions, and DAXX is a multi-function protein with particular role in histone H3.3 deposition due to its chaperone characteristic. Abnormalities in this complex have been associated with telomere dysfunction and consequently with activation of alternative lengthening of telomeres mechanism, genomic instability, and tumor progression in different types of cancer. However, the characterization of this complex is still incomplete in meningioma. We analyzed ATRX, DAXX and H3.3 expressions and the telomere length in a cohort of meningioma of different malignant grades. We observed ATRX upregulation at gene and protein levels in grade II/III meningiomas. A low variability of telomere length was observed in meningiomas across different ages and malignant grades, in contrast to the shortening of telomere length with aging in normal controls.},
}
@article {pmid34624021,
year = {2021},
author = {Morgunova, V and Kordyukova, M and Mikhaleva, EA and Butenko, I and Pobeguts, OV and Kalmykova, A},
title = {Loss of telomere silencing is accompanied by dysfunction of Polo kinase and centrosomes during Drosophila oogenesis and early development.},
journal = {PloS one},
volume = {16},
number = {10},
pages = {e0258156},
pmid = {34624021},
issn = {1932-6203},
mesh = {Animals ; Cell Death ; Centrioles/metabolism ; Centrosome/*metabolism ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/*embryology/*metabolism ; Embryo, Nonmammalian/metabolism ; *Embryonic Development ; Mitosis ; *Oogenesis ; Protein Binding ; Protein Serine-Threonine Kinases/*metabolism ; RNA/metabolism ; Retroelements/genetics ; Ribonucleoproteins/metabolism ; Telomere/*metabolism ; Zygote/metabolism ; },
abstract = {Telomeres are nucleoprotein complexes that protect the ends of eukaryotic linear chromosomes from degradation and fusions. Telomere dysfunction leads to cell growth arrest, oncogenesis, and premature aging. Telomeric RNAs have been found in all studied species; however, their functions and biogenesis are not clearly understood. We studied the mechanisms of development disorders observed upon overexpression of telomeric repeats in Drosophila. In somatic cells, overexpression of telomeric retrotransposon HeT-A is cytotoxic and leads to the accumulation of HeT-A Gag near centrosomes. We found that RNA and RNA-binding protein Gag encoded by the telomeric retrotransposon HeT-A interact with Polo and Cdk1 mitotic kinases, which are conserved regulators of centrosome biogenesis and cell cycle. The depletion of proteins Spindle E, Ccr4 or Ars2 resulting in HeT-A overexpression in the germline was accompanied by mislocalization of Polo as well as its abnormal stabilization during oogenesis and severe deregulation of centrosome biogenesis leading to maternal-effect embryonic lethality. These data suggest a mechanistic link between telomeric HeT-A ribonucleoproteins and cell cycle regulators that ensures the cell response to telomere dysfunction.},
}
@article {pmid34618297,
year = {2021},
author = {Wang, F and Chamani, IJ and Luo, D and Chan, K and Navarro, PA and Keefe, DL},
title = {Inhibition of LINE-1 retrotransposition represses telomere reprogramming during mouse 2-cell embryo development.},
journal = {Journal of assisted reproduction and genetics},
volume = {38},
number = {12},
pages = {3145-3153},
pmid = {34618297},
issn = {1573-7330},
support = {6-FY14-432//march of dimes foundation/ ; Stanley H. Kaplan Endowment//nyu langone medical center/ ; },
mesh = {Animals ; Cell Differentiation/genetics/physiology ; Embryo, Mammalian/*physiology ; Embryonic Development/*genetics/physiology ; Mice ; Mouse Embryonic Stem Cells/physiology ; RNA-Binding Proteins/*genetics ; Telomere/*genetics ; Zygote/physiology ; },
abstract = {PURPOSE: To investigate whether inhibition of LINE-1 affects telomere reprogramming during 2-cell embryo development.<br><br>METHODS: Mouse zygotes were cultured with or without 1&#xa0;&#xb5;M azidothymidine (AZT) for up to 15&#xa0;h (early 2-cell, G1/S) or 24&#xa0;h (late 2-cell, S/G2). Gene expression and DNA copy number were determined by RT-qPCR and qPCR respectively. Immunostaining and telomeric PNA-FISH were performed for co-localization between telomeres and ZSCAN4 or LINE-1-Orf1p.<br><br>RESULTS: LINE-1 copy number was remarkably reduced in later 2-cell embryos by exposure to 1&#xa0;&#xb5;M AZT, and telomere lengths in late 2-cell embryos with AZT were significantly shorter compared to control embryos (P&#x2009;=&#x2009;0.0002). Additionally, in the absence of LINE-1 inhibition, Dux, Zscan4, and LINE-1 were highly transcribed in early 2-cell embryos, as compared to late 2-cell embryos (P&#x2009;<&#x2009;0.0001), suggesting that these 2-cell genes are activated at the early 2-cell stage. However, in early 2-cell embryos with AZT treatment, mRNA levels of Dux, Zscan4, and LINE-1 were significantly decreased. Furthermore, both Zscan4 and LINE-1 encoded proteins localized to telomere regions in 2-cell embryos, but this co-localization was dramatically reduced after AZT treatment (P&#x2009;<&#x2009;0.001).<br><br>CONCLUSIONS: Upon inhibition of LINE-1 retrotransposition in mouse 2-cell embryos, Dux, Zscan4, and LINE-1 were significantly downregulated, and telomere elongation was blocked. ZSCAN4 foci and their co-localization with telomeres were also significantly decreased, indicating that ZSCAN4 is an essential component of the telomere reprogramming that occurs in mice at the 2-cell stage. Our findings also suggest that LINE-1 may directly contribute to telomere reprogramming in addition to regulating gene expression.},
}
@article {pmid34617352,
year = {2021},
author = {Borie, R and Renzoni, E},
title = {Pulmonary fibrosis associated with telomere-related gene mutations: A complex inheritance.},
journal = {Respirology (Carlton, Vic.)},
volume = {26},
number = {12},
pages = {1098-1100},
doi = {10.1111/resp.14168},
pmid = {34617352},
issn = {1440-1843},
mesh = {Humans ; Multifactorial Inheritance ; Mutation ; *Pulmonary Fibrosis/genetics ; Telomere/genetics ; Telomere Shortening ; },
}
@article {pmid34616503,
year = {2021},
author = {Tung, KTS and Hung, CMW and Chan, KL and Wong, RS and Tsang, HW and Wong, WHS and Lo, CKM and Tso, WWY and Chua, GT and Yee, BK and Wong, ICK and Leung, WC and Ip, P},
title = {Influence of Maternal Infection and Pregnancy Complications on Cord Blood Telomere Length.},
journal = {Oxidative medicine and cellular longevity},
volume = {2021},
number = {},
pages = {3339456},
pmid = {34616503},
issn = {1942-0994},
mesh = {Adult ; Anemia/*epidemiology ; Female ; Fetal Blood/*cytology ; Gestational Age ; Hong Kong/epidemiology ; Humans ; Hypertension, Pregnancy-Induced/*epidemiology ; Infant, Newborn ; Longitudinal Studies ; Male ; Pregnancy ; Pregnancy Complications, Infectious/*epidemiology ; Quality of Life ; *Telomere ; *Telomere Homeostasis ; *Telomere Shortening ; },
abstract = {BACKGROUND: Exposure to suboptimal intrauterine environment might induce structural and functional changes that can affect neonatal health. Telomere length as an important indicator of cellular health has been associated with increased risk for disease development.<br><br>OBJECTIVES: This study was aimed to examine the independent and combined effects of maternal, obstetric, and foetal factors on cord blood telomere length (TL).<br><br>METHODS: Pregnant women at the gestational age of 20[th] to 24[th] week who attended the antenatal clinic of a major local hospital in Hong Kong were recruited. Participants were asked to complete a questionnaire on demographics, health-related quality of life, and history of risk behaviors. Medical history including pregnancy complications and neonatal outcomes was obtained from electronic medical records of both mother and neonate. Umbilical cord blood was collected at delivery for TL determination.<br><br>RESULTS: A total of 753 pregnant women (average age: 32.18 &#xb1; 4.51 years) were recruited. The prevalence of maternal infection, anaemia, and hypertension during pregnancy was 30.8%, 30.0%, and 6.0%, respectively. The adjusted regression model displayed that maternal infection was negatively associated with cord blood TL (&#x3b2; = -0.18, p = 0.026). This association became even stronger in the presence of antenatal anaemia, hypertension, delivery complications, or neonatal jaundice (&#x3b2; = -0.25 to -0.45).<br><br>CONCLUSIONS: This study consolidates evidence on the impact of adverse intrauterine environment at the cellular level. Maternal infection was significantly associated with shorter cord blood TL in a unique manner such that its presence may critically determine the susceptibility of telomere to other factors.},
}
@article {pmid34611362,
year = {2021},
author = {Codd, V and Wang, Q and Allara, E and Musicha, C and Kaptoge, S and Stoma, S and Jiang, T and Hamby, SE and Braund, PS and Bountziouka, V and Budgeon, CA and Denniff, M and Swinfield, C and Papakonstantinou, M and Sheth, S and Nanus, DE and Warner, SC and Wang, M and Khera, AV and Eales, J and Ouwehand, WH and Thompson, JR and Di Angelantonio, E and Wood, AM and Butterworth, AS and Danesh, JN and Nelson, CP and Samani, NJ},
title = {Polygenic basis and biomedical consequences of telomere length variation.},
journal = {Nature genetics},
volume = {53},
number = {10},
pages = {1425-1433},
pmid = {34611362},
issn = {1546-1718},
support = {MR/L003120/1/MRC_/Medical Research Council/United Kingdom ; MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; RG/13/13/30194/BHF_/British Heart Foundation/United Kingdom ; MR/M012816/1/MRC_/Medical Research Council/United Kingdom ; CH/12/2/29428/BHF_/British Heart Foundation/United Kingdom ; R/L003120/1/MRC_/Medical Research Council/United Kingdom ; RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; SP/16/4/32697/BHF_/British Heart Foundation/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; K08 HG010155/HG/NHGRI NIH HHS/United States ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Genome, Human ; Genome-Wide Association Study ; Humans ; Mendelian Randomization Analysis ; Multifactorial Inheritance/*genetics ; Quantitative Trait Loci ; Telomere Homeostasis/*genetics ; },
abstract = {Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 new). Genetically determined differences in LTL were associated with multiple biological traits, ranging from height to bone marrow function, as well as several diseases spanning neoplastic, vascular and inflammatory pathologies. Finally, we estimated that, at the age of 40 years, people with an LTL >1 s.d. shorter than the population mean had a 2.5-year-lower life expectancy compared with the group with ≥1 s.d. longer LDL. Overall, we furnish new insights into the genetic regulation of LTL, reveal wide-ranging influences of LTL on physiological traits, diseases and longevity, and provide a powerful resource available to the global research community.},
}
@article {pmid34611226,
year = {2021},
author = {Zhao, H and Shen, J and Chang, D and Ye, Y and Wu, X and Chow, WH and Zhang, K},
title = {Land use mix and leukocyte telomere length in Mexican Americans.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {19742},
pmid = {34611226},
issn = {2045-2322},
mesh = {Adult ; Aging ; Biomarkers ; *Built Environment ; Female ; Humans ; *Leukocytes ; Male ; Mexican Americans/*genetics ; Middle Aged ; *Models, Theoretical ; Telomere/*genetics ; Telomere Homeostasis ; Young Adult ; },
abstract = {It has been well-known that built environment features influence the risk of chronic diseases. However, the existing data of its relationship with telomere length, a biomarker of biological aging, is still limited, with no study available for Mexican Americans. This study investigates the relationship between several factors of the built environment with leukocyte telomere length among 5508 Mexican American adults enrolled in Mano-A-Mano, the Mexican American Cohort Study (MACS). Based on the quartile levels of telomere length, the study population was categorized into four groups, from the lowest (1st quartile) to the highest telomere length group (4th quartile). For individual built environment factors, their levels did not differ significantly across four groups. However, in the multinominal logistic regression analysis, increased Rundle's land use mixture (LUM) and Frank's LUM were found statistically significantly associated with increased odds of having high levels of telomere length (Rundle's LUM: 2nd quartile: Odds ratio (OR) 1.26, 95% Confidence interval (CI) 1.07, 1.48; 3rd quartile: OR 1.25, 95% CI 1.06, 1.46; 4th quartile: OR 1.19, 95% CI 1.01, 1.41; Frank's LUM: 2nd quartile: OR 1.34, 95% CI 1.02, 2.63; 3rd quartile: OR 1.55, 95% CI 1.04, 2.91; 4th quartile: OR 1.36, 95% CI 1.05, 2.72, respectively). The associations for Rundle's LUM remained significant after further adjusting other non-redundant built environment factors. Finally, in stratified analysis, we found the association between Rundle's LUM and telomere length was more evident among younger individuals (< 38 years old), women, and those with obesity, born in Mexico, having low levels of physical activity, and having low levels of acculturation than their relative counterparts. In summary, our results indicate that land use mixture may impact telomere length in leukocytes in Mexican Americans.},
}
@article {pmid34605011,
year = {2022},
author = {Barade, A and Aboobacker, F and Korula, A and Lakshmi, K and Devasia, A and Abraham, A and Mathews, V and Edison, E and George, B},
title = {Impact of donor telomere length on survival in patients undergoing matched sibling donor transplantation for aplastic anaemia.},
journal = {British journal of haematology},
volume = {196},
number = {3},
pages = {724-734},
doi = {10.1111/bjh.17880},
pmid = {34605011},
issn = {1365-2141},
mesh = {Adolescent ; Adult ; Age Factors ; Anemia, Aplastic/*mortality/*therapy ; Child ; Child, Preschool ; Female ; Graft Rejection ; Graft Survival ; *Hematopoietic Stem Cell Transplantation/methods/mortality ; Humans ; Male ; Middle Aged ; Prognosis ; *Siblings ; Telomere/*genetics ; *Telomere Homeostasis ; *Tissue Donors ; Transplantation Conditioning/methods ; Treatment Outcome ; Young Adult ; },
abstract = {Although telomere shortening is seen frequently in patients with aplastic anaemia (AA), there are no data on its association in matched sibling donor (MSD) transplants. We evaluated the effect of pre-transplant telomere length of patients and donors, measured by quantitative real-time polymerase chain reaction in 163 recipients undergoing MSD transplants. The median age of patients and donors was 24 and 26 years, respectively. Fludarabine and cyclophosphamide was the main conditioning regimen used and all received peripheral blood stem cell grafts. Engraftment occurred in 89% with graft failure (primary and secondary) in 6%. Acute and chronic graft-versus-host disease (GVHD) occurred in 28% and 24%, respectively. At a median follow-up of 37 months, 117 patients (72%) were alive. All patients and donors were divided into short and long telomere length based on their median and quartile values. Patient telomere length was not associated with severity of AA, neutrophil recovery, graft failure, acute GVHD or chronic GVHD. Longer donor telomere length was associated with better overall survival [hazard ratio (HR) = 0·2, P = 0·006] but did not influence neutrophil recovery, graft failure, acute or chronic GVHD. The five-year overall survival was significantly better (94·9 ± 3·5% vs 65·4 ± 4·3%, P = 0·002) for donors with long (highest quartile, DTL-HQ) versus short (lower three quartiles, DTL-LQ) telomeres, respectively. On multivariate analysis, longer donor telomere length, recipient age and acute GVHD continued to remain significant. This is the first study demonstrating an association of donor telomere length on overall survival following MSD transplant for AA but it needs to be confirmed in larger studies.},
}
@article {pmid34604243,
year = {2021},
author = {Jeon, HJ and Oh, JS},
title = {TRF1 Depletion Reveals Mutual Regulation Between Telomeres, Kinetochores, and Inner Centromeres in Mouse Oocytes.},
journal = {Frontiers in cell and developmental biology},
volume = {9},
number = {},
pages = {749116},
pmid = {34604243},
issn = {2296-634X},
abstract = {In eukaryotic chromosomes, the centromere and telomere are two specialized structures that are essential for chromosome stability and segregation. Although centromeres and telomeres often are located in close proximity to form telocentric chromosomes in mice, it remained unclear whether these two structures influence each other. Here we show that TRF1 is required for inner centromere and kinetochore assembly in addition to its role in telomere protection in mouse oocytes. TRF1 depletion caused premature chromosome segregation by abrogating the spindle assembly checkpoint (SAC) and impairing kinetochore-microtubule (kMT) attachment, which increased the incidence of aneuploidy. Notably, TRF1 depletion disturbed the localization of Survivin and Ndc80/Hec1 at inner centromeres and kinetochores, respectively. Moreover, SMC3 and SMC4 levels significantly decreased after TRF1 depletion, suggesting that TRF1 is involved in chromosome cohesion and condensation. Importantly, inhibition of inner centromere or kinetochore function led to a significant decrease in TRF1 level and telomere shortening. Therefore, our results suggest that telomere integrity is required to preserve inner centromere and kinetochore architectures, and vice versa, suggesting mutual regulation between telomeres and centromeres.},
}
@article {pmid34603596,
year = {2021},
author = {Hao, L and Chen, Q and Chen, X and Zhou, Q},
title = {Association of Serum Total Bilirubin Concentration with Telomere Length: The National Health and Nutrition Examination Survey.},
journal = {Oxidative medicine and cellular longevity},
volume = {2021},
number = {},
pages = {4688900},
pmid = {34603596},
issn = {1942-0994},
mesh = {Adult ; Aged ; Bilirubin/*blood ; Female ; Humans ; Linear Models ; Male ; Middle Aged ; Nutrition Surveys ; Regression Analysis ; Telomere/*metabolism ; Telomere Shortening ; United States ; },
abstract = {INTRODUCTION: Mildly increased bilirubin concentration has a protective effect on oxidative stress-related diseases. However, it remains unknown whether elevated circulating bilirubin is associated with longer telomere length. The aim of this cross-sectional study was to examine the association between total bilirubin concentration and telomere length.<br><br>METHODS: We used the data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. The multivariable linear regression model was used to examine the association between total bilirubin concentration and telomere length. The nonlinear relationship was analyzed using a generalized additive model with the smoothing plot.<br><br>RESULTS: A total of 7818 participants with a mean age of 49.20 &#xb1; 18.82 years were included. Compared with the lowest concentration of total bilirubin (Q1), the highest quartile of total bilirubin concentration was associated with longer telomere length in male (&#x3b2; = 0.04, 95 CI%: 0.00, 0.07, P = 0.024) and female (&#x3b2; = 0.04, 95 CI%: 0.02, 0.04, P = 0.002). Furthermore, an inverted U-shaped relationship between total bilirubin and telomere length was found. On the left of turning points (total&#x2009;bilirubin < 0.5&#x2009;mg/dL), total bilirubin concentration was positively associated with telomere length (&#x3b2; = 0.23, 95 CI%: 0.14, 0.32, P < 0.001). However, the association between total bilirubin concentration and telomere length was not significant (&#x3b2; = 0.01, 95% CI: -0.01, 0.04, P = 0.346) above the turning point.<br><br>CONCLUSION: This is the first evidence based on a nationally representative survey demonstrating a positive and nonlinear association between total bilirubin concentration and telomere length. Future large-scale prospective studies are warranted to confirm our findings.},
}
@article {pmid34603389,
year = {2021},
author = {Hastings, WJ and Eisenberg, DTA and Shalev, I},
title = {Impact of Amplification Efficiency Approaches on Telomere Length Measurement via Quantitative-Polymerase Chain Reaction.},
journal = {Frontiers in genetics},
volume = {12},
number = {},
pages = {728603},
pmid = {34603389},
issn = {1664-8021},
support = {T32 AG049676/AG/NIA NIH HHS/United States ; U01 ES030949/ES/NIEHS NIH HHS/United States ; },
abstract = {Background: Precise determination of amplification efficiency is critical for reliable conversion of within-sample changes in fluorescence occurring on a logarithmic scale to between-sample differences in DNA content occurring on a linear scale. This endeavor is especially challenging for the telomere length (TL) quantitative-PCR (qPCR) assay, where amplification efficiency can vary between reactions targeting telomeric repeats (T) and those targeting a single-copy gene (S) to calculate TL as the T/S ratio. Methods: We compared seven different approaches toward estimating amplification efficiency, including the standard-curve method utilized by the qPCR instrument software, and alternative approaches which estimate efficiency on a reaction-by-reaction basis using the stand-alone program LinRegPCR. After calculating T/S ratios using efficiency estimates from each approach (N = 363), we tested their relative performance on metrics of assay precision and correlates of external validity including chronological age (age range = 1-72 years), across tissues within-person (leukocyte-buccal), and between parents and offspring. Results: Estimated amplification efficiency for telomere reactions was significantly lower than estimates for single-copy gene reactions. Efficiency estimates for both reaction sets were significantly higher when estimated with the standard-curve method utilized by the qPCR instrument relative to estimates reconstructed during the log-linear phase with LinRegPCR. While estimates of single-copy gene efficiency reconstructed using LinRegPCR measured within 90% of perfect exponential doubling (E = 1.92), estimates generated using the standard-curve method were inflated beyond 100% (E = 2.10-2.12), indicating poor fidelity. Despite differences in raw value, TL measurements calculated with LinRegPCR efficiency estimates exhibited similar relationships with external validity correlates to measurements generated using the qPCR instrument software. Conclusion: Since methods to estimate amplification efficiency can vary across qPCR instruments, we suggest that future analyses empirically consider external methods of efficiency calculations such as LinRegPCR, and that already generated data be re-analyzed to glean possible improvements.},
}
@article {pmid34602328,
year = {2021},
author = {Bosquet Enlow, M and Kane-Grade, F and De Vivo, I and Petty, CR and Nelson, CA},
title = {Corrigendum to "Patterns of change in telomere length over the first three years of life in healthy children" [Psychoneuroendocrinology 115 (2020) 104602].},
journal = {Psychoneuroendocrinology},
volume = {133},
number = {},
pages = {105419},
doi = {10.1016/j.psyneuen.2021.105419},
pmid = {34602328},
issn = {1873-3360},
}
@article {pmid34597314,
year = {2021},
author = {Zane, L and Ensminger, DC and Vázquez-Medina, JP},
title = {Short-term elevations in glucocorticoids do not alter telomere lengths: A systematic review and meta-analysis of non-primate vertebrate studies.},
journal = {PloS one},
volume = {16},
number = {10},
pages = {e0257370},
pmid = {34597314},
issn = {1932-6203},
mesh = {Animals ; Glucocorticoids/*blood ; Hypothalamo-Hypophyseal System/*physiology ; Pituitary-Adrenal System/*physiology ; *Telomere Shortening ; Vertebrates ; },
abstract = {BACKGROUND: The neuroendocrine stress response allows vertebrates to cope with stressors via the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis, which ultimately results in the secretion of glucocorticoids (GCs). Glucocorticoids have pleiotropic effects on behavior and physiology, and might influence telomere length dynamics. During a stress event, GCs mobilize energy towards survival mechanisms rather than to telomere maintenance. Additionally, reactive oxygen species produced in response to increased GC levels can damage telomeres, also leading to telomere shortening. In our systematic review and meta-analysis, we tested whether GC levels impact telomere length and if this relationship differs among time frame, life history stage, or stressor type. We hypothesized that elevated GC levels are linked to a decrease in telomere length.<br><br>METHODS: We conducted a literature search for studies investigating the relationship between telomere length and GCs in non-human vertebrates using four search engines: Web of Science, Google Scholar, Pubmed and Scopus, last searched on September 27th, 2020. This review identified 31 studies examining the relationship between GCs and telomere length. We pooled the data using Fisher's Z for 15 of these studies. All quantitative studies underwent a risk of bias assessment. This systematic review study was registered in the Open Science Framework Registry (https://osf.io/rqve6).<br><br>RESULTS: The pooled effect size from fifteen studies and 1066 study organisms shows no relationship between GCs and telomere length (Fisher's Z = 0.1042, 95% CI = 0.0235; 0.1836). Our meta-analysis synthesizes results from 15 different taxa from the mammalian, avian, amphibian groups. While these results support some previous findings, other studies have found a direct relationship between GCs and telomere dynamics, suggesting underlying mechanisms or concepts that were not taken into account in our analysis. The risk of bias assessment revealed an overall low risk of bias with occasional instances of bias from missing outcome data or bias in the reported result.<br><br>CONCLUSION: We highlight the need for more targeted experiments to understand how conditions, such as experimental timeframes, stressor(s), and stressor magnitudes can drive a relationship between the neuroendocrine stress response and telomere length.},
}
@article {pmid34597213,
year = {2020},
author = {Gaydosh, L and Mitchell, C and Notterman, D and Schneper, L and Brooks-Gunn, J and Wagner, B and Koss, K and McLanahan, S},
title = {Demographic and developmental patterns in telomere length across adolescence.},
journal = {Biodemography and social biology},
volume = {66},
number = {3-4},
pages = {208-219},
pmid = {34597213},
issn = {1948-5573},
support = {P2C HD042849/HD/NICHD NIH HHS/United States ; R01 HD076592/HD/NICHD NIH HHS/United States ; R01 MD011716/MD/NIMHD NIH HHS/United States ; R24 AG037898/AG/NIA NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Biomarkers ; *Cellular Senescence ; Child ; Demography ; Humans ; *Telomere/genetics ; Telomere Shortening ; },
abstract = {Telomere length is often used in studies of adults as a biomarker of cellular aging and an indicator of stress exposure. However, we know little about how telomeres change over time, particularly over the course of the important developmental period of adolescence. We use data on telomere length collected at two points in time spanning adolescence (Years 9 and 15) from the Fragile Families and Child Wellbeing Study to examine longitudinal patterns (n = 1,654) in telomere length. We find a quantitatively small but significant average lengthening in telomere length across adolescence and little evidence of associations between telomere length and pubertal development.},
}
@article {pmid34591601,
year = {2021},
author = {Peng, Q and Zhou, M and Zuo, S and Liu, Y and Li, X and Yang, Y and He, Q and Yu, X and Zhou, J and He, Z and He, Q},
title = {Nuclear Factor Related to KappaB Binding Protein (NFRKB) Is a Telomere-Associated Protein and Involved in Liver Cancer Development.},
journal = {DNA and cell biology},
volume = {40},
number = {10},
pages = {1298-1307},
doi = {10.1089/dna.2021.0486},
pmid = {34591601},
issn = {1557-7430},
mesh = {Biomarkers, Tumor/genetics/*metabolism ; Carcinogenesis/genetics/metabolism ; Carcinoma, Hepatocellular/genetics/*metabolism/pathology ; DNA-Binding Proteins/genetics/*metabolism ; HEK293 Cells ; HeLa Cells ; Hep G2 Cells ; Hepatocytes/metabolism ; Humans ; K562 Cells ; Liver Neoplasms/genetics/*metabolism/pathology ; MCF-7 Cells ; Protein Binding ; Telomere/metabolism ; },
abstract = {Alternative lengthening of telomeres (ALT) is a homologous recombination-based telomere maintenance mechanism activated in 10-15% of human cancers. Although significant progress has been made, the key regulators of the ALT pathway and its role in cancer development remain elusive. Bioinformatics methods were used to predict novel telomere-associated proteins (TAPs) by analysis of large-scale ChIP-Seq data. Immunostaining and fluorescence in situ hybridization experiments were applied to detect the subcellular location of target genes and telomeres. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used to examine the expression of targeting genes. Overall survival (OS) analyses were used to evaluate the relationship between gene expression and survival time; immunohistochemistry was used to detect the distribution of target genes in liver cancer tissues. We found that nuclear factor related to kappaB binding protein (NFRKB), a metazoan-specific subunit of the INO80 complex, can associate with telomeres in human ALT cells. Loss of NFRKB induces dysfunction of telomeres and less PML bodies in U2OS cells. In addition, NFRKB is low/moderately expressed in cytoplasm of normal hepatocytes but heavily accumulating in the nucleus of liver cancer cells. Finally, the high expression of NFRKB is associated with short OS time and poor prognosis. NFRKB is a TAP and protects telomeres from DNA damage in ALT cells. It is highly expressed in hepatocellular carcinoma (HCC) cells and predicts a poor prognosis. NFRKB may be a promising prognostic biomarker for the treatment of HCC in the future.},
}
@article {pmid34589726,
year = {2021},
author = {Fritz, MM and Walsh, LC and Cole, SW and Epel, E and Lyubomirsky, S},
title = {Kindness and cellular aging: A pre-registered experiment testing the effects of prosocial behavior on telomere length and well-being.},
journal = {Brain, behavior, &amp; immunity - health},
volume = {11},
number = {},
pages = {100187},
pmid = {34589726},
issn = {2666-3546},
abstract = {OBJECTIVE: Prosocial behavior can improve psychological well-being and physical health. However, the underlying biological mechanisms that mediate the relationship between prosociality and health remain unclear. In this pre-registered experiment, we tested whether a 4-week kindness intervention could slow leukocyte telomere shortening and increase well-being.<br><br>METHODS: Community adults (N&#xa0;&#x200b;=&#xa0;&#x200b;230) were randomly assigned to complete 1 of 3 activities, each week for 4 weeks: to perform 3 kind acts for other people, to perform 3 kind acts for themselves, or to list daily activities. At baseline and post-intervention, participants came to the lab to provide a small dried blood spot (DBS) sample via finger prick for analysis of telomere length. Participants completed psychological measures (e.g., loneliness, life satisfaction) at baseline, post-intervention, and at the 2-week follow up.<br><br>RESULTS: Participants who performed kind acts for others did not demonstrate hypothesized changes in well-being, nor in telomere length, relative to controls. Exploratory analyses revealed that, relative to controls, participants who did kind acts for others showed reductions in loneliness through the 2-week follow up.<br><br>CONCLUSIONS: The salubrious effects of prosocial behavior in the short term are not likely due to the inhibition of cellular aging (at least as indexed by telomere length). However, extending kindness to others holds promise as a future research direction for interventions to alleviate loneliness.},
}
@article {pmid34588995,
year = {2021},
author = {Wang, DX and Zhu, XD and Ma, XR and Wang, LB and Dong, ZJ and Lin, RR and Cao, YN and Zhao, JW},
title = {Loss of Growth Differentiation Factor 11 Shortens Telomere Length by Downregulating Telomerase Activity.},
journal = {Frontiers in physiology},
volume = {12},
number = {},
pages = {726345},
pmid = {34588995},
issn = {1664-042X},
abstract = {Maintenance of telomere length is essential to delay replicative cellular senescence. It is controversial on whether growth differentiation factor 11 (GDF11) can reverse cellular senescence, and this work aims to establish the causality between GDF11 and the telomere maintenance unequivocally. Using CRISPR/Cas9 technique and a long-term in vitro culture model of cellular senescence, we show here that in vitro genetic deletion of GDF11 causes shortening of telomere length, downregulation of telomeric reverse transcriptase (TERT) and telomeric RNA component (TERC), the key enzyme and the RNA component for extension of the telomere, and reduction of telomerase activity. In contrast, both recombinant and overexpressed GDF11 restore the transcription of TERT in GDF11[KO] cells to the wild-type level. Furthermore, loss of GDF11-induced telomere shortening is likely caused by enhancing the nuclear entry of SMAD2 which inhibits the transcription of TERT and TERC. Our results provide the first proof-of-cause-and-effect evidence that endogenous GDF11 plays a causal role for proliferative cells to maintain telomere length, paving the way for potential rejuvenation of the proliferative cells, tissues, and organs.},
}
@article {pmid34587336,
year = {2022},
author = {Rouan, A and Pousse, M and Tambutté, E and Djerbi, N and Zozaya, W and Capasso, L and Zoccola, D and Tambutté, S and Gilson, E},
title = {Telomere dysfunction is associated with dark-induced bleaching in the reef coral Stylophora pistillata.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6087-6099},
doi = {10.1111/mec.16199},
pmid = {34587336},
issn = {1365-294X},
mesh = {Animals ; *Anthozoa/genetics ; Ecosystem ; Phylogeny ; Coral Reefs ; Symbiosis/genetics ; },
abstract = {Telomere DNA length is a complex trait controlled by both multiple loci and environmental factors. A growing number of studies are focusing on the impact of stress and stress accumulation on telomere length and the link with survival and fitness in ecological contexts. Here, we investigated the telomere changes occurring in a symbiotic coral, Stylophora pistillata, that has experienced continuous darkness over 6 months. This stress condition led to the loss of its symbionts in a similar manner to that observed during large-scale bleaching events due to climate changes and anthropogenic activities, threatening reef ecosystems worldwide. We found that continuous darkness was associated with telomere length shortening. This result, together with a phylogenetic analysis of the telomere coral proteins and a transcriptome survey of the continuous darkness condition, paves the way for future studies on the role of telomeres in the coral stress response and the importance of environmentally induced telomere shortening in endangered coral species.},
}
@article {pmid34586731,
year = {2021},
author = {Sung, JY and Cheong, JH},
title = {Alternative lengthening of telomeres is mechanistically linked to potential therapeutic vulnerability in the stem-like subtype of gastric cancer.},
journal = {Clinical and translational medicine},
volume = {11},
number = {9},
pages = {e561},
pmid = {34586731},
issn = {2001-1326},
support = {HI14C1324//Ministry of Health and Welfare, Republic of Korea/ ; HI14C1324//Korea Health Industry Development Institute/ ; 2018R1A5A2025079//National Research Foundation (NRF), Ministry of Science and ICT, KOREA/ ; },
mesh = {Drug Resistance, Neoplasm/genetics ; Energy Metabolism/genetics ; Epithelial-Mesenchymal Transition/genetics ; Humans ; Protein Interaction Maps/genetics ; *Stomach Neoplasms/genetics/pathology ; Telomere/*genetics ; Telomere Homeostasis/*genetics ; },
}
@article {pmid34585887,
year = {2021},
author = {Chandru, S and Prabhu, P and Balasubramanyam, M and Subhashini, R and Tiwaskar, M and Pramodkumar, TA and Pradeepa, R and Anjana, RM and Mohan, V},
title = {Beneficial Primary Outcomes of Metabolic Surgery with Changes in Telomere Length and Mitochondrial DNA in Obese Asian Indians with Dysglycemia.},
journal = {The Journal of the Association of Physicians of India},
volume = {69},
number = {9},
pages = {11-12},
pmid = {34585887},
issn = {0004-5772},
mesh = {*Bariatric Surgery ; DNA, Mitochondrial/genetics ; *Diabetes Mellitus, Type 2/complications/genetics ; Follow-Up Studies ; Humans ; Obesity/complications/genetics ; Prospective Studies ; Telomere/genetics ; },
abstract = {INTRODUCTION: Although metabolic surgery has been shown to offer beneficial primary outcome results in obese individuals / obese Type 2 diabetes mellitus (T2DM) patients, there is paucity of information on the underlying mechanisms. In the recent years, estimations of non-invasive molecular parameters viz., telomere length and mtDNA copy number (mtDNAcn) assume significance as robust biomarkers. However, there is lack of evidence about this especially, in the Indian context. To assess the changes in the telomere length and mtDNAcn levels after metabolic surgery in obese Asian Indians with dysglycemia along with routine measurements of anthropometry, glycemic/lipidimic parameters and inflammatory markers.<br><br>METHODS: This study is a prospective one-year follow-up study of 16 obese individuals with dysglycemia who underwent metabolic surgery at a tertiary diabetes centre in South India. Telomere length, mtDNAcn, serum adiponectin, glycated haemoglobin and high- sensitivity C-reactive protein (hs-CRP) levels were analysed before surgery and at 6 and 12 months after surgery.<br><br>RESULTS: There was a significant reduction in weight (p<0.001), BMI (p<0.001), waist circumference (p<0.001), fasting and postprandial glucose (p<0.05), HbA1c (p<0.001), triglycerides (p<0.05), hs CRP (p<0.05) and increase in serum adiponectin (p<0.05) at 6 and 12 months post-surgery compared to the preoperative status. There was a significant reduction in mtDNAcn (p<0.001) and a significant increase in telomere length (p<0.001) at 6 and 12 months post metabolic surgery.<br><br>CONCLUSION: We report an increase in telomere length and decrease in circulatory mtDNA copy number levels at 6 and 12 months post metabolic surgery in obese individuals with T2DM in India.},
}
@article {pmid34585163,
year = {2021},
author = {Tichy, ED and Mourkioti, F},
title = {Telomere length assessments of muscle stem cells in rodent and human skeletal muscle sections.},
journal = {STAR protocols},
volume = {2},
number = {4},
pages = {100830},
pmid = {34585163},
issn = {2666-1667},
support = {R01 AR075914/AR/NIAMS NIH HHS/United States ; R01 HL146662/HL/NHLBI NIH HHS/United States ; },
mesh = {Animals ; Humans ; Muscle Fibers, Skeletal ; Muscle, Skeletal ; *Myoblasts ; *Rodentia ; Telomere/genetics ; },
abstract = {Measurements of telomere length in skeletal muscle stem cells (MuSCs), a rare cell population within muscles, provide insights into cellular dysfunction in diseased conditions. Here, we describe a protocol (cryosection muscle quantitative fluorescent in situhybridization) using skeletal muscle cryosections for assessments of telomere length in MuSCs, in their native environment. Using a free software, telomere length measurements are assessed on a single-cell level. We also provide methodology to perform data analyses in several ways. For complete details on the use and execution of this protocol, please refer to Tichy et al. (2021).},
}
@article {pmid34583600,
year = {2020},
author = {Cuevas, AG and Greatorex-Voith, S and Abuelezam, N and Eckert, N and Assari, S},
title = {Educational mobility and telomere length in middle-aged and older adults: testing three alternative hypotheses.},
journal = {Biodemography and social biology},
volume = {66},
number = {3-4},
pages = {220-235},
doi = {10.1080/19485565.2021.1983760},
pmid = {34583600},
issn = {1948-5573},
mesh = {Aged ; Cross-Sectional Studies ; Educational Status ; Humans ; Middle Aged ; *Social Class ; *Sociodemographic Factors ; Telomere/genetics ; Telomere Shortening ; },
abstract = {Critical period, social mobility, and social accumulation are three hypotheses that may explain how educational mobility impacts health. Thus far, there is little evidence on how these processes are associated with biological aging as measured by telomere length. Using cross-sectional data from the 2008 Health and Retirement Study, we examined the association between educational mobility (parental education and contemporaneous education) and telomere length. The final model is adjusted for sociodemographic factors and socioeconomic status, childhood adversity, and health behaviors/risk factors, as well as depressive symptoms. A total of 1,894 participants were included in the main analyses. High parental education was associated with longer telomere length in a fully adjusted model (B = 0.03, CI [0.002,0.07]). Downwardly mobile individuals (high parental education and low contemporaneous education) had longer telomere length compared to stably low individuals in a fully adjusted model (B = 0.05, CI [0.004,0.09]). There was support for the critical period hypothesis and partial support for the change hypothesis. There was no evidence to support the social accumulation hypothesis. Prospective studies are needed to understand the mechanism that can help further explain the association between educational mobility and telomere length.},
}
@article {pmid34580961,
year = {2021},
author = {van der Vis, JJ and van der Smagt, JJ and van Batenburg, AA and Goldschmeding, R and van Es, HW and Grutters, JC and van Moorsel, CHM},
title = {Pulmonary fibrosis in non-mutation carriers of families with short telomere syndrome gene mutations.},
journal = {Respirology (Carlton, Vic.)},
volume = {26},
number = {12},
pages = {1160-1170},
doi = {10.1111/resp.14145},
pmid = {34580961},
issn = {1440-1843},
mesh = {Humans ; Mutation ; *Pulmonary Fibrosis/genetics ; *Telomerase/genetics ; Telomere/genetics ; Telomere Shortening ; },
abstract = {BACKGROUND AND OBJECTIVE: Diagnostic and predictive genetic testing for disease cause and risk estimation is common in many countries. For genetic diseases, predictive test results are commonly straightforward: presence of the mutation involves increased risk for disease and absence of the mutation involves no inherit risk for disease. Germline mutations in telomere-related genes (TRGs) can lead to telomere shortening and are associated with short telomere syndrome (STS). Telomere length is heritable, and in families with STS due to a TRG mutation, progeny with and without the TRG mutation is known to have shorter than average telomeres. We hypothesize that progeny of TRG mutation carriers who did not inherit the TRG mutation may still develop pulmonary fibrosis.<br><br>METHODS: A genetic screen of 99 unrelated families with familial pulmonary fibrosis revealed five patients with features of pulmonary fibrosis but without carrying the familial disease-causing TRG mutation.<br><br>RESULTS: Features of STS were present in each family, including short telomeres in blood and tissue of the non-mutation carrying patients. Additional genetic, clinical or environmental risk factors for pulmonary fibrosis were present in each non-mutation carrying patient.<br><br>CONCLUSION: Our study shows that non-mutation carrying first-degree relatives in families with STS are at increased risk for pulmonary fibrosis. Disease development may be triggered by inherited short telomeres and additional risk factors for disease. This observation has profound consequences for genetic counselling. Unlike any other genetic syndrome, absence of the mutation does not imply absence of disease risk. Therefore, clinical follow-up is still urged for non-mutation carrying first-degree family members.},
}
@article {pmid34576030,
year = {2021},
author = {Huang, YC and Wang, CY},
title = {Telomere Attrition and Clonal Hematopoiesis of Indeterminate Potential in Cardiovascular Disease.},
journal = {International journal of molecular sciences},
volume = {22},
number = {18},
pages = {},
pmid = {34576030},
issn = {1422-0067},
support = {NHRIEX106-10617SI, NHRI-110A1-CSCO-17212418//National Health Research Institutes/ ; 105-2628-B-182-009-MY4 and 109-2314-B-182-070-MY3//National Science Council/ ; CMRPG3H0133, CMRPG3I0322, CMRPG3H0843, and CORPG3K0011//Chang Gung Memorial Hospital/ ; },
mesh = {Aging/genetics/pathology ; Atherosclerosis/*genetics/pathology ; Cardiovascular Diseases/*genetics/pathology ; Clonal Evolution/genetics ; Clonal Hematopoiesis/genetics ; DNA (Cytosine-5-)-Methyltransferases/*genetics ; DNA Methyltransferase 3A ; DNA-Binding Proteins/*genetics ; Dioxygenases/*genetics ; Humans ; Mutation/genetics ; Repressor Proteins/*genetics ; Telomere/genetics ; },
abstract = {Clinical evidence suggests that conventional cardiovascular disease (CVD) risk factors cannot explain all CVD incidences. Recent studies have shown that telomere attrition, clonal hematopoiesis of indeterminate potential (CHIP), and atherosclerosis (telomere-CHIP-atherosclerosis, TCA) evolve to play a crucial role in CVD. Telomere dynamics and telomerase have an important relationship with age-related CVD. Telomere attrition is associated with CHIP. CHIP is commonly observed in elderly patients. It is characterized by an increase in blood cell clones with somatic mutations, resulting in an increased risk of hematological cancer and atherosclerotic CVD. The most common gene mutations are DNA methyltransferase 3 alpha (DNMT3A), Tet methylcytosine dioxygenase 2 (TET2), and additional sex combs-like 1 (ASXL1). Telomeres, CHIP, and atherosclerosis increase chronic inflammation and proinflammatory cytokine expression. Currently, their epidemiology and detailed mechanisms related to the TCA axis remain incompletely understood. In this article, we reviewed recent research results regarding the development of telomeres and CHIP and their relationship with atherosclerotic CVD.},
}
@article {pmid34572228,
year = {2021},
author = {Monnin, A and Vizeneux, A and Nagot, N and Eymard-Duvernay, S and Meda, N and Singata-Madliki, M and Ndeezi, G and Tumwine, JK and Kankasa, C and Goga, A and Tylleskär, T and Van de Perre, P and Molès, JP},
title = {Longitudinal Follow-Up of Blood Telomere Length in HIV-Exposed Uninfected Children Having Received One Year of Lopinavir/Ritonavir or Lamivudine as Prophylaxis.},
journal = {Children (Basel, Switzerland)},
volume = {8},
number = {9},
pages = {},
pmid = {34572228},
issn = {2227-9067},
support = {ANRS#12274//Agence Nationale de Recherches sur le Sida et les H&#xe9;patites Virales/ ; ANRS12174-B90//Agence Nationale de Recherches sur le Sida et les H&#xe9;patites Virales/ ; #CT.2006.33020.004//European and Developing Countries Clinical Trials Partnership/ ; GlobVac grant # 183600//Royal council of Norway/ ; AP-FPB-2013-2/09//Pierre Berg&#xe9; fundation/ ; },
abstract = {Telomere shortening can be enhanced upon human immunodeficiency virus (HIV) infection and by antiretroviral (ARV) exposures. The aim of this study was to evaluate the acute and long-term effect on telomere shortening of two ARV prophylaxes, lopinavir/ritonavir (LPV/r) and lamivudine (3TC), administered to children who are HIV-exposed uninfected (CHEU) to prevent HIV acquisition through breastfeeding during the first year of life, and to investigate the relationship between telomere shortening and health outcomes at six years of age. We included 198 CHEU and measured telomere length at seven days of life, at week-50 and at six years (year-6) using quantitative polymerase chain reaction. At week-50, telomere shortening was observed among 44.3% of CHEU, irrespective of the prophylactic treatment. Furthermore, this telomere shortening was neither associated with poor growth indicators nor neuropsychological outcomes at year-6, except for motor abilities (MABC test n = 127, β = -3.61, 95%CI: -7.08, -0.14; p = 0.04). Safety data on telomere shortening for infant HIV prophylaxis are scarce. Its association with reduced motor abilities deserves further attention among CHEU but also HIV-infected children receiving ARV treatment.},
}
@article {pmid34565437,
year = {2021},
author = {Tometten, M and Kirschner, M and Isfort, S and Berres, ML and Brümmendorf, TH and Beier, F},
title = {Transient elastography in adult patients with cryptic dyskeratosis congenita reveals subclinical liver fibrosis: a retrospective analysis of the Aachen telomere biology disease registry.},
journal = {Orphanet journal of rare diseases},
volume = {16},
number = {1},
pages = {395},
pmid = {34565437},
issn = {1750-1172},
mesh = {Adult ; Biology ; *Dyskeratosis Congenita/genetics ; *Elasticity Imaging Techniques ; Humans ; Liver/diagnostic imaging ; Liver Cirrhosis/diagnostic imaging/genetics ; Registries ; Retrospective Studies ; Telomere/genetics ; },
abstract = {BACKGROUND: Telomere biology disorders (TBD) such as dyskeratosis congenita (DKC) lead to progressive multi-organ failure as impaired telomere maintenance disturbs cellular proliferative capacity. A wide range of hepatic manifestations from asymptomatic liver enzyme elevation to overt liver fibrosis/cirrhosis can be observed in TBD patients. However, the incidence of hepatic involvement remains unknown. Non-invasive transient elastography (TE) predicts early fibrosis by measuring liver stiffness and may uncover subclinical liver damage in TBD patients.<br><br>METHODS: Liver screening procedures of nine TBD patients from the Aachen TBD Registry are being presented retrospectively. Following clinical suspicion, TBD was diagnosed using flow-FISH with telomere length (TL) below the 1% percentile and confirmed by next-generation sequencing (NGS) detecting pathogenic mutations in telomere maintenance genes TERC or TERT.<br><br>RESULTS: In all patients, TBD was first diagnosed in adulthood. Patients showed normal to slightly elevated liver function test parameters. Hepatic ultrasound revealed inhomogeneous parenchyma in seven (77.7%) and increased liver echogenicity in four patients (44.4%). Median liver stiffness was 10.7 kilopascal (kPa) (interquartile range 8.4, 15.7&#xa0;kPa). Using 7.1&#xa0;kPa as cut-off, 88.8% of patients were classified as moderate fibrosis to cirrhosis.<br><br>CONCLUSION: Subclinical chronic liver involvement is frequent in patients with adult-onset TBD. TE could have a valuable role in the routine work-up of patients with telomere disorders including DKC for early detection of patients at risk for liver function impairment.},
}
@article {pmid34564066,
year = {2022},
author = {Nickels, M and Mastana, S and Codd, V and Denniff, M and Akam, E},
title = {Comparison of Telomere Length in Young and Master Endurance Runners and Sprinters.},
journal = {Journal of aging and physical activity},
volume = {30},
number = {3},
pages = {510-516},
doi = {10.1123/japa.2021-0236},
pmid = {34564066},
issn = {1543-267X},
mesh = {Athletes ; Humans ; Middle Aged ; Nutritional Status ; Physical Endurance/genetics ; *Running ; Telomere ; },
abstract = {It is unclear how running modality influences telomere length (TL). This single laboratory visit study compared the TL of master sprinters and endurance runners with their young counterparts. The correlation between leukocyte and buccal cell TL in athletes was also explored. Participants consisted of 11 young controls, 11 young sprinters, 12 young endurance runners, 12 middle-aged controls, 11 master sprinters, and 12 master endurance runners. Blood and buccal samples were collected and randomized for analysis of TL by quantitative polymerase chain reaction. Young endurance runners displayed longer telomeres than master athletes (p < .05); however, these differences were not significant when controlled for covariates (p > .05). A positive correlation existed between leukocyte and buccal cell TL in athletes (r = .567, p < .001). In conclusion, young endurance runners possess longer telomeres than master endurance runners and sprinters, a consequence of lower body mass index and visceral fat.},
}
@article {pmid34562085,
year = {2022},
author = {Lyu, L and Yu, J and Liu, Y and He, S and Zhao, Y and Qi, M and Ping, F and Xu, L and Li, W and Zhang, H and Li, Y},
title = {High Hemoglobin Glycation Index Is Associated With Telomere Attrition Independent of HbA1c, Mediated by TNFα.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {107},
number = {2},
pages = {462-473},
doi = {10.1210/clinem/dgab703},
pmid = {34562085},
issn = {1945-7197},
mesh = {Adult ; Cross-Sectional Studies ; DNA Copy Number Variations ; DNA, Mitochondrial/genetics ; Female ; Glycated Hemoglobin/analysis/*metabolism ; Glycosylation ; Humans ; Male ; Middle Aged ; Oxidative Stress/genetics ; Telomere/metabolism ; *Telomere Shortening ; Tumor Necrosis Factor-alpha/*metabolism ; },
abstract = {CONTEXT: The hemoglobin glycation index (HGI) is correlated with metabolic diseases and inflammation. Whether the HGI is associated with the aging process and how inflammation and oxidative stress affect the relationship remain unclear.<br><br>OBJECTIVE: We aimed to analyze links between the HGI and aging biomarkers, and to explore a potential role of inflammation and oxidative stress in the correlations.<br><br>METHODS: A cross-sectional study of 434 subjects with different glucose intolerances in a rural community was enrolled. The HGI was calculated as the difference between the measured and predicted hemoglobin A1c (HbA1c). The population was categorized into tertiles of the HGI. Telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) determined by polymerase chain reaction assay. Tumor necrosis factor (TNF) &#x3b1; and interleukin (IL) 6, 8-oxo-2'-deoxyguanosine (8-oxo-dG), superoxide dismutase (SOD) activities, and glutathione reductase (GR) were measured.<br><br>RESULTS: Participants in the high HGI group were older and reported a shorter LTL, higher levels of TNF&#x3b1;, SOD activities, and HbA1c. Correlation analyses demonstrated that HGI was correlated with LTL (r = -0.25, P < .001) and TNF&#x3b1; (r = 0.19, P < .001) regardless of HbA1c levels. No relationship was found between HGI and mtDNAcn. HGI (&#x3b2; = -0.238, 95% CI -0.430, -0.046, P = .015) and TNF&#x3b1; (&#x3b2; = -0.02, 95% CI -0.030, -0.014, P < .001) were proved to be correlated with LTL independently, using multiple linear regression analysis. Ordinal logistic regression models showed that compared with subjects the high HGI group, the possibilities of a higher-level LTL was 5.29-fold in the low HGI group (OR 5.29, 95% CI (2.45, 11.41), P < .001), 2.41-fold in the moderate HGI group (OR 2.41, 95% CI 1.35, 4.30, P = .003) after controlling for confounding variables. Mediation analyses indicated that TNF&#x3b1; accounted for 30.39% of the effects of the HGI on LTL.<br><br>CONCLUSION: HGI was negatively related to telomere attrition, independent of HbA1c. TNF&#x3b1; acted as a mediator of the relationship between HGI and LTL.},
}
@article {pmid34559557,
year = {2021},
author = {Lee, L and Perez Oliva, AB and Martinez-Balsalobre, E and Churikov, D and Peter, J and Rahmouni, D and Audoly, G and Azzoni, V and Audebert, S and Camoin, L and Mulero, V and Cayuela, ML and Kulathu, Y and Geli, V and Lachaud, C},
title = {UFMylation of MRE11 is essential for telomere length maintenance and hematopoietic stem cell survival.},
journal = {Science advances},
volume = {7},
number = {39},
pages = {eabc7371},
pmid = {34559557},
issn = {2375-2548},
abstract = {Ubiquitin-fold modifier 1 (UFM1) is involved in neural and erythroid development, yet its biological roles in these processes are unknown. Here, we generated zebrafish models deficient in Ufm1 and Ufl1 that exhibited telomere shortening associated with developmental delay, impaired hematopoiesis and premature aging. We further report that HeLa cells lacking UFL1 have instability of telomeres replicated by leading-strand synthesis. We uncover that MRE11 UFMylation is necessary for the recruitment of the phosphatase PP1-α leading to dephosphorylation of NBS1. In the absence of UFMylation, NBS1 remains phosphorylated, thereby reducing MRN recruitment to telomeres. The absence of MRN at telomeres favors the formation of the TRF2-Apollo/SNM1 complex consistent with the loss of leading telomeres. These results suggest that MRE11-UFMylation may serve as module to recruit PP1-α. Last, zebrafish expressing Mre11 that cannot be UFMylated phenocopy Ufm1-deficient zebrafish, demonstrating that UFMylation of MRE11 is a previously undescribed evolutionarily conserved mechanisms regulating telomere length.},
}
@article {pmid34559348,
year = {2022},
author = {Aida, J and Takubo, K and Vieth, M and Neuhaus, H and Fujiwara, M and Arai, T and Ishiwata, T},
title = {Telomere lengths in Barrett's esophagus as a precancerous lesion.},
journal = {Esophagus : official journal of the Japan Esophageal Society},
volume = {19},
number = {2},
pages = {287-293},
pmid = {34559348},
issn = {1612-9067},
mesh = {*Barrett Esophagus/genetics/pathology ; Humans ; Intestines/pathology ; Mucous Membrane/pathology ; *Precancerous Conditions/genetics/pathology ; Telomere/genetics/pathology ; },
abstract = {BACKGROUND: We have reported that precancerous conditions and lesions invariably have shorter telomeres and associated chromosomal instability relative to normal tissue.<br><br>METHODS: Using the Q-FISH method and our original software, Tissue Telo, we estimated telomere lengths in cardiac- and intestinal-type mucosae in 48 cases of Barrett's esophagus (short-segment (SS) n&#x2009;=&#x2009;18; long-segment (LS) n&#x2009;=&#x2009;30).<br><br>RESULTS: There were no significant differences in telomere length between the cardiac and intestinal types in any of the 48 cases, suggesting that the presence or absence of goblet cells in the columnar segments is unrelated to telomere-dependent chromosomal instability in Barrett's esophagus. In LS Barrett's esophagus, telomeres were shorter in cardiac-type than in intestinal-type mucosa, suggesting that the former may play a more important role than the latter as a precancerous lesion in LS. Telomeres in cardiac-type mucosa were longer in SS than in LS, supporting the possibility that cardiac-type LS may pose a higher risk as a precancerous lesion than cardiac-type SS.<br><br>CONCLUSIONS: Although it has been considered that Barrett's carcinoma arises only from intestinal-type mucosa, our present findings support previous histogenetic studies suggesting that cardiac-type mucosa is more important as a precancerous condition in Barrett's esophagus than anticipated.},
}
@article {pmid34558851,
year = {2022},
author = {Rattan, P and Penrice, DD and Ahn, JC and Ferrer, A and Patnaik, M and Shah, VH and Kamath, PS and Mangaonkar, AA and Simonetto, DA},
title = {Inverse Association of Telomere Length With Liver Disease and Mortality in the US Population.},
journal = {Hepatology communications},
volume = {6},
number = {2},
pages = {399-410},
pmid = {34558851},
issn = {2471-254X},
support = {U01 AA026886/AA/NIAAA NIH HHS/United States ; },
mesh = {Adult ; Aged ; Aged, 80 and over ; Cause of Death ; Disease Progression ; Female ; Humans ; Leukocytes/cytology ; Linear Models ; Liver Diseases/*genetics/*mortality ; Male ; Middle Aged ; Nutrition Surveys ; Proportional Hazards Models ; *Telomere Shortening ; United States/epidemiology ; Young Adult ; },
abstract = {Physiologic aging leads to attrition of telomeres and replicative senescence. An acceleration of this process has been hypothesized in the progression of chronic liver disease. We sought to examine the association of telomere length (TL) with liver disease and its impact on mortality risk. A cohort of 7,072 adults with leukocyte TL measurements from the National Health and Nutrition Examination Survey 1999-2002 with mortality follow-up through 2015 was analyzed. Liver disease was defined by aminotransferase levels and classified into etiology-based and advanced fibrosis categories. Multivariable-adjusted linear regression models estimated effect sizes, with 95% confidence intervals (CIs), of the presence of liver disease on TL. Cox regression models evaluated associations between TL and all-cause mortality risk using adjusted hazard ratios (HRs). The cohort was representative of the US population with mean age 46.1 years and mean TL 5.79 kilobase pairs. No overall association between TL and liver disease was found; however, there was a significant negative association of TL and advanced liver fibrosis in individuals aged 65 and above. The liver disease cohort (HR 1.22, 95% CI 0.99-1.51) and those with metabolic syndrome (HR 1.26, 95% CI 0.96-1.67) had increased mortality risk with shorter TL. The relationship between TL and all-cause mortality was stronger in women (HR 1.51, 95% CI 1.02-2.23) and in non-Hispanic Whites (HR 1.37, 95% CI 1.02-1.84). Conclusion: Shortened leukocyte TL is independently associated with advanced liver disease at older ages, and with a higher risk of all-cause mortality in those with liver disease. These associations reaffirm the need to better understand the role of telomeres in the progression of liver disease.},
}
@article {pmid34558545,
year = {2022},
author = {Polho, GB and Cardillo, GM and Kerr, DS and Chile, T and Gattaz, WF and Forlenza, OV and Brentani, HP and De-Paula, VJ},
title = {Antipsychotics preserve telomere length in peripheral blood mononuclear cells after acute oxidative stress injury.},
journal = {Neural regeneration research},
volume = {17},
number = {5},
pages = {1156-1160},
pmid = {34558545},
issn = {1673-5374},
abstract = {Antipsychotics may prolong or retain telomere length, affect mitochondrial function, and then affect the metabolism of nerve cells. To validate the hypothesis that antipsychotics can prolong telomere length after oxidative stress injury, leukocytes from healthy volunteers were extracted using Ficoll-Histopaque density gradient. The mononuclear cells layer was resuspended in cell culture medium. Oxidative stress was induced with hydrogen peroxide in cultured leukocytes. Four days later, leukocytes were treated with aripiprazole, haloperidol or clozapine for 7 days. Real-time PCR revealed that treatments with aripiprazole and haloperidol increased the telomere length by 23% and 20% in peripheral blood mononuclear cells after acute oxidative stress injury. These results suggest that haloperidol and aripiprazole can reduce the damage to telomeres induced by oxidative stress. The experiment procedure was approved by the Ethics Committee of Faculty of Medicine of the University of São Paulo (FMUSP/CAAE approval No. 52622616.8.0000.0065).},
}
@article {pmid34556550,
year = {2021},
author = {Garus, A and Autexier, C},
title = {Dyskerin: an essential pseudouridine synthase with multifaceted roles in ribosome biogenesis, splicing, and telomere maintenance.},
journal = {RNA (New York, N.Y.)},
volume = {27},
number = {12},
pages = {1441-1458},
pmid = {34556550},
issn = {1469-9001},
support = {PJT-166130//CIHR/Canada ; },
mesh = {*Alternative Splicing ; Cell Cycle Proteins/genetics/*metabolism ; Dyskeratosis Congenita ; Humans ; Intramolecular Transferases/genetics/*metabolism ; *Mutation ; Nuclear Proteins/genetics/*metabolism ; *RNA Processing, Post-Transcriptional ; Ribosomes/*metabolism ; Telomere/*physiology ; },
abstract = {Dyskerin and its homologs are ancient and conserved enzymes that catalyze the most common post-transcriptional modification found in cells, pseudouridylation. The resulting pseudouridines provide stability to RNA molecules and regulate ribosome biogenesis and splicing events. Dyskerin does not act independently-it is the core component of a protein heterotetramer, which associates with RNAs that contain the H/ACA motif. The variety of H/ACA RNAs that guide the function of this ribonucleoprotein (RNP) complex highlights the diversity of cellular processes in which dyskerin participates. When associated with small nucleolar (sno) RNAs, it regulates ribosomal (r) RNAs and ribosome biogenesis. By interacting with small Cajal body (sca) RNAs, it targets small nuclear (sn) RNAs to regulate pre-mRNA splicing. As a component of the telomerase holoenzyme, dyskerin binds to the telomerase RNA to modulate telomere maintenance. In a disease context, dyskerin malfunction can result in multiple detrimental phenotypes. Mutations in DKC1, the gene that encodes dyskerin, cause the premature aging syndrome X-linked dyskeratosis congenita (X-DC), a still incurable disorder that typically leads to bone marrow failure. In this review, we present the classical and most recent findings on this essential protein, discussing the evolutionary, structural, and functional aspects of dyskerin and the H/ACA RNP. The latest research underscores the role that dyskerin plays in the regulation of gene expression, translation efficiency, and telomere maintenance, along with the impacts that defective dyskerin has on aging, cell proliferation, haematopoietic potential, and cancer.},
}
@article {pmid34553645,
year = {2023},
author = {Güneşliol, BE and Karaca, E and Ağagündüz, D and Acar, ZA},
title = {Association of physical activity and nutrition with telomere length, a marker of cellular aging: A comprehensive review.},
journal = {Critical reviews in food science and nutrition},
volume = {63},
number = {5},
pages = {674-692},
doi = {10.1080/10408398.2021.1952402},
pmid = {34553645},
issn = {1549-7852},
mesh = {*Nutritional Status ; *Telomere Shortening ; Telomere ; Exercise ; },
abstract = {The aging of the population has great social and economic effects because it is characterized by a gradual loss in physiological integrity, resulting in functional decline, thereby loss of ability to move independently. Telomeres, the hallmarks of biological aging, play a protective role in both cell death and aging. Critically short telomeres give rise to a metabolically active cell that is unable to repair damage or divide, thereby leading to aging. Lifestyle factors such as physical activity (PA) and nutrition could be associated with telomere length (TL). Indeed, regular PA and healthy nutrition as integral parts of our lifestyle can slow down telomere shortening, thereby delaying aging. In this context, the present comprehensive review summarizes the data from recent literature on the association of PA and nutrition with TL.},
}
@article {pmid34551154,
year = {2022},
author = {Sheldon, EL and Ton, R and Boner, W and Monaghan, P and Raveh, S and Schrey, AW and Griffith, SC},
title = {Associations between DNA methylation and telomere length during early life: Insight from wild zebra finches (Taeniopygia guttata).},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6261-6272},
doi = {10.1111/mec.16187},
pmid = {34551154},
issn = {1365-294X},
mesh = {Animals ; *Finches/genetics ; DNA Methylation/genetics ; Australia ; Aging/genetics ; Telomere/genetics ; },
abstract = {Telomere length and DNA methylation (DNAm) are two promising biomarkers of biological age. Environmental factors and life history traits are known to affect variation in both these biomarkers, especially during early life, yet surprisingly little is known about their reciprocal association, especially in natural populations. Here, we explore how variation in DNAm, growth rate, and early-life conditions are associated with telomere length changes during development. We tested these associations by collecting data from wild, nestling zebra finches in the Australian desert. We found that increases in the level of DNAm were negatively correlated with telomere length changes across early life. We also confirm previously documented effects of post hatch growth rate and clutch size on telomere length in a natural ecological context for a species that has been extensively studied in the laboratory. However, we did not detect any effect of ambient temperature during developmental on telomere length dynamics. We also found that the absolute telomere length of wild zebra finches, measured using the in-gel TRF method, was similar to that of captive birds. Our findings highlight exciting new opportunities to link and disentangle potential relationships between DNA based biomarkers of ageing, and of physiological reactions to environmental change.},
}
@article {pmid34549596,
year = {2021},
author = {Nolte, J},
title = {Lrrc34 Interacts with Oct4 and Has an Impact on Telomere Length in Mouse Embryonic Stem Cells.},
journal = {Stem cells and development},
volume = {30},
number = {22},
pages = {1093-1102},
doi = {10.1089/scd.2021.0113},
pmid = {34549596},
issn = {1557-8534},
mesh = {Animals ; Cellular Reprogramming ; *Induced Pluripotent Stem Cells/metabolism ; Mice ; Mouse Embryonic Stem Cells/metabolism ; *Octamer Transcription Factor-3/metabolism ; *Repressor Proteins/metabolism ; *Telomerase/genetics/metabolism ; Telomere/genetics ; Telomere Homeostasis ; },
abstract = {Telomere length maintenance in pluripotent stem cells (PSCs) is a main characteristic and a major premise for their undifferentiated long-term survival. However, little is known about the factors that control telomere length and elongation in these cells. Here, I describe Lrrc34 (leucine-rich repeat 34) as a novel telomere length regulating gene in murine embryonic stem cells. Downregulation of Lrrc34 results in significant reduction of telomerase activity and telomere length over time while also influencing the expression of known telomere length-associated genes. Generating induced PSCs (iPSCs) with Lrrc34 as a fifth factor in classical Yamanaka reprogramming increases the efficiency but did not have an impact on telomere length in the resulting iPSCs. Moreover, Lrrc34 was found to interact with Oct4, connecting the pluripotency network to telomere length regulation.},
}
@article {pmid34547897,
year = {2021},
author = {Bazaz, MR and Balasubramanian, R and Monroy-Jaramillo, N and Dandekar, MP},
title = {Linking the Triad of Telomere Length, Inflammation, and Gut Dysbiosis in the Manifestation of Depression.},
journal = {ACS chemical neuroscience},
volume = {12},
number = {19},
pages = {3516-3526},
doi = {10.1021/acschemneuro.1c00457},
pmid = {34547897},
issn = {1948-7193},
mesh = {Depression ; *Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; Telomere ; },
abstract = {Telomere length is an indispensable marker for cellular and biological aging, and it also represents an individual's physical and mental health status. Telomere shortening has been observed in chronic inflammatory conditions, which in turn accelerates aging and risk for psychiatric disorders, including depression. Considering the influence of inflammation and telomere shortening on the gut-brain axis, herein we describe a plausible interplay between telomere attrition, inflammation, and gut dysbiosis in the neurobiology of depression. Telomere shortening and hyperinflammation are well reported in depression. A negative impact of augmented inflammation has been noted on the intestinal permeability and microbial consortia and their byproducts in depressive patients. Moreover, gut dysbiosis provokes host-immune responses. As the gut microbiome is gaining importance in the manifestation and management of depression, herein we discuss whether telomere attrition is connected with the perturbation of commensal microflora. We also describe a pathological connection of cortisol with hyperinflammation, telomere shortening, and gut dysbiosis occurring in depression. This review summarizes how the triad of telomere attrition, inflammation, and gut dysbiosis is interconnected and modulates the risk for depression by regulating the systemic cortisol levels.},
}
@article {pmid34545641,
year = {2021},
author = {Peña, E and León-Mengíbar, J and Powell, TR and Caixàs, A and Cardoner, N and Rosa, A},
title = {Telomere length in patients with obesity submitted to bariatric surgery: A systematic review.},
journal = {European eating disorders review : the journal of the Eating Disorders Association},
volume = {29},
number = {6},
pages = {842-853},
doi = {10.1002/erv.2865},
pmid = {34545641},
issn = {1099-0968},
support = {MR/N014863/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Adult ; *Bariatric Surgery ; Humans ; Obesity/genetics/surgery ; Prospective Studies ; *Telomere ; Telomere Shortening ; },
abstract = {BACKGROUND: Patients with obesity show evidence of increased levels of inflammation, oxidative stress and premature ageing. Telomere length (TL) is a key marker of cellular ageing, and patients with obesity often present shorter TL. Bariatric surgery (BS) is currently the most effective treatment for severe obesity. The aim of this systematic review was to explore whether the beneficial health effects observed after surgery in obese patients correspond to a restoration in TL or slower rates of shortening. As a secondary aim, we evaluated, at baseline and post-surgery, the relationship between TL and different factors that could play a role in TL changes along time.<br><br>METHODS: Searches for relevant articles were performed in MEDLINE, Web of Knowledge and SCOPUS. Prospective longitudinal studies that evaluated leukocyte TL in adult patients who had undergone BS were included. Data were extracted and evaluated by two independent researchers. The protocol was registered in PROSPERO with the number CRD42020197711.<br><br>RESULTS: Seven studies based on independent samples that fulfilled our inclusion criteria were included. Obese patients showed shorter telomeres compared to healthy individuals. Long-term studies (>2&#xa0;years) seem to suggest an improvement in TL after surgery presumably due to the improvement of the inflammatory and oxidative levels of the patients induced by weight loss.<br><br>CONCLUSION: Studies seem to point towards a beneficial long-term effect of BS on TL recovery. However, the scarce number of studies and the heterogeneity in the variables analysed in the different cohorts make it difficult to draw a firm conclusion. More studies are needed to evaluate long-term changes to TL following BS.},
}
@article {pmid34535663,
year = {2021},
author = {Gu, P and Jia, S and Takasugi, T and Tesmer, VM and Nandakumar, J and Chen, Y and Chang, S},
title = {Distinct functions of POT1 proteins contribute to the regulation of telomerase recruitment to telomeres.},
journal = {Nature communications},
volume = {12},
number = {1},
pages = {5514},
pmid = {34535663},
issn = {2041-1723},
support = {R01 GM141350/GM/NIGMS NIH HHS/United States ; R01 AG050509/AG/NIA NIH HHS/United States ; R01 GM120094/GM/NIGMS NIH HHS/United States ; R01 CA202816/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; CRISPR-Cas Systems/genetics ; DNA Mutational Analysis ; DNA-Binding Proteins/*metabolism ; Mice ; Protein Binding ; Rad51 Recombinase/metabolism ; Sarcoma/pathology ; Telomerase/*metabolism ; Telomere/*metabolism ; Telomere-Binding Proteins/*metabolism ; },
abstract = {Human shelterin components POT1 and TPP1 form a stable heterodimer that protects telomere ends from ATR-dependent DNA damage responses and regulates telomerase-dependent telomere extension. Mice possess two functionally distinct POT1 proteins. POT1a represses ATR/CHK1 DNA damage responses and the alternative non-homologous end-joining DNA repair pathway while POT1b regulates C-strand resection and recruits the CTC1-STN1-TEN1 (CST) complex to telomeres to mediate C-strand fill-in synthesis. Whether POT1a and POT1b are involved in regulating the length of the telomeric G-strand is unclear. Here we demonstrate that POT1b, independent of its CST function, enhances recruitment of telomerase to telomeres through three amino acids in its TPP1 interacting C-terminus. POT1b thus coordinates the synthesis of both telomeric G- and C-strands. In contrast, POT1a negatively regulates telomere length by inhibiting telomerase recruitment to telomeres. The identification of unique amino acids between POT1a and POT1b helps us understand mechanistically how human POT1 switches between end protective functions and promoting telomerase recruitment.},
}
@article {pmid34534358,
year = {2021},
author = {Pignolo, RJ and Johnson, FB},
title = {Do the telomere ends justify the physical means?.},
journal = {Journal of the American Geriatrics Society},
volume = {69},
number = {11},
pages = {3071-3073},
pmid = {34534358},
issn = {1532-5415},
support = {P01 AG062413/AG/NIA NIH HHS/United States ; P01 AG062413/NH/NIH HHS/United States ; },
mesh = {Humans ; *Telomere ; },
}
@article {pmid34534325,
year = {2021},
author = {Xiong, F and Frasch, WD},
title = {ΩqPCR measures telomere length from single-cells in base pair units.},
journal = {Nucleic acids research},
volume = {49},
number = {20},
pages = {e120},
pmid = {34534325},
issn = {1362-4962},
mesh = {Cell Line ; Humans ; Limit of Detection ; Polymerase Chain Reaction/*methods/standards ; Single-Cell Analysis/*methods/standards ; Telomere/*chemistry/genetics ; *Telomere Homeostasis ; },
abstract = {ΩqPCR determines absolute telomere length in kb units from single cells. Accuracy and precision of ΩqPCR were assessed using 800 bp and 1600 bp synthetic telomeres inserted into plasmids, which were measured to be 819 ± 19.6 and 1590 ± 42.3 bp, respectively. This is the first telomere length measuring method verified in this way. The approach uses Ω-probes, a DNA strand containing sequence information that enables: (i) hybridization with the telomere via the 3' and 5' ends that become opposed; (ii) ligation of the hybridized probes to circularize the Ω-probes and (iii) circularized-dependent qPCR due to sequence information for a forward primer, and for a reverse primer binding site, and qPCR hydrolysis probe binding. Read through of the polymerase during qPCR occurs only in circularized Ω-probes, which quantifies their number that is directly proportional to telomere length. When used in concert with information about the cell cycle stage from a single-copy gene, and ploidy, the MTL of single cells measured by ΩqPCR was consistent with that obtained from large sample sizes by TRF.},
}
@article {pmid34532917,
year = {2022},
author = {Bauch, C and Boonekamp, JJ and Korsten, P and Mulder, E and Verhulst, S},
title = {High heritability of telomere length and low heritability of telomere shortening in wild birds.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6308-6323},
pmid = {34532917},
issn = {1365-294X},
mesh = {Animals ; *Telomere Shortening/genetics ; Animals, Wild/genetics ; Birds/genetics ; Biological Evolution ; Telomere/genetics ; *Crows/genetics ; },
abstract = {Telomere length and telomere shortening predict survival in many organisms. This raises the question of the contribution of genetic and environmental effects to variation in these traits, which is still poorly known, particularly for telomere shortening. We used experimental (cross-fostering) and statistical (quantitative genetic "animal models") means to disentangle and estimate genetic and environmental contributions to telomere length variation in pedigreed free-living jackdaws (Corvus monedula). Telomere length was measured twice in nestlings, at ages 4 (n = 715) and 29 days (n = 474), using telomere restriction fragment (TRF) analysis, adapted to exclude interstitial telomeric sequences. Telomere length shortened significantly over the nestling period (10.4 ± 0.3 bp day[-1]) and was highly phenotypically (rP = 0.95 ± 0.01) and genetically (rG > 0.99 ± 0.01) correlated within individuals. Additive genetic effects explained a major part of telomere length variation among individuals, with its heritability estimated at h[2] = 0.74 on average. We note that TRF-based studies reported higher heritabilities than qPCR-based studies, and we discuss possible explanations. Parent-offspring regressions yielded similar heritability estimates for mothers and fathers when accounting for changes in paternal telomere length over life. Year effects explained a small but significant part of telomere length variation. Heritable variation for telomere shortening was low (h[2] = 0.09 ± 0.11). The difference in heritability between telomere length (high) and telomere shortening (low) agrees with evolutionary theory, in that telomere shortening has stronger fitness consequences in this population. Despite the high heritability of telomere length, its evolvability, which scales the additive genetic variance by mean telomere length, was on average 0.48%. Hence, evolutionary change of telomere length due to selection is likely to be slow.},
}
@article {pmid34532611,
year = {2021},
author = {Nassour, J and Schmidt, TT and Karlseder, J},
title = {Telomeres and Cancer: Resolving the Paradox.},
journal = {Annual review of cancer biology},
volume = {5},
number = {1},
pages = {59-77},
pmid = {34532611},
issn = {2472-3428},
support = {R01 CA227934/CA/NCI NIH HHS/United States ; R01 CA234047/CA/NCI NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; R01 CA228211/CA/NCI NIH HHS/United States ; K99 CA252447/CA/NCI NIH HHS/United States ; },
abstract = {Decades of study on cell cycle regulation have provided great insight into human cellular life span barriers, as well as their dysregulation during tumorigenesis. Telomeres, the extremities of linear chromosomes, perform an essential role in implementing these proliferative boundaries and preventing the propagation of potentially cancerous cells. The tumor-suppressive function of telomeres relies on their ability to initiate DNA damage signaling pathways and downstream cellular events, ranging from cell cycle perturbation to inflammation and cell death. While the tumor-suppressor role of telomeres is undoubtable, recent advances have pointed to telomeres as a major source of many of the genomic aberrations found in both early- and late-stage cancers, including the most recently discovered mutational phenomenon of chromothripsis. Telomere shortening appears as a double-edged sword that can function in opposing directions in carcinogenesis. This review focuses on the current knowledge of the dual role of telomeres in cancer and suggests a new perspective to reconcile the paradox of telomeres and their implications in cancer etiology.},
}
@article {pmid34531540,
year = {2022},
author = {Wang, L and Song, L and Liu, B and Zhang, L and Wu, M and Liu, Y and Bi, J and Yang, S and Cao, Z and Xia, W and Li, Y and Tian, Y and Zhang, B and Xu, S and Zhou, A and Wang, Y},
title = {Association between maternal urinary selenium during pregnancy and newborn telomere length: results from a birth cohort study.},
journal = {European journal of clinical nutrition},
volume = {76},
number = {5},
pages = {716-721},
pmid = {34531540},
issn = {1476-5640},
mesh = {Birth Cohort ; Child ; Cohort Studies ; Creatinine ; Female ; Humans ; Infant, Newborn ; *Maternal Exposure ; Mothers ; Pregnancy ; *Selenium ; Telomere ; },
abstract = {BACKGROUND: Newborn telomere length is considered as an effective predictor of lifespan and health outcomes in later life. Selenium is an essential trace element for human health, and its antioxidation is of great significance for the prevention of telomere erosion.<br><br>METHODS: We recruited 746 mother-newborn pairs in Wuhan Children's Hospital between 2013 and 2015. Urine samples were repeatedly collected at three time points during pregnancy, and umbilical cord blood samples were collected right after parturition. Urinary selenium concentration was detected using inductively coupled plasma mass spectrometry, and newborn telomere length was measured using quantitative real-time polymerase chain reaction. We applied general estimating equations to examine the trimester-specific association between maternal urinary selenium during pregnancy and newborn telomere length.<br><br>RESULTS: The median of creatinine-corrected selenium concentrations during pregnancy were 16.29, 18.08, and 18.35&#x2009;&#x3bc;g/g&#xb7;creatinine in the first, second, and third trimesters, respectively. Selenium concentrations in all the three trimesters were significantly associated with newborn telomere length. Per doubling of maternal urinary selenium concentrations was associated with 6.44% (95% CI: 0.92, 12.25), 6.54% (95% CI: 0.17, 13.31), and 6.02% (95% CI: 0.29, 12.09) longer newborn telomere length in the first, second, and third trimesters, respectively, after adjusting for potential confounders.<br><br>CONCLUSIONS: This is the first study to provide evidence for the effect of maternal selenium levels on fetal telomere erosion. Findings from our study suggested that maternal urinary selenium was positively associated with newborn telomere length, indicating that intrauterine selenium exposure might have effect on initial setting of human telomere length.},
}
@article {pmid34525499,
year = {2021},
author = {García-García, C and Shin, C and Baik, I},
title = {Association between body temperature and leukocyte telomere length in Korean middle-aged and older adults.},
journal = {Epidemiology and health},
volume = {43},
number = {},
pages = {e2021063},
pmid = {34525499},
issn = {2092-7193},
support = {2019R1A2C2084000)//National Research Foundation of Korea/ ; 2011-E71004-00//Korea Centers for Disease Control and Prevention/Republic of Korea ; 2012-E71005-00//Korea Centers for Disease Control and Prevention/Republic of Korea ; },
mesh = {Aged ; *Body Temperature ; Female ; Humans ; Leukocytes ; Longitudinal Studies ; Male ; Middle Aged ; Republic of Korea ; *Telomere/genetics ; Temperature ; },
abstract = {OBJECTIVES: Data on associations between body temperature (BT) and leukocyte telomere length (LTL), which has been widely used as a biomarker of cellular senescence in recent epidemiological studies, are limited. Therefore, this study aimed to explore the associations between a normal BT range (35.0-37.5°C) and LTL via 6-year longitudinal observations of 2,004 male and female adults aged 50 or older.<br><br>METHODS: BT was obtained by measuring the tympanic temperature, and relative LTL was determined by real-time polymerase chain reaction. Robust regression analysis was used to evaluate the association between the baseline and follow-up LTL values and their differences.<br><br>RESULTS: A significant inverse association was found between BT and LTL at baseline. The regression coefficient estimate was -0.03 (95% confidence interval, -0.07 to -0.001; p<0.05). This association was stronger in participants with a body mass index >25 kg/m2 and males (p<0.01). However, there were no associations between BT and LTL at follow-up or BT and 6-year longitudinal differences in LTL.<br><br>CONCLUSIONS: These findings suggest that having a high BT between 35&#xb0;C and 37.5&#xb0;C (95&#xb0;F and 99&#xb0;F) may be detrimental for obese individuals in terms of biological aging.},
}
@article {pmid34522616,
year = {2021},
author = {Roake, CM and Juntilla, M and Agarwal-Hashmi, R and Artandi, S and Kuo, CS},
title = {Tissue-specific telomere shortening and degenerative changes in a patient with TINF2 mutation and dyskeratosis congenita.},
journal = {Human pathology (New York)},
volume = {25},
number = {},
pages = {},
pmid = {34522616},
issn = {2214-3300},
support = {P30 CA124435/CA/NCI NIH HHS/United States ; R01 AG056575/AG/NIA NIH HHS/United States ; T32 GM007365/GM/NIGMS NIH HHS/United States ; },
abstract = {Dyskeratosis congenita is a disease of impaired tissue maintenance downstream of telomere dysfunction. Characteristically, patients present with the clinical triad of nail dystrophy, oral leukoplakia, and skin pigmentation defects, but the disease involves degenerative changes in multiple organs. Mutations in telomere-binding proteins such as TINF2 (TRF1-interacting nuclear factor 2) or in telomerase, the enzyme that counteracts age related telomere shortening, are causative in dyskeratosis congenita. We present a patient who presented with severe hypoxemia at age 13. The patient had a history of myelodysplastic syndrome treated with bone marrow transplant at the age of 5. At age 18 she was hospitalized for an acute pneumonia progressing to respiratory failure, developed renal failure and ultimately, she and her family opted to withdraw support as she was not a candidate for a lung transplant. Sequencing of the patient's TINF2 locus revealed a heterozygous mutation (c.844C > T, Arg282Cys) which has previously been reported in a subset of dyskeratosis congenita patients. Tissue sections from multiple organs showed degenerative changes including disorganized bone remodeling, diffuse alveolar damage and small vessel proliferation in the lung, and hyperkeratosis with hyperpigmentation of the skin. Autopsy samples revealed a bimodal distribution of telomere length, with telomeres from donor hematopoietic tissues being an age-appropriate length and those from patient tissues showing pathogenic shortening, with the shortest telomeres in lung, liver, and kidney. We report for the first time a survey of degenerative changes and telomere lengths in multiple organs in a patient with dyskeratosis congenita.},
}
@article {pmid34514660,
year = {2022},
author = {Ravindran, S and Froy, H and Underwood, SL and Dorrens, J and Seeker, LA and Watt, K and Wilbourn, RV and Pilkington, JG and Harrington, L and Pemberton, JM and Nussey, DH},
title = {The association between female reproductive performance and leukocyte telomere length in wild Soay sheep.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6184-6196},
doi = {10.1111/mec.16175},
pmid = {34514660},
issn = {1365-294X},
support = {BB/L020769/1 and University of Edinburgh Wellcome Trust PhD programme grant//Biotechnology and Biological Sciences Research Council/United Kingdom ; 108905/Z/15/Z//Wellcome Trust/United Kingdom ; },
mesh = {Animals ; Sheep/genetics ; Female ; *Longevity ; *Reproduction/genetics ; Telomere Shortening ; Leukocytes ; Telomere/genetics ; },
abstract = {Telomere length (TL), typically measured across a sample of blood cells, has emerged as an exciting potential marker of physiological state and of the costs of investment in growth and reproduction within evolutionary ecology. While there is mounting evidence from studies of wild vertebrates that short TL predicts raised subsequent mortality risk, the relationship between reproductive investment and TL is less clear cut, and previous studies report both negative and positive associations. In this study, we examined the relationship between TL and different aspects of maternal reproductive performance in a free-living population of Soay sheep. We find evidence for shorter TL in females that bred, and thus paid any costs of gestation, compared to females that did not breed. However, we found no evidence for any association between TL and litter size. Furthermore, females that invested in gestation and lactation actually had longer TL than females who only invested in gestation because their offspring died shortly after birth. We used multivariate models to decompose these associations into among- and within-individual effects, and discovered that within-individual effects were driving both the negative association between TL and gestation, and the positive association between TL and lactation. This suggests that telomere dynamics may reflect recent physiologically costly investment or variation in physiological condition, depending on the aspect of reproduction being investigated. Our results highlight the physiological complexity of vertebrate reproduction, and the need to better understand how and why different aspects of physiological variation underpinning life histories impact blood cell TL.},
}
@article {pmid34508574,
year = {2022},
author = {Dhillon, VS and Deo, P and Chua, A and Thomas, P and Fenech, M},
title = {Sleep Duration, Health Promotion Index, sRAGE, and ApoE-ε4 Genotype Are Associated With Telomere Length in Healthy Australians.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {77},
number = {2},
pages = {243-249},
doi = {10.1093/gerona/glab264},
pmid = {34508574},
issn = {1758-535X},
mesh = {*Apolipoprotein E4/genetics ; *Apolipoproteins E/genetics ; Australia ; Female ; Genotype ; Health Promotion ; Humans ; Male ; Middle Aged ; Receptor for Advanced Glycation End Products/genetics ; Sleep/genetics ; Telomere/genetics ; },
abstract = {Significant alterations in sleep duration and/or quality of sleep become more pronounced as people get older. Poor sleep in elderly people is associated with adverse health outcomes and cellular aging. We examined the relationship between telomere length (TL) and sleep duration, Health Promotion Index (HPI), and tested whether the presence of Apolipoprotein-E4 (ApoE-ε4) allele affects both sleep and TL. The present study was carried out in 174 healthy participants (21% male; mean age 53.79 years) from South Australia. Lymphocyte TL was measured by real-time quantitative PCR (qPCR) and ApoE genotype was determined by TaqMan assay. HPI was calculated from a questionnaire regarding 8 lifestyle habits, including sleeping hours. Multivariate regression analysis was used to establish these associations adjusted for specified confounders. TL was found to be inversely associated with age (r = -0.199; p = .008) and body mass index (r = -0.121; p = .11), and was significantly shorter in participants who slept for less than 7 hours (p = .001) relative to those sleeping ≥7 hours. TL was positively correlated with HPI (r = 0.195; p = .009). ApoE-ε4 allele carriers who slept for less than 7 hours had shortest TL (p = .01) compared to noncarriers. Plasma soluble receptor for advanced glycation end product (sRAGE) level was significantly (p = .001) lower in individuals who sleep less than 7 hours and ApoE-ε4 carriers. Our results suggest that inadequate sleep duration or poor HPI is associated with shorter TL in cognitively normal people and that carriage of APOE-ε4 genotype may influence the extent of these effects.},
}
@article {pmid34504179,
year = {2021},
author = {Shin, HK and Park, JH and Yu, JH and Jin, YJ and Suh, YJ and Lee, JW and Kim, W and , },
title = {Association between telomere length and hepatic fibrosis in non-alcoholic fatty liver disease.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {18004},
pmid = {34504179},
issn = {2045-2322},
mesh = {Adult ; Age Factors ; Aged ; Alanine Transaminase/blood ; Alkaline Phosphatase/blood ; Aspartate Aminotransferases/blood ; Cholesterol, HDL/blood ; Cross-Sectional Studies ; Female ; Humans ; Liver/metabolism/pathology ; Liver Cirrhosis/blood/diagnosis/*genetics/pathology ; Logistic Models ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/blood/diagnosis/*genetics/pathology ; Odds Ratio ; Severity of Illness Index ; Telomere/*chemistry ; *Telomere Homeostasis ; gamma-Glutamyltransferase/blood ; },
abstract = {Telomere length has been linked to the prevalence and progression of metabolic disease. However, clinical implications of telomere length in biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients remain unclear. Therefore, this study aimed to investigate the association of telomere length with the histological severity of NAFLD. The cross-sectional data derived from the prospectively enrolled Boramae NAFLD registry (n = 91) were analyzed. The liver tissues and clinical information were obtained from both NAFLD patients and non-NAFLD subjects. Binary logistic regression was performed to identify the independent association between telomere length and the histological severity of NAFLD. A total of 83 subjects with or without biopsy-proven NAFLD were included for analysis: non-NAFLD in 23 (27.7%), non-alcoholic fatty liver in 15 (18.1%), and non-alcoholic steatohepatitis (NASH) in 45 (54.2%). Telomere length measured from liver tissues showed a strong negative correlation (p < 0.001) with age, regardless of NAFLD status. Therefore, telomere length was corrected for age. Age-adjusted telomere length than decreased gradually with an increasing severity of fibrosis in patients with NAFLD (p < 0.028). In multivariate analysis, age-adjusted telomere length (odds ratio [OR] 0.59; 95% CI 0.37-0.92; p = 0.019) and high-density lipoprotein cholesterol (OR 0.94; 95% CI 0.80-0.99; p = 0.039) were independently associated with significant fibrosis. The age-adjusted telomere length tends to decrease along with the fibrosis stage of NAFLD. In particular, among the histological components of NAFLD, fibrosis severity seems to be related to telomere length in the liver.},
}
@article {pmid34494545,
year = {2021},
author = {Lin, A and Mertens, AN and Arnold, BF and Tan, S and Lin, J and Stewart, CP and Hubbard, AE and Ali, S and Benjamin-Chung, J and Shoab, AK and Rahman, MZ and Famida, SL and Hossen, MS and Mutsuddi, P and Akther, S and Rahman, M and Unicomb, L and Naved, RT and Mamun, MMA and Parvin, K and Dhabhar, FS and Kariger, P and Fernald, LC and Luby, SP and Colford, JM},
title = {Telomere length is associated with growth in children in rural Bangladesh.},
journal = {eLife},
volume = {10},
number = {},
pages = {},
pmid = {34494545},
issn = {2050-084X},
support = {K01 AI136885/AI/NIAID NIH HHS/United States ; },
mesh = {Bangladesh ; *Child Development ; Child, Preschool ; Cross-Sectional Studies ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Rural Population ; Telomere/*chemistry/metabolism ; *Telomere Homeostasis ; },
abstract = {BACKGROUND: Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth.<br><br>METHODS: We measured relative TL in whole blood from 713 children. We reported differences between the 10th percentile and 90th percentile of TL or change in TL distribution using generalized additive models, adjusted for potential confounders.<br><br>RESULTS: In cross-sectional analyses, long TL was associated with a higher length-for-age Z score at age 1 year (0.23 SD adjusted difference in length-for-age Z score [95% CI 0.05, 0.42; FDR-corrected p-value = 0.01]). TL was not associated with other outcomes.<br><br>CONCLUSIONS: Consistent with the metabolic telomere attrition hypothesis, our previous trial findings support an adaptive role for telomere attrition, whereby active TL regulation is employed as a strategy to address 'emergency states' with increased energy requirements such as rapid growth during the first year of life. Although short periods of active telomere attrition may be essential to promote growth, this study suggests that a longer overall initial TL setting in the first 2 years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories.<br><br>FUNDING: Funded by the Bill and Melinda Gates Foundation.<br><br>CLINICAL TRIAL NUMBER: NCT01590095.},
}
@article {pmid34493830,
year = {2021},
author = {Belser, C and Baurens, FC and Noel, B and Martin, G and Cruaud, C and Istace, B and Yahiaoui, N and Labadie, K and Hřibová, E and Doležel, J and Lemainque, A and Wincker, P and D'Hont, A and Aury, JM},
title = {Telomere-to-telomere gapless chromosomes of banana using nanopore sequencing.},
journal = {Communications biology},
volume = {4},
number = {1},
pages = {1047},
pmid = {34493830},
issn = {2399-3642},
support = {ANR-10-LABX-0001-01//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-10-INBS-09-08//Agence Nationale de la Recherche (French National Research Agency)/ ; },
mesh = {Chromosomes, Plant/*genetics ; *Genome, Plant ; Musa/*genetics ; Nanopore Sequencing ; Nanopores ; *Telomere ; },
abstract = {Long-read technologies hold the promise to obtain more complete genome assemblies and to make them easier. Coupled with long-range technologies, they can reveal the architecture of complex regions, like centromeres or rDNA clusters. These technologies also make it possible to know the complete organization of chromosomes, which remained complicated before even when using genetic maps. However, generating a gapless and telomere-to-telomere assembly is still not trivial, and requires a combination of several technologies and the choice of suitable software. Here, we report a chromosome-scale assembly of a banana genome (Musa acuminata) generated using Oxford Nanopore long-reads. We generated a genome coverage of 177X from a single PromethION flowcell with near 17X with reads longer than 75 kbp. From the 11 chromosomes, 5 were entirely reconstructed in a single contig from telomere to telomere, revealing for the first time the content of complex regions like centromeres or clusters of paralogous genes.},
}
@article {pmid34493579,
year = {2021},
author = {Shi, S and Zhou, Y and Lu, Y and Sun, H and Xue, J and Wu, Z and Lei, M},
title = {Ccq1-Raf2 interaction mediates CLRC recruitment to establish heterochromatin at telomeres.},
journal = {Life science alliance},
volume = {4},
number = {11},
pages = {},
pmid = {34493579},
issn = {2575-1077},
mesh = {Cell Cycle Proteins/genetics/metabolism ; Chromatin Assembly and Disassembly/*genetics/physiology ; Heterochromatin/metabolism ; Histone-Lysine N-Methyltransferase/genetics/metabolism ; Methylation ; Schizosaccharomyces/genetics/metabolism ; Schizosaccharomyces pombe Proteins/genetics/*metabolism ; Shelterin Complex/metabolism/physiology ; Telomere/metabolism ; },
abstract = {Telomeres, highly ordered DNA-protein complexes at eukaryotic linear chromosome ends, are specialized heterochromatin loci conserved among eukaryotes. In Schizosaccharomyces pombe, the shelterin complex is important for subtelomeric heterochromatin establishment. Despite shelterin has been demonstrated to mediate the recruitment of the Snf2/histone deacetylase-containing repressor complex (SHREC) and the Clr4 methyltransferase complex (CLRC) to telomeres, the mechanism involved in telomeric heterochromatin assembly remains elusive due to the multiple functions of the shelterin complex. Here, we found that CLRC plays a dominant role in heterochromatin establishment at telomeres. In addition, we identified a series of amino acids in the shelterin subunit Ccq1 that are important for the specific interaction between Ccq1 and the CLRC subunit Raf2. Finally, we demonstrated that the Ccq1-Raf2 interaction is essential for the recruitment of CLRC to telomeres, that contributes to histone H3 lysine 9 methylation, nucleosome stability and the shelterin-chromatin association, promoting a positive feedback mechanism for the nucleation and spreading of heterochromatin at subtelomeres. Together, our findings provide a mechanistic understanding of subtelomeric heterochromatin assembly by shelterin-dependent CLRC recruitment to chromosomal ends.},
}
@article {pmid34490122,
year = {2021},
author = {Rolles, B and Gorgulho, J and Tometten, M and Roderburg, C and Vieri, M and Abels, A and Vucur, M and Heymann, F and Tacke, F and Brümmendorf, TH and Luedde, T and Beier, F and Loosen, SH},
title = {Telomere Shortening in Peripheral Leukocytes Is Associated With Poor Survival in Cancer Patients Treated With Immune Checkpoint Inhibitor Therapy.},
journal = {Frontiers in oncology},
volume = {11},
number = {},
pages = {729207},
pmid = {34490122},
issn = {2234-943X},
abstract = {BACKGROUND: Immune checkpoint inhibitor (ICI) therapy represents a new standard of care for an increasing number of malignancies. Nevertheless, response rates and outcome of ICI treatment vary between individuals and the identification of predictive markers or hints towards immune cell exhaustion during therapy has remained a major challenge. Leukocyte telomere length is an established predictive biomarker of replicative aging and cellular proliferative potential in various hematological diseases. However, its relevance in the context of ICI therapy has not been investigated to date. Here, we analyze the age-adapted delta telomere length (ΔTL) of peripheral leukocytes as a potential predictive and prognostic marker in patients undergoing ICI therapy.<br><br>METHODS: Age-adapted delta telomere length (&#x394;TL) of 84 patients treated with ICIs for solid malignancies was measured via quantitative real-time PCR. &#x394;TL was correlated with outcome and clinical data.<br><br>RESULTS: &#x394;TL was not significantly altered between patients with different tumor entities or tumor stages and did not predict tumor response to ICI therapy. However, &#x394;TLs at initiation of treatment were a prognostic marker for overall survival (OS). When using a calculated ideal cut-off value, the median OS in patients with shorter &#x394;TL was 5.7 months compared to 18.0 months in patients showing longer &#x394;TL. The prognostic role of age-adapted &#x394;TL was further confirmed by uni- and multivariate Cox-regression analyses.<br><br>CONCLUSION: In the present study, we demonstrate that shorter telomere lengths in peripheral blood leukocytes are associated with a significantly impaired outcome in patients receiving ICI therapy across different malignancies. We explain our findings by hypothesizing an older replicative age in peripheral leukocytes of patients with an impaired overall survival, reflected by a premature TL shortening. Whether this association is ICI-specific remains unknown. Further follow-up studies are needed to provide insights about the exact mechanism of how shortened telomeres eventually affect OS and could help guiding therapeutic decisions in future.},
}
@article {pmid34488828,
year = {2021},
author = {Yang, L and Wang, B and Jiao, X and Zhou, C and Chen, S and Gao, X and Sun, W and Song, S and Li, J and Liu, J and Wang, Y and Liu, P},
title = {TAZ maintains telomere length in TNBC cells by mediating Rad51C expression.},
journal = {Breast cancer research : BCR},
volume = {23},
number = {1},
pages = {89},
pmid = {34488828},
issn = {1465-542X},
mesh = {Cell Line, Tumor ; Cell Proliferation/genetics ; Cellular Senescence/genetics ; DNA Damage/genetics ; DNA-Binding Proteins/*genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Shelterin Complex/genetics/metabolism ; Telomerase/genetics/metabolism ; Telomere/genetics/metabolism/pathology ; Telomere Homeostasis/*genetics ; Telomere Shortening/genetics ; Transcription Factors/genetics ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/genetics/*metabolism ; Triple Negative Breast Neoplasms/*genetics/pathology ; },
abstract = {BACKGROUND: Telomere maintenance is crucial for the unlimited proliferation of cancer cells and essential for the "stemness" of multiple cancer cells. TAZ is more extensively expressed in triple negative breast cancers (TNBC) than in other types of breast cancers, and promotes proliferation, transformation and EMT of cancer cells. It was reported that TAZ renders breast cancer cells with cancer stem cell features. However, whether TAZ regulates telomeres is still unclear. In this study, we explored the roles of TAZ in the regulation of telomere maintenance in TNBC cells.<br><br>METHODS: siRNA and shRNA was used to generate TAZ-depleted TNBC cell lines. qPCR and Southern analysis of terminal restriction fragments techniques were used to test telomere length. Co-immunoprecipitation, Western blotting, immunofluorescence, Luciferase reporter assay and Chromatin-IP were conducted to investigate the underlying mechanism.<br><br>RESULTS: By knocking down the expression of TAZ in TNBC cells, we found, for the first time, that TAZ is essential for the maintenance of telomeres in TNBC cells. Moreover, loss of TAZ causes senescence phenotype of TNBC cells. The observed extremely shortened telomeres in late passages of TAZ knocked down cells correlate with an elevated hTERT expression, reductions of shelterin proteins, and an activated DNA damage response pathway. Our data also showed that depletion of TAZ results in overexpression of TERRAs, which are a group of telomeric repeat-containing RNAs and regulate telomere length and integrity. Furthermore, we discovered that TAZ maintains telomere length of TNBC cells likely by facilitating the expression of Rad51C, a crucial element of homologous recombination pathway that promotes telomere replication.<br><br>CONCLUSIONS: This study supports the notion that TAZ is an oncogenic factor in TNBC, and further reveals a novel telomere-related pathway that is employed by TAZ to regulate TNBC.},
}
@article {pmid34486664,
year = {2021},
author = {Dogan, F and Forsyth, NR},
title = {Epigenetic features in regulation of telomeres and telomerase in stem cells.},
journal = {Emerging topics in life sciences},
volume = {5},
number = {4},
pages = {497-505},
doi = {10.1042/ETLS20200344},
pmid = {34486664},
issn = {2397-8554},
mesh = {Cellular Senescence ; Epigenesis, Genetic ; *Pluripotent Stem Cells/metabolism ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {The epigenetic nature of telomeres is still controversial and different human cell lines might show diverse histone marks at telomeres. Epigenetic modifications regulate telomere length and telomerase activity that influence telomere structure and maintenance. Telomerase is responsible for telomere elongation and maintenance and is minimally composed of the catalytic protein component, telomerase reverse transcriptase (TERT) and template forming RNA component, telomerase RNA (TERC). TERT promoter mutations may underpin some telomerase activation but regulation of the gene is not completely understood due to the complex interplay of epigenetic, transcriptional, and posttranscriptional modifications. Pluripotent stem cells (PSCs) can maintain an indefinite, immortal, proliferation potential through their endogenous telomerase activity, maintenance of telomere length, and a bypass of replicative senescence in vitro. Differentiation of PSCs results in silencing of the TERT gene and an overall reversion to a mortal, somatic cell phenotype. The precise mechanisms for this controlled transcriptional silencing are complex. Promoter methylation has been suggested to be associated with epigenetic control of telomerase regulation which presents an important prospect for understanding cancer and stem cell biology. Control of down-regulation of telomerase during differentiation of PSCs provides a convenient model for the study of its endogenous regulation. Telomerase reactivation has the potential to reverse tissue degeneration, drive repair, and form a component of future tissue engineering strategies. Taken together it becomes clear that PSCs provide a unique system to understand telomerase regulation fully and drive this knowledge forward into aging and therapeutic application.},
}
@article {pmid34486523,
year = {2021},
author = {Hu, K and Ghandi, M and Huang, FW},
title = {Integrated evaluation of telomerase activation and telomere maintenance across cancer cell lines.},
journal = {eLife},
volume = {10},
number = {},
pages = {},
pmid = {34486523},
issn = {2050-084X},
mesh = {Cell Line, Tumor ; Epigenesis, Genetic ; Humans ; Neoplasms/genetics ; Telomerase/genetics/*metabolism ; Telomere/*metabolism ; *Telomere Homeostasis ; },
abstract = {In cancer, telomere maintenance is critical for the development of replicative immortality. Using genome sequences from the Cancer Cell Line Encyclopedia and Genomics of Drug Sensitivity in Cancer Project, we calculated telomere content across 1299 cancer cell lines. We find that telomerase reverse transcriptase (TERT) expression correlates with telomere content in lung, central nervous system, and leukemia cell lines. Using CRISPR/Cas9 screening data, we show that lower telomeric content is associated with dependency of CST telomere maintenance genes. Increased dependencies of shelterin members are associated with wild-type TP53 status. Investigating the epigenetic regulation of TERT, we find widespread allele-specific expression in promoter-wildtype contexts. TERT promoter-mutant cell lines exhibit hypomethylation at PRC2-repressed regions, suggesting a cooperative global epigenetic state in the reactivation of telomerase. By incorporating telomere content with genomic features across comprehensively characterized cell lines, we provide further insights into the role of telomere regulation in cancer immortality.},
}
@article {pmid34484375,
year = {2021},
author = {Peng, X and Huang, J and Xia, S and Yang, Y and Dong, K},
title = {Association of leukocyte telomere length with metabolic syndrome in type 2 diabetes mellitus.},
journal = {Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences},
volume = {26},
number = {},
pages = {43},
pmid = {34484375},
issn = {1735-1995},
abstract = {BACKGROUND: Leukocyte telomere length (LTL) has been revealed to be associated with aging-related diseases such as metabolic syndrome (MetS) and Type 2 diabetes mellitus (T2DM). We aimed to investigate the correlation of LTL with MetS and its components in T2DM patients in this cross-sectional study.<br><br>MATERIALS AND METHODS: A total of 344 T2DM patients were enrolled into this study. LTL was measured by Southern blot-based terminal restriction fragment length analysis. MetS was clinically defined by 2007 Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults.<br><br>RESULTS: Of 344 T2DM patients, 53% had MetS. T2DM patients with MetS had significantly longer LTL than those without MetS (6451.95 &#xb1; 51.10 base pairs vs. 6076.13 &#xb1; 55.13 base pairs, P < 0.001), especially when T2DM patients had poor glycemic control (hemoglobin A1c &#x2265;7%). Meanwhile, the trend of longer LTL was associated with the increased components of MetS in T2DM patient. Finally, LTL had a significant association with MetS (odds ratio [OR]: 2.096, 95% confidence interval [CI] 1.337-3.285, P = 0.001), low levels of high-density lipoprotein-cholesterol (HDL-C) (OR: 2.412, 95% CI 1.350-4.308, P = 0.003) in T2DM patients.<br><br>CONCLUSION: T2DM patients with MetS had a significantly longer LTL than those without MetS. The longer LTL was especially evident in T2DM patients with poor glycemic control. Longer LTL was positively associated with MetS, particularly low levels of HDL-C in T2DM patients.},
}
@article {pmid34482039,
year = {2021},
author = {Darvishi, FZ and Saadat, M},
title = {Morphine treatment is associated with diminished telomere length together with down-regulated TERT and TERF2 mRNA levels.},
journal = {Drug and alcohol dependence},
volume = {227},
number = {},
pages = {108982},
doi = {10.1016/j.drugalcdep.2021.108982},
pmid = {34482039},
issn = {1879-0046},
mesh = {Down-Regulation ; Humans ; Morphine/pharmacology ; RNA, Messenger/genetics ; *Telomerase/genetics/metabolism ; *Telomere/genetics/metabolism ; Telomeric Repeat Binding Protein 2 ; },
abstract = {BACKGROUND: Drug dependence promotes accelerated aging and higher mortality compare with the general population. Telomere length is a biomarker of determination of cellular aging. Telomere attrition has been reported in heroin dependent patients. To investigate whether telomere length is affected by morphine or not, the expressions of hTERT and TERF2 in morphine treated human SH-SY5Y cells were determined and compared with untreated cells.<br><br>METHODS: The SH-SY5Y cells were treated with 1 and 5&#x2009;&#x3bc;M concentrations of morphine for different exposure times (1d, 2d, 3d, 7d and 60 days). The mRNA levels of hTERT and TERF2 were determined using quantitative real-time RCR. The relative telomere length was measured as the ratio of telomere/36B4.<br><br>RESULTS: The hTERT and TERF2 mRNA levels were down regulated in morphine treated cells as a function of exposure duration. These alterations were reversible if morphine was removed from the culture medium. No reduction in the relative expression of hTERT and TERF2 in the cells exposed to N-acetyl cysteine (NAC) plus morphine was observed. In the SH-SY5Y cells treated by 5&#x2009;&#x3bc;M morphine for 60 consecutive days, the hTERT and TERF2 mRNA levels and relative telomere lengths remarkably decreased.<br><br>CONCLUSIONS: Reversible alteration of mRNA levels by removing morphine from culture medium, and effect of NAC in co-treatment of morphine plus NAC, emphasize the role of reactive oxygen species in down-regulation of the expression of hTERT and TERF2 by morphine. Telomere attrition in morphine treated cells is a consequence of down-regulation of the expression of hTERT and TERF2.},
}
@article {pmid34478576,
year = {2022},
author = {Atema, E and van Noordwijk, AJ and Verhulst, S},
title = {Telomere dynamics in relation to experimentally increased locomotion costs and fitness in great tits.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6208-6215},
pmid = {34478576},
issn = {1365-294X},
mesh = {Animals ; Male ; *Aging ; Ecology ; *Passeriformes ; *Telomere/genetics ; Telomere Shortening/genetics ; },
abstract = {Evidence that telomere length (TL) and dynamics can be interpreted as proxy for 'life stress' experienced by individuals stems largely from correlational studies. We tested for effects of an experimental increase of workload on telomere dynamics by equipping male great tits (Parus major) with a 0.9 g backpack for a full year. In addition, we analysed associations between natural life-history variation, TL and TL dynamics. Carrying 5% extra weight for a year did not significantly accelerate telomere attrition. This agrees with our earlier finding that this experiment did not affect survival or future reproduction. Apparently, great tit males were able to compensate behaviourally or physiologically for the increase in locomotion costs we imposed. We found no cross-sectional association between reproductive success and TL, but individuals with higher reproductive success (number of recruits) lost fewer telomere base pairs in the subsequent year. We used the TRF method to measure TL, which method yields a TL distribution for each sample, and the association between reproductive success and telomere loss was more pronounced in the higher percentiles of the telomere distribution, in agreement with the higher impact of ageing on longer telomeres within individuals. Individuals with longer telomeres and less telomere shortening were more likely to survive to the next breeding season, but these patterns did not reach statistical significance. Whether successful individuals are characterized by losing fewer or more base pairs from their telomeres varies between species, and we discuss aspects of ecology and social organisation that may explain this variation.},
}
@article {pmid34477880,
year = {2022},
author = {Saunders, CN and Kinnersley, B and Culliford, R and Cornish, AJ and Law, PJ and Houlston, RS},
title = {Relationship between genetically determined telomere length and glioma risk.},
journal = {Neuro-oncology},
volume = {24},
number = {2},
pages = {171-181},
pmid = {34477880},
issn = {1523-5866},
support = {C1298/A8362//Cancer Research UK/United Kingdom ; },
mesh = {*Genome-Wide Association Study ; *Glioma/genetics/metabolism ; Humans ; Leukocytes/metabolism ; Polymorphism, Single Nucleotide ; Risk Factors ; Telomere/genetics ; Telomere Homeostasis/genetics ; },
abstract = {BACKGROUND: Telomere maintenance is increasingly recognized as being fundamental to glioma oncogenesis with longer leukocyte telomere length (LTL) reported to increase risk of glioma. To gain further insight into the relationship between telomere genetics and risk of glioma, we conducted several complementary analyses, using genome-wide association studies data on LTL (78 592 individuals) and glioma (12 488 cases and 18 169 controls).<br><br>METHODS: We performed both classical and summary Mendelian randomization (SMR), coupled with heterogeneity in dependent instruments tests, at genome-wide significant LTL loci to examine if an association was mediated by the same causal variant in glioma. To prioritize genes underscoring glioma-LTL associations, we analyzed gene expression and DNA methylation data.<br><br>RESULTS: Genetically increased LTL was significantly associated with increased glioma risk, random-effects inverse variance weighted ORs per 1 SD unit increase in the putative risk factor (odds ratio [OR]SD) 4.79 (95% confidence interval: 2.11-10.85; P = 1.76 &#xd7; 10-4). SMR confirmed the previously reported LTL associations at 3q26.2 (TERC; PSMR = 1.33 &#xd7; 10-5), 5p15.33 (TERT; PSMR = 9.80 &#xd7; 10-27), 10q24.33 (STN1 alias OBFC1; PSMR = 4.31 &#xd7; 10-5), and 20q13.3 (STMN3/RTEL1; PSMR = 2.47 &#xd7; 10-4) glioma risk loci. Our analysis implicates variation at 1q42.12 (PSMR = 1.55 &#xd7; 10-2), 6p21.3 (PSMR = 9.76 &#xd7; 10-3), 6p22.2 (PSMR = 5.45 &#xd7; 10-3), 7q31.33 (PSMR = 6.52 &#xd7; 10-3), and 11q22.3 (PSMR = 8.89 &#xd7; 10-4) as risk factors for glioma risk. While complicated by patterns of linkage disequilibrium, genetic variation involving PARP1, PRRC2A, CARMIL1, POT1, and ATM-NPAT1 was implicated in the etiology of glioma.<br><br>CONCLUSIONS: These observations extend the role of telomere-related genes in the development of glioma.},
}
@article {pmid34477845,
year = {2021},
author = {Purdue-Smithe, AC and Kim, K and Andriessen, VC and Pollack, AZ and Sjaarda, LA and Silver, RM and Schisterman, EF and Mumford, SL},
title = {Preconception leukocyte telomere length and pregnancy outcomes among women with demonstrated fecundity.},
journal = {Human reproduction (Oxford, England)},
volume = {36},
number = {12},
pages = {3122-3130},
pmid = {34477845},
issn = {1460-2350},
mesh = {Adolescent ; Adult ; Aged ; Cross-Sectional Studies ; Female ; *Fertility ; Humans ; Leukocytes ; Pregnancy ; *Pregnancy Outcome ; Prospective Studies ; Telomere ; Young Adult ; },
abstract = {STUDY QUESTION: Is preconception leukocyte telomere length associated with fecundability, pregnancy loss and live birth among women attempting natural conception with a history of 1-2 prior pregnancy losses?<br><br>SUMMARY ANSWER: Preconception leukocyte telomere length is not associated with fecundability, pregnancy loss or live birth.<br><br>WHAT IS KNOWN ALREADY: As women increasingly delay childbearing, accessible preconception biomarkers to predict pregnancy outcomes among women seeking natural conception could improve preconception counseling. Findings of small case-control or cross-sectional studies suggest that telomere attrition is associated with adverse pregnancy outcomes among women undergoing fertility treatment, but prospective studies in non-clinical populations are lacking.<br><br>STUDY DESIGN, SIZE, DURATION: Participants included 1228 women aged 18-40&#x2009;years with a history of 1-2 prior pregnancy losses who were recruited at four university medical centers (2006-2012).<br><br>Preconception leukocyte telomere length was measured at baseline using PCR and reported as a ratio (T/S) in relation to population-specific standard reference DNA. Women were followed for up to six cycles while attempting to conceive. Associations of telomere length with fecundability, live birth and pregnancy loss were estimated using discrete Cox proportional hazards models and log-binomial models.<br><br>After adjustment for age, BMI, smoking and other factors, preconception telomere length was not associated with fecundability (Q4 vs Q1 FOR = 1.00; 95% CI = 0.79, 1.27), live birth (Q4 vs Q1 RR = 1.00; 95% CI = 0.85, 1.19), or pregnancy loss (Q4 vs Q1 RR = 1.12; 95% CI = 0.78, 1.62).<br><br>Telomere length was measured in leukocytes, which is an accessible tissue in women attempting natural conception but may not reflect telomere length in oocytes. Most women were younger than 35&#x2009;years, limiting our ability to evaluate associations among older women. Participants had a history of 1-2 prior pregnancy losses; therefore, our findings may not be widely generalizable.<br><br>Despite prior research suggesting that telomere length may be associated with pregnancy outcomes among women seeking fertility treatment, our findings suggest that leukocyte telomere length is not a suitable biomarker of pregnancy establishment or maintenance among women attempting natural conception.<br><br>This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (National Institutes of Health, Bethesda, MD, USA; contract numbers HHSN267200603423, HHSN267200603424 and HHSN267200603426). The authors have no conflicts of interest to disclose.<br><br>TRIAL REGISTRATION NUMBER: The trial was registered with ClinicalTrials.gov, number NCT00467363.},
}
@article {pmid34469544,
year = {2021},
author = {Pennarun, G and Picotto, J and Etourneaud, L and Redavid, AR and Certain, A and Gauthier, LR and Fontanilla-Ramirez, P and Busso, D and Chabance-Okumura, C and Thézé, B and Boussin, FD and Bertrand, P},
title = {Increase in lamin B1 promotes telomere instability by disrupting the shelterin complex in human cells.},
journal = {Nucleic acids research},
volume = {49},
number = {17},
pages = {9886-9905},
pmid = {34469544},
issn = {1362-4962},
mesh = {Cells, Cultured ; Humans ; Lamin Type B/chemistry/*metabolism ; Shelterin Complex/*metabolism ; Telomere/*metabolism ; Telomere-Binding Proteins/metabolism ; Telomeric Repeat Binding Protein 2/chemistry/*metabolism ; },
abstract = {Telomere maintenance is essential to preserve genomic stability and involves telomere-specific proteins, DNA replication and repair proteins. Lamins are key components of the nuclear envelope and play numerous roles, including maintenance of the nuclear integrity, regulation of transcription, and DNA replication. Elevated levels of lamin B1, one of the major lamins, have been observed in some human pathologies and several cancers. Yet, the effect of lamin B1 dysregulation on telomere maintenance remains unknown. Here, we unveil that lamin B1 overexpression drives telomere instability through the disruption of the shelterin complex. Indeed, lamin B1 dysregulation leads to an increase in telomere dysfunction-induced foci, telomeric fusions and telomere losses in human cells. Telomere aberrations were preceded by mislocalizations of TRF2 and its binding partner RAP1. Interestingly, we identified new interactions between lamin B1 and these shelterin proteins, which are strongly enhanced at the nuclear periphery upon lamin B1 overexpression. Importantly, chromosomal fusions induced by lamin B1 in excess were rescued by TRF2 overexpression. These data indicated that lamin B1 overexpression triggers telomere instability through a mislocalization of TRF2. Altogether our results point to lamin B1 as a new interacting partner of TRF2, that is involved in telomere stability.},
}
@article {pmid34468230,
year = {2023},
author = {Zadeh, FA and Bokov, DO and Yasin, G and Vahdat, S and Abbasalizad-Farhangi, M},
title = {Central obesity accelerates leukocyte telomere length (LTL) shortening in apparently healthy adults: A systematic review and meta-analysis.},
journal = {Critical reviews in food science and nutrition},
volume = {63},
number = {14},
pages = {2119-2128},
doi = {10.1080/10408398.2021.1971155},
pmid = {34468230},
issn = {1549-7852},
mesh = {Humans ; Adult ; *Obesity, Abdominal ; Risk Factors ; Body Mass Index ; *Obesity ; Leukocytes ; Telomere ; },
abstract = {Shorter telomere length is associated with numerous comorbidities; central obesity might trigger leukocyte telomere shortening; in the current meta-analysis we evaluated the association of central obesity with leukocyte telomere length among adults. A systematic search from Scopus, PubMed, Embase and Proquest electronic databases up to May 2021 was done. The final screening, provided five articles to be included in final meta-analysis. Those in the highest category of telomere length had 3.72 cm lower waist circumference (WC) compared with those in the lowest category (WMD=-3.718; CI=-7.180, -0.257 P = 0.035; I[2] = 95.4%). Also, those in the highest LTL category had 0.02 lower waist to hip ratio (WHR) compared with those in the lowest category, although this association was not significant (WMD: -0.02; CI=-0.04, 0.01; P = 0.19; I[2]= 90.7%). In quality assessment of included studies, all of the studies had moderate or high quality score and there was no study with poor quality. Higher leukocyte telomere length was accompanied with lower WC among adults. This association was not significant for difference in WHR. Because of the high heterogeneity values and also because of the observational design of included studies, the inference of causality of these associations needs further investigations.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1971155 .},
}
@article {pmid34458916,
year = {2021},
author = {Hailu, EM and Lewis, TT and Needham, BL and Lin, J and Seeman, TE and Mujahid, MS},
title = {Longitudinal Associations Between Discrimination, Neighborhood Social Cohesion, and Telomere Length: The Multi-Ethnic Study of Atherosclerosis.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/gerona/glab193},
pmid = {34458916},
issn = {1758-535X},
support = {T32 HD101364/HD/NICHD NIH HHS/United States ; R01HL101161/NH/NIH HHS/United States ; N01-HC-95159/HL/NHLBI NIH HHS/United States ; },
abstract = {BACKGROUND: We aimed to examine if neighborhood social cohesion moderated longitudinal associations between baseline reports of discrimination and 10-year changes in leukocyte telomere length (LTL).<br><br>METHODS: Data are from the Multi-Ethnic Study of Atherosclerosis (N = 1064; age range 45-84 years). Baseline discrimination was measured using the Major Experiences of Discrimination Scale (MDS; none, 1 domain, &#x2265;2 domains) and the Experiences of Discrimination Scale (EDS; none, moderate, high). Neighborhood social cohesion at baseline was assessed via a community survey within census tract-defined neighborhoods. 10-year change in LTL was defined as regression to the mean-corrected 10-year difference in the ratio of telomeric DNA to a single-copy gene (T/S).<br><br>RESULTS: In linear mixed-effects models, we found that neighborhood social cohesion modified the effect of baseline reports of MDS on 10-year changes in LTL, independent of sociodemographic characteristics, health behaviors, and health conditions (p(&#x3c7;&#x200a;2) = .01). Among those residing in neighborhoods with low social cohesion, experiencing major discrimination in &#x2265;2 domains was associated with faster LTL attrition over 10 years, compared to reporting no discrimination (&#x3b2; = -0.03; 95% confidence interval: -0.06, -0.003). We found no main associations for either discrimination measure and no interaction between EDS and neighborhood social cohesion.<br><br>CONCLUSIONS: Results indicate that neighborhood social cohesion is an important dimension of the neighborhood context that may moderate the impact of major experiences of discrimination on telomere length attrition. These findings help advance our understanding of the integral role that neighborhood environments play in attenuating the effect of discrimination on accelerated cell aging.},
}
@article {pmid34455645,
year = {2022},
author = {Kärkkäinen, T and Briga, M and Laaksonen, T and Stier, A},
title = {Within-individual repeatability in telomere length: A meta-analysis in nonmammalian vertebrates.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6339-6359},
doi = {10.1111/mec.16155},
pmid = {34455645},
issn = {1365-294X},
mesh = {Animals ; Phylogeny ; *Telomere/genetics ; *Vertebrates/genetics ; Biomarkers ; Telomere Shortening ; },
abstract = {Telomere length is increasingly used as a biomarker of long-term somatic state and future survival prospects. While most studies have overlooked this aspect, biological interpretations based on a given telomere length will benefit from considering the level of within-individual repeatability of telomere length through time. Therefore, we conducted a meta-analysis on 74 longitudinal studies in nonmammalian vertebrates, with the aim to establish the current pattern of within-individual repeatability in telomere length and to identify the methodological (e.g., qPCR/TRF) and biological factors (e.g., age class, phylogeny) that may affect it. While the median within-individual repeatability of telomere length was moderate to high (R = 0.55; 95% CI: 0.05-0.95; N = 82), marked heterogeneity between studies was evident. Measurement method affected the repeatability estimate strongly, with TRF-based studies exhibiting high repeatability (R = 0.80; 95% CI: 0.34-0.96; N = 25), while repeatability of qPCR-based studies was markedly lower and more variable (R = 0.46; 95% CI: 0.04-0.82; N = 57). While phylogeny explained some variance in repeatability, phylogenetic signal was not significant (λ = 0.32; 95% CI: 0.00-0.83). None of the biological factors investigated here significantly explained variation in the repeatability of telomere length, being potentially obscured by methodological differences. Our meta-analysis highlights the high variability in within-individual repeatability estimates between studies and the need to put more effort into separating technical and biological explanations. This is important to better understand to what extent biological factors can affect the repeatability of telomere length and thus the interpretation of telomere length data.},
}
@article {pmid34454696,
year = {2021},
author = {Bolzán, AD},
title = {Mutagen-induced telomere instability in human cells.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {868-869},
number = {},
pages = {503387},
doi = {10.1016/j.mrgentox.2021.503387},
pmid = {34454696},
issn = {1879-3592},
mesh = {Animals ; Cellular Senescence/drug effects/genetics ; Chromosomal Instability/*drug effects/genetics ; DNA/genetics ; DNA Breaks, Double-Stranded/drug effects ; Genomic Instability/*drug effects/genetics ; Humans ; Mutagens/*toxicity ; Telomere/*drug effects/genetics ; },
abstract = {Telomere instability is one of the main sources of genome instability and may result from chromosome end loss (due to chromosome breakage at one or both ends) or, more frequently, telomere dysfunction. Dysfunctional telomeres arise when they lose their end-capping function or become critically short, which causes chromosomal termini to behave like a DNA double-strand break. Telomere instability may occur at the chromosomal or at the molecular level, giving rise, respectively, to telomere-related chromosomal aberrations or the loss or modification of any of the components of the telomere (telomere DNA, telomere-associated proteins, or telomere RNA). Since telomeres play a fundamental role in maintaining genome stability, the study of telomere instability in cells exposed to mutagens is of great importance to understand the telomere-driven genomic instability present in those cells. In the present review, we will focus on the current knowledge about telomere instability induced by physical, chemical, and biological mutagens in human cells.},
}
@article {pmid34454691,
year = {2021},
author = {Bull, C and Mayrhofer, G and Fenech, M},
title = {Exposure to hypomethylating 5-aza-2'-deoxycytidine (decitabine) causes rapid, severe DNA damage, telomere elongation and mitotic dysfunction in human WIL2-NS cells.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {868-869},
number = {},
pages = {503385},
doi = {10.1016/j.mrgentox.2021.503385},
pmid = {34454691},
issn = {1879-3592},
mesh = {Biomarkers/metabolism ; Cell Line ; Chromosomal Instability/drug effects ; Cytokinesis/drug effects ; DNA Damage/*drug effects ; DNA Methylation/*drug effects ; Decitabine/*pharmacology ; Humans ; Lymphocytes/drug effects ; Micronucleus Tests/methods ; Mitosis/drug effects ; Telomere/*drug effects ; },
abstract = {BACKGROUND: 5-aza-2'-deoxycytidine (5azadC, decitabine) is a DNA hypomethylating agent used in the treatment of myelodysplastic syndromes. Due to cytotoxic side effects dose optimization is essential. The aim of this study was to define and quantify the effects of 5azadC on biomarkers of chromosomal stability, and telomere length, in human lymphoblastoid cell line, WIL2-NS, at clinically relevant dosages.<br><br>METHODS: Human WIL2-NS cells were maintained in complete medium containing 0, 0.2 or 1.0 &#x3bc;M 5azadC for four days, and analysed daily for telomere length (flow cytometry), chromosomal stability (cytokinesis-block micronucleus cytome (CBMN-cyt) assay), and global methylation (%5me-C).<br><br>RESULTS: DNA methylation decreased significantly in 1.0 &#x3bc;M 5azadC, relative to control (p < 0.0001). Exposure to 1.0 &#x3bc;M 5azadC resulted in 1.7-fold increase in telomere length (p < 0.0001), in parallel with rapid increase in biomarkers of DNA damage; (micronuclei (MN, 6-fold increase), nucleoplasmic bridges (NPB, a 12-fold increase), and nuclear buds (NBud, a 13-fold increase) (all p < 0.0001). Fused nuclei (FUS), indicative of mitotic dysfunction, showed a 5- and 13-fold increase in the 0.2 &#x3bc;M and 1.0 &#x3bc;M conditions, respectively (p = 0.001) after 4 days.<br><br>CONCLUSIONS: These data show that (i) clinically relevant concentrations of 5azadC are highly genotoxic; (ii) hypomethylation was associated with increased TL and DNA damage; and (iii) longer TL was associated with chromosomal instability. These findings suggest that lower doses of 5azdC may be effective as a hypomethylating agent, while potentially reducing DNA damage and risk for secondary disease.},
}
@article {pmid34454526,
year = {2021},
author = {Clarity, C and Trowbridge, J and Gerona, R and Ona, K and McMaster, M and Bessonneau, V and Rudel, R and Buren, H and Morello-Frosch, R},
title = {Associations between polyfluoroalkyl substance and organophosphate flame retardant exposures and telomere length in a cohort of women firefighters and office workers in San Francisco.},
journal = {Environmental health : a global access science source},
volume = {20},
number = {1},
pages = {97},
pmid = {34454526},
issn = {1476-069X},
support = {R01 ES027051/ES/NIEHS NIH HHS/United States ; T42 OH008429/OH/NIOSH CDC HHS/United States ; },
mesh = {Adult ; Biological Monitoring ; Cohort Studies ; Fatty Acids/*blood ; Female ; *Firefighters ; Flame Retardants/*analysis ; Fluorocarbons/*blood ; Humans ; Leukocytes/metabolism ; Middle Aged ; Occupational Exposure/analysis ; Organophosphates/*urine ; San Francisco ; Sulfonic Acids/*blood ; *Telomere ; },
abstract = {BACKGROUND: Environmental chemical exposures can affect telomere length, which in turn has been associated with adverse health outcomes including cancer. Firefighters are occupationally exposed to many hazardous chemicals and have higher rates of certain cancers. As a potential biomarker of effect, we assessed associations between chemical exposures and telomere length in women firefighters and office workers from San Francisco, CA.<br><br>METHODS: We measured serum concentrations of polyfluoroalkyl substances (PFAS), urinary metabolites of flame retardants, including organophosphate flame retardants (OPFRs), and telomere length in peripheral blood leukocytes in women firefighters (N&#xa0;=&#x2009;84) and office workers (N&#xa0;=&#x2009;79) who participated in the 2014-15 Women Workers Biomonitoring Collaborative. Multiple linear regression models were used to assess associations between chemical exposures and telomere length.<br><br>RESULTS: Regression results revealed significant positive associations between perfluorooctanoic acid (PFOA) and telomere length and perfluorooctanesulfonic acid (PFOS) and telomere length among the whole cohort. Models stratified by occupation showed stronger and more significant associations among firefighters as compared to office workers. Among firefighters in models adjusted for age, we found positive associations between telomere length and log-transformed PFOA (&#x3b2; (95%CI)&#x2009;=&#x2009;0.57(0.12, 1.02)), PFOS (0.44 (0.05, 0.83)), and perfluorodecanoic acid (PFDA) (0.43 (0.02, 0.84)). Modeling PFAS as categories of exposure showed significant associations between perfluorononanoic acid (PFNA) and telomere length among firefighters. Significant associations between OPFR metabolites and telomere length were seen for bis (1,3-dichloro-2-propyl) phosphate (BDCPP) and telomere length among office workers (0.21(0.03, 0.40)) and bis (2-chloroethyl) phosphate (BCEP) and telomere length among firefighters (-&#x2009;0.14(-&#x2009;0.28, -&#x2009;0.01)). For OPFRs, the difference in the direction of effect by occupational group may be due to the disparate detection frequencies and concentrations of exposure between the two groups and/or potential unmeasured confounding.<br><br>CONCLUSION: Our findings suggest positive associations between PFAS and telomere length in women workers, with larger effects seen among firefighters as compared to office workers. The OPFR metabolites BDCPP and BCEP are also associated with telomere length in firefighters and office workers. Associations between chemical exposures and telomere length reported here and by others suggest mechanisms by which these chemicals may affect carcinogenesis and other adverse health outcomes.},
}
@article {pmid34451431,
year = {2021},
author = {Li, B and Zhao, Y},
title = {Regulation of Antigenic Variation by Trypanosoma brucei Telomere Proteins Depends on Their Unique DNA Binding Activities.},
journal = {Pathogens (Basel, Switzerland)},
volume = {10},
number = {8},
pages = {},
pmid = {34451431},
issn = {2076-0817},
support = {R01 AI066095/AI/NIAID NIH HHS/United States ; AI066095//National Institute of Allergy and Infectious Diseases/ ; JCYJ20170818104619974//Shenzhen Fundamental Research Program/ ; PolyU 151062/18M//Research Grants Council Hong Kong/ ; },
abstract = {Trypanosoma brucei causes human African trypanosomiasis and regularly switches its major surface antigen, Variant Surface Glycoprotein (VSG), to evade the host immune response. Such antigenic variation is a key pathogenesis mechanism that enables T. brucei to establish long-term infections. VSG is expressed exclusively from subtelomere loci in a strictly monoallelic manner, and DNA recombination is an important VSG switching pathway. The integrity of telomere and subtelomere structure, maintained by multiple telomere proteins, is essential for T. brucei viability and for regulating the monoallelic VSG expression and VSG switching. Here we will focus on T. brucei TRF and RAP1, two telomere proteins with unique nucleic acid binding activities, and summarize their functions in telomere integrity and stability, VSG switching, and monoallelic VSG expression. Targeting the unique features of TbTRF and TbRAP1's nucleic acid binding activities to perturb the integrity of telomere structure and disrupt VSG monoallelic expression may serve as potential therapeutic strategy against T. brucei.},
}
@article {pmid34449264,
year = {2022},
author = {Gleason, JL and Thoma, ME and Zukerman Willinger, N and Shenassa, ED},
title = {Endometriosis and Uterine Fibroids and Their Associations with Elevated C-Reactive Protein and Leukocyte Telomere Length Among a Representative Sample of U.S. Women: Data from the National Health and Nutrition Examination Survey, 1999-2002.},
journal = {Journal of women's health (2002)},
volume = {31},
number = {7},
pages = {1020-1028},
doi = {10.1089/jwh.2021.0044},
pmid = {34449264},
issn = {1931-843X},
mesh = {Biomarkers ; C-Reactive Protein/metabolism ; Chronic Disease ; *Endometriosis ; Female ; Humans ; Inflammation ; *Leiomyoma/epidemiology ; Leukocytes/metabolism ; Nutrition Surveys ; Telomere/metabolism ; },
abstract = {Background: Recent studies have suggested a link between reproductive health and later-life chronic conditions, yet the mechanism remains unclear. One proposed mechanism is through chronic inflammation. The objective of this study was to examine the association between endometriosis and uterine fibroids and biomarkers of inflammation and cellular aging. Materials and Methods: We used data from the National Health and Nutrition Examination Survey (N = 2342; 1999-2002). Adjusted logistic and linear regression were used to examine the association between these two reproductive conditions and elevated C-reactive protein (CRP; >3.0 mg/L) and leukocyte telomere length (T/S ratio), respectively. Given that a greater length of time spent with a condition may represent persistence of an inflammatory process, we further examined the association between time since disease diagnosis on telomere length among the subset of women with diagnosed endometriosis and fibroids. Results: Women with endometriosis had greater odds of having elevated CRP than those without endometriosis (OR = 1.60; 95% CI: 1.05 to 2.45). Women with endometriosis had a shorter telomere length than women without endometriosis (-3.4, 95% CI: -7.3 to -0.3 in age-adjusted models and -2.9, 95% CI: -8.8 to 3.5 in fully adjusted models). Telomeres were 1% (95% CI: -1.2 to -0.6) shorter for every elapsed year since endometriosis diagnosis. No substantive patterns emerged between uterine fibroids and CRP or telomere length. Conclusions: Women with endometriosis (or a longer duration of time spent with endometriosis) had higher inflammatory markers and shorter mean telomere length. These results provide further insights into potential mechanisms linking endometriosis to chronic disease and later-life health.},
}
@article {pmid34448287,
year = {2022},
author = {Friesen, CR and Wapstra, E and Olsson, M},
title = {Of telomeres and temperature: Measuring thermal effects on telomeres in ectothermic animals.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6069-6086},
doi = {10.1111/mec.16154},
pmid = {34448287},
issn = {1365-294X},
mesh = {Animals ; Temperature ; *Vertebrates ; *Biological Evolution ; Reproduction ; Telomere/genetics ; },
abstract = {Ectotherms are classic models for understanding life-history tradeoffs, including the reproduction-somatic maintenance tradeoffs that may be reflected in telomere length and their dynamics. Importantly, life-history traits of ectotherms are tightly linked to their thermal environment, with diverse or synergistic mechanistic explanations underpinning the variation. Telomere dynamics potentially provide a mechanistic link that can be used to monitor thermal effects on individuals in response to climatic perturbations. Growth rate, age and developmental stage are all affected by temperature, which interacts with telomere dynamics in complex and intriguing ways. The physiological processes underpinning telomere dynamics can be visualized and understood using thermal performance curves (TPCs). TPCs reflect the evolutionary history and the thermal environment during an individual's ontogeny. Telomere maintenance should be enhanced at or near the thermal performance optimum of a species, population and individual. The thermal sensitivity of telomere dynamics should reflect the interacting TPCs of the processes underlying them. The key processes directly underpinning telomere dynamics are mitochondrial function (reactive oxygen production), antioxidant activity, telomerase activity and telomere endcap protein status. We argue that identifying TPCs for these processes will significantly help design robust, repeatable experiments and field studies of telomere dynamics in ectotherms. Conceptually, TPCs are a valuable framework to predict and interpret taxon- and population-specific telomere dynamics across thermal regimes. The literature of thermal effects on telomeres in ectotherms is sparse and mostly limited to vertebrates, but our conclusions and recommendations are relevant across ectothermic animals.},
}
@article {pmid34448238,
year = {2021},
author = {},
title = {Retraction statement: Wang Z, Li J, Liu J, Wang L, Lu Y, Liu J-P. Molecular insight into the selective binding between human telomere G-quadruplex, a negatively charged stabilizer. Clin Exp Pharmacol Physiol. 2020;47:892-902. https://doi.org/10.1111/1440-1681.13249.},
journal = {Clinical and experimental pharmacology &amp; physiology},
volume = {48},
number = {9},
pages = {1300},
doi = {10.1111/1440-1681.13558},
pmid = {34448238},
issn = {1440-1681},
}
@article {pmid34448146,
year = {2021},
author = {Womersley, JS and Spies, G and Tromp, G and Seedat, S and Hemmings, SMJ},
title = {Longitudinal telomere length profile does not reflect HIV and childhood trauma impacts on cognitive function in South African women.},
journal = {Journal of neurovirology},
volume = {27},
number = {5},
pages = {735-749},
pmid = {34448146},
issn = {1538-2443},
support = {P30 AI036214/AI/NIAID NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; },
mesh = {*Adverse Childhood Experiences ; Cognition ; Cross-Sectional Studies ; Female ; *HIV Infections/complications/genetics ; Humans ; Longitudinal Studies ; Telomere/genetics ; },
abstract = {HIV-associated neurocognitive disorders (HAND) present a challenge in South Africa where the burden of HIV infection is the highest. Identification of biological correlates of HAND is required to improve diagnosis and inform interventions. Telomeres maintain genomic integrity and their shortening is a marker of biological aging sensitive to environmental influences. This study examined relative telomere length (rTL) as a predictor of cognitive function in the context of HIV and childhood trauma (CT), a risk factor for HAND. Two hundred and eighty-six women completed a neurocognitive assessment battery and the Childhood Trauma Questionnaire-Short Form (CTQ). Quantitative polymerase chain reaction for amplification of telomeric repeats and the reference gene human beta-globin was used to calculate rTL. Neurocognitive and rTL assessments were repeated at 1 year in 110 participants. Cross-sectional and longitudinal data were assessed using linear and mixed models, respectively. Participants with HIV (n = 135 in cross-sectional and n = 62 in longitudinal study groups) reported more severe CT and had shorter baseline rTL compared to seronegative controls. Participants without HIV had a greater 1-year decline in rTL. Global cognitive and attention/working memory scores declined in participants with HIV. Our data indicate that baseline rTL in the context of CT and HIV did not predict decline in cognitive scores. HIV-associated pathophysiological processes driving cognitive decline may also engage mechanisms that protect against telomere shortening. The results highlight the importance of examining biological correlates in longitudinal studies.},
}
@article {pmid34446526,
year = {2021},
author = {Salehian, S and Semple, T and Pabary, R},
title = {Childhood interstitial lung disease: short lessons from telomeres.},
journal = {Thorax},
volume = {76},
number = {12},
pages = {1250-1252},
doi = {10.1136/thoraxjnl-2021-217479},
pmid = {34446526},
issn = {1468-3296},
mesh = {Child ; Humans ; *Lung Diseases, Interstitial/genetics ; Telomere/genetics ; },
}
@article {pmid34444842,
year = {2021},
author = {Paltoglou, G and Raftopoulou, C and Nicolaides, NC and Genitsaridi, SM and Karampatsou, SI and Papadopoulou, M and Kassari, P and Charmandari, E},
title = {A Comprehensive, Multidisciplinary, Personalized, Lifestyle Intervention Program Is Associated with Increased Leukocyte Telomere Length in Children and Adolescents with Overweight and Obesity.},
journal = {Nutrients},
volume = {13},
number = {8},
pages = {},
pmid = {34444842},
issn = {2072-6643},
support = {(project code: T1EDK-01386, MIS: 5030543, Acronym: PEDOBESITY).//This research has been co-financed by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH - CREATE - INNOVATE/ ; },
mesh = {Adolescent ; Aging/*genetics ; Behavior Therapy/methods ; Body Composition ; Body Mass Index ; Child ; Exercise/physiology ; Female ; Humans ; Leukocytes/*pathology ; Life Style ; Male ; Pediatric Obesity/blood/*genetics/therapy ; Program Evaluation ; Prospective Studies ; Telomere/*pathology ; Treatment Outcome ; Waist Circumference ; Weight Reduction Programs/*methods ; },
abstract = {Leucocyte telomere length (LTL) is a robust marker of biological aging and is associated with obesity and cardiometabolic risk factors in childhood and adolescence. We investigated the effect of a structured, comprehensive, multidisciplinary, personalized, lifestyle intervention program of healthy diet and physical exercise on LTL in 508 children and adolescents (239 males, 269 females; 282 prepubertal, 226 pubertal), aged 10.14 ± 0.13 years. Participants were classified as obese (n = 267, 52.6%), overweight (n = 174, 34.2%), or of normal BMI (n = 67, 13.2%) according to the International Obesity Task Force (IOTF) cutoff points and were studied prospectively for one year. We demonstrated that LTL increased significantly after 1 year of the lifestyle interventions, irrespective of gender, pubertal status, or body mass index (BMI). Waist circumference was the best negative predictor of LTL at initial assessment. The implementation of the lifestyle interventions also resulted in a significant improvement in clinical (BMI, BMI z-score and waist to height ratio) and body composition indices of obesity, inflammatory markers, hepatic enzymes, glycated hemoglobin (HbA1C), quantitative insulin sensitivity check index (QUICKI), and lipid profile in all participants. These findings indicate that the increased LTL may be associated with a more favorable metabolic profile and decreased morbidity later in life.},
}
@article {pmid34444746,
year = {2021},
author = {Ruiz-Narváez, EA and Baylin, A and Azofeifa, J and Leal, A and Rosero-Bixby, L},
title = {Diet and Leukocyte Telomere Length in a Population with Extended Longevity: The Costa Rican Longevity and Healthy Aging Study (CRELES).},
journal = {Nutrients},
volume = {13},
number = {8},
pages = {},
pmid = {34444746},
issn = {2072-6643},
support = {072406/Z/03/Z/WT_/Wellcome Trust/United Kingdom ; P30 AG012839/AG/NIA NIH HHS/United States ; R01 AG031716/AG/NIA NIH HHS/United States ; },
mesh = {Aged ; Aged, 80 and over ; Aging ; Costa Rica ; *Diet ; Fabaceae ; Female ; Food ; Healthy Aging ; Humans ; *Leukocytes ; *Longevity ; Male ; *Telomere ; },
abstract = {Elderly Costa Ricans have lower mortality rates compared to their counterparts from developed countries. Reasons for this survival advantage are not completely known. In the present study, we aimed to identify dietary factors associated with leukocyte telomere length (LTL), a marker of biologic aging, in the elderly population of Costa Rica. We conducted prospective analysis in 909 participants aged 60+ years from the Costa Rican Longevity and Healthy Aging Study (CRELES). We used a food frequency questionnaire to assess usual diet. We calculated dietary patterns using Principal Component Analysis (PCA). We used generalized linear models to examine the association of dietary patterns and food groups with leukocyte telomere length. We found two major dietary patterns explaining 9.15% and 7.18% of the total variation of food intake, respectively. The first dietary pattern, which represents a traditional Costa Rican rice and beans pattern, was more frequent in rural parts of the country and was positively associated with baseline LTL: β (95% CI) = 42.0 base-pairs (bp) (9.9 bp, 74.1 bp) per one-unit increase of the traditional dietary pattern. In analysis of individual food groups, intake of grains was positively associated with baseline LTL: β (95% CI) = 43.6 bp (13.9 bp, 73.3 bp) per one-serving/day increase of consumption of grains. Our results suggest that dietary factors, in particular a traditional food pattern, are associated with telomere length and may contribute to the extended longevity of elderly Costa Ricans.},
}
@article {pmid34441997,
year = {2021},
author = {Pavanello, S and Campisi, M and Grassi, A and Mastrangelo, G and Durante, E and Veronesi, A and Gallucci, M},
title = {Longer Leukocytes Telomere Length Predicts a Significant Survival Advantage in the Elderly TRELONG Cohort, with Short Physical Performance Battery Score and Years of Education as Main Determinants for Telomere Elongation.},
journal = {Journal of clinical medicine},
volume = {10},
number = {16},
pages = {},
pmid = {34441997},
issn = {2077-0383},
support = {175721//Universit&#xe0; degli Studi di Padova/ ; },
abstract = {Leukocyte telomere length (LTL) represents a key integrating component of the cumulative effects of environmental, lifestyle, and genetic factors. A question, however, remains on whether LTL can be considered predictive for a longer and healthier life. Within the elderly prospective TRELONG cohort (n = 612), we aimed to investigate LTL as a predictor of longevity and identify the main determinants of LTL among many different factors (physiological and lifestyle characteristics, physical performance and frailty measures, chronic diseases, biochemical measurements and apolipoprotein E genotyping). We found an ever-increasing relationship between LTL quartiles and survival. Hazard ratio analysis showed that for each unit increase in LTL and Short Physical Performance Battery (SPPB) scores, the mortality risk was reduced by 22.41% and 8.78%, respectively. Conversely, male gender, Charlson Comorbidity Index, and age threatened survival, with mortality risk growing by 74.99%, 16.57% and 8.5%, respectively. Determinants of LTL elongation were SPPB scores (OR = 1.1542; p = 0.0066) and years of education (OR = 1.0958; p = 0.0065), while male gender (OR = 0.4388; p = 0.0143) and increased Disease Count Index (OR = 0.6912; p = 0.0066) were determinants of LTL attrition. Longer LTL predicts a significant survival advantage in elderly people. By identifying determinants of LTL elongation, we provided additional knowledge that could offer a potential translation into prevention strategies.},
}
@article {pmid34440635,
year = {2021},
author = {Kordowitzki, P},
title = {Oxidative Stress Induces Telomere Dysfunction and Shortening in Human Oocytes of Advanced Age Donors.},
journal = {Cells},
volume = {10},
number = {8},
pages = {},
pmid = {34440635},
issn = {2073-4409},
mesh = {Adult ; Age Factors ; DNA Damage ; Female ; Humans ; Maternal Age ; *Oocyte Donation/adverse effects ; Oocytes/*metabolism/pathology ; *Oxidative Stress ; Reactive Oxygen Species/*metabolism ; Risk Assessment ; Risk Factors ; Telomere/*metabolism/pathology ; *Telomere Shortening ; *Tissue Donors ; },
abstract = {Research from the past decades provided strong evidence that in humans the pool of oocytes starts to decline already before the birth of a female individual, and from menarche to menopause the oocyte is exposed to different environmental stimuli. Since more and more women of the 21st century in developed countries wish to postpone the first pregnancy to their thirties, higher rates of miscarriage and chromosomal non-disjunction might occur. In oocytes of advanced maternal age, meaning above 35 years of age, characteristics such as chromosomal instabilities/abnormalities, spindle defects, decreased mitochondrial function and telomere shortening become more prevalent than in younger counterparts. Telomere attrition belongs to the so-called "hallmarks of aging" which are also relevant for the female germ-line cells. In oocytes, telomeres shorten with advancing maternal age due to the effects of reactive oxygen species and not upon replicative senescence, similar to how it is common in dividing cells.},
}
@article {pmid34440552,
year = {2021},
author = {Carugno, M and Borroni, E and Fedrizzi, L and Hoxha, M and Vigna, L and Consonni, D and Bollati, V and Pesatori, AC},
title = {Long- and Short-Term Exposures to PM10 Can Shorten Telomere Length in Individuals Affected by Overweight and Obesity.},
journal = {Life (Basel, Switzerland)},
volume = {11},
number = {8},
pages = {},
pmid = {34440552},
issn = {2075-1729},
support = {ERC-2011-StG 282413/ERC_/European Research Council/International ; },
abstract = {Reduced telomere length (TL) has been associated with increased risk of age-related diseases, most likely through oxidative stress and inflammation, which have also been claimed as mechanisms underlying health effects of air pollution exposure. We aimed to verify whether exposure to particulate matter with diameter ≤10 µm (PM10) affects TL. We recruited 1792 participants with overweight/obesity in Milan (Italy) in 2010-2015 who completed a structured questionnaire on sociodemographic data, gave a blood sample for TL measurement by real-time PCR, and were assigned air pollution and meteorological data of their residential address. In multivariate mixed-effects linear models (with a random intercept on PCR plate), we observed a -0.51% change in TL (95% confidence interval (CI): -0.98; -0.05)) per 10 µg/m[3] increase in PM10 at the day of recruitment. A similar decreasing trend in TL was observed up to two weeks before withdrawal, with percentage changes as low as -1.53% (average exposure of the 12 days before recruitment). Mean annual exposure to PM10 was associated with -2.57% TL reduction (95%CI: -5.06; -0.08). By showing consistent associations between short- and long-term PM10 exposures and reduced TL, our findings shed light on the potential mechanisms responsible for the excess of age-related diseases associated with air pollution exposure.},
}
@article {pmid34439779,
year = {2021},
author = {Akter, J and Kamijo, T},
title = {How Do Telomere Abnormalities Regulate the Biology of Neuroblastoma?.},
journal = {Biomolecules},
volume = {11},
number = {8},
pages = {},
pmid = {34439779},
issn = {2218-273X},
mesh = {Antineoplastic Agents/therapeutic use ; Child ; Gene Expression Regulation, Neoplastic ; *Genome, Human ; Genomic Instability ; Humans ; Mutation ; N-Myc Proto-Oncogene Protein/*genetics/metabolism ; Neoplasm Metastasis ; Nervous System Neoplasms/drug therapy/*genetics/mortality/pathology ; Neuroblastoma/drug therapy/*genetics/mortality/pathology ; Risk Factors ; Signal Transduction ; Survival Analysis ; Telomerase/*genetics/metabolism ; Telomere/*chemistry/drug effects/pathology ; Telomere Homeostasis ; X-linked Nuclear Protein/*genetics/metabolism ; },
abstract = {Telomere maintenance plays important roles in genome stability and cell proliferation. Tumor cells acquire replicative immortality by activating a telomere-maintenance mechanism (TMM), either telomerase, a reverse transcriptase, or the alternative lengthening of telomeres (ALT) mechanism. Recent advances in the genetic and molecular characterization of TMM revealed that telomerase activation and ALT define distinct neuroblastoma (NB) subgroups with adverse outcomes, and represent promising therapeutic targets in high-risk neuroblastoma (HRNB), an aggressive childhood solid tumor that accounts for 15% of all pediatric-cancer deaths. Patients with HRNB frequently present with widely metastatic disease, with tumors harboring recurrent genetic aberrations (MYCN amplification, TERT rearrangements, and ATRX mutations), which are mutually exclusive and capable of promoting TMM. This review provides recent insights into our understanding of TMM in NB tumors, and highlights emerging therapeutic strategies as potential treatments for telomerase- and ALT-positive tumors.},
}
@article {pmid34437736,
year = {2022},
author = {Remot, F and Ronget, V and Froy, H and Rey, B and Gaillard, JM and Nussey, DH and Lemaitre, JF},
title = {Decline in telomere length with increasing age across nonhuman vertebrates: A meta-analysis.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {5917-5932},
doi = {10.1111/mec.16145},
pmid = {34437736},
issn = {1365-294X},
support = {P51 RR000165/RR/NCRR NIH HHS/United States ; P51 RR013986/RR/NCRR NIH HHS/United States ; },
mesh = {Adult ; Humans ; Animals ; *Aging/genetics ; *Vertebrates/genetics ; Telomere/genetics ; Telomere Shortening/genetics ; },
abstract = {The prediction that telomere length (TL) shortens with increasing age is a major element in considering the role of telomeres as a key player in evolution. While telomere attrition is found in humans both in vitro and in vivo, the increasing number of studies reporting diverse age-specific patterns of TL challenges the hypothesis of a universal decline of TL with increasing age. Here, we performed a meta-analysis to estimate the relationship between TL and age across 175 estimates encompassing 98 species of vertebrates. We found that, on average, TL does decline with increasing age during adulthood. However, this decline was weak and variable across vertebrate classes, and we also found evidence for a publication bias that might weaken our current evidence of decreasing TL with increasing age. We found no evidence for a faster decline in TL with increasing age when considering the juvenile stage (from birth to age at first reproduction) compared to the adult stage. Heterogeneity in TL ageing rates was explained by the method used to measure telomeres: detectable TL declines with increasing age were found only among studies using TRF with in-gel hybridisation and qFISH methods, but not in studies using qPCR and Southern blot-based TRF methods. While we confirmed that TL declines with increasing age in most adult vertebrates, our results identify an influence of telomere measurement methodology, which highlights the need to examine more thoroughly the effect of the method of measurement on TL estimates.},
}
@article {pmid34436787,
year = {2021},
author = {Glousker, G and Lingner, J},
title = {Challenging endings: How telomeres prevent fragility.},
journal = {BioEssays : news and reviews in molecular, cellular and developmental biology},
volume = {43},
number = {10},
pages = {e2100157},
doi = {10.1002/bies.202100157},
pmid = {34436787},
issn = {1521-1878},
mesh = {Chromatin/genetics ; DNA Repair/genetics ; *DNA Replication/genetics ; Homologous Recombination ; *Telomere/genetics ; },
abstract = {It has become apparent that difficulties to replicate telomeres concern not only the very ends of eukaryotic chromosomes. The challenges already start when the replication fork enters the telomeric repeats. The obstacles encountered consist mainly of noncanonical nucleic acid structures that interfere with replication if not resolved. Replication stress at telomeres promotes the formation of so-called fragile telomeres displaying an abnormal appearance in metaphase chromosomes though their exact molecular nature remains to be elucidated. A substantial number of factors is required to counteract fragility. In this review we promote the hypothesis that telomere fragility is not caused directly by an initial insult during replication but it results as a secondary consequence of DNA repair of damaged replication forks by the homologous DNA recombination machinery. Incomplete DNA synthesis at repair sites or partial chromatin condensation may become apparent as telomere fragility. Fragility and DNA repair during telomere replication emerges as a common phenomenon which exacerbates in multiple disease conditions.},
}
@article {pmid34435398,
year = {2022},
author = {Metcalfe, NB and Olsson, M},
title = {How telomere dynamics are influenced by the balance between mitochondrial efficiency, reactive oxygen species production and DNA damage.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6040-6052},
doi = {10.1111/mec.16150},
pmid = {34435398},
issn = {1365-294X},
mesh = {Humans ; Reactive Oxygen Species/metabolism ; *DNA Damage ; *Oxidative Stress/genetics ; Mitochondria/genetics/metabolism ; Telomere/genetics ; Adenosine Triphosphate/metabolism ; },
abstract = {It is well known that oxidative stress is a major cause of DNA damage and telomere attrition. Most endogenous reactive oxygen species (ROS) are produced in the mitochondria, producing a link between mitochondrial function, DNA integrity and telomere dynamics. In this review we will describe how ROS production, rates of damage to telomeric DNA and DNA repair are dynamic processes. The rate of ROS production depends on mitochondrial features such as the level of inner membrane uncoupling and the proportion of time that ATP is actively being produced. However, the efficiency of ATP production (the ATP/O ratio) is positively related to the rate of ROS production, so leading to a trade-off between the body's energy requirements and its need to prevent oxidative stress. Telomeric DNA is especially vulnerable to oxidative damage due to features such as its high guanine content; while repair to damaged telomere regions is possible through a range of mechanisms, these can result in more rapid telomere shortening. There is increasing evidence that mitochondrial efficiency varies over time and with environmental context, as do rates of DNA repair. We argue that telomere dynamics can only be understood by appreciating that the optimal solution to the trade-off between energetic efficiency and telomere protection will differ between individuals and will change over time, depending on resource availability, energetic demands and life history strategy.},
}
@article {pmid34434216,
year = {2021},
author = {Rahnama, M and Wang, B and Dostart, J and Novikova, O and Yackzan, D and Yackzan, A and Bruss, H and Baker, M and Jacob, H and Zhang, X and Lamb, A and Stewart, A and Heist, M and Hoover, J and Calie, P and Chen, L and Liu, J and Farman, ML},
title = {Telomere Roles in Fungal Genome Evolution and Adaptation.},
journal = {Frontiers in genetics},
volume = {12},
number = {},
pages = {676751},
pmid = {34434216},
issn = {1664-8021},
support = {P30 CA177558/CA/NCI NIH HHS/United States ; },
abstract = {Telomeres form the ends of linear chromosomes and usually comprise protein complexes that bind to simple repeated sequence motifs that are added to the 3' ends of DNA by the telomerase reverse transcriptase (TERT). One of the primary functions attributed to telomeres is to solve the "end-replication problem" which, if left unaddressed, would cause gradual, inexorable attrition of sequences from the chromosome ends and, eventually, loss of viability. Telomere-binding proteins also protect the chromosome from 5' to 3' exonuclease action, and disguise the chromosome ends from the double-strand break repair machinery whose illegitimate action potentially generates catastrophic chromosome aberrations. Telomeres are of special interest in the blast fungus, Pyricularia, because the adjacent regions are enriched in genes controlling interactions with host plants, and the chromosome ends show enhanced polymorphism and genetic instability. Previously, we showed that telomere instability in some P. oryzae strains is caused by novel retrotransposons (MoTeRs) that insert in telomere repeats, generating interstitial telomere sequences that drive frequent, break-induced rearrangements. Here, we sought to gain further insight on telomeric involvement in shaping Pyricularia genome architecture by characterizing sequence polymorphisms at chromosome ends, and surrounding internalized MoTeR loci (relics) and interstitial telomere repeats. This provided evidence that telomere dynamics have played historical, and likely ongoing, roles in shaping the Pyricularia genome. We further demonstrate that even telomeres lacking MoTeR insertions are poorly preserved, such that the telomere-adjacent sequences exhibit frequent presence/absence polymorphism, as well as exchanges with the genome interior. Using TERT knockout experiments, we characterized chromosomal responses to failed telomere maintenance which suggested that much of the MoTeR relic-/interstitial telomere-associated polymorphism could be driven by compromised telomere function. Finally, we describe three possible examples of a phenomenon known as "Adaptive Telomere Failure," where spontaneous losses of telomere maintenance drive rapid accumulation of sequence polymorphism with possible adaptive advantages. Together, our data suggest that telomere maintenance is frequently compromised in Pyricularia but the chromosome alterations resulting from telomere failure are not as catastrophic as prior research would predict, and may, in fact, be potent drivers of adaptive polymorphism.},
}
@article {pmid34430678,
year = {2021},
author = {Kotah, JM and Hoeijmakers, L and Nutma, E and Lucassen, PJ and Korosi, A},
title = {Early-life stress does not alter spatial memory performance, hippocampal neurogenesis, neuroinflammation, or telomere length in 20-month-old male mice.},
journal = {Neurobiology of stress},
volume = {15},
number = {},
pages = {100379},
pmid = {34430678},
issn = {2352-2895},
abstract = {Early-life stress (ES) increases the risk for psychopathology and cognitive decline later in life. Because the neurobiological substrates affected by ES (i.e., cognition, neuroplasticity, and neuroinflammation) are also altered in aging, we set out to investigate if and how ES in the first week of life affects these domains at an advanced age, and how ES modulates the aging trajectory per se. We subjected C57BL/6j mice to an established ES mouse model from postnatal days 2-9. Mice underwent behavioral testing at 19 months of age and were sacrificed at 20 months to investigate their physiology, hippocampal neuroplasticity, neuroinflammation, and telomere length. ES mice, as a group, did not perform differently from controls in the open field or Morris water maze (MWM). Hippocampal neurogenesis and synaptic marker gene expression were not different in ES mice at this age. While we find aging-associated alterations to neuroinflammatory gene expression and telomere length, these were unaffected by ES. When integrating the current data with those from our previously reported 4- and 10-month-old cohorts, we conclude that ES leads to a 'premature' shift in the aging trajectory, consisting of early changes that do not further worsen at the advanced age of 20 months. This could be explained e.g. by a 'floor' effect in ES-induced impairments, and/or age-induced impairments in control mice. Future studies should help understand how exactly ES affects the overall aging trajectory.},
}
@article {pmid34428605,
year = {2021},
author = {Niu, Z and Wen, X and Buka, SL and Wang, M and Tian, L and Loucks, EB and Kubzansky, LD and Mu, L},
title = {Associations of telomere length at birth with predicted atherosclerotic lesions and cardiovascular disease risk factors in midlife: A 40-year longitudinal study.},
journal = {Atherosclerosis},
volume = {333},
number = {},
pages = {67-74},
doi = {10.1016/j.atherosclerosis.2021.08.013},
pmid = {34428605},
issn = {1879-1484},
support = {R21 HD091515/HD/NICHD NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; *Atherosclerosis/diagnosis/epidemiology/genetics ; *Cardiovascular Diseases/diagnosis/epidemiology/genetics ; Female ; Humans ; Longitudinal Studies ; Middle Aged ; Pregnancy ; Risk Factors ; Telomere ; },
abstract = {BACKGROUND AND AIMS: Adult telomere length (TL) is substantially determined by birth TL, but associations of birth TL with cardiovascular disease (CVD) are unknown.<br><br>METHODS: We included 144 adult offspring born in 1959-1966 from the Collaborative Perinatal Project, a US birth cohort. Birth TL was measured from banked cord blood with quantitative polymerase chain reaction. Atherosclerotic lesions were predicted by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) score that was based on blood pressure, lipids, hemoglobin A1c, and body weight at the midlife follow-up in 2003-2008 (average age: 42 years). Information on midlife CVD risk factors including the age at first diagnoses of hypertension, hypercholesterolemia, and diabetes was also collected. We used linear and logistic regression models to analyze associations of birth TL with the continuous PDAY score and categorical CVD risk factors, respectively, adjusting for prenatal confounders.<br><br>RESULTS: At midlife follow-up, 31.2% and 18.7% of participants had ever been diagnosed with hypercholesterolemia and hypertension, respectively, and 8.3% met the criteria for metabolic syndrome. Short birth TL (Quartile 1, Q1) was associated with a higher PDAY score (adjusted &#x3b2;: 1.78, 95% CI: 0.31, 3.25), increased odds of hypercholesterolemia (adjusted odds ratio [OR]: 3.23, 95% CI: 1.28, 8.18) and the presence of any cardiometabolic abnormalities (adjusted OR: 2.54, 95% CI: 1.00, 6.48) as compared to longer birth TL (Q2-Q4) after adjusting for prenatal confounders.<br><br>CONCLUSIONS: People born with short TL may be at increased risk of predicted midlife atherosclerotic lesions and hypercholesterolemia. Future studies with larger sample sizes and CVD morbidities are warranted to replicate our findings.},
}
@article {pmid34421981,
year = {2021},
author = {Sellami, M and Bragazzi, N and Prince, MS and Denham, J and Elrayess, M},
title = {Regular, Intense Exercise Training as a Healthy Aging Lifestyle Strategy: Preventing DNA Damage, Telomere Shortening and Adverse DNA Methylation Changes Over a Lifetime.},
journal = {Frontiers in genetics},
volume = {12},
number = {},
pages = {652497},
pmid = {34421981},
issn = {1664-8021},
abstract = {Exercise training is one of the few therapeutic interventions that improves health span by delaying the onset of age-related diseases and preventing early death. The length of telomeres, the 5'-TTAGGG [n] -3' tandem repeats at the ends of mammalian chromosomes, is one of the main indicators of biological age. Telomeres undergo shortening with each cellular division. This subsequently leads to alterations in the expression of several genes that encode vital proteins with critical functions in many tissues throughout the body, and ultimately impacts cardiovascular, immune and muscle physiology. The sub-telomeric DNA is comprised of heavily methylated, heterochromatin. Methylation and histone acetylation are two of the most well-studied examples of the epigenetic modifications that occur on histone proteins. DNA methylation is the type of epigenetic modification that alters gene expression without modifying gene sequence. Although diet, genetic predisposition and a healthy lifestyle seem to alter DNA methylation and telomere length (TL), recent evidence suggests that training status or physical fitness are some of the major factors that control DNA structural modifications. In fact, TL is positively associated with cardiorespiratory fitness, physical activity level (sedentary, active, moderately trained, or elite) and training intensity, but is shorter in over-trained athletes. Similarly, somatic cells are vulnerable to exercise-induced epigenetic modification, including DNA methylation. Exercise-training load, however, depends on intensity and volume (duration and frequency). Training load-dependent responses in genomic profiles could underpin the discordant physiological and physical responses to exercise. In the current review, we will discuss the role of various forms of exercise training in the regulation of DNA damage, TL and DNA methylation status in humans, to provide an update on the influence exercise training has on biological aging.},
}
@article {pmid34408079,
year = {2021},
author = {Koneru, B and Farooqi, A and Nguyen, TH and Chen, WH and Hindle, A and Eslinger, C and Makena, MR and Burrow, TA and Wilson, J and Smith, A and Pilla Reddy, V and Cadogan, E and Durant, ST and Reynolds, CP},
title = {ALT neuroblastoma chemoresistance due to telomere dysfunction-induced ATM activation is reversible with ATM inhibitor AZD0156.},
journal = {Science translational medicine},
volume = {13},
number = {607},
pages = {},
pmid = {34408079},
issn = {1946-6242},
support = {R01 CA217251/CA/NCI NIH HHS/United States ; R01 CA221957/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; *Ataxia Telangiectasia ; Ataxia Telangiectasia Mutated Proteins ; Drug Resistance, Neoplasm ; Humans ; Mice ; Neoplasm Recurrence, Local ; *Neuroblastoma/drug therapy ; Pyridines ; Quinolines ; Telomere ; Telomere Homeostasis ; },
abstract = {Cancers overcome replicative immortality by activating either telomerase or an alternative lengthening of telomeres (ALT) mechanism. ALT occurs in ~25% of high-risk neuroblastomas, and progression in patients with ALT neuroblastoma during or after front-line therapy is frequent and often fatal. Temozolomide + irinotecan is commonly used as salvage therapy for neuroblastoma. Patient-derived cell lines and xenografts established from patients with relapsed ALT neuroblastoma demonstrated de novo resistance to temozolomide + irinotecan [SN-38 in vitro, P < 0.05; in vivo mouse event-free survival (EFS), P < 0.0001] vs. telomerase-positive neuroblastomas. We observed that ALT neuroblastoma cells manifested constitutive ataxia-telangiectasia mutated (ATM) activation due to spontaneous telomere dysfunction which was not observed in telomerase-positive neuroblastoma cells. We demonstrated that induction of telomere dysfunction resulted in ATM activation that, in turn, conferred resistance to temozolomide + SN-38 (4.2-fold change in IC50, P < 0.001). ATM knockdown (shRNA) or inhibition using a clinical-stage small-molecule inhibitor (AZD0156) reversed resistance to temozolomide + irinotecan in ALT neuroblastoma cell lines in vitro (P < 0.001) and in four ALT xenografts in vivo (EFS, P < 0.0001). AZD0156 showed modest to no enhancement of temozolomide + irinotecan activity in telomerase-positive neuroblastoma cell lines and xenografts. Ataxia telangiectasia and Rad3 related (ATR) inhibition using AZD6738 did not enhance temozolomide + SN-38 activity in ALT neuroblastoma cells. Thus, ALT neuroblastoma chemotherapy resistance occurs via ATM activation and is reversible with ATM inhibitor AZD0156. Combining AZD0156 with temozolomide + irinotecan warrants clinical testing for neuroblastoma.},
}
@article {pmid34407217,
year = {2022},
author = {Jeon, HJ and Kang, M and Kim, JS and Oh, JS},
title = {TCTP overexpression reverses age-associated telomere attrition by upregulating telomerase activity in mouse oocytes.},
journal = {Journal of cellular physiology},
volume = {237},
number = {1},
pages = {833-845},
doi = {10.1002/jcp.30557},
pmid = {34407217},
issn = {1097-4652},
mesh = {Animals ; Female ; Mice ; Oocytes/metabolism ; Oogenesis ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Telomere Shortening ; Tumor Protein, Translationally-Controlled 1/*metabolism ; },
abstract = {A prolonged time span between ovulation and fertilization can cause postovulatory aging of oocytes, which impairs oocyte quality and subsequent embryo development. Telomere attrition has long been considered as the primary hallmark of aging or the cause of age-associated diseases. However, the status of telomere and its regulation during postovulatory oocyte aging are poorly understood. Here we found that oocytes experience telomere shortening during postovulatory aging, although they have the capacity to maintain telomere length. However, translationally controlled tumor protein (TCTP) overexpression could reverse age-associated telomere shortening by upregulating telomerase activity in mouse oocytes. Telomere length in mature oocytes gradually decreased with postovulatory aging, which was associated with a marked reduction in TRF1 expression, decreased telomerase activity, and decreased homologous combination (HR)-based alternative lengthening of telomeres (ALT) with a concomitant increase in oxidative stress. Surprisingly, however, overexpression of TCTP led to a remarkable increase in telomere length during postovulatory aging. Notably, neither TRF1 nor BRCA1 level was altered by TCTP overexpression. Moreover, TCTP-mediated telomere lengthening was not blocked by HR inhibition. In striking contrast, telomerase activity, as well as TERT and TERC levels, increased after TCTP overexpression. Importantly, unlike the chromosome-wide distribution of endogenous TCTP, overexpressed TCTP was ectopically localized at telomeres, implying that TCTP overexpression is required to increase telomerase activity. Collectively, our results demonstrate that TCTP prevents telomere attrition during postovulatory aging by upregulating telomerase activity in mouse oocytes.},
}
@article {pmid34407110,
year = {2021},
author = {Geronimus, AT and Bound, J and Mitchell, C and Martinez-Cardoso, A and Evans, L and Hughes, L and Schneper, L and Notterman, DA},
title = {Coming up short: Comparing venous blood, dried blood spots &amp; saliva samples for measuring telomere length in health equity research.},
journal = {PloS one},
volume = {16},
number = {8},
pages = {e0255237},
pmid = {34407110},
issn = {1932-6203},
support = {T32 AG000221/AG/NIA NIH HHS/United States ; T32 HD007339/HD/NICHD NIH HHS/United States ; P30 AG012846/AG/NIA NIH HHS/United States ; R01 MD011716/MD/NIMHD NIH HHS/United States ; P2C HD041028/HD/NICHD NIH HHS/United States ; R01 AG047167/AG/NIA NIH HHS/United States ; R01 HD076592/HD/NICHD NIH HHS/United States ; },
mesh = {Adult ; Dried Blood Spot Testing/*methods ; *Health Equity ; Humans ; Leukocytes, Mononuclear/metabolism ; Michigan ; Middle Aged ; *Research ; Saliva/*metabolism ; *Telomere Homeostasis ; },
abstract = {BACKGROUND: Telomere length (TL) in peripheral blood mononuclear cells (PBMC) from fresh venous blood is increasingly used to estimate molecular impacts of accumulated social adversity on population health. Sometimes, TL extracted from saliva or dried blood spots (DBS) are substituted as less invasive and more scalable specimen collection methods; yet, are they interchangeable with fresh blood? Studies find TL is correlated across tissues, but have not addressed the critical question for social epidemiological applications: Do different specimen types show the same association between TL and social constructs?<br><br>METHODS: We integrate expertise in social epidemiology, molecular biology, and the statistical impact of measurement error on parameter estimates. Recruiting a diverse sample of 132 Metro-Detroit women, we measure TL for each woman from fresh blood PBMC, DBS, and saliva. Using regression methods, we estimate associations between social characteristics and TL, comparing estimates across specimen types for each woman.<br><br>RESULTS: Associations between TL and social characteristics vary by specimen type collected from the same woman, sometimes qualitatively altering estimates of the magnitude or direction of a theorized relationship. Being Black is associated with shorter TL in PBMC, but longer TL in saliva or DBS. Education is positively associated with TL in fresh blood, but negatively associated with TL using DBS.<br><br>CONCLUSION: Findings raise concerns about the use of TL measures derived from different tissues in social epidemiological research. Investigators need to consider the possibility that associations between social variables and TL may be systematically related to specimen type, rather than be valid indicators of socially-patterned biopsychosocial processes.},
}
@article {pmid34406239,
year = {2021},
author = {Teixeira, MZ},
title = {Telomere length: biological marker of cellular vitality, aging, and health-disease process.},
journal = {Revista da Associacao Medica Brasileira (1992)},
volume = {67},
number = {2},
pages = {173-177},
doi = {10.1590/1806-9282.67.02.20200655},
pmid = {34406239},
issn = {1806-9282},
mesh = {Aging/genetics ; Biomarkers ; *COVID-19 ; Humans ; Pandemics ; SARS-CoV-2 ; *Telomere/genetics ; },
abstract = {The aging process occurs due to the decline of vital physiological functions and adaptability of the body, being influenced by genetics and lifestyle. With advances in genetics, biological aging can be calculated by telomere length. Telomeres are regions at the ends of chromosomes that play a role in the maintenance and integrity of DNA. With biological aging, telomere shortening occurs, causing cellular senescence. Several studies show that shorter telomeres are associated with acute and chronic diseases, stress, addictions, and intoxications. Even in the current COVID-19 pandemic, telomere shortening is proposed as a marker of severity in individuals infected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). On the other hand, healthy lifestyle habits increase telomere length and balance of various cellular functions, preventing diseases.},
}
@article {pmid34401283,
year = {2021},
author = {Singh, M and Merwat, SK and Fair, JH and Duarte, AG},
title = {Liver transplant recipient with respiratory failure due to pulmonary fibrosis related to telomere disease requiring lung transplantation.},
journal = {Respiratory medicine case reports},
volume = {33},
number = {},
pages = {101443},
pmid = {34401283},
issn = {2213-0071},
abstract = {Short telomere syndrome (STS) is characterized as multiorgan dysfunction presenting with unexplained cytopenias, cryptogenic cirrhosis and pulmonary fibrosis. We present a liver transplant recipient that gradually developed hypoxic respiratory failure attributed to idiopathic pulmonary fibrosis associated telomere disease that culminated in a successful single lung transplantation.},
}
@article {pmid34395476,
year = {2021},
author = {Planas-Cerezales, L and Arias-Salgado, EG and Berastegui, C and Montes-Worboys, A and González-Montelongo, R and Lorenzo-Salazar, JM and Vicens-Zygmunt, V and Garcia-Moyano, M and Dorca, J and Flores, C and Perona, R and Román, A and Molina-Molina, M},
title = {Lung Transplant Improves Survival and Quality of Life Regardless of Telomere Dysfunction.},
journal = {Frontiers in medicine},
volume = {8},
number = {},
pages = {695919},
pmid = {34395476},
issn = {2296-858X},
abstract = {Introduction: Fibrotic interstitial lung diseases (ILDs) are the first indication for lung transplantation (LT). Telomere dysfunction has been associated with poor post-transplant outcomes. The aim of the study was to evaluate the morbi-mortality and quality of life in fibrotic ILDs after lung transplant depending on telomere biology. Methods: Fibrotic ILD patients that underwent lung transplant were allocated to two arms; with or without telomere dysfunction at diagnosis based on the telomere length and telomerase related gene mutations revealed by whole-exome sequencing. Post-transplant evaluation included: (1) short and long-term mortality and complications and (2) quality of life. Results: Fifty-five percent of patients that underwent LT carried rare coding mutations in telomerase-related genes. Patients with telomere shortening more frequently needed extracorporeal circulation and presented a higher rate of early post-transplant hematological complications, longer stay in the intensive care unit (ICU), and a higher number of long-term hospital admissions. However, post-transplant 1-year survival was higher than 80% regardless of telomere dysfunction, with improvement in the quality of life and oxygen therapy withdrawal. Conclusions: Post-transplant morbidity is higher in patients with telomere dysfunction and differs according to elapsed time from transplantation. However, lung transplant improves survival and quality of life and the associated complications are manageable.},
}
@article {pmid34395152,
year = {2021},
author = {Adibkia, K and Ehsani, A and Jodaei, A and Fathi, E and Farahzadi, R and Barzegar-Jalali, M},
title = {Silver nanoparticles induce the cardiomyogenic differentiation of bone marrow derived mesenchymal stem cells via telomere length extension.},
journal = {Beilstein journal of nanotechnology},
volume = {12},
number = {},
pages = {786-797},
pmid = {34395152},
issn = {2190-4286},
abstract = {Finding new strategies for the treatment of heart failures using stem cells has attracted a lot of attention. Meanwhile, nanotechnology-based approaches to regenerative medicine hypothesize a possible combination of stem cells and nanotechnology in the treatment of diseases. This study aims to investigate the in vitro effect of silver nanoparticles (Ag-NPs) on the cardiomyogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) through detection of cardiac markers. For this purpose, MSCs were isolated from bone marrow resident and differentiated to the cardiac cells using a dedicated medium with Ag-NPs. Also, the cardiomyogenic differentiation of BM-MSCs was confirmed using immunocytochemistry. Then, real-time PCR and western blotting assay were used for measuring absolute telomere length (TL) measurement, and gene and protein assessment of the cells, respectively. It was found that 2.5 µg/mL Ag-NPs caused elongation of the telomeres and altered VEGF, C-TnI, VWF, SMA, GATA-4, TERT, and cyclin D protein and gene expression in the cardiomyogenically differentiated BM-MSCs. Also, there was a significant increase in the protein and gene expression of Wnt3 and β-catenin as main components of pathways. We concluded that Ag-NPs could change the in vitro expression of cardiac markers of BM-MSCs via the Wnt3/β-catenin signaling pathway.},
}
@article {pmid34393992,
year = {2021},
author = {Zhang, Y and Xu, Z and Yang, Y and Cao, S and Lyu, S and Duan, W},
title = {Association Between Weight Change and Leukocyte Telomere Length in U.S. Adults.},
journal = {Frontiers in endocrinology},
volume = {12},
number = {},
pages = {650988},
pmid = {34393992},
issn = {1664-2392},
mesh = {Adult ; Aged ; *Aging ; Body Mass Index ; *Body Weight ; Cross-Sectional Studies ; Female ; Humans ; Leukocytes/*cytology/metabolism ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Nutrition Surveys ; Obesity/complications/genetics ; Overweight ; Telomere/*ultrastructure ; Telomere Shortening ; United States ; *Weight Gain ; },
abstract = {OBJECTIVE: To investigate the association of dynamic weight change in adulthood with leukocyte telomere length among U.S. adults.<br><br>METHODS: This study included 3,886 subjects aged 36-75 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 cycle. Survey-weighted multivariable linear regression with adjustments for potential confounders was utilized.<br><br>RESULTS: 3,386 individuals were finally included. People with stable obesity had a 0.130 kbp (95% CI: 0.061-0.198, P=1.97E-04) shorter leukocyte telomere length than those with stable normal weight (reference group) during the 10-year period, corresponding to approximately 8.7 years of aging. Weight gain from non-obesity to obesity shortened the leukocyte telomere length by 0.094 kbp (95% CI: 0.012-0.177, P=0.026), while normal weight to overweight or remaining overweight shortened the leukocyte telomere length by 0.074 kbp (95% CI: 0.014-0.134, P=0.016). The leukocyte telomere length has 0.003 kbp attrition on average for every 1&#xa0;kg increase in weight from a mean age of 41 years to 51 years. Further stratified analysis showed that the associations generally varied across sex and race/ethnicity.<br><br>CONCLUSIONS: This study found that weight changes during a 10-year period was associated with leukocyte telomere length and supports the theory that weight gain promotes aging across adulthood.},
}
@article {pmid34390428,
year = {2021},
author = {Page, RL and Han, G and Akinlotan, M and Patron, MP and Gandhi, H and Kochan, KJ},
title = {Telomere Length and Preterm Birth in Pregnant Mexican-Origin Women.},
journal = {Maternal and child health journal},
volume = {25},
number = {11},
pages = {1798-1805},
pmid = {34390428},
issn = {1573-6628},
mesh = {Female ; Humans ; Infant, Newborn ; Pilot Projects ; Pregnancy ; Pregnant Women ; *Premature Birth/epidemiology ; Prospective Studies ; Telomere ; Telomere Shortening ; },
abstract = {OBJECTIVES: Despite the obstacles of limited education and employment opportunities-and the stress associated with immigration and pregnancy-Mexican immigrant women have low rates of preterm birth (PTB) compared to the US national average for all races and ethnicities. Stressors during pregnancy, and stressors associated with acculturation, may accelerate cellular aging manifested by shortened telomere length (TL) in pregnant women. Our objectives were to: (1) determine whether women with PTBs had shorter telomere lengths compared to women who had full term births; (2) assess the association of acculturation with TL and PTB.<br><br>METHODS: This prospective pilot study collected data from 100 self-identified Mexican-origin pregnant women. Survey data included self-administered sociodemographic and acculturation measures and was collected from participants via paper and pen, while biologic data was collected via a single blood draw during a regularly scheduled prenatal visit between 26 and 36&#xa0;weeks gestation. PTB data was collected from the participant's medical record after delivery.<br><br>RESULTS: TL was significantly associated with PTB; the median TL of the women with PTB was less than the median TL for the full sample (p&#x2009;=&#x2009;0.02). Based on regression analysis for PTB vs acculturation, we found no significant associations between acculturation and PTB or TL.<br><br>CONCLUSIONS FOR PRACTICE: This study provides important evidence of the association between shortened maternal TL and adverse birth outcomes. By linking social, clinical and biologic data, we can enhance our understanding of social determinants that may affect racial and ethnic disparities in preterm birth.},
}
@article {pmid34390055,
year = {2021},
author = {Shan, W and Kubová, M and Mandáková, T and Lysak, MA},
title = {Nuclear organization in crucifer genomes: nucleolus-associated telomere clustering is not a universal interphase configuration in Brassicaceae.},
journal = {The Plant journal : for cell and molecular biology},
volume = {108},
number = {2},
pages = {528-540},
doi = {10.1111/tpj.15459},
pmid = {34390055},
issn = {1365-313X},
mesh = {Arabidopsis/genetics ; Arabis/genetics ; Brassicaceae/*genetics ; Cell Nucleolus/*genetics ; Centromere/genetics ; Chromatin/genetics ; DNA, Ribosomal/genetics ; Genome Size ; *Genome, Plant ; Heterochromatin/genetics ; In Situ Hybridization, Fluorescence ; Interphase ; Phylogeny ; Telomere/*genetics ; },
abstract = {Arabidopsis thaliana has become a major plant research model, where interphase nuclear organization exhibits unique features, including nucleolus-associated telomere clustering. The chromocenter (CC)-loop model, or rosette-like configuration, describes intranuclear chromatin organization in Arabidopsis as megabase-long loops anchored in, and emanating from, peripherally positioned CCs, with those containing telomeres associating with the nucleolus. To investigate whether the CC-loop organization is universal across the mustard family (crucifers), the nuclear distributions of centromeres, telomeres and nucleoli were analyzed by fluorescence in situ hybridization in seven diploid species (2n = 10-16) representing major crucifer clades with an up to 26-fold variation in genome size (160-4260 Mb). Nucleolus-associated telomere clustering was confirmed in Arabidopsis (157 Mb) and was newly identified as the major nuclear phenotype in other species with a small genome (215-381 Mb). In large-genome species (2611-4264 Mb), centromeres and telomeres adopted a Rabl-like configuration or dispersed distribution in the nuclear interior; telomeres only rarely associated with the nucleolus. In Arabis cypria (381 Mb) and Bunias orientalis (2611 Mb), tissue-specific patterns deviating from the major nuclear phenotypes were observed in anther and stem tissues, respectively. The rosette-like configuration, including nucleolus-associated telomere clustering in small-genome species from different infrafamiliar clades, suggests that genomic properties rather than phylogenetic position determine the interphase nuclear organization. Our data suggest that nuclear genome size, average chromosome size and degree of longitudinal chromosome compartmentalization affect interphase chromosome organization in crucifer genomes.},
}
@article {pmid34388352,
year = {2021},
author = {Degradi, L and Tava, V and Kunova, A and Cortesi, P and Saracchi, M and Pasquali, M},
title = {Telomere to Telomere Genome Assembly of Fusarium musae F31, Causal Agent of Crown Rot Disease of Banana.},
journal = {Molecular plant-microbe interactions : MPMI},
volume = {34},
number = {12},
pages = {1455-1457},
doi = {10.1094/MPMI-05-21-0127-A},
pmid = {34388352},
issn = {0894-0282},
mesh = {*Fusarium/genetics ; *Musa ; Plant Diseases ; Telomere ; },
abstract = {Fusarium musae causes crown rot of banana and it is also associated to clinical fusariosis. A chromosome-level genome assembly of F. musae F31 obtained combining Nanopore long reads and Illumina paired-end reads resulted in 12 chromosomes plus one contig with overall N50 of 4.36 Mb, and is presented together with its mitochondrial genome (58,072 bp). The F31 genome includes telomeric regions for 11 of the 12 chromosomes representing one of the most complete genomes available in the Fusarium fujikuroi species complex. The high-quality assembly of the F31 genome will be a valuable resource for studying the pathogenic interactions occurring between F. musae and banana. Moreover, it represents an important resource for understanding the genome evolution in the F. fujikuroi species complex.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.},
}
@article {pmid34388328,
year = {2022},
author = {Schroder, JD and de Araújo, JB and de Oliveira, T and de Moura, AB and Fries, GR and Quevedo, J and Réus, GZ and Ignácio, ZM},
title = {Telomeres: the role of shortening and senescence in major depressive disorder and its therapeutic implications.},
journal = {Reviews in the neurosciences},
volume = {33},
number = {3},
pages = {227-255},
doi = {10.1515/revneuro-2021-0070},
pmid = {34388328},
issn = {2191-0200},
mesh = {Aging/genetics ; Animals ; *Depressive Disorder, Major/genetics/therapy ; Humans ; Pituitary-Adrenal System/metabolism ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; },
abstract = {Major depressive disorder (MDD) is one of the most prevalent and debilitating psychiatric disorders, with a large number of patients not showing an effective therapeutic response to available treatments. Several biopsychosocial factors, such as stress in childhood and throughout life, and factors related to biological aging, may increase the susceptibility to MDD development. Included in critical biological processes related to aging and underlying biological mechanisms associated with MDD is the shortening of telomeres and changes in telomerase activity. This comprehensive review discusses studies that assessed the length of telomeres or telomerase activity and function in peripheral blood cells and brain tissues of MDD individuals. Also, results from in vitro protocols and animal models of stress and depressive-like behaviors were included. We also expand our discussion to include the role of telomere biology as it relates to other relevant biological mechanisms, such as the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, inflammation, genetics, and epigenetic changes. In the text and the discussion, conflicting results in the literature were observed, especially considering the size of telomeres in the central nervous system, on which there are different protocols with divergent results in the literature. Finally, the context of this review is considering cell signaling, transcription factors, and neurotransmission, which are involved in MDD and can be underlying to senescence, telomere shortening, and telomerase functions.},
}
@article {pmid34387012,
year = {2022},
author = {Power, ML and Foley, NM and Jones, G and Teeling, EC},
title = {Taking flight: An ecological, evolutionary and genomic perspective on bat telomeres.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6053-6068},
doi = {10.1111/mec.16117},
pmid = {34387012},
issn = {1365-294X},
mesh = {Animals ; *Chiroptera/genetics ; *Telomerase/genetics ; Biological Evolution ; Mammals/genetics ; Genomics ; Telomere/genetics ; },
abstract = {Over 20% of all living mammals are bats (order Chiroptera). Bats possess extraordinary adaptations including powered flight, laryngeal echolocation and a unique immune system that enables them to tolerate a diversity of viral infections without presenting clinical disease symptoms. They occupy multiple trophic niches and environments globally. Significant physiological and ecological diversity occurs across the order. Bats also exhibit extreme longevity given their body size with many species showing few signs of ageing. The molecular basis of this extended longevity has recently attracted attention. Telomere maintenance potentially underpins bats' extended healthspan, although functional studies are still required to validate the causative mechanisms. In this review, we detail the current knowledge on bat telomeres, telomerase expression, and how these relate to ecology, longevity and life-history strategies. Patterns of telomere shortening and telomerase expression vary across species, and comparative genomic analyses suggest that alternative telomere maintenance mechanisms evolved in the longest-lived bats. We discuss the unique challenges faced when working with populations of wild bats and highlight ways to advance the field including expanding long-term monitoring across species that display contrasting life-histories and occupy different environmental niches. We further review how new high quality, chromosome-level genome assemblies can enable us to uncover the molecular mechanisms governing telomere dynamics and how phylogenomic analyses can reveal the adaptive significance of telomere maintenance and variation in bats.},
}
@article {pmid34385579,
year = {2021},
author = {Sonnenberg, ASM and Sedaghat-Telgerd, N and Lavrijssen, B and Ohm, RA and Hendrickx, PM and Scholtmeijer, K and Baars, JJP and van Peer, A},
title = {Author Correction: Telomere-to-telomere assembled and centromere annotated genomes of the two main subspecies of the button mushroom Agaricus bisporus reveal especially polymorphic chromosome ends.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {16734},
doi = {10.1038/s41598-021-96123-y},
pmid = {34385579},
issn = {2045-2322},
}
@article {pmid34383056,
year = {2021},
author = {},
title = {Erratum to: Correlation Between Telomere Attrition of Zona Fasciculata and Adrenal Weight Reduction in Older Men.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {106},
number = {12},
pages = {e5283},
doi = {10.1210/clinem/dgab534},
pmid = {34383056},
issn = {1945-7197},
support = {//Daiwa Securities Health Foundation/ ; },
}
@article {pmid34375555,
year = {2021},
author = {Salmón, P and Millet, C and Selman, C and Monaghan, P},
title = {Growth acceleration results in faster telomere shortening later in life.},
journal = {Proceedings. Biological sciences},
volume = {288},
number = {1956},
pages = {20211118},
pmid = {34375555},
issn = {1471-2954},
mesh = {Acceleration ; Animals ; Longevity ; *Songbirds ; Telomere/genetics ; *Telomere Shortening ; },
abstract = {There is a wealth of evidence for a lifespan penalty when environmental conditions influence an individual's growth trajectory, such that growth rate is accelerated to attain a target size within a limited time period. Given this empirically demonstrated relationship between accelerated growth and lifespan, and the links between lifespan and telomere dynamics, increased telomere loss could underpin this growth-lifespan trade. We experimentally modified the growth trajectory of nestling zebra finches (Taeniopygia guttata), inducing a group of nestlings to accelerate their growth between 7 and 15 days of age, the main phase of body growth. We then sequentially measured their telomere length in red blood cells at various time points from 7 days to full adulthood (120 days). Accelerated growth between 7 and 15 days was not associated with a detectable increase in telomere shortening during this period compared with controls. However, only in the treatment group induced to show growth acceleration was the rate of growth during the experimental period positively related to the amount of telomere shortening between 15 and 120 days. Our findings provide evidence of a long-term influence of growth rate on later-life telomere shortening, but only when individuals have accelerated growth in response to environmental circumstances.},
}
@article {pmid34371369,
year = {2021},
author = {Miner, AE and Graves, JS},
title = {What telomeres teach us about MS.},
journal = {Multiple sclerosis and related disorders},
volume = {54},
number = {},
pages = {103084},
doi = {10.1016/j.msard.2021.103084},
pmid = {34371369},
issn = {2211-0356},
mesh = {Age Factors ; *Aging/genetics ; Female ; Humans ; Leukocytes ; Phenotype ; *Telomere ; },
abstract = {While the precise mechanisms driving progressive forms of MS are not fully understood, patient age has clear impact on disease phenotype. The very young with MS have high relapse rates and virtually no progressive disease, whereas older patients tend to experience more rapid disability accumulation with few relapses. Defining a patient's biological age may offer more precision in determining the role of aging processes in MS phenotype and pathophysiology than just working with an individual's birthdate. The most well recognized measurement of an individual's "biological clock" is telomere length (TL). While TL may differ across tissue types in an individual, most cells TL correlate well with leukocyte TL (LTL), which is the most common biomarker used for aging. LTL has been associated with risk for aging related diseases and most recently with higher levels of disability and brain atrophy in people living with MS. LTL explains 15% of the overall association of chronological age with MS disability level. While LTL may be used just as a biomarker of overall somatic aging processes, triggering of the DNA damage response by telomere attrition leads to senescence pathways that are likely highly relevant to a chronic autoimmune disease. Considering reproductive aging factors, particularly ovarian aging in women, which correlates with LTL and oocyte telomere length, may complement measurements of somatic aging in understanding MS progression. The key to stopping non-relapse related progression in MS might lie in targeting pathways related to biological aging effects on the immune and nervous systems.},
}
@article {pmid34369610,
year = {2021},
author = {Amirzadegan, M and Sadeghi, N and Tavalaee, M and Nasr-Esfahani, MH},
title = {Analysis of leukocyte and sperm telomere length in oligozoospermic men.},
journal = {Andrologia},
volume = {53},
number = {10},
pages = {e14204},
doi = {10.1111/and.14204},
pmid = {34369610},
issn = {1439-0272},
mesh = {Humans ; *Infertility, Male/genetics ; Leukocytes ; Male ; Sperm Count ; Spermatozoa ; *Telomere/genetics ; },
abstract = {Telomere length is considered one of the most relevant biological markers of genomic stability since it protects DNA from impairment and also ensures chromosome alignment during DNA replication. The negative impact of telomere shortening on sperm quality has been suggested as an important indicator of male infertility. Therefore, we aimed to assess leucocyte and sperm telomere length (LTL&amp;STL), as well as sperm parameters, DNA damage and protamine deficiency in men with oligozoospermia as compared to fertile men. Our results demonstrated a significant reduction in sperm parameters (concentration, motility, morphology), LTL &amp; STL and a significant increase in sperm DNA damage and protamine deficiency in oligozoospermic men compared with fertile individuals. These outcomes revealed that low sperm concentration in men is possibly a sign of impaired meiotic and/or meiotic division during the spermatogenesis process. It is not only associated with proper chromatin packaging but also with telomere length as a key player in the process of mitosis and meiosis, assisting in chromosomal alignment, pairing, synapsis and crossing over during spermatogenesis.},
}
@article {pmid34369336,
year = {2021},
author = {Ferensztajn-Rochowiak, E and Kurczewska, E and Rubiś, B and Lulkiewicz, M and Hołysz, H and Rybakowski, F and Rybakowski, JK},
title = {Decreased leucocyte telomere length in male patients with chronic bipolar disorder: lack of effect of long-term lithium treatment.},
journal = {Acta neuropsychiatrica},
volume = {33},
number = {6},
pages = {299-306},
doi = {10.1017/neu.2021.20},
pmid = {34369336},
issn = {1601-5215},
mesh = {*Bipolar Disorder/drug therapy/genetics ; Female ; Humans ; Leukocytes ; Lithium ; Male ; Telomere/genetics ; Telomere Shortening ; },
abstract = {OBJECTIVES: Bipolar disorder (BD) may be connected with accelerated aging, the marker of this can be shorter telomere length (TL). Some data suggest that lithium may exert a protective effect against telomere shortening. The study aimed to compare the TL between patients with BD and control subjects. The effect of long-term lithium treatment was also assessed.<br><br>METHODS: The study group comprised 41 patients with BD, including 29 patients treated longitudinally with lithium (mean 16.5 years) and 20 healthy people. TL was assessed by the quantitative polymerase chain reaction (qPCR).<br><br>RESULTS: In the control group, the TL was significantly longer in males than in females. Male bipolar patients had significantly shorter TL compared with the control male group. In bipolar patients, there was no correlation between TL and duration of treatment. The TL was negatively correlated with age in male bipolar patients.<br><br>CONCLUSIONS: The study did not confirm the lithium effect on TL in bipolar patients. TL showed gender differences, being shorter in BD males, compared to control males, and longer in healthy males, compared to control females.},
}
@article {pmid34368190,
year = {2021},
author = {Campisi, M and Liviero, F and Maestrelli, P and Guarnieri, G and Pavanello, S},
title = {DNA Methylation-Based Age Prediction and Telomere Length Reveal an Accelerated Aging in Induced Sputum Cells Compared to Blood Leukocytes: A Pilot Study in COPD Patients.},
journal = {Frontiers in medicine},
volume = {8},
number = {},
pages = {690312},
pmid = {34368190},
issn = {2296-858X},
abstract = {Aging is the predominant risk factor for most degenerative diseases, including chronic obstructive pulmonary disease (COPD). This process is however very heterogeneous. Defining the biological aging of individual tissues may contribute to better assess this risky process. In this study, we examined the biological age of induced sputum (IS) cells, and peripheral blood leukocytes in the same subject, and compared these to assess whether biological aging of blood leukocytes mirrors that of IS cells. Biological aging was assessed in 18 COPD patients (72.4 ± 7.7 years; 50% males). We explored mitotic and non-mitotic aging pathways, using telomere length (TL) and DNA methylation-based age prediction (DNAmAge) and age acceleration (AgeAcc) (i.e., difference between DNAmAge and chronological age). Data on demographics, life style and occupational exposure, lung function, and clinical and blood parameters were collected. DNAmAge (67.4 ± 5.80 vs. 61.6 ± 5.40 years; p = 0.0003), AgeAcc (-4.5 ± 5.02 vs. -10.8 ± 3.50 years; p = 0.0003), and TL attrition (1.05 ± 0.35 vs. 1.48 ± 0.21 T/S; p = 0.0341) are higher in IS cells than in blood leukocytes in the same patients. Blood leukocytes DNAmAge (r = 0.927245; p = 0.0026) and AgeAcc (r = 0.916445; p = 0.0037), but not TL, highly correlate with that of IS cells. Multiple regression analysis shows that both blood leukocytes DNAmAge and AgeAcc decrease (i.e., younger) in patients with FEV1% enhancement (p = 0.0254 and p = 0.0296) and combined inhaled corticosteroid (ICS) therapy (p = 0.0494 and p = 0.0553). In conclusion, new findings from our work reveal a differential aging in the context of COPD, by a direct quantitative comparison of cell aging in the airway with that in the more accessible peripheral blood leukocytes, providing additional knowledge which could offer a potential translation into the disease management.},
}
@article {pmid34362683,
year = {2021},
author = {Sun, J and Liu, W and Guo, Y and Zhang, H and Jiang, D and Luo, Y and Liu, R and Chen, C},
title = {Characterization of tree shrew telomeres and telomerase.},
journal = {Journal of genetics and genomics = Yi chuan xue bao},
volume = {48},
number = {7},
pages = {631-639},
doi = {10.1016/j.jgg.2021.06.004},
pmid = {34362683},
issn = {1673-8527},
mesh = {*Telomerase ; },
abstract = {The use of tree shrews as experimental animals for biomedical research is a new practice. Several recent studies suggest that tree shrews are suitable for studying cancers, including breast cancer, glioblastoma, lung cancer, and hepatocellular carcinoma. However, the telomeres and the telomerase of tree shrews have not been studied to date. Here, we characterize telomeres and telomerase in tree shrews. The telomere length of tree shrews is approximately 23 kb, which is longer than that of primates and shorter than that of mice, and it is extended in breast tumor tissues according to Southern blot and flow-fluorescence in situ hybridization (FISH) analyses. Tree shrew spleen, bone marrow, testis, ovary, and uterus show high telomerase activities, which are increased in breast tumor tissues by telomeric repeat amplification protocol assays. The telomere length becomes shorter, and telomerase activity decreases with age. The tree shrew TERT and TERC are more highly similar to primates than to rodents. These findings lay a solid foundation for using tree shrews to study aging and cancers.},
}
@article {pmid34359923,
year = {2021},
author = {Ghilain, C and Gilson, E and Giraud-Panis, MJ},
title = {Multifunctionality of the Telomere-Capping Shelterin Complex Explained by Variations in Its Protein Composition.},
journal = {Cells},
volume = {10},
number = {7},
pages = {},
pmid = {34359923},
issn = {2073-4409},
support = {TELOCHROM//Agence Nationale de la Recherche/ ; Programme//Fondation ARC pour la Recherche sur le Cancer/ ; AGEMED//Institut National de la Sant&#xe9; et de la Recherche M&#xe9;dicale/ ; },
mesh = {Animals ; DNA/metabolism ; DNA Replication ; Humans ; Models, Molecular ; Protein Structure, Quaternary ; Telomere/*metabolism ; Telomere-Binding Proteins/chemistry/*metabolism ; },
abstract = {Protecting telomere from the DNA damage response is essential to avoid the entry into cellular senescence and organismal aging. The progressive telomere DNA shortening in dividing somatic cells, programmed during development, leads to critically short telomeres that trigger replicative senescence and thereby contribute to aging. In several organisms, including mammals, telomeres are protected by a protein complex named Shelterin that counteract at various levels the DNA damage response at chromosome ends through the specific function of each of its subunits. The changes in Shelterin structure and function during development and aging is thus an intense area of research. Here, we review our knowledge on the existence of several Shelterin subcomplexes and the functional independence between them. This leads us to discuss the possibility that the multifunctionality of the Shelterin complex is determined by the formation of different subcomplexes whose composition may change during aging.},
}
@article {pmid34359743,
year = {2021},
author = {Li, Y and Sundquist, K and Wang, X and Zhang, N and Hedelius, A and Sundquist, J and Memon, AA},
title = {Association of Mitochondrial DNA Copy Number and Telomere Length with Prevalent and Incident Cancer and Cancer Mortality in Women: A Prospective Swedish Population-Based Study.},
journal = {Cancers},
volume = {13},
number = {15},
pages = {},
pmid = {34359743},
issn = {2072-6694},
abstract = {Changes in mitochondrial DNA copy number (mtDNA-CN) and telomere length have, separately, been proposed as risk factors for various cancer types. However, those results are conflicting. Here, mtDNA-CN and relative telomere length were measured in 3225 middle-aged women included in a large population-based prospective cohort. The baseline mtDNA-CN in patients with prevalent breast cancer was significantly higher (12.39 copies/µL) than cancer-free individuals. During an average of 15.2 years of follow-up, 520 patients were diagnosed with cancer. Lower mtDNA-CN was associated with decreased risk of genital organ cancer (hazard ratio (HR), 0.84), and shorter telomere length was associated with increased risk of urinary system cancer (HR, 1.79). Furthermore, mtDNA-CN was inversely associated with all-cause (HR, 1.20) and cancer-specific mortality (HR, 1.21) when considering all cancer types. Surprisingly, shorter telomere length was associated with decreased risk of cancer-specific mortality when considering all cancer types (HR, 0.85). Finally, lower mtDNA-CN and shorter telomere length were associated with increased risk of both all-cause and cancer-specific mortality in genital organ cancer patients. In this study population, we found that mtDNA-CN and telomere length were significantly associated with prevalent and incident cancer and cancer mortality. However, these associations were cancer type specific and need further investigation.},
}
@article {pmid34359672,
year = {2021},
author = {Zheng, X and Wezel, F and Azoitei, A and Meessen, S and Wang, W and Najjar, G and Wang, X and Kraus, JM and Kestler, HA and John, A and Zengerling, F and Bolenz, C and Günes, C},
title = {Shorter Leukocyte Telomere Length Is Associated with Worse Survival of Patients with Bladder Cancer and Renal Cell Carcinoma.},
journal = {Cancers},
volume = {13},
number = {15},
pages = {},
pmid = {34359672},
issn = {2072-6694},
abstract = {BACKGROUND: Telomeres are protein-DNA complexes at the tips of linear chromosomes. They protect the DNA from end-to-end fusion and exonucleolytic degradation. Shortening of telomeric DNA during aging can generate dysfunctional telomeres, promoting tumorigenesis. More recent data indicate that both short and long telomeres of peripheral blood leukocyte (PBL) cells can serve as prognostic biomarkers for cancer risk and may be associated with survival of patients with solid cancers. Telomere length in PBL cells could also be a potential prognostic biomarker for survival in bladder cancer (BC) or renal cell carcinoma (RCC).<br><br>METHODS: The relative telomere length (RTL) of PBL cells was assessed in patients with BC (n = 144) and RCC (n = 144) by using qPCR. A control population of patients without malignant disease (NC, n = 73) was included for comparison. The correlation and association of RTL with histopathological parameters and overall survival (OS) were evaluated.<br><br>RESULTS: Patients with BC and RCC had significantly shorter telomeres compared to patients without malignant disease. Within the cancer cohorts, multivariate analysis revealed that short RTL is an independent predictor of worse survival in BC (p = 0.039) and RCC (p = 0.041).<br><br>CONCLUSION: Patients with BC and RCC had significantly shorter telomeres compared to the normal population. Shorter RTL in BC and RCC was an independent predictor of reduced survival.},
}
@article {pmid34358137,
year = {2021},
author = {Hsiao, CB and Bedi, H and Gomez, R and Khan, A and Meciszewski, T and Aalinkeel, R and Khoo, TC and Sharikova, AV and Khmaladze, A and Mahajan, SD},
title = {Telomere Length Shortening in Microglia: Implication for Accelerated Senescence and Neurocognitive Deficits in HIV.},
journal = {Vaccines},
volume = {9},
number = {7},
pages = {},
pmid = {34358137},
issn = {2076-393X},
abstract = {The widespread use of combination antiretroviral therapy (cART) has led to the accelerated aging of the HIV-infected population, and these patients continue to have a range of mild to moderate HIV-associated neurocognitive disorders (HAND). Infection results in altered mitochondrial function. The HIV-1 viral protein Tat significantly alters mtDNA content and enhances oxidative stress in immune cells. Microglia are the immune cells of the central nervous system (CNS) that exhibit a significant mitotic potential and are thus susceptible to telomere shortening. HIV disrupts the normal interplay between microglia and neurons, thereby inducing neurodegeneration. HIV cART contributes to the inhibition of telomerase activity and premature telomere shortening in activated peripheral blood mononuclear cells (PBMC). However, limited information is available on the effect of cART on telomere length (TL) in microglia. Although it is well established that telomere shortening induces cell senescence and contributes to the development of age-related neuro-pathologies, the effect of HIV-Tat on telomere length in human microglial cells and its potential contribution to HAND are not well understood. It is speculated that in HAND intrinsic molecular mechanisms that control energy production underlie microglia-mediated neuronal injury. TL, telomerase and mtDNA expression were quantified in microglial cells using real time PCR. Cellular energetics were measured using the Seahorse assay. The changes in mitochondrial function were examined by Raman Spectroscopy. We have also examined TL in the PBMC obtained from HIV-1 infected rapid progressors (RP) on cART and those who were cART naïve, and observed a significant decrease in telomere length in RP on cART as compared to RP's who were cART naïve. We observed a significant decrease in telomerase activity, telomere length and mitochondrial function, and an increase in oxidative stress in human microglial cells treated with HIV Tat. Neurocognitive impairment in HIV disease may in part be due to accelerated neuro-pathogenesis in microglial cells, which is attributable to increased oxidative stress and mitochondrial dysfunction.},
}
@article {pmid34357912,
year = {2021},
author = {Kaali, S and Jack, D and Opoku-Mensah, J and Bloomquist, T and Aanaro, J and Quinn, A and Boamah-Kaali, EA and Kinney, P and Mujtaba, MN and Agyei, O and Yawson, AK and Osei-Owusu, S and Delimini, R and Wylie, B and Ae-Ngibise, KA and Baccarelli, A and Owusu-Agyei, S and Chillrud, SN and Asante, KP and Lee, A},
title = {Prenatal Household Air Pollution Exposure, Cord Blood Mononuclear Cell Telomere Length and Age Four Blood Pressure: Evidence from a Ghanaian Pregnancy Cohort.},
journal = {Toxics},
volume = {9},
number = {7},
pages = {},
pmid = {34357912},
issn = {2305-6304},
support = {ES019547/NH/NIH HHS/United States ; R21 TW010957/TW/FIC NIH HHS/United States ; TW010957/TW/FIC NIH HHS/United States ; ES026991/NH/NIH HHS/United States ; R01 ES026991/ES/NIEHS NIH HHS/United States ; K23 HL135349/HL/NHLBI NIH HHS/United States ; ES009089/NH/NIH HHS/United States ; P30 ES009089/ES/NIEHS NIH HHS/United States ; },
abstract = {Associations between prenatal household air pollution exposure (HAP), newborn telomere length and early childhood blood pressure are unknown. Methods: Pregnant women were randomized to liquefied petroleum gas (LPG) stove, improved biomass stove or control (traditional, open fire cook stove). HAP was measured by personal carbon monoxide (CO) (n = 97) and fine particulate matter (PM2.5) (n = 60). At birth, cord blood mononuclear cells (CBMCs) were collected for telomere length (TL) analyses. At child age four years, we measured resting blood pressure (BP) (n = 97). We employed multivariable linear regression to determine associations between prenatal HAP and cookstove arm and assessed CBMC relative to TL separately. We then examined associations between CBMC TL and resting BP. Results: Higher prenatal PM2.5 exposure was associated with reduced TL (β = -4.9% (95% CI -8.6, -0.4), p = 0.03, per 10 ug/m[3] increase in PM2.5). Infants born to mothers randomized to the LPG cookstove had longer TL (β = 55.3% (95% CI 16.2, 109.6), p < 0.01)) compared with control. In all children, shorter TL was associated with higher systolic BP (SBP) (β = 0.35 mmHg (95% CI 0.001, 0.71), p = 0.05, per 10% decrease in TL). Increased prenatal HAP exposure is associated with shorter TL at birth. Shorter TL at birth is associated with higher age four BP, suggesting that TL at birth may be a biomarker of HAP-associated disease risk.},
}
@article {pmid34354128,
year = {2021},
author = {Guillén, R and Otero, F and Mosquera, A and Vázquez-Mosquera, M and Rego-Pérez, I and Blanco, FJ and Fernández, JL},
title = {Association of accelerated dynamics of telomere sequence loss in peripheral blood leukocytes with incident knee osteoarthritis in Osteoarthritis Initiative cohort.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {15914},
pmid = {34354128},
issn = {2045-2322},
mesh = {Aging ; Cohort Studies ; Follow-Up Studies ; Humans ; Incidence ; Knee Joint/pathology ; Leukocytes/pathology ; Leukocytes, Mononuclear/pathology ; Osteoarthritis/genetics/metabolism/pathology ; Osteoarthritis, Knee/*genetics/metabolism/pathology ; Prospective Studies ; Risk Factors ; Telomere/metabolism/*pathology/physiology ; Telomere Homeostasis/genetics/*physiology ; },
abstract = {Osteoarthritis (OA) is a chronic degenerative joint disease, being the main cause of laboral inability. Decreased telomere size in peripheral blood leukocytes (PBL) has been correlated with age-related pathologies, like knee OA. In a dynamic approach, telomere-qPCR was performed to evaluate the relative percentage of PBL telomere loss after a 6-year follow-up, in 281 subjects from the prospective osteoarthritis initiative (OAI) cohort. A radiological Kellgren-Lawrence (KL) grade ≥ 2 was indicative of knee OA. Individuals with knee OA at recruitment (n = 144) showed a higher PBL telomere loss after 6 years than those without knee OA at baseline (n = 137; p = 0.018). Moreover, individuals that developed knee OA during the follow-up (n = 39) exhibited a higher telomere loss compared to those that remained without OA (n = 98; p < 0.001). Logistic regression analysis showed that PBLs telomere loss was not significantly associated with knee OA at recruitment, but behaves as an independent risk factor associated with incidence after follow-up (OR: 1.043; p = 0.041), together with maximum KL grade (OR: 3.627; p = 0.011), body mass index-BMI (OR: 1.252; p < 0.001) and WOMAC-index (OR: 1.247; p = 0.021), at recruitment. The telomere decay in PBLs is faster in individuals with incident knee OA, possibly reflecting a systemic-global accelerated aging that enhances the cartilage degeneration.},
}
@article {pmid34353674,
year = {2021},
author = {Tian, XP and Qian, D and He, LR and Huang, H and Mai, SJ and Li, CP and Huang, XX and Cai, MY and Liao, YJ and Kung, HF and Zeng, YX and Xie, D},
title = {Corrigendum to "The telomere/telomerase binding factor PinX1 regulates paclitaxel sensitivity depending on spindle assembly checkpoint in human cervical squamous cell carcinomas" [Canc. Lett. 353 (2014) 104-114].},
journal = {Cancer letters},
volume = {519},
number = {},
pages = {345},
doi = {10.1016/j.canlet.2021.07.043},
pmid = {34353674},
issn = {1872-7980},
}
@article {pmid34348341,
year = {2022},
author = {Ban, X and Mo, S and Lu, Z and Jia, C and Shao, H and Yan, J and Chang, X and Mao, X and Wu, Y and Zhang, Y and Fan, X and Yu, S and Chen, J},
title = {Alternative Lengthening of Telomeres Phenotype Predicts Progression Risk in Noninsulinomas in a Chinese Cohort.},
journal = {Neuroendocrinology},
volume = {112},
number = {5},
pages = {510-522},
doi = {10.1159/000518413},
pmid = {34348341},
issn = {1423-0194},
mesh = {Adaptor Proteins, Signal Transducing/metabolism ; China ; Co-Repressor Proteins/genetics/metabolism ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Molecular Chaperones/genetics/metabolism ; *Neuroendocrine Tumors/pathology ; *Pancreatic Neoplasms/pathology ; Phenotype ; Telomere/genetics/metabolism/pathology ; Telomere Homeostasis/genetics ; X-linked Nuclear Protein/genetics/metabolism ; },
abstract = {INTRODUCTION: Recent studies have suggested that alternative lengthening of telomeres (ALT) is associated with metastasis and poor survival in pancreatic neuroendocrine tumors (PanNETs). This study evaluated whether this association is applicable to Chinese patients as well as the potential somatic mutations associated with ALT.<br><br>METHODS: We assessed the prevalence of ALT by performing telomere-specific fluorescence in situ hybridization and analyzed DAXX/ATRX expression using immunohistochemistry in 112 Chinese patients with PanNETs to evaluate the association between ALT and clinical outcomes. A subset of the noninsulinoma samples (28/60) was subjected to Sanger sequencing and targeted sequencing.<br><br>RESULTS: The ALT-positive phenotype was identified in 23.2% (26/112) of the samples. The clinicopathologic factors significantly associated with progression in the noninsulinoma (n = 60) cohort were the female sex (p = 0.006), Ki-67 index (p < 0.001), World Health Organization grade (p = 0.031), and ALT positivity (p = 0.013). Patients with ALT-positive PanNETs had significantly shorter progression-free survival than those with ALT-negative PanNETs in the entire cohort (p < 0.001), noninsulinoma subgroup (p = 0.01), and G2 subgroup (p = 0.001). ALT-positive samples frequently harbored somatic mutations in DAXX, ATRX, MEN1, SETBP1, PRKDC, and GNAS.<br><br>CONCLUSIONS: We confirmed that ALT positivity is an effective risk predictor, especially in the noninsulinoma and G2 subgroups. ALT is also related to somatic mutations in MEN1, SETBP1, PRKDC, and GNAS, in addition to DAXX and ATRX.},
}
@article {pmid34347924,
year = {2021},
author = {Sun, G and Cao, H and Bai, Y and Wang, J and Zhou, Y and Li, K and Xiao, JH},
title = {A novel multiplex qPCR method for assessing the comparative lengths of telomeres.},
journal = {Journal of clinical laboratory analysis},
volume = {35},
number = {9},
pages = {e23929},
pmid = {34347924},
issn = {1098-2825},
support = {2017SHZDZX01//Shanghai Municipal Science and Technology Major Project/ ; },
mesh = {DNA/analysis/*genetics ; HEK293 Cells ; HeLa Cells ; Humans ; Real-Time Polymerase Chain Reaction/*methods ; Telomere/*genetics ; *Telomere Homeostasis ; },
abstract = {BACKGROUND: The comparative length of telomeres is considered to be related to diseases such as cancer, aging, and cardiovascular diseases. qPCR is currently one of the main methods for detecting telomere length. However, due to the unique sequence of telomeres (highly repetitive six-base sequence), it is difficult to design primers and probes to expand and detect telomere and to put internal reference gene and telomere into the same tube for detection to reduce the possible inter-pore errors and improve amplification efficiency. Besides, the stability and accuracy of the test results are greatly affected by the difference between reference genes and telomere copy number.<br><br>METHODS: In this study, the single-copy genes were replaced with high-copy genes (300 copies) as the internal control to reduce the copy number difference of the internal genes and telomere. In addition, a multiplex qPCR system was constructed to detect the telomeres and an internal reference gene product. We also detected the lengths of telomeres in the genomic DNA in immortalized cells (293T and Hela) from different generations of cells.<br><br>RESULTS: We detected the comparative telomere lengths of 1500 random Chinese volunteers of different ages with the multiplex qPCR method; the result shows that the comparative length of telomeres is negatively related to age. In addition, we compared our qPCR detection method with a terminal restriction fragmentation (TRF) method. Both of them were highly consistent, indicating that the qPCR method was reliable.<br><br>CONCLUSIONS: In conclusion, we developed a stable, convenient, and accurate comparative telomere length detection method.},
}
@article {pmid34343614,
year = {2021},
author = {Kodali, HP and Borrell, LN},
title = {Telomere length and mortality risk among adults in the United States: The role of age and race and ethnicity.},
journal = {Annals of epidemiology},
volume = {63},
number = {},
pages = {68-74},
doi = {10.1016/j.annepidem.2021.07.013},
pmid = {34343614},
issn = {1873-2585},
mesh = {Adult ; *Cardiovascular Diseases/genetics ; *Ethnicity ; Humans ; Nutrition Surveys ; Retrospective Studies ; Telomere ; United States/epidemiology ; },
abstract = {PURPOSE: To examine whether there was an association of leucocyte telomere length (LTL) with all-cause, cardiovascular (CVD)- and cancer-specific mortality risks among U.S. adults; and whether these associations vary with race and ethnicity and age.<br><br>METHODS: We conducted a retrospective cohort using data from the National Health and Nutrition Examination Survey, 1999 to 2002 and the 2015 Linked Mortality File on adults 25 years or older (n&#xa0;=&#xa0;6,526 and 1,753 deaths). Cox proportional hazards regression was used to quantify the association of LTL with each outcome adjusting for baseline sociodemographic and health-related characteristics. We tested a three-way interaction for LTL, race and ethnicity, and age groups.<br><br>RESULTS: After adjustment, the rate of dying for all-cause and CVD-specific mortality was at least 24% lower for a 1 kilobase increase in LTL. When compared with adults with the shortest telomere, the rates of dying were at least 17% lower for all-cause and CVD-specific mortality for those with longer telomere. For all-cause mortality, increase LTL was associated with lower rate of dying among non-Hispanic Blacks 45 years or older, and non-Hispanic Whites 65 years or older.<br><br>CONCLUSIONS: We found that increase telomere length was associated with lower all-cause and CVD-specific mortality rates among U.S. adults. For all-cause mortality, this association varies within racial and ethnic groups across age groups.},
}
@article {pmid34343137,
year = {2021},
author = {Schratz, KE and Gaysinskaya, V and Cosner, ZL and DeBoy, EA and Xiang, Z and Kasch-Semenza, L and Florea, L and Shah, PD and Armanios, M},
title = {Somatic reversion impacts myelodysplastic syndromes and acute myeloid leukemia evolution in the short telomere disorders.},
journal = {The Journal of clinical investigation},
volume = {131},
number = {18},
pages = {},
pmid = {34343137},
issn = {1558-8238},
support = {F32 HL142207/HL/NHLBI NIH HHS/United States ; R01 HL119476/HL/NHLBI NIH HHS/United States ; T32 GM007309/GM/NIGMS NIH HHS/United States ; T32 GM136577/GM/NIGMS NIH HHS/United States ; T32 HL007525/HL/NHLBI NIH HHS/United States ; R01 CA225027/CA/NCI NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Child ; Female ; Germ-Line Mutation ; High-Throughput Nucleotide Sequencing ; Humans ; Leukemia, Myeloid, Acute/*genetics ; Male ; Middle Aged ; Mutation ; Myelodysplastic Syndromes/*genetics ; Promoter Regions, Genetic ; RNA/genetics ; Shelterin Complex ; Telomerase/genetics ; Telomere/*genetics ; Telomere Shortening/genetics ; Telomere-Binding Proteins/genetics ; Young Adult ; },
abstract = {BACKGROUNDGermline mutations in telomerase and other telomere maintenance genes manifest in the premature aging short telomere syndromes. Myelodysplastic syndromes and acute myeloid leukemia (MDS/AML) account for 75% of associated malignancies, but how these cancers overcome the inherited telomere defect is unknown.METHODSWe used ultra-deep targeted sequencing to detect somatic reversion mutations in 17 candidate telomere lengthening genes among controls and patients with short telomere syndromes with and without MDS/AML, and we tested the functional significance of these mutations.RESULTSWhile no controls carried somatic mutations in telomere maintenance genes, 29% (16 of 56) of adults with germline telomere maintenance defects carried at least 1 (P < 0.001), and 13% (7 of 56) had 2 or more. In addition to TERT promoter mutations, which were present in 19%, another 13% of patients carried a mutation in POT1 or TERF2IP. POT1 mutations impaired telomere binding in vitro and some mutations were identical to ones seen in familial melanoma associated with longer telomere length. Exclusively in patients with germline defects in telomerase RNA (TR), we identified somatic mutations in nuclear RNA exosome genes RBM7, SKIV2L2, and DIS3, where loss-of-function upregulates mature TR levels. Somatic reversion events in 6 telomere-related genes were more prevalent in patients who were MDS/AML-free (P = 0.02, RR 4.4, 95% CI 1.2-16.7), and no patient with MDS/AML had more than 1 reversion mutation.CONCLUSIONOur data indicate that diverse adaptive somatic mutations arise in the short telomere syndromes. Their presence may alleviate the telomere crisis that promotes transformation to MDS/AML.FUNDINGThis work was supported by the NIH, the Commonwealth Foundation, the S&amp;R Foundation Kuno Award, the Williams Foundation, the Vera and Joseph Dresner Foundation, the MacMillan Pathway to Independence Award, the American Society of Hematology Scholar Award, the Johns Hopkins Research Program for Medical Students, and the Turock Scholars Fund.},
}
@article {pmid34341708,
year = {2021},
author = {Bühring, J and Hecker, M and Fitzner, B and Zettl, UK},
title = {Systematic Review of Studies on Telomere Length in Patients with Multiple Sclerosis.},
journal = {Aging and disease},
volume = {12},
number = {5},
pages = {1272-1286},
pmid = {34341708},
issn = {2152-5250},
abstract = {Telomeres are protective cap structures at the end of chromosomes that are essential for maintaining genomic stability. Accelerated telomere shortening is related to premature cellular senescence. Shortened telomere lengths (TL) have been implicated in the pathogenesis of various chronic immune-mediated and neurological diseases. We aimed to systematically review the current literature on the association of TL as a measure of biological age and multiple sclerosis (MS). A comprehensive literature search was conducted to identify original studies that presented data on TL in samples from persons with MS. Quantitative and qualitative information was extracted from the articles to summarize and compare the studies. A total of 51 articles were screened, and 7 of them were included in this review. In 6 studies, average TL were analyzed in peripheral blood cells, whereas in one study, bone marrow-derived cells were used. Four of the studies reported significantly shorter leukocyte TL in at least one MS subtype in comparison to healthy controls (p=0.003 in meta-analysis). Shorter telomeres in patients with MS were found to be associated, independently of age, with greater disability, lower brain volume, increased relapse rate and more rapid conversion from relapsing to progressive MS. However, it remains unclear how telomere attrition in MS may be linked to oxidative stress, inflammation and age-related disease processes. Despite few studies in this field, there is substantial evidence on the association of TL and MS. Variability in TL appears to reflect heterogeneity in clinical presentation and course. Further investigations in large and well-characterized cohorts are warranted. More detailed studies on TL of individual chromosomes in specific cell types may help to gain new insights into the pathomechanisms of MS.},
}
@article {pmid34339747,
year = {2021},
author = {Park, S and Lee, S and Kim, Y and Cho, S and Kim, K and Kim, YC and Han, SS and Lee, H and Lee, JP and Joo, KW and Lim, CS and Kim, YS and Kim, DK},
title = {A Mendelian randomization study found causal linkage between telomere attrition and chronic kidney disease.},
journal = {Kidney international},
volume = {100},
number = {5},
pages = {1063-1070},
doi = {10.1016/j.kint.2021.06.041},
pmid = {34339747},
issn = {1523-1755},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Aged ; Genome-Wide Association Study ; Glomerular Filtration Rate/genetics ; Humans ; *Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; *Renal Insufficiency, Chronic/epidemiology/genetics ; Telomere/genetics ; },
abstract = {Chronic kidney disease (CKD) is highly prevalent in the elderly population. However, it is rarely investigated whether kidney function is causally linked to biological aging itself. In this Mendelian randomization study, genetic instruments for telomere attrition were applied to a CKDGen genome wide association study results for 41,395 cases of CKD among 480,698 individuals as summary-level Mendelian randomization. A replicative analysis was performed by polygenic score analysis using independent United Kingdom Biobank data for 8,118 cases of CKD among 321,024 white individuals of British ancestry. Reverse-direction Mendelian randomization analysis was performed utilizing genetic instruments for log-estimated glomerular filtration rate change with Z-standardized telomere length outcome data for 326,075 participants in the UK Biobank. Genetic predisposition toward telomere attrition (one Z score decrease in length) was found to be a causative factor for a higher CKD risk [Odds Ratio 1.20 (95% confidence interval 1.08‒1.33)], as supported by pleiotropy-robust Mendelian randomization sensitivity analyses implemented using the CKDGen data. Based on United Kingdom Biobank data, the polygenic score for telomere attrition was significantly associated with a higher risk of CKD [1.20 (1.04‒1.39)]. In reverse-direction Mendelian randomization, the genetically predicted kidney function decrease was significantly associated with a higher degree of telomere attrition [beta 0.039 (0.009‒0.069)]. Thus, our study supports the causal linkage between telomere attrition and kidney function impairment.},
}
@article {pmid34337078,
year = {2021},
author = {Qi, YY and Liu, XR and He, YX and Zhou, M and Ning, XH and Zhai, YL and Zhang, XX and Wang, XY and Zhao, YF and Cui, Y and Zhao, ZZ},
title = {Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations.},
journal = {Journal of immunology research},
volume = {2021},
number = {},
pages = {7079359},
pmid = {34337078},
issn = {2314-7156},
mesh = {Adolescent ; Adult ; Asian People/genetics ; Case-Control Studies ; Cell Cycle Proteins/*genetics/metabolism ; China/epidemiology ; Female ; *Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Lupus Erythematosus, Systemic/blood/epidemiology/*genetics ; Male ; Polymorphism, Single Nucleotide ; Telomere Homeostasis/genetics ; Tumor Suppressor Proteins/*genetics/metabolism ; Young Adult ; },
abstract = {A recent genome-wide association study (GWAS) of Asian ancestry reported that single nucleotide polymorphism (SNP) in TERT (telomerase reverse transcriptase) was associated with systemic lupus erythematosus (SLE). TERT has a critical role in maintaining the chromosomal stability and the length of telomere. Given that only a small portion of the genetic heritability of SLE has been explained so far, we aimed to identify novel loci in telomere-related genes responsible for SLE susceptibility in Chinese populations. We performed a comprehensive genetic association analysis of SLE with telomere-related genes. To identify functional significance, we analyzed the publicly available HaploReg v4.1 and RegulomeDB databases. Differential gene expression analysis was also performed using ArrayExpress. A novel signal of PINX1 rs6984094 was identified (P discovery = 4.13 × 10[-2], OR = 0.58, 95% CI 0.35-0.98) and successfully replicated (P replication = 5.73 × 10[-3], OR = 0.45, 95% CI 0.26-0.81). Multiple layers of functional analysis suggested that the PINX1 rs6984094 risk T allele exhibited increased nuclear protein binding. We also observed an increased expression of PINX1 mRNA in peripheral blood mononuclear cells from SLE patients compared with healthy controls. Overall, we observed a novel genetic association between PINX1 (encodes the PinX1 protein, an inhibitory telomerase enzyme that lengthens telomeres) and SLE susceptibility in Chinese populations.},
}
@article {pmid34335309,
year = {2021},
author = {Marques, A and Peralta, M and Marconcin, P and Henriques-Neto, D and Gouveia, &#xc9;R and Ferrari, G and Martins, J and Sarmento, H and Ihle, A},
title = {A Systematic Review of the Association Between Muscular Fitness and Telomere Length Across the Adult Lifespan.},
journal = {Frontiers in physiology},
volume = {12},
number = {},
pages = {706189},
pmid = {34335309},
issn = {1664-042X},
abstract = {This study aimed to systematically review the association between telomere length (TL) and muscular fitness. In October 2020, an articles search was applied to PubMed, Scopus, and Web of Science. Eligibility criteria included: cross-sectional, prospective, and experimental study design; outcomes included TL; results expressed the relationship between muscular fitness and TL; studies published in English, Portuguese, or Spanish. Nine studies were included in the review. Results from the four prospective studies are mixed. In one study, the changes in TL were associated with grip strength. Another study concluded that longer mid-life TL was associated with increased grip strength later in life. However, in the other two studies, the association between TL and sarcopenia was not strong. Nevertheless, longer TL was associated with a slower decline in grip strength in older people. From the four cross-sectional studies, three indicated that TL was associated with muscular fitness. On the other hand, in a study with powerlifters, TL remained within the range of values found in subjects with no history of regular strength training, supporting the notion that muscular fitness was not associated with TL. The cross-sectional and prospective studies showed that the relationship between TL and muscular fitness is not conclusive. It seems that there is a positive association between TL and muscular fitness in middle-aged and older adults. However, among younger adults, this relationship was not observed.},
}
@article {pmid34333383,
year = {2021},
author = {Duan, X and Wang, H and Yang, Y and Wang, P and Zhang, H and Liu, B and Wei, W and Yao, W and Zhou, X and Zhao, J and Wang, W},
title = {Genetic variants in telomerase-associated protein 1 are associated with telomere damage in PAH-exposed workers.},
journal = {Ecotoxicology and environmental safety},
volume = {223},
number = {},
pages = {112558},
doi = {10.1016/j.ecoenv.2021.112558},
pmid = {34333383},
issn = {1090-2414},
mesh = {*Environmental Pollutants ; Humans ; *Polycyclic Aromatic Hydrocarbons/analysis/toxicity ; *Telomerase/genetics ; Telomere/genetics ; Telomere Shortening ; },
abstract = {Telomeres are functional complexes at the ends of linear chromosomes, and telomerase aids in their maintenance and replication. Additionally, accumulating evidence suggests that telomerase-associated protein 1 (TEP1) is a component of the telomerase ribonucleoprotein complex and is responsible for catalyzing the addition of new synthetic telomere sequences to chromosome ends. In our previous study, we found that genetic variants of the TERT gene participated in the regulation of telomere length. Exposure to particulate matter, environmental pollutants, oxidative stress, and pesticides is associated with shortening of telomere length. However, it is unknown whether genetic variants in the TEP1 gene may affect telomere length (TL) in polycyclic aromatic hydrocarbon (PAH)-exposed workers. Therefore, we measured the peripheral leukocyte TL and genotyped the polymorphism loci in the TEP1 gene among 544 PAH-exposed workers and 238 healthy controls. Covariance analysis showed that the individuals carrying TEP1 rs1760903 CC and TEP1 rs1760904 TT had longer TL in the control group (P < 0.05). In the generalized linear model, we found that rs1760903 CC was a protective factor against TL shortening, and PAH exposure could promote telomere shortening (P < 0.05). Thus, this study reinforces the roles of environmental factors and genetic variations in telomere damage, and provides a theoretical foundation for the early detection of susceptible populations and the establishment of occupational standards.},
}
@article {pmid34333235,
year = {2021},
author = {Aviv, A},
title = {Short telomeres and severe COVID-19: The connection conundrum.},
journal = {EBioMedicine},
volume = {70},
number = {},
pages = {103513},
pmid = {34333235},
issn = {2352-3964},
support = {R01 HL134840/HL/NHLBI NIH HHS/United States ; U01 AG066529/AG/NIA NIH HHS/United States ; },
mesh = {*COVID-19 ; Humans ; SARS-CoV-2 ; *Telomere ; Telomere Shortening ; },
}
@article {pmid34332790,
year = {2021},
author = {Lyons, LA},
title = {Cats - telomere to telomere and nose to tail.},
journal = {Trends in genetics : TIG},
volume = {37},
number = {10},
pages = {865-867},
doi = {10.1016/j.tig.2021.06.001},
pmid = {34332790},
issn = {0168-9525},
mesh = {Animals ; Cat Diseases/*genetics ; Cats ; Chromosomes, Mammalian/genetics ; Evolution, Molecular ; Gene Expression Regulation ; Genetic Speciation ; Genetic Variation ; Genome/*genetics ; *Genomic Medicine ; *Genomics ; Humans ; Pets/*genetics ; Telomere/*genetics ; *Veterinary Medicine ; },
abstract = {Feline genomic medicine can decode human variants of uncertain significance (VUSs). Telomere-to-telomere genome assemblies are feasible for all felid species, supporting genetic evolution and speciation studies. Their highly conserved genomic organization compared to humans suggests cats may also decipher the intergenic variation affecting the 3D chromosome structures influencing gene regulation.},
}
@article {pmid34331967,
year = {2022},
author = {Penrice, DD and Havlichek, D and Kamath, PS and Simonetto, DA},
title = {Outcomes following liver transplant in adults with telomere biology disorders.},
journal = {Journal of hepatology},
volume = {76},
number = {1},
pages = {214-216},
doi = {10.1016/j.jhep.2021.07.022},
pmid = {34331967},
issn = {1600-0641},
mesh = {Adult ; Aged ; Humans ; Liver Transplantation/methods/*standards/trends ; Male ; Middle Aged ; Telomere Shortening/immunology/*physiology ; Treatment Outcome ; },
}
@article {pmid34330985,
year = {2021},
author = {Kosebent, EG and Ozturk, S},
title = {Telomere associated gene expression as well as TERT protein level and telomerase activity are altered in the ovarian follicles of aged mice.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {15569},
pmid = {34330985},
issn = {2045-2322},
mesh = {Animals ; Female ; Mice ; Ovarian Follicle/metabolism ; RNA/metabolism ; Telomerase/*metabolism ; Telomere/*metabolism/pathology ; },
abstract = {Telomeres cap the ends of eukaryotic chromosomes to maintain genomic stability and integrity during an organism's lifespan. The length of telomeres inevitably shortens due to DNA replication, genotoxic agents, and biological aging. A limited number of cell types, e.g., stem cells, germline cells, and early embryos can elongate shortened telomeres via the enzymatic action of telomerase, which is composed of telomerase reverse transcriptase (TERT) and telomerase RNA component (Terc). Additionally, telomere-associated proteins including telomeric repeat binding factor 1 (TRF1) and 2 (TRF2), as well as protection of telomeres 1a (POT1a), bind to telomeres to maintain their structural integrity and length. During ovarian aging in mammals, telomeres progressively shorten, accompanied by fertility loss; however, the molecular mechanism underlying this attrition during follicle development remains unclear. In this study, the primary, secondary, preantral, and antral follicles were obtained either from 6-week-old adult (n = 19) or 52-week-old aged (n = 12) mice. We revealed that the Tert, Terc, Trf1, Trf2, and Pot1a gene expression (P < 0.001) and TERT protein (P < 0.01) levels significantly decreased in certain ovarian follicles of the aged group when compared to those of the adult group. Also, telomerase activity exhibited remarkable changes in the follicles of both groups. Consequently, altered telomere-associated gene expression and reduced TERT protein levels in the follicles of aged mice may be a determinant of telomere shortening during ovarian aging, and infertility appearing in the later decades of reproductive lifespan. Further investigations are required to determine the molecular mechanisms underlying these alterations in the follicles during ovarian aging.},
}
@article {pmid34330324,
year = {2021},
author = {Wang, C and Songyang, Z and Huang, Y},
title = {TRIM28 inhibits alternative lengthening of telomere phenotypes by protecting SETDB1 from degradation.},
journal = {Cell &amp; bioscience},
volume = {11},
number = {1},
pages = {149},
pmid = {34330324},
issn = {2045-3701},
support = {81871109//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: About 10-15% of tumor cells extend telomeres through the alternative lengthening of telomeres (ALT) mechanism, which is a recombination-dependent replication pathway. It is generally believed that ALT cells are related to the chromatin modification of telomeres. However, the mechanism of ALT needs to be further explored.<br><br>RESULTS: Here we found that TRIM28/KAP1 is preferentially located on the telomeres of ALT cells and interacts with telomeric shelterin/telosome complex. Knocking down TRIM28 in ALT cells delayed cell growth, decreased the level of C-circle which is one kind of extrachromosomal circular telomeric DNA, increased the frequency of ALT-associated promyelocytic leukemia bodies (APBs), led to telomere prolongation and increased the telomere sister chromatid exchange in ALT cells. Mechanistically, TRIM28 protects telomere histone methyltransferase SETDB1 from degradation, thus maintaining the H3K9me3 heterochromatin state of telomere DNA.<br><br>CONCLUSIONS: Our work provides a model that TRIM28 inhibits alternative lengthening of telomere phenotypes by protecting SETDB1 from degradation. In general, our results reveal the mechanism of telomere heterochromatin maintenance and its effect on ALT, and TRIM28 may serve as a target for the treatment of ALT tumor cells.},
}
@article {pmid34329803,
year = {2021},
author = {Parolini, M and De Felice, B and Mondellini, S and Caprioli, M and Possenti, CD and Rubolini, D},
title = {Prenatal exposure to triclosan induced brain telomere shortening in a wild bird species.},
journal = {Environmental toxicology and pharmacology},
volume = {87},
number = {},
pages = {103718},
doi = {10.1016/j.etap.2021.103718},
pmid = {34329803},
issn = {1872-7077},
mesh = {Animals ; Anti-Infective Agents/*toxicity ; Brain/*drug effects/embryology/metabolism ; Charadriiformes/*embryology/*genetics ; DNA Damage ; Embryo, Nonmammalian/drug effects/metabolism ; Female ; Male ; Oxidative Stress/drug effects ; Telomere Shortening/*drug effects ; Triclosan/*toxicity ; },
abstract = {Exposure to the antimicrobial agent Triclosan (TCS) induces oxidative stress in diverse organisms, including birds. However, whether TCS-induced oxidative stress effectively translates into detrimental effects is still unclear. The present study examined whether prenatal TCS exposure induces oxidative stress and telomere shortening in the brain and the liver of near-term embryos of the yellow-legged gull (Larus michahellis). Prenatal TCS exposure caused a significant overproduction of reactive oxygen species (ROS) in the brain, but no oxidative damage occurred. Telomeres of TCS-exposed embryos had brain telomeres 30 % shorter compared to controls, probably because the relatively modest antioxidant defenses of this organ during prenatal development cannot counteract the impact of the TCS-induced ROS. No telomere shortening was observed in the liver. Our results demonstrated that prenatal exposure to TCS in wild bird species can modulate the oxidative status and induce telomere shortening in the brain of the yellow-legged gull embryos.},
}
@article {pmid34324695,
year = {2021},
author = {Kohlrausch, FB and Wang, F and Chamani, I and Keefe, DL},
title = {Telomere Shortening and Fusions: A Link to Aneuploidy in Early Human Embryo Development.},
journal = {Obstetrical &amp; gynecological survey},
volume = {76},
number = {7},
pages = {429-436},
doi = {10.1097/OGX.0000000000000907},
pmid = {34324695},
issn = {1533-9866},
mesh = {Aged ; Aneuploidy ; Animals ; Cattle ; *Embryonic Development/genetics ; Female ; Humans ; Mice ; Oocytes ; Pregnancy ; Telomere/genetics ; *Telomere Shortening ; },
abstract = {IMPORTANCE: It is known that oocytes undergo aging that is caused by exposure to an aged ovarian microenvironment. Telomere length in mouse and bovine oocytes declines with age, and age-associated telomere shortening in oocytes is considered a sign of poor development competency. Women with advanced age undergoing assisted reproductive technologies have poor outcomes because of increasing aneuploidy rates with age. Research has shown that aneuploidy is associated with DNA damage, reactive oxygen species, and telomere dysfunction.<br><br>OBJECTIVE: In this review, we focus on the possible relationship between telomere dysfunction and aneuploidy in human early embryo development and several reproductive and perinatal outcomes, discussing the mechanism of aneuploidy caused by telomere shortening and fusion in human embryos.<br><br>EVIDENCE ACQUISITION: We reviewed the current literature evidence concerning telomere dysfunction and aneuploidy in early human embryo development.<br><br>RESULTS: Shorter telomeres in oocytes, leukocytes, and granulosa cells, related to aging in women, were associated with recurrent miscarriage, trisomy 21, ovarian insufficiency, and decreasing chance of in vitro fertilization success. Telomere length and telomerase activity in embryos have been related to the common genomic instability at the cleavage stage of human development. Complications of assisted reproductive technology pregnancies, such as miscarriage, birth defects, preterm births, and intrauterine growth restriction, also might result from telomere shortening as observed in oocytes, polar body, granulosa cells, and embryos.<br><br>CONCLUSIONS AND RELEVANCE: Telomere length clearly plays an important role in the development of the embryo and fetus, and the abnormal shortening of telomeres is likely involved in embryo loss during early human development. However, telomere fusion studies have yet to be performed in early human development.},
}
@article {pmid34321211,
year = {2021},
author = {Lee, JH and Hong, J and Zhang, Z and de la Peña Avalos, B and Proietti, CJ and Deamicis, AR and Guzmán G, P and Lam, HM and Garcia, J and Roudier, MP and Sisk, AE and De La Rosa, R and Vu, K and Yang, M and Liao, Y and Scheirer, J and Pechacek, D and Yadav, P and Rao, MK and Zheng, S and Johnson-Pais, TL and Leach, RJ and Elizalde, PV and Dray, E and Xu, K},
title = {Regulation of telomere homeostasis and genomic stability in cancer by N [6]-adenosine methylation (m[6]A).},
journal = {Science advances},
volume = {7},
number = {31},
pages = {},
pmid = {34321211},
issn = {2375-2548},
support = {P30 CA054174/CA/NCI NIH HHS/United States ; },
abstract = {The role of RNA methylation on N [6]-adenosine (m[6]A) in cancer has been acknowledged, but the underlying mechanisms remain obscure. Here, we identified homeobox containing 1 (HMBOX1) as an authentic target mRNA of m[6]A machinery, which is highly methylated in malignant cells compared to the normal counterparts and subject to expedited degradation upon the modification. m[6]A-mediated down-regulation of HMBOX1 causes telomere dysfunction and inactivation of p53 signaling, which leads to chromosome abnormalities and aggressive phenotypes. CRISPR-based, m[6]A-editing tools further prove that the methyl groups on HMBOX1 per se contribute to the generation of altered cancer genome. In multiple types of human cancers, expression of the RNA methyltransferase METTL3 is negatively correlated with the telomere length but favorably with fractions of altered cancer genome, whereas HMBOX1 mRNA levels show the opposite patterns. Our work suggests that the cancer-driving genomic alterations may potentially be fixed by rectifying particular epitranscriptomic program.},
}
@article {pmid34319984,
year = {2021},
author = {Rosin, LF and Gil, J and Drinnenberg, IA and Lei, EP},
title = {Oligopaint DNA FISH reveals telomere-based meiotic pairing dynamics in the silkworm, Bombyx mori.},
journal = {PLoS genetics},
volume = {17},
number = {7},
pages = {e1009700},
pmid = {34319984},
issn = {1553-7404},
mesh = {Animals ; Bombyx/*genetics ; Cell Cycle Proteins/genetics ; Centromere/metabolism ; Chromosomal Proteins, Non-Histone/genetics ; Chromosome Pairing/*genetics ; Chromosome Segregation/genetics ; Chromosomes/genetics ; DNA/genetics ; Female ; Male ; Meiosis/genetics ; Microtubules/metabolism ; Synaptonemal Complex/metabolism ; Telomere/*genetics ; },
abstract = {Accurate chromosome segregation during meiosis is essential for reproductive success. Yet, many fundamental aspects of meiosis remain unclear, including the mechanisms regulating homolog pairing across species. This gap is partially due to our inability to visualize individual chromosomes during meiosis. Here, we employ Oligopaint FISH to investigate homolog pairing and compaction of meiotic chromosomes and resurrect a classical model system, the silkworm Bombyx mori. Our Oligopaint design combines multiplexed barcoding with secondary oligo labeling for high flexibility and low cost. These studies illustrate that Oligopaints are highly specific in whole-mount gonads and on meiotic squashes. We show that meiotic pairing is robust in both males and females and that pairing can occur through numerous partially paired intermediate structures. We also show that pairing in male meiosis occurs asynchronously and seemingly in a transcription-biased manner. Further, we reveal that meiotic bivalent formation in B. mori males is highly similar to bivalent formation in C. elegans, with both of these pathways ultimately resulting in the pairing of chromosome ends with non-paired ends facing the spindle pole. Additionally, microtubule recruitment in both C. elegans and B. mori is likely dependent on kinetochore proteins but independent of the centromere-specifying histone CENP-A. Finally, using super-resolution microscopy in the female germline, we show that homologous chromosomes remain associated at telomere domains in the absence of chiasma and after breakdown and modification to the synaptonemal complex in pachytene. These studies reveal novel insights into mechanisms of meiotic homolog pairing both with or without recombination.},
}
@article {pmid34319229,
year = {2022},
author = {Ren, CY and Liu, PP and Li, J and Li, YQ and Zhang, LJ and Chen, GH and Dong, FY and Hu, D and Zhang, M},
title = {Changes in telomere length and serum neurofilament light chain levels in female patients with chronic insomnia disorder.},
journal = {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine},
volume = {18},
number = {2},
pages = {383-392},
pmid = {34319229},
issn = {1550-9397},
mesh = {Biomarkers ; *Cognitive Dysfunction ; Female ; Humans ; Intermediate Filaments ; Sleep ; *Sleep Initiation and Maintenance Disorders ; Telomere ; },
abstract = {STUDY OBJECTIVES: The aims of this study were to explore changes in the telomere length (relative telomere repeat copy/single-copy gene [T/S ratio]) and serum neurofilament light chain (sNfL) levels in female patients with chronic insomnia disorder (CID), examine their relationships with emotional abnormalities and cognitive impairment, and determine whether these 2 indicators were independently associated with sleep quality.<br><br>METHODS: The CID group contained 80 patients diagnosed with CID, and 51 individuals constituted a healthy control group. Participants completed sleep, emotion, and cognition assessments. Telomere length was detected through quantitative real-time polymerase chain reaction. Enzyme-linked immunosorbent assay was used to determine sNfL concentrations.<br><br>RESULTS: Relative to the healthy control group, the CID group had elevated Pittsburgh Sleep Quality Index, Hamilton Anxiety Scale-14, and Hamilton Depression Rating Scale-17 scores and reduced Montreal Cognitive Assessment scale scores, a decreased T/S ratio, and an increased sNfL concentration. Subgroup analysis according to various CID-associated sleep factors showed that poor sleep performance corresponded to a lower T/S ratio. Higher anxiety levels and more cognitive dysfunction correlated with shorter telomere lengths. The T/S ratio negatively correlated with age, whereas the sNfL concentration positively correlated with age in the CID group. The Pittsburgh Sleep Quality Index score negatively correlated with the T/S ratio but did not correlate with sNfL levels. Multiple linear regression analysis showed that the T/S ratio had a negative and independent effect on Pittsburgh Sleep Quality Index scores.<br><br>CONCLUSIONS: The CID group had shorter telomeres and higher sNfL concentrations, and reduced telomere length independently affected sleep quality.<br><br>CITATION: Ren C-Y, Liu P-P, Li J, et&#xa0;al. Changes in telomere length and serum neurofilament light chain levels in female patients with chronic insomnia disorder. J Clin Sleep Med. 2022;18(2):383-392.},
}
@article {pmid34316718,
year = {2021},
author = {Yang, SY and Chang, EYC and Lim, J and Kwan, HH and Monchaud, D and Yip, S and Stirling, PC and Wong, JMY},
title = {G-quadruplexes mark alternative lengthening of telomeres.},
journal = {NAR cancer},
volume = {3},
number = {3},
pages = {zcab031},
pmid = {34316718},
issn = {2632-8674},
abstract = {About 10-15% of all human cancer cells employ a telomerase-independent recombination-based telomere maintenance method, known as alternative lengthening of telomere (ALT), of which the full mechanism remains incompletely understood. While implicated in previous studies as the initiating signals for ALT telomere repair, the prevalence of non-canonical nucleic acid structures in ALT cancers remains unclear. Extending earlier reports, we observe higher levels of DNA/RNA hybrids (R-loops) in ALT-positive (ALT+) compared to telomerase-positive (TERT+) cells. Strikingly, we observe even more pronounced differences for an associated four-stranded nucleic acid structure, G-quadruplex (G4). G4 signals are found at the telomere and are broadly associated with telomere length and accompanied by DNA damage markers. We establish an interdependent relationship between ALT-associated G4s and R-loops and confirm that these two structures can be spatially linked into unique structures, G-loops, at the telomere. Additionally, stabilization of G4s and R-loops cooperatively enhances ALT-activity. However, co-stabilization at higher doses resulted in cytotoxicity in a synergistic manner. Nuclear G4 signals are significantly and reproducibly different between ALT+ and TERT+ low-grade glioma tumours. Together, we present G4 as a novel hallmark of ALT cancers with potential future applications as a convenient biomarker for identifying ALT+ tumours and as therapeutic targets.},
}
@article {pmid34316326,
year = {2021},
author = {Petrov, N and Lee, HS and Liskovykh, M and Teulade-Fichou, MP and Masumoto, H and Earnshaw, WC and Pommier, Y and Larionov, V and Kouprina, N},
title = {Terpyridine platinum compounds induce telomere dysfunction and chromosome instability in cancer cells.},
journal = {Oncotarget},
volume = {12},
number = {15},
pages = {1444-1456},
pmid = {34316326},
issn = {1949-2553},
abstract = {Telomerase/telomere-targeting therapy is a potentially promising approach for cancer treatment because even transient telomere dysfunction can induce chromosomal instability (CIN) and may be a barrier to tumor growth. We recently developed a dual-HAC (Human Artificial Chromosome) assay that enables identification and ranking of compounds that induce CIN as a result of telomere dysfunction. This assay is based on the use of two isogenic HT1080 cell lines, one carrying a linear HAC (containing telomeres) and the other carrying a circular HAC (lacking telomeres). Disruption of telomeres in response to drug treatment results in specific destabilization of the linear HAC. Results: In this study, we used the dual-HAC assay for the analysis of the platinum-derived G4 ligand Pt-tpy and five of its derivatives: Pt-cpym, Pt-vpym, Pt-ttpy, Pt(PA)-tpy, and Pt-BisQ. Our analysis revealed four compounds, Pt-tpy, Pt-ttpy, Pt-vpym and Pt-cpym, that induce a specific loss of a linear but not a circular HAC. Increased CIN after treatment by these compounds correlates with the induction of double-stranded breaks (DSBs) predominantly localized at telomeres and reflecting telomere-associated DNA damage. Analysis of the mitotic phenotypes induced by these drugs revealed an elevated rate of chromatin bridges (CBs) in late mitosis and cytokinesis. These terpyridine platinum-derived G4 ligands are promising compounds for cancer treatment.},
}
@article {pmid34313963,
year = {2022},
author = {Xie, H and Ma, Y and Shao, M and Kong, J and Zhou, T and Wang, F and Cai, G and Xu, S and Pan, F},
title = {Telomere length in patients with osteoarthritis: a systematic review and meta-analysis.},
journal = {Aging clinical and experimental research},
volume = {34},
number = {3},
pages = {495-503},
pmid = {34313963},
issn = {1720-8319},
support = {81773514//National Natural Science Foundation of China/ ; 82073655//National Natural Science Foundation of China/ ; },
mesh = {Aging ; Biomarkers ; Humans ; *Osteoarthritis/genetics ; Publication Bias ; Telomere ; },
abstract = {BACKGROUND: Telomere length (TL) as a biomarker of aging was associated with many age-related diseases. The relationship between TL and osteoarthritis (OA), the most common form of joint diseases, had been investigated in a number of studies, but with the result inconsistent.<br><br>AIMS: The purpose of this study was to systematically evaluate the relationship between TL and OA.<br><br>METHODS: Until January 1, 2021, PubMed, Web of Science and Cochrane Library were comprehensively retrieved for relevant literatures. Quality of included literature was assessed using the Newcastle-Ottawa Scale (NOS) assessment scale. The pooled standard mean difference (SMD) with 95% confidence interval (CI) of Leukocytes TL was calculated using random-effect model. Subgroup analysis and meta-regression were used to investigate the potential source of heterogeneity.<br><br>RESULTS: Six original studies containing 678 OA patients and 1457 healthy controls were included in this meta-analysis. All six included studies were case-control designed. Pooled results showed that patients with OA had a shorter TL in peripheral blood leukocytes (PBLs) compared with healthy controls, (SMD&#x2009;=&#x2009;-&#xa0;0.32, 95% CI -&#xa0;0.57 to -&#xa0;0.06, Z&#x2009;=&#x2009;-&#xa0;2.45, P&#x2009;=&#x2009;0.014). Subgroup and meta-regression analysis showed that sex ratio and body mass index (BMI) were possible sources of heterogeneity. Publication bias was not observed.<br><br>CONCLUSION: The TL of PBLs in patients with OA was shorter than that of healthy controls, suggesting that PBLs TL may be closely associated with the pathogenesis and progression of OA.},
}
@article {pmid34312982,
year = {2021},
author = {Loh, NY and Noordam, R and Christodoulides, C},
title = {Telomere length and metabolic syndrome traits: A Mendelian randomisation study.},
journal = {Aging cell},
volume = {20},
number = {8},
pages = {e13445},
pmid = {34312982},
issn = {1474-9726},
support = {FS/16/45/32359/BHF_/British Heart Foundation/United Kingdom ; },
mesh = {Humans ; Mendelian Randomization Analysis/*methods ; Metabolic Syndrome/*genetics ; Telomere/*genetics ; },
abstract = {Observational studies have revealed associations between short leucocyte telomere length (LTL), a TL marker in somatic tissues and multiple Metabolic Syndrome (MetS) traits. Animal studies have supported these findings by showing that increased telomere attrition leads to adipose tissue dysfunction and insulin resistance. We investigated the associations between genetically instrumented LTL and MetS traits using Mendelian Randomisation (MR). Fifty-two independent variants identified at FDR<0.05 from a genome-wide association study (GWAS) including 78,592 Europeans and collectively accounting for 2.93% of LTL variance were selected as genetic instruments for LTL. Summary-level data for MetS traits and for the MetS as a binary phenotype were obtained from the largest publicly available GWAS and two-sample MR analyses were used to estimate the associations of LTL with these traits. The combined effect of the genetic instruments was modelled using inverse variance weighted regression and sensitivity analyses with MR-Egger, weighted-median and MR-PRESSO were performed to test for and correct horizonal pleiotropy. Genetically instrumented longer LTL was associated with higher waist-to-hip ratio adjusted for body mass index (β = 0.045 SD, SE = 0.018, p = 0.01), raised systolic (β = 1.529 mmHg, SE = 0.332, p = 4x10[-6]) and diastolic (β = 0.633 mmHg, SE = 0.222, p = 0.004) blood pressure, and increased MetS risk (OR = 1.133, 95% CI 1.057-1.215). Consistent results were obtained in sensitivity analyses, which provided no evidence of unbalanced horizontal pleiotropy. Telomere shortening might not be a major driver of cellular senescence and dysfunction in human adipose tissue. Future experimental studies should examine the mechanistic bases for the links between longer LTL and increased upper-body fat distribution and raised blood pressure.},
}
@article {pmid34311139,
year = {2021},
author = {Kim, EJ and Koh, SH and Ha, J and Na, DL and Seo, SW and Kim, HJ and Park, KW and Lee, JH and Roh, JH and Kwon, JC and Yoon, SJ and Jung, NY and Jeong, JH and Jang, JW and Kim, HJ and Park, KH and Choi, SH and Kim, S and Park, YH and Kim, BC and Kim, YE and Kwon, HS and Park, HH and Jin, JH},
title = {Increased telomere length in patients with frontotemporal dementia syndrome.},
journal = {Journal of the neurological sciences},
volume = {428},
number = {},
pages = {117565},
doi = {10.1016/j.jns.2021.117565},
pmid = {34311139},
issn = {1878-5883},
mesh = {*Alzheimer Disease ; *Amyotrophic Lateral Sclerosis ; *Frontotemporal Dementia/genetics ; Humans ; Syndrome ; Telomere/genetics ; },
abstract = {BACKGROUND: Telomeres are repetitive DNA sequences of TTAGGG at the ends of chromosomes. Many studies have shown that telomere shortening is associated with aging-related diseases, such as cardiovascular diseases, hypertension, diabetes, cancer, and various neurodegenerative diseases, including Alzheimer's disease, vascular dementia, Parkinson's disease, and dementia with Lewy bodies. However, changes in telomere length (TL) in patients with frontotemporal dementia (FTD) syndrome are unclear. Accordingly, in this study, we assessed TL in blood samples from patients with FTD syndrome.<br><br>METHODS: Absolute TL was measured in peripheral blood leukocytes from 53 patients with FTD syndromes (25 with behavioral variant FTD, 19 with semantic variant primary progressive aphasia [PPA], six with nonfluent/agrammatic variant PPA, and three with amyotrophic lateral sclerosis [ALS] plus) and 28 cognitively unimpaired (CU) controls using terminal restriction fragment analysis.<br><br>RESULTS: TL was significantly longer in the FTD group than in the CU group. All FTD subtypes had significantly longer TL than controls. There were no significant differences in TL among FTD syndromes. No significant correlations were found between TL and demographic factors in the FTD group.<br><br>CONCLUSIONS: Longer telomeres were associated with FTD syndrome, consistent with a recent report demonstrating that longer telomeres are related to ALS. Therefore, our results may support a shared biology between FTD and ALS. More studies with larger sample sizes are needed.},
}
@article {pmid34310343,
year = {2021},
author = {Alcaraz, MJ and Alcaraz, A and Teruel-Montoya, R and Campillo, JA and de la Torre, A and Muñoz, &#xc1; and Tomás, C and Puche, G and Báguena, C and Cano, A and Minguela, A and Bernal, E},
title = {Subclinical atherosclerosis and immune activation in young HIV-infected patients with telomere shortening.},
journal = {Aging},
volume = {13},
number = {14},
pages = {18094-18105},
pmid = {34310343},
issn = {1945-4589},
mesh = {Adult ; *Aging, Premature ; Anti-Retroviral Agents/therapeutic use ; Atherosclerosis/diagnostic imaging/*immunology/virology ; Biomarkers ; CD8-Positive T-Lymphocytes/immunology ; Carotid Arteries/diagnostic imaging ; *Carotid Intima-Media Thickness ; Cross-Sectional Studies ; Female ; HIV Infections/drug therapy/*immunology ; Humans ; Logistic Models ; Lymphocyte Activation ; Male ; Middle Aged ; *Telomere Shortening ; },
abstract = {BACKGROUND: To date, available data on premature aging in young HIV-infected adults are scarce and no reports offer comprehensive assessment of telomere shortening (TS) in relation to subclinical atherosclerosis (SCA). In this study, we investigate if telomere shortening and immune activation markers are associated with SCA, which is one of the main degenerative diseases in young HIV-infected adults.<br><br>METHODS: A descriptive cross-sectional study was carried out in 149 HIV-infected patients on stable antiretroviral regimen (ART). Carotid intima-media thickness (cIMT) was estimated by carotid ultrasound. Quantitative singleplex PCR was performed to evaluate TS. The expression of activation/senescence markers was evaluated by multiparametric flow cytometry.<br><br>RESULTS: TS was observed in 73 patients (49%). Higher cIMT was observed in patients with TS than those without it (0.86 vs. 0.80 mm; p=0.041). Patients under the age of 50 (defined as young adults) with TS showed higher absolute numbers of activated lymphocyte T cells CD8+CD38+ (3.94 vs. 2.34 cell/&#x3bc;l; p=0.07) and lymphocyte B cells CD19+CD38+ (3.07 vs. 2.10 cell/&#x3bc;l; p=0.004) compared to those without TS. In the multivariate analysis, the only factor independently associated with TS was the absolute number of lymphocyte T cells CD8+CD38+ T cells (OR = 1.18; 95%-CI = 1.00-1.39; p = 0.05).<br><br>CONCLUSION: Young HIV-infected adults show premature biological aging with accentuated immune activation. Chronic inflammation with excessive T-cells activation could be associated to TS, premature aging, and SCA in young HIV-infected adults.},
}
@article {pmid34307383,
year = {2021},
author = {Novo, CL},
title = {A Tale of Two States: Pluripotency Regulation of Telomeres.},
journal = {Frontiers in cell and developmental biology},
volume = {9},
number = {},
pages = {703466},
pmid = {34307383},
issn = {2296-634X},
support = {/WT_/Wellcome Trust/United Kingdom ; },
abstract = {Inside the nucleus, chromatin is functionally organized and maintained as a complex three-dimensional network of structures with different accessibility such as compartments, lamina associated domains, and membraneless bodies. Chromatin is epigenetically and transcriptionally regulated by an intricate and dynamic interplay of molecular processes to ensure genome stability. Phase separation, a process that involves the spontaneous organization of a solution into separate phases, has been proposed as a mechanism for the timely coordination of several cellular processes, including replication, transcription and DNA repair. Telomeres, the repetitive structures at the end of chromosomes, are epigenetically maintained in a repressed heterochromatic state that prevents their recognition as double-strand breaks (DSB), avoiding DNA damage repair and ensuring cell proliferation. In pluripotent embryonic stem cells, telomeres adopt a non-canonical, relaxed epigenetic state, which is characterized by a low density of histone methylation and expression of telomere non-coding transcripts (TERRA). Intriguingly, this telomere non-canonical conformation is usually associated with chromosome instability and aneuploidy in somatic cells, raising the question of how genome stability is maintained in a pluripotent background. In this review, we will explore how emerging technological and conceptual developments in 3D genome architecture can provide novel mechanistic perspectives for the pluripotent epigenetic paradox at telomeres. In particular, as RNA drives the formation of LLPS, we will consider how pluripotency-associated high levels of TERRA could drive and coordinate phase separation of several nuclear processes to ensure genome stability. These conceptual advances will provide a better understanding of telomere regulation and genome stability within the highly dynamic pluripotent background.},
}
@article {pmid34304048,
year = {2021},
author = {Wang, Q and Codd, V and Raisi-Estabragh, Z and Musicha, C and Bountziouka, V and Kaptoge, S and Allara, E and Angelantonio, ED and Butterworth, AS and Wood, AM and Thompson, JR and Petersen, SE and Harvey, NC and Danesh, JN and Samani, NJ and Nelson, CP},
title = {Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank.},
journal = {EBioMedicine},
volume = {70},
number = {},
pages = {103485},
pmid = {34304048},
issn = {2352-3964},
support = {MC_PC_17228/MRC_/Medical Research Council/United Kingdom ; MR/L003120/1/MRC_/Medical Research Council/United Kingdom ; RG/13/13/30194/BHF_/British Heart Foundation/United Kingdom ; MC_PC_21003/MRC_/Medical Research Council/United Kingdom ; FS/17/81/33318/BHF_/British Heart Foundation/United Kingdom ; RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; MC_PC_21001/MRC_/Medical Research Council/United Kingdom ; MC_QA137853/MRC_/Medical Research Council/United Kingdom ; MR/M012816/1/MRC_/Medical Research Council/United Kingdom ; CH/12/2/29428/BHF_/British Heart Foundation/United Kingdom ; },
mesh = {Aged ; Biological Specimen Banks ; COVID-19/pathology/*virology ; Cohort Studies ; Female ; Humans ; Leukocytes/*pathology ; Male ; Mendelian Randomization Analysis ; Middle Aged ; Risk Factors ; SARS-CoV-2/*genetics ; Telomere/*genetics ; United Kingdom ; },
abstract = {Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05-1·30; P = 0·004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.},
}
@article {pmid34299219,
year = {2021},
author = {Turner, KJ and Watson, EM and Skinner, BM and Griffin, DK},
title = {Telomere Distribution in Human Sperm Heads and Its Relation to Sperm Nuclear Morphology: A New Marker for Male Factor Infertility?.},
journal = {International journal of molecular sciences},
volume = {22},
number = {14},
pages = {},
pmid = {34299219},
issn = {1422-0067},
support = {TBC/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Biomarkers/metabolism ; Case-Control Studies ; Cell Nucleus/genetics/metabolism/pathology ; Cohort Studies ; *DNA Damage ; Humans ; Infertility, Male/genetics/*metabolism/*pathology ; Male ; Sperm Head/metabolism/*pathology ; Telomere/genetics/*metabolism ; },
abstract = {Infertility is a problem affecting an increasing number of couples worldwide. Currently, marker tests for male factor infertility are complex, highly technical and relatively subjective. Up to 40% of cases of male factor infertility are currently diagnosed as idiopathic therefore, there is a clear need for further research into better ways of diagnosing it. Changes in sperm telomere length have been associated with infertility and closely linked to DNA damage and fragmentation, which are also known to be related to infertility. However, telomere distribution is a parameter thus far underexplored as an infertility marker. Here, we assessed morphological parameters of sperm nuclei in fertile control and male factor infertile cohorts. In addition, we used 2D and 3D fluorescence in situ hybridization (FISH) to compare telomere distribution between these two groups. Our findings indicate that the infertile cohort sperm nuclei were, on average, 2.9% larger in area and showed subtle differences in sperm head height and width. Telomeres were mainly distributed towards the periphery of the nuclei in the control cohort, with diminishing telomere signals towards the center of the nuclei. Sperm nuclei of infertile males, however, had more telomere signals towards the center of the nuclei, a finding supported by 3D imaging. We conclude that, with further development, both morphology and telomere distribution may prove useful investigative tools in the fertility clinic.},
}
@article {pmid34299077,
year = {2021},
author = {Garcia-Martin, I and Penketh, RJA and Garay, SM and Jones, RE and Grimstead, JW and Baird, DM and John, RM},
title = {Symptoms of Prenatal Depression Associated with Shorter Telomeres in Female Placenta.},
journal = {International journal of molecular sciences},
volume = {22},
number = {14},
pages = {},
pmid = {34299077},
issn = {1422-0067},
support = {29202/CRUK_/Cancer Research UK/United Kingdom ; MR/M013960/1/MRC_/Medical Research Council/United Kingdom ; C17199/A18246/A29202/CRUK_/Cancer Research UK/United Kingdom ; MR/N013794/1/MRC_/Medical Research Council/United Kingdom ; },
mesh = {Anxiety Disorders/*complications/psychology ; Depression/*complications/psychology ; Female ; Gestational Age ; Humans ; Infant ; Male ; Maternal Age ; Placenta/metabolism/*pathology ; Pregnancy ; Sex Factors ; *Telomere Shortening ; },
abstract = {BACKGROUND: Depression is a common mood disorder during pregnancy impacting one in every seven women. Children exposed to prenatal depression are more likely to be born at a low birth weight and develop chronic diseases later in life. A proposed hypothesis for this relationship between early exposure to adversity and poor outcomes is accelerated aging. Telomere length has been used as a biomarker of cellular aging. We used high-resolution telomere length analysis to examine the relationship between placental telomere length distributions and maternal mood symptoms in pregnancy.<br><br>METHODS: This study utilised samples from the longitudinal Grown in Wales (GiW) study. Women participating in this study were recruited at their presurgical appointment prior to a term elective caesarean section (ELCS). Women completed the Edinburgh Postnatal Depression Scale (EPDS) and trait subscale of the State-Trait Anxiety Inventory (STAI). Telomere length distributions were generated using single telomere length analysis (STELA) in 109 term placenta (37-42 weeks). Multiple linear regression was performed to examine the relationship between maternally reported symptoms of depression and anxiety at term and mean placental telomere length.<br><br>RESULTS: Prenatal depression symptoms were significantly negatively associated with XpYp telomere length in female placenta (B = -0.098, p = 0.026, 95% CI -0.184, -0.012). There was no association between maternal depression symptoms and telomere length in male placenta (B = 0.022, p = 0.586, 95% CI -0.059, 0.103). There was no association with anxiety symptoms and telomere length for either sex.<br><br>CONCLUSION: Maternal prenatal depression is associated with sex-specific differences in term placental telomeres. Telomere shortening in female placenta may indicate accelerated placental aging.},
}
@article {pmid34294626,
year = {2021},
author = {Joo, EJ and Ahn, YM and Park, M and Kim, SA},
title = {Significant Shortening of Leukocyte Telomere Length in Korean Patients with Bipolar Disorder 1.},
journal = {Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology},
volume = {19},
number = {3},
pages = {559-563},
pmid = {34294626},
issn = {1738-1088},
abstract = {OBJECTIVE: Telomere shortening has been seen in major psychiatric disorders, including major depressive disorder. However, only a few small studies have examined this in bipolar disorder (BD). We compared the telomere length in patients with BD1 or BD2 with that in matched healthy controls.<br><br>METHODS: We included 215 patients with BD (128 BD1, 87 BD2) and 204 age- and sex-matched healthy controls. Relative telomere length was determined by quantitative polymerase chain reaction. The patients and controls were compared separately for age groups, sex, and BD subgroups (BD1 and BD2).<br><br>RESULTS: We found significant telomere shortening in patients with BD1 (p < 0.001), but not in patients with BD2. In male patients with BD1, the 30-39 year age group had significant shortening of telomere length than controls (p = 0.01). Female patients with BD1 in the 19-29-year age group had significantly shortened telomeres compared to the controls (p < 0.01).<br><br>CONCLUSION: Our results suggest a significant reduction in telomere length in BD1. Telomere shortening would be a potential biomarker for BD.},
}
@article {pmid34291629,
year = {2021},
author = {Kang, JI and Park, CI and Lin, J and Kim, ST and Kim, HW and Kim, SJ},
title = {Alterations of cellular aging markers in obsessive- compulsive disorder: mitochondrial DNA copy number and telomere length.},
journal = {Journal of psychiatry &amp; neuroscience : JPN},
volume = {46},
number = {4},
pages = {E451-E458},
pmid = {34291629},
issn = {1488-2434},
mesh = {Adult ; Biomarkers ; Cellular Senescence/*genetics ; Cross-Sectional Studies ; DNA Copy Number Variations/*genetics ; DNA, Mitochondrial/*genetics ; Female ; Humans ; Male ; Middle Aged ; Obsessive-Compulsive Disorder/*genetics ; Telomere/*genetics ; Telomere Shortening/genetics ; Young Adult ; },
abstract = {BACKGROUND: The present study examined whether mitochondrial DNA copy number (mtDNAcn) and telomere length - key markers of cellular aging - were altered in male and female participants with obsessive-compulsive disorder (OCD) compared to healthy controls. We also tested for associations between these alterations and OCD-related clinical features and inflammatory index.<br><br>METHODS: A total of 235 patients with OCD (38.7% female) and 234 healthy controls (41.5% female) were included. We quantified whole-blood mtDNAcn and leukocyte telomere length using quantitative polymerase chain reaction. We also calculated the neutrophil-to-lymphocyte ratio from complete blood cell counts.<br><br>RESULTS: Multivariate analysis of covariance showed that OCD status had a significant overall effect on cellular aging markers in men (Wilks &#x3bb; = 0.889, F2,275 = 17.13, p < 0.001) and women (Wilks &#x3bb; = 0.742, F2,182 = 31.61, p < 0.001) after controlling for age, body mass index and childhood trauma. In post-hoc comparisons, men with OCD had lower mtDNAcn than controls (p < 0.001), but we found no between-group difference for telomere length (p = 0.55). Women with OCD had a significantly lower mtDNAcn (p < 0.001) and shortened telomere length (p = 0.023) compared to controls. Moreover, the lower mtDNAcn shown in the OCD group was significantly correlated with an increase in systemic inflammation for both sexes, as measured by neutrophil-to-lymphocyte ratio.<br><br>LIMITATIONS: The present cross-sectional design did not allow us to infer a causal relationship between OCD disease status and cellular aging markers.<br><br>CONCLUSION: The present study is, to our knowledge, the first to demonstrate alterations in mtDNAcn and telomere shortening in OCD. These results suggest that aging-associated molecular mechanisms may be important in the pathophysiology of OCD.},
}
@article {pmid34291053,
year = {2021},
author = {Li, B},
title = {Keeping Balance Between Genetic Stability and Plasticity at the Telomere and Subtelomere of Trypanosoma brucei.},
journal = {Frontiers in cell and developmental biology},
volume = {9},
number = {},
pages = {699639},
pmid = {34291053},
issn = {2296-634X},
support = {R01 AI066095/AI/NIAID NIH HHS/United States ; },
abstract = {Telomeres, the nucleoprotein complexes at chromosome ends, are well-known for their essential roles in genome integrity and chromosome stability. Yet, telomeres and subtelomeres are frequently less stable than chromosome internal regions. Many subtelomeric genes are important for responding to environmental cues, and subtelomeric instability can facilitate organismal adaptation to extracellular changes, which is a common theme in a number of microbial pathogens. In this review, I will focus on the delicate and important balance between stability and plasticity at telomeres and subtelomeres of a kinetoplastid parasite, Trypanosoma brucei, which causes human African trypanosomiasis and undergoes antigenic variation to evade the host immune response. I will summarize the current understanding about T. brucei telomere protein complex, the telomeric transcript, and telomeric R-loops, focusing on their roles in maintaining telomere and subtelomere stability and integrity. The similarities and differences in functions and underlying mechanisms of T. brucei telomere factors will be compared with those in human and yeast cells.},
}
@article {pmid34288423,
year = {2021},
author = {Gu, R and Cao, J and Wei, S and Gong, X and Wang, Y and Mi, Y and Zhang, J and Qiu, S and Rao, Q and Wang, M and Wei, H and Wang, J},
title = {Evaluation of pretreatment telomere length as a prognostic marker in intermediate-risk acute myeloid leukemia.},
journal = {International journal of laboratory hematology},
volume = {43},
number = {6},
pages = {1510-1515},
doi = {10.1111/ijlh.13665},
pmid = {34288423},
issn = {1751-553X},
support = {81830005//State Key Program of National Natural Science of China/ ; 82000131//National Natural Science Foundation of China/ ; 81770181//National Natural Science Foundation of China/ ; 81800173//National Natural Science Foundation of China/ ; 2019YFC0840605//National Key Research and Development Program of China/ ; 18JCZDJC45000//Tianjin Natural Science Foundation/ ; 2020-I2M-C&amp;T-B-084//CAMS Innovation Fund for Medical Sciences/ ; },
mesh = {Adult ; *Biomarkers, Tumor ; Disease Progression ; Humans ; Leukemia, Myeloid, Acute/diagnosis/*genetics/*mortality/therapy ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Recurrence ; Telomere/*genetics ; Telomere Shortening ; Treatment Outcome ; },
abstract = {INTRODUCTION: The current framework for risk stratification is still insufficient for highly heterogeneous intermediate-risk acute myeloid leukemia (IRC-AML), which lacks specific genomic abnormalities.<br><br>METHODS: In order to incorporate novel biomarkers to refine current risk stratification strategies for patients with this subtype, we investigated pretreatment telomere length (TL), which is essential for maintaining genomic stability, in 204 adults with de novo AML (non-acute promyelocytic leukemia).<br><br>RESULTS: We found that TL measured at diagnosis did not decrease with advancing age in 204 patients with AML (R[2] &#xa0;=&#xa0;0.001, P&#xa0;=&#xa0;.695). A multivariate analysis demonstrated that short TL was independently associated with an inferior relapse-free survival (hazard ratio [HR] 3.08, 95% confidence interval [CI] 1.48-6.41, P&#xa0;=&#xa0;.003); event-free survival (HR 2.14, 95% CI 1.12-4.08, P&#xa0;=&#xa0;.021); and overall survival (HR 2.26, 95% CI 1.09-4.67, P&#xa0;=&#xa0;.028) in IRC-AML patients. In addition, IRC-AML patients with short TL also exhibited an increased cumulative incidence of hematologic relapse (HR 2.32, 95% CI 1.08-5.26, P&#xa0;=&#xa0;.032).<br><br>CONCLUSION: Short TL is an independent prognostic factor for poor prognosis in patients with IRC-AML and may represent a novel mechanism that links genomic stability and disease progression.},
}
@article {pmid34285374,
year = {2021},
author = {Seimiya, H and Nagasawa, K and Shin-Ya, K},
title = {Chemical targeting of G-quadruplexes in telomeres and beyond for molecular cancer therapeutics.},
journal = {The Journal of antibiotics},
volume = {74},
number = {10},
pages = {617-628},
pmid = {34285374},
issn = {1881-1469},
mesh = {Animals ; Antineoplastic Agents/chemistry/*pharmacology ; *Drug Delivery Systems ; *G-Quadruplexes ; Humans ; Neoplasms/*drug therapy ; *Telomere ; },
abstract = {G-quadruplexes (G4s) are higher-order structures formed by guanine-rich sequences of nucleic acids, such as the telomeric 5'-TTAGGG-3'/5'-UUAGGG-3' repeats and those in gene regulatory regions. G4s regulate various biological events, including replication, transcription, and translation. Imbalanced G4 dynamics is associated with diseases, such as cancer and neurodegenerative diseases. Telomestatin is a natural macrocyclic compound derived from Streptomyces anulatus 3533-SV4. It interacts with the guanine quartet via π-π stacking and potently stabilizes G4. Because G4 stabilization at the telomeric repeat inhibits the telomere-synthesizing enzyme telomerase, telomestatin was originally identified as a telomerase inhibitor. Whereas non-toxic doses of telomestatin induce gradual shortening of telomeres and eventual crisis in human cancer cells, higher doses trigger prompt replication stress and DNA damage responses, resulting in acute cell death. Suppression of the transcription and translation of G4-containing genes is also implicated in the anticancer effects of telomestatin. Because telomestatin is rare, labile, and insoluble, synthetic oxazole telomestatin derivatives have been developed and verified for their therapeutic efficacies in preclinical cancer models. Furthermore, a variety of G4-stabilizing compounds have been reported as promising seeds for molecular cancer therapeutics. To improve the design of future clinical studies, it will be important to identify predictive biomarkers of drug efficacy.},
}
@article {pmid34282826,
year = {2021},
author = {Hailu, EM and Lewis, TT and Needham, BL and Lin, J and Seeman, TE and Mujahid, MS},
title = {Longitudinal Associations between Discrimination, Neighborhood Social Cohesion, and Telomere Length: The Multi-Ethnic Study of Atherosclerosis (MESA).},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/gerona/glab193},
pmid = {34282826},
issn = {1758-535X},
abstract = {BACKGROUND: We aimed to examine if neighborhood social cohesion moderated longitudinal associations between baseline reports of discrimination and 10-year changes in Leukocyte Telomere Length (LTL).<br><br>METHODS: Data are from the Multi-Ethnic Study of Atherosclerosis (MESA; N=1,064; age range 45-84 years). Baseline discrimination was measured using the Major Experiences of Discrimination Scale (MDS; none, 1 domain, &#x2265;2 domains) and the Experiences of Discrimination Scale (EDS; none, moderate, high). Neighborhood social cohesion at baseline was assessed via a community survey within census tract defined neighborhoods. 10-year change in LTL was defined as Regression to the Mean corrected 10-year difference in the ratio of telomeric DNA to a single copy gene (T/S).<br><br>RESULTS: In linear mixed effects models, we found that neighborhood social cohesion modified the effect of baseline reports of MDS on 10-year changes in LTL, independent of sociodemographic characteristics, health behaviors, and health conditions (p(&#x3c7; 2)=0.01). Among those residing in neighborhoods with low social cohesion, experiencing major discrimination in &#x2265;2 domains was associated with faster LTL attrition over 10-years, compared to reporting no discrimination (&#x3b2;=-0.03; 95% CI: -0.06, -0.003). We found no main associations for either discrimination measure and no interaction between EDS and neighborhood social cohesion.<br><br>CONCLUSIONS: Results indicate that neighborhood social cohesion is an important dimension of the neighborhood context that may moderate the impact of major experiences of discrimination on telomere length attrition. These findings help advance our understanding of the integral role that neighborhood environments play in attenuating the effect of discrimination on accelerated cell aging.},
}
@article {pmid34282343,
year = {2021},
author = {Lakota, K and Varga, J},
title = {Linking autoimmunity, short telomeres and lung fibrosis in SSc.},
journal = {Nature reviews. Rheumatology},
volume = {17},
number = {9},
pages = {511-512},
pmid = {34282343},
issn = {1759-4804},
mesh = {*Autoimmunity/genetics ; Fibrosis ; Humans ; *Pulmonary Fibrosis/genetics ; Telomere/genetics ; },
}
@article {pmid34278498,
year = {2021},
author = {Wang, Z and Wu, X},
title = {Abnormal function of telomere protein TRF2 induces cell mutation and the effects of environmental tumor‑promoting factors (Review).},
journal = {Oncology reports},
volume = {46},
number = {2},
pages = {},
pmid = {34278498},
issn = {1791-2431},
mesh = {Cell Cycle ; Gene Expression Regulation, Neoplastic ; Humans ; Mutation ; Neoplasm Proteins/*genetics ; Neoplasms/*genetics/metabolism ; Telomeric Repeat Binding Protein 2/*metabolism ; },
abstract = {Recent studies have found that somatic gene mutations and environmental tumor‑promoting factors are both indispensable for tumor formation. Telomeric repeat‑binding factor (TRF)2 is the core component of the telomere shelterin complex, which plays an important role in chromosome stability and the maintenance of normal cell physiological states. In recent years, TRF2 and its role in tumor formation have gradually become a research hot topic, which has promoted in‑depth discussions into tumorigenesis and treatment strategies, and has achieved promising results. Some cells bypass elimination, due to either aging, apoptosis via mutations or abnormal prolongation of the mitotic cycle, and enter the telomere crisis period, where large‑scale DNA reorganization occurs repeatedly, which manifests as the precancerous cell cycle. Finally, at the end of the crisis cycle, the mutation activates either the expression level of telomerase or activates the alternative lengthening of telomere mechanism to extend the local telomeres. Under the protection of TRF2, chromosomes are gradually stabilized, immortal cells are formed and the stagewise mutation‑driven transformation of normal cells to cancer cells is completed. In addition, TRF2 also shares the characteristics of environmental tumor‑promoting factors. It acts on multiple signal transduction pathway‑related proteins associated with cell proliferation, and affects peripheral angiogenesis, inhibits the immune recognition and killing ability of the microenvironment, and maintains the stemness characteristics of tumor cells. TRF2 levels are abnormally elevated by a variety of tumor control proteins, which are more conducive to the protection of telomeres and the survival of tumor cells. In brief, the various regulatory mechanisms which tumor cells rely on to survive are organically integrated around TRF2, forming a regulatory network, which is conducive to the optimization of the survival direction of heterogeneous tumor cells, and promotes their survival and adaptability. In terms of clinical application, TRF2 is expected to become a new type of cancer prognostic marker and a new tumor treatment target. Inhibition of TRF2 overexpression could effectively cut off the core network regulating tumor cell survival, reduce drug resistance, or bypass the mutation under the pressure of tumor treatment selection, which may represent a promising therapeutic strategy for the complete eradication of tumors in the clinical setting. Based on recent research, the aim of the present review was to systematically elaborate on the basic structure and functional characteristics of TRF2 and its role in tumor formation, and to analyze the findings indicating that TRF2 deficiency or overexpression could cause severe damage to telomere function and telomere shortening, and induce DNA damage response and chromosomal instability.},
}
@article {pmid34277003,
year = {2021},
author = {García-Martínez, S and González-Gamo, D and Fernández-Marcelo, T and Tesolato, S and De La Serna, S and Domínguez-Serrano, I and Cano-Valderrama, O and Barabash, A and De Juan, C and Torres-García, A and Iniesta, P},
title = {Obesity and telomere status in the prognosis of patients with colorectal cancer submitted to curative intention surgical treatment.},
journal = {Molecular and clinical oncology},
volume = {15},
number = {3},
pages = {184},
pmid = {34277003},
issn = {2049-9469},
abstract = {The risk of colorectal cancer (CRC) development has been associated with telomere dysfunction and obesity. However, clinical relevance of these parameters in CRC prognosis is not clear. Therefore, the aim of the present study was to evaluate the impact of obesity and telomere status in the prognosis of patients affected by CRC and submitted to curative surgical treatment. According to published data, this is the first work in which obesity and telomere status are jointly considered in relation to CRC prognosis. A prospective study including 162 patients with CRC submitted to curative surgical treatment was performed. Subjects were classified according to their BMI. Telomere status was established through telomere length and telomerase activity evaluation. Statistical analyses were performed using the SPSS software package version 22. Telomere shortening was inversely associated with BMI in patients with CRC. Notably, among patients with CRC, subjects with obesity exhibited less shortening of tumor telomeres than non-obese patients (P=0.047). Patients with shorter telomeres, both in the tumor (median telomere length <6.5 kb) and their non-tumor paired tissues (median telomere length <7.1 kb), had the best clinical evolution, regardless of the Dukes' stage of cancers (P=0.025, for tumor samples; P=0.003, for non-tumor samples). Additionally, subjects with a BMI >31.85 kg/m[2] showed the worse clinical outcomes compared with subjects with other BMI values. Interestingly, the impact of BMI showed sex dependence, since only the group of men displayed significant differences in CRC prognosis in relation to obesity status (P=0.037). From the results of the present study, based on a multivariate prediction model to establish prognosis, it was concluded that telomere length is a useful biomarker to predict prognosis in patients with CRC. Regardless of BMI values, the improved clinical evolution was associated with shorter telomeres. The impact of BMI seems to be associated with other factors, such as sex.},
}
@article {pmid34273872,
year = {2021},
author = {Farzan, SF and Shahriar, M and Kibriya, MG and Jasmine, F and Sarwar, G and Slavkovic, V and Graziano, JH and Ahsan, H and Argos, M},
title = {Urinary arsenic and relative telomere length in 5-7 year old children in Bangladesh.},
journal = {Environment international},
volume = {156},
number = {},
pages = {106765},
pmid = {34273872},
issn = {1873-6750},
support = {K99 ES024144/ES/NIEHS NIH HHS/United States ; R00 ES024144/ES/NIEHS NIH HHS/United States ; R01 ES024423/ES/NIEHS NIH HHS/United States ; },
mesh = {*Arsenic/toxicity ; Bangladesh ; Child ; Child, Preschool ; Humans ; Telomere ; Telomere Homeostasis ; Telomere Shortening ; },
abstract = {BACKGROUND: Telomere length has been associated with the occurrence and progression of common chronic and age-related diseases, and in younger populations, may represent a biomarker of disease susceptibility. Early childhood is a critical period for telomere biology as this period is characterized by a rapid decline in telomere length due to a large turnover of highly proliferative cells and may represent a period of unique sensitivity to environmental insults. Arsenic (As) exposure has been associated with both telomere lengthening and shortening in adults and children and some evidence suggests the effects may differ by level and timing of exposure.<br><br>OBJECTIVES: Given the lack of clarity across studies, we investigated the association between urinary As and leukocyte telomere length among 476 five- to seven-year-old children enrolled in the Bangladesh Environmental Research in Children's Health (BiRCH) cohort.<br><br>METHODS: In a series of multivariable models, adjusted for key covariates, we examined associations between urinary As and relative telomere length (RTL) of whole blood DNA.<br><br>RESULTS: We observed small but consistent, negative associations between urinary As and RTL, such that a doubling of urinary As was associated with a -0.017 (95% CI: -0.030, -0.005; p&#xa0;=&#xa0;0.0056) decrease in RTL, in fully adjusted models. We also observed a somewhat stronger inverse relationship between urinary As concentration and RTL among children born to fathers&#xa0;&#x2265;&#xa0;30&#xa0;years of age at the time of birth, than those&#xa0;<&#xa0;30&#xa0;years; however, we did not observe a statistically significant interaction.<br><br>DISCUSSION: Our study suggests that As influences RTL, with detectable associations in early to mid-childhood. Further studies are needed to confirm our findings and investigate the potential long-term impacts of telomere shortening in childhood on later life health outcomes. Additional studies exploring how dose and timing of exposure may relate to RTL are critical to understanding As's relationship to telomere length.},
}
@article {pmid34272332,
year = {2021},
author = {Liu, S and Chung, MP and Ley, B and French, S and Elicker, BM and Fiorentino, DF and Chung, LS and Boin, F and Wolters, PJ},
title = {Peripheral blood leucocyte telomere length is associated with progression of interstitial lung disease in systemic sclerosis.},
journal = {Thorax},
volume = {76},
number = {12},
pages = {1186-1192},
pmid = {34272332},
issn = {1468-3296},
support = {R01 HL139897/HL/NHLBI NIH HHS/United States ; T32 AR050942/AR/NIAMS NIH HHS/United States ; },
mesh = {Humans ; *Idiopathic Pulmonary Fibrosis ; Lung ; *Lung Diseases, Interstitial/genetics ; Retrospective Studies ; *Scleroderma, Systemic/complications/genetics ; Telomere ; },
abstract = {BACKGROUND: Peripheral blood leucocyte telomere length (PBL-TL) is associated with outcomes in patients with idiopathic pulmonary fibrosis. Whether PBL-TL is associated with progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is unknown.<br><br>METHODS: A retrospective observational cohort study was performed using prospectively collected data from 213 patients with SSc followed at the University of California San Francisco (UCSF) Scleroderma Center. PBL-TL was measured by quantitative PCR of DNA isolated from peripheral blood. Associations between PBL-TL and pulmonary function test trends in patients with SSc-ILD were assessed by longitudinal analysis using Generalised Linear Mixed Models. Findings were validated in a cohort of 61 patients with SSc-ILD enrolled in the Stanford University Scleroderma Center database.<br><br>RESULTS: Patients with UCSF SSc with ILD were found to have shorter PBL-TL compared with those without ILD (6554&#xb1;671&#x2009;base pairs (bp) vs 6782&#xb1;698&#x2009;bp, p=0.01). Shorter PBL-TL was associated with the presence of ILD (adjusted OR 2.1 per 1000&#x2009;bp TL decrease, 95%&#x2009;CI [1.25 to 3.70], p=0.006). PBL-TL was shorter in patients with SSc-ILD lacking SSc-specific autoantibodies compared with seropositive subjects (6237&#xb1;647&#x2009;bp vs 6651&#xb1;653&#x2009;bp, p=0.004). Shorter PBL-TL was associated with increased risk for lung function deterioration with an average of 67&#x2009;mL greater loss in per year for every 1000&#x2009;bp decrease in PBL-TL in the combined SSc-ILD cohorts (longitudinal analysis, adjusted model: 95%&#x2009;CI -104 mL to -33&#x2009;mL, p<0.001).<br><br>CONCLUSIONS: These findings suggest that telomere dysfunction may be associated with SSc-ILD progression and that PBL-TL measurement may be useful for stratifying risk for SSc-ILD progression.},
}
@article {pmid34270368,
year = {2022},
author = {Bailey, SM and Luxton, JJ and McKenna, MJ and Taylor, LE and George, KA and Jhavar, SG and Swanson, GP},
title = {Ad Astra - telomeres in space!.},
journal = {International journal of radiation biology},
volume = {98},
number = {3},
pages = {395-403},
doi = {10.1080/09553002.2021.1956010},
pmid = {34270368},
issn = {1362-3095},
mesh = {*Aging ; Female ; Humans ; Laboratories ; Male ; Middle Aged ; *Space Flight ; Telomere ; },
abstract = {PURPOSE: My journey to the stars began as I - along with the whole world - stood still and watched Neil Armstrong take those first small steps on the Moon. Fast forward 50 years and NASA astronauts Scott Kelly and Christina Koch each spend nearly a year in space aboard the International Space Station (ISS), a remarkable multinational collaborative project and floating U.S. National Laboratory that has supported continuous human presence in low Earth orbit for the past 20 years. Marking a new era of human space exploration, the first commercial rocket, SpaceX Falcon 9, recently launched NASA astronauts Doug Hurley and Bob Behnken in the Crew Dragon spacecraft Endeavor to the ISS and returned safely to Earth. NASA and its commercial partners are rapidly advancing innovative space technologies, and with the recently announced Artemis team of astronauts, plans to send the first woman and next man back to the moon and establish sustainable exploration by the end of the decade. Humankind will then be poised to take the next giant leap - pioneering human exploration of Mars.<br><br>CONCLUSIONS: Historically, fewer than 600 individuals have participated in spaceflight, the vast majority of whom have been middle aged males (35-55&#x2009;years) on short duration missions (less than 20&#x2009;days). Thus, as the number and diversity of space travelers increase, a better understanding of how long-duration spaceflight affects human health is essential to maintaining individual astronaut performance during, and improving disease and aging trajectories following, future exploration missions. Here, I review findings from our NASA Twins Study and Telomeres investigations, highlighting potential mechanistic roles of chronic space radiation exposure in changes in telomere length and persistent DNA damage responses associated with long-duration spaceflight. Importantly, similar trends were observed in prostate cancer patients undergoing intensity-modulated radiation therapy (IMRT), additional support specifically for the role of radiation exposure. Individual differences in response were also observed in both cohorts, underscoring the importance of developing personalized approaches for evaluating human health effects and long-term outcomes associated with radiation exposures, whether on Earth or living in the extreme environment of space.},
}
@article {pmid34269919,
year = {2021},
author = {Luchini, C and Lawlor, RT and Bersani, S and Vicentini, C and Paolino, G and Mattiolo, P and Pea, A and Cingarlini, S and Milella, M and Scarpa, A},
title = {Alternative Lengthening of Telomeres (ALT) in Pancreatic Neuroendocrine Tumors: Ready for Prime-Time in Clinical Practice?.},
journal = {Current oncology reports},
volume = {23},
number = {9},
pages = {106},
pmid = {34269919},
issn = {1534-6269},
support = {203885/2017//Fondazione Cariverona/ ; J38D19000690001//Fondazione italiana Malattie Pancreas/ ; 12182//Associazione Italiana per la Ricerca sul Cancro/ ; },
mesh = {Biomarkers, Tumor/genetics/metabolism ; Co-Repressor Proteins/genetics ; Genetic Predisposition to Disease/*genetics ; Humans ; In Situ Hybridization, Fluorescence/methods ; Molecular Chaperones/genetics ; *Mutation ; Neuroendocrine Tumors/*genetics/metabolism/pathology ; Pancreatic Neoplasms/*genetics/metabolism/pathology ; Telomere/*genetics ; *Telomere Homeostasis ; X-linked Nuclear Protein/genetics/metabolism ; },
abstract = {PURPOSE OF REVIEW: Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism used by some types of malignancies, including pancreatic neuroendocrine tumors, to overcome the issue of telomere shortening, thus supporting tumor growth and cell proliferation. This review is focused on the most important achievements and opportunities deriving from ALT assessment in PanNET onco-pathology, highlighting the most promising fields in which such biomarker could be implemented in clinical practice.<br><br>RECENT FINDINGS: In pancreatic neuroendocrine tumors (PanNET), ALT is strongly correlated with the mutational status of two chromatin remodeling genes, DAXX and ATRX. Recent advances in tumor biology permitted to uncover important roles of ALT in the landscape of PanNET, potentially relevant for introducing this biomarker into clinical practice. Indeed, ALT emerged as a reliable indicator of worse prognosis for PanNET, helping in clinical stratification and identification of "high-risk" patients. Furthermore, it is a very specific marker supporting the pancreatic origin of neuroendocrine neoplasms and can be used for improving the diagnostic workflow of patients presenting with neuroendocrine metastasis from unknown primary. The activation of this process can be determined by specific FISH analysis. ALT should be introduced in clinical practice for identifying "high-risk" PanNET patients and improving their clinical management, and as a marker of pancreatic origin among neuroendocrine tumors.},
}
@article {pmid34268523,
year = {2021},
author = {Anderson, JJ and Susser, E and Arbeev, KG and Yashin, AI and Levy, D and Verhulst, S and Aviv, A},
title = {Short Telomeres and a T-Cell Shortfall in COVID-19: The Aging Effect.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {34268523},
support = {R01 HL134840/HL/NHLBI NIH HHS/United States ; RF1 AG046860/AG/NIA NIH HHS/United States ; U01 AG066529/AG/NIA NIH HHS/United States ; U24 AG066528/AG/NIA NIH HHS/United States ; },
abstract = {UNLABELLED: The slow pace of global vaccination and the rapid emergence of SARS-CoV-2 variants suggest recurrent waves of COVID-19 in coming years. Therefore, understanding why deaths from COVID-19 are highly concentrated among older adults is essential for global health. Severe COVID-19 T-cell lymphopenia is more common among older adults, and it entails poor prognosis. Much about the primary etiology of this form of lymphopenia remains unknown, but regardless of its causes, offsetting the decline in T-cell count during SARS-CoV-2 infection demands fast and massive T-cell clonal expansion, which is telomere length (TL)-dependent. We have built a model that captures the effect of age-dependent TL shortening in hematopoietic cells and its effect on T-cell clonal expansion capacity. The model shows that an individual with average hematopoietic cell TL (HCTL) at age twenty years maintains maximal T-cell clonal expansion capacity until the 6th decade of life when this capacity plummets by more than 90% over the next ten years. The collapse coincides with the steep increase in COVID-19 mortality with age. HCTL metrics may thus explain the vulnerability of older adults to COVID-19. That said, the wide inter-individual variation in HCTL across the general population means that some younger adults with inherently short HCTL might be at risk of severe COVID-19 lymphopenia and mortality from the disease.<br><br>SIGNIFICANCE STATEMENT: Declining immunity with advancing age is a general explanation for the increased mortality from COVID-19 among older adults. This mortality far exceeds that from viral illnesses such as the seasonal influenza, and it thus requires specific explanations. One of these might be diminished ability with age to offset the development of severe T-cell lymphopenia (a low T-cell count in the blood) that often complicates COVID-19. We constructed a model showing that age-dependent shortening of telomeres might constrain the ability of T-cells of some older COVID-19 patients to undertake the massive proliferation required to clear the virus that causes the infection. The model predicts that individuals with short telomeres, principally seniors, might be at a higher risk of death from COVID-19.},
}
@article {pmid34267850,
year = {2021},
author = {Harrigan, AM and MacDonald, S and Crooks, B and Dyack, S and Trottier, AM},
title = {A Case Series of TERC Variant Telomere Biology Disorders in Unrelated Families From Atlantic Canada.},
journal = {Journal of hematology},
volume = {10},
number = {3},
pages = {130-135},
pmid = {34267850},
issn = {1927-1220},
abstract = {TERC variant telomere biology disorders (TBDs) are a rare, heterogenous group of disorders that arise from germline variants in TERC, a gene that encodes for the RNA component of telomerase. Variants in TERC lead to accelerated telomere attrition and can manifest as many different phenotypes. In this case series, we aimed to add to the literature describing TERC variant TBDs by reporting cases from two unrelated families from Atlantic Canada. The first case, a previously described germline TERC variant, n.107G>T (NR_001566.1), was identified in a young woman with myelodysplastic syndrome (MDS) and found to segregate with cytopenias in the family. This case represents a unique phenotypic presentation: this variant has not previously been described in patients with MDS and adds important segregation data to the literature. The second case, a novel TERC n.437T>G variant, was identified in a patient with both aplastic anemia and pulmonary fibrosis manifesting in his early 30s. We report these novel cases of germline TERC variants in order to help clinicians recognize TBDs, as well as to add important supporting information for the pathogenicity of these variants.},
}
@article {pmid34266503,
year = {2021},
author = {Hackenhaar, FS and Josefsson, M and Adolfsson, AN and Landfors, M and Kauppi, K and Hultdin, M and Adolfsson, R and Degerman, S and Pudas, S},
title = {Short leukocyte telomeres predict 25-year Alzheimer's disease incidence in non-APOE ε4-carriers.},
journal = {Alzheimer's research &amp; therapy},
volume = {13},
number = {1},
pages = {130},
pmid = {34266503},
issn = {1758-9193},
mesh = {*Alzheimer Disease/epidemiology/genetics ; *Apolipoprotein E4/genetics ; Apolipoproteins E/genetics ; Genotype ; Humans ; Incidence ; Leukocytes ; Risk Factors ; Telomere ; },
abstract = {BACKGROUND: Leukocyte telomere length (LTL) has been shown to predict Alzheimer's disease (AD), albeit inconsistently. Failing to account for the competing risks between AD, other dementia types, and mortality, can be an explanation for the inconsistent findings in previous time-to-event analyses. Furthermore, previous studies indicate that the association between LTL and AD is non-linear and may differ depending on apolipoprotein E (APOE) ε4 allele carriage, the strongest genetic AD predictor.<br><br>METHODS: We analyzed whether baseline LTL in interaction with APOE &#x3b5;4 predicts AD, by following 1306 initially non-demented subjects for 25 years. Gender- and age-residualized LTL (rLTL) was categorized into tertiles of short, medium, and long rLTLs. Two complementary time-to-event models that account for competing risks were used; the Fine-Gray model to estimate the association between the rLTL tertiles and the cumulative incidence of AD, and the cause-specific hazard model to assess whether the cause-specific risk of AD differed between the rLTL groups. Vascular dementia and death were considered competing risk events. Models were adjusted for baseline lifestyle-related risk factors, gender, age, and non-proportional hazards.<br><br>RESULTS: After follow-up, 149 were diagnosed with AD, 96 were diagnosed with vascular dementia, 465 died without dementia, and 596 remained healthy. Baseline rLTL and other covariates were assessed on average 8 years before AD onset (range 1-24). APOE &#x3b5;4-carriers had significantly increased incidence of AD, as well as increased cause-specific AD risk. A significant rLTL-APOE interaction indicated that short rLTL at baseline was significantly associated with an increased incidence of AD among non-APOE &#x3b5;4-carriers (subdistribution hazard ratio = 3.24, CI 1.404-7.462, P = 0.005), as well as borderline associated with increased cause-specific risk of AD (cause-specific hazard ratio = 1.67, CI 0.947-2.964, P = 0.07). Among APOE &#x3b5;4-carriers, short or long rLTLs were not significantly associated with AD incidence, nor with the cause-specific risk of AD.<br><br>CONCLUSIONS: Our findings from two complementary competing risk time-to-event models indicate that short rLTL may be a valuable predictor of the AD incidence in non-APOE &#x3b5;4-carriers, on average 8 years before AD onset. More generally, the findings highlight the importance of accounting for competing risks, as well as the APOE status of participants in AD biomarker research.},
}
@article {pmid34265700,
year = {2021},
author = {Heba, AC and Toupance, S and Arnone, D and Peyrin-Biroulet, L and Benetos, A and Ndiaye, NC},
title = {Telomeres: New players in immune-mediated inflammatory diseases?.},
journal = {Journal of autoimmunity},
volume = {123},
number = {},
pages = {102699},
doi = {10.1016/j.jaut.2021.102699},
pmid = {34265700},
issn = {1095-9157},
mesh = {Arthritis, Rheumatoid/etiology ; Humans ; Inflammation/*etiology/immunology ; Inflammatory Bowel Diseases/etiology ; Psoriasis/etiology ; Spondylarthritis/etiology ; Telomere/*physiology ; Uveitis/etiology ; },
abstract = {Telomeres are repetitive DNA sequences located at the ends of linear chromosomes that preserve the integrity and stability of the genome. Telomere dysfunctions due to short telomeres or altered telomere structures can ultimately lead to replicative cellular senescence and chromosomal instability, both mechanisms being hallmarks of ageing. Chronic inflammation, oxidative stress and finally telomere length (TL) dynamics have been shown to be involved in various age-related non-communicable diseases (NCDs). Immune-mediated inflammatory diseases (IMIDs), including affections such as inflammatory bowel disease, psoriasis, rheumatoid arthritis, spondyloarthritis and uveitis belong to this group of age-related NCDs. Although in recent years, we have witnessed the emergence of studies in the literature linking these IMIDs to TL dynamics, the causality between these diseases and telomere attrition is still unclear and controversial. In this review, we provide an overview of available studies on telomere dynamics and discuss the utility of TL measurements in immune-mediated inflammatory diseases.},
}
@article {pmid34265046,
year = {2021},
author = {Lee, RS and Zandi, PP and Santos, A and Aulinas, A and Carey, JL and Webb, SM and McCaul, ME and Resmini, E and Wand, GS},
title = {Cross-species Association Between Telomere Length and Glucocorticoid Exposure.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {106},
number = {12},
pages = {e5124-e5135},
pmid = {34265046},
issn = {1945-7197},
support = {U01 AA020890/AA/NIAAA NIH HHS/United States ; NIAAA U01 AA020890/NH/NIH HHS/United States ; },
mesh = {Adult ; *Aging ; Animals ; Case-Control Studies ; Cushing Syndrome/etiology/metabolism/*pathology ; *Disease Models, Animal ; Female ; Follow-Up Studies ; Glucocorticoids/*adverse effects ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Rats ; Rats, Sprague-Dawley ; Species Specificity ; *Stress, Physiological ; *Telomere Shortening ; },
abstract = {CONTEXT: Chronic exposure to glucocorticoids (GCs) or stress increases the risk of medical disorders, including cardiovascular and neuropsychiatric disorders. GCs contribute to accelerated aging; however, while the link between chronic GC exposure and disease onset is well established, the underpinning mechanisms are not clear.<br><br>OBJECTIVE: We explored the potential nexus between GCs or stress exposure and telomere length.<br><br>METHODS: In addition to rats exposed to 3 weeks of chronic stress, an iatrogenic mouse model of Cushing syndrome (CS), and a mouse neuronal cell line, we studied 32 patients with CS and age-matched controls and another cohort of 75 healthy humans.<br><br>RESULTS: (1) Exposure to stress in rats was associated with a 54.5% (P&#x2005;=&#x2005;0.036) reduction in telomere length in T cells. Genomic DNA (gDNA) extracted from the dentate gyrus of stressed and unstressed rats showed 43.2% reduction in telomere length (P&#x2005;=&#x2005;0.006). (2) Mice exposed to corticosterone had a 61.4% reduction in telomere length in blood gDNA (P&#x2005;=&#x2005;5.75&#x2005;&#xd7;&#x2005;10-5) and 58.8% reduction in telomere length in the dentate gyrus (P&#x2005;= 0.002). (3) We observed a 40.8% reduction in the telomere length in patients with active CS compared to healthy controls (P&#x2005;=&#x2005;0.006). There was a 17.8% reduction in telomere length in cured CS patients, which was not different from that of healthy controls (P&#x2005;=&#x2005;0.08). For both cured and active CS, telomere length correlated significantly with duration of hypercortisolism (R2&#x2005;=&#x2005;0.22, P&#x2005;=&#x2005;0.007). (4) There was a 27.6% reduction in telomere length between low and high tertiles in bedtime cortisol levels of healthy participants (P&#x2005;=&#x2005;0.019).<br><br>CONCLUSION: Our findings demonstrate that exposure to stress and/or GCs is associated with shortened telomeres, which may be partially reversible.},
}
@article {pmid34256387,
year = {2022},
author = {Aguiar, SS and Rosa, TS and Neves, RVP and Leite, PLA and Maciel, LA and Gutierrez, SD and Rosa, EC and Andrade, RV and Degens, H and Korhonen, MT and Lewis, JE and Simões, HG},
title = {Telomere Length, SIRT1, and Insulin in Male Master Athletes: The Path to Healthy Longevity?.},
journal = {International journal of sports medicine},
volume = {43},
number = {1},
pages = {29-33},
doi = {10.1055/a-1510-9259},
pmid = {34256387},
issn = {1439-3964},
support = {Funda&#xe7;&#xe3;o de Apoio &#xe0; Pesquisa do Distrito Federal (FAP/DF)//0193.001762/2017/ ; },
mesh = {Adult ; Aging ; *Athletes ; Cross-Sectional Studies ; Humans ; Insulin/*blood ; Leukocytes ; *Longevity ; Male ; Middle Aged ; *Sirtuin 1/genetics ; Telomere/*ultrastructure ; },
abstract = {Lower SIRT1 and insulin resistance are associated with accelerated telomere shortening. This study investigated whether the lifestyle of master athletes can attenuate these age-related changes and thereby slow aging. We compared insulin, SIRT1, and telomere length in highly trained male master athletes (n=52; aged 49.9±7.2 yrs) and age-matched non-athletes (n=19; aged 47.3±8.9 yrs). This is a cross-sectional study, in which all data were collected in one visit. Overnight fasted SIRT1 and insulin levels in whole blood were assessed using commercial kits. Relative telomere length was determined in leukocytes through qPCR analyses. Master athletes had higher SIRT1, lower insulin, and longer telomere length than age-matched non-athletes (p<0.05 for all). Insulin was inversely associated with SIRT1 (r=-0.38; p=0.001). Telomere length correlated positively with SIRT1 (r=0.65; p=0.001), whereas telomere length and insulin were not correlated (r=0.03; p=0.87). In conclusion, master athletes have higher SIRT1, lower insulin, and longer telomeres than age-matched non-athletes. Furthermore, SIRT1 was negatively associated with insulin and positively associated with telomere length. These findings suggest that in this sample of middle-aged participants reduced insulin, increased SIRT1 activity, and attenuation of biological aging are connected.},
}
@article {pmid34255844,
year = {2021},
author = {Liu, J and Hu, X and Bao, K and Kim, JK and Zhang, C and Jia, S and Qiao, F},
title = {The cooperative assembly of shelterin bridge provides a kinetic gateway that controls telomere length homeostasis.},
journal = {Nucleic acids research},
volume = {49},
number = {14},
pages = {8110-8119},
pmid = {34255844},
issn = {1362-4962},
support = {R01 GM098943/GM/NIGMS NIH HHS/United States ; R35 GM126910/GM/NIGMS NIH HHS/United States ; },
mesh = {Chromosomes/genetics ; DNA/genetics ; DNA, Single-Stranded/genetics ; DNA-Binding Proteins/*genetics ; Humans ; Kinetics ; Multiprotein Complexes/genetics/ultrastructure ; Mutation ; Schizosaccharomyces/genetics ; Schizosaccharomyces pombe Proteins/*genetics ; Shelterin Complex ; Telomere/genetics ; Telomere Homeostasis/*genetics ; Telomere-Binding Proteins/*genetics/ultrastructure ; },
abstract = {Shelterin is a six-protein complex that coats chromosome ends to ensure their proper protection and maintenance. Similar to the human shelterin, fission yeast shelterin is composed of telomeric double- and single-stranded DNA-binding proteins, Taz1 and Pot1, respectively, bridged by Rap1, Poz1 and Tpz1. The assembly of the proteinaceous Tpz1-Poz1-Rap1 complex occurs cooperatively and disruption of this shelterin bridge leads to unregulated telomere elongation. However, how this biophysical property of bridge assembly is integrated into shelterin function is not known. Here, utilizing synthetic bridges with a range of binding properties, we find that synthetic shelterin bridge lacking cooperativity requires a linker pair that matches the native bridge in complex lifespan but has dramatically higher affinity. We find that cooperative assembly confers kinetic properties on the shelterin bridge allowing disassembly to function as a molecular timer, regulating the duration of the telomere open state, and consequently telomere lengthening to achieve a defined species-specific length range.},
}
@article {pmid34253611,
year = {2021},
author = {Chakravarti, D and Lee, R and Multani, AS and Santoni, A and Keith, Z and Hsu, WH and Chang, K and Reyes, L and Rashid, A and Wu, CJ and Li, J and Zhang, J and Shim, HS and Chandra, K and Deng, P and Spring, DJ and Nielsen, OH and Riis, LB and Mayigegowda, KK and Blutt, SE and Zhang, J and Younes, M and DuPont, A and Thirumurthi, S and Vilar, E and Estes, MK and Colla, S and Shroyer, NF and DePinho, RA},
title = {Telomere dysfunction instigates inflammation in inflammatory bowel disease.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {118},
number = {29},
pages = {},
pmid = {34253611},
issn = {1091-6490},
support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 DK118904/DK/NIDDK NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 CA084628/CA/NCI NIH HHS/United States ; T32 CA186892/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Ataxia Telangiectasia Mutated Proteins/genetics/immunology ; Humans ; Inflammatory Bowel Diseases/genetics/*immunology ; Interleukin-18/genetics/immunology ; Intestinal Mucosa/immunology ; Mice ; Telomerase/genetics/immunology ; Telomere/genetics/*immunology ; YAP-Signaling Proteins/genetics/immunology ; },
abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory condition driven by diverse genetic and nongenetic programs that converge to disrupt immune homeostasis in the intestine. We have reported that, in murine intestinal epithelium with telomere dysfunction, DNA damage-induced activation of ataxia-telangiectasia mutated (ATM) results in ATM-mediated phosphorylation and activation of the YAP1 transcriptional coactivator, which in turn up-regulates pro-IL-18, a pivotal immune regulator in IBD pathogenesis. Moreover, individuals with germline defects in telomere maintenance genes experience increased occurrence of intestinal inflammation and show activation of the ATM/YAP1/pro-IL-18 pathway in the intestinal epithelium. Here, we sought to determine the relevance of the ATM/YAP1/pro-IL-18 pathway as a potential driver of IBD, particularly older-onset IBD. Analysis of intestinal biopsy specimens and organoids from older-onset IBD patients documented the presence of telomere dysfunction and activation of the ATM/YAP1/precursor of interleukin 18 (pro-IL-18) pathway in the intestinal epithelium. Employing intestinal organoids from healthy individuals, we demonstrated that experimental induction of telomere dysfunction activates this inflammatory pathway. In organoid models from ulcerative colitis and Crohn's disease patients, pharmacological interventions of telomerase reactivation, suppression of DNA damage signaling, or YAP1 inhibition reduced pro-IL-18 production. Together, these findings support a model wherein telomere dysfunction in the intestinal epithelium can initiate the inflammatory process in IBD, pointing to therapeutic interventions for this disease.},
}
@article {pmid34253240,
year = {2021},
author = {Xue, L and Gao, Y and Wu, M and Tian, T and Fan, H and Huang, Y and Huang, Z and Li, D and Xu, L},
title = {Telomere-to-telomere assembly of a fish Y chromosome reveals the origin of a young sex chromosome pair.},
journal = {Genome biology},
volume = {22},
number = {1},
pages = {203},
pmid = {34253240},
issn = {1474-760X},
support = {J 4477/FWF_/Austrian Science Fund FWF/Austria ; },
mesh = {Animals ; Centromere ; Eels/*genetics ; Fish Proteins/genetics/metabolism ; Gene Expression ; *Genome ; HMGN Proteins/*genetics/metabolism ; Heterochromatin/chemistry ; Karyotype ; Male ; *Sex Determination Processes ; *Telomere ; Testis/growth &amp; development/metabolism ; X Chromosome ; Y Chromosome/*chemistry ; },
abstract = {BACKGROUND: The origin of sex chromosomes requires the establishment of recombination suppression between the proto-sex chromosomes. In many fish species, the sex chromosome pair is homomorphic with a recent origin, providing species for studying how and why recombination suppression evolved in the initial stages of sex chromosome differentiation, but this requires accurate sequence assembly of the X and Y (or Z and W) chromosomes, which may be difficult if they are recently diverged.<br><br>RESULTS: Here we produce a haplotype-resolved genome assembly of zig-zag eel (Mastacembelus armatus), an aquaculture fish, at the chromosomal scale. The diploid assembly is nearly gap-free, and in most chromosomes, we resolve the centromeric and subtelomeric heterochromatic sequences. In particular, the Y chromosome, including its highly repetitive short arm, has zero gaps. Using resequencing data, we identify a ~7 Mb fully sex-linked region (SLR), spanning the sex chromosome centromere and almost entirely embedded in the pericentromeric heterochromatin. The SLRs on the X and Y chromosomes are almost identical in sequence and gene content, but both are repetitive and heterochromatic, consistent with zero or low recombination. We further identify an HMG-domain containing gene HMGN6 in the SLR as a candidate sex-determining gene that is expressed at the onset of testis development.<br><br>CONCLUSIONS: Our study supports the idea that preexisting regions of low recombination, such as pericentromeric regions, can give rise to SLR in the absence of structural variations between the proto-sex chromosomes.},
}
@article {pmid34245740,
year = {2021},
author = {Chico-Sordo, L and Córdova-Oriz, I and Polonio, AM and S-Mellado, LS and Medrano, M and García-Velasco, JA and Varela, E},
title = {Reproductive aging and telomeres: Are women and men equally affected?.},
journal = {Mechanisms of ageing and development},
volume = {198},
number = {},
pages = {111541},
doi = {10.1016/j.mad.2021.111541},
pmid = {34245740},
issn = {1872-6216},
mesh = {*Aging/pathology/physiology ; Cellular Senescence/*physiology ; Female ; *Genitalia/metabolism/physiopathology ; Gonadal Steroid Hormones/*metabolism ; Humans ; *Infertility/etiology/physiopathology ; Male ; Oocytes/*physiology ; Reproduction/physiology ; Spermatozoa/*physiology ; Telomere Homeostasis/*physiology ; },
abstract = {Successful reproduction is very important for individuals and for society. Currently, the human health span and lifespan are the object of intense and productive investigation with great achievements, compared to the last century. However, reproduction span does not progress concomitantly with lifespan. Reproductive organs age, decreasing the levels of sexual hormones, which are protectors of health through their action on several organs of the body. Thus, this is the starting point of the organismal decay and infertility. This starting point is easily detected in women. In men, it goes under the surface, undetected, but it goes, nevertheless. Regarding fertility, aging alters the hormonal equilibrium, decreases the potential of reproductive organs, diminishes the quality of the gametes and worsen the reproductive outcomes. All these events happen at a different pace and affecting different organs in women and men. The question is what molecular pathways are involved in reproductive aging and if there is a possible halting or even reversion of the aging events. Answers to all these points will be explained in the present review.},
}
@article {pmid34244792,
year = {2021},
author = {Apte, MS and Masuda, H and Wheeler, DL and Cooper, JP},
title = {RNAi and Ino80 complex control rate limiting translocation step that moves rDNA to eroding telomeres.},
journal = {Nucleic acids research},
volume = {49},
number = {14},
pages = {8161-8176},
pmid = {34244792},
issn = {1362-4962},
mesh = {Chromosomes/genetics ; DNA, Ribosomal/*genetics ; Multiprotein Complexes/genetics ; RNA Interference ; Schizosaccharomyces/genetics ; Schizosaccharomyces pombe Proteins/*genetics ; Telomerase/genetics ; Telomere/*genetics ; Transcription Factors/*genetics ; Translocation, Genetic/*genetics ; },
abstract = {The discovery of HAATIrDNA, a telomerase-negative survival mode in which canonical telomeres are replaced with ribosomal DNA (rDNA) repeats that acquire chromosome end-protection capability, raised crucial questions as to how rDNA tracts 'jump' to eroding chromosome ends. Here, we show that HAATIrDNA formation is initiated and limited by a single translocation that juxtaposes rDNA from Chromosome (Chr) III onto subtelomeric elements (STE) on Chr I or II; this rare reaction requires RNAi and the Ino80 nucleosome remodeling complex (Ino80C), thus defining an unforeseen relationship between these two machineries. The unique STE-rDNA junction created by this initial translocation is efficiently copied to the remaining STE chromosome ends, independently of RNAi or Ino80C. Intriguingly, both RNAi and Ino80C machineries contain a component that plays dual roles in HAATI subtype choice. Dcr1 of the RNAi pathway and Iec1 of Ino80C both promote HAATIrDNA formation as part of their respective canonical machineries, but both also inhibit formation of the exceedingly rare HAATISTE (where STE sequences mobilize throughout the genome and assume chromosome end protection capacity) in non-canonical, pathway-independent manners. This work provides a glimpse into a previously unrecognized crosstalk between RNAi and Ino80C in controlling unusual translocation reactions that establish telomere-free linear chromosome ends.},
}
@article {pmid34237641,
year = {2021},
author = {Chang-Chien, J and Huang, JL and Tsai, HJ and Wang, SL and Kuo, ML and Yao, TC},
title = {Particulate matter causes telomere shortening and increase in cellular senescence markers in human lung epithelial cells.},
journal = {Ecotoxicology and environmental safety},
volume = {222},
number = {},
pages = {112484},
doi = {10.1016/j.ecoenv.2021.112484},
pmid = {34237641},
issn = {1090-2414},
mesh = {Cellular Senescence ; Epithelial Cells/metabolism ; Humans ; Lung/metabolism ; *Particulate Matter/toxicity ; Telomere ; *Telomere Shortening ; Tumor Suppressor Protein p53/genetics ; },
abstract = {Exposure to particulate matter (PM) has been associated with DNA damage, but the relationships between PM, telomere length and cellular senescence remain unclear. This study aimed to investigate the effects and potential mechanisms of PM on telomere length and cellular senescence in human lung epithelial cells. Human lung epithelial A549 cells were exposed to PM for 24 h. Cell viability and cytotoxicity were measured by the WST-1 assay and the lactate dehydrogenase release, respectively. Cellular uptake of PM was observed using transmission electron microscopy. Telomere length was measured using qPCR and expressed as T/S ratio. Cell cycle progression was analyzed by flow cytometry. Expression of human telomerase reverse transcriptase (hTERT) and cell cycle regulators was measured using mRNA by qPCR and protein levels by Western blot. Cellular senescence was determined by the expression of senescence-associated β-galactosidase (SA-β-Gal) with fluorescent microscopy and flow cytometry. Exposed to PM at the concentration of 200 μg/ml decreased cell viability and increased LDH levels in culture medium. Remarkably increased uptake of PM, shortening of telomere length, induction of G0/G1 phase arrest, and increased expression of senescence hallmarks were observed after exposure to PM in A549 cells. PM exposure induced upregulation of p21 and downregulation of proliferating cell nuclear antigen (PCNA) and hTERT expression, but no significant change in p53 expression, in A549 cells. Overall, exposure to PM may downregulate hTERT and PCNA through p53-independent induction of p21 expression, leading to telomere shortening, G0/G1 arrest and the onset of cellular senescence in human lung epithelial cells.},
}
@article {pmid34235373,
year = {2021},
author = {Wojcicki, JM and Lustig, RH and Jacobs, LM and Mason, AE and Hartman, A and Leung, C and Stanhope, K and Lin, J and Schmidt, LA and Epel, ES},
title = {Longer Leukocyte Telomere Length Predicts Stronger Response to a Workplace Sugar-Sweetened Beverage Sales Ban: An Exploratory Study.},
journal = {Current developments in nutrition},
volume = {5},
number = {7},
pages = {nzab084},
pmid = {34235373},
issn = {2475-2991},
support = {P30 DK092926/DK/NIDDK NIH HHS/United States ; P30 DK098722/DK/NIDDK NIH HHS/United States ; },
abstract = {BACKGROUND: Shorter leukocyte telomere length (LTL) is associated with increased risk of a number of metabolic diseases including insulin resistance and the development of type 2 diabetes mellitus. Shorter LTL is also associated with stress reactivity suggestive of a possible role for LTL to predict response to behavioral interventions. However, few studies have evaluated how interventions, such as weight loss or dietary changes, are associated with LTL changes or whether LTL can predict behavioral responses to interventions.<br><br>OBJECTIVES: We evaluated metabolic changes in relation to LTL changes and LTL at baseline in a cohort of at-risk adults in response to a 10-mo workplace-based sugar-sweetened beverage (SSB) intervention.<br><br>METHODS: At baseline, metabolic health and LTL measurements were assessed through standard blood draws on 212 participants. Multivariable linear regression models were used to assess changes in anthropometrics, SSB consumption, and 13 blood-based metabolic risk factors, in relation to LTL at baseline and changes in LTL.<br><br>RESULTS: Longer LTL at baseline was associated with decreases in SSB consumption over the 6-mo follow-up period (B = -29.67; P&#xa0;=&#xa0;0.04). Slower LTL attrition rates were associated with decreases in waist circumference (B = -0.27; P&#xa0;&#xa0;=&#xa0;0.03), HDL cholesterol (B = -0.20; P&#xa0;&#xa0;=&#xa0;0.05), and apoA1 (B = -0.09; P&#xa0;=&#xa0;0.01).<br><br>CONCLUSIONS: Longer LTL at baseline predicted a favorable overall response to a behavioral intervention: decreases in SSB consumption. Abdominal adiposity losses paralleled slower declines in LTL suggestive of overall health benefits, but we found differences in the relations between metabolic changes and LTL at baseline compared with LTL attrition rates. Longer LTL may be a proxy marker of a positive behavioral response.This trial was registered at clinicaltrials.gov as NCT02585336.},
}
@article {pmid34228441,
year = {2021},
author = {Jin, M and Li, J and Chen, Y and Zhao, J and Zhang, J and Zhang, Z and Du, P and Zhang, L and Lu, X},
title = {Near-Infrared Small Molecule as a Specific Fluorescent Probe for Ultrasensitive Recognition of Antiparallel Human Telomere G-Quadruplexes.},
journal = {ACS applied materials &amp; interfaces},
volume = {13},
number = {28},
pages = {32743-32752},
doi = {10.1021/acsami.1c07101},
pmid = {34228441},
issn = {1944-8252},
mesh = {DNA/*analysis/genetics ; Fluorescent Dyes/chemical synthesis/*chemistry ; *G-Quadruplexes ; HeLa Cells ; Humans ; Limit of Detection ; Microscopy, Fluorescence ; Quinolines/chemical synthesis/*chemistry ; Quinolizines/chemical synthesis/*chemistry ; RNA/analysis/genetics ; Telomere/*chemistry ; },
abstract = {In the past 10 years, many fluorescent probes have been developed to recognize G-quadruplexes (G4s) since G4s play an important role in biological systems. However, the selectivity and sensitivity of existing probes for G4s limit their further applications. Herein, we design and synthesize a new probe (TOVJ) by introducing 9-vinyljulolidine into TO. The new probe exhibits almost no fluorescence in an aqueous solution. Upon interacting with G4s, especially the antiparallel G4s, the fluorescence intensity was greatly enhanced (maximum 2742-fold) with a large Stokes shift of 198 nm and the maximum emission peak at 694 nm (near-infrared region). TOVJ showed high sensitivity and selectivity to G4s over other DNA topologies (ssDNA/dsDNA), especially to antiparallel G4s. For antiparallel human telomere G4 detection, the limits of detection of Hum24 and 22AG Na[+] were as low as 164 and 231 pM, respectively. This indicates that TOVJ is a highly sensitive fluorescence sensor that can be effectively used for antiparallel human telomere G4 detection. The result of live-cell imaging showed that TOVJ could enter live cells and locate in the mitochondria.},
}
@article {pmid34225037,
year = {2021},
author = {Needham, BL and Straight, B and Hilton, CE and Olungah, CO and Lin, J},
title = {Family socioeconomic status and child telomere length among the Samburu of Kenya.},
journal = {Social science &amp; medicine (1982)},
volume = {283},
number = {},
pages = {114182},
doi = {10.1016/j.socscimed.2021.114182},
pmid = {34225037},
issn = {1873-5347},
mesh = {Animals ; Cattle ; Child ; Educational Status ; Family ; Female ; Humans ; Kenya ; Sheep ; *Social Class ; Socioeconomic Factors ; *Telomere ; },
abstract = {Previous research in high-income countries suggests that children from families with lower socioeconomic status (SES) tend to have shorter telomere length - a biomarker of stress and cell aging - than children from families with greater social and economic resources. However, little is known about predictors of child telomere length in low-income settings. Data for the current study are from a sample of 214 Samburu children aged 1-9 years. The Samburu are semi-nomadic pastoralists who live in the Rift Valley of north-central Kenya. Samburu livelihood is based primarily on livestock, and polygynous marriage is common. Drawing on prior ethnographic research, we measured 14 culturally relevant indicators of family SES, including mother's education, head of household's education, whether the child is currently attending school, household spending, mother's employment history, head of household's employment history, mother's perceived wealth, whether the child lives in a modern house, livestock holdings (total, cows, sheep/goats, and camels), mother's wife number, and whether the child lives in a polygynous household. Telomere length was measured in salivary DNA by the quantitative polymerase chain reaction (qPCR) method. Using latent class analysis, we identified four groups of children that are similar based on the 14 indicators of family SES: Lower SES; Middle SES, Traditional; Middle SES, Modern; and Higher SES. SES classes were not significantly associated with child telomere length. In models examining individual indicators of SES, we found that telomere length was 0.57 standard deviations greater for children who lived in families in the lowest quartile of total livestock holdings compared to those in the highest quartile (b = 0.57, p = 0.03). While additional research is needed to identify the mechanisms underlying this counterintuitive finding, the current study highlights the importance of cultural context in shaping the social gradient in health.},
}
@article {pmid34223882,
year = {2022},
author = {Li, Z and Zhou, D and Zhang, D and Zhao, J and Li, W and Sun, Y and Chen, Y and Liu, H and Wilson, JX and Qian, Z and Huang, G},
title = {Folic Acid Inhibits Aging-Induced Telomere Attrition and Apoptosis in Astrocytes In Vivo and In Vitro.},
journal = {Cerebral cortex (New York, N.Y. : 1991)},
volume = {32},
number = {2},
pages = {286-297},
doi = {10.1093/cercor/bhab208},
pmid = {34223882},
issn = {1460-2199},
mesh = {Aging ; Animals ; Apoptosis ; *Astrocytes ; *Folic Acid/pharmacology ; Mice ; Telomere ; },
abstract = {Folic acid (FA) has been reported to inhibit astrocyte apoptosis and improve aging-induced disorders; however, its role in telomere attrition remains unclear. In present study, 4-month-old senescence-accelerated mouse prone 8 (SAMP8) mice were assigned to four treatment groups for the in vivo experiment: FA-deficient diet (FA-D) group, FA-normal diet (FA-N) group, low FA-supplemented diet (FA-L) group, and high FA-supplemented diet (FA-H) group. These mice were euthanized when 10 months old. There was also a young SAMP8 (4 months old) control group (Con-Y) fed with FA-normal diet. In in vitro study, primary cultures of astrocytes from hippocampus and cerebral cortex were incubated for five generations with various concentrations of FA (0-40 μM) and were assigned to five groups: FA 0 μM (generation 5), FA 10 μM (generation 5), FA 20 μM (generation 5), FA 40 μM (generation 5), and FA 10 μM (generation 1). The results showed that FA supplementation inhibited aging-induced astrocytosis, astrocyte apoptosis, neurodegeneration, and prevented telomere attrition in hippocampus and cortex of SAMP8 mice. FA supplementation also decreased apoptosis and telomere attrition, and increased telomerase activity, in primary cultures of astrocytes. These results showed that it may be one of the mechanisms that FA inhibiting aging-induced apoptosis of astrocyte by alleviating telomere attrition.},
}
@article {pmid34221339,
year = {2021},
author = {Piplani, S and Prabhu, M and Alemao, NN and Akash, C and Ram, P and Ambar, S and Kumbar, V and Chugh, Y and Raychauduri, SP and Chugh, SK},
title = {Conventional Risk Factors, Telomere Length, and Ischemic Heart disease: Insights into the Mediation Analysis.},
journal = {Genome integrity},
volume = {12},
number = {},
pages = {1},
pmid = {34221339},
issn = {2041-9414},
abstract = {Telomere length is regarded as a potential biomarker of biological ageing and is associated with various age-related diseases, such as ischemic heart disease (IHD), myocardial infarction, peripheral vascular disease, and cancer. As there is a paucity of study that deals with this influence, this study aimed to assess how the cardiovascular risk factors influence the risk of IHD by performing mediation analysis. A total of 407 males were included in the study. IHD was diagnosed through echocardiography and coronary angiography by determining the number of coronary vessels involved. Demographic data, clinical history, and laboratory investigations such as random blood sugar (RBS), fasting lipid profile, serum creatinine, and serum urea levels of all the subjects were measured and recorded. Serum uric acid and blood urea nitrogen (BUN) levels were significantly higher in IHD subjects compared to non-IHD subjects (P < 0.05). Body mass index (BMI), glycosylated hemoglobin (HbA1c), RBS, serum uric acid, serum creatinine, BUN, total cholesterol, triglycerides, and telomere length significantly differed between subjects with and without IHD (P < 0.05). Further, telomere length (P < 0.001), BMI (P < 0.001), and total cholesterol level (P < 0.001) were risk factors that significantly affected the incidence of IHD, as proved by logistic regression. It indicates that shorter telomeres contribute to increased risk of IHD, influenced by BMI, HbA1c, BUN, total cholesterol levels, and RBS (P < 0.001). The study established a link between telomere shortening, conventional risk factors, and IHD; moreover, the study takes care in the role of mediation analysis which is a novel idea as little is done in this area of biostatistics with telomere length. Overall, this further establishes that telomeres length might serve as the promising biomarkers in predicting the risk of IHD.},
}
@article {pmid34219315,
year = {2022},
author = {Brown, TJ and Spurgin, LG and Dugdale, HL and Komdeur, J and Burke, T and Richardson, DS},
title = {Causes and consequences of telomere lengthening in a wild vertebrate population.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {5933-5945},
doi = {10.1111/mec.16059},
pmid = {34219315},
issn = {1365-294X},
support = {BB/M011216/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; },
mesh = {Humans ; Animals ; Male ; Adult ; Female ; *Telomere Homeostasis ; *Vertebrates ; Telomere Shortening/genetics ; Biological Evolution ; Telomere/genetics ; },
abstract = {Telomeres have been advocated to be important markers of biological age in evolutionary and ecological studies. Telomeres usually shorten with age and shortening is frequently associated with environmental stressors and increased subsequent mortality. Telomere lengthening - an apparent increase in telomere length between repeated samples from the same individual - also occurs. However, the exact circumstances, and consequences, of telomere lengthening are poorly understood. Using longitudinal data from the Seychelles warbler (Acrocephalus sechellensis), we tested whether telomere lengthening - which occurs in adults of this species - is associated with specific stressors (reproductive effort, food availability, malarial infection and cooperative breeding) and predicts subsequent survival. In females, telomere shortening was observed under greater stress (i.e., low food availability, malaria infection), while telomere lengthening was observed in females experiencing lower stress (i.e., high food availability, assisted by helpers, without malaria). The telomere dynamics of males were not associated with the key stressors tested. These results indicate that, at least for females, telomere lengthening occurs in circumstances more conducive to self-maintenance. Importantly, both females and males with lengthened telomeres had improved subsequent survival relative to individuals that displayed unchanged, or shortened, telomeres - indicating that telomere lengthening is associated with individual fitness. These results demonstrate that telomere dynamics are bidirectionally responsive to the level of stress that an individual faces, but may poorly reflect the accumulation of stress over an individuals lifetime.},
}
@article {pmid34214617,
year = {2021},
author = {Hu, X and Gao, S and Wang, P and Zhou, Y and Chen, K and Chen, Q and Wang, B and Hu, W and Cheng, P and Eid, R and Giraud-Panis, MJ and Wang, L and Gilson, E and Ye, J and Lu, Y},
title = {The knockdown efficiency of telomere associated genes with specific methodology in a zebrafish cell line.},
journal = {Biochimie},
volume = {190},
number = {},
pages = {12-19},
doi = {10.1016/j.biochi.2021.06.013},
pmid = {34214617},
issn = {1638-6183},
mesh = {Animals ; Cell Line ; DNA-Binding Proteins/genetics/metabolism ; Gene Knockdown Techniques/*methods ; Gene Silencing/drug effects ; Monomeric GTP-Binding Proteins/genetics ; Morpholinos/pharmacology ; Shelterin Complex/genetics ; Telomere/*genetics/*metabolism ; Telomere-Binding Proteins/genetics ; Telomeric Repeat Binding Protein 1/genetics ; Transfection/methods ; Zebrafish ; Zebrafish Proteins/genetics/metabolism ; },
abstract = {Zebrafish is broadly used as a model organism in gene loss-of-function studies in vivo, but its employment in vitro is greatly limited by the lack of efficient gene knockdown approaches in zebrafish cell lines such as ZF4. In this article, we attempted to induce silencing of telomere associated genes in ZF4 by applying the frequently-used siRNA transfection technology and a novel moiety-linked morpholino (vivo-MO). By proceeding with integrated optimization of siRNAs transfection and vivo-MOs treatment, we compared five transfection reagents and vivo-MOs simultaneously to evaluate the efficiency of terfa silencing in ZF4. 48 h after siRNAs transfection, Lipofectamine™ 3000 and X-tremeGENE™ HP leaded to knockdown in 35% and 43% of terfa transcription, respectively, while vivo-MO-terfa modulated 58% down-expression of zfTRF2 in contrast to vivo-MO-ctrl 72 h after treatment. Further siRNAs transfection targeting telomere associated genes by X-tremeGENE™ HP showed silencing in 40-68% of these genes without significant cytotoxicity and off-target effect. Our results confirmed the feasibility of gene loss-of-function studies in a zebrafish cell line, offered a systematic optimizing strategy to employ gene silencing experiments, and presented Lipofectamine™ 3000, X-tremeGENE™ HP and vivo-morpholinos as candidate gene silencing approaches for zebrafish in vitro gene loss-of-function studies. Successfully knockdown of shelterin genes further opened a new field for telomeric study in zebrafish.},
}
@article {pmid34214172,
year = {2021},
author = {Chatain, J and Blond, A and Phan, AT and Saintomé, C and Alberti, P},
title = {GGGCTA repeats can fold into hairpins poorly unfolded by replication protein A: a possible origin of the length-dependent instability of GGGCTA variant repeats in human telomeres.},
journal = {Nucleic acids research},
volume = {49},
number = {13},
pages = {7588-7601},
pmid = {34214172},
issn = {1362-4962},
mesh = {DNA/chemistry ; G-Quadruplexes ; Humans ; Nucleic Acid Conformation ; Nucleotide Motifs ; Oligonucleotides/chemistry ; Repetitive Sequences, Nucleic Acid ; Replication Protein A/*metabolism ; Shelterin Complex ; Telomere/*chemistry/metabolism ; Telomere-Binding Proteins/metabolism ; },
abstract = {Human telomeres are composed of GGGTTA repeats and interspersed with variant repeats. The GGGCTA variant motif was identified in the proximal regions of human telomeres about 10 years ago and was shown to display a length-dependent instability. In parallel, a structural study showed that four GGGCTA repeats folded into a non-canonical G-quadruplex (G4) comprising a Watson-Crick GCGC tetrad. It was proposed that this non-canonical G4 might be an additional obstacle for telomere replication. In the present study, we demonstrate that longer GGGCTA arrays fold into G4 and into hairpins. We also demonstrate that replication protein A (RPA) efficiently binds to GGGCTA repeats structured into G4 but poorly binds to GGGCTA repeats structured into hairpins. Our results (along with results obtained with a more stable variant motif) suggest that GGGCTA hairpins are at the origin of GGGCTA length-dependent instability. They also suggest, as working hypothesis, that failure of efficient binding of RPA to GGGCTA structured into hairpins might be involved in the mechanism of GGGCTA array instability. On the basis of our present and past studies about telomeric G4 and their interaction with RPA, we propose an original point of view about telomeric G4 and the evolution of telomeric motifs.},
}
@article {pmid34208129,
year = {2021},
author = {Daneels, L and Martens, DS and Arredouani, S and Billen, J and Koppen, G and Devlieger, R and Nawrot, TS and Ghosh, M and Godderis, L and Pauwels, S},
title = {Maternal Vitamin D and Newborn Telomere Length.},
journal = {Nutrients},
volume = {13},
number = {6},
pages = {},
pmid = {34208129},
issn = {2072-6643},
support = {12W8618N//Fonds Wetenschappelijk Onderzoek/ ; },
mesh = {Dietary Supplements ; Female ; Humans ; *Infant, Newborn ; Male ; Nutritional Status ; Pregnancy ; Pregnancy Trimesters ; *Prenatal Nutritional Physiological Phenomena ; *Telomere ; Vitamin D/*administration &amp; dosage/analogs &amp; derivatives/blood ; Vitamins/*administration &amp; dosage ; },
abstract = {Nutrition is important during pregnancy for offspring health. Gestational vitamin D intake may prevent several adverse outcomes and might have an influence on offspring telomere length (TL). In this study, we want to assess the association between maternal vitamin D intake during pregnancy and newborn TL, as reflected by cord blood TL. We studied mother-child pairs enrolled in the Maternal Nutrition and Offspring's Epigenome (MANOE) cohort, Leuven, Belgium. To calculate the dietary vitamin D intake, 108 women were asked to keep track of their diet using the seven-day estimated diet record (EDR) method. TL was assessed in 108 cord blood using a quantitative real-time PCR method. In each trimester of pregnancy, maternal serum 25-hydroxyvitamin D (25-OHD) concentration was measured. We observed a positive association (β = 0.009, p-value = 0.036) between newborn average relative TL and maternal vitamin D intake (diet + supplement) during the first trimester. In contrast, we found no association between average relative TL of the newborn and mean maternal serum 25-OHD concentrations during pregnancy. To conclude, vitamin D intake (diet + supplements), specifically during the first trimester of pregnancy, is an important factor associated with TL at birth.},
}
@article {pmid34206297,
year = {2021},
author = {Karow, A and Haubitz, M and Oppliger Leibundgut, E and Helsen, I and Preising, N and Steiner, D and Dantonello, TM and Ammann, RA and Roessler, J and Kartal-Kaess, M and Röth, A and Baerlocher, GM},
title = {Targeting Telomere Biology in Acute Lymphoblastic Leukemia.},
journal = {International journal of molecular sciences},
volume = {22},
number = {13},
pages = {},
pmid = {34206297},
issn = {1422-0067},
support = {no grant number//Geron Corporation/ ; },
mesh = {Adolescent ; Antineoplastic Agents/pharmacology/therapeutic use ; Apoptosis ; Biomarkers, Tumor/analysis ; Child ; Child, Preschool ; Female ; Humans ; Male ; Oligonucleotides/*pharmacology/therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/genetics/metabolism/physiopathology ; Prognosis ; Telomerase/*antagonists &amp; inhibitors/metabolism ; Telomere/*metabolism ; Telomere Homeostasis ; },
abstract = {Increased cell proliferation is a hallmark of acute lymphoblastic leukemia (ALL), and genetic alterations driving clonal proliferation have been identified as prognostic factors. To evaluate replicative history and its potential prognostic value, we determined telomere length (TL) in lymphoblasts, B-, and T-lymphocytes, and measured telomerase activity (TA) in leukocytes of patients with ALL. In addition, we evaluated the potential to suppress the in vitro growth of B-ALL cells by the telomerase inhibitor imetelstat. We found a significantly lower TL in lymphoblasts (4.3 kb in pediatric and 2.3 kb in adult patients with ALL) compared to B- and T-lymphocytes (8.0 kb and 8.2 kb in pediatric, and 6.4 kb and 5.5 kb in adult patients with ALL). TA in leukocytes was 3.2 TA/C for pediatric and 0.7 TA/C for adult patients. Notably, patients with high-risk pediatric ALL had a significantly higher TA of 6.6 TA/C compared to non-high-risk patients with 2.2 TA/C. The inhibition of telomerase with imetelstat ex vivo led to significant dose-dependent apoptosis of B-ALL cells. These results suggest that TL reflects clonal expansion and indicate that elevated TA correlates with high-risk pediatric ALL. In addition, telomerase inhibition induces apoptosis of B-ALL cells cultured in vitro. TL and TA might complement established markers for the identification of patients with high-risk ALL. Moreover, TA seems to be an effective therapeutic target; hence, telomerase inhibitors, such as imetelstat, may augment standard ALL treatment.},
}
@article {pmid34205622,
year = {2021},
author = {Krapivin, MI and Tikhonov, AV and Efimova, OA and Pendina, AA and Smirnova, AA and Chiryaeva, OG and Talantova, OE and Petrova, LI and Dudkina, VS and Baranov, VS},
title = {Telomere Length in Chromosomally Normal and Abnormal Miscarriages and Ongoing Pregnancies and Its Association with 5-hydroxymethylcytosine Patterns.},
journal = {International journal of molecular sciences},
volume = {22},
number = {12},
pages = {},
pmid = {34205622},
issn = {1422-0067},
support = {19-75-00023//Russian Science Foundation/ ; AAAA-A19-119021290033-1//Ministry of Science and Higher Education of the Russian Federation/ ; },
mesh = {5-Methylcytosine/analogs &amp; derivatives/metabolism ; Abortion, Spontaneous/*pathology ; Case-Control Studies ; Chorion/pathology ; DNA Methylation ; Female ; Humans ; Lymphocytes/pathology ; Pregnancy ; Pregnancy Trimester, First ; Telomere/*pathology ; *Telomere Homeostasis ; Trophoblasts/*pathology ; },
abstract = {The present study investigates telomere length (TL) in dividing chorionic cytotrophoblast cells from karyotypically normal and abnormal first trimester miscarriages and ongoing pregnancies. Using Q-FISH, we measured relative TLs in the metaphase chromosomes of 61 chorionic villous samples. Relative TLs did not differ between karyotypically normal samples from miscarriages and those from ongoing pregnancies (p = 0.3739). However, among the karyotypically abnormal samples, relative TLs were significantly higher in ongoing pregnancies than in miscarriages (p < 0.0001). Relative TLs were also significantly higher in chorion samples from karyotypically abnormal ongoing pregnancies than in those from karyotypically normal ones (p = 0.0018) in contrast to miscarriages, where relative TL values were higher in the karyotypically normal samples (p = 0.002). In the karyotypically abnormal chorionic cytotrophoblast, the TL variance was significantly lower than in any other group (p < 0.05). Assessed by TL ratios between sister chromatids, interchromatid TL asymmetry demonstrated similar patterns across all of the chorion samples (p = 0.22) but significantly exceeded that in PHA-stimulated lymphocytes (p < 0.0001, p = 0.0003). The longer telomere was predominantly present in the hydroxymethylated sister chromatid in chromosomes featuring hemihydroxymethylation (containing 5-hydroxymethylcytosine in only one sister chromatid)-a typical sign of chorionic cytotrophoblast cells. Our results suggest that the phenomena of interchromatid TL asymmetry and its association to 5hmC patterns in chorionic cytotrophoblast, which are potentially linked to telomere lengthening through recombination, are inherent to the development programme. The TL differences in chorionic cytotrophoblast that are associated with karyotype and embryo viability seem to be determined by heredity rather than telomere elongation mechanisms. The inheritance of long telomeres by a karyotypically abnormal embryo promotes his development, whereas TL in karyotypically normal first-trimester embryos does not seem to have a considerable impact on developmental capacity.},
}
@article {pmid34205609,
year = {2021},
author = {Azcona-Sanjulian, MC},
title = {Telomere Length and Pediatric Obesity: A Review.},
journal = {Genes},
volume = {12},
number = {6},
pages = {},
pmid = {34205609},
issn = {2073-4425},
mesh = {Adolescent ; Child ; Humans ; Pediatric Obesity/*genetics ; *Telomere Homeostasis ; },
abstract = {Obesity is a chronic disease, which needs to be early detected early and treated in order prevent its complications. Changes in telomere length (TL) have been associated with obesity and its complications, such as diabetes mellitus and metabolic syndrome. Therefore, we conducted a systematic review to summarize results of studies that have measured TL in children and adolescents with obesity. Fourteen studies aiming to assess TL in pediatric patients with either obesity or who were overweight were included in this review. In conclusion, obesity and adiposity parameters are negatively associated with TL. Shorter telomeres are observed in children with obesity compared with their lean counterparts. Factors involved in obesity etiology, such as diet and physical activity, may contribute to maintenance of TL integrity. In the long term, TL change could be used as a biomarker to predict response to obesity treatment.},
}
@article {pmid34205454,
year = {2021},
author = {Rassoulzadegan, M and Sharifi-Zarchi, A and Kianmehr, L},
title = {DNA-RNA Hybrid (R-Loop): From a Unified Picture of the Mammalian Telomere to the Genome-Wide Profile.},
journal = {Cells},
volume = {10},
number = {6},
pages = {},
pmid = {34205454},
issn = {2073-4409},
support = {2019-2020 Minoo Rassoulzadegan//La Fondation Nestl&#xe9; France/ ; },
mesh = {Animals ; *DNA/genetics/metabolism ; Genome-Wide Association Study ; Male ; Mice ; *R-Loop Structures ; *RNA, Long Noncoding/genetics/metabolism ; *Telomere/genetics/metabolism ; },
abstract = {Local three-stranded DNA/RNA hybrid regions of genomes (R-loops) have been detected either by binding of a monoclonal antibody (DRIP assay) or by enzymatic recognition by RNaseH. Such a structure has been postulated for mouse and human telomeres, clearly suggested by the identification of the complementary RNA Telomeric repeat-containing RNA "TERRA". However, the tremendous disparity in the information obtained with antibody-based technology drove us to investigate a new strategy. Based on the observation that DNA/RNA hybrids in a triplex complex genome co-purify with the double-stranded chromosomal DNA fraction, we developed a direct preparative approach from total protein-free cellular extract without antibody that allows their physical isolation and determination of their RNA nucleotide sequence. We then define in the normal mouse and human sperm genomes the notion of stable DNA associated RNA terminal R-loop complexes, including TERRA molecules synthesized from local promoters of every chromosome. Furthermore, the first strong evidence of all telomeric structures, applied additionally to the whole murine sperm genome compared to the testes, showed reproducible R-loop complexes of the whole genome and suggesting a defined profile in the sperm genome for the next generation.},
}
@article {pmid34204343,
year = {2021},
author = {Chronowski, C and Akhanov, V and Chan, D and Catic, A and Finegold, M and Sahin, E},
title = {Fructose Causes Liver Damage, Polyploidy, and Dysplasia in the Setting of Short Telomeres and p53 Loss.},
journal = {Metabolites},
volume = {11},
number = {6},
pages = {},
pmid = {34204343},
issn = {2218-1989},
support = {R01 AG047924/AG/NIA NIH HHS/United States ; R01 DK115454/DK/NIDDK NIH HHS/United States ; R01AG047924/GF/NIH HHS/United States ; },
abstract = {Studies in humans and model systems have established an important role of short telomeres in predisposing to liver fibrosis through pathways that are incompletely understood. Recent studies have shown that telomere dysfunction impairs cellular metabolism, but whether and how these metabolic alterations contribute to liver fibrosis is not well understood. Here, we investigated whether short telomeres change the hepatic response to metabolic stress induced by fructose, a sugar that is highly implicated in non-alcoholic fatty liver disease. We find that telomere shortening in telomerase knockout mice (TKO) imparts a pronounced susceptibility to fructose as reflected in the activation of p53, increased apoptosis, and senescence, despite lower hepatic fat accumulation in TKO mice compared to wild type mice with long telomeres. The decreased fat accumulation in TKO is mediated by p53 and deletion of p53 normalizes hepatic fat content but also causes polyploidy, polynuclearization, dysplasia, cell death, and liver damage. Together, these studies suggest that liver tissue with short telomers are highly susceptible to fructose and respond with p53 activation and liver damage that is further exacerbated when p53 is lost resulting in dysplastic changes.},
}
@article {pmid34203694,
year = {2021},
author = {Jacczak, B and Rubiś, B and Totoń, E},
title = {Potential of Naturally Derived Compounds in Telomerase and Telomere Modulation in Skin Senescence and Aging.},
journal = {International journal of molecular sciences},
volume = {22},
number = {12},
pages = {},
pmid = {34203694},
issn = {1422-0067},
support = {502-20-33184320//Poznan University of Medical Sciences/ ; 2016/21/B/NZ7/01079//Narodowe Centrum Nauki/ ; },
mesh = {Aging/*metabolism ; Animals ; Biological Products/*pharmacology ; Humans ; Skin/drug effects/*pathology ; Telomerase/*metabolism ; Telomere/*metabolism ; },
abstract = {Proper functioning of cells-their ability to divide, differentiate, and regenerate-is dictated by genomic stability. The main factors contributing to this stability are the telomeric ends that cap chromosomes. Telomere biology and telomerase activity have been of interest to scientists in various medical science fields for years, including the study of both cancer and of senescence and aging. All these processes are accompanied by telomere-length modulation. Maintaining the key levels of telomerase component (hTERT) expression and telomerase activity that provide optimal telomere length as well as some nontelomeric functions represents a promising step in advanced anti-aging strategies, especially in dermocosmetics. Some known naturally derived compounds contribute significantly to telomere and telomerase metabolism. However, before they can be safely used, it is necessary to assess their mechanisms of action and potential side effects. This paper focuses on the metabolic potential of natural compounds to modulate telomerase and telomere biology and thus prevent senescence and skin aging.},
}
@article {pmid34203235,
year = {2021},
author = {Sellami, M and Al-Muraikhy, S and Al-Jaber, H and Al-Amri, H and Al-Mansoori, L and Mazloum, NA and Donati, F and Botre, F and Elrayess, MA},
title = {Age and Sport Intensity-Dependent Changes in Cytokines and Telomere Length in Elite Athletes.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {10},
number = {7},
pages = {},
pmid = {34203235},
issn = {2076-3921},
support = {UREP26-043-3-018//Qatar National Research Fund/ ; },
abstract = {BACKGROUND: Exercise-associated immune response plays a crucial role in the aging process. The aim of this study is to investigate the effect of sport intensity on cytokine levels, oxidative stress markers and telomere length in aging elite athletes.<br><br>METHODS: In this study, 80 blood samples from consenting elite athletes were collected for anti-doping analysis at an anti-doping laboratory in Italy (FMSI). Participants were divided into three groups according to their sport intensity: low-intensity skills and power sports (LI, n = 18); moderate-intensity mixed soccer players (MI, n = 31); and high-intensity endurance sports (HI, n = 31). Participants were also divided into two age groups: less than 25 (n = 45) and above 25 years old (n = 35). Serum levels of 10 pro and anti-inflammatory cytokines and two antioxidant enzymes were compared in age and sport intensity groups and telomere lengths were measured in their respective blood samples.<br><br>RESULTS: Tumor necrosis factor-alpha (TNF-&#x3b1;) was the only cytokine showing significantly higher concentration in older athletes, regardless of sport intensity. Interleukin (IL)-10 increased significantly in HI regardless of age group, whereas IL-6 concentration was higher in the older HI athletes. IL-8 showed a significant interaction with sport intensity in different age groups. Overall, significant positive correlations among levels of IL-6, IL-10, IL-8 and TNF-&#x3b1; were identified. The antioxidant catalase activity was positively correlated with levels of TNF-&#x3b1;. Telomere length increased significantly with sport intensity, especially in the younger group.<br><br>CONCLUSION: HI had longer telomeres and higher levels of pro- and anti-inflammatory cytokines, suggesting less aging in HI compared to low and moderate counterparts in association with heightened immune response. Investigation of the functional significance of these associations on the health and performance of elite athletes is warranted.},
}
@article {pmid34202278,
year = {2021},
author = {Maestri, E and Duszka, K and Kuznetsov, VA},
title = {Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction.},
journal = {Cancers},
volume = {13},
number = {13},
pages = {},
pmid = {34202278},
issn = {2072-6694},
support = {The EMPIRE innovative program//State University of New York/ ; },
abstract = {Systems cancer biology analysis of calorie restriction (CR) mechanisms and pathways has not been carried out, leaving therapeutic benefits unclear. Using metadata analysis, we studied gene expression changes in normal mouse duodenum mucosa (DM) response to short-term (2-weeks) 25% CR as a biological model. Our results indicate cancer-associated genes consist of 26% of 467 CR responding differential expressed genes (DEGs). The DEGs were enriched with over-expressed cell cycle, oncogenes, and metabolic reprogramming pathways that determine tissue-specific tumorigenesis, cancer, and stem cell activation; tumor suppressors and apoptosis genes were under-expressed. DEG enrichments suggest telomeric maintenance misbalance and metabolic pathway activation playing dual (anti-cancer and pro-oncogenic) roles. The aberrant DEG profile of DM epithelial cells is found within CR-induced overexpression of Paneth cells and is coordinated significantly across GI tract tissues mucosa. Immune system genes (ISGs) consist of 37% of the total DEGs; the majority of ISGs are suppressed, including cell-autonomous immunity and tumor-immune surveillance. CR induces metabolic reprogramming, suppressing immune mechanics and activating oncogenic pathways. We introduce and argue for our network pro-oncogenic model of the mucosa multicellular tissue response to CR leading to aberrant transcription and pre-malignant states. These findings change the paradigm regarding CR's anti-cancer role, initiating specific treatment target development. This will aid future work to define critical oncogenic pathways preceding intestinal lesion development and biomarkers for earlier adenoma and colorectal cancer detection.},
}
@article {pmid34200513,
year = {2021},
author = {Pousa, PA and Souza, RM and Melo, PHM and Correa, BHM and Mendonça, TSC and Simões-E-Silva, AC and Miranda, DM},
title = {Telomere Shortening and Psychiatric Disorders: A Systematic Review.},
journal = {Cells},
volume = {10},
number = {6},
pages = {},
pmid = {34200513},
issn = {2073-4409},
mesh = {Humans ; Mental Disorders/genetics/*metabolism ; Mitochondria/genetics/*metabolism ; *Oxidative Stress ; Telomere/genetics/*metabolism ; *Telomere Shortening ; },
abstract = {Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological distress lead to alterations to telomere length (TL), corroborating the hypothesis that mental disorders might have a deeper impact on our physiology and aging than it was previously thought. A systematic search of the literature using MeSH descriptors of psychological distress ("Traumatic Stress Disorder" or "Anxiety Disorder" or "depression") and telomere length ("cellular senescence", "oxidative stress" and "telomere") was conducted on PubMed, Cochrane Library and ScienceDirect databases. A total of 56 studies (113,699 patients) measured the TL from individuals diagnosed with anxiety, depression and posttraumatic disorders and compared them with those from healthy subjects. Overall, TL negatively associates with distress-related mental disorders. The possible underlying molecular mechanisms that underly psychiatric diseases to telomere shortening include oxidative stress, inflammation and mitochondrial dysfunction linking. It is still unclear whether psychological distress is either a cause or a consequence of telomere shortening.},
}
@article {pmid34200325,
year = {2021},
author = {Mongelli, A and Barbi, V and Gottardi Zamperla, M and Atlante, S and Forleo, L and Nesta, M and Massetti, M and Pontecorvi, A and Nanni, S and Farsetti, A and Catalano, O and Bussotti, M and Dalla Vecchia, LA and Bachetti, T and Martelli, F and La Rovere, MT and Gaetano, C},
title = {Evidence for Biological Age Acceleration and Telomere Shortening in COVID-19 Survivors.},
journal = {International journal of molecular sciences},
volume = {22},
number = {11},
pages = {},
pmid = {34200325},
issn = {1422-0067},
support = {PRIN2017S55RXB//Ministero dell'Educazione, Universit&#xe0; e ricerca/ ; PRIN2015HPMLFY//Ministero dell'Istruzione, dell'Universit&#xe0; e della Ricerca/ ; RF 2010-2318330//Ministero della Salute/ ; "RicercaCorrente" and "Progetto di Rete Cardiovascolare IRCCS: CardioCovid"//Ministero della Salute/ ; 446 GGP19035A//Fondazione Telethon/ ; 23054//Fondazione Telethon/ ; 101016072//Horizon 2020/ ; 22858//Associazione Italiana per la Ricerca sul Cancro/ ; },
mesh = {Adult ; Aged ; Aging/*genetics ; Angiotensin-Converting Enzyme 2/blood ; Biomarkers ; COVID-19/complications/etiology/*genetics/*physiopathology ; *CpG Islands ; DNA Methylation ; Dipeptidyl Peptidase 4/blood ; Epigenomics ; Female ; High-Throughput Nucleotide Sequencing ; Host Microbial Interactions ; Humans ; Male ; Middle Aged ; Risk Factors ; Survivors ; Telomere/*metabolism ; *Telomere Shortening ; Post-Acute COVID-19 Syndrome ; },
abstract = {The SARS-CoV-2 infection determines the COVID-19 syndrome characterized, in the worst cases, by severe respiratory distress, pulmonary and cardiac fibrosis, inflammatory cytokine release, and immunosuppression. This condition has led to the death of about 2.15% of the total infected world population so far. Among survivors, the presence of the so-called persistent post-COVID-19 syndrome (PPCS) is a common finding. In COVID-19 survivors, PPCS presents one or more symptoms: fatigue, dyspnea, memory loss, sleep disorders, and difficulty concentrating. In this study, a cohort of 117 COVID-19 survivors (post-COVID-19) and 144 non-infected volunteers (COVID-19-free) was analyzed using pyrosequencing of defined CpG islands previously identified as suitable for biological age determination. The results show a consistent biological age increase in the post-COVID-19 population, determining a DeltaAge acceleration of 10.45 ± 7.29 years (+5.25 years above the range of normality) compared with 3.68 ± 8.17 years for the COVID-19-free population (p < 0.0001). A significant telomere shortening parallels this finding in the post-COVID-19 cohort compared with COVID-19-free subjects (p < 0.0001). Additionally, ACE2 expression was decreased in post-COVID-19 patients, compared with the COVID-19-free population, while DPP-4 did not change. In light of these observations, we hypothesize that some epigenetic alterations are associated with the post-COVID-19 condition, particularly in younger patients (< 60 years).},
}
@article {pmid34197088,
year = {2021},
author = {Gao, K and Zhou, Y and Lu, Q and Lu, J and Su, L and Su, R and Zhang, M and Tian, Y and Wu, L and Yan, X},
title = {High-Throughput Human Telomere Length Analysis at the Single-Chromosome Level by FISH Coupled with Nano-Flow Cytometry.},
journal = {Analytical chemistry},
volume = {93},
number = {27},
pages = {9531-9540},
doi = {10.1021/acs.analchem.1c01544},
pmid = {34197088},
issn = {1520-6882},
mesh = {Flow Cytometry ; Humans ; In Situ Hybridization, Fluorescence ; *Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; *Telomere/genetics ; },
abstract = {Telomere length (TL) is a highly relevant biomarker for age-associated diseases and cancer, yet its clinical applications have been hindered by the inability of existing methods to rapidly measure the TL distribution and the percentage of chromosomes with critically short telomeres (CSTs, < 3 kb). Herein, we report the development of a high-throughput method to measure TL at the single-chromosome level. Metaphase chromosomes are isolated, hybridized with the Alexa Fluor 488-labeled telomeric peptide nucleic acid probe, and analyzed using a laboratory-built ultrasensitive nano-flow cytometer. The fluorescence intensity of individual chromosomes is converted to TL in kilobases upon external calibration. With an analysis rate of several thousand chromosomes per minute, a statistically robust TL distribution histogram is acquired in minutes, and the percentage of chromosomes with CSTs can be quickly assessed. By analyzing peripheral blood lymphocytes of 158 healthy donors, TL is found to shorten with age at a rate of 64 ± 3 bp/year and the percentage of chromosomes with CSTs increases with age at a rate of 0.32 ± 0.02%/year. Moreover, the data of 28 patients with chronic myeloid leukemia (CML) indicate that telomeres are significantly shorter at the time of diagnosis and the clinical phases of CML are closely associated with TL and the percentage of chromosomes with CSTs. This powerful tool could greatly deepen our understanding of telomere biology and improve the clinical utility of telomere biomarkers.},
}
@article {pmid34196896,
year = {2021},
author = {Dweck, A and Maitra, R},
title = {The advancement of telomere quantification methods.},
journal = {Molecular biology reports},
volume = {48},
number = {7},
pages = {5621-5627},
pmid = {34196896},
issn = {1573-4978},
mesh = {Chromosomal Instability ; DNA Replication ; Genetic Testing/*methods/standards ; Humans ; In Situ Hybridization, Fluorescence ; Real-Time Polymerase Chain Reaction ; Telomere/*genetics/metabolism ; *Telomere Homeostasis ; Telomere Shortening/genetics ; },
abstract = {Telomeres, guanine rich DNA sequences, which are found at both ends of human chromosomes, play a vital role in genome protection. These repetitive nucleotide sequences protect the genome from nucleolytic degradation, unnecessary recombination, and interchromosomal fusion. Though, as somatic cells go through replication cycles, their telomeres shrink until they reach a critical length called the Hayflick limit. At this limit, cellular senescence, an irreversible cell cycle arrest, is prompted. For all the above reasons, telomere length is a hopeful biomarker for age-associated diseases and cancer. While there are numerous methods for telomere measurement and quantification, there are still challenges for routine analysis in clinics as these methods are not simple and rapid. Recently, a new method has been developed that measures absolute length and absolute quantities of single telomere molecules. This method, single telomere absolute-length rapid (STAR) assay, which promises to measure telomere length rapidly and accurately, is also expected to be scalable. This review will discuss different telomere length measurement methods, including STAR assay, and will highlight each of their advantages and drawbacks. It will culminate in determining if STAR assay has the potential to be the superior method for telomere measurement.},
}
@article {pmid34195674,
year = {2021},
author = {Wang, L and Wang, Z and Liu, JP},
title = {Identification of peptidomimetic telomere dysfunction inhibitor (TELODIN) through telomere dysfunction-induced foci (TIF) assay.},
journal = {STAR protocols},
volume = {2},
number = {3},
pages = {100620},
pmid = {34195674},
issn = {2666-1667},
mesh = {Cells, Cultured ; Humans ; *Peptidomimetics ; Telomere/*drug effects ; },
abstract = {Telomere dysfunction-induced focus (TIF) assay allows efficient profiling of telomere dysfunctions in cells and tissues. Here, we describe the use of the TIF assay to screen synthetic peptides from E3 ubiquitin ligase FBW7, a tumor suppressor gene product, to prevent TIFs caused by environmental radiation stress. We demonstrate peptidomimetic telomere dysfunction inhibitor as a potentially intervening therapeutic drug candidate in aging-related diseases. This work demonstrates a novel utility of the TIF assay protocol in identifying telomere dysfunction inhibitors. For complete details on the use and execution of this protocol, please refer to Wang et al (2020).},
}
@article {pmid34193151,
year = {2021},
author = {Eick, SM and Goin, DE and Cushing, L and DeMicco, E and Park, JS and Wang, Y and Smith, S and Padula, AM and Woodruff, TJ and Morello-Frosch, R},
title = {Mixture effects of prenatal exposure to per- and polyfluoroalkyl substances and polybrominated diphenyl ethers on maternal and newborn telomere length.},
journal = {Environmental health : a global access science source},
volume = {20},
number = {1},
pages = {76},
pmid = {34193151},
issn = {1476-069X},
support = {U24 AG066528/AG/NIA NIH HHS/United States ; UH3 OD023272/OD/NIH HHS/United States ; UG3 OD023272/OD/NIH HHS/United States ; P30 ES030284/ES/NIEHS NIH HHS/United States ; P01 ES022841/ES/NIEHS NIH HHS/United States ; P20 ES018135/ES/NIEHS NIH HHS/United States ; },
mesh = {Adult ; Biological Monitoring ; Environmental Pollutants/analysis/*toxicity ; Fatty Acids/analysis/toxicity ; Female ; Flame Retardants/analysis/*toxicity ; Fluorocarbons/analysis/*toxicity ; Halogenated Diphenyl Ethers/analysis/*toxicity ; Humans ; Infant, Newborn ; Male ; Maternal Exposure ; Maternal-Fetal Exchange ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Sulfonic Acids/analysis/toxicity ; Telomere/*drug effects ; },
abstract = {BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are endocrine disrupting chemicals with widespread exposures across the U.S. given their abundance in consumer products. PFAS and PBDEs are associated with reproductive toxicity and adverse health outcomes, including certain cancers. PFAS and PBDEs may affect health through alternations in telomere length. In this study, we examined joint associations between prenatal exposure to PFAS, PBDEs, and maternal and newborn telomere length using mixture analyses, to characterize effects of cumulative environmental chemical exposures.<br><br>METHODS: Study participants were enrolled in the Chemicals in Our Bodies (CIOB) study, a demographically diverse cohort of pregnant people and children in San Francisco, CA. Seven PFAS (ng/mL) and four PBDEs (ng/g lipid) were measured in second trimester maternal serum&#xa0;samples. Telomere length (T/S ratio) was measured in delivery cord blood of 292 newborns and 110&#xa0;second trimester maternal whole blood samples. Quantile g-computation was used to assess the joint associations between groups of PFAS and PBDEs and newborn and maternal telomere length. Groups considered were: (1) all PFAS and PBDEs combined, (2) PFAS, and (3) PBDEs. Maternal and newborn telomere length were modeled as separate outcomes.<br><br>RESULTS: T/S ratios in newborn cord and maternal whole blood were moderately correlated (Spearman &#x3c1;&#x2009;=&#x2009;0.31). In mixtures analyses, a simultaneous one quartile increase in all PFAS and PBDEs was associated with a small increase in newborn (mean change per quartile increase&#x2009;=&#x2009;0.03, 95% confidence interval [CI]&#x2009;=&#x2009;-0.03, 0.08) and maternal telomere length (mean change per quartile increase&#x2009;=&#x2009;0.03 (95% CI&#x2009;=&#x2009;-0.03, 0.09). When restricted to maternal-fetal paired samples (N&#x2009;=&#x2009;76), increasing all PFAS and PBDEs combined was associated with a strong, positive increase in newborn telomere length (mean change per quartile increase&#x2009;=&#x2009;0.16, 95% CI&#x2009;=&#x2009;0.03, 0.28). These associations were primarily driven by PFAS (mean change per quartile increase&#x2009;=&#x2009;0.11 [95% CI&#x2009;=&#x2009;0.01, 0.22]). No associations were observed with maternal telomere length among paired samples.<br><br>CONCLUSIONS: Our findings suggest that PFAS and PBDEs may be positively associated with newborn telomere length.},
}
@article {pmid34192361,
year = {2021},
author = {Marasco, V and Boner, W and Griffiths, K and Heidinger, B and Monaghan, P},
title = {Repeated exposure to challenging environmental conditions influences telomere dynamics across adult life as predicted by changes in mortality risk.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {35},
number = {8},
pages = {e21743},
doi = {10.1096/fj.202100556R},
pmid = {34192361},
issn = {1530-6860},
support = {268926/ERC_/European Research Council/International ; M 2520/FWF_/Austrian Science Fund FWF/Austria ; },
mesh = {Aging/*genetics/*physiology ; Animals ; Environment ; Female ; Finches/blood/*genetics/*physiology ; Longevity/*genetics/*physiology ; Risk Factors ; Stress, Physiological/genetics ; Telomere Homeostasis/*genetics/*physiology ; Telomere Shortening/genetics/physiology ; },
abstract = {The effects of stress exposure are likely to vary depending on life-stage and stressor. While it has been postulated that mild stress exposure may have beneficial effects, the duration of such effects and the underlying mechanisms are unclear. While the long-term effects of early-life stress are relatively well studied, we know much less about the effects of exposure in adulthood since the early- and adult-life environments are often similar. We previously reported that repeated experimental exposure to a relatively mild stressor in female zebra finches, first experienced in young adulthood, initially had no effect on mortality risk, reduced mortality in middle age, but the apparently beneficial effects disappeared in old age. We show here that this is underpinned by differences between the control and stress-exposed group in the pattern of telomere change, with stress-exposed birds showing reduced telomere loss in middle adulthood. We thereby provide novel experimental evidence that telomere dynamics play a key role linking stress resilience and aging.},
}
@article {pmid34187905,
year = {2021},
author = {Robinson, NJ and Miyagi, M and Scarborough, JA and Scott, JG and Taylor, DJ and Schiemann, WP},
title = {SLX4IP promotes RAP1 SUMOylation by PIAS1 to coordinate telomere maintenance through NF-κB and Notch signaling.},
journal = {Science signaling},
volume = {14},
number = {689},
pages = {},
pmid = {34187905},
issn = {1937-9145},
support = {S10 RR031537/RR/NCRR NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; TL1 TR002549/TR/NCATS NIH HHS/United States ; R01 CA236273/CA/NCI NIH HHS/United States ; S10 OD016164/OD/NIH HHS/United States ; F30 CA213892/CA/NCI NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; R01 GM133841/GM/NIGMS NIH HHS/United States ; R01 CA240993/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Carrier Proteins/*genetics ; Cell Line, Tumor ; Mice ; NF-kappa B/genetics ; Protein Inhibitors of Activated STAT/*metabolism ; Receptors, Notch ; Signal Transduction ; *Sumoylation ; *Telomerase/genetics/metabolism ; Telomere/genetics/metabolism ; Ubiquitin-Protein Ligases/metabolism ; rap1 GTP-Binding Proteins/*metabolism ; },
abstract = {The maintenance of telomere length supports repetitive cell division and therefore plays a central role in cancer development and progression. Telomeres are extended by either the enzyme telomerase or the alternative lengthening of telomeres (ALT) pathway. Here, we found that the telomere-associated protein SLX4IP dictates telomere proteome composition by recruiting and activating the E3 SUMO ligase PIAS1 to the SLX4 complex. PIAS1 SUMOylated the telomere-binding protein RAP1, which disrupted its interaction with the telomere-binding protein TRF2 and facilitated its nucleocytoplasmic shuttling. In the cytosol, RAP1 bound to IκB kinase (IKK), resulting in activation of the transcription factor NF-κB and its induction of Jagged-1 expression, which promoted Notch signaling and the institution of ALT. This axis could be targeted therapeutically in ALT-driven cancers and in tumor cells that develop resistance to antitelomerase therapies. Our results illuminate the mechanisms underlying SLX4IP-dependent telomere plasticity and demonstrate the role of telomere proteins in directly coordinating intracellular signaling and telomere maintenance dynamics.},
}
@article {pmid34184077,
year = {2021},
author = {Oh, BK and Choi, Y and Choi, JS},
title = {Telomere shortening and expression of TRF1 and TRF2 in uterine leiomyoma.},
journal = {Molecular medicine reports},
volume = {24},
number = {2},
pages = {},
doi = {10.3892/mmr.2021.12243},
pmid = {34184077},
issn = {1791-3004},
mesh = {Adult ; Cell Cycle Proteins/genetics/metabolism ; Cell Transformation, Neoplastic/genetics ; Correlation of Data ; Female ; Humans ; Leiomyoma/*genetics/*metabolism ; Middle Aged ; Myometrium/metabolism ; Telomere/chemistry/metabolism ; Telomere Shortening/*genetics ; Telomeric Repeat Binding Protein 1/*genetics/*metabolism ; Telomeric Repeat Binding Protein 2/*genetics/*metabolism ; Tumor Suppressor Proteins/genetics/metabolism ; },
abstract = {Uterine leiomyoma is a benign smooth muscle tumor of the uterus that can exhibit histopathological traits that mimic malignancy. Telomere shortening is an early event in tumorigenesis and telomerase activation facilitates tumor progression later in the course of carcinogenesis. Telomeric repeat‑binding factor (TRF)1 and TRF2 protect telomeres, and their gene expression levels are dysregulated in various cancer types. However, the roles of telomeres and telomere protection proteins in uterine leiomyoma remain largely unknown. In this study, telomere length and the mRNA levels of various telomere‑related genes in normal tissues and leiomyoma were determined, and their relationships were evaluated. Uterine leiomyoma and normal myometrium were surgically obtained from 18 and 13 patients, respectively. Telomere length and gene expression were determined by Southern blot analysis and reverse transcription‑quantitative PCR, respectively. In matched samples, telomeres were consistently shorter in leiomyoma tissue than in adjacent normal tissue. TRF1, TRF2, PIN2‑interacting telomerase inhibitor 1 (PINX1), and telomerase RNA component were expressed at comparable levels in both leiomyoma and normal tissues. None of these genes were associated with telomere length in leiomyoma. All tested tissues were negative for telomerase reverse transcriptase, which encodes the catalytic component of telomerase, indicating that cells in uterine leiomyoma were not immortalized. In summary, telomere erosion, which reflects active proliferation during tumor evolution, was evident in uterine leiomyoma. Steady‑state expression of TRF1, TRF2 and PINX1 may be important for maintenance of telomere integrity in leiomyoma, where telomere length is shortened.},
}
@article {pmid34182850,
year = {2021},
author = {Moore, S and Patel, R and Stewart, J and McLain, AC and Heiney, S},
title = {Social inequalities in accelerated aging among southern U.S. women: an analysis of the biosocial and behavioral pathways linking social determinants to telomere length.},
journal = {Biodemography and social biology},
volume = {66},
number = {2},
pages = {118-131},
doi = {10.1080/19485565.2020.1869918},
pmid = {34182850},
issn = {1948-5573},
mesh = {Aging/genetics ; Female ; Humans ; Social Class ; *Social Determinants of Health ; Socioeconomic Factors ; *Telomere/genetics ; },
abstract = {Few studies have examined the biosocial pathways linking socioeconomic status (SES) to accelerated aging in a population-based sample of southern US women. Even fewer have examined the importance of chronic compared to perceived stress in linking SES to women's salivary telomere length (STL). Using data from a probability-based sample of 156 US women and structural equation modeling, we examined three pathways - chronic stress exposure, stress appraisal, and coping behavior - linking SES to STL. SES was positively associated with STL (βTE = 0.16, p < .05). Everyday discrimination was negatively associated with STL (βDE = -0.21, p < .05), but perceived stress was positively associated with STL (βDE = 0.20, p < .05). Current smoking decreased STL (βDE = -0.19, p < .01). Perceived stress acted to suppress the negative relationship of chronic stress exposure on STL. Given the dearth of STL studies that include measures of both perceived and chronic stress, our study supports the importance of disentangling stress measures and a biosocial approach to the study of accelerated aging.},
}
@article {pmid34180971,
year = {2022},
author = {Watanabe, S and Hibiya, S and Katsukura, N and Kitagawa, S and Sato, A and Okamoto, R and Watanabe, M and Tsuchiya, K},
title = {Importance of Telomere Shortening in the Pathogenesis of Ulcerative Colitis: A New Treatment From the Aspect of Telomeres in Intestinal Epithelial Cells.},
journal = {Journal of Crohn's &amp; colitis},
volume = {16},
number = {1},
pages = {109-121},
doi = {10.1093/ecco-jcc/jjab115},
pmid = {34180971},
issn = {1876-4479},
support = {17H06654//Japanese Ministry of Education, Culture, Sports, Science and Technology/ ; 18bm03041h0006//Japan Agency for Medical Research and Development/ ; //Naoki Tsuchida Research/ ; },
mesh = {Animals ; Biopsy ; Cell Proliferation ; Clustered Regularly Interspaced Short Palindromic Repeats ; Colitis, Ulcerative/*pathology ; Colonoscopy ; Epithelial Cells/*pathology ; Humans ; Intestinal Mucosa/*cytology ; Mice ; Organoids/metabolism/pathology/transplantation ; Reactive Oxygen Species/metabolism ; Telomerase/metabolism ; *Telomere Shortening ; Transplantation, Heterologous ; },
abstract = {BACKGROUND AND AIMS: Ulcerative colitis [UC] is a chronic inflammatory disease of the colon with frequent relapses. Telomere shortening in intestinal epithelial cells has been reported in severe or longstanding cases. However, its influence on UC pathogenesis remains unelucidated. To this end, we evaluated telomere shortening using a long-term organoid inflammation model that we had originally established.<br><br>METHODS: A UC model using human colon organoids was established to assess telomere changes chronologically. MST-312 was used for the telomerase inhibition assay. The potential of telomerase activators as a novel UC treatment was evaluated with an in vitro model, including microarray analysis, and histological changes were assessed using xenotransplantation into mouse colonic mucosa.<br><br>RESULTS: Our UC model reproduced telomere shortening in vitro, which was induced by the continuous suppression of telomerase activity via P53. MST-312-based analysis revealed that telomere shortening was involved in the pathogenesis of UC. Madecassoside [MD] improved the telomere length of the UC model and UC patient-derived organoids, which further promoted cell proliferation in vitro and improved the graft take-rate of xenotransplantation. Moreover, histological analysis revealed that MD induced normal crypt structure with abundant goblet cells.<br><br>CONCLUSIONS: This study is the first to reveal the mechanism and importance of telomere shortening in the pathogenesis of UC. MD could be a novel candidate for UC treatment beyond endoscopic mucosal healing.},
}
@article {pmid34173371,
year = {2021},
author = {Casavant, SG and Li, H and Reese, B and Chen, MH and Cong, XS},
title = {Pilot Study of Absolute Telomere Lengths in Preterm Infants.},
journal = {Nursing research},
volume = {70},
number = {6},
pages = {481-486},
pmid = {34173371},
issn = {1538-9847},
support = {F32 NR018591/NR/NINR NIH HHS/United States ; R01 NR016928/NR/NINR NIH HHS/United States ; },
mesh = {*Feeding Behavior ; Female ; Growth and Development/*genetics ; Humans ; Infant, Newborn ; Infant, Premature/*growth &amp; development ; Male ; Neurodevelopmental Disorders/*diagnosis/*genetics ; Pain/*genetics ; Pilot Projects ; Telomere/*genetics ; },
abstract = {BACKGROUND: Annually, approximately 15 million babies are born preterm (<37 weeks gestational age) globally. In the neonatal intensive care unit (NICU) environment, infants are exposed to repeated stressful or painful procedures as part of routine lifesaving care. These procedures have been associated with epigenetic alterations that may lead to an increased risk of neurodevelopmental disorders. Telomere length has been negatively associated with adverse life experiences in studies of adults.<br><br>OBJECTIVES: This pilot study aimed to describe telomere length in a sample of preterm infants at NICU discharge and examine any associations with pain, feeding method, and neurodevelopment.<br><br>METHODS: This descriptive pilot study sample includes baseline absolute telomere length (aTL) of 36 preterm infants immediately prior to discharge. Quantitative polymerase chain reaction was used to determine aTL. Infant demographics, pain/stress, type of feeding, antibiotic use, neurodevelopment, and buccal swab data were collected. Descriptive data analysis was used to describe the telomere length using graphs.<br><br>RESULTS: Among our preterm infant samples, the mean aTL was far greater than the average adult telomere length. Although no significant associations were found between aTL and pain, feeding method, and neurodevelopment, a trend between sex was noted where male telomere lengths were shorter than females as they aged.<br><br>DISCUSSION: This is one of few studies to evaluate preterm infant telomere length. Although other researchers have used relative telomere length, we used the more accurate aTL. We found nonsignificant shorter telomere lengths among males. Additional large-scale, longitudinal studies are needed to better identify the predictors of telomere length at the time of discharge from NICU.},
}
@article {pmid34162976,
year = {2021},
author = {Kychygina, A and Dall'Osto, M and Allen, JAM and Cadoret, JC and Piras, V and Pickett, HA and Crabbe, L},
title = {Progerin impairs 3D genome organization and induces fragile telomeres by limiting the dNTP pools.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {13195},
pmid = {34162976},
issn = {2045-2322},
mesh = {Adult ; Animals ; Cells, Cultured ; Cellular Senescence/genetics ; Chromatin/*ultrastructure ; DNA Damage ; DNA Replication ; Deoxyribonucleotides/*metabolism ; Fibroblasts ; Genes, Reporter ; Green Fluorescent Proteins ; Histone Code ; Humans ; Infant, Newborn ; Lamin Type A/analysis/deficiency/genetics/*physiology ; Lamin Type B/analysis ; Mice ; Mice, Knockout ; Nuclear Lamina/*pathology ; Progeria/*genetics/pathology ; Recombinant Fusion Proteins/metabolism ; Skin/pathology ; Telomere/*pathology ; Telomere Homeostasis/*genetics ; },
abstract = {Chromatin organization within the nuclear volume is essential to regulate many aspects of its function and to safeguard its integrity. A key player in this spatial scattering of chromosomes is the nuclear envelope (NE). The NE tethers large chromatin domains through interaction with the nuclear lamina and other associated proteins. This organization is perturbed in cells from Hutchinson-Gilford progeria syndrome (HGPS), a genetic disorder characterized by premature aging features. Here, we show that HGPS-related lamina defects trigger an altered 3D telomere organization with increased contact sites between telomeres and the nuclear lamina, and an altered telomeric chromatin state. The genome-wide replication timing signature of these cells is perturbed, with a shift to earlier replication for regions that normally replicate late. As a consequence, we detected a higher density of replication forks traveling simultaneously on DNA fibers, which relies on limiting cellular dNTP pools to support processive DNA synthesis. Remarkably, increasing dNTP levels in HGPS cells rescued fragile telomeres, and improved the replicative capacity of the cells. Our work highlights a functional connection between NE dysfunction and telomere homeostasis in the context of premature aging.},
}
@article {pmid34162698,
year = {2021},
author = {Grigorev, K and Foox, J and Bezdan, D and Butler, D and Luxton, JJ and Reed, J and McKenna, MJ and Taylor, L and George, KA and Meydan, C and Bailey, SM and Mason, CE},
title = {Haplotype diversity and sequence heterogeneity of human telomeres.},
journal = {Genome research},
volume = {31},
number = {7},
pages = {1269-1279},
pmid = {34162698},
issn = {1549-5469},
support = {R01 CA249054/CA/NCI NIH HHS/United States ; R01 MH117406/MH/NIMH NIH HHS/United States ; R01 AI151059/AI/NIAID NIH HHS/United States ; P01 HD067244/HD/NICHD NIH HHS/United States ; P01 CA214274/CA/NCI NIH HHS/United States ; R01 NS076465/NS/NINDS NIH HHS/United States ; },
abstract = {Telomeres are regions of repetitive nucleotide sequences capping the ends of eukaryotic chromosomes that protect against deterioration, and whose lengths can be correlated with age and adverse health risk factors. Yet, given their length and repetitive nature, telomeric regions are not easily reconstructed from short-read sequencing, thus making telomere sequencing, mapping, and variant resolution challenging problems. Recently, long-read sequencing, with read lengths measuring in hundreds of kilobase pairs, has made it possible to routinely read into telomeric regions and inspect their sequence structure. Here, we describe a framework for extracting telomeric reads from whole-genome single-molecule sequencing experiments, including de novo identification of telomere repeat motifs and repeat types, and also describe their sequence variation. We find that long, complex telomeric stretches and repeats can be accurately captured with long-read sequencing, observe extensive sequence heterogeneity of human telomeres, discover and localize noncanonical telomere sequence motifs (both previously reported, as well as novel), and validate them in short-read sequence data. These data reveal extensive intra- and inter-population diversity of repeats in telomeric haplotypes, reveal higher paternal inheritance of telomeric variants, and represent the first motif composition maps of multi-kilobase-pair human telomeric haplotypes across three distinct ancestries (Ashkenazi, Chinese, and Utah), which can aid in future studies of genetic variation, aging, and genome biology.},
}
@article {pmid34161613,
year = {2021},
author = {Valente, C and Andrade, R and Alvarez, L and Rebelo-Marques, A and Stamatakis, E and Espregueira-Mendes, J},
title = {Effect of physical activity and exercise on telomere length: Systematic review with meta-analysis.},
journal = {Journal of the American Geriatrics Society},
volume = {69},
number = {11},
pages = {3285-3300},
doi = {10.1111/jgs.17334},
pmid = {34161613},
issn = {1532-5415},
mesh = {Bias ; Exercise/*physiology ; Humans ; *Sedentary Behavior ; Telomere/*physiology ; },
abstract = {PURPOSE: To compare a physically active lifestyle or structured exercise program to physically inactive lifestyle or control groups on telomere length (TL).<br><br>METHOD: We searched PubMed, EMBASE, Cochrane Library, and Open Gray databases up to March 31, 2020. We calculated standardized mean differences (SMD) with 95% confidence intervals (CI) of TL comparing physically active to physically inactive individuals and exercise intervention to control groups. Risk of bias was judged using the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) for physical activity (PA) studies and the Cochrane risk-of-bias (RoB2) for exercise intervention studies. Certainty of evidence was judged using Grading of Recommendations Assessment, Development and Evaluation (GRADE).<br><br>RESULTS: We included 30 studies (24 assessing the effects of PA and 6 assessing the effects of exercise interventions) comprising 7418 individuals. Physically active individuals had longer telomeres (SMD&#xa0;=&#xa0;0.70, 95% CI 0.12-1.28, very-low certainty), especially in middle-aged individuals (SMD&#xa0;=&#xa0;0.90, 95% CI 0.08-1.72, very-low certainty) and when considering only athletes (SMD&#xa0;=&#xa0;0.54, 95% CI 0.18-0.90, very-low certainty). Trim-and-fill analyses revealed that most of the pooled effects were overestimated. Exercise interventions did not yield any significant effect on TL.<br><br>CONCLUSION: There is very-low certainty that physically active individuals have longer telomeres with a moderate effect, but this effect is probably overestimated.},
}
@article {pmid34158470,
year = {2021},
author = {Khayat, F and Cannavo, E and Alshmery, M and Foster, WR and Chahwan, C and Maddalena, M and Smith, C and Oliver, AW and Watson, AT and Carr, AM and Cejka, P and Bianchi, A},
title = {Inhibition of MRN activity by a telomere protein motif.},
journal = {Nature communications},
volume = {12},
number = {1},
pages = {3856},
pmid = {34158470},
issn = {2041-1723},
support = {/WT_/Wellcome Trust/United Kingdom ; 110047/Z/15/Z/WT_/Wellcome Trust/United Kingdom ; C28567/A12720/CRUK_/Cancer Research UK/United Kingdom ; G0701428/MRC_/Medical Research Council/United Kingdom ; },
mesh = {*Amino Acid Motifs ; Amino Acid Sequence ; DNA Breaks, Double-Stranded ; DNA End-Joining Repair ; DNA Helicases/genetics/*metabolism ; DNA, Fungal/genetics/metabolism ; Endodeoxyribonucleases/genetics/*metabolism ; Exodeoxyribonucleases/genetics/*metabolism ; Genomic Instability ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Origin Recognition Complex/genetics/metabolism ; Protein Serine-Threonine Kinases/genetics/metabolism ; Saccharomyces cerevisiae/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Sequence Homology, Amino Acid ; Telomere/genetics/*metabolism ; Telomere-Binding Proteins/genetics/metabolism ; },
abstract = {The MRN complex (MRX in Saccharomyces cerevisiae, made of Mre11, Rad50 and Nbs1/Xrs2) initiates double-stranded DNA break repair and activates the Tel1/ATM kinase in the DNA damage response. Telomeres counter both outcomes at chromosome ends, partly by keeping MRN-ATM in check. We show that MRX is disabled by telomeric protein Rif2 through an N-terminal motif (MIN, MRN/X-inhibitory motif). MIN executes suppression of Tel1, DNA end-resection and non-homologous end joining by binding the Rad50 N-terminal region. Our data suggest that MIN promotes a transition within MRX that is not conductive for endonuclease activity, DNA-end tethering or Tel1 kinase activation, highlighting an Achilles' heel in MRN, which we propose is also exploited by the RIF2 paralog ORC4 (Origin Recognition Complex 4) in Kluyveromyces lactis and the Schizosaccharomyces pombe telomeric factor Taz1, which is evolutionarily unrelated to Orc4/Rif2. This raises the possibility that analogous mechanisms might be deployed in other eukaryotes as well.},
}
@article {pmid34153093,
year = {2021},
author = {Gao, X and Li, S and Dong, S and Li, J and Yan, Y and Zhang, T and Chen, W},
title = {Association Between Body Weight and Telomere Length Is Predominantly Mediated Through C-Reactive Protein.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {106},
number = {11},
pages = {e4634-e4640},
doi = {10.1210/clinem/dgab455},
pmid = {34153093},
issn = {1945-7197},
mesh = {Adult ; Aged ; Aged, 80 and over ; Aging ; Biomarkers/*metabolism ; Body Mass Index ; *Body Weight ; C-Reactive Protein/*metabolism ; Cohort Studies ; Cross-Sectional Studies ; Female ; Follow-Up Studies ; Humans ; Inflammation/*epidemiology/metabolism/pathology ; Leukocytes/metabolism/pathology ; Male ; Middle Aged ; Nutrition Surveys ; Obesity/*complications ; Prognosis ; Telomere/genetics/*metabolism ; United States/epidemiology ; Young Adult ; },
abstract = {CONTEXT: Both obesity and inflammation are related to accelerated aging. It is not yet known whether inflammation mediates the effects of obesity on aging.<br><br>OBJECTIVE: This work aims to dissect the direct effect of body mass index (BMI) and its indirect effect through C-reactive protein (CRP) on leukocyte telomere length (LTL) to determine the mediation effect of CRP on the BMI-LTL association.<br><br>METHODS: The study cohort included 5451 adults (1404 Mexican American, 3114 White, and 933 Black individuals; 53.5% male; mean age&#x2005;=&#x2005;49.2 years) from the 1999 to 2002 National Health and Nutrition Examination Survey. General mediation models were used to examine the mediation effect of CRP on the BMI-LTL association.<br><br>RESULTS: After adjusting for age, race, sex, physical activity, alcohol use, and serum cotinine, the total effect of BMI on LTL was significant (standardized regression coefficient, &#x3b2;&#x2005;=&#x2005;-.054, P&#x2005;<&#x2005;.001) without CRP included in the model. With inclusion of CRP in the model, the indirect effect of BMI on LTL through CRP was estimated at &#x3b2; equal to -.023 (P&#x2005;<&#x2005;.001), and the direct effect of BMI on LTL in its absolute value decreased to &#x3b2; equal to -.031 (P&#x2005;=&#x2005;.025). The mediation effect of CRP was estimated at 42.6%. The mediation model parameters did not differ significantly between race and sex groups.<br><br>CONCLUSION: These results suggest that the inverse BMI-LTL association is partly mediated by obesity-induced inflammation. The significant direct effect of BMI on LTL with removal of the mediation effect through CRP indicates that obesity is associated with LTL attrition also through other noninflammatory mechanisms.},
}
@article {pmid34152657,
year = {2021},
author = {Manoli, F and Doria, F and Colombo, G and Zambelli, B and Freccero, M and Manet, I},
title = {The Binding Pocket at the Interface of Multimeric Telomere G-quadruplexes: Myth or Reality?.},
journal = {Chemistry (Weinheim an der Bergstrasse, Germany)},
volume = {27},
number = {45},
pages = {11707-11720},
pmid = {34152657},
issn = {1521-3765},
support = {IG 14708//Associazione Italiana per la Ricerca sul Cancro/ ; },
mesh = {Circular Dichroism ; DNA ; *G-Quadruplexes ; Humans ; Ligands ; Telomere ; },
abstract = {Human telomeric DNA with hundreds of repeats of the 5'-TTAGGG-3' motif plays a crucial role in several biological processes. It folds into G-quadruplex (G4) structures and features a pocket at the interface of two contiguous G4 blocks. Up to now no structural NMR and crystallographic data are available for ligands interacting with contiguous G4s. Naphthalene diimide monomers and dyads were investigated as ligands of a dimeric G4 of human telomeric DNA comparing the results with those of the model monomeric G4. Time-resolved fluorescence, circular dichroism, isothermal titration calorimetry and molecular modeling were used to elucidate binding features. Ligand fluorescence lifetime and induced circular dichroism unveiled occupancy of the binding site at the interface. Thermodynamic parameters confirmed the hypothesis as they remarkably change for the dyad complexes of the monomeric and dimeric telomeric G4. The bi-functional ligand structure of the dyads is a fundamental requisite for binding at the G4 interface as only the dyads engage in complexes with 1 : 1 stoichiometry, lodging in the pocket at the interface and establishing multiple interactions with the DNA skeleton. In the absence of NMR and crystallographic data, our study affords important proofs of binding at the interface pocket and clues on the role played by the ligand structure.},
}
@article {pmid34152095,
year = {2021},
author = {Mendes-Silva, AP and Vieira, ELM and Xavier, G and Barroso, LSS and Bertola, L and Martins, EAR and Brietzke, EM and Belangero, SIN and Diniz, BS},
title = {Telomere shortening in late-life depression: A potential marker of depression severity.},
journal = {Brain and behavior},
volume = {11},
number = {8},
pages = {e2255},
pmid = {34152095},
issn = {2162-3279},
mesh = {Aged ; Depression/genetics ; *Depressive Disorder, Major/genetics ; Humans ; Leukocytes ; Telomere/genetics ; *Telomere Shortening ; },
abstract = {OBJECTIVES: Telomeres are structures at the extremity of chromosomes that prevents genomic instability, and its shortening seems to be a hallmark of cellular aging. Past studies have shown contradictory results of telomere length (TL) in major depression, and are a few studies in late-life depression (LLD). This explores the association between TL as a molecular marker of aging and diagnosis of LLD, the severity of depressive symptoms, and cognitive performance in older adults.<br><br>METHODS/DESIGN: We included 78 older adults (45 with LLD and 33 nondepressed controls, according to DSM-V criteria), aged 60-90 years. TL was measured in leukocytes by a quantitative polymerase chain reaction, determining the relative ratio (T/S) between the telomere region copy number (T) and a single copy gene (S), using a relative standard curve.<br><br>RESULTS: TL was significantly shorter in the LLD compared with control participants (p&#xa0;=&#xa0;.039). Comparing groups through the severity of depressive symptoms, we found a negative correlation with the severity of depressive symptoms (Hamilton Depression Rating Scale-21, r&#xa0;=&#xa0;-0.325, p&#xa0;=&#xa0;.004) and medical burden (r&#xa0;=&#xa0;-0.271, p&#xa0;=&#xa0;.038). There was no significant correlation between TL and cognitive performance (Mattis Dementia Rating Scale, r&#xa0;=&#xa0;0.152, p&#xa0;=&#xa0;.21).<br><br>CONCLUSIONS: We found that older adults with LLD have shorter telomere than healthy controls, especially those with a more severe depressive episode. Our findings suggest that shorter TL can be a marker of the severity of depressive episodes in older adults and indicate that these individuals may be at higher risk of age-associated adverse outcomes linked to depression.},
}
@article {pmid34151032,
year = {2021},
author = {Dos Santos, GA and Pimenta, R and Viana, NI and Guimarães, VR and Romão, P and Candido, P and de Camargo, JA and Hatanaka, DM and Queiroz, PG and Teruya, A and Leite, KRM and Srougi, V and Srougi, M and Reis, ST},
title = {Shorter leukocyte telomere length is associated with severity of COVID-19 infection.},
journal = {Biochemistry and biophysics reports},
volume = {27},
number = {},
pages = {101056},
pmid = {34151032},
issn = {2405-5808},
support = {CH/12/2/29428/BHF_/British Heart Foundation/United Kingdom ; RG/13/13/30194/BHF_/British Heart Foundation/United Kingdom ; RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; },
abstract = {The infection by COVID-19 is a serious global public health problem. An efficient way to improve this disease's clinical management would be to characterize patients at higher risk of progressing to critically severe infection using prognostic biomarkers. The telomere length could be used for this purpose. Telomeres are responsible for controlling the number of maximum cell divisions. The telomere length is a biomarker of aging and several diseases. We aimed to compare leukocyte telomere length (LTL) between patients without COVID-19 and patients with different clinical severity of the infection. Were included 53 patients who underwent SARS-CoV-2 PCR divided in four groups. The first group was composed by patients with a negative diagnosis for COVID-19 (n = 12). The other three groups consisted of patients with a confirmed diagnosis of COVID-19 divided according to the severity of the disease: mild (n = 15), moderate (n = 17) and severe (n = 9). The LTL was determined by Q-PCR. The severe group had the shortest LTL, followed by the moderate group. The negative and mild groups showed no differences. There is an increase of patients with hypertension (p = 0.0099) and diabetes (p = 0.0067) in moderate and severe groups. Severe group was composed by older patients in comparison with the other three groups (p = 0.0083). Regarding sex, there was no significant difference between groups (p = 0.6279). In an ordinal regression model, only LTL and diabetes were significantly associated with disease severity. Shorter telomere length was significantly associated with the severity of COVID-19 infection, which can be useful as a biomarker or to better understand the SARS-CoV-2 pathophysiology.},
}
@article {pmid34149773,
year = {2021},
author = {Aguilar, M and Prieto, P},
title = {Telomeres and Subtelomeres Dynamics in the Context of Early Chromosome Interactions During Meiosis and Their Implications in Plant Breeding.},
journal = {Frontiers in plant science},
volume = {12},
number = {},
pages = {672489},
pmid = {34149773},
issn = {1664-462X},
abstract = {Genomic architecture facilitates chromosome recognition, pairing, and recombination. Telomeres and subtelomeres play an important role at the beginning of meiosis in specific chromosome recognition and pairing, which are critical processes that allow chromosome recombination between homologs (equivalent chromosomes in the same genome) in later stages. In plant polyploids, these terminal regions are even more important in terms of homologous chromosome recognition, due to the presence of homoeologs (equivalent chromosomes from related genomes). Although telomeres interaction seems to assist homologous pairing and consequently, the progression of meiosis, other chromosome regions, such as subtelomeres, need to be considered, because the DNA sequence of telomeres is not chromosome-specific. In addition, recombination operates at subtelomeres and, as it happens in rye and wheat, homologous recognition and pairing is more often correlated with recombining regions than with crossover-poor regions. In a plant breeding context, the knowledge of how homologous chromosomes initiate pairing at the beginning of meiosis can contribute to chromosome manipulation in hybrids or interspecific genetic crosses. Thus, recombination in interspecific chromosome associations could be promoted with the aim of transferring desirable agronomic traits from related genetic donor species into crops. In this review, we summarize the importance of telomeres and subtelomeres on chromatin dynamics during early meiosis stages and their implications in recombination in a plant breeding framework.},
}
@article {pmid34148055,
year = {2022},
author = {Pepper, AGS and Zucchetto, A and Norris, K and Tissino, E and Polesel, J and Soe, Z and Allsup, D and Hockaday, A and Ow, PL and Hillmen, P and Rawstron, A and Catovsky, D and Bulian, P and Bomben, R and Baird, DM and Fegan, CD and Gattei, V and Pepper, C},
title = {Combined analysis of IGHV mutations, telomere length and CD49d identifies long-term progression-free survivors in TP53 wild-type CLL treated with FCR-based therapies.},
journal = {Leukemia},
volume = {36},
number = {1},
pages = {271-274},
pmid = {34148055},
issn = {1476-5551},
support = {25447/CRUK_/Cancer Research UK/United Kingdom ; 29202/CRUK_/Cancer Research UK/United Kingdom ; MR/V009095/1/MRC_/Medical Research Council/United Kingdom ; /DH_/Department of Health/United Kingdom ; },
mesh = {Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Biomarkers, Tumor/analysis ; Cyclophosphamide/administration &amp; dosage ; Follow-Up Studies ; Humans ; Immunoglobulin Heavy Chains/*genetics ; Immunoglobulin Variable Region/*genetics ; Integrin alpha4/genetics/*metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/genetics/*mortality/pathology ; *Mutation ; Neoplasm Recurrence, Local/drug therapy/genetics/mortality/pathology ; Prognosis ; Rituximab/administration &amp; dosage ; Survival Rate ; *Telomere Homeostasis ; Tumor Suppressor Protein p53/*genetics ; Vidarabine/administration &amp; dosage/analogs &amp; derivatives ; },
}
@article {pmid34148053,
year = {2022},
author = {Boyle, EM and Williams, L and Blaney, P and Ashby, C and Bauer, M and Walker, BA and Ghamlouch, H and Choi, J and Perrial, E and Wang, Y and Caro, J and Stoeckle, JH and Arbini, A and Kaminetzky, D and Braunstein, M and Bruno, B and Razzo, B and Diamond, B and Maclachlan, K and Maura, F and Landgren, O and Litke, R and Fegan, CD and Keats, J and Auclair, D and Davies, FE and Morgan, GJ},
title = {Improving prognostic assignment in older adults with multiple myeloma using acquired genetic features, clonal hemopoiesis and telomere length.},
journal = {Leukemia},
volume = {36},
number = {1},
pages = {221-224},
pmid = {34148053},
issn = {1476-5551},
mesh = {Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/*genetics ; *Clonal Hematopoiesis ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Multiple Myeloma/genetics/*pathology/therapy ; Prognosis ; RNA-Seq ; Survival Rate ; *Telomere Homeostasis ; },
}
@article {pmid34146858,
year = {2021},
author = {Akcha, F and Cahuc, C and Rouxel, J and Munschy, C and Aminot, Y and Chouvelon, T and Mahe, K and Budzinski, H and Mauffret, A},
title = {Development in the European flounder (Platichthys flesus) of a q-PCR assay for the measurement of telomere length, a potential biomarker of pollutant effects for biomonitoring studies.},
journal = {Marine pollution bulletin},
volume = {170},
number = {},
pages = {112610},
doi = {10.1016/j.marpolbul.2021.112610},
pmid = {34146858},
issn = {1879-3363},
mesh = {Animals ; Biological Monitoring ; Biomarkers ; Child, Preschool ; Environmental Monitoring ; *Environmental Pollutants ; *Flounder/genetics ; Humans ; Liver/chemistry ; Polymerase Chain Reaction ; Telomere/chemistry ; *Water Pollutants, Chemical/analysis/toxicity ; },
abstract = {Telomeres protect the coding sequence of chromosome ends and Telomere Length (TL) has been proposed as a biomarker of cellular aging, cumulative stress exposure and life-span in humans. With the aim to propose new biomarkers, a q-PCR protocol was adapted for the measurement of TL in the European flounder Platichthys flesus. The protocol was then applied in 2-year-old flounders from the Seine Estuary. The absolute TL in the flounder is 54 ± 13 kbp per genome (mean ± standard error). Considering relative or absolute TL, no correlation was observed with DNA damage and any of the measured contaminant concentrations (trace elements, metabolites of polycyclic aromatic hydrocarbons, polychlorobiphenyls, organochlorinated pesticides, polybrominated diphenyl ethers, perfluoroalkyl substances). Because sampling was limited, further investigations are required to state a possible impact of chemical pollution on flatfish telomeres. This is motivated by correlations observed with organochlorinated compounds when decreasing statistical significance (p ≤ 0.10).},
}
@article {pmid34145295,
year = {2021},
author = {Silva, B and Arora, R and Bione, S and Azzalin, CM},
title = {TERRA transcription destabilizes telomere integrity to initiate break-induced replication in human ALT cells.},
journal = {Nature communications},
volume = {12},
number = {1},
pages = {3760},
pmid = {34145295},
issn = {2041-1723},
mesh = {Cell Line, Tumor ; Chromosome Breakage ; DNA Damage/genetics ; DNA Replication/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Neoplasms/genetics ; RNA, Long Noncoding/*genetics ; Telomere/*genetics ; Telomere Homeostasis/*genetics ; Transcription, Genetic/*genetics ; },
abstract = {Alternative Lengthening of Telomeres (ALT) is a Break-Induced Replication (BIR)-based mechanism elongating telomeres in a subset of human cancer cells. While the notion that spontaneous DNA damage at telomeres is required to initiate ALT, the molecular triggers of this physiological telomere instability are largely unknown. We previously proposed that the telomeric long noncoding RNA TERRA may represent one such trigger; however, given the lack of tools to suppress TERRA transcription in cells, our hypothesis remained speculative. We have developed Transcription Activator-Like Effectors able to rapidly inhibit TERRA transcription from multiple chromosome ends in an ALT cell line. TERRA transcription inhibition decreases marks of DNA replication stress and DNA damage at telomeres and impairs ALT activity and telomere length maintenance. We conclude that TERRA transcription actively destabilizes telomere integrity in ALT cells, thereby triggering BIR and promoting telomere elongation. Our data point to TERRA transcription manipulation as a potentially useful target for therapy.},
}
@article {pmid34142138,
year = {2021},
author = {Noguera, JC and Velando, A},
title = {Telomerase activity can mediate the effects of growth on telomeres during post-natal development in a wild bird.},
journal = {The Journal of experimental biology},
volume = {224},
number = {12},
pages = {},
doi = {10.1242/jeb.242465},
pmid = {34142138},
issn = {1477-9145},
mesh = {Animals ; Animals, Wild ; Charadriiformes/*growth &amp; development ; *Telomerase/genetics ; *Telomere/genetics ; Telomere Shortening ; },
abstract = {In wild animals, telomere attrition during early development has been linked with several fitness disadvantages throughout life. Telomerase enzyme can elongate telomeres, but it is generally assumed that its activity is suppressed in most somatic tissues upon birth. However, recent evidence suggests that this may not be the case for long-lived bird species. We have therefore investigated whether telomerase activity is maintained during the postnatal growth period in a wild yellow-legged gull (Larus michahellis) population. Our results indicate that telomerase activity is not negligible in the blood cells, but activity levels sharply decline from hatching to fledging following a similar pattern to the reduction observed in telomere length. Our results further suggest that the observed variation in telomere length may be the result of a negative effect of fast growth on telomerase activity, thus providing a new mechanism through which growth rates may affect telomere dynamics and potentially life-history trajectories.},
}
@article {pmid34141465,
year = {2021},
author = {Delgado, M and Buffington, CAT and Bain, M and Smith, DL and Vernau, K},
title = {Early maternal separation is not associated with changes in telomere length in domestic kittens (Felis catus).},
journal = {PeerJ},
volume = {9},
number = {},
pages = {e11394},
pmid = {34141465},
issn = {2167-8359},
abstract = {OBJECTIVE: Studies of multiple species have found that adverse early life experiences, including childhood trauma and maternal separation, can result in accelerated telomere shortening. The objective of this study was to determine if premature separation from the mother affected telomere length in domestic kittens (Felis catus). Subjects were 42 orphaned kittens and 10 mother-reared kittens from local animal rescue groups and shelters. DNA was extracted from whole blood collected from kittens at approximately 1 week and 2 months of age. Telomere length was assessed by qPCR (quantitative polymerase chain reaction) from a total of 86 samples and expressed as a ratio of telomere PCR relative to a single copy gene PCR (T/S).<br><br>RESULTS: A generalized linear mixed model found there were no detectable differences in telomere length based on survival (F 1, 76.2 = 3.35, p = 0.07), orphan status (F 1, 56.5 = 0.44, p = 0.51), time point (F 1, 43.5 = 0.19, p = 0.67), or the interaction between orphan status and time (F 1, 43.5 = 0.86, p = 0.36). Although in other species telomere shortening is commonly associated with aging, even early in life, we did not find evidence for telomere shortening by two months of age. Our results suggest that the experience of early maternal separation in domestic cats who are subsequently hand-reared by humans does not accelerate telomere shortening compared to mother-reared kittens, at least in the first few months of life.},
}
@article {pmid34140564,
year = {2021},
author = {Peska, V and Fajkus, P and Bubeník, M and Brázda, V and Bohálová, N and Dvořáček, V and Fajkus, J and Garcia, S},
title = {Extraordinary diversity of telomeres, telomerase RNAs and their template regions in Saccharomycetaceae.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {12784},
pmid = {34140564},
issn = {2045-2322},
mesh = {Base Sequence ; Benzothiazoles/metabolism ; Fluorescence ; G-Quadruplexes ; *Genetic Variation ; RNA/*genetics ; Reproducibility of Results ; Saccharomycetales/*genetics ; Telomerase/*genetics ; Telomere/*genetics ; *Templates, Genetic ; },
abstract = {Telomerase RNA (TR) carries the template for synthesis of telomere DNA and provides a scaffold for telomerase assembly. Fungal TRs are long and have been compared to higher eukaryotes, where they show considerable diversity within phylogenetically close groups. TRs of several Saccharomycetaceae were recently identified, however, many of these remained uncharacterised in the template region. Here we show that this is mainly due to high variability in telomere sequence. We predicted the telomere sequences using Tandem Repeats Finder and then we identified corresponding putative template regions in TR candidates. Remarkably long telomere units and the corresponding putative TRs were found in Tetrapisispora species. Notably, variable lengths of the annealing sequence of the template region (1-10 nt) were found. Consequently, species with the same telomere sequence may not harbour identical TR templates. Thus, TR sequence alone can be used to predict a template region and telomere sequence, but not to determine these exactly. A conserved feature of telomere sequences, tracts of adjacent Gs, led us to test the propensity of individual telomere sequences to form G4. The results show highly diverse values of G4-propensity, indicating the lack of ubiquitous conservation of this feature across Saccharomycetaceae.},
}
@article {pmid34136834,
year = {2021},
author = {Idilli, AI and Segura-Bayona, S and Lippert, TP and Boulton, SJ},
title = {A C-circle assay for detection of alternative lengthening of telomere activity in FFPE tissue.},
journal = {STAR protocols},
volume = {2},
number = {2},
pages = {100569},
pmid = {34136834},
issn = {2666-1667},
support = {FC0010048/CRUK_/Cancer Research UK/United Kingdom ; FC0010048/MRC_/Medical Research Council/United Kingdom ; FC0010048/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Humans ; In Situ Hybridization, Fluorescence/methods ; *Telomere ; *Telomere Homeostasis ; },
abstract = {Alternative lengthening of telomeres (ALT) is a telomerase-independent, recombination-based telomere maintenance mechanism that allows cancer cells to acquire unlimited proliferative capacity. The C-circle assay (CCA) has emerged as the gold standard for quantitative measurement of ALT activity. Here, we present a modified CCA protocol to examine ALT activity in formalin-fixed paraffin-embedded specimens. We optimized several aspects of the procedure including genomic DNA isolation and hybridization steps, which allows for sensitive and robust quantitation of ALT activity in patient biopsies. For complete details on the use and execution of this protocol, please refer to Lippert et al. (2021).},
}
@article {pmid34133663,
year = {2021},
author = {Santos, GAD and Reis, ST and Leite, KRM and Srougi, M},
title = {Telomere Attrition and p53 Response 1 (TAPR1): a new player in cancer biology?.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {76},
number = {},
pages = {e2997},
pmid = {34133663},
issn = {1980-5322},
mesh = {Humans ; *Neoplasms/genetics ; Proteins/*genetics ; },
}
@article {pmid34125900,
year = {2021},
author = {Pobiega, S and Alibert, O and Marcand, S},
title = {A new assay capturing chromosome fusions shows a protection trade-off at telomeres and NHEJ vulnerability to low-density ionizing radiation.},
journal = {Nucleic acids research},
volume = {49},
number = {12},
pages = {6817-6831},
pmid = {34125900},
issn = {1362-4962},
mesh = {Centromere ; *Chromosome Aberrations ; DNA End-Joining Repair/*radiation effects ; Genetic Techniques ; Radiation, Ionizing ; Saccharomyces cerevisiae/genetics ; *Telomere/metabolism ; Telomere Homeostasis ; },
abstract = {Chromosome fusions threaten genome integrity and promote cancer by engaging catastrophic mutational processes, namely chromosome breakage-fusion-bridge cycles and chromothripsis. Chromosome fusions are frequent in cells incurring telomere dysfunctions or those exposed to DNA breakage. Their occurrence and therefore their contribution to genome instability in unchallenged cells is unknown. To address this issue, we constructed a genetic assay able to capture and quantify rare chromosome fusions in budding yeast. This chromosome fusion capture (CFC) assay relies on the controlled inactivation of one centromere to rescue unstable dicentric chromosome fusions. It is sensitive enough to quantify the basal rate of end-to-end chromosome fusions occurring in wild-type cells. These fusions depend on canonical nonhomologous end joining (NHEJ). Our results show that chromosome end protection results from a trade-off at telomeres between positive effectors (Rif2, Sir4, telomerase) and a negative effector partially antagonizing them (Rif1). The CFC assay also captures NHEJ-dependent chromosome fusions induced by ionizing radiation. It provides evidence for chromosomal rearrangements stemming from a single photon-matter interaction.},
}
@article {pmid34119568,
year = {2023},
author = {Xu, Y and Xie, CB and Yang, J and Xing, YJ and Xia, WP and Liu, Y and Xi, WB and Li, ZJ and Tu, WF and Zhang, JL},
title = {Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study.},
journal = {Brazilian journal of anesthesiology (Elsevier)},
volume = {73},
number = {6},
pages = {764-768},
pmid = {34119568},
issn = {2352-2291},
mesh = {Humans ; Aged ; *Propofol/pharmacology ; Anesthetics, Intravenous/pharmacology ; Anesthesia, General ; DNA ; Leukocytes ; Body Weight ; Telomere ; Electroencephalography ; },
abstract = {INTRODUCTION: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly.<br><br>METHODS: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery.<br><br>RESULTS: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found.<br><br>CONCLUSIONS: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.},
}
@article {pmid34117333,
year = {2021},
author = {Bijnens, EM and Derom, C and Thiery, E and Martens, DS and Loos, RJF and Weyers, S and Nawrot, TS},
title = {Serum gamma-glutamyl transferase, a marker of alcohol intake, is associated with telomere length and cardiometabolic risk in young adulthood.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {12407},
pmid = {34117333},
issn = {2045-2322},
mesh = {Adolescent ; Adult ; Alcohol Drinking/*blood ; Female ; Humans ; Male ; Metabolic Syndrome/*epidemiology ; Risk Factors ; *Telomere ; Young Adult ; gamma-Glutamyltransferase/*blood ; },
abstract = {Studies based on self-reported alcohol consumption and telomere length show inconsistent results. Therefore, we studied the association between gamma-glutamyl transferase (GGT), a widely used biomarker of alcohol intake, and telomere length. The possible health relevance in young adulthood was explored by investigating cardiometabolic risk factors. Mixed modelling was performed to examine GGT and alcohol consumption in association with telomere length in buccal cells of 211 adults between 18 and 30 years old of the East Flanders Prospective Twin Survey. In addition, we investigated the association between GGT and cardiometabolic risk factors; waist circumference, systolic blood pressure, fasting glucose, HDL cholesterol, and triglycerides. Although we did not observe an association between self-reported alcohol consumption and telomere length, our results show that a doubling in serum GGT is associated with 7.80% (95% CI - 13.9 to - 1.2%; p = 0.02) shorter buccal telomeres, independently from sex, chronological age, educational level, zygosity and chorionicity, waist-to-hip ratio and smoking. The association between GGT was significant for all five cardiometabolic risk factors, while adjusting for age. We show that GGT, a widely used biomarker of alcohol consumption, is associated with telomere length and with risk factors of cardiometabolic syndrome, despite the young age of this study population.},
}
@article {pmid34114988,
year = {2021},
author = {Wang, S and Gao, Y and Zhao, L and Hu, R and Yang, X and Liu, Y},
title = {Shortened leukocyte telomere length as a potential biomarker for predicting the progression of atrial fibrillation from paroxysm to persistence in the short-term.},
journal = {Medicine},
volume = {100},
number = {23},
pages = {e26020},
pmid = {34114988},
issn = {1536-5964},
support = {81700295//National Natural Science Foundation of China/ ; 81670214//National Natural Science Foundation of China/ ; },
mesh = {*Atrial Fibrillation/diagnosis/epidemiology/genetics ; China/epidemiology ; Cross-Sectional Studies ; *Disease Progression ; Female ; Genetic Markers/physiology ; Humans ; Leukocytes/*physiology ; Male ; Middle Aged ; Risk Factors ; Telomere Homeostasis ; Telomere Shortening/*physiology ; },
abstract = {This study aimed to assess the role of leukocyte telomere length (LTL) in the development of atrial fibrillation (AF) among Chinese patients.This is a cross-sectional study. A total of 350 patients from June 2016 to December 2017 were retrospectively analyzed. These included 219 AF patients and 131 with sinus rhythm in the control group. Quantitative real-time PCR was used to measure relative LTL.The relative LTLs of all subjects (n = 350) ranged from 0.4 to 2.41 (0.98 ± 0.29), showing a significant negative correlation (P < .001) with age. The AF-group had significantly shorter LTLs (0.93 ± 0.26 vs 1.07 ± 0.33, P < .001) and were older (61.50 ± 6.49 vs 59.95 ± 6.17, P = .028) than controls. LTLs among patients with persistent AF (PsAF), paroxysmal AF (PAF), and controls were significantly different (P < .001), with LTLs of PsAF patients being the shortest and controls being the longest. After adjusting for possible confounding factors, the PsAF group still showed significantly shorter LTLs than the PAF and control groups (P = .013 and P = .001, respectively). After an 18-month follow-up, 20 out of 119 PAF patients had progressed into PsAF and a relative LTL of ≤0.73 was an independent predictor for progression of PAF into PsAF.LTL was found to be shorter in patients with AF than in age-matched individuals with sinus rhythm and positively correlated with severity of AF. LTL shortening could be an independent risk factor for progression from paroxysmal AF to persistent AF in the short term.},
}
@article {pmid34113796,
year = {2021},
author = {AlDehaini, DMB and Al-Bustan, SA and Malalla, ZHA and Ali, ME and Sater, M and Giha, HA},
title = {Analogous telomeres shortening and different metabolic profile: hypertension versus hypertension/type 2 diabetes mellitus comorbidity.},
journal = {Cardiovascular endocrinology &amp; metabolism},
volume = {10},
number = {2},
pages = {106-112},
pmid = {34113796},
issn = {2574-0954},
abstract = {BACKGROUND: Eukaryotes chromosomal ends are capped and protected by telomeres, which are noncoding DNA repeats synthesized by telomerase enzyme. The telomerase enzyme is a nucleoprotein encoded by TERC and TERT genes. Naturally, the length of the telomeres shortens with each cell cycle but the shortening is fastened in certain age-related diseases like hypertension (HTN) and type 2 diabetes mellitus (T2DM).<br><br>MATERIALS AND METHODS: Blood samples (n&#x2009;=&#x2009;171) were obtained from Kuwaiti subjects with HTN, and HTN/T2DM comorbidity (HTN-DM) and healthy subjects. The leukocyte telomere length (LTL) was measured by SYBR green quantitative rtPCR, and plasma telomerase enzyme was measured by ELISA, in addition, three single nucleotide polymorphisms (SNPs) in telomere-related genes; TERC rs12696304GC, TERT rs2736100CA, and ACYP2 rs6713088GC were genotyped by real-time PCR.<br><br>RESULTS: Marked LTL shortening in subjects with HTN and HTN-DM compared to healthy subjects, P&#x2009;=&#x2009;0.043 and P&#x2009;<&#x2009;0.001, respectively, was noticed. On the contrary, the plasma telomerase enzyme levels and minor allele frequencies and genotypes of the tested SNPs were comparable between the study groups, except for TERT (CA) genotype which was over-represented in HTN (P&#x2009;=&#x2009;0.037). Furthermore, the comparisons between HTN and HTN-DM revealed significantly higher total cholesterol (P&#x2009;=&#x2009;0.015) and LDL-C (P&#x2009;=&#x2009;0.008) in HTN, while higher insulin levels (P&#x2009;<&#x2009;001), HOMA-IR (P&#x2009;<&#x2009;001), and BMI (P&#x2009;=&#x2009;0.004) were observed in HTN-DM.<br><br>CONCLUSION: This study showed comparable LTL shortening in HTN and HTN-DM, irrespective of plasma telomerase enzyme levels or tested TERC, TERT, and ACYP2 gene polymorphisms, although HTN and HTN-DM differed in several metabolic markers. More studies are required to affirm these observations.},
}
@article {pmid34103668,
year = {2021},
author = {Brosnan-Cashman, JA and Davis, CM and Diplas, BH and Meeker, AK and Rodriguez, FJ and Heaphy, CM},
title = {SMARCAL1 loss and alternative lengthening of telomeres (ALT) are enriched in giant cell glioblastoma.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {34},
number = {10},
pages = {1810-1819},
pmid = {34103668},
issn = {1530-0285},
support = {T32 CA009110/CA/NCI NIH HHS/United States ; P30 CA006973/CA/NCI NIH HHS/United States ; },
mesh = {Adolescent ; Adult ; Aged ; Biopsy ; Brain Neoplasms/genetics/*metabolism/pathology ; Child, Preschool ; DNA Helicases/genetics/*metabolism ; Female ; Glioblastoma/genetics/*metabolism/pathology ; Humans ; Isocitrate Dehydrogenase/genetics/metabolism ; Male ; Middle Aged ; Mutation ; Telomere Homeostasis/*genetics ; X-linked Nuclear Protein/genetics/metabolism ; Young Adult ; },
abstract = {Subsets of high-grade gliomas, including glioblastoma (GBM), are known to utilize the alternative lengthening of telomeres (ALT) pathway for telomere length maintenance. However, the telomere maintenance profile of one subtype of GBM-giant cell GBM-has not been extensively studied. Here, we investigated the prevalence of ALT, as well as ATRX and SMARCAL1 protein loss, in a cohort of classic giant cell GBM and GBM with giant cell features. To determine the presence of ALT, a telomere-specific fluorescence in situ hybridization assay was performed on 15 cases of classic giant cell GBM, 28 additional GBMs found to have giant cell features, and 1 anaplastic astrocytoma with giant cell features. ATRX, SMARCAL1, and IDH1 protein status were assessed in a proportion of cases by immunohistochemistry and were compared to clinical-pathologic and molecular characteristics. In the overall cohort of 44 cases, 19 (43%) showed evidence of ALT. Intriguingly, of the ALT-positive cases, only 9 (47.4%) displayed loss of the ALT suppressor ATRX by immunohistochemistry. Since inactivating mutations in SMARCAL1 have been identified in ATRX wild-type ALT-positive gliomas, we developed an immunohistochemistry assay for SMARCAL1 protein expression using genetically validated controls. Of the 19 ALT-positive cases, 6 (31.5%) showed loss or mis-localization of SMARCAL1 by immunohistochemistry. Of these cases, four retained ATRX protein expression, while two cases also displayed ATRX loss. Additionally, we assessed five cases from which multiple temporal samples were available and ALT status was concordant between both tumor biopsies. In summary, we have identified a subset of giant cell GBM that utilize the ALT telomere maintenance mechanism. Importantly, in addition to ATRX loss, ALT-positive tumors harboring SMARCAL1 alterations are prevalent in giant cell GBM.},
}
@article {pmid34101921,
year = {2022},
author = {Bae, J and Bertucci, EM and Bock, SL and Hale, MD and Moore, J and Wilkinson, PM and Rainwater, TR and Bowden, JA and Koal, T and PhamTuan, H and Parrott, BB},
title = {Intrinsic and extrinsic factors interact during development to influence telomere length in a long-lived reptile.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {6114-6127},
doi = {10.1111/mec.16017},
pmid = {34101921},
issn = {1365-294X},
mesh = {Animals ; *Glucocorticoids ; *Alligators and Crocodiles ; Aging ; Telomere/genetics ; },
abstract = {The mechanisms connecting environmental conditions to plasticity in biological aging trajectories are fundamental to understanding individual variation in functional traits and life history. Recent findings suggest that telomere biology is especially dynamic during early life stages and has long-term consequences for subsequent reproduction and survival. However, our current understanding is mostly derived from studies investigating ecological and anthropogenic factors separately, leaving the effects of complex environmental interactions unresolved. American alligators (Alligator mississippiensis) are long-lived apex predators that rely on incubation temperature during a discrete period during development and endocrine cues to determine sex, making them especially vulnerable to current climatic variability and exposure to anthropogenic contaminants interfering with hormone function. Here, we combine field studies with a factorial design to understand how the developmental environment, along with intrinsic biological variation contribute to persistent telomere variation. We found that exposure to a common endocrine disrupting contaminant, DDE, affects telomere length, but that the directionality is highly dependent upon incubation temperature. Variation in hatchling growth, underlies a strong clutch effect. We also assess concentrations of a panel of glucocorticoid hormones and find that contaminant exposure elicits an increase in circulating glucocorticoids. Consistent with emerging evidence linking stress and aging trajectories, GC levels also appear to trend with shorter telomere length. Thus, we add support for a mechanistic link between contaminants and glucocorticoid signalling, which interacts with ecological aspects of the developmental environment to alter telomere dynamics.},
}
@article {pmid34101279,
year = {2022},
author = {van Lieshout, SHJ and Badás, EP and Bright Ross, JG and Bretman, A and Newman, C and Buesching, CD and Burke, T and Macdonald, DW and Dugdale, HL},
title = {Early-life seasonal, weather and social effects on telomere length in a wild mammal.},
journal = {Molecular ecology},
volume = {31},
number = {23},
pages = {5993-6007},
doi = {10.1111/mec.16014},
pmid = {34101279},
issn = {1365-294X},
mesh = {Animals ; Seasons ; *Weather ; Longevity/genetics ; Telomere Shortening/genetics ; *Mustelidae/genetics ; Telomere/genetics ; },
abstract = {Early-life environmental conditions can provide a source of individual variation in life-history strategies and senescence patterns. Conditions experienced in early life can be quantified by measuring telomere length, which can act as a biomarker of survival probability in some species. Here, we investigate whether seasonal changes, weather conditions and group size are associated with early-life and/or early-adulthood telomere length in a wild population of European badgers (Meles meles). We found substantial intra-annual changes in telomere length during the first 3 years of life, where within-individual effects showed shorter telomere lengths in the winter following the first spring and a trend for longer telomere lengths in the second spring compared to the first winter. In terms of weather conditions, cubs born in warmer, wetter springs with low rainfall variability had longer early-life (3-12 months old) telomeres. Additionally, cubs born in groups with more cubs had marginally longer early-life telomeres, providing no evidence of resource constraint from cub competition. We also found that the positive association between early-life telomere length and cub survival probability remained when social and weather variables were included. Finally, after sexual maturity, in early adulthood (i.e., 12-36 months) we found no significant association between same-sex adult group size and telomere length (i.e., no effect of intrasexual competition). Overall, we show that controlling for seasonal effects, which are linked to food availability, is important in telomere length analyses, and that variation in telomere length in badgers reflects early-life conditions and also predicts first year cub survival.},
}
@article {pmid34101251,
year = {2021},
author = {Lin, L and Qin, K and Chen, D and Lu, C and Chen, W and Guo, VY},
title = {Systematic review and meta-analysis of the association between paediatric obesity and telomere length.},
journal = {Acta paediatrica (Oslo, Norway : 1992)},
volume = {110},
number = {10},
pages = {2695-2703},
doi = {10.1111/apa.15971},
pmid = {34101251},
issn = {1651-2227},
support = {51000-18841211//The Start-up Fund from Sun Yat-sen University/ ; 2021qntd42//The Fundamental Research Funds for the Central Universities/ ; },
mesh = {Child ; Female ; Humans ; Male ; Overweight/genetics ; *Pediatric Obesity/genetics ; Research Design ; Telomere/genetics ; Telomere Shortening ; },
abstract = {AIM: This systematic review and meta-analysis aimed to assess the association between paediatric obesity and telomere length.<br><br>METHODS: We conducted a comprehensive literature search for original studies assessing the associations between obesity and telomere length in children. Fixed or random effects with inverse-variance meta-analysis were used to estimate the standardised mean difference (SMD) and its 95% confidence interval (95% CI) between overweight or obese and normal-weight children. Heterogeneity was assessed using the I[2] statistic, and meta-regression analyses were used to evaluate the potential source of heterogeneity. Subgroup analysis was further conducted by sex.<br><br>RESULTS: A total of 11 studies were included. The meta-analysis showed that children who were overweight or obese had shorter telomere length than normal-weight children (SMD: -0.85; 95% CI: -1.42 to -0.28; p&#xa0;<&#xa0;0.01). However, significant heterogeneity was present (I[2] &#xa0;=&#xa0;97%; p&#xa0;<&#xa0;0.01). Study design, methods used for measuring telomere length, tissue types, mean age, and percentage of boys were not the source of heterogeneity revealed by meta-regression analysis. The inverse trend was significant only in boys, but not in girls.<br><br>CONCLUSION: There was a negative association between paediatric obesity and telomere length. Weight control in children might have beneficial effect on telomere length.},
}
@article {pmid34091434,
year = {2021},
author = {Tian, XP and Qian, D and He, LR and Huang, H and Mai, SJ and Li, CP and Huang, XX and Cai, MY and Liao, YJ and Kung, HF and Zeng, YX and Xie, D},
title = {Corrigendum to ‟The telomere/telomerase binding factor PinX1 regulates paclitaxel sensitivity depending on spindle assembly checkpoint in human cervical squamous cell carcinomas" [Canc. Lett. 353 (2014) 104-114].},
journal = {Cancer letters},
volume = {516},
number = {},
pages = {61-63},
doi = {10.1016/j.canlet.2021.05.023},
pmid = {34091434},
issn = {1872-7980},
}
@article {pmid34086604,
year = {2021},
author = {Wang, C and Nawrot, TS and Van Der Stukken, C and Tylus, D and Sleurs, H and Peusens, M and Alfano, R and Langie, SAS and Plusquin, M and Martens, DS},
title = {Different epigenetic signatures of newborn telomere length and telomere attrition rate in early life.},
journal = {Aging},
volume = {13},
number = {11},
pages = {14630-14650},
pmid = {34086604},
issn = {1945-4589},
mesh = {Child, Preschool ; CpG Islands/genetics ; DNA Methylation/genetics ; *Epigenesis, Genetic ; Female ; *Gene Expression Profiling ; Genome-Wide Association Study ; Humans ; Infant, Newborn ; Male ; Models, Genetic ; Telomere Homeostasis/*genetics ; Telomere Shortening/*genetics ; },
abstract = {Telomere length (TL) and telomere shortening are biological indicators of aging, and epigenetic associates have been found for TL in adults. However, the role of epigenetic signatures in setting newborn TL and early life telomere dynamics is unknown. In the present study, based on 247 participating newborns from the ENVIRONAGE birth cohort, whole-genome DNA methylation, profiled on the Illumina MethylationEPIC BeadChip microarray, and TL were measured in cord blood. In a follow-up visit at a mean age of 4.58 years, leukocyte TL was evaluated. We combined an epigenome-wide association study and a statistical learning method with re-sampling to select CpGs and their two-way interactions to model baseline (cord blood) TL and early-life telomere attrition rate, where distinct epigenetic signatures were identified for the two outcomes. In addition, a stronger epigenetic regulation was suggested in setting newborn TL than that of telomere dynamics in early life: 47 CpGs and 7 between-CpG interactions explained 76% of the variance in baseline TLs, while 72% of the total variance in telomere attrition rate was explained by 31 CpGs and 5 interactions. Functional enrichment analysis based on the selected CpGs in the two models revealed GLUT4 translocation and immune cell signaling pathways, respectively. These CpGs and interactions, as well as the cellular pathways, are potential novel targets of further investigation of telomere biology and aging.},
}
@article {pmid34084786,
year = {2021},
author = {van Batenburg, AA and Kazemier, KM and van Oosterhout, MFM and van der Vis, JJ and Grutters, JC and Goldschmeding, R and van Moorsel, CHM},
title = {Telomere shortening and DNA damage in culprit cells of different types of progressive fibrosing interstitial lung disease.},
journal = {ERJ open research},
volume = {7},
number = {2},
pages = {},
pmid = {34084786},
issn = {2312-0541},
abstract = {Pulmonary fibrosis is strongly associated with telomere shortening and increased DNA damage. Key cells in the pathogenesis involve alveolar type 2 (AT2) cells, club cells and myofibroblasts; however, to what extent these cells are affected by telomere shortening and DNA damage is not yet known. We sought to determine the degree of, and correlation between, telomere shortening and DNA damage in different cell types involved in the pathogenesis of progressive fibrosing interstitial lung disease. Telomere length and DNA damage were quantified, using combined fluorescence in situ hybridisation and immunofluorescence staining techniques, in AT2 cells, club cells and myofibroblasts of controls and patients with pulmonary fibrosis and a telomerase reverse transcriptase mutation (TERT-PF), idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP). In IPF and TERT-PF lungs, AT2 cells contained shorter telomeres and expressed higher DNA damage signals than club cells and myofibroblasts. In fHP lungs, club cells contained highly elevated levels of DNA damage, while telomeres were not obviously short. In vitro, we found significantly shorter telomeres and higher DNA damage levels only in AT2 surrogate cell lines treated with telomerase inhibitor BIBR1532. Our study demonstrated that in IPF and TERT-PF lungs, telomere shortening and accumulation of DNA damage primarily affects AT2 cells, further supporting the importance of AT2 cells in these diseases, while in fHP the particularly high telomere-independent DNA damage signals in club cells underscores its bronchiolocentric pathogenesis. These findings suggest that cell type-specific telomere shortening and DNA damage may help to discriminate between different drivers of fibrogenesis.},
}
@article {pmid34083495,
year = {2021},
author = {Pearce, EE and Horvath, S and Katta, S and Dagnall, C and Aubert, G and Hicks, BD and Spellman, SR and Katki, H and Savage, SA and Alsaggaf, R and Gadalla, SM},
title = {DNA-methylation-based telomere length estimator: comparisons with measurements from flow FISH and qPCR.},
journal = {Aging},
volume = {13},
number = {11},
pages = {14675-14686},
pmid = {34083495},
issn = {1945-4589},
support = {U01 AG060908/AG/NIA NIH HHS/United States ; U24 CA076518/CA/NCI NIH HHS/United States ; },
mesh = {Adult ; DNA Methylation/*genetics ; Female ; Humans ; *In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; *Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; Telomere Homeostasis/*genetics ; Young Adult ; },
abstract = {Telomere length (TL) is a marker of biological aging associated with several health outcomes. High throughput reproducible TL measurements are needed for large epidemiological studies. We compared the novel DNA methylation-based estimator (DNAmTL) with the high-throughput quantitative PCR (qPCR) and the highly accurate flow cytometry with fluorescent in situ hybridization (flow FISH) methods using blood samples from healthy adults. We used Pearson's correlation coefficient, Bland Altman plots and linear regression models for statistical analysis. Shorter DNAmTL was associated with older age, male sex, white race, and cytomegalovirus seropositivity (p<0.01 for all). DNAmTL was moderately correlated with qPCR TL (N=635, r=0.41, p < 0.0001) and flow FISH total lymphocyte TL (N=144, r=0.56, p < 0.0001). The agreements between flow FISH TL and DNAmTL or qPCR were acceptable but with wide limits of agreement. DNAmTL correctly classified >70% of TL categorized above or below the median, but the accuracy dropped with increasing TL categories. The ability of DNAmTL to detect associations with age and other TL-related factors in the absence of strong correlation with measured TL may indicate its capture of aspects of telomere maintenance mechanisms and not necessarily TL. The inaccuracy of DNAmTL prediction should be considered during data interpretation and across-study comparisons.},
}
@article {pmid34072630,
year = {2021},
author = {Steele, SL and Hsieh, AYY and Gadawski, I and Kroeun, H and Barr, SI and Devlin, AM and Côté, HCF and Karakochuk, CD},
title = {Daily Oral Supplementation with 60 mg of Elemental Iron for 12 Weeks Alters Blood Mitochondrial DNA Content, but Not Leukocyte Telomere Length in Cambodian Women.},
journal = {Nutrients},
volume = {13},
number = {6},
pages = {},
pmid = {34072630},
issn = {2072-6643},
support = {N/A//International Life Sciences Institute/ ; N/A/CAPMC/CIHR/Canada ; N/A//Micronutrient Initiative/ ; N/A//Sight and Life Foundation/ ; Scholar Award//Michael Smith Foundation for Health Research/ ; },
mesh = {Adult ; Antioxidants/administration &amp; dosage/pharmacology ; Cambodia ; *DNA, Mitochondrial/blood/drug effects ; *Dietary Supplements ; Female ; Humans ; *Iron/administration &amp; dosage/pharmacology ; Leukocytes/*drug effects ; Oxidative Stress/drug effects ; Telomere/*drug effects ; Young Adult ; },
abstract = {There is limited evidence regarding the potential risk of untargeted iron supplementation, especially among individuals who are iron-replete or have genetic hemoglobinopathies. Excess iron exposure can increase the production of reactive oxygen species, which can lead to cellular damage. We evaluated the effect of daily oral supplementation on relative leukocyte telomere length (rLTL) and blood mitochondrial DNA (mtDNA) content in non-pregnant Cambodian women (18-45 years) who received 60 mg of elemental iron as ferrous sulfate (n = 190) or a placebo (n = 186) for 12 weeks. Buffy coat rLTL and mtDNA content were quantified by monochrome multiplex quantitative polymerase chain reaction. Generalized linear mixed-effects models were used to predict the absolute and percent change in rLTL and mtDNA content after 12 weeks. Iron supplementation was not associated with an absolute or percent change in rLTL after 12 weeks compared with placebo (ß-coefficient: -0.04 [95% CI: -0.16, 0.08]; p = 0.50 and ß-coefficient: -0.96 [95% CI: -2.69, 0.77]; p = 0.28, respectively). However, iron supplementation was associated with a smaller absolute and percent increase in mtDNA content after 12 weeks compared with placebo (ß-coefficient: -11 [95% CI: -20, -2]; p = 0.02 and ß-coefficient: -11 [95% CI: -20, -1]; p= 0.02, respectively). Thus, daily oral iron supplementation for 12 weeks was associated with altered mitochondrial homeostasis in our study sample. More research is needed to understand the risk of iron exposure and the biological consequences of altered mitochondrial homeostasis in order to inform the safety of the current global supplementation policy.},
}
@article {pmid34071160,
year = {2021},
author = {Glover, LM and Cené, CW and Reiner, A and Gebreab, S and Williams, DR and North, KE and Sims, M},
title = {Discrimination and Leukocyte Telomere Length by Depressive Symptomatology: The Jackson Heart Study.},
journal = {Healthcare (Basel, Switzerland)},
volume = {9},
number = {6},
pages = {},
pmid = {34071160},
issn = {2227-9032},
support = {HHSN268201800012C/HL/NHLBI NIH HHS/United States ; HHSN268201800014C/HL/NHLBI NIH HHS/United States ; T32 HL129982/HL/NHLBI NIH HHS/United States ; HHSN268201800013I/MD/NIMHD NIH HHS/United States ; HHSN268201800011C/HL/NHLBI NIH HHS/United States ; HHSN268201800015I/HB/NHLBI NIH HHS/United States ; },
abstract = {BACKGROUND: Psychosocial stressors, such as perceived discrimination and depressive symptoms, may shorten telomeres and exacerbate aging-related illnesses.<br><br>METHODS: Participants from the Jackson Heart Study at visit 1 (2000-2004) with LTL data and Center for Epidemiological Studies-Depression (CES-D) scores (n = 580 men, n = 910 women) were utilized. The dimensions of discrimination scores (everyday, lifetime, burden of lifetime, and stress from lifetime discrimination) were standardized and categorized as low, moderate, and high. Coping responses to everyday and lifetime discrimination were categorized as passive and active coping. Multivariable linear regression analyses were performed to estimate the mean difference (standard errors-SEs) in LTL by dimensions of discrimination and coping responses stratified by CES-D scores < 16 (low) and &#x2265; 16 (high) and sex. Covariates were age, education, waist circumference, smoking and CVD status.<br><br>RESULTS: Neither everyday nor lifetime discrimination was associated with mean differences in LTL for men or women by levels of depressive symptoms. Burden of lifetime discrimination was marginally associated with LTL among women who reported low depressive symptoms after full adjustment (b = 0.11, SE = 0.06, p = 0.08). Passive coping with lifetime discrimination was associated with longer LTL among men who reported low depressive symptoms after full adjustment (b = 0.18, SE = 0.09, p < 0.05); and active coping with lifetime discrimination was associated with longer LTL among men who reported high depressive symptoms after full adjustment (b = 1.18, SE = 0.35, p < 0.05).<br><br>CONCLUSIONS: The intersection of perceived discrimination and depressive symptomatology may be related to LTL, and the effects may vary by sex.},
}
@article {pmid34070406,
year = {2021},
author = {Pendina, AA and Krapivin, MI and Efimova, OA and Tikhonov, AV and Mekina, ID and Komarova, EM and Koltsova, AS and Gzgzyan, AM and Kogan, IY and Chiryaeva, OG and Baranov, VS},
title = {Telomere Length in Metaphase Chromosomes of Human Triploid Zygotes.},
journal = {International journal of molecular sciences},
volume = {22},
number = {11},
pages = {},
pmid = {34070406},
issn = {1422-0067},
support = {18-75-10046//Russian Science Foundation/ ; },
mesh = {Chromosomes, Human/*metabolism ; Fertilization in Vitro ; Humans ; *Metaphase ; Telomere/*metabolism/pathology ; *Telomere Homeostasis ; *Triploidy ; Zygote/*metabolism/pathology ; },
abstract = {The human lifespan is strongly influenced by telomere length (TL) which is defined in a zygote-when two highly specialised haploid cells form a new diploid organism. Although TL is a variable parameter, it fluctuates in a limited range. We aimed to establish the determining factors of TL in chromosomes of maternal and paternal origin in human triploid zygotes. Using Q-FISH, we examined TL in the metaphase chromosomes of 28 human triploid zygotes obtained from 22 couples. The chromosomes' parental origin was identified immunocytochemically through weak DNA methylation and strong hydroxymethylation in the sperm-derived (paternal) chromosomes versus strong DNA methylation and weak hydroxymethylation in the oocyte-derived (maternal) ones. In 24 zygotes, one maternal and two paternal chromosome sets were identified, while the four remaining zygotes contained one paternal and two maternal sets. For each zygote, we compared mean relative TLs between parental chromosomes, identifying a significant difference in favour of the paternal chromosomes, which attests to a certain "imprinting" of these regions. Mean relative TLs in paternal or maternal chromosomes did not correlate with the respective parent's age. Similarly, no correlation was observed between the mean relative TL and sperm quality parameters: concentration, progressive motility and normal morphology. Based on the comparison of TLs in chromosomes inherited from a single individual's gametes with those in chromosomes inherited from different individuals' gametes, we compared intraindividual (intercellular) and interindividual variability, obtaining significance in favour of the latter and thus validating the role of heredity in determining TL in zygotes. A comparison of the interchromatid TL differences across the chromosomes from sets of different parental origin with those from PHA-stimulated lymphocytes showed an absence of a significant difference between the maternal and paternal sets but a significant excess over the lymphocytes. Therefore, interchromatid TL differences are more pronounced in zygotes than in lymphocytes. To summarise, TL in human zygotes is determined both by heredity and parental origin; the input of other factors is possible within the individual's reaction norm.},
}
@article {pmid34069972,
year = {2021},
author = {Tung, KTS and Wong, RS and Tsang, HW and Chua, GT and Chan, D and Chan, KC and Wong, WHS and Yam, JC and Ho, M and Tham, CC and Wong, ICK and Chan, GCF and Ip, P},
title = {Impact of Snoring on Telomere Shortening in Adolescents with Atopic Diseases.},
journal = {Genes},
volume = {12},
number = {5},
pages = {},
pmid = {34069972},
issn = {2073-4425},
mesh = {Adolescent ; Aging/genetics ; Asthma/genetics ; Female ; Food Hypersensitivity/genetics ; Humans ; Male ; Oxidative Stress/genetics ; Snoring/*genetics ; Telomere Shortening/*genetics ; },
abstract = {Atopic diseases can impose a significant burden on children and adolescents. Telomere length is a cellular marker of aging reflecting the impact of cumulative stress exposure on individual health. Since elevated oxidative stress and inflammation burden induced by chronic atopy and snoring may impact telomere length, this study aimed to investigate whether snoring would moderate the relationship between atopic diseases and telomere length in early adolescence. We surveyed 354 adolescents and their parents. Parents reported the adolescents' history of atopic diseases, recent snoring history as well as other family sociodemographic characteristics. Buccal swab samples were also collected from the adolescents for telomere length determination. Independent and combined effects of atopic diseases and snoring on telomere length were examined. Among the surveyed adolescents, 174 were reported by parents to have atopic diseases (20 had asthma, 145 had allergic rhinitis, 53 had eczema, and 25 had food allergy). Shorter TL was found in participants with a history of snoring and atopic diseases (β = -0.34, p = 0.002) particularly for asthma (β = -0.21, p = 0.007) and allergic rhinitis (β = -0.22, p = 0.023). Our findings suggest that snoring in atopic patients has important implications for accelerated telomere shortening. Proper management of atopic symptoms at an early age is important for the alleviation of long-term health consequences at the cellular level.},
}
@article {pmid34068820,
year = {2021},
author = {Maugeri, A and Barchitta, M and Magnano San Lio, R and La Rosa, MC and La Mastra, C and Favara, G and Ferlito, M and Giunta, G and Panella, M and Cianci, A and Agodi, A},
title = {The Effect of Alcohol on Telomere Length: A Systematic Review of Epidemiological Evidence and a Pilot Study during Pregnancy.},
journal = {International journal of environmental research and public health},
volume = {18},
number = {9},
pages = {},
pmid = {34068820},
issn = {1660-4601},
mesh = {Cohort Studies ; *Ethanol ; Female ; Humans ; Infant, Newborn ; Leukocytes ; Pilot Projects ; Pregnancy ; *Telomere/genetics ; },
abstract = {Several studies-albeit with still inconclusive and limited findings-began to focus on the effect of drinking alcohol on telomere length (TL). Here, we present results from a systematic review of these epidemiological studies to investigate the potential association between alcohol consumption, alcohol-related disorders, and TL. The analysis of fourteen studies-selected from PubMed, Medline, and Web of Science databases-showed that people with alcohol-related disorders exhibited shorter TL, but also that alcohol consumption per se did not appear to affect TL in the absence of alcohol abuse or dependence. Our work also revealed a lack of studies in the periconceptional period, raising the need for evaluating this potential relationship during pregnancy. To fill this gap, we conducted a pilot study using data and samples form the Mamma &amp; Bambino cohort. We compared five non-smoking but drinking women with ten non-smoking and non-drinking women, matched for maternal age, gestational age at recruitment, pregestational body mass index, and fetal sex. Interestingly, we detected a significant difference when analyzing relative TL of leukocyte DNA of cord blood samples from newborns. In particular, newborns from drinking women exhibited shorter relative TL than those born from non-drinking women (p = 0.024). Although these findings appeared promising, further research should be encouraged to test any dose-response relationship, to adjust for the effect of other exposures, and to understand the molecular mechanisms involved.},
}
@article {pmid34054718,
year = {2021},
author = {Velazquez, ME and Millan, AL and Rojo, M and Abruzzese, GA and Cocucci, SE and Iglesias Molli, AE and Frechtel, GD and Motta, AB and Cerrone, GE},
title = {Telomere Length Differently Associated to Obesity and Hyperandrogenism in Women With Polycystic Ovary Syndrome.},
journal = {Frontiers in endocrinology},
volume = {12},
number = {},
pages = {604215},
pmid = {34054718},
issn = {1664-2392},
mesh = {Adult ; Argentina/epidemiology ; Body Mass Index ; Case-Control Studies ; Female ; Humans ; Hyperandrogenism/complications/epidemiology/*genetics ; Obesity/complications/epidemiology/*genetics ; Polycystic Ovary Syndrome/complications/epidemiology/*genetics ; Retrospective Studies ; Telomere/chemistry/*metabolism ; Telomere Homeostasis/physiology ; Testosterone/blood ; },
abstract = {BACKGROUND: Polycystic Ovary Syndrome (PCOS) often present metabolic disorders and hyperandrogenism (HA), facts that may influence the telomere length (TL).<br><br>AIMS: To compare the absolute TL (aTL) between women with PCOS and control women, and their association with the presence of obesity and HA parameters.<br><br>MATERIALS AND METHODS: The PCOS group included 170 unrelated women outpatients and the control group, 64 unrelated donor women. Anthropometric, biochemical-clinical parameters and androgen profile were determined. The PCOS patients were divided accordingly to the presence of obesity and androgenic condition. The aTL was determined from peripheral blood leukocytes by Real Time quantitative PCR.<br><br>RESULTS: Women with PCOS exhibited a significantly longer aTL than controls after age adjustment (p=0.001). A stepwise multivariate linear regression in PCOS women, showed that WC (waist circumference) contributed negatively (b=-0.17) while testosterone levels contributed positively (b=7.24) to aTL. The non-Obese PCOS (noOB-PCOS) presented the longest aTL when compared to controls (p=0.001). Meanwhile, the aTL was significantly higher in the hyperandrogenic PCOS phenotype (HA-PCOS) than in the controls (p=0.001) and non hyperandrogenic PCOS phenotype (NHA-PCOS) (p=0.04). Interestingly, when considering obesity and HA parameters in PCOS, HA exerts the major effect over the aTL as non-obese HA exhibited the lengthiest aTL (23.9 &#xb1; 13.13 Kbp). Conversely, the obese NHA patients showed the shortest aTL (16.5 &#xb1; 10.59 Kbp).<br><br>CONCLUSIONS: Whilst a shorter aTL could be related to the presence of obesity, a longer aTL would be associated with HA phenotype. These findings suggest a balance between the effect produced by the different metabolic and hormonal components, in PCOS women.},
}
@article {pmid34051657,
year = {2021},
author = {Ämmälä, AJ and Suvisaari, J and Kananen, L and Lönnqvist, J and Ripatti, S and Pirkola, S and Paunio, T and Hovatta, I},
title = {Childhood adversities are associated with shorter leukocyte telomere length at adult age in a population-based study.},
journal = {Psychoneuroendocrinology},
volume = {130},
number = {},
pages = {105276},
doi = {10.1016/j.psyneuen.2021.105276},
pmid = {34051657},
issn = {1873-3360},
mesh = {Child ; Humans ; Leukocytes ; *Sleep Wake Disorders ; *Sociodemographic Factors ; Telomere/genetics ; Telomere Shortening ; },