@article {pmid40280966,
year = {2025},
author = {Zhao, D and Zang, Z and Li, H and Li, R and Wang, G and Zhang, K and Diao, T and Fu, Q},
title = {Telomere-related gene risk model predicts prognostic and immune microenvironment alterations in prostate cancer.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {14536},
pmid = {40280966},
issn = {2045-2322},
support = {ZR2021QH366//Natural Science Foundation of Shandong Province/ ; 2021YFC2009300//National Key Research and Development Program of China/ ; 82071635//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Prostatic Neoplasms/genetics/immunology/pathology/mortality ; Male ; *Tumor Microenvironment/immunology/genetics ; Prognosis ; *Telomere/genetics ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; Dendritic Cells/immunology/metabolism ; Biomarkers, Tumor/genetics ; },
abstract = {The improvement of the prediction of prostate cancer (PCa) is a major challenge in disease management. This study analysed a total of 147,856 cells and identified 15 distinct cell types using single-cell RNA-sequencing (scRNA-seq) and bulk RNA-seq data from TCGA and GEO databases. Of these cells, 31,256 exhibited a high telomere-related gene score and were predominantly composed of myeloid dendritic cells (mDCs). Simultaneously, pseudo-temporal analysis indicated that mDCs are in the later stages of the differentiation trajectory, suggesting the significant role of mDCs as telomere-active cells in the development of PCa. Analysis of cell-cell communication revealed significant differences, particularly an increase in communication between mDCs and CTLs, alongside a decrease in communication between mDCs and B cells. These variations may represent critical nodes influencing the development of PCa. Additionally, two hub genes were utilized to create risk models, with ROC curves confirming their predictive efficacy for 3-, 5-, and 10-year survival rates in patients. Functional analysis of these genes was conducted, and NPY siRNA transfection notably inhibited proliferation in LNCaP and DU145 cells. Furthermore, the models demonstrated that high-risk patients had poorer overall survival, greater immune infiltration, and reduced sensitivity to chemotherapeutic drugs.},
}

Humans
*Prostatic Neoplasms/genetics/immunology/pathology/mortality
Male
*Tumor Microenvironment/immunology/genetics
Prognosis
*Telomere/genetics
Gene Expression Regulation, Neoplastic
Cell Line, Tumor
Dendritic Cells/immunology/metabolism
Biomarkers, Tumor/genetics

@article {pmid40278882,
year = {2025},
author = {Zhang, H and Zhou, J and Cao, Y and Zhang, X and Chang, H and Zhao, Y and Bo, Y and Zhang, H and Yu, Z and Zhao, X},
title = {Association between telomere length and psychiatric disorders: a bidirectional Mendelian randomization study.},
journal = {European archives of psychiatry and clinical neuroscience},
volume = {},
number = {},
pages = {},
pmid = {40278882},
issn = {1433-8491},
support = {SBGJ202101020//Tianjian Laboratory of Advanced Biomedical Sciences and Major Project of Medical Science and Technology Jointly Constructed by the Provincial and Ministerial Departments/ ; },
abstract = {Observational studies have suggested that shorter telomere length (TL) may be a risk factor for psychiatric disorders. However, whether this association underlie causal effects remains unknown. This study aims to investigate the potential association between TL and psychiatric disorders by conducting a bidirectional Mendelian randomization (MR) study. Summary statistics for TL were obtained from the UK Biobank (n = 472,174), while summary statistics for ten psychiatric disorders were acquired from the Psychiatric Genomics Consortium (PGC). The inverse-variance weighted (IVW) method was used as primary analysis, with the MR-Egger, weighted median, MR-PRESSO, simple mode, and weighted mode approaches were utilized as sensitivity analyses. Our findings indicated a potential association between genetic predisposition to attention deficit hyperactivity disorder (ADHD) and shortened TL (Beta = - 0.039, SE = 0.011, P = 4.00E-04). Additionally, posttraumatic stress disorder (PTSD) may be was potentially associated with TL (Beta = - 0.014, SE = 0.006, P = 0.019). Our findings suggest a potential correlation between ADHD and TL, yet no significant association exists between TL and other psychiatric disorders. Nevertheless, considering the small effect size and the fact that it might have limited practical clinical significance, TL may not function as a biomarker for psychiatric disorders.},
}

@article {pmid40278194,
year = {2025},
author = {Foffa, I and Esposito, A and Simonini, L and Berti, S and Vecoli, C},
title = {Telomere Length and Clonal Hematopoiesis of Indeterminate Potential: A Loop Between Two Key Players in Aortic Valve Disease?.},
journal = {Journal of cardiovascular development and disease},
volume = {12},
number = {4},
pages = {},
pmid = {40278194},
issn = {2308-3425},
abstract = {Aortic valve stenosis (AVS) is the most common valvular heart disease that was considered, for a long time, a passive degenerative disease due to physiological aging. More recently, it has been recognized as an active, modifiable disease in which many cellular processes are involved. Nevertheless, since aging remains the major risk factor for AVS, a field of research has focused on the role of early (biological) aging and its dependent pathways in the initiation and progression of AVS. Telomeres are regions at the ends of chromosomes that are critical for maintaining genome stability in eukaryotic cells. Telomeres are the hallmarks and molecular drivers of aging and age-related degenerative pathologies. Clonal hematopoiesis of indeterminate potential (CHIP), a condition caused by somatic mutations of leukemia-associated genes in individuals without hematologic abnormalities or clonal disorders, has been reported to be associated with aging. CHIP represents a new and independent risk factor in cardiovascular diseases, including AVS. Interestingly, evidence suggests a causal link between telomere biology and CHIP in several pathological disorders. In this review, we discussed the current knowledge of telomere biology and CHIP as possible mechanisms of aortic valve degeneration. We speculated on how a better understanding of the complex relationship between telomere and CHIP might provide great potential for an early diagnosis and for developing novel medical therapies to reduce the constant increasing health burden of AVS.},
}

@article {pmid40274277,
year = {2025},
author = {Hanley, SM and Schutte, NS and Bellamy, J and Denham, J},
title = {Shorter Telomeres and Faster Telomere Attrition in Individuals With Five Syndromic Forms of Intellectual Disability: A Systematic Review and Meta-Analysis.},
journal = {Journal of intellectual disability research : JIDR},
volume = {},
number = {},
pages = {},
doi = {10.1111/jir.13244},
pmid = {40274277},
issn = {1365-2788},
abstract = {BACKGROUND: People with intellectual disability suffer complex challenges due to adaptive functioning limitations, high rates of chronic diseases and shortened lifespans compared with the general population. Telomere shortening is a hallmark of ageing, and short telomeres are linked to neurological disorders. The main objective of this systematic review and meta-analysis was to identify any differences in telomere length and the rate of telomere attrition in leukocytes and fibroblasts from people with intellectual disability and controls.

METHODS: PubMed, Scopus and ScienceDirect were searched. Articles that compared telomere length in individuals with intellectual disability to apparently healthy age-matched controls were included. Risk of bias was assessed using the AXIS tool and data were analysed using CMA.

RESULTS: Fifteen studies comprised of 17 comparisons provided data and were included in meta-analyses. Compared with healthy controls (N = 481), people with intellectual disability (N = 366) from a known genetic syndrome (Cri du chat, Down, Hoyeraal-Hreidarsson, Williams or Nicolaides-Baraitser) possessed shorter leukocyte telomeres (SMD: -0.853 [95% CI: -1.622 to -0.084], p = 0.03). Similarly, relative to controls (N = 16), people with syndromic intellectual disability (N = 21) possessed shorter fibroblast telomeres (-1.389 [-2.179 to -0.599], p = 0.001). Furthermore, people with syndromic forms of intellectual disability also demonstrated a faster rate (2.09-fold) of telomere shortening.

CONCLUSIONS: Consistent with epidemiological findings on mortality and morbidity risk, people with syndromic intellectual disability appear to undergo a faster rate of biological ageing compared to the general population. These findings emphasise the need for healthy ageing lifestyle (i.e., exercise and stress management) and therapeutic interventions for people with syndromic intellectual disability.},
}

@article {pmid40272729,
year = {2025},
author = {Valeeva, EV and Nikitin, DO and Nikiforova, LS and Semina, II and Ahmetov, II},
title = {Effects of Pharmacological Treatment on Telomere Length and the Expression of Telomerase/Shelterin-Related Genes in Rat Models of Autism.},
journal = {Journal of molecular neuroscience : MN},
volume = {75},
number = {2},
pages = {55},
pmid = {40272729},
issn = {1559-1166},
support = {23-25-00325//Russian Science Foundation/ ; 23-25-00325//Russian Science Foundation/ ; 23-25-00325//Russian Science Foundation/ ; 23-25-00325//Russian Science Foundation/ ; },
mesh = {Animals ; Male ; Rats ; *Telomerase/genetics/metabolism ; Rats, Wistar ; Female ; Valproic Acid/toxicity ; Risperidone/pharmacology/therapeutic use ; *Telomere-Binding Proteins/genetics/metabolism ; Hippocampus/metabolism/drug effects ; *Telomere/metabolism/drug effects ; Shelterin Complex ; Prefrontal Cortex/metabolism/drug effects ; *Telomere Homeostasis/drug effects ; Antipsychotic Agents/pharmacology/therapeutic use ; },
abstract = {Telomeres are increasingly recognized for their potential role in the etiology of autism spectrum disorder (ASD) due to their involvement in cellular aging and telomerase-shelterin function. Although shorter telomeres have been observed in individuals with ASD, studies linking telomere dynamics in blood cells and brain regions remain limited. Using the valproic acid (VPA, 500 mg/kg) rodent model, this study aimed to assess the impact of three drugs commonly used in ASD treatment (amitriptyline, risperidone, and nooclerin) on telomere length and the expression of telomerase/shelterin-related genes (Dkc1, Gar1, Pot1a, Pot1b, Tep1, Terc, Terf2ip, Tert, Tinf2, Tnks, Tpp1, Trf1, and Trf2) in blood cells, the prefrontal cortex, and hippocampus of VPA-exposed Wistar rats. Telomere length and gene expression were measured using quantitative PCR. Risperidone treatment in VPA males resulted in telomere elongation and increased expression of Tnks in blood cell and Trf1, Trf2 genes in prefrontal cortex. Nooclerin treatment also showed beneficial effects on telomere length of blood cell in males, alongside increased Trf1 expression. Long telomeres in male blood cells were associated with reduced anxiety, while a positive correlation was found between Tpp1 expression and stereotypical behavior in both male and female VPA rats. These findings suggest that nooclerin and risperidone influence telomere length and gene expression related to the telomere-telomerase complex in a sex-dependent manner, offering insights into the neurobiological mechanisms underlying ASD.},
}

Animals
Male
Rats
*Telomerase/genetics/metabolism
Rats, Wistar
Female
Valproic Acid/toxicity
Risperidone/pharmacology/therapeutic use
*Telomere-Binding Proteins/genetics/metabolism
Hippocampus/metabolism/drug effects
*Telomere/metabolism/drug effects
Shelterin Complex
Prefrontal Cortex/metabolism/drug effects
*Telomere Homeostasis/drug effects
Antipsychotic Agents/pharmacology/therapeutic use

@article {pmid40269921,
year = {2025},
author = {Jiang, Q and Yu, C and Zhu, S and Liu, Y and Ye, M},
title = {Bidirectional Mendelian randomization reveals associations between telomere length and autoimmune diseases.},
journal = {Trials},
volume = {26},
number = {1},
pages = {137},
pmid = {40269921},
issn = {1745-6215},
mesh = {Humans ; *Mendelian Randomization Analysis ; *Autoimmune Diseases/genetics/diagnosis ; *Telomere/genetics ; Genetic Predisposition to Disease ; *Telomere Homeostasis/genetics ; Risk Factors ; *Telomere Shortening ; },
abstract = {BACKGROUND: Autoimmune diseases are a group of complex chronic illnesses that affect multiple organs or body systems. These diseases are characterized by tissue damage, impaired organ function, and increased risk of malignancies, and elevated mortality. Nevertheless, the casual correlation between autoimmune diseases and telomere length remains uncertain.

OBJECTIVE: Our bidirectional Mendelian randomization analysis was aimed to evaluate the causal association between autoimmune diseases and telomere length.

METHODS: To minimize bias, four demographic factors including body mass index (BMI), alcohol consumption, smoking, and income were assessed using two-sample Mendelian randomization analysis. Furthermore, this analysis was conducted to explore the causal relationships between telomere length and autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D), Graves' disease (GD), and psoriasis using two separate datasets from FinnGen and the UK Biobank.

RESULTS: When using inverse variance weighting (IVW) to assess the relationship between four available demographic factors and overall autoimmune diseases, no significant association was found (p > 0.05). However, a significant negative causal effect of telomere length on autoimmune diseases was observed (IVW: OR = 0.906, 95% CI = 0.832-0.986, p = 0.022). Reverse Mendelian randomization analysis revealed no significant correlation. Further analysis using two separate datasets for five common autoimmune diseases confirmed significant negative associations between telomere length and RA (UKB biobank: OR = 0.997, 95% CI 0.994-0.999, p = 0.025; FinnGen: OR = 0.860, 95% CI 0.741-0.998, p = 0.047), GD (UK Biobank: OR = 0.519, 95% CI 0.430-0.625, p < 0.001; FinnGen: OR = 0.623, 95% CI 0.496-0.785, p < 0.001), and psoriasis (UK Biobank: OR = 0.772, 95%CI = 0.642-0.928, p = 0.006; FinnGen: OR = 0.841, 95%CI = 0.727-0.973, p = 0.020). A significant positive association was found for SLE in the UK Biobank (OR = 1.718, 95% CI = 95% CI 1.155-2.558, p = 0.007). Reverse Mendelian randomization analysis identified a significant negative association between telomere length and SLE (UK Biobank: OR = 0.995, 95% CI 0.991-0.998, p = 0.014; FinnGen: OR = 0.988, 95% CI 0.977-0.998, p = 0.029) and psoriasis (FinnGen: OR = 0.992, 95% CI 0.988-0.997, P = 0.005), and a positive association with RA (UK Biobank: OR = 1.988 95% CI 1.056-3.743, p = 0.031).

CONCLUSIONS: This Mendelian randomization analysis reveals a significant association between telomere length and autoimmune diseases such as RA, GD, and psoriasis, while a positive relationship was validated with SLE. These findings underscore the need for further investigation to better understand the underlying mechanisms and their potential clinical applications.},
}

Humans
*Mendelian Randomization Analysis
*Autoimmune Diseases/genetics/diagnosis
*Telomere/genetics
Genetic Predisposition to Disease
*Telomere Homeostasis/genetics
Risk Factors
*Telomere Shortening

@article {pmid40261310,
year = {2025},
author = {Shibuya, H},
title = {Telomeres, the nuclear lamina, and membrane remodeling: Orchestrating meiotic chromosome movements.},
journal = {The Journal of cell biology},
volume = {224},
number = {5},
pages = {},
pmid = {40261310},
issn = {1540-8140},
support = {//RIKEN/ ; },
mesh = {Humans ; *Telomere/metabolism/genetics ; Animals ; *Meiosis ; *Nuclear Lamina/metabolism/genetics ; *Nuclear Envelope/metabolism/genetics ; *Chromosomes/metabolism ; },
abstract = {Telomeres, the DNA-protein complex located at the ends of linear eukaryotic chromosomes, not only safeguard genetic information from DNA erosion and aberrant activation of the DNA damage response pathways but also play a pivotal role in sexual reproduction. During meiotic prophase I, telomeres attach to the nuclear envelope and migrate along its surface, facilitating two-dimensional DNA homology searches that ensure precise pairing and recombination of the paternal and maternal chromosomes. Recent studies across diverse model systems have revealed intricate molecular mechanisms, including modifications to telomere- and nuclear envelope-binding proteins, the nuclear lamina, and even membrane composition. Emerging evidence reveals mutations in the genes encoding these meiotic telomere and nuclear envelope-associated proteins among infertile patients. This review highlights recent advances in the field of meiotic telomere research, particularly emphasizing mammalian model systems, contextualizes these findings through comparisons with other eukaryotes, and concludes by exploring potential future research directions in the field.},
}

Humans
*Telomere/metabolism/genetics
Animals
*Meiosis
*Nuclear Lamina/metabolism/genetics
*Nuclear Envelope/metabolism/genetics
*Chromosomes/metabolism

@article {pmid40259036,
year = {2025},
author = {Castro, JDS and Teixeira, CM and Rocha, DMUP and Ribeiro, AQ and Kravchychyn, ACP and Hermsdorff, HHM},
title = {Dietary inflammatory index (DII) and telomere length: a systematic review.},
journal = {Biogerontology},
volume = {26},
number = {3},
pages = {95},
pmid = {40259036},
issn = {1573-6768},
support = {001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior , Brasil/ ; },
mesh = {Humans ; *Inflammation ; *Diet/adverse effects ; *Telomere ; Aged ; *Telomere Homeostasis ; *Aging/genetics ; Middle Aged ; Male ; Female ; Adult ; Aged, 80 and over ; Adolescent ; *Telomere Shortening ; },
abstract = {Dietary intake influences inflammation and may impact telomere length (TL), a biomarker of biological aging. However, the relationship between the inflammatory potential of the diet and TL remains unclear. This review systematically assessed whether higher Dietary Inflammatory Index (DII) scores, indicative of pro-inflammatory diets, are associated with shorter TL. Searches in PubMed, Embase, Scopus, Web of Science, and Cochrane up to October 2024 identified nine eligible studies, involving 123,923 participants (53% women), aged 9-80 years. Seven studies were cross-sectional, and two were longitudinal, with follow-ups of 5-10 years. Most studies (n = 4) examined adult and older adult populations of both sexes. DII values ranged from -6.48 (anti-inflammatory) to 3.98 (pro-inflammatory). None included all DII parameters, and three adjusted for energy intake. Four studies linked higher DII to shorter TL, focusing on European adults with and without cardiovascular risk, healthy American adults, and Chinese older adults with mild cognitive impairment. This systematic review presents limited data to provide a definitive conclusion on the association between higher DII and shorter TL. Additional studies that address the limitations identified in this review are needed.},
}

Humans
*Inflammation
*Diet/adverse effects
*Telomere
Aged
*Telomere Homeostasis
*Aging/genetics
Middle Aged
Male
Female
Adult
Aged, 80 and over
Adolescent
*Telomere Shortening

@article {pmid40258723,
year = {2025},
author = {Wei, Z and Hu, Y and Zhang, Y and Wang, G and Zhou, C and Wang, Y},
title = {Identification of a telomere-related gene signature for the prognostic and immune landscape prediction in head and neck squamous cell carcinoma by integrated analysis of machine learning and Mendelian randomization.},
journal = {Medicine},
volume = {104},
number = {16},
pages = {e42211},
doi = {10.1097/MD.0000000000042211},
pmid = {40258723},
issn = {1536-5964},
support = {2023S078//Ningbo Social Public Welfare Research Project/ ; },
mesh = {Humans ; *Squamous Cell Carcinoma of Head and Neck/genetics/immunology/mortality ; *Machine Learning ; Prognosis ; *Head and Neck Neoplasms/genetics/immunology/mortality ; Mendelian Randomization Analysis ; *Telomere/genetics ; Male ; Female ; Biomarkers, Tumor/genetics ; Middle Aged ; },
abstract = {Telomere-related genes (TRGs) are vital in diverse tumor types. Nevertheless, there is a notable lack of in-depth research concerning their significance in head and neck squamous cell carcinoma (HNSCC). In this context, the present study aims to assess the predictive value of TRGs in HNSCC. Gene expression data and clinical data for HNSCC were sourced from The Cancer Genome Atlas and the Gene Expression Omnibus database. A new prognostic signature for TRGs was formulated through the application of machine learning techniques. Based on this signature, risk scores were computed for individual samples, effectively classifying individuals into low- and high-risk categories. The signature was evaluated in terms of its association with survival outcomes, tumor mutation burden, functional enrichment, immune cell infiltration, and its predictive capacity regarding immunotherapy efficacy. Additionally, Mendelian randomization analysis was utilized to ascertain the potential causal association between the expression of model genes and the development of HNSCC. A sum of 24 TRGs was recognized and utilized to develop the predictive signature. The areas under the receiver operating characteristic (ROC) curves for 1-, 3-, and 5-year overall survival were computed as 0.654, 0.734, and 0.711, respectively. Kaplan-Meier survival analysis demonstrated that individuals classified as high-risk had notably poorer prognoses relative to those placed in the low-risk. Those with lower risk scores demonstrated better survival outcomes, marked by elevated immune scores, augmented immune-related functions, and greater immune cell infiltration. Furthermore, these lower-risk patients exhibited an enhanced response to immunotherapy in comparison to high-risk patients. Mendelian randomization findings indicated a possible causal link between MAD1L1 expression and the occurrence of HNSCC. This research established an innovative TRG-based risk model to forecast the survival outcomes and immune landscape of individuals with HNSCC. This reliable and validated prognostic indicator has the potential to inform and enhance the creation of innovative treatment approaches for individuals with HNSCC.},
}

Humans
*Squamous Cell Carcinoma of Head and Neck/genetics/immunology/mortality
*Machine Learning
Prognosis
*Head and Neck Neoplasms/genetics/immunology/mortality
Mendelian Randomization Analysis
*Telomere/genetics
Male
Female
Biomarkers, Tumor/genetics
Middle Aged

@article {pmid40257417,
year = {2025},
author = {Gheytaspour, P and Bahadoran, S and Hassanpour, H},
title = {The Impact of Dietary Melatonin on Heart and Lung Telomere Length and Shelterin Protein Gene Expression of Pulmonary Hypertensive Broiler Chickens.},
journal = {Veterinary medicine and science},
volume = {11},
number = {3},
pages = {e70355},
doi = {10.1002/vms3.70355},
pmid = {40257417},
issn = {2053-1095},
mesh = {Animals ; *Melatonin/administration & dosage/pharmacology/metabolism ; *Chickens ; *Poultry Diseases/drug therapy/genetics/metabolism ; Lung/drug effects/metabolism ; Dietary Supplements/analysis ; *Hypertension, Pulmonary/veterinary/drug therapy/genetics/metabolism ; Diet/veterinary ; *Telomere/drug effects ; Male ; Animal Feed/analysis ; *Gene Expression/drug effects ; Avian Proteins/metabolism/genetics ; Myocardium/metabolism ; *Antioxidants/administration & dosage/pharmacology ; *Telomere-Binding Proteins/genetics/metabolism ; Shelterin Complex ; Heart/drug effects ; },
abstract = {OBJECTIVES: Pulmonary hypertension syndrome (PHS) is a common metabolic disease in broiler chickens linked to oxidative stress. This study explored the potential of melatonin, an antioxidant, to improve PHS response and telomere structure in chickens with cold-induced PHS.

METHODS: We investigated the effects of dietary melatonin supplementation on telomere length and the expression of genes related to telomere protection (shelterin genes) in the heart and lungs of broiler chickens with PHS.

RESULTS: Melatonin supplementation improved telomere length in the heart tissue of chickens with PHS. We also observed changes in the expression of genes (TRF1, RAP1, and TPP1) responsible for protecting telomeres, suggesting a potential mechanism for melatonin's beneficial effects. Melatonin's impact was more pronounced in the heart than in the lungs.

CONCLUSIONS: Melatonin may help protect cardiac cells during PHS by improving telomere length and influencing the activity of genes involved in telomere protection. These findings suggest that melatonin could be a valuable tool in managing heart cell dysfunction associated with PHS in poultry.},
}

Animals
*Melatonin/administration & dosage/pharmacology/metabolism
*Chickens
*Poultry Diseases/drug therapy/genetics/metabolism
Lung/drug effects/metabolism
Dietary Supplements/analysis
*Hypertension, Pulmonary/veterinary/drug therapy/genetics/metabolism
Diet/veterinary
*Telomere/drug effects
Male
Animal Feed/analysis
*Gene Expression/drug effects
Avian Proteins/metabolism/genetics
Myocardium/metabolism
*Antioxidants/administration & dosage/pharmacology
*Telomere-Binding Proteins/genetics/metabolism
Shelterin Complex
Heart/drug effects

@article {pmid40254557,
year = {2025},
author = {Xu, S and Ye, J and Cai, X},
title = {Identification of telomere-related diagnostic markers in osteoarthritis based on bioinformatics analysis and machine learning.},
journal = {The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology},
volume = {29},
number = {3},
pages = {359-372},
doi = {10.4196/kjpp.24.322},
pmid = {40254557},
issn = {1226-4512},
abstract = {Osteoarthritis (OA) is one of the most prevalent joint disorders, with aging considered a primary, irreversible factor contributing to its progression. Telomere-related cellular senescence may be a crucial factor influencing the OA process, yet biomarkers for OA based on telomere-related genes have not been clearly identified. The datasets GSE51588, GSE12021, and GSE55457 were retrieved from the Gene Expression Omnibus database. Initially, R software was utilized to identify differentially expressed genes between OA and normal samples. Subsequently, differentially expressed telomere-related genes (DETMRGs) were obtained, and their functional enrichment was analyzed. Feature genes for OA diagnosis were selected from DETMRGs using a combination of least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and Random Forest algorithms. The diagnostic value of these feature genes was then validated through receiver operating characteristic (ROC) curves and decision curve analysis. Additionally, CIBERSORT and xCell were employed to assess the infiltration of immune cells in OA tissues. Finally, potential drugs targeting candidate genes were predicted. Three telomere-related genes, PGD, SLC7A5, and TKT, have been identified as biomarkers for OA diagnosis and were confirmed through ROC diagnostic tests. The immune infiltration of mast cells, neutrophils, common lymphoid precursors, and eosinophils associated with PGD, SLC7A5, and TKT was reduced. Recognizing telomere-related genes PGD, SLC7A5, and TKT as potential diagnostic biomarkers for OA is significant, as it offers valuable insights into the role of telomere-related genes in OA. This discovery also provides valuable information for the diagnosis and treatment of OA.},
}

@article {pmid40253647,
year = {2025},
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 Hogan, KJ 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 = {Journal of aging and health},
volume = {},
number = {},
pages = {8982643251331260},
doi = {10.1177/08982643251331260},
pmid = {40253647},
issn = {1552-6887},
abstract = {ObjectiveAccelerated 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.MethodsThis study included data on telomere length and neuropsychological 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.ResultsNested multivariable regression models revealed preliminary evidence for associations between telomere length and cognitive performance, and these associations were partially independent of chronological age.DiscussionSmall 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 {pmid40252362,
year = {2025},
author = {Wai, KM and Paing, AM and Swe, T},
title = {Understanding physical aging in relation to biological aging, telomere length: A systematic review.},
journal = {Archives of gerontology and geriatrics},
volume = {134},
number = {},
pages = {105854},
doi = {10.1016/j.archger.2025.105854},
pmid = {40252362},
issn = {1872-6976},
abstract = {BACKGROUND: Telomere length (TL) serves as a marker for biological aging, influenced by chronological aging but distinct from it. This systematic review aims to synthesize the evidence on the associations between components of physical aging and TL in the elderly population.

METHODS: A comprehensive search was conducted in online databases of PubMed, Web of Science, ProQuest, and ScienceDirect to identify the eligible papers published until 1st August 2024. The authors independently extracted data using the standardized form. The quality of the included studies was evaluated for the risks of biases.

RESULTS: A total of 1080 records were initially identified using the predefined search strategy. A total of 40 eligible records were included in this review. When assessing physical aging, the nature and type of measurements across studies vary, including subjective, objective, and a combination of both approaches. Subjective assessments of general health or physical limitations may be linked with TL, while frailty, whether measured subjectively or objectively, shows associations with TL in less than 35 percent of total studies. In contrast, composite measures of physical performance/ability are consistently associated with TL in the elderly population.

CONCLUSIONS: In conclusion, we demonstrated that the associations between physical aging and TL varies depending on the type and nature of physical aging assessments. Composite measures of physical performance/ability demonstrate a strong and consistent parameter of physical aging to link with TL. Future research should prioritize standardized, multidimensional approaches to measure physical aging to understand better its association with TL to support healthy aging strategies.},
}

@article {pmid40250166,
year = {2025},
author = {Tian, Y and Kong, S and Mao, L and Wang, G and He, J and Lei, F and Lin, L and Li, J},
title = {Association of life's essential 8 with leukocyte telomere length and mitochondrial DNA copy number: Findings from the population-based UK Biobank study.},
journal = {The journal of nutrition, health & aging},
volume = {29},
number = {7},
pages = {100557},
doi = {10.1016/j.jnha.2025.100557},
pmid = {40250166},
issn = {1760-4788},
abstract = {OBJECTIVES: To explore the association of Life's Essential 8 (LE8) levels with leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN).

DESIGN: A cross-sectional study.

SETTING AND PARTICIPANTS: 225,692 participants aged 37-73 year from the UK Biobank cohort enrolled from 2006 to 2010.

MEASUREMENTS: The LE8 score (0-100) was divided into low (<50), moderate (50-79), and high cardiovascular health (CVH) (≥80) categories, based on health behaviors and factors defined by the American Heart Association. LTL was measured by a validated quantitative polymerase chain reaction method. mtDNA-CN was reacted by standardized SNP probe intensities. The association of CVH (as both a continuous and categorical variable) with LTL and mtDNA-CN was examined using multiple linear regression.

RESULTS: Of 225,692 participants, 5.3% had low CVH, 81.2% had moderate CVH, and 13.4% had high CVH. Participants with higher CVH were usually younger, female, better educated, of higher socioeconomic status, and with a lower prevalence of comorbidities. After adjusting for confounders, a higher LE8 score is associated with longer LTL (Beta = 0.075, P < 0.05) and increased mtDNA-CN (Beta = 0.094, P < 0.05). We also observed that this association was evident in the health behavior score (diet, physical activity, nicotine exposure, and sleep) and the health factors score (BMI, non-HDL cholesterol, blood glucose, and blood pressure), with a stronger positive association of health factors with LTL and mtDNA-CN (Beta = 0.019, P < 0.05; Beta = 0.037, P < 0.05).

CONCLUSIONS: Higher CVH is associated with longer LTL and increased mtDNA-CN.},
}

@article {pmid40247641,
year = {2025},
author = {Ryall, C and Denham, J},
title = {A systematic review and meta-analysis highlights a link between aerobic fitness and telomere maintenance.},
journal = {The journals of gerontology. Series A, Biological sciences and medical sciences},
volume = {},
number = {},
pages = {},
doi = {10.1093/gerona/glaf068},
pmid = {40247641},
issn = {1758-535X},
abstract = {Cardiorespiratory fitness declines with ageing and is a major risk factor of cardiometabolic diseases and early death. Although the benefits of regular exercise are well established, whether maximal oxygen uptake (V̇O2max) is associated with biological ageing remains unclear. Given that telomere shortening is a hallmark of ageing, the purpose of this systematic review and meta-analysis was to determine the association between V̇O2max and telomere length. Articles were retrieved from PubMed, Scopus, and ScienceDirect and deemed eligible if they: 1) involved human participants with relatively low and high V̇O2max values objectively assessed by pulmonary analysis; 2) quantified telomere length using an established technique; and 3) were peer-reviewed journal articles written in English. Relative to individuals with below average V̇O2max based on age- and sex-adjusted norms, fit participants with relative V̇O2max values in the 70th percentile or higher possessed longer telomeres (SMD [95%CI]: 0.36 [0.14-0.59], p=0.002). A similar difference was observed between individuals with below average V̇O2max and those above the 90th percentile (0.28 [0.03-0.53], p=0.03). However, no statistically significant telomere length differences were observed between individuals in the 70th to 90th percentile compared to those above the 90th (-0.08 [-0.40-0.24], p=0.62). The findings provide evidence linking metabolism to telomere biology. They encourage individuals to regularly engage in endurance exercise to attenuate telomere attrition and promote healthy biological ageing. Importantly, the results suggest that extensive endurance training may not be required to protect the telomeres, rather moderate amounts of training may be sufficient to reach more achievable V̇O2max targets.},
}

@article {pmid40246468,
year = {2025},
author = {Ma, N and Yip, R and Woodward, M and Lewis, S and Crane, M and Jirapatnakul, A and Aloman, C and Bansal, MB and Dieterich, D and Gros, L and Valvi, D and Colicino, E and Yankelevitz, D and Henschke, C and Branch, AD},
title = {Mixture analysis of associations between environmental and workplace toxins and liver damage and telomere length, stratified by race/ethnicity.},
journal = {Journal of environmental sciences (China)},
volume = {155},
number = {},
pages = {316-328},
doi = {10.1016/j.jes.2024.08.020},
pmid = {40246468},
issn = {1001-0742},
mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Cadmium ; Cross-Sectional Studies ; *Environmental Exposure/statistics & numerical data ; *Environmental Pollutants/toxicity/blood ; Ethnicity/statistics & numerical data ; Lead ; Liver/drug effects ; Nutrition Surveys ; *Occupational Exposure/statistics & numerical data ; Polychlorinated Biphenyls ; *Telomere ; United States/epidemiology ; Racial Groups ; White ; Black or African American ; },
abstract = {This study aimed to identify the worst "bad actors" in mixtures of pollutants contributing to liver damage and shorter telomeres in the U.S. population, using weighted quantile sum (WQS) modeling with stratification by race/ethnicity. We conducted a comprehensive cross-sectional analysis of mixtures of pollutants in National Health and Nutrition Examination Survey datasets: (1) 33,979 adults with blood levels of cadmium (Cd), lead (Pb), and mercury, including subsets with measurements of per-/polyfluoroalkyl substances (PFAS), and polychlorinated biphenyls (PCBs)/polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs); and (2) 7360 adults with measurements of telomeres, Cd, and Pb. Multivariable-adjusted WQS regression examined associations between WQS mixture indices and liver injury (alanine aminotransferase (ALT)-elevation), advanced liver-fibrosis (LF), and telomere length. WQSmetal indices were associated with advanced-LF in all racial/ethnic groups. The top contributor was Cd in the total population and in non-Hispanic Whites (NHW), while Pb was the top contributor in non-Hispanic Blacks (NHB). The WQSmetal-PCB-PCDD/F index was associated with ALT-elevation, with PCB126, Cd and Pb as main contributors; the odds ratio (OR) per decile was 1.50 (95 % CI, 1.26-1.78), while the OR per decile of the WQSmetal-PFAS index was 1.03 (95 % CI, 0.98-1.05), not significant. WQSmetal indices were associated with shorter telomeres. Cd was main contributor associated with advanced-LF in NHW, while Pb was the major bad actor in NHB, suggesting that NHB may be especially susceptible to Pb toxicity. Metals were associated with shorter telomeres. Metal and PCB/PCDD/F mixtures were associated with ALT-elevation. Heavy metals and organic chemicals may contribute to liver-related morbidity and healthcare disparities.},
}

Adult
Female
Humans
Male
Middle Aged
Cadmium
Cross-Sectional Studies
*Environmental Exposure/statistics & numerical data
*Environmental Pollutants/toxicity/blood
Ethnicity/statistics & numerical data
Lead
Liver/drug effects
Nutrition Surveys
*Occupational Exposure/statistics & numerical data
Polychlorinated Biphenyls
*Telomere
United States/epidemiology
Racial Groups
White
Black or African American

@article {pmid40245101,
year = {2025},
author = {Calugaru, K and Yu, EY and Huang, S and González-Rodríguez, N and Coloma, J and Lue, NF},
title = {The yeast CST and Polα/primase complexes act in concert to ensure proper telomere maintenance and protection.},
journal = {Nucleic acids research},
volume = {53},
number = {7},
pages = {},
doi = {10.1093/nar/gkaf245},
pmid = {40245101},
issn = {1362-4962},
support = {MCB-2246561//National Science Foundation/ ; GM107287/NH/NIH HHS/United States ; AEI/10.13039/501100011 033//Agencia Estatal de Investigación/ ; PID2020-114429RB-I00//Ministerio de Ciencia e Innovación/ ; //National Institute of Health Carlos III/ ; },
mesh = {*DNA Polymerase I/metabolism/genetics/chemistry ; *DNA Primase/metabolism/genetics/chemistry/ultrastructure ; *Telomere/metabolism/genetics ; *Telomere-Binding Proteins/genetics/metabolism/chemistry ; *Telomere Homeostasis/genetics ; Telomerase/metabolism/genetics/chemistry ; *Saccharomyces cerevisiae Proteins/genetics/metabolism/chemistry ; Humans ; Cryoelectron Microscopy ; Candida glabrata/genetics/metabolism ; Mutation ; DNA Replication ; Cell Cycle Proteins/genetics/metabolism ; Saccharomyces cerevisiae/genetics ; },
abstract = {Polα/primase (PP), the polymerase that initiates DNA synthesis at replication origins, also completes the task of genome duplication by synthesizing the telomere C-strand under the control of the CTC1/CDC13-STN1-TEN1 (CST) complex. Using cryo-electron microscopy (cryo-EM) structures of the human CST-Polα/primase-DNA complex as guides in conjunction with AlphaFold modeling, we identified structural elements in yeast CST and PP that promote complex formation. Mutating these structures in Candida glabrata Stn1, Ten1, Pri1, and Pri2 abrogated the stimulatory activity of CST on PP in vitro, supporting the functional relevance of the physical contacts in cryo-EM structures as well as the conservation of mechanisms between yeast and humans. Introducing these mutations into C. glabrata yielded two distinct groups of mutants. One group exhibited progressive, telomerase-dependent telomere elongation without evidence of DNA damage. The other manifested slow growth, telomere length heterogeneity, single-stranded DNA accumulation and elevated C-circles, which are indicative of telomere deprotection. These telomere deprotection phenotypes are altered or suppressed by mutations in multiple DNA damage response (DDR) and DNA repair factors. We conclude that in yeast, the telomerase inhibition and telomere protection function previously ascribed to the CST complex are mediated jointly by both CST and Polα/primase, highlighting the critical importance of a replicative DNA polymerase in telomere regulation.},
}

*DNA Polymerase I/metabolism/genetics/chemistry
*DNA Primase/metabolism/genetics/chemistry/ultrastructure
*Telomere/metabolism/genetics
*Telomere-Binding Proteins/genetics/metabolism/chemistry
*Telomere Homeostasis/genetics
Telomerase/metabolism/genetics/chemistry
*Saccharomyces cerevisiae Proteins/genetics/metabolism/chemistry
Humans
Cryoelectron Microscopy
Candida glabrata/genetics/metabolism
Mutation
DNA Replication
Cell Cycle Proteins/genetics/metabolism
Saccharomyces cerevisiae/genetics

@article {pmid40244253,
year = {2025},
author = {Murillo-Ortiz, BO and Romero-Vázquez, MJ and Luevanos-Aguilera, AJ and Meza-Herrán, PM and Ramos-Rodriguez, EM and Martínez-Garza, S and Murguia-Perez, M},
title = {Association Between Telomere Shortening and Erythropoietin Resistance in Patients with Chronic Kidney Disease Undergoing Hemodialysis.},
journal = {International journal of molecular sciences},
volume = {26},
number = {7},
pages = {},
doi = {10.3390/ijms26073405},
pmid = {40244253},
issn = {1422-0067},
mesh = {Humans ; *Renal Dialysis ; Female ; Male ; *Erythropoietin/therapeutic use ; *Renal Insufficiency, Chronic/therapy/genetics ; Middle Aged ; *Drug Resistance/genetics ; *Telomere Shortening ; Cross-Sectional Studies ; Aged ; Anemia/drug therapy ; Hematinics/therapeutic use ; Telomere ; Adult ; },
abstract = {The relationship between telomere shortening and patients with chronic kidney disease (CKD) has recently been investigated. Although most patients respond adequately to erythropoiesis-stimulating agents (ESAs), approximately 10% do not, and this is referred to as ESA resistance. The aim of our study was to investigate the relationship between telomere shortening and erythropoietin resistance in patients with CKD on hemodialysis. This cross-sectional, comparative, analytical, and observational study was conducted in patients of both sexes over 18 years of age diagnosed with CKD. Two groups of patients were identified. The first group consisted of 40 patients receiving erythropoiesis-stimulating agents with erythropoietin resistance. The second group consisted of 40 patients with the same characteristics but without erythropoietin resistance. Telomere length was measured by real-time PCR. Eighty patients were included in the study. Mean hemoglobin levels were lower in the erythropoietin resistance group (8.8 ± 1.67 vs. 11.95 ± 1.81, p = 0.001). Differences were observed in hematocrit and albumin levels, which were lower in patients with erythropoietin resistance, while PTH levels were higher in this group (788 ± 538.47 vs. 535.65 ± 603.06, p = 0.001). A significant difference in telomere length (T/S) was observed between the two groups, with shorter telomere length in the erythropoietin resistance group (0.45 ± 0.04 vs. 0.56 ± 0.03, p = 0.01). Telomere shortening may be associated with anemia and erythropoietin resistance in patients with CKD undergoing hemodialysis. This relationship suggests the need to explore whether telomere length recovery improves the response to ESAs.},
}

Humans
*Renal Dialysis
Female
Male
*Erythropoietin/therapeutic use
*Renal Insufficiency, Chronic/therapy/genetics
Middle Aged
*Drug Resistance/genetics
*Telomere Shortening
Cross-Sectional Studies
Aged
Anemia/drug therapy
Hematinics/therapeutic use
Telomere
Adult

@article {pmid40243865,
year = {2025},
author = {Dos Reis, GG and Silvestre, RT and Alves, G and Delmonico, L and Chantre-Justino, M and Moreira, ADS and Müller, BLA and do Nascimento, CR and da Silva, DLP and Dos Santos, LS and Mattos-Guaraldi, AL and Ornellas, MH},
title = {Leukocyte telomere length and telomerase activity in Long COVID patients from Rio de Janeiro, Brazil.},
journal = {Memorias do Instituto Oswaldo Cruz},
volume = {120},
number = {},
pages = {e240129},
doi = {10.1590/0074-02760240129},
pmid = {40243865},
issn = {1678-8060},
mesh = {Humans ; *Telomerase/blood/metabolism ; *COVID-19/enzymology ; Male ; Female ; *Leukocytes/enzymology ; *Telomere/genetics ; Middle Aged ; Brazil ; Real-Time Polymerase Chain Reaction ; Adult ; SARS-CoV-2 ; Case-Control Studies ; Aged ; },
abstract = {BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by the new coronavirus 2 (severe acute respiratory syndrome coronavirus 2 - SARS-CoV-2). Long COVID is a new condition associated with persistent COVID-19 symptoms and/or new emerging symptoms. Telomeres are specialised structures for genome protection at the end of chromosomes and telomerase is the enzyme that synthesises telomere DNA.

OBJECTIVES: Patients with Long COVID symptoms were recruited at the Pedro Ernesto University Hospital (HUPE) in Rio de Janeiro, Brazil, with the main purpose of investigating the association between telomere length and Long COVID.

METHODS: Leukocyte telomere length (LTL) was determined by quantitative real-time polymerase chain reaction (qPCR) in 34 Long COVID patients compared to a control group (n = 122). Telomerase activity was determined by qPCR assays using the commercial kit from ScienCell. A questionnaire on symptoms, vaccine doses and blood count was completed.

FINDINGS: The Long COVID patients were found to have an increase in LTL. Telomerase activity was also examined in a smaller number of patients and found to be reactivated in the blood.

MAIN CONCLUSIONS: It will be necessary to conduct further studies and monitor Long COVID patients to determine if future health issues could be linked to telomerase activity and elongated telomeres.},
}

Humans
*Telomerase/blood/metabolism
*COVID-19/enzymology
Male
Female
*Leukocytes/enzymology
*Telomere/genetics
Middle Aged
Brazil
Real-Time Polymerase Chain Reaction
Adult
SARS-CoV-2
Case-Control Studies
Aged

@article {pmid40243583,
year = {2025},
author = {Dmitrenko, O and Karpova, N and Nurbekov, M},
title = {Increased Preeclampsia Risk in GDM Pregnancies: The Role of SIRT1 rs12778366 Polymorphism and Telomere Length.},
journal = {International journal of molecular sciences},
volume = {26},
number = {7},
pages = {},
doi = {10.3390/ijms26072967},
pmid = {40243583},
issn = {1422-0067},
support = {FGFU-2025-0007: Search for diagnostically significant biochemical, immunological and other markers of disorders of normal functioning of organs and systems.//Federal State Budgetary Institution the "Research Institute of Pathology and Pathophysiology"/ ; },
mesh = {Humans ; Female ; Pregnancy ; *Pre-Eclampsia/genetics ; *Sirtuin 1/genetics ; *Diabetes, Gestational/genetics ; Adult ; *Polymorphism, Single Nucleotide ; *Telomere/genetics ; *Genetic Predisposition to Disease ; Case-Control Studies ; Risk Factors ; Genotype ; *Telomere Homeostasis ; Telomere Shortening ; },
abstract = {Preeclampsia (PE) and gestational diabetes mellitus (GDM) are common pregnancy disorders with shared pathophysiological mechanisms. This study examined the association between SIRT1 polymorphisms (rs12778366 and rs7895833) and relative telomere length (RTL) in women with PE and GDM. The DNA from pregnant women with GDM with and without PE was analyzed. The RTL and genotyping were measured using quantitative real-time PCR. The women with GDM and PE had significantly shorter telomeres. The rs12778366 TC genotype was associated with a 4.48-fold increased risk of PE (OR = 4.48; 95% CI 1.54-13.08; p = 0.003). The PE group had a higher prevalence of the heterozygous TC rs12778366 genotype with short telomeres. The SIRT1 variant rs12778366 is associated with shorter telomeres and an increased risk of developing preeclampsia, suggesting it may be a useful biomarker for preeclampsia risk assessment in GDM pregnancies.},
}

Humans
Female
Pregnancy
*Pre-Eclampsia/genetics
*Sirtuin 1/genetics
*Diabetes, Gestational/genetics
Adult
*Polymorphism, Single Nucleotide
*Telomere/genetics
*Genetic Predisposition to Disease
Case-Control Studies
Risk Factors
Genotype
*Telomere Homeostasis
Telomere Shortening

@article {pmid40239997,
year = {2025},
author = {Pirota, V and Iachettini, S and Platella, C and Zizza, P and Fracchioni, G and Di Vito, S and Carachino, A and Battistini, F and Orozco, M and Freccero, M and Biroccio, A and Montesarchio, D and Doria, F},
title = {Naphthalene diimide-naphthalimide dyads promote telomere damage by selectively targeting multimeric G-quadruplexes.},
journal = {Nucleic acids research},
volume = {53},
number = {7},
pages = {},
doi = {10.1093/nar/gkaf301},
pmid = {40239997},
issn = {1362-4962},
support = {//European Union/ ; //Fondazione Umberto Veronesi/ ; 21579//National Center for Gene Therapy and Drugs/ ; 25046//Fondazione AIRC/ ; },
mesh = {*G-Quadruplexes/drug effects ; *Telomere/drug effects/chemistry ; Humans ; *Imides/chemistry/pharmacology ; *Naphthalenes/chemistry/pharmacology ; *Naphthalimides/chemistry/pharmacology ; *Antineoplastic Agents/pharmacology/chemistry/chemical synthesis ; Cell Line, Tumor ; Ligands ; Cell Survival/drug effects ; },
abstract = {G-quadruplex (G4) nucleic acid ligands have attracted significant attention as putative anticancer agents for selectively stabilizing telomeric structures. In our pursuit of targeting the most biologically relevant telomeric structures, we have investigated a new class of naphthalene diimide (NDI)-based ligands designed to bind multimeric G4s. The NDI unit covalently linked with one 1,8-naphthalimide (NI) moiety, results in ligands able to fold into a sandwich-like conformation fitting into the binding pockets of telomeric multimeric G4s, thus optimizing binding complementarity. Varying the NDI decorations, we synthesized a small library of NDI-NI dyads and then examined their capability of stabilizing G4s by biophysical assays. Given the relevance of G4 stabilizing agents in fighting cancer, the most promising NDI-NIs were evaluated for their antitumoral activity on a panel of human cell lines originating from different tumor histotypes. Obtained results evidenced that three of the selected ligands promoted an accumulation of telomere-localized damage leading to a robust impairment of cell viability, regardless of homologous recombination status. These data, then confirmed in advanced 3D models, paved the way for the advancement of NDI-NIs as a new class of clinically relevant antitumoral agents. Finally, computational analyses gained deeper insight into their binding modality.},
}

*G-Quadruplexes/drug effects
*Telomere/drug effects/chemistry
Humans
*Imides/chemistry/pharmacology
*Naphthalenes/chemistry/pharmacology
*Naphthalimides/chemistry/pharmacology
*Antineoplastic Agents/pharmacology/chemistry/chemical synthesis
Cell Line, Tumor
Ligands
Cell Survival/drug effects

@article {pmid40236780,
year = {2025},
author = {Zong, W and Chen, L and Zhang, D and Zhang, Y and Wang, J and Hou, X and Chai, J and An, Y and Tian, M and He, X and Song, C and He, J and Liu, X and Wang, L and D'Alessandro, E and Wang, L and Yin, Y and Li, M and Liu, D and Wang, J and Zhang, L},
title = {Two telomere-to-telomere pig genome assemblies and pan-genome analyses provide insights into genomic structural landscape and genetic adaptations.},
journal = {iMeta},
volume = {4},
number = {2},
pages = {e70013},
pmid = {40236780},
issn = {2770-596X},
abstract = {This study presented two high-precision telomere-to-telomere genome assemblies for Min and Rongchang pigs, including a detailed exploration of the telomeric and centromeric regions. By integrating pan-genome and multi-omics analyses, structural variations linked to genetic adaptation were identified, providing a valuable resource for advancing pig breeding and genetic improvement.},
}

@article {pmid40236733,
year = {2025},
author = {Song, WL and Chen, BZ and Feng, L and Chen, G and He, SM and Hao, B and Zhang, GH and Dong, Y and Yang, SC},
title = {Telomere-to-telomere genome assembly and 3D chromatin architecture of Centella asiatica insight into evolution and genetic basis of triterpenoid saponin biosynthesis.},
journal = {Horticulture research},
volume = {12},
number = {5},
pages = {uhaf037},
pmid = {40236733},
issn = {2662-6810},
abstract = {Centella asiatica is renowned for its medicinal properties, particularly due to its triterpenoid saponins, such as asiaticoside and madecassoside, which are in excess demand for the cosmetic industry. However, comprehensive genomic resources for this species are lacking, which impedes the understanding of its biosynthetic pathways. Here, we report a telomere-to-telomere (T2T) C. asiatica genome. The genome size is 438.12 Mb with a contig N50 length of 54.12 Mb. The genome comprises 258.87 Mb of repetitive sequences and 25 200 protein-coding genes. Comparative genomic analyses revealed C. asiatica as an early-diverging genus within the Apiaceae family with a single whole-genome duplication (WGD, Apiaceae-ω) event following the ancient γ-triplication, contrasting with Apiaceae species that exhibit two WGD events (Apiaceae-α and Apiaceae-ω). We further constructed 3D chromatin structures, A/B compartments, and topologically associated domains (TADs) in C. asiatica leaves, elucidating the influence of chromatin organization on expression WGD-derived genes. Additionally, gene family and functional characterization analysis highlight the key role of CasiOSC03 in α-amyrin production while also revealing significant expansion and high expression of CYP716, CYP714, and UGT73 families involved in asiaticoside biosynthesis compared to other Apiaceae species. Notably, a unique and large UGT73 gene cluster, located within the same TAD, is potentially pivotal for enhancing triterpenoid saponin. Weighted gene coexpression network analysis (WGCNA) further highlighted the pathways modulated in response to methyl jasmonate (MeJA), offering insights into the regulatory networks governing saponin biosynthesis. This work not only provides a valuable genomic resource for C. asiatica but also sheds light on the molecular mechanisms driving the biosynthesis of pharmacologically important metabolites.},
}

@article {pmid40235556,
year = {2025},
author = {You, Y and Wang, D and Ding, H and Wang, W and Liu, Q and Zhang, D and Chen, Y and Ma, X},
title = {Mediation role of telomere length in the relationship between physical activity and PhenoAge: A population-based study.},
journal = {Journal of exercise science and fitness},
volume = {23},
number = {3},
pages = {149-156},
pmid = {40235556},
issn = {1728-869X},
abstract = {BACKGROUND: The relationship between physical activity (PA), telomere length, and phenotypic age (PhenoAge) represents a pivotal area of investigation in aging research.

METHODS: The study encompassed a cohort of 6200 participants aged 20 years and above, sourced from the National Health and Nutrition Examination Survey (NHANES). Physical activity (PA) levels were assessed employing the Global Physical Activity Questionnaire, while DNA samples were collected to determine telomere length, measured in base pairs. PhenoAge, an emerging aging index relying on nine distinct chemical biomarkers, was computed.

RESULTS: Incorporating a fully adjusted model, our analysis showed significant correlations between PA engagement and PhenoAge [Low PA, β (95 % CI): 0.039(-0.071,-0.008), p = 0.021; Moderate PA, β (95 % CI): 0.058(-0.082,-0.034), p < 0.001; High PA, β (95 % CI): 0.069(-0.096,-0.042), p < 0.001]. Furthermore, a positive link emerged between elevated PA levels and telomere length, with a β (95 % CI) of 0.011(0.001, 0.022), p = 0.034. A mediation analysis was performed, demonstrating that telomere length mediated the connection between PA and PhenoAge, with a proportion mediated calculated at 3.57 %.

CONCLUSIONS: Our findings suggest that PA may play a key role in mitigating aging processes by preserving telomere length, highlighting the potential of PA as a target for interventions aimed at promoting healthy aging and longevity.},
}

@article {pmid40234460,
year = {2025},
author = {Chen, G and Wang, S and Mo, X and Zhu, W and Wang, R and Song, X},
title = {Leukocyte telomere length serves as the novel prognostic biomarker for the resectable NSCLC.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {13002},
pmid = {40234460},
issn = {2045-2322},
support = {202315021029//Medical and Health Science and Technology Development Project of Shandong Province/ ; LJ232411258025//Fundamental Research Funds for the Higher Education Institutions of Education Bureau of Liaoning Province/ ; ZR2023LZL011//Shandong Natural Science Foundation Innovation and Development Joint Fund/ ; No. tsqn202312366//Taishan Youth Scholar Program of Shandong Province/ ; },
mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/surgery/pathology/genetics/mortality ; Female ; Male ; *Leukocytes/metabolism ; *Lung Neoplasms/surgery/pathology/genetics/mortality ; Middle Aged ; Prognosis ; *Biomarkers, Tumor/genetics ; *Telomere/genetics ; Aged ; Neoplasm Staging ; Adult ; Disease-Free Survival ; *Telomere Homeostasis ; },
abstract = {The relationship of Leukocyte telomere length (LTL) dynamic changes with resectable NSCLC progression remains unclear. This study aims to reveal its clinical utility for prognosis of the resectable NSCLC. LTL was measured in 76 resectable NSCLC patients and 80 healthy controls using peripheral blood samples. Pre-operation LTL (Pre-LTL) and post-operation LTL (Po-LTL) were analyzed in relation to TNM stage, metastasis, and survival outcomes. The prognostic value was evaluated by disease-free survival (DFS) and overall survival (OS). NSCLC patients had significantly shorter LTL compared to controls, with LTL inversely correlated to disease stage. Po-LTL increased significantly and was associated with better OS. Combining Po-LTL with TNM stage improved prognostic prediction for OS and DFS. LTL is a promising biomarker for predicting prognosis in resectable NSCLC. Po-LTL, as well as in combination with TNM stage, enhances predictive accuracy for OS and DFS.},
}

Humans
*Carcinoma, Non-Small-Cell Lung/surgery/pathology/genetics/mortality
Female
Male
*Leukocytes/metabolism
*Lung Neoplasms/surgery/pathology/genetics/mortality
Middle Aged
Prognosis
*Biomarkers, Tumor/genetics
*Telomere/genetics
Aged
Neoplasm Staging
Adult
Disease-Free Survival
*Telomere Homeostasis

@article {pmid40231186,
year = {2025},
author = {Jinesh, S and Özüpek, B and Aditi, P},
title = {Premature aging and metabolic diseases: the impact of telomere attrition.},
journal = {Frontiers in aging},
volume = {6},
number = {},
pages = {1541127},
pmid = {40231186},
issn = {2673-6217},
abstract = {Driven by genetic and environmental factors, aging is a physiological process responsible for age-related degenerative changes in the body, cognitive decline, and impaired overall wellbeing. Notably, premature aging as well as the emergence of progeroid syndromes have posed concerns regarding chronic health conditions and comorbidities in the aging population. Accelerated telomere attrition is also implicated in metabolic dysfunction and the development of metabolic disorders. Impaired metabolic homeostasis arises secondary to age-related increases in the synthesis of free radicals, decreased oxidative capacity, impaired antioxidant defense, and disrupted energy metabolism. In particular, several cellular and molecular mechanisms of aging have been identified to decipher the influence of premature aging on metabolic diseases. These include defective DNA repair, telomere attrition, epigenetic alterations, and dysregulation of nutrient-sensing pathways. The role of telomere attrition premature aging in the pathogenesis of metabolic diseases has been largely attributed to pro-inflammatory states that promote telomere shortening, genetic mutations in the telomerase reverse transcriptase, epigenetic alteration, oxidative stress, and mitochondrial dysfunctions. Nonetheless, the therapeutic interventions focus on restoring the length of telomeres and may include treatment approaches to restore telomerase enzyme activity, promote alternative lengthening of telomeres, counter oxidative stress, and decrease the concentration of pro-inflammatory cytokines. Given the significance and robust potential of delaying telomere attrition in age-related metabolic diseases, this review aimed to explore the molecular and cellular mechanisms of aging underlying premature telomere attrition and metabolic diseases, assimilating evidence from both human and animal studies.},
}

@article {pmid40228359,
year = {2025},
author = {Thurin, J and Etain, B and Bellivier, F and Marie-Claire, C},
title = {Telomerase activity and telomere homeostasis in major depressive disorder, schizophrenia and bipolar disorder: a systematic review.},
journal = {Journal of psychiatric research},
volume = {186},
number = {},
pages = {98-107},
doi = {10.1016/j.jpsychires.2025.04.013},
pmid = {40228359},
issn = {1879-1379},
abstract = {INTRODUCTION: Life expectancy is decreased in individuals diagnosed with Major depressive disorder (MDD), Schizophrenia (SCZ) or Bipolar disorder (BD), which suggests cellular ageing. Telomere length (TL), a biomarker of cellular ageing, has been consistently reported as shorter in these individuals, but the mechanisms involved remain unknown.

METHOD: A literature search was conducted which included studies focusing on telomerase activity and markers involved in telomere homeostasis (Single nucleotide polymorphisms, gene expression, protein levels). We also searched for articles investigating the impact of psychotropic medications and other interventions on any of these markers.

RESULTS: We identified 25 articles among which individuals with MDD were overrepresented (n = 16). Telomerase was the most studied marker in terms of activity and gene expression, and few studies included analyses of other markers. Five studies out of seven reported an elevated telomerase activity in individuals with MDD. Seven of the twelve clinical trials identified, measured the impact of interventions in MDD (antidepressants, electroconvulsive therapy and yoga) with heterogeneous designs.

CONCLUSION: Literature suggests that telomerase activity is increased in MDD, with no major changes following exposure to antidepressants. Case-control and clinical intervention studies in BD and SCZ are too scarce to conclude. Furthermore, this review highlights that the complexity of telomere homeostasis has been overlooked in the literature thus limiting the understanding of the underlying molecular mechanisms. Future research should include larger and trans-nosographic samples, adopt more homogeneous designs for clinical trials, and perform more comprehensive analyses of the TL homeostasis markers.},
}

@article {pmid40227701,
year = {2025},
author = {Giunco, S and Petrara, MR and Indraccolo, S and Ciminale, V and De Rossi, A},
title = {Beyond Telomeres: Unveiling the Extratelomeric Functions of TERT in B-Cell Malignancies.},
journal = {Cancers},
volume = {17},
number = {7},
pages = {},
pmid = {40227701},
issn = {2072-6694},
abstract = {The reactivation of telomerase enables cancer cells to maintain the telomere length, bypassing replicative senescence and achieving cellular immortality. In addition to its canonical role in telomere maintenance, accumulating evidence highlights telomere-length-independent functions of TERT, the catalytic subunit of telomerase. These extratelomeric functions involve the regulation of signaling pathways and transcriptional networks, creating feed-forward loops that promote cancer cell proliferation, resistance to apoptosis, and disease progression. This review explores the complex mechanisms by which TERT modulates key signaling pathways, such as NF-κB, AKT, and MYC, highlighting its role in driving autonomous cancer cell growth and resistance to therapy in B-cell malignancies. Furthermore, we discuss the therapeutic potential of targeting TERT's extratelomeric functions. Unlike telomere-directed approaches, which may require prolonged treatment to achieve effective telomere erosion, inhibiting TERT's extratelomeric functions offers the prospect of rapid tumor-specific effects. This strategy could complement existing chemotherapeutic regimens, providing an innovative and effective approach to managing B-cell malignancies.},
}

@article {pmid40226919,
year = {2025},
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 = {Nucleic acids research},
volume = {53},
number = {7},
pages = {},
doi = {10.1093/nar/gkaf298},
pmid = {40226919},
issn = {1362-4962},
support = {R35GM151945/GM/NIGMS NIH HHS/United States ; 21-00580S//Grantová Agentura České Republiky/ ; },
mesh = {*Telomere/genetics ; Animals ; Humans ; *Hominidae/genetics ; *Genome ; *DNA/chemistry/genetics ; G-Quadruplexes ; Nucleotide Motifs ; Pan troglodytes/genetics ; Genome, Human ; Repetitive Sequences, Nucleic Acid ; },
abstract = {Non-canonical (non-B) DNA structures-e.g. bent DNA, hairpins, G-quadruplexes (G4s), 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. G4s and Z-DNA are enriched at promoters and enhancers, as well as at origins of replication. Repetitive sequences harbor more non-B DNA motifs than non-repetitive sequences, especially in the short arms of acrocentric chromosomes. 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.},
}

*Telomere/genetics
Animals
Humans
*Hominidae/genetics
*Genome
*DNA/chemistry/genetics
G-Quadruplexes
Nucleotide Motifs
Pan troglodytes/genetics
Genome, Human
Repetitive Sequences, Nucleic Acid

@article {pmid40225862,
year = {2025},
author = {Zhao, X and Kong, W and Luo, D and Xie, Y and Zhang, H},
title = {How telomere maintenance affects endometriosis development: a preliminary study.},
journal = {International journal of medical sciences},
volume = {22},
number = {8},
pages = {1944-1957},
pmid = {40225862},
issn = {1449-1907},
mesh = {Humans ; Female ; *Endometriosis/genetics/pathology ; Endometrium/pathology ; *Telomere Homeostasis/genetics ; *Telomere/genetics/metabolism ; Cell Proliferation/genetics/drug effects ; Middle Aged ; Telomerase/antagonists & inhibitors/genetics ; In Situ Hybridization, Fluorescence ; Adult ; Postmenopause ; Stromal Cells/pathology ; },
abstract = {Background: Endometriosis results in dysmenorrhea, dyspareunia, chronic pelvic pain and infertility in reproductive-age women. However, no effective treatment methods have been applied to the disease, and the pathogenesis of endometriosis is unclear. Purpose: This study was performed to investigate the association between telomere maintenance and endometriosis development. Materials and methods: The telomere length of the postmenopausal endometria, eutopic endometria and their matched ectopic lesions in the proliferative and secretory phases was detected using fluorescence in situ hybridization (FISH) methods, and the effect of telomere length maintenance on the proliferation of endometrial cells derived from endometriotic patients was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with BIBR1532 treatment. Then all of the telomere maintenance genes were extracted from the Telnet database, and bioinformatics analysis was performed to uncover the role of telomere maintenance genes in endometriosis development. Results: Telomere length was longer in endometriotic patients' eutopic endometria during the proliferative and secretory phases, and treatment with a telomerase inhibitor inhibited the proliferation of epithelial cells and stromal cells. Furthermore, the telomere maintenance genes were enriched in several hormone-related pathways, with several genes differentially expressed between normal endometria and endometria derived from endometriotic patients. The nomogram constructed based on telomere maintenance genes also displayed good predictive value. Conclusions: Telomere maintenance may contribute to the development of endometriosis, with several related genes involved.},
}

Humans
Female
*Endometriosis/genetics/pathology
Endometrium/pathology
*Telomere Homeostasis/genetics
*Telomere/genetics/metabolism
Cell Proliferation/genetics/drug effects
Middle Aged
Telomerase/antagonists & inhibitors/genetics
In Situ Hybridization, Fluorescence
Adult
Postmenopause
Stromal Cells/pathology

@article {pmid40224331,
year = {2025},
author = {Yu, H and Wang, H and Liang, X and Liu, J and Jiang, C and Chi, X and Zhi, N and Su, P and Zha, L and Gui, S},
title = {Telomere-to-telomere gap-free genome assembly provides genetic insight into the triterpenoid saponins biosynthesis in Platycodon grandiflorus.},
journal = {Horticulture research},
volume = {12},
number = {5},
pages = {uhaf030},
pmid = {40224331},
issn = {2662-6810},
abstract = {Platycodon grandiflorus has been widely used in Asia as a medicinal herb and food because of its anti-inflammatory and hepatoprotective properties. P. grandiflorus has important clinical value because of the active triterpenoid saponins in its roots. However, the biosynthetic pathway of triterpenoid saponins in P. grandiflorus remains unclear, and the related genes remain unknown. Therefore, in this study, we assembled a high-quality and integrated telomere-to-telomere P. grandiflorus reference genome and combined time-specific transcriptome and metabolome profiling to identify the cytochrome P450s (CYPs) responsible for the hydroxylation processes involved in triterpenoid saponin biosynthesis. Nine chromosomes were assembled without gaps or mismatches, and nine centromeres and 18 telomere regions were identified. This genome eliminated redundant sequences from previous genome versions and incorporated structural variation information. Comparative analysis of the P. grandiflorus genome revealed that P. grandiflorus underwent a core eudicot γ-WGT event. We screened 211 CYPs and found that tandem and proximal duplications may be crucial for the expansion of CYP families. We outlined the proposed hydroxylation steps, likely catalyzed by the CYP716A/72A/749A families, in platycodin biosynthesis and identified three PgCYP716A, seven PgCYP72A, and seven PgCYP749A genes that showed a positive correlation with platycodin biosynthesis. By establishing a T2T assembly genome, transcriptome, and metabolome resource for P. grandiflorus, we provide a foundation for the complete elucidation of the platycodins biosynthetic pathway, which consequently leads to heterologous bioproduction, and serves as a fundamental genetic resource for molecular-assisted breeding and genetic improvement of P. grandiflorus.},
}

@article {pmid40223756,
year = {2025},
author = {Fogel-Yaakobi, S and Gordon, I and Lavidor, M and Burstein, O and Salomon, N and Shai, D},
title = {The association between parenting quality and offspring's biological aging evaluated by telomere length: A systematic review and meta-analysis.},
journal = {Development and psychopathology},
volume = {},
number = {},
pages = {1-11},
doi = {10.1017/S095457942500015X},
pmid = {40223756},
issn = {1469-2198},
abstract = {There is widespread agreement that offspring are shaped by the parenting they receive in early childhood. This development is intertwined with offspring's biological functioning, evidenced by their telomeres length (TL)-a key biomarker of aging. Until recently, most studies have focused on the detrimental implications of negative parenting for offspring's TL. Contemporary research is oriented toward exploring the possible resilience-promoting effect of positive parenting on the biological aging of the offspring. We conducted a meta-analysis synthesizing the findings regarding the association between parenting quality and offspring's TL. It examines whether positive parenting delays aging processes and whether such processes are exacerbated by exposure to negative parenting. An analysis of 15 studies (k = 23; N = 3,599, M mean cohort's age = 15.5, SD = 17.5) revealed a significant association between positive parenting and offspring's longer TL (r = .16, 95% CI [.11, .20]). Negative parenting was associated with an increased risk of TL erosion (r = -.17, 95% CI [-.28, -.06]). Moreover, this negative association became more robust as offspring grew older (β = -.01, p < .001). Future investigations would benefit from probing associations between parental quality and offspring's development. Interventions fostering positive parenting might also scaffold these biological processes.},
}

@article {pmid40220459,
year = {2025},
author = {Kramna, D and Machaczka, O and Riedlova, P and Janulkova, T and Ostrizkova, S and Siemiatkowski, G and Osrodka, L and Krajny, E and Jirik, V},
title = {Exploring the relationship between air pollution and telomere length: Baseline findings from a comprehensive ambispective cohort study.},
journal = {International journal of hygiene and environmental health},
volume = {267},
number = {},
pages = {114577},
doi = {10.1016/j.ijheh.2025.114577},
pmid = {40220459},
issn = {1618-131X},
abstract = {BACKGROUND: Telomere length is a biomarker of cellular aging, influenced by various environmental and lifestyle factors. Air pollution is a known environmental stressor that may impact telomere dynamics. This study aimed to investigate the effect of age, lifetime exposure to air pollution, inflammatory parameters and selected lifestyle factors on telomere length.

METHODS: The study included 356 participants aged 35-65 living in two regions with varying pollution. Telomere length was measured using qPCR. Individual lifetime exposures to PM10, PM2.5, NO2, benzo(a)pyrene and benzene were calculated based on historical air quality data. Statistical analysis of age, pollution exposure, inflammatory parameters, and lifestyle factors on telomere length was performed using logistic regression and generalized linear models, with odds ratios calculated.

RESULTS: Unexpectedly, higher air pollutants lifetime exposures were associated with longer telomeres, particularly for PM10 51-55 μg/m[3] (OR = 5.67, p < 0.001), PM2.5 42-45 μg/m[3] (OR = 6.56, p < 0.001), B(a)P 6.9-8.3 ng/m[3] (OR = 5.25, p = 0.002), NO2 26-27 μg/m[3] (OR = 5.22, p = 0.001) and benzene 2.45-2.75 μg/m[3] (OR = 6.13, p < 0.001). Age significantly affected telomere length, with older individuals having shorter telomeres. Socioeconomic factors such as college education were positively associated with longer telomeres, while lifestyle factors did not show significant associations. IL-8 was identified as a significant inflammatory marker negatively associated with very long telomeres.

CONCLUSION: These baseline findings bring new perspective to the relationship between air pollution and telomere length. Contrary to traditional views, the results suggest potential adaptive responses, highlighting the need for further longitudinal research to explore telomere dynamics over time in conjunction with other factors.},
}

@article {pmid40220244,
year = {2025},
author = {Wang, Q and Liu, F and Cai, B and Wang, X and Deng, Y and Chen, T},
title = {Telomere Length, Brain Imaging-Derived Phenotypes, and Alzheimer's Disease: Mendelian Randomization Analysis.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
pmid = {40220244},
issn = {1559-1182},
support = {81060096//National Natural Science Foundation of China/ ; },
abstract = {Previous studies have reported a correlation between telomere length (TL) and Alzheimer's disease (AD); however, the specific biological mechanisms supporting this association remain unclear. We used two-sample Mendelian randomization (MR) to systematically explore the putative causal relationships between TL, brain imaging-derived phenotypes (IDPs), and AD, while further evaluating the mediating role of IDPs using both two-step MR and multivariable MR. In addition, we utilized several independent validation cohorts to repeat the analysis, further strengthening our inferences. The MR analysis showed that a longer TL was causally associated with a lower risk for AD (OR, 0.84; 95% CI, 0.75 to 0.93; P = 0.001). In addition, the subsequent two-step MR results indicate that nine brain IDPs partially mediate the effect of TL on AD. The inverse association of genetically predicted TL with AD was attenuated after adjusting for these IDPs in multivariable MR. Our study provides further evidence for the causal relationship between TL and AD, with IDPs potentially partially mediating this association. Therefore, telomere biology may be a potential pathway involved in AD development, and identifying the important role of telomeres can draw more attention to the development of telomere-related diagnostics, treatments, and AD therapies.},
}

@article {pmid40219969,
year = {2025},
author = {Nguyen, TT and Mazzucco, G and Kyriacou, E and Lunardi, T and Brandl, L and Ahmed, W and Doksani, Y and Lingner, J},
title = {Oxidative stress at telomeres triggers internal DNA loops, TRF1 dissociation, and TRF2-dependent R-loops.},
journal = {Nucleic acids research},
volume = {53},
number = {7},
pages = {},
doi = {10.1093/nar/gkaf285},
pmid = {40219969},
issn = {1362-4962},
support = {310030_214833/SNSF_/Swiss National Science Foundation/Switzerland ; 205601//National Centre of Competence in Research/ ; //Initial Training Network (ITN)/ ; 812829//European Commission Seventh Framework Programme/ ; 532515//Peter and Traudl Engelhorn Stiftung/ ; //Concern Foundation Conquer Cancer/ ; IG 28954//Associazione Italiana per la Ricerca sul Cancro/ ; //NAR/ ; },
mesh = {*Oxidative Stress/genetics ; *Telomeric Repeat Binding Protein 2/metabolism/genetics ; *Telomere/metabolism/genetics/chemistry ; *Telomeric Repeat Binding Protein 1/metabolism/genetics ; Humans ; *R-Loop Structures ; RNA, Long Noncoding/genetics/metabolism ; DNA Damage ; DNA/chemistry ; Shelterin Complex ; Vitamin K 3/pharmacology ; },
abstract = {Telomeres are the nucleoprotein structures at chromosome ends. Telomeres are particularly sensitive to oxidative stress, which can induce telomere damage, shortening, and premature cellular senescence. How oxidative damage influences telomere structure has not been defined. Here, we induce oxidative damage at telomeres using menadione, which damages mitochondria mimicking intrinsic oxidative stress. We find that oxidative stress induces at telomeres single-stranded DNA breaks, internal DNA loop structures, dissociation of the shelterin component TRF1, upregulation of TERRA long noncoding RNA, and increased DNA:RNA hybrid structures known as R-loops. R-loop formation is enhanced not only in cis at telomeres, which show increased TERRA transcription, but also in trans at telomeres at which TERRA transcription is not induced indicating post-transcriptional R-loop formation. Finally, we show that oxidative damage induced R-loop formation requires TRF2, whose R-loop promoting activity may be unleashed upon TRF1 dissociation from telomeres. Altogether, our findings uncover in response to oxidative stress major remodelling of telomeric DNA, RNA, and shelterin complexes, and they unravel a physiological role of TRF2's ability to stimulate TERRA R-loop formation. We propose that the identified structural changes may facilitate DNA damage signalling and repair pathways to maintain telomere integrity during development and aging.},
}

*Oxidative Stress/genetics
*Telomeric Repeat Binding Protein 2/metabolism/genetics
*Telomere/metabolism/genetics/chemistry
*Telomeric Repeat Binding Protein 1/metabolism/genetics
Humans
*R-Loop Structures
RNA, Long Noncoding/genetics/metabolism
DNA Damage
DNA/chemistry
Shelterin Complex
Vitamin K 3/pharmacology

@article {pmid40218281,
year = {2025},
author = {Hong, Y and Lee, JM and Lee, C and Na, D and Jung, J and Ahn, A and Yoo, JW and Lee, JW and Chung, NG and Kim, M and Kim, Y},
title = {Telomere Length and Genetic Variations in Acquired Pediatric Aplastic Anemia: A Flow-FISH Study in Korean Patients.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {7},
pages = {},
doi = {10.3390/diagnostics15070931},
pmid = {40218281},
issn = {2075-4418},
support = {22202MFDS127//Ministry of Food and Drug Safety/ ; },
abstract = {Background: Aplastic anemia (AA) is a rare bone marrow failure syndrome characterized by notably short telomere length, which is associated with treatment responses. In this study, we measured telomere lengths in Korean pediatric AA patients using flow-fluorescence in situ hybridization (Flow-FISH) and explored their shortening in relation to disease characteristics, genetic conditions and patient outcomes. Methods: We analyzed peripheral blood samples from 75 AA patients and 101 healthy controls. Telomere lengths were measured using Flow-FISH, and relative telomere length (RTL) and delta RTL assessments were conducted. Genetic evaluations included karyotyping, chromosome breakage tests and clinical exome sequencing (CES) to identify inherited bone marrow failure syndrome (IBMFS)-associated genetic variants. Results: Telomere lengths in AA patients were significantly lower than those of age-adjusted healthy controls. Patients receiving immunosuppressive therapy tended to have long telomeres, as indicated by high delta RTL values. Patients with genetic abnormalities, including karyotype abnormalities (n = 2) and genetic variants (n = 11) such as carrier genes of IBMFS or variants of unclear significance, showed significantly short telomere lengths. Conclusions: This study reinforces the importance of telomere length as a biomarker in acquired AA. Utilizing Flow-FISH, we were able to accurately measure telomere lengths and establish confidence in this method as an appropriate laboratory test. We found significant reduction in telomere lengths in AA patients, and importantly, longer telomeres were correlated with better outcomes in immunosuppressive therapy. Additionally, our genetic analysis underscored the relevance of variants in IBMFS-associated genes to the pathophysiology of short telomeres.},
}

@article {pmid40215816,
year = {2025},
author = {Wang, J and Zhao, Y and Wei, Y and Li, T and Huang, T and Pan, T and Wu, J and Bai, L and Zhu, D and Zhao, Q and Wang, Z and Feng, F and Zhou, X},
title = {Mai-wei-yang-fei decoction protects against pulmonary fibrosis by reducing telomere shortening and inhibiting AECII senescence via FBW7/TPP1 regulation.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {141},
number = {},
pages = {156682},
doi = {10.1016/j.phymed.2025.156682},
pmid = {40215816},
issn = {1618-095X},
abstract = {BACKGROUND: Pulmonary fibrosis (PF) is a fatal disease associated with ageing. The senescence of alveolar epithelial type II cells (AECIIs) can drive PF. Therefore, reducing AECII senescence is a promising treatment to prevent PF. Mai-wei-yang-fei decoction (MWYF) has shown significant clinical efficacy in the treatment of patients with PF. However, its mechanism of action remains unclear.

PURPOSE: To investigate the role and underlying mechanism of MWYF in protecting against PF.

METHODS: The main chemical components of MWYF were identified using UPLC-MS. The mouse and in vitro cell models of PF were established using BLM. Micro-CT, H&E, and Masson staining were used to observe the protective effect of MWYF on mice with PF. Immunohistochemistry, β-galactosidase staining, and IF-FISH were used to observe the inhibitory effect of MWYF on senescence and telomere shortening in mouse lung tissue or A549 cells. The Transwell assay and cell co-culture method were used to observe the effect of MWYF on the migration and activation of lung fibroblasts by inhibiting AECII senescence. Finally, lentiviral vector was used to overexpress FBW7 gene in A549 cells in vitro to observe the mechanism pathway of MWYF inhibiting AECII senescence and telomere shortening.

RESULTS: MWYF was effective in protecting against bleomycin (BLM)-induced PF. Furthermore, MWYF alleviated cellular senescence by reducing the DNA damage response (DDR) and shortening of the telomere in AECⅡs in mouse lung tissues. Mechanistically, genes related to telomere disorders were detected in BLM-induced PF mouse models using q-PCR. MWYF mainly inhibited telomere shortening by regulating FBW7 and reducing the degradation of TPP1. In vitro, MWYF reduced BLM-induced senescence in A549 cells, as well as proliferation and migration of MRC5 cells, by inhibiting DDR and telomere shortening via regulation of the FBW7/TPP1 axis.

CONCLUSION: MWYF is a potential therapeutic agent against PF, as it inhibits telomere shortening and reduces AECII senescence by regulating FBW7/TPP1.},
}

@article {pmid40215293,
year = {2025},
author = {Sanz-Moreno, A and Becker, L and Xie, K and da Silva-Buttkus, P and Dragano, NRV and Aguilar-Pimentel, A and Amarie, OV and Calzada-Wack, J and Kraiger, M and Leuchtenberger, S and Seisenberger, C and Marschall, S and Rathkolb, B and Scifo, E and Liu, T and Thanabalasingam, A and Sanchez-Vazquez, R and Martinez, P and Blasco, MA and Savage, SA and Fuchs, H and Ehninger, D and Gailus-Durner, V and de Angelis, MH},
title = {Loss of Ten1 in mice induces telomere shortening and models human dyskeratosis congenita.},
journal = {Science advances},
volume = {11},
number = {15},
pages = {eadp8093},
pmid = {40215293},
issn = {2375-2548},
mesh = {Animals ; *Dyskeratosis Congenita/genetics/pathology/metabolism ; Mice ; *Telomere Shortening/genetics ; Disease Models, Animal ; Mice, Knockout ; Humans ; Apoptosis/genetics ; Tumor Suppressor Protein p53/metabolism ; Telomere/genetics/metabolism ; *Telomere-Binding Proteins/genetics/deficiency ; Signal Transduction ; },
abstract = {Telomere length regulation is essential for genome stability as short telomeres can trigger cellular senescence and apoptosis constituting an integral aspect of biological aging. Telomere biology disorders (TBDs) such as dyskeratosis congenita (DC) are rare, inherited diseases with known mutations in at least 16 different genes encoding components of the telomere maintenance complexes. The precise role of TEN1, part of the CST complex (CTC1, STN1, and TEN1), and the consequences of its loss of function in vivo are not yet known. We investigated the first viable murine model of Ten1 deficiency created by CRISPR-Cas9-mediated exon 3 deletion. Ten1 homozygous knockout mice present with telomere attrition, short life span, skin hyperpigmentation, aplastic anemia, and cerebellar hypoplasia. Molecular analyses revealed a reduction of proliferating cells, increased apoptosis, and stem cell depletion with activation of the p53/p21 signaling pathway. Our data demonstrate that Ten1 deficiency causes telomere shortening and associates with accelerated aging.},
}

Animals
*Dyskeratosis Congenita/genetics/pathology/metabolism
Mice
*Telomere Shortening/genetics
Disease Models, Animal
Mice, Knockout
Humans
Apoptosis/genetics
Tumor Suppressor Protein p53/metabolism
Telomere/genetics/metabolism
*Telomere-Binding Proteins/genetics/deficiency
Signal Transduction

@article {pmid40214910,
year = {2025},
author = {Xu, Z and Wang, H and Tian, H and Wang, W and Hua, D},
title = {Identification of telomere maintenance-driven molecular subtypes in hepatocellular carcinoma: implications for prognosis and targeted therapy via KPNA2.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {516},
pmid = {40214910},
issn = {2730-6011},
support = {WX18IVJN017//Wuxi Municipal Bureau on Science and Technology/ ; },
abstract = {BACKGROUND: Telomere maintenance (TM) plays a pivotal role in regulating the pathogenesis of hepatocellular carcinoma (HCC) and is crucial for defining the clinical characteristics of patients. Despite previous publications highlighting the correlation between individual TM-related genes and HCC, comprehensive exploration and systematic analysis of these genes are still lacking.

METHODS: Through the analysis of transcriptome data, we identified two distinct clusters (termed telomere maintenance-associated clusters, or TCs) that exhibited marked heterogeneity in clinical traits and the tumor microenvironment. Following this, we conducted an exhaustive screening process to select 15 prognostic genes related to telomere maintenance and developed corresponding TM scores for these genes. Additionally, we rigorously validated the expression and oncogenic functions of karyopherin subunit alpha 2 (KPNA2) in both HCC tissues and cell lines.

RESULTS: TC1 demonstrated a significant correlation with cellular differentiation and the fatty acid metabolism pathway, while also predicting a low tumor mutation burden (TMB) alongside favorable prognostic outcomes. In contrast, TC2 was intricately linked to TM, cell cycle regulation, and DNA repair. When examining the relationship between TMB and overall survival rates. Notably, substantial heterogeneity was observed among the various TCs. Furthermore, KPNA2 exhibited upregulation and has the potential to enhance HCC proliferation and migration.

CONCLUSION: In summary, through the integration of bioinformatics and functional experimentation, we have delineated two distinct molecular classifications predicated on their association with TM-related genes in HCC. This groundbreaking discovery holds the potential to introduce innovative concepts and novel biomarkers into clinical practice.},
}

@article {pmid40210914,
year = {2025},
author = {Ma, L and Zeng, X and Wang, J and Xiong, H and Yu, Y and Liu, H and Yang, QY and Yang, R and Yang, X},
title = {Telomere-to-telomere gapless genome assembly of Triplophysa yaopeizhii.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {597},
pmid = {40210914},
issn = {2052-4463},
support = {31971421//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {*Telomere ; *Genome ; Animals ; Tibet ; },
abstract = {The genus Triplophysa exhibits remarkable adaptability to the unique environment found at the Qinghai-Tibet Plateau (QTP). Higher quality genomes are helpful to the study of the adaptability to the extreme environment in the plateau. This study utilized PacBio HiFi, Ultra-long ONT, and Hi-C sequencing of Triplophysa yaopeizhii to construct the first telomere-to-telomere (T2T) gapless genome assembly of the genus Triplophysa. The genome size is 671.58 Mb, with a contig N50 length of 26.04 Mb. The sequences were anchored onto 25 chromosomes with all centromeres and telomeres. Furthermore, 293.98 Mb (43.77%) of repetitive sequences and 26,487 protein-coding genes were identified. Comparative analyses with the genomes of closely related species demonstrated high completeness, continuity, and accuracy of the genome. The genomic quality was further substantiated by the QV of 31.82 with 96.60% of BUSCO. This study provides a valuable genetic resource of the genus Triplophysa and serves as an essential reference for elucidating the adaptive genetic mechanisms of plateau fish to the high altitude.},
}

*Telomere
*Genome
Animals
Tibet

@article {pmid40210446,
year = {2025},
author = {Coulon, S},
title = {Shedding Light on Telomere Replication, Insights from the Fission Yeast Schizosaccharomyces pombe.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041704},
pmid = {40210446},
issn = {1943-0264},
abstract = {Over the years, the fission yeast has become a reference model for telomere biology studies as this organism shares with mammals a highly conserved telomere composition. Here, we highlight the latest discoveries in telomere replication in fission yeast and show how this research brings new insights into the understanding of the replication and maintenance of mammalian telomeres.},
}

@article {pmid40210445,
year = {2025},
author = {Gao, J and Pickett, HA},
title = {Therapeutic Opportunities for Alternative Lengthening of Telomeres (ALT) Cancers.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041691},
pmid = {40210445},
issn = {1943-0264},
abstract = {Cancers that rely on activation of the alternative lengthening of telomeres (ALT) pathway predominantly affect children and adolescents, and are associated with catastrophic outcomes due to a lack of clinically effective, targeted therapeutics. The exponential rise in our understanding of the ALT mechanism in recent years has led to the identification of many therapeutic targets and strategies for patients suffering from these cancers. These include targeting replication fork remodelers and DNA damage response pathways to exacerbate telomere-specific replication stress, inhibiting ALT-mediated telomere synthesis to induce telomere dysfunction, and using oncolytic viruses to selectively kill ALT cancer cells. Herein we will evaluate the advantages and shortfalls of these therapeutic strategies, and discuss current diagnostic opportunities that are a necessary accompaniment to direct ALT therapeutics to patients.},
}

@article {pmid40209537,
year = {2025},
author = {Sánchez-González, JL and Sánchez-Gil, A and Vicente-Muñoz, E and Navarro-López, V and Martín-Vallejo, J and Perez, J},
title = {Pharmacological interventions and telomere length in patients with schizophrenia and bipolar disorder: A systematic review and meta-analysis.},
journal = {Journal of psychiatric research},
volume = {186},
number = {},
pages = {33-49},
doi = {10.1016/j.jpsychires.2025.04.001},
pmid = {40209537},
issn = {1879-1379},
abstract = {BACKGROUND: Patients with schizophrenia and bipolar disorder have a life expectancy shorter than the general population. Cellular mechanisms underlying accelerated ageing, such as telomere shortening, may contribute to this premature mortality. We aimed to provide a comprehensive evaluation of the impact of pharmacological treatments for schizophrenia and bipolar disorder on telomere length.

METHOD: PRISMA/MOOSE systematic review and meta-analysis from inception to June 2024. PubMed, Cochrane Library, SCOPUS, Web of Science, Embase and PsycInfo databases were searched for eligible studies. Methodological quality and risk of bias were evaluated with the Newcastle-Ottawa Scale and the Risk of Bias In Non-randomized Studies - of Exposure (ROBINS-E) respectively.

RESULTS: An initial search retrieved 2133 articles. However, only 28 studies were finally included in qualitative synthesis and 19 in meta-analysis. All studies identified in the review were observational. Random-effects model analysis was used to quantify the difference in telomere length between cohorts of patients with schizophrenia or bipolar disorder and healthy control groups. The meta-analysis confirmed that telomere length was shorter in patients with schizophrenia (SMD = 0.35, 95 % CI 0.11 to 0.60; p=<0.0001) and bipolar disorder (SMD = 0.18, 95 % CI -0.04 to 0.39 p=<0.0001) than in healthy controls. This difference was not modified by predominant treatment with either lithium (SMD = 0.37, 95 % CI 0.04 to 0.69; p=<0.0001) or antipsychotics (SMD = 0.20, 95 % CI 0.02 to 0.38; p=<0.0001) at cohort level across studies.

CONCLUSIONS: Patients with schizophrenia or bipolar disorder have shorter telomeres than healthy populations. Predominant treatment with lithium or antipsychotics at cohort level did not have an impact on such shortening difference.

REGISTRATION: PROSPERO CRD42024598840.},
}

@article {pmid40195562,
year = {2025},
author = {Liu, S and Li, K and Dai, X and Qin, G and Lu, D and Gao, Z and Li, X and Song, B and Bian, J and Ren, D and Liu, Y and Chen, X and Xu, Y and Liu, W and Yang, C and Liu, X and Chen, S and Li, J and Li, B and He, H and Deng, XW},
title = {A telomere-to-telomere genome assembly coupled with multi-omic data provides insights into the evolution of hexaploid bread wheat.},
journal = {Nature genetics},
volume = {57},
number = {4},
pages = {1008-1020},
pmid = {40195562},
issn = {1546-1718},
mesh = {*Triticum/genetics ; *Genome, Plant/genetics ; *Telomere/genetics ; *Polyploidy ; *Evolution, Molecular ; Centromere/genetics ; DNA Transposable Elements/genetics ; Chromosomes, Plant/genetics ; Transcriptome ; Bread ; Multiomics ; },
abstract = {The complete assembly of vast and complex plant genomes, like the hexaploid wheat genome, remains challenging. Here we present CS-IAAS, a comprehensive telomere-to-telomere (T2T) gap-free Triticum aestivum L. genome, encompassing 14.51 billion base pairs and featuring all 21 centromeres and 42 telomeres. Annotation revealed 90.8 Mb additional centromeric satellite arrays and 5,611 rDNA units. Genome-wide rearrangements, centromeric elements, transposable element expansion and segmental duplications were deciphered during tetraploidization and hexaploidization, providing a comprehensive understanding of wheat subgenome evolution. Among them, transposable element insertions during hexaploidization greatly influenced gene expression balances, thus increasing the genome plasticity of transcriptional levels. Additionally, we generated 163,329 full-length cDNA sequences and proteomic data that helped annotate 141,035 high-confidence protein-coding genes. The complete T2T reference genome (CS-IAAS), along with its transcriptome and proteome, represents a significant step in our understanding of wheat genome complexity and provides insights for future wheat research and breeding.},
}

*Triticum/genetics
*Genome, Plant/genetics
*Telomere/genetics
*Polyploidy
*Evolution, Molecular
Centromere/genetics
DNA Transposable Elements/genetics
Chromosomes, Plant/genetics
Transcriptome
Bread
Multiomics

@article {pmid40191747,
year = {2025},
author = {Zhu, Q and Zhang, T and Sun, Y and Liu, J and Liu, Z and Wei, F and Jin, Y},
title = {Association of metallic elements with telomere length in children with autism spectrum disorder.},
journal = {PeerJ},
volume = {13},
number = {},
pages = {e19174},
pmid = {40191747},
issn = {2167-8359},
mesh = {Humans ; *Autism Spectrum Disorder/blood/genetics ; Male ; Child ; Female ; *Metals/blood ; Child, Preschool ; *Telomere ; Manganese/blood ; Magnesium/blood ; Zinc/blood ; Copper/blood ; Iron/blood ; Case-Control Studies ; Calcium/blood ; *Telomere Homeostasis ; },
abstract = {BACKGROUND: Imbalances in metal elements have been identified as a potential risk factor for autism spectrum disorder (ASD), and shortened telomere length (TL) is commonly observed in children with ASD. Metal elements may influence telomere homeostasis through oxidative stress, which could contribute to the pathogenesis of autism. However, studies examining the combined effects of metal elements on TL in children with ASD are limited. To fill the gaps in the current literature, this study aimed to investigate the relationship between six metallic elements: manganese (Mn), copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), and iron (Fe), and TL in the whole blood of children with ASD.

METHODS: A total of 83 children with ASD and 95 typically developing children were recruited. TL was measured using digital PCR, while metal concentrations were assessed using inductively coupled plasma mass spectrometry (ICP-MS). Linear regression analysis was first conducted to explore the correlations between metal elements and TL in both groups. Additionally, Bayesian Kernel Machine Regression (BKMR) was used to further examine the combined effects and potential interactions of these metals on TL in the ASD group.

RESULTS: In the ASD group, Ca was found to have a protective effect on TL (β = 0.07, 95% CI [0.01-0.13], P = 0.027). In contrast, Mg showed a protective effect on TL in the control group (β = 0.10, 95% CI [0.01-0.18], P = 0.027). The BKMR model revealed a significant positive combined effect of the metal mixtures on TL in the ASD group, with Ca having the largest individual effect (PIP = 0.45). Further analysis indicated that increases in Zn and Mn concentrations from the 25th to the 75th percentile were negatively correlated with TL, while higher concentrations of Cu, Ca, Mg, and Fe were positively associated with TL. No significant interactions among the metals were observed.

CONCLUSIONS: This study suggests a potential link between metallic elements and TL in children with ASD, with Ca having the greatest effect. Our findings highlight the potential benefits of appropriate calcium supplementation as a protective strategy for lengthening telomeres in children with ASD, emphasizing the importance of early nutritional interventions to improve their overall health.},
}

Humans
*Autism Spectrum Disorder/blood/genetics
Male
Child
Female
*Metals/blood
Child, Preschool
*Telomere
Manganese/blood
Magnesium/blood
Zinc/blood
Copper/blood
Iron/blood
Case-Control Studies
Calcium/blood
*Telomere Homeostasis

@article {pmid40191408,
year = {2025},
author = {Chik, HYJ and Sibma, A and Mannarelli, ME and Dos Remedios, N and Simons, MJP and Burke, T and Dugdale, HL and Schroeder, J},
title = {Heritability and age-dependent changes in genetic variation of telomere length in a wild house sparrow population.},
journal = {Evolution letters},
volume = {9},
number = {2},
pages = {209-220},
pmid = {40191408},
issn = {2056-3744},
abstract = {Telomere length (TL) and/or its rate of change are popular biomarkers of senescence, as telomere dynamics are linked with survival and lifespan. However, the evolutionary potential of telomere dynamics has received mixed support in natural populations. To better understand how telomere dynamics evolve, it is necessary to quantify genetic variation in TL and how such variation changes with age. Here, we analyzed 2,083 longitudinal samples from 1,225 individuals across 16 years, collected from a wild, insular house sparrow (Passer domesticus) population with complete life history and genetic relatedness data. Using a series of "animal" models, we confirmed that TL changes with age, reflecting senescence in this population. We found TL to be repeatable (14.0%, 95% CrI: 9.1%-19.9%) and heritable (12.3%, 95% CrI: 7.5%-18.2%); and detected a genotype-by-age interaction, meaning that genotypes differ in their rate of change of TL, and additive genetic variance increases at older ages. Our findings provide empirical evidence from a wild population that supports hypotheses explaining the evolution of senescence and highlight the importance of telomere dynamics as a key biomarker of body physiology for the evolution of senescence.},
}

@article {pmid40186152,
year = {2025},
author = {Etzel, L and Ye, Q and Apsley, AT and Chiaro, C and Petri, LE and Kozlosky, J and Propper, C and Mills-Koonce, R and Short, SJ and Garrett-Peters, P and Shalev, I},
title = {Maternal telomere length and oxidative stress in pregnancy: cross-sectional analysis with an exploratory examination of systemic inflammation.},
journal = {BMC pregnancy and childbirth},
volume = {25},
number = {1},
pages = {395},
pmid = {40186152},
issn = {1471-2393},
support = {R01 HD091148/HD/NICHD NIH HHS/United States ; R01 HD091148/HD/NICHD NIH HHS/United States ; R01 HD091148/HD/NICHD NIH HHS/United States ; R01 NR019610/NR/NINR NIH HHS/United States ; R01 NR019610/NR/NINR NIH HHS/United States ; },
mesh = {Humans ; Female ; Pregnancy ; *Oxidative Stress/physiology ; Adult ; Cross-Sectional Studies ; *Inflammation/blood/metabolism ; Young Adult ; Adolescent ; Middle Aged ; Interleukin-6/blood ; *Telomere ; *Telomere Homeostasis ; Saliva/chemistry ; Pregnancy Trimester, Second ; Pregnancy Trimester, Third ; },
abstract = {BACKGROUND: Telomere length (TL) is a marker of cellular aging associated with risk for age-related diseases and is known to be influenced by various factors, including oxidative stress and inflammation, in the contexts of stress and aging. The physiological demands of pregnancy may impact maternal TL, though research in this area is sparse. We tested oxidative stress and explored inflammation as predictors of maternal TL in a sample of women with normative pregnancies.

METHODS: Participants (N = 88, aged 18 to 46 years, 25% non-Hispanic Black, 65% non-Hispanic White) were recruited during their 2nd or 3rd trimester. TL was measured using saliva via qPCR as absolute TL. Oxidative stress was derived from principal component analysis of selected metabolites measured via urinary metabolomics. Inflammation was quantified as total IL-6 in serum. Hypotheses were tested with stepwise generalized linear models.

RESULTS: Longer TL was predicted by higher oxidative stress (b = 0.20 ± 0.08; P =.019), controlling for maternal age, gestational age, race/ethnicity, maternal BMI, and income-to-needs ratio. In our exploratory analysis, longer TL was also predicted by higher IL-6 (b = 0.76 ± 0.20; P =.0003) controlling for covariates. There was no significant interaction between oxidative stress and inflammation predicting TL.

CONCLUSION: Our findings suggest that in normative pregnancies, both oxidative stress and inflammation are independently associated with longer telomere length. Given that these associations are inconsistent with the role of oxidative stress and inflammation on telomere biology in non-pregnant samples, future work should aim to replicate these findings in both normal and high-risk pregnancies, explore mechanisms underlying these associations using longitudinal designs, and examine how these relationships influence maternal and fetal health.},
}

Humans
Female
Pregnancy
*Oxidative Stress/physiology
Adult
Cross-Sectional Studies
*Inflammation/blood/metabolism
Young Adult
Adolescent
Middle Aged
Interleukin-6/blood
*Telomere
*Telomere Homeostasis
Saliva/chemistry
Pregnancy Trimester, Second
Pregnancy Trimester, Third

@article {pmid40186023,
year = {2025},
author = {Jiang, H and Inoue, S and Hatakeyama, J and Liu, P and Zhao, T and Zhang, Y and Liu, B and He, C and Moriyama, H},
title = {Effects of aging and resistance exercise on muscle strength, physiological properties, longevity proteins, and telomere length in SAMP8 mice.},
journal = {Biogerontology},
volume = {26},
number = {2},
pages = {88},
pmid = {40186023},
issn = {1573-6768},
support = {19H04050//Japan Society for the Promotion of Science/ ; 19H04050//Japan Society for the Promotion of Science/ ; 19H04050//Japan Society for the Promotion of Science/ ; 19H04050//Japan Society for the Promotion of Science/ ; 19H04050//Japan Society for the Promotion of Science/ ; 19H04050//Japan Society for the Promotion of Science/ ; 19H04050//Japan Society for the Promotion of Science/ ; 19H04050//Japan Society for the Promotion of Science/ ; 19H04050//Japan Society for the Promotion of Science/ ; },
mesh = {Animals ; Mice ; *Aging/physiology/genetics/metabolism ; *Muscle Strength/physiology ; *Muscle, Skeletal/physiology/metabolism ; *Longevity/physiology ; Sirtuin 1/metabolism ; *Resistance Training ; *Physical Conditioning, Animal/physiology ; TOR Serine-Threonine Kinases/metabolism ; Male ; AMP-Activated Protein Kinases/metabolism ; *Telomere/metabolism ; *Telomere Homeostasis ; },
abstract = {Skeletal muscle aging, characterized by progressive declines in muscle mass and strength, correlates with reduced quality of life and increased mortality. Resistance exercise is known to be critical for maintaining skeletal muscle health. This study investigated the effects of aging and resistance exercise on muscle strength, physiological properties, longevity proteins, and telomere length in mice. Twenty-eight-week-old senescence-accelerated mouse prone 8 (SAMP8) mice were used as a model for muscle aging, with senescence-accelerated mouse resistant 1 (SAMR1) mice serving as healthy controls. The mice underwent a 12-week regimen of ladder-climbing training, a form of resistance exercise, performed three days per week. After the training, muscle strength and muscle weight were measured. Levels of the longevity proteins adenosine monophosphate-activated kinase (AMPK), mammalian target of rapamycin (mTOR), and sirtuin 1 (SIRT1) were assessed via western blotting, and telomere length was evaluated by qPCR. SAMP8 mice exhibited significantly lower muscle mass and strength than SAMR1 mice, while resistance exercise attenuated these deficits in SAMP8 mice. SAMP8 mice showed elevated AMPK phosphorylation and SIRT1 levels compared to SAMR1 mice; resistance exercise normalized AMPK phosphorylation levels to approximate those of SAMR1 mice. mTOR activity was significantly reduced in SAMP8 mice but tended to be restored by resistance exercise. Telomere length remained unchanged in SAMP8 mice after resistance exercise compared to their sedentary controls. In conclusion, aging reduces muscle function and disrupts levels of longevity proteins. Resistance exercise mitigates these effects by improving muscle function and restoring molecular balance.},
}

Animals
Mice
*Aging/physiology/genetics/metabolism
*Muscle Strength/physiology
*Muscle, Skeletal/physiology/metabolism
*Longevity/physiology
Sirtuin 1/metabolism
*Resistance Training
*Physical Conditioning, Animal/physiology
TOR Serine-Threonine Kinases/metabolism
Male
AMP-Activated Protein Kinases/metabolism
*Telomere/metabolism
*Telomere Homeostasis

@article {pmid40181549,
year = {2025},
author = {Zhang, YM and Wei, ZY and Yang, CA and Feng, XY and Wang, Y and Li, SX and Sun, XQ and Shao, ZQ and Xue, JY},
title = {A telomere-to-telomere genome assembly for greater yam (Dioscorea alata).},
journal = {Plant communications},
volume = {},
number = {},
pages = {101326},
doi = {10.1016/j.xplc.2025.101326},
pmid = {40181549},
issn = {2590-3462},
}

@article {pmid40180259,
year = {2025},
author = {Hautekiet, P and Nawrot, TS and Martens, DS and Bijnens, EM and De Keersmaecker, SCJ and Van der Heyden, J and De Clercq, EM and Saenen, ND},
title = {Recent and chronic ambient air pollution exposure in association with telomere length and mitochondrial DNA content in the general population.},
journal = {Environmental research},
volume = {276},
number = {},
pages = {121525},
doi = {10.1016/j.envres.2025.121525},
pmid = {40180259},
issn = {1096-0953},
abstract = {Telomere length (TL) and mitochondrial DNA content (mtDNAc) are biomarkers of biological ageing that respond to multiple stressors, including air pollution. Despite growing research interest, the association between recent and chronic air pollution and these biomarkers in the general population remains unclear. This study investigated the association between air pollution exposure and TL and mtDNAc using data from the 2018 Belgian Health Examination Survey. Multivariable adjusted generalised linear mixed models were applied to assess the exposure to nitrogen dioxide (NO2), fine particulate matter ≤2.5 μm (PM2.5), and black carbon (BC) over 1-week (recent) and 1-year (chronic) periods prior to participation, estimated with a high-resolution spatiotemporal model. Leucocyte TL and mtDNAc were measured using qPCR. A total of 756 participants (mean age 50.6 years, 49.9 % women) were included in the study. Recent exposure to PM2.5 was associated with a 2.40 % (95 % CI: 0.16, 4.69; p = 0.036) longer TL per IQR increment. Trends of lower mtDNAc were observed for chronic exposure to BC (-3.11, 95 % CI: -6.19, 0.07; p = 0.055) and NO2 (-4.02, 95 % CI: -8.22, 0.36; p = 0.072) per IQR increment. No significant associations were observed between chronic air pollution and TL or recent exposure and mtDNAc. These results suggest an inverse association between chronic air pollution and mtDNAc, and a positive association between recent exposure and TL, providing insight into the time-sensitive and air pollutant effects on ageing biomarkers.},
}

@article {pmid40179146,
year = {2025},
author = {Sande, CM and Chen, S and Mitchell, DV and Lin, P and Abraham, DM and Cheng, JM and Gebhard, T and Deolikar, RJ and Freeman, C and Zhou, M and Kumar, S and Bowman, M and Bowman, RL and Zheng, S and Munkhbileg, B and Chen, Q and Stanley, NL and Guo, K and Lapite, A and Hausler, R and Taylor, DM and Corines, J and Morrissette, JJ and Lieberman, DB and Yang, G and Shestova, O and Gill, S and Zheng, J and Smith-Simmer, K and Banaszak, LG and Shoger, KN and Reinig, EF and Peterson, M and Nicholas, P and Walne, AJ and Dokal, I and Rosenheck, JP and Oetjen, KA and Link, DC and Gelman, AE and Reilly, CR and Dutta, R and Lindsley, RC and Brundige, KJ and Agarwal, S and Bertuch, AA and Churpek, JE and Tague, LK and Johnson, FB and Olson, TS and Babushok, DV},
title = {ATM-dependent DNA damage response constrains cell growth and drives clonal hematopoiesis in telomere biology disorders.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI181659},
pmid = {40179146},
issn = {1558-8238},
abstract = {Telomere biology disorders (TBD) are genetic diseases caused by defective telomere maintenance. TBD patients often develop bone marrow failure and have an increased risk of myeloid neoplasms. To better understand the factors underlying hematopoietic outcomes in TBD, we comprehensively evaluated acquired genetic alterations in hematopoietic cells from 166 pediatric and adult TBD patients. 47.6% of patients (28.8% of children, 56.1% of adults) had clonal hematopoiesis. Recurrent somatic alterations involved telomere maintenance genes (7.6%), spliceosome genes (10.4%, mainly U2AF1 p.S34), and chromosomal alterations (20.2%), including 1q gain (5.9%). Somatic variants affecting the DNA damage response (DDR) were identified in 21.5% of patients, including 20 presumed loss-of-function variants in ATM. Using multimodal approaches, including single-cell sequencing, assays of ATM activation, telomere dysfunction-induced foci analysis, and cell growth assays, we demonstrate telomere dysfunction-induced activation of ATM-dependent DDR pathway with increased senescence and apoptosis in TBD patient cells. Pharmacologic ATM inhibition, modeling the effects of somatic ATM variants, selectively improved TBD cell fitness by allowing cells to bypass DDR-mediated senescence without detectably inducing chromosomal instability. Our results indicate that ATM-dependent DDR induced by telomere dysfunction is a key contributor to TBD pathogenesis and suggest dampening hyperactive ATM-dependent DDR as a potential therapeutic intervention.},
}

@article {pmid40176558,
year = {2025},
author = {Cheng, S and Wang, H},
title = {Aging and atrial fibrillation: Role of telomere dysfunction.},
journal = {Chinese medical journal},
volume = {},
number = {},
pages = {},
pmid = {40176558},
issn = {2542-5641},
}

@article {pmid40172909,
year = {2025},
author = {Gomes, D and Zhao, J and Malovichko, MV and Haberzettl, P and Conklin, DJ and O'Toole, TE},
title = {Inhalation of Concentrated Ambient PM2.5 (CAP) Promotes Inactivation of Telomerase Reverse Transcriptase, Telomere Shortening, and Senescence of Multiple Cell Types in Mice.},
journal = {Toxicological sciences : an official journal of the Society of Toxicology},
volume = {},
number = {},
pages = {},
doi = {10.1093/toxsci/kfaf045},
pmid = {40172909},
issn = {1096-0929},
abstract = {While some prior studies have identified an association between exposure to fine air borne particulate matter (PM2.5) and indices of aging, the extent of these associations and their underlying mechanisms are uncertain. In this study we exposed male C57BL/6J mice to filtered air and concentrated ambient PM2.5 (CAP) and assessed two common hallmarks of aging, telomere shortening and a senescent phenotype. Of the cell types examined, peripheral blood mononuclear cells (PBMNCs), endothelial progenitor cells (EPCs), and bone marrow-derived c-kit+ cells, all three demonstrated shortened telomeres when isolated from CAP-exposed mice as compared with cells derived from filtered air controls. We found that telomere attrition in PBMNCs and EPCs was mitigated in those CAP-exposed mice receiving water supplemented with the antioxidant, carnosine and was reversible in PBMNCs, but not EPCs, when CAP-exposed mice were allowed to recover in normal air conditions. Telomere attrition in these cell types appeared to result from the attenuated catalytic activity of telomerase reverse transcriptase (Tert). PBMNCs and EPCs obtained from CAP-exposed mice also displayed increased β-galactosidase activity and expression of genes characteristic of the senescence-activated secretory phenotype. Of PBMNC subtypes, the increase of β-galactosidase activity was greatest in CD8+ T-cells. Our results suggest that the pro-aging effects of PM2.5 impacts multiple cell types, including bone marrow stem cells, and that telomere attrition resulted from attenuated Tert activity. The aging and senescence of multiple cell types, including bone marrow stem cells, may underlie the diverse pathological outcomes of PM2.5 exposure.},
}

@article {pmid40172572,
year = {2025},
author = {Iyer, HS and Rebbeck, TR and Elliott, EG and Holmes, MD and De Vivo, I and Laden, F and Hart, JE},
title = {Cross-sectional associations of neighborhood social and environmental contextual factors with telomere length in male and female health professionals.},
journal = {Cancer epidemiology, biomarkers & 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-25-0061},
pmid = {40172572},
issn = {1538-7755},
abstract = {BACKGROUND: Telomere length attrition has been proposed as a mediator through which adverse neighborhood social and environmental context affects cancer risk through stress-related pathways, but associations have been inconsistent. We examined associations between neighborhood social and environmental factors in a population with extensive capture of behavioral factors and comorbidities.

METHODS: Data were pooled from nested case-control studies using blood samples collected in two large prospective US-based cohorts of male (n=3065) and female (n=9993) health professionals. Relative leukocyte telomere length (rLTL) was assayed using quantitative polymerase chain reaction and geospatial measures of socioeconomic status, air pollution, green space, and temperature were linked to participants' address at blood draw.

RESULTS: After adjusting for sociodemographic and lifestyle covariates, no statistically significant associations of rLTL with any of the address-level neighborhood socioeconomic or environmental factors were observed.

CONCLUSIONS: In this large nation-wide cross-sectional study of male and female health professionals in the US, neighborhood social and environmental contextual factors were not associated with telomere length.

IMPACT: Further cross-sectional studies of associations between neighborhood social and environmental factors and telomere length are unlikely to improve understanding of this potential mediating mechanism. Studies with repeated measures may be required.},
}

@article {pmid40169648,
year = {2025},
author = {Yue, X and Liu, H and Guo, W and Gao, Y and Shi, S},
title = {Causal association between dietary factors and telomere length revealed by mendelian randomization.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {11082},
pmid = {40169648},
issn = {2045-2322},
support = {YXMJ-QNMZY-13//XingLiaoYingCai Program/ ; YXMJ-QNMZY-13//XingLiaoYingCai Program/ ; YXMJ-QNMZY-13//XingLiaoYingCai Program/ ; YXMJ-QNMZY-13//XingLiaoYingCai Program/ ; },
mesh = {*Mendelian Randomization Analysis ; Humans ; *Diet ; *Telomere/genetics ; *Genome-Wide Association Study ; *Telomere Homeostasis ; Polymorphism, Single Nucleotide ; Fruit/genetics ; },
abstract = {Observational studies have reported associations between dietary factors and telomere length. However, the inherent limitations of observational study designs render them susceptible to confounding and reverse causation biases. Therefore, this study aims to explore the association between dietary factors and telomere length using Mendelian Randomization (MR) to minimize the influence of confounding factors and reverse causality. The IEU Open GWAS project was the source of exposure and outcome datasets. The exposure datasets included 20 dietary factors. We conducted MR analyses to explore the relationship between dietary factors and telomere length. We used MRPRESSO and Radial-MR test to identify any level of multi-effect outliers. Heterogeneity and pleiotropic analysis were performed to ensure the accuracy of the results. The stability of the effect of significant results is assessed using multivariable Mendelian randomization (MVMR) and MR-lap. Two-sample MR analysis revealed a statistically significant association between dried fruit intake and telomere length (β = 0.223, 95% CI 0.091 to 0.356, PIVW=9.089 × 10^-4). After removing outliers and reanalyzing the data, the association remained significant (β = 0.163, 95% CI: 0.163 0.090 to 0.235, PIVW-FE=7.323 × 10^-5), with no significant pleiotropy detected in sensitivity analyses. Following adjustment for confounders, the MVMR results and MR-lap results continued to support a causal relationship between dried fruit intake and telomere length. Other dietary factors' effects on telomere length still need further confirmation. Our findings suggest a potential causal relationship between dried fruit intake and longer telomere length. This finding highlights potential dietary strategies for exploring the beneficial effects of dried fruit intake on preventing diseases and extending lifespan.},
}

*Mendelian Randomization Analysis
Humans
*Diet
*Telomere/genetics
*Genome-Wide Association Study
*Telomere Homeostasis
Polymorphism, Single Nucleotide
Fruit/genetics

@article {pmid40169380,
year = {2025},
author = {Chung, G and Piano, F and Gunsalus, KC},
title = {TeloSearchLR: an algorithm to detect novel telomere repeat motifs using long sequencing reads.},
journal = {G3 (Bethesda, Md.)},
volume = {},
number = {},
pages = {},
doi = {10.1093/g3journal/jkaf062},
pmid = {40169380},
issn = {2160-1836},
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 {pmid40167991,
year = {2025},
author = {Qi, Z and Liu, Q and Li, H and Zhang, Y and Yu, Z and Luo, W and Wang, K and Zhang, Y and Pan, S and Wang, C and Jiang, H and Qiu, Q and Wang, W and Fan, G and Li, Y},
title = {Telomere-to-telomere genome assembly of Electrophorus electricus provides insights into the evolution of electric eels.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf024},
pmid = {40167991},
issn = {2047-217X},
support = {31900312//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Electrophorus/genetics ; *Telomere/genetics ; *Genome ; Evolution, Molecular ; Molecular Sequence Annotation ; Phylogeny ; Genomics/methods ; },
abstract = {BACKGROUND: Electric eels evolved remarkable electric organs that enable them to instantaneously discharge hundreds of volts for predation, defense, and communication. However, the absence of a high-quality reference genome has extremely constrained the studies of electric eels in various aspects.

RESULTS: Using high-depth, multiplatform sequencing data, we successfully assembled the first telomere-to-telomere high-quality reference genome of Electrophorus electricus, which has a genome size of 833.43 Mb and comprises 26 chromosomes. Multiple evaluations, including N50 statistics (30.38 Mb), BUSCO scores (97.30%), and mapping ratio of short-insert sequencing data (99.91%), demonstrate the high contiguity and completeness of the electric eel genome assembly we obtained. Genome annotation predicted 396.63 Mb repetitive sequences and 20,992 protein-coding genes. Furthermore, evolutionary analyses indicate that Gymnotiformes, which the electric eel belongs to, has a closer relationship with Characiformes than Siluriformes and diverged from Characiformes 95.00 million years ago. Pairwise sequentially Markovian coalescent analysis found a sharply decreased trend of the population size of E. electricus over the past few hundred thousand years. Furthermore, many regulatory factors related to neurotransmitters and classical signaling pathways during embryonic development were significantly expanded, potentially contributing to the generation of high-voltage electricity.

CONCLUSIONS: This study not only provided the first high-quality telomere-to-telomere reference genome of E. electricus but also greatly enhanced our understanding of electric eels.},
}

Animals
*Electrophorus/genetics
*Telomere/genetics
*Genome
Evolution, Molecular
Molecular Sequence Annotation
Phylogeny
Genomics/methods

@article {pmid40164629,
year = {2025},
author = {Dong, Z and Gao, J and Zhao, Y and Gao, J and Guo, Y and Wang, Z and Zhang, N},
title = {Near telomere-to-telomere genome assembly of the blackspot tuskfish (Choerodon schoenleinii).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {537},
pmid = {40164629},
issn = {2052-4463},
mesh = {*Genome ; *Telomere/genetics ; Animals ; Molecular Sequence Annotation ; Tetraodontiformes/genetics ; },
abstract = {Choerodon schoenleinii, commonly known as the blackspot tuskfish, widely recognized for its vibrant coloration, unique small black spot on the dorsal fin, and high value in both ornamental and culinary markets. Here, we report a high-quality near telomere-to-telomere (T2T) genome assembly of C. schoenleinii, generated using PacBio HiFi and Hi-C technologies. The assembly spans 865.99 Mb, achieving chromosome-level resolution with 24 chromosomes anchored. Notably, telomeres were identified at both ends of 23 chromosomes, with 14 being completely gapless and only 12 gaps detected across the remaining nine. A total of 24,524 protein-coding genes were annotated, with 96.25% assigned functional annotations. The assembly quality was validated with a BUSCO score of 99.80%. The gene annotation was further evaluated using OMArk, with 23,590 proteins (96.19%) consistent with the Clade Teleostei, highlighting the high-quality and taxonomic relevance of the gene set. This reference genome provides a valuable resource for advancing research in the genetics, evolutionary biology, conservation, and breeding of C. schoenleinii, a species currently listed as "Near Threatened" by the IUCN.},
}

*Genome
*Telomere/genetics
Animals
Molecular Sequence Annotation
Tetraodontiformes/genetics

@article {pmid40159528,
year = {2025},
author = {Liu, Z and Sun, C and Zhang, Z and Jiang, Y and Zhao, C},
title = {Telomeres in skin aging.},
journal = {Biogerontology},
volume = {26},
number = {2},
pages = {83},
pmid = {40159528},
issn = {1573-6768},
mesh = {*Skin Aging/physiology/genetics ; Humans ; *Telomere/metabolism ; Skin/metabolism ; Telomerase/metabolism ; Telomere Homeostasis/physiology ; Animals ; Telomere Shortening ; },
abstract = {Skin aging is influenced by both intrinsic and extrinsic factors. The gradual manifestation of changes in telomere length and telomerase activity, as crucial indicators of aging, elucidates the underlying mechanism of skin aging. This review aims to comprehensively analyze the association between telomeres and aging, along with their impact on skin biological function. Firstly, we summarize the structure and function of telomeres and their role in cell division. Subsequently, we discuss the mechanisms through which telomere regulation contributes to aging processes while analyzing its involvement in skin aging by elaborating on biological markers. Furthermore, this paper presents a summary of recent research progress that reveals the correlation between telomere length and skin aging as well as model building methods; it also proposes telomere length as a potential indicator for predicting skin aging. Finally, anti-aging strategies based on telomere protection are discussed including drug therapy and lifestyle adjustments. This paper provides a systematic overview of the role played by telomeres in the field of skin aging for the first time, offering new perspectives and ideas for future prevention and treatment.},
}

*Skin Aging/physiology/genetics
Humans
*Telomere/metabolism
Skin/metabolism
Telomerase/metabolism
Telomere Homeostasis/physiology
Animals
Telomere Shortening

@article {pmid40155615,
year = {2025},
author = {Chen, XY and Lo, CKM and Chen, Q and Ho, FK and Leung, WC and Chan, KL},
title = {Associations between maternal adversity and health and children's telomere length.},
journal = {Translational psychiatry},
volume = {15},
number = {1},
pages = {106},
pmid = {40155615},
issn = {2158-3188},
mesh = {Humans ; Female ; Pregnancy ; Longitudinal Studies ; Male ; Child, Preschool ; *Adverse Childhood Experiences ; Adult ; *Depression/genetics ; *Telomere/genetics ; Mothers/psychology ; Telomere Shortening/genetics ; Prenatal Exposure Delayed Effects/genetics ; Chronic Disease ; },
abstract = {Maternal adversity (e.g., adverse childhood experiences, ACEs) and health (e.g., depressive symptoms and chronic illness) negatively impact offspring's health. One possible mechanism is via premature/accelerated biological aging, as indicated in telomere length. In this 3-year longitudinal study, we examined the association between maternal adversity and health and children's buccal telomere length (bTL) at age 3. Data from 122 mother-child dyads were analyzed. Maternal history of ACEs and chronic illness were collected at baseline (during 20-24 weeks of gestation). Their depressive symptoms across three periods (during pregnancy, 4 weeks after childbirth, and 3 years after childbirth) were also collected. Children's TL were extracted from their buccal swab samples at age 3. The children's bTL was quantified using the quantitative PCR method and expressed in T/S ratio (the ratio of telomere repeats copy numbers to single-copy gene numbers). Results showed pregnant women experienced distinctive trajectories of depressive symptoms over time. Children of mothers with relapsing/remitting depressive symptoms had shorter bTL (β = -0.19, 95% CI = -0.14 to -0.005) than mothers who had low-stable symptoms. This finding remained significant even after accounting for maternal ACEs and chronic illness. Additionally, maternal ACEs, together with depressive symptoms, may affect children's bTL. This study provides relatively comprehensive evidence on the effects of maternal stressors, highlighting the relevance of maternal adversity and depressive symptom patterns as predictors of offspring telomere biology.},
}

Humans
Female
Pregnancy
Longitudinal Studies
Male
Child, Preschool
*Adverse Childhood Experiences
Adult
*Depression/genetics
*Telomere/genetics
Mothers/psychology
Telomere Shortening/genetics
Prenatal Exposure Delayed Effects/genetics
Chronic Disease

@article {pmid40151802,
year = {2025},
author = {Baylie, T and Jemal, M and Baye, G and Getinet, M and Amare, GA and Adugna, A and Abebaw, D and Hibstu, Z and Tegegne, BA and Gugsa, E and Adane, T and Getie, G and Ashenef, B and Sinamaw, D},
title = {The role of telomere and telomerase in cancer and novel therapeutic target: narrative review.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1542930},
pmid = {40151802},
issn = {2234-943X},
abstract = {Telomeres are dynamic complexes at the ends of chromosomes that are made up of protective proteins and tandem repeating DNA sequences. In the large majority of cancer cells, telomere length is maintained by telomerase, an enzyme that elongates telomeres. Telomerase activation is seen in the majority of cancer, which permits uncontrol cell proliferation. About 90% of human malignancies show telomere dysfunction and telomerase reactivation; as a result, telomerase activation plays a special role as a practically universal stage on the way to malignancy. This review understands the structural and functional of telomere and telomerase, mechanisms of telomerase activation in oncogenesis, biomarkers and therapeutic targets. Therapeutic strategies targeting telomerase, including antisense oligonucleotides, G-quadruplex stabilizers, immunotherapy, small-molecule inhibitors, gene therapy, Telomerase-Responsive Drug Release System, have shown promise in preclinical and clinical settings. Advances in telomere biology not only illuminate the complex interplay between telomeres, telomerase, and cancer progression but also open avenues for innovative, targeted cancer therapies.},
}

@article {pmid40149509,
year = {2025},
author = {Sater, MS and AlDehaini, DMB and Malalla, ZHA and Ali, ME and Giha, HA},
title = {A Perceived Dissociation Between Systemic Chronic Inflammation, Age, and the Telomere/Telomerase System in Type 2 Diabetes.},
journal = {Biomedicines},
volume = {13},
number = {3},
pages = {},
doi = {10.3390/biomedicines13030531},
pmid = {40149509},
issn = {2227-9059},
abstract = {Background: Chronic inflammation is associated with leukocyte telomere length (LTL) shortening and type 2 diabetes (T2D). The latter is also associated with LTL shortening, while the three variables are associated with aging. Objective: It is tempting to test whether inflammation, age, or both are behind the telomere system aberrations in diabetic patients. Methods: In this cross-sectional observational study, blood samples collected from 118 T2D patients were analyzed via ELISA to estimate the plasma levels of four inflammatory markers, IL6, IL8, TREM1, and uPAR, and the telomerase enzyme (TE). Moreover, the extracted DNA was used for the LTL estimation via qPCR and for single nucleotide polymorphisms (SNP) genotyping of TE genes (TERT, TERC, and ACYP2) via rtPCR. Results: The results showed no correlation between the levels of all tested inflammatory markers and the LTL, TE level, and age. There were no significant differences between the marker levels in diabetic patients in the four quartiles of the LTL and TE levels. Moreover, there were no significant differences in the levels of the markers between carriers of the different TE genotypes. Conclusions: There were no associations between the tested inflammatory markers' levels and the LTL, TE plasma levels, or age in T2D. Explanations for the dissociation between the above-known associations in T2D were proposed; however, the subject is worth further investigation.},
}

@article {pmid40149420,
year = {2025},
author = {Cruz-Ramos, JA and de la Mora-Jiménez, E and Llanes-Cervantes, BA and Damián-Mejía, MÁ},
title = {MicroRNAs in the Mitochondria-Telomere Axis: Novel Insights into Cancer Development and Potential Therapeutic Targets.},
journal = {Genes},
volume = {16},
number = {3},
pages = {},
doi = {10.3390/genes16030268},
pmid = {40149420},
issn = {2073-4425},
support = {appac-2025//Universidad de Guadalajara/ ; },
mesh = {Humans ; *MicroRNAs/genetics ; *Neoplasms/genetics/metabolism/pathology ; *Mitochondria/metabolism/genetics ; *Telomere/genetics/metabolism ; Animals ; Gene Expression Regulation, Neoplastic ; },
abstract = {The mitochondria-telomere axis is recognized as an important factor in the processes of metabolism, aging and oncogenesis. MicroRNAs (miRNAs) play an essential function in this complex interaction, having an impact on aspects such as cellular homeostasis, oxidative responses and apoptosis. In recent years, miRNAs have been found to be crucial for telomeric stability, as well as for mitochondrial behavior, factors that influence cell proliferation and viability. Furthermore, mitochondrial miRNAs (mitomiRs) are associated with gene expression and the activity of the cGAS/STING pathway activity, linking mitochondrial DNA recognition to immune system responses. Hence, miRNAs maintain a link to mitochondrial biogenesis, metabolic changes in cancer and cellular organelles. This review focuses on the roles of a variety of miRNAs in cancer progression and their potential application as biomarkers or therapeutic agents.},
}

Humans
*MicroRNAs/genetics
*Neoplasms/genetics/metabolism/pathology
*Mitochondria/metabolism/genetics
*Telomere/genetics/metabolism
Animals
Gene Expression Regulation, Neoplastic

@article {pmid40148339,
year = {2025},
author = {Mannherz, W and Crompton, A and Lampl, N and Agarwal, S},
title = {Metabolic constraint of human telomere length by nucleotide salvage efficiency.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {3000},
pmid = {40148339},
issn = {2041-1723},
mesh = {Humans ; *Telomerase/metabolism/genetics ; *Telomere/metabolism/genetics ; Animals ; *Telomere Homeostasis ; *Purine-Nucleoside Phosphorylase/metabolism/genetics ; Drosophila melanogaster/metabolism/genetics ; Deoxycytidine Kinase/metabolism/genetics ; Guanosine/metabolism ; Nucleotides/metabolism ; SAM Domain and HD Domain-Containing Protein 1/metabolism/genetics ; Hypoxanthine Phosphoribosyltransferase/metabolism/genetics ; Phosphotransferases (Alcohol Group Acceptor) ; },
abstract = {Human telomere length is tightly regulated and associated with diseases at either extreme, but how these bounds are established remains incompletely understood. Here, we developed a rapid cell-based telomere synthesis assay and found that nucleoside salvage bidirectionally constrains human telomere length. Metabolism of deoxyguanosine (dG) or guanosine via purine nucleoside phosphorylase (PNP) and hypoxanthine-guanine phosphoribosyltransferase to form guanine ribonucleotides strongly inhibited telomerase and shortened telomeres. Conversely, salvage of dG to its nucleotide forms via deoxycytidine kinase drove potent telomerase activation, the extent of which was controlled by the dNTPase SAMHD1. Circumventing limits on salvage by expressing Drosophila melanogaster deoxynucleoside kinase or augmenting dG metabolism using the PNP inhibitor ulodesine robustly lengthened telomeres in human cells, including those from patients with lethal telomere diseases. Our results provide an updated paradigm for telomere length control, wherein telomerase reverse transcriptase activity is actively and bidirectionally constrained by the availability of its dNTP substrates, in a manner that may be therapeutically actionable.},
}

Humans
*Telomerase/metabolism/genetics
*Telomere/metabolism/genetics
Animals
*Telomere Homeostasis
*Purine-Nucleoside Phosphorylase/metabolism/genetics
Drosophila melanogaster/metabolism/genetics
Deoxycytidine Kinase/metabolism/genetics
Guanosine/metabolism
Nucleotides/metabolism
SAM Domain and HD Domain-Containing Protein 1/metabolism/genetics
Hypoxanthine Phosphoribosyltransferase/metabolism/genetics
Phosphotransferases (Alcohol Group Acceptor)

@article {pmid40141057,
year = {2025},
author = {Huang, CM and Shen, YL and Ho, CL and Chen, TE and Hsia, HY and Songyang, Z and Chen, LY},
title = {C-Terminal Extended Domain-Independent Telomere Maintenance: Modeling the Function of TIN2 Isoforms in Mus musculus.},
journal = {International journal of molecular sciences},
volume = {26},
number = {6},
pages = {},
pmid = {40141057},
issn = {1422-0067},
support = {AS-GCP-113-L02//Academia Sinica/ ; },
mesh = {Animals ; Mice ; *Protein Isoforms/genetics/metabolism ; *Telomere/metabolism/genetics ; *Telomere-Binding Proteins/metabolism/genetics ; Humans ; Telomere Homeostasis ; Fibroblasts/metabolism ; Alleles ; Alternative Splicing ; Protein Domains ; },
abstract = {TIN2 (TERF1 interacting nuclear factor 2) is a telomeric shelterin complex component, essential for telomere protection and early embryonic development in mammals. In humans, TIN2 isoforms arise from alternative splicing, but their specific roles in vivo remain unclear. Here, we explore TIN2 isoform functions in the laboratory mouse Mus musculus. Our comparative analysis of TIN2 protein sequences reveals that mouse TIN2 (TINF2) closely resembles the human TIN2L isoform, both of which harbor a C-terminal extended domain (CTED) absent from the human TIN2 small (TIN2S) isoform. To further characterize the functions of TIN2 isoforms, we generated a Tinf2 LD (long-form deficiency) allele in M. musculus encoding a short form of TINF2 lacking the CTED. Mice heterozygous or homozygous for this Tinf2 LD allele were viable, fertile, and showed no tissue abnormalities. Furthermore, protein product of Tinf2 LD allele localized to telomeres and maintained telomere integrity in mouse embryonic fibroblasts, demonstrating that the CTED is dispensable for telomere protection and normal development in mice. These findings indicate functional redundancy among TIN2 isoforms and underscore the utility of the Tinf2 LD model for uncovering isoform-specific mechanisms of telomere regulation.},
}

Animals
Mice
*Protein Isoforms/genetics/metabolism
*Telomere/metabolism/genetics
*Telomere-Binding Proteins/metabolism/genetics
Humans
Telomere Homeostasis
Fibroblasts/metabolism
Alleles
Alternative Splicing
Protein Domains

@article {pmid40145120,
year = {2024},
author = {Bordas-Martinez, J and Miedema, JR and Mathot, BJ and Seghers, L and Galjaard, RH and Raaijmakers, MHGP and Aalbers, AM and Wijsenbeek, M and Molina-Molina, M and Hellemons, ME},
title = {Outcomes of lung transplantation in patients with telomere-related forms of progressive fibrosing interstitial lung disease pulmonary fibrosis: A systematic review.},
journal = {JHLT open},
volume = {3},
number = {},
pages = {100054},
pmid = {40145120},
issn = {2950-1334},
abstract = {BACKGROUND: Lung transplantation (LTX) is the last life-extending option for patients with progressive fibrosing interstitial lung diseases (fILD). Between 12% and 71% of patients with fILD are patients with underlying telomere-dysfunction (trILD) related to pathogenic telomere-related gene (TRG) variants and/or short telomere length. TrILD patients tend to have earlier disease onset, faster progression, and worse prognosis causing them to be referred for LTX more often. Regarding LTX outcomes in trILD, there are contradictory reports on patient and graft survival, as well as numerous other outcomes. There is no consensus on whether trILD is associated with poorer outcomes after LTX and what considerations regarding candidacy are appropriate.

METHODS: We aimed to systematically review LTX outcomes of patients with trILD in comparison to those with non-trILD.

RESULTS: A systematic literature search yielded 13 studies that met the inclusion criteria including 933 LTX, 281 in trILD, and 652 in non-trILD. Despite large heterogeneity in the methodological study quality and reported outcomes among the studies, patient and graft survival after LTX in trILD did not evidently seem inferior to LTX in non-trILD. However, there may be increased risk of specific complications, such as cytopenias, airway complications, and cytomegalovirus-reactivation.

CONCLUSIONS: In summary, due to large heterogeneity in methodological study quality and reported outcomes, no firm conclusions can be drawn. Patient and graft survival do not seem unequivocally inferior in patients with trILD deemed eligible for LTX. On top of limited available high-quality data, specific patient selection and post-transplant management strategies may affect the currently acquired results. As such, differences may exist regarding transplant-related outcomes, which could require special attention and consideration. Further high-quality comparative studies on LTX outcomes in trILD are needed to draw final conclusions and provide recommendations regarding patient selection and post-transplantation management.},
}

@article {pmid40139649,
year = {2025},
author = {da Cruz, NFS and Sengillo, JD and Negron, CI and Berrocal, AM},
title = {Telomere Biology Disorders: Microvascular Abnormalities on Optical Coherence Tomography.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2025.03.027},
pmid = {40139649},
issn = {1879-1891},
abstract = {BACKGROUND AND OBJECTIVE: Telomere biology disorders (TBDs) are inherited conditions caused by telomere dysfunction, impacting systemic and ocular health. We aim to explore the role of optical coherence tomography angiography (OCTA) in identifying retinal microvascular abnormalities in TBDs.

DESIGN: Retrospective case series.

METHODS: The electronic medical records of pediatric patients with TBD at a tertiary referral eye center were reviewed from January 2019 to July 2023. OCTA images were reviewed for anomalies of the retinal vasculature.

RESULTS: In total, 13 eyes of 7 patients were included in the study. All patients were genetically confirmed to have TBD. The most common genetic variants were CTC1 (5 patients; 71.4%), ACD (1 patient; 14.3%) and RTEL1 (1 patient; 14.3%). On OCTA, all 13 eyes showed some degree of macular microvascular abnormality in both the SVC and DVC. The most common microvascular abnormality seen in the SVC was blood vessels anastomosis (11; 84.6%), and in the DVC was decreased vessel density (9; 69.2%).

CONCLUSIONS: OCTA imaging reveals a high prevalence of microvascular abnormalities in patients with TBD, highlighting its potential role in assessing retinal vascular changes associated with the disease.},
}

@article {pmid40138850,
year = {2025},
author = {Thirumoorthy, C and Rekha, RP and Deepa, M and Ram, U and Shalu, D and Venkatesan, U and Srikumar, BN and Anjana, RM and Balasubramanyam, M and Mohan, V and Saravanan, P and Govindaraj, P and Gokulakrishnan, K},
title = {Association of early pregnancy telomere length and mitochondrial copy number with gestational diabetes mellitus and depressive symptoms.},
journal = {Psychoneuroendocrinology},
volume = {176},
number = {},
pages = {107431},
doi = {10.1016/j.psyneuen.2025.107431},
pmid = {40138850},
issn = {1873-3360},
abstract = {AIM: A bidirectional link exists between depression and gestational diabetes mellitus (GDM). While telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) alterations have been reported either in GDM or depression, their predictive ability of GDM with coexisting depression remains unexplored. We, therefore, prospectively investigated the relationship of TL and mtDNA-CN in blood leukocytes during early pregnancy and explored their potential as predictive biomarkers for identifying the risk of developing GDM with depressive symptoms later in pregnancy.

METHODS: A nested cohort of 301 women with normal fasting glucose and without depressive symptoms in early pregnancy (<16 weeks) were selected from the STratification of Risk of Diabetes in Early Pregnancy (STRiDE) study. At 24-28 weeks (OGTT visit), a 75 g OGTT and PHQ-9 were performed. Women were categorized into four groups: NGT without depressive symptoms (n = 80), NGT with depressive symptoms (n = 105), GDM without depressive symptoms (n = 75), and GDM with depressive symptoms (n = 41). Blood leukocyte TL and mtDNA-CN were assessed using qRT-PCR.

RESULTS: TL and mtDNA-CN at early pregnancy were lower in women with GDM, depressive symptoms or both, compared to NGT without depressive symptoms at OGTT visit. TL and mtDNA-CN at early pregnancy were negatively associated with PHQ-9 score and OGTT blood glucose levels at OGTT visit after adjusting for age, pre-pregnancy BMI and family history of diabetes. Higher levels of both TL and mtDNA-CN in early pregnancy were associated with lower adjusted Relative Risk (aRR) (TL; aRR: 0.34; 95 % CI: 0.28, 0.41, mtDNA-CN; aRR: 0.83; 95 % CI: 0.74, 0.93) of GDM with depressive symptoms at OGTT visit.

CONCLUSION: Lower levels of TL and mtDNA-CN in early pregnancy are significantly associated with the later development of GDM and depressive symptoms at OGTT visit. Our findings indicate that early trimester TL and mtDNA-CN could be potential predictive biomarkers for predicting GDM with depressive symptoms and emphasize their potential for improved risk assessment so as to adopt preventive strategies targeting these conditions.},
}

@article {pmid40134806,
year = {2025},
author = {Liu, S and Xu, L and Cheng, Y and Liu, D and Zhang, B and Chen, X and Zheng, M},
title = {Methylation of the telomerase gene promoter region in umbilical cord blood of patients with gestational diabetes mellitus is associated with decreased telomerase expression levels and shortened telomere length.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1502329},
pmid = {40134806},
issn = {1664-2392},
mesh = {Humans ; *Telomerase/genetics ; *Diabetes, Gestational/genetics/blood ; Female ; Pregnancy ; *Promoter Regions, Genetic ; *DNA Methylation ; *Fetal Blood/metabolism ; Adult ; Case-Control Studies ; CpG Islands ; Prospective Studies ; Telomere Shortening/genetics ; Telomere/genetics ; Infant, Newborn ; Telomere Homeostasis ; },
abstract = {OBJECTIVE: This study speculates that gestational diabetes mellitus (GDM) may reduce fetal telomere length (TL),which may be related to modification of methylation in the promoter region of the telomerase (TE) gene promoter region.

METHODS: In this study, umbilical cord blood samples from patients with and without GDM (N = 100 each) were analyzed by prospective case-control. The TL, TE expression levels, and methylation levels of TERT and TERC gene promoter regions in two groups were measured. The significance of the methylation level of each CpG locus employed logistic regression analysis of R software, and the analysis of covariance (ANCOVA) was used to control the influence of confounding factors. Correlation analysis was performed by the Spearman.

RESULTS: The TL and TE expression levels of the offspring of GDM patients were decreased despite adjusting for PBMI, PWG, and TG. A total of two CpG islands were screened in the promoter region of the TERT gene and three fragments (TERT_2, TERT_3, and TERT_4) containing a total of 70 CpG sites were designed. Additionally, four CpG sites of the TERT gene in the GDM group (TERT_2_40, TERT_2_47, TERT_3_46, and TERT_3_212) showed increased methylation levels compared with the control group (all P < 0.05). In the promoter region of the TERC gene, one CpG island containing 19 CpG loci was screened and designed, and the methylation levels of the two CpG sites were significantly different in TERC_1_67 (0.65 ± 0.21 versus 0.57 ± 0.30; P = 0.040) and TERC_1_120 (0.68 ± 0.23 versus 0.59 ± 0.27; P = 0.014). The methylation levels of TERC gene fragments of GDM patients were significantly higher than those of the control group (0.69 ± 0.06 versus 0.65 ± 0.08, P = 0.001).

CONCLUSION: This study revealed that GDM may induce decreased TE expression by increasing the methylation levels of TE genes promoter region, thereby reducing the TL.},
}

Humans
*Telomerase/genetics
*Diabetes, Gestational/genetics/blood
Female
Pregnancy
*Promoter Regions, Genetic
*DNA Methylation
*Fetal Blood/metabolism
Adult
Case-Control Studies
CpG Islands
Prospective Studies
Telomere Shortening/genetics
Telomere/genetics
Infant, Newborn
Telomere Homeostasis

@article {pmid40133370,
year = {2025},
author = {Wan, L and Deng, C and Liu, B and Su, S and Zhang, Z and Jiang, Y and Zou, B and Liu, J and Du, Z and Zhang, Y and Chen, P and Xiao, W},
title = {Telomere-to-telomere genome assemblies of three silkworm strains with long-term pupal characteristics.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {501},
pmid = {40133370},
issn = {2052-4463},
mesh = {Animals ; *Bombyx/genetics ; *Genome, Insect ; *Telomere/genetics ; *Pupa/genetics ; },
abstract = {The domesticated silkworm (Bombyx mori) is both economically significant and a valuable model organism. However, challenges persist in silk production, particularly in preserving silkworm cocoons. The wild silkworm (Bombyx mandarina), a close relative, with long-term pupal characteristics, could address storage and industrial silk production issues. We conducted interspecies hybridization between domestic and wild silkworms, successfully introducing the long-pupal period trait into the domestic silkworm through genomic integration. Here, we presented the telomere-to-telomere genome assemblies of three silkworm strains (KA, L, and M) with long-term pupal characteristics. The genome assembly sizes ranged from 453.82 Mb to 461.92 Mb, with high contig N50 values and completeness. We predicted over 14,000 protein-coding genes and identified strain-specific fragments. This research enriches the domestic silkworm pan-genome project and provides a foundation for further genetic studies. By introducing the trait, we have for the first time reported a phenomenon of genomic introgression between domestic and wild silkworm, and have also opened up a new avenue for silkworm breeding.},
}

Animals
*Bombyx/genetics
*Genome, Insect
*Telomere/genetics
*Pupa/genetics

@article {pmid40132391,
year = {2025},
author = {Guillén-Vicente, I and Rodríguez-Íñigo, E and Guillén-Vicente, M and Samper, E and López-Alcorocho, JM and Orgaz, L and Fernández Jaén, TF and González, P and Abelow, S and García, I and de Pedro, N and Guillén-García, P},
title = {Comparing telomere lengths in chondrocytes from intact cartilage and those isolated from loose bodies.},
journal = {Tissue & cell},
volume = {95},
number = {},
pages = {102868},
doi = {10.1016/j.tice.2025.102868},
pmid = {40132391},
issn = {1532-3072},
abstract = {INTRODUCTION: Given the intrinsic connection between telomeres, cell replication, and aging, telomere length serves as a valuable biomarker for evaluating cell quality and viability. Studying telomeres can offer vital insights into the suitability of cells within articular loose bodies for autologous chondrocyte implantation in treating chondral lesions. The aim of this study was to assess cell quality by analyzing telomere profiles in isolated cells from loose bodies.

METHODS: Chondrocytes from loose bodies and intact cartilage from 3 patients with osteochondritis dissecans who underwent a High Density-Autologous Chondrocyte Implantation (HD-ACI), were isolated and cultured. Telomere length was determined by High-Throughput Quantitative Fluorescence in situ Hybridization (HT-Q-FISH). Percentile of telomere length, percentages of telomere length values (QuantiTel), percentages of cells with specific telomere values (QuantiCell) were estimated in each sample.

RESULTS: Percentile and QuantiTel showed lower telomere lengths in chondrocytes from loose bodies than in those from intact cartilage. QuantiCell demonstrated that the percentage of cells with shorter telomeres was higher in cells from loose bodies than in intact cartilage. Median telomere length was statistically higher in chondrocytes from intact biopsies than in loose bodies.

CONCLUSION: Chondrocytes isolated from loose bodies exhibits a telomere distribution shorter than those from intact cartilage.},
}

@article {pmid40129738,
year = {2025},
author = {Wang, L and Jia, KH},
title = {Editorial: Precision exploration of plant germplasm resources: breakthroughs and applications in telomere-to-telomere (T2T) genomics.},
journal = {Frontiers in plant science},
volume = {16},
number = {},
pages = {1573144},
doi = {10.3389/fpls.2025.1573144},
pmid = {40129738},
issn = {1664-462X},
}

@article {pmid40128533,
year = {2025},
author = {Bian, C and Hu, C and He, Z and Li, Z and Shi, Q},
title = {A complete telomere-to-telomere chromosome-level genome assembly of X-ray tetra (Pristella maxillaris).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {496},
pmid = {40128533},
issn = {2052-4463},
mesh = {*Telomere/genetics ; Animals ; *Genome ; Chromosomes ; },
abstract = {X-ray tetra (Pristella maxillaris) originates from the lower Amazon basin in South America. It is renowned for its strikingly transparent body, which has drawn significant interests in biomedical research and the world ornamental fish industry. Nevertheless, genomic resources for this interesting fish species remains scarce, hindering exploration of the molecular basis behind its unique transparency. To address this gap, we constructed the first complete telomere-to-telomere (T2T) chromosome-scale genome assembly of the X-ray tetra by integration of PacBio HiFi, ONT ultra-long, and Hi-C sequencing technologies. This haplotypic assembly spans approximately 1.1 Gb, with a contig N50 of 42.8 Mb. It is anchored onto 25 chromosomes, highlighting a complete set of 50 telomeres and 25 centromeres. We predicted 514.3 Mb of repetitive sequences and annotated 28,456 protein-coding genes in the assembled genome. Subsequent BUSCO analysis discovered high genome completeness (98.0%). This high-quality T2T genome assembly provides a valuable genetic resource for investigating the molecular mechanisms underlying transparency, and supporting in-depth studies on functional genomics, genetic diversity, and selective breeding for this economically important species.},
}

*Telomere/genetics
Animals
*Genome
Chromosomes

@article {pmid40122884,
year = {2025},
author = {Bian, C and Li, D and Wang, Y and He, Z and Chen, WT and Chong, CM and Zhou, H and Shi, Q},
title = {A telomere-to-telomere chromosome-scale genome assembly of glass catfish (Kryptopterus vitreolus).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {483},
pmid = {40122884},
issn = {2052-4463},
mesh = {Animals ; *Catfishes/genetics ; *Telomere/genetics ; *Genome ; *Chromosomes ; },
abstract = {Glass catfish (Kryptopterus vitreolus) is commonly distributed in several Asian countries, such as Thailand, Malaysia, and Indonesia. It is renowned for its near-transparent appearance, which has drawn considerable attention for biomedical research and the tropical ornamental fish industry. Here, we successfully constructed the first telomere-to-telomere (T2T) chromosome-scale genome assembly for glass catfish, by integration of PacBio HiFi, Nanopore ONT ultra-long, and Hi-C sequencing technologies. The haplotypic assembly covers approximately 687.7 Mb in length, featuring a high contig N50 of 21.3 Mb. This assembly was then anchored into 32 chromosomes, presenting a complete set of 64 telomeres and 32 centromeres. It was predicted with 252.4 Mb of repetitive sequences and annotated with a total of 24,696 protein-coding genes. Subsequent BUSCO analysis revealed high genome completeness (up to 96.4%). This high-quality T2T genome assembly not only provides a valuable genetic resource for investigating the molecular mechanisms underlying transparency, but also supports in-depth studies on functional genomics, genetic diversity, and selective breeding for this economically important fish species.},
}

Animals
*Catfishes/genetics
*Telomere/genetics
*Genome
*Chromosomes

@article {pmid40119960,
year = {2025},
author = {Pandey, A and Mancuso, T and Velsher, L and Kennedy, JA},
title = {Azacitidine and venetoclax for the treatment of AML arising from an underlying telomere biology disorder.},
journal = {Familial cancer},
volume = {24},
number = {2},
pages = {31},
pmid = {40119960},
issn = {1573-7292},
mesh = {Humans ; *Bridged Bicyclo Compounds, Heterocyclic/therapeutic use ; *Leukemia, Myeloid, Acute/drug therapy/genetics ; *Azacitidine/therapeutic use ; Middle Aged ; *Sulfonamides/therapeutic use ; Male ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Telomere/drug effects ; },
abstract = {Telomere biology disorders (TBDs) are a group of genetic conditions characterized by defects in telomere maintenance leading to multisystemic organ involvement and a predisposition to hematologic malignancies. The management of patients with TBDs who develop acute myeloid leukemia (AML) presents a significant challenge due to their limited bone marrow reserve and non-hematopoietic organ dysfunction. We present the case of a 45-year-old patient with a previously unrecognized TBD who presented with AML. The patient's history of longstanding cytopenias, idiopathic avascular necrosis, and pulmonary fibrosis were suggestive of a TBD, which was confirmed through telomere length testing and the presence of a TERT variant. Due to his underlying TBD, he was treated with dose-reduced azacitidine and venetoclax, adapting the approach commonly employed in elderly, co-morbid AML patients ineligible for intensive chemotherapy. This resulted in a complete remission with incomplete count recovery that has persisted for greater than 12 months to date. Aside from prolonged myelosuppression, the patient tolerated the regimen well with minimal toxicity. To our knowledge, this is the first report of the successful utilization of azacitidine and venetoclax as an AML treatment modality in TBD patients and underscores the potential of this regimen as an effective non-intensive treatment strategy for high grade myeloid neoplasms arising in the context of inherited bone marrow failure syndromes.},
}

Humans
*Bridged Bicyclo Compounds, Heterocyclic/therapeutic use
*Leukemia, Myeloid, Acute/drug therapy/genetics
*Azacitidine/therapeutic use
Middle Aged
*Sulfonamides/therapeutic use
Male
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Telomere/drug effects

@article {pmid40119470,
year = {2025},
author = {Wojcicki, JM and Epel, E and Lin, J and Tai, V and Schwarz, JM and Noworolski, SM and Erkin-Cakmak, A and Mulligan, K and Gugliucci, A and Lustig, RH},
title = {Leukocyte telomere length change in children with obesity in the context of an isocaloric fructose restriction intervention.},
journal = {Diabetology & metabolic syndrome},
volume = {17},
number = {1},
pages = {94},
pmid = {40119470},
issn = {1758-5996},
abstract = {BACKGROUND: Few studies have evaluated changes in leukocyte telomere length (LTL) over a short time period (e.g. 1 week). LTL shortening is accelerated by exposure to inflammation and reactive oxygen species (ROS) damage.

METHODS: In the context of an isocaloric fructose restriction study that was conducted with 43 Black and Latinx children over a 9-day period, we evaluated the relationship between metabolic health at baseline and metabolic changes and LTL at baseline and %LTL change over the follow-up period. Linear regression models were used to assess associations between metabolic correlates and LTL at baseline and LTL changes over 9 days.

RESULTS: Overall children lost - 0.05 ± 0.14 T/S units or - 2.98 ± 8.74% total change over the follow-up period. Higher concentrations of HDL-C, APO-AI and a greater % of large HDL-C at baseline were associated with reduced LTL attrition rates at day 10 (p < 0.01; p < 0.01 and p = 0.02 respectively). Increases in APO-AI over the follow-up period were associated with increased LTL attrition over the follow-up period (p = 0.03).

CONCLUSIONS: In this short term isocaloric fructose restriction study, LTL at baseline and changes in LTL over 9 days were associated with HDL-C and APO-AI and not with any other non-HDL-C lipids. Additional, larger studies are necessary to better understand the interplay between short term fructose restriction, LTL changes and HDL-C/APO-AI.},
}

@article {pmid40117028,
year = {2025},
author = {Ding, S and Gu, Q and Zhao, Z and Xie, Y and Wang, F and Liu, J and Li, H and Su, H and Wei, Q and Pi, S and Chen, F and Xiao, B and He, Y},
title = {Role of Glucose Metabolism in the Effects of Serum Metals on Telomere Length: Findings in Chinese Diabetic Population.},
journal = {Biological trace element research},
volume = {},
number = {},
pages = {},
pmid = {40117028},
issn = {1559-0720},
abstract = {The effects of metal exposure on telomere length have attracted considerable attention, but definitive evidence is still lacking in the diabetic population. Thus, this study was conducted to explore the associations of metal mixture with telomere length and the mediated effects of glucose metabolism among the Chinese diabetic population. Eleven metals in serum and relative telomere length of leucocyte were quantified among 1516 diabetic population based on a large-scale diabetic retinopathy screening program in southern China. Multiple statistical models were used to evaluate the single and joint effects of metal mixture on telomere length. Moreover, to assess the mediating roles of glucose metabolism in the associations between metals and telomere length, mediation analyses were performed. In single-exposure models, serum levels of nickel and thallium were identified to be negatively associated with telomere length, while magnesium showed an inverted U-shaped association with telomere length. Consistent findings from three mixed-exposure analyses indicated that increased serum level of metal mixture was associated with decreased telomere length, with nickel playing a major role in the joint effects of the metals. Mediation analyses further revealed that the associations of nickel and metal mixture with telomere length were partially mediated by glycated hemoglobin, and the mediated proportions were 4.26% and 4.38%, respectively. Moreover, the associations between metals exposure and telomere length were observed to be more prominent in males. Our results indicated that exposure to metal mixture was associated with shortened telomere length, which may be partially mediated by glycated hemoglobin.},
}

@article {pmid40113806,
year = {2025},
author = {Jiang, C and Du, Y and Lou, Z and Zhang, Y and Wang, T},
title = {Telomere-to-telomere reference genome of Rhinogobio nasutus, an endangered endemic fish from the Yellow River.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {462},
pmid = {40113806},
issn = {2052-4463},
mesh = {Animals ; *Endangered Species ; *Genome ; China ; *Telomere/genetics ; Rivers ; Fishes/genetics ; },
abstract = {Rhinogobio nasutus is an endemic fish species native to the middle and upper reaches of the Yellow River in China, renowned for its high economic and nutritional value. However, due to overfishing, human activities, and environmental pollution, it is now critically endangered. This study presents the construction of a telomere-to-telomere (T2T) reference genome for R. nasutus by integrating PacBio HiFi reads, Oxford Nanopore Technologies and Hi-C data. The assembled genome has a total size of 953.38 Mb and is anchored to 25 autosomes. Multiple assessments confirmed the high quality of the genome in terms of mapping rate (99.77% and 99.85%), completeness (BUSCO: 99.31%), and accuracy (QV: 47.05 and 53.10). Functional annotation was achieved for 98.16% of the 24,677 protein-coding genes, with a BUSCO score of 99.81%. This work not only facilitates the genetic conservation of R. nasutus but also provides a valuable resource for related evolutionary studies.},
}

Animals
*Endangered Species
*Genome
China
*Telomere/genetics
Rivers
Fishes/genetics

@article {pmid40112135,
year = {2025},
author = {Feng, K and Liu, JL and Sun, N and Zhou, ZQ and Yang, ZY and Lv, H and Yao, C and Zou, JP and Zhao, SP and Wu, P and Li, LJ},
title = {Telomere-to-telomere genome assembly reveals insights into the adaptive evolution of herbivore-defense mediated by volatile terpenoids in Oenanthe javanica.},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.70062},
pmid = {40112135},
issn = {1467-7652},
support = {JBGS[2021]017//Jiangsu seed industry revitalization project/ ; CARS-24//Agriculture Research System of China/ ; 32102368//National Natural Science Foundation of China/ ; },
abstract = {Releasing large quantities of volatiles is a defense strategy used by plants to resist herbivore attack. Oenanthe javanica, a perennial herb of the Apiaceae family, has a distinctive aroma due to volatile terpenoid accumulation. At present, the complete genome and genetic characteristics of volatile terpenoids in O. javanica remain largely unclear. Here, the telomere-to-telomere genome of O. javanica, with a size of 1012.13 Mb and a contig N50 of 49.55 Mb, was established by combining multiple sequencing technologies. Comparative genome analysis revealed that O. javanica experienced a recent species-specific whole-genome duplication event during the evolutionary process. Numerous gene family expansions were significantly enriched in the terpenoid biosynthesis process, monoterpenoid, and diterpenoid biosynthesis pathways, which resulted in abundant volatile substance accumulation in O. javanica. The volatile terpenoids of O. javanica showed repellent effects on herbivores. Terpenoid biosynthesis was activated by wounding signals under exogenous stimuli. The TPS gene family was significantly expanded in O. javanica compared to those in other species, and the members (OjTPS1, OjTPS3, OjTPS4, OjTPS5, OjTPS7, OjTPS16, OjTPS18, OjTPS30 and OjTPS58) responsible for different terpenoid biosynthesis were functionally characterized. These results reveal the genome evolution and molecular characteristics of volatile terpenoids in the process of plant-herbivore interactions. This study also provides genomic resources for genetic and molecular biology research on O. javanica and other plants.},
}

@article {pmid40108243,
year = {2025},
author = {Wang, F and Bao, J and Zhang, H and Zhai, G and Song, T and Liu, Z and Han, Y and Yu, F and Zou, G and Zhu, Y},
title = {A telomere-to-telomere genome assembly of Chinese grain sorghum 654.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {460},
pmid = {40108243},
issn = {2052-4463},
mesh = {*Sorghum/genetics ; *Genome, Plant ; *Telomere/genetics ; East Asian People ; },
abstract = {The grain sorghum inbred line 654 serves as a parent for numerous Chinese commercial hybrids and recombinant inbred lines (RILs), which have played a pivotal role in the cloning of several agronomically important traits. In this study, we present a telomere-to-telomere (T2T) genome assembly of the inbred line 654 (728.81 Mb) using PacBio HiFi, ultra-long Oxford Nanopore Technology, and Hi-C sequencing data. The T2T genome assembly has high integrity (contains all of 10 centromeres and 20 telomeres without any gaps), high contiguity (contig N90: 52.02 Mb), high completeness (98.33% BUSCO completeness, 98.88% k-mer completeness, and LAI 24.38), and extremely low base error (3.37 × 10[-7], QV: 64.72). A total of 62.34% sequences were identified as repetitive, and rest region contained 44,399 protein-coding genes, of which 30,245 were functionally annotated. The gap-free T2T genome assembly enables the full picture of the potential translational genomics, and provides the highest resolution genetic map for future studies on genome evolution, structure variation, and the genetic control of agronomic traits in sorghum breeding.},
}

*Sorghum/genetics
*Genome, Plant
*Telomere/genetics
East Asian People

@article {pmid40107013,
year = {2025},
author = {Fostitsch, AJ and Schwarzer, G and Buchgeister, M and Surbeck, W and Lahmann, C and Spiegelhalder, K and Frase, L and Spieler, D},
title = {The association between sleep quality and telomere attrition: A systematic review and meta-analysis comprising 400,212 participants.},
journal = {Sleep medicine reviews},
volume = {80},
number = {},
pages = {102073},
doi = {10.1016/j.smrv.2025.102073},
pmid = {40107013},
issn = {1532-2955},
abstract = {Psychosocial stressors accelerate telomere attrition, a biomarker of cell aging, whereas good sleep is hypothesized to be a mitigating factor. However, methodological aspects - particularly underpowered studies, inconsistent findings, and multiple approaches to assessing sleep - demonstrate the need for a meta-analysis. After PROSPERO registration, we conducted a systematical search of the following databases until June 2024 to identify studies examining the relationship between sleep quality and telomere length in adult humans: CINAHL, Cochrane Library, MEDLINE, PsychINFO, PubMed, Web of Science, and Google Scholar. In total, 29 studies met inclusion criteria for the systematic review according to the preferred reporting items for systematic reviews and meta-analysis guidelines (PRISMA), 19 of which provided data that was appropriate for meta-analytic calculations. We identified the Pittsburgh sleep quality index (PSQI) global score (odds ratio (OR) 1.24, CI 95 % [1.03; 1.50], p = 0.02), sleep-related daytime impairments (OR 1.01 [1.00; 1.02], p = 0.04), and wake after sleep onset (WASO) time (OR 1.28 [1.12; 1.47], p < 0.01) as to be significantly associated with telomere attrition. Thus, the subtle telomere attrition-mitigating role of sleep has been demonstrated based on a sufficiently large body of data and defined aspects of sleep quality.},
}

@article {pmid40109908,
year = {2023},
author = {Bloom, SI and Tuday, E and Islam, T and Gogulamudi, VR and Lesniewski, LA and Donato, AJ},
title = {Senolytics Reduce Endothelial Cell DNA Damage and Telomere Dysfunction Despite Reductions in Telomere Length.},
journal = {Aging biology},
volume = {1},
number = {},
pages = {},
pmid = {40109908},
issn = {2994-2578},
abstract = {Aging results in cellular damage that can induce cell cycle arrest known as cellular senescence. Endothelial cells are one of the first cell types to become senescent in advancing age and contribute to age-related cardiovascular diseases. Drugs known as senolytics reduce endothelial cell senescence in cell culture. From a translational perspective, a key question is whether this occurs in vivo and if remaining cells appear healthier and display fewer hallmarks of cellular aging. In this study, we treated old mice with the senolytic cocktail dasatinib and quercetin (D+Q) or a vehicle control. In 24-month-old mice, D+Q treatment reduced p21 gene expression in carotid artery endothelial cells, indicative of reductions in senescence. In lung endothelial cells, we examined DNA damage, telomere dysfunction (DNA damage signaling at telomeres), and telomere length, which are hallmarks of aging associated with senescence and other deleterious effects on cellular function. D+Q treatment resulted in fewer endothelial cells with DNA damage and dysfunctional telomeres. Surprisingly, D+Q reduced endothelial cell telomere length, yet this did not result in critically short telomeres and thus telomere dysfunction. Mice have longer telomeres than humans; therefore, future studies on the effect of senolytics on telomere length are warranted. Collectively, this study provides important evidence on the effect of senolytics, including that they clear senescent endothelial cells in vivo, which reduces DNA damage and telomere dysfunction. These data indicate that the clearing of senescent endothelial cells in old age leaves behind a population of cells that exhibit fewer hallmarks of vascular aging.},
}

@article {pmid40106431,
year = {2025},
author = {Lee Lynskey, M 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 = {44},
number = {3},
pages = {115497},
doi = {10.1016/j.celrep.2025.115497},
pmid = {40106431},
issn = {2211-1247},
}

@article {pmid40104396,
year = {2025},
author = {Xie, R and Chen, S and Li, X and Lan, Z},
title = {Assessment of the causal association between obstructive sleep apnea and telomere length: a bidirectional mendelian randomization study.},
journal = {Frontiers in genetics},
volume = {16},
number = {},
pages = {1294105},
pmid = {40104396},
issn = {1664-8021},
abstract = {BACKGROUND: A plethora of observational studies has established a significant correlation between Obstructive Sleep Apnea (OSA) and Telomere Length (TL). Nevertheless, a universal consensus on precise causal association and its directionality has not yet been achieved. To shed light on this, we employed Mendelian Randomization (MR) to investigate the bidirectional causal association between OSA and TL.

METHOD: Utilizing publicly accessible Genome-Wide Association Studies (GWAS) datasets, we procured genetic data pertinent to MR analysis. The study incorporated samples from both the OSA (n = 217,955) and TL (n = 472,174) cohorts. In the forward MR analysis, OSA served as the exposure variable and TL as the outcome. Conversely, the reverse MR analysis treated TL as the exposure and OSA as the outcome. We employed the Inverse variance weighted (IVW) as the primary methodology for MR analysis. To ensure the robustness of our MR findings, multiple sensitivity analyses were performed.

RESULTS: In the forward MR analysis, a negative correlation was indicated between OSA and TL (IVW: odds ratio (OR) = 0.964, 95% confidence interval (CI): 0.939-0.980, P = 0.006 < 0.05). However, no significant association was identified between TL and the risk of OSA in the reverse MR analysis (IVW: OR = 0.965, 95% CI: 0.870-1.070, P = 0.499 > 0.05).

CONCLUSION: Our study indicated a potential association between OSA and the increased risk of shorter TL, offering vital academic support for future clinical studies on this association.},
}

@article {pmid40102883,
year = {2025},
author = {Lu, Z and Chai, X and Li, S},
title = {Machine learning-based identification of telomere-related gene signatures for prognosis and immunotherapy response in hepatocellular carcinoma.},
journal = {Molecular cytogenetics},
volume = {18},
number = {1},
pages = {6},
pmid = {40102883},
issn = {1755-8166},
abstract = {Telomere in cancers shows a main impact on maintaining chromosomal stability and unlimited proliferative capacity of tumor cells to promote cancer development and progression. So, we targeted to detect telomere-related genes(TRGs) in hepatocellular carcinoma (HCC) to develop a novel predictive maker and response to immunotherapy. We sourced clinical data and gene expression datasets of HCC patients from databases including TCGA and GEO database. The TelNet database was utilized to identify genes associated with telomeres. Genes with altered expression from TCGA and GSE14520 were intersected with TRGs, and Cox regression analysis was conducted to pinpoint genes strongly linked to survival prognosis. The risk model was developed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression technique. Subsequently, evaluation of the risk model focused on immune cell infiltration, checkpoint genes, drug responsiveness, and immunotherapy outcomes across both high- and low-risk patient groups. We obtained 25 TRGs from the overlapping set of 34 genes using Cox regression analysis. Finally, six TRGs (CDC20, TRIP13, EZH2, AKR1B10, ESR1, and DNAJC6) were identified to formulate the risk score (RS) model, which independently predicted prognosis for HCC. The high-risk group demonstrated worse survival outcomes and showed elevated levels of infiltration by Macrophages M0 and Tregs. Furthermore, a notable correlation was observed between the genes in the risk model and immune checkpoint genes. The RS model, derived from TRGs, has been validated for its predictive value in immunotherapy outcomes. In conclusion, this model not only predicted the prognosis of HCC patients but also their immune responses, providing innovative strategies for cancer therapy.},
}

@article {pmid40100529,
year = {2025},
author = {Jahn, K and Chatterjee, S and Sinke, C and Koberschinski, JJR and Jünemann, K and James, CE and Worschech, F and Marie, D and Altenmüller, E and Bär, C and Krüger, THC},
title = {An incidental finding during a brain plasticity study: substantial telomere length shortening after COVID-19 lockdown in the older population.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {40100529},
issn = {2509-2723},
support = {100019E-170410//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; 323965454//Deutsche Forschungsgemeinschaft/ ; BA 5631/5-1//Deutsche Forschungsgemeinschaft/ ; },
abstract = {The detrimental effects of lockdowns have already been proven by numerous studies, mainly using psychometric measurements. Since telomere shortening is a driver of aging and aging-associated disorders, including cognitive decline, the telomere length in the older population has been investigated in the current study. Measurements were taken over a 6-month period just before and during the 6 months that included the first lockdown. The cohort of 55 persons aged 64 to 70 years was investigated in the context of a study focusing on neuroplasticity. Participants were recruited in Germany and Switzerland and characterized by psychometric measurements concerning neurocognition and neuroplasticity. Telomere lengths were measured by real-time PCR-based LTL measurement. We found an impressive and significant decline in telomere lengths in the period that included the lockdown (2.33 (± 0.1) at T1 vs. 1.35 (± 0.1) at T2), whereas it was stable in the phase before the lockdown in the same individuals (T0 was 2.25 (± 0.1 S.E.M.) vs. T1, 2.33 (± 0.1)). Correlation of the sudden decrease revealed no linkage to health issues or general physical activity but was in trend related to a decline in the WHOQOL-BREF Social Score referring to the social interaction of the study participants. Our data support, at a biological level, the results of clinical and psychosocial studies showing the detrimental effects of lockdowns.},
}

@article {pmid40097825,
year = {2025},
author = {Paltoglou, G},
title = {Invited Commentary: "Is physical fitness associated with leukocyte telomere length in youth with type 1 diabetes?".},
journal = {Pediatric research},
volume = {},
number = {},
pages = {},
pmid = {40097825},
issn = {1530-0447},
}

@article {pmid40097785,
year = {2025},
author = {Hu, G and Wang, Z and Tian, Z and Wang, K and Ji, G and Wang, X and Zhang, X and Yang, Z and Liu, X and Niu, R and Zhu, D and Zhang, Y and Duan, L and Ma, X and Xiong, X and Kong, J and Zhao, X and Zhang, Y and Zhao, J and He, S and Grover, CE and Su, J and Feng, K and Yu, G and Han, J and Zang, X and Wu, Z and Pan, W and Wendel, JF and Ma, X},
title = {A telomere-to-telomere genome assembly of cotton provides insights into centromere evolution and short-season adaptation.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {40097785},
issn = {1546-1718},
abstract = {Cotton (Gossypium hirsutum L.) is a key allopolyploid crop with global economic importance. Here we present a telomere-to-telomere assembly of the elite variety Zhongmian 113. Leveraging technologies including PacBio HiFi, Oxford Nanopore Technology (ONT) ultralong-read sequencing and Hi-C, our assembly surpasses previous genomes in contiguity and completeness, resolving 26 centromeric and 52 telomeric regions, 5S rDNA clusters and nucleolar organizer regions. A phylogenetically recent centromere repositioning on chromosome D08 was discovered specific to G. hirsutum, involving deactivation of an ancestral centromere and the formation of a unique, satellite repeat-based centromere. Genomic analyses evaluated favorable allele aggregation for key agronomic traits and uncovered an early-maturing haplotype derived from an 11 Mb pericentric inversion that evolved early during G. hirsutum domestication. Our study sheds light on the genomic origins of short-season adaptation, potentially involving introgression of an inversion from primitively domesticated forms, followed by subsequent haplotype differentiation in modern breeding programs.},
}

@article {pmid40097392,
year = {2025},
author = {Romero-Zamora, D and Rogers, S and Low, RRJ and Page, SG and Lane, BJE and Kosaka, S and Robinson, AB and French, L and Lamm, N and Ishikawa, F and Hayashi, MT and Cesare, AJ},
title = {A CPC-shelterin-BTR axis regulates mitotic telomere deprotection.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {2277},
pmid = {40097392},
issn = {2041-1723},
support = {1106241//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 1162886//Department of Health | National Health and Medical Research Council (NHMRC)/ ; },
mesh = {Humans ; *Telomere/metabolism ; *Mitosis ; *Telomeric Repeat Binding Protein 2/metabolism/genetics ; *Aurora Kinase B/metabolism ; Phosphorylation ; Telomeric Repeat Binding Protein 1/metabolism ; Ataxia Telangiectasia Mutated Proteins/metabolism/genetics ; DNA Damage ; RecQ Helicases/metabolism/genetics ; DNA-Binding Proteins/metabolism/genetics ; Telomere-Binding Proteins/metabolism/genetics ; Cell Cycle Proteins/metabolism/genetics ; Shelterin Complex/metabolism ; },
abstract = {Telomeres prevent ATM activation by sequestering chromosome termini within telomere loops (t-loops). Mitotic arrest promotes telomere linearity and a localized ATM-dependent telomere DNA damage response (DDR) through an unknown mechanism. Using unbiased interactomics, biochemical screening, molecular biology, and super-resolution imaging, we found that mitotic arrest-dependent (MAD) telomere deprotection requires the combined activities of the Chromosome passenger complex (CPC) on shelterin, and the BLM-TOP3A-RMI1/2 (BTR) complex on t-loops. During mitotic arrest, the CPC component Aurora Kinase B (AURKB) phosphorylated both the TRF1 hinge and TRF2 basic domains. Phosphorylation of the TRF1 hinge domain enhances CPC and TRF1 interaction through the CPC Survivin subunit. Meanwhile, phosphorylation of the TRF2 basic domain promotes telomere linearity, activates a telomere DDR dependent on BTR-mediated double Holliday junction dissolution, and leads to mitotic death. We identify that the TRF2 basic domain functions in mitosis-specific telomere protection and reveal a regulatory role for TRF1 in controlling a physiological ATM-dependent telomere DDR. The data demonstrate that MAD telomere deprotection is a sophisticated active mechanism that exposes telomere ends to signal mitotic stress.},
}

Humans
*Telomere/metabolism
*Mitosis
*Telomeric Repeat Binding Protein 2/metabolism/genetics
*Aurora Kinase B/metabolism
Phosphorylation
Telomeric Repeat Binding Protein 1/metabolism
Ataxia Telangiectasia Mutated Proteins/metabolism/genetics
DNA Damage
RecQ Helicases/metabolism/genetics
DNA-Binding Proteins/metabolism/genetics
Telomere-Binding Proteins/metabolism/genetics
Cell Cycle Proteins/metabolism/genetics
Shelterin Complex/metabolism

@article {pmid40097157,
year = {2025},
author = {Savage, SA},
title = {Telomeres and Human Disease.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041684},
pmid = {40097157},
issn = {1943-0264},
abstract = {Telomeres, the long nucleotide repeats, and protein complex at chromosome ends, are central to genomic integrity. Telomere length (TL) varies widely between populations due to germline genetics, environmental exposures, and other factors. Very short telomeres caused by pathogenic germline variants in telomere maintenance genes cause the telomere biology disorders, a spectrum of life-threatening conditions including bone marrow failure, liver and lung disease, cancer, and other complications. Cancer predisposition with long telomeres is caused by rare pathogenic germline variants in components of the shelterin telomere protection protein complex and associated primarily with elevated risk of melanoma, thyroid cancer, sarcoma, and lymphoproliferative malignancies. In the middle, studies of the general population at risk of common illnesses, such as cardiovascular disease and cancer, have found statistically significant differences in TL but uncertain clinical applicability. This work reviews connections between telomere biology and human disease focusing on similarities and differences across the phenotypic spectrum.},
}

@article {pmid40097156,
year = {2025},
author = {Bettin, N and Vaurs, M and Decottignies, A},
title = {Epigenetics of Human Telomeres.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041706},
pmid = {40097156},
issn = {1943-0264},
abstract = {Human telomeric heterochromatin is unusual in that it does not show the enrichment of canonical repressive histone marks H3K9me3 or H4K20me3 seen in constitutive heterochromatin. Instead, human telomeres exhibit both facultative heterochromatin and euchromatin marks, consistent with their epigenetically regulated transcription into TERRA noncoding RNA. Additionally, telomeric DNA is out of phase with the DNA helical repeat and has no nucleosome positioning signal. Yet, human telomeric DNA forms a columnar structure of tightly stacked nucleosomes, alternating with open states, and regulated by histone tails and shelterin protein binding. We discuss the proposed mechanisms regulating human telomeric chromatin and the consequences that telomeric chromatin properties have on various cellular processes, such as telomere transcription, the regulation of shelterin binding, and the activation of the alternative lengthening of telomeres mechanism. Together, we summarize current evidence on the combination of hetero- and euchromatic properties of human telomeres that may help explain their crucial protective functions and plasticity to regulate telomere maintenance pathways and damage signaling.},
}

@article {pmid40097153,
year = {2025},
author = {Zanella, E and Doksani, Y},
title = {In the Loop: Unusual DNA Structures at Telomeric Repeats and Their Impact on Telomere Function.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041694},
pmid = {40097153},
issn = {1943-0264},
abstract = {Telomeric repeats recruit the shelterin complex to prevent activation of the double-strand break response at chromosome ends. Thousands of TTAGGG repeats are present at each chromosome end to ensure telomere function. This abundance of G-rich repeats comes with the propensity to generate unusual DNA structures. The telomere loop (t-loop) structure, generated by strand invasion of the 3' overhang in the internal repeats, contributes to telomere function. G4-DNA is promoted by the stretches of G-rich repeats in a single-stranded form and may affect telomere replication and elongation by telomerase. The intramolecular homology can lead to the formation of internal loops (i-loops) via intramolecular recombination at sites of telomeric damage, which can promote the excision of telomeric repeats as extrachromosomal circular DNA. Shelterin promotes t-loops, counteracting the accumulation of pathological structures either directly or via the recruitment of specialized helicases. Here, we will discuss the current evidence for the formation of unusual DNA structures at telomeres and possible implications for telomere function.},
}

@article {pmid40097124,
year = {2025},
author = {Bollu, VS and Chen, YC and Zhang, F and Gowda, K and Amin, S and Sharma, AK and Schell, TD and Zhu, J and Robertson, GP},
title = {Managing Telomerase and Telomere Dysfunction in Acral Melanoma.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {107700},
doi = {10.1016/j.phrs.2025.107700},
pmid = {40097124},
issn = {1096-1186},
abstract = {Acral Lentiginous Melanoma is a rare and aggressive subtype of melanoma that commonly affects the palms, soles, and nail beds. It is more prevalent in individuals with darker skin tones, including Asian, African, and Hispanic populations. Unlike cutaneous melanomas, acral melanoma is not associated with UV exposure and has a distinct genetic and molecular profile, underscoring the need for tailored research and treatment strategies. Standard treatments, such as surgery, chemotherapy, immunotherapy, and targeted therapies, have shown limited success for this melanoma subtype, highlighting the urgency of developing more effective interventions. Telomerase is an enzyme that extends telomeres and is a key target in acral melanoma which exhibits' high telomerase activity, driven by mutations in the telomerase reverse transcriptase TERT promoter, which contributes to uncontrolled tumor cell proliferation, cancer cell immortality, and resistance to conventional therapies. Therefore, targeting telomerase presents a promising therapeutic avenue for acral melanoma patients who do not respond well to current treatments. Several approaches for targeting telomerase deregulation have been developed, and their potential for the management of acral melanoma is discussed in this review. Specifically, the promise of telomerase-targeted therapies for acral melanoma is emphasized and explores how these strategies could improve outcomes for patients with this challenging skin cancer. By focusing on the role of telomerase in tumorigenesis and treatment resistance, telomerase-targeted strategies hold potential as a foundational component of therapies for acral melanoma, complementing existing approaches.},
}

@article {pmid40096055,
year = {2025},
author = {Sirovnik, J and Simon, R and Vogt, A and Barth, K and Smith, S and Waiblinger, S and Lühken, G and König von Borstel, U},
title = {Relative telomere length in dairy calves and dams undergoing two different methods of weaning and separation after three months of contact.},
journal = {PloS one},
volume = {20},
number = {3},
pages = {e0319156},
doi = {10.1371/journal.pone.0319156},
pmid = {40096055},
issn = {1932-6203},
mesh = {Animals ; Cattle ; *Weaning ; Female ; Telomere/genetics ; Behavior, Animal ; Telomere Homeostasis ; Stress, Physiological ; },
abstract = {Telomere length (i.e., the length of the repeated sequences of DNA at the end of chromosomes) is a promising indicator of overall stress. Our study aimed to compare the effects of a stress-inducing separation process between dams and their calves, with either a gradual or a nose-flap separation method after a three-months dam-calf contact since calving, on relative telomere length (RTL). Due to their nature, the nose-flap and gradual separation method have different effects on behaviour, stress hormone levels and physical development during and after dam-calf separation, which requires an overall measure of the weaning and separation stress during both procedures. We also investigated correlations between behavioural and other physiological stress indicators on RTL. We found no significant effect of the weaning and separation method on RTL in dairy calves after weaning and separation from their dams, but a tendency for shorter RTL in gradually separated dams compared to nose-flap separated dams. No correlations between behavioural and other physiological stress indicators and RTL were found, which may be due to a short interval between the two RTL measurement points. Future studies should aim to analyse the effect of various separation methods over a longer period and preferably include a non-separation group as reference.},
}

Animals
Cattle
*Weaning
Female
Telomere/genetics
Behavior, Animal
Telomere Homeostasis
Stress, Physiological

@article {pmid40087886,
year = {2025},
author = {Wu, G and Taylor, E and Youmans, DT and Arnoult, N and Cech, TR},
title = {Rapid dynamics allow the low-abundance RTEL1 helicase to promote telomere replication.},
journal = {Nucleic acids research},
volume = {53},
number = {5},
pages = {},
pmid = {40087886},
issn = {1362-4962},
support = {R35GM143108/NH/NIH HHS/United States ; DGE 2040434//GRFP/ ; /HHMI/Howard Hughes Medical Institute/United States ; },
mesh = {Humans ; *DNA Helicases/metabolism/genetics ; *Telomere/metabolism ; *DNA Replication ; *Telomeric Repeat Binding Protein 2/metabolism/genetics ; S Phase/genetics ; Single Molecule Imaging ; Chromatin/metabolism ; Cell Nucleus/metabolism/genetics ; CRISPR-Cas Systems ; Protein Binding ; HeLa Cells ; G-Quadruplexes ; },
abstract = {Regulator of telomere length 1 (RTEL1) helicase facilitates telomere replication by disassembling DNA secondary structures, such as G-quadruplexes and telomeric loops (t-loops), at the ends of the chromosomes. The recruitment of RTEL1 to telomeres occurs during the S-phase of the cell cycle, but the dynamics of the process has not been studied. Here, we utilized CRISPR genome editing and single-molecule imaging to monitor RTEL1 movement within human cell nuclei. RTEL1 utilizes rapid three-dimensional diffusion to search for telomeres and other nuclear targets. Only 5% of the chromatin-bound RTEL1 is associated with telomeres at any time in the S-phase, but the telomere-bound RTEL1 has much more extended associations. This binding is enhanced by the interaction between RTEL1 and the telomeric protein TRF2 but is largely independent of RTEL1 ATPase activity. The absence of RTEL1 catalytic activity leads to severe defects in cell proliferation, slow progression out of S-phase, and chromosome end-to-end fusion events. We propose that the rapid diffusion of RTEL1 allows this low-abundance protein to explore the nucleus, bind TRF2, and be recruited to telomeres.},
}

Humans
*DNA Helicases/metabolism/genetics
*Telomere/metabolism
*DNA Replication
*Telomeric Repeat Binding Protein 2/metabolism/genetics
S Phase/genetics
Single Molecule Imaging
Chromatin/metabolism
Cell Nucleus/metabolism/genetics
CRISPR-Cas Systems
Protein Binding
HeLa Cells
G-Quadruplexes

@article {pmid40087268,
year = {2025},
author = {Winstanley, YE and Rose, RD and Sobinoff, AP and Wu, LL and Adhikari, D and Zhang, QH and Wells, JK and Wong, LH and Szeto, HH and Piltz, SG and Thomas, PQ and Febbraio, MA and Carroll, J and Pickett, HA and Russell, DL and Robker, RL},
title = {Telomere length in offspring is determined by mitochondrial-nuclear communication at fertilization.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {2527},
pmid = {40087268},
issn = {2041-1723},
support = {APP1130364//Department of Health | National Health and Medical Research Council (NHMRC)/ ; APP1117975//Department of Health | National Health and Medical Research Council (NHMRC)/ ; APP1194141//Department of Health | National Health and Medical Research Council (NHMRC)/ ; 20669397//Channel 7 Children's Research Foundation (CRF)/ ; },
mesh = {Animals ; *Mitochondria/metabolism/drug effects/genetics ; Female ; *Telomere/metabolism/genetics ; Mice ; *Zygote/metabolism/drug effects ; *Fertilization ; Cell Nucleus/metabolism/drug effects ; Telomere Homeostasis/drug effects ; Blastocyst/metabolism/drug effects ; Male ; Mice, Inbred C57BL ; Rotenone/pharmacology ; Pregnancy ; },
abstract = {The initial setting of telomere length during early life in each individual has a major influence on lifetime risk of aging-associated diseases; however there is limited knowledge of biological signals that regulate inheritance of telomere length, and whether it is modifiable is not known. We now show that when mitochondrial activity is disrupted in mouse zygotes, via exposure to 20% O2 or rotenone, telomere elongation between the 8-cell and blastocyst stage is impaired, with shorter telomeres apparent in the pluripotent Inner Cell Mass (ICM) and persisting after organogenesis. Identical defects of elevated mtROS in zygotes followed by impaired telomere elongation, occurred with maternal obesity or advanced age. We further demonstrate that telomere elongation during ICM formation is controlled by mitochondrial-nuclear communication at fertilization. Using mitochondrially-targeted therapeutics (BGP-15, MitoQ, SS-31, metformin) we demonstrate that it is possible to modulate the preimplantation telomere resetting process and restore deficiencies in neonatal telomere length.},
}

Animals
*Mitochondria/metabolism/drug effects/genetics
Female
*Telomere/metabolism/genetics
Mice
*Zygote/metabolism/drug effects
*Fertilization
Cell Nucleus/metabolism/drug effects
Telomere Homeostasis/drug effects
Blastocyst/metabolism/drug effects
Male
Mice, Inbred C57BL
Rotenone/pharmacology
Pregnancy

@article {pmid40082356,
year = {2025},
author = {Dragona, E and Gagos, S},
title = {Two-Replication Round, Telomere Strand-Specific, Chromosome Orientation Fluorescent In Situ Hybridization.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2906},
number = {},
pages = {177-188},
pmid = {40082356},
issn = {1940-6029},
mesh = {*Telomere/genetics ; *In Situ Hybridization, Fluorescence/methods ; *DNA Replication ; Humans ; *Sister Chromatid Exchange/genetics ; },
abstract = {Telomere strand-specific, two-replication-round, chromosome orientation fluorescence in situ hybridization (2R telomeric-CO-FISH) is a molecular cytogenetic protocol that allows simultaneous detection of genomic and telomeric sister chromatid exchanges along with telomeric intrachromosomal conservative break-induced replication. The combination of differential sister-chromatid and strand-specific telomeric labeling, provides information about intrachromosomal DNA recombinational events occurring in the last two consequent replication rounds of living cells grown in the presence of nucleic acid analogs. Despite a plethora of research applications, this methodology can be used to validate the extent of exposure to genotoxic agents and efficiency of recombinational DNA repair.},
}

*Telomere/genetics
*In Situ Hybridization, Fluorescence/methods
*DNA Replication
Humans
*Sister Chromatid Exchange/genetics

@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.

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).

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 = 0.046) and a significantly shorter aGvHD-free survival (p = 0.041). The latter association was further confirmed in a Cox proportional hazards model (p = 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 day after HSCT (p = 0.011).

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.},
}

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

@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 & 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.

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.

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.

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 & 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.

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.

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).

CONCLUSION: Our findings suggest that longer telomere length increases the risk of various cancers in East Asian populations.

IMPACT: Genetically determined longer telomere length may contribute to a risk of certain cancers.},
}