@article {pmid40044947,
year = {2025},
author = {Huang, X and Huang, L and Lu, J and Cheng, L and Wu, D and Li, L and Zhang, S and Lai, X and Xu, L},
title = {The relationship between telomere length and aging-related diseases.},
journal = {Clinical and experimental medicine},
volume = {25},
number = {1},
pages = {72},
pmid = {40044947},
issn = {1591-9528},
support = {2023C03166//the Department of Science and Technology of Zhejiang Province/ ; 2023C03166//the Department of Science and Technology of Zhejiang Province/ ; 2023C03166//the Department of Science and Technology of Zhejiang Province/ ; 4285C50223204005//Hangzhou Normal University/ ; 4285C50223204005//Hangzhou Normal University/ ; },
mesh = {Humans ; *Aging/genetics ; *Telomere Shortening ; *Telomere ; Cellular Senescence/genetics ; Telomere Homeostasis ; },
abstract = {The intensifying global phenomenon of an aging population has spurred a heightened emphasis on studies on aging and disorders associated with aging. Cellular senescence and aging are known to be caused by telomere shortening. Telomere length (TL) has emerged as a biomarker under intense scrutiny, and its widespread use in investigations of diseases tied to advancing age. This review summarizes the current knowledge of the association between telomeres and aging-related diseases, explores the important contribution of dysfunctional telomeres to the development and progression of these diseases, and aims to provide valuable insights for the development of novel therapeutic strategies.},
}

Humans
*Aging/genetics
*Telomere Shortening
*Telomere
Cellular Senescence/genetics
Telomere Homeostasis

@article {pmid40043570,
year = {2025},
author = {Gonçalves, JPB and Chile, T and de Paula, VJR and Teixeira, MZ and Ribeiz, SR and Schalling, M and Busatto Filho, G and Lucchetti, G and Vallada, H},
title = {Exploring the relationship between religiosity and telomere length in older individuals.},
journal = {Journal of psychosomatic research},
volume = {191},
number = {},
pages = {112085},
doi = {10.1016/j.jpsychores.2025.112085},
pmid = {40043570},
issn = {1879-1360},
abstract = {OBJECTIVES: Although telomere length is an established marker of biological aging, the impact of religious beliefs on telomere length remains uncertain.

METHODS: This cross-sectional study investigated the relationship between religiosity and telomere length among senior Brazilians, aged 60 and older. The study examined the association between organizational, non-organizational, and intrinsic religiosity with telomere length, adjusting for sociodemographic, mental, physical health, and medication. Hierarchical linear regression models were used.

RESULTS: 821 participants (62.2 % female, mean age 68.9 years, SD = 6.48) were studied. Female gender and younger age were linked to longer telomeres, but no significant associations were found between religious beliefs and telomere length in adjusted or unadjusted models.

CONCLUSIONS: This study found no evidence of an association between religiosity and telomere length among older Brazilian adults. While prior research highlights religiosity's positive health effects, its direct influence on telomere length remains unclear, warranting further exploration.},
}

@article {pmid40038488,
year = {2025},
author = {Le Bras, A},
title = {A new mouse model with human-like telomeres.},
journal = {Lab animal},
volume = {54},
number = {3},
pages = {63},
doi = {10.1038/s41684-025-01530-7},
pmid = {40038488},
issn = {1548-4475},
}

@article {pmid40035723,
year = {2025},
author = {De Benedittis, G and Latini, A and Morgante, C and Bonini, C and Cela, E and Kroegler, B and Luciano, A and Chiocchi, M and Cavalli, F and Ora, J and Rogliani, P and Novelli, G and Ciccacci, C and Chimenti, MS and Conigliaro, P and Borgiani, P},
title = {Alteration of telomere length and mtDNA copy number in interstitial lung disease associated with rheumatoid arthritis.},
journal = {Autoimmunity},
volume = {58},
number = {1},
pages = {2473741},
doi = {10.1080/08916934.2025.2473741},
pmid = {40035723},
issn = {1607-842X},
mesh = {Humans ; *Arthritis, Rheumatoid/genetics/complications ; *DNA, Mitochondrial/genetics ; Female ; Male ; *Lung Diseases, Interstitial/genetics ; Middle Aged ; *DNA Copy Number Variations ; Aged ; *Telomere/genetics ; Adult ; DNA-Binding Proteins/genetics ; Telomere Shortening ; Telomere Homeostasis/genetics ; Case-Control Studies ; Gene Dosage ; },
abstract = {Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA). The inflammatory response in lung disease is characterized by severe oxidative stress, which enhances cellular senescence. Telomeric shortening and mitochondria dysregulation represent two hallmarks of cellular senescence. The maintenance of telomere length (TL) and mitochondrial DNA (mtDNA) copy number is preserved by many proteins, such as TERF1 and TFAM, respectively. Our aim was to evaluate the TL, the mtDNA copy number and the expression of two regulator gene factors in RA patients with (RA-ILD) and without lung involvement (RA-NILD). Eighty-five RA patients and 21 healthy subjects were enrolled. Relative TL, mtDNA copy number, and expression analysis of TERF1 and TFAM genes were measured using qPCR assay. All RA patients present a statistically significant telomere shortening; in particular, RA-ILD patients show shorter TL compared to both controls and RA-NILD. Patients with Usual Interstitial Pneumonia pattern show a more evident shortening of TL. Lastly, both RA-ILD and RA-NILD patients present a significant decrease in mtDNA copy number compared to controls. The analysis of regulatory genes showed an increase in TERF1 expression in RA patients compared to controls, also after stratification in the two subgroups, and a decrease in TFAM expression in RA patients compared to controls. These results show that the alteration of TL and mtDNA copy number in RA patients is more evident in the presence of ILD. The hypothesis is that, in these patients, oxidative stress could accelerate the shortening of telomeres and the decrease of mtDNA copy number.},
}

Humans
*Arthritis, Rheumatoid/genetics/complications
*DNA, Mitochondrial/genetics
Female
Male
*Lung Diseases, Interstitial/genetics
Middle Aged
*DNA Copy Number Variations
Aged
*Telomere/genetics
Adult
DNA-Binding Proteins/genetics
Telomere Shortening
Telomere Homeostasis/genetics
Case-Control Studies
Gene Dosage

@article {pmid40029527,
year = {2025},
author = {Jebaraj, BMC},
title = {Quantification of Telomere Length in Peripheral Blood Mononuclear Cells Using Quantitative Polymerase Chain Reaction.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2909},
number = {},
pages = {257-267},
pmid = {40029527},
issn = {1940-6029},
mesh = {*Leukocytes, Mononuclear/metabolism ; Humans ; *Telomere/genetics ; *Real-Time Polymerase Chain Reaction/methods ; Telomere Homeostasis ; },
abstract = {Telomeres are crucial biomarkers of cellular aging and health, providing insights into various physiological and pathological processes. Large variety of methods are described for telomere length measurements, each with their own advantages and disadvantages. This chapter explains a quantitative polymerase chain reaction (qPCR)-based method for measuring telomere length in peripheral blood mononuclear cells (PBMCs), with special focus on ways to limit variability between qPCR run and improve comparability of telomere length values. With methodology of relative and absolute quantification, troubleshooting tips, and other guidelines, this chapter serves as a resource for researchers to benefit from this cost-effective and high-throughput assay.},
}

*Leukocytes, Mononuclear/metabolism
Humans
*Telomere/genetics
*Real-Time Polymerase Chain Reaction/methods
Telomere Homeostasis

@article {pmid40028272,
year = {2025},
author = {Huang, W and Wang, W and Dong, TZ},
title = {Telomere Maintenance-Related Genes are Essential for Prognosis in Breast Cancer.},
journal = {Breast cancer (Dove Medical Press)},
volume = {17},
number = {},
pages = {225-239},
pmid = {40028272},
issn = {1179-1314},
abstract = {OBJECTIVE: Telomere maintenance mechanism significantly impacts the metastasis, progression, and survival of breast cancer (BC) patients. This study aimed to investigate the role of telomere maintenance-related genes (TMRGs) in BC prognosis and to construct a related prognostic model.

METHODS: Differentially expressed genes were identified from the TCGA-BC cohort, and functional enrichment analysis was conducted. TMRGs were sourced from the literature and intersected with DEGs. Candidate genes were selected using machine learning algorithms, including Lasso Cox, Random Forest, and XGBoost. Multivariate Cox regression analysis was conducted to construct a prognostic model and identify hub genes. Subsequent analyses included survival analysis, gene set enrichment analysis (GSEA), immune infiltration analysis, and drug sensitivity analysis of the hub genes. Finally, in vitro experiments were conducted to validate the expression of the hub genes.

RESULTS: A total of 1329 differentially expressed TMRGs were analyzed, with 128 significantly associated with overall survival. Machine learning identified 7 prognosis-related TMRGs: MECP2, PCMT1, PFKL, PTMA, TAGLN2, TRMT5, and XRCC4. These genes were used to construct a prognostic model, with MECP2, PCMT1, PFKL, TAGLN2, and XRCC4 as harmful factors, while PTMA and TRMT5 were protective. The model demonstrated a significant prognostic value (AUC: 0.81, 0.72, 0.69 for 1-, 3-, and 5-year, respectively). Survival analysis confirmed the prognostic relevance of these genes, and GSEA highlighted their roles in oxidative phosphorylation, glycolysis, and PI3K/AKT/mTOR signaling.

CONCLUSION: The study identified 7 key TMRGs with significant prognostic value in BC. The constructed model effectively stratifies patient risk, providing a foundation for targeted therapies and personalized treatment strategies.},
}

@article {pmid40027133,
year = {2025},
author = {Zheng, JH and Shi, D and Chen, YJ and Liu, JP and Zhou, Z},
title = {Develop a prognostic and drug therapy efficacy prediction model for hepatocellular carcinoma based on telomere maintenance-associated genes.},
journal = {Frontiers in oncology},
volume = {15},
number = {},
pages = {1544173},
pmid = {40027133},
issn = {2234-943X},
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) poses a substantial global health challenge because of its grim prognosis and limited therapeutic options. Telomere maintenance mechanisms (TMM) significantly influence cancer progression, yet their prognostic value in HCC remains largely unexamined. This research aims to establish a telomere maintenance-associated genes(TMGs)-based prognostic model using transcriptomic and clinical data to evaluate its effectiveness in predicting patient outcomes in HCC.

METHODS: The identified differentially expressed genes (DEGs) were derived from the analysis of transcriptomic and clinical information sourced from the database of the Cancer Genome Atlas (TCGA) and were cross-referenced with TMGs. Candidate risk factors were initially assessed using univariate Cox regression, subsequently followed by LASSO, and then refined through multivariate Cox regression to establish a risk prediction model. This model's predictive accuracy was validated through Kaplan-Meier(K-M) survival analysis, with external validation in the Gene Expression Omnibus (GEO) dataset. Additionally, a nomogram incorporating age and tumor stage was developed. Tumor mutation burden (TMB), immune profile, and drug sensitivity in HCC were also analyzed. Furthermore, we employed RT-PCR to confirm the expression levels of the genes related to TMGs in HepG2 cell lines.

RESULTS: A prognostic model comprising 3 core genes was constructed, with high-risk individuals showing significantly lower overall survival (OS). The association between elevated TMB and diminished survival in high-risk patients was uncovered through TMB analysis. Immune profiling indicated notable disparities in immune infiltration among these groups, with high-risk patients displaying elevated Tumor Immune Dysfunction and Exclusion (TIDE) scores, suggesting potential immune evasion.

CONCLUSION: In short, our prognosis model based on TMGs effectively categorized HCC patients using risk scores, enabling dependable prognostic forecasts and identification of potential therapeutic targets for personalized treatment in HCC management. Future studies should explore integrating this model into clinical practice to improve patient outcomes.},
}

@article {pmid40022541,
year = {2025},
author = {Aviv, A and Verhulst, S},
title = {Telomeres in Space.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70030},
doi = {10.1111/acel.70030},
pmid = {40022541},
issn = {1474-9726},
support = {1U24AG066528/NH/NIH HHS/United States ; R01ES035760/NH/NIH HHS/United States ; U01AG066529/NH/NIH HHS/United States ; #262700//Research Council of Norway/ ; },
abstract = {Recent studies have reported that the spaceflight environment lengthens leukocyte telomeres. We propose that this baffling finding reflects changes in the composition of leukocyte subsets rather than an actual increase in telomere length within individual leukocytes. Since leukocyte telomere length is associated with aging-related diseases and longevity in humans, it is crucial to understand the underlying factors driving telomere length changes in space.},
}

@article {pmid40016654,
year = {2025},
author = {Kang, K and Nie, H and Kuang, W and Li, X and Zhou, Y},
title = {A novel telomere-associated genes signature for the prediction of prognosis and treatment responsiveness of hepatocellular carcinoma.},
journal = {Biological procedures online},
volume = {27},
number = {1},
pages = {8},
pmid = {40016654},
issn = {1480-9222},
support = {1053320221933//the Graduate Student Innovation Fund of Central South University/ ; 82203353//National Natural Science Foundation of China/ ; 2022M723565//Fellowship of China Postdoctoral Science Foundation/ ; 2022JJ40851//Natural Science Foundation of Hunan Province for Youth Foundation/ ; 2021Q16//Youth Research Foundation of Xiangya Hospital, Central South University/ ; },
abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent malignancy worldwide, characterized by its high malignancy and poor prognosis. Telomeres, crucial components of eukaryotic chromosomes, have been increasingly recognized for their involvement in tumorigenesis, development, and impact on the prognosis of cancer patients. However, the precise role of telomere-associated genes in HCC remains incompletely elucidated.

METHODS: The Cancer Genome Atlas (TCGA) database was utilized to download data from 374 HCC and 50 normal liver tissue samples. Differential genes were screened and intersected with 2093 telomere-related genes (TRGs) in GeneCards, resulting in the identification of 704 TRGs exhibiting survival differences. Through univariate Cox regression analysis, multivariate Cox regression analysis, and LASSO regression, a prognostic model consisting of 18 TRGs for HCC risk assessment was developed. The single-cell and spatial transcriptomics were utilized to analyze the expression and distribution of 18 TRGs in HCC. Subsequently, Mendelian randomization (MR) analysis confirmed a causal relationship between ASF1A and alcoholic HCC among the identified 18 TRGs. The expression and functional significance of ASF1A in HCC cell lines were investigated through colony formation assays, Transwell migration assays, and wound healing experiments.

RESULTS: We developed a prognostic risk model for HCC incorporating 18 TRGs. Kaplan-Meier analysis demonstrated that the overall survival (OS) rate of the high-risk group was significantly inferior to that of the low-risk group. Cox regression analysis identified age (HR = 1.017, 95% CI: 1.002-1.032, P = 0.03), stage (HR = 1.389, 95% CI: 1.111-1.737, P = 0.004), and risk score (HR = 5.097, 95% CI: 3.273-7.936, P < 0.001) as three independent risk factors for HCC patients. The five-year receiver operating characteristic curve (ROC) and multivariate Cox regression analysis further validated the accuracy of our model. Time-dependent ROC results revealed that the 1-year, 3-year, and 5-year AUC values were AUC = 0.801, AUC = 0.734, and AUC = 0.690, respectively. The expression and distribution of 18 TRGs in HCC were further validated through single-cell and spatial transcriptomics data. Additionally, immune subtype analysis indicated a significantly lower proportion of C3 and C4 subtypes in the high-risk TRG group compared to the low-risk group. Meanwhile, tumor immune dysfunction and exclusion (TIDE) were significantly higher in the high-risk group than in the low-risk group. Furthermore, we observed differences in IC50 values among nine chemotherapeutic drugs across different TRG risk subtypes which partially confirmed our model's predictive efficacy for immunotherapy. Amongst these eighteen TRGs analyzed by MR analysis, ASF1A was found to be associated with alcoholic HCC pathogenesis. We further confirmed ASF1A was significant overexpression in HCC by Western blotting. We also explored it's the carcinogenic role of ASF1A in HCC via the transwell, wound healing, and clone formation experiments.

CONCLUSION: In this study, we developed a novel prognostic model comprising 18 TRGs for HCC, which exhibited remarkable accuracy in predicting HCC patients' prognosis. Additionally, through MR analysis, we have successfully established a causal relationship between ASF1A and alcoholic HCC for the first time, which also provided a new theoretical foundation for the management of alcoholic HCC.},
}

@article {pmid40016428,
year = {2025},
author = {Salgado, S and Abreu, PL and Moleirinho, B and Guedes, DS and Larcombe, L and Azzalin, CM},
title = {Author Correction: Human PC4 supports telomere stability and viability in cells utilizing the alternative lengthening of telomeres mechanism.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s44319-025-00408-6},
pmid = {40016428},
issn = {1469-3178},
}

@article {pmid40016269,
year = {2025},
author = {Zhang, K and Guo, S and Yang, S and Zhou, W and Wu, J and Zhang, X and Shi, Q and Deng, L},
title = {A telomere-to-telomere genome assembly of the protandrous hermaphrodite blackhead seabream, Acanthopagrus schlegelii.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {350},
pmid = {40016269},
issn = {2052-4463},
mesh = {Animals ; *Sea Bream/genetics ; *Genome ; *Telomere/genetics ; Male ; Female ; },
abstract = {A remarkable life cycle of the protandrous blackhead seabream (Acanthopagrus schlegelii), initiating as a male during the first two years and then naturally transforming to a female since the third year, makes this fish a valuable model for studying molecular mechanisms of sex change. Here, we constructed a gap-free telomere-to-telomere (T2T) genome assembly for a male blackhead seabream, by integration of PacBio HiFi, Ultra-long ONT and Hi-C sequencing techniques. With 97.87% of the entire sequences anchored into 24 chromosomes, this haplotypic genome assembly spans 714.98 Mb. In terms of correctness (quality value QV: 52.95) and completeness (BUSCO score: 99.9%), this chromosome-scale assembly is indeed of high quality. It has been annotated with 24,581 protein-coding genes, and predicted with low percentage (30.95%) of repetitive sequences. As the first reference T2T-level genome assembly of various protandrous fishes, it provides a valuable genetic resource for expansion of fish genomics database. It will also allow for in-depth genomic comparisons among diverse hermaphrodite vertebrates, as well as offer fundamental genome data to support extensive research on blackhead seabream.},
}

Animals
*Sea Bream/genetics
*Genome
*Telomere/genetics
Male
Female

@article {pmid40015989,
year = {2025},
author = {Martin, A and Schabort, J and Bartke-Croughan, R and Tran, S and Preetham, A and Lu, R and Ho, R and Gao, J and Jenkins, S and Boyle, J and Ghanim, GE and Jagota, M and Song, YS and Li, H and Hockemeyer, D},
title = {Active telomere elongation by a subclass of cancer-associated POT1 mutations.},
journal = {Genes & development},
volume = {},
number = {},
pages = {},
doi = {10.1101/gad.352492.124},
pmid = {40015989},
issn = {1549-5477},
abstract = {Mutations in the shelterin protein POT1 are associated with diverse cancers and thought to drive carcinogenesis by impairing POT1's suppression of aberrant telomere elongation. To classify clinical variants of uncertain significance (VUSs) and identify cancer-driving loss-of-function mutations, we developed a locally haploid human stem cell system to evaluate >1900 POT1 mutations, including >600 VUSs. Unexpectedly, many validated familial cancer-associated POT1 (caPOT1) mutations are haplosufficient for cellular viability, indicating that some pathogenic alleles do not act through a loss-of-function mechanism. Instead, POT1's DNA damage response suppression and telomere length control are genetically separable. ATR inhibition enables isolation of frameshift mutants, demonstrating that the only essential function of POT1 is to repress ATR. Furthermore, comparison of caPOT1 and frameshift alleles reveals a class of caPOT1 mutations that elongate telomeres more rapidly than full loss-of-function alleles. This telomere length-promoting activity is independent from POT1's role in overhang sequestration and fill-in synthesis.},
}

@article {pmid40011224,
year = {2025},
author = {Yi, J and Jiang, C and Xia, L},
title = {Mediated roles of oxidative stress and kidney function to leukocyte telomere length and prognosis in chronic kidney disease.},
journal = {Renal failure},
volume = {47},
number = {1},
pages = {2464828},
pmid = {40011224},
issn = {1525-6049},
mesh = {Humans ; *Oxidative Stress ; Male ; Female ; Middle Aged ; *Renal Insufficiency, Chronic/physiopathology/mortality ; *Leukocytes/metabolism ; Prognosis ; Aged ; *Glomerular Filtration Rate ; *Telomere ; *Nutrition Surveys ; Cardiovascular Diseases ; Neoplasms/mortality/genetics ; Risk Factors ; Adult ; Proportional Hazards Models ; Hypertension ; },
abstract = {BACKGROUND: Few studies have focused on the correlation between leukocyte telomere length (LTL) and cancer-related mortality or identified potential factors that mediate the relationship between LTL and mortality among chronic kidney disease (CKD) patients. Our study aimed to explore the associations between LTL and all-cause and cause-specific mortality and to identify the underlying mediators.

METHODS: CKD patients were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Cox regression analysis and restricted cubic spline analysis were used to explore the associations between LTL and all-cause or specific-cause mortality and their nonlinear connections. Stratified analyses were executed to assess the relationships among the different subgroups. The latent mediated factors were confirmed using mediation analysis. Sensitivity analyses were used to evaluate the robustness of our findings.

RESULTS: Longer LTL associated with the lower risk of all-cause mortality, cardiovascular disease (CVD) and cancer-related mortality, and U-shaped relationships were detected. Patients younger than 65 years with greater LTL or who had hypertension had better prognoses. Age and history of hypertension were associated with LTL and overall mortality. In addition, estimated glomerular filtration rate (eGFR), albumin, and total bilirubin mediated the association, and the proportions of indirect effects were 7.81%, 3.77%, and 2.50%, respectively. Six sensitivity analyses confirmed the robustness of our findings.

CONCLUSIONS: This study revealed that LTL was a protective factor for survival among patients with CKD and emphasized the mediating roles of oxidative stress and kidney function.},
}

Humans
*Oxidative Stress
Male
Female
Middle Aged
*Renal Insufficiency, Chronic/physiopathology/mortality
*Leukocytes/metabolism
Prognosis
Aged
*Glomerular Filtration Rate
*Telomere
*Nutrition Surveys
Cardiovascular Diseases
Neoplasms/mortality/genetics
Risk Factors
Adult
Proportional Hazards Models
Hypertension

@article {pmid40011083,
year = {2025},
author = {Zeng, Y and Yuan, X and Zi, J and Hu, Y and Wang, X and Cheng, G and Xiong, J},
title = {Telomere length mediates the causal effects of excess adiposity on cardiovascular risk: A two-step Mendelian randomization study.},
journal = {Nutrition, metabolism, and cardiovascular diseases : NMCD},
volume = {},
number = {},
pages = {103904},
doi = {10.1016/j.numecd.2025.103904},
pmid = {40011083},
issn = {1590-3729},
abstract = {BACKGROUND AND AIMS: Excess adiposity correlate to cardiovascular diseases, inflammation, and telomere shortening, while the latter two are associated with cardiovascular risks. Whether inflammation and telomere length mediate the excess adiposity-cardiovascular relationship is unclear.

METHODS AND RESULTS: We performed a two-step Mendelian randomization analysis utilizing data from the latest genome-wide association studies: body mass index (BMI, n = 681,275), waist-to-hip ratio (WHR, n = 697,734) and BMI adjusted WHR (WHRadjBMI, n = 694,649), telomere length (n = 472,174), C-reactive protein (n = 204,402), interleukin-6 and interleukin-1 receptor antagonist (n = 21,758), tumor necrosis factor-α (n = 3454), hypertension (n = 463,010), coronary artery disease (n = 547,261), heart failure (n = 977,323), stroke (n = 446,696), ischemic stroke (n = 440,328), intracerebral hemorrhage (n = 343,663), aortic aneurysm (n = 356,934), transient ischemic attack (n = 360,692), peripheral vascular disease (n = 463,010), systolic and diastolic blood pressure changes (n = 757,601). We observed casual effects of excess adiposity on eight cardiovascular diseases, hypertension and blood pressure changes. Telomere length is causally associated with hypertension, blood pressure, coronary artery disease, aortic aneurysm, and intracerebral hemorrhage, mediates BMI's effect on coronary artery disease (2.41 %) and aortic aneurysm (4.97 %), and plays a suppressive role between WHR and systolic blood pressure changes (2.39 %).

CONCLUSION: Telomere length mediates the causal effects of excess adiposity on the risks of coronary artery disease, aortic aneurysm, and systolic blood pressure changes.},
}

@article {pmid40008862,
year = {2025},
author = {Wąsowicz, W and Janasik, B and Reszka, E and Kasperczyk, E and Chrzanowski, J and Fendler, W},
title = {Metals (Cr, Mn, Co, Ni) concentration in the blood plasma and urine od Polish welders and telomere length as an potential indicator of toxicity of metals welding fumes exposure.},
journal = {International journal of occupational medicine and environmental health},
volume = {},
number = {},
pages = {},
doi = {10.13075/ijomeh.1896.02493},
pmid = {40008862},
issn = {1896-494X},
abstract = {OBJECTIVES: The study investigated the concentrations of metals (chromium [Cr], manganese [Mn], cobalt [Co], nickel [Ni]) in the blood plasma and urine of Polish welders exposed to these elements contained in welding dust/fumes based on the results of biological monitoring, analyze the interrelationships between these elements, and attempt to correlate these data with telomere length. It is believed that telomere length can be considered a marker of exposure, including occupational. Analysis of questionnaire surveys was also taken into consideration.

MATERIAL AND METHODS: The study included 118 male welders and 51 age-matched male controls. Metals analysis in plasma and urine were determined by ICP-MS technique. Telomere length was measured in blood genomic DNA using the qRT-PCR method.

RESULTS: Welders had significantly higher plasma levels of Cr, Ni, and Mn (p < 0.0001, respectively). Total concentrations of Cr, Ni, and Mn in the urine of pre-shift subjects were significantly higher compared to controls. Cobalt concentration in urine of exposed welders was significantly higher (p < 0.02) than in control group. Telomere length was exactly the same in the welder group compared to the control (mean ± standard deviation 0.99±0.41 vs. 0.99±0.52, respectively). Plasma and urine metal concentrations and telomere length were also studied in groups of welders in relation to personal protection equipment. Differences were found in plasma and urine metal concentrations according to the aspirators used. Statistically significant linear correlations were found between plasma and urine concentrations of the determined elements both before and after the work shift.

CONCLUSIONS: The findings suggest a positive relationship between Ni and Mn (end-shift) concentrations and telomere length, the effect which remained statistically significant even after adjusting for age and metabolic status. This indicates a complex interplay between metal exposure and biological aging markers. However, the relationship between exposure to welding fumes and changes in telomere length in welders requires further in-depth research. Int J Occup Med Environ Health. 2025;38(1).},
}

@article {pmid40004056,
year = {2025},
author = {Yan, B and Suen, MC and Xu, N and Lu, C and Liu, C and Zhu, G},
title = {G-Quadruplex Structures Formed by Human Telomere and C9orf72 GGGGCC Repeats.},
journal = {International journal of molecular sciences},
volume = {26},
number = {4},
pages = {},
doi = {10.3390/ijms26041591},
pmid = {40004056},
issn = {1422-0067},
support = {32071188//National Scientific Foundation of China/ ; 16101120, 161011121, AoE/M-403-16, AoE/M-401/20//Research Grants Council of the Hong Kong Special Administrative Region, China/ ; BGF.2023.019//Hong Kong University of Science and Technology, China/ ; 2021A1515220104//Guangdong Basic and Applied Basic Research Foundation, China/ ; 32301012//Young Scientists Fund of the National Natural Science Foundation of China/ ; },
mesh = {*G-Quadruplexes ; Humans ; *Telomere/genetics ; *C9orf72 Protein/genetics ; *DNA Repeat Expansion/genetics ; *Amyotrophic Lateral Sclerosis/genetics ; Frontotemporal Dementia/genetics/pathology ; },
abstract = {G-quadruplexes (G4s) are unique nucleic acid structures composed of guanine-rich (G-rich) sequences that can form diverse topologies based on the arrangement of their four strands. G4s have attracted attention for their potential roles in various biological processes and human diseases. In this review, we focus on the G4 structures formed by human telomeric sequences, (GGGTTA)n, and the hexanucleotide repeat expansion, (GGGGCC)n, in the first intron region of the chromosome 9 open reading frame 72 (C9orf72) gene, highlighting their structural diversity and biological significance. Human telomeric G4s play crucial roles in telomere retention and gene regulation. In particular, we provide an in-depth summary of known telomeric G4s and focus on our recently discovered chair-type conformation, which exhibits distinct folding patterns. The chair-type G4s represent a novel folding pattern with unique characteristics, expanding our knowledge of telomeric G4 structural diversity and potential biological functions. Specifically, we emphasize the G4s formed by the (GGGGCC)n sequence of the C9orf72 gene, which represents the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The thorough structural analysis in this review advances our comprehension of the disease mechanism and provides valuable insights into developing targeted therapeutic strategies in ALS/FTD.},
}

*G-Quadruplexes
Humans
*Telomere/genetics
*C9orf72 Protein/genetics
*DNA Repeat Expansion/genetics
*Amyotrophic Lateral Sclerosis/genetics
Frontotemporal Dementia/genetics/pathology

@article {pmid40004050,
year = {2025},
author = {Anatskaya, OV and Ponomartsev, SV and Elmuratov, AU and Vinogradov, AE},
title = {Transcriptome-Wide Insights: Neonatal Lactose Intolerance Promotes Telomere Damage, Senescence, and Cardiomyopathy in Adult Rat Heart.},
journal = {International journal of molecular sciences},
volume = {26},
number = {4},
pages = {},
doi = {10.3390/ijms26041584},
pmid = {40004050},
issn = {1422-0067},
support = {Agreement No. 075-15-2021-1075//Ministry of Science and Higher Education of the Russian Federation/ ; },
mesh = {Animals ; Rats ; *Cardiomyopathies/genetics/metabolism/pathology/etiology ; *Transcriptome ; *Myocytes, Cardiac/metabolism/pathology ; *Animals, Newborn ; Telomere/genetics/metabolism ; Oxidative Stress/genetics ; Cellular Senescence/genetics ; Gene Expression Profiling ; DNA Damage ; Male ; Lactose/metabolism ; },
abstract = {Cardiovascular diseases (CVD) are the primary cause of mortality globally. A significant aspect of CVD involves their association with aging and susceptibility to neonatal programming. These factors suggest that adverse conditions during neonatal development can disrupt cardiomyocyte differentiation, thereby leading to heart dysfunction. This study focuses on the long-term effects of inflammatory and oxidative stress due to neonatal lactose intolerance (NLI) on cardiomyocyte transcriptome and phenotype. Our recent bioinformatic study focused on toggle genes indicated that NLI correlates with the switch off of some genes in thyroid hormone, calcium, and antioxidant signaling pathways, alongside the switch-on/off genes involved in DNA damage response and inflammation. In the presented study, we evaluated cardiomyocyte ploidy in different regions of the left ventricle (LV), complemented by a transcriptomic analysis of genes with quantitative (gradual) difference in expression. Cytophotometric and morphologic analyses of LV cardiomyocytes identified hyperpolyploidy and bridges between nuclei suggesting telomere fusion. Transcriptomic profiling highlighted telomere damage, aging, and chromatin decompaction, along with the suppression of pathways governing muscle contraction and energy metabolism. Echocardiography revealed statistically significant LV dilation and a decrease in ejection fraction. The estimation of survival rates indicated that NLI shortened the median lifespan by approximately 18% (p < 0.0001) compared with the control. Altogether, these findings suggest that NLI may increase susceptibility to cardiovascular diseases by accelerating aging due to oxidative stress and increased telomere DNA damage, leading to hyperpolyploidization and reduced cardiac contractile function. Collectively, our data emphasize the importance of the early identification and management of neonatal inflammatory and metabolic stressors, such as NLI, to mitigate long-term cardiovascular risks.},
}

Animals
Rats
*Cardiomyopathies/genetics/metabolism/pathology/etiology
*Transcriptome
*Myocytes, Cardiac/metabolism/pathology
*Animals, Newborn
Telomere/genetics/metabolism
Oxidative Stress/genetics
Cellular Senescence/genetics
Gene Expression Profiling
DNA Damage
Male
Lactose/metabolism

@article {pmid40003720,
year = {2025},
author = {Chaithanya, V and Kumar, J and Vajravelu Leela, K and Baig, HA and Soliman, M and Alenezy, A and Shalaby, NM},
title = {Multistrain Probiotics and Telomere Length in Type 2 Diabetes: A 24-Week Randomized Controlled Trial.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {2},
pages = {},
doi = {10.3390/life15020311},
pmid = {40003720},
issn = {2075-1729},
support = {SRMIST/R/AR(A)/SERI2023/174/21-3866.//SRM Institute of Science and Technology/ ; },
abstract = {BACKGROUND: This 24-week randomized controlled trial aimed to evaluate the impact of multistrain probiotic supplementation on telomere length in patients with type 2 diabetes (T2DM). The study also assessed secondary outcomes including high-sensitivity C-reactive protein (hs-CRP) and glycated hemoglobin (HbA1c).

METHODS: A total of 124 participants with T2DM were randomly assigned to either a probiotic group (n = 62) or a placebo group (n = 62). Participants in the probiotic group consumed a supplement containing fourteen live microbial strains, including Lactobacillus plantarum, L. fermentum, L. acidophilus, L. casei, L. rhamnosus, L. reuteri, L. salivarius, L. paracasei, L. gasseri, Bifidobacterium bifidum, B. lactis, B. breve, Streptococcus thermophilus, and Saccharomyces boulardii, with each strain providing 2.148 billion CFUs per capsule, totaling 30 billion CFUs. The placebo group received vitamin B12 capsules without probiotics. The primary outcome was telomere length, and secondary outcomes included hs-CRP and HbA1c levels. Data were analyzed using intention-to-treat (ITT) and per-protocol (PP) methods.

RESULTS: The probiotic group exhibited a statistically significant decrease in telomere shortening compared to the placebo group (p < 0.001). The hs-CRP levels decreased more significantly in the probiotic group (p < 0.001), suggesting potential anti-inflammatory effects. The HbA1c levels improved in the probiotic group, with a reduction of 0.44% (p = 0.004). An age-stratified analysis revealed more substantial improvements in the 30-49 years cohort, which showed greater reductions in telomere shortening, inflammatory markers, and metabolic indicators compared to the 50-69 years group.

CONCLUSIONS: Multistrain probiotic supplementation shows potential benefits in reducing telomere shortening and improving glycemic control. However, further long-term studies are needed to understand the underlying mechanisms and therapeutic implications of probiotics in T2DM.

TRIAL REGISTRATION: This trial was registered at the Clinical Trials Registry-India (CTRI/2023/07/055647).},
}

@article {pmid40002919,
year = {2025},
author = {Rajkumar, RP},
title = {Telomere Dynamics in Post-Traumatic Stress Disorder: A Critical Synthesis.},
journal = {Biomedicines},
volume = {13},
number = {2},
pages = {},
doi = {10.3390/biomedicines13020507},
pmid = {40002919},
issn = {2227-9059},
abstract = {Post-traumatic stress disorder (PTSD), a mental disorder caused by exposure to traumatic stress, affects 5-10% of the world's population. There is some evidence that PTSD is associated with accelerated cellular aging, leading to an increased risk of medical and neurodegenerative comorbidities. Alterations in telomere length (TL) and telomerase enzyme activity have been proposed as biomarkers of this process. This hypothesis was seemingly confirmed in preliminary research, but more recent studies have yielded mixed results. The current narrative review was conducted to provide a critical synthesis of existing research on telomere length and telomerase in PTSD. Data from 26 clinical studies suggest that TL in PTSD is highly variable and may be influenced by methodological, demographic, trauma-related, and psychosocial factors. There is no evidence for altered telomerase activity in PTSD. In contrast, animal research suggests that exposure to traumatic stress does lead to TL shortening. Overall, it is likely that TL is not, by itself, a reliable biomarker of cellular aging in PTSD. Other markers of cellular senescence, such as epigenetic changes, may prove to be more specific in measuring this process in patients with PTSD.},
}

@article {pmid40002695,
year = {2025},
author = {Lee, J and Choi, E and Kim, H and Kim, YJ and Kim, SH},
title = {NELL2-PAX7 Transcriptional Cascade Suggests Activation Mechanism for RAD52-Dependent Alternative Lengthening of Telomeres During Malignant Transformation of Malignant Peripheral Nerve Sheath Tumors: Elongation of Telomeres and Poor Survival.},
journal = {Biomedicines},
volume = {13},
number = {2},
pages = {},
doi = {10.3390/biomedicines13020281},
pmid = {40002695},
issn = {2227-9059},
support = {2017M3A9A7050614//National Research Foundation of Korea/ ; 2017R1D1A1B03031717//National Research Foundation of Korea/ ; 6-2016-0101//Yonsei University College of Medicine/ ; 2019-32-0024//Yonsei University College of Medicine/ ; },
abstract = {Background: In eukaryotes with a double-stranded linear DNA genome, the loss of terminal DNA during replication is inevitable due to an end-replication problem; here, telomeres serve as a buffer against DNA loss. Thus, the activation of the telomere maintenance mechanism (TMM) is a prerequisite for malignant transformation. Methods: We compared neurofibroma (NF, benign) and malignant peripheral nerve sheath tumors (MPNSTs) occurring in the same patient with type 1 neurofibromatosis, where each NF-MPNST pair shared the same genetic background and differentiation lineage; this minimizes the genetic bias and contrasts only those changes that are related to malignant transformation. A total of 20 NF-MPNST pairs from 20 NF1 patients were analyzed. Whole-transcriptome sequencing (WTS) was conducted to profile the transcriptional relationship, and whole-genome sequencing (WGS) was performed to measure the telomere length. Results: We identified 22 differentially expressed genes (DEGs) during the malignant transformation of MPNSTs. Among them, NELL2 activated PAX7, which sequentially activated RAD52, the recombinase of RAD52-dependent alternative lengthening of telomeres (ALT). RAD52 elongated MPNSTs-telomeres (p = 0.017). Otherwise, neither NELL2 nor PAX7 affected telomere length (p = 0.647 and p = 0.354, respectively). RAD52 increased MPNSTs-telomeres length, independently of NELL2 and PAX7 in multiple analyses (p = 0.021). The group with increased telomere length during the malignant transformation showed inferior overall survival (OS) (HR = 3.809, p = 0.038) to the group without increased telomere length. Accordingly, the group with increased PAX7 showed inferior OS (HR = 4.896, p = 0.046) and metastasis-free survival (MFS) (HR = 9.129, p = 0.007) in comparison to the group without increased PAX7; the group with increased RAD52 showed inferior MFS (HR = 8.669, p = 0.011) in comparison to the group without increased RAD52. Conclusions: We suggest that the NELL2-PAX7 transcriptional cascade activates RAD52-dependent ALT to increase telomere length during the malignant transformation of MPNSTs, resulting in a poor prognosis.},
}

@article {pmid39999893,
year = {2025},
author = {Burraco, P and Metcalfe, NB and Monaghan, P},
title = {Telomere dynamics in maturing frogs vary among organs.},
journal = {Biology letters},
volume = {21},
number = {2},
pages = {20240626},
doi = {10.1098/rsbl.2024.0626},
pmid = {39999893},
issn = {1744-957X},
support = {//ERC/ ; //Ramón y Cajal Fellowship/ ; //Spanish Ministry of Science and Innovation/ ; //European Union/ ; },
mesh = {Animals ; *Telomere ; *Xenopus laevis/genetics/physiology ; Male ; Female ; Liver/metabolism ; Temperature ; Aging ; Larva/growth & development/physiology/genetics ; Telomere Shortening ; Muscle, Skeletal/growth & development/metabolism/physiology ; Myocardium/metabolism ; Metamorphosis, Biological ; },
abstract = {It is important to know whether organs age at the same rate and are equally affected by developmental conditions as this provides insights into causes of ageing. However, data on organ-specific telomere dynamics remain scant. In a previous study of the early life of the amphibian Xenopus laevis, we detected changes in telomere lengths in gut cells, while liver, heart and muscle telomeres were unchanged; larval rearing temperature had minimal effects. Here, we extend that study to examine telomere dynamics in the same four organs and larval temperature treatments from 70-day post-metamorphic juvenile Xenopus through to sexually mature (2-year-old) adults. Telomeres shortened from juvenile to adult in the gut, heart and hindlimb muscle. In contrast, liver telomere lengths did not change with age but were shorter if the early life temperature was warm. Organ telomere lengths were influenced by sex only in adults. Warmer larval temperatures were also associated with longer gut telomeres in juveniles. Hence, pre-metamorphic conditions can influence post-metamorphic telomere dynamics, and telomere loss between juvenile and adult life stages occurs in different organs from those affected earlier in life. These findings indicate the existence of organ-dependent ageing rates across lifetimes, potentially related to developmental and environmental history.},
}

Animals
*Telomere
*Xenopus laevis/genetics/physiology
Male
Female
Liver/metabolism
Temperature
Aging
Larva/growth & development/physiology/genetics
Telomere Shortening
Muscle, Skeletal/growth & development/metabolism/physiology
Myocardium/metabolism
Metamorphosis, Biological

@article {pmid39998303,
year = {2025},
author = {Myers, KC and Davies, SM and Lutzko, C and Wahle, R and Grier, DD and Aubert, G and Norris, K and Baird, DM and Koga, M and Ko, AC and Amano, T and Amano, M and Yu, H and Ko, MSH},
title = {Clinical Use of ZSCAN4 for Telomere Elongation in Hematopoietic Stem Cells.},
journal = {NEJM evidence},
volume = {4},
number = {3},
pages = {EVIDoa2400252},
doi = {10.1056/EVIDoa2400252},
pmid = {39998303},
issn = {2766-5526},
mesh = {Humans ; Male ; Female ; *Hematopoietic Stem Cells/metabolism ; *Telomere/metabolism ; Adult ; Dyskeratosis Congenita/genetics/pathology/therapy ; Transcription Factors/genetics/metabolism ; Hematopoietic Stem Cell Transplantation/methods ; Hematopoietic Stem Cell Mobilization ; Adolescent ; Young Adult ; Antigens, CD34/metabolism ; },
abstract = {BACKGROUND: Extremely short telomeres in patients with dyskeratosis congenita and related telomere biology disorders (TBDs) lead to premature cellular senescence and bone marrow failure. Zinc finger and SCAN domain-containing 4 (ZSCAN4) elongates telomeres by recombination.

METHODS: We report a clinical study in which EXG34217, the term given for autologous CD34+ hematopoietic stem cells from patients with TBD exposed to a temperature-sensitive Sendai virus vector encoding human ZSCAN4 at 33°C for 24 hours, was infused into patients without preconditioning.

RESULTS: Four patients were enrolled; two experienced successful CD34+ mobilization during the second mobilization attempt and underwent apheresis and EXG34217 infusion, with follow-up of 5 and 24 months (both ongoing). We observed telomere elongation (1.06- to 1.34-fold) in CD34+ cells ex vivo. In one patient, the treatment was associated with a change in the mean absolute neutrophil count (ANC) from 1.78×10[3] to 3.18×10[3] cells/μl; the lymphocyte subpopulation telomere length changed from 3.6 to 6.7 kb (50th percentile for age). In the other patient, the treatment was associated with a change in the lowest ANC from 0.6×10[3]/μl to 1.2×10[3]/μl; this has occurred in 5 months without the patient receiving prior intermittent low-dose granulocyte-colony-stimulating factor injections. During mobilization, all patients experienced mild to moderate bone pain or pain after line replacement, and one patient had a blood infection associated with fever and hypoxemia. After EXG34217 infusion, no acute safety issues were noted; in one patient mild to moderate long-term cardiac and pulmonary adverse events were noted; these were similar to symptoms of the patient's underlying conditions.

CONCLUSIONS: Although definitive conclusions cannot be drawn from the two EXG34217-treated patients, these results warrant further investigation of CD34+ cells exposed to ZSCAN4 for treating TBDs. (Funded by Elixirgen Therapeutics; ClinicalTrials.gov number, NCT04211714.).},
}

Humans
Male
Female
*Hematopoietic Stem Cells/metabolism
*Telomere/metabolism
Adult
Dyskeratosis Congenita/genetics/pathology/therapy
Transcription Factors/genetics/metabolism
Hematopoietic Stem Cell Transplantation/methods
Hematopoietic Stem Cell Mobilization
Adolescent
Young Adult
Antigens, CD34/metabolism

@article {pmid39992010,
year = {2025},
author = {},
title = {Expression of Concern: Mitogen Stimulation Cooperates with Telomere Shortening To Activate DNA Damage Responses and Senescence Signaling.},
journal = {Molecular and cellular biology},
volume = {},
number = {},
pages = {1},
doi = {10.1080/10985549.2025.2462481},
pmid = {39992010},
issn = {1098-5549},
}

@article {pmid39990381,
year = {2025},
author = {Quintanilla, I and Azeroglu, B and Sagar, MAK and Stracker, TH and Lazzerini Denchi, E and Pegoraro, G},
title = {Optical Pooled Screening for the Discovery of Regulators of the Alternative Lengthening of Telomeres Pathway.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.02.15.638448},
pmid = {39990381},
issn = {2692-8205},
abstract = {Telomere elongation is essential for the proliferation of cancer cells. Telomere length control is achieved by either the activation of the telomerase enzyme or the recombination-based Alternative Lengthening of Telomeres (ALT) pathway. ALT is active in about 10-15% of human cancers, but its molecular underpinnings remain poorly understood, preventing the discovery of potential novel therapeutic targets. Pooled CRISPR-based functional genomic screens enable the unbiased discovery of molecular factors involved in cancer biology. Recently, Optical Pooled Screens (OPS) have significantly extended the capabilities of pooled functional genomics screens to enable sensitive imaging-based readouts at the single cell level and large scale. To gain a better understanding of the ALT pathway, we developed a novel OPS assay that employs telomeric native DNA FISH (nFISH) as an optical quantitative readout to measure ALT activity. The assay uses standard OPS protocols for library preparation and sequencing. As a critical element, an optimized nFISH protocol is performed before in situ sequencing to maximize the assay performance. We show that the modified nFISH protocol faithfully detects changes in ALT activity upon CRISPR knock-out (KO) of the FANCM and BLM genes which were previously implicated in ALT. Overall, the OPS-nFISH assay is a reliable method that can provide deep insights into the ALT pathway in a high-throughput format.},
}

@article {pmid39986429,
year = {2025},
author = {Erickson, PA and Chang, VC and He, S and Dagnall, C and Teshome, K and Machiela, MJ and Barry, KH and Pereira, EFR and Gadalla, SM and Parks, CG and Berndt, SI and Beane Freeman, LE and Andreotti, G and Hofmann, JN},
title = {Occupational Pesticide Use and Relative Leukocyte Telomere Length in the Biomarkers of Exposure and Effect in Agriculture Study.},
journal = {Environmental research},
volume = {},
number = {},
pages = {121174},
doi = {10.1016/j.envres.2025.121174},
pmid = {39986429},
issn = {1096-0953},
abstract = {Previous epidemiological studies have reported increased risks of certain cancers in relation to pesticide exposures. Although the biologic mechanisms underlying these associations are not well understood, altered telomere length has been hypothesized to play a role. We examined associations between occupational use of specific pesticides and leukocyte telomere length in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiological investigation of pesticide applicators in Iowa and North Carolina. Relative telomere length (RTL) was measured using quantitative polymerase chain reaction in leukocytes from 1,539 male pesticide applicators ≥50 years of age. We evaluated lifetime use of 47 pesticides in terms of self-reported ever use and intensity-weighted lifetime days (IWLDs), a metric integrating lifetime days of use and other factors influencing exposure. Multivariable linear regression was used to estimate percent difference in geometric mean RTL in relation to ever (vs. never) use, IWLDs of use, and timing of use [recent (last 12 months) and former vs. never use]. Mean RTL was significantly longer among ever users of the insecticides lindane (percent difference=2.20%, 95%CI: 0.45%, 3.99%) and aldicarb (percent difference=3.27%, 95%CI: 0.23%, 6.40%). Longer RTL was also associated with increasing IWLDs of lindane (highest quartile vs. never use: percent difference=4.51%, 95%CI: -0.22%, 9.46%; p-trend=0.048) and the insecticide diazinon (4.77%, 95%CI: 0.17%, 9.58%; p-trend=0.055), and with recent use of the insecticide dichlorvos (vs. never use: 8.15%, 95%CI: 1.31%, 15.46%). Increasing IWLDs of the insecticide heptachlor and the herbicide 2,4,5-TP and recent use of the herbicide metolachlor were significantly associated with shorter RTL. Our findings provide novel evidence suggesting that use of certain pesticides is associated with altered leukocyte telomere length. Notably, diazinon and lindane have previously been associated with increased risks of lung and lymphoid malignancies, respectively, and longer leukocyte telomere length has been implicated in the development of these cancers.},
}

@article {pmid39983997,
year = {2025},
author = {Page, J and Stephens, C and Richard, M and Lyons, E and Baumler, E and Verklan, MT and Lorenzo, E},
title = {The relationship between physical activity and telomere length in women: A systematic review.},
journal = {Mechanisms of ageing and development},
volume = {},
number = {},
pages = {112042},
doi = {10.1016/j.mad.2025.112042},
pmid = {39983997},
issn = {1872-6216},
abstract = {Telomere length (TL) is a biomarker of cellular aging with variations observed by sex, age, race, and ethnicity. Prior studies have suggested that physical activity (PA) may positively impact TL by potentially elongating telomeres and slowing cellular aging. However, research examining the optimal type and intensity of PA needed to elicit these changes specific to women remains limited. This systematic review aimed to investigate variations in TL in response to PA among women, exploring how these effects differ by age, race, or ethnicity. Following PRISMA guidelines, searches across five databases identified 17 relevant studies published from 2008 to 2022. A narrative synthesis of study findings indicated PA did not have a significant relationship with TL in women. However, a possible positive relationship was noted between specific types of PA and TL, specific to combined aerobic and strength-training PA and high intensity interval training interventions. The impact of PA on TL appeared to be age-dependent as well, showing significant positive relationships between PA and TL in early and later adulthood but not in middle adulthood. Findings related to race or ethnicity were inconclusive due to limited analyses from the included studies. The studies varied greatly by PA type, intensity, duration, and frequency, which, along with the reliance on self-reported PA measures in the observational studies, impacted the ability to draw firm conclusions. This review underscores the necessity for future research in large cohort studies using objectively measured PA interventions to further clarify the complex associations between PA and TL in women.},
}

@article {pmid39983416,
year = {2025},
author = {Liu, Z and Liu, X},
title = {Prognostic model of osteosarcoma based on telomere-related genes and analysis of immune characteristics.},
journal = {International immunopharmacology},
volume = {151},
number = {},
pages = {114198},
doi = {10.1016/j.intimp.2025.114198},
pmid = {39983416},
issn = {1878-1705},
abstract = {OBJECTIVE: Osteosarcoma is a malignant tumor with significant challenges in treatment and prognosis. Telomeres play a crucial role in genetic stability and tumor development, and telomere-related genes (TRGs) have shown considerable prognostic potential in various cancers. However, the prognostic significance of TRGs in osteosarcoma and their involvement in the tumor immune microenvironment (TIME) remain poorly understood.

METHOD: This study initially identified 2086 TRGs from the TelNet database as candidate genes. Using RNA sequencing and clinical data from osteosarcoma patients available in the TARGET and GEO public databases, we developed a TRG-based prognostic scoring model through univariate, LASSO regression, and multivariate Cox regression analyses, with its predictive performance subsequently validated. Unsupervised clustering was performed on TRGs associated with prognosis. To investigate the TIME, we utilized several algorithms including ESTIMATE, CIBERSORT, xCELL, and ssGSEA to analyze the immune landscape associated with TRG patterns. Additionally, functional enrichment analysis of different subtypes was conducted using KEGG, GO, and GSVA approaches. We also performed single-cell localization and drug sensitivity analysis on the prognostic model genes. Finally, the predictive results were preliminarily validated through a series of in vitro experiments.

RESULT: Differential expression analysis revealed 841 TRGs with significant changes in osteosarcoma, where P-value < 0.05 and |logFC| ≥ 1. Based on the prognostic relevance of these TRGs, we successfully identified two subtypes with distinct clinical and immune characteristics. Immune infiltration levels between Cluster 1 and Cluster 2 were significantly different, as assessed by multiple algorithms. Furthermore, we constructed a prognostic scoring model based on TRGs, which demonstrated excellent predictive performance, with AUC values for 1-year, 3-year, and 5-year ROC curves being 92.43 %, 87.08 %, and 84.34 % in the training cohort, respectively, and 74.49 %, 87.77 %, and 94.52 % in the validation cohort, indicating good stability of the model. Notably, functional enrichment analysis highlighted a strong association between immune dysfunction and poor prognosis, while drug sensitivity analysis offered personalized chemotherapy recommendations for osteosarcoma patients with different subtypes. We observed that Fludarabine had a higher IC50 value in the high-risk group compared to the low-risk group, and it showed a strong correlation with the prognostic model genes, with all P-values less than 0.05.

CONCLUSION: This study successfully constructed a prognostic risk prediction model for osteosarcoma by systematically analyzing the expression patterns of TRGs. Fludarabine may represent a promising therapeutic option for patients with osteosarcoma.},
}

@article {pmid39982908,
year = {2025},
author = {Armendáriz-Castillo, I and García-Cárdenas, J and Espinosa, P and Hidalgo-Fernández, K and Peña-Zúñiga, L and Martínez, R and Moromenacho, J and Herrera-Yela, A and Cruz-Varela, J and Saucedo-Sariñana, A and Cerdán, ME and López-Cortés, A and Guerrero, S},
title = {Metabolic pathways of Alternative Lengthening of Telomeres in pan-carcinoma.},
journal = {PloS one},
volume = {20},
number = {2},
pages = {e0314012},
doi = {10.1371/journal.pone.0314012},
pmid = {39982908},
issn = {1932-6203},
mesh = {Humans ; *Telomere Homeostasis ; *Metabolic Networks and Pathways ; Neoplasms/metabolism/pathology/genetics ; Telomere/metabolism/genetics ; Purines/metabolism ; Metabolomics/methods ; },
abstract = {Alternative Lengthening of Telomeres (ALT) is a telomerase-independent mechanism deployed by several aggressive cancers to maintain telomere length. This contributes to their malignancy and resistance to conventional therapies. In prior studies, we have identified key proteins linked to the ALT process using multi-omic data integration strategies. In this work, we combined metabolomic datasets with our earlier results to identify targetable metabolic pathways for ALT-positive tumors. 39 ALT-related proteins were found to interact with 42 different metabolites in our analysis. Additional networking analysis revealed a complex interaction between metabolites and ALT-related proteins, suggesting that pan-cancer oncogenes may have an impact on these pathways. Three metabolic pathways have been primarily related with the ALT mechanism: purine metabolism, cysteine and methionine metabolism, and nicotinate and nicotinamide metabolism. Lastly, we prioritized FDA-approved drugs (azathioprine, thioguanine, and mercaptopurine) that could target ALT-positive tumors through purine metabolism. This work provides a wide perspective of the metabolomic pathways associated with ALT and reveals potential therapeutic targets that require further experimental validation.},
}

Humans
*Telomere Homeostasis
*Metabolic Networks and Pathways
Neoplasms/metabolism/pathology/genetics
Telomere/metabolism/genetics
Purines/metabolism
Metabolomics/methods

@article {pmid39982852,
year = {2025},
author = {Jiang, D and Li, Y and Zhuge, F and Zhou, Q and Zong, W and Liu, X and Shen, X},
title = {The telomere-to-telomere genome of flowering cherry (Prunus campanulata) reveals genomic evolution of the subgenus Cerasus.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf009},
pmid = {39982852},
issn = {2047-217X},
support = {2021C02071-4//Zhejiang Science and Technology Major Program on Agricultural New Variety Breeding/ ; 2023F1068-2//Special Support Funds of Zhejiang for Scientific Research Institutes/ ; 32101585//National Natural Science Foundation of China/ ; },
mesh = {*Genome, Plant ; *Telomere/genetics ; *Evolution, Molecular ; *Prunus/genetics ; Genomics/methods ; Phylogeny ; Molecular Sequence Annotation ; High-Throughput Nucleotide Sequencing ; },
abstract = {BACKGROUND: Prunus campanulata, a species of ornamental cherry, holds significant genetic and horticultural value. Despite the availability of various cherry genomes, a fully resolved telomere-to-telomere (T2T) assembly for this species has been lacking. Recent advancements in long-read sequencing technologies have made it possible to generate gap-free genome assemblies, providing comprehensive insights into genomic structures that were previously inaccessible.

FINDINGS: We present the first T2T genome assembly for P. campanulata "Lianmeiren" (v2.0), achieved through the integration of PacBio HiFi, ultra-long Oxford Nanopore Technologies, Illumina, and Hi-C sequencing. The assembly resulted in a highly contiguous genome with a total size of 266.23 Mb and a contig N50 of 31.6 Mb. The genome exhibits remarkable completeness (98.9% BUSCO) and high accuracy (quality value of 48.75). Additionally, 13 telomeres and putative centromere regions were successfully identified across the 8 pseudochromosomes. Comparative analysis with the previous v1.0 assembly revealed 336,943 single nucleotide polymorphisms, 107,521 indels, and 1,413 structural variations, along with the annotation of 1,402 new genes.

CONCLUSIONS: This T2T genome assembly of P. campanulata "Lianmeiren" provides a critical reference for understanding the genetic architecture of the species. It enhances our ability to study structural variations, gene function, and evolutionary biology within the Prunus genus.},
}

*Genome, Plant
*Telomere/genetics
*Evolution, Molecular
*Prunus/genetics
Genomics/methods
Phylogeny
Molecular Sequence Annotation
High-Throughput Nucleotide Sequencing

@article {pmid39981889,
year = {2025},
author = {Andreikos, D and Spandidos, DA and Georgakopoulou, VE},
title = {Telomeres and telomerase in mesothelioma: Pathophysiology, biomarkers and emerging therapeutic strategies (Review).},
journal = {International journal of oncology},
volume = {66},
number = {3},
pages = {},
doi = {10.3892/ijo.2025.5729},
pmid = {39981889},
issn = {1791-2423},
mesh = {Humans ; *Telomerase/genetics/metabolism ; *Biomarkers, Tumor/genetics/metabolism ; *Telomere/genetics/metabolism ; *Mesothelioma, Malignant/genetics/pathology/drug therapy ; Mesothelioma/genetics/pathology ; Lung Neoplasms/genetics/pathology ; Prognosis ; Polymorphism, Single Nucleotide ; Mutation ; Promoter Regions, Genetic ; },
abstract = {Malignant mesothelioma (MM) is a rare but aggressive cancer linked to asbestos exposure and characterized by advanced‑stage disease at presentation. Despite advances in treatment, prognosis remains abysmal, highlighting the imperative for the development of novel biomarkers and treatment approaches. Telomere biology plays a pivotal role in the tumorigenic process and has emerged as a key area in oncology research. Short telomeres have been associated with genomic instability, and substantially shorter telomere length (TL) has been identified in MM, showcasing the potential of TL in risk assessment, early detection, and disease progression monitoring. MM predominantly maintains TL through telomerase activity (TA), which in research has been identified in >90% of MM cases, underscoring the potential of TA as a biomarker in MM. Telomerase reverse transcriptase (TERT) polymorphisms may serve as valuable biomarkers, with research identifying associations between single nucleotide polymorphisms (SNPs) and the risk and prognosis of MM. Additionally, TERT promoter mutations have been associated with poor prognosis and advanced‑stage disease, with the non‑canonical functions of TERT hypothesized to contribute to the development of MM. TERT promoter mutations occur in ~12% of MM cases; C228T, C250T and A161C are the most common, while the distribution and frequency differ depending on histological subtype. Research reveals the promise of the various approaches therapeutically targeting telomerase, with favorable results in pre‑clinical models and inconclusive findings in clinical trials. The present review examines the role of telomere biology in MM and its implications in diagnosis, prognosis, and therapy.},
}

Humans
*Telomerase/genetics/metabolism
*Biomarkers, Tumor/genetics/metabolism
*Telomere/genetics/metabolism
*Mesothelioma, Malignant/genetics/pathology/drug therapy
Mesothelioma/genetics/pathology
Lung Neoplasms/genetics/pathology
Prognosis
Polymorphism, Single Nucleotide
Mutation
Promoter Regions, Genetic

@article {pmid39980969,
year = {2024},
author = {Li, S and Zhang, L and Zhang, H},
title = {A telomere-related signature for predicting prognosis and assessing immune microenvironment in osteosarcoma.},
journal = {Frontiers in pharmacology},
volume = {15},
number = {},
pages = {1532610},
pmid = {39980969},
issn = {1663-9812},
abstract = {OBJECTIVE: Osteosarcoma is the most common primary bone cancer with a high propensity for local invasion and metastasis. An increasing number of research studies show that telomeres play an important role in the occurrence and development of cancer. Thus, we established a telomere-related signature in osteosarcoma to comprehensively evaluate the pathogenic roles of telomeres in this disease.

METHODS: The data on osteosarcoma were collected from the TARGET and Gene Expression Omnibus databases. First, we constructed a telomere-related signature using univariate and LASSO Cox regression analyses. Subsequently, we analyzed the prognostic value, functional annotation, immune microenvironment, and cell communication patterns of the telomere-related signature in osteosarcoma via comprehensive bioinformatics analyses. Cell proliferation was analyzed using the CCK-8 assay, and cell migration and invasion capabilities were evaluated using the Transwell assay.

RESULTS: Based on the SP110, HHAT, TUBB, MORC4, TERT, PPARG, MAP3K5, PAGE5, MAP7, and CAMK1G, a telomere-related signature was built in osteosarcoma patients. The telomere-related signature could effectively predict the prognosis of osteosarcoma patients. The osteosarcoma patients in the high TELscore group exhibited poor prognosis. In addition, the telomere-related signature demonstrated predictive value for the immune microenvironment and drug sensitivity in osteosarcoma. Finally, we discovered significant reduction in MAP7 expression in osteosarcoma cells, and patients with low MAP7 expression had poor prognosis. Moreover, the overexpression of MAP7 significantly reduced cell proliferation, the ability of cell migration, and invasion in osteosarcoma cells.

CONCLUSION: A telomere-related signature was constructed in osteosarcoma patients, offering predictive values into prognosis, the immune microenvironment, and drug sensitivity. Moreover, MAP7 might serve as a prognostic marker for osteosarcoma patients.},
}

@article {pmid39979386,
year = {2025},
author = {Oraon, PK and Ambreen, H and Yadav, P and Ramarao, S and Goel, S},
title = {A chromosome-scale reference assembly of Vigna radiata enables delineation of centromeres and telomeres.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {305},
pmid = {39979386},
issn = {2052-4463},
support = {IOE/FRP/LS/2020/27//University of Delhi (Delhi University)/ ; BT/190/NE/TBP/2011//Department of Biotechnology, Ministry of Science and Technology (DBT)/ ; BT/PR24637/NER/95/787/2017//Department of Biotechnology, Ministry of Science and Technology (DBT)/ ; 09/0045(1617)/2019-EMR-I//Council of Scientific and Industrial Research (CSIR)/ ; 09/0045(1624)/2019-EMR-I//Council of Scientific and Industrial Research (CSIR)/ ; },
mesh = {*Centromere/genetics ; *Vigna/genetics ; *Telomere/genetics ; *Genome, Plant ; *Chromosomes, Plant/genetics ; },
abstract = {Vigna radiata (L.) R. Wilczek var. radiata (mungbean) is a pulse crop important for both the global protein security and sustainable crop production. Here, to facilitate genomics-assisted breeding programs in mungbean, we present a high-quality reference genome originating from the crop's centre of origin, India. In this study, we present a significantly continuous genome assembly of V. radiata Indian cultivar, achieved through a combination of long-read PacBio HiFi sequencing and Hi-C sequencing. The total assembled genome size is ~596 Mb equating to ~98% of the predicted genome size complemented by a contig N50 value of 10.35 Mb and a BUSCO score of 98.5%. Around 502 Mb of the assembled genome is anchored on 11 pseudochromosomes conforming to the chromosome count in the crop with distinctly identified telomeres and centromeres. We predicted a total of 43,147 gene models of which 39,144 protein coding genes were functionally annotated. The present assembly was able to resolve several gaps in the genome and provides a high-quality genomic resource for accelerating mungbean breeding programs.},
}

*Centromere/genetics
*Vigna/genetics
*Telomere/genetics
*Genome, Plant
*Chromosomes, Plant/genetics

@article {pmid39978211,
year = {2025},
author = {Brown, RA and Koss, KJ},
title = {The role of optimism, connectedness, and neighborhood collective efficacy as moderators of harsh parenting on telomere length.},
journal = {Psychoneuroendocrinology},
volume = {174},
number = {},
pages = {107373},
doi = {10.1016/j.psyneuen.2025.107373},
pmid = {39978211},
issn = {1873-3360},
abstract = {Research to date has examined telomere length in relation to adverse childhood events but few studies have examined whether protective factors act as a buffer to offset this effect. Further, research is lacking examining whether protective factors vary among minoritized youth. Data were from the Future Families and Child Wellbeing Study, a stratified, multistage sample of 4898 children born in large U.S. cities between 1998 and 2000. Births to unmarried mothers were oversampled by a 3-1 ratio, which resulted in the inclusion of a multi-ethnic and economically diverse sample (48 % Black; 27 % Hispanic; 21 % White; 4 % other racial and ethnic minorities). The current study examined optimism, social connectedness, and neighborhood collective efficacy at age 15 as potential protective factors against the effects of harsh parenting on telomere length in adolescence (analytic N = 1168 youth). This study examines cumulative exposure to harsh parenting across childhood (ages 3, 5, and 9 years). Results from analyses stratified by race/ethnicity show optimism, connectedness, and neighborhood collective efficacy serve as protective factors; however, unique protective factors emerged among different racial and ethnic youth suggesting the need to examine context-specific protective factors. Implications of these findings provide evidence for considering intersectionality in terms of protective factors for biomarkers among minoritized youth.},
}

@article {pmid39977333,
year = {2025},
author = {},
title = {Correction for Qian et al., Chemoptogenetic damage to mitochondria causes rapid telomere dysfunction.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {122},
number = {10},
pages = {e2501913122},
doi = {10.1073/pnas.2501913122},
pmid = {39977333},
issn = {1091-6490},
}

@article {pmid39975089,
year = {2025},
author = {Jeon, HJ and Levine, MT and Lampson, MA},
title = {A parent-of-origin effect on embryonic telomere elongation determines telomere length inheritance.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.01.28.635226},
pmid = {39975089},
issn = {2692-8205},
abstract = {Telomere length is inherited directly as a DNA sequence and as a classic quantitative trait controlled by many genes across the genome. Here, we show that neither paradigm fully accounts for telomere length inheritance, which also depends on a parent-of-origin effect on telomere elongation in the early embryo. By reciprocally crossing mouse strains with different telomere lengths, we find that telomeres elongate in hybrid embryos only when maternal telomeres are short and paternal telomeres are long. In the reciprocal cross, telomeres shorten. These differences in embryonic telomere elongation, which emerge before zygotic genome activation, predict adult telomere length. Moreover, when telomeres do elongate, we find molecular signatures of a recombination-based mechanism of telomere elongation, called the Alternative Lengthening of Telomeres (ALT) pathway, previously suggested to elongate telomeres in the pre-implantation embryo. We propose that ALT is triggered by a combination of genetic asymmetry in telomere length and epigenetic asymmetry between maternal and paternal chromosomes in the zygote. Our findings offer new insight into the complex interaction of genetic and epigenetic determinants of telomere length inheritance.},
}

@article {pmid39975053,
year = {2025},
author = {Sanford, SL and Badstübner, M and Gerber, M and Mannherz, W and Lampl, N and Dannenberg, R and Hinchie, A and Schaich, MA and Myong, S and Hedglin, M and Agarwal, S and Alder, J and Stone, MD and Opresko, PL},
title = {6-thio-2'-deoxyguanosine inhibits telomere elongation by inducing a non-productive stalled telomerase complex.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.02.05.636339},
pmid = {39975053},
issn = {2692-8205},
abstract = {Most cancers upregulate the telomere lengthening enzyme telomerase for unlimited cell division. The therapeutic nucleoside 6-thio-2'-deoxyguanosine (6-thio-dG) inhibits telomere maintenance in telomerase- expressing cancer cells and tumors by an unknown mechanism. Here, we demonstrate that telomerase insertion of 6-thio-dGTP prevents synthesis of additional telomeric repeats but does not disrupt telomerase binding to telomeres. Specifically, 6-thio-dG inhibits telomere extension after telomerase translocates along its product DNA to reposition the template, thereby inducing a non-productive complex rather than enzyme dissociation upon movement. We provide direct evidence that 6-thio-dG treatment inhibits telomere synthesis by telomerase in cancer cells. Furthermore, telomerase-expressing cancer cells harboring critically short telomeres are more sensitive to 6-thio-dG and show a greater induction of telomere losses, compared to cancer cells with long telomere reserves. Collectively, our studies reveal the molecular mechanism of 6-thio-dG inhibition of telomere maintenance in cancer cells is by producing a bound non-productive telomerase complex after 6-thio-dGTP insertion.},
}

@article {pmid39974130,
year = {2025},
author = {Toor, AA and Horton, M and Khalid, H and Krieger, E and Lai, TP and Spellman, SR and Levine, JE and Saber, W and Aviv, A and Stewart, V and Gadalla, SM},
title = {Understanding Telomere Biology in Hematopoietic Cell Transplantation: A Dynamical Systems Perspective.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.01.20.24319630},
pmid = {39974130},
abstract = {BACKGROUND: T cell proliferation and repertoire reconstitution is a hallmark of successful hematopoietic cell transplantation (HCT). This process may be modeled as a dynamical system and in such a system, precise telomere length (TL) measurement may reflect the proliferative capacity of donor T cells. TL for different chromosomes span a few orders of magnitude, and different T cell clones will display variable TL; these differences across the population are not represented when examining average TL. This study aims to develop a method that integrates the entire spectrum of TL observed within a sample to better understand the influence on clinical outcomes following HCT.

METHODS: To better reflect the entire span of TL , we used data generated using the TeLSA PCR technique that provided discrete measurments of individual telomeres for each DNA sample for 72 stem cell transplant (SCT) donor-recipient pairs. Donor and recipient TeSLA TL measurements was performed on samples taken before and 90 days post HCT, respectively. Set correspondence mathematical techniques and area under the curve (AUC) calculations were used to measured donor-recipient TL differences (delta-TL) incorporating the full distribution of measured TL from each sample.

RESULTS: Telomere band lengths ranged from 350 basepairs (BP) to 16.7 kilobases with a logarithmically declining distribution in all samples when arrayed in a descending order. Set correspondence methods yielded TL averages which were highly correlated with AUC calculations (r >0.9, p<0.001 for all) The AUC delta-TL method predicted patient overall survival (P-log rank <0.0001). HCT recipients with intermediate degrees of telomere attrition (25 [th] -75 [th] percentile) post-HCT experienced the best outcomes (2 years overall survival; OS=92%), whilst donors with the least (<25 [th] percentile; 2 years OS=33%; adjusted HR vs. intermediate shortening=9.3, p=0.001) and the greatest (>75 [th] percentile; 2 years OS=59%; adjusted HR=6.0, p=0.01) shortening had worse outcomes. By contrast, using the traditional method based on donor-recipient difference in TeSLA mean telomere length did not demonstrate survival association in this small sample set (p log-rank=0.95).

CONCLUSION: The findings described herein suggest that the degree of donor telomere attrition may reflect T cell proliferation and alloreactivity following transplant. Accounting for the entire span of telomere lengths, could better identify post-transplant risk groups.},
}

@article {pmid39972993,
year = {2025},
author = {Jin, T and Yang, R and Cheng, Y and Cao, Z and He, Z and Guo, S},
title = {Causality between Autism Spectrum Disorder and Telomere Length.},
journal = {Brain and behavior},
volume = {15},
number = {2},
pages = {e70362},
doi = {10.1002/brb3.70362},
pmid = {39972993},
issn = {2162-3279},
support = {2020KY443,2022KY506,2023KY044and2024KY025//the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission/ ; GZY-ZJ-KJ-23055//Zhejiang Provincial TCM Science and Technology Plan Project/ ; },
mesh = {*Autism Spectrum Disorder/genetics ; Humans ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; Telomere ; Telomere Shortening ; Causality ; },
abstract = {BACKGROUND: The association between telomere length (TL) and autism spectrum disorder (ASD) has received much attention. However, previous observational studies have yielded inconclusive evidence regarding this relationship. Our study aims to elucidate the causal relationship between TL and ASD using bidirectional Mendelian randomization (MR).

METHODS: We employed the largest genome-wide association studies (GWAS) summary statistics for TL (sample size = 472,174) and ASD (sample size = 46,351). The primary MR analysis method was the inverse-variance weighted (IVW) method, complemented by the MR-Egger method, weighted median (WM) method, and MR-PRESSO. Additionally, sensitivity analyses including Cochran's Q test, the intercept of MR-Egger regression, the global test of MR-PRESSO, and the leave-one-out analysis were conducted in our study.

RESULTS: The primary MR analysis indicated a significant association between ASD and shorter TL (IVW: OR = 0.98, 95% CI: 0.96-0.99, p = 0.03). However, no significant association was found in the reverse direction MR analysis (IVW: OR = 1.06, 95% CI: 0.94-1.23, p = 0.35). Raw and outlier-corrected MR estimates from MR-PRESSO were consistent with the IVW results. Sensitivity analyses confirmed the robustness of these findings.

CONCLUSIONS: Our study indicated that individuals with ASD have shorter TL, however, shorter TL does not appear to increase the risk of ASD.},
}

*Autism Spectrum Disorder/genetics
Humans
*Mendelian Randomization Analysis
*Genome-Wide Association Study
Telomere
Telomere Shortening
Causality

@article {pmid39971959,
year = {2025},
author = {Guerrero-López, R and Manguán-García, C and Carrascoso-Rubio, C and Lozano, ML and Toldos-Torres, M and García-Castro, L and Sánchez-Dominguez, R and Alberquilla, O and Sánchez-Pérez, I and Molina-Molina, M and Bueren, JA and Guenechea, G and Perona, R and Sastre, L},
title = {Premature ageing of lung alveoli and bone marrow cells from Terc deficient mice with different telomere lengths.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {6102},
pmid = {39971959},
issn = {2045-2322},
mesh = {Animals ; *Telomerase/genetics ; Mice ; *Telomere/genetics/metabolism ; *Aging, Premature/genetics/pathology ; *Mice, Inbred C57BL ; *RNA/genetics/metabolism ; *Bone Marrow Cells/metabolism ; Pulmonary Alveoli/pathology/metabolism ; Disease Models, Animal ; Telomere Homeostasis ; Mutation ; Male ; Telomere Shortening ; },
abstract = {Telomeres are terminal protective chromosome structures. Genetic variants in genes coding for proteins required for telomere maintenance cause rare, life-threatening Telomere Biology Disorders (TBDs) such as dyskeratosis congenita, aplastic anemia or pulmonary fibrosis. The more frequently used mice strains have telomeres much longer than the human ones which question their use as in vivo models for TBDs. One mice model with shorter telomeres based on the CAST/EiJ mouse strain carrying a mutation in the Terc gene, coding for the telomerase RNA component, has been studied in comparison with C57BL/6J mice, carrying the same mutation and long telomeres. The possible alterations produced in lungs and the haematopoietic system, frequently affected in TBD patients, were determined at different ages of the mice. Homozygous mutant mice presented a very shortened life span, more notorious in the short-telomeres CAST/EiJ strain. The lungs of mutant mice presented a transitory increase in fibrosis and a significant decrease in the relative amount of the alveolar epithelial type 2 cells from six months of age. This decrease was larger in mutant homozygous animals but was also observed in heterozygous animals. On the contrary the expression of the senescence-related protein P21 increased from six months of age in mutant mice of both strains. The analysis of the haematopoietic system indicated a decrease in the number of megakaryocyte-erythroid progenitors in homozygous mutants and an increase in the clonogenic potential of bone marrow and LSK cells. Bone marrow cells from homozygous mutant animals presented decreasing in vitro expansion capacity. The alterations observed are compatible with precocious ageing of lung alveolar cells and the bone marrow cells that correlate with the alterations observed in TBD patients. The alterations seem to be more related to the genotype of the animals that to the basal telomere length of the strains although they are more pronounced in the short-telomere CAST/EiJ-derived strain than in C57BL/6J animals. Therefore, both animal models, at ages over 6-8 months, could represent valuable and convenient models for the study of TBDs and for the assay of new therapeutic products.},
}

Animals
*Telomerase/genetics
Mice
*Telomere/genetics/metabolism
*Aging, Premature/genetics/pathology
*Mice, Inbred C57BL
*RNA/genetics/metabolism
*Bone Marrow Cells/metabolism
Pulmonary Alveoli/pathology/metabolism
Disease Models, Animal
Telomere Homeostasis
Mutation
Male
Telomere Shortening

@article {pmid39970292,
year = {2025},
author = {Goncalves, T and Cunniffe, S and Ma, TS and Mattis, N and Rose, AW and Kent, T and Mole, DR and Geiller, HEB and van Bijsterveldt, L and Humphrey, TC and Hammond, EM and Gibbons, RJ and Clynes, D and Rose, AM},
title = {Elevated reactive oxygen species can drive the alternative lengthening of telomeres pathway in ATRX-null cancers.},
journal = {Nucleic acids research},
volume = {53},
number = {4},
pages = {},
doi = {10.1093/nar/gkaf061},
pmid = {39970292},
issn = {1362-4962},
support = {CL-2018-13-005//National Institute of Health and Care Research Clinical Lectureship/ ; SGL023\1055//Academy of Medical Sciences Starter/ ; 0 011 483//University of Oxford Medical Sciences/ ; 15-202//Children with Cancer UK/ ; 101 136 835//EU Horizon Europe Research and Innovation program Cancer Mission 'HIT-GLIO'/ ; C6078/A28736/CRUK_/Cancer Research UK/United Kingdom ; //MRC DPhil Studentship/ ; },
mesh = {*X-linked Nuclear Protein/genetics/metabolism ; *Reactive Oxygen Species/metabolism ; Humans ; *Telomere Homeostasis/genetics ; Cell Line, Tumor ; *Telomere/metabolism/genetics ; Glioma/genetics/metabolism/pathology ; R-Loop Structures ; Ribonuclease H/metabolism/genetics ; Tumor Microenvironment/genetics ; Osteosarcoma/genetics/pathology/metabolism ; Mutation ; },
abstract = {The alternative lengthening of telomeres (ALT) pathway is a telomerase-independent mechanism for immortalization in cancer cells and is commonly activated in low-grade and high-grade glioma, as well as osteosarcoma. The ALT pathway can be activated under various conditions and has often been shown to include mutational loss of ATRX. However, this is insufficient in isolation and so other cellular event must also be implicated. It has been shown that excessive accumulation of DNA:RNA hybrid structures (R-loops) and/or formation of DNA-protein crosslinks (DPCs) can be other important driving factors. The underlying cellular events leading to R-loop and DPC formation in ALT cancer cells to date remain unclear. Here, we demonstrate that excessive cellular reactive oxygen species (ROS) is an important causative factor in the evolution of ALT-telomere maintenance in ATRX-deficient glioma. We identified three sources of elevated ROS in ALT-positive gliomas: co-mutation of SETD2, downregulation of DRG2, and hypoxic tumour microenvironment. We demonstrate that elevated ROS leads to accumulation of R-loops and, crucially, resolution of R-loops by the enzyme RNase H1 prevents ALT pathway activity in cells exposed to elevated ROS. Further, we found a possible causal link between the formation of R-loops and the accumulation of DPCs, in particular, formation of TOP1 complexes covalently linked to DNA (Top1cc). We also demonstrate that elevation of ROS can trigger over-activity of the ALT pathway in osteosarcoma and glioma cell lines, resulting in excessive DNA damage and cell death. This work presents important mechanistic insights into the endogenous origin of excessive R-loops and DPCs in ALT-positive cancers, as well as highlighting potential novel therapeutic approaches in these difficult-to-treat cancer types.},
}

*X-linked Nuclear Protein/genetics/metabolism
*Reactive Oxygen Species/metabolism
Humans
*Telomere Homeostasis/genetics
Cell Line, Tumor
*Telomere/metabolism/genetics
Glioma/genetics/metabolism/pathology
R-Loop Structures
Ribonuclease H/metabolism/genetics
Tumor Microenvironment/genetics
Osteosarcoma/genetics/pathology/metabolism
Mutation

@article {pmid39969640,
year = {2025},
author = {Dutson, U and Lin, J and Jelliffe-Pawlowski, LL and Coleman-Phox, K and Rand, L and Wojcicki, JM},
title = {The Association Between Longer Maternal Leukocyte Telomere Length in the Immediate Postpartum Period and Preterm Birth in a Predominately Latina Cohort of Mothers.},
journal = {Maternal and child health journal},
volume = {},
number = {},
pages = {},
pmid = {39969640},
issn = {1573-6628},
support = {Wojcicki//UCSF Preterm Birth Initiative/ ; },
abstract = {OBJECTIVES: We investigated the association between maternal leukocyte telomere length (LTL) in the immediate postpartum period and moderate to late preterm birth (32- < 37 weeks) among Latinas, a population at high risk for preterm birth.

METHODS: Maternal LTL was measured using quantitative polymerase chain reaction at delivery in a prospective San Francisco primarily Latina birth cohort. Logistic regression models were used to investigate the association between postpartum maternal LTL and preterm birth. Maternal LTL was analyzed as a continuous predictor.

RESULTS: Out of 194 participants, 23 (11.9%) had preterm delivery. Longer postnatal maternal LTL was associated with preterm birth (crude OR 4.68; 95% confidence interval (CI) 1.07, 20.6, p = 0.039; adjusted OR 12.8, 95% CI 1.83, 99.9, p = 0.010). Age-stratified analysis showed that being under 35 years increased the effect size of the association between maternal LTL and preterm birth (adjusted OR 32.5, 95% CI 2.58, 597, p < 0.01).

CONCLUSIONS FOR PRACTICE: Latina mothers with moderate to late preterm infants had longer LTL in the immediate postpartum period compared to those with term infants. This association was stronger for mothers under the age of 35 years. LTL may serve as a biomarker to better understand the pathophysiology and risk of preterm birth and could inform targeted interventions for prevention and early detection. Future studies are needed to understand physiological changes in maternal LTL from the prenatal to postnatal period in relation to birth outcomes.},
}

@article {pmid39967905,
year = {2025},
author = {Darvishi, FZ and Saadat, M},
title = {Association between leukocytes telomere length and parental consanguineous marriage.},
journal = {EXCLI journal},
volume = {24},
number = {},
pages = {177-178},
pmid = {39967905},
issn = {1611-2156},
}

@article {pmid39964637,
year = {2025},
author = {Mishra, A and Patel, TN},
title = {Locking the gates of immortality: targeting alternative lengthening of telomeres (ALT) pathways.},
journal = {Medical oncology (Northwood, London, England)},
volume = {42},
number = {3},
pages = {78},
pmid = {39964637},
issn = {1559-131X},
mesh = {Humans ; *Telomere Homeostasis/physiology ; *Neoplasms/genetics/pathology/metabolism ; Telomere ; Animals ; X-linked Nuclear Protein/genetics/metabolism ; Telomerase/metabolism/genetics ; },
abstract = {Telomere maintenance is essential for the unlimited proliferation of cancer cells. While most cancers reactivate telomerase to preserve telomeres, approximately 10-15% utilize the alternative lengthening of telomeres (ALT), a telomerase-independent mechanism driven by homologous recombination. ALT is primarily observed in sarcomas and neuroepithelial tumors and it is characterized by hallmarks such as heterogeneous telomere lengths, the presence of ALT-associated PML bodies (APBs), extrachromosomal telomeric repeats (ECTRs), and elevated replication stress. This review has a threefold aim: (1) to examine the mechanisms of ALT activation, (2) to highlight existing therapeutic interventions targeting ALT components and telosomic complexes, and, (3) to pinpoint potential molecular targets for novel anticancer treatments. Therapeutic strategies focus on disrupting APBs, stabilizing G-quadruplex structures, and inhibiting replication stress proteins such as FANCM and SMARCAL1. Emerging evidence highlights the role of shelterin proteins like TRF1 and TRF2, chromatin remodeling factors such as ATRX and DAXX, and the dysregulated cGAS-STING pathway in facilitating ALT activity. Moreover, the inhibitory role of RAP1-SUN1 protein interactions in telomere recombination provides a novel therapeutic avenue. Recent advances have elucidated the intricate balance of replication stress, DNA damage response, and recombination in ALT regulation. These insights can help overcome challenges posed by ALT + cancers, including their ability to transition from telomerase-dependent states. Targeting ALT-specific vulnerabilities offers a promising direction for developing innovative therapies that exploit the unique biology of ALT-driven tumors.},
}

Humans
*Telomere Homeostasis/physiology
*Neoplasms/genetics/pathology/metabolism
Telomere
Animals
X-linked Nuclear Protein/genetics/metabolism
Telomerase/metabolism/genetics

@article {pmid39964064,
year = {2025},
author = {Shi, Y and Huang, H and Zhang, R and Yin, L},
title = {Causal association between telomere length and female cancers: a two-sample Mendelian randomization study.},
journal = {Postgraduate medical journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/postmj/qgaf028},
pmid = {39964064},
issn = {1469-0756},
abstract = {PURPOSE: To explore the causal associations between genetically predicted telomere length and gynecologic and breast cancers.

METHODS: This Mendelian randomization study used data from genome-wide association studies on telomere length and breast (BC), cervical cancer, endometrial (EC), and ovarian (OC) cancers. The primary analysis was performed using the inverse variance weighted (IVW) method, with confirmation using the weighted median, weighted mode, and MR-Egger methods. Heterogeneity was detected using Cochran's Q-test, horizontal pleiotropy using MR-Egger regression, outliers using MR-PRESSO, and discordant single-nucleotide polymorphisms using the leave-one-out method.

RESULTS: The genetic prediction results indicated causal associations between the risk of telomere length and EC [IVW; OR = 1.29, 95% confidence interval (95%CI): 1.05-1.59, P = .02], leukocyte telomere length and EC (IVW; OR = 1.23, 95%CI: 1.01-1.51, P = .04), telomere length and OC (IVW; OR = 1.27, 95%CI: 1.01-1.60, P = .04), telomere length and BC (IVW; OR = 1.12, 95%CI: 1.01-1.23, P = .03), and leukocyte telomere length and BC (IVW; OR = 1.12, 95%CI: 1.02-1.24, P = .02). Cochran's Q-test revealed heterogeneity for telomere length and BC (P < .001), leukocyte telomere length and BC (P < .001), and B-cell telomere length and BC (P = .012). The MR-Egger regression results suggest that the analyses of telomere length and BC (P = .014) and leukocyte telomere length and BC (P = .044) were influenced by horizontal pleiotropy. The MR-PRESSO analysis indicated the presence of outliers in the analyses of telomere length and BC and leukocyte telomere length and breast cancer. After removing the outliers, the statistical significance remained.

CONCLUSION: This MR study suggests a causal association between telomere length and BC, EC, and OC, warranting additional study. Key message What is already known on this topic?  Previous research has indicated an association between telomere length and the risk of various cancers, including breast and gynecologic cancers. However, the causal relationship remained unclear, necessitating further exploration to establish whether telomere length could be a modifiable risk factor for these cancers. What this study adds?  This study provides robust evidence of a causal relationship between genetically predicted telomere length and an increased risk of breast cancer, endometrial cancer, and ovarian cancer, with specific odds ratios indicating a significant association. It highlights that both leukocyte and overall telomere length are important factors in cancer risk. How this study might affect research, practice, or policy?  The findings could inform future research into telomere length as a biomarker for cancer risk, promote investigations into telomere-targeting interventions, and influence guidelines on screening and preventive strategies for at-risk populations based on genetic predispositions.},
}

@article {pmid39963020,
year = {2025},
author = {Chan, RNC and Huang, C and Ng, NYH and Tam, HCH and Tam, CHT and Cheng, F and Wong, KK and Shi, M and Ng, ACW and Tsang, AYT and Wang, CC and Cheung, LP and Tam, WH and Joglekar, MV and Hardikar, AA and Jenkins, AJ and Chan, JCN and Lim, CKP and Ma, RCW},
title = {Shortened Relative Leukocyte Telomere Length Is Associated With Polycystic Ovary Syndrome and Metabolic Traits.},
journal = {Endocrinology, diabetes & metabolism},
volume = {8},
number = {2},
pages = {e70030},
doi = {10.1002/edm2.70030},
pmid = {39963020},
issn = {2398-9238},
support = {//University Grants Committee Research Grants Matching Scheme/ ; //Chinese University of Hong Kong Direct Grant/ ; 14102719//RGC General Research Fund/ ; 14110415//RGC General Research Fund/ ; CUHK471713//RGC General Research Fund/ ; CUHK473408//RGC General Research Fund/ ; //Croucher Foundation Senior Medical Research Fellowship/ ; R4012-18//Research Grants Council Research Impact Fund/ ; },
mesh = {Humans ; *Polycystic Ovary Syndrome/genetics ; Female ; Adult ; *Leukocytes/metabolism ; *Mendelian Randomization Analysis ; *Telomere ; Telomere Shortening ; Case-Control Studies ; },
abstract = {BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the commonest gyneco-endocrine disorders amongst women of reproductive age. Whether PCOS and cardiometabolic traits in PCOS patients are associated with shortened telomere length (TL) or relative leukocyte telomere length (rLTL) remains unclear.

METHODS: 214 women with PCOS and 214 age-matched women were recruited. rLTL was measured with an updated quantitative real-time PCR protocol and reported as ΔΔCt between telomere and a single-copy gene encoding β-globin relative to a normalisation control. A two-way Mendelian randomization analysis using the UK Biobank Resource was performed to assess the causal relationship between rLTL and PCOS.

RESULTS: Women with PCOS had significantly shortened rLTL (PCOS: 0.5 ± 0.7; control: 0.8 ± 0.6; p < 0.001). Longer rLTL was associated with a lower risk of PCOS after adjusting for age, history of smoking and other cardiometabolic traits (OR: 0.503; 95% CI: 0.342-0.730; p < 0.001). Longer rLTL was associated with reduced risk of dyslidpidemia (OR: 0.563; 95% CI: 0.450-0.968; p = 0.042) in PCOS patients. PCOS subjects with rLTL shorter than mean of the rLTL of control subjects had an elevated risk of dysglycemia (OR: 2.09; 95% CI: 1.04-4.29; p = 0.040). No causal relationships were found between rLTL and PCOS in the Mendelian randomization study.

CONCLUSIONS: Women with PCOS have significantly reduced rLTL and shorter LTL may be associated with cardiometabolic risk factors in PCOS subjects. There are no causal relationship between genetically determined PCOS and TL or vice versa.},
}

Humans
*Polycystic Ovary Syndrome/genetics
Female
Adult
*Leukocytes/metabolism
*Mendelian Randomization Analysis
*Telomere
Telomere Shortening
Case-Control Studies

@article {pmid39962352,
year = {2025},
author = {Helia, O and Matúšová, B and Havlová, K and Hýsková, A and Lyčka, M and Beying, N and Puchta, H and Fajkus, J and Fojtová, M},
title = {Chromosome engineering points to the cis-acting mechanism of chromosome arm-specific telomere length setting and robustness of plant phenotype, chromatin structure and gene expression.},
journal = {The Plant journal : for cell and molecular biology},
volume = {121},
number = {4},
pages = {e70024},
pmid = {39962352},
issn = {1365-313X},
support = {CZ.02.01.01/00/22_008/0004581//European Regional Development Fund/ ; 22-04364S//Grantová Agentura České Republiky/ ; },
mesh = {*Arabidopsis/genetics ; *Telomere/genetics/metabolism ; *Phenotype ; *Chromatin/genetics/metabolism ; *Chromosomes, Plant/genetics ; Gene Expression Regulation, Plant ; Translocation, Genetic ; CRISPR-Cas Systems ; Telomere Homeostasis/genetics ; Genetic Engineering/methods ; Genome, Plant/genetics ; },
abstract = {The study investigates the impact of targeted chromosome engineering on telomere dynamics, chromatin structure, gene expression, and phenotypic stability in Arabidopsis thaliana. Using precise CRISPR/Cas-based engineering, reciprocal translocations of chromosome arms were introduced between non-homologous chromosomes. The subsequent homozygous generations of plants were assessed for phenotype, transcriptomic changes and chromatin modifications near translocation breakpoints, and telomere length maintenance. Phenotypically, translocated lines were indistinguishable from wild-type plants, as confirmed through morphological assessments and principal component analysis. Gene expression profiling detected minimal differential expression, with affected genes dispersed across the genome, indicating negligible transcriptional impact. Similarly, ChIPseq analysis showed no substantial alterations in the enrichment of key histone marks (H3K27me3, H3K4me1, H3K56ac) near junction sites or across the genome. Finally, bulk and arm-specific telomere lengths remained stable across multiple generations, except for minor variations in one translocation line. These findings highlight the remarkable genomic and phenotypic robustness of A. thaliana despite large-scale chromosomal rearrangements. The study offers insights into the cis-acting mechanisms underlying chromosome arm-specific telomere length setting and establishes the feasibility of chromosome engineering for studies of plant genome evolution and crop improvement strategies.},
}

*Arabidopsis/genetics
*Telomere/genetics/metabolism
*Phenotype
*Chromatin/genetics/metabolism
*Chromosomes, Plant/genetics
Gene Expression Regulation, Plant
Translocation, Genetic
CRISPR-Cas Systems
Telomere Homeostasis/genetics
Genetic Engineering/methods
Genome, Plant/genetics

@article {pmid39958913,
year = {2025},
author = {Lukhtanov, VA},
title = {Telomere DNA in the insect order Dermaptera and the first evidence for the non-canonical telomeric motif TTCGG in Arthropoda.},
journal = {Comparative cytogenetics},
volume = {19},
number = {},
pages = {13-18},
pmid = {39958913},
issn = {1993-0771},
abstract = {Despite recent advances in telomere research, the telomere DNA organization remains unknown for representatives of several insect orders. In this study, analysis of the chromosome-level genome assembly shows that the telomeric DNA of the earwig Labiaminor (Linnaeus, 1758) (Polyneoptera, Dermaptera, Spongiphoridae) consists of repeats of the 5 bp motif TTCGG/CCGAA. This is the first record describing the structure of telomeric DNA in the order Dermaptera. This record expands the spectrum of the known telomeric sequences, since the TTCGG motif has not been reported for insects previously.},
}

@article {pmid39955882,
year = {2025},
author = {Martino, P and Perez-Alarcón, M and Deconinck, L and De Raedt, R and Vanderhasselt, MA and Kozusznik, MW and Kooy, F and Hidalgo, V and Venero, C and Salvador, A and Baeken, C and Pulopulos, MM},
title = {Corrigendum to "Stress and telomere length in leukocytes: Investigating the role of GABRA6 gene polymorphism and cortisol" [Psychoneuroendocrinology (2025) 107358].},
journal = {Psychoneuroendocrinology},
volume = {174},
number = {},
pages = {107404},
doi = {10.1016/j.psyneuen.2025.107404},
pmid = {39955882},
issn = {1873-3360},
}

@article {pmid39955535,
year = {2025},
author = {Shen, J and Sun, J and Lin, S and Du, J},
title = {Association of leukocyte telomere length with periodontal attachment loss based on a cross-sectional study.},
journal = {BMC oral health},
volume = {25},
number = {1},
pages = {241},
pmid = {39955535},
issn = {1472-6831},
mesh = {Humans ; Cross-Sectional Studies ; Male ; *Leukocytes ; *Periodontal Attachment Loss ; Female ; Middle Aged ; *Telomere ; Aged ; Aged, 80 and over ; Nutrition Surveys ; United States ; },
abstract = {BACKGROUND: Leukocyte telomere length (LTL) has been implicated in various health outcomes, but its association with attachment loss in periodontal health remains underexplored.

METHODS: A total of 2521 US adults (Age: 61-85; Men: 50.5%) from the National Health and Nutrition Examination Survey (1999-2002) were included in this cross-sectional study. Baseline demographics were obtained from the questionaries, and LTL was determined using a polymerase chain reaction, and periodontal attachment loss was defined according to a professional physical examination. Multivariable regression analyses were conducted to assess the association between LTL, treated as a categorical and continuous variable, and periodontal attachment loss. The sensitivity analysis was verified by subgroup analyse, where interaction terms were used to examine the heterogeneity in associations across different subgroups.

RESULTS: Compared to the lowest quartile, the highest LTL quartile exhibited a significant positive association with periodontal attachment loss in the fully-adjusted model (β: 1.54 to 1.71, P < 0.05). When LTL was treated as a continuous variable, a positive association persisted in the fully-adjusted model (β: 2.22 to 3.24, P < 0.05). Subgroup analyses revealed a consistent positive association between LTL and periodontal attachment loss.

CONCLUSIONS: This study provides evidence of a positive association between leukocyte telomere length and attachment loss in periodontal health. Our results suggested that LTL may serve as a potential biomarker for periodontal health, emphasizing the importance of considering telomere length in understanding and managing periodontal conditions.},
}

Humans
Cross-Sectional Studies
Male
*Leukocytes
*Periodontal Attachment Loss
Female
Middle Aged
*Telomere
Aged
Aged, 80 and over
Nutrition Surveys
United States

@article {pmid39955533,
year = {2025},
author = {Wang, Q and Gao, Y and Taiwaikuli, D and Ding, H and Song, J and Yang, X and Tang, B and Zhou, X},
title = {DNA methylation-based telomere length is more strongly associated with long-term all-cause mortality than quantitative polymerase chain reaction-based telomere length among middle-aged and older hypertensive adults.},
journal = {Clinical epigenetics},
volume = {17},
number = {1},
pages = {22},
pmid = {39955533},
issn = {1868-7083},
support = {82260064//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Male ; Female ; *DNA Methylation/genetics ; Middle Aged ; *Hypertension/genetics/mortality ; Aged ; *Telomere/genetics ; Nutrition Surveys ; Cohort Studies ; Proportional Hazards Models ; Polymerase Chain Reaction/methods ; Telomere Homeostasis/genetics ; Cardiovascular Diseases/genetics/mortality ; },
abstract = {BACKGROUND: Telomere length (TL) has been linked to mortality risk across various populations. However, its predictive value for mortality risk specifically in hypertensive adults remains unclear.

METHODS: This cohort study utilized data from the 1999-2000 and 2001-2002 cycles of the National Health and Nutrition Examination Survey (NHANES). TL was assessed using DNA methylation (DNAmTL) and quantitative polymerase chain reaction (qPCRTL). Cox proportional hazards models were employed to examine the relationship between TL and mortality risk.

RESULTS: This study included 1601 participants, with 988 deaths occurring during a median follow-up of 184 months, including 279 from cardiovascular disease (CVD). Deceased participants exhibited significantly lower levels of DNAmTL (6.45 ± 0.30 vs. 6.70 ± 0.28, P < 0.001) and qPCRTL (0.89 ± 0.22 vs. 0.99 ± 0.24, P < 0.001) compared to survivors. After full adjustment, each 1-kb decrement in DNAmTL and qPCRTL was associated with a 52% and 38% reduction in all-cause mortality risk, respectively. Participants in the highest TL quartile (Q4) for DNAmTL and qPCRTL had a 36% and 25% reduced risk of all-cause mortality than those in the lowest quartile (Q1), respectively. Receiver operating characteristic (ROC) curves demonstrated that DNAmTL had superior predictive value compared to qPCRTL (area under curve [AUC] 0.73 vs. 0.63, P < 0.001).

CONCLUSION: TL is inversely associated with all-cause mortality risk in middle-aged and older hypertensive adults, with DNAmTL showing greater predictive accuracy for long-term mortality than qPCRTL.},
}

Humans
Male
Female
*DNA Methylation/genetics
Middle Aged
*Hypertension/genetics/mortality
Aged
*Telomere/genetics
Nutrition Surveys
Cohort Studies
Proportional Hazards Models
Polymerase Chain Reaction/methods
Telomere Homeostasis/genetics
Cardiovascular Diseases/genetics/mortality

@article {pmid39954068,
year = {2025},
author = {Ozcan, M and Burus, A and Mender, I and Dikmen, ZG and Gryaznov, SM and Bastug, T and Bayazit, Y},
title = {Investigation of the inhibitory effects of the telomere-targeted compounds on glutathione S-transferase P1.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {39954068},
issn = {1432-1912},
abstract = {Glutathione S-transferase P1 (GSTP1) plays a significant role in cancer progression and chemotherapy resistance, with its overexpression diminishing chemotherapeutic efficacy across various tumor types. This study evaluates the inhibitory effects of 6-thio-2'-deoxyguanosine (6-thio-dG) and its dimeric form (6-thio-2'-dG-Dimer) on GSTP1. Enzyme inhibition assays with recombinant human GSTP1, kinetic analysis, molecular docking, and molecular dynamic simulations were employed. Enzymatic assays were performed in 0.1 M phosphate buffer (pH 6.5) at 30 °C, containing 1 mM EDTA, 1 mM GSH, and 1 mM CDNB. The compounds 6-thio-dG and its dimer were dissolved in 2.5% DMSO for the experiments. The IC50 values indicated that the dimer exhibited a higher potency (IC50: 0.339 μM) than the monomer (IC50: 15.14 μM). Kinetic analysis revealed noncompetitive inhibition with glutathione (Ki: 12.26 μM) and mixed inhibition with CDNB (Ki: 11.41 μM) for the monomer, whereas the dimer showed mixed inhibition with glutathione (Ki: 0.972 μM) and competitive inhibition with CDNB (Ki: 0.723 μM). Molecular docking confirmed the higher binding affinity of the dimer (binding energy: - 7.9 kcal/mol, Ki: 1.595 μM) compared to the monomer (binding energy: - 6.2 kcal/mol, Ki: 28.21 μM). The dimer form of 6-thio-dG shows strong potential to enhance chemotherapeutic efficacy by effectively inhibiting GSTP1 and overcoming drug resistance. Its superior inhibitory properties make it a valuable candidate for targeted cancer therapies.},
}

@article {pmid39952372,
year = {2025},
author = {Lanna, A},
title = {Unexpected links between cancer and telomere state.},
journal = {Seminars in cancer biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.semcancer.2025.01.006},
pmid = {39952372},
issn = {1096-3650},
abstract = {Eukaryotes possess chromosome ends known as telomeres. As telomeres shorten, organisms age, a process defined as senescence. Although uncontrolled telomere lengthening has been naturally connected with cancer developments and immortalized state, many cancers are instead characterized by extremely short, genomically unstable telomeres that may hide cancer cells from immune attack. By contrast, other malignancies feature extremely long telomeres due to absence of 'shelterin' end cap protecting factors. The reason for rampant telomere extension in these cancers had remained elusive. Hence, while telomerase supports tumor progression and escape in cancers with very short telomeres, it is possible that different - transfer based or alternative - lengthening pathways be involved in the early stage of tumorigenesis, when telomere length is intact. In this Review, I hereby discuss recent discoveries in the field of telomeres and highlight unexpected links connecting cancer and telomere state. We hope these parallelisms may inform new therapies to eradicate cancers.},
}

@article {pmid39945220,
year = {2025},
author = {Gudmundsdottir, H and Graham, RP and Greipp, PT and Habermann, EB and Knudson, RA and Brandt, CA and Starlinger, P and Thiels, CA and Warner, SG and Smoot, RL and Truty, MJ and Kendrick, ML and Nagorney, DM and Cleary, SP and Halfdanarson, TR},
title = {Alternative lengthening of telomeres and Ki-67 proliferation index provide complementary information on recurrence risk after resection of pancreatic neuroendocrine tumors.},
journal = {Journal of neuroendocrinology},
volume = {},
number = {},
pages = {e70003},
doi = {10.1111/jne.70003},
pmid = {39945220},
issn = {1365-2826},
support = {//Robert D. and Patricia E Kern Center for the Science of Health Care Delivery/ ; //Department of Surgery at Mayo Clinic/ ; },
abstract = {Given the heterogeneous clinical behavior of pancreatic neuroendocrine tumors (pNETs), improved prognostic markers are needed to guide management and post-resection surveillance. Patients who underwent resection of large (≥3 cm) sporadic well-differentiated pNETs from 2000 to 2019 were identified. The Ki-67 proliferation index was determined using immunohistochemistry, and alternative lengthening of telomeres (ALT) status was assessed using fluorescence in situ hybridization. Recurrence-free and overall survival were estimated using Kaplan-Meier analysis. Multivariable Cox regression analysis evaluated factors associated with recurrence-free survival. A total of 106 patients were identified. ALT was positive in 57 (54%) and negative in 49 (46%). Ki-67 was ≥3% in 74 (70%) and <3% in 32 (30%). Tumors with Ki-67 ≥3% were more likely to be ALT positive (61% vs. 38%, p = .046). Stratifying by ALT status and Ki-67 proliferation index, median recurrence-free survival was 4.6 years for patients with ALT-positive/Ki-67 ≥3% tumors, 3.1 years for patients with ALT-positive/Ki-67 <3% tumors, 12.4 years for patients with ALT-negative/Ki-67 ≥3% tumors, and 20.2 years for patients with ALT-negative/Ki-67 <3% tumors (p < .001). Initial recurrence was distant in 82% and locoregional in 18%. Across all groups, overall survival was similar (p = .19). In multivariable analysis, advanced age, ALT positivity, perineural invasion, and lymph node metastases were associated with increased recurrence risk (all p < .05). ALT and Ki-67 provide complementary information on post-resection recurrence risk, which can guide subsequent surveillance and management strategies. These data support the incorporation of ALT testing into routine clinical practice.},
}

@article {pmid39943745,
year = {2025},
author = {Edwards, RJ and Chen, SH and Halliday, B and Bragg, JG},
title = {Small but mitey: a gapless telomere-to-telomere assembly of an unidentified mite with a streamlined genome.},
journal = {Genome biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/gbe/evaf023},
pmid = {39943745},
issn = {1759-6653},
abstract = {A draft assembly of the rainforest tree Rhodamnia argentea Benth. (malletwood, Myrtaceae) revealed contaminating DNA sequences that most closely matched those from mites in the family Eriophyidae. Eriophyoid mites are plant parasites that often induce galls or other deformities on their host plants. They are notable for their small size (averaging 200 μm), distinctive four-legged body structure, and heavily streamlined genomes, which are among the smallest known of all arthropods. Contaminating mite sequences were assembled into a high-quality gapless telomere-to-telomere nuclear genome. The entire genome was assembled on two fully contiguous chromosomes, capped with a novel TTTGG or TTTGGTGTTGG telomere sequence, and exhibited clear signs of genome reduction (34.5 Mbp total length, 68.6% arachnid BUSCO completeness). Phylogenomic analysis confirmed that this genome is that of a previously unsequenced eriophyoid mite. Despite its unknown identity, this complete nuclear genome provides a valuable resource to investigate invertebrate genome reduction.},
}

@article {pmid39943216,
year = {2025},
author = {Vernick, J and Martin, C and Montelpare, W and Dunham, AE and Overall, KL},
title = {Understanding the Influence of Early-Life Stressors on Social Interaction, Telomere Length, and Hair Cortisol Concentration in Homeless Kittens.},
journal = {Animals : an open access journal from MDPI},
volume = {15},
number = {3},
pages = {},
doi = {10.3390/ani15030446},
pmid = {39943216},
issn = {2076-2615},
support = {22-004//VetSRA/ ; W21-15//EveryCat/ ; 21-015//Winn Foundation/ ; 6010435//Sir James Dunn Animal Welfare Center/ ; 6010567//Companion Animal Trust Fund/ ; 6010567//AVC Internal Research Fund/ ; },
abstract = {The early postnatal period is a critical neurodevelopmental stage characterized by rapid neural maturation and is adversely affected by early-life stressors. This study explored the behavioural, physiological, and epigenetic consequences of early-life stress in a population of homeless rescue kittens. This longitudinal study included 50 kittens rescued and placed into foster care by the Prince Edward Island Humane Society. They underwent behavioural testing at 8, 10, and 12 weeks of age. Hair cortisol concentration was measured at 8 weeks and served as a physiological marker of the previous 3 months' cumulative stress response, which, for these kittens, included the late gestation period. A blood sample for relative telomere length measurement was taken at 10-12 weeks to estimate epigenetic changes as young kittens. Data were analyzed with respect to age and performance in all repeated measures tests, status as a stray or a surrender, and the presence of the dam in their foster homes. As expected, the performance of kittens in all tests changed over the 5 weeks of testing. Kittens separated from their mothers exhibited significantly higher hair cortisol concentrations (p = 0.02) and elongated relative telomere lengths (p = 0.04). No correlation was found between hair cortisol concentration and relative telomere lengths (p = 0.99). These results support the need for further study on the effects of epigenetics and early-life stress, both in kittens and across species.},
}

@article {pmid39940930,
year = {2025},
author = {Baldazzi, C and Bandini, L and Robustelli, V and Patuelli, A and Venturi, C and Grassi, A and Marzocchi, G and Ielpo, A and Solli, V and Bochicchio, MT and Paolini, S and Sartor, C and Zingarelli, F and Curti, A and Ottaviani, E and Testoni, N},
title = {Emergence and Cytogenetic Clonal Evolution of Chromosome 7 Abnormalities in Myeloid Malignancies: Investigating the Role of Telomere Dysfunction.},
journal = {International journal of molecular sciences},
volume = {26},
number = {3},
pages = {},
doi = {10.3390/ijms26031162},
pmid = {39940930},
issn = {1422-0067},
support = {GR-2018-12365278//Italian Ministry of Health/ ; },
mesh = {Humans ; *Chromosomes, Human, Pair 7/genetics ; *Clonal Evolution/genetics ; *Telomere/genetics ; Male ; Female ; *Chromosome Deletion ; Aged ; Middle Aged ; Chromosome Aberrations ; Adult ; Chromosomal Instability/genetics ; Aged, 80 and over ; Mutation ; Myeloproliferative Disorders/genetics/pathology ; },
abstract = {Monosomy 7 and deletion 7q are common chromosomal abnormalities in myeloid malignancies, and they are associated with a poor prognosis. The mechanism underlying their acquisition remains elusive. We identified a cohort of 24 patients exhibiting clones with different chromosome 7 abnormalities, such as deletion 7q, unstable derivatives (ring chromosomes or 'naked' centromeres), and monosomy 7. We designated this group as having cytogenetic clonal evolution of chromosome 7 abnormalities (CCE7). In some cases, CCE7 correlated with disease progression, suggesting that deletions or other derivatives involving the q-arm of chromosome 7 may arise early in the disease course. These abnormalities may be transient but can potentially evolve into monosomy 7. Within the CCE7 group, telomere loss or shortening may contribute to chromosomal instability and the emergence of unstable derivatives, as the chromosome 7 derivatives displayed loss or rearrangement of subtelomeric regions. Moreover, we identified variants in genes implicated in telomere biology disorders and observed specific genetic mutation profiles associated with different chromosome 7 abnormalities. These findings shed light on a potential mechanism leading to monosomy 7 through the evolution of chromosome 7q abnormalities. Identifying patients at risk of developing monosomy 7, based on the presence of unstable derivatives with telomere loss or a specific mutation profile, could potentially enhance patient management and guide the development of novel therapeutic strategies.},
}

Humans
*Chromosomes, Human, Pair 7/genetics
*Clonal Evolution/genetics
*Telomere/genetics
Male
Female
*Chromosome Deletion
Aged
Middle Aged
Chromosome Aberrations
Adult
Chromosomal Instability/genetics
Aged, 80 and over
Mutation
Myeloproliferative Disorders/genetics/pathology

@article {pmid39940762,
year = {2025},
author = {Assalve, G and Lunetti, P and Rocca, MS and Cosci, I and Di Nisio, A and Ferlin, A and Zara, V and Ferramosca, A},
title = {Exploring the Link Between Telomeres and Mitochondria: Mechanisms and Implications in Different Cell Types.},
journal = {International journal of molecular sciences},
volume = {26},
number = {3},
pages = {},
doi = {10.3390/ijms26030993},
pmid = {39940762},
issn = {1422-0067},
support = {2022KREEEF and P2022AXRW7//Ministero dell'università e della ricerca/ ; },
mesh = {Humans ; *Mitochondria/metabolism ; *Telomere/metabolism/genetics ; Animals ; *Reactive Oxygen Species/metabolism ; Oxidative Stress ; DNA Damage ; Telomere Shortening ; Aging/metabolism/genetics ; Telomerase/metabolism ; Telomere Homeostasis ; },
abstract = {Telomeres protect chromosome ends from damage, but they shorten with each cell division due to the limitations of DNA replication and are further affected by oxidative stress. This shortening is a key feature of aging, and telomerase, an enzyme that extends telomeres, helps mitigate this process. Aging is also associated with mitochondrial dysfunction, leading to increased reactive oxygen species (ROS) that exacerbate cellular damage and promote apoptosis. Elevated ROS levels can damage telomeres by oxidizing guanine and disrupting their regulation. Conversely, telomere damage impacts mitochondrial function, and activation of telomerase has been shown to reverse this decline. A critical link between telomere shortening and mitochondrial dysfunction is the DNA damage response, which activates the tumor suppressor protein p53, resulting in reduced mitochondrial biogenesis and metabolic disruptions. This highlights the bidirectional relationship between telomere maintenance and mitochondrial function. This review explores the complex interactions between telomeres and mitochondria across various cell types, from fibroblasts to sperm cells, shedding light on the interconnected mechanisms underlying aging and cellular function.},
}

Humans
*Mitochondria/metabolism
*Telomere/metabolism/genetics
Animals
*Reactive Oxygen Species/metabolism
Oxidative Stress
DNA Damage
Telomere Shortening
Aging/metabolism/genetics
Telomerase/metabolism
Telomere Homeostasis

@article {pmid39938003,
year = {2025},
author = {Tometten, M and Beier, F and Kirschner, M and Schumacher, Y and Walter, J and Vieri, M and Kricheldorf, K and Röth, A and Platzbecker, U and Radsak, MP and Schafhausen, P and Corbacioglu, S and Höchsmann, B and Balabanov, S and Hinze, CH and Chromik, J and Heuser, M and Kreuter, M and Wlodarski, MW and Elbracht, M and Kurth, I and Koschmieder, S and Panse, JP and Meyer, R and Brümmendorf, TH},
title = {Late-Onset Telomere Biology Disorders: Clinical Insights and Treatment Outcomes from a Retrospective Registry Cohort.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2024014632},
pmid = {39938003},
issn = {2473-9537},
abstract = {Pathogenic germline variants affecting proper telomere maintenance result in premature telomere shortening and cause telomere biology disorders (TBDs). While classical dyskeratosis congenita in children is rather well defined, late-onset ("cryptic") TBDs remain underrecognized, resulting in underdiagnosis and inadequate treatment in affected adults. Here, we present a series of adult TBD cases collected through the German TBD reference center between 2014 and 2024. Patients ≥18 years with an age-matched telomere length (TL) < 10th percentile in lymphocytes and detection of either a variant of uncertain significance, a pathogenic or a likely pathogenic variant in TBD-associated genes, and available clinical data were included in this analysis. On this basis, a novel point-based algorithm for categorization into proven, probable and suspected-only TBD cases, respectively, was developed. Out of a total of 1,537 TL analyses, 42 patients with proven (n=29) or probable (n=13) TBD were identified. Median age at first clinical manifestation and at diagnosis was 20.0 years and 34.1 years, respectively. Bone marrow failure (BMF) was the most frequent manifestation observed in our cohort (73.8%), followed by liver or interstitial lung diseases (50.0% and 41.5%, respectively). Immunosuppressive therapy was carried out in six patients with BMF, none of them responded. In comparison, eight of eight evaluable patients treated with androgen derivatives showed hematologic response. Our data provide novel real-world insight into the clinical manifestation spectrum, diagnosis as well as clinical course and treatment of TBD in adult, late-onset cases of this hereditary disease.},
}

@article {pmid39937009,
year = {2025},
author = {Levstek, T and Bahčič, E and Vujkovac, B and Cokan Vujkovac, A and Tesovnik, T and Remec, ŽI and Čuk, V and Trebušak Podkrajšek, K},
title = {Telomere Length, Oxidative Stress, and Kidney Damage Biomarkers in Fabry Nephropathy.},
journal = {Cells},
volume = {14},
number = {3},
pages = {},
doi = {10.3390/cells14030218},
pmid = {39937009},
issn = {2073-4409},
support = {P1-0170//The Slovenian Research and Innovation Agency/ ; J3-50113//The Slovenian Research and Innovation Agency/ ; NA//Takeda Pharmaceuticals/ ; },
mesh = {Humans ; *Oxidative Stress ; *Fabry Disease/urine/genetics/pathology/metabolism ; Male ; *Biomarkers/urine/blood/metabolism ; Female ; Adult ; *Telomere/metabolism ; *Kidney Diseases/urine/pathology/genetics ; Middle Aged ; Kidney/pathology/metabolism ; Case-Control Studies ; Telomere Homeostasis ; Glomerular Filtration Rate ; },
abstract = {Fabry nephropathy is a life-threatening complication of Fabry disease characterized by complex and incompletely understood pathophysiological processes possibly linked to premature aging. We aimed to investigate leukocyte telomere length (LTL), oxidative stress, and kidney damage biomarkers in relation to kidney function. The study included 35 Fabry patients and 35 age and sex-matched control subjects. Based on the estimated slope of the glomerular filtration rate, the patients were divided into two groups. Relative LTL was quantified by qPCR, urinary biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) by UHPLC-MS/MS, and kidney damage biomarkers by flow cytometry. There was no statistically significant difference in LTL between Fabry patients and controls. However, a significant difference was observed in male patients compared to their matched control subjects (p = 0.013). Oxidative stress biomarkers showed no differences between patients and controls, while significant differences were observed in urinary IGFBP7, EGF, and OPN levels between Fabry patients with stable kidney function and those with progressive nephropathy (FDR = 0.021, 0.002, and 0.013, respectively). Significant differences were also observed in plasma levels of cystatin C, TFF3, and uromodulin between patients with progressive nephropathy and controls (all FDR = 0.039). Along with these biomarkers (FDR = 0.007, 0.017, and 0.010, respectively), NGAL also exhibited a significant difference between the two patient groups (FDR = 0.017). This study indicates accelerated telomere attrition, which may be related to disease burden in males. Furthermore, analyses of urinary oxidative stress markers revealed no notable disparities between the different kidney function groups, indicating their limited utility. However, promising differences were found in some biomarkers of kidney damage in urine and plasma.},
}

Humans
*Oxidative Stress
*Fabry Disease/urine/genetics/pathology/metabolism
Male
*Biomarkers/urine/blood/metabolism
Female
Adult
*Telomere/metabolism
*Kidney Diseases/urine/pathology/genetics
Middle Aged
Kidney/pathology/metabolism
Case-Control Studies
Telomere Homeostasis
Glomerular Filtration Rate

@article {pmid39934464,
year = {2025},
author = {Soares, MR and de Carvalho, RM and Dos Santos Cirino, H and Martins, R and Miranda Furtado, CL and Santana, BAA and Calado, RT and Ferriani, RA and Dos Reis, RM},
title = {Effect of SARS-CoV-2 infection on sperm telomere length.},
journal = {Journal of assisted reproduction and genetics},
volume = {},
number = {},
pages = {},
pmid = {39934464},
issn = {1573-7330},
support = {465482/2014-7//INCT - Institutos Nacionais de Ciência e Tecnologia/ ; 465482/2014-7//INCT - Institutos Nacionais de Ciência e Tecnologia/ ; 176841/2022-9//INCT - Institutos Nacionais de Ciência e Tecnologia/ ; 13012/2023-7//CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 306289/2022-9//CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
abstract = {PURPOSE: The repercussions and outcomes of the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has raised concerns about potential adverse effects on the male reproductive system. Telomeres are crucial in maintaining the integrity and stability of genomic DNA, and viral infections can induce changes in telomere biology. In this study, the repercussions of SARS-CoV-2 infection in male reproductive health were analyzed.

METHODS: This case-control study enrolled subjects who donated blood and semen samples. Fifty-six men with and 56 without prior COVID-19 infection, ages 18-45 years, were included. Semen analysis and hormonal levels were evaluated. The presence of SARS-CoV-2 RNA in semen and the sperm telomere length were assessed by quantitative polymerase chain reaction and associated with clinical and laboratory data. To reduce interference factors, known variables that influence telomere length were analyzed independently.

RESULTS: Sperm telomere length was significantly diminished in the COVID-19 positive group with a mean difference of 0.635 compared to the negative group (p = 0.041). Most individuals in the COVID-19 positive group were clinically classified as asymptomatic/mild illness, and all samples were collected more than 90 days after recovery. No statistically significant differences were observed between the groups in terms of clinical data, semen parameters, and serum levels of follicle-stimulation hormone, estradiol, and testosterone. Persistent or subgenomic SARS-CoV-2 RNA was not detected in the semen samples.

CONCLUSION: This study revealed that SARS-CoV-2 infection reduced sperm telomere length without alterations in semen parameters or hormonal levels. These results provide further evidence that SARS-CoV-2 infection can induce genomic alterations in human sperm.},
}

@article {pmid39933571,
year = {2025},
author = {Blanco, MB and Smith, DL and Greene, LK and Lin, J and Klopfer, PH},
title = {Food deprivation is associated with telomere elongation during hibernation in a primate.},
journal = {Biology letters},
volume = {21},
number = {2},
pages = {20240531},
doi = {10.1098/rsbl.2024.0531},
pmid = {39933571},
issn = {1744-957X},
support = {//Duke Lemur Center/ ; },
mesh = {Animals ; *Hibernation/physiology ; *Cheirogaleidae/physiology/genetics ; *Telomere/physiology ; *Food Deprivation ; Male ; Female ; Telomere Homeostasis ; },
abstract = {Telomeres, the protective ends of chromosomes, progressively shorten due to incomplete mitotic replication and oxidative stress. In some organisms, transient telomere elongation may occur, for example, when individuals have an energy surplus to counter stress-induced life events or when elongating telomeres is a last chance to increase fitness. Mammalian hibernators are good models to test telomere dynamics, as they cycle between prolonged bouts of metabolic depression (torpor) punctuated by short surges to euthermia (arousals). We studied captive fat-tailed dwarf lemurs (Cheirogaleus medius), strepsirrhine primate hibernators, that were food-deprived (n = 8) or fed daily (n = 7) during hibernation (4.5 months). We compared telomere lengths, assayed via qPCR from oral swabs, at five strategic time points that span a full year. Food-deprived subjects underwent multi-day torpor/arousal cycles, lost considerable body mass and elongated telomeres during hibernation but shortened them upon emergence. In contrast, food-provisioned subjects ate daily, lost body mass more slowly, underwent shallower and shorter torpor bouts and experienced little change in telomere lengths during the same periods. Our results highlight a complex relationship between telomere dynamics, energy balance and torpor expression. Further investigation is warranted to elucidate the regulation of protective mechanisms in these primate hibernators.},
}

Animals
*Hibernation/physiology
*Cheirogaleidae/physiology/genetics
*Telomere/physiology
*Food Deprivation
Male
Female
Telomere Homeostasis

@article {pmid39933569,
year = {2025},
author = {Shephard, AM and Ledón-Rettig, CC},
title = {A novel carnivorous diet reduces brain telomere length.},
journal = {Biology letters},
volume = {21},
number = {2},
pages = {20240593},
doi = {10.1098/rsbl.2024.0593},
pmid = {39933569},
issn = {1744-957X},
mesh = {Animals ; *Brain/metabolism ; *Diet ; *Telomere ; Larva/growth & development/physiology/genetics ; Anura/physiology/genetics ; Carnivory ; Telomere Shortening ; },
abstract = {Developmental conditions can profoundly influence adult survival or longevity. One established correlate of longevity is the length of telomeres-non-coding DNA regions that protect chromosomal ends. Telomere length in adulthood can be influenced by environmental conditions during development, such as nutrient restriction. Yet, we lack experimental studies of how adult telomere length is affected by a different form of nutritional variation: diet type. Here, we asked how diet-type variation during larval development affects telomere length in multiple post-metamorphic somatic tissues of the Mexican spadefoot (Spea multiplicata), an anuran species whose larvae develop on two qualitatively distinct diets: an ancestral omnivorous diet of detritus or a more novel carnivorous diet of live shrimp. We found that larvae developing on the novel shrimp diet developed into post-metamorphic frogs with shorter telomeres in the brain-a structure that is particularly vulnerable to harmful effects of nutritional adversity, such as oxidative stress. Given known links between telomere length and neurological health outcomes, our study suggests that a dietary transition to carnivory might carry costs in terms of compromised neural integrity later in life. This work highlights the lasting impact of a developmental diet on somatic maintenance and health.},
}

Animals
*Brain/metabolism
*Diet
*Telomere
Larva/growth & development/physiology/genetics
Anura/physiology/genetics
Carnivory
Telomere Shortening

@article {pmid39932851,
year = {2025},
author = {Gao, Z and Yu, Y and Eckel-Mahan, K and Kolonin, MG},
title = {Caloric Restriction and Telomere Preservation in TERT Knockout Adipocyte Progenitors Does Not Rescue Mice From Metabolic Dysfunction due to a TERT Function in Adipocyte Mitochondria.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e14499},
doi = {10.1111/acel.14499},
pmid = {39932851},
issn = {1474-9726},
support = {R01DK125922/NH/NIH HHS/United States ; },
abstract = {Inactivation of telomerase (TERT) in adipocyte progenitor cells (APC) expedites telomere attrition, and the onset of diabetes in mice fed high-fat diet (HFD), which promotes APC over-proliferation and replicative senescence. Here, we show that time-restricted feeding or caloric restriction in the postnatal development of mice subsequently subjected to HFD prevents telomere attrition but not glucose intolerance. This metabolic effect of dietary intervention was not observed for mice with TERT KO in endothelial or myeloid cells. To characterize the telomere-independent effects of TERT in the APC lineage, we analyzed mice with TERT knockout in mature adipocytes (AD-TERT-KO), which do not proliferate and avoid telomere attrition. Analysis of adipocytes from AD-TERT-KO mice indicated reliance on glycolysis and decreased mitochondrial oxidative metabolism. We show that AD-TERT-KO mice have reduced cold tolerance and metabolism abnormality indicating a defect in adaptive thermogenesis, characteristic of aging. Conversely, ectopic TERT expression in brown adipocytes-induced mitochondrial oxidation and thermogenic gene expression. We conclude that TERT plays an important non-canonical function in the mitochondria of adipocytes.},
}

@article {pmid39929725,
year = {2025},
author = {Opresko, PL and Sanford, SL and De Rosa, M},
title = {Oxidative Stress and DNA Damage at Telomeres.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041707},
pmid = {39929725},
issn = {1943-0264},
abstract = {Oxidative stress is associated with increasing telomere shortening and telomere dysfunction, as well as with numerous pathologies in humans, including inflammatory diseases and cancer. Critically short and dysfunctional telomeres lose their ability to protect chromosome ends, which triggers irreversible growth arrest, termed senescence, or genomic instability. Telomeres are highly sensitive to damage from reactive oxygen species, which increase under conditions of oxidative stress. This work covers the evidence that oxidative damage to telomeric DNA alters telomere maintenance by various mechanisms and describes the DNA repair pathways important for preserving telomere function under oxidative stress conditions.},
}

@article {pmid39928198,
year = {2025},
author = {Zhao, J and Ye, L and Yan, W and Huang, W and Wang, G},
title = {Exploration of telomere-related biomarkers for lung adenocarcinoma and targeted drug prediction.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {148},
pmid = {39928198},
issn = {2730-6011},
abstract = {AIM: Bioinformatics analyses were performed to identify telomere biomarkers to develop a diagnostic model for lung adenocarcinoma (LUAD) and to predict potential target drugs for patients with LUAD.

BACKGROUND: Telomeres function crucially in maintaining genome stability and chromosome integrity, and telomere-related genes (TRGs) serve as potential prognostic markers in a variety of cancers. However, studies focusing on TRGs in LUAD are limited.

OBJECTIVE: To screen key telomere-related markers for LUAD and to evaluate their potential impact on the occurrence and development of LUAD.

METHODS: LUAD samples were collected from University of California Santa Cruz (UCSC) Xena and 2093 telomere-related genes (TRGs) were obtained from TelNet database. Hub genes were screened using "WGCNA" package. Differentially expressed genes (DEGs) between tumor and control samples were filtered using "DESeq" package. Protein-protein interaction (PPI) network analysis was performed to select candidate genes, from which telomere-related biomarkers were identified by machine learning and used to develop a nomogram. Functional enrichment pathways of the biomarkers were analyzed using "clusterProfiler" package. Correlation between immune cell infiltration and the biomarkers was examined by Spearman method. Targeted drugs were predicted and molecular docking models were developed using AutoDockTools. Finally, the screened biomarkers were validated by performing in vitro cellular assays.

RESULTS: A total of 259 hub genes, 2848 DEGs, and 48 differentially expressed TRGs in LUAD were screened. Subsequently, 13 candidate genes were obtained by PPI network analysis. LASSO and support vector machine-recursive feature elimination (SVM-RFE) algorithms further reduced the number of telomere-related biomarkers to four (CCNB1, CDC20, PLK1, and TOP2A). A nomogram with a strong predictive performance was created. These four biomarkers were mainly enriched in the mitogenic pathways and exhibited a strong correlation with immune cell infiltration. Three drugs (Lucanthone, Fulvestrant, and Myricetin) targeting the four biomarkers were predicted to be able to treat LUAD. Finally, in vitro cellular experiments demonstrated that CCNB1 and PLK1 have potential effects on proliferation, migration, invasion and AKT/mTOR signaling pathway in LUAD cells.

CONCLUSION: This study provided novel diagnostic biomarkers, therapeutic targets, and potential drugs for LUAD.},
}

@article {pmid39925560,
year = {2025},
author = {Shakeri, F and Nabi, A and Farashahi, E and Erfanian, S and Agha-Rahimi, A},
title = {Selected Spermatozoa at Conventional Magnification Cannot Guarantee in Obtaining Spermatozoa With Long Telomere Length in Severe Teratozoospermia Patients.},
journal = {Cureus},
volume = {17},
number = {1},
pages = {e77240},
pmid = {39925560},
issn = {2168-8184},
abstract = {Background Sperm selection from the population of processed spermatozoa cells after density gradient centrifugation (DGC) can assist embryologists in selecting high-quality sperm. Sperm selection of low-quality and chromatin-damaged spermatozoa is inevitable in severe teratozoospermia semen specimens. This study was conducted to evaluate whether sperm selection at ×400 magnification enables embryologists to select a population of spermatozoa with low DNA fragmentation and high sperm telomere length (STL) in semen samples with severe teratozoospermia. Methods A total of 23 infertile men characterized by severe teratozoospermia were selected. Sperm DNA fragmentation (SDF) and relative STL (r-STL) were evaluated at three stages: specimen collection, after DGC, and during the single selection of spermatozoa at ×400 magnification (single selection). The 23 patients were divided into two groups, including 14 with normal morphology ≤1% and nine with normal morphology of 2%. SDF and r-STL were compared between the two groups at three stages. Results The results of this study showed that although SDF decreased remarkably after DGC and single selection (F=64.327, P-value=0.000), the DNA fragmentation index obtained for each semen sample was more than the cutoff point of 18% based on the Halo sperm test. No statistically significant differences were observed in r-STL after DGC and single selection (F=1.978, P-value=0.163). Meanwhile, the pairwise comparison of r-STL showed that in the 2% normal morphology group, the mean relative telomere length was significantly higher in the selected spermatozoa compared to the semen specimen (P=0.014). This increase can be attributed to DGC and single selection by the embryologist. Also, there was no correlation between SDF and r-STL in the semen samples with severe teratozoospermia (r=0.01, P-value=0.964). Conclusions This study suggests that investing more time in sperm selection can decrease SDF, but r-STL of spermatozoa selected by the embryologist does not increase in severe teratozoospermia semen samples with morphology ≤1%.},
}

@article {pmid39921881,
year = {2025},
author = {Hernández-Silva, D and López-Abellán, MD and Martínez-Navarro, FJ and García-Castillo, J and Cayuela, ML and Alcaraz-Pérez, F},
title = {Development of a Short Telomere Zebrafish Model for Accelerated Aging Research and Antiaging Drug Screening.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70007},
doi = {10.1111/acel.70007},
pmid = {39921881},
issn = {1474-9726},
support = {PI22/00861//Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union/ ; },
abstract = {Increased life expectancy is associated with a higher risk of age-related diseases, which represent a major public health challenge. Animal models play a crucial role in aging research, enabling the study of diseases at the organism level and facilitating drug development and repurposing. Among these models, zebrafish stands out as an excellent in vivo system due to its unique characteristics. However, the longevity of zebrafish is a limitation for research, as it often takes too long to obtain results within a reasonable timeframe. To address this, we have developed a short telomere zebrafish line (ST2) with a premature aging phenotype during the larval stage. Although less extreme than the tert-deficient G2 larvae, ST2 larvae exhibit reduced telomerase expression and activity, along with shortened telomeres. they also exhibit increased cellular senescence, apoptosis, and premature death. As a proof of concept, we evaluated the antiaging effects of two compounds: resveratrol (a polyphenol) and navitoclax (a senolytic). Our results confirm the antiaging properties of resveratrol, which improves telomere maintenance. However, navitoclax does not attenuate the ST2 phenotype. Taking advantage of the zebrafish larval model, this premature aging system provides a valuable platform for in vivo testing of rejuvenating molecules through drug screening, using telomere length or survival as a readout.},
}

@article {pmid39921567,
year = {2025},
author = {Goncalves, T and Cunniffe, S and Ma, TS and Mattis, N and Rose, AW and Kent, T and Mole, DR and Geiller, HEB and van Bijsterveldt, L and Humphrey, TC and Hammond, EM and Gibbons, RJ and Clynes, D and Rose, AM},
title = {Elevated reactive oxygen species can drive the alternative lengthening of telomeres pathway in ATRX-null cancers.},
journal = {Nucleic acids research},
volume = {53},
number = {4},
pages = {},
pmid = {39921567},
issn = {1362-4962},
support = {CL-2018-13-005//National Institute of Health and Care Research Clinical Lectureship/ ; SGL023\1055//Academy of Medical Sciences Starter/ ; 0 011 483//University of Oxford Medical Sciences/ ; 15-202//Children with Cancer UK/ ; 101 136 835//EU Horizon Europe Research and Innovation program Cancer Mission 'HIT-GLIO'/ ; C6078/A28736/CRUK_/Cancer Research UK/United Kingdom ; //MRC DPhil Studentship/ ; },
mesh = {*X-linked Nuclear Protein/genetics/metabolism ; *Reactive Oxygen Species/metabolism ; Humans ; *Telomere Homeostasis/genetics ; Cell Line, Tumor ; *Telomere/metabolism/genetics ; Glioma/genetics/metabolism/pathology ; R-Loop Structures ; Ribonuclease H/metabolism/genetics ; Tumor Microenvironment/genetics ; Osteosarcoma/genetics/pathology/metabolism ; Mutation ; },
abstract = {The alternative lengthening of telomeres (ALT) pathway is a telomerase-independent mechanism for immortalization in cancer cells and is commonly activated in low-grade and high-grade glioma, as well as osteosarcoma. The ALT pathway can be activated under various conditions and has often been shown to include mutational loss of ATRX. However, this is insufficient in isolation and so other cellular event must also be implicated. It has been shown that excessive accumulation of DNA:RNA hybrid structures (R-loops) and/or formation of DNA-protein crosslinks (DPCs) can be other important driving factors. The underlying cellular events leading to R-loop and DPC formation in ALT cancer cells to date remain unclear. Here, we demonstrate that excessive cellular reactive oxygen species (ROS) is an important causative factor in the evolution of ALT-telomere maintenance in ATRX-deficient glioma. We identified three sources of elevated ROS in ALT-positive gliomas: co-mutation of SETD2, downregulation of DRG2, and hypoxic tumour microenvironment. We demonstrate that elevated ROS leads to accumulation of R-loops and, crucially, resolution of R-loops by the enzyme RNase H1 prevents ALT pathway activity in cells exposed to elevated ROS. Further, we found a possible causal link between the formation of R-loops and the accumulation of DPCs, in particular, formation of TOP1 complexes covalently linked to DNA (Top1cc). We also demonstrate that elevation of ROS can trigger over-activity of the ALT pathway in osteosarcoma and glioma cell lines, resulting in excessive DNA damage and cell death. This work presents important mechanistic insights into the endogenous origin of excessive R-loops and DPCs in ALT-positive cancers, as well as highlighting potential novel therapeutic approaches in these difficult-to-treat cancer types.},
}

*X-linked Nuclear Protein/genetics/metabolism
*Reactive Oxygen Species/metabolism
Humans
*Telomere Homeostasis/genetics
Cell Line, Tumor
*Telomere/metabolism/genetics
Glioma/genetics/metabolism/pathology
R-Loop Structures
Ribonuclease H/metabolism/genetics
Tumor Microenvironment/genetics
Osteosarcoma/genetics/pathology/metabolism
Mutation

@article {pmid39918489,
year = {2025},
author = {Nagao, K and Watanuki, M and Hayashi, H and Kawamata, N and Kuroiwa, K and Narita, H and Okamura, R and Shimada, S and Arai, N and Kawaguchi, Y and Yanagisawa, K and Hattori, N},
title = {Clinical impact of donor telomere length after umbilical cord blood transplantation.},
journal = {Cytotherapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcyt.2025.01.011},
pmid = {39918489},
issn = {1477-2566},
abstract = {BACKGROUND AND AIMS: Several studies have shown that the telomere length of engrafted donor cells affects the clinical outcomes in patients with hematologic diseases after allogeneic stem-cell transplantation (allo-SCT). However, the relationship between donor telomere length and clinical outcomes after umbilical-cord blood transplantation (UCBT) remains unknown. The study aim was to assess the relationship between donor telomere length and transplantation outcomes.

METHODS: We measured donor-derived relative telomere length (RTL) in 75 patients after single-unit UCBT and evaluated the association between telomere length and transplantation outcomes.

RESULTS: Compared with patients with shorter RTL, patients with longer RTL had a higher risk of bacterial and bloodstream infections [hazard ratio (HR), 4.79; 95% confidence interval (CI), 1.70-13.46; P = 0.003 and HR, 3.43; 95% CI, 1.19-9.82; P = 0.022, respectively] and was possibly associated with reduced relapse (HR 0.44, 95% CI 0.15-1.27, P = 0.13) by multivariate analysis.

CONCLUSIONS: Patients after UCBT who received engrafted donor cells with longer RTL had a higher risk of bacterial and bloodstream infections. The measured donor-derived RTL at engraftment after UCBT may predict clinical outcomes.},
}

@article {pmid39911301,
year = {2025},
author = {Light, J and Schratz, KE and Nanegrungsunk, O and Rudnick, N and Armanios, M and Bressler, NM},
title = {Adult-Onset Presentations of Retinopathy Associated With Short Telomere Syndromes.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251316324},
pmid = {39911301},
issn = {2474-1272},
abstract = {Purpose: To describe the association between short telomere syndrome and exudative retinopathies in adults. Methods: This case series compared the presentation, course of treatment, and visual outcomes of 2 patients with adult-onset retinopathy associated with short telomere syndrome. Results: In Case 1, a 53-year-old man initially presented with bilateral retinal telangiectasias and preretinal hemorrhage in the left eye, which was followed by multiple vitreous hemorrhages. In the subsequent 15 years, the patient was diagnosed with pulmonary fibrosis, liver cirrhosis, and a RTEL1 gene mutation, consistent with short telomere syndrome. In Case 2, a previously asymptomatic 26-year-old man with paternally inherited short telomere syndrome (TERC gene mutation) presented with floaters, bilateral peripheral retinal capillary nonperfusion, and an aneurysmal lesion with surrounding exudation. Conclusions: Short telomere syndromes, with systemic features that can be life-threatening, can manifest initially in adulthood with retinal telangiectasia, aneurysmal lesions, exudation, or peripheral retinal capillary nonperfusion, preceding systemic manifestations. Because the systemic manifestations of retinal telangiectasia and peripheral retinal capillary nonperfusion are progressive and can be life-threatening, recognizing these findings in adults with retinal telangiectasia is crucial.},
}

@article {pmid39911233,
year = {2024},
author = {Zhu, S and Hao, Z and Chen, Q and Liu, X and Wu, W and Zhang, F},
title = {A two-sample bidirectional Mendelian randomization analysis between telomere length and hyperthyroidism.},
journal = {Frontiers in endocrinology},
volume = {15},
number = {},
pages = {1369800},
pmid = {39911233},
issn = {1664-2392},
mesh = {Humans ; *Mendelian Randomization Analysis ; *Hyperthyroidism/genetics ; *Genome-Wide Association Study ; *Polymorphism, Single Nucleotide ; Telomere/genetics ; Telomere Homeostasis/genetics ; Female ; Genetic Predisposition to Disease ; },
abstract = {BACKGROUND: hyperthyroidism characterized by low thyrotropin, highlighting complications and risks, including cardiac issues, osteoporosis, adverse pregnancy outcomes, unintentional weight loss, and increased mortality associated with untreated hyperthyroidism. However, the casual association between telomere length (TL) and hyperthyroidism remains unclear.

OBJECTIVE: We aim to explore the casual relationship between TL and hyperthyroidism.

METHODS: A two-sample bidirectional Mendelian randomization (MR) analysis employed the inverse variance weighted (IVW) method, supplemented by additional approaches such as Weighted Median (WM), and MR Egger.

RESULTS: The summary statistics for TL were derived from the UK Biobank, comprising 472,174 individuals, while the data for hyperthyroidism were sourced from the GWAS Catalog and the FinnGen database, encompassing cohorts of 460,499 and 173,938 individuals, respectively. Utilizing 139 genome-wide significant single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for TL, forward MR analyses indicated a negative causal effect of TL on hyperthyroidism. The risk of hyperthyroidism decreased as genetically predicted TL increased by one standard deviation, as determined by the IVW form GWAS Catalog (OR:0.659,95%CI: 0.541-0.802, p <0.001) and IVW from FinnGen(OR:0.634, 95%CI: 0.479-0.840, p = 0.001). Other MR methods exhibited a consistent trend in the impact of TL on hyperthyroidism. Reverse MR analysis suggested no causal association between TL and hyperthyroidism (p > 0.05). Sensitivity analyses confirmed the robustness of these results, suggesting minimal susceptibility to confounding factors and bias.

CONCLUSION: The finding that longer telomeres reduce hyperthyroidism risk highlights the need to validate hyperthyroidism's impact on telomere length, offering valuable insights for prevention and treatment.},
}

Humans
*Mendelian Randomization Analysis
*Hyperthyroidism/genetics
*Genome-Wide Association Study
*Polymorphism, Single Nucleotide
Telomere/genetics
Telomere Homeostasis/genetics
Female
Genetic Predisposition to Disease

@article {pmid39908316,
year = {2025},
author = {Weixlbraun, J and Chapagain, D and Cornils, JS and Smith, S and Schwarzenberger, F and Hoelzl, F},
title = {Impact of trainability on telomere dynamics of pet dogs (Canis lupus familiaris): An explorative study in aging dogs.},
journal = {PloS one},
volume = {20},
number = {2},
pages = {e0317332},
pmid = {39908316},
issn = {1932-6203},
mesh = {Animals ; Dogs ; *Aging/physiology/genetics ; *Telomere/genetics/metabolism ; Male ; Female ; Pets ; Cognition/physiology ; Behavior, Animal/physiology ; Telomere Homeostasis ; Telomere Shortening ; },
abstract = {This research studied the impact of various factors (including social and physiological parameters) on telomere dynamics in pet dogs. Telomeres, essential for maintaining genomic integrity, undergo shortening with each cell division, leading to cellular senescence. Previous studies in humans have linked cognitive and social factors with telomere dynamics but in animals, such associations remain understudied. This study is based on a previous study, where behavioral and cognitive changes in aging pet dogs were investigated. Together with standard variables (sex, age, body weight, diet), behavioral predictors that were assessed in the "Modified Vienna Canine Cognitive Battery" were used. This study aimed to investigate the influence of these factors on telomere dynamics in aging pet dogs. The relative telomere length of 63 dogs was measured, using a qPCR method and a model selection approach was applied to assess which variables can explain the found telomere patterns. Results revealed a strong association of the behavioral factor called trainability and telomere change. Trainability was the best predictor for telomere change over time and was the only predictor having a relative variable importance (RVI) above 0.7. This finding suggests that higher trainability positively affects telomere dynamics in aging dogs and factors like age, sex, diet, and other cognitive parameters are less important. The study sheds light on the potential role of cognitive factors in canine aging and offers insights into improving the quality of life for aging dogs, but further research is needed to comprehensively understand the interplay between behavior, cognition, and telomere dynamics in dogs.},
}

Animals
Dogs
*Aging/physiology/genetics
*Telomere/genetics/metabolism
Male
Female
Pets
Cognition/physiology
Behavior, Animal/physiology
Telomere Homeostasis
Telomere Shortening

@article {pmid39905075,
year = {2025},
author = {Zhang, F and Cheng, D and Porter, KI and Heck, EA and Wang, S and Zhang, H and Davis, CJ and Robertson, GP and Zhu, J},
title = {Modification of the telomerase gene with human regulatory sequences resets mouse telomeres to human length.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {1211},
pmid = {39905075},
issn = {2041-1723},
support = {R01AG073423//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R35GM149529//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; ME220261//United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP)/ ; ME220261//United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP)/ ; },
mesh = {Animals ; *Telomerase/genetics/metabolism ; Humans ; *Telomere/metabolism/genetics ; Mice ; *Mice, Knockout ; Male ; Telomere Homeostasis/genetics ; Female ; Telomere Shortening/genetics ; Regulatory Sequences, Nucleic Acid/genetics ; Aging/genetics ; Mice, Inbred C57BL ; },
abstract = {Telomeres shorten with each cell division, serving as biomarkers of aging, with human tissues exhibiting short telomeres and restricted telomerase expression. In contrast, mice have longer telomeres and widespread telomerase activity, limiting their relevance as models for human telomere biology. To address this, we engineer a mouse strain with a humanized mTert gene (hmTert), replacing specific non-coding sequences with human counterparts. The hmTert gene, which is repressed in adult tissues except the gonads and thymus, closely mimics human TERT regulation. This modification rescues telomere dysfunction in mTert-knockout mice. Successive intercrosses of Tert[h/-] mice stabilized telomere length below 10 kb, while Tert[h/h] mice achieve a human-like average length of 10-12 kb, compared to 50 kb in wildtype mice. Despite shortened telomeres, Tert[h/h] mice maintain normal body weight and cell homeostasis. These mice, with humanized telomere regulation, represent a valuable model to study human aging and cancer.},
}

Animals
*Telomerase/genetics/metabolism
Humans
*Telomere/metabolism/genetics
Mice
*Mice, Knockout
Male
Telomere Homeostasis/genetics
Female
Telomere Shortening/genetics
Regulatory Sequences, Nucleic Acid/genetics
Aging/genetics
Mice, Inbred C57BL

@article {pmid39904253,
year = {2025},
author = {Yu, J and Liu, Y and Zhang, H and Ping, F and Li, W and Xu, L and Li, Y},
title = {Serum Growth Differentiation Factor 15 is Negatively Associated with Leukocyte Telomere Length.},
journal = {The journal of nutrition, health & aging},
volume = {29},
number = {4},
pages = {100493},
doi = {10.1016/j.jnha.2025.100493},
pmid = {39904253},
issn = {1760-4788},
abstract = {BACKGROUND: Telomere length(TL)and mitochondrial DNA copy number(mtDNAcn) are classic biomarker of aging. Recently, growth differentiation factor 15(GDF15) has attracted considerable attention as a vital component in the aging process.

METHODS: The present study aimed to study the relationship between GDF15 and telomere length and mtDNAcn.This was a cross-sectional analysis nested in a longitudinal cohort study conducted in Changping District, Beijing, from 2014 to 2021. Serum GDF15,leukocyte lelomere length(LTL) and mtDNAcn were determined in 802 subjects.LTL and mtDNAcn was quantified by real-time PCR assay. Multivariate linear regression and restricted cubic spline diagram were used for statistical analysis.

RESULTS: Subjects with higher GDF15 were older,had larger waist circumference, higher systolic blood pressure and glycated hemoglobin A1c (HbA1c),shorter LTL and tended to had less mtDNAcn. In correlation analysis, GDF15 was positively correlated with age, while LTL and mtDNAcn were negatively correlated with age.After adjusting for confounding factors,GDF15 was negatively associated with LTL (β = -0.120, 95%CI [-0.197, -0.042], p = 0.003) and the association was linear(p for nonlinear = 0.645), while the negative association between GDF15 and mtDNAcn did not reach significance.In the stratified analyses,the negative associations between GDF15 and LTL were more prominent in women, overweight individuals, or subjects with abnormal glucose tolerance (AGT), but similar results were observed in younger and older subjects.

CONCLUSIONS: This study found a linear negative association between GDF 15 and LTL,which was more prominent in women, overweight or AGT subjects.These results supported that GDF15 might be a reliable biomarker of aging.},
}

@article {pmid39903555,
year = {2025},
author = {Stajnko, A and Pineda, D and Klus, JK and Love, TM and Thurston, SW and Mulhern, MS and Strain, JJ and McSorley, EM and Myers, GJ and Watson, GE and Shroff, E and Shamlaye, CF and Yeates, AJ and van Wijngaarden, E and Broberg, K},
title = {Associations of Prenatal Mercury Exposure and PUFA with Telomere Length and mtDNA Copy Number in 7-Year-Old Children in the Seychelles Child Development Nutrition Cohort 2.},
journal = {Environmental health perspectives},
volume = {133},
number = {2},
pages = {27002},
doi = {10.1289/EHP14776},
pmid = {39903555},
issn = {1552-9924},
mesh = {Humans ; Female ; Seychelles ; Child ; Pregnancy ; *Mercury/blood ; *Telomere/drug effects ; *Prenatal Exposure Delayed Effects ; Fatty Acids, Unsaturated ; Male ; DNA, Mitochondrial ; DNA Copy Number Variations ; Hair/chemistry ; Cohort Studies ; Fetal Blood/chemistry ; Environmental Pollutants/blood ; Environmental Exposure/statistics & numerical data ; },
abstract = {BACKGROUND: Telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) variations are linked to age-related diseases and are associated with environmental exposure and nutritional status. Limited data, however, exist on the associations with mercury exposure, particularly early in life.

OBJECTIVE: We examined the association between prenatal mercury (Hg) exposure and TL and mtDNAcn in 1,145 Seychelles children, characterized by a fish-rich diet.

METHODS: Total mercury (THg) was determined in maternal hair at delivery and cord blood. TL and mtDNAcn were determined relative to a single-copy hemoglobin beta gene in the saliva of 7-y-old children. Linear regression models assessed associations between THg and relative TL (rTL) and relative mtDNAcn (rmtDNAcn) while controlling for maternal and cord serum polyunsaturated fatty acid (PUFA) status and sociodemographic factors. Interactions between THg and child sex, PUFA, and telomerase genotypes were evaluated for rTL and rmtDNAcn.

RESULTS: Higher THg concentrations in maternal hair and cord blood were associated with longer rTL [β=0.009; 95% confidence interval (CI): 0.002, 0.016 and β=0.002; 95% CI: 0.001, 0.003, respectively], irrespective of sex, PUFA, or telomerase genotypes. Maternal serum n-6 PUFA and n-6/n-3 ratio were associated with shorter [β=-0.24; 95% CI: -0.33, -0.15 and β=-0.032; 95% CI: -0.048, -0.016, respectively] and n-3 PUFA with longer (β=0.34; 95% CI: 0.032, 0.65) rTL. Cord blood n-6 PUFA was associated with longer (β=0.15; 95% CI: 0.050, 0.26) rTL. Further analyses revealed linoleic acid in maternal blood and arachidonic acid in cord blood as the main drivers of the n-6 PUFA associations. No associations were observed for THg and PUFA with rmtDNAcn.

DISCUSSION: Our results indicate that prenatal THg exposure and PUFA status are associated with rTL later in childhood, although not consistently aligned with our initial hypothesis. Subsequent research is needed to confirm this finding, further evaluate the potential confounding of fish intake, and investigate the underlying molecular mechanisms to verify the use of rTL as a true biomarker of THg exposure. https://doi.org/10.1289/EHP14776.},
}

Humans
Female
Seychelles
Child
Pregnancy
*Mercury/blood
*Telomere/drug effects
*Prenatal Exposure Delayed Effects
Fatty Acids, Unsaturated
Male
DNA, Mitochondrial
DNA Copy Number Variations
Hair/chemistry
Cohort Studies
Fetal Blood/chemistry
Environmental Pollutants/blood
Environmental Exposure/statistics & numerical data

@article {pmid39901177,
year = {2025},
author = {Polli, A and Godderis, L and Martens, DS and Patil, MS and Hendrix, J and Wyns, A and Van Campenhout, J and Richter, E and Fanning, L and Vandekerckhove, O and Claeys, E and Janssens, W and Lorent, N},
title = {Exploring DNA methylation, telomere length, mitochondrial DNA, and immune function in patients with Long-COVID.},
journal = {BMC medicine},
volume = {23},
number = {1},
pages = {60},
pmid = {39901177},
issn = {1741-7015},
mesh = {Humans ; Male ; Female ; *COVID-19/immunology/epidemiology ; Middle Aged ; Prospective Studies ; Longitudinal Studies ; *DNA, Mitochondrial/genetics ; *DNA Methylation ; *SARS-CoV-2/genetics ; Aged ; Adult ; Telomere ; Post-Acute COVID-19 Syndrome ; },
abstract = {BACKGROUND: Long-COVID is defined as the persistency or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. Common persistent symptoms are fatigue, sleep disturbances, post-exertional malaise (PEM), pain, and cognitive problems. Long-COVID is estimated to be present in about 65 million people. We aimed to explore clinical and biological factors that might contribute to Long-COVID.

METHODS: Prospective longitudinal cohort study including patients infected with SARS-CoV-2 between March 2020 and March 2022. Patients were assessed between 4 and 12 months after infection at the COVID follow-up clinic at UZ Leuven. We performed a comprehensive clinical assessment (including questionnaires and the 6-min walking test) and biological measures (global DNA methylation, telomere length, mitochondrial DNA copy number, inflammatory cytokines, and serological markers such as C-reactive protein, D-dimer, troponin T).

RESULTS: Of the 358 participants, 328 were hospitalised, of which 130 had severe symptoms requiring intensive care admission; 30 patients were ambulatory referrals. Based on their clinical presentation, we could identify 6 main clusters. One-hundred and twenty-seven patients (35.4%) belonged to at least one cluster. The bigger cluster included PEM, fatigue, sleep disturbances, and pain (n = 57). Troponin T and telomere shortening were the two main markers predicting Long-COVID and PEM-fatigue symptoms.

CONCLUSIONS: Long-COVID is not just one entity. Different clinical presentations can be identified. Cardiac involvement (as measured by troponin T levels) and telomere shortening might be a relevant risk factor for developing PEM-fatigue symptoms and deserve further exploring.},
}

Humans
Male
Female
*COVID-19/immunology/epidemiology
Middle Aged
Prospective Studies
Longitudinal Studies
*DNA, Mitochondrial/genetics
*DNA Methylation
*SARS-CoV-2/genetics
Aged
Adult
Telomere
Post-Acute COVID-19 Syndrome

@article {pmid39900600,
year = {2025},
author = {Ashraf, R and Polasek-Sedlackova, H and Marini, V and Prochazkova, J and Hasanova, Z and Zacpalova, M and Boudova, M and Krejci, L},
title = {RECQ4-MUS81 interaction contributes to telomere maintenance with implications to Rothmund-Thomson syndrome.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {1302},
pmid = {39900600},
issn = {2041-1723},
support = {21-22593X//Grantová Agentura České Republiky (Grant Agency of the Czech Republic)/ ; },
mesh = {Humans ; *RecQ Helicases/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *Telomere/metabolism/genetics ; *DNA Replication ; *Rothmund-Thomson Syndrome/genetics/metabolism ; *Endonucleases/metabolism/genetics ; Telomere Homeostasis ; Chromosome Segregation ; Mutation ; Chromosomal Instability ; Protein Binding ; },
abstract = {Replication stress, particularly in hard-to-replicate regions such as telomeres and centromeres, leads to the accumulation of replication intermediates that must be processed to ensure proper chromosome segregation. In this study, we identify a critical role for the interaction between RECQ4 and MUS81 in managing such stress. We show that RECQ4 physically interacts with MUS81, targeting it to specific DNA substrates and enhancing its endonuclease activity. Loss of this interaction, results in significant chromosomal segregation defects, including the accumulation of micronuclei, anaphase bridges, and ultrafine bridges (UFBs). Our data further demonstrate that the RECQ4-MUS81 interaction plays an important role in ALT-positive cells, where MUS81 foci primarily colocalise with telomeres, highlighting its role in telomere maintenance. We also observe that a mutation associated with Rothmund-Thomson syndrome, which produces a truncated RECQ4 unable to interact with MUS81, recapitulates these chromosome instability phenotypes. This underscores the importance of RECQ4-MUS81 in safeguarding genome integrity and suggests potential implications for human disease. Our findings demonstrate the RECQ4-MUS81 interaction as a key mechanism in alleviating replication stress at hard-to-replicate regions and highlight its relevance in pathological conditions such as RTS.},
}

Humans
*RecQ Helicases/metabolism/genetics
*DNA-Binding Proteins/metabolism/genetics
*Telomere/metabolism/genetics
*DNA Replication
*Rothmund-Thomson Syndrome/genetics/metabolism
*Endonucleases/metabolism/genetics
Telomere Homeostasis
Chromosome Segregation
Mutation
Chromosomal Instability
Protein Binding

@article {pmid39895528,
year = {2025},
author = {Pradhan, K and Neupane, B and Niehues, P and Kirschner, M and Beier, F and Kuo, CC and Hilbold, EA and Bär, C and Thoma, OM and Waldner, M and Vieri, M and Brümmendorf, TH and Tharmapalan, V and Wagner, W and Kleines, M and Emrani, M and Zink, MD and Napp, A and Marx, N and Gramlich, M},
title = {Telomere Length Is Associated With Adverse Atrial Remodeling in Patients With Atrial Fibrillation.},
journal = {Journal of the American Heart Association},
volume = {},
number = {},
pages = {e037512},
doi = {10.1161/JAHA.124.037512},
pmid = {39895528},
issn = {2047-9980},
abstract = {BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia with a massive burden on global health. The prevalence of AF increases dramatically with age and can be up to 18% in patients older than 80 years. Telomeres, which are short, repeated DNA sequences at the end of chromosomes, are known to act as a biological aging marker. In this study, we investigated the relation of telomere shortening and AF in the context of atrial remodeling. Furthermore, we assessed changes in the gene expression profiles of patients with AF according to telomere length (TL) and left atrial fibrosis.

METHODS: We included 72 patients undergoing catheter ablation for AF. Bipolar voltage maps were obtained to determine left atrial low voltage areas as a surrogate for atrial fibrosis. TL was quantified and correlated to low voltage areas. 3' mRNA sequencing was performed for gene expression profiling. Clonal hematopoiesis of indeterminate potential was assessed by next generation sequencing. Telomerase reverse transcriptase knockout (Tert[-/-]) and telomerase RNA component knockout (Terc[-/-]) mice were used to investigate the mechanistic impact of telomere shortening on atrial remodeling.

RESULTS: Patients with advanced left atrial fibrosis had shorter telomeres compared with patients with healthy left atria. Furthermore, there was a strong correlation between the extent of left atrial low voltage areas, TL, and outcome after catheter ablation of AF. 24 months after ablation, only 26.5% of patients with advanced fibrosis and short TL were in sinus rhythm compared with 62.5% of patients with no/low fibrosis and long TL. Gene expression profiles and clonal hematopoiesis of indeterminate potential frequency differed in patients with AF with short and long telomeres. Finally, atrial tissue of mouse models with shortened telomeres showed marked left atrial fibrosis and over-expression of fibrosis-related genes.

CONCLUSIONS: Telomere shortening is correlated with left atrial remodeling. Shorter telomeres are associated with a series of molecular events which could eventually lead to cardiac fibrosis and perpetuate AF.},
}

@article {pmid39891610,
year = {2025},
author = {Horwath, O and Montiel-Rojas, D and Ponsot, E and Féasson, L and Kadi, F},
title = {Increased muscle satellite cell content and preserved telomere length in response to combined exercise training in patients with FSHD.},
journal = {The Journal of physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/JP287033},
pmid = {39891610},
issn = {1469-7793},
support = {16122-15383//Association Francaise contre les myopathies (AFM)/ ; },
abstract = {Facioscapulohumeral muscular dystrophy (FSHD) is an inherited muscle disease characterized by weakness and muscle wasting. In the absence of available treatments, exercise training has emerged as a potential strategy to attenuate muscle tissue deterioration. However, little is known about the impact of chronic exercise on degenerative events and regenerative capacity in FSHD muscle. Muscle biopsies were obtained from 16 FSHD patients before and after a 24 week training program combining aerobic-, strength- and high-intensity exercise (Control; n = 8, Training; n = 8). Histochemical and immunohistochemical approaches were applied to assess histopathological signs, markers of regeneration, inflammatory infiltrates and satellite cell content. Muscle telomere length was measured as an indicator of the remaining regenerative capacity. The proportion of muscle fibres expressing developmental myosins and centralized myonuclei was not exacerbated after the intervention. Similarly, no alterations were observed in the number of inflammatory infiltrates (CD68[+] cells). Alongside muscle hypertrophy in slow (P = 0.022) and fast fibres (P = 0.022 and P = 0.008), satellite cell content increased specifically in fast fibres (+75 %, P = 0.015), indicating a functional satellite cell pool in FSHD muscle. Importantly, exercise training was not associated with a shortening of muscle telomere length, suggesting that muscle cell turnover was not accelerated despite an expansion of the satellite cell pool. Our findings suggest that combined exercise training elicits beneficial muscular adaptations without impairing important indicators of skeletal muscle regenerative capacity in patients with FSHD. KEY POINTS: A 24 week combined exercise training program is a safe and well-tolerated strategy to attenuate skeletal muscle deterioration in facioscapulohumeral muscular dystrophy (FSHD) patients. Markers of histopathology, muscle fibre regeneration and inflammatory infiltrates were not exacerbated following exercise training in FSHD muscle. Here, we show novel data that exercise training in FSHD patients induced muscle fibre hypertrophy and triggered an expansion of the satellite cell pool specifically in fast fibres. Exercise training in these patients is not associated with a shortening of muscle telomere length thereby indicating a preserved capacity for muscle regeneration.},
}

@article {pmid39889303,
year = {2025},
author = {Fajkus, P and Fajkus, J},
title = {Telomerase RNA evolution: a journey from plant telomeres to broader eukaryotic diversity.},
journal = {The Biochemical journal},
volume = {482},
number = {3},
pages = {},
doi = {10.1042/BCJ20240501},
pmid = {39889303},
issn = {1470-8728},
mesh = {*Telomerase/genetics/metabolism ; *Telomere/metabolism/genetics ; *RNA/genetics/metabolism ; *Evolution, Molecular ; Animals ; Phylogeny ; Plants/genetics ; Viridiplantae/genetics/metabolism ; },
abstract = {Telomeres, essential for maintaining genomic stability, are typically preserved through the action of telomerase, a ribonucleoprotein complex that synthesizes telomeric DNA. One of its two core components, telomerase RNA (TR), serves as the template for this synthesis, and its evolution across different species is both complex and diverse. This review discusses recent advancements in understanding TR evolution, with a focus on plants (Viridiplantae). Utilizing novel bioinformatic tools and accumulating genomic and transcriptomic data, combined with corresponding experimental validation, researchers have begun to unravel the intricate pathways of TR evolution and telomere maintenance mechanisms. Contrary to previous beliefs, a monophyletic origin of TR has been demonstrated first in land plants and subsequently across the broader phylogenetic megagroup Diaphoretickes. Conversely, the discovery of plant-type TRs in insects challenges assumptions about the monophyletic origin of TRs in animals, suggesting evolutionary innovations coinciding with arthropod divergence. The review also highlights key challenges in TR identification and provides examples of how these have been addressed. Overall, this work underscores the importance of expanding beyond model organisms to comprehend the full complexity of telomerase evolution, with potential applications in agriculture and biotechnology.},
}

*Telomerase/genetics/metabolism
*Telomere/metabolism/genetics
*RNA/genetics/metabolism
*Evolution, Molecular
Animals
Phylogeny
Plants/genetics
Viridiplantae/genetics/metabolism

@article {pmid39884801,
year = {2025},
author = {Murillo Ortiz, BO and Ramírez Emiliano, J and Romero Vázquez, MJ and Amador Medina, LF and Martínez Garza, S and Ramos Rodríguez, EM},
title = {Impact of iron chelation with deferasirox on telomere length and oxidative stress in hemodialysis patients: A randomized study.},
journal = {Nefrologia},
volume = {45},
number = {1},
pages = {68-76},
doi = {10.1016/j.nefroe.2025.01.003},
pmid = {39884801},
issn = {2013-2514},
mesh = {Humans ; *Deferasirox/therapeutic use ; *Oxidative Stress/drug effects ; *Renal Dialysis ; *Iron Chelating Agents/therapeutic use ; Male ; Female ; Middle Aged ; *Benzoates/therapeutic use/pharmacokinetics ; *Telomere/drug effects ; *Triazoles/therapeutic use ; *Ferritins/blood ; Aged ; Adult ; Kidney Failure, Chronic/therapy/blood ; },
abstract = {BACKGROUND: Recent studies have demonstrated the effectiveness, safety, and tolerability of deferasirox in patients in peritoneal dialysis, however, its effect has not been studied in patients undergoing hemodialysis.

OBJECTIVE: To investigate the impact of iron chelation on telomere length, oxidative stress, and ferritin levels in patients undergoing hemodialysis.

METHODS: This is an open-label study, with a control group of patients undergoing hemodialysis, who will receive treatment with deferasirox 15mg/kg/day for 6 months for iron chelation. Telomere length was measured using real-time PCR. Serum ferritin levels and oxidation markers were evaluated. To evaluate the pharmacokinetics and safety of deferasirox, plasma concentrations were analyzed by HPLC.

RESULTS: Fifty-four patients were included to receive deferasirox, and a control group of 50 patients. Significant differences were observed in serum ferritin levels (p<0.0001), TBARS (thiobarbituric acid reactive substances) (p<0.01). Telomere length had a significant increase after chelation (p<0.001). The serum deferasirox concentration at zero time at 48h was maintained within a range of 2.67-23.78mmol/L.

CONCLUSIONS: Our results demonstrate that iron chelation in hemodialysis patients significantly reduces ferritin and TBARS, resulting in an increase in telomere length. Deferasirox proves to be beneficial for patients with iron overload undergoing hemodialysis.},
}

Humans
*Deferasirox/therapeutic use
*Oxidative Stress/drug effects
*Renal Dialysis
*Iron Chelating Agents/therapeutic use
Male
Female
Middle Aged
*Benzoates/therapeutic use/pharmacokinetics
*Telomere/drug effects
*Triazoles/therapeutic use
*Ferritins/blood
Aged
Adult
Kidney Failure, Chronic/therapy/blood

@article {pmid39884423,
year = {2025},
author = {Marciau, C and Bestley, S and Costantini, D and Hicks, O and Hindell, M and Kato, A and Raclot, T and Ribout, C and Ropert-Coudert, Y and Angelier, F},
title = {Sibling similarity in telomere length in Adélie penguin chicks.},
journal = {Comparative biochemistry and physiology. Part A, Molecular & integrative physiology},
volume = {},
number = {},
pages = {111818},
doi = {10.1016/j.cbpa.2025.111818},
pmid = {39884423},
issn = {1531-4332},
abstract = {Early life telomere length is thought to influence and predict an individual's fitness. It has been shown to vary significantly in early life compared to adulthood. Investigating the factors influencing telomere length in young individuals is therefore of particular interest, especially as the relative importance of heredity compared to post-natal conditions remains largely uncertain. Adélie penguins are eco-indicators of the Antarctic ecosystem and their population are currently undergoing variable trajectories due to climate change. Here, we conducted a correlative study to investigate how telomere length was influenced by external and internal factors in Adélie penguin chicks. We found that most of the parameters we tested, including sex, body mass, brood size and hatching order as well as parental foraging trip duration, did not significantly influence chick telomere length at 32 days. However, siblings had similar telomere length, suggesting that hereditary factors play a stronger role in determining telomere length at this stage compared to the post-natal environment. In addition, telomere length and oxidative damage did not directly correlate but did interact in a complex way mediated by chick mass. High levels of oxidative damage were associated with longer telomeres in heavy chicks, whereas they were associated with shorter telomeres in light chicks. Although this mass-dependent relationship between telomere length and oxidative damage needs to be confirmed in future studies, it could reflect two different scenarios: (1) short telomeres may mimic the cost of poor nutritional conditions and oxidative damage in light chicks; (2) long telomeres may be maintained despite high oxidative damage in heavy chicks thanks to optimal nutritional conditions.},
}

@article {pmid39884762,
year = {2025},
author = {Shah, PD and Armanios, M},
title = {Pre- and post-lung transplant considerations for patients with ultra-short telomere length.},
journal = {The European respiratory journal},
volume = {},
number = {},
pages = {},
doi = {10.1183/13993003.01545-2024},
pmid = {39884762},
issn = {1399-3003},
}

@article {pmid39883078,
year = {2025},
author = {Tedaldi, AM and Behrouzi, P and Grootswagers, P},
title = {Diet, lifestyle and telomere length: using Copula Graphical Models on NHANES data.},
journal = {Aging},
volume = {17},
number = {},
pages = {},
doi = {10.18632/aging.206194},
pmid = {39883078},
issn = {1945-4589},
abstract = {Telomere length has been related to human health and ageing in multiple studies. However, these studies have analyzed a small set of variables, according to pre-formulated hypotheses. We used data from NHANES 1999-2002 to perform a preregistered cross-sectional analysis. From these four years we selected the participants with available leukocyte telomere length measure and with plausible daily energy intake, leading to a total study population of 7096 participants. Then, we divided the participants in three groups according to age: Young 20-39 (n = 2623), Middle 40-59 (n = 2210), Old 60-84 (n = 2263). On each group we performed Copula Graphical Modelling (CGM) to capture the links between the variables of interest, and we conducted certainty and sensitivity analyses to understand the robustness of the results. Blood levels of C-reactive protein and γ-tocopherol, and intake of caffeine and fibers are inversely related to telomere length across the age strata. Sex, race, smoking, physical activity and indicators of socioeconomic status have almost no direct connection with telomeres; however, they are directly linked to C-reactive protein, which in turn is connected to leukocyte telomere length. C-reactive protein is therefore a possible central mediator of the effect of these factors on telomeres.},
}

@article {pmid39878307,
year = {2025},
author = {Campos-Sánchez, I and Navarrete-Muñoz, EM and Martens, DS and Riaño-Galán, I and Lertxundi, A and Llop, S and Guxens, M and Rodríguez-Dehli, C and Lertxundi, N and Soler-Blasco, R and Vrijheid, M and Nawrot, TS and Wright, J and Yang, TC and McEachan, R and Gützkow, KB and Chatzi, VL and Vafeiadi, M and Kampouri, M and Grazuleviciene, R and Andrusaityte, S and Lepeule, J and Valera-Gran, D},
title = {Telomere Length and Symptoms of Attention Deficit and Hyperactivity Disorder in Children at 6-12 Years.},
journal = {Journal of attention disorders},
volume = {},
number = {},
pages = {10870547251314923},
doi = {10.1177/10870547251314923},
pmid = {39878307},
issn = {1557-1246},
abstract = {OBJECTIVE: To explore the association between telomere length (TL) and attention deficit hyperactivity disorder (ADHD) symptoms in children at 6-12 years.

METHOD: Data from 1,759 children belonging to the HELIX project cohorts and the Asturias, Gipuzkoa and Valencia cohorts of INMA project were included. TL was determined by blood sample using a PCR protocol. ADHD symptoms were described by parents using the Conners' Parent Rating Scale-Revised: Short Form. Multiple negative binomial regression models adjusted for potential confounders were used to estimate associations.

RESULTS: Overall estimates showed no associations between TL and ADHD symptoms. However, we observed that a longer TL was significantly associated with a lower risk of presenting hyperactivity symptoms in children belonging to the HELIX project (IRR = 0.93, 95% CI [0.87, 0.99]; p = .022).

CONCLUSION: While our study did not find a consistent association between TL and ADHD symptoms across all cohorts, the significant association found within the HELIX cohort suggests that longer TL may be linked to a lower risk of hyperactivity symptoms. Further research is needed to explore this association in more detail.},
}

@article {pmid39874713,
year = {2025},
author = {Li, X and Yu, X and Lian, X and Kang, L and Yang, L and Ba, F},
title = {Maternal urinary levels of PAH metabolites, umbilical cord blood telomere length and anthropometric indices in newborns.},
journal = {Ecotoxicology and environmental safety},
volume = {291},
number = {},
pages = {117767},
doi = {10.1016/j.ecoenv.2025.117767},
pmid = {39874713},
issn = {1090-2414},
abstract = {The existing evidence indicating that prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with a range of adverse outcomes, including alterations in anthropometric indices, underscores the need for further investigation into the underlying mechanisms. This study aims to examine the effects of prenatal PAH exposure on anthropometric indices and telomere length (TL), as well as to explore whether changes in TL can serve as a predictor of alterations in anthropometric measures. The study was conducted in Shenyang, China, with 2460 pregnant women participating between 2022 and 2023. Maternal urine samples were analyzed for eleven PAH metabolites, and neonatal outcomes, such as birth weight (BW), birth length (BL), and head circumference (HC), were extracted from medical records as anthropometric indices. We employed multiple linear regression (MLR), generalized quantile g-computation (g-comp), Bayesian Kernel Machine Regression (BKMR), and mediation analysis to comprehensively assess the associations between PAH exposure and umbilical TL and neonatal outcomes. Notably, significant negative associations were found between several PAH metabolites and umbilical telomere length (TL). These metabolites included 2-hydroxy naphthalene (2-OH Nap), 1-hydroxy pyrene (1-OH Pyr), 6-hydroxy chrysene (6-OH Chr), 9-hydroxy benzo(a)pyrene (9-OH Bap), and the sum of hydroxylated PAHs (Σ-OH PAHs). Additionally, negative correlations were identified between specific PAH metabolites and HC, although no significant associations were found for BW. Birth weight showed a significant inverse relationship with metabolites such as 1-hydroxy phenanthrene (1-OH Phe), 9-hydroxy phenanthrene (9-OH Phe), and 1-hydroxy naphthalene(1-OH Nap). Results from g-comp analysis and BKMR indicated significant mixture effects of PAHs on umbilical TL and HC, with more heterogeneous effects on BW and BL. Mediation analysis indicated that alterations in umbilical TL partially mediated the associations between PAH exposure and BW and HC. Notably, metabolites such as 2-OH Nap and the Σ-OH PAHs demonstrated substantial mediation effects. Overall, our findings suggest that changes in umbilical TL partially mediate the associations between prenatal PAH exposure and HC and BW, highlighting the complex pathways through which PAH metabolites may influence neonatal development.},
}

@article {pmid39871386,
year = {2025},
author = {Shou, S and Maolan, A and Zhang, D and Jiang, X and Liu, F and Li, Y and Zhang, X and Geer, E and Pu, Z and Hua, B and Guo, Q and Zhang, X and Pang, B},
title = {Telomeres, telomerase, and cancer: mechanisms, biomarkers, and therapeutics.},
journal = {Experimental hematology & oncology},
volume = {14},
number = {1},
pages = {8},
pmid = {39871386},
issn = {2162-3619},
support = {ZYYCXTD-C-202205//the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine/ ; CI2021B009//the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences/ ; HLCMHPP2023085//the High Level Chinese Medical Hospital Promotion Project/ ; HLCMHPP202308506//the High Level Chinese Medical Hospital Promotion Project/ ; HLCMHPP2023005//the High Level Chinese Medical Hospital Promotion Project/ ; 81774294//the National Natural Science Foundation of China/ ; 82104961//the National Natural Science Foundation of China/ ; ZZ14-YQ-016//the Fundamental Research Funds for the Central public welfare research institutes/ ; ZZ13-YQ-028//the Fundamental Research Funds for the Central public welfare research institutes/ ; CI2021A01816//CACMS Innovation Fund/ ; CI2021A01814//CACMS Innovation Fund/ ; CI2021A01805//CACMS Innovation Fund/ ; },
abstract = {Telomeres and telomerase play crucial roles in the initiation and progression of cancer. As biomarkers, they aid in distinguishing benign from malignant tissues. Despite the promising therapeutic potential of targeting telomeres and telomerase for therapy, translating this concept from the laboratory to the clinic remains challenging. Many candidate drugs remain in the experimental stage, with only a few advancing to clinical trials. This review explores the relationship between telomeres, telomerase, and cancer, synthesizing their roles as biomarkers and reviewing the outcomes of completed trials. We propose that changes in telomere length and telomerase activity can be used to stratify cancer stages. Furthermore, we suggest that differential expression of telomere and telomerase components at the subcellular level holds promise as a biomarker. From a therapeutic standpoint, combining telomerase-targeted therapies with drugs that mitigate the adverse effects of telomerase inhibition may offer a viable strategy.},
}

@article {pmid39871190,
year = {2025},
author = {Wang, C and Martens, DS and Bustamante, M and Alfano, R and Plusquin, M and Maitre, L and Wright, J and McEachan, RRC and Lepeule, J and Slama, R and Vafeiadi, M and Chatzi, L and Grazuleviciene, R and Gutzkow, KB and Keun, H and Borràs, E and Sabidó, E and Carracedo, A and Escarami, G and Anguita-Ruiz, A and Pelegrí-Sisó, D and Gonzalez, JR and Vrijheid, M and Nawrot, TS},
title = {The multi-omics signatures of telomere length in childhood.},
journal = {BMC genomics},
volume = {26},
number = {1},
pages = {75},
pmid = {39871190},
issn = {1471-2164},
support = {IJC2018-035394-I//Spanish Ministerio de Economía, Industria y Competitividad/ ; },
mesh = {Humans ; Child ; Female ; Male ; *Telomere/genetics/metabolism ; *DNA Methylation ; Telomere Homeostasis/genetics ; Body Mass Index ; CpG Islands ; Genomics/methods ; MicroRNAs/genetics ; Multiomics ; },
abstract = {BACKGROUND: Telomere length is an important indicator of biological age and a complex multi-factor trait. To date, the telomere interactome for comprehending the high-dimensional biological aspects linked to telomere regulation during childhood remains unexplored. Here we describe the multi-omics signatures associated with childhood telomere length.

METHODS: This study included 1001 children aged 6 to 11 years from the Human Early-life Exposome (HELIX) project. Telomere length was quantified via qPCR in peripheral blood of the children. Blood DNA methylation, gene expression, miRNA expression, plasma proteins and serum and urinary metabolites were measured through microarrays or (semi-) targeted assays. The association between each individual omics feature and telomere length was assessed in omics-wide association analyses. In addition, a literature-guided, sparse supervised integration method was applied to multiple omics, and latent components were extracted as predictors of child telomere length. The association of these latent components with early-life aging risk factors (child lifestyle, body mass index (BMI), exposure to smoking, etc.), were interrogated.

RESULTS: After multiple-testing correction, only two CpGs (cg23686403 and cg16238918 at PARD6G gene) out of all the omics features were significantly associated with child telomere length. The supervised multi-omics integration approach revealed robust associations between latent components and child BMI, with metabolites and proteins emerging as the primary contributing features. In these latent components, the contributing molecular features were known as involved in metabolism and immune regulation-related pathways.

CONCLUSIONS: Findings of this multi-omics study suggested an intricate interplay between telomere length, metabolism and immune responses, providing valuable insights into the molecular underpinnings of the early-life biological aging.},
}

Humans
Child
Female
Male
*Telomere/genetics/metabolism
*DNA Methylation
Telomere Homeostasis/genetics
Body Mass Index
CpG Islands
Genomics/methods
MicroRNAs/genetics
Multiomics

@article {pmid39866942,
year = {2025},
author = {Pazhakh, V and Fox, LC and Elzen, ND and Emerson, MR and Cohen, SB and Bryan, TM and Norris, K and Baird, DM and Cochrane, T and Mackintosh, J and Scott, A and Blombery, P},
title = {A novel TERT variant associated with a telomere biology disorder and challenges in variant classification.},
journal = {EJHaem},
volume = {6},
number = {1},
pages = {e1066},
pmid = {39866942},
issn = {2688-6146},
abstract = {Telomere biology disorders (TBDs) are inherited conditions associated with multisystem manifestations. We describe clinical and functional characterisation of a novel TERT variant. Whole-genome sequencing was performed along with single telomere length analysis (STELA). Telomerase activity and processivity were assessed. A novel TERT variant (K710R) was detected in a patient with classic TBD features showing reduced telomerase activity and processivity. Despite clinical and functional evidence, the variant was classified as a variant of uncertain significance. We have described a novel TERT variant and highlighted the need for further refinement of variant classification specific for TBDs.},
}

@article {pmid39864119,
year = {2025},
author = {Martino, P and Perez-Alarcón, M and Deconinck, L and De Raedt, R and Vanderhasselt, MA and Kozusznik, MW and Kooy, F and Hidalgo, V and Venero, C and Salvador, A and Baeken, C and Pulopulos, MM},
title = {Stress and telomere length in leukocytes: Investigating the role of GABRA6 gene polymorphism and cortisol.},
journal = {Psychoneuroendocrinology},
volume = {173},
number = {},
pages = {107358},
doi = {10.1016/j.psyneuen.2025.107358},
pmid = {39864119},
issn = {1873-3360},
abstract = {Telomere length (TL) is considered a biomarker of aging, and short TL in leukocytes is related to age and stress-related health problems. Cumulative lifetime stress exposure has also been associated with shorter TL and age-related health problems, but the mechanisms are not well understood. We tested in 108 individuals whether shorter TL in leukocytes is observed in individuals with the GABRA6 TT genotype, which has been associated with dysregulation of hypothalamic-pituitary-adrenal axis activity (the main biological stress system) compared to the CC genotype. We also investigated if individuals carrying the TT genotype show higher stress-induced and diurnal cortisol secretion and if cortisol explains the interindividual variability in TL. The analysis pipeline of this study was pre-registered, and the results showed that GABRA6 TT carriers had shorter TL in CD8+CD28+ cells (Bonferroni corrected). In contrast to previous studies, no differences between groups in cortisol secretion were observed, and TL and cortisol did not show significant associations. This study shows, for the first time, shorter TL in CD8+CD28+ cells in TT carriers for GABRA6 compared to CC carriers, suggesting accelerated cellular aging. Although this difference could be linked to an increased susceptibility to stress in the TT carriers, this could not be attributed to the direct influence of cortisol, suggesting the involvement of other mechanisms.},
}

@article {pmid39864023,
year = {2025},
author = {Benetos, A and Coudray, O and Gégout-Petit, A and Lenôtre, L and Toupance, S and Villemonais, D},
title = {A branching model for intergenerational telomere length dynamics.},
journal = {Journal of mathematical biology},
volume = {90},
number = {2},
pages = {21},
pmid = {39864023},
issn = {1432-1416},
support = {ANR-15-IDEX-04-LUE//Lorraine Université d'Excellence/ ; },
mesh = {Humans ; *Mathematical Concepts ; *Telomere Homeostasis ; *Telomere/genetics ; *Models, Genetic ; *Computer Simulation ; Male ; Female ; Animals ; },
abstract = {We build and study an individual based model of the telomere length's evolution in a population across multiple generations. This model is a continuous time typed branching process, where the type of an individual includes its gamete mean telomere length and its age. We study its Malthusian's behaviour and provide numerical simulations to understand the influence of biologically relevant parameters.},
}

Humans
*Mathematical Concepts
*Telomere Homeostasis
*Telomere/genetics
*Models, Genetic
*Computer Simulation
Male
Female
Animals

@article {pmid39863614,
year = {2025},
author = {Rat, A and Martinez Fernandez, V and Doumic, M and Teixeira, MT and Xu, Z},
title = {Mathematical model linking telomeres to senescence in Saccharomyces cerevisiae reveals cell lineage versus population dynamics.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {1024},
pmid = {39863614},
issn = {2041-1723},
support = {ANR-16-CE12-0026//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-11-LABX-0011-01//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-16-CE12-0026//Agence Nationale de la Recherche (French National Research Agency)/ ; ANR-16-CE12-0026//Agence Nationale de la Recherche (French National Research Agency)/ ; PLBIO20-312 INCa_15192//Institut National Du Cancer (French National Cancer Institute)/ ; PLBIO20-312 INCa_15192//Institut National Du Cancer (French National Cancer Institute)/ ; PLBIO20-312 INCa_15192//Institut National Du Cancer (French National Cancer Institute)/ ; Equipe Labellisée//Fondation pour la Recherche Médicale (Foundation for Medical Research in France)/ ; SKIPPERAD 306321//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; },
mesh = {*Saccharomyces cerevisiae/genetics/metabolism ; *Telomere/metabolism/genetics ; *Cell Lineage/genetics ; Telomere Shortening ; Cellular Senescence/genetics ; Telomerase/metabolism/genetics ; Models, Theoretical ; Genomic Instability ; Models, Biological ; },
abstract = {Telomere shortening ultimately causes replicative senescence. However, identifying the mechanisms driving replicative senescence in cell populations is challenging due to the heterogeneity of telomere lengths and the asynchrony of senescence onset. Here, we present a mathematical model of telomere shortening and replicative senescence in Saccharomyces cerevisiae which is quantitatively calibrated and validated using data of telomerase-deficient single cells. Simulations of yeast populations, where cells with varying proliferation capacities compete against each other, show that the distribution of telomere lengths of the initial population shapes population growth, especially through the distribution of cells' shortest telomere lengths. We also quantified how factors influencing cell viability independently of telomeres can impact senescence rates. Overall, we demonstrate a temporal evolution in the composition of senescent cell populations-from a state directly linked to critically short telomeres to a state where senescence onset becomes stochastic. This population structure may promote genome instability and facilitate senescence escape.},
}

*Saccharomyces cerevisiae/genetics/metabolism
*Telomere/metabolism/genetics
*Cell Lineage/genetics
Telomere Shortening
Cellular Senescence/genetics
Telomerase/metabolism/genetics
Models, Theoretical
Genomic Instability
Models, Biological

@article {pmid39862003,
year = {2025},
author = {Ma, L and Liu, C and Song, R and Qian, Y and Zhang, F},
title = {Telomere Length and Oxidative Damage in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.},
journal = {Journal of integrative neuroscience},
volume = {24},
number = {1},
pages = {24948},
doi = {10.31083/JIN24948},
pmid = {39862003},
issn = {0219-6352},
mesh = {Humans ; *Autism Spectrum Disorder/metabolism ; *Oxidative Stress/physiology ; Adolescent ; Child ; Telomere/metabolism ; },
abstract = {BACKGROUND: Autism spectrum disorder (ASD) has been reported to confer an increased risk of natural premature death. Telomere erosion caused by oxidative stress is a common consequence in age-related diseases. However, whether telomere length (TL) and oxidative indicators are significantly changed in ASD patients compared with controls remains controversial. The aim of this study was to determine the associations of ASD with TL and oxidative indicators by performing a meta-analysis of all published evidence.

METHODS: The PubMed and Embase databases were searched for articles published up to April, 2024. The effect size was expressed as standardized mean difference (SMD) and 95% confidence interval (CI) via Stata 15.0 software.

RESULTS: Thirty-nine studies were included. Pooled results showed that compared with controls, children and adolescents with ASD were associated with significantly shorter TL (SMD = -0.48; 95% CI = -0.66- -0.29; p < 0.001; particularly in males), lower total antioxidant capacity (TAC: SMD = -1.15; 95% CI = -2.01- -0.30; p = 0.008), and higher oxidative DNA (8-hydroxy-2[']-deoxyguanosine, 8-OHdG: SMD = 0.63; 95% CI = 0.03-1.23; p = 0.039), lipid (hexanolyl-lysine, HEL: SMD = 0.37; 95% CI = 0.13-0.62; p = 0.003), and protein (3-nitrotyrosine, 3-NT: SMD = 0.86; 95% CI = 0.21-1.51; p = 0.01; dityrosine, DT: SMD = 0.66; 95% CI = 0.521-0.80; p < 0.01) damage. There were no significant differences between ASD and controls in 8-isoprostane and oxidative stress index after publication bias correction, and in N-formylkynurenine during overall meta-analysis.

CONCLUSIONS: TL, 8-OHdG, TAC, HEL, 3-NT, and DT represent potential biomarkers for prediction of ASD in children and adolescents.},
}

Humans
*Autism Spectrum Disorder/metabolism
*Oxidative Stress/physiology
Adolescent
Child
Telomere/metabolism

@article {pmid39861449,
year = {2025},
author = {De la Fuente, B and Milagro, FI and Cuervo, M and Martínez, JA and Riezu-Boj, JI and Zalba, G and Marti Del Moral, A and García-Calzón, S},
title = {Beneficial Effects of a Moderately High-Protein Diet on Telomere Length in Subjects with Overweight or Obesity.},
journal = {Nutrients},
volume = {17},
number = {2},
pages = {},
doi = {10.3390/nu17020319},
pmid = {39861449},
issn = {2072-6643},
support = {PT024//Gobierno de Navarra/ ; CB12/03/30002//Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition/ ; IJC2019-040796-I//Ministerio de Ciencia, Innovación y Universidades/ ; },
mesh = {Humans ; Male ; Female ; Adult ; Middle Aged ; *Obesity/diet therapy/genetics ; *Diet, High-Protein ; *Overweight/diet therapy ; Young Adult ; Aged ; Adolescent ; Telomere ; Diet, Fat-Restricted/methods ; Telomere Shortening ; Weight Loss ; Diet, Reducing/methods ; Dietary Proteins/administration & dosage ; },
abstract = {BACKGROUND AND AIM: Telomere length (TL) is a key biomarker of cellular aging, with shorter telomeres associated with age-related diseases. Lifestyle interventions mitigating telomere shortening are essential for preventing such conditions. This study aimed to examine the effects of two weight loss dietary strategies, based on a moderately high-protein (MHP) diet and a low-fat (LF) diet on TL in individuals with overweight or obesity.

METHODS AND RESULTS: A total of 164 participants, aged 18-65 years from the OBEKIT trial received the MHP (n = 83) or the LF diet (n = 81) for 4 months and had TL data for analyses. TL was measured at baseline and after 4 months of the intervention using monochrome multiplex quantitative polymerase chain reaction (MMqPCR). Both groups experienced significant improvements in anthropometric and biochemical parameters after the dietary intervention (p < 0.001). The MHP group showed an increase in TL (+0.16 ± 0.13) compared to the LF group (-0.05 ± 0.13) in multiple-adjusted models (p = 0.016). An interaction was observed between the sex and dietary group, where women in the MHP group had increased TL (+0.23 ± 0.16) after 4 months compared to women in the LF group (-0.13 ± 0.15; p = 0.001); no differences between dietary groups were found in men. This increase in TL for women was associated with an increase in protein intake (p = 0.006), measured through dietary questionnaires.

CONCLUSION: This study shows that a MHP diet may have a protective effect on TL during weight loss, particularly in women, potentially contributing to healthier aging. These results highlight the importance of considering macronutrient composition in dietary interventions aimed at preserving TL.},
}

Humans
Male
Female
Adult
Middle Aged
*Obesity/diet therapy/genetics
*Diet, High-Protein
*Overweight/diet therapy
Young Adult
Aged
Adolescent
Telomere
Diet, Fat-Restricted/methods
Telomere Shortening
Weight Loss
Diet, Reducing/methods
Dietary Proteins/administration & dosage

@article {pmid39858038,
year = {2025},
author = {Iskandar, M and Xiao Barbero, M and Jaber, M and Chen, R and Gomez-Guevara, R and Cruz, E and Westerheide, S},
title = {A Review of Telomere Attrition in Cancer and Aging: Current Molecular Insights and Future Therapeutic Approaches.},
journal = {Cancers},
volume = {17},
number = {2},
pages = {},
doi = {10.3390/cancers17020257},
pmid = {39858038},
issn = {2072-6694},
abstract = {BACKGROUND/OBJECTIVES: As cells divide, telomeres shorten through a phenomenon known as telomere attrition, which leads to unavoidable senescence of cells. Unprotected DNA exponentially increases the odds of mutations, which can evolve into premature aging disorders and tumorigenesis. There has been growing academic and clinical interest in exploring this duality and developing optimal therapeutic strategies to combat telomere attrition in aging and cellular immortality in cancer. The purpose of this review is to provide an updated overview of telomere biology and therapeutic tactics to address aging and cancer.

METHODS: We used the Rayyan platform to review the PubMed database and examined the ClinicalTrial.gov registry to gain insight into clinical trials and their results.

RESULTS: Cancer cells activate telomerase or utilize alternative lengthening of telomeres to escape telomere shortening, leading to near immortality. Contrarily, normal cells experience telomeric erosion, contributing to premature aging disorders, such as Werner syndrome and Hutchinson-Gilford Progeria, and (2) aging-related diseases, such as neurodegenerative and cardiovascular diseases.

CONCLUSIONS: The literature presents several promising therapeutic approaches to potentially balance telomere maintenance in aging and shortening in cancer. This review highlights gaps in knowledge and points to the potential of these optimal interventions in preclinical and clinical studies to inform future research in cancer and aging.},
}

@article {pmid39857599,
year = {2024},
author = {Vostatek, R and Ay, C},
title = {Biological Aging and Venous Thromboembolism: A Review of Telomeres and Beyond.},
journal = {Biomedicines},
volume = {13},
number = {1},
pages = {},
doi = {10.3390/biomedicines13010015},
pmid = {39857599},
issn = {2227-9059},
abstract = {Although venous thromboembolism (VTE) is the third most common cardiovascular disease, and the risk of VTE increases sharply with advancing age, approximately 40% of VTE cases are currently classified as unprovoked, highlighting the importance of risk factor research. While chronological aging is associated with the risk of VTE, the association with biological aging remains unclear. Biological aging is highly complex, influenced by several dysregulated cellular and biochemical mechanisms. In the last decade, advancements in omics methodologies provided insights into the molecular complexity of biological aging. Techniques such as high-throughput genomics, epigenomics, transcriptomics, proteomics, and metabolomics analyses identified and quantified numerous epigenetic markers, transcripts, proteins, and metabolites. These methods have also revealed the molecular alterations organisms undergo as they age. Despite the progress, there is still a lack of consensus regarding the methods for assessing and validating these biomarkers, and their application lacks standardization. This review gives an overview of biomarkers of biological aging, including telomere length, and their potential role for VTE. Furthermore, we critically examine the advantages and disadvantages of the proposed methods and discuss possible future directions for investigating biological aging in VTE.},
}

@article {pmid39857597,
year = {2024},
author = {Liu, S and Fu, Z and Liu, H and Wang, Y and Zhou, M and Ding, Z and Feng, Z},
title = {Lipid Profiles, Telomere Length, and the Risk of Malignant Tumors: A Mendelian Randomization and Mediation Analysis.},
journal = {Biomedicines},
volume = {13},
number = {1},
pages = {},
doi = {10.3390/biomedicines13010013},
pmid = {39857597},
issn = {2227-9059},
support = {82103785 and 82273582//This research was funded by the National Natural Science Foundation of China/ ; },
abstract = {Background/Objectives: The relationship between lipid profiles, telomere length (TL), and cancer risk remains unclear. Methods: This study employed two-sample Mendelian randomization (MR) with mediation analysis to investigate their causal relationships, examining lipid profiles as exposure, TL as mediator, and nine cancer types as outcomes. We conducted our analysis using two-stage least squares (2SLS) regression integrated with inverse variance weighted (IVW) methods to address potential endogeneity and strengthen our causal inference. Results: we found that unfavorable lipid profiles were causally linked to increased TL (p < 0.05). TL showed positive causal associations with lung and hematologic cancers (OR > 1, p < 0.05). Direct associations were observed between total and low-density lipoprotein (LDL) cholesterol and gastric cancer (OR < 1, p < 0.05), and between remnant cholesterol and colorectal cancer (OR > 1, p < 0.05). Mediation analysis revealed TL as a significant mediator in the pathway from lipid profiles to cancer development (p < 0.05). No horizontal pleiotropy was detected. Conclusions: Our findings suggest that lipid metabolism disorders may influence cancer development through telomere regulation, particularly in lung and hematologic cancers. This emphasizes the importance of lipid management in cancer prevention and treatment, especially for these cancer types.},
}

@article {pmid39849018,
year = {2025},
author = {Wong, KK and Maser, RS and Bachoo, RM and Menon, J and Carrasco, DR and Gu, Y and Alt, FW and DePinho, RA},
title = {Editorial Expression of Concern: Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing.},
journal = {Nature},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41586-025-08654-3},
pmid = {39849018},
issn = {1476-4687},
}

@article {pmid39846264,
year = {2025},
author = {Sánchez-González, JL and Sánchez-Rodríguez, JL and González-Sarmiento, R and Navarro-López, V and Juárez-Vela, R and Pérez, J and Martín-Vallejo, J},
title = {Effect of Physical Exercise on Telomere Length: Umbrella Review and Meta-Analysis.},
journal = {JMIR aging},
volume = {8},
number = {},
pages = {e64539},
doi = {10.2196/64539},
pmid = {39846264},
issn = {2561-7605},
mesh = {Humans ; *Exercise/physiology ; Telomere/metabolism ; Telomere Homeostasis/physiology ; Persons with Disabilities/rehabilitation ; },
abstract = {BACKGROUND: Telomere length (TL) is a marker of cellular health and aging. Physical exercise has been associated with longer telomeres and, therefore, healthier aging. However, results supporting such effects vary across studies. Our aim was to synthesize existing evidence on the effect of different modalities and durations of physical exercise on TL.

OBJECTIVE: The aim of this study was to explore the needs and expectations of individuals with physical disabilities and their interventionists for the use of a virtual reality physical activity platform in a community organization.

METHODS: We performed an umbrella review and meta-analysis. Data sources included PubMed, Embase, Web of Science, Cochrane Library, and Scopus. We selected systematic reviews and meta-analyses of randomized and nonrandomized controlled clinical trials evaluating the effect of physical exercise on TL.

RESULTS: Our literature search retrieved 12 eligible systematic reviews, 5 of which included meta-analyses. We identified 22 distinct primary studies to estimate the overall effect size of physical exercise on TL. The overall effect size was 0.28 (95% CI 0.118-0.439), with a heterogeneity test value Q of 43.08 (P=.003) and I² coefficient of 51%. The number of weeks of intervention explained part of this heterogeneity (Q_B=8.25; P=.004), with higher effect sizes found in studies with an intervention of less than 30 weeks. Exercise modality explained additional heterogeneity within this subgroup (Q_B=10.28, P=.02). The effect sizes were small for aerobic exercise and endurance training, and moderate for high-intensity interval training.

CONCLUSIONS: Our umbrella review and meta-analysis detected a small-moderate positive effect of physical exercise on TL, which seems to be influenced by the duration and type of physical exercise. High quality studies looking into the impact of standardized, evidence-based physical exercise programs on TL are still warranted.},
}

Humans
*Exercise/physiology
Telomere/metabolism
Telomere Homeostasis/physiology
Persons with Disabilities/rehabilitation

@article {pmid39844515,
year = {2025},
author = {Gao, B and Zhao, J and Li, X and Zhang, J and Oliver, MJ and Zhang, D},
title = {Telomere-to-telomere genome of the desiccation-tolerant desert moss Syntrichia caninervis illuminates Copia-dominant centromeric architecture.},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.14549},
pmid = {39844515},
issn = {1467-7652},
support = {32100256//National Natural Science Foundation of China/ ; },
}