@article {pmid41120532,
year = {2025},
author = {Xiong, Y and Melgar, J and Tobler, M and Hasselquist, D},
title = {Assortative breeding experiment in a songbird suggests telomere length is determined during early life rather than at conception.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {36510},
pmid = {41120532},
issn = {2045-2322},
mesh = {Animals ; Female ; Male ; *Telomere/genetics ; *Telomere Shortening ; *Finches/genetics ; *Fertilization ; *Breeding ; *Telomere Homeostasis ; *Songbirds/genetics ; },
abstract = {Telomere length (TL) early in life often shows high heritability and may predict telomere shortening later in life and life expectancy. Yet, there is limited data about what influences TL and TL change at early developmental stages. It is debated whether early-life TL is determined at conception or shaped by early environmental conditions. Here, we investigate whether TL and telomere shortening are set close to conception. We assortatively paired zebra finches (Taeniopygia guttata) based on their TL when nestlings, forming two parental pair groups with either 'short' or 'long' TL. We then measured TL in the offspring of these pairs at the embryo and nestling stages. In embryos, TL did not differ between offspring from the two parental pair groups. However, in nestlings, particularly in sons, offspring TL matched parental TL. Our results suggest that early-life TL itself is not determined at conception. Instead, telomere shortening rate before and just after hatching appears to determine early postnatal TL. These findings highlight that early development is critical for telomere shortening during early life stages and that it may be a key process underlying the similarity in early-life TL between parents and offspring, potentially affecting telomere dynamics throughout life.},
}

Animals
Female
Male
*Telomere/genetics
*Telomere Shortening
*Finches/genetics
*Fertilization
*Breeding
*Telomere Homeostasis
*Songbirds/genetics

@article {pmid41120504,
year = {2025},
author = {Iannuzzi, A and Albarella, S and Del Piano, F and Pistucci, R and Parma, P and D'Anza, E and Piccolo, G and Ferrante, MC and Ciotola, F and Peretti, V},
title = {Telomere length as a genomic biomarker for assessing microplastic-induced damage in farmed gilthead sea bream.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {36598},
pmid = {41120504},
issn = {2045-2322},
support = {IZS ME 06/19, CUP number C75J19000170001//Ministero della Salute/ ; },
mesh = {Animals ; *Microplastics/toxicity ; *Sea Bream/genetics ; *Water Pollutants, Chemical/toxicity ; Biomarkers ; *Telomere/drug effects/genetics ; Aquaculture ; Environmental Monitoring/methods ; *Telomere Homeostasis/drug effects ; },
abstract = {Microplastics are widespread pollutants in aquatic environments and pose significant risks to aquatic organisms, including species vital to aquaculture. The gilthead sea bream, extensively farmed in the Mediterranean, is frequently exposed to these contaminants, leading to potential long-term health consequences. Telomere length, a reliable marker of genomic integrity and cellular aging, offers a promising approach for assessing the biological effects of environmental stressors like microplastics. This study investigates the impact of microplastic exposure on telomere length in gilthead sea bream, evaluating its potential as a genomic biomarker for detecting microplastic-induced damage. Juvenile sea breams were divided into three groups: a control group and two experimental groups exposed to relatively low (25 mg/kg b.w./day) and high (250 mg/kg b.w./day) doses of polystyrene microplastics for 21 days. Telomere length was measured using qPCR, and statistical analyses were conducted to compare the T/S ratio between the groups. The results showed significantly shorter telomeres in fish exposed to both low and high doses of polystyrene microplastics compared to controls, with a clear dose-dependent effect (p < 0.05). These findings indicate that microplastic exposure compromises genomic stability in gilthead sea bream, supporting the use of telomere length as a rapid and sensitive biomarker for environmental monitoring in aquaculture. The study highlights the potential of telomere length as a valuable tool for evaluating fish health in polluted environments, contributing to the development of sustainable practices in aquaculture.},
}

Animals
*Microplastics/toxicity
*Sea Bream/genetics
*Water Pollutants, Chemical/toxicity
Biomarkers
*Telomere/drug effects/genetics
Aquaculture
Environmental Monitoring/methods
*Telomere Homeostasis/drug effects

@article {pmid41120001,
year = {2025},
author = {Westneat, DF and Kucera, AC and Young, RC and Heidinger, BJ},
title = {Repeated experimental challenges do not shorten adult telomeres in a songbird.},
journal = {Proceedings. Biological sciences},
volume = {292},
number = {2057},
pages = {20251774},
pmid = {41120001},
issn = {1471-2954},
support = {//Division of Integrative Organismal Systems/ ; },
mesh = {Animals ; *Sparrows/physiology/genetics ; *Telomere Shortening ; *Telomere/physiology ; *Stress, Physiological ; Male ; Female ; },
abstract = {Responding to environmental challenges can have both positive and negative effects on fitness, but the mechanisms and/or biomarkers underlying these links are not well understood. Telomeres-repetitive sections of DNA that form protective caps at chromosome ends, which enhance genome integrity and often predict organismal lifespan-may be important in this context. Some evidence suggests that stress exposure shortens telomeres, but most studies are correlational and/or conducted during early life; thus, how stress exposure influences telomeres in adulthood is not well known. Here, we experimentally exposed wild-captured adult house sparrows (Passer domesticus) to a series of standardized protocols of repeated, rotating stressors (including threats, unpredictable food availability and immune challenges) designed to increase stress levels. Although there were some effects of the treatment on glucocorticoid levels and mass dynamics, there were no effects on telomeres during any of the 6-11-month studies. Taken together, these results suggest that telomeres are robust or resilient to a range of stressors in adulthood. The effects of stress exposures on telomeres are likely to be highly context-dependent and to vary depending on the timing, intensity and duration of the stress exposures, as well as an individual's life stage.},
}

Animals
*Sparrows/physiology/genetics
*Telomere Shortening
*Telomere/physiology
*Stress, Physiological
Male
Female

@article {pmid41118293,
year = {2025},
author = {Tavares Silvestre, R and Chantre Justino, M and Massao Murata, M and da Silva Dantas, FJ and da Silva Figueiredo, J and Moreira de Sousa, CA and Delmonico, L and Medeiros, DG and Alves, G and Ornellas, MH},
title = {The impact of gasoline exposure on telomeres of gas station workers in Rio de Janeiro.},
journal = {International journal of environmental health research},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/09603123.2025.2571409},
pmid = {41118293},
issn = {1369-1619},
abstract = {Gasoline contains BTEX solvents (benzene, toluene, ethylbenzene, and xylenes), with benzene recognized as a known human carcinogen. Occupational exposure to benzene presents significant health risks for gas station workers, potentially leading to genomic instability and an increased risk of cancer. This study investigated telomere DNA length in leukocytes of 58 gas station workers compared to 58 control subjects. While no overall difference in relative telomere length was observed between the groups, a significant finding emerged in workers with prolonged BTEX exposure (>100 months): their telomeres were longer (p = 0.04). This suggests that long-term exposure may eventually lead to genomic instability. Complementary analysis of telomerase activity in the leukocytes of a subset of workers (n = 9) revealed levels eight times higher than in the control group (n = 9). Notably, one female worker had a history of breast cancer diagnosed 5 years prior, probably linked to carcinogen exposure; and another female worker exhibited a high index of DNA damage, as measured by comet assay, alongside elevated telomerase activity. The transition to biofuel use in vehicles is strongly recommended as a crucial measure to protect the health of these workers and to mitigate the climate change impacts associated with the combustion of fossil fuels.},
}

@article {pmid41117740,
year = {2025},
author = {},
title = {Correction to: Long telomere inheritance through budding yeast sexual cycles.},
journal = {Genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/genetics/iyaf188},
pmid = {41117740},
issn = {1943-2631},
}

@article {pmid41115928,
year = {2025},
author = {Birwatkar, S and Ghosh, T and Selukar, R and Lopes, R and Khare, NK and Raghuram, GV and Shabrish, S and Mittra, I},
title = {DsDNA breaks inflicted by cell-free chromatin particles selectively target telomeres.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {36470},
pmid = {41115928},
issn = {2045-2322},
mesh = {Humans ; *Telomere/metabolism/genetics/radiation effects ; *Chromatin/metabolism/genetics ; *DNA Breaks, Double-Stranded/radiation effects ; Gamma Rays ; DNA Damage ; DNA Repair ; },
abstract = {Telomere damage can lead to senescence, aging and aging-related disorders, and cancer. Previously, we reported that cell-free chromatin particles (cfChPs) that circulate in human blood can readily enter healthy cells and damage their DNA. Herein, we show that dsDNA breaks inflicted by cfChPs selectively target telomeres, with the resulting DNA damage remaining unrepaired over time, whereas dsDNA breaks inflicted by γ-rays are not specific to telomeres and have a faster repair kinetics. We propose that cfChPs that are released from the billions of dying cells to enter the blood circulation are natural DNA damaging agents with a unique mechanism of action.},
}

Humans
*Telomere/metabolism/genetics/radiation effects
*Chromatin/metabolism/genetics
*DNA Breaks, Double-Stranded/radiation effects
Gamma Rays
DNA Damage
DNA Repair

@article {pmid41115243,
year = {2025},
author = {Lee, NC and Gutierrez-Rodrigues, F and Shalhoub, RN and Machado, T and Lotter, J and Alemu, L and Quinones Raffo, D and Paul, S and Kajigaya, S and Aubert, G and Wu, CO and Young, NS and Patel, BA and Groarke, EM},
title = {Danazol treatment for telomere biology disorders: long-term results of a phase I/II study.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025017860},
pmid = {41115243},
issn = {2473-9537},
}

@article {pmid41115213,
year = {2025},
author = {Mitra, T and Vardhana, SA},
title = {Between ROS and a hard place: telomere damage as a driver of T cell exhaustion.},
journal = {Cancer research},
volume = {},
number = {},
pages = {},
doi = {10.1158/0008-5472.CAN-25-4716},
pmid = {41115213},
issn = {1538-7445},
abstract = {In recent years, accumulation of mitochondrial reactive oxygen species (ROS) has been shown to limit the proliferative capacity and intratumoral persistence of CD8+ T cells, but the molecular mechanisms by which ROS produce functional defects in exhausted CD8+ T cells remain incompletely understood. Using a series of elegant genetic tools, Rivadeneira and colleagues demonstrate that accumulation of mitochondrial reactive oxygen species (ROS) is sufficient to directly compromise telomere integrity. The authors induced singlet oxygen within specific subcellular compartments in T cells, achieving precise temporal and spatial control over ROS production. Genetically driven mitochondrial ROS accumulation reproduced hallmarks of intratumoral T cell dysfunction while also producing marked telomere fragility. Consistent with these findings, tumor-infiltrating CD8+ T cells from patients with melanoma and head and neck cancers exhibited substantial accumulation of DNA damage at telomeres compared with healthy donor or autologous peripheral T cells. Moreover, restricting ROS generation specifically to telomeres was sufficient to reproduce T cell dysfunction, while targeting the antioxidant enzyme GPX1 to telomeres reduced DNA damage and enhanced T cell effector functions, leading to improved tumor control. These findings reveal telomeres as key mediators of redox stress-driven T cell dysfunction and suggest that interventions aimed at protecting chromosome ends may represent a novel strategy to enhance antitumor immunity.},
}

@article {pmid41115150,
year = {2025},
author = {Sung, JY and Kim, JH},
title = {Telomere-metabolism-immunity axis in sarcoma: Immune evasion mechanisms and therapeutic strategies.},
journal = {Clinical and translational medicine},
volume = {15},
number = {10},
pages = {e70504},
pmid = {41115150},
issn = {2001-1326},
support = {2024-ER0511-01/NH/NIH HHS/United States ; RS-2024-00440273//Korean Government (MSIT)/ ; },
mesh = {Humans ; *Telomere/metabolism/immunology ; *Sarcoma/immunology/metabolism/genetics/therapy ; *Immune Evasion/immunology ; Immunotherapy/methods ; Tumor Microenvironment/immunology ; },
abstract = {Sarcomas are a heterogeneous group of mesenchymal malignancies with poor prognosis and limited response to standard therapies, including immune checkpoint inhibitors (ICIs). Tumour-intrinsic factors-such as telomere maintenance mechanisms (TMMs) and metabolic reprogramming-play central roles in driving immune evasion and therapeutic resistance. Telomerase activation and alternative lengthening of telomeres sustain replicative immortality while influencing the tumour immune microenvironment. In parallel, metabolic adaptations, including glutamine dependency and arginine auxotrophy, further suppress antitumour immunity. Together, TMMs and metabolism form an integrated axis that shapes immune modulation and treatment outcomes. Recent advances-ranging from telomerase-based vaccines and TMM-targeted immunotherapies to metabolic modulators combined with ICIs-demonstrate the translational promise of targeting this axis. This review synthesises current knowledge on telomere‒metabolism crosstalk in sarcomas, highlights its impact on immunotherapy response, and outlines future directions for biomarker-driven, combinatorial strategies to overcome resistance and improve patient outcomes. KEY POINTS: Telomere maintenance mechanisms (telomerase reverse transcriptase and alternative lengthening of telomeres) reprogram metabolism and dampen innate immune sensing in sarcomas. Metabolic rewiring (glutamine addiction, glycolysis and fatty acid oxidation) fosters T-cell dysfunction and myeloid-derived suppressor cell accumulation. Targeting the telomere‒metabolism‒immunity axis offers strategies to overcome immunotherapy resistance.},
}

Humans
*Telomere/metabolism/immunology
*Sarcoma/immunology/metabolism/genetics/therapy
*Immune Evasion/immunology
Immunotherapy/methods
Tumor Microenvironment/immunology

@article {pmid41108082,
year = {2025},
author = {Liu, Y and Song, YE and Lynn, A and Wang, W and Miskimen, K and Fuzzell, SL and Hochstetler, SD and Laux, RA and Caywood, LJ and Clouse, JE and Herington, SD and Wang, P and Gulyayev, A and Dorfsman, DA and Moore, NC and Main, LR and Prough, MB and Zaman, AF and Adams, LD and Whitehead, P and Ogrocki, P and Lerner, AJ and Vance, JM and Cuccaro, ML and Scott, WK and Pericak-Vance, MA and Haines, JL},
title = {Telomere Length, Aging, and Cognitive Function in the Midwestern Amish.},
journal = {HGG advances},
volume = {},
number = {},
pages = {100533},
doi = {10.1016/j.xhgg.2025.100533},
pmid = {41108082},
issn = {2666-2477},
abstract = {Telomere length (TL) is a key indicator of biological aging. Understanding the association between TL and cognitive impairment may provide important insights into disease mechanisms for age-related neurodegenerative disorders, such as Alzheimer disease (AD). However, the relationship between TL and cognitive function remains controversial, with studies reporting positive, negative, or no associations between them. This inconsistency may be attributed to genetic and environmental variations or differences in TL measurement methods. We conducted a comprehensive characterization of DNA-sequence determined telomere length and analyzed its association with cognitive function in the Midwestern Amish. The Midwestern Amish are a founder population demonstrating reduced genetic and environmental variation compared to the general European population. This unique population structure allowed us to better control for potential confounding by non-telomere genetic and environmental factors. Our study confirmed the expected telomere shortening with age and provided both SNP-based and pedigree-based TL heritability estimates. No significant correlation was observed between telomere length and cognitive function. However, a genome-wide association study (GWAS) of TL revealed three loci associated with TL, each containing Amish-enriched rare variants.},
}

@article {pmid41107286,
year = {2025},
author = {Zheng, W and Cui, A and Meng, Z and Zhang, N and Jiang, Y and Zheng, J and Zhao, R and Xu, W and Xu, Y},
title = {Gap-free telomere-to-telomere genome assembly of marbled flounder (Pseudopleuronectes yokohamae).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {1652},
pmid = {41107286},
issn = {2052-4463},
mesh = {Animals ; *Flounder/genetics ; *Telomere/genetics ; *Genome ; },
abstract = {Marbled flounder (Pseudopleuronectes yokohamae) is becoming a commercially important flatfish species in Northeast Asia due to its strong environmental adaptability and excellent nutritional value. However, no high-quality marbled flounder reference genome was reported to date, which greatly limits the studies of evolutionary and functional genomics. Here, we reported the first gap-free T2T genome in flatfish (marbled flounder), with length of 582.73 Mb (contig N50: 26.29 Mb) combing short reads, PacBio HiFi long reads, ONT ultra-long reads, and Hi-C data. All of the genome sequences were assembled onto 24 chromosomes, and 48 telomeres were identified on both ends of all chromosomes. 99.29% complete BUSCOs were identified, demonstrating a high level of completeness. The average mapping ratio of short reads, PacBio HiFi reads, and ONT ultra-long reads aligned to the genome was more than 99.89%. 121.02 Mb repeating elements and 22,778 protein-coding genes were identified in the genome assembly. These results provide valuable resources for the evolutionary genomics research and the identification of key candidate genes for economic traits in marbled flounder.},
}

Animals
*Flounder/genetics
*Telomere/genetics
*Genome

@article {pmid41105808,
year = {2025},
author = {Baek, Y and Ban, HJ and Jeong, K and Lee, S and Jin, HJ},
title = {Association of Hypertension With Telomere Length, Considering Non-Genetic and Genetic Factors, in Middle-Aged Koreans.},
journal = {Journal of clinical hypertension (Greenwich, Conn.)},
volume = {27},
number = {10},
pages = {e70163},
pmid = {41105808},
issn = {1751-7176},
support = {KSN1739121//Korea Institute of Oriental Medicine/ ; },
mesh = {Humans ; Middle Aged ; Male ; *Hypertension/genetics/epidemiology ; Female ; Republic of Korea/epidemiology ; Adult ; Risk Factors ; *Telomere/genetics ; Genome-Wide Association Study/methods ; Leukocytes/metabolism ; Asian People/genetics ; Cohort Studies ; *Telomere Homeostasis/genetics ; East Asian People ; },
abstract = {Leukocyte telomere length (LTL) has been associated with hypertension. However, this association remains unclear in middle-aged populations. This study aimed to investigate the association between LTL and hypertension in middle-aged Koreans, considering genetic and non-genetic factors. We used baseline data from middle-aged participants (aged 30-55 years) in the Korean Medicine Daejeon Citizen Cohort. LTL was measured in 1914 participants using quantitative polymerase chain reaction. We calculated the genome-wide association study-based polygenic risk score (PRS) for telomere length. Multivariable regression analysis was conducted to examine the association between LTL and hypertension and to explore this association based on non-genetic and genetic factors. After adjusting most variables (Model 1), individuals in the highest LTL quartile showed an inverse association with hypertension compared to those in the lowest quartile (odds ratio [OR] = 0.60, 95% confidence interval [CI] 0.41-0.86). When further adjusted for antihypertensive medication (Model 2), the association remained but was borderline (OR = 0.66, 95% CI = 0.42-1.04). This inverse association was more clearly observed in stratified subgroups of younger individuals (<45 years), those with optimal low-density lipoprotein cholesterol levels (<130 mg/dL), and those with adequate sleep duration (≥ 6 h). Hypertension showed a weak association with PRS; there was no significant relationship between PRS and age. Our findings suggest that LTL is independently associated with hypertension in middle-aged populations; this association varied according to non-genetic factors. These results demonstrate the potential of using LTL as a measure for hypertension screening and for the development of personalized intervention strategies in healthy populations.},
}

Humans
Middle Aged
Male
*Hypertension/genetics/epidemiology
Female
Republic of Korea/epidemiology
Adult
Risk Factors
*Telomere/genetics
Genome-Wide Association Study/methods
Leukocytes/metabolism
Asian People/genetics
Cohort Studies
*Telomere Homeostasis/genetics
East Asian People

@article {pmid41094168,
year = {2025},
author = {Houmel, M and Pellaton, N and Anchimiuk, A and Gruber, S},
title = {Phage-encoded TelN inhibits bacterial Mre11-Rad50 nuclease to protect hairpin telomeres.},
journal = {The EMBO journal},
volume = {},
number = {},
pages = {},
pmid = {41094168},
issn = {1460-2075},
support = {320030-227915/SNSF_/Swiss National Science Foundation/Switzerland ; },
abstract = {Ends of linear chromosomes require protection from host repair machinery that otherwise will mistake them for damaged DNA. The E. coli bacteriophage N15 harbors a linear genome with covalently closed hairpin ends formed by the phage-encoded telomere resolvase TelN. The double-strand break repair complex Mre11-Rad50 (MR, SbcCD in E. coli) specifically targets DNA termini, yet how hairpin telomeres evade host nuclease degradation in bacteria remains unknown. Here, we demonstrate that TelN is essential and sufficient to protect N15 phage-derived hairpin telomeres from MR processing in E. coli. Using a combination of genetic and biochemical approaches, we show that this protective function requires both TelN sequence-specific DNA binding and species-specific protein-protein interactions. Notably, we found that protection is independent of TelN's resolution activity and does not require the C-terminal domains of TelN. Our findings reveal a potentially broad mechanism of telomere protection, providing insights into a conserved regulation of MR activity at chromosome ends across the tree of life.},
}

@article {pmid41094142,
year = {2025},
author = {Loegler, V and Thiele, P and Teyssonnière, E and Tsouris, A and Brach, G and Cruaud, C and Payen, E and Engelen, S and Dunham, MJ and Hou, J and Friedrich, A and Schacherer, J},
title = {From genotype to phenotype with 1,086 near telomere-to-telomere yeast genomes.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {41094142},
issn = {1476-4687},
abstract = {Unravelling the genetic basis of the remarkable phenotypic diversity observed in natural populations remains a central challenge in biology[1-4]. Despite major advances[5-19], no species has yet been characterized with a truly comprehensive atlas of genetic variation. Here we present an extensive genomic and phenotypic resource for the yeast Saccharomyces cerevisiae based on near telomere-to-telomere assemblies of 1,086 natural isolates. Leveraging these high-contiguity assemblies, we generated a highly complete species-wide structural variant atlas, gene-based pangenome and graph pangenome. By incorporating the full spectrum of genetic variation captured across the species, we conducted genome-wide association studies across 8,391 molecular and organismal traits[19-22]. The inclusion of structural variants and small insertion-deletion mutations improved heritability estimates by an average of 14.3% compared with analyses based only on single-nucleotide polymorphisms. Structural variants were more frequently associated with traits and exhibited greater pleiotropy than other variant types. Notably, the genetic architecture of molecular and organismal traits differed markedly. Together, this work provides a unique dataset that illuminates how diverse forms of genetic variation shape phenotypic diversity and lays the groundwork for integrative, genome-scale studies in other eukaryotic systems.},
}

@article {pmid41092893,
year = {2025},
author = {Wesolowski, AJ and Roychoudhuri, R},
title = {Burning the candle at both ends: ROS-mediated telomere damage drives T cell dysfunction.},
journal = {Immunity},
volume = {58},
number = {10},
pages = {2362-2363},
doi = {10.1016/j.immuni.2025.09.016},
pmid = {41092893},
issn = {1097-4180},
mesh = {*Reactive Oxygen Species/metabolism ; Humans ; *Telomere/metabolism/genetics ; *T-Lymphocytes/immunology/metabolism ; Animals ; Lymphocyte Activation/immunology ; Mitochondria/metabolism ; DNA Damage ; },
abstract = {T cells need reactive oxygen species (ROS) for activation and memory formation, yet excessive ROS can drive dysfunction. Rivadeneira et al. show that chronic T cell activation in tumors exposes telomeres to damaging mitochondrial ROS, contributing to T cell dysfunction.},
}

*Reactive Oxygen Species/metabolism
Humans
*Telomere/metabolism/genetics
*T-Lymphocytes/immunology/metabolism
Animals
Lymphocyte Activation/immunology
Mitochondria/metabolism
DNA Damage

@article {pmid41091956,
year = {2025},
author = {Wheeler, AG and Dollerschell, K and Gibbons, MA and Yang, ML},
title = {Quadruple the Considerations: Four Genetic Conditions Unveiled in the Setting of Developmental Delays Including a Complex DMD Rearrangement, Telomere Biology Disorder, and Neurodevelopmental Disorders.},
journal = {Journal of child neurology},
volume = {},
number = {},
pages = {8830738251383989},
doi = {10.1177/08830738251383989},
pmid = {41091956},
issn = {1708-8283},
abstract = {We present a patient with dystrophinopathy and additional complex genetic variants to highlight potential challenges in directing the care and discussion of treatment options. A 12-month-old male child presented to neurology with global delays, including gross motor and speech delay, macrocephaly with frontal bossing, short stature, and hypertelorism. He underwent extensive genetic workup, which identified 4 genetic diagnoses including an intragenic DMD inversion flanked by single exon deletions, a telomere biology disorder, and 2 neurodevelopmental conditions. Our case highlights the need for heightened awareness of atypical dystrophinopathy phenotypes and utility of emerging genetic testing technologies. In an era of novel therapeutics, including genetically-based treatments, the constellation of genetic variants poses potentially interesting and unique challenges for treatment.},
}

@article {pmid41089569,
year = {2025},
author = {Zhu, D and Patel, NB and Pishko, AM and Weinberg, EM and Takako, TI and Kallish, S and Johnson, FB and Babushok, DV and Courtwright, AM},
title = {Evaluation of a screening protocol for telomere biology disorders in individuals with interstitial lung disease undergoing lung transplant evaluation.},
journal = {ERJ open research},
volume = {11},
number = {5},
pages = {},
pmid = {41089569},
issn = {2312-0541},
abstract = {BACKGROUND: Because of the potential for extrapulmonary disease, it is important for lung transplant programmes to identify telomere biology disorder (TBD)-related interstitial lung disease (ILD). The aim of this study was to evaluate a TBD phenotype screen among ILD patients undergoing lung transplant evaluation, including the sensitivity and specificity of individual phenotype screening questions and the characteristics of patients with TBD identified outside of the screening protocol.

METHODS: This was a retrospective cohort study of adults with ILD who underwent lung transplant evaluation from 1 January 2018 to 28 February 2023. The TBD phenotype screen included early greying, family history of ILD and unexplained liver disease, cytopenias or macrocytosis. TBD screen-positive patients underwent telomere length (TL) testing.

RESULTS: Among 383 patients evaluated, 92 (24.0%) had a positive phenotype screen. 58 (63.0%) had early greying, 39 (42.4%) had a first-degree relative with ILD and 29 (31.5%) had unexplained macrocytosis or cytopenias. Using granulocyte and lymphocyte TL <10th percentile, 51 (55.4%) patients met criteria for a TBD. Early greying had the highest sensitivity for TBD (72.5%) with specificity increasing with the number of positive screening questions. Among the 23 patients who underwent TL testing outside of the screening protocol, most commonly because of an early age of onset of ILD, eight (34.8%) had TL between the 1st and 10th percentile.

CONCLUSIONS: Lymphocyte and granulocyte TL <10th is common among TBD phenotype screen-positive ILD patients undergoing transplant evaluation. Inclusion of additional screening questions related to age of onset of ILD could improve the sensitivity of the protocol for short TL.},
}

@article {pmid41088905,
year = {2025},
author = {Tang, M and Yang, M and Wen, J and Liu, X and Xu, L and Ma, Q and Zhong, X and Guo, X},
title = {Targeting Telomere Shelterin Protein TPP1 with Elbasvir: Induction of Autophagy and Suppression of Esophageal Cancer Tumorigenesis.},
journal = {Anti-cancer agents in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715206393619250911115554},
pmid = {41088905},
issn = {1875-5992},
abstract = {INTRODUCTION: Esophageal cancer often develops insidiously, with most cases diagnosed at an advanced stage. Currently, the pathogenesis of esophageal cancer remains unclear, treatment outcomes are poor, and the five-year survival rate is low. To tackle the significant clinical challenges of difficult diagnosis and unfavorable prognosis, it is crucial to actively investigate the disease's pathogenesis. This study explored the involvement of telomere shelterin protein TPP1 in the pathogenesis of esophageal cancer and identified potential therapeutic agents for its treatment.

METHODS: The expression level of TPP1 protein in 54 pairs of esophageal cancer tissues and paired adjacent tissues was detected via immunohistochemistry. The impact of TPP1 silencing and Elbasvir administration on the growth of KYSE150 and TE1 esophageal cancer cell lines was assessed utilizing Cell Counting Kit-8 and colony formation assays. Cell migration was assessed through Transwell and scratch assays. Fluorescence microscopy was employed to observe autophagosome formation, while flow cytometry measured the fluorescence intensity of autophagy markers LC3 and P62 in TPP1-silenced KYSE150 and TE1 cells. Western blotting was utilized to examine the alterations in TPP1, the AKT-mTOR signaling pathway, autophagy-related proteins, and other associated proteins.

RESULTS: TPP1 levels were notably elevated in esophageal squamous cell carcinoma tissues relative to adjacent normal tissues. Suppression of TPP1 substantially reduced the growth and movement of esophageal cancer cells in vitro, while triggering autophagy via the AKT-mTOR signaling pathway, highlighting TPP1's cancerpromoting function in esophageal cancer.

DISCUSSION: Elbasvir effectively suppressed the growth and spread of KYSE150 and TE1 cell lines in vitro, downregulating TPP1 protein expression in relation to time and dosage. Additional investigations revealed that Elbasvir also inhibited the AKT-mTOR signaling axis and induced autophagy by targeting TPP1. Notably, rescue experiments demonstrated that 3-MA could reverse the inhibitory effects on proliferation, migration, and autophagy induced by TPP1 silencing or Elbasvir treatment in KYSE150 and TE1 cells.

CONCLUSION: TPP1 emerges as a compelling diagnostic indicator and a potential treatment focus in esophageal cancer, with Elbasvir offering promise as a novel therapeutic agent.},
}

@article {pmid41088698,
year = {2025},
author = {Liu, W and Lv, Y and Chen, J and Li, X and Huang, Q and Wen, Z and Linghu, X and Wa, Q},
title = {The association between C-reactive protein-to-lymphocyte ratio and telomere length: A cross-sectional population-based study.},
journal = {Medicine},
volume = {104},
number = {41},
pages = {e45106},
pmid = {41088698},
issn = {1536-5964},
support = {No. [2021] 5613//the Program for Science and Technology Project of Guizhou [Province Qiankehe Platform Talents/ ; No. ZK [2021] 007//the Key Program for Science and Technology Project of Guizhou Province/ ; 82160577//the National Natural Science Foundation of China/ ; },
mesh = {Humans ; Cross-Sectional Studies ; Male ; Female ; *C-Reactive Protein/analysis ; Middle Aged ; Adult ; *Lymphocytes ; Nutrition Surveys ; *Telomere ; Aged ; Inflammation/blood ; United States ; },
abstract = {The association of inflammation and telomere length (TL) have drawn much attention. However, the association between the C-reactive protein-to-lymphocyte ratio (CLR) and TL has never been reported before. The authors aimed to investigate the association between CLR and TL in US population. Data for this cross-sectional analysis were extracted from the 1999 to 2001 National Health and Nutrition Examination Survey, including only participants with complete data on CLR and TL. We employed multivariable regression and logistic regression analyses to investigate the independent association between CLR and TL. Additionally, subgroup analyses and interaction tests were conducted to further explore these relationships. A total of 5517 participants were enrolled in the study, with those in the highest quartile of CLR exhibiting a tendency toward shorter TL. The mean TL was 5747.491 ± 677.02 base pairs. Individuals in quartiles with shorter TL showed a trend toward higher CLR values (quartile 1: 5866.17 ± 831.57; quartile 2: 5756.49 ± 632.42; quartile 3: 5704.13 ± 585.09; quartile 4: 5663.31 ± 614.61; P < .001). Those in the highest CLR quartile displayed a mean TL that was 202.86 base pairs shorter (β = -202.86, 95% CI: -253.09 to -152.63). Subgroup analyses and interaction tests revealed that the negative association between CLR and TL was consistent across populations with varying demographics, including gender, race, smoking, and alcohol consumption, suggesting its applicability to diverse population settings. Higher CLR was significantly associated with shorter TL, suggesting a link between systemic inflammation and telomere attrition.},
}

Humans
Cross-Sectional Studies
Male
Female
*C-Reactive Protein/analysis
Middle Aged
Adult
*Lymphocytes
Nutrition Surveys
*Telomere
Aged
Inflammation/blood
United States

@article {pmid41083479,
year = {2025},
author = {Huang, L and Wei, Z and Xu, X},
title = {Telomere-to-telomere gapless genome assembly of Acorus tatarinowii.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {1640},
pmid = {41083479},
issn = {2052-4463},
mesh = {*Telomere/genetics ; *Genome, Plant ; *Acorus/genetics ; Molecular Sequence Annotation ; },
abstract = {Acorus tatarinowii, a medicinal herb belonging to the Acoraceae family, is widely used in aromatherapy and cognitive enhancement due to its rich repertoire of over 160 natural products. Phylogenetically, it holds a key position as the sister lineage to all other monocots, underscoring the need for a high-quality genome assembly to facilitate in-depth evolutionary and functional studies. In this study, we present a telomere-to-telomere (T2T) genome assembly of A. tatarinowii, spanning 359.36 Mb with a scaffold N50 of 32.54 Mb. The assembly demonstrates reference-grade quality, supported by a consensus quality value (QV) of 45.41 and a long terminal repeat assembly index (LAI) of 10.04. BUSCO analysis of the genome revealed 97.6% complete alignments, confirming the assembly's high continuity and completeness. Genome annotation identified 24,879 protein-coding genes, with repetitive sequences comprising 57.51% of the genome. BUSCO assessment of gene models further validated 97.2% completeness. This high-quality T2T genome assembly not only elucidates the genomic features of this early-diverging monocot species but also provides a robust foundation for future functional genomics research.},
}

*Telomere/genetics
*Genome, Plant
*Acorus/genetics
Molecular Sequence Annotation

@article {pmid41078913,
year = {2025},
author = {Banach, M and Fronczek, M and Goc, A and Lejawa, M and Boniewska-Bernacka, E and Osadnik, T and Pańczyszyn, A and Strzelczyk, JK and Pawlas, N and Gierlotka, M and Goławski, M and Krystek, K and Gach, A and Osadnik, K and Jóźwiak, J},
title = {Telomere length across the spectrum of metabolic health: an analysis from the LIPIDOGEN2015 study.},
journal = {Archives of medical science : AMS},
volume = {21},
number = {4},
pages = {1213-1221},
pmid = {41078913},
issn = {1734-1922},
abstract = {INTRODUCTION: Telomere length is a cellular aging marker and correlates with various cardiovascular disease (CVD) risk factors. The current study assessed the association between obesity, metabolic syndrome (MetS), and telomere length.

MATERIAL AND METHODS: The LIPIDOGRAM&LIPIDOGEN2015 study was conducted in primary care in 2015-2016. Patients recruited to the LIPIDOGEN2015 cohort (n = 1788) were a random subset of patients of the LIPIDOGRAM2015 (n = 13,724) study. For the aims of this analysis, the recruited patients were divided into four groups based on the presence of MetS: healthy slim (HS), metabolically healthy obese (MHO), non-obese with MetS (NOMS), and metabolically unhealthy obese (MUO). Relative telomere length (RTL) was measured using quantitative polymerase chain reaction (qPCR).

RESULTS: 1516 patients (85% of the total group; 59.7% female, mean age 50.3 years) were included in the final analyses. Increases in body mass index (BMI), waist circumference, prevalence of diabetes mellitus, hypertension, dyslipidemia, and history of myocardial infarction moving from HS to MUO were observed. The MUO group exhibited the highest triglyceride and lowest high-density lipoprotein (HDL-C) levels. In the univariate regression analyses, NOMS (p = 0.038) and MUO (p = 0.003) were associated with significantly decreased RTL. After adjusting for age, gender, education, smoking, place of residence, and myocardial infarction, the association was no longer statistically significant.

CONCLUSIONS: Despite the lack of statistical significance in the multivariate analysis, the univariate results suggest that both MUO and NOMS phenotypes contribute to the shortening of telomere length. These results may also indicate that MetS, irrespectively of obesity occurrence, is responsible for the shortened lifespan.},
}

@article {pmid41072589,
year = {2025},
author = {Wakai, TN and Fiamitia, C and Oba, EB and Chinedu, SN and Afolabi, IS},
title = {Malaria infection and telomere length: A review.},
journal = {Microbial pathogenesis},
volume = {209},
number = {},
pages = {108072},
doi = {10.1016/j.micpath.2025.108072},
pmid = {41072589},
issn = {1096-1208},
abstract = {Telomere shortening is a key hallmark of cellular aging, and its association with various infectious diseases is well-documented. However, the role of telomere dynamics in malaria pathogenesis remains underexplored. In addition to its influence, malaria infection not only modulates signals within immune cells but also drives telomere shortening in these cells via diverse mechanisms, potentially leaving long-term imprints on human health. Acute malaria infections initiate rapid telomere degradation, promote accelerated cellular senescence, and suppress telomerase expression with possible partial recovery as the parasite clears during treatment. Conversely, prolonged exposure to Plasmodium infection, prevalent among individuals residing in highly endemic regions like Africa, is often aggravated by coexisting infections, potentially exacerbating malaria pathogenesis, accelerating telomere length shortening, and increasing susceptibility to age-related ailments. Herein, we review recent findings into the effects of malaria on telomere attrition, shedding light on possible mechanisms and key factors contributing to this process. Additionally, we present an overview of how oxidative stress and inflammatory mediators contribute to telomere length shortening in malaria. Furthermore, we discuss the potential of telomere length as a biomarker for malaria severity and treatment outcomes.},
}

@article {pmid41069997,
year = {2025},
author = {Page, J and Stephens, C and Richard, MA and Lyons, E and Baumler, E and Verklan, MT and Lorenzo, E},
title = {Examining the relationship between cardiometabolic risk factors and telomere length in women: a systematic review.},
journal = {Innovation in aging},
volume = {9},
number = {9},
pages = {igaf091},
pmid = {41069997},
issn = {2399-5300},
abstract = {BACKGROUND AND OBJECTIVES: Cardiometabolic syndrome (CMS) poses a significant public health challenge due to its rising prevalence in aging and significant healthcare costs. Recent studies have suggested telomere length (TL), a marker of cellular aging, may be impacted by CMS among women, but comprehensive evidence remains limited. This study aimed to examine the association between CMS risk factors (increased waist circumference [WC], elevated blood pressure, impaired fasting blood glucose, elevated triglycerides, decreased high-density lipoproteins) and TL in women, with consideration of age and race or ethnicity.

RESEARCH DESIGN AND METHODS: A systematic review was conducted following PRISMA guidelines, with searches across five databases. Thirteen relevant studies published between 2007 and 2022 were included. A narrative synthesis was performed to evaluate associations between CMS risk factors and TL.

RESULTS: Findings revealed individual CMS risk factors did not demonstrate relationships with TL; however, a link was identified between collective CMS risk factors and decreased TL. The influence of CMS on TL varied by mean sample age, where increased WC was associated with decreased TL for middle adulthood women. Findings based on race or ethnicity were inconclusive due to limited analyses, but examination by continent revealed a relationship between increased WC and decreased TL in Asia and North America.

DISCUSSION AND IMPLICATIONS: There was high heterogeneity among diagnostic criteria for CMS risk factors across studies, potentially limiting findings. This review highlights the need for further research to clarify the complex associations between CMS and TL in women throughout the lifespan. Future large cohort studies using standardized CMS diagnostic criteria should examine variations by age and race or ethnicity to enhance understanding of these relationships.},
}

@article {pmid41061379,
year = {2025},
author = {Cha, L and Rinne, GR and Carroll, JE and Shalowitz, MU and Ramey, SL and Dunkel Schetter, C and Sumner, JA},
title = {A lifespan approach to biological aging: Early adversity, past-year trauma, and telomere length in women.},
journal = {Psychoneuroendocrinology},
volume = {182},
number = {},
pages = {107645},
doi = {10.1016/j.psyneuen.2025.107645},
pmid = {41061379},
issn = {1873-3360},
abstract = {Adverse experiences over the lifespan can increase risk for poor health outcomes, likely operating in part through accelerated biological aging. From a life course perspective, the extent to which adverse experiences in adulthood predict biological aging will vary as a function of early life adversity, yet few studies have tested this. In this cross-sectional, pre-registered study, we examined associations of early life adversity and past-year potentially traumatic events and their interaction with telomere length in a sample of racially and ethnically diverse and predominantly low-income women (n = 127). We also tested hair cortisol as a potential pathway linking early life adversity and potentially traumatic events with telomere length. Women reported on experiences of early life adversity and the number and negative impact of past-year potentially traumatic events during interviews. Buccal cells and hair samples were collected to assess telomere length and cortisol, respectively. More negative impact of past-year potentially traumatic events was associated with shorter telomere length. However, the strength of this association was conditional on early life adversity and strongest at lower levels of early life adversity. Both greater early life adversity and more negative impact of potentially traumatic events were associated with higher hair cortisol, but hair cortisol was not associated with telomere length. Results suggest that early life adversity modifies the association between subsequent trauma and telomere length and advances understanding of how lifespan adversity shapes biological aging. These findings may inform future research to examine dynamic biological processes linking lifespan adverse experiences to health using longitudinal designs.},
}

@article {pmid41060547,
year = {2025},
author = {Wang, L and Yang, JW and Wang, KY and Chen, SY and Yang, L},
title = {Exploring the shared genetic architecture between leukocyte telomere length and renal cell carcinoma: a cross-trait analysis.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {1826},
pmid = {41060547},
issn = {2730-6011},
support = {24YFFA049//Gansu Province Science and Technology Grant/ ; 25JRRA584//Gansu Provincial Department of Science and Technology, Natural Science Foundation/ ; },
abstract = {BACKGROUND: While epidemiological studies suggest an association between leukocyte telomere length (LTL) and renal cell carcinoma (RCC), the genetic basis underlying this relationship remains to be elucidated.

METHODS: We analyzed genome-wide association studies (GWAS) summary statistics from LTL (n = 472,174) and RCC(3,926 cases; 378,749 controls) cohorts. Comprehensive cross-trait analyses examined genetic correlations, causality, tissue enrichment, and pleiotropic loci.

RESULTS: We identified significant genetic correlation between LTL and RCC (correlation = 0.0379, p = 0.0012) at both genome-wide and local levels. Meta-analysis revealed 25 novel pleiotropic loci, including a co-localized variant (rs1874330). Novel tissue-specific enrichment was observed in uterine and testicular tissues, with shared functional genes affecting both traits. Mendelian randomization provided evidence for a causal effect of LTL on RCC risk.

CONCLUSION: This study establishes genetic links between LTL and RCC through shared architecture, tissue-specific patterns, and causal pathways, suggesting potential therapeutic targets and risk markers for future validation.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-025-03565-1.},
}

@article {pmid41053437,
year = {2025},
author = {Au Young, SWS and Teo, CH and Parhar, IS and Soga, T},
title = {Role of telomere length and telomerase activity in accelerated cellular aging and major depressive disorder: a systematic review.},
journal = {Molecular psychiatry},
volume = {},
number = {},
pages = {},
pmid = {41053437},
issn = {1476-5578},
abstract = {Recent research has increasingly focused on understanding the relationship between cellular aging and mental health, particularly Major Depressive Disorder (MDD). Telomeres, protective structures at the end of chromosomes, and telomerase, an enzyme responsible for their maintenance, have emerged as potential markers of cellular aging and targets for therapeutic interventions in MDD. This review synthesizes findings from 30 studies conducted over the past 15 years, examining alterations in telomere length (TL) and telomerase activity (TA) in individuals with MDD compared to healthy controls. Most studies reported shorter TL in MDD patients, particularly in cases of chronic or severe depression, determined by the duration of illness or illness episode and by measurements of depression severity (e.g. HAM-D, BDI, etc.), suggesting an association between MDD and accelerated cellular aging. Elevated TA was also observed in MDD, with potential implications for treatment response. However, conflicting findings and methodological variations highlight the complexity of the relationship between TL, TA, and MDD, warranting further research. Additionally, studies investigating other biomarkers of cellular aging, such as mitochondrial DNA, provide further insights into the pathophysiology of MDD. Studies on brain cells reveal regional variations in telomere dynamics, suggesting a nuanced relationship between depression and cellular aging across different brain regions. While evidence suggests a potential reversibility of TL alterations in MDD, further research is needed to elucidate underlying mechanisms and develop targeted interventions. Overall, this review underscores the importance of understanding cellular aging processes in MDD and their potential implications for diagnosis, treatment, and the development of novel therapeutic strategies.},
}

@article {pmid41041314,
year = {2025},
author = {Liu, X and Yang, W and Chen, X and Liu, Y and Zhao, Y and Li, Y and Chen, N and Cui, J},
title = {Association between human herpesvirus 6 status and sarcopenia risk: a UK biobank cohort study with sex-specific patterns and telomere length modification.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1623291},
pmid = {41041314},
issn = {1664-3224},
mesh = {Humans ; *Sarcopenia/epidemiology/virology/etiology/genetics ; Male ; Female ; Aged ; United Kingdom/epidemiology ; *Herpesvirus 6, Human/genetics ; Biological Specimen Banks ; Middle Aged ; Risk Factors ; Sex Factors ; Cohort Studies ; *Roseolovirus Infections/virology/complications/epidemiology ; *Telomere ; *Telomere Homeostasis ; Aged, 80 and over ; UK Biobank ; },
abstract = {BACKGROUND: Sarcopenia represents a significant global health concern affecting older adults, yet its relationship with infectious agents remains poorly understood. This study investigated the association between human herpesvirus 6 (HHV-6) status and sarcopenia risk, examining potential sex-specific differences and biological modifiers.

METHODS: We analyzed data from 339,085 UK Biobank participants for baseline assessment and 27,030 participants for follow-up analysis. HHV-6 status was determined using TaqMan qPCR assay targeting conserved viral regions (DR1 and U7). Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. Multivariable logistic and Cox proportional hazards regression models were employed to assess associations, adjusting for comprehensive demographic, behavioral, and clinical covariates.

RESULTS: Individuals with DR-only positive HHV-6 status exhibited significantly elevated odds of sarcopenia at baseline (OR = 3.77, 95% CI: 1.44-8.08) and approximately fivefold increased risk during follow-up (HR = 4.76, 95% CI: 1.19-19.10). Sex-stratified analyses revealed pronounced male vulnerability to DR-only positivity (OR = 5.23, 95% CI: 1.74-12.60), while females showed associations only with typical positive status (OR = 1.63, 95% CI: 1.00-2.49). Telomere length significantly modified these relationships, with stronger associations among males with longer telomeres (OR = 6.57, 95% CI: 1.43-30.16) and females with shorter telomeres (OR = 1.94, 95% CI: 1.08-3.49). Results remained consistent across sensitivity analyses using alternative sarcopenia definitions.

CONCLUSIONS: This study identifies novel associations between HHV-6 status, particularly DR-only positivity, and increased sarcopenia risk in a sex-specific manner. These associations are further modified by telomere length, indicating potential interactions between viral integration, cellular senescence, and muscle health. Our findings contribute to emerging research on infectious correlates of age-related muscle deterioration and may inform future investigations into preventive strategies.},
}

Humans
*Sarcopenia/epidemiology/virology/etiology/genetics
Male
Female
Aged
United Kingdom/epidemiology
*Herpesvirus 6, Human/genetics
Biological Specimen Banks
Middle Aged
Risk Factors
Sex Factors
Cohort Studies
*Roseolovirus Infections/virology/complications/epidemiology
*Telomere
*Telomere Homeostasis
Aged, 80 and over
UK Biobank

@article {pmid41038681,
year = {2025},
author = {Chen, J and Liu, Z and Nan, Y and Liu, H and Ren, Z and Liu, J and Liu, D and Qi, R},
title = {Causal association of dietary intake habits and telomere lengths: A Mendelian randomization study.},
journal = {Asia Pacific journal of clinical nutrition},
volume = {34},
number = {5},
pages = {783-795},
pmid = {41038681},
issn = {1440-6047},
support = {No. LJKQZ20222359//Scientific Research Fund of Liaoning Provincial Education Department/ ; No. 2023-BS-089//Natural Science Research Start-up Foundation for Doctors of Liaoning Province/ ; No. LJ212410140093//Program for Liaoning Provincial Department of Education/ ; No. 2024-BSLH-102//Liaoning Province science and technology plan joint project/ ; },
mesh = {Humans ; *Mendelian Randomization Analysis ; *Diet ; *Telomere ; *Feeding Behavior ; *Telomere Shortening ; *Telomere Homeostasis ; },
abstract = {BACKGROUND AND OBJECTIVES: Healthy diets are crucial in disease prevention and balanced diets can slow te-lomere shortening. Currently, it is still unclear which dietary factors are causally related to telomere length.

METHODS AND STUDY DESIGN: The inverse variance weighted, Mendelian Randomization-Egger, weighted median, simple mode, and weighted mode methods were used. Additionally, heterogeneity, pleiotropy, MR-PRESSO and leave-one-out tests were conducted to ensure accuracy. Outcomes included granulocyte, lym-phocyte, naive T-cell, memory T-cell, B-cell, and natural killer-cell telomere lengths. Exposures included alcohol intake frequency, alcoholic drinks per week, average weekly beer plus cider intake, average weekly red wine intake, intake of beef, bread, cereal, coffee, cooked vegetable, dried fruit, fresh fruit, lamb/mutton, non-oily fish, oily fish, pork, processed meat, salad/raw vegetable, tea and water.

RESULTS: The positive causal relationships were found between dried fruit intake and granulocyte telomere length (OR: 4.31; 95% CI: 1.29 to 14.4; p = 0.02), lymphocyte telomere length (OR: 4.22; 95% CI: 1.21 to 14.7; p = 0.02), naive T-cell telomere length (OR: 5.49; 95% CI: 1.58 to 19.0; p = 0.01). Oily fish intake was positively associated with memory T-cell telomere length (OR: 2.55; 95% CI: 1.16 to 5.58; p = 0.02). No significant causal relationships were found between other exposures and outcomes.

CONCLUSIONS: This study found positive causal associations between telomere length and the intake of dried fruit and oily fish. No significant causal relationships were observed with other dietary factors. These findings provide insights into how specific dietary components may help maintain telomere length.},
}

Humans
*Mendelian Randomization Analysis
*Diet
*Telomere
*Feeding Behavior
*Telomere Shortening
*Telomere Homeostasis

@article {pmid41038571,
year = {2025},
author = {Hu, MY and Rowe, M and Tigue, M and Reizel, Y and Smoom, R and Tzfati, Y and Kaestner, KH},
title = {Human-length Telomeres Limit Regeneration of Liver Epithelial Cells in Mice.},
journal = {Cellular and molecular gastroenterology and hepatology},
volume = {},
number = {},
pages = {101655},
doi = {10.1016/j.jcmgh.2025.101655},
pmid = {41038571},
issn = {2352-345X},
abstract = {BACKGROUND & AIMS: Telomeres, or the ends of linear chromosomes, are critical for maintaining genomic integrity. The commonly used C57BL/6 mouse strain has telomeres about 5 times longer than those present in humans. We recently engineered the C57BL/6 "Telomouse" to enable the study of human length telomeres, which we used here to study the effects of shortened telomeres on liver regeneration.

METHODS: We performed partial hepatectomy experiments with Telomice using wild type C57BL/6 mice as controls. Staggered injections of the thymidine analogs CldU and IdU were used to analyze their incorporation into nuclear DNA during cells' S-phase to assess proliferation. In a second model, we employed a competitive hepatocyte repopulation assay in Fah (fumarylacetoacetate hydrolase) null mice.

RESULTS: We found that human-length telomeres limit the proliferative capacity of cholangiocytes and hepatocytes in short-term liver regeneration. Control mice exhibited significant cholangiocyte proliferation at 36 hours post-PHx, which remained stable at 46 hours post-PHx. In contrast, Telomice exhibited decreased cholangiocyte proliferation at 36 hours post-PHx which further decreased at 46 hours post-PHx. Both control and Telomice exhibit increased hepatocyte proliferation at 46 hours compared to 36 hours post-PHx. However, Telomice exhibit less proliferation than controls at both time points. Compared to controls, Telomice exhibit an increased DNA damage response in the liver after partial hepatectomy. In a second model, Telomice hepatocytes also exhibited reduced efficacy in a competitive repopulation study using the Fah null mouse model of conditional hepatocyte ablation.

CONCLUSIONS: Short telomeres induce DNA damage in the regenerating liver, hampering its ability to accelerate cell proliferation and regenerate the liver.},
}

@article {pmid41037913,
year = {2025},
author = {Qiu, F and Wan, Y and Wang, A and Mahai, G and He, Y and Zhou, W and Zhu, Y and Xia, W and Xu, S and Li, Y},
title = {Prospective associations of in utero exposure to multiple insecticides with cord blood mitochondria DNA copy number and longitudinal offspring telomere length shortening.},
journal = {Journal of hazardous materials},
volume = {498},
number = {},
pages = {140019},
doi = {10.1016/j.jhazmat.2025.140019},
pmid = {41037913},
issn = {1873-3336},
abstract = {Widespread insecticide exposure can cause adverse health outcomes in offspring due to maternal exposure via elevating oxidative stress levels, which may be evidenced through variations in telomere length (TL) and mitochondrial DNA copy number (mtDNAcn). However, the potential risks of in-utero exposure to multiple classes of insecticides at environmentally relevant doses on offspring's TL and mtDNAcn in early life are still poorly understood. This study aimed to elucidate associations between in-utero exposure to organophosphates, pyrethroids, neonicotinoids and cord blood mtDNAcn and offspring TL shortening. Maternal urinary metabolites of these insecticides were repeatedly measured in three trimesters. Relative mtDNAcn (n = 520) in cord blood and relative TL (n = 299) in cord blood & blood samples of three years old toddlers were also measured. The results showed that the first-, second-, and third-trimester insecticide mixtures were all significantly associated with reduced cord blood mtDNAcn, and the association was primarily driven by desmethyl-clothianidin (DM-CLO). Additionally, the second-trimester insecticide mixture was significantly associated with TL attrition, with DM-CLO being the primary contributor. Our findings showed that in-utero insecticide mixture exposure was related to decreased cord blood mtDNAcn and accelerated longitudinal offspring TL attrition, with DM-CLO being the major contributor.},
}

@article {pmid41035407,
year = {2025},
author = {Franke, M and Ferrer, A and Patnaik, MM},
title = {Diagnosis and management of adult telomere biology disorders.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2025.287739},
pmid = {41035407},
issn = {1592-8721},
abstract = {Telomere biology disorders (TBDs) comprise a heterogenous group of inherited conditions characterized by impaired telomere maintenance, resulting in abnormal telomere lengths and/or telomere dysfunction. The clinical spectrum of TBDs is broad, spanning bone marrow failure, pulmonary fibrosis, liver disease, and an increased predisposition to malignancy, complicating timely diagnosis and management. In this review, we explore the evolving clinical landscape and diagnostic strategies for TBDs, while highlighting the diverse phenotypic presentations. We further examine the role of telomere dysfunction in driving cancer development and clonal hematopoiesis. Finally, we discuss current and emerging therapeutic approaches for TBDs, emphasizing the need for individualized and multidisciplinary management to optimize patient outcomes.},
}

@article {pmid41035087,
year = {2025},
author = {Ferrari, L and Comotti, A and Fattori, A and Barnini, T and Laurino, M and Bufano, P and Albetti, B and Hoxha, M and Russo, S and Ciocan, C and Bonzini, M},
title = {Impact of night shift work on telomere length and epigenetic age in older workers.},
journal = {Journal of occupational medicine and toxicology (London, England)},
volume = {20},
number = {1},
pages = {31},
pmid = {41035087},
issn = {1745-6673},
support = {ID 8192866//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; ID 8192866//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; ID 8192866//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; ID 8192866//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; ID 8192866//Istituto Nazionale per l'Assicurazione Contro Gli Infortuni sul Lavoro/ ; },
abstract = {BACKGROUND: Night shift work disrupts circadian rhythms and has been associated with various health disorders, particularly in older adults. Biological age indicators, such as telomere length (TL) and DNA methylation (DNAm) age, offer effective tools to assess early ageing-related changes Linked to occupational exposures. This study aims to investigate the association between night shift work and biological ageing markers among workers aged over 50 years.

METHODS: Participants were classified as current, former, or never night shift workers. TL was measured via quantitative PCR, and DNAm age was estimated based on methylation at five CpG sites. Age acceleration (AA) was calculated as the residual from regressing DNAm age on chronological age. Associations between shift work and ageing markers were evaluated using univariate and multivariate analyses.

RESULTS: Out of 330 workers invited, a total of 262 (response rate 79.6%) were recruited, predominantly male (87%) with a mean age of 54.5 ± 3.1 years. Current night shift workers exhibited significantly shorter telomeres compared to non-current shift workers (adjusted β = -0.07, p = 0.03). Among former shift workers, longer cumulative exposure was associated with reduced TL (β = -0.01, p = 0.004). Additionally, TL increased and AA decreased with each year since night shift cessation (β = 0.01, p=0.001 and β = -0.08, p=0.05, respectively).

CONCLUSIONS: Prolonged night shift work is associated with telomere shortening, suggesting increased cellular ageing, partially reversible after night-shift cessation. DNAm age appears less sensitive to recent or cumulative shift work exposure.},
}

@article {pmid41029149,
year = {2025},
author = {Feng, C and Zhong, S and Li, R and Lin, Y and Zhu, J and Liang, X and Xiao, C and Qin, C},
title = {Impact of smoking and alcohol consumption on telomere length: A univariable and multivariable Mendelian randomization study.},
journal = {Medicine},
volume = {104},
number = {39},
pages = {e44685},
doi = {10.1097/MD.0000000000044685},
pmid = {41029149},
issn = {1536-5964},
support = {Grant No.82060226//The National Natural Sciences Foundation of China/ ; GuikeAA22096030//The Guangxi Science and Technology Major Project/ ; },
mesh = {Humans ; Mendelian Randomization Analysis ; *Alcohol Drinking/genetics/adverse effects/epidemiology ; *Smoking/genetics/adverse effects/epidemiology ; *Telomere Shortening/genetics ; *Telomere/genetics ; Male ; },
abstract = {Telomere length is a potential biomarker for biological aging and is associated with many age-related pathologies. Although observational evidence has linked modifiable lifestyle factors to telomere attrition, the causal relationship between smoking, alcohol consumption, and telomere length remains controversial. This study aimed to investigate the causal effects of smoking and alcohol consumption on telomere length using Mendelian randomization (MR) analysis. Genetic data on smoking initiation (N = 805,431), alcohol consumption (N = 666,978), and telomere length (N = 472,174) were extracted from published summary statistics. Univariable and multivariable MR analyses were performed to comprehensively estimate the independent causal effects of smoking and alcohol consumption on telomere length. Cochran Q test and the MR Egger intercept test were used to detect heterogeneity and pleiotropy. A Steiger filtering test was conducted to confirm directional causal effects. Further sensitivity analyses were performed using the leave-one-out method and funnel plots. Inverse variance weighted (IVW) analysis showed that genetically predicted smoking initiation was significantly associated with shorter telomere length (univariable IVW: β = -0.08, 95% confidence interval [CI] = -0.11 to -0.04, P < .001; multivariable IVW: β = -0.06, 95% CI = -0.11 to -0.02, P = .007). Similarly, genetic predisposition to alcohol consumption was causally associated with shorter telomere length (univariable IVW: β = -0.06, 95% CI = -0.10 to -0.02, P = .006; multivariable IVW: β = -0.06, 95% CI = -0.11 to -0.01, P = .030). No pleiotropy was identified in either univariable or multivariable MR analyses. The Steiger filtering test validated the accuracy of directional causality (P < .001). Finally, leave-one-out analysis and funnel plots further confirmed the robustness and reliability of the findings. This study provides genetic evidence for the causal effects of smoking and alcohol consumption on telomere shortening. Interventions targeting tobacco smoking and alcohol consumption may slow down cellular senescence and mitigate the risk of age-related diseases.},
}

Humans
Mendelian Randomization Analysis
*Alcohol Drinking/genetics/adverse effects/epidemiology
*Smoking/genetics/adverse effects/epidemiology
*Telomere Shortening/genetics
*Telomere/genetics
Male

@article {pmid41027922,
year = {2025},
author = {Qiao, J and Wang, Q and Zhao, Y and Chang, M and Sun, S and Zhang, P and Yao, K and Chen, M and Zheng, L and Xing, X and Cai, L and Jegga, AG and Jiang, L and Pauklin, S and Zou, R and Yang, Y and Feng, Y},
title = {Contribution of leukocyte telomere length to cardiovascular disease onset from genome-wide cross-trait analysis.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {8677},
pmid = {41027922},
issn = {2041-1723},
support = {C59392/A25064//Cancer Research UK (CRUK)/ ; },
mesh = {Humans ; *Leukocytes/metabolism ; Genome-Wide Association Study ; *Cardiovascular Diseases/genetics ; *Telomere/genetics/metabolism ; Mendelian Randomization Analysis ; *Telomere Homeostasis/genetics ; Male ; Female ; Genetic Predisposition to Disease ; *Telomere Shortening/genetics ; Polymorphism, Single Nucleotide ; Middle Aged ; },
abstract = {Telomere shortening is a well-established marker of cellular aging and genomic instability. While the relationship between leukocyte telomere length and cardiovascular diseases has long been of interest, their genetic interplay remains incompletely understood. In this study, we observe substantial genetic overlap beyond genome-wide correlations and identify a potential causal relationship between leukocyte telomere length and coronary artery disease. Specifically, we discover 248 pleiotropic loci, 22 of which show strong evidence of colocalization. Some shared loci implicate multiple pleiotropic genes across different trait pairs, including ALDH2, ACAD10, TMEM116, SH2B3 (all at 12q24.12), TMED6 (16q22.1), SERPINF1 (17p13.3), and XPO7 (8p21.3). Functional analysis highlights key pathways involved in DNA biosynthesis and telomere maintenance. Notably, SH2B3 is validated through proteome-wide Mendelian randomization analysis, suggesting its potential as a therapeutic target. Here we report the shared genetic basis between leukocyte telomere length and cardiovascular diseases, providing valuable insights into future therapeutic developments.},
}

Humans
*Leukocytes/metabolism
Genome-Wide Association Study
*Cardiovascular Diseases/genetics
*Telomere/genetics/metabolism
Mendelian Randomization Analysis
*Telomere Homeostasis/genetics
Male
Female
Genetic Predisposition to Disease
*Telomere Shortening/genetics
Polymorphism, Single Nucleotide
Middle Aged

@article {pmid41027193,
year = {2025},
author = {Yang, L and Wang, W and Zhang, A},
title = {PARP1 promoter hypermethylation promotes arsenic-induced skin damage by driving telomere dysfunction-mediated keratinocyte senescence.},
journal = {Ecotoxicology and environmental safety},
volume = {304},
number = {},
pages = {119108},
doi = {10.1016/j.ecoenv.2025.119108},
pmid = {41027193},
issn = {1090-2414},
abstract = {Arsenic, a common environmental pollutant, causes skin damage with long-term exposure. Although its pathogenic mechanism remains unclear, skin cell senescence creates a microenvironment that promotes cancer development, with the mechanisms accelerating disease progression in arsenic-induced skin damage attracting significant attention. This study utilised previously collected skin samples to evaluate the associations between skin senescence and damage indicators. According to the presence or absence of arsenic exposure, participants were divided into a reference group and an arsenic exposure group. Additionally, the arsenic exposure group was further divided into a common pathological changes group, a hyperkeratosis group, and a skin cancer group, based on skin histopathological examination. Compared with the reference group, the arsenic exposure group exhibited increased expression of senescence-associated secretory phenotypes (IL-6 and IL-17) and shortened relative telomere length (RTL). With increasing severity of skin damage, IL-6 and IL-17 levels progressively increased, while RTL progressively decreased. Examination of representative indicators of arsenic-induced skin damage (epithelial-mesenchymal transition [EMT] indicators) revealed decreased E-cadherin expression and increased vimentin expression. With increasing severity of skin damage, E-cadherin expression progressively decreased, while vimentin expression progressively increased. Moreover, clear correlations were observed between senescence-related markers (IL-6, IL-17, and RTL) and arsenic-induced skin damage markers (E-cadherin, vimentin) in the human samples. In vitro experiments demonstrated that arsenic induced lower expression of the telomere-related gene PARP1, reducing its binding to TERF2 and weakening its recruitment of BLM, thereby causing telomere dysfunction, promoting the senescence of HaCaT cells, and resulting in EMT. Additionally, arsenic exposure induced high expression of DNMT3, which mediated PARP1 hypermethylation and low expression. Treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine restored PARP1 expression in arsenic-treated HaCaT cells, regulated telomere dysfunction, improved cellular senescence, and alleviated EMT. This study provides new insights into the mechanisms underlying arsenic-induced skin damage from an epigenetic and genetic perspective.},
}

@article {pmid41026782,
year = {2025},
author = {Sengupta, A and Vinayagamurthy, S and Soni, D and Deb, R and Mukherjee, AK and Dutta, S and Jaiswal, J and Yadav, M and Sharma, S and Bagri, S and Roy, SS and Poonia, P and Singh, A and Khanna, D and Bhatt, AKK and Sharma, A and Saurav, S and Motiani, RK and Chowdhury, S},
title = {Telomeres control human telomerase (TERT) expression through non-telomeric TRF2.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {41026782},
issn = {2050-084X},
support = {IA/S/18/2/504021//Wellcome Trust/DBT India Alliance/ ; },
mesh = {Humans ; *Telomerase/genetics/metabolism/biosynthesis ; *Telomeric Repeat Binding Protein 2/metabolism ; *Telomere/metabolism ; Promoter Regions, Genetic ; Cell Line, Tumor ; },
abstract = {The function of the human telomerase reverse transcriptase (referred hereafter as TERT) in the synthesis and maintenance of chromosome ends, or telomeres, is widely understood. Whether and how telomeres, on the other hand, influence TERT regulation is relatively less studied. We found TERT was transcriptionally altered depending on telomere length (TL). This resulted from TL-dependent binding of TRF2 between telomeres and the TERT promoter. TERT promoter-bound TRF2 was non-telomeric and did not involve the looping of telomeres to the TERT promoter. Cell lines from different tissue types fibrosarcoma (HT1080), colon cancer (HCT116), and breast cancer (MDA-MB-231), engineered for either telomere elongation/shortening, gave an increase/decrease in TERT, respectively. Mechanistically, we show TERT promoter-bound non-telomeric TRF2 recruits the canonical PRC2-complex, inducing repressor histone H3K27-trimethylation in a TL-dependent fashion. This was further supported by TL-dependent promoter activity from an exogenously inserted TERT reporter. Increase in TL over days followed by a gradual decline, resulted in activation followed by repression of TERT in a concerted manner, further implicating TL as a key factor for TERT regulation. Notably, on reprogramming primary fibroblasts to induced pluripotent stem cells (iPSCs), TRF2 loss from the TERT promoter was evident along with telomere elongation and TERT upregulation. Conversely, on telomere shortening in iPSCs, TERT promoter-bound TRF2 was restored with a marked reduction in TERT, further supporting the causal role of TL in TERT transcription. Mechanisms of tight control of TERT by TL shown here are likely to have major implications in telomere-related physiologies, particularly, cancer, ageing, and pluripotency.},
}

Humans
*Telomerase/genetics/metabolism/biosynthesis
*Telomeric Repeat Binding Protein 2/metabolism
*Telomere/metabolism
Promoter Regions, Genetic
Cell Line, Tumor

@article {pmid41026280,
year = {2025},
author = {Zhao, J and Zhu, J and Zhu, K and Wang, M and Gong, W and Wang, J and Liu, S},
title = {TERT links telomere length to cancer risk by integrating genomic instability and immune modulation.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {1788},
pmid = {41026280},
issn = {2730-6011},
support = {No. 82303289//Young Scientists Fund of the National Natural Science Foundation of China/ ; No. 23YF1426000//Shanghai Sailing Program/ ; },
abstract = {BACKGROUND: Telomere homeostasis serves as a key regulatory mechanism linking aging and cancer. While telomere attrition imposes a proliferative barrier by inducing cellular senescence, abnormal telomere elongation circumvents this constraint, thereby granting malignant cells unlimited replicative capacity. This study systematically explores the causal relationship between telomere length and cancer risk, with the goal of elucidating the molecular pathways involved in telomere-driven tumorigenesis.

METHOD: Mendelian randomization (MR) was employed to establish a causal link between telomere length and pan-cancer susceptibility. Multiple MR models were employed to ensure the robustness of the results. Telomere-associated genes were identified through SNPense analysis, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Key gene regulatory networks were identified and visualized using the MCODE and cytoHubba algorithms. The expression profile of TERT across diverse cancer types was analyzed using TCGA datasets, and its diagnostic potential was evaluated via receiver operating characteristic (ROC) curve analysis. Correlations between TERT expression and immune cell infiltration were further explored.

RESULTS: Longer telomere length was significantly associated with an increased risk of 33 cancer types (IVW OR = 1.27-1.41, all P < 0.001). A total of 143 telomere-related genes were identified, with functional enrichment highlighting their involvement in genome integrity and telomere maintenance. TERT emerged as the most influential hub gene (MCC score = 169). Transcriptomic analyses from TCGA demonstrated widespread TERT overexpression in 16 cancers (e.g., CHOL, LIHC, LUAD), a finding corroborated by RT-qPCR validation. TERT exhibited high diagnostic performance (AUC > 0.85 in 16 cancers, peaking at AUC = 0.97 in LUSC). Immune infiltration analysis revealed a positive correlation with Th2 cells (r = 0.42) but negative correlations with dendritic cells (r = - 0.38) and macrophages (r = - 0.31).

CONCLUSION: This study proposes a comprehensive framework linking telomere length regulation to cancer progression through the TERT axis. Telomere dysfunction contributes to tumorigenesis via two key mechanisms: promoting genomic instability and altering the immune microenvironment. These findings offer new insights into telomere-driven oncogenesis and lay a conceptual foundation for precision diagnostics and targeted therapies in oncology.},
}

@article {pmid41024124,
year = {2025},
author = {Palomares, D and Vanparys, AAT and Jorgji, J and Paître, E and Kienlen-Campard, P and Suelves, N},
title = {Telomere-driven senescence accelerates tau pathology, neuroinflammation and neurodegeneration in a tauopathy mouse model.},
journal = {Acta neuropathologica communications},
volume = {13},
number = {1},
pages = {206},
pmid = {41024124},
issn = {2051-5960},
support = {40015405/40030154//FRS-FNRS (Fonds National pour la Recherche Scientifique)/ ; FNRS J.0106.22//FRS-FNRS (Fonds National pour la Recherche Scientifique)/ ; SAO-FRA 2018/0025//SAO-FRA Alzheimer Research Foundation/ ; SAO-FRA 2020/0028//SAO-FRA Alzheimer Research Foundation/ ; ARC21/26-114//UCLouvain Action de Recherche Concertée/ ; FMRE AlzHex//Queen Elisabeth Medical Foundation/ ; },
mesh = {Animals ; *Tauopathies/pathology/metabolism/genetics ; Mice ; *tau Proteins/metabolism/genetics ; Disease Models, Animal ; *Telomere/pathology/metabolism ; *Neuroinflammatory Diseases/pathology/metabolism ; *Cellular Senescence/physiology ; *Brain/pathology/metabolism ; Mice, Knockout ; Mice, Transgenic ; *Aging/pathology ; Mice, Inbred C57BL ; *Nerve Degeneration/pathology/metabolism ; Male ; },
abstract = {The connection between aging and neurodegenerative pathologies like Alzheimer's disease (AD) has long been recognized, with senescent brain cells building up in the brains of AD patients. A causal link has been established between senescence and AD-related tauopathy, but the mechanisms underlying these pathological changes remain largely unknown. To unravel the precise role of cellular senescence in tau-mediated neuropathology, we crossed the Terc knockout (Terc[-/-]) mouse model of telomere-induced senescence with the P301S tauopathy model (PS19 line). Using brain sections and protein extracts, an array of biochemical and molecular techniques was applied to investigate the expression of tau-related neuropathological features within a senescent context. Our results showed that the brains of 6- and 9-month-old Terc[-/-] mice exhibit significant telomere attrition and signs of cellular senescence. Additionally, we found evidence that the introduction of a senescent phenotype in a tauopathy mouse model results in increased tau phosphorylation at key residues, particularly in the hippocampus. Over time, this leads to enhanced tau truncation and aggregation, accompanied by exacerbated astrocyte and microglial activation, as well as selective neuronal loss in vulnerable brain regions. Overall, these findings place senescence as a key upstream regulator of tau pathology and tau-related neurodegeneration, suggesting that targeting senescent cells and their detrimental effects may offer promising therapeutic strategies for AD and other related tauopathies.},
}

Animals
*Tauopathies/pathology/metabolism/genetics
Mice
*tau Proteins/metabolism/genetics
Disease Models, Animal
*Telomere/pathology/metabolism
*Neuroinflammatory Diseases/pathology/metabolism
*Cellular Senescence/physiology
*Brain/pathology/metabolism
Mice, Knockout
Mice, Transgenic
*Aging/pathology
Mice, Inbred C57BL
*Nerve Degeneration/pathology/metabolism
Male

@article {pmid41024106,
year = {2025},
author = {Tire, B and Talibova, G and Bilmez, Y and Ozturk, S},
title = {Superovulation alters telomere length and telomerase component levels in mouse oocytes.},
journal = {Journal of ovarian research},
volume = {18},
number = {1},
pages = {210},
pmid = {41024106},
issn = {1757-2215},
mesh = {Animals ; *Telomerase/metabolism/genetics ; *Oocytes/metabolism ; *Superovulation ; Female ; Mice ; *Telomere/metabolism ; Estradiol/blood ; Progesterone/blood ; *Telomere Homeostasis ; },
abstract = {Assisted reproductive technologies (ARTs) are widely used to treat infertility and include the fundamental step, controlled ovarian stimulation (also known as superovulation). Superovulation involves the administration of gonadotropins to produce a sufficient number of oocytes, either through single or repeated applications. However, superovulation can cause certain adverse effects such as increased oxidative stress, decreased oocyte quality, and mitochondrial dysfunction. As oxidative stress and mitochondrial dysfunction are closely associated with alterations in telomere length, we investigated the effects of single and repeated superovulation on expression of the telomerase components and telomere length in mouse oocytes at germinal vesicle (GV) or metaphase II (MII) stage. Additionally, we measured serum levels of estradiol, progesterone, and oxidative markers. Our findings revealed that superovulation significantly affected telomere length, TERT protein level, telomerase RNA component (Terc), and telomerase reverse transcriptase (Tert) mRNA levels in these oocytes possibly due to altered estradiol and progesterone profiles (P < 0.05). These results suggest that altered telomerase expression and telomere length may contribute to emerging adverse effects of superovulation during oocyte maturation and early embryo development.},
}

Animals
*Telomerase/metabolism/genetics
*Oocytes/metabolism
*Superovulation
Female
Mice
*Telomere/metabolism
Estradiol/blood
Progesterone/blood
*Telomere Homeostasis

@article {pmid41022004,
year = {2025},
author = {Yang, Z and Li, J and Jin, W and Cai, D and Zhang, J and Hong, S},
title = {Kisspeptin-54 ameliorates chondrocyte senescence in osteoarthritis via SIRT3-mediated telomere protection and p53 acetylation inhibition.},
journal = {Neuropeptides},
volume = {114},
number = {},
pages = {102562},
doi = {10.1016/j.npep.2025.102562},
pmid = {41022004},
issn = {1532-2785},
abstract = {BACKGROUND: Osteoarthritis (OA), characterized by chondrocyte senescence and oxidative stress, affects over 300 million people globally. Kisspeptin-54, a neuropeptide with pleiotropic protective effects, was investigated for its role in chondrocyte senescence and its underlying mechanisms.

METHODS: Oxidative stress and senescence were induced in primary mouse chondrocytes by treating them with TBHP. Kisspeptin-54 was administered at varying concentrations (10-1000 nM) to assess cytoprotection, while SIRT3 was knocked down using adenoviral shRNA to validate mechanistic pathways. Telomere length, mTERT expression, telomerase activity, and p53 acetylation were evaluated via Southern blot, RT-PCR, and western blot techniques. Furthermore, senescence was evaluated through the application of SA-β-galactosidase staining alongside the measurement of PAI-1 expression.

RESULTS: TBHP induced dose-dependent GPR54 downregulation, oxidative stress (260 % increase in ROS), telomere attrition (41 % reduction in length), and senescence (270 % increase in SA-β-galactosidase-positive cells). Kisspeptin-54 (≤200 nM) rescued cell viability, reduced LDH release (57 % at 200 nM), and mitigated ROS and SOD activity decline. Mechanistically, Kisspeptin-54 restored SIRT3 expression, suppressed p53 acetylation (Acetyl-p53[K382] reduced by 56 % at 200 nM), and preserved telomere function (telomere length restored to 91 % of control). SIRT3 knockdown abrogated these effects, confirming its critical role.

CONCLUSION: Kisspeptin-54 alleviates chondrocyte senescence via a dual mechanism: (1) SIRT3-mediated restoration of mitochondrial antioxidant capacity and telomere homeostasis; (2) inhibition of p53 hyperacetylation and downstream senescence signaling. These findings establish Kisspeptin-54 as an innovative therapeutic candidate for OA acting through the modulation of the SIRT3/p53 axis to combat oxidative stress and telomere dysfunction.},
}

@article {pmid41016118,
year = {2025},
author = {Bountziouka, V and Nelson, CP and Codd, V and Samani, NJ},
title = {Higher dietary n - 3 PUFA and fiber intake are associated with longer leukocyte telomere length: Evidence from a substitution model analysis in the UK Biobank.},
journal = {Nutrition research (New York, N.Y.)},
volume = {142},
number = {},
pages = {63-75},
doi = {10.1016/j.nutres.2025.08.009},
pmid = {41016118},
issn = {1879-0739},
abstract = {Telomere attrition is a biomarker of cellular aging, influenced by lifestyle and dietary exposures. The specific role of macronutrient composition, particularly polyunsaturated fatty acids (PUFAs), in telomere dynamics remains insufficiently explored. We hypothesized that higher intake of specific macronutrients, particularly PUFAs, would be positively associated with leukocyte telomere length (LTL). In this cross-sectional study of 143,553 UK Biobank participants aged 40-69 years, we examined associations between macronutrient intake and standardized LTL (z-LTL), measured as the log-transformed telomere repeat to single-copy gene ratio. Dietary intake was assessed using repeated 24-hour web-based dietary recalls. Multivariable linear regression models were used to estimate associations between macronutrients (% of total energy intake) and z-LTL, adjusting for demographic, lifestyle, and clinical covariates. Effect estimates were translated into age-equivalent changes in LTL. Carbohydrate and total fat intake were positively associated with z-LTL, corresponding to age-related LTL differences of approximately 30-40 days. In energy substitution models, n - 3 PUFA intake showed a stronger positive association with z-LTL than other fats, with adherence to recommended intake associated with differences equivalent to over 2 years (P < .0001) of age-related telomere shortening, whereas no evidence of an association for MUFA was observed. Energy-adjusted fibre intake was associated with an age-related change of LTL equivalent to 1 year (P < .0001). These findings suggest that dietary composition, particularly n - 3 PUFA intake, may be linked with LTL in a manner consistent with healthier cellular aging. Further longitudinal and experimental studies are needed to confirm these associations and explore their implications for dietary guidance.},
}

@article {pmid41016064,
year = {2025},
author = {Shen, T and Ning, Y and Wang, Y and Song, Z and Xi, M and Pan, H and Xu, M},
title = {Haplotype-resolved telomere-to-telomere genome assembly of Populus lasiocarpa unveils retrotransposon-driven centromere evolution.},
journal = {The Plant journal : for cell and molecular biology},
volume = {123},
number = {6},
pages = {e70504},
doi = {10.1111/tpj.70504},
pmid = {41016064},
issn = {1365-313X},
support = {2022YFD2200301//National Key Research and Development Program of China/ ; },
mesh = {*Retroelements/genetics ; *Centromere/genetics ; *Populus/genetics ; *Telomere/genetics ; *Genome, Plant/genetics ; Evolution, Molecular ; Haplotypes/genetics ; Chromosomes, Plant/genetics ; },
abstract = {Centromeres, essential for chromosome segregation, exhibit remarkable evolutionary dynamism in sequence composition and structural organization. Here, we report the first haplotype-resolved, telomere-to-telomere genome assembly of Populus lasiocarpa (PLAS) and precisely map all 38 functional centromeres through CENH3 ChIP-Seq. Unlike classical satellite-rich centromeres in model plants, PLAS centromeres lack abundant satellite arrays but are dominated by retrotransposons, particularly RLG and RIL elements, which form intricate nested TE arrays within the functional centromeric regions, disrupting their structural integrity and driving their evolution. Comparative analysis with P. trichocarpa reveals a conserved retrotransposon-dominated architecture, despite minimal sequence conservation. We propose a cyclic model of centromere evolution in which autonomous retrotransposons destabilize functional centromeres through epigenetic erosion, triggering neocentromere formation at pericentromeric sites enriched in transposable elements (TEs) and tandem repeats (TRs). These neocentromeres either succumb to recurrent retrotransposon invasions or stabilize through KARMA-mediated TR expansion, ultimately giving rise to satellite-rich centromeres. Our work redefines centromeres as dynamic, epigenetically plastic domains shaped by retrotransposon-TR antagonism, challenging the satellite-centric paradigm and offering novel insights into plant genome evolution.},
}

*Retroelements/genetics
*Centromere/genetics
*Populus/genetics
*Telomere/genetics
*Genome, Plant/genetics
Evolution, Molecular
Haplotypes/genetics
Chromosomes, Plant/genetics

@article {pmid41015547,
year = {2025},
author = {Ginevičienė, V and Pranckevičienė, E and Urnikytė, A and Jurkūnaitė, L and Gutauskaitė, K and Dadelienė, R and Kilaitė, J and Jamontaitė, IE and Mastavičiūtė, A and Ahmetov, II and Alekna, V},
title = {A multi-omics investigation of sarcopenia and frailty: Integrating genomic, epigenomic and telomere length data.},
journal = {Experimental physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/EP092853},
pmid = {41015547},
issn = {1469-445X},
support = {S-MIP-22-36//Research Council of Lithuania (LMTLT)/ ; },
abstract = {Sarcopenia and frailty are complex geriatric syndromes influenced by a combination of genetic and environmental factors. Recent studies suggest that specific genetic variants, DNA methylation patterns and shortened telomeres are associated with age-related diseases and might contribute to the development of both sarcopenia and frailty. In this study, we investigated the contribution of multi-omics data to sarcopenia, frailty, lean mass index (LMI) and handgrip strength in an elderly Lithuanian population. A total of 204 participants (age 82.2 ± 7.6 years) were included, comprising 122 individuals diagnosed with sarcopenia and/or frailty and 82 healthy, community-dwelling older adults. The results showed that LMI was associated with various health and lifestyle factors. Two genetic variants, CLIC5 rs75652203 and GHITM rs17102732, were found to be significantly associated with handgrip strength at the genome-wide level. Additionally, 12 polymorphisms previously linked to sarcopenia were replicated in relationship to LMI: BOK rs76993203, VAMP5 rs1374370, TMEM18 rs12714414, SFMBT1 rs36033494, BANK1 rs13136118, TET2 rs2647239, FOXO3 rs9384679, L3MBTL3 rs13209574, ZFAT rs13267329, CEP57 rs35793328, PCGF2 rs1985352 and MC4R rs66922415. Furthermore, several genes, many of which are involved in immune system processes, were significantly enriched with differentially methylated sites associated with LMI. Shorter telomeres were also associated with both sarcopenia and frailty. Notably, a significant relationship was observed between telomere length and methylation levels in genes related to lifestyle traits and the risk of developing these conditions. These findings provide new insights into the biological mechanisms underlying sarcopenia and frailty, underscoring the important roles of genetic and epigenetic factors in their pathogenesis among older adults.},
}

@article {pmid41014975,
year = {2025},
author = {Liu, Q and Lei, X and Fu, W and Fan, G and Fang, Q and Luo, F and Huang, X and Li, H and Guo, W and Liu, B and Yan, L and Wei, J and Wang, Y and Song, L and Hu, L},
title = {Associations of greenness and air pollution with leukocyte telomere length in Chinese children and adolescents.},
journal = {Ecotoxicology and environmental safety},
volume = {304},
number = {},
pages = {119122},
doi = {10.1016/j.ecoenv.2025.119122},
pmid = {41014975},
issn = {1090-2414},
abstract = {Evidence on the associations of greenness and air pollution with telomere length (TL) in children and adolescents remains scarce, and the potential role of air pollution in the greenness-TL association is unclear. We aimed to evaluate the relationships of greenness and air pollution with leukocyte TL (LTL) in children and adolescents and further explore further explore the interaction and mediation of air pollution on the greenness-LTL association. In this cross-sectional study, 1151 children and adolescents aged 6-18 years were recruited from Liuzhou, China. Greenness (measured by the soil-adjusted vegetation index [SAVI], normalized difference vegetation index [NDVI], and enhanced vegetation index [EVI]) and air pollution (PM2.5, PM10, NO2, SO2, and CO) were estimated based on participants' school and home addresses. Multiple linear regression models were employed to assess the associations of greenness and air pollution with LTL. An interquartile range (IQR) increment in SAVI500 m was associated 3.32 % (95 % confidence interval [CI]: 1.17 %, 5.51 %) longer LTL, while an IQR increment in PM2.5, PM10, NO2, SO2, and CO were associated with 2.26 % (95 % CI: -4.32 %, -0.16 %), 5.20 % (95 % CI: -7.48 %, -2.85 %), 9.90 % (95 % CI: -13.33 %, -6.34 %), 7.64 % (95 % CI: -11.21 %, -3.91 %), and 6.61 % (95 % CI: -9.77 %, -3.35 %) shorter LTL, respectively. Interaction and mediation were identified for PM10, SO2, NO2, and CO in the greenness-LTL association with mediation proportions from 37.90 % to 68.69 %. In conclusion, greenness exposure was positively associated with leukocyte telomere length in children and adolescents, and this association is primarily mediated by the attenuation of air pollution exposure.},
}

@article {pmid41013913,
year = {2025},
author = {Liu, Y and Zong, H and Xing, Y and Jiao, X and Liu, Z and Niu, Y and Yang, Z and Liu, S and Wang, Y and Zhao, H and Chen, X and Li, Z and Wang, X and Cai, J and Wang, W and Wang, Z},
title = {A Near Telomere-To-Telomere Genome Assembly of Coffea arabica (Mundo Novo) Provides Insights Into Its Secondary Metabolism.},
journal = {Molecular ecology resources},
volume = {},
number = {},
pages = {e70053},
doi = {10.1111/1755-0998.70053},
pmid = {41013913},
issn = {1755-0998},
support = {//The New Cornerstone Science Foundation (to WW)/ ; 32371499//National Natural Science Foundation of China/ ; },
abstract = {Arabica coffee (Coffea arabica) dominates global coffee production, accounting for over 60% of the world's coffee trade. The Mundo Novo cultivar, predominantly grown in Yunnan, China, represents a significant germplasm resource. However, the absence of a high-quality reference genome has hindered comprehensive genetic research and in-depth investigation of secondary metabolic pathways in Arabica. In this study, we present the first near telomere-to-telomere (T2T) genome assembly of Arabica, achieved through the integration of PacBio HiFi, Oxford Nanopore ultra-long, and Hi-C sequencing technologies, representing the highest-quality Arabica genome to date. Phylogenetic analysis of N-methyltransferases (NMTs), the key enzymes responsible for caffeine biosynthesis, revealed their independent evolution across caffeine-producing clades including coffee, cacao, and tea. Furthermore, GO enrichment analysis of expanded gene families at the Arabica ancestral node, combined with fruit-specific transcriptomic profiling, revealed that glycosyltransferases likely play a critical role in the secondary metabolism of Arabica. Notably, functional characterisation demonstrated that a UGT (uridine diphosphate glycosyltransferase, UGT) from the UGT29 subfamily, which exhibited increased gene copy number in the Arabica subgenome C than its ancestor, can directly convert Rebaudioside A (Reb A) into Rebaudioside M (Reb M) through a single-step enzymatic glycosylation. This direct pathway represents a crucial advancement over conventional multi-UGTs biosynthetic routes of Reb M, which is a highly desirable sweetener whereas with limited natural abundance. Taken together, this study not only provides a valuable genomic resource for studying the unique secondary metabolic processes in C. arabica but also accelerates innovative research frontiers for the synthetic biological production of the valuable sweetener Reb M.},
}

@article {pmid41010500,
year = {2025},
author = {Farhat, G and Malla, J and Hanson, L and Vadher, J and Al-Dujaili, EAS},
title = {Effects of Pomegranate Extract on IGF-1 Levels and Telomere Length in Older Adults (55-70 Years): Findings from a Randomised Double-Blinded Controlled Trial.},
journal = {Nutrients},
volume = {17},
number = {18},
pages = {},
pmid = {41010500},
issn = {2072-6643},
support = {Euromed Spain (No number)//Euromedik/ ; },
mesh = {Humans ; *Pomegranate/chemistry ; Middle Aged ; Double-Blind Method ; Aged ; *Insulin-Like Growth Factor I/metabolism ; Male ; Female ; *Plant Extracts/pharmacology ; *Telomere/drug effects ; Antioxidants/pharmacology ; },
abstract = {Background: Emerging evidence suggests that polyphenols may contribute to the attenuation of telomere attrition and the upregulation of insulin-like growth factor 1 (IGF-1), primarily in animal and cell studies, and to a lesser extent in humans. Pomegranate extract, known for its high antioxidant capacity, has shown promise in preventing telomere shortening and enhancing IGF-1 levels, but evidence in humans is lacking. Objective: To investigate the effects of pomegranate extract on telomere length and serum IGF-1 levels in older adults aged 55-70 years. Methods: Participants took part in a two-arm double-blind parallel trial, receiving either placebo capsules (maltodextrin) or pomegranate extract (740 mg) daily for 12 weeks. At baseline, week 6 and week 12, anthropometric measurements, blood pressure readings and blood samples were collected. Telomere length and serum IGF-1 levels were assessed. Results: A total of 72 participants completed the study. Analysis showed a significant effect of treatment and time on IGF-1 ((F2,136 = 3.43, p = 0.04), with levels significantly increasing in the pomegranate extract group at week 12. No significant effects on telomere length were noted. Weight status, physical activity, age, gender and energy intake did not impact the outcomes. Conclusions: Pomegranate extract significantly increased IGF-1 levels and could exert a positive role on vascular ageing. Further research is needed to replicate these findings and confirm its long-term benefits. Extended studies are required to elucidate its potential to counteract telomere shortening.},
}

Humans
*Pomegranate/chemistry
Middle Aged
Double-Blind Method
Aged
*Insulin-Like Growth Factor I/metabolism
Male
Female
*Plant Extracts/pharmacology
*Telomere/drug effects
Antioxidants/pharmacology

@article {pmid41010410,
year = {2025},
author = {Lin, CY and Chen, CW and Chu, PL},
title = {Examining the Relationships Between Blood Cadmium, DNA Methylation Biomarker, Telomere Length, and Their Associations with Mortality in U.S. Adults.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {9},
pages = {},
pmid = {41010410},
issn = {2075-1729},
abstract = {Cadmium exposure has been associated with shortened telomeres, alterations in DNA methylation patterns, and increased mortality. However, the role of DNA methylation in mediating the relationship between cadmium and telomere dynamics is still unclear. Additionally, it is unknow how telomere dynamics and DNA methylation alterations may affect the association between cadmium exposure and mortality outcomes. We utilized data from 8716 National Health and Nutrition Examination Survey (NHANES) participants aged 18 and above, collected between 1999 and 2002, and linked these to mortality outcomes from the National Center for Health Statistics (NCHS) through 2019. In the final model, ln-blood cadmium was significantly and inversely associated with ln-T/S ratio (β = -0.043, 95% CI: -0.059 to -0.027, p < 0.001), while ln-Horvath DNAmTL was strongly and positively associated with ln-T/S ratio (β = 1.782, 95% CI: 1.467 to 2.097, p < 0.001). Moreover, ln-blood cadmium also showed a significant inverse association with ln-Horvath DNAmTL (β = -0.010, 95% CI: -0.014 to -0.006, p < 0.001). Structural equation modeling showed that the association between cadmium and T/S ratio was mediated by Horvath DNAmTL, with a total effect of -0.044, a direct effect of -0.027, and an indirect effect of -0.017. Furthermore, stratified analyses revealed that a 1-unit increase in ln-blood cadmium was associated with higher all-cause mortality, with hazard ratios (HR) of 1.47 for participants with T/S ratio below the median and 1.41 for those above. Similar patterns were observed for cardiovascular (HR = 1.68 vs. 1.30) and cancer mortality (HR = 1.75 vs. 1.42). For Horvath DNAmTL, the association was significant only for all-cause mortality (HR = 1.36 vs. 1.31). However, no significant interactions were detected. In conclusion, our findings suggest that Horvath DNAmTL is associated with the relationship between cadmium and telomere length, suggesting a potential DNA methylation pathway that warrants further longitudinal investigation. Individuals with lower T/S ratios or Horvath DNAmTL appear to be more susceptible to cadmium-related mortality. Further research is necessary to confirm these results.},
}

@article {pmid41006252,
year = {2025},
author = {Fernandez, A and Zhou, T and Lei, Y and Liu, N and Esworthy, S and Shen, C and Liu, H and Hess, JD and Yuan, H and Shi, G and Zhou, M and Shen, L and Zhang, S and Kosiyatrakul, S and Gaur, V and Sommers, JA and Srivastava, N and Edelmann, W and Li, GM and Brosh, RM and Chai, W and Lee, MYWT and Zhang, D and Schildkraut, C and Zheng, L and Shen, B},
title = {DNA2 and MSH2 cooperatively repair stabilized G4 and allow efficient telomere replication.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {8519},
pmid = {41006252},
issn = {2041-1723},
support = {R01 CA085344/CA/NCI NIH HHS/United States ; R50 CA211397/CA/NCI NIH HHS/United States ; },
mesh = {*MutS Homolog 2 Protein/metabolism/genetics ; *Telomere/metabolism/genetics ; *DNA Replication ; *G-Quadruplexes ; Humans ; *DNA Helicases/metabolism/genetics ; *DNA Repair ; Animals ; },
abstract = {G-quadruplexes (G4s) are widely existing stable DNA secondary structures in mammalian cells. A long-standing hypothesis is that timely resolution of G4s is needed for efficient and faithful DNA replication. In vitro, G4s may be unwound by helicases or alternatively resolved via DNA2 nuclease mediated G4 cleavage. However, little is known about the biological significance and regulatory mechanism of the DNA2-mediated G4 removal pathway. Here, we report that DNA2 deficiency or its chemical inhibition leads to a significant accumulation of G4s and stalled replication forks at telomeres, which is demonstrated by a high-resolution technology: Single molecular analysis of replicating DNA (SMARD). We further identify that the DNA repair complex MutSα (MSH2-MSH6) binds G4s and stimulates G4 resolution via DNA2-mediated G4 excision. MSH2 deficiency, like DNA2 deficiency or inhibition, causes G4 accumulation and defective telomere replication. Meanwhile, G4-stabilizing environmental compounds block G4 unwinding by helicases but not G4 cleavage by DNA2. Consequently, G4 stabilizers impair telomere replication and cause telomere instabilities, especially in cells deficient in DNA2 or MSH2.},
}

*MutS Homolog 2 Protein/metabolism/genetics
*Telomere/metabolism/genetics
*DNA Replication
*G-Quadruplexes
Humans
*DNA Helicases/metabolism/genetics
*DNA Repair
Animals

@article {pmid41004216,
year = {2025},
author = {Liu, X and Liu, S and Yu, Y and Song, P and Yang, L and Liu, Z and Zhou, J and Yan, X and Ma, K and Qiu, H and Wang, X and Dong, Q},
title = {Phenotypic and genetically predicted leukocyte telomere length and prostate cancer risk: results from a large-scale longitudinal cohort study.},
journal = {Journal of global health},
volume = {15},
number = {},
pages = {04228},
pmid = {41004216},
issn = {2047-2986},
mesh = {Humans ; Male ; *Prostatic Neoplasms/genetics/epidemiology ; *Leukocytes ; Longitudinal Studies ; Middle Aged ; Aged ; *Telomere/genetics ; Mendelian Randomization Analysis ; United Kingdom/epidemiology ; Prospective Studies ; Phenotype ; Risk Factors ; Proportional Hazards Models ; },
abstract = {BACKGROUND: Previous studies on the correlation between leukocyte telomere length (LTL) and prostate cancer (PCa) have shown inconsistent results. We aimed to clarify this association by leveraging a large-scale prospective design and Mendelian randomisation.

METHODS: We enrolled a total of 229 022 male individuals from the UK Biobank (UKB) to investigate the association between LTL and PCa risk. We employed both unadjusted and covariates-adjusted Cox proportional hazards regression models to assess this relationship. We defined the primary outcome as the diagnosis of incident PCa using in-patient data and the death registry of the UK Biobank cohort. To validate the reliability of the primary findings, we conducted secondary analyses, including Mendelian randomisation.

RESULTS: The primary analysis demonstrated that longer LTL was substantially associated with higher risk of PCa, with associations remaining robust after adjusting for potential covariates (hazard ratio (HR) = 1.444; 95% confidence interval (CI) = 1.247, 1.673, P < 0.001). We observed similar results when LTL was analysed as both a continuous and categorical variable, and the association was shown to be inversely U-shaped. We further validated the association at the genetic level using Mendelian randomisation across different PCa databases, with results consistent with our primary analysis.

CONCLUSIONS: Our findings offer evidence that leukocyte telomere length is an important risk factor for PCa. Further studies are needed to elucidate the underlying mechanisms linking leukocyte telomere length to PCa risk.},
}

Humans
Male
*Prostatic Neoplasms/genetics/epidemiology
*Leukocytes
Longitudinal Studies
Middle Aged
Aged
*Telomere/genetics
Mendelian Randomization Analysis
United Kingdom/epidemiology
Prospective Studies
Phenotype
Risk Factors
Proportional Hazards Models

@article {pmid41002620,
year = {2025},
author = {Canale, P and Andreassi, MG},
title = {Targeting Telomere Shortening in Vascular Aging and Atherosclerosis: Therapeutic Promise of Astragalus membranaceus.},
journal = {Journal of cardiovascular development and disease},
volume = {12},
number = {9},
pages = {},
pmid = {41002620},
issn = {2308-3425},
abstract = {Telomere dysfunction has emerged as a pivotal contributor to vascular senescence, a fundamental process in the pathogenesis of age-related cardiovascular diseases such as atherosclerosis. This connection underscores the therapeutic potential of targeting telomere biology to prevent or mitigate the progression of vascular aging. In this context, Astragalus membranaceus and its bioactive constituents, including astragaloside IV, cycloastragenol, and the commercial telomerase activator TA-65, demonstrate significant promise in attenuating vascular aging and atherosclerotic disease. These compounds exert a range of pleiotropic effects, including anti-inflammatory, antioxidant, endothelial-protective, and lipid-modulating actions, while also modulating telomerase activity and supporting telomere maintenance. This review provides an overview of the mechanistic basis underlying the anti-atherosclerotic effects of Astragalus-derived compounds and underscores critical key knowledge gaps. It also outlines future research directions necessary to validate their efficacy and therapeutic potential in the prevention and treatment of atherosclerosis and other age-related vascular disorders.},
}

@article {pmid41001417,
year = {2025},
author = {Wakai, TN and Anzaku, DO and Afolabi, IS},
title = {Plasmodium telomere maintenance: uncovering the Achilles' heel for novel antimalarials.},
journal = {Frontiers in cellular and infection microbiology},
volume = {15},
number = {},
pages = {1659175},
pmid = {41001417},
issn = {2235-2988},
mesh = {*Antimalarials/pharmacology ; *Telomere/metabolism/drug effects/genetics ; Humans ; *Plasmodium/drug effects/genetics ; Telomerase/metabolism/antagonists & inhibitors ; Malaria/drug therapy/parasitology ; Animals ; G-Quadruplexes/drug effects ; *Telomere Homeostasis/drug effects ; Telomere-Binding Proteins/metabolism ; Protozoan Proteins/metabolism ; },
abstract = {This review examines the potential of disrupting telomere maintenance in Plasmodium as a novel antimalarial strategy. Telomeres are repetitive DNA-protein structures located at chromosome termini, where they preserve genome stability and protect against degradation. Telomere maintenance is crucial for rapid growth, genome integrity, and immune evasion in Plasmodium parasites. Unlike humans, Plasmodium maintains continuous telomerase activity and uses unique telomere-binding proteins across its lifecycle. These features drive parasite virulence and antigenic variation. Emerging evidence suggests that Plasmodium telomeres harbor G-quadruplex (G4) DNA structures, which help stabilize telomeres during replication and may be good targets for small molecules to disrupt their function. Additionally, the parasite depends heavily on its telomerase catalytic subunit, PfTERT, for survival. Inhibiting PfTERT has shown promising results in blocking telomere elongation and impairing replication. Targeting this parasite-specific telomere-telomerase axis may offer a strategic means to destabilize chromosomes, weaken immune evasion, and limit parasite survival, making it a promising antimalarial approach. However, researchers must consider the risks of off-target effects in future drug designs. Though current studies are limited and remain inconclusive, we suggest that future research should investigate combining telomere-directed therapies with existing antimalarials to help overcome resistance and improve treatment outcomes. Herein, we review advances in understanding Plasmodium telomere biology, highlighting its distinct structures, critical telomere-associated proteins, and roles in pathogenesis. We further explore how selective targeting could exploit an Achilles' heel in parasite survival, offering fresh possibilities for next-generation, parasite-specific malaria therapies.},
}

*Antimalarials/pharmacology
*Telomere/metabolism/drug effects/genetics
Humans
*Plasmodium/drug effects/genetics
Telomerase/metabolism/antagonists & inhibitors
Malaria/drug therapy/parasitology
Animals
G-Quadruplexes/drug effects
*Telomere Homeostasis/drug effects
Telomere-Binding Proteins/metabolism
Protozoan Proteins/metabolism

@article {pmid41000148,
year = {2025},
author = {Zhang, F and Cheng, D and Porter, KI and Wang, S and Zhu, J},
title = {Genetic Engineering of Humanized Telomere Mice.},
journal = {Bio-protocol},
volume = {15},
number = {18},
pages = {e5445},
pmid = {41000148},
issn = {2331-8325},
abstract = {Telomere shortening is a hallmark of human aging, and telomerase regulation plays a critical role in cellular proliferation and replicative senescence. In human cells, telomere length imposes a limit on proliferative potential, a phenomenon known as the Hayflick limit. However, species-specific differences in telomere dynamics and telomerase regulation between humans and mice present challenges to using mice as accurate models for human telomere-related research. To address this limitation, we engineered a humanized telomerase gene (hmTert) in mice by replacing the non-coding sequences within the mouse Tert locus (mTert) with corresponding regulatory sequences from the human TERT gene. Breeding of these genetically modified mice resulted in progressive telomere shortening over successive generations, ultimately reaching human-like lengths (below 10 kb). This protocol outlines the development of this humanized telomere mouse model, referred to as HuT mice, offering a robust platform for studying human telomere biology and aging-related diseases. Key features • This protocol describes methods to increase the success rates of knocking in large genomic fragments (~47 kb) by integrating CRISPR-Cas9 with homologous recombination. • It enables precise engineering of a humanized telomerase gene (hmTert), faithfully recapitulating human TERT regulation and telomere length dynamics in mice.},
}

@article {pmid40995488,
year = {2025},
author = {Tian, C and Wu, Q and Chen, F and Wu, Y and Wang, J and Zhang, A and Wang, W},
title = {Dynamic Telomere Length Response to Neurodevelopmental Arsenic Exposure: Insights into Transcriptional Regulation and Neuronal Morphogenesis.},
journal = {Environment & health (Washington, D.C.)},
volume = {3},
number = {9},
pages = {1031-1042},
pmid = {40995488},
issn = {2833-8278},
abstract = {Developmental exposure to arsenic (As) has been linked to irreversible adverse health outcomes in offspring. However, the underlying molecular mechanisms remain a mystery. Here, maternal mice were exposed to As via drinking water. Subsequently, the hippocampi of their offspring were collected at different developmental stages to explore the dynamic changes during hippocampal maturation and the effects of As. Time-series RNA-seq analysis revealed a significant temporal correlation between As neurodevelopmental toxicity and the mRNA expression profile of the hippocampal region during critical postnatal developmental windows. Further, downregulation of genes associated with neurogenesis and telomere maintenance was observed. Notably, dynamic changes in hippocampal telomeres were observed in response to As exposure, with critically shortened telomeres inhibiting neural stem cells (NSCs) proliferation, impairing neuroblast maturation, and reducing the number and size of neurospheres. Additionally, the populations of BrdU[+] and MAP2[+] cells were decreased while GFAP[+] cells were increased, indicating a decline in NSCs stemness. Furthermore, As exposure significantly impaired dendritic complexity in the hippocampus of mice, altered dendritic spine morphology, and disrupted synaptic ultrastructure, ultimately leading to cognitive impairment. These findings highlight the importance of analyzing telomere dynamics in environmental toxicology and offer insights into the neurotoxic mechanisms of maternal As on offspring development.},
}

@article {pmid40995413,
year = {2024},
author = {Hong, HG and Graubard, BI and Gastwirth, JL and Kim, MO},
title = {QUANTILE REGRESSION DECOMPOSITION ANALYSIS OF DISPARITY RESEARCH USING COMPLEX SURVEY DATA: APPLICATION TO DISPARITIES IN BMI AND TELOMERE LENGTH BETWEEN U.S. MINORITY AND WHITE POPULATION GROUPS.},
journal = {The annals of applied statistics},
volume = {18},
number = {3},
pages = {2012-2033},
pmid = {40995413},
issn = {1932-6157},
support = {Z99 CA999999/ImNIH/Intramural NIH HHS/United States ; },
abstract = {We develop a quantile regression decomposition (QRD) method for analyzing observed disparities (OD) between population groups in socioeconomic and health-related outcomes for complex survey data. The conventional decomposition approaches use the conditional mean regression to decompose the disparity into two parts, the part explained by the difference arising from the different distributions in the explanatory covariates and the remaining part, which is unexplained by the covariates. Many socioeconomic and health outcomes exhibit heteroscedastic distributions, where the magnitude of observed disparities varies across different quantiles of these outcomes. Thus, differences in the explanatory covariates may account for varying differences in the OD across the quantiles of the outcome. The QRD can identify where there are greater differences in the outcome distribution, for example, 90th quantile, and how important the covariates are in explaining those differences. Much socioeconomic and health research relies on complex surveys, such as the National Health and Nutrition Examination Survey (NHANES), that oversample individuals from disadvantaged/minority population groups in order to provide improved precision. QRD has not been extended to the complex survey setting. We improve the QRD approach proposed in Machado and Mata (2005) to yield more reliable estimates at the quantiles, where the data are sparse, and extend it to the complex survey setting. We also propose a perturbation-based variance estimation method. Simulation studies indicate that the estimates of the unexplained portions of the OD across quantiles are unbiased and the coverage of the confidence intervals are close to nominal value. This methodology is used to study disparities in body mass index (BMI) and telomere length between race/ethnic groups estimated from the NHANES data.},
}

@article {pmid40994876,
year = {2025},
author = {Farrukh, S and Baig, S and Hussain, R},
title = {Paternal contributions to telomere reprogramming in fetal development.},
journal = {International journal of biochemistry and molecular biology},
volume = {16},
number = {2},
pages = {16-23},
pmid = {40994876},
issn = {2152-4114},
abstract = {OBJECTIVES: Telomere length, the markers of biological aging, can be influenced by risk factors that may lead to health issues like chronic non-communicable diseases. This study explored the paternal telomere length influenced by diseases like diabetes and hypertension with age and its association with newborn telomere length (TL) and the telomerase gene.

METHODS: In this cross-sectional study, 204 father-newborn dyads were recruited. The qPCR was used for the quantification of TL (T/S ratio), and Sanger sequencing was done for telomerase (TERT) genotype identification. Statistical Package for Social Sciences (SPSS) and GraphPad Prism Software were used for data analysis. The Spearman correlation was used to find an association between father and newborn TL. The Kruskal-Wallis and Mann-Whitney test was used to find differences among disease groups and TL. The P<0.05 was considered statistically significant.

RESULTS: A positive correlation (r=0.39) (P<0.0001) was seen among fathers and newborn TL. The mean TL (T/S ratio) was found to be longer in healthy fathers and their newborns (1.67±1.18, 2.36±1.39), whereas significantly shorter TL (1.41±0.98, 2.02±1.58) (P=0.000) was seen in fathers suffering from diseases. The healthy fathers and their newborns TL (2.94±0.72, 3.10±0.61) were seen longer in the 15-20 (yrs) age category. Moreover, newborns of fathers (41-45 yrs) with both diabetes and hypertension had significantly longer telomere length (3.20±2.92) compared to their fathers (1.15±1.65) (P=0.006). The TERT risk genotype AC (rs2736100) was the most prevalent among the newborn girls.

CONCLUSION: A positive association with shorter TL in newborns was found in fathers having chronic diseases such as diabetes and hypertension, highlighting the contribution of fathers in reprogramming newborns' telomere biology.},
}

@article {pmid40994006,
year = {2025},
author = {Wei, Q and Wang, W and Wang, Y and Ai, J and Hu, T and Hu, H and Wang, J and Yan, Y and Pang, H and Hu, N and Bao, C},
title = {A complete telomere-to-telomere genome assembly of Solanum melongena uncovers key regulators in pan-tissue anthocyanin biosynthesis.},
journal = {Plant communications},
volume = {},
number = {},
pages = {101533},
doi = {10.1016/j.xplc.2025.101533},
pmid = {40994006},
issn = {2590-3462},
abstract = {We present the first gap-free and integrated cytogenetic T2T genome assembly of eggplant (Smel HQ v2.0) and shed lights into the specific roles of the SmeMYBs in anthocyanin biosynthesis across various tissues. The complete T2T eggplant genome could substantially facilitate in-depth and refined genetic and genomic studies in eggplants.},
}

@article {pmid40988089,
year = {2025},
author = {DeCleene, NF and Nguyen, DT and Kirk, SE and Helber, HL and Sasa, GS and Bertuch, AA},
title = {The diagnostic performance of the basic versus the detailed telomere Flow FISH test in young patients with aplastic anaemia.},
journal = {British journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/bjh.70155},
pmid = {40988089},
issn = {1365-2141},
support = {GM136554/GM/NIGMS NIH HHS/United States ; },
abstract = {Identifying telomere biology disorders (TBDs) in patients with aplastic anaemia (AA) is essential for guiding appropriate care. Telomere length (TL) measurement by flow cytometry with fluorescence in situ hybridization supports diagnosis, but the real-world performance of the basic test (lymphocytes and granulocytes) versus the detailed test (which includes four lymphocyte subsets) remains unclear. We retrospectively reviewed 439 patients who underwent detailed TL testing at our institution from 2008 to 2022. Haematological disease was present in 87%, with AA comprising 56%. We classified 23 subjects with TBD independently of TL, only one of whom had severe AA (SAA) at initial presentation. Granulocyte numbers were insufficient for TL analysis in 28% of subjects, precluding a rigorous assessment of the impact of granulocyte TL on identification of TBD. Very low TL in lymphocytes or ≥3 lymphocyte subsets identified all TBD cases across AA severity. However, positive predictive value (PPV) was low, particularly in SAA. The detailed test had greater specificity and PPV, particularly in mild AA, which had the greatest proportion of TBD cases among those with AA, supporting its use. However, additional diagnostics, such as genetic testing, remain necessary in many cases to confirm TBD and avoid misclassification.},
}

@article {pmid40987793,
year = {2025},
author = {Raza, W and Pudas, S and Kanninen, KM and Flanagan, E and Degerman, S and Adolfsson, R and Giugno, R and Topinka, J and Zeng, XW and Oudin, A},
title = {Associations between air pollution and relative leukocyte telomere length among northern Swedish adults based on findings from the Betula study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {32660},
pmid = {40987793},
issn = {2045-2322},
mesh = {Humans ; Sweden/epidemiology ; Male ; Female ; *Air Pollution/adverse effects ; *Leukocytes/metabolism ; Aged ; Middle Aged ; *Environmental Exposure/adverse effects ; *Telomere ; *Dementia/epidemiology/etiology/genetics ; *Telomere Homeostasis ; Adult ; Particulate Matter/adverse effects ; Air Pollutants/adverse effects ; Risk Factors ; },
abstract = {Air pollution is increasingly discussed as a risk factor for dementia, but the biological mechanisms are not yet fully understood. Biological markers like telomere length are relevant to study with air pollution, as they are associated with aging and dementia. The study aimed to investigate the relationship between source-specific air pollution exposure and telomere length in a low-level air pollution area, and whether this potential relationship depended on future dementia status. The data originated from the Betula study in Northern Sweden, where 509 participants recruited between 1988 and 1995 were included to investigate the association between annual mean air pollution concentrations at the participants' residences and relative leukocyte telomere length using a linear regression model. No association was observed between air pollution and telomere length, with regression slope estimates close to zero and p-values > 0.10 (e.g. PM2.5_total: β = 0.01 (-0.011, 0.025) and BC_total: β = 0.03 (95% CI: -0.046, 0.114). There were indications of a positive association between longer telomere length and higher exposure to air pollution among individuals later diagnosed with dementia (N = 74), but these findings were not conclusive (p-values > 0.10) (PM2.5_total: β = 0.03, p-value = 0.12; BC_total: β = 0.11, p-value = 0.17). Although not statistically significant, our findings contribute to the evidence from low-exposure settings, and it is important to report these types of findings for a balanced understanding of potential health effects.},
}

Humans
Sweden/epidemiology
Male
Female
*Air Pollution/adverse effects
*Leukocytes/metabolism
Aged
Middle Aged
*Environmental Exposure/adverse effects
*Telomere
*Dementia/epidemiology/etiology/genetics
*Telomere Homeostasis
Adult
Particulate Matter/adverse effects
Air Pollutants/adverse effects
Risk Factors

@article {pmid40987381,
year = {2025},
author = {Davis, RL and Mason, SD and Wake, C and Fabozzi, G and Catalano, WL and Schramm, CA and Henry, AR and Parker, CL and Laboune, F and McLaughlin, CL and Kittilson, JD and Swaddle, JP and Cristol, DA and Heidinger, BJ and Douek, DC},
title = {Chronic Sublethal Exposure to Methylmercury Lengthens Telomeres in Developing Zebra Finches.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {},
number = {},
pages = {127148},
doi = {10.1016/j.envpol.2025.127148},
pmid = {40987381},
issn = {1873-6424},
abstract = {Methylmercury (MeHg) is a widespread environmental pollutant known to cause DNA and chromosomal damage, in part through reactive oxygen species (ROS). Telomeres, essential for chromosomal protection, are highly sensitive to oxidative damage and consequent shortening. While ROS-dependent oxidative stress accelerates telomere attrition in vitro, the mechanisms by which chronic exposure to ROS-inducing exogenous agents affects telomere length in vivo remain unclear. We studied effects of sublethal, multi-generational MeHg exposure on telomere dynamics during early life in zebra finches (Taeniopygia guttata). Continuous exposure to an environmentally relevant concentration of dietary MeHg (1.2 mg/kg) resulted in longer relative telomeres in red blood cells, brain, liver, kidney and lung by sexual maturity. No evidence of selection for longer telomeres across generations of MeHg exposure was observed. Lung protein expression of proliferating cell nuclear antigen (PCNA), a DNA synthesis marker, remained unchanged, suggesting telomere maintenance or elongation occurs independently of proliferation. However, β-Catenin expression, a key transcription factor in Wnt signaling, increased in young MeHg-exposed birds. Transcriptomic analysis of bone marrow revealed up-regulation of oncogenic and pro-inflammatory signaling pathways and down-regulation of mitotic cell cycle pathways. Combined, our data reveal cellular processes reminiscent of tumorigenesis and suggestive of replicative immortality of telomeres under chronic stress.},
}

@article {pmid40986533,
year = {2025},
author = {Tunnicliffe, L and Muzambi, R and Bartlett, JW and Howe, LD and Basit, KA and Asare, K and Gore-Langton, G and Mansfield, KE and Codd, V and Warren-Gash, C},
title = {Infection and telomere length: A systematic review.},
journal = {PloS one},
volume = {20},
number = {9},
pages = {e0333107},
pmid = {40986533},
issn = {1932-6203},
mesh = {Humans ; *Telomere/genetics ; *Telomere Homeostasis ; HIV Infections/genetics ; *Telomere Shortening ; *Infections/genetics ; Aging/genetics ; },
abstract = {BACKGROUND: Infections may increase the risk of age-related diseases such as dementia. Accelerated immunological ageing, measurable by telomere length (TL), may be a potential mechanism. However, the relationship between different infections and TL or telomere attrition remains unclear. This systematic review synthesises existing evidence on whether infections contribute to TL or telomere attrition and highlights research gaps to inform future studies.

OBJECTIVE: To summarise the literature on associations between infections and telomere length or attrition.

METHODS: We conducted comprehensive searches across six databases (MEDLINE, EMBASE, Web of Science, Scopus, Global Health, Cochrane Library) from inception to 22 May 2025, using concepts of infections, TL, and study type. Two researchers independently screened studies, extracted data, and assessed risk of bias (ROB) using the ROBINS-E tool. Meta-analysis was unfeasible due to heterogeneity, so a narrative synthesis was conducted. Studies were grouped by infection type, telomere measurement assay, cell type, and statistical approach. A GRADE assessment was performed to evaluate evidence quality.

RESULTS: Our searches identified 10,349 studies, of which 73 met eligibility criteria. Most (59) were cross-sectional and most were published after 2000, with the earliest from 1996. Most studies were from the USA (17). HIV was the most frequently studied infection (35 studies), with 79% (excluding overlapping samples) reporting an association between HIV and reduced TL or increased telomere attrition. Findings for other infections, including herpesviruses and Human Papillomavirus were more variable. Variation in infection type, measurement assay, cell type, and statistical approach made cross-study comparisons challenging. Most studies had a high ROB, mainly due to unmeasured confounding. The GRADE assessment rated evidence quality as very low.

CONCLUSIONS: Our review highlights a potential link between HIV and TL and telomere attrition. More robust longitudinal studies with standardised measurements and better confounder control are needed, particularly for non-HIV infections. PROSPERO (ID:CRD42023444854).},
}

Humans
*Telomere/genetics
*Telomere Homeostasis
HIV Infections/genetics
*Telomere Shortening
*Infections/genetics
Aging/genetics

@article {pmid40983946,
year = {2025},
author = {Nguyen, L and Choi, JY},
title = {Topsicle: a method for estimating telomere length from whole genome long-read sequencing data.},
journal = {Genome biology},
volume = {26},
number = {1},
pages = {295},
pmid = {40983946},
issn = {1474-760X},
support = {R35 GM154595/GM/NIGMS NIH HHS/United States ; R35GM154595/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Telomere/genetics ; *Whole Genome Sequencing/methods ; *Telomere Homeostasis ; *Software ; },
abstract = {Telomeres protect chromosome ends and their length varies significantly between organisms. Because telomere length variation is associated with various biomedical and eco-evolutionary phenotypes, many biological fields are interested in understanding its biological significance. Here, we introduce Topsicle, a computational method that estimates telomere length from whole genome long-read sequencing data using k-mer and change-point detection analysis. Simulations show Topsicle is robust to sequencing errors and coverage. Application of Topsicle to plant and human cancer cells shows high accuracy and comparable results to direct telomere length measurements. We predict Topsicle will be a useful tool for studying telomere biology.},
}

Humans
*Telomere/genetics
*Whole Genome Sequencing/methods
*Telomere Homeostasis
*Software

@article {pmid40983034,
year = {2025},
author = {Guarnera, L and Wahida, A and Gurnari, C and Hutter, S and Stainczyk, SA and Williams, N and Durmaz, A and Kubota, Y and Bravo-Perez, C and Kawashima, N and Orland, MD and Pagliuca, S and Huang, Y and LaFramboise, T and Visconte, V and Walter, W and Meggendorfer, M and Kern, W and Westermann, F and Feuerbach, L and Haferlach, T and Maciejewski, JP},
title = {Determining telomere content and genomics of myeloid neoplasia by whole-genome sequencing.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2025028644},
pmid = {40983034},
issn = {1528-0020},
abstract = {Telomere length shortening has been associated with genomic instability and acquisition of molecular lesions, but these processes have not been systematically studied across large cohorts of myeloid neoplasia (MN). As proof of concept for a novel, cross-validated WGS-based method of telomere content (TC) determination combined with mutations, transcriptomics, and functional assays, we studied TC in correlation with specific molecular features of a large cohort (n=1804) of MN patients including acute myeloid leukemia (AML) and myelodysplastic syndrome. When compared to healthy subjects and patients with non-clonal diseases such as persistent polyclonal B cell lymphocytosis, both MN and non-malignant controls with clonal disease, such as paroxysmal nocturnal hemoglobinuria and aplastic anemia, exhibited decreased TC. Furthermore, we show that TC is lowered in adult MN abrogating correlation with age with considerable TC diversification among certain morphologic and molecular subtypes. For instance, AML harbored the lowest TC. Furthermore, MN originating from a more mature cell of origin (e.g., APL), and those characterized by hyperproliferative driver mutations (e.g., RAS pathway genes) had lower TC, possibly indicating a loss of telomere maintenance capacity. In contrast, MN subtypes arising in a context of profound genetic alterations, such as TP53 mutations and complex karyotype, exhibited a relatively higher/preserved TC compared to other mutations. This phenomenon did not involve alternative lengthening processes but was rather consistent with an increased TC due to preserved activity of the telomerase complex. Our results describe a common and genotype-specific telomeric make-up of a large cohort of patients with MN providing a molecular benchmark for future therapeutic targeting of the telomere machinery.},
}

@article {pmid40982395,
year = {2025},
author = {Clatterbuck Soper, SF and Meltzer, PS},
title = {A Flexible Procedure for Performing Telomere FISH and Immunofluorescence in Cells Expressing Fluorescent Proteins.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {223},
pages = {},
doi = {10.3791/68977},
pmid = {40982395},
issn = {1940-087X},
mesh = {*In Situ Hybridization, Fluorescence/methods ; *Telomere/genetics/chemistry/metabolism ; Humans ; *Luminescent Proteins/genetics/biosynthesis/analysis/chemistry ; *Fluorescent Antibody Technique/methods ; },
abstract = {Visualizing telomeres using fluorescence in situ hybridization (TelFISH) has long been an essential tool in telomere biology experiments. Combining TelFISH with immunofluorescence (IF) is also a well-established method (IF-TelFISH), for example, in identifying telomere dysfunction-induced foci, where telomeres co-localize with 53BP1. More recently, native telomere FISH (nTelFISH) has become an important tool for assaying Alternative Lengthening of Telomeres, a telomere maintenance mechanism used in some tumor cells. Expressing fluorescent proteins is also an essential tool in cell biology, allowing visualization of proteins and structures that may remain undetectable by other methods. Because FISH buffers denature proteins, performing the assay in cells with an expressed fluorescent protein (FP) results in loss of FP signal. A method for integrating IF and telomere FISH in cells with an expressed fluorescent protein that preserves the FP signal even after FISH is described here. Alternatives are provided for denaturing and native telomere FISH in combination with several IF and FP scenarios. Taken together, this protocol offers a flexible framework for exploring telomere biology in both normal and tumor cells.},
}

*In Situ Hybridization, Fluorescence/methods
*Telomere/genetics/chemistry/metabolism
Humans
*Luminescent Proteins/genetics/biosynthesis/analysis/chemistry
*Fluorescent Antibody Technique/methods

@article {pmid40982211,
year = {2025},
author = {Ruano, JL and Bejarano, L and Serrano, R and Diaz, RA and Flores, JM and López, AC and Blasco, MA},
title = {Depletion of the TRF1 telomere-binding protein leads to leaner mice with altered metabolic profiles.},
journal = {Aging},
volume = {17},
number = {},
pages = {},
doi = {10.18632/aging.206320},
pmid = {40982211},
issn = {1945-4589},
abstract = {TRF1, a component of the telomere shelterin complex, plays crucial roles in telomere protection, telomere length regulation, and stemness. Here, we describe a previously unknown connection between TRF1 and metabolism. Telomere attrition has been linked to obesity. Our study reveals that Trf1-deficient mice exhibit a leaner phenotype, reduced adiposity, and improved glucose tolerance, even when subjected to a high-fat diet, independently of telomere shortening. These findings uncover a previously unknown role of TRF1 in regulating metabolism.},
}

@article {pmid40981352,
year = {2025},
author = {Ruiz-Arias, MA and Bernal-Hernández, YY and Medina-Díaz, IM and Herrera-Moreno, JF and Barrón-Vivanco, BS and Verdín-Betancourt, FA and González-Arias, CA and Flores-Alfaro, E and Ramos, KS and Ostrosky-Wegman, P and Rojas-García, AE},
title = {Comprehensive Biomarker Assessment of Pesticide Exposure and Telomere Attrition in Mexican Children from Agricultural Communities.},
journal = {Journal of xenobiotics},
volume = {15},
number = {5},
pages = {},
pmid = {40981352},
issn = {2039-4713},
support = {This work was partially supported by CONAHCyT (Grant #314829).//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; },
abstract = {Children are more vulnerable to the adverse effects of pesticides due to physiological factors and behavioral habits. This study aimed to evaluate the impact of pesticide exposure on telomere length (TL) and the enzymatic activity of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and β-glucuronidase (β-Glu) in children ages 6 to 12 from an agricultural area in Mexico. A cross-sectional, descriptive, and analytical study was conducted involving 471 children. Blood samples were collected to assess TL through qPCR and enzymatic activity using established protocols. A pesticide exposure index (PEI) was developed incorporating biomarker levels, urinary dialkylphosphates (DAP), and proximity to farmland. No significant differences were observed in AChE activity across communities; however, BuChE activity was significantly higher in agricultural communities, while β-Glu activity varied among communities. Notably, children aged 6 in agricultural areas showed TL values similar to 12-year-old children in the reference community. Adjusted regression models revealed significantly shorter TL in children from agricultural communities and in children with moderate to high PEI. The findings indicate that chronic pesticide exposure was associated with telomere shortening in children, suggesting accelerated biological aging and potential genomic instability during critical developmental periods.},
}

@article {pmid40979377,
year = {2025},
author = {Ershova, ES and Umriukhin, PE and Zinchenko, RA and Vasilieva, TP and Kostyuk, SE and Shabalin, NY and Salimova, TA and Malinovskaya, EM and Veiko, NN and Kostyuk, SV},
title = {Variation in the Content of Three Tandem Repeats of the Human Genome (Ribosomal, Satellite III, and Telomere) in Peripheral Blood Leukocyte DNA of People of Different Ages (5-101 Years).},
journal = {Journal of aging research},
volume = {2025},
number = {},
pages = {8847073},
pmid = {40979377},
issn = {2090-2204},
abstract = {The variation of ribosomal (parameter R), satellite III (1q12) (parameter S), and telomere (parameter T) tandem repeats content of the human genome was studied in DNA samples isolated from blood leukocytes of 535 people whose age varied from 5 to 101 years. For analysis we used the method of nonradioactive quantitative hybridization. The group of centenarians (90-101 years old, N = 106) differs from other age groups by a significantly narrower distribution of the ribosomal repeat content in DNA, a much higher content of satellite III, and a lower content of telomere repeat. A negative correlation was found between the S and T parameters (p < 10[-4]). The findings of this study suggest that the calculated parameters S/T and S/(R∗T) exhibit a marked increase with age, culminating in maximal values within the cohort of centenarians. These results imply that the parameters R, S/T, and S/(R∗T) may hold the potential to serve as reliable predictors of life expectancy for individuals in advanced age.},
}

@article {pmid40975488,
year = {2025},
author = {Xu, S and Liu, Q and Yang, T and Han, Z},
title = {A telomere-to-telomere genome assembly of the large yellow croaker provides insights into evolution of golden-yellow coloration.},
journal = {Journal of genetics and genomics = Yi chuan xue bao},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jgg.2025.09.006},
pmid = {40975488},
issn = {1673-8527},
abstract = {The large yellow croaker (Larimichthys crocea) is a flagship marine fish in China given its extreme commercial value and golden-yellow coloration. However, the genetic mechanisms underlying golden-yellow coloration remain unclear. Here, we construct a telomere-to-telomere gap-free genome assembly (T2T-Larcro_1.0) spanning 716.87 Mb, with a contig N50 of 31.75 Mb. Compared to the current reference genome (L_crocea_2.0), T2T-Larcro_1.0 incorporates 112.70 Mb of previously unassembled regions and 2368 newly anchored genes. This assembly facilitates comparative genomics analyses in sciaenids by identifying several candidate genes (e.g., OPNVA, nNOS, RDH13) potentially involved in evolution of golden-yellow coloration. Transcriptomic analyses further confirm expression of OPNVA-encoded vertebrate ancient opsin (VA opsin) in skin tissues of the large yellow croaker, suggesting its role as an extraretinal photoreceptor regulating localized golden-yellow coloration. Integrating genomics and transcriptomics results, our results uncover the triggering effect of VA opsin linking skin and neural photoreception to physiological regulation of body color change (golden-yellow to silvery-white) in L. crocea. Collectively, our findings provide molecular evidence that elucidate the underlying evolutionary mechanism of golden-yellow coloration in L. crocea. This high-quality genome assembly also serves as an improved resource for biological evolution, genetic improvement, and selective breeding of L. crocea.},
}

@article {pmid40975053,
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 = {Current biology : CB},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.cub.2025.08.052},
pmid = {40975053},
issn = {1879-0445},
abstract = {Telomeres are composed of specialized DNA, RNA, and proteins that interact to preserve the integrity of chromosome termini.[1][,][2] Despite this vital function, telomere length varies dramatically within and between species. Genome-wide association studies have identified multiple genes that explain a portion of this variation,[3] suggesting that telomere length is inherited as a classic quantitative trait. However, telomere length is also directly inherited as a DNA sequence. Here, we show that neither the polygenic nor the direct inheritance 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 observed differences in 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 {pmid40973456,
year = {2025},
author = {Červenák, F and Virágová, S and Sopkovičová, M and Kodada, D and Galla, E and Sepšiová, R and Procházková, K and Tomáška, Ľ},
title = {Runaway evolution of telomeres in ascomycetous yeasts was accompanied by the replacement of ancestral telomeric proteins.},
journal = {Nucleic acids research},
volume = {53},
number = {17},
pages = {},
pmid = {40973456},
issn = {1362-4962},
support = {APVV-19-0068//Slovak Research and Development Agency/ ; APVV-23-0056//Slovak Research and Development Agency/ ; 1/0031/24//Ministry of Education, Science, Research and Sport of the Slovak republic/ ; 1R01ES031635-05/NH/NIH HHS/United States ; //European Regional Development Fund/ ; APVV-23-0056//Slovak Research and Development Agency/ ; },
mesh = {*Telomere-Binding Proteins/metabolism/genetics/chemistry ; *Telomere/metabolism/genetics/chemistry ; *Evolution, Molecular ; Schizosaccharomyces pombe Proteins/metabolism/genetics/chemistry ; Schizosaccharomyces/genetics/metabolism ; Saccharomyces cerevisiae Proteins/metabolism/genetics/chemistry ; Saccharomyces cerevisiae/genetics/metabolism ; Yarrowia/genetics ; Phylogeny ; Shelterin Complex ; *Fungal Proteins/metabolism/genetics/chemistry ; Protein Binding ; },
abstract = {Telomeres are crucial parts of eukaryotic chromosomes, contributing to DNA replication, chromosome segregation, and genome stability. While in most phylogenetic lineages, telomere-maintenance systems are conserved, ascomycetous yeasts exhibit a high degree of variability in telomeric repeats and the associated proteins. The determinants that enabled this divergent evolutionary process, however, have been unclear. Here, we show that DNA-binding properties of yeast telomere-binding proteins (TBPs) support the scenario where the gradual divergence of telomeric repeats led to their replacement. We analyzed the DNA-protein interactions between Tay1p from Yarrowia lipolytica, Rap1p from Saccharomyces cerevisiae, and Taz1p from Schizosaccharomyces pombe and a set of telomeric repeats from several yeast species and delineated how the ancestral (Tay1p-like) TBPs were replaced by Rap1p (in budding yeasts) or Taz1p (in fission yeasts). We also postulate two different driving forces for these replacements: (i) Tay1p-to-Rap1p transition appears to be driven by differences in sequence preferences of Tay1p and Rap1p, while (ii) Taz1p became the principal TBP in fission yeast presumably due to its DNA-binding flexibility. Together, our results suggest that in telomeric DNA-protein complexes, the replacement of protein component triggered by the initial variation in DNA sequence space opens the door to further divergence in a runaway-style evolution.},
}

*Telomere-Binding Proteins/metabolism/genetics/chemistry
*Telomere/metabolism/genetics/chemistry
*Evolution, Molecular
Schizosaccharomyces pombe Proteins/metabolism/genetics/chemistry
Schizosaccharomyces/genetics/metabolism
Saccharomyces cerevisiae Proteins/metabolism/genetics/chemistry
Saccharomyces cerevisiae/genetics/metabolism
Yarrowia/genetics
Phylogeny
Shelterin Complex
*Fungal Proteins/metabolism/genetics/chemistry
Protein Binding

@article {pmid40969732,
year = {2025},
author = {Bragina, A and Tarzimanova, A and Druzhinina, N and Vasileva, L and Novikov, K and Loriya, I and Avdeenko, O and Samohlib, Y and Vlasova, N and Savina, E and Makarenko, P and Podzolkov, V},
title = {Telomere Length in Young Patients: Relationship With Metabolic Syndrome and Its Components.},
journal = {Journal of clinical medicine research},
volume = {17},
number = {8},
pages = {460-467},
pmid = {40969732},
issn = {1918-3003},
abstract = {BACKGROUND: Previous studies have reported inconsistent findings on the relationship between telomere length and metabolic syndrome (MS). The aim of the work was to study leukocyte telomere length in young patients without cardiovascular diseases and its relationship with MS and its components.

METHODS: This study included 450 Caucasian patients with a median age of 30 (21 - 42) years. Glycemic parameters and lipid profile components were determined using the CardioChek PA (USA, 2017). Integral metabolic indices were calculated in all patients. To investigate leukocyte telomere length, 45 were randomly selected from the total cohort of 450 participants.

RESULTS: The selected patients were divided into two groups according to the presence of MS. The median telomere length in MS patients (7.36 (6.96 - 8.67) pn) was significantly lower than in the comparison group (8.72 (8.37 - 8.96) pn) (P = 0.016). Correlation analysis was performed to assess the relationship between telomere length and various traditional cardiovascular risk factors (sex, age, smoking, and blood pressure levels), MS components, and integral metabolic indices. Several linear regression analysis models were constructed to assess the independent associations between various factors and telomere length. Age, smoking, neck circumference, triglycerides, high-density lipoprotein levels, LAP index, and the presence of dyslipidemia were significantly associated with telomere length.

CONCLUSION: Our results are consistent with the notion of shorter leukocyte telomere length in individuals with MS and support an association with dyslipidemia in premature shortening of telomere length. The causal relationship between these changes requires further study.},
}

@article {pmid40967766,
year = {2025},
author = {El Husseini, K and Lee, JS and Juge, PA and Ebstein, E and Ottaviani, S and Borie, R and Bancal, C and Debray, MP and Kannengiesser, C and Ba, I and Marchand-Adam, S and Richez, C and Nunes, H and Avouac, J and Flipo, RM and Wemeau, L and Boissier, MC and Schaeverbeke, T and Kermanac'h, NS and Kawano-Dourado, L and Cottin, V and Wolters, PJ and Granger, B and Dieudé, P and Crestani, B},
title = {Short telomere length is associated with accelerated lung disease progression in rheumatoid arthritis-associated interstitial lung disease.},
journal = {The European respiratory journal},
volume = {},
number = {},
pages = {},
doi = {10.1183/13993003.00587-2025},
pmid = {40967766},
issn = {1399-3003},
abstract = {BACKGROUND: Shorter leukocyte telomere length (LTL) has been reported in patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) and linked to increased disease severity and mortality in idiopathic pulmonary fibrosis, which shares similarities with RA-ILD. We aimed to evaluate the impact of short LTL on baseline respiratory disease severity, disease progression and survival in patients with RA-ILD.

METHODS: Patients diagnosed with RA-ILD following multidisciplinary assessment were enrolled in a prospective French observational study. LTL was measured at enrolment using qPCR. Short LTL was defined as age-adjusted LTL<10th percentile. Lung disease progression was defined as death, lung transplant or functional respiratory decline (absolute decrease in forced vital capacity (FVC) ≥5%predicted, transfer capacity (TLCO) ≥10%predicted).

RESULTS: Among 101 patients with RA-ILD, 46% were male, mean age at enrolment was 66±10 years and 43 (43%) had short LTL. Patients with short LTL had lower FVC (82% versus 93%predicted) and TLCO (49% versus 63%predicted) at enrolment, and greater 12-months decline in FVC and DLCO in mixed effects models (-7.7%pred. 95%CI[-11.6,-3.8] p<0.001, -4.5%pred. [-7.2, -1.8] p=0.001, respectively), although transplant-free survival was similar over a median follow-up of 3.6 years (IQR[1.8,7.0]). Lung disease progression was observed within 12 months of enrolment in 33 patients (33%), more frequently in patients with short LTL (47% versus 22%, p univariate=0.011) and lower FVC at enrolment. Multivariate logistic regression identified lower FVC and short LTL as predictors of 12-month progression (OR 0.97 95%CI[0.94,1.00] p=0.031 and 2.80 [0.99,8.29] p=0.056, respectively).

CONCLUSIONS: Short LTL is associated with baseline severity and 12-month progression in RA-ILD.},
}

@article {pmid40964771,
year = {2025},
author = {Yang, MM and Liu, S and Wax, M and Lee, S and French, S and Wolters, PJ and Boin, F},
title = {Telomere Length of Peripheral Blood Leukocytes Predicts Disease Severity and Worse Survival in Systemic Sclerosis.},
journal = {Arthritis & rheumatology (Hoboken, N.J.)},
volume = {},
number = {},
pages = {},
doi = {10.1002/art.43400},
pmid = {40964771},
issn = {2326-5205},
abstract = {OBJECTIVE: Peripheral blood leukocyte telomere length (PBL-TL) shortening is associated with systemic sclerosis related interstitial lung disease (SSc-ILD). However, its association with other organ involvement, disease severity, and survival remains unclear. This study aimed to define the relationship of TL with SSc-specific disease manifestations and outcomes.

METHOD: PBL-TL was measured by quantitative PCR in 244 patients with SSc and 314 healthy controls. Multivariate modeling was utilized to assess the association of PBL-TL with disease severity and event-free survival. Longitudinal changes in PBL-TL were measured in a subset of patients. Telomere length was quantified in SSc skin and lung tissues by telomere fluorescence in situ hybridization.

RESULTS: PBL-TL was significantly shorter in patients with SSc than healthy controls. Shortened PBL-TL was associated with presence and severity of ILD and pulmonary hypertension (PH) with the shortest PBL-TL found in subjects with concurrent ILD and PH (p=0.04). PBL-TL was not associated with skin disease or peripheral vascular disease. Shorter PBL-TL was associated with hospitalizations (p<0.01) and worse event-free survival (p=0.03). Patients with early SSc had a faster rate of PBL-TL shortening compared to patients with longer disease duration (p = 0.04). TL was shorter in SSc-ILD lung epithelial cells (p=0.01) while no difference was found in epithelial cells of SSc skin (p=0.82).

CONCLUSION: Short PBL-TL is associated with pulmonary disease severity and predicts worse SSc clinical outcomes. This study provides rationale to further investigate the role of telomere dysfunction in SSc pathogenesis and validate TL as a prognostic biomarker in SSc.},
}

@article {pmid40958330,
year = {2025},
author = {Liu, Q and Gu, Y and Huang, H and Ren, J and Liu, Y and Wang, D},
title = {Platelet-to-lymphocyte ratio and telomere length in older adults: An inverted U-shaped nonlinear relationship: A nationwide cohort study.},
journal = {Medicine},
volume = {104},
number = {37},
pages = {e44188},
pmid = {40958330},
issn = {1536-5964},
support = {2024ZZ2072//Shanghai Municipal Health Commission Medical New Technology Research and Transformation Seed Project/ ; 2024MZYS09//Training Program for High-Level Specialist Physicians under the Collaborative Health Service System of Education, Research, and Clinical Practice in Minhang District, Shanghai City(2024-2027)/ ; 2023MHZ046//The Natural Science Research Project in Minhang District, Shanghai City/ ; },
mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; *Blood Platelets ; *Lymphocytes ; *Telomere ; Cohort Studies ; Platelet Count ; Nutrition Surveys ; Nonlinear Dynamics ; *Telomere Homeostasis ; Aged, 80 and over ; },
abstract = {This study aimed to investigate the association between the platelet-to-lymphocyte ratio (PLR) Log and telomere length in older adults, focusing on the potential nonlinear relationship within a nationwide cohort. Data were obtained from the National Health and Nutrition Examination Survey 1999 to 2000 and 2001 to 2002 cycles, including 2660 participants aged 60 years and older. PLR Log was calculated as the log-transformed value of PLR, which was further analyzed as both a continuous variable and in quartiles. Mean telomere length (TeloMean) was measured using quantitative PCR. Linear regression, trend tests, smooth curve fitting, and segmented regression were employed to evaluate the relationship between PLR Log and TeloMean, adjusting for potential confounders. Subgroup analyses were conducted to assess variations in associations across age, sex, and other variables. An inverted U-shaped nonlinear relationship was identified between PLR Log and TeloMean. Trend analysis demonstrated a significant trend across quartiles of PLR Log in both the minimally adjusted (P for trend = .021) and fully adjusted models (P for trend = .048). Threshold effect analysis identified a breakpoint at PLR Log = 5.564, where TeloMean significantly increased with PLR Log when below this threshold (β1 = 0.034, 95% CI: 0.012-0.057, P = .003), but decreased when PLR Log exceeded this threshold (β2 = -0.115, 95% CI: -0.221 to -0.009, P = .033). This association was more pronounced in participants aged 66 to 74 years (P for interaction = .005). This study provides new insights into the relationship between systemic inflammation and telomere dynamics in older adults. The observed inverted U-shaped relationship suggests that moderate levels of inflammation may help maintain telomere integrity, possibly through improved immune regulation, while excessive inflammation may accelerate telomere attrition due to increased oxidative stress and impaired DNA repair mechanisms. These findings highlight PLR Log as a potential inflammatory biomarker for aging-related telomere dynamics and emphasize the need for further longitudinal studies to validate these associations.},
}

Humans
Male
Female
Aged
Middle Aged
*Blood Platelets
*Lymphocytes
*Telomere
Cohort Studies
Platelet Count
Nutrition Surveys
Nonlinear Dynamics
*Telomere Homeostasis
Aged, 80 and over

@article {pmid40954016,
year = {2025},
author = {Sánchez-Vázquez, R and Burgaz García-Oteyza, S and Serrano, R and Flores, JM and Martínez, P and Blasco, MA},
title = {Mice carrying the homologous human shelterin POT1-L259S mutation linked to pulmonary fibrosis show a telomerase deficiency-like phenotype with telomere shortening with increasing mouse generations.},
journal = {Genes & development},
volume = {},
number = {},
pages = {},
doi = {10.1101/gad.352855.125},
pmid = {40954016},
issn = {1549-5477},
abstract = {Pulmonary fibrosis is a lethal disease associated with damaging insults to the lung and with organismal aging. The presence of short and dysfunctional telomeres has been placed at the origin of this disease in a percentage of both familial and sporadic cases. Recently, a mutation in the telomere-binding protein protection of telomeres 1 in humans (hPOT1), the hPOT1 L259S mutation, was found in families with idiopathic pulmonary fibrosis. Here, we generated a Pot1a [L261S] knock-in mouse harboring the murine homologous hPOT1 L259S mutation. We found that the homozygous Pot1a [L261S] mice show shorter telomeres and degenerative pathologies in the intestine, testes, and lungs at old ages, a phenotype that is aggravated with increasing mouse generations, in striking analogy to the telomerase-deficient mouse models. Furthermore, we found that the POT1a-L261S mutant protein binds more strongly to TPP1 and to telomerase and impedes telomerase-dependent telomere lengthening in vivo. We show that telomerase activity at telomeres is reduced in the presence of POT1a-L261S, which behaves as a dominant negative mutant, thus providing a potential mechanism by which Pot1a [L261S] knock-in mice phenocopy the short telomere phenotype of the telomerase knockout model.},
}

@article {pmid40953361,
year = {2025},
author = {Le, AD},
title = {Tracing Toxic Stress Through Telomeres: A Future Physician-Scientist's Path.},
journal = {Academic medicine : journal of the Association of American Medical Colleges},
volume = {},
number = {},
pages = {},
doi = {10.1097/ACM.0000000000006283},
pmid = {40953361},
issn = {1040-2446},
}

@article {pmid40950970,
year = {2025},
author = {Matviichuk, A and Krasnienkov, D and Yerokhovych, V and Ilkiv, Y and Korcheva, V and Gurbych, O and Shcherbakova, A and Botsun, P and Falalyeyeva, T and Sulaieva, O and Kobyliak, N},
title = {Association of leukocyte telomere length and HbA1c with post-COVID-19 syndrome in type 2 diabetes: a cross-sectional pilot study.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1628156},
pmid = {40950970},
issn = {2296-858X},
abstract = {INTRODUCTION: Leukocyte telomere length is considered a promising prognostic marker associated with COVID-19 severity, adverse outcomes (hospital admission, need for critical care, and respiratory support), and mortality. However, the contribution of telomere length to post-COVID-19 syndrome (PCS) development is unclear.

AIM: This study aimed to evaluate the association between telomere shortening and the course of PCS in patients with type 2 diabetes (T2D) and to determine whether telomere length is linked to clinical phenotype, gender, and biological age.

MATERIALS AND METHODS: In this cross-sectional study, 66 T2D patients who had recovered from COVID-19 were enrolled. Patients were divided into two groups depending on PCS development: the PCS group (n = 44) and patients who did not develop PCS (n = 22) within 6 months after COVID-19 infection. Relative telomere length was determined using the standardized method proposed by Cawthon et al. A range of machine learning models was developed for PCS prediction. These models underwent training utilizing a cross-validation approach, as well as internal validation.

RESULTS: We observed a significantly lower mean of telomere length in T2D patients with PCS as compared to those without it (1.09 ± 0.19 and 1.28 ± 0.24; p = 0.001). In the sub-analysis, shorter telomeres were observed in female patients and patients of older age in both groups. The mean telomere length did not differ significantly among clinical phenotypes of PCS (p = 0.193). The best model generated for PCS prediction was the gradient boosting machine (GBM), which achieved an AUC of 0.753. The most influential variables across the top 10 models included telomere length, HbA1c, vitamin D3, waist circumference, ApoA1, C peptide, ApoB, COVID-19 severity, duration of T2D, IL-6, cholesterol, BMI, and age. Leukocyte telomere length and HbA1c exhibited significantly greater impact than other features.

CONCLUSION: Shorter telomere length and higher HbA1c levels were significantly associated with the presence of PCS in our cohort of individuals with T2D. These factors may represent potential biomarkers that warrant further investigation.},
}

@article {pmid40947687,
year = {2025},
author = {Khodabandelu, S and Jahankhah, S and Shabestari, NM and Eghbal, Y and Khaleghi, S and Hajizadeh, A and Ghaheri, SZ and Jafari, M and Vosough, M and Rahmanian, M},
title = {The Association Between Telomere Length and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.},
journal = {Current molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115665240360593250805102356},
pmid = {40947687},
issn = {1875-5666},
abstract = {INTRODUCTION: Studies have stated that there has been a close association between the telomere length (TL) and the incidence of non-alcoholic fatty liver disease (NAFLD). The goal of this report is to explore the possible association between TL and NAFLD.

METHODS: This study adhered to the PRISMA guidelines for systematic reviews. An extensive literature search was conducted in the Cochrane Library, CINAHL, Scopus, PubMed, and Web of Science. The "meta" package in the R programming language, version 4.3.1, was used for statistical analysis.

RESULTS: The meta-analysis of the included studies showed a pooled standard mean difference (SMD) of -0.25 (95% CI: -0.39 to -0.10), indicating shorter TL in NAFLD patients. Subgroup analyses revealed significant TL shortening in NAFLD patients with body mass index (BMI) <28 (SMD = -0.68, 95% CI: -0.96 to -0.39) and in case-control (-0.35, 95% CI: -0.51 to -0.20) and cohort studies (-0.68, 95% CI: -1.19 to -0.17). An odds ratio (OR) meta-analysis of six studies found that individuals with short TL had 1.72 times higher odds of NAFLD, which was statistically significant (95% CI: 1.23- 2.42, I2 = 85%). Excluding one study reduced heterogeneity (I2 = 37%) and increased the OR to 1.93 (95% CI: 1.45-2.56), confirming a strong association between short TL and NAFLD risk.

DISCUSSION: The findings suggest a potential link between shorter TL and NAFLD. The odds ratio analyses further emphasized the increased risk of NAFLD in individuals with short TL. Nevertheless, the residual heterogeneity highlights the need for further high-quality, standardized research.

CONCLUSION: Our findings supported the connection between reduced TL and NAFLD. Regardless of significant between-study diversity, the results remained consistent even after repeated sensitivity evaluations. Despite these findings, the high heterogeneity highlights the need for further well-designed studies to confirm TL as a reliable biomarker for NAFLD risk and progression.},
}

@article {pmid40936085,
year = {2025},
author = {Giffoni, FC and Gomes, TEC and de Souza, PN and Silva, PVE and Magno, LAV and Cândido, AL and Lasmar, MF and de Oliveira Neto, SG and Ferreira, MVL and Araujo, TMG and Dos Santos, LI and Chrcanovic, BR and Gomez, RS and Martins-Chaves, RR},
title = {Investigation of the Telomere Length in PERI-Implant Oral Mucosa Cells.},
journal = {Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology},
volume = {},
number = {},
pages = {},
doi = {10.1111/jop.70061},
pmid = {40936085},
issn = {1600-0714},
support = {//Fundação de Amparo à Pesquisa do Estado de Minas Gerais/ ; //Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; },
abstract = {BACKGROUND: The biological effects of dental implants on peri-implant tissues have been widely investigated. Recent reports of oral squamous cell carcinoma (OSCC) cases adjacent to dental implants have raised concerns regarding the potential impact of implant materials on cellular aging and oncogenic transformation. Telomeres, which protect chromosome ends, undergo progressive shortening and play a critical role in cellular senescence and tumorigenesis. However, the impact of dental implants on telomere length in peri-implant mucosa remains unclear.

OBJECTIVE: This study aimed to compare telomere length in mucosa adjacent to dental implants with that of gingival tissue associated with healthy teeth.

METHODS: A paired cross-sectional study was conducted with 16 patients who had dental implants for at least 1 year. Swabs were collected from the peri-implant mucosa and healthy gingival mucosa of the same patient. Telomere length was assessed using quantitative PCR, with the relative telomere-to-single-copy-gene ratio (T/C) calculated using the 2[-∆∆Cq] method.

RESULTS: Telomere length in the peri-implant mucosa was not significantly different from that in the healthy gingival mucosa (p = 0.117).

CONCLUSION: These findings suggest that dental implants do not alter telomere length in adjacent mucosal cells.},
}

@article {pmid40934081,
year = {2025},
author = {Dufourd, J and Huynh, THY and Sauzet, S and Lai, QH and Abagnale, F and Zitouni, S and Giraud-Panis, MJ and Urbach, S and Gilson, E and Tardat, M and Déjardin, J},
title = {TELS1 stabilizes t-loops independently of TRF2 and controls telomere length in pluripotent cells.},
journal = {Cell reports},
volume = {44},
number = {9},
pages = {116260},
doi = {10.1016/j.celrep.2025.116260},
pmid = {40934081},
issn = {2211-1247},
abstract = {Telomeric loops (t-loops) are thought to protect chromosome ends, with their stabilization generally requiring the shelterin protein TRF2. However, the mechanisms operating in pluripotent cells remain unknown. Here, we identify TELS1 as a TRF2-independent t-loop stabilizer in pluripotent cells. TELS1 binds single-stranded, G-rich telomeric DNA tracts likely present within duplex telomeric regions and promotes strand invasion in vitro, consistent with a direct role in t-loop formation. When targeted to telomeres in differentiated cells, TELS1 is able to substitute for TRF2 in making the t-loop, which partially protects from ATM activation. In TELS1-deficient pluripotent cells, telomeres lack t-loops but remain protected and become more accessible to telomerase, resulting in elongation. A genome-wide CRISPR screen identifies Ubr5 as essential for this tolerance. These findings validate the t-loop as an essential structure for end protection and uncover a telomere protection pathway unique to pluripotent cells that appears to function independently of shelterin.},
}

@article {pmid40930178,
year = {2025},
author = {Wen, DN and Hu, JH and Ji, T and Xiao, XY and Huang, CX and Zhang, JF and Feng, WB and Zheng, S and Xiong, ZY and Hou, CL},
title = {Alterations of telomere length and mitochondrial DNA copy number in depressive adolescents with non-suicidal self-injury.},
journal = {Journal of affective disorders},
volume = {},
number = {},
pages = {120268},
doi = {10.1016/j.jad.2025.120268},
pmid = {40930178},
issn = {1573-2517},
abstract = {BACKGROUND: NSSI among adolescents is highly prevalent and serves as a significant indicator of subsequent suicidal ideation and behaviors. Recent studies have demonstrated a connection between accelerated cellular aging and a range of psychiatric conditions. The present study explored whether depressive adolescents with NSSI exhibited alterations in telomere length (TL) and mitochondrial DNA copy number (mtDNAcn), both critical markers of cellular aging.

METHODS: The study comprised 70 depressive adolescents with NSSI (84.3 % female) and 34 depressive adolescents without NSSI (61.8 % female). The TL and mtDNAcn were determined by calculating the ratio of telomere repeats to the single-copy gene β-globin, or by measuring the relative quantity of mtDNA compared to β-globin.

RESULTS: In this study, the NSSI group demonstrated significantly shorter TL than the non-NSSI group (P < 0.01). This difference persisted after controlling for age, family history, sex, suicidality, childhood maltreatment, depressive symptoms, and psychotic symptoms (P = 0.005). Furthermore, regression analysis showed that TL was considerably shorter in the female NSSI group than in the non-NSSI group after adjusting for age, family history, suicidality, childhood maltreatment, depressive symptoms, and psychotic symptoms (P < 0.001). After controlling for these variables, mtDNAcn was markedly reduced in the male NSSI group compared to the non-NSSI group (P < 0.001).

CONCLUSIONS: This work is, to our knowledge, the first to demonstrate that NSSI correlates with alterations in TL and mtDNAcn. These findings suggest that molecular pathways associated with aging may play a crucial role in the pathogenesis of NSSI.},
}

@article {pmid40930086,
year = {2025},
author = {Rivadeneira, DB and Thosar, S and Quann, K and Gunn, WG and Dean, VG and Xie, B and Parise, A and McGovern, AC and Spahr, K and Lontos, K and Barnes, RP and Bruchez, MP and Opresko, PL and Delgoffe, GM},
title = {Oxidative-stress-induced telomere instability drives T cell dysfunction in cancer.},
journal = {Immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.immuni.2025.08.008},
pmid = {40930086},
issn = {1097-4180},
abstract = {The tumor microenvironment (TME) imposes immunologic and metabolic stresses sufficient to deviate immune cell differentiation into dysfunctional states. Oxidative stress originating in the mitochondria can induce DNA damage, most notably telomeres. Here, we show that dysfunctional T cells in cancer did not harbor short telomeres indicative of replicative senescence but rather harbored damaged telomeres, which we hypothesized arose from oxidative stress. Chemo-optogenetic induction of highly localized mitochondrial or telomeric reactive oxygen species (ROS) using a photosensitizer caused the accumulation of DNA damage at telomeres, driving telomere fragility. Telomeric damage was sufficient to drive a dysfunctional state in T cells, showing a diminished capability for cytokine production. Localizing the ROS scavenger GPX1 directly to telomeres reduced telomere fragility in tumors and improved the function of therapeutic T cells. Protecting telomeres through expression of a telomere-targeted antioxidant may preserve T cell function in the TME and drive superior responses to cell therapies.},
}

@article {pmid40926757,
year = {2025},
author = {Pott, J and Höing, AS and Volk, A and Well, L and Beier, F and Lebrecht, D and Harbaum, L and Klose, H and Oqueka, T},
title = {Telomere biology disorder associated lung disease- case report of a TERT gene variant as the cause of pleuroparenchymal fibroelastosis.},
journal = {Chronic respiratory disease},
volume = {22},
number = {},
pages = {14799731251370357},
pmid = {40926757},
issn = {1479-9731},
mesh = {Humans ; Genetic Testing ; *Lung Diseases, Interstitial/genetics ; *Telomerase/genetics ; Telomere/genetics ; *Telomere Shortening/genetics ; Tomography, X-Ray Computed ; },
abstract = {Case presentationDescription of a patient with a progressive destructive lung disease resembling pleuroparenchymal fibroelastosis, liver cirrhosis and bone marrow changes. Genetic workup identified a rare heterozygous coding variant in the TERT (telomerase reverse transcriptase) gene c.472 C>T; p.(Leu158Phe) and telomere length testing revealed significant telomere shortening, supporting the diagnosis of telomere biology disorder (TBD).DiscussionTBD is an underrecognized cause of interstitial lung disease (ILD). It is a heterogeneous disease that can affect different organs, including lungs, liver and bone marrow. Genetic testing in ILD is crucial for early diagnosis, risk assessment, and family screening. Identifying this variant enables targeted genetic testing for relatives, allowing preventive measures and lifestyle modifications.},
}

Humans
Genetic Testing
*Lung Diseases, Interstitial/genetics
*Telomerase/genetics
Telomere/genetics
*Telomere Shortening/genetics
Tomography, X-Ray Computed

@article {pmid40925232,
year = {2025},
author = {Tara, SA and Zekri, A and Sotoodehnejadnematalahi, F and Modarressi, MH},
title = {Aurora B inhibition induces polyploidy and mitotic catastrophe in HER2-amplified breast cancer: Telomere shortening as a potential anticancer mechanism of AZD1152-HQPA.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {191},
number = {},
pages = {118509},
doi = {10.1016/j.biopha.2025.118509},
pmid = {40925232},
issn = {1950-6007},
abstract = {Polyploidy, a conserved mechanism involved in normal development and tissue homeostasis, plays a paradoxical role in cancer by facilitating both tumor progression and therapeutic vulnerability. Although polyploidization may confer survival advantages to cancer cells, its controlled induction could represent an effective anticancer strategy. Aurora B kinase, a critical regulator of mitosis, plays a pivotal role in ensuring chromosomal integrity and preventing polyploidy. However, its role in chromosome ploidy and telomere length maintenance in breast cancer remains insufficiently explored. In this study, we identified a significant association between Aurora B overexpression and poor prognosis exclusively in patients with HER2-amplified breast cancer. Treatment with AZD1152-HQPA, a selective Aurora B kinase inhibitor, significantly reduced cell viability and colony-forming potential, with a pronounced effect on HER2-amplified breast cancer cell lines. Importantly, we found that Aurora B inhibition is sufficient to induce polyploidy/multinucleation (8 N and 16 N), cellular enlargement, and mitotic catastrophe. Furthermore, we observed telomere shortening, downregulation of the human telomerase reverse transcriptase (hTERT) and TERRA (telomeric repeat-containing RNA), and a concomitant increase in ROS production following Aurora B inhibition and polyploidization. Mechanistically, we investigated the protein-protein interaction between Aurora B kinase and upstream regulators of hTERT. Collectively, this study elucidates a novel anticancer mechanism associated with Aurora B inhibition, revealing that AZD1152-HQPA not only impairs mitotic fidelity and promotes polyploidization but also compromises the telomere/telomerase maintenance system. These findings highlight the therapeutic potential of Aurora B inhibitors in targeting telomere-associated vulnerabilities in polyploid cancer cells.},
}

@article {pmid40923810,
year = {2025},
author = {Wang, Y and Zhang, J and Chang, K and Liu, S and Ji, J and Han, M and Wei, J},
title = {Relationship between biotransformation enzyme genes in polycyclic aromatic hydrocarbon metabolism, telomere length and missed abortion.},
journal = {International journal of environmental health research},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/09603123.2025.2557430},
pmid = {40923810},
issn = {1369-1619},
abstract = {The mechanism underlying the effects of Polycyclic aromatic hydrocarbons (PAHs) on missed abortion (MA) remains unclear. This study explored the relationship between PAHs exposure, telomere length (TL), metabolizing enzyme gene polymorphism, and MA in a case-control study with 253 pregnant women. A competitive enzyme-linked immunosorbent assay (ELISA) was used to quantify PAH-DNA adducts. The DNA was extracted from villi tissue for the analysis of TL using the real-time quantitative polymerase chain reaction (qPCR) method. Single nucleotide polymorphism (SNP) genotyping was performed using multiplex PCR amplification and high-throughput sequencing methods. The adjusted logistic regression model was used to reveal the relationship between PAH-DNA adducts, TL and MA pairs. The Generalized Multifactor Dimensionality Reduction (GMDR) was used to analyze gene-gene and gene-environment interactions. Results showed higher PAH-DNA adducts in the case group (P = 0.009), shorter TL in MA cases (Z = -4.02, P < 0.001), and a variant site in glutathione S-transferase M1 (GSTM1) (rs1065411) were associated with MA. Higher PAH-DNA adducts level was significantly associated with MA occurrence. Significant interactions were observed between GSTM1 gene and GSTM1 (rs1065411) and PAH-DNA adducts. These findings highlight the importance of PAHs exposure in MA etiology.},
}

@article {pmid40923756,
year = {2025},
author = {Sepšiová, R and Procházková, K and Červenák, F and Majerčík, D and Hanáková, K and Lattová, E and Hajikazemi, M and Zdráhal, Z and Virágová, S and Brzáčová, Z and Paeschke, K and Nosek, J and Tomáška, Ľ},
title = {Poly (ADP-ribose) polymerase in yeasts: characterization and involvement in telomere maintenance.},
journal = {Nucleic acids research},
volume = {53},
number = {17},
pages = {},
pmid = {40923756},
issn = {1362-4962},
support = {APVV-23-0056//Slovak Research and Development Agency/ ; APVV-19-0068//Slovak Research and Development Agency/ ; APVV 22-0144//Slovak Research and Development Agency/ ; //Ministry of Education/ ; 1/0031/24//Sport of the Slovak republic/ ; 1/0234/23//Sport of the Slovak republic/ ; 1R01ES031635-01/NH/NIH HHS/United States ; //Operation Program of Integrated Infrastructure/ ; //European Regional Development Fund/ ; //MEYS/ ; //CR/ ; //CEITEC institutional/ ; //CANTAR project/ ; Az. 10.21.1.027MN//Fritz Thyssen Foundation/ ; },
mesh = {*Telomere Homeostasis ; *Yarrowia/enzymology/genetics ; *Poly(ADP-ribose) Polymerases/metabolism/genetics/chemistry ; *Telomere/metabolism ; *Fungal Proteins/metabolism/genetics/chemistry ; Telomerase/metabolism/genetics ; },
abstract = {Poly (ADP-ribose) polymerases (PARPs) are enzymes catalyzing the post-translational addition of chains of ADP-ribose moieties to proteins. In most eukaryotic cells, their primary protein targets are involved in DNA recombination, repair, and chromosome maintenance. Even though this group of enzymes is quite common in both eukaryotes and prokaryotes, no PARP homologs have been described so far in ascomycetous yeasts, leaving their potential roles in this group of organisms unexplored. Here, we characterize Pyl1 protein of Yarrowia lipolytica as the first candidate of PARP in yeasts. We show that the expression of PYL1 gene is increased in mutants lacking either subunit of telomerase and identified several of its candidate protein targets in vivo. We demonstrate that Pyl1p is a functional PARP that undergoes auto-PARylation and PARylates YlKu70/80 complex. We also show that overexpression of PYL1 in Y. lipolytica cells results in dissociation of YlKu80 from telomeres in vivo, supporting the role of Pyl1p in telomere protection and maintenance. Based on our observations, we propose Pyl1p and its homologs identified in other yeast species represent a distinct class of PARPs, thus substantiating a more detailed investigation of their roles in these organisms.},
}

*Telomere Homeostasis
*Yarrowia/enzymology/genetics
*Poly(ADP-ribose) Polymerases/metabolism/genetics/chemistry
*Telomere/metabolism
*Fungal Proteins/metabolism/genetics/chemistry
Telomerase/metabolism/genetics

@article {pmid40913436,
year = {2025},
author = {Conklin, QA and Smith, DL and Dai, G and King, BG and Saron, CD and Lin, J},
title = {Remote Blood Collection for Telomere Length Measurement: Assessing the Impact of Sample Characteristics and Handling on DNA Quality and Assay Outcomes.},
journal = {American journal of human biology : the official journal of the Human Biology Council},
volume = {37},
number = {9},
pages = {e70128},
pmid = {40913436},
issn = {1520-6300},
support = {//Hershey Family Foundation/ ; //Yoga Science Foundation/ ; R24AG048024/AG/NIA NIH HHS/United States ; U01AG064785/NH/NIH HHS/United States ; //Mind and Life Institute/ ; R24 AG048024/AG/NIA NIH HHS/United States ; 4333//Fetzer Institute/ ; //Tom and Nancy Driscoll Foundation/ ; U01 AG064785/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Blood Specimen Collection/methods ; *DNA ; Male ; Female ; Middle Aged ; Real-Time Polymerase Chain Reaction ; Adult ; *Telomere ; Aged ; Reproducibility of Results ; },
abstract = {BACKGROUND: Telomere length (TL) is a valuable marker of aging and stress that reflects both genetic and environmental influences. Quantitative PCR (qPCR) TL measurement is a powerful and cost-effective assay, especially in population studies with limited quantities of source material. Nevertheless, collecting and transporting high-quality blood samples can be logistically challenging, and research suggests that several preanalytical and analytical factors can influence the reliability and precision of the qPCR assay. Here we describe a procedure for collecting blood remotely in a large-scale study. We then assess the influence of various features of the samples, as well as their collection, transportation, and storage on DNA quality and TL assay outcomes.

METHOD: Participants used at-home collection kits to collect a few drops of whole blood in BD Microtainers during a baseline (n = 265) and 1-year follow-up (n = 178) assessment. DNA was extracted using a magnetic-bead method, and DNA yield, purity, and integrity were assessed. TL was measured using qPCR. To assess inter-assay variation, the coefficient of variation (CV) was calculated across repeated TL measurements (three runs) for each sample. When there was adequate material for duplicate extractions of DNA from the same blood samples, we calculated the intra-class correlation (ICC) of the resultant TL values to assess assay precision.

RESULTS: Our analyses revealed that as little as 50 μL of blood yielded sufficient DNA for highly precise TL measurement (ICC = 0.962, n = 365). Transportation time and an additional year of storage time at -80°C did not meaningfully affect DNA quality or assay outcomes. However, blood clotting was associated with longer telomere estimates, whereas greater temperature exposure was related to shorter telomere estimates.

CONCLUSIONS: We established that whole blood collected remotely in BD Microtainers can provide a valid sample source for qPCR TL measurement. We also outline important logistical considerations related to sample collection and handling and provide recommendations for researchers who want to use this method.},
}

Humans
*Blood Specimen Collection/methods
*DNA
Male
Female
Middle Aged
Real-Time Polymerase Chain Reaction
Adult
*Telomere
Aged
Reproducibility of Results

@article {pmid40909680,
year = {2025},
author = {Rowe, M and Tober, J and Ortiz, V and Smoom, R and Tzfati, Y and Speck, N and Kaestner, KH},
title = {Human length telomeres restrict the regenerative potential of hematopoietic stem cells in mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {40909680},
issn = {2692-8205},
support = {R01 CA249929/CA/NCI NIH HHS/United States ; R01 DK139049/DK/NIDDK NIH HHS/United States ; R01 HL091724/HL/NHLBI NIH HHS/United States ; },
abstract = {Extremely short telomeres cause bone marrow failure in telomere biology disorder (TBDs) patients. Here, we employed the recently developed 'Telomouse' with human-length telomeres resulting from a single amino acid substitution in the helicase Rtel1 (Rtel1 [M492K/M492K]) to determine the effects of the short telomeres on the bone marrow and hematopoiesis. Under homeostatic conditions, Telomice have notably short telomeres but normal hematopoiesis. However, when forced to repopulate following repeated treatment with 5-fluoro-uracil or upon bone marrow transplantation into lethally irradiated mice, bone marrow progenitor cells are significantly depleted in Telomice compared to wild-type controls. This effect is associated with increased frequency of telomere repeat arrays too short to be detected by fluorescence in situ hybridization in the bone marrow of Telomice.},
}

@article {pmid40908429,
year = {2025},
author = {Al-Dulaimi, S and Thomas, R and Matta, S and Roberts, T},
title = {Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity.},
journal = {Biogerontology},
volume = {26},
number = {5},
pages = {178},
pmid = {40908429},
issn = {1573-6768},
mesh = {Humans ; *Telomerase/metabolism/genetics ; Up-Regulation/drug effects ; *Telomere Homeostasis/drug effects ; Cell Line, Tumor ; *Telomere/drug effects/metabolism ; *Oligopeptides/pharmacology ; Female ; RNA, Messenger/metabolism ; Fibroblasts/drug effects ; Breast Neoplasms/genetics/enzymology ; Cell Line ; },
abstract = {Epitalon, a naturally occurring tetrapeptide, is known for its anti-aging effects on mammalian cells. This happens through the induction of telomerase enzyme activity, resulting in the extension of telomere length. A strong link exists between telomere length and aging-related diseases. Therefore, telomeres are considered to be one of the biomarkers of aging, and increasing or maintaining telomere length may contribute to healthy aging and longevity. Epitalon has been the subject of several anti-aging studies however, quantitative data on the biomolecular pathway leading to telomere length increase, hTERT mRNA expression, telomerase enzyme activity, and ALT activation have not been extensively studied in different cell types. In this article, the breast cancer cell lines 21NT, BT474, and normal epithelial and fibroblast cells were treated with epitalon then DNA, RNA, and proteins were extracted. qPCR and Immunofluorescence analysis demonstrated dose-dependent telomere length extension in normal cells through hTERT and telomerase upregulation. In cancer cells, significant telomere length extension also occurred through ALT (Alternative Lengthening of Telomeres) activation. Only a minor increase in ALT activity was observed in Normal cells, thereby showing that it was specific to cancer cells. Our data suggests that epitalon can extend telomere length in normal healthy mammalian cells through the upregulation of hTERT mRNA expression and telomerase enzyme activity.},
}

Humans
*Telomerase/metabolism/genetics
Up-Regulation/drug effects
*Telomere Homeostasis/drug effects
Cell Line, Tumor
*Telomere/drug effects/metabolism
*Oligopeptides/pharmacology
Female
RNA, Messenger/metabolism
Fibroblasts/drug effects
Breast Neoplasms/genetics/enzymology
Cell Line

@article {pmid40908046,
year = {2025},
author = {Yu, J and Zhang, Y and Ho, M and Kam, KW and Young, AL and Pang, CP and Tham, CC and Yam, JC and Chen, LJ},
title = {Association of leucocyte telomere length with incident age-related macular degeneration: a prospective UK Biobank Study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327492},
pmid = {40908046},
issn = {1468-2079},
abstract = {PURPOSE: There have been conflicting findings on the role of leucocyte telomere length (LTL) in the risk of age-related macular degeneration (AMD). In this study, we evaluated the associations between LTL and the risk of incident AMD and explored whether age, sex and/or genetic predisposition to AMD can modify these associations.

METHODS: We conducted a longitudinal cohort study involving 332 123 AMD-free participants with complete baseline covariates and LTL data from the UK Biobank. We employed multivariable Cox proportional hazards models to test the association between LTL and AMD incidence, estimating the HRs and 95% CIs. Genetic risk was assessed using polygenic risk score (PRS).

RESULTS: During a median follow-up of 13.63 years, 6754 participants (2.03%) developed AMD. Shorter LTL was not associated with incident AMD risk (HR=1.042, 95% CI: 0.992 to 1.094; p=0.10) after adjusting for multiple confounders. Sex showed an interactive effect with LTL (p=0.01 for interaction) on incident AMD risk, while age and PRS did not modify these associations. We identified a significant association between shorter LTL and incident AMD risk in females (HR=1.093, 95% CI: 1.025 to 1.166; p=0.007), but not in males. Moreover, shorter LTL was associated with thinner photoreceptor segments only in females at both baseline and repeated assessments (β=-0.141 µm, 95% CI: -0.267 to -0.016; β=-0.345 µm, 95% CI: -0.649 to -0.041, p<0.05).

CONCLUSIONS: Shorter LTL increased the risk of incident AMD in females, suggesting LTL as a potential biomarker for AMD development with sex-specific function.},
}

@article {pmid40907145,
year = {2025},
author = {Goetz, SMM and Lucas, T and Finegood, E and Lin, J and Granger, D},
title = {Age and gender intersectionality among African Americans: Salivary uric acid is associated with shorter telomere length in younger adults and men.},
journal = {Psychoneuroendocrinology},
volume = {181},
number = {},
pages = {107588},
doi = {10.1016/j.psyneuen.2025.107588},
pmid = {40907145},
issn = {1873-3360},
abstract = {Age related diseases present disproportionately among African Americans and have been tied to broad social inequalities and accompanying stress. Yet, there is considerable variability among African Americans in susceptibility, highlighting potential connections to both intersectionality and stress-related biological processes. A growing body of research links exposure to racism and discrimination to telomere length (TL)-an indicator of biological aging that is increasingly implicated in explaining stress-related racial health disparities. However, few studies have examined links to accompanying stress processes that may precede TL shortening. This includes examining Uric Acid (UA), which growing evidence suggests may comprise a unique biological aspect of the acute stress response, with implications for both racial health disparities and within-race heterogeneity. In a secondary analysis of a sample of healthy African Americans (N = 103, 33 men; M age = 31.41 years), we assessed the relationship between salivary UA (sUA) and TL. With an eye towards within-group heterogeneity, we also considered the moderating role of age and gender. Our findings revealed a negative association between UA and TL that was most pronounced in African American men and among younger African Americans. We apply an intersectional lens to interpret these results, revealing that different intersections of identity operate through distinct mechanisms. Among men, UA consistently predicted shorter telomeres regardless of discrimination exposure, suggesting biological pathways may be primary. However, among women, the UA/TL relationship was moderated by discrimination-with UA positively predicting TL under low discrimination but showing negative associations under high discrimination conditions. These findings demonstrate that intersectionality operates through multiple pathways simultaneously, with some intersections characterized by biological vulnerabilities while others are defined by social moderation effects. Future research directions should consider the multifaceted influences of UA on TL, recognizing that different intersectional positions may require examination of distinct biological and social mechanisms including potential interventions targeting UA levels to mitigate age-related illnesses and address health disparities among African Americans. Additionally, future studies should examine how additional intersecting systems of oppression might moderate the relationship between UA and TL.},
}

@article {pmid40907117,
year = {2025},
author = {Hu, G and Yu, Y and Yin, Y and Yang, X and Yu, R and Xiang, Q},
title = {Impact of telomere length on autoimmune thyroid disease in Europeans: insights from Mendelian randomization.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {80},
number = {},
pages = {100765},
doi = {10.1016/j.clinsp.2025.100765},
pmid = {40907117},
issn = {1980-5322},
abstract = {OBJECTIVE: This study aimed to investigate the causal relationship between Telomere Length (TL) and Autoimmune Thyroid Disease (AITD) in Europeans using Mendelian Randomization (MR).

METHODS: Single nucleotide polymorphisms associated with TL and AITD were obtained from genome-wide association studies. MR analysis was conducted using inverse variance weighted as the primary method. Cochran's Q test and leave-one-out sensitivity analysis were employed to assess heterogeneity and robustness, respectively.

RESULTS: TL was significantly associated with reduced genetic susceptibility to Graves' Disease (GD) in Europeans (Odds Ratio [OR = 0.776], 95 % Confidence Interval [95 %CI 0.625-0.964]; p = 0.022). However, no association was found between TL and Autoimmune Thyroiditis (AIT) (OR = 1.474, 95 % CI 0.870-2.497; p = 0.149). Cochran's Q test and leave-one-out sensitivity analysis confirmed that the findings were free of heterogeneity and robust.

CONCLUSION: MR analysis revealed that TL shortening is associated with increased genetic susceptibility to GD in Europeans, but no such association was observed for AIT. Further research is needed to elucidate the mechanisms through which TL influences AITD.},
}

@article {pmid40905409,
year = {2025},
author = {He, H and Yang, X and Wang, K and Ye, Q},
title = {Oxidative DNA damage may promote the development of endometriosis by activating telomerase and extending telomere length: a meta-analysis.},
journal = {Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals},
volume = {},
number = {},
pages = {1-20},
doi = {10.1080/1354750X.2025.2557452},
pmid = {40905409},
issn = {1366-5804},
abstract = {OBJECTIVE: To investigate the associations between oxidative DNA damage biomarkers [levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), telomere length (TL), human telomerase reverse transcriptase (hTERT), telomerase activity (TA) and polymorphisms of human 8-oxoguanine glycosylase 1 (hOGG1) or X-ray repair cross-complementing group 4 (XRCC4)] and endometriosis (EMT) by a meta-analysis.

METHODS: Five databases were searched until August 2024. Stata 15.0 was used to estimate pooled odds ratio (OR) or standardized mean difference (SMD) with 95% confidence intervals (CIs).

RESULTS: Forty-two studies were included. Overall meta-analysis revealed significantly elevated 8-OHdG (SMD = 1.84; 95%CI = 1.29 - 2.39), TA (SMD = 3.03; 95%CI = 2.07 - 4.00) and hTERT (SMD = 2.55; 95%CI = 1.55 - 3.55) in EMT women compared to controls. Women carrying GG genotype (vs GC + CC: OR = 1.34; 95%CI = 1.00 - 1.78) of hOGG1 rs1052133, TT genotype (vs TG + GG: OR = 2.67; 95%CI = 1.63 - 4.38) and T allele (vs G: OR = 3.49; 95%CI = 2.27 - 5.35) of XRCC4 rs6869366 had a higher risk of developing EMT. Subgroup and trim-and-fill analyses indicated longer TL was a risk factor for EMT.

CONCLUSIONS: 8-OHdG, TA, hTERT, TL, rs1052133 and rs6869366 represent potential prediction biomarkers and treatment targets for EMT.},
}

@article {pmid40903918,
year = {2025},
author = {Lowran, K and Campbell, L and Cismas, E and Wu, CG},
title = {Domain-Specific DNA Binding Activities of BRCA1 Reveal Substrate Preferences for Homologous Recombination and Telomere Regulation.},
journal = {Biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.biochem.5c00333},
pmid = {40903918},
issn = {1520-4995},
abstract = {BRCA1 is a crucial component of homologous recombination (HR), a high-fidelity pathway for repairing double-stranded DNA breaks (DSBs) in human cells. The central region of the BRCA1 protein contains two putative DNA binding domains (DBDs), yet their relative substrate specificities and functional contributions to HR remain unclear. Here, we characterized the DNA binding properties of DBD1 (amino acids 330-554), DBD2 (amino acids 894-1057), and BRCA1 C-terminal (BRCT) repeats using biolayer interferometry. Affinities were determined for single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), and G-quadruplex (G4) DNA. DBD2 exhibited strong and nearly identical binding to all three substrates (Kd = ∼35-44 nM), while the BRCT also bound to each structure similarly, but with lower affinity (Kd = ∼149-184 nM). In contrast, DBD1 showed a distinct preference for dsDNA, binding approximately 2-fold tighter compared to ssDNA or G4. These findings support a model in which BRCA1 uses modular DNA binding domains to recognize diverse repair targets; DBD2 serves as a primary anchor to associate with a broad range of DNA structures with BRCT contributing to the contacts. DBD1 acts as the determinant of DNA structure-specific localization that may help direct BRCA1 to DSB sites during HR or to noncanonical elements such as chromatin and telomeres. These insights lay the groundwork for future studies examining how cancer-associated variants affect the DNA binding and repair phenotypes of BRCA1 and may inform the interpretation of variants of unknown clinical significance.},
}

@article {pmid40901206,
year = {2025},
author = {Luo, S and Chai, J and Cai, Y and Ding, L and Tang, S},
title = {Causality between telomere length and breast diseases: a two-sample bidirectional Mendelian randomization study.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {9},
pages = {5551-5556},
pmid = {40901206},
issn = {2049-0801},
abstract = {BACKGROUND: The relationship between telomere length and breast diseases remains unclear, with conflicting evidence for breast cancer. Using an innovative genetic approach, we were the first to comprehensively assess their bidirectional causal relationship.

METHODS: Telomere length, breast cancer, benign neoplasm of breast, and breast inflammation were extracted from the genome-wide Association study (GWAS) database as the basis for large-scale population studies. The interaction of telomere length and breast diseases as exposure and outcome factors was analyzed by Mendelian randomization (MR).

RESULTS: When telomere length was used as an exposure factor and breast diseases as an outcome, the P value of MR was less than 0.05. Breast cancer (odds ratio (OR) = 1.130, 95% confidence interval (CI) = 1.047-1.219, P = 0.0016), benign neoplasm of breast (OR = 1.002, 95%CI = 1.001-1.004, P = 0.0007) and breast inflammation (OR = 1.487, 95%CI = 1.008-2.191, P = 0.0453). When breast diseases were taken as an exposure factor and telomere length was taken as an outcome, the P value of MR between breast cancer, benign neoplasm of breast, and telomere length was greater than 0.05, and breast inflammation could not be calculated by MR.

CONCLUSION: Telomere length is a risk factor for breast diseases, and longer telomeres increase the risk of breast cancer, benign neoplasm of breast, and breast inflammation. However, the reverse study showed no causal association between breast cancer, benign neoplasm of breast and telomere length, and the causal association between breast inflammation and telomere length was not clear. Moreover, further studies are needed to validate our findings in non-European populations.},
}

@article {pmid40900359,
year = {2025},
author = {Jaiswal, RK and Garibo Domingo, T and Grunchec, H and Singh, K and Pirooznia, M and Elhaik, E and Cohn, M},
title = {Subtelomeric elements provide stability to short telomeres in telomerase-negative cells of the budding yeast Naumovozyma castellii.},
journal = {Current genetics},
volume = {71},
number = {1},
pages = {19},
pmid = {40900359},
issn = {1432-0983},
mesh = {*Telomerase/genetics/metabolism ; *Telomere/genetics ; *Saccharomycetales/genetics ; *Telomere Homeostasis/genetics ; Telomere-Binding Proteins/genetics/metabolism ; *Telomere Shortening/genetics ; },
abstract = {Telomerase plays an important role in sustaining eukaryotic linear chromosomes, as elongation of telomeres is needed to counterbalance the shortening occurring in each replication round. Nevertheless, in telomerase-deficient cells, Alternative Lengthening of Telomeres (ALT) pathways can maintain telomeres by employing recombination-based mechanisms. In the budding yeast Naumovozyma castellii, effective activation of the ALT pathway leads to bypass of senescence and supports long-term growth. We found that telomere structures in N. castellii ALT cells are stably maintained at a shortened uniform length over extensive numbers of generations. This is correlated to the spreading of a subtelomeric sequence, TelKO element, to all telomeres. Genome sequencing of the wild-type strain revealed variants of the TelKO element, differing in their lengths, and separate ALT strains are maintained by spreading of distinct TelKO element variants. Although short uniform telomere structures are predominant, sporadic telomere lengthening events occur by addition of long repeated arrays of TelKO elements. The telomere-binding protein Rap1 can bind to TelKO sequences in vitro, indicating a functional role of TelKO elements in providing stability to shortened ALT telomeres. Our results suggest that stable maintenance and telomere functionality may be achieved by incorporating the distal subtelomeric TelKO sequences into the telomeric chromatin cap.},
}

*Telomerase/genetics/metabolism
*Telomere/genetics
*Saccharomycetales/genetics
*Telomere Homeostasis/genetics
Telomere-Binding Proteins/genetics/metabolism
*Telomere Shortening/genetics

@article {pmid40894009,
year = {2025},
author = {Jain, N and Luo, J and Yang, Y and Aschebrook-Kilfoy, B and Ahsan, H and Chen, L and Pierce, B},
title = {Determinants of chromosome-specific telomere lengths among 2,573 All of Us participants.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7293781/v1},
pmid = {40894009},
issn = {2693-5015},
abstract = {Telomeres are DNA-protein structures that protect chromosome ends. The DNA component of telomeres shortens as cells divide, and telomere length (TL) is a key biomarker of aging and disease risk. Most previous studies in humans of TL have analyzed average TL; thus, our knowledge of TL variability across chromosome arms remains limited. The availability of long-read whole-genome sequencing (lrWGS) data has enabled the development of computational methods to measure chromosome-specific TL (csTL). We generated lrWGS-based csTLs for > 2,500 All of Us participants and characterized variability in csTL attributable to individuals, chromosome arms, participant characteristics, and technical factors. We found that TL varies by chromosome arm (9.1% of the variance in csTL), mirroring patterns observed in prior studies and highlighting the potential for chromosome-specific mechanisms of TL regulation. Substantial variance in csTL (8.9%) was attributable to individual, independent of age, supporting the hypothesis that individuals are endowed with short or long TL in early development, which is maintained throughout life. While age is inversely associated with TL across all arms, the strength of the association varied, with longer arms showing stronger associations. We demonstrate that csTL estimates can be used to estimate disease associations at individual telomeres, including outlying values in the csTL distribution. Our work identifies lrWGS quality metrics that impact csTL estimation, providing a framework to guide future studies. This study demonstrates the utility of lrWGS data for csTL profiling in population cohorts. Larger studies of csTL are needed to advance our understanding of telomeres in aging and disease.},
}

@article {pmid40893773,
year = {2025},
author = {Bansal, A and Phogat, P and Kukreti, S},
title = {Na[+] selective structural switch from an intramolecular triplex to tetrad stabilised by non-canonical mispairs in double repeat of Arabidopsis thaliana telomere (T3AG3)2.},
journal = {Biochemistry and biophysics reports},
volume = {43},
number = {},
pages = {102203},
pmid = {40893773},
issn = {2405-5808},
abstract = {DNA is polymorphic, as with four nucleobases, it can be configured in a number of secondary structures. The four-stranded DNA structures consisting of G-tetrads have especially been intriguing because of their proven existence in human cells. Due to the high prevalence of putative G-quadruplex-forming sequence motifs in the human genome, scientists in recent years have highlighted the potential of exploiting these exotic structures for targeted therapies for various cancers. G-quadruplexes are the most common and well-studied arrangements of four guanines; however, other possible non-canonical arrangements of nucleobases have also been reported. Herein, using Gel electrophoresis, Circular Dichroism, UV & CD-thermal denaturation methods, and NMR, we suggested that a double repeat of Arabidopsis thaliana telomere (T3AG3)2 shows a structural switch from a non-canonical intramolecular triplex to a non-conventional tetrad other than an antiparallel G-quadruplex. This transition is mediated by increasing Na[+] cation concentration from 0.1 M to 1.0 M, and the tetrad is fairly stabilised by a hydrogen-bonded cyclic array of non-canonical/mismatch base pairs (G∗G, G∗T, and T∗T). Intriguingly, such a structural transition was not manifested in the presence of K[+] ions. To the best of our knowledge, such a cation-specific non-canonical structural switch, in a telomeric sequence, has not been proposed to date.},
}

@article {pmid40891961,
year = {2025},
author = {Nasiri, L and Vaez-Mahdavi, MR and Ghazanfari, T and Hassanpour, H and Kaboudanian-Ardestani, S},
title = {Expression of telomere length and shelterin genes in men and women leukocytes and their correlations with lipid peroxidation in sulfur mustard gas intoxication.},
journal = {Drug and chemical toxicology},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/01480545.2025.2553203},
pmid = {40891961},
issn = {1525-6014},
abstract = {Sulfur mustard (SM), a chemical warfare agent, inflicts severe acute and chronic health effects. This study investigates the impact of SM-induced oxidative stress on telomere length (TL) and shelterin gene expression, which are crucial for telomere maintenance in exposed veterans. This study involved SM-exposed veterans and non-exposed controls. The SM-exposed group was divided into three subgroups based on exposure severity (severe, mild, and asymptomatic) and gender. Leukocyte TL, transcript of shelterin genes (TPP1, POT1, TIN2, TRF1, TRF2, RAP1), and plasma MDA were measured. TL was decreased in the SM-exposed group compared to the non-exposed group, while the MDA level was increased. The SM-exposed group showed lower expression of TIN2, TRF2, and the composite shelterin genes compared to the control group. In the SM-exposed subgroups, TL, TRF2 transcript, and composite shelterin gene expression were reduced compared to the non-exposed group, while the MDA levels were significantly increased. There are negative correlations between MDA and both TIN2/TRF2 expression and TL, and positive correlations between TL and composite shelterin gene expression. In the gender comparison, there were different effects of SM toxicity on TIN2, TPP1, TRF2, and the composite of shelterin gene expression between SM-exposed men and women. SM-exposed men had significantly higher MDA levels, while women showed no significant change. Also, there was no difference between non-exposed men and women. It is concluded that SM exposure increases lipid peroxidation, shortens telomeres, and alters shelterin genes in a gender-specific manner, suggesting accelerated biological aging as a delayed toxic effect.},
}

@article {pmid40884660,
year = {2025},
author = {M'kacher, R and Colicchio, B and Junker, S and Schabat, S and Belaiba, R and Sontos, L and Heidingsfelder, L and Najar, W and Plesch, A and Voisin, P and Dieterlen, A and Jeandidier, E and Carde, P},
title = {DNA Damage, Telomere and Centromere Dysfunction in Chromothripsis Rearrangements.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2968},
number = {},
pages = {441-455},
pmid = {40884660},
issn = {1940-6029},
mesh = {Humans ; *Chromothripsis ; *Telomere/genetics/metabolism ; *Centromere/genetics/metabolism ; *DNA Damage ; Neoplasms/genetics ; Chromosomal Instability ; Genomic Instability ; },
abstract = {The analysis of the origin of chromothripsis, catastrophic chromosomal rearrangements, has provided exceptional insights into various aspects of tumor progression and genetic disorders. Findings in chromothripsis have not only enhanced our understanding of genomic instability mechanisms, but also reshaped our views on chromosome mechanics. To date, the major mechanisms of chromothripsis described involve the incorporation of micronuclei into the primary nucleus and telomere crisis through the formation of dicentric chromosomes. Here, we reevaluated the impact of telomere and centromere sequences in the formation of micronuclei and anaphase bridges in cancer patients using our high throughput technique for the detection of telomere and centromere dysfunction and chromosomal instability biomarkers. We also discuss the emerging potential of exploiting telomere and centromere dysfunction combined with DNA damage as prognostic biomarkers and tools for personalized patient management.},
}

Humans
*Chromothripsis
*Telomere/genetics/metabolism
*Centromere/genetics/metabolism
*DNA Damage
Neoplasms/genetics
Chromosomal Instability
Genomic Instability

@article {pmid40879844,
year = {2025},
author = {Zhao, X and Shi, Y and Tang, M},
title = {Exploring the mediating role of telomere length in the association between physical activity and bone mineral density.},
journal = {Aging clinical and experimental research},
volume = {37},
number = {1},
pages = {263},
pmid = {40879844},
issn = {1720-8319},
mesh = {Humans ; *Bone Density/genetics/physiology ; *Exercise/physiology ; Female ; Middle Aged ; Male ; Aged ; *Telomere ; *Telomere Shortening ; Nutrition Surveys ; Osteoporosis/genetics ; DNA Methylation ; Telomere Homeostasis ; },
abstract = {BACKGROUND: Physical activity may mitigate osteoporosis progression by modulating telomere shortening processes.

AIMS: To explore the mediating role of telomere length (TL) in the relationship between physical activity and bone mineral density (BMD).

METHODS: This study enrolled 2,394 participants aged 50 years and older from the U.S. National Health and Nutrition examination Surveys. TL was measured by quantitative polymerase chain reaction (qPCR) method (TeloMean) and DNA methylation data (HorvathTelo), and accelerated telomere attrition was assessed through residual-based indices of TeloMeanAccel and HorvathTeloAccel. Physical activity was assessed via questionnaire and BMD was measured at multiple body sites. Multiple linear regression models were utilized to evaluate associations between TL metrics, physical activity, and BMD. Mediation analysis, restrict cubic spline (RCS) modeling, subgroup analyses and sensitivity analyses were further conducted.

RESULTS: After adjusting for covariates, TL metrics of TeloMean and HorvathTelo were found significantly positive correlations with BMD. HorvathTeloAccel, reflecting accelerated telomere shortening, also exhibited significant association with BMD. Physical activity demonstrated a significant positive association with total BMD (β = 0.046, 95%CI: 0.004-0.088). Mediation analysis revealed that TeloMean and HorvathTelo accounted for 4.78% and 20.86% of the total effect of physical activity on BMD, respectively, while HorvathTeloAccel explained 5.24% of the observed association.

CONCLUSION: Reduced physical activity and accelerated telomere attrition were related with BMD decline, and TL partially mediated the association. These findings suggest that enhancing physical activity could mitigate telomere shortening and promote bone health.},
}

Humans
*Bone Density/genetics/physiology
*Exercise/physiology
Female
Middle Aged
Male
Aged
*Telomere
*Telomere Shortening
Nutrition Surveys
Osteoporosis/genetics
DNA Methylation
Telomere Homeostasis