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Paternal age and telomere length in twins: the germ stem cell selection paradigm.

ABSTRACT: Telomere length, a highly heritable trait, is longer in offspring of older fathers. This perplexing feature has been attributed to the longer telomeres in sperm of older men and it might be an 'epigenetic' mechanism through which paternal age plays a role in telomere length regulation in humans. Based on two independent (discovery and replication) twin studies, comprising 889 twin pairs, we show an increase in the resemblance of leukocyte telomere length between dizygotic twins of older fathers, which is not seen in monozygotic twins. This phenomenon might result from a paternal age-dependent germ stem cell selection process, whereby the selected stem cells have longer telomeres, are more homogenous with respect to telomere length, and share resistance to aging.

SUBMITTER: Hjelmborg JB

PROVIDER: S-EPMC4531084 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Paternal age and telomere length in twins: the germ stem cell selection paradigm.

Hjelmborg Jacob B JB Dalgård Christine C Mangino Massimo M Spector Tim D TD Halekoh Ulrich U Möller Sören S Kimura Masayuki M Horvath Kent K Kark Jeremy D JD Christensen Kaare K Kyvik Kirsten O KO Aviv Abraham A

Aging cell 20150410 4

Telomere length, a highly heritable trait, is longer in offspring of older fathers. This perplexing feature has been attributed to the longer telomeres in sperm of older men and it might be an 'epigenetic' mechanism through which paternal age plays a role in telomere length regulation in humans. Based on two independent (discovery and replication) twin studies, comprising 889 twin pairs, we show an increase in the resemblance of leukocyte telomere length between dizygotic twins of older fathers, ...[more]

PMID: 25865872

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Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm.

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Paternal Age and Transgenerational Telomere Length Maintenance: A Simulation Model.

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| S-EPMC6328556 | biostudies-other

Leukocyte telomere length and physical ability among Danish twins age 70+.

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Genetically Inferred Telomere Length and Testicular Germ Cell Tumor Risk.

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Predicted leukocyte telomere length and risk of germ cell tumours.

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The paternal age at conception effect on offspring telomere length: mechanistic, comparative and adaptive perspectives.

Project description:Telomeres are repeating DNA found at the ends of chromosomes that, in the absence of restorative processes, shorten with cell replications and are implicated as a cause of senescence. It appears that sperm telomere length (TL) increases with age in humans, and as a result offspring of older fathers inherit longer telomeres. We review possible mechanisms underlying this paternal age at conception (PAC) effect on TL, including sperm telomere extension due to telomerase activity, age-dependent changes in the spermatogonial stem cell population (possibly driven by 'selfish' spermatogonia) and non-causal confounding. In contrast to the lengthening of TL with PAC, higher maternal age at conception appears to predict shorter offspring TL in humans. We review evidence for heterogeneity across species in the PAC effect on TL, which could relate to differences in statistical power, sperm production rates or testicular telomerase activity. Finally, we review the hypothesis that the PAC effect on TL may allow a gradual multi-generational adaptive calibration of maintenance effort, and reproductive lifespan, to local demographic conditions: descendants of males who reproduced at a later age are likely to find themselves in an environment where increased maintenance effort, allowing later reproduction, represents a fitness improving resource allocation.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.

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Telomere length and heredity: Indications of paternal inheritance.

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Age-adjusted recipient pretransplantation telomere length and treatment-related mortality after hematopoietic stem cell transplantation.

Project description:Telomere attrition induces cell senescence and apoptosis. We hypothesized that age-adjusted pretransplantation telomere length might predict treatment-related mortality (TRM) after hematopoietic stem cell transplantation (HSCT). Between 2000 and 2005, 178 consecutive patients underwent HSCT from HLA-identical sibling donors after myeloablative conditioning regimens, mainly for hematologic malignancies (n = 153). Blood lymphocytes' telomere length was measured by real-time quantitative PCR before HSCT. Age-adjusted pretransplantation telomere lengths were analyzed for correlation with clinical outcomes. After age adjustment, patients' telomere-length distribution was similar among all 4 quartiles except for disease stage. There was no correlation between telomere length and engraftment, GVHD, or relapse. The overall survival was 62% at 5 years (95% confidence interval [CI], 54-70). After a median follow-up of 51 months (range, 1-121 months), 43 patients died because of TRM. The TRM rate inversely correlated with telomere length. TRM in patients in the first (lowest telomere length) quartile was significantly higher than in patients with longer telomeres (P = .017). In multivariate analysis, recipients' age (hazard ratio, 1.1; 95% CI, .0-1.1; P = .0001) and age-adjusted telomere length (hazard ratio, 0.4; 95% CI; 0.2-0.8; P = .01) were independently associated with TRM. In conclusion, age-adjusted recipients' telomere length is an independent biologic marker of TRM after HSCT.

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| S-EPMC4827700 | biostudies-literature

Leukocyte telomere length, T cell composition and DNA methylation age.

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| S-EPMC5636670 | biostudies-literature

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