Telomere instability in the male germline

Baird, Duncan Martin; Britt-Compton, Bethan; Rowson, J. M.; Amso, Nazar Najib; Gregory, Linda; Kipling, David

doi:10.1093/hmg/ddi424

Cited by 141 publications

(121 citation statements)

References 53 publications

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“…The key might be age-dependent telomere dynamics in sperm. Mean telomere length in sperm does not decrease, and, in fact, increases with the donor's age [34,35], a phenomenon we confirmed. The donor's age effect on sperm telomere length was not due to the change in the sperm profile of MMP, a parameter serving as an indicator of sperm motility and 'fertilizing' capacity [36].…”

Section: Discussionsupporting

confidence: 74%

Offspring's Leukocyte Telomere Length, Paternal Age, and Telomere Elongation in Sperm

Kimura¹,

Cherkas²,

Kato³

et al. 2005

PLoS Genet

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Leukocyte telomere length (LTL) is a complex genetic trait. It shortens with age and is associated with a host of agingrelated disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n¼3365), aged 18-94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring), the NHLBI Family Heart Study (NHLBI-Heart), the Longitudinal Study of Aging Danish Twins (Danish Twins), and the UK Adult Twin Registry (UK Twins). Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (,30 years) and older (.50 years) donors. Paternal age had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice of the annual attrition in LTL with age. Moreover, sperm telomere length analyses were compatible with the emergence in older men of a subset of sperm with elongated telomeres. Paternal age exerts a considerable effect on the offspring's LTL, a phenomenon which might relate to telomere elongation in sperm from older men. The implications of this effect deserve detailed study.Citation: Kimura M, Cherkas LF, Kato BS, Demissie S, Hjelmborg JB, et al. (2008) Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm. PLoS Genet 4(2): e37.

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Section: Discussionsupporting

confidence: 74%

Offspring's Leukocyte Telomere Length, Paternal Age, and Telomere Elongation in Sperm

Kimura¹,

Cherkas²,

Kato³

et al. 2005

PLoS Genet

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“…caused by increases in sperm TL as a man ages. Although longer sperm TL in older men compared with younger men (4,14,15) provides convergent evidence for this prominent hypothesis, it is also known that sperm donors represent nonrandom samples of the population (35,36). It is possible that older men who volunteer to donate sperm have better reproductive health and longer sperm TL and that a similar selection bias results in men with longer sperm TL tending to reproduce at later ages.…”

Section: Discussionmentioning

confidence: 92%

“…The longer TL among offspring of older fathers has been explained by the fact that sperm TL are longer in older men (4,14,15), with high telomerase activity in testes being the most common explanation for the increase in sperm TL seen with age (16,31). Because men produce an estimated 100 million sperm cells daily (32)(33)(34), telomere maintenance mechanisms are required to avoid rapid telomere shortening (17).…”

Section: Discussionmentioning

confidence: 99%

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Delayed paternal age of reproduction in humans is associated with longer telomeres across two generations of descendants

Eisenberg

Hayes

Kuzawa

2012

Proc. Natl. Acad. Sci. U.S.A.

185

170

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Telomeres are repeating DNA sequences at the ends of chromosomes that protect and buffer genes from nucleotide loss as cells divide. Telomere length (TL) shortens with age in most proliferating tissues, limiting cell division and thereby contributing to senescence. However, TL increases with age in sperm, and, correspondingly, offspring of older fathers inherit longer telomeres. Using data and samples from a longitudinal study from the Philippines, we first replicate the finding that paternal age at birth is associated with longer TL in offspring (n = 2,023, P = 1.84 × 10 −6 ). We then show that this association of paternal age with offspring TL is cumulative across multiple generations: in this sample, grandchildren of older paternal grandfathers at the birth of fathers have longer telomeres (n = 234, P = 0.038), independent of, and additive to, the association of their father's age at birth with TL. The lengthening of telomeres predicted by each year that the father's or grandfather's reproduction are delayed is equal to the yearly shortening of TL seen in middle-age to elderly women in this sample, pointing to potentially important impacts on health and the pace of senescent decline in tissues and systems that are cell-replication dependent. This finding suggests a mechanism by which humans could extend late-life function as average age at reproduction is delayed within a lineage.adaptation | epigenetics | evolution | parental effects | transgenerational plasticity T elomeres are repeating DNA sequences at the ends of chromosomes that protect and buffer genes from nucleotide loss as cells divide (1). In many tissues, telomere lengths (TL) are shortened by cellular proliferation, and as a result TL tends to decline with age (2-5). As cell replication generally requires a minimal TL, shortened TL is thought to contribute to senescence (6). Consistent with this, elderly persons with shorter telomeres (in blood) for their age have reduced survival (7-13).Although it is well established that TL shortens with age in most proliferating tissues (e.g., 4, 5), sperm TL is an exceptionolder men have sperm with longer telomeres (4,14,15). This may be explained by the fact that the activity of telomerase (an enzyme that extends TL) is high in testes (16,17). Consistent with the fact that offspring inherit half their chromosomes from sperm, offspring of older fathers tend to have longer telomeres (4,18,19). In contrast, because the pool of ova is established in utero, TL in ova are thought to be stable with age, and there is no evidence for a maternal age effect on TL in offspring (e.g., 4, 20).We recently hypothesized that the age-related TL increase in sperm could lead to cumulative, and thus more biologically significant, multigenerational lengthening or shortening of TL in response to population trends in reproductive scheduling (21). If average reproductive age of recent patrilineal ancestors cumulatively influences TL, this might also lead to changes in TL of sufficient magnitude to influence late-life function and l...

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“…In contrast Baird et al (2005;Hewakapuge et al, 2008;Karlsson et al, 2008) confirmed that age estimation based on telomere shortening measured with real-time PCR is not appropriate for age estimation in forensic practice, as there was a relatively large variation between individuals, e.g., in the study of Karlsson et al (2008), R 2 = 0.3 with standard error of age prediction estimated to be much higher as ±22 years, while in the study of Hewakapuge et al (2008), R 2 value was 0.037 which was significantly low.…”

Section: Discussionmentioning

confidence: 88%

Telomere Length Measurement by Quantitative Real-time PCR: A Molecular Marker for Human Age Prediction

Alhusseini¹,

Madboly²

2016

American Journal of Biochemistry and Biotechnology

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The fact that telomere shortening occurs with aging leads to the hypothesis that a correlation could be made between Telomere Length (TL) and suspect age. This study aimed to assess if TL can be used as an investigational tool to predict human age through developing a formula based on this correlation with accuracy suitable to be applied in forensic practice. A quantitative real-time PCR study was carried out on 80 Egyptians, ranging in age from 1-79 years. The results confirmed that the relative TL significantly shortened with aging; "r" = -0.903 (p<0.001). The human age could be determined by the following formula: (Y = 66.9-28X), (Y: Age in years; X: Relative TL), with a regression analysis between relative TL and age had an R 2 = 0.815. The standard error of age estimate was ±10.14 years. The present study concluded that estimation of human age based on the relative TL measured by quantitative real-time PCR may be a useful method for age prediction, especially when there is no morphologic information in the biological samples, but the estimated standard error of age prediction in this study was quite high (±10 years) to be used with certainty in forensic investigations. Inter-individual variations in TL and variability among the gender must be also considered when applying this method. So, this method could only give a rough estimation of age and it may be a complementary method for age estimation from soft tissues.

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Telomere instability in the male germline

Cited by 141 publications

References 53 publications

Offspring's Leukocyte Telomere Length, Paternal Age, and Telomere Elongation in Sperm

Offspring's Leukocyte Telomere Length, Paternal Age, and Telomere Elongation in Sperm

Delayed paternal age of reproduction in humans is associated with longer telomeres across two generations of descendants

Telomere Length Measurement by Quantitative Real-time PCR: A Molecular Marker for Human Age Prediction

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