The “telomere clock” — the progressive shortening of telomeres at every cell division — limits replicative capacity in culture and (judging from the progressive generational deterioration of telomerase knockout mouse lines) in vivo as well. Telomere length shows an inverse relationship with both chronological age and stress (though this latter point is controversial: it is based on measurements of peripheral blood leukocytes, in which stress-associated infection may cause hyperproliferation; some consider this a potential trivial explanation of the observations).
Telomere length is heterogeneous, both among cell lineages within an individual and between individuals. Given that telomere length governs replicative (and therefore tissue-regenerative) capacity and has some (negative) correlation with stress, it seems logical to ask whether telomere length is associated with lifespan.
Njajou et al. address this question by looking at the heritability of telomere length in a genetically homogeneous population (the Amish, who eschew much modern technology but are apparently kind enough to share their blood samples with those who do not). They find that telomere length is indeed heritable, but asymmetrically between parents: Dad’s telomeres matter more than Mom’s.
Telomere length is paternally inherited and is associated with parental lifespan
Telomere length (TL) is emerging as a biomarker for aging and survival. To evaluate factors influencing this trait, we measured TL in a large homogeneous population, estimated the heritability (h(2)), and tested for parental effects on TL variation. Our sample included 356 men and 551 women, aged 18-92 years, from large Amish families. Mean TL in leukocytes was measured by quantitative PCR (mean: 6,198 +/- 1,696 bp). The h(2) of TL was 0.44 +/- 0.06 (P < 0.001), after adjusting for age, sex, and TL assay batch. As expected, TL was negatively correlated with age (r = -0.40; P < 0.001). There was no significant difference in TL between men and women, consistent with our previous findings that Amish men lived as long as Amish women. There was a stronger and positive correlation and association between TL in the offspring and paternal TL (r = 0.46, P < 0.001; beta = 0.22, P = 0.006) than offspring and maternal TL (r = 0.18, P = 0.04; beta = -0.02, P = 0.4). Furthermore, we observed a positive correlation and association between daughter’s TL and paternal lifespan (r = 0.20, P < 0.001; beta = 0.21, P = 0.04), but not between daughter’s TL and maternal lifespan (r = -0.01, beta = 0.04; both P = not significant). Our data, which are based on one of the largest family studies of human TL, support a link between TL and aging and lifespan and suggest a strong genetic influence, possibly via an imprinting mechanism, on TL regulation.
The authors use DNA samples from, which are more than a few cell divisions removed from the germ line. Thus the heritability of telomere length is an important finding all by itself, because it suggests that blood leukocyte telomere length is representative of the “inherent” telomere length of an individual.
The paper’s key finding (from my perspective, at least) didn’t make it into the title: Telomere length is positively correlated with lifespan. While I’m aware of studies linking telomerase activity in animal species to lifespan, the growing consensus seems to be that this is a corollary of the relationship between telomerase and body mass, which in turn is correlated with lifespan; furthermore, the relationship is the opposite of the one here (larger, longer-lived animals tend to have lower telomerase activity than smaller, shorter-lived animals with a similar body plan; see our earlier article Telomerase correlates negatively with body mass). This is the first study I’m aware of in which human-to-human variation in telomere length (which occupies a concept space somewhere between the strictly genetic and the strictly epigenetic) has been shown to correlate with lifespan.
The key issue now, of course: Where are the causal links, if any, between the telomeres a person inherits and their life expectancy?