Divergence of sperm and leukocyte age-dependent telomere dynamics: implications for male-driven evolution of telomere length in humans

作者：Aston Kenneth I; Hunt Steven C; Susser Ezra; Kimura Masayuki; Factor Litvak Pam; Carrell Douglas; Aviv Abraham^*

来源：Molecular Human Reproduction, 2012, 18(11): 517-522.

DOI：10.1093/molehr/gas028

• sperm telomere length
• leukocyte telomere length
• paternal age
• telomere evolution

Telomere length (TL) dynamics in vivo are defined by TL and its age-dependent change, brought about by cell replication. Leukocyte TL (LTL), which reflects TL in hematopoietic stem cells (HSCs), becomes shorter with age. In contrast, sperm TL, which reflects TL in the male germ cells, becomes longer with age. Moreover, offspring of older fathers display longer LTL. Thus far, no study has examined LTL and sperm TL relations with age in the same individuals, nor considered their implications for the paternal age at conception (PAC) effect on offspring LTL. We report that in 135 men (mean age: 34.4 years; range: 1868 years) on average, LTL became shorter by 19 bp/year (r 0.3; P 0.0004), while sperm TL became longer by 57 bp/year (r 0.32; P 0.0002). Based on previously reported replication rates of HSCs and male germ cells, we estimate that HSCs lose 26 bp per replication. However, male germ cells gain only 2.48 bp per replication. As TL is inherited in an allele-specific manner, the magnitude of the PAC effect on the offsprings LTL should be approximately half of age-dependent sperm-TL elongation. When we compared the PAC effect data from previous studies with sperm-TL data from this study, the result was consistent with this prediction. As older paternal age is largely a feature of contemporary humans, we suggest that there may be progressive elongation of TL in future generations. In this sense, germ cell TL dynamics could be driving the evolution of TL in modern humans and perhaps telomere-related diseases in the general population.

• 出版日期2012-11