Divergence of sperm and leukocyte age-dependent telomere dynamics: implications for male-driven evolution of telomere length in humans.
Divergence of sperm and leukocyte age-dependent telomere dynamics: implications for male-driven evolution of telomere length in humans.
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DOI：
10.1093/molehr/gas028
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发表时间：
2012-11
影响因子：
4
通讯作者：
Aviv A
中科院分区：
文献类型：
--
作者：
Aston KI;Hunt SC;Susser E;Kimura M;Factor-Litvak P;Carrell D;Aviv A
体内端粒长度的动态变化是由端粒长度及其随年龄的变化所决定的，端粒长度是由细胞复制引起的。白细胞TL(LTL)反映了造血干细胞(HSCs)中的TL，随着年龄的增长而变短。相比之下，精子TL反映了男性生殖细胞中的TL，随着年龄的增长而变长。此外，年长父亲的后代表现出更长的LTL。到目前为止，还没有研究研究LTL和精子TL与年龄的关系，也没有研究它们对父亲受孕年龄(PAC)对后代LTL的影响。我们报告了135名男性(平均年龄：34.4岁；范围：18-68岁)的下丘脑平均缩短19BP/年(r=−0.3；P=0.0004)，而精子下垂平均延长57BP/年(r=0.32；P=0.0002)。基于先前报道的HSCs和雄性生殖细胞的复制率，我们估计HSCs每次复制会损失26bp。然而，雄性生殖细胞每次复制仅增加2.48个碱基对。由于TL是以等位基因特异的方式遗传的，PAC对后代LTL的影响的幅度应该大约是年龄相关的精子TL延伸率的一半。当我们将先前研究的PAC效应数据与本研究的精子TL数据进行比较时，结果与这一预测一致。由于父性年龄较大是现代人的一个主要特征，我们认为在未来几代人中，TL可能会逐渐延长。从这个意义上说，生殖细胞TL的动力学可能推动了现代人TL的进化，也可能推动了普通人群中端粒相关疾病的进化。
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: 18–68 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 offspring's 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.
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DOI：
10.1073/pnas.0702703104
发表时间：
2007-07-17
影响因子：
11.1
作者：
Njajou, Omer T.;Cawthon, Richard M.;Hsueh, Wen-Chi
通讯作者：
Hsueh, Wen-Chi
影响因子：
64.8
作者：
Morrison, Sean J.;Kimble, Judith
通讯作者：
Kimble, Judith
影响因子：
--
作者：
Frans, Emma M.;Sandin, Sven;Hultman, Christina M.
通讯作者：
Hultman, Christina M.
后代的白细胞端粒长度，父亲时代和精子中的端粒伸长率。
影响因子：
4.5
作者：
Kimura, Masayuki;Cherkas, Lynn F.;Kato, Bernet S.;Demissie, Serkalem;Hjelmborg, Jacob B.;Brimacombe, Michael;Cupples, Adrienne;Hunkin, Janice L.;Gardner, Jefferey P.;Lu, Xiaobin;Cao, Xiaojian;Sastrasinh, Malinee;Province, Michael A.;Hunt, Steven C.;Christensen, Kaare;Levy, Daniel;Spector, Tim D.;Aviv, Abraham
通讯作者：
Aviv, Abraham
DOI：
10.1016/j.mrfmmm.2011.05.001
发表时间：
2012-02-01
影响因子：
2.3
作者：
Aviv, Abraham
通讯作者：
Aviv, Abraham