Telomere Length and the Cancer-Atherosclerosis Trade-Off.
Telomere Length and the Cancer-Atherosclerosis Trade-Off.
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DOI：
10.1371/journal.pgen.1006144
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发表时间：
2016-07
期刊：
影响因子：
4.5
通讯作者：
Aviv A
中科院分区：
文献类型：
--
作者：
Stone RC;Horvath K;Kark JD;Susser E;Tishkoff SA;Aviv A
现代人类是最长寿的陆生哺乳动物，与大多数寿命短的小型哺乳动物相比，其体细胞组织中的端粒较短，端粒酶活性受到抑制。与寿命短的小型哺乳动物相比，短端粒和受抑制的端粒酶的双重特征可能使人类对癌症具有相对抵抗力。然而，癌症抗性的权衡是表面上增加了与年龄相关的退行性疾病，主要是动脉粥样硬化的形式。在这次交流中，我们讨论了（a）人类端粒长度的遗传学，这是一个高度遗传的复杂性状，受遗传祖先，性别和父亲受孕年龄的影响，（B）癌症如何在哺乳动物端粒生物学的进化中发挥作用，（c）现代人类端粒长度是决定因素的证据。（而不仅仅是一个生物标志物）的癌症和动脉粥样硬化，和（d）相对较新的进化力量在形成人群之间和人群内的端粒长度变化的潜在影响，以及它们对人类主要疾病的可能持久影响。最后，我们提出了人类端粒遗传学在塑造现代人类寿命的潜在作用的背景下，未来的研究场所。
Modern humans, the longest-living terrestrial mammals, display short telomeres and repressed telomerase activity in somatic tissues compared with most short-living small mammals. The dual trait of short telomeres and repressed telomerase might render humans relatively resistant to cancer compared with short-living small mammals. However, the trade-off for cancer resistance is ostensibly increased age-related degenerative diseases, principally in the form of atherosclerosis. In this communication, we discuss (a) the genetics of human telomere length, a highly heritable complex trait that is influenced by genetic ancestry, sex, and paternal age at conception, (b) how cancer might have played a role in the evolution of telomere biology across mammals, (c) evidence that in modern humans telomere length is a determinant (rather than only a biomarker) of cancer and atherosclerosis, and (d) the potential influence of relatively recent evolutionary forces in fashioning the variation in telomere length across and within populations, and their likely lasting impact on major diseases in humans. Finally, we propose venues for future research on human telomere genetics in the context of its potential role in shaping the modern human lifespan.