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衰老可以被编程吗?

Can Aging be Programmed?

作者信息

Mitteldorf J

机构信息

National Institute of Biological Sciences, Beijing, 102206, China.

出版信息

Biochemistry (Mosc). 2018 Dec;83(12):1524-1533. doi: 10.1134/S0006297918120106.

DOI:10.1134/S0006297918120106
PMID:30878027
Abstract

Aging diminishes individual fitness, and aging could never evolve as an adaptive program according to the most prevalent model of evolutionary theory. On the other hand, some mechanisms of aging have been found to be conserved since the Cambrian explosion, and the physiology of aging sometimes looks like programmed self-destruction. Biostatisticians find evidence of an epigenetic aging clock, extending the clock that controls the growth and development into a realm of inexorably increasing mortality. These and other observations have suggested to some biologists that our understanding of aging is being constrained by restrictive evolutionary paradigms. Several computational models have been proposed; but evolution of an aging program requires group selection on a scale that goes beyond the theory of multilevel selection, a perspective that is already controversial. So, the question whether plausible models exist that can account for aging as a group-selected adaptation is central to our understanding of what aging is, where it comes from and, importantly, how anti-aging medicine might most propitiously be pursued. In a 2016 Aging Cell article, Kowald and Kirkwood reviewed computational models that evolve aging as an adaptation. They find fault with each of these models in turn, based on theory alone, and on this basis, they endorse the standing convention that aging must be understood in terms of trade-off models. But consideration of the corpus of experimental evidence creates a picture that stands in counterpoint to the conclusions of that review. Presented herein is a broad summary of that evidence, together with a description of one model that Kowald and Kirkwood omitted, the demographic theory of aging, which may be the most conservative, and therefore most plausible of the alternative evolutionary theories, and which is the subject of a book by the present author, published contemporaneously with Kowald and Kirkwood.

摘要

衰老会降低个体的适应性,根据进化理论中最流行的模型,衰老永远不可能作为一种适应性程序进化而来。另一方面,人们发现一些衰老机制自寒武纪大爆发以来就一直存在,而且衰老的生理过程有时看起来像是程序性的自我毁灭。生物统计学家发现了表观遗传衰老时钟的证据,将控制生长和发育的时钟扩展到了死亡率无情上升的领域。这些以及其他观察结果向一些生物学家表明,我们对衰老的理解正受到限制性进化范式的制约。已经提出了几种计算模型;但是衰老程序的进化需要超出多级选择理论范围的群体选择,而这一观点本身就存在争议。所以,是否存在合理的模型能够将衰老解释为群体选择的适应性,这个问题对于我们理解衰老是什么、它从何而来,以及重要的是如何最有利地开展抗衰老医学研究至关重要。在2016年发表于《衰老细胞》的一篇文章中,科瓦尔德和柯克伍德回顾了将衰老作为一种适应性进化的计算模型。他们依次基于理论对这些模型中的每一个都提出了批评,并在此基础上支持传统观点,即必须根据权衡模型来理解衰老。但是对实验证据整体的考量呈现出一幅与该综述结论相反的图景。本文呈现了该证据的广泛总结,以及对科瓦尔德和柯克伍德遗漏的一个模型——衰老的人口统计学理论的描述,该理论可能是最保守的,因此也是替代进化理论中最合理的,并且是本文作者与科瓦尔德和柯克伍德同期出版的一本书的主题。

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Evolutionary theories of aging and longevity.衰老与长寿的进化理论。
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Demographic evidence for adaptive theories of aging.人口统计学证据支持衰老的适应性理论。
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