Robins Chloe, Conneely Karen N
Department of Human Genetics, Box 110, Emory University School of Medicine, 615 Michael St. NE, Atlanta, GA, 30322, USA,
Hum Genet. 2014 Dec;133(12):1451-65. doi: 10.1007/s00439-014-1492-7. Epub 2014 Oct 8.
From an evolutionary perspective, the existence of senescence is a paradox. Why has senescence not been more effectively selected against given its associated decreases in Darwinian fitness? Why does senescence exist and how has it evolved? Three major theories offer explanations: (1) the theory of mutation accumulation suggested by PB Medawar; (2) the theory of antagonistic pleiotropy suggested by GC Williams; and (3) the disposable soma theory suggested by TBL Kirkwood. These three theories differ in the underlying causes of aging that they propose but are not mutually exclusive. This paper compares the specific biological predictions of each theory and discusses the methods and results of previous empirical tests. Lifespan is found to be the most frequently used estimate of senescence in evolutionary investigations. This measurement acts as a proxy for an individual's rate of senescence, but provides no information on an individual's senescent state or "biological age" throughout life. In the future, use of alternative longitudinal measures of senescence may facilitate investigation of previously neglected aspects of evolutionary models, such as intra- and inter-individual heterogeneity in the process of aging. DNA methylation data are newly proposed to measure biological aging and are suggested to be particularly useful for such investigations.
从进化的角度来看，衰老的存在是一个悖论。鉴于衰老会导致达尔文适应性下降，为什么衰老没有被更有效地淘汰呢？衰老为何存在以及它是如何进化的？有三种主要理论提供了解释：（1）PB·梅达沃提出的突变积累理论；（2）GC·威廉姆斯提出的拮抗多效性理论；（3）TBL·柯克伍德提出的可抛弃体细胞理论。这三种理论提出的衰老潜在原因各不相同，但并非相互排斥。本文比较了每种理论的具体生物学预测，并讨论了先前实证检验的方法和结果。在进化研究中，寿命被发现是最常用来估计衰老的指标。这种测量可作为个体衰老速率的替代指标，但无法提供个体一生中衰老状态或“生物年龄”的信息。未来，使用衰老的替代纵向测量方法可能有助于研究进化模型中先前被忽视的方面，例如衰老过程中的个体内和个体间异质性。新提出的DNA甲基化数据可用于测量生物衰老，并被认为对这类研究特别有用。
