老化
蛋白质稳态
表型
生物
DNA损伤
DNA
机制(生物学)
表观遗传学
计算生物学
神经科学
遗传学
DNA甲基化
基因
基因表达
认识论
哲学
作者
Björn Schumacher,Joris Pothof,Jan Vijg,Jan H.J. Hoeijmakers
出处
期刊:Nature
[Springer Nature]
日期:2021-04-28
卷期号:592 (7856): 695-703
被引量:316
标识
DOI:10.1038/s41586-021-03307-7
摘要
Ageing is a complex, multifaceted process leading to widespread functional decline that affects every organ and tissue, but it remains unknown whether ageing has a unifying causal mechanism or is grounded in multiple sources. Phenotypically, the ageing process is associated with a wide variety of features at the molecular, cellular and physiological level-for example, genomic and epigenomic alterations, loss of proteostasis, declining overall cellular and subcellular function and deregulation of signalling systems. However, the relative importance, mechanistic interrelationships and hierarchical order of these features of ageing have not been clarified. Here we synthesize accumulating evidence that DNA damage affects most, if not all, aspects of the ageing phenotype, making it a potentially unifying cause of ageing. Targeting DNA damage and its mechanistic links with the ageing phenotype will provide a logical rationale for developing unified interventions to counteract age-related dysfunction and disease.
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