Journal
NATURE
Volume 592, Issue 7856, Pages 695-703Publisher
NATURE RESEARCH
DOI: 10.1038/s41586-021-03307-7
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Funding
- NHLBI NIH HHS [U01 HL145560] Funding Source: Medline
- NIA NIH HHS [U19 AG056278, P01 AG017242, P01 AG047200, P30 AG038072] Funding Source: Medline
- NIEHS NIH HHS [U01 ES029519] Funding Source: Medline
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Ageing is a complex process that affects every organ and tissue in the body, but the causal mechanism behind it remains unclear. Accumulating evidence suggests that DNA damage may play a central role in driving ageing, providing a potential unified approach to combat age-related diseases.
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. This Review examines the evidence showing that DNA damage is associated with ageing phenotypes, suggesting that it may have a central role as the cause of ageing.
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