The central role of DNA damage in the ageing process

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 fe...

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Bibliographic Details
Published in:Nature (London) 2021-04, Vol.592 (7856), p.695-703
Main Authors: Schumacher, Björn, Pothof, Joris, Vijg, Jan, Hoeijmakers, Jan H. J.
Format: Article
Language:English
Subjects:
631/136/7
631/208/211
631/337/1427
631/80/509
Age
Aging
Aging - genetics
Animals
Cancer
Cell cycle
Cell Differentiation
Cell division
Cell Lineage
Damage accumulation
Deoxyribonucleic acid
Deregulation
Disease
DNA
DNA Damage
DNA methylation
DNA Repair
Epigenetics
Genetic aspects
Genomes
Genotype & phenotype
Humanities and Social Sciences
Humans
Mammals
multidisciplinary
Mutation
Phenotypes
Physiological aspects
Review
review-article
Science
Science (multidisciplinary)
Signalling systems
Telomerase
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Summary: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.
ISSN:0028-0836
1476-4687
DOI:10.1038/s41586-021-03307-7