The central role of DNA damage in the ageing process

Björn Schumacher, Joris Pothof, Jan Vijg, Jan H.J. Hoeijmakers

Research output: Contribution to journalReview articlepeer-review

291 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)695-703
Number of pages9
Issue number7856
Publication statusPublished - 29 Apr 2021


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