Nuclear Genomic Instability and Aging

Laura J. Niedernhofer, Aditi U. Gurkar, Yinsheng Wang, Jan Vijg, Jan H.J. Hoeijmakers, Paul D. Robbins

Onderzoeksoutput: Bijdrage aan tijdschriftArtikel recenserenpeer review

172 Citaten (Scopus)

Samenvatting

The nuclear genome decays as organisms age. Numerous studies demonstrate that the burden of several classes of DNA lesions is greater in older mammals than in young mammals. More challenging is proving this is a cause rather than a consequence of aging. The DNA damage theory of aging, which argues that genomic instability plays a causal role in aging, has recently gained momentum. Support for this theory stems partly from progeroid syndromes in which inherited defects in DNA repair increase the burden of DNA damage leading to accelerated aging of one or more organs. Additionally, growing evidence shows that DNA damage accrual triggers cellular senescence and metabolic changes that promote a decline in tissue function and increased susceptibility to age-related diseases. Here, we examine multiple lines of evidence correlating nuclear DNA damage with aging. We then consider how, mechanistically, nuclear genotoxic stress could promote aging. We conclude that the evidence, in toto, supports a role for DNA damage as a nidus of aging.

Originele taal-2Engels
Pagina's (van-tot)295-322
Aantal pagina's28
TijdschriftAnnual Review of Biochemistry
Volume87
DOI's
StatusGepubliceerd - 20 jun. 2018
Extern gepubliceerdJa

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