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Nuclear Genomic Instability and Aging.
- Source :
-
Annual review of biochemistry [Annu Rev Biochem] 2018 Jun 20; Vol. 87, pp. 295-322. - Publication Year :
- 2018
-
Abstract
- 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.
- Subjects :
- Aging drug effects
Aging radiation effects
Animals
Autophagy genetics
Cellular Senescence genetics
DNA Damage genetics
DNA Repair genetics
Humans
Longevity genetics
Mitochondria genetics
Mitochondria metabolism
Models, Genetic
Mutation
Neoplasms genetics
Neoplasms therapy
Proteostasis genetics
Regeneration genetics
Signal Transduction genetics
Aging genetics
Cell Nucleus genetics
Genomic Instability
Subjects
Details
- Language :
- English
- ISSN :
- 1545-4509
- Volume :
- 87
- Database :
- MEDLINE
- Journal :
- Annual review of biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 29925262
- Full Text :
- https://doi.org/10.1146/annurev-biochem-062917-012239