DNA damage, cellular senescence and organismal ageing: causal or correlative?
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Publication Date
2007Journal Title
Nucleic Acids Res
ISSN
0305-1048
Publisher
Oxford University Press (OUP)
Volume
35
Issue
22
Pages
7417-7428
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Chen, J., Hales, C. N., & Ozanne, S. (2007). DNA damage, cellular senescence and organismal ageing: causal or correlative?. Nucleic Acids Res, 35 (22), 7417-7428. https://doi.org/10.1093/nar/gkm681
Abstract
Cellular senescence has long been used as a cellular model for understanding mechanisms underlying the ageing process. Compelling evidence obtained in recent years demonstrate that DNA damage is a common mediator for both replicative senescence, which is triggered by telomere shortening, and premature cellular senescence induced by various stressors such as oncogenic stress and oxidative stress. Extensive observations suggest that DNA damage accumulates with age and that this may be due to an increase in production of reactive oxygen species (ROS) and a decline in DNA repair capacity with age. Mutation or disrupted expression of genes that increase DNA damage often result in premature ageing. In contrast, interventions that enhance resistance to oxidative stress and attenuate DNA damage contribute towards longevity. This evidence suggests that genomic instability plays a causative role in the ageing process. However, conflicting findings exist which indicate that ROS production and oxidative damage levels of macromolecules including DNA do not always correlate with lifespan in model animals. Here we review the recent advances in addressing the role of DNA damage in cellular senescence and organismal ageing.
Keywords
Animals, Humans, DNA Damage, DNA, Mitochondrial, Aging, Cellular Senescence
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/E002161/1)
Biotechnology and Biological Sciences Research Council (BB/E00797X/1)
Identifiers
External DOI: https://doi.org/10.1093/nar/gkm681
This record's URL: https://www.repository.cam.ac.uk/handle/1810/309090
Rights
Attribution-NonCommercial 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc/4.0/
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