Journal
AGEING RESEARCH REVIEWS
Volume 8, Issue 3, Pages 189-198Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.arr.2009.04.004
Keywords
DNA damage; Chromatin; Sirtuin; DNA repair; Ageing
Categories
Funding
- National Space Biomedical Research Institute [PF00903]
- Leukemia and Lymphoma Society
- NIH [RO1GM068072, RO1AG19719]
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Of all the proposed causes of ageing, DNA damage remains a leading, though still debated theory. Unlike most other types of age-related cellular damage, which can hypothetically be reversed, mutations in DNA are permanent. Such errors result in the accumulation of changes to RNA and protein sequences with age, and are tightly linked to cellular senescence and overall organ dysfunction. Over the past few years, an additional, more global role has emerged for the contribution of DNA damage and genomic instability to the ageing process. We, and others have found that DNA damage and the concomitant repair process can induce genome-wide epigenetic changes, which may promote a variety of age-related transcriptional and functional changes. Here, we discuss the link between DNA damage, chromatin alterations and ageing, an interplay that explains how seemingly random DNA damage could manifest in predictable phenotypic changes that define ageing, changes that may ultimately be reversible. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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