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Ageing Res Rev. 2009 Jul;8(3):189-98. doi: 10.1016/j.arr.2009.04.004. Epub 2009 May 9.

The ageing epigenome: damaged beyond repair?

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1
The Paul F. Glenn Laboratories for the Biological Mechanisms of Ageing, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA. David_Sinclair@hms.harvard.edu

Abstract

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.

PMID:
19439199
PMCID:
PMC2696802
DOI:
10.1016/j.arr.2009.04.004
[Indexed for MEDLINE]
Free PMC Article
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