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Does age influence loss of heterozygosity?

Carr, Laurie L and Gottschling, Daniel E (2008) Does age influence loss of heterozygosity? Experimental gerontology, 43 (3). pp. 123-129. ISSN 0531-5565

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Article URL: http://dx.doi.org/10.1016/j.exger.2007.10.010

Abstract

The striking correlation between advanced age and an increased incidence of cancer has led investigators to examine the influence of aging on genome maintenance. Because loss of heterozygosity (LOH) can lead to the inactivation of tumor suppressor genes, and thus carcinogenesis, understanding the affect of aging on this type of mutation event is particularly important. Several factors may affect the rate of LOH, including an increase in the amount of DNA damage, specifically double-strand breaks (DSBs), and the ability to efficiently repair this damage via pathways that minimize the loss of genetic information. Because of experimental constraints, there is only suggestive evidence for a change in the rate of DNA damage as humans age. However, recent studies in model organisms find that there are increased rates of LOH with age, and that repair of DNA damage occurs via a different pathway in old cells versus young cells. We speculate that the age-dependent change in DNA repair may explain why there is increased LOH, and that the findings from these model organisms may extend to humans.

Item Type: Article
Additional Information: This article is available to subscribers only via the URL above.
DOI: 10.1016/j.exger.2007.10.010
PubMed ID: 18054191
Grant Numbers: R01 AG023779
Keywords or MeSH Headings: Aging/genetics; Animals; Cell Aging/genetics; DNA Damage/physiology; DNA Repair/physiology; Humans; Loss of Heterozygosity;
Subjects: Cellular and Organismal Processes > Aging
Cellular and Organismal Processes > Genetic processes > Mutation
Cellular and Organismal Processes > Genetic processes > DNA damage and repair
Depositing User: Library Staff
Date Deposited: 29 Jun 2009 22:53
Last Modified: 14 Feb 2012 14:42
URI: http://authors.fhcrc.org/id/eprint/306

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