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Cell. 2005 Feb 25;120(4):497-512.

DNA repair, genome stability, and aging.

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  • 1Howard Hughes Medical Institute, The Children's Hospital, Department of Genetics, Harvard Medical School and, The CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA.


Aging can be defined as progressive functional decline and increasing mortality over time. Here, we review evidence linking aging to nuclear DNA lesions: DNA damage accumulates with age, and DNA repair defects can cause phenotypes resembling premature aging. We discuss how cellular DNA damage responses may contribute to manifestations of aging. We review Sir2, a factor linking genomic stability, metabolism, and aging. We conclude with a general discussion of the role of mutant mice in aging research and avenues for future investigation.

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