Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Animals
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Antigens, Nuclear / genetics
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Antigens, Nuclear / metabolism
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Cellular Senescence / genetics
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Cellular Senescence / physiology*
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DNA Damage / genetics
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DNA Damage / physiology
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DNA Repair / genetics
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DNA Repair / physiology*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Genomic Instability / genetics
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Genomic Instability / physiology*
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Ku Autoantigen
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Longevity / genetics
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Longevity / physiology*
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Mice
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Rad51 Recombinase
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Reactive Oxygen Species / metabolism*
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Sirtuins / genetics
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Sirtuins / metabolism
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
Substances
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Antigens, Nuclear
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DNA-Binding Proteins
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Reactive Oxygen Species
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Tumor Suppressor Protein p53
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Rad51 Recombinase
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Rad51 protein, mouse
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Sirtuins
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Xrcc6 protein, mouse
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Ku Autoantigen