DNA repair, genome stability, and aging.
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.
Lombard
David B
DB
Howard Hughes Medical Institute, The Children's Hospital, Department of Genetics, Harvard Medical School and, The CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA.
Chua
Katrin F
KF
Mostoslavsky
Raul
R
Franco
Sonia
S
Gostissa
Monica
M
Alt
Frederick W
FW
D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D042822:Genomic Instability / Q000235:genetics / Q000502:physiology*; D000072200:Ku Autoantigen; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D051379:Mice; D051135:Rad51 Recombinase; D017382:Reactive Oxygen Species / Q000378:metabolism*; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse; D037761:Sirtuins; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen