p66(Shc): at the crossroad of oxidative stress and the genetics of aging.
The biology of aging has been mysterious for centuries. Removal of the p66(Shc) gene, which encodes an adaptor protein for cell signaling, extends lifespan by approximately 30% in mice and confers resistance to oxidative stress. The absence of p66(Shc) correlates with reduced levels of apoptosis. Oxidants induce phosphorylation of serine36 on p66(Shc), contributing to inactivation of members of the Forkhead transcription factor family, some of which appear to regulate the expression of antioxidant genes. The expression of p66(Shc) is regulated by the methylation status of its promoter. This leads us to hypothesize that increased methylation of the p66(Shc) promoter might contribute to the absence of its expression and therefore extended longevity in particular individuals.
Purdom
Sally
S
Interdisciplinary Graduate Program for Genetics and Genomics, University of Arizona, 1501 N. Campbell, Tucson, AZ 85724, USA.
Chen
Qin M
QM
D048868:Adaptor Proteins, Signal Transducing; D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D019175:DNA Methylation; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
D048868:Adaptor Proteins, Signal Transducing; D011506:Proteins; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1