Abstract
p66 shc−/− mice exhibit prolonged lifespan and increased resistance to oxidative and hypoxic stress. To investigate p66 shc involvement in human longevity, p66 shc mRNA and protein were evaluated in fibroblasts from young people, elderly and centenarians, exposed to oxidative or hypoxic stress. Unexpectedly, centenarians showed the highest basal levels of p66 shc . Oxidative stress induced p66 shc in all samples. At variance, hypoxic stress caused p66 shc reduction only in cells from centenarians. These changes occurred in absence of any modification of p66 shc promoter methylation pattern. Intriguingly, in cells from centenarians, p66 shc induction was affected by p53 codon 72 polymorphism. Thus, cells from centenarians present a peculiar regulation of p66 shc , suggesting that its role in mammalian longevity is more complex than previously thought.
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