p66(shc) is highly expressed in fibroblasts from centenarians.
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.
Department of Experimental Pathology, University of Bologna, via S. Giacomo 12, 40126 Bologna, Italy.
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Pandolfi
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Bonafè
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Di Tella
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Tiberi
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Salvioli
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Monti
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Sorbi
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Franceschi
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015153:Blotting, Western; D002478:Cells, Cultured; D003062:Codon; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D019175:DNA Methylation; D018076:DNA, Complementary / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D003855:Deoxyribose / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia; D008136:Longevity; D008875:Middle Aged; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013447:Sulfites / Q000737:chemistry; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D003062:Codon; D018076:DNA, Complementary; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013447:Sulfites; D016159:Tumor Suppressor Protein p53; D003855:Deoxyribose; D012313:RNA; D004247:DNA; D003676:Deferoxamine