IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice

Article

关键词: INSULIN-RECEPTOR;    GROWTH-HORMONE;    DWARF MICE;    LONGEVITY;    GENE;    MUTATIONS;    EXTENSION;    CANCER;    TISSUE;   

DOI  :  10.1038/nature01298

来源: SCIE

【 摘 要 】

Studies in invertebrates have led to the identification of a number of genes that regulate lifespan, some of which encode components of the insulin or insulin-like signalling pathways(1-3). Examples include the related tyrosine kinase receptors InR (Drosophila melanogaster) and DAF-2 (Caenorhabditis elegans) that are homologues of the mammalian insulin-like growth factor type 1 receptor (IGF-1R). To investigate whether IGF-1R also controls longevity in mammals, we inactivated the IGF-1R gene in mice (Igf1r). Here, using heterozygous knockout mice because null mutants are not viable, we report that Igf1r (+/-) mice live on average 26% longer than their wild-type littermates (P < 0.02). Female Igf1r (+/-) mice live 33% longer than wild-type females (P < 0.001), whereas the equivalent male mice show an increase in lifespan of 16%, which is not statistically significant. Long-lived Igf1r (+/-) mice do not develop dwarfism, their energy metabolism is normal, and their nutrient uptake, physical activity, fertility and reproduction are unaffected. The Igf1r (+/-) mice display greater resistance to oxidative stress, a known determinant of ageing. These results indicate that the IGF-1 receptor may be a central regulator of mammalian lifespan.

【 授权许可】

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