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I.R.F. / Aging news / General / 03012101

IGF-1R and Lifespan
Posted on: January 21, 2003

Recent studies of positive IGF-1 influence on lifespan showed that it is highly involved into the regulation of individual's longevity and response to oxidative stress. One more study just confirms recent results*. 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. 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, scientists have inactivated the IGF-1R gene in mice (Igf1r). In this study heterozygous knockout mice were used, because null mutants are not viable, and it was concluded that Igf1r+/- mice lived on average 26% longer than their wild-type littermates (P < 0.02). Female Igf1r+/- mice lived 33% longer than wild-type females (P < 0.001), whereas the equivalent male mice showed an increase in lifespan of 16%, which is not statistically significant. Long-lived Igf1r+/- mice didn't develop dwarfism, their energy metabolism was normal, and their nutrient uptake, physical activity, fertility and reproduction were unaffected. The Igf1r+/- mice displayed greater resistance to oxidative stress, a known determinant of ageing. Such results indicated that the IGF-1 receptor may be a central regulator of mammalian lifespan.

Figure: IGF-1
Source: *Nature 421, 182 - 187 (2003); IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice; Martin Holzenberger et al.
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