IGF-1 receptor regulates lifespan and resistance to oxidative...

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

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, 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.


Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, Even PC, Cervera P, Le Bouc Y.
Nature 2003 Jan 9;421(6919):182-7
Institut National de la Sante et de la Recherche Medicale U515, Hopital Saint-Antoine, 75571 Paris 12, France. holzenberger@st-antoine.inserm.fr
PMID: 12483226 [PubMed - indexed for MEDLINE]