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

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Holzenberger, Martin | Dupont, Joëlle | Ducos, Bertrand | Leneuve, Patricia | Geloen, Alain | Even, Patrick, C. | Cervera, Pascale | Le Bouc, Yves

Edité par CCSD ; Nature Publishing Group -

International audience. InR and DAF-2 have been shown to regulate longevity in insects and worms, respectively. These evolutionarily related tyrosine kinase receptors are structurally similar to both the insulin receptor (IR) and insulin-like growth factor type 1 receptor (IGF-1R) of mammals. To investigate whether IGF-1R also controls longevity in mammals, we inactivated the IGF-1R gene in the mouse. We used heterozygous knockout mice (IGF-1R +/-) because null mutants were not viable. We demonstrated that IGF-1R +/-mice had half the normal number of receptors and were healthy. IGF-1R +/-mutants lived a mean of 26% longer than their wild-type littermates (P < 0.02). When evaluated separately, female mutants lived 33% (P < 0.001) longer than wild-type females, whereas the increase in longevity of male mutants (+16%) was not significant. Long-lived IGF-1R +/-mice did not develop dwarfism, their energy metabolism was normal, and their nutrient uptake, physical activity, fertility and reproduction were unaffected. IGF-1R +/-mutants showed greater resistance in vivo to oxidative stress, a major determinant of

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