IGF-1 Receptor Regulates Lifespan and Resistance to Oxidative Stress in Mice

Nature. 2003 Jan 9;421(6919):182-7. doi: 10.1038/nature01298. Epub 2002 Dec 4.

Abstract

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.

MeSH terms

  • Aging / genetics
  • Animals
  • Blood Glucose / analysis
  • Cells, Cultured
  • Female
  • Fertility / genetics
  • Fibroblasts
  • Gene Deletion
  • Glucose Tolerance Test
  • Ligands
  • Longevity* / genetics
  • Male
  • Mice
  • Mice, Knockout
  • Oxidative Stress* / genetics
  • Phenotype
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism*
  • Sexual Maturation / genetics
  • Signal Transduction

Substances

  • Blood Glucose
  • Ligands
  • Receptor, IGF Type 1