Extended longevity in mice lacking the insulin receptor in adipose tissue

Science. 2003 Jan 24;299(5606):572-4. doi: 10.1126/science.1078223.


Caloric restriction has been shown to increase longevity in organisms ranging from yeast to mammals. In some organisms, this has been associated with a decreased fat mass and alterations in insulin/insulin-like growth factor 1 (IGF-1) pathways. To further explore these associations with enhanced longevity, we studied mice with a fat-specific insulin receptor knockout (FIRKO). These animals have reduced fat mass and are protected against age-related obesity and its subsequent metabolic abnormalities, although their food intake is normal. Both male and female FIRKO mice were found to have an increase in mean life-span of approximately 134 days (18%), with parallel increases in median and maximum life-spans. Thus, a reduction of fat mass without caloric restriction can be associated with increased longevity in mice, possibly through effects on insulin signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipose Tissue / anatomy & histology*
  • Adipose Tissue / metabolism*
  • Aging
  • Animals
  • Body Constitution
  • Body Weight
  • Caloric Restriction
  • Eating
  • Female
  • Insulin / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Longevity*
  • Male
  • Mice
  • Mice, Knockout
  • Receptor, Insulin / genetics*
  • Receptor, Insulin / metabolism
  • Signal Transduction
  • Thinness*


  • Insulin
  • Insulin-Like Growth Factor I
  • Receptor, Insulin