Insulin-like signaling, nutrient homeostasis, and life span

Annu Rev Physiol. 2008;70:191-212. doi: 10.1146/annurev.physiol.70.113006.100533.


Insulin-like signaling is critical for nutrient homeostasis, growth and survival. However, work with lower metazoans-Caenorhabditis elegans and Drosophila-shows that reduced insulin-like signaling extends life span. In addition, reduced insulin signaling in higher animals-rodents and humans-causes glucose intolerance and hyperinsulinemia that progresses to diabetes and shortens the life span of affected individuals. Hyperinsulinemia usually develops to maintain glucose homeostasis and prevent the progression toward life-threatening type 2 diabetes; however, increased circulating insulin may have negative effects on the brain that promote age-related disease. We discuss the possibility that the brain is the site where reduced insulin-like signaling can consistently extend mammalian life span-just as reduced insulin-like signaling extends the life span of lower metazoans.

Publication types

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

MeSH terms

  • Animals
  • Food
  • Homeostasis / physiology*
  • Humans
  • Insulin / metabolism*
  • Life Expectancy*
  • Receptor, Insulin / metabolism*
  • Signal Transduction / physiology*


  • Insulin
  • Receptor, Insulin