The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

Elife. 2012 Oct 15;1:e00065. doi: 10.7554/eLife.00065.

Abstract

Fibroblast growth factor-21 (FGF21) is a hormone secreted by the liver during fasting that elicits diverse aspects of the adaptive starvation response. Among its effects, FGF21 induces hepatic fatty acid oxidation and ketogenesis, increases insulin sensitivity, blocks somatic growth and causes bone loss. Here we show that transgenic overexpression of FGF21 markedly extends lifespan in mice without reducing food intake or affecting markers of NAD+ metabolism or AMP kinase and mTOR signaling. Transcriptomic analysis suggests that FGF21 acts primarily by blunting the growth hormone/insulin-like growth factor-1 signaling pathway in liver. These findings raise the possibility that FGF21 can be used to extend lifespan in other species.DOI:http://dx.doi.org/10.7554/eLife.00065.001.

Keywords: Mouse; caloric restriction; fibroblast growth factor; growth hormone; liver; longevity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Adenylate Kinase / genetics
  • Adenylate Kinase / metabolism
  • Animals
  • Bone Resorption / genetics
  • Bone Resorption / metabolism
  • Caloric Restriction
  • Fasting / metabolism
  • Fatty Acids / metabolism
  • Female
  • Fibroblast Growth Factors / genetics*
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation
  • Growth Hormone / genetics*
  • Growth Hormone / metabolism
  • Insulin Resistance
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor I / metabolism
  • Ketone Bodies / metabolism
  • Lipid Metabolism
  • Liver / metabolism*
  • Longevity / genetics*
  • Male
  • Mice
  • Mice, Transgenic
  • NAD / metabolism
  • Oxidation-Reduction
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Transgenes*

Substances

  • Fatty Acids
  • Ketone Bodies
  • fibroblast growth factor 21
  • insulin-like growth factor-1, mouse
  • NAD
  • Fibroblast Growth Factors
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Adenylate Kinase