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

• DOI: 10.7554/elife.00065
• Publication Date: 2012-10-15T16:36:40Z
• Authors: Yuan Zhang; Yang Xie; Eric D Berglund; Katie Colbert Coate; Tian Teng He; Takeshi Katafuchi; Guanghua Xiao; Matthew J Potthoff; Wei Wei; Yihong Wan; Ruth T Yu; Ronald M Evans; Steven A Kliewer; David J Mangelsdorf
• Keywords: Male; QH301-705.5; Science; Longevity; Mice, Transgenic; Ketone Bodies; liver; Mice; longevity; fibroblast growth factor; Animals; Biology (General); Bone Resorption; Insulin-Like Growth Factor I; Caloric Restriction; 2. Zero hunger; Q; Adenylate Kinase; Fatty Acids; R; Fasting; Lipid Metabolism; Adaptation, Physiological; Fibroblast Growth Factors; Gene Expression Regulation; Liver; Genes and Chromosomes; Growth Hormone; growth hormone; Medicine; Female; caloric restriction; Insulin Resistance

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.