The starvation hormone, fibroblast growth factor-21, extends lifespan in mice.
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.
Department of Pharmacology ,  University of Texas Southwestern Medical Center ,  Dallas ,  United States.
Yuan
Y
Zhang
Yang
Y
Xie
Eric D
ED
Berglund
Katie Colbert
KC
Coate
Tian Teng
TT
He
Takeshi
T
Katafuchi
Guanghua
G
Xiao
Matthew J
MJ
Potthoff
Wei
W
Wei
Yihong
Y
Wan
Ruth T
RT
Yu
Ronald M
RM
Evans
Steven A
SA
Kliewer
David J
DJ
Mangelsdorf
D000222:Adaptation, Physiological; D000263:Adenylate Kinase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism; D031204:Caloric Restriction; D005215:Fasting / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
D005227:Fatty Acids; D007657:Ketone Bodies; C414620:fibroblast growth factor 21; C519530:insulin-like growth factor-1, mouse; D009243:NAD; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase