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

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

doi:10.7554/eLife.00065

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

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

Research output: Contribution to journal › Article › peer-review

290 Scopus citations

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.

Original language	English (US)
Article number	e00065
Journal	eLife
Volume	2012
Issue number	1
DOIs	https://doi.org/10.7554/eLife.00065
State	Published - Oct 15 2012

ASJC Scopus subject areas

General Immunology and Microbiology
General Biochemistry, Genetics and Molecular Biology
General Neuroscience

Access to Document

10.7554/eLife.00065

Cite this

@article{ddaaf140e5f44250a1e7a0c267efe941,

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

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.",

author = "Yuan Zhang and Yang Xie and Berglund, {Eric D.} and {Colbert Coate}, Katie and He, {Tian Teng} and Takeshi Katafuchi and Guanghua Xiao and Potthoff, {Matthew J.} and Wei Wei and Yihong Wan and Yu, {Ruth T.} and Evans, {Ronald M.} and Kliewer, {Steven A.} and Mangelsdorf, {David J.}",

year = "2012",

month = oct,

day = "15",

doi = "10.7554/eLife.00065",

language = "English (US)",

volume = "2012",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

number = "1",

}

TY - JOUR

T1 - The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

AU - Zhang, Yuan

AU - Xie, Yang

AU - Berglund, Eric D.

AU - Colbert Coate, Katie

AU - He, Tian Teng

AU - Katafuchi, Takeshi

AU - Xiao, Guanghua

AU - Potthoff, Matthew J.

AU - Wei, Wei

AU - Wan, Yihong

AU - Yu, Ruth T.

AU - Evans, Ronald M.

AU - Kliewer, Steven A.

AU - Mangelsdorf, David J.

PY - 2012/10/15

Y1 - 2012/10/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84881508008&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881508008&partnerID=8YFLogxK

U2 - 10.7554/eLife.00065

DO - 10.7554/eLife.00065

M3 - Article

C2 - 23066506

AN - SCOPUS:84881508008

SN - 2050-084X

VL - 2012

JO - eLife

JF - eLife

IS - 1

M1 - e00065

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this