The starvation hormone, fibroblast growth factor-21, extends lifespan in mice
Open accessAbstract
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.
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Mice with transgenic overexpression of fibroblast growth factor 21 (FGF21), a fasting hormone, can extend life span when maintained on an ad libitum diet.
“Interestingly, a recent report showed that mice with transgenic overexpression of fibroblast growth factor 21 (FGF21), a fasting hormone, can extend life span when maintained on an ad libitum diet (Zhang et al., 2012).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Zhang et al., 2012
Prolonged overexpression of FGF21 in mice increases insulin sensitivity and extends lifespan.
“prolonged overexpression of FGF21 in mice increases insulin sensitivity and extends lifespan64,79.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [64]
FGF21 is markedly induced in response to protein restriction but not caloric restriction.
“FGF21 is markedly induced in response to protein restriction (25, 73, 85) but not caloric restriction (73, 148).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [148]
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- Authors
- Zhang, Y., Xie, Y., Berglund, E. D., Coate, K. C., He, T. T., Katafuchi, T., Xiao, G., Potthoff, M. J., Wei, W., Wan, Y., Yu, R. T., Evans, R. M., Kliewer, S. A., & Mangelsdorf, D. J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Salk Institute for Biological Studies (US)
- Corresponding author
- Kliewer, Steven A
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2012-10-15
- Volume
- 1
- Pages
- e00065-e00065
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC3466591
- OpenAlex
- W2165852917
- Cited by
- 420
- References
- 42
- Citations by year
- 2026: 27 · 2025: 31 · 2024: 27 · 2023: 27 · 2022: 27 · 2021: 41 · 2020: 33 · 2019: 38 · 2018: 30 · 2017: 22 · 2016: 40 · 2015: 38 · 2014: 25 · 2013: 13 · 2012: 1
- FWCI
- 9.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Howard Hughes Medical Institute
- Leona M and Harry B Helmsley Charitable Trust
- UTSW Endowed Scholar Startup Fund
- National Institutes of Health (CA152301, DK057978, DK062434, DK089113, DK092083, RL1GM084436)
- Robert A Welch Foundation (I-1275, I-1558, I-1751)
- CPRIT (RP100841)
- Glenn Foundation
- Leona M. and Harry B. Helmsley Charitable Trust
- Welch Foundation (I-1275, I-1558, I-1751)
- Cancer Prevention and Research Institute of Texas (RP100841)
- Glenn Foundation for Medical Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- FGF21, lifespan extension, aging, fasting response, liver, transgenic overexpression, insulin sensitivity, ketogenesis, hepatic fatty acid oxidation, bone loss, physical growth
- MeSH terms
- Adaptation, Physiological, Adenylate Kinase, Animals, Bone Resorption, Fasting, Fatty Acids, Female, Fibroblast Growth Factors, Gene Expression Regulation, Insulin Resistance, Insulin-Like Growth Factor I, Ketone Bodies, Liver, Longevity, Male, Mice, Transgenic, NAD, Oxidation-Reduction, Growth Hormone, Signal Transduction, Transgenes, Caloric Restriction, Lipid Metabolism, Mice, TOR Serine-Threonine Kinases
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