FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice

Cristal M. Hill (), Diana C. Albarado, Lucia G. Coco, Redin A. Spann, Md Shahjalal Khan, Emily Qualls-Creekmore, David H. Burk, Susan J. Burke, J. Jason Collier, Sangho Yu, David H. McDougal, Hans-Rudolf Berthoud, Heike Münzberg, Andrzej Bartke and Christopher D. Morrison ()
Additional contact information
Cristal M. Hill: Pennington Biomedical Research Center
Diana C. Albarado: Pennington Biomedical Research Center
Lucia G. Coco: Pennington Biomedical Research Center
Redin A. Spann: Pennington Biomedical Research Center
Md Shahjalal Khan: Pennington Biomedical Research Center
Emily Qualls-Creekmore: Pennington Biomedical Research Center
David H. Burk: Pennington Biomedical Research Center
Susan J. Burke: Pennington Biomedical Research Center
J. Jason Collier: Pennington Biomedical Research Center
Sangho Yu: Pennington Biomedical Research Center
David H. McDougal: Pennington Biomedical Research Center
Hans-Rudolf Berthoud: Pennington Biomedical Research Center
Heike Münzberg: Pennington Biomedical Research Center
Andrzej Bartke: Southern Illinois University School of Medicine
Christopher D. Morrison: Pennington Biomedical Research Center

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Dietary protein restriction is increasingly recognized as a unique approach to improve metabolic health, and there is increasing interest in the mechanisms underlying this beneficial effect. Recent work indicates that the hormone FGF21 mediates the metabolic effects of protein restriction in young mice. Here we demonstrate that protein restriction increases lifespan, reduces frailty, lowers body weight and adiposity, improves physical performance, improves glucose tolerance, and alters various metabolic markers within the serum, liver, and adipose tissue of wildtype male mice. Conversely, mice lacking FGF21 fail to exhibit metabolic responses to protein restriction in early life, and in later life exhibit early onset of age-related weight loss, reduced physical performance, increased frailty, and reduced lifespan. These data demonstrate that protein restriction in aging male mice exerts marked beneficial effects on lifespan and metabolic health and that a single metabolic hormone, FGF21, is essential for the anti-aging effect of this dietary intervention.

Date: 2022
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DOI: 10.1038/s41467-022-29499-8

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