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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 & , 2022. "FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29499-8
    DOI: 10.1038/s41467-022-29499-8
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    Cited by:

    1. Thomas Agius & Raffaella Emsley & Arnaud Lyon & Michael R. MacArthur & Kevin Kiesworo & Anna Faivre & Louis Stavart & Martine Lambelet & David Legouis & Sophie Seigneux & Déla Golshayan & Francois Laz, 2024. "Short-term hypercaloric carbohydrate loading increases surgical stress resilience by inducing FGF21," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Reji Babygirija & Michelle M. Sonsalla & Jericha Mill & Isabella James & Jessica H. Han & Cara L. Green & Mariah F. Calubag & Gina Wade & Anna Tobon & John Michael & Michaela M. Trautman & Ryan Matosk, 2024. "Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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