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MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis

Author

Listed:
  • Joseph C. Reynolds

    (Leonard Davis School of Gerontology, University of Southern California)

  • Rochelle W. Lai

    (Leonard Davis School of Gerontology, University of Southern California)

  • Jonathan S. T. Woodhead

    (Discipline of Nutrition, Faculty of Medical and Health Sciences, The University of Auckland
    The University of Auckland)

  • James H. Joly

    (USC Mork Family Department of Chemical Engineering and Materials Science)

  • Cameron J. Mitchell

    (The University of Auckland
    University of British Colombia)

  • David Cameron-Smith

    (The University of Auckland)

  • Ryan Lu

    (Leonard Davis School of Gerontology, University of Southern California)

  • Pinchas Cohen

    (Leonard Davis School of Gerontology, University of Southern California
    USC Norris Comprehensive Cancer Center)

  • Nicholas A. Graham

    (USC Mork Family Department of Chemical Engineering and Materials Science
    USC Norris Comprehensive Cancer Center)

  • Bérénice A. Benayoun

    (Leonard Davis School of Gerontology, University of Southern California
    USC Norris Comprehensive Cancer Center
    USC Stem Cell Initiative)

  • Troy L. Merry

    (The University of Auckland
    University of British Colombia)

  • Changhan Lee

    (Leonard Davis School of Gerontology, University of Southern California
    USC Norris Comprehensive Cancer Center
    Biomedical Science, Graduate School, Ajou University)

Abstract

Healthy aging can be promoted by enhanced metabolic fitness and physical capacity. Mitochondria are chief metabolic organelles with strong implications in aging that also coordinate broad physiological functions, in part, using peptides that are encoded within their independent genome. However, mitochondrial-encoded factors that actively regulate aging are unknown. Here, we report that mitochondrial-encoded MOTS-c can significantly enhance physical performance in young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice. MOTS-c can regulate (i) nuclear genes, including those related to metabolism and proteostasis, (ii) skeletal muscle metabolism, and (iii) myoblast adaptation to metabolic stress. We provide evidence that late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) can increase physical capacity and healthspan in mice. In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation. Our data indicate that aging is regulated by genes encoded in both of our co-evolved mitochondrial and nuclear genomes.

Suggested Citation

  • Joseph C. Reynolds & Rochelle W. Lai & Jonathan S. T. Woodhead & James H. Joly & Cameron J. Mitchell & David Cameron-Smith & Ryan Lu & Pinchas Cohen & Nicholas A. Graham & Bérénice A. Benayoun & Troy , 2021. "MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20790-0
    DOI: 10.1038/s41467-020-20790-0
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    Cited by:

    1. Seul Ki Kim & Le Trung Tran & Cherl NamKoong & Hyung Jin Choi & Hye Jin Chun & Yong-ho Lee & MyungHyun Cheon & ChiHye Chung & Junmo Hwang & Hyun-Ho Lim & Dong Min Shin & Yun-Hee Choi & Ki Woo Kim, 2023. "Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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