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Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle

Author

Listed:
  • Daniel J. Ham

    (University of Basel)

  • Anastasiya Börsch

    (University of Basel)

  • Kathrin Chojnowska

    (University of Basel)

  • Shuo Lin

    (University of Basel)

  • Aurel B. Leuchtmann

    (University of Basel)

  • Alexander S. Ham

    (University of Basel)

  • Marco Thürkauf

    (University of Basel)

  • Julien Delezie

    (University of Basel)

  • Regula Furrer

    (University of Basel)

  • Dominik Burri

    (University of Basel)

  • Michael Sinnreich

    (University of Basel)

  • Christoph Handschin

    (University of Basel)

  • Lionel A. Tintignac

    (University of Basel)

  • Mihaela Zavolan

    (University of Basel)

  • Nitish Mittal

    (University of Basel)

  • Markus A. Rüegg

    (University of Basel)

Abstract

Preserving skeletal muscle function is essential to maintain life quality at high age. Calorie restriction (CR) potently extends health and lifespan, but is largely unachievable in humans, making “CR mimetics” of great interest. CR targets nutrient-sensing pathways centering on mTORC1. The mTORC1 inhibitor, rapamycin, is considered a potential CR mimetic and is proven to counteract age-related muscle loss. Therefore, we tested whether rapamycin acts via similar mechanisms as CR to slow muscle aging. Here we show that long-term CR and rapamycin unexpectedly display distinct gene expression profiles in geriatric mouse skeletal muscle, despite both benefiting aging muscles. Furthermore, CR improves muscle integrity in mice with nutrient-insensitive, sustained muscle mTORC1 activity and rapamycin provides additive benefits to CR in naturally aging mouse muscles. We conclude that rapamycin and CR exert distinct, compounding effects in aging skeletal muscle, thus opening the possibility of parallel interventions to counteract muscle aging.

Suggested Citation

  • Daniel J. Ham & Anastasiya Börsch & Kathrin Chojnowska & Shuo Lin & Aurel B. Leuchtmann & Alexander S. Ham & Marco Thürkauf & Julien Delezie & Regula Furrer & Dominik Burri & Michael Sinnreich & Chris, 2022. "Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29714-6
    DOI: 10.1038/s41467-022-29714-6
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    References listed on IDEAS

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    4. Sung Hee Um & Francesca Frigerio & Mitsuhiro Watanabe & Frédéric Picard & Manel Joaquin & Melanie Sticker & Stefano Fumagalli & Peter R. Allegrini & Sara C. Kozma & Johan Auwerx & George Thomas, 2004. "Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity," Nature, Nature, vol. 431(7005), pages 200-205, September.
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