The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia

Daniel J. Ham, Anastasiya Börsch, Shuo Lin, Marco Thürkauf, Martin Weihrauch, Judith R. Reinhard, Julien Delezie, Fabienne Battilana, Xueyong Wang, Marco S. Kaiser, Maitea Guridi, Michael Sinnreich, Mark M. Rich, Nitish Mittal, Lionel A. Tintignac, Christoph Handschin, Mihaela Zavolan and Markus A. Rüegg ()
Additional contact information
Daniel J. Ham: Biozentrum, University of Basel
Anastasiya Börsch: Biozentrum, University of Basel
Shuo Lin: Biozentrum, University of Basel
Marco Thürkauf: Biozentrum, University of Basel
Martin Weihrauch: Biozentrum, University of Basel
Judith R. Reinhard: Biozentrum, University of Basel
Julien Delezie: Biozentrum, University of Basel
Fabienne Battilana: Biozentrum, University of Basel
Xueyong Wang: Wright State University
Marco S. Kaiser: Biozentrum, University of Basel
Maitea Guridi: Biozentrum, University of Basel
Michael Sinnreich: University of Basel
Mark M. Rich: Wright State University
Nitish Mittal: Biozentrum, University of Basel
Lionel A. Tintignac: University of Basel
Christoph Handschin: Biozentrum, University of Basel
Mihaela Zavolan: Biozentrum, University of Basel
Markus A. Rüegg: Biozentrum, University of Basel

Nature Communications, 2020, vol. 11, issue 1, 1-21

Abstract: Abstract With human median lifespan extending into the 80s in many developed countries, the societal burden of age-related muscle loss (sarcopenia) is increasing. mTORC1 promotes skeletal muscle hypertrophy, but also drives organismal aging. Here, we address the question of whether mTORC1 activation or suppression is beneficial for skeletal muscle aging. We demonstrate that chronic mTORC1 inhibition with rapamycin is overwhelmingly, but not entirely, positive for aging mouse skeletal muscle, while genetic, muscle fiber-specific activation of mTORC1 is sufficient to induce molecular signatures of sarcopenia. Through integration of comprehensive physiological and extensive gene expression profiling in young and old mice, and following genetic activation or pharmacological inhibition of mTORC1, we establish the phenotypically-backed, mTORC1-focused, multi-muscle gene expression atlas, SarcoAtlas (https://sarcoatlas.scicore.unibas.ch/), as a user-friendly gene discovery tool. We uncover inter-muscle divergence in the primary drivers of sarcopenia and identify the neuromuscular junction as a focal point of mTORC1-driven muscle aging.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18140-1

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DOI: 10.1038/s41467-020-18140-1

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