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

Ham, Daniel J. and Börsch, Anastasiya and Lin, Shuo and Thürkauf, Marco and Weihrauch, Martin and Reinhard, Judith R. and Delezie, Julien and Battilana, Fabienne and Wang, Xueyong and Kaiser, Marco S. and Guridi, Maitea and Sinnreich, Michael and Rich, Mark M. and Mittal, Nitish and Tintignac, Lionel A. and Handschin, Christoph and Zavolan, Mihaela and Rüegg, Markus A.. (2020) The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia. Nature Communications, 11 (1). p. 4510.

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Official URL: https://edoc.unibas.ch/78545/

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Neuromuscular Research (Sinnreich)
05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin)
05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Zavolan, Mihaela and Rüegg, Markus A. and Handschin, Christoph and Ham, Daniel Jacob and Börsch, Anastasiya and Lin, Shuo and Thürkauf, Marco and Weihrauch, Martin and Reinhard, Judith and Delezie, Julien and Battilana, Fabienne and Kaiser, Marco and Guridi Ormazabal, Maitea and Sinnreich, Michael and Mittal, Nitish and Tintignac, Lionel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
e-ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:30 Dec 2020 08:33
Deposited On:30 Dec 2020 08:33

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