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The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia
Nat Commun. 2020 Sep 9;11(1):4510. doi: 10.1038/s41467-020-18140-1.
Daniel J Ham # 1, Anastasiya Börsch # 1, Shuo Lin 1, Marco Thürkauf 1, Martin Weihrauch 1, Judith R Reinhard 1, Julien Delezie 1, Fabienne Battilana 1, Xueyong Wang 2, Marco S Kaiser 1, Maitea Guridi 1, Michael Sinnreich 3, Mark M Rich 2, Nitish Mittal 1, Lionel A Tintignac 3, Christoph Handschin 1, Mihaela Zavolan # 1, Markus A Rüegg # 4
Abstract:
...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.
PMID: 32908143
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481251/
Tags: mice, mTORC1, rapamycin, sarcopenia, software