The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia.
Aging
/ drug effects
Animals
Cell Line
Disease Models, Animal
Electromyography
Gene Expression Regulation
/ drug effects
Humans
Laser Capture Microdissection
Male
Mechanistic Target of Rapamycin Complex 1
/ antagonists & inhibitors
Mice
Muscle Fibers, Skeletal
/ pathology
Myoblasts
Neuromuscular Junction
/ drug effects
Patch-Clamp Techniques
RNA-Seq
Sarcopenia
/ genetics
Signal Transduction
/ drug effects
Sirolimus
/ administration & dosage
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 09 2020
09 09 2020
Historique:
received:
13
12
2019
accepted:
05
08
2020
entrez:
10
9
2020
pubmed:
11
9
2020
medline:
2
10
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32908143
doi: 10.1038/s41467-020-18140-1
pii: 10.1038/s41467-020-18140-1
pmc: PMC7481251
doi:
Substances chimiques
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4510Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR074985
Pays : United States
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