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

被引：139

作者：

Ham, Daniel J. ^{[1
]}

Borsch, Anastasiya ^{[1
]}

Lin, Shuo ^{[1
]}

Thurkauf, Marco ^{[1
]}

Weihrauch, Martin ^{[1
]}

Reinhard, Judith R. ^{[1
]}

Delezie, Julien ^{[1
]}

Battilana, Fabienne ^{[1
]}

Wang, Xueyong ^{[2
]}

Kaiser, Marco S. ^{[1
]}

Guridi, Maitea ^{[1
]}

Sinnreich, Michael ^{[3
]}

Rich, Mark M. ^{[2
]}

Mittal, Nitish ^{[1
]}

Tintignac, Lionel A. ^{[3
]}

Handschin, Christoph ^{[1
]}

Zavolan, Mihaela ^{[1
]}

Ruegg, Markus A. ^{[1
]}

机构：

[1] Univ Basel, Biozentrum, Basel, Switzerland

[2] Wright State Univ, Dept Neurol Neurosci Cell Biol & Physiol, Dayton, OH 45435 USA

[3] Univ Basel, Dept Biomed, Pharmazentrum, Basel, Switzerland

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

瑞士国家科学基金会;

关键词：

WHOLE VASTUS LATERALIS; AGE-RELATED-CHANGES; SKELETAL-MUSCLE; LIFE-SPAN; GENE-EXPRESSION; CALORIC RESTRICTION; REDUCTION; RAPAMYCIN; ATROPHY; MICE;

D O I：

10.1038/s41467-020-18140-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：21

共 92 条

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