Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration
- University of Rochester Medical Center, United States
- University of Rochester, United States
- University of Nevada, United States
- Tsinghua University, China
Abstract
Neuromuscular junction degeneration is a prominent aspect of sarcopenia, the age-associated loss of skeletal muscle integrity. Previously, we showed that muscle stem cells activate and contribute to mouse neuromuscular junction regeneration in response to denervation (1). Here, we examined gene expression profiles and neuromuscular junction integrity in aged mouse muscles, and unexpectedly found limited denervation despite a high level of degenerated neuromuscular junctions. Instead, degenerated neuromuscular junctions were associated with reduced contribution from muscle stem cells. Indeed, muscle stem cell depletion was sufficient to induce neuromuscular junction degeneration at a younger age. Conversely, prevention of muscle stem cell and derived myonuclei loss was associated with attenuation of age-related neuromuscular junction degeneration, muscle atrophy, and the promotion of aged muscle force generation. Our observations demonstrate that deficiencies in muscle stem cell fate and post-synaptic myogenesis provide a cellular basis for age-related neuromuscular junction degeneration and associated skeletal muscle decline.
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Funding
National Institute on Aging (RO1AG051456)
- Joe V Chakkalakal
Congressionally Directed Medical Research Programs (W81XWH-14-1-0454)
- Joe V Chakkalakal
NYSTEM (C026877)
- Wenxuan Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Work with mice was conducted in accordance with protocols approved by the University Committee on Animal Resources, University of Rochester Medical Center protocol(#101565/2013-002)
Copyright
© 2017, Liu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration
eLife 6:e26464.
https://doi.org/10.7554/eLife.26464
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