Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration
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 (Liu et al., 2015). 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 06, 2017
- Source ID
- 10.7554/elife.26464
Entities
People
- Aidi Tan
- Alanna Klose
- Joe V. Chakkalakal
- Lan Wei-lapierre
- Mariela Cortés-lópez
- Morgan Flaherty
- Nicole D Paris
- Pedro Miura
- Robert T. Dirksen
- Sophie Forman
- Wenxuan Liu
Organizations
- Congressionally Directed Medical Research Programs
- National Institute on Aging
- New York Stem Cell Foundation
- Tsinghua National Laboratory for Information Science and Technology
- Tsinghua University
- University of Nevada, Reno
- University of Rochester