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Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration

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 exa...

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Autores principales: Liu, Wenxuan, Klose, Alanna, Forman, Sophie, Paris, Nicole D, Wei-LaPierre, Lan, Cortés-Lopéz, Mariela, Tan, Aidi, Flaherty, Morgan, Miura, Pedro, Dirksen, Robert T, Chakkalakal, Joe V
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462534/
https://www.ncbi.nlm.nih.gov/pubmed/28583253
http://dx.doi.org/10.7554/eLife.26464
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author Liu, Wenxuan
Klose, Alanna
Forman, Sophie
Paris, Nicole D
Wei-LaPierre, Lan
Cortés-Lopéz, Mariela
Tan, Aidi
Flaherty, Morgan
Miura, Pedro
Dirksen, Robert T
Chakkalakal, Joe V
author_facet Liu, Wenxuan
Klose, Alanna
Forman, Sophie
Paris, Nicole D
Wei-LaPierre, Lan
Cortés-Lopéz, Mariela
Tan, Aidi
Flaherty, Morgan
Miura, Pedro
Dirksen, Robert T
Chakkalakal, Joe V
author_sort Liu, Wenxuan
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.26464.001
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spelling pubmed-54625342017-06-09 Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration Liu, Wenxuan Klose, Alanna Forman, Sophie Paris, Nicole D Wei-LaPierre, Lan Cortés-Lopéz, Mariela Tan, Aidi Flaherty, Morgan Miura, Pedro Dirksen, Robert T Chakkalakal, Joe V eLife Developmental Biology and Stem Cells 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. DOI: http://dx.doi.org/10.7554/eLife.26464.001 eLife Sciences Publications, Ltd 2017-06-06 /pmc/articles/PMC5462534/ /pubmed/28583253 http://dx.doi.org/10.7554/eLife.26464 Text en © 2017, Liu et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology and Stem Cells
Liu, Wenxuan
Klose, Alanna
Forman, Sophie
Paris, Nicole D
Wei-LaPierre, Lan
Cortés-Lopéz, Mariela
Tan, Aidi
Flaherty, Morgan
Miura, Pedro
Dirksen, Robert T
Chakkalakal, Joe V
Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration
title Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration
title_full Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration
title_fullStr Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration
title_full_unstemmed Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration
title_short Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration
title_sort loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration
topic Developmental Biology and Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462534/
https://www.ncbi.nlm.nih.gov/pubmed/28583253
http://dx.doi.org/10.7554/eLife.26464
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