RRC ID 58396
Author Saito Y, Chikenji TS, Matsumura T, Nakano M, Fujimiya M.
Title Exercise enhances skeletal muscle regeneration by promoting senescence in fibro-adipogenic progenitors.
Journal Nat Commun
Abstract Idiopathic inflammatory myopathies cause progressive muscle weakness and degeneration. Since high-dose glucocorticoids might not lead to full recovery of muscle function, physical exercise is also an important intervention, but some exercises exacerbate chronic inflammation and muscle fibrosis. It is unknown how physical exercise can have both beneficial and detrimental effects in chronic myopathy. Here we show that senescence of fibro-adipogenic progenitors (FAPs) in response to exercise-induced muscle damage is needed to establish a state of regenerative inflammation that induces muscle regeneration. In chronic inflammatory myopathy model mice, exercise does not promote FAP senescence or resistance against tumor necrosis factor-mediated apoptosis. Pro-senescent intervention combining exercise and pharmacological AMPK activation reverses FAP apoptosis resistance and improves muscle function and regeneration. Our results demonstrate that the absence of FAP senescence after exercise leads to muscle degeneration with FAP accumulation. FAP-targeted pro-senescent interventions with exercise and pharmacological AMPK activation may constitute a therapeutic strategy for chronic inflammatory myopathy.
Volume 11(1)
Pages 889
Published 2020-2-14
DOI 10.1038/s41467-020-14734-x
PII 10.1038/s41467-020-14734-x
PMID 32060352
PMC PMC7021787
MeSH Aging Animals Apoptosis Exercise Therapy* Female Humans Mesenchymal Stem Cells / cytology* Mice Mice, Inbred BALB C Mice, Inbred C57BL Muscle, Skeletal / immunology Muscle, Skeletal / physiopathology* Muscular Diseases / immunology Muscular Diseases / physiopathology Muscular Diseases / therapy* Regeneration*
IF 12.121
Times Cited 3
Mice RBRC01361