Exercise enhances skeletal muscle regeneration by promoting senescence in fibro-adipogenic progenitors

Saito, Yuki; Chikenji, Takako S.; Matsumura, Takashi; Nakano, Masako; Fujimiya, Mineko

doi:10.1038/s41467-020-14734-x


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Exercise enhances skeletal muscle regeneration by promoting senescence in fibro-adipogenic progenitors

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Title:	Exercise enhances skeletal muscle regeneration by promoting senescence in fibro-adipogenic progenitors
Authors:	Saito, Yuki Browse this author →KAKEN DB
	Chikenji, Takako S. Browse this author →KAKEN DB
	Matsumura, Takashi Browse this author →KAKEN DB
	Nakano, Masako Browse this author →KAKEN DB
	Fujimiya, Mineko Browse this author →KAKEN DB
Issue Date:	14-Feb-2020
Publisher:	Nature Publishing Group
Journal Title:	Nature communications
Volume:	11
Issue:	1
Start Page:	889
Publisher DOI:	10.1038/s41467-020-14734-x
PMID:	32060352
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.
Rights:	https://creativecommons.org/licenses/by/4.0/
Type:	article
URI:	http://hdl.handle.net/2115/79255
Appears in Collections:	保健科学院・保健科学研究院 (Graduate School of Health Sciences / Faculty of Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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