Academic Journal
Senescence as a regulatory mechanism in skeletal muscle repair in young mice.
| Τίτλος: | Senescence as a regulatory mechanism in skeletal muscle repair in young mice. |
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| Συγγραφείς: | Johnson AL; Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada., Bevington RT; Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada., Parise G; Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada. |
| Πηγή: | American journal of physiology. Cell physiology [Am J Physiol Cell Physiol] 2026 Aug 01; Vol. 331 (2), pp. C316-C327. Date of Electronic Publication: 2026 Jun 18. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901225 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1563 (Electronic) Linking ISSN: 03636143 NLM ISO Abbreviation: Am J Physiol Cell Physiol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Bethesda, Md. : American Physiological Society |
| Ιατρικοί όροι (MeSH): | Muscle, Skeletal*/drug effects , Muscle, Skeletal*/pathology , Muscle, Skeletal*/metabolism , Cellular Senescence*/drug effects , Cellular Senescence*/physiology , Regeneration*/drug effects , Regeneration*/physiology , Wound Healing*/drug effects , Aging*, Macrophages/drug effects ; Macrophages/metabolism ; Satellite Cells, Skeletal Muscle/drug effects ; Satellite Cells, Skeletal Muscle/metabolism ; Satellite Cells, Skeletal Muscle/pathology ; Senotherapeutics/pharmacology ; Quercetin/pharmacology ; Animals ; Mice ; Mice, Inbred C57BL ; Male |
| Περίληψη: | Senescence is broadly considered an age-related phenomenon; however, it also been implicated in normal tissue repair and wound healing. Skeletal muscle repair is a complex process that requires the coordination of several different cell populations, but the role of senescence in skeletal muscle repair has yet to be fully elucidated. We hypothesize that senescence serves as a control mechanism throughout the regenerative process, and the removal of senescent cells through senolytics will negatively impact the repair process in young mice. Briefly, young mice were exposed to either 1) vehicle (VEH), receiving only a cardiotoxin (CTx) injection in one hindlimb, or 2) 7 days of senolytic treatment (SEN) pre-CTx and 3×/week for 4 wk post-CTx. Dasatinib + Quercetin (D + Q) was used to selectively eliminate senescent cells. There were no significant differences between groups in functional measures such as hindlimb grip strength and cross-sectional area. eMHC+ fibers remained elevated at D28 in the SEN group. Macrophage infiltration was twice as high in the SEN group compared with VEH at D7. Satellite cell quantity and fibrotic area were significantly increased at D14 in the SEN group compared with VEH. We conclude that reducing senescent cells during muscle repair in young mice significantly altered the kinetics of muscle repair. Therefore, senescent cells may act as a regulatory mechanism in skeletal muscle to orchestrate the activity of the different cell populations involved in repair and regeneration, such as immune cells, satellite cells, and fibrotic cells.NEW & NOTEWORTHY Senolytic treatment in young mice results in a transient delay in the repair kinetics of satellite cells, macrophages, and fibrosis without disrupting functional repair of skeletal muscle. Fibers associated with a p21+ nucleus were smaller in size than myofibers not associated with a p21+ nucleus, possibly signifying areas with delayed or incomplete repair or where greater senescence-associated signalling is needed to regulate nearby cell populations. |
| Grant Information: | Canadian Institutes of Health Research (CIHR); Natural Sciences and Engineering Research Council of Canada (NSERC); RGPIN-2021-04008 Natural Sciences and Engineering Research Council of Canada (NSERC) |
| Contributed Indexing: | Keywords: repair; satellite cells; senescence; skeletal muscle |
| Substance Nomenclature: | 0 (Senotherapeutics) 9IKM0I5T1E (Quercetin) |
| Entry Date(s): | Date Created: 20260618 Date Completed: 20260710 Latest Revision: 20260710 |
| Update Code: | 20260711 |
| DOI: | 10.1152/ajpcell.00154.2026 |
| PMID: | 42314772 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1522-1563 |
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| DOI: | 10.1152/ajpcell.00154.2026 |