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When cells enter senescence, they secrete a host of proinflammatory factors known as the senescence-associated secretory phenotype, which has deleterious effects on surrounding cells and tissues. Little is known of the role of senescence in Duchenne muscular dystrophy (DMD), the fatal X-linked neuromuscular disorder typified by chronic inflammation, extracellular matrix remodeling, and a progressive loss in muscle mass and function. Here, we demonstrate using C57- mdx (8-wk-old) and D2- mdx (4-wk-old and 8-wk-old) mice, two mouse models of DMD, that cells displaying canonical markers of senescence are found within the skeletal muscle. Eight-week-old D2- mdx mice, which display severe muscle pathology, had greater numbers of senescent cells associated with areas of inflammation, which were mostly Cdkn1a-positive macrophages, whereas in C57- mdx muscle, senescent populations were endothelial cells and macrophages localized to newly regenerated myofibers. Interestingly, this pattern was similar to cardiotoxin (CTX)-injured wild-type (WT) muscle, which experienced a transient senescent response. Dystrophic muscle demonstrated significant upregulations in senescence pathway genes [ Cdkn1a (p21), Cdkn2a (p16<jats:sup>INK4A<\/jats:sup>), and Trp53 (p53)], which correlated with the quantity of senescence-associated \u03b2-galactosidase (SA-\u03b2-Gal)-positive cells. These results highlight an underexplored role for cellular senescence in murine dystrophic muscle. <\/jats:p>","DOI":"10.1152\/ajpcell.00397.2020","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T19:50:38Z","timestamp":1620849038000},"page":"C94-C103","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Loss of dystrophin expression in skeletal muscle is associated with senescence of macrophages and endothelial cells"],"prefix":"10.1152","volume":"321","author":[{"given":"Laura V.","family":"Young","sequence":"first","affiliation":[{"name":"Department of Applied Human Sciences, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Applied Human Sciences, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Applied Human Sciences, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma C.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Applied Human Sciences, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel G.","family":"Arsenault","sequence":"additional","affiliation":[{"name":"Department of Applied Human Sciences, University of Prince Edward Island, Charlottetown, Prince Edward Island, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athan G.","family":"Dial","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Bellissimo","sequence":"additional","affiliation":[{"name":"School of Kinesiology and Health Sciences, Muscle Health Research Centre, York University, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8087-9021","authenticated-orcid":true,"given":"Christopher G. 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