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However, the specific role of cardiolipin in myogenesis has not been determined. This study investigated the crucial role of mitochondrial cardiolipin and cardiolipin synthase 1 (Crls1) in age-related muscle deterioration and myogenesis. Our findings demonstrated that cardiolipin and Crls1 are downregulated in aged skeletal muscle. Moreover, the knockdown of\n                    <jats:italic>Crls1<\/jats:italic>\n                    in myoblasts reduced mitochondrial mass, activity, and OXPHOS complex IV expression and disrupted the structure of the mitochondrial cristae. AAV9-shCrls1-mediated downregulation of\n                    <jats:italic>Crls1<\/jats:italic>\n                    impaired muscle regeneration in a mouse model of cardiotoxin (CTX)-induced muscle damage, whereas AAV9-mCrls1-mediated\n                    <jats:italic>Crls1<\/jats:italic>\n                    overexpression improved regeneration. Overall, our results highlight that the age-dependent decrease in CRLS1 expression contributes to muscle loss by diminishing mitochondrial quality in skeletal muscle myoblasts. Hence, modulating CRLS1 expression is a promising therapeutic strategy for mitigating muscle deterioration associated with aging, suggesting potential avenues for developing interventions to improve overall muscle health and quality of life in elderly individuals.\n                  <\/jats:p>","DOI":"10.1038\/s12276-024-01199-x","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T22:08:41Z","timestamp":1711922921000},"page":"922-934","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Age-dependent loss of Crls1 causes myopathy and skeletal muscle regeneration failure"],"prefix":"10.1038","volume":"56","author":[{"given":"Youngbum","family":"Yoo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MyeongHoon","family":"Yeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Kyung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon-Bin","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Min","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0114-1142","authenticated-orcid":false,"given":"Mee-Sup","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunju","family":"Ro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3743-8431","authenticated-orcid":false,"given":"Young-Kyo","family":"Seo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,1]]},"reference":[{"key":"1199_CR1","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s00223-014-9915-y","volume":"96","author":"WR Frontera","year":"2015","unstructured":"Frontera, W. 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