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Among the drivers of intracellular and ultrastructural changes of muscle fibers in sarcopenia, mitochondria and their quality control pathways play relevant roles. Mononucleated muscle stem cells\/satellite cells (MSCs) have been attributed a critical role in muscle repair after an injury. The involvement of mitochondria in supporting MSC-directed muscle repair is unclear. There is evidence that a reduction in mitochondrial biogenesis blunts muscle repair, thus indicating that the delivery of functional mitochondria to injured muscles can be harnessed to limit muscle fibrosis and enhance restoration of muscle function. Injection of autologous respiration-competent mitochondria from uninjured sites to damaged tissue has been shown to reduce infarct size and enhance cell survival in preclinical models of ischemia\u2013reperfusion. Furthermore, the incorporation of donor mitochondria into MSCs enhances lung and cardiac tissue repair. This strategy has also been tested for regeneration purposes in traumatic muscle injuries. Indeed, the systemic delivery of mitochondria promotes muscle regeneration and restores muscle mass and function while reducing fibrosis during recovery after an injury. In this review, we discuss the contribution of altered MSC function to sarcopenia and illustrate the prospect of harnessing mitochondrial delivery and restoration of MSCs as a therapeutic strategy against age-related sarcopenia.<\/jats:p>","DOI":"10.3390\/biom14040415","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T12:52:12Z","timestamp":1711630332000},"page":"415","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Restoring Mitochondrial Function and Muscle Satellite Cell Signaling: Remedies against Age-Related Sarcopenia"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9567-6983","authenticated-orcid":false,"given":"Emanuele","family":"Marzetti","sequence":"first","affiliation":[{"name":"Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy"},{"name":"Department of Geriatrics, Orthopedics and Rheumatology, Universit\u00e0 Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biliana","family":"Lozanoska-Ochser","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, LUM University, 70010 Casamassima, Italy"},{"name":"DAHFMO Unit of Histology and Medical Embryology, Sapienza Universit\u00e0 di Roma, P.le Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5472-2365","authenticated-orcid":false,"given":"Riccardo","family":"Calvani","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy"},{"name":"Department of Geriatrics, Orthopedics and Rheumatology, Universit\u00e0 Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Landi","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy"},{"name":"Department of Geriatrics, Orthopedics and Rheumatology, Universit\u00e0 Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7482-9514","authenticated-orcid":false,"given":"H\u00e9lio Jos\u00e9","family":"Coelho-J\u00fanior","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Orthopedics and Rheumatology, Universit\u00e0 Cattolica del Sacro Cuore, L.go F. Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-3487","authenticated-orcid":false,"given":"Anna","family":"Picca","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCCS, L.go A. Gemelli 8, 00168 Rome, Italy"},{"name":"Department of Medicine and Surgery, LUM University, 70010 Casamassima, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1093\/ageing\/afz046","article-title":"Sarcopenia: Revised European consensus on definition and diagnosis","volume":"48","author":"Bahat","year":"2019","journal-title":"Age Ageing"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1200\/JCO.21.00102","article-title":"Sarcopenia in the older adult with cancer","volume":"39","author":"Williams","year":"2021","journal-title":"J. Clin. 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