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Among the factors underlying the development of sarcopenia are the progressive demise of motor neurons, the transition from fast to slow myosin isoform (type II to type I fiber switch), and the decrease in satellite cell number and function. Mitochondrial dysfunction has been indicated as a key contributor to skeletal myocyte decline and loss of physical performance with aging. Several systems have been implicated in the regulation of muscle plasticity and trophism such as the fine-tuned and complex regulation between the stimulator of protein synthesis, mechanistic target of rapamycin (mTOR), and the inhibitor of mTOR, AMP-activated protein kinase (AMPK), that promotes muscle catabolism. Here, we provide an overview of the molecular mechanisms linking mitochondrial signaling and quality with muscle homeostasis and performance and discuss the main pathways elicited by their imbalance during age-related muscle wasting. We also discuss lifestyle interventions (i.e., physical exercise and nutrition) that may be exploited to preserve mitochondrial function in the aged muscle. Finally, we illustrate the emerging possibility of rescuing muscle tissue homeostasis through mitochondrial transplantation.<\/jats:p>","DOI":"10.3390\/ijms25042052","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T03:36:17Z","timestamp":1707363377000},"page":"2052","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Mitochondrial Quantity and Quality in Age-Related Sarcopenia"],"prefix":"10.3390","volume":"25","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, 00618 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, 00618 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, 00618 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, 00618 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, SS100 km 18, 70010 Casamassima, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1152\/jappl.2000.89.1.81","article-title":"Skeletal muscle mass and distribution in 468 men and women aged 18\u201388 yr","volume":"89","author":"Janssen","year":"2000","journal-title":"J. Appl. Physiol. (1985)"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1042\/CS20220636","article-title":"Structural functionality of skeletal muscle mitochondria and its correlation with metabolic diseases","volume":"136","author":"Swalsingh","year":"2022","journal-title":"Clin. 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