{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:15:14Z","timestamp":1788570914474,"version":"build-2803163510"},"reference-count":66,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Sarcopenia, the aging\u2010related loss of muscle mass and function, is a debilitating process negatively impacting the quality of life of affected individuals. Although the mechanisms underlying sarcopenia are incompletely understood, impairments in mitochondrial dynamics, including mitochondrial fusion, have been proposed as a contributing factor. However, the potential of upregulating mitochondrial fusion proteins to alleviate the effects of aging on skeletal muscles remains unexplored. We therefore hypothesized that overexpressing Mitofusin 2 (MFN2) in skeletal muscle in\u00a0vivo would mitigate the effects of aging on muscle mass and improve mitochondrial function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MFN2 was overexpressed in young (7 mo) and old (24 mo) male mice for 4\u2009months through intramuscular injections of an adeno\u2010associated viruses. The impacts of MFN2 overexpression on muscle mass and fiber size (histology), mitochondrial respiration, and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> emission (Oroboros fluororespirometry), and various signaling pathways (qPCR and western blotting) were investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MFN2 overexpression increased muscle mass and fiber size in both young and old mice. No sign of fibrosis, necrosis, or inflammation was found upon MFN2 overexpression, indicating that the hypertrophy triggered by MFN2 overexpression was not pathological. MFN2 overexpression even reduced the proportion of fibers with central nuclei in old muscles. Importantly, MFN2 overexpression had no impact on muscle mitochondrial respiration and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> emission in both young and old mice. MFN2 overexpression attenuated the increase in markers of impaired autophagy in old muscles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MFN2 overexpression may be a viable approach to mitigate aging\u2010related muscle atrophy and may have applications for other muscle disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.14119","type":"journal-article","created":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T07:49:10Z","timestamp":1708760950000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["<scp>MFN2<\/scp> overexpression in skeletal muscles of young and old mice causes a mild hypertrophy without altering mitochondrial respiration and <scp>H<sub>2<\/sub>O<sub>2<\/sub><\/scp> emission"],"prefix":"10.1111","volume":"240","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1898-4119","authenticated-orcid":false,"given":"Marina","family":"Cefis","sequence":"first","affiliation":[{"name":"D\u00e9partement des sciences de l'activit\u00e9 physique, Facult\u00e9 des Sciences UQ\u00c0M  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Dargegen","sequence":"additional","affiliation":[{"name":"D\u00e9partement des sciences de l'activit\u00e9 physique, Facult\u00e9 des Sciences UQ\u00c0M  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Marcangeli","sequence":"additional","affiliation":[{"name":"D\u00e9partement des sciences de l'activit\u00e9 physique, Facult\u00e9 des Sciences UQ\u00c0M  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"D\u00e9partement des sciences biologiques, Facult\u00e9 des Sciences UQ\u00c0M  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0759-2076","authenticated-orcid":false,"given":"Shima","family":"Taherkhani","sequence":"additional","affiliation":[{"name":"D\u00e9partement des sciences de l'activit\u00e9 physique, Facult\u00e9 des Sciences UQ\u00c0M  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"D\u00e9partement des sciences biologiques, Facult\u00e9 des Sciences UQ\u00c0M  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maude","family":"Dulac","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine McGill University  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Philippe","family":"Leduc\u2010Gaudet","sequence":"additional","affiliation":[{"name":"Research Group in Cellular Signaling, Department of Medical Biology Universit\u00e9 du Qu\u00e9bec \u00c0 Trois\u2010Rivi\u00e8res  Trois\u2010Rivi\u00e8res Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Mayaki","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine McGill University  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Meakins\u2010Christie Laboratories and Translational Research in Respiratory Diseases Program, Department of Critical Care Research Institute of the McGill University Health Centre  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabah N. 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