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Recently, the coincidence of obesity and aging has gained attention due to the intersection of the obesity epidemic with an aging demographic. Both aging and obesity are associated with marked defects in skeletal muscle metabolic health. Despite these findings, we have a poor understanding of how obesity and aging may interact to impact skeletal muscle mass and metabolic health. Therefore, we investigated the impact of high-fat diet (HFD)-induced obesity on skeletal muscle mass, mitochondrial function, transcriptomics, and whole-body metabolism in young and aged mice. We observed main effects of diet and age on several measures of whole-body metabolic function (VO\n                    <jats:sub>2<\/jats:sub>\n                    , VCO\n                    <jats:sub>2<\/jats:sub>\n                    , and RER). Complex I-driven mitochondrial proton leak was significantly elevated by HFD-induced obesity across both age groups; however, a main effect of aging for reduced complex I leak was detected in the soleus muscle. Interestingly, aged animals fed a HFD did not exhibit lower muscle mass than chow-fed young animals, but did present with stark increases in muscle triglyceride content and a unique transcriptional response to HFD. HFD-induced obesity impacted the muscle transcriptome differently in the muscles of young and aged mice, indicating that obesity can change altered gene expression with age. Our findings suggest that the presence of obesity can both compound and counteract age-associated changes to muscle mass, gene expression, and mitochondrial function.\n                  <\/jats:p>","DOI":"10.1007\/s11357-025-01726-2","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T08:29:40Z","timestamp":1749716980000},"page":"1219-1240","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Impact of sarcopenia and obesity on skeletal muscle size, gene expression, and mitochondrial function"],"prefix":"10.1007","volume":"48","author":[{"given":"Hector G.","family":"Paez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Pitzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Halle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Ferrandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Carson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junaith S.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0378-4707","authenticated-orcid":false,"given":"Stephen E.","family":"Alway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"issue":"5","key":"1726_CR1","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1046\/j.1532-5415.2002.50216.x","volume":"50","author":"I Janssen","year":"2002","unstructured":"Janssen I, Heymsfield SB, Ross R. 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