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Its onset compromises the health and longevity of older adults by increasing susceptibility to falls, fractures, and various comorbid conditions, thereby diminishing quality of life and capacity for independent living. Accumulating evidence indicates that moderate-intensity aerobic exercise is an effective strategy for promoting overall health in older adults and exerts a beneficial effect that mitigates age-related sarcopenia. However, the underlying molecular mechanisms through which exercise confers these protective effects remain incompletely understood. Methods: In this study, we established a naturally aging mouse model to investigate the effects of a 16-week treadmill-based aerobic exercise regimen on skeletal muscle physiology. Results: Results showed that aerobic exercise mitigated age-related declines in muscle mass and function, enhanced markers associated with protein synthesis, reduced oxidative stress, and modulated the expression of genes and proteins implicated in mitochondrial quality control. Notably, a single session of aerobic exercise acutely elevated circulating levels of \u03b2-hydroxybutyrate (\u03b2-HB) and upregulated the expression of BDH1, HCAR2, and PPARG in the skeletal muscle, suggesting a possible role of \u03b2-HB\u2013related signaling in exercise-induced muscle adaptations. However, although these findings support the beneficial effects of aerobic exercise on skeletal muscle aging, further investigation is warranted to elucidate the causal relationships and to characterize the chronic signaling mechanisms involved. Conclusions: This study offers preliminary insights into how aerobic exercise may modulate mitochondrial quality control and \u03b2-HB\u2013associated signaling pathways during aging.<\/jats:p>","DOI":"10.3390\/metabo15070472","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T10:26:53Z","timestamp":1752229613000},"page":"472","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Aerobic Exercise Delays Age-Related Sarcopenia in Mice via Alleviating Imbalance in Mitochondrial Quality Control"],"prefix":"10.3390","volume":"15","author":[{"given":"Danlin","family":"Zhu","sequence":"first","affiliation":[{"name":"Shanghai Key Lab of Human Performance, Shanghai University of Sport, 650 Qingyuan Ring Road, Yangpu District, Shanghai 200438, China"},{"name":"School of Humanities and Social Sciences, Shanghai Lida University, Shanghai 201608, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Key Lab of Human Performance, Shanghai University of Sport, 650 Qingyuan Ring Road, Yangpu District, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyang","family":"Gao","sequence":"additional","affiliation":[{"name":"Shanghai Key Lab of Human Performance, Shanghai University of Sport, 650 Qingyuan Ring Road, Yangpu District, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Key Lab of Human Performance, Shanghai University of Sport, 650 Qingyuan Ring Road, Yangpu District, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Key Lab of Human Performance, Shanghai University of Sport, 650 Qingyuan Ring Road, Yangpu District, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Ma","sequence":"additional","affiliation":[{"name":"Shanghai Key Lab of Human Performance, Shanghai University of Sport, 650 Qingyuan Ring Road, Yangpu District, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanghai Key Lab of Human Performance, Shanghai University of Sport, 650 Qingyuan Ring Road, Yangpu District, Shanghai 200438, China"},{"name":"School of Physical Education, Shanghai Normal University, Shanghai 200234, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Xiao","sequence":"additional","affiliation":[{"name":"Shanghai Key Lab of Human Performance, Shanghai University of Sport, 650 Qingyuan Ring Road, Yangpu District, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/1747-0080.12287","article-title":"Sarcopenia and hospitalisation costs in older adults: A cross-sectional study","volume":"74","author":"Antunes","year":"2017","journal-title":"Nutr. 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