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Evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) has been shown to be a crucial adaptor for inflammation and mitochondrial function; however, little is known about the action of ECSIT in skeletal muscle atrophy. First, the young and middle-aged mice underwent exercise training, and then skeletal muscle atrophy, mitochondrial quality control, and mitochondrial complex in skeletal muscle were detected. Then, we analyzed the Gene Expression Omnibus (GEO) database and performed in vivo experiments to determine the effect of exercise on ECSIT expression. Furthermore, ECSIT was knockdown in myoblasts to examine its effects on muscle atrophy, mitochondrial quality control, and mitochondrial complex. Compared with young mice, middle-aged mice exhibited significant reductions in relative weights of skeletal muscles, grip strength, hang time, and exhaustion exercise performance, while exercise restored these deficits dramatically. Consistently, exercise promoted protein synthesis and inhibited protein degradation in the gastrocnemius of middle-aged mice. Therefore, exercise significantly mitigated skeletal muscle atrophy in middle-aged mice. Concomitantly, exercise alleviated the impaired mitophagy in the gastrocnemius of middle-aged mice. ECSIT expression was elevated in the gastrocnemius of middle-aged mice but was reversed by exercise intervention. Mechanistically, ECSIT knockdown impaired myoblast differentiation, mitochondrial complex, and mitochondrial quality control in myoblasts. Collectively, this study reveals, for the first time, that ECSIT is important for myogenesis by maintaining mitochondrial quality control, thereby facilitating exercise-induced amelioration of skeletal muscle atrophy during aging.<\/jats:p>","DOI":"10.1093\/gerona\/glag065","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T12:22:59Z","timestamp":1773058979000},"source":"Crossref","is-referenced-by-count":0,"title":["Evolutionarily conserved signaling intermediate in Toll pathways facilitates exercise-induced amelioration of skeletal muscle atrophy by maintaining mitochondrial quality control in middle-aged mice"],"prefix":"10.1093","volume":"81","author":[{"given":"Jingcheng","family":"Fan","sequence":"first","affiliation":[{"name":"School of Exercise and Health, Shanghai University of Sport , Shanghai,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Wen","sequence":"additional","affiliation":[{"name":"School of Exercise and Health, Shanghai University of Sport , Shanghai,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Duan","sequence":"additional","affiliation":[{"name":"School of Exercise and Health, Shanghai University of Sport , Shanghai,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Sports Medicine and Health, Chengdu Sport University , Chengdu,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8357-7966","authenticated-orcid":false,"given":"Tan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Exercise and Health, Shanghai University of Sport , 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