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It is a potent physiological stimulus that activates conserved molecular signaling pathways. Through the coordinated integration of multiple molecules, pathways, and systems, it leads to systemic health benefits. However, most studies focus on individual systems or molecular mechanisms, lacking systematic integration of the cross\u2010system regulation induced by exercise. We summarize the molecular mechanisms of exercise in the musculoskeletal, cardiovascular, nervous systems, among others. Exercise induces the release of exerkines (e.g., irisin, interleukin\u20106, and brain\u2010derived neurotrophic factor) and extracellular vesicles, which activate key signaling pathways to enhance mitochondrial function, metabolism and physiological adaptation, while suppressing inflammation and oxidative stress, thereby alleviating diseases and delaying aging through cross\u2010system coordination. We further explore exercise\u2010induced adaptive regulation in extreme environments, including microgravity, hyperbaria, and hypoxia, offering a multifaceted perspective on organismal health regulation. Finally, we outline the prospects and challenges of multiomics, artificial intelligence\u2010driven precision medicine, personalized exercise prescriptions, and exercise mimetics. Overall, this review provides a more integrated perspective on the molecular basis of exercise and offers directions for future mechanistic and translational studies.<\/jats:p>","DOI":"10.1002\/mco2.70926","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:52:05Z","timestamp":1788504725000},"source":"Crossref","is-referenced-by-count":1,"title":["The Health Benefits of Exercise: Molecular and Cellular Mechanisms"],"prefix":"10.1002","volume":"7","author":[{"given":"Peifeng","family":"Ying","sequence":"first","affiliation":[{"name":"Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine Vision and Brain Health) Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Wang","sequence":"additional","affiliation":[{"name":"Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine Vision and Brain Health) Wenzhou Medical University  Wenzhou Zhejiang 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