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Physical exercise therapy, as a non-pharmacological intervention, shows unique advantages in preventing musculoskeletal degeneration and restoring metabolic homeostasis. Evidence indicates that regular aerobic and resistance exercise promotes osteogenesis and muscle protein synthesis while inhibiting bone and muscle loss through mechanical loading, regulation of myokines and osteokines, and energy metabolism remodeling. Key molecular pathways include activation of the SIRT1\/AMPK\/PGC-1\u03b1 axis, modulation of mTOR signaling, and suppression of inflammatory cytokines such as IL-6 and TNF-\u03b1, which collectively enhance mitochondrial function and reduce oxidative stress. Moreover, physical exercise strengthens muscle\u2013bone crosstalk via factors like irisin, myostatin, osteocalcin, and sclerostin, exerting systemic anti-aging effects. Future studies should emphasize personalized physical exercise prescriptions combined with biomarker monitoring and smart technologies to achieve sustainable musculoskeletal health and promote healthy aging.<\/jats:p>","DOI":"10.3389\/fragi.2026.1791384","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T06:17:25Z","timestamp":1779949045000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Physical exercise therapy as an anti-aging strategy for osteosarcopenia: a narrative review"],"prefix":"10.3389","volume":"7","author":[{"given":"Ting ting","family":"Liu","sequence":"first","affiliation":[{"name":"Gansu University of Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Gansu University of Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan tao","family":"Dong","sequence":"additional","affiliation":[{"name":"Gansu University of Chinese Medicine","place":["Lanzhou, China"]},{"name":"Affiliated Hospital of Gansu University of Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan long","family":"Gong","sequence":"additional","affiliation":[{"name":"Gansu University of Chinese Medicine","place":["Lanzhou, China"]},{"name":"Affiliated Hospital of Gansu University of Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi jie","family":"Fang","sequence":"additional","affiliation":[{"name":"Gansu University of Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Gansu University of Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ma","sequence":"additional","affiliation":[{"name":"Gansu University of Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.3390\/antiox12051075","article-title":"PGC-1\u03b1 is a master regulator of mitochondrial lifecycle and ROS stress response","volume":"12","author":"Abu Shelbayeh","year":"2023","journal-title":"Antioxidants (Basel)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"4377","DOI":"10.3390\/nu15204377","article-title":"The role of vitamin D in skeletal muscle repair and regeneration in animal models and humans: a systematic review","volume":"15","author":"Agoncillo","year":"2023","journal-title":"Nutrients"},{"key":"B3","doi-asserted-by":"publisher","first-page":"9268","DOI":"10.3390\/ijms26199268","article-title":"Rheumatoid arthritis and osteoporosis as prototypes of immunosenescence in osteoimmunology: molecular pathways of inflammaging and targeted therapies","volume":"26","author":"Aitella","year":"2025","journal-title":"Int. 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