{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:01:58Z","timestamp":1791511318698,"version":"4.3.4"},"reference-count":247,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T00:00:00Z","timestamp":1760745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Council for Scientific and Technological Development\u2014CNPq","award":["132435\/2024-1"],"award-info":[{"award-number":["132435\/2024-1"]}]},{"name":"National Council for Scientific and Technological Development\u2014CNPq","award":["380361\/2024-8"],"award-info":[{"award-number":["380361\/2024-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aging is a multifactorial process that progressively disrupts cellular and tissue homeostasis, affecting all organ systems at distinct rates and predisposing individuals to chronic diseases such as cancer, type II diabetes, and sarcopenia. Among these systems, skeletal muscle plays a central role in healthspan decline, yet the precise onset of its deterioration remains unclear. Most studies emphasize late-life models, overlooking the transitional phase of middle age, when initial alterations emerge. Evidence indicates that middle-aged muscle exhibits aberrant metabolism, impaired insulin sensitivity, and an early, gradual reduction in mass, suggesting that decline begins long before overt sarcopenia. This narrative review synthesizes current findings on linear and non-linear molecular biomarkers associated with the onset of skeletal muscle aging, aiming to improve early detection of muscular alterations and support the development of interventions that delay or prevent functional decline.<\/jats:p>","DOI":"10.3390\/ijms262010145","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T08:18:54Z","timestamp":1760948334000},"page":"10145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Molecular Framework of the Onset and Progression of Skeletal Muscle Aging"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6506-0605","authenticated-orcid":false,"given":"Thomas","family":"Horlem","sequence":"first","affiliation":[{"name":"Laboratory of Cellular Metabolism, Physiology Department, Federal University of Paran\u00e1, Curitiba 80060-000, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie Rubianne Silva","family":"Carvalhal","sequence":"additional","affiliation":[{"name":"Laboratory of Human Molecular Genetics, Genetics Department, Federal University of Paran\u00e1, Curitiba 80060-000, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7262-3766","authenticated-orcid":false,"given":"Sandro Jos\u00e9 Ribeiro","family":"Bonatto","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Metabolism, Physiology Department, Federal University of Paran\u00e1, Curitiba 80060-000, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Cl\u00e1udio","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Metabolism, Physiology Department, Federal University of Paran\u00e1, Curitiba 80060-000, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41392-022-01251-0","article-title":"Aging and Aging-Related Diseases: From Molecular Mechanisms to Interventions and Treatments","volume":"7","author":"Guo","year":"2022","journal-title":"Signal Transduct. 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