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While age-related muscle decline represents the most common form, sarcopenia may also develop as a secondary condition associated with chronic diseases, including cancer, diabetes, chronic obstructive pulmonary disease, and autoimmune disorders. It increases frailty, disability, and fall risk among the elderly while also raising hospitalization rates and associated healthcare costs. Although no pharmaceutical agents have been specifically approved for the treatment of sarcopenia to date, elucidating its underlying molecular mechanisms of sarcopenia through systems biology approaches is essential for the development of novel therapeutic strategies and preventive interventions. This review examines the current definitions of sarcopenia, recent advancements in its management, and the emerging role of systems biology in uncovering potential biomarkers and therapeutic targets. We discuss how these approaches may contribute to the development of novel interventions aimed at enhancing muscle health and improving the quality of life in older adults and provide a summary of the current progress achieved through systems biology methodologies in sarcopenia research.<\/jats:p>","DOI":"10.3390\/ijms26178527","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:02:57Z","timestamp":1756825377000},"page":"8527","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Unravelling the Complexity of Sarcopenia Through a Systems Biology Approach"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7279-7482","authenticated-orcid":false,"given":"Atakan Burak","family":"Ceyhan","sequence":"first","affiliation":[{"name":"Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King\u2019s College London, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozlem","family":"Altay","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, KTH\u2014Royal Institute of Technology, SE-17165 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3721-8586","authenticated-orcid":false,"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, KTH\u2014Royal Institute of Technology, SE-17165 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9802-0880","authenticated-orcid":false,"given":"Sehime Gulsun","family":"Temel","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Bursa Uludag University, Bursa 16059, Turkey"},{"name":"Department of Translational Medicine, Institute of Health Science, Bursa Uludag University, Bursa 16059, Turkey"},{"name":"Department of Histology and Embryology, Faculty of Medicine, Bursa Uludag University, Bursa 16059, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7046-8990","authenticated-orcid":false,"given":"Hasan","family":"Turkez","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, Atat\u00fcrk University, Erzurum 25240, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4254-6090","authenticated-orcid":false,"given":"Adil","family":"Mardinoglu","sequence":"additional","affiliation":[{"name":"Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King\u2019s College London, London SE1 9RT, UK"},{"name":"Science for Life Laboratory, KTH\u2014Royal Institute of Technology, SE-17165 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101319","DOI":"10.1016\/j.mam.2024.101319","article-title":"Muscle Aging and Sarcopenia: The Pathology, Etiology, and Most Promising Therapeutic Targets","volume":"100","author":"Campanario","year":"2024","journal-title":"Mol. 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