{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:56:31Z","timestamp":1793372191156,"version":"4.5.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Growth Differentiation Factor 15 (GDF15) is a mitokine expressed in response to various stresses whose circulating levels increase with age and are associated with numerous pathological conditions, including muscle wasting and sarcopenia. However, the use of circulating GDF15 (c-GDF15) as a biomarker of sarcopenia is still debated. Moreover, the role of GDF15 intracellular precursor, pro-GDF15, in human skeletal muscle (SM-GDF15) is not totally understood. In order to clarify these points, the association of both forms of GDF15 with parameters of muscle strength, body composition, metabolism and inflammation was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>the levels of c-GDF15 and SM-GDF15 were evaluated in plasma and muscle biopsies, respectively, of healthy subjects (HS) and patients with lower limb mobility impairment (LLMI), either young (&amp;lt;40 years-old) or old (&amp;gt;70 years-old). Other parameters included in the analysis were Isometric Quadriceps Strength (IQS), BMI, lean and fat mass percentage, <jats:italic>Vastus lateralis<\/jats:italic> thickness, as well as circulating levels of Adiponectin, Leptin, Resistin, IGF-1, Insulin, IL6, IL15 and c-PLIN2. Principal Component Analysis (PCA), Canonical Discriminant Analysis (CDA) and Receiving Operating Characteristics (ROC) analysis were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>c-GDF15 but not SM-GDF15 levels resulted associated with decreased IQS and IGF-1 levels in both HS and LLMI, while only in LLMI associated with increased levels of Resistin. Moreover, in LLMI both c-GDF15 and SM-GDF15 levels were associated with IL-6 levels, but interestingly SM-GDF15 is lower in LLMI with respect to HS. Furthermore, a discrimination of the four groups of subjects based on these parameters was possible with PCA and CDA. In particular HS, LLMI over 70 years or under 40 years of age were discriminated based on SM-GDF15, c-GDF15 and Insulin levels, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>our data support the idea that c-GDF15 level could be used as a biomarker of decreased muscle mass and strength. Moreover, it is suggested that c-GDF15 has a different diagnostic significance with respect to SM-GDF15, which is likely linked to a healthy and active state.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1404047","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T04:47:29Z","timestamp":1715662049000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Different roles of circulating and intramuscular GDF15 as markers of skeletal muscle health"],"prefix":"10.3389","volume":"15","author":[{"given":"Antonio","family":"Chiariello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Conte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Rossetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Trofarello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Salvioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Conte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2009.06.001","article-title":"Age-related changes in total and regional fat distribution","volume":"8","author":"Kuk","year":"2009","journal-title":"Ageing Res Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073709","article-title":"Increased Plin2 expression in human skeletal muscle is associated with sarcopenia and muscle weakness","volume":"8","author":"Conte","year":"2013","journal-title":"PloS One"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00114","article-title":"The dual role of the pervasive \"Fattish\" Tissue remodeling with age","volume":"10","author":"Conte","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17051708","article-title":"The association between sedentary behavior and sarcopenia among adults aged \u226565 years in lowand middle-income countries","volume":"17","author":"Smith","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e328358d59b","article-title":"Sarcopenia in older adults","volume":"24","author":"Walston","year":"2012","journal-title":"Curr Opin Rheumatol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.arr.2017.01.006","article-title":"Frailty and sarcopenia: The potential role of an aged immune system","volume":"36","author":"Wilson","year":"2017","journal-title":"Ageing Res Rev"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s41999-019-00233-w","article-title":"Special Interest Groups in Systematic Reviews and Meta-analyses for healthy ageing Sarcopenia and Frailty and resilience in older persons of the European Geriatric Medicine Society (EuGMS). 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