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Its multifactorial causes including poor nutrition, physical inactivity, and underlying diseases. Research suggests a role for C-peptide in muscle regulation, but its link to sarcopenia is unclear. We hypothesized that low C-peptide associates with sarcopenia and fractures, and that it promotes myogenesis and protects muscle cells from atrophic damage in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this cross-sectional study, we analysed data from 191 individuals aged 50 or older, including serum C-peptide and appendicular skeletal muscle mass measurements, along with falls and fractures assessed at follow-up. Skeletal muscle parameters were evaluated using bioelectrical impedance analysis. In parallel, in vitro experiments were performed in C2C12 cells to investigate the effects of C-peptide on myogenic differentiation and its protective role against muscle damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Individuals in the lowest C-peptide tertile had significantly less appendicular skeletal muscle\/sarcopenia than those in the highest (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Lower C-peptide significantly increased sarcopenia odds (OR: 0.34;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). These individuals also showed higher falls (32%) and fractures (17%) rates compared to the highest tertile (14% and 0%). Fractures were linked to falls and low C-peptide levels (OR: 0.29;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01). In vitro, C-peptide promotes myogenic differentiation and reduced muscle damage in C2C12 myotubes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest the protective role of C-peptide in musculoskeletal health, demonstrating that higher levels are associated with a reduced risk of having low appendicular skeletal muscle mass\/sarcopenia and fractures in adults and the elderly. Moreover, C-peptide enhances myogenic differentiation and protects against in vitro nutrient-deprivation muscle damage. Further studies are warranted to explore the therapeutic utility of C-peptide for the prevention of sarcopenia and fractures in adulthood and aging.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-07983-9","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T13:48:28Z","timestamp":1773236908000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["C-peptide promotes myogenic differentiation in vitro and low serum levels are associated with sarcopenia in adults and the elderly"],"prefix":"10.1186","volume":"24","author":[{"given":"Yvelise","family":"Ferro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Castagna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7644-1337","authenticated-orcid":false,"given":"Samantha","family":"Maurotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Rita","family":"Noto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Mazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Pujia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Galluccio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Sciacqua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Gazzaruso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Romeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Pujia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Montalcini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"7983_CR1","doi-asserted-by":"publisher","first-page":"160","DOI":"10.3390\/cells11010160","volume":"11","author":"J Bilski","year":"2022","unstructured":"Bilski J, Pierzchalski P, Szczepanik M, Bonior J, Zoladz JA. 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