{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:03:20Z","timestamp":1784887400838,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ceramides have garnered considerable attention as pro\u2010aging bioactive lipids implicated in both metabolic dysfunction and musculoskeletal decline. Among these, C18:0 and C24:1 ceramides may play a role in the pathophysiology of sarcopenia, a key manifestation of age\u2010related deterioration. However, their specific contributions to muscle degeneration remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>C2C12 myoblasts and primary myoblasts were treated with C18:0 or C24:1 ceramides during differentiation to assess myotube formation, migration and intracellular reactive oxygen species (ROS) levels. Three\u2010month\u2010old C57BL\/6 mice received daily intraperitoneal injections of C18:0 or C24:1 ceramides for 4\u2009weeks to evaluate muscle morphology and function. In a human cohort of 165 community\u2010dwelling older adults (\u2265\u200965\u2009years), serum ceramide levels were measured via LC\u2013MS\/MS and analysed in relation to sarcopenia parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both C18:0 and C24:1 ceramides significantly impaired myogenic differentiation in\u00a0vitro, as evidenced by reduced myotube number, total myotube area, average area per myotube, nuclei count per myotube and fusion index, through ROS\u2010mediated mechanisms (with up to an 8.6\u2010fold increase in ROS production). Consistently, C18:0 and C24:1 ceramides markedly downregulated key myogenic markers and inhibited ITGB1\u2010FAK\u2010AKT signalling while promoting nuclear activation of FoxO\u2010associated catabolic pathways. These deleterious effects were attenuated by treatment with the antioxidant N\u2010acetylcysteine. In mice, systemic administration of either ceramide resulted in reduced muscle fibre cross\u2010sectional area in the tibialis anterior (by 20.5% and 20.9% for C18:0 and C24:1, respectively) and soleus muscles (by 18.1% and 16.1%), accompanied by decreased grip strength, shorter grid hanging times and reduced latency to fall in the rotarod test. Clinically, in a cohort of 165 older adults (80.6% female; mean age 75.2\u2009\u00b1\u20095.2\u2009years in controls and 79.7\u2009\u00b1\u20094.8\u2009years in the sarcopenia group), serum levels of C18:0 and C24:1 ceramides were 27% and 14% higher, respectively, in individuals with sarcopenia compared to controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001 and 0.018). Furthermore, each standard deviation increase in serum C18:0 and C24:1 ceramide levels was associated with a 2.0\u2010 and 1.6\u2010fold increased risk of sarcopenia, respectively (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003 and 0.040).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings reveal that circulating C18:0 and C24:1 ceramides are significantly associated with sarcopenia in older adults, while experimental models demonstrate they promote muscle atrophy through oxidative stress\u2010induced impairment of myogenesis and muscle function. These ceramides may serve as minimally invasive biomarkers and potential therapeutic targets for age\u2010related muscle decline. Interventions aimed at modulating ceramide metabolism could offer new avenues for sarcopenia prevention and treatment in aging populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70310","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T07:51:22Z","timestamp":1777621882000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Elevated Circulating Ceramides 18:0 and 24:1 as a Risk Factor for Sarcopenia: In\u00a0Vitro, Animal, and Clinical Evidence"],"prefix":"10.1002","volume":"17","author":[{"given":"So Jeong","family":"Park","sequence":"first","affiliation":[{"name":"Asan Institute for Life Sciences Asan Medical Center, University of Ulsan College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Yeon","family":"Baek","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine Asan Medical Center, University of Ulsan College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibo","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Engineering Gwangju Institute of Science and Technology  Gwangju South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Asan Institute for Life Sciences Asan Medical Center, University of Ulsan College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuna","family":"Lee","sequence":"additional","affiliation":[{"name":"Asan Institute for Life Sciences Asan Medical Center, University of Ulsan College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang\u2010Hoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Asan Institute for Life Sciences Asan Medical Center, University of Ulsan College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il\u2010Young","family":"Jang","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine Asan Medical Center, University of Ulsan College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyuk","family":"Sakong","sequence":"additional","affiliation":[{"name":"Asan Institute for Life Sciences Asan Medical Center, University of Ulsan College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Ju","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Convergence Medicine, Asan Institute for Life Sciences Asan Medical Center, University of Ulsan College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee\u2010Won","family":"Jung","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine Asan Medical Center, University of Ulsan College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunju","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine Asan Medical Center, University of Ulsan College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Convergence Medicine, Asan Institute for Life Sciences Asan Medical Center, University of Ulsan College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunju","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Microbiology Wonkwang University School of Medicine  Iksan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyunggon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Digital Medicine, BK21 Project University of Ulsan College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongryeol","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Engineering Gwangju Institute of Science and Technology  Gwangju South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8591-1759","authenticated-orcid":false,"given":"Beom\u2010Jun","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine Asan Medical Center, University of Ulsan College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2019.05.016"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr1407158"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251141"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10357"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2025.2600"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2024.2002"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2025.2656"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-017-4151-8"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12491"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.024261"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.03.011"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102389"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8010037"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-25-0234"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.70144"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4116"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12767"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01259-6"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.11005\/jbm.2024.31.1.1"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31138-9"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25084300"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700300R"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12131792"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11602"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.132"},{"key":"e_1_2_8_27_1","first-page":"11","article-title":"Oxidative Stress and Cell Senescence Process","volume":"11","author":"Faraonio R.","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.101943"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13241"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00400-3"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20123-1"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13133285"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2025.2488563"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51687"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13111623"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-11219-3"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05613-7"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114746"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2024.111099"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11100675"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2024.100726"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70310","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.70310","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70310","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T09:18:44Z","timestamp":1784884724000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.70310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/jcsm.70310"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.70310","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,1]]},"assertion":[{"value":"2025-06-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70310"}}