{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:49:03Z","timestamp":1790671743930,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T00:00:00Z","timestamp":1572998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Loss of skeletal muscle mass is one of the most widespread and deleterious processes in aging humans. However, the mechanistic metabolic principles remain poorly understood. In the framework of a multi\u2010organ investigation of age\u2010associated changes of ceramide species, a unique and distinctive change pattern of C<jats:sub>16:0<\/jats:sub> and C<jats:sub>18:0<\/jats:sub> ceramide species was detected in aged skeletal muscle. Consistently, the expression of <jats:italic>CerS1<\/jats:italic> and <jats:italic>CerS5<\/jats:italic> mRNA, encoding the ceramide synthases (CerS) with substrate preference for C<jats:sub>16:0<\/jats:sub> and C<jats:sub>18:0<\/jats:sub> acyl chains, respectively, was down\u2010regulated in skeletal muscle of aged mice. Similarly, an age\u2010dependent decline of both <jats:italic>CerS1<\/jats:italic> and <jats:italic>CerS5<\/jats:italic> mRNA expression was observed in skeletal muscle biopsies of humans. Moreover, <jats:italic>CerS1<\/jats:italic> and <jats:italic>CerS5<\/jats:italic> mRNA expression was also reduced in muscle biopsies from patients in advanced stage of chronic heart failure (CHF) suffering from muscle wasting and frailty. The possible impact of CerS1 and <jats:italic>CerS<\/jats:italic>5 on muscle function was addressed by reversed genetic analysis using <jats:italic>CerS1<\/jats:italic><jats:sup>\u0394\/\u0394<\/jats:sup> and <jats:italic>CerS5<\/jats:italic><jats:sup>\u0394\/\u0394<\/jats:sup> knockout mice. Skeletal muscle from mice deficient of either <jats:italic>CerS1<\/jats:italic> or <jats:italic>CerS5<\/jats:italic> showed reduced caliber sizes of both slow (type 1) and fast (type 2) muscle fibers, fiber grouping, and fiber switch to type 1 fibers. Moreover, <jats:italic>CerS1<\/jats:italic>\u2010 and <jats:italic>CerS5<\/jats:italic>\u2010deficient mice exhibited reduced twitch and tetanus forces of <jats:italic>musculus extensor digitorum longus<\/jats:italic>. The findings of this study link CerS1 and CerS5 to histopathological changes and functional impairment of skeletal muscle in mice that might also play a functional role for the aging skeletal muscle and for age\u2010related muscle wasting disorders in humans.<\/jats:p>","DOI":"10.1111\/acel.13049","type":"journal-article","created":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T12:40:29Z","timestamp":1573044029000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["A tissue\u2010specific screen of ceramide expression in aged mice identifies ceramide synthase\u20101 and ceramide synthase\u20105 as potential regulators of fiber size and strength in skeletal muscle"],"prefix":"10.1111","volume":"19","author":[{"given":"Bettina","family":"Tosetti","sequence":"first","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Hygiene University Hospital Cologne Cologne Germany"},{"name":"Cologne 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