{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T08:54:27Z","timestamp":1779353667199,"version":"3.51.4"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022S1A5A2A03055843"],"award-info":[{"award-number":["2022S1A5A2A03055843"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The cellular prion protein (PrP\n                      <jats:sup>C<\/jats:sup>\n                      ), a glycoprotein encoded by the\n                      <jats:italic>PRNP<\/jats:italic>\n                      gene, is known to modulate muscle mass and exercise capacity. However, the role of PrP\n                      <jats:sup>C<\/jats:sup>\n                      in the maintenance and regeneration of skeletal muscle during ageing remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study investigated the change in PrP\n                      <jats:sup>C<\/jats:sup>\n                      expression during muscle formation using C2C12 cells and evaluated muscle function in\n                      <jats:italic>Prnp<\/jats:italic>\n                      wild\u2010type (WT) and knock\u2010out (KO) mice at different ages (1, 9 and 15\u2009months). To determine the role of PrP\n                      <jats:sup>C<\/jats:sup>\n                      in skeletal muscle homeostasis during ageing, we conducted regeneration experiments via cardiotoxin injection in\n                      <jats:italic>Prnp<\/jats:italic>\n                      mice to assess the effects of PrP\n                      <jats:sup>C<\/jats:sup>\n                      deficiency on the senescence of satellite stem cells (SCs) and regenerative capacity in skeletal muscle.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our data demonstrate that PrP\n                      <jats:sup>C<\/jats:sup>\n                      expression increased significantly during muscle differentiation (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), correlating with myogenin (immunofluorescence at the differentiation stage). PrP\n                      <jats:sup>C<\/jats:sup>\n                      deficiency disrupted muscle homeostasis, leading to age\u2010associated mitochondrial autophagy (Pink\u20101, +180%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; Parkin, +161%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and endoplasmic reticulum stress (SERCA, \u221226%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05; IRE1\n                      <jats:italic>\u03b1<\/jats:italic>\n                      , +195%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) while decreasing the level of mitochondrial biogenesis (SIRT\u20101, \u221250%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01; PGC\u20101\n                      <jats:italic>\u03b1<\/jats:italic>\n                      , \u221236%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05; VDAC, \u221227%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and activated oxidative stress (serum myoglobin, +23%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; MDA, +23%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05; NF\n                      <jats:italic>\u03ba<\/jats:italic>\n                      B, +117%, p\u2009&lt;\u20090.05) during ageing, which accelerated reduced muscle growth or mass accumulation (tibialis anterior muscle mass, \u221223%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; gastrocnemius muscle mass, \u221230%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; muscle fibre size, \u221248%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05; MSTN, +160%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01; MAFbx, +83%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Furthermore, PrP\n                      <jats:sup>C<\/jats:sup>\n                      deficiency induced the senescence (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010galactosidase, +60%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05; p16, +103%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) of SCs, which was directly related to the defect in muscle recovery, with the senescence\u2010mediated enhancement of adipogenesis (PPAR\n                      <jats:italic>\u03b3<\/jats:italic>\n                      , +74%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) during the regeneration process after cardiotoxin\u2010induced muscle injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings demonstrate that PrP\n                      <jats:sup>C<\/jats:sup>\n                      is indispensable for maintaining skeletal muscle homeostasis during ageing by modulating the functional integrity of mitochondria, ER and SCs.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13706","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T05:01:53Z","timestamp":1738040513000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["PrP\n                    <sup>C<\/sup>\n                    Glycoprotein Is Indispensable for Maintenance of Skeletal Muscle Homeostasis During Aging"],"prefix":"10.1002","volume":"16","author":[{"given":"Wenduo","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Sports Science, College of Natural Science Jeonbuk National University  Jeonju 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