{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:52:16Z","timestamp":1788324736472,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"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":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Regenerative capacity of skeletal muscles decreases with age. Deficiency in cystic fibrosis transmembrane conductance regulator (CFTR) is associated with skeletal muscle weakness as well as epithelial cell senescence. However, whether and how CFTR plays a role in skeletal muscle regeneration and aging were unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Vastus lateralis biopsy samples from male and female human subjects (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200923) of 7\u2010 to 86\u2010year\u2010old and gastrocnemii tissues from mice of 4\u2010 to 29\u2010month\u2010old were examined for CFTR expression. Skeletal muscle tissues or cultured myoblasts from mice carrying CFTR mutation (DF508) at 4\u2010 to 18\u2010month\u2010old were used for assessment of muscle mass, contractile force and regenerative capacity as well as myogenic and autophagy signalling. Overexpression of LC3\u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      , an autophagy mediator, was conducted to reverse myogenic defects in DF508 myoblasts. Adenoviruses containing CFTR gene or pharmaceuticals that enhance CFTR (VX809) were locally injected into the gastrocnemius or femoris quadricep to rescue age\u2010related skeletal muscle defects in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      mRNA levels of CFTR in human vastus lateralis exhibited significantly negative correlations with age (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.87 in males and \u22120.62 in females,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Gastrocnemius mRNA level of CFTR decreased by 77.7\u2009\u00b1\u20094.6% in 29\u2010month\u2010old wild\u2010type mice compared to the 4\u2010month\u2010old. At 18\u2010month\u2010old, DF508 mice showed significantly reduced lean mass (by 35.6%), lower specific twitch force of the gastrocnemius (by 46.2%), decrease in fast\/slow\u2010twitch muscle isoform ratio as well as downregulation of myogenic (e.g., MYOD and MYOG) or autophagy\/mitophagy (e.g., LC3\u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      ) genes, compared to age\u2010matched wild\u2010types. Post\u2010injury gastrocnemius regeneration was found impaired in DF508 mice. Myoblast cultures from DF508 mice showed defective myogenic differentiation, which was reversed by overexpressing LC3\u2010\u03b2. In aged (&gt;\u200915\u2010month\u2010old) mice, overexpressing CFTR or VX809 restored the expression of autophagy or myogenic genes, increased mitochondrial LC3\u2010\u03b2 level and improved skeletal muscle mass and function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Age\u2010related reduction in skeletal muscle expression of CFTR impairs autophagy and myogenesis, exacerbating skeletal muscle aging. Enhancing CFTR might be a potential treatment strategy for age\u2010related skeletal muscle disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13708","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T02:04:51Z","timestamp":1738202691000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Defective Cystic Fibrosis Transmembrane Conductance Regulator Accelerates Skeletal Muscle Aging by Impairing Autophagy\/Myogenesis"],"prefix":"10.1002","volume":"16","author":[{"given":"Ziyi","family":"Chen","sequence":"first","affiliation":[{"name":"Musculoskeletal Research Laboratory, Department of Orthopedics &amp; Traumatology The Chinese University of Hong Kong  Hong Kong China"},{"name":"Department of Biomedical Engineering, Faculty of Engineering The Hong Kong Polytechnic University  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiankun","family":"Xu","sequence":"additional","affiliation":[{"name":"Musculoskeletal Research Laboratory, Department of Orthopedics &amp; Traumatology The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peijie","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering The Hong Kong Polytechnic University  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanting","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering The Hong Kong Polytechnic University  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering The Hong Kong Polytechnic University  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering The Hong Kong Polytechnic University  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Respiratory Disease for Allergy Shenzhen Key Laboratory of Allergy &amp; Immunology School of Medicine Shenzhen University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayang","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Centre for Cell &amp; Developmental Biology and State Key Laboratory of Agrobiotechnology The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuantao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Musculoskeletal Research Laboratory, Department of Orthopedics &amp; Traumatology The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyang","family":"Dai","sequence":"additional","affiliation":[{"name":"Musculoskeletal Research Laboratory, Department of Orthopedics &amp; Traumatology The Chinese University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangshuai","family":"Nie","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Centre, Department of Orthopaedics The First Affiliated Hospital of Shantou University Medical College  Shantou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hu","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Centre, Department of Orthopaedics The First Affiliated Hospital of Shantou University Medical College  Shantou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangbin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Musculoskeletal Research Laboratory, Department of Orthopedics &amp; 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