{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:59:11Z","timestamp":1787018351526,"version":"build-2736575974"},"reference-count":103,"publisher":"American Society for Clinical Investigation","issue":"1","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["HL049426"],"award-info":[{"award-number":["HL049426"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["HL160661"],"award-info":[{"award-number":["HL160661"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["HL130704"],"award-info":[{"award-number":["HL130704"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,9]]},"abstract":"<jats:p>\n                    Both CO\n                    <jats:sub>2<\/jats:sub>\n                    retention, or hypercapnia, and skeletal muscle dysfunction predict higher mortality in critically ill patients. Mechanistically, muscle injury and reduced myogenesis contribute to critical illness myopathy, and while hypercapnia causes muscle wasting, no research has been conducted on hypercapnia-driven dysfunctional myogenesis in vivo. Autophagy flux regulates myogenesis by supporting skeletal muscle stem cell \u2014 satellite cell \u2014 activation, and previous data suggest that hypercapnia inhibits autophagy. We tested whether hypercapnia worsens satellite cell autophagy flux and myogenic potential and if autophagy induction reverses these deficits. Satellite cell transplantation and lineage-tracing experiments showed that hypercapnia undermined satellite cells\u2019 activation, replication, and myogenic capacity. Bulk and single-cell sequencing analyses indicated that hypercapnia disrupts autophagy, senescence, and other satellite cell programs. Autophagy activation was reduced in hypercapnic cultured myoblasts, and autophagy genetic knockdown phenocopied these changes in vitro. Rapamycin stimulation led to AMPK activation and downregulation of the mTOR pathway, which are both associated with accelerated autophagy flux and cell replication. Moreover, hypercapnic mice receiving rapamycin showed improved satellite cell autophagy flux, activation, replication rate, and posttransplantation myogenic capacity. In conclusion, we have shown that hypercapnia interferes with satellite cell activation, autophagy flux, and myogenesis, and systemic rapamycin administration improves these outcomes.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.182842","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T12:00:32Z","timestamp":1732622432000},"source":"Crossref","is-referenced-by-count":9,"title":["Rapamycin improves satellite cells\u2019 autophagy and muscle regeneration during hypercapnia"],"prefix":"10.1172","volume":"10","author":[{"given":"Joseph","family":"Balnis","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine and"},{"name":"Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily L.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular 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