{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:44:31Z","timestamp":1792611871200,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":["Aging Cell"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Sarcopenia in chronic obstructive pulmonary disease (COPD) is driven by elevated tumor necrosis factor\u2010alpha (TNF\u2010\u03b1), yet the underlying mechanism remains unclear. Here, we identify the mitochondrial metabolic enzyme Prodh2 as a pivotal mediator. Prodh2 was significantly upregulated in sarcopenic COPD patients and a corresponding mouse model. Mechanistically, TNF\u2010\u03b1 induced Prodh2 transcription in myoblasts via a p53\u2010dependent pathway. This upregulation triggered excessive mitochondrial reactive oxygen species, leading to the release of mitochondrial DNA (mtDNA). Cytosolic mtDNA subsequently activated the cGAS\/STING innate immune pathway, causing myoblast apoptosis, proliferation arrest, and atrophy. While Prodh2 knockdown reversed these effects in\u00a0vitro, muscle\u2010specific knockdown of Prodh2 in\u00a0vivo critically ameliorated muscle atrophy and restored strength. Our study unveils a novel TNF\u2010\u03b1\u2010p53\u2010Prodh2\u2010cGAS\/STING axis that links chronic inflammation to sarcopenia through metabolic\u2010immune crosstalk, validating Prodh2 as a promising therapeutic target.<\/jats:p>","DOI":"10.1111\/acel.70739","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:35:52Z","timestamp":1790922952000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prodh2\u2010Mediated Mitochondrial Stress Drives\n                    <scp>TNF<\/scp>\n                    \u2010\u03b1\u2010Induced Myoblast Dysfunction and Sarcopenia in\n                    <scp>COPD<\/scp>"],"prefix":"10.1111","volume":"25","author":[{"given":"Gang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthopedics Fujian Medical University Union Hospital  Fuzhou Fujian 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