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Our study focuses on PTCHD4, a transmembrane protein with previously undefined physiological functions in aging processes. We found that PTCHD4 expression was increased across multiple cellular senescence models and showed an age\u2010associated increase in mouse tissues and human lung transcriptomic datasets. Functionally, PTCHD4 deficiency attenuated senescence progression, whereas its overexpression promoted this process. In\u00a0vivo, PTCHD4 deficiency alleviated D\u2010galactose\u2010induced aging\u2010related phenotypes and functional deterioration, accompanied by an extension of median lifespan in mice. In a bleomycin\u2010induced pulmonary fibrosis model, PTCHD4 deficiency reduced collagen deposition, attenuated senescence\u2010 and inflammation\u2010associated signals, and preserved pulmonary function. Mechanistically, PTCHD4 promoted aging\u2010associated AKT activation, and restoration of AKT signaling reversed the anti\u2010senescent effects of PTCHD4 deficiency. Taken together, these findings support PTCHD4 as a contributor to cellular senescence and age\u2010associated tissue dysfunction, and suggest that the PTCHD4\u2010AKT axis warrants further investigation as a candidate target in senescence\u2010associated diseases.<\/jats:p>","DOI":"10.1111\/acel.70711","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:30:42Z","timestamp":1789133442000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transmembrane Protein\n                    <scp>PTCHD4<\/scp>\n                    Is a Novel Regulator of Cellular Senescence and Age\u2010Related Pathologies"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3005-120X","authenticated-orcid":false,"given":"Mingyue","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences Peking 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