{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:57:05Z","timestamp":1791460625219,"version":"4.3.4"},"reference-count":19,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T00:00:00Z","timestamp":1697241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001489"],"award-info":[{"award-number":["82001489"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aging is a major risk factor for cardiovascular diseases. Our previous studies demonstrate that aging impairs the caveolar T\u2010type Ca<jats:sub>V<\/jats:sub>3.2\u2010RyR axis for extracellular Ca<jats:sup>2+<\/jats:sup> influx to trigger Ca<jats:sup>2+<\/jats:sup> sparks in vascular smooth muscle cells (VSMCs). We hypothesize that the administration of senolytics, which can selectively clear senescent cells, could preserve the caveolar Ca<jats:sub>V<\/jats:sub>3.2\u2010RyR axis in aging VSMCs. In this study, 10\u2010month\u2010old mice were administered the senolytics cocktail consisting of dasatinib (5\u2009mg\/kg) and quercetin (50\u2009mg\/kg) or vehicle bi\u2010weekly for 4\u2009months. Using VSMCs from mouse mesenteric arteries, we found that Ca<jats:sup>2+<\/jats:sup> sparks were diminished after caveolae disruption by methyl\u2010\u03b2\u2010cyclodextrin (10\u2009mM) in cells from D\u2009+\u2009Q treated but not vehicle\u2010treated 14\u2010month\u2010old mice. D\u2009+\u2009Q treatment promoted the expression of Ca<jats:sub>V<\/jats:sub>3.2 in 14\u2010month\u2010old mesenteric arteries. Structural analysis using electron tomography and immunofluorescence staining revealed the remodeling of caveolae and co\u2010localization of Ca<jats:sub>V<\/jats:sub>3.2\u2010Cav\u20101 in D\u2009+\u2009Q treatment aged mesenteric arteries. In keeping with theoretical observations, Ca<jats:sub>v<\/jats:sub>3.2 channel inhibition by Ni<jats:sup>2+<\/jats:sup> (50\u2009\u03bcM) suppressed Ca<jats:sup>2+<\/jats:sup> in VSMCs from the D\u2009+\u2009Q group, with no effect observed in vehicle\u2010treated arteries. Our study provides evidence that age\u2010related caveolar Ca<jats:sub>V<\/jats:sub>3.2\u2010RyR axis malfunction can be alleviated by pharmaceutical intervention targeting cellular senescence. Our findings support the potential of senolytics for ameliorating age\u2010associated cardiovascular disease.<\/jats:p>","DOI":"10.1111\/acel.14002","type":"journal-article","created":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T16:40:29Z","timestamp":1697301629000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Senolytics prevent caveolar <scp>Ca<sub>V<\/sub>3<\/scp>.<scp>2\u2010RyR<\/scp> axis malfunction in old vascular smooth muscle"],"prefix":"10.1111","volume":"22","author":[{"given":"Jie","family":"Lin","sequence":"first","affiliation":[{"name":"Cardiology Department The first Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"Guo","sequence":"additional","affiliation":[{"name":"Sports Medicine Center Huazhong University of Science and Technology Union Shenzhen Hospital, the 6th affiliated Hospital of Shenzhen University Medical School  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingtian","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Huazhong University of Science and Technology Union Shenzhen Hospital, the 6th affiliated Hospital of Shenzhen University Medical School  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Neurology Department Huazhong University of Science and Technology Union Shenzhen Hospital, the 6th affiliated Hospital of Shenzhen University Medical School  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Wan","sequence":"additional","affiliation":[{"name":"Sports Medicine Center Huazhong University of Science and Technology Union Shenzhen Hospital, the 6th affiliated Hospital of Shenzhen University Medical School  Shenzhen 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