{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:30:02Z","timestamp":1789648202409,"version":"4.0.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Cellular senescence influences organismal aging and increases predisposition to age-related diseases, in particular cardiovascular disease, a leading cause of death and disability worldwide. Peroxisome proliferator-activated receptor \u03b3 coactivator-1\u03b1 (PGC-1\u03b1) is a master regulator of mitochondrial biogenesis and function, oxidative stress, and insulin resistance. Senescence is associated with telomere and mitochondrial dysfunction and oxidative stress, implying a potential causal role of PGC-1\u03b1 in senescence pathogenesis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              We generated a PGC-1\u03b1\n              <jats:sup>+\/\u2013<\/jats:sup>\n              \/apolipoprotein E\n              <jats:sup>\u2013\/\u2013<\/jats:sup>\n              mouse model and showed that PGC-1\u03b1 deficiency promotes a vascular senescence phenotype that is associated with increased oxidative stress, mitochondrial abnormalities, and reduced telomerase activity. PGC-1\u03b1 disruption results in reduced expression of the longevity-related deacetylase sirtuin 1 (SIRT1) and the antioxidant catalase, and increased expression of the senescence marker p53 in aortas. Further, angiotensin II, a major hormonal inducer of vascular senescence, induces prolonged lysine acetylation of PGC-1\u03b1 and releases the PGC-1\u03b1\u2013FoxO1 complex from the SIRT1 promoter, thus reducing SIRT1 expression. The phosphorylation-defective mutant PGC-1\u03b1 S570A is not acetylated, is constitutively active for forkhead box O1-dependent SIRT1 transcription, and prevents angiotensin II\u2013induced senescence. Acetylation of PGC-1\u03b1 by angiotensin II interrupts the PGC-1\u03b1\u2013forkhead box O1\u2013SIRT1 feed-forward signaling circuit leading to SIRT1 and catalase downregulation and vascular senescence.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>PGC-1\u03b1 is a primary negative regulator of vascular senescence. Moreover, the central role of posttranslational modification of PGC-1\u03b1 in regulating angiotensin II\u2013induced vascular senescence may inform development of novel therapeutic strategies for mitigating age-associated diseases, such as atherosclerosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.112.301019","type":"journal-article","created":{"date-parts":[[2013,2,22]],"date-time":"2013-02-22T05:30:24Z","timestamp":1361511024000},"page":"988-998","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":75,"title":["Peroxisome Proliferator-Activated Receptor \u03b3 Coactivator-1\u03b1 Is a Central Negative Regulator of Vascular Senescence"],"prefix":"10.1161","volume":"33","author":[{"given":"Shiqin","family":"Xiong","sequence":"first","affiliation":[{"name":"From the Division of Cardiology (S.X., G.S., N.P., M.M., F.F., L.H., R.W.A.) and Department of Medicine (R.W.A.), Emory University Hospital, Emory University School of Medicine, Atlanta, GA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Salazar","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (S.X., G.S., N.P., M.M., F.F., L.H., R.W.A.) and Department of Medicine (R.W.A.), Emory University Hospital, Emory University School of Medicine, Atlanta, GA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay","family":"Patrushev","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (S.X., G.S., N.P., M.M., F.F., L.H., R.W.A.) and Department of Medicine (R.W.A.), Emory University Hospital, Emory University School of Medicine, Atlanta, GA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhui","family":"Ma","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (S.X., G.S., N.P., M.M., F.F., L.H., R.W.A.) and Department of Medicine (R.W.A.), Emory University Hospital, Emory University School of Medicine, Atlanta, GA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farshad","family":"Forouzandeh","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (S.X., G.S., N.P., M.M., F.F., L.H., R.W.A.) and Department of Medicine (R.W.A.), Emory University Hospital, Emory University School of Medicine, Atlanta, GA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lula","family":"Hilenski","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology (S.X., G.S., N.P., M.M., F.F., L.H., R.W.A.) and Department of Medicine (R.W.A.), Emory University Hospital, Emory University School of Medicine, Atlanta, GA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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