{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:28:51Z","timestamp":1788445731563,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T00:00:00Z","timestamp":1653782400000},"content-version":"vor","delay-in-days":148,"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":["82001465"],"award-info":[{"award-number":["82001465"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>Pioglitazone hydrochloride (PGZ), a nuclear receptor peroxisome proliferator\u2010activated receptor gamma (PPAR\u2010<jats:italic>\u03b3<\/jats:italic>) agonist, is a universally adopted oral agent for the treatment of type 2 diabetes (T2D). Previous studies reported that PGZ could ameliorate the symptoms of aging\u2010related diseases and Alzheimer\u2019s disease. However, whether PGZ participates in aging regulation and the underlying mechanism remain undetermined. Here, we found that PGZ significantly prolonged the lifespan and healthspan of <jats:italic>Caenorhabditis elegans<\/jats:italic> (<jats:italic>C<\/jats:italic>. <jats:italic>elegans<\/jats:italic>). We found that a variety of age\u2010related pathways and age\u2010related genes are required for PGZ\u2010induced lifespan extension. The transcription factors DAF\u201016\/FOXO, HSF\u20101, and SKN\u20101\/NRF2, as well as the nuclear receptors DAF\u201012 and NHR\u201049, all functioned in the survival advantage conferred by PGZ. Moreover, our results demonstrated that PGZ induced lifespan extension through the inhibition of insulin\/insulin\u2010like signaling (IIS) and reproductive signaling pathways, as well as the activation of dietary restriction\u2010 (DR\u2010) related pathways. Additionally, our results also indicated that beneficial longevity mediated by PGZ is linked to its antioxidative activity. Our research may provide a basis for further research on PGZ, as an anti\u2010T2D drug, to interfere with aging and reduce the incidence of age\u2010related diseases in diabetic patients.<\/jats:p>","DOI":"10.1155\/2022\/8496063","type":"journal-article","created":{"date-parts":[[2022,5,30]],"date-time":"2022-05-30T05:05:17Z","timestamp":1653887117000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Pioglitazone Hydrochloride Extends the Lifespan of <i>Caenorhabditis elegans<\/i> by Activating DAF\u201016\/FOXO\u2010 and SKN\u20101\/NRF2\u2010Related Signaling 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