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Besides, RAS activation promotes age\u2010related changes and age\u2010associated diseases, which are attenuated\/abolished by RAS\u2010blockade in several mammalian species. RAS\u2010blockers also increase rodent lifespan. In previous work, we discussed how RAS\u2010blockade downregulates mTOR and growth hormone\/IGF\u20101 signaling, and stimulates AMPK activity (together with klotho, sirtuin, and vitamin D\u2010receptor upregulation), and proposed that at least some of RAS\u2010blockade's aging benefits are mediated through regulation of these intermediaries and their signaling to mitochondria. Here, we included RAS\u2010blockade's impact on other aging regulatory pathways, that is, TGF\u2010\u00df, NF\u2010kB, PI3K, MAPK, PKC, Notch, and Wnt, all of which affect mitochondria. No direct evidence is available on RAS\/RAS\u2010blockade\u2010aging regulatory pathway\u2013mitochondria interactions. However, existing results allow to conjecture that RAS\u2010blockers neutralize mitochondrial dysfunction by acting on the discussed pathways. The reviewed evidence led us to propose that the foundation is laid for conducting clinical trials aimed at testing whether angiotensin\u2010converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)\u2014even at subclinical doses\u2014offer the possibility to live longer and in better health. As ACEi and ARB are low cost and well\u2010tolerated anti\u2010hypertension therapies in use for over 35\u2009years, investigating their administration to attenuate\/prevent aging effects seems simple to implement.<\/jats:p>","DOI":"10.14814\/phy2.16094","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T05:45:00Z","timestamp":1719380700000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Renin\u2013angiotensin system inhibitors positively impact on multiple aging regulatory pathways: Could they be used to protect against human aging?"],"prefix":"10.14814","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8752-8518","authenticated-orcid":false,"given":"Elena M. 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