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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,11,18]]},"abstract":"<jats:p>\n                    Mice overexpressing Sirt6 or fed a caloric restriction (CR) diet live longer with improved health. CR increases Sirt6 levels, and its beneficial effects are mediated by the gasotransmitter H\n                    <jats:sub>2<\/jats:sub>\n                    S, a one-carbon pathway product. Yet, the role of this pathway in Sirt6-regulated longevity remains elusive. Here, we show that Sirt6 controls hepatic one-carbon metabolism, preventing the aging-dependent H\n                    <jats:sub>2<\/jats:sub>\n                    S reduction, and the elevation of the methyl donor, S-adenosylmethionine (SAM). Sirt6 downregulates Slc7a11 expression in an Sp1-dependent manner, decreasing cystine uptake and increasing Cgl H\n                    <jats:sub>2<\/jats:sub>\n                    S production activity. Additionally, comparative acetylome in old livers revealed Sirt6-related differential acetylation of most of the one-carbon enzymes. Specifically, Sirt6-dependent Mat\u03b11 K235 deacetylation reduces its SAM production activity and Cbs binding, thereby reducing its activation of Cbs-dependent H\n                    <jats:sub>2<\/jats:sub>\n                    S production. The net outcome is H\n                    <jats:sub>2<\/jats:sub>\n                    S and SAM levels as observed in young animals. Thus, we unveil a fundamental mechanism for the promotion of healthy longevity by Sirt6.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2514084122","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T19:06:16Z","timestamp":1762887976000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Sirt6 prevents the age-related decline of H\n                    <sub>2<\/sub>\n                    S through the control of one-carbon metabolism"],"prefix":"10.1073","volume":"122","author":[{"given":"Noga","family":"Touitou","sequence":"first","affiliation":[{"name":"The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University","place":["Ramat-Gan, Israel"]},{"name":"The Sagol Healthy Human Longevity Center, Bar-Ilan University","place":["Ramat-Gan, 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