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It has long been established that ARHL is more prevalent, is more severe, and tends to occur earlier in men than in women. A key factor contributing to ARHL is oxidative stress, which harms the inner ear cells. Sirtuins are a family of proteins that play critical roles in cellular regulation, particularly in response to stress and aging, and have demonstrated anti-aging effects. Cocoa flavonoids, due to their antioxidant properties, have been reported to provide numerous health benefits. The present study aimed to evaluate the efficacy of cocoa in preventing oxidative damage in the cochlea of aging mice mediated by Sirtuins, as well as to determine possible differences between sexes. Female and male C57Bl\/6\u00a0J mice were randomly assigned to two study groups: standard diet and cocoa-supplemented diet. At the ages of 6, 14, and 22\u00a0months, the animals were sacrificed, and cochleae were harvested to measure the expression of Sirtuins-1, -3, forkhead box O3 (FOXO3), p53, antioxidant enzymes, oxidative DNA damage, and levels of reactive oxidative species (ROS). Our results indicated that cocoa attenuated oxidative DNA damage, reduced ROS levels, and induced the expression of SIRT1, -3, FOXO3, and p53 in the cochlea of \u200b\u200baged mice. Furthermore, the activity of antioxidant enzymes in aged mice was restored with the cocoa diet. Sex differences were observed in several of these variables. These results indicate that cocoa protects against oxidative damage through Sirtuins. In conclusion, cocoa may have therapeutic potential against ARHL.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s11357-025-01847-8","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T21:27:14Z","timestamp":1755725234000},"page":"2987-3006","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Sirtuins mediate the reduction of age-related oxidative damage in the cochlea under a cocoa-rich diet"],"prefix":"10.1007","volume":"48","author":[{"given":"Rosal\u00eda F\u00e1tima","family":"Heredia-Molina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0297-2711","authenticated-orcid":false,"given":"Juan Ignacio","family":"Riestra-Ayora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6990-0619","authenticated-orcid":false,"given":"Israel John Thuissard","family":"Vasallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4990-8859","authenticated-orcid":false,"given":"Ricardo","family":"Sanz-Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6246-0449","authenticated-orcid":false,"given":"Carolina","family":"S\u00e1nchez-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"1847_CR1","doi-asserted-by":"publisher","DOI":"10.1097\/01.moo.0000134450.99615.22","author":"KK Ohlemiller","year":"2004","unstructured":"Ohlemiller KK. 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