{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:28:49Z","timestamp":1760149729843,"version":"build-2065373602"},"reference-count":64,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"TIMA Establishment","award":["20170101"],"award-info":[{"award-number":["20170101"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex neurodegenerative disease characterized by cognitive and short-term memory impairments. The disease involves multiple pathological factors such as amyloid plaque formation, mitochondrial dysfunction, and telomere shortening; however, oxidative stress and diabetes mellitus are significant risk factors. The onset of AD begins approximately 20 years before clinical symptoms manifest; therefore, treating AD after symptoms become evident is possibly too late to have a significant effect. As such, preventing AD or using an effective treatment at an early stage is important. Twendee X\u00ae\u00a0(TwX) is an antioxidant formulation consisting of eight ingredients. TwX has been proven to prevent the progression to dementia in patients with mild cognitive impairment (MCI) in a multicenter, randomized, double-blind, placebo-controlled, prospective intervention trial. As well, positive data has already been obtained in several studies using AD model mice. Since both diabetes and aging are risk factors for AD, we examined the mechanisms behind the effects of TwX on AD using the spontaneous hyperglycemia model and the senescence model of aged C57BL\/6 mice in this study. TwX was administered daily, and its effects on diabetes, autophagy in the brain, neurogenesis, and telomere length were examined. We observed that TwX protected the mitochondria from oxidative stress better than a single antioxidant. TwX not only lowered blood glucose levels but also suppressed brain neurogenesis and autophagy. Telomeres in TWX-treated mice were significantly longer than those in non-treated mice. There are many factors that can be implicated in the development and progression of dementia; however, multiple studies on TwX suggest that it may offer protection against dementia, not only through the effects of its antioxidants but also by targeting multiple mechanisms involved in its development and progression, such as diabetes, brain neurogenesis, telomere deficiency, and energy production.<\/jats:p>","DOI":"10.3390\/ijms241613018","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T08:53:31Z","timestamp":1692608011000},"page":"13018","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Why Does the Antioxidant Complex Twendee X\u00ae\u00a0Prevent Dementia?"],"prefix":"10.3390","volume":"24","author":[{"given":"Fukka","family":"You","sequence":"first","affiliation":[{"name":"Division of Anti-Oxidant Research, Life Science Research Center, Gifu University, Yanagito 1-1, Gifu 501-1194, Japan"},{"name":"Anti-Oxidant Research Laboratory, Louis Pasteur Center for Medical Research, Tanakamonzen-cho 103-5, Sakyo-ku, Kyoto 606-8225, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiaki","family":"Harakawa","sequence":"additional","affiliation":[{"name":"Division of Anti-Oxidant Research, Life Science Research Center, Gifu University, Yanagito 1-1, Gifu 501-1194, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshikazu","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Louis Pasteur Center for Medical Research, Tanakamonzen-cho 103-5, Sakyo-ku, Kyoto 606-8225, Japan"},{"name":"School of Medicine, Kyoto Prefectural University of Medicine, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruhiko","family":"Inufusa","sequence":"additional","affiliation":[{"name":"Division of Anti-Oxidant Research, Life Science Research Center, Gifu University, Yanagito 1-1, Gifu 501-1194, Japan"},{"name":"Anti-Oxidant Research Laboratory, Louis Pasteur Center for Medical Research, Tanakamonzen-cho 103-5, Sakyo-ku, Kyoto 606-8225, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dominguez, L.J., Veronese, N., Vernuccio, L., Catanese, G., Inzerillo, F., Salemi, G., and Barbagallo, M. 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