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Protection against oxidative damage largely relies on the reductive power of NAPDH, whose levels are mostly determined by the enzyme glucose-6-phosphate dehydrogenase (G6PD). Here, we report a transgenic mouse model with moderate overexpression of human G6PD under its endogenous promoter. Importantly, G6PD-Tg mice have higher levels of NADPH, lower levels of ROS-derived damage, and better protection from ageing-associated functional decline, including extended median lifespan in females. The G6PD transgene has no effect on tumour development, even after combining with various tumour-prone genetic alterations. We conclude that a modest increase in G6PD activity is beneficial for healthspan through increased NADPH levels and protection from the deleterious effects of ROS.<\/jats:p>","DOI":"10.1038\/ncomms10894","type":"journal-article","created":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T10:18:41Z","timestamp":1458037121000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":231,"title":["G6PD protects from oxidative damage and improves healthspan in mice"],"prefix":"10.1038","volume":"7","author":[{"given":"Sandrina","family":"N\u00f3brega-Pereira","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3515-4125","authenticated-orcid":false,"given":"Pablo J.","family":"Fernandez-Marcos","sequence":"additional","affiliation":[]},{"given":"Thomas","family":"Brioche","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4000-1684","authenticated-orcid":false,"given":"Mari Carmen","family":"Gomez-Cabrera","sequence":"additional","affiliation":[]},{"given":"Andrea","family":"Salvador-Pascual","sequence":"additional","affiliation":[]},{"given":"Juana M.","family":"Flores","sequence":"additional","affiliation":[]},{"given":"Jose","family":"Vi\u00f1a","sequence":"additional","affiliation":[]},{"given":"Manuel","family":"Serrano","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,3,15]]},"reference":[{"key":"BFncomms10894_CR1","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1038\/nrm2256","volume":"8","author":"B D\u2019Autr\u00e9aux","year":"2007","unstructured":"D\u2019Autr\u00e9aux, B. & Toledano, M. 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