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oai:repisalud.isciii.es:20.500.12105/78692024-11-29T22:37:15Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Nóbrega-Pereira, Sandrina author Fernandez-Marcos, Pablo J author Brioche, Thomas author Gomez-Cabrera, Mari Carmen author Salvador-Pascual, Andrea author Flores, Juana M author Viña, Jose author Serrano Marugan, Manuel author 2016-03-15 Reactive oxygen species (ROS) are constantly generated by cells and ROS-derived damage contributes to ageing. 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. Nat Commun. 2016;7:11739 10.1038/ncomms10894 2041-1723 2041-1723 Nature communications 26976705 http://hdl.handle.net/20.500.12105/7869 G6PD protects from oxidative damage and improves healthspan in mice