G6PD protects from oxidative damage and improves healthspan in mice

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Nobrega-Pereira, Sandrina | Fernandez-Marcos, Pablo J. | Brioche, Thomas | Gomez-Cabrera, Mari Carmen | Salvador-Pascual, Andrea | M. Flores, Juana | Viña, José | Serrano, Manuel

Edité par CCSD ; Nature Publishing Group -

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 micehave 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.

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