Nóbrega-Pereira Sandrina, Fernandez-Marcos Pablo J, Brioche Thomas, Gomez-Cabrera Mari Carmen, Salvador-Pascual Andrea, Flores Juana M, Viña Jose, Serrano Manuel
Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid E28029, Spain.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Nat Commun. 2016 Mar 15;7:10894. doi: 10.1038/ncomms10894.
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.
活性氧（ROS）由细胞持续产生，ROS引发的损伤会导致衰老。对抗氧化损伤很大程度上依赖于烟酰胺腺嘌呤二核苷酸磷酸（NADPH）的还原能力，其水平主要由葡萄糖-6-磷酸脱氢酶（G6PD）决定。在此，我们报告一种转基因小鼠模型，该模型在其内源启动子作用下适度过表达人G6PD。重要的是，G6PD转基因小鼠具有更高水平的NADPH、更低水平的ROS引发的损伤，并且能更好地抵御与衰老相关的功能衰退，包括雌性小鼠中位寿命的延长。即使与各种易患肿瘤的基因改变相结合，G6PD转基因对肿瘤发生也没有影响。我们得出结论，G6PD活性的适度增加通过提高NADPH水平和抵御ROS的有害影响，对健康寿命有益。
