title: G6PD protects from oxidative damage and improves healthspan in mice.
abstract: 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.
authors.affiliation: 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.
authors.forename: Sandrina
authors.initials: S
authors.lastname: Nóbrega-Pereira
authors.affiliation: Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid E28029, Spain.|Bioactive Products and Metabolic Syndrome Group, Madrid Institute of Advanced Studies (IMDEA) Food, Madrid E28049, Spain.
authors.forename: Pablo J
authors.identifier: http://orcid.org/0000-0003-3515-4125
authors.initials: PJ
authors.lastname: Fernandez-Marcos
authors.affiliation: Université de Montpellier, INRA, UMR866, Dynamique Musculaire et Métabolisme, F-34060 Montpellier, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brioche
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia and Investigaciòn Hospital Clínico Universitario (INCLIVA), Valencia E46010, Spain.
authors.forename: Mari Carmen
authors.identifier: http://orcid.org/0000-0003-4000-1684
authors.initials: MC
authors.lastname: Gomez-Cabrera
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia and Investigaciòn Hospital Clínico Universitario (INCLIVA), Valencia E46010, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Salvador-Pascual
authors.affiliation: Animal Surgery and Medicine Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Madrid E28040, Spain.
authors.forename: Juana M
authors.initials: JM
authors.lastname: Flores
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia and Investigaciòn Hospital Clínico Universitario (INCLIVA), Valencia E46010, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Viña
authors.affiliation: Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid E28029, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Serrano
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics*; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009249:NADP / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D009249:NADP; D005954:Glucosephosphate Dehydrogenase