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RESEARCH PRODUCT
G6PD protects from oxidative damage and improves healthspan in mice
Pablo J. Fernandez-marcosJuana M. FloresThomas BriocheManuel SerranoJose ViñaMa Carmen Gómez-cabreraSandrina Nóbrega-pereiraAndrea Salvador-pascualsubject
Male0301 basic medicineAgingCellGeneral Physics and AstronomyDehydrogenaseEndogenymedicine.disease_causestressMicehemic and lymphatic diseasesratmécanismegenesreactive oxygen specieschemistry.chemical_classificationMultidisciplinary[SDV.BA]Life Sciences [q-bio]/Animal biologyQvieillissementCell biologymedicine.anatomical_structureanimal transgéniqueFemaleGenetically modified mouse[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT]congenital hereditary and neonatal diseases and abnormalitiesScienceTransgeneLongevityMice TransgenicGlucosephosphate DehydrogenaseBiologyGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesparasitic diseasesmedicineAnimalsHumansReactive oxygen speciesgènenutritional and metabolic diseasesGeneral ChemistrycellMolecular biologytransgenic mouseOxidative Stress030104 developmental biologymechanistic theorychemistryageingenzyme antioxydanteAgeingespèce reactive de l'oxygènecelluleReactive Oxygen SpeciesNADPOxidative stressdescription
S.N.-P. and P.J.F.-M. have been funded by the Spanish Association Against Cancer(aecc). Work in the laboratory of M.S. is funded by the CNIO and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund(SAF project), the European Research Council (ERC Advanced Grant), the Regional Government of Madrid co-funded by the European Social Fund (ReCaRe project), the European Union (RISK-IR project), the Botin Foundation and Banco Santander(Santander Universities Global Division), the Ramon Areces Foundation, and the AXA Foundation. Work in the laboratory of J.V. was supported by grants SAF2013-44663-R,from the Spanish Ministry of Education and Science (MEC); ISCIII2012-RED-43-029from RETICEF; PROMETEO2014/056 from "Conselleria d’Educacio , Cultura i Esport de la Generalitat Valenciana"; RS2012-609 Intramural Grant from INCLIVA and EUFunded CM1001 andFRAILOMIC-HEALTH.2012.2.1.1-2. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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. Sí
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-03-15 | Nature Communications |