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G6PD protects from oxidative damage and improves healthspan in mice

Author

Listed:
  • Sandrina Nóbrega-Pereira

    (Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO)
    Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa)

  • Pablo J. Fernandez-Marcos

    (Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO)
    Bioactive Products and Metabolic Syndrome Group, Madrid Institute of Advanced Studies (IMDEA) Food)

  • Thomas Brioche

    (Université de Montpellier, INRA, UMR866, Dynamique Musculaire et Métabolisme)

  • Mari Carmen Gomez-Cabrera

    (Faculty of Medicine, University of Valencia and Investigaciòn Hospital Clínico Universitario (INCLIVA))

  • Andrea Salvador-Pascual

    (Faculty of Medicine, University of Valencia and Investigaciòn Hospital Clínico Universitario (INCLIVA))

  • Juana M. Flores

    (Faculty of Veterinary Sciences, Complutense University of Madrid)

  • Jose Viña

    (Faculty of Medicine, University of Valencia and Investigaciòn Hospital Clínico Universitario (INCLIVA))

  • Manuel Serrano

    (Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO))

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.

Suggested Citation

  • Sandrina Nóbrega-Pereira & Pablo J. Fernandez-Marcos & Thomas Brioche & Mari Carmen Gomez-Cabrera & Andrea Salvador-Pascual & Juana M. Flores & Jose Viña & Manuel Serrano, 2016. "G6PD protects from oxidative damage and improves healthspan in mice," Nature Communications, Nature, vol. 7(1), pages 1-9, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10894
    DOI: 10.1038/ncomms10894
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