Overexpression of G6PD as a model of robustness

Frailty is a major geriatric syndrome that has been associated to oxidative stress. The antioxidant system is largely based on the reducing power of NADPH, whose levels are mainly determined by the enzyme glucose-6-phosphate dehydrogenase (G6PD). Material and methods:Using old female Tg-mice overexpressing G6PD (18 to 26 months old), we measured frailty and different muscle parameters: oxidative stress, cross-sectional area (CSA), markers regulating protein synthesis, mitochondrial dynamics, and apoptosis. Results: Our results show that 18–24 months old G6PD-Tg animals performed better in the motor coordination and grip strength test than the WT. We also found lower changes in body weight and improved performance in the running speed in the G6PD-Tg mice. Taking into account the five frailty components, we found that the percentage of mice considered as frail was higher in the WT than in the G6PD-Tg group. G6PD-Tg mice exhibited higher GSH over GSSG ratio, reduced apoptosis (Bax/Bcl2), lower intramuscular adipocyte markers (FABP4, PDGFR α) and a higher mitochondrial content (COXIV) than the WT. Conclusion. Our results show that the overexpression of G6PD prevents frailty in 18 to 26 months old mice modulating the oxidative stress and markers of muscle quality