0000000000142762
AUTHOR
Pablo J. Fernandez-marcos
Overexpression of G6PD as a model of robustness
Introduction 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 b…
G6PD Overexpression Protects Mice Against Associated Oxidative Stress and Delays the Occurrence of Frailty
To assess the impact of lifelong overexpression of G6PD on reactive oxygen species (ROS)-derived damage and the prevention of frailty, we measured the levels of macromolecular oxidative damage in young and old mice and the we tested the neuromuscular fitness and the grip strength in old mice. Old G6PD-Tg male and female mice showed diminished accumulation of DNA oxidation (measured as 8-hydroxyguanosine or 8-OHdG) in liver and brain. Old females also showed reduced lipid oxidation (measured as malondialdehyde or MDA) in the liver. Old G6PD-Tg males, but not females, presented a small but significant increase in brain protein carbonylation. In accordance with these findings, liver from 2-yea…
Telomerase Reverse Transcriptase Delays Aging in Cancer-Resistant Mice
Summary Telomerase confers limitless proliferative potential to most human cells through its ability to elongate telomeres, the natural ends of chromosomes, which otherwise would undergo progressive attrition and eventually compromise cell viability. However, the role of telomerase in organismal aging has remained unaddressed, in part because of the cancer-promoting activity of telomerase. To circumvent this problem, we have constitutively expressed telomerase reverse transcriptase (TERT), one of the components of telomerase, in mice engineered to be cancer resistant by means of enhanced expression of the tumor suppressors p53, p16, and p19ARF. In this context, TERT overexpression improves …
G6PD protects from oxidative damage and improves healthspan in mice
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…
Glucose 6-P dehydrogenase delays the onset of frailty by protecting against muscle damage.
Background: Frailty is a major age-associated syndrome leading to disability. Oxidative damage plays a significant role in the promotion of frailty. The cellular antioxidant system relies on reduced nicotinamide adenine dinucleotide phosphate (NADPH) that is highly dependent on glucose 6-P dehydrogenase (G6PD). The G6PD-overexpressing mouse (G6PD-Tg) is protected against metabolic stresses. Our aim was to examine whether this protection delays frailty. Methods: Old wild-type (WT) and G6PD-Tg mice were evaluated longitudinally in terms of frailty. Indirect calorimetry, transcriptomic profile, and different skeletal muscle quality markers and muscle regenerative capacity were also investigate…