2 -Deoxy – d-glucose at chronic low dose acts as a caloric restriction mimetic through a mitohormetic induction of ROS in the brain of accelerated senescence model of rat

Aging induces significant molecular alteration in brain morphology. Glycolytic inhibitor 2-Deoxy-d-glucose (2-DG) is considered to act as a caloric restriction mimetic (CRM) but it is correlated with elevated mortality risk in rats at persistent high dosage. In young and d-galactose induced accelerated senescent rat aging models, we tested a persistent low-dose dietary 2-DG administration and evaluated various aging biomarkers in brain tissue. A significant increase in reactive oxygen species (ROS) was observed in 2-DG treated (both young and accelerated senescent rat model). Increased Ferric reducing antioxidant potential (FRAP) value, Superoxide Dismutase (SOD), Catalase (CAT), and activity of mitochondrial complexes I and IV was observed. There was also significant improvements in the autophagy expression of genes (Beclin-1 and Atg-3) after 2- DG treatment. We propose that 2-DG induces a mitohormetic effect through elevation of ROS which reinforces defensive mechanism(s) through increased FRAP, SOD, CAT and autophagy gene expression. Our observations indicate that a consistently low dose 2-DG could be a valuable CRM.