Glycolytic inhibitor 2-deoxy-D-glucose at chronic low dose mimics calorie restriction in rats through mitohormetic induction of ROS.

Caloric restriction mimetics (CRMs) provide an exciting anti-aging intervention strategy. 2-deoxy-D-glucose (2-DG), a glycolytic inhibitor is known to works as a CRM at high doses, however chronic high dose has been linked to increased mortality in rats. We have investigated chronic low dose dietary administration of 2-DG on age-related stress protection in young and old age male wistar rats by evaluating age-dependent biomarkers in plasma and erythrocytes. Significant increase was observed in ROS generation in 2-DG treated rats (both young and old), concomitant with increase in erythrocyte plasma membrane redox system (PMRS), catalase (CAT) and superoxide dismutase (SOD). 2-DG treatment also decreased plasma sialic acid and advanced glycation end products (AGEs). We propose that 2-DG induces a mitohormetic response resulting in augmentation of defence mechanism(s) manifested by higher activity of PMRS, CAT and SOD. Our findings provide evidence that at chronic low dose 2-DG could be a potential CRM.