Glycolytic Inhibitor 2-Deoxy- D -Glucose at Chronic Low Dose Mimics Calorie Restriction in Rats Through Mitohormetic Induction of Reactive Oxygen Species

Abstract

Caloric restriction mimetics (CRMs) provide an exciting antiaging intervention strategy. 2-Deoxy-D-glucose (2-DG), a glycolytic inhibitor, is known to work as a CRM at high doses; however, at chronic high dose it 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 male Wistar rats by evaluating age-dependent biomarkers in plasma and erythrocytes. Significant increase was observed in reactive oxygen species levels in 2-DG-treated rats (both young and old), concomitant with increase in activities of 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. We propose that 2-DG induces a mitohormetic response resulting in augmentation of defense 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.