Loss of CNDP causes a shorter lifespan and higher sensitivity to oxidative stress in drosophila melanogaster

Abstract

Increasing oxidative stress seems to be the result of an imbalance between free radical production and antioxidant defenses. During the course of aging, oxidative stress causes tissue/cellular dam-age, which is implicated in numerous age-related diseases. Carnosinase (CN or CNDP) is dipepti-dase, which is associated with carnosine and/or glutathione (GSH) metabolism, those are the most abundant naturally occurring endogenous dipeptide and tripeptides with antioxidant and free radical scavenger properties. In the present study, we generated Drosophila cndp (dcndp) mutant flies using the CRISPR/Cas9 system to study the roles of dcndp in vivo. We demonstrate that dcndp mutant flies exhibit shorter lifespan and increased sensitivity to paraquat or hydrogen peroxide (H2O2) induced oxidative stress. These results suggest that dcndp maintains homeostatic condi-tions, protecting cells and tissues against the harmful effects of oxidative stress in the course of aging.