Ezetimibe increases resistance to oxidative stress and extends lifespan mimicking dietary restriction in Caenorhabditis elegans

Ezetimibe is an approved drug for lowering plasma LDL (low-density lipoprotein) level via inhibition of cholesterol absorption. Derivatives ezetimibe reduce inflammatory response and oxidative stress. In the present study, we investigated effect dietary supplementation with in to environmental stressors found that increases resistance stress ultraviolet irradiation. also significantly extended lifespan accompanying reduced fertility, which a common trade-off longevity C. elegans. Cellular reactive oxygen species was increased expression stress-responsive genes, hsp-16.2 sod-3, induced by ezetimibe, suggesting hormetic on lifespan. prevented amyloid beta-induced toxicity completely reversed mortality high-glucose diet. Nuclear localization DAF-16 required prevention enhanced supplementation. Lifespan assay using known long-lived mutants, age-1, clk-1, eat-2, revealed extension specifically overlapped eat-2 are genetic models restriction. Effect worms fed diluted bacteria suggested mimics restriction These findings suggest exhibits anti-oxidative anti-aging effects through hormesis works as dietary-restriction mimetic extension.