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- Title
EZETIMIBE INCREASES RESISTANCE TO OXIDATIVE STRESS AND EXTENDS LIFESPAN MIMICKING DIETARY RESTRICTION IN Caenorhabditis elegans.
- Authors
Suhyeon PARK; Ji-Soo PARK; Sang-Kyu PARK
- Abstract
Ezetimibe is an approved drug for lowering plasma LDL (low-density lipoprotein) level via inhibition of cholesterol absorption. Derivatives of ezetimibe reduce inflammatory response and oxidative stress. In the present study, we investigated the effect of dietary supplementation with ezetimibe in response to environmental stressors and found that ezetimibe increases resistance to oxidative stress and ultraviolet irradiation. Ezetimibe also significantly extended lifespan accompanying reduced fertility, which is a common trade-off for longevity in C. elegans. Cellular level of reactive oxygen species was increased and the expression of stress-responsive genes, hsp-16.2 and sod-3, was induced by dietary supplementation with ezetimibe, suggesting a hormetic effect on oxidative stress response and lifespan. Ezetimibe also significantly prevented amyloid beta-induced toxicity and completely reversed increased mortality by highglucose diet. Nuclear localization of DAF-16 required for the prevention of amyloid beta-induced toxicity was enhanced by ezetimibe supplementation. Lifespan assay using known long-lived mutants, age-1, clk-1, and eat-2, revealed that lifespan extension by ezetimibe specifically overlapped with that of eat-2 mutants, which are genetic models of dietary restriction. Effect of ezetimibe on lifespan of worms fed with diluted bacteria suggested that ezetimibe mimics the effect of dietary restriction on lifespan. These findings suggest that ezetimibe exhibits anti-oxidative and anti-aging effects through hormesis and works as a dietary-restriction mimetic on lifespan extension.
- Subjects
EZETIMIBE; OXIDATIVE stress; CAENORHABDITIS elegans; DIETARY supplements; REACTIVE oxygen species
- Publication
Bioscience Journal, 2023, Vol 39, p1
- ISSN
1516-3725
- Publication type
Article
- DOI
10.14393/BJ-v39n0a2023-65305