Ezetimibe increases resistance to oxidative stress and extends lifespan mimicking dietary restriction in Caenorhabditis elegans
Biosci. j. (Online)
;
39: e39027, 2023.
Artigo
em Inglês
| LILACS
| ID: biblio-1425190
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 high-glucose 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.
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Assuntos
Texto completo:
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Índice:
LILACS (Américas)
Assunto principal:
Estresse Fisiológico
/
Caenorhabditis elegans
/
Dietoterapia
/
Ezetimiba
/
Longevidade
Tipo de estudo:
Estudo prognóstico
Idioma:
Inglês
Revista:
Biosci. j. (Online)
Assunto da revista:
Agricultura
/
Disciplinas das Cincias Biol¢gicas
/
Pesquisa Interdisciplinar
Ano de publicação:
2023
Tipo de documento:
Artigo
País de afiliação:
Coréia do Sul
Instituição/País de afiliação:
Soonchunhyang University/KR
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