Ezetimibe increases resistance to oxidative stress and extends lifespan mimicking dietary restriction in Caenorhabditis elegans
Biosci. j. (Online)
; 39: e39027, 2023.
Article
en En
| LILACS
| ID: biblio-1425190
Biblioteca responsable:
BR396.1
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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Asunto(s)Palabras clave
Texto completo:
1
Índice:
LILACS
Asunto principal:
Estrés Fisiológico
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Caenorhabditis elegans
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Dietoterapia
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Ezetimiba
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Longevidad
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Biosci. j. (Online)
Asunto de la revista:
Agricultura
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Disciplinas das Cincias Biol¢gicas
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Pesquisa Interdisciplinar
Año:
2023
Tipo del documento:
Article