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Reduced ech-6 expression attenuates fat-induced lifespan shortening in C. elegans

Deregulated energy homeostasis represents a hallmark of aging and results from complex gene-by-environment interactions. Here, we discovered that reducing the expression of the gene ech-6 encoding enoyl-CoA hydratase remitted fat diet-induced deleterious effects on lifespan in Caenorhabditis elegans...

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Detalles Bibliográficos
Autores principales: Liu, Yasmine J., Gao, Arwen W., Smith, Reuben L., Janssens, Georges E., Panneman, Daan M., Jongejan, Aldo, van Weeghel, Michel, Vaz, Frédéric M., Silvestrini, Melissa J., Lapierre, Louis R., MacInnes, Alyson W., Houtkooper, Riekelt H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888598/
https://www.ncbi.nlm.nih.gov/pubmed/35233004
http://dx.doi.org/10.1038/s41598-022-07397-9
Descripción
Sumario:Deregulated energy homeostasis represents a hallmark of aging and results from complex gene-by-environment interactions. Here, we discovered that reducing the expression of the gene ech-6 encoding enoyl-CoA hydratase remitted fat diet-induced deleterious effects on lifespan in Caenorhabditis elegans, while a basal expression of ech-6 was important for survival under normal dietary conditions. Lipidomics revealed that supplementation of fat in ech-6-silenced worms had marginal effects on lipid profiles, suggesting an alternative fat utilization for energy production. Transcriptomics further suggest a causal relation between the lysosomal pathway, energy production, and the longevity effect conferred by the interaction between ech-6 and fat diets. Indeed, enhancing energy production from endogenous fat by overexpressing lysosomal lipase lipl-4 recapitulated the lifespan effects of fat diets on ech-6-silenced worms. Collectively, these results suggest that the gene ech-6 is potential modulator of metabolic flexibility and may be a target for promoting metabolic health and longevity.