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Riboflavin depletion promotes longevity and metabolic hormesis in Caenorhabditis elegans

Riboflavin is an essential cofactor in many enzymatic processes and in the production of flavin adenine dinucleotide (FAD). Here, we report that the partial depletion of riboflavin through knockdown of the C. elegans riboflavin transporter 1 (rft‐1) promotes metabolic health by reducing intracellula...

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Detalles Bibliográficos
Autores principales: Yerevanian, Armen, Murphy, Luke M., Emans, Sinclair, Zhou, Yifei, Ahsan, Fasih M., Baker, Daniel, Li, Sainan, Adedoja, Adebanjo, Cedillo, Lucydalila, Stuhr, Nicole L., Gnanatheepam, Einstein, Dao, Khoi, Jain, Mohit, Curran, Sean P., Georgakoudi, Irene, Soukas, Alexander A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9649603/
https://www.ncbi.nlm.nih.gov/pubmed/36181246
http://dx.doi.org/10.1111/acel.13718
Descripción
Sumario:Riboflavin is an essential cofactor in many enzymatic processes and in the production of flavin adenine dinucleotide (FAD). Here, we report that the partial depletion of riboflavin through knockdown of the C. elegans riboflavin transporter 1 (rft‐1) promotes metabolic health by reducing intracellular flavin concentrations. Knockdown of rft‐1 significantly increases lifespan in a manner dependent upon AMP‐activated protein kinase (AMPK)/aak‐2, the mitochondrial unfolded protein response, and FOXO/daf‐16. Riboflavin depletion promotes altered energetic and redox states and increases adiposity, independent of lifespan genetic dependencies. Riboflavin‐depleted animals also exhibit the activation of caloric restriction reporters without any reduction in caloric intake. Our findings indicate that riboflavin depletion activates an integrated hormetic response that promotes lifespan and healthspan in C. elegans.