| Autor: |
Michael Angelo Petr, Lina M Carmona-Marin, Tulika Tulika, Stella Kristensen, Simon Reves, Daniela Bakula, Guido Keijzers, Brenna Osborne, Sarah J Mitchell, Sam Hamilton, Jonathan Kato, Irene Alfaras, Amanuel A. Teklu, Indra Heckenbach, Jakob Madsen, Michael Ben Ezra, Garik Mkrtchyan, Erika Varner, Benjamin Fink, Eliana von Krusenstiern, Nathaniel W Snyder, Hector Herranz, Rafael de Cabo, Morten Scheibye-Knudsen |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.03.08.483430 |
| Popis: |
SUMMARYThere is currently no established intervention for Cockayne syndrome, a disease characterized by progressive early onset neurodegeneration with features of premature aging. Here, we tested if acetyl-CoA precursors, citrate and beta-hydroxybutyrate, could reduce features of Cockayne syndrome in three model systems. We identified the gene Helicase 89B as a homologue of CSB in drosophila and found that the ketone beta-hydroxybutyrate rescued features of premature aging in Hel89B deficient flies. In mammals, loss of the citrate carrier Indy exacerbated the phenotype of Csbm/m mice which was rescued by a ketogenic diet. The rescue effect appeared to be mediated through ketone stimulated histone acetylation and facilitation of transcriptional readthrough of secondary DNA structures. These findings link a ketogenic diet with transcriptional resolution of secondary structures and DNA repair. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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