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| Title / Description | A High-Fat Diet and NAD+ Rescue Premature Aging in Cockayne Syndrome |
| Accession | GSE62194 |
| Summary | Cockayne syndrome (CS) is an accelerated aging disorder characterized by progressive neurodegeneration caused by mutations in the genes encoding the DNA repair proteins CSA or CSB. Csbm/m mice were given a high-fat, caloric-restricted or resveratrol-supplemented diet. The high-fat diet rescued the phenotype of Csbm/m mice at the metabolic, transcriptomic and behavioral levels. Additional analysis suggests that the premature aging seen in CS mice, nematodes and human cells results from aberrant PARP activation due to deficient DNA repair leading to decreased SIRT1 activity and mitochondrial dysfunction. Notably, β-hydroxybutyrate levels are increased by the high-fat diet; and β-hydroxybutyrate, PARP inhibition, or NAD+ supplementation can activate SIRT1 and rescue CS-associated phenotypes. Mechanistically, CSB is able to displace activated PARP1 from damaged DNA to limit its activity. This study connects two emerging longevity metabolites, β-hydroxybutyrate and NAD+, through the deacetylase SIRT1 and suggests possible interventions for CS. |
| Organism | Mus musculus |
| Platform | GPL6885 |
| Normalized | False |
| Parsed SOFT file |
| Differential expression method | Characteristic Direction |
| Cutoff | 500 |
| Organism | Mus musculus |
| Cell | cerebellum |
| Perturbation | resveratrol |
| Concentration | 100 mg/kg |
| Relevant information | Standard diet supplemented with resveratrol_Ad Lib (WT mouse) |
| Gene lists | Enrichr | L1000CDS2 | PAEA | |
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