The NAD-dependent deacetylase SIRT1 regulates lipid and carbohydrate metabolism and has been shown to extend life span in several species. In a recent issue of Molecular Cell, Li et al. (2007) demonstrate that SIRT1 deacetylates and activates the nuclear receptor LXR by favoring its ligand-dependent proteasomal degradation, thereby potentially regulating reverse cholesterol transport.