Figure 7.

NAD⁺/nicotinamide levels may serve as converging points for interaction of PARP-1 and SIRT1 pathways. It is conceivable that poly(ADP-ribose) metabolism can downregulate SIRT1 through NAD⁺ depletion and nicotinamide production during oxidative stress. Reciprocally, regulation by SIRT1 deacetylation for expressing genes related to apoptosis or longevity may depend on PARP-1 activity. PARP-1 inhibitors maintain NAD⁺ levels and suppress the nicotinamide surge, and therefore may indirectly serve as SIRT1 enhancers. The interactions of PARP-1/SIRT1 pathways provide a network for multicellular eukaryotes to effectively deal with nutritional supply and oxidative stress.