Figure 6. NAD+ as a nodal point for metabolic regulation.
Most evidence to date points out that NAD+ could be rate-limiting for the SIRT1 reaction in diverse conditions. SIRT1 activity would hence be stimulated by interventions which increase NAD+ levels, such as AMPK activation, enhancement of NAD+ biosynthesis through precursor (NA, NR, NMN) supplementation, or through inhibition of alternative NAD+ consuming activities, such as PARPs or CD38. The stimulation of SIRT1 activity by these distinct means improves the capacity of the cells/organism to adapt to external metabolic cues.