Salvage Pathway

NAMPT is the rate-limiting enzyme in the salvage pathway that converts nicotinamide back into functional NAD. Cells respond to accumulated nicotinamide by upregulating NNMT, which methylates nicotinamide so it can be excreted, permanently losing NAD raw material. In young cells, NAD is maintained primarily through recycling of nicotinamide rather than de novo synthesis. NAMPT expression declines significantly as cells age, preventing efficient nicotinamide recycling. NNMT-mediated methylation depletes methyl donors needed for epigenetic regulation, and this depletion is the primary cause of side effects from IV NAD infusions.