NAMPT (NAD+ salvage pathway)

NAMPT (nicotinamide phosphoribosyltransferase) is the rate-limiting enzyme of the NAD+ 'salvage pathway'. That is the main route your cells use to remake NAD+ from nicotinamide (NAM), the leftover when NAD+-consuming enzymes (like sirtuins and PARPs) do their work. NAMPT converts NAM and PRPP into NMN; then another enzyme (NMNAT) finishes the job to NAD+. There are two forms. iNAMPT works inside the cell to make NAD+. eNAMPT is secreted, circulates in extracellular vesicles, and delivers NMN-making capacity to the hypothalamus, hippocampus, and retina. Circulating eNAMPT follows a daily rhythm, peaking in the early afternoon in humans, and it entrains hypothalamic NAD+ synthesis, SIRT1/SIRT2-FOXO1 signaling, and activity (Park et al., 2023). NAMPT declines with age. Yoshida et al. (2019, Cell Metabolism) found that plasma eNAMPT tracks linearly with an individual mouse's remaining lifespan, and that boosting NAMPT in fat extended median female lifespan by about 13%. Whether tweaking eNAMPT helps human longevity is an open question. The evidence is largely preclinical, and human NMN trials show effects on muscle insulin sensitivity, but not yet on lifespan.

Last reviewed: June 22, 2026

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