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Resveratrol is a polyphenol with major health benefits that is thought to operate through direct activation of the &amp;apos;anti-aging&amp;apos; enzyme SIRT1. However recent reports have challenged this &amp;apos;direct-activation&amp;apos; hypothesis, suggesting the mechanism by which resveratrol increases SIRT1 function is still unknown. We report for the first time that resveratrol induces a dose dependent increase in activity of the NAD+ synthetic enzyme nicotinamide mononucleotide adenylyl transferase (NMNAT1). Activation of NMNAT1 by resveratrol in cultured primary human astrocytes and neurons increased NAD+ levels by up to 5 fold. As SIRT1 requires NAD+ as a substrate to perform its gene silencing function, higher NAD+ levels will enhance SIRT1 activity. This finding suggests that resveratrol may promote SIRT1 function by enhancing NAD+ synthesis in whole cell systems without requiring direct activation.

Resveratrol Increases Intracellular NAD+ Levels Through Up regulation of The NAD+ Synthetic Enzyme Nicotinamide Mononucleotide Adenylyltransferase