Resveratrol

Resveratrol's primary longevity mechanism involves activation of SIRT1 — a NAD+-dependent deacetylase that regulates stress response, inflammation, DNA repair, and metabolic genes. SIRT1 activation mimics aspects of caloric restriction at the gene expression level, including upregulation of mitochondrial biogenesis through PGC-1α. Resveratrol also inhibits mTOR signaling, activates AMPK, has direct antioxidant activity, inhibits NF-κB-mediated inflammation, and modulates estrogen receptor signaling. Its cardiovascular benefits appear mediated through endothelial nitric oxide synthase upregulation, platelet aggregation inhibition, and LDL oxidation reduction. Bioavailability is a significant limitation — resveratrol is rapidly metabolized and has low oral bioavailability, which has led to development of pterostilbene and other analogs with improved pharmacokinetics.