Polyphenols

Polyphenols are a structurally diverse class of plant secondary metabolites — numbering over 8,000 known compounds — defined by one or more aromatic rings bearing hydroxyl groups. Major subclasses include flavonoids (quercetin, catechins, anthocyanins), stilbenes (resveratrol), phenolic acids, and lignans. At physiological concentrations, polyphenols act less as direct antioxidants than as hormetic stressors and xenohormetic signals: they activate Nrf2, AMPK, and SIRT1, inducing mitochondrial biogenesis, autophagy, and anti-inflammatory gene programs. At least 62 polyphenols have extended lifespan or improved aging biomarkers in model organisms. In humans, a 2024 meta-analysis of seven cohort studies (178,657 participants) associated higher polyphenol intake with a 7% reduction in all-cause mortality risk, and a 2024 systematic review of RCTs (Mekhora, Lamport & Spencer) found supplementation significantly improved verbal memory and executive function while reducing interleukin-6, though effect sizes were modest. A central limitation is bioavailability: most polyphenols are poorly absorbed, undergo extensive first-pass metabolism, and reach systemic circulation at low micromolar concentrations; gut-microbiota composition critically shapes conversion of glycosides into bioactive aglycones and urolithins. Causal evidence for lifespan extension in humans is absent; current data support polyphenol-rich dietary patterns rather than isolated high-dose supplements.