Natural-Product-Derived Antioxidants and DNA Methylation-Based Epigenetic Aging: A Systematic Review of Human Intervention Studies.

DNA methylation clocks provide a tractable molecular readout for testing whether nutritional and natural-product interventions can modify biological aging. Natural-product-derived antioxidants are biologically plausible candidates because they influence redox signaling, inflammation, mitochondrial function, microbial metabolism and epigenetic regulation, yet their effects on DNA methylation-based aging remain difficult to interpret. Here, we systematically synthesize human intervention studies evaluating antioxidant-rich dietary patterns, botanical and food-derived extracts, marine omega-3 fatty acids, multi-component nutraceuticals and related lifestyle-based interventions with DNA methylation-clock outcomes. The available evidence does not support a uniform epigenetic anti-aging effect. Instead, methylation-age responses were clock-specific, exposure-dependent and often most apparent in metabolically or biologically responsive subgroups. Longer randomized or trial-embedded studies provided the most credible signals, whereas small uncontrolled studies mainly generated hypotheses. Future trials should move beyond claims of epigenetic age reversal and test whether objectively verified natural-product-derived antioxidant exposures produce reproducible, mechanistically linked, and clinically meaningful changes in aging biology.