Consuming a plant-rich diet, restricting the number of calories consumed, engaging in endurance exercise and including omega-3 fatty acids or a multivitamin-multimineral in the diet are among interventions that can decrease epigenetic age as determined by next-generation aging clocks.

"Epigenetic aging clocks estimate age from DNA methylation patterns and have become central tools in longevity research," authors Adiv A. Johnson, PhD, and David A. Sinclair, PhD, of Harvard Medical School explained. "More recently, next-generation clocks have been developed to better compensate for the known divergence between chronological age and epigenetic age in ways that relate to lifestyle, health, and age-related disease."

"Although epigenetic clocks represent investigational biomarkers, these newer models are more strongly associated with all-cause mortality risk than first-generation clocks," they noted. "As such, interventions that modify them are of interest."

Lifestyle interventions that set back epigenetic age as estimated by one or more next-generation clocks included omega-3 fatty acids, a plant-rich diet, multivitamin-minerals, calorie restriction and endurance exercise. Of note, omega-3 was associated with a 6.1-year improvement, which was one of the largest epigenetic age reductions. Among pharmaceuticals, favorable effects were found for the GLP-1 receptor agonist semaglutide, the cholesterol-lowering drug pitavastatin, metformin and other drugs.

"Over the past several years, the field of longevity science has expanded rapidly, with new studies regularly reporting the effects of lifestyles and interventions on biomarkers of aging," Dr. Sinclair stated. "What has been missing is a comprehensive assessment of the human evidence. This review helps clarify where the strongest signals exist, where findings are mixed, and where additional research is needed."

Drs. Sinclair and Johnson identified and reviewed 41 clinical trials that involved next-generation epigenetic aging clocks. The effects of pharmaceutical, lifestyle and nutrient, and nonpharmaceutical clinical or psychosocial interventions were evaluated. The findings were reported May 29, 2026, in Frontiers in Genetics.¹