Semaglutide, exercise, and plant-rich diets decrease next-generation epigenetic aging clocks in humans

Epigenetic aging clocks, based on DNA methylation patterns, serve as crucial biomarkers in longevity research, estimating biological age. While first-generation clocks correlated with chronological age, next-generation models offer superior compensation for lifestyle and health factors, showing stronger associations with all-cause mortality risk. This enhanced predictive power makes interventions capable of modifying these clocks highly relevant. Understanding which pharmaceutical, lifestyle, and supplemental strategies can effectively 'turn back' these advanced biological age markers is critical for developing actionable longevity protocols and therapeutic targets.

Researchers conducted a comprehensive systematic review, performing a series of systematic searches to identify 41 human studies that reported the effects of various interventions on at least one next-generation epigenetic clock. The review categorized interventions into diverse groups, including pharmaceutical, lifestyle, supplementation, non-pharmaceutical clinical, and psychosocial approaches. The primary objective was to summarize and compare the reported effect sizes of these interventions, assessing their capacity to decrease epigenetic age and evaluating the responsiveness of different next-generation clocks to these modifications. The analysis also considered the frequency of use for various clock models.

The systematic review revealed that a wide array of interventions can effectively decrease next-generation epigenetic age in humans. These include lifestyle modifications such as exercise and a plant-rich diet, alongside pharmaceutical agents like the GLP-1R agonist semaglutide and the cholesterol-lowering drug pitavastatin. Other effective interventions encompassed caloric restriction, ketamine, omega-3 fatty acids, a multivitamin-multimineral supplement, and umbilical cord plasma. The review also summarized reported effect sizes for these interventions, although specific numerical data for individual effects were not detailed in the abstract. > Conversely, certain interventions showed no detectable effect on epigenetic aging, including nicotinamide riboside, rapamycin, and various senolytics. Intriguingly, some therapeutics, such as plasmapheresis, were found to accelerate epigenetic aging, highlighting the complex and sometimes counterintuitive nature of biological age modification. The study further compared next-generation clocks based on their frequency of use and responsiveness to these interventions.