Recently, a paper emerged in Frontiers in Genetics with Dr. Adiv Johnson as the first and corresponding author. This talk focuses in on the results of that research, which began by scouring the literature to identify human interventional studies that explored the impact of a therapeutic on ta least one next-generation epigenetic aging clock. Unlike first-generation models that are simply trained to predict chronological age, next-generation clocks are more responsive to interventions, are more significantly associated with all-cause mortality risk in longitudinal data, and are more adept at capturing health and disease signals.

A systematic search-based approach unveiled 41 studies that collectively explored a variety of interventions in humans. The research found that, on the whole, these next-generation models are responsive to pharmacological, lifestyle, nutraceutical, psychosocial, and more experimental interventions, including exercise, a plant-rich diet, omega-3 fatty acids, the GLP-1 receptor agonist semaglutide, and ketamine. Many therapeutics failed to move the needle on these clocks, such as rapamycin or nicotinamide riboside. Prominent differences were also observed in terms of clock usage and performance. This broad analysis of the literature additionally highlighted areas where next-generation clocks could be furthered improved, which is critical as a major goal of the aging clock field is to develop biomarkers that act as surrogates for lifespan and healthspan. If such surrogates could be created, then the ability to run expedited human longevity studies would be unlocked.