Turning back time: a comprehensive list of interventions that decrease next-generation epigenetic aging clocks in humans.
Level 2 - randomized trial
Systematic review of heterogeneous human intervention studies (randomized and non-randomized)
PubMed 42294499 · doi:10.3389/fgene.2026.1836446
What was done
The authors conducted systematic searches to identify human studies examining the effects of pharmaceutical, lifestyle, nutritional, psychosocial, or clinical interventions on at least one next-generation epigenetic aging clock derived from DNA methylation patterns. A total of 41 human studies were identified and reviewed.
What was found
The abstract reports no numerical effect sizes or statistical values. Directionally, reductions in epigenetic age were reported for exercise, a plant-rich diet, caloric restriction, semaglutide, ketamine, omega-3 fatty acids, multivitamin-multimineral supplementation, umbilical cord plasma, and pitavastatin. Conversely, nicotinamide riboside, rapamycin, and senolytics showed no detectable effect, while plasmapheresis and select other therapeutics accelerated epigenetic aging.
Why it matters
Next-generation epigenetic clocks track all-cause mortality risk better than first-generation models, making this systematic catalog useful for identifying which longevity interventions meaningfully alter validated human biological aging biomarkers.
Limits
The abstract provides no specific effect sizes, confidence intervals, or sample sizes across the included studies. Epigenetic clocks remain investigational surrogate biomarkers rather than direct clinical outcomes, and substantial heterogeneity exists among clock types, intervention designs, and study populations.
Cited by
- contradicts On the Horvath epigenetic clock, the only two interventions demonstrated to decrease biological aging are exercise and GLP-1 receptor agonist drugs.