Alexandre Tavartkiladze, Gaiane Simonia, Dinara Kasradze, Russel J Reiter, Ruite Lou, Nana Okrostsvaridze, Pati Revazishvili, Irine Andronikashvili, Pirdara Nozadze, Givi Tavartkiladze and Malvina Javakhadze
Background: Epigenetic clocks that quantify cytosine methylation drift are now accepted surrogates of biological age. Interventions that reverse—not merely decelerate—these clocks could compress morbidity and expand health adjusted life expectancy (HALE). Melatonin, the master chronobiotic hormone, orchestrates circadian oscillations in DNA repair, autophagy, and redox tone; yet its dietary availability is negligible and endogenous output declines with age.
Objective: To determine whether AminoTriComplerex™ (ATC)—a Georgian food supplement that couples full daily dose natural melatonin with a Nano catalytically activated polyphenol adaptogen amino acid matrix—can safely reprogram the epigenome toward youthfulness in vitro, in rodents, and in humans over a four-year translational program.
Methods: A three stage, 48-month investigation was executed: (i) two step cell culture screen (dermal fibroblasts, endothelial cells, iPSC derived neurons); (ii) longitudinal mouse and rat studies (n = 640) incorporating serial blood/tissue methylation clocks, frailty indices, cardiometabolic panels, and GLP toxicology; (iii) an open label, single arm, 90 participant human pilot (55–70 y). Primary endpoint across all tiers was percentage change in consolidated DNA methylation age (Horvath Skin&Blood, PhenoAge, GrimAge). Secondary endpoints covered telomere attrition, γ H2AX foci, karyotype integrity, systemic biomarkers, and safety.
Results: ATC lowered cellular DNAmAge by 27 ± 4 % within 28 days in vitro, 24 ± 5 % in rodents, and 19 ± 3 % in humans (p < 0.001 for all vs. baseline) without increasing micronuclei, aneuploidy, or oncogenic expression. Mice on lifelong ATC displayed a 12.6 % median lifespan extension and a 42 % compression of late life frailty. No hepatorenal toxicity or QT prolongation emerged at human equivalent doses 10× higher than the intended label.
Conclusion: ATC integrates the informational rejuvenation paradigm with caloric restriction mimetics and senolytics, positioning itself as the third pillar of gerotherapy. Its oral, low cost configuration and supply chain reliance on agro botanical inputs render global deployment feasible, with particular impact projected for resource limited regions.