Nucleotides as an Anti‐Aging Supplementation in Older Adults: A Randomized Controlled Trial (TALENTs study)

Aging impairs nutrient metabolism and accelerates biological aging, negatively affecting health and longevity. The Targeting Aging and Longevity with Exogenous Nucleotides (TALENTs) trial (ClinicalTrials.gov: NCT05243108) aimed to explore whether nucleotides (NTs) supplementation can delay biological aging and improve health outcomes in the elderly. The trial is a 19-week, double-blind, randomized, placebo-controlled study in Chengdu, China, with 121 participants (60-70 years). Participants are randomly assigned to either NTs (1.2 g day^-1) or placebo group (1:1). The results of primary outcomes showed that NTs had significantly greater reduction in median DNA methylation age compared to placebo over 19 weeks (β = -3.08 years, 95% CI: -5.07 to -1.10, P = 0.0023), with a trend toward reduction observed over 11 weeks (β = -1.94 years, 95% CI: -4.32 to 0.45, P = 0.11); whereas no significant difference changes of leukocyte telomere length are showed between groups (week 11: β = 0.09, 95% CI: -0.10 to 0.29, P = 0.36; week 19: β = 0.12, 95% CI: -0.05 to 0.28, P = 0.18). Insulin sensitivity improved in the NTs group, with a significant reduction in HOMA-IR over 19 weeks (β = -0.45, 95% CI: -0.86 to -0.04, P = 0.033). No severe adverse events or significant changes in safety indicators are reported. Together, our findings establish that NTs may delay biological aging and improve insulin sensitivity with a well-tolerated safety profile.