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

作者：Shuyue Wang, Lixia Song, Rui Fan, Qianqian Chen, Rongfeng Fu, Mei You, Yuxiao Wu, Meng Cai, Yong Li, Meihong Xu · 发表于：Advanced Science · 年份：2025 · DOI：10.1002/advs.202417728 · 被引用次数：4 · 研究领域：Epigenetics and DNA Methylation、Telomeres, Telomerase, and Senescence、Genetics and Neurodevelopmental Disorders

Abstract 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.