Exogenous nucleotide supplementation produces genotype-dependent anti-aging effects in older adults, with outcomes determined by individual urate metabolism genetics. High genetic risk for elevated urate shows reduced epigenetic aging; low genetic risk shows preserved telomere length and improved immune tolerance.
Key Points
- Nucleotide response depends on urate metabolism genetic variants
- High urate-risk individuals show reduced DNA methylation age
- Low urate-risk individuals preserve telomere length, improve immunity
Longevity Analysis
This research demonstrates that a single intervention—nucleotide supplementation—produces fundamentally different aging trajectories based on individual genetic architecture. The same nutrient substrate is allocated differently within the body depending on genotype: in some individuals, nucleotides are redirected toward epigenetic stabilization and DNA repair capacity; in others, toward immune regulation and inflammatory resolution. This allocation pattern reflects how the body decodes its own oxidative state through urate-mediated signaling and responds by prioritizing whichever aging process is most vulnerable given that individual's genetic susceptibility. The implication is direct: blanket supplementation protocols fail to account for this metabolic bifurcation. Effective aging interventions require understanding not just what to add, but which individuals gain advantage from a given input based on their underlying metabolic architecture.
Original published by Wiley Aging Cell, by Ruisheng Fu, Shuyue Wang, Yuxiao Wu, Xueying Qin, Tao Huang, Yong Li, Meihong Xu .