For years, anti-aging drugs and supplements have been competing fiercely—from rapamycin and metformin to the "longevity molecules" NMN and ergothioneine—all achieving impressive lifespan-extending effects in various animal studies. But no matter how compelling their stories are, they all face one "ultimate question":
How effective are these substances in humans?
How effective are these substances in humans?
Indeed, the true test of an anti-aging agent lies in clinical trials. Today’s focus is on a substance you may never have associated with anti-aging, yet it stands out with solid, eye-catching human data.
Recently, a groundbreaking study led by a team from Peking University and published in the authoritative journal Advanced Science uncovered a new anti-aging contender: nucleotides (NTs). The researchers found that after 19 weeks of continuous supplementation, healthy seniors aged 60–70 successfully reversed their biological age by 3.08 years!
Part 1: The Greatest Longevity Supplement May Hide in Basic Substances
Compared to other anti-aging drugs and supplements, nucleotides (NTs) have an unassuming identity: they are the building blocks of genetic material. Every DNA and RNA strand in our bodies is formed by countless nucleotides "linked hand in hand," serving as the fundamental raw material for life replication, repair, and all metabolic processes.
Figure Note: Structure of a nucleotide—composed of phosphate, pentose sugar, and nitrogenous base.
So, how does this "ubiquitous" basic substance become a powerful anti-aging agent?
The answer lies in the "aging" of genetic replication. As key components of DNA and RNA, nucleotides play a critical role in cell repair, energy metabolism, and genomic stability. In youth, our genetic material replicates efficiently, synthesizing enough nucleotides to meet the body’s needs for growth and repair. However, this production efficiency inevitably declines with age.
When nucleotide supply is insufficient, the body’s repair and growth efficiency decreases, and microscopic replication processes suffer errors—such as slowed cell renewal, faulty DNA repair, and weakened immunity. This is one of the underlying mechanisms of aging.
Researchers thus hypothesized: If internal production cannot keep up, could external supplementation of high-quality nucleotides reduce the relentless, subtle aging caused by genetic replication errors?
This hypothesis is well-founded:
- In animal studies, dietary nucleotides extended the lifespan of rats by 26% and reduced cancer incidence[1].
- They have also been shown to improve metabolism, regulate immunity, strengthen muscles[2; 3], and act as prebiotics to enhance gut microbiota composition.
- Nucleotides even appear in infant formula, highlighting their safety[4].
Figure Note: Nutrition label of a formula powder showing nucleotides as an ingredient (sources: 5'-Adenosine Monophosphate, 5'-Cytidine Monophosphate, etc.).
However, effectiveness in animals does not guarantee effectiveness in humans. This rigorous randomized, double-blind, placebo-controlled human clinical study was designed to answer this ultimate question.
Part 2: Dual Rejuvenation of Metabolism and Body Composition
The researchers recruited 121 healthy seniors aged 60–70, randomly dividing them into two groups:
- Experimental group: 61 participants took 1.2g of nucleotide supplements daily.
- Control group: 62 participants took "starch tablets" (placebo) identical in appearance, taste, and packaging.
For 19 weeks (approximately 133 days), all participants were unaware of which product they were taking.
Figure Note: TALENTs trial flowchart—screening (301 assessed, 178 excluded), randomization (123 assigned), follow-up (121 completed analysis: 61 in nucleotide group, 62 in control group). Exclusion criteria included renal/liver dysfunction, tumor history, and use of nucleic acid supplements.
When the study ended and data was unblinded, the results were striking:
1. Reversed Biological Age
Biological age truly reflects the body’s actual aging state. DNA methylation age (DNAmAge)—which assesses aging by detecting the "on/off" status of gene methylation—is currently recognized as one of the most accurate "biological clocks" for measuring biological age.
The study found that over 19 weeks:
- The control group’s biological age increased naturally over time.
- The experimental group’s biological age not only did not increase but significantly reversed: compared to the control group, the nucleotide group had a median DNA methylation age that was 3.08 years younger!
Figure Note: DNA methylation age of experimental (NTs) and control groups at baseline (T0), 11 weeks (T1), and 19 weeks (T2)—showing significant reversal in the nucleotide group.
2. Improved Metabolic Health
Aging impairs metabolic function, most notably reducing the body’s ability to regulate blood sugar (e.g., insulin resistance, which can lead to diabetes and other age-related diseases).
Tests of metabolic markers showed that participants in the nucleotide group had:
- Significantly lower insulin levels.
- Reduced insulin resistance index (HOMA-IR).
This indicates a younger, healthier metabolic state.
Figure Note: Changes in glucose-lipid metabolism profiles (insulin, HOMA-IR, total cholesterol, fasting blood glucose, LDL-C) in experimental vs. control groups—showing favorable improvements in the nucleotide group.
3. Increased Muscle Mass and Reduced Fat
Aging causes muscle loss (sarcopenia) and increased fat accumulation in the abdomen and viscera. Nucleotide supplementation produced visible improvements in body composition:
- Skeletal muscle mass increased by an average of 0.5kg.
- Limb fat mass decreased by 0.33kg.
- Body fat percentage dropped by 0.8%.
- Visceral fat rating decreased by 0.4.
Figure Note: Changes in body composition (body fat percentage, visceral fat grade, trunk fat/muscle mass, skeletal muscle mass) in experimental vs. control groups—showing "more muscle, less belly fat" in the nucleotide group.
In short: "Muscles grew, bellies shrank, and the body became younger!"
In summary, nucleotides demonstrated age-reversing potential across multiple dimensions—from the molecular-level aging clock (DNA methylation age) to systemic metabolic health, and finally to macroscopic body shape.
However, despite these impressive results, nucleotides are not a panacea. Researchers tested many other indicators, with less favorable outcomes:
Part 3: Not Universal, But Still Valuable
1. No Significant Effect on Telomere Length
Telomere length—another "aging clock" that shortens with age—showed no significant difference between the nucleotide group and the control group.
Figure Note: Leukocyte telomere length (T/S ratio) in experimental vs. control groups at T0 and T1—no notable changes in the nucleotide group.
2. No Improvements in Immunity or Quality of Life
- T-cell subsets (e.g., CD3+, CD4+, CD8+) and key inflammatory factors (TNF-α, IL-6) showed no significant differences between groups.
- Assessments of cognitive function (MoCA), sleep quality (PSQI), mental health (K10), and overall health (SF-12) revealed no significant benefits—except for reduced fatigue.
In other words, while nucleotides may rejuvenate the body’s "hardware" (e.g., muscles), they have limited short-term effects on "software" like mood, cognition, and sleep.
Possible Reasons
- Insufficient supplementation duration: 19 weeks may be too short for telomere repair (a slow process) and improvements in quality of life (which require long-term, multi-faceted adjustments).
- Complex factors affecting telomeres: Telomere length is influenced by genetics, lifestyle, and environment, and measurement methods may have inherent errors.
- External stress during the study: Midway through the trial, 76.86% (93/121) of participants were affected by a public health emergency (referred to as "mask period"), which may have accelerated aging temporarily (e.g., telomere shortening in both groups).
Nevertheless, the nucleotide group still achieved significant reductions in methylation age, improved metabolism, and enhanced muscle mass under this stress—further confirming its anti-aging efficacy, with excellent safety.
Part 4: How to Supplement Nucleotides?
1. Dietary Sources
Nucleotides are abundant in foods with high metabolic activity and rapid cell renewal, such as:
- Animal offal (pig liver, chicken liver).
- Deep-sea fish (salmon, tuna).
- Mushrooms, beans, and bean products.
However, while high-protein foods provide nucleotides, moderate protein restriction is linked to lifespan extension. Thus, direct nucleotide supplements (as used in this study) are a viable alternative.
2. Recommended Dosage
Refer to the study’s daily dose of 1.2g of nucleotides—consistent with previous research[5] and within the scope approved for Chinese health foods. No significant adverse reactions were reported in the trial.
3. Precautions
Not everyone is suitable for nucleotide supplementation:
- Nucleotides metabolize into uric acid, so people with high uric acid, gout, or impaired liver/kidney function should use them with caution.
Acknowledgments
This study, titled Nucleotides as an Anti-Aging Supplementation in Older Adults: A Randomized Controlled Trial (TALENTs study), was published in Advanced Science. The corresponding author is Meihong Xu (Peking University), and the first author is Shuyue Wang.
References
[1] Xu, M., Liang, R., Guo, Q., Wang, S., Zhao, M., Zhang, Z., . . . Li, Y. (2013). Dietary nucleotides extend the life span in Sprague-Dawley rats. The Journal of Nutrition, Health and Aging, 17(3), 223-229. doi:https://doi.org/10.1007/s12603-012-0399-z
[2] Wu, X., Zhu, N., He, L., Xu, M., & Li, Y. (2024). 5′-Cytidine Monophosphate Ameliorates H₂O₂-Induced Muscular Atrophy in C2C12 Myotubes by Activating IRS-1/Akt/S6K Pathway. Antioxidants, 13(2). doi:10.3390/antiox13020249
[3] Ding, T., Xu, M., & Li, Y. (2022). An Overlooked Prebiotic: Beneficial Effect of Dietary Nucleotide Supplementation on Gut Microbiota and Metabolites in Senescence-Accelerated Mouse Prone-8 Mice. Frontiers in Nutrition, 9.
[4] Yu, V. Y. (1998). The role of dietary nucleotides in neonatal and infant nutrition. Singapore Medical Journal, 39(4), 145-150.
[5] Tressler, R. L., Ramstack, M. B., White, N. R., Molitor, B. E., Chen, N. R., Alarcon, P., & Masor, M. L. (2003). Determination of total potentially available nucleosides in human milk from Asian women. Nutrition, 19(1), 16-20. doi:https://doi.org/10.1016/S0899-9007(02)00843-2
[2] Wu, X., Zhu, N., He, L., Xu, M., & Li, Y. (2024). 5′-Cytidine Monophosphate Ameliorates H₂O₂-Induced Muscular Atrophy in C2C12 Myotubes by Activating IRS-1/Akt/S6K Pathway. Antioxidants, 13(2). doi:10.3390/antiox13020249
[3] Ding, T., Xu, M., & Li, Y. (2022). An Overlooked Prebiotic: Beneficial Effect of Dietary Nucleotide Supplementation on Gut Microbiota and Metabolites in Senescence-Accelerated Mouse Prone-8 Mice. Frontiers in Nutrition, 9.
[4] Yu, V. Y. (1998). The role of dietary nucleotides in neonatal and infant nutrition. Singapore Medical Journal, 39(4), 145-150.
[5] Tressler, R. L., Ramstack, M. B., White, N. R., Molitor, B. E., Chen, N. R., Alarcon, P., & Masor, M. L. (2003). Determination of total potentially available nucleosides in human milk from Asian women. Nutrition, 19(1), 16-20. doi:https://doi.org/10.1016/S0899-9007(02)00843-2