NMN has long been marketed as an "anti-aging supplement," but few studies have directly linked it to telomere length—one of the most recognized biological markers of aging.
Previous animal experiments have confirmed that NMN supplementation helps maintain telomere length, inhibit DNA damage responses, and improve mitochondrial function, thereby treating conditions closely associated with telomere shortening (such as liver fibrosis).
Recently, a joint study by institutions including the Chinese Academy of Sciences (CAS) and Chongqing Medical University successfully "turned back the telomere clock" using NMN[1].
1. NMN Extends Telomeres in Both Mice and Humans
Researchers divided 16-month-old male pre-aging mice (equivalent to 45-55 years old in humans) into two groups: one group was given drinking water containing NMN. After 40 days, PCR testing showed that the telomere length of mice in the NMN group was significantly longer than that in the control group.
Figure A Note: Telomere length ratio (Control vs. NMN).
In addition, the study recruited 8 healthy male volunteers aged 45-60. They took 300mg of NMN supplement with warm water half an hour before breakfast daily for 90 days. During this period, their telomeres "lengthened day by day"—by the end of the 90 days, their average telomere length was nearly twice as long as the baseline.
Figure B Note: Telomere length changes at 0d, 30d, 60d, and 90d.
2. NMN Alters Serum Metabolome and Gut Microbiota
During the animal experiment, researchers also collected blood and fecal samples from mice for analysis. Unexpectedly, they found that the serum metabolome and gut microbiota of mice in the NMN group had changed.
(1) Changes in Serum Metabolites
Targeted metabolomics analysis revealed that the serum metabolite profile of mice taking NMN changed significantly: 58 metabolites were downregulated, and 266 were upregulated—many of which are associated with the aging process.
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Downregulated metabolites: Substances such as D-proline, pipecolic acid, and (E)-5-(3,4,5,6-tetrahydro-3-pyridylidenemethyl)-2-furanmethanol. Proline is known to be linked to aging in fruit flies, with higher levels in older flies than in younger ones.
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Upregulated metabolites: These can be mainly divided into two categories, corresponding to the structure of NMN (nicotinamide mononucleotide, composed of nicotinamide and adenine nucleotide):
- Nicotinamide-related metabolites: Including nicotinamide, 1-methylnicotinamide, nicotinamide N-oxide, and N1-methyl-4-pyridone-3-carboxamide. These products come from NAD+ (elevated by NMN) and are generated after the action of NAD+-dependent enzymes (such as "longevity proteins" Sirtuins, DNA repair enzyme PARP, and CD38). Beyond being "byproducts," they may also contribute to some of NMN’s anti-aging effects that cannot be explained by current mechanisms.
- Adenylate-related metabolites: Such as hypoxanthine, inosine, and guanine. These three substances are important intermediates and end products of purine nucleotide synthesis, providing raw materials for DNA synthesis and repair. A recent study also suggests that NMN metabolism helps maintain the balance of the mitochondrial nucleotide pool and plays a role in mitochondrial DNA (mtDNA) replication[3].
Additionally, synthesizing ATP (the "energy currency of cells") through the recycling of hypoxanthine is much more efficient than de novo synthesis[4]. Thus, NMN supplementation may enhance cellular "energy production" efficiency. Since mitochondrial ATP synthesis is always accompanied by heat release, the increased heat production observed in NMN-group mice in this experiment supports this hypothesis.
(2) Unexpected Benefits for Gout Sufferers
ATP synthesis deficiency is considered the root cause of mitochondrial dysfunction-related diseases (mt-disease). Improving mitochondrial function by enhancing ATP synthesis efficiency helps treat such diseases[4].
If you are a gout patient being treated with xanthine oxidase inhibitors (such as allopurinol or febuxostat) and happen to take NMN, this "energy-boosting" effect will be more pronounced for you. The combination of inosine and febuxostat—by expanding the recycling pool and blocking uric acid excretion—greatly increases cellular ATP. Small-scale clinical trials have already used this combination to treat mitochondrial myopathy[5] and Parkinson’s disease[6].
It is important to note that allopurinol and febuxostat have clear and serious adverse reactions (e.g., allergic edema, cardiovascular events). Moreover, in people with normal uric acid metabolism, uric acid itself has anti-aging effects due to its strong antioxidant properties. Non-gout/hyperuricemia patients are not advised to take allopurinol or febuxostat for health maintenance without a doctor’s order.
(3) Changes in Gut Microbiota
Other metabolites (e.g., tryptophan, histidine, and indole derivatives) also increased after NMN supplementation, which researchers partially attributed to changes in gut microbiota. Key changes in gut bacteria include:
- Increased abundance of Turicibacter: This genus of bacteria regulates muscle function and combats fatigue—explaining the increased energy levels reported by NMN users.
- Mixed changes: The abundance of Helicobacter (a genus that includes the well-known pathogenic Helicobacter pylori) increased, while the abundance of Akkermansia (a famous probiotic) decreased—suggesting a potential "incompatibility" between NMN and Akkermansia.
3. Key Takeaways from the Study
The study focuses on three core findings: NMN lengthens telomeres, alters the serum metabolome, and modifies gut microbiota. There is no clear direct link between telomere lengthening and the latter two effects.
However, clues from metabolite changes (e.g., mtDNA and ATP synthesis) are closely related to normal mitochondrial function—helping to further explain the mechanism by which NMN improves mitochondrial function. Research on the metabolome and gut microbiome will also guide future clinical studies on NMN, making them more targeted.
Researchers revealed that they are planning a more comprehensive study to explore NMN’s impact on intestinal health in aging mice, and will include data from some cross-sectional human clinical studies. They will focus on the abundance of Helicobacter and Akkermansia to further uncover the hidden mechanisms of NMN.
References
[1] Niu KM, Bao T, Gao L, Ru M, Li Y, Jiang L, Ye C, Wang S, Wu X. The Impacts of Short-Term NMN Supplementation on Serum Metabolism, Fecal Microbiota, and Telomere Length in Pre-Aging Phase. Front Nutr. 2021 Nov 29;8:756243. doi: 10.3389/fnut.2021.756243.
[2] Nejabati HR, Schmeisser K, Shahnazi V, Samimifar D, Faridvand Y, Bahrami-Asl Z, Fathi-Maroufi N, Nikanfar S, Nouri M. N1-Methylnicotinamide: An Anti-Ovarian Aging Hormetin? Ageing Res Rev. 2020 Sep;62:101131.
[3] Nomiyama T, Setoyama D, Yasukawa T, Kang D. Mitochondria Metabolomics Reveals a Role of β-Nicotinamide Mononucleotide Metabolism in Mitochondrial DNA Replication. J Biochem. 2021 Dec 4:mvab136.
[4] Johnson TA, Jinnah HA, Kamatani N. Shortage of Cellular ATP as a Cause of Diseases and Strategies to Enhance ATP. Front Pharmacol. 2019 Feb 19;10:98.
[5] Kamatani N, Kushiyama A, Toyo-Oka L, Toyo-Oka T. Treatment of two mitochondrial disease patients with a combination of febuxostat and inosine that enhances cellular ATP. J Hum Genet. 2019 Apr;64(4):351-353.
[6] Watanabe H, Hattori T, Kume A, Misu K, Ito T, Koike Y, Johnson TA, Kamitsuji S, Kamatani N, Sobue G. Improved Parkinson’s disease motor score in a single-arm open-label trial of febuxostat and inosine. Medicine. 2020;99(35):e21576.
[2] Nejabati HR, Schmeisser K, Shahnazi V, Samimifar D, Faridvand Y, Bahrami-Asl Z, Fathi-Maroufi N, Nikanfar S, Nouri M. N1-Methylnicotinamide: An Anti-Ovarian Aging Hormetin? Ageing Res Rev. 2020 Sep;62:101131.
[3] Nomiyama T, Setoyama D, Yasukawa T, Kang D. Mitochondria Metabolomics Reveals a Role of β-Nicotinamide Mononucleotide Metabolism in Mitochondrial DNA Replication. J Biochem. 2021 Dec 4:mvab136.
[4] Johnson TA, Jinnah HA, Kamatani N. Shortage of Cellular ATP as a Cause of Diseases and Strategies to Enhance ATP. Front Pharmacol. 2019 Feb 19;10:98.
[5] Kamatani N, Kushiyama A, Toyo-Oka L, Toyo-Oka T. Treatment of two mitochondrial disease patients with a combination of febuxostat and inosine that enhances cellular ATP. J Hum Genet. 2019 Apr;64(4):351-353.
[6] Watanabe H, Hattori T, Kume A, Misu K, Ito T, Koike Y, Johnson TA, Kamitsuji S, Kamatani N, Sobue G. Improved Parkinson’s disease motor score in a single-arm open-label trial of febuxostat and inosine. Medicine. 2020;99(35):e21576.