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Epitranscriptomic analysis reveals features of NAD-capped RNAs upon supplementation of nicotinamide mononucleotide in human

Shuwen Ge, Yandong Liu, Dean Li, Guojing Han, Kongyan Niu, Hujun Ju, Hao Zhou, Rui Liu, Zhengjiang Zhu, Nan Liu, Lefeng Qu
Experimental Cell Research 2025 453(1):114780

Bibliography

PubMed
PMID 41072840
DOI
10.1016/j.yexcr.2025.114780
Funding
Supported by National Natural Science Foundation of China grants 32470616 (Nan Liu) and 8237020490 (Lefeng Qu), Shanghai Key Laboratory of Aging Studies grant 19DZ2260400, Outstanding Academic/Technical Leaders Program of the Shanghai Municipal Commission of Science and Technology grant 20XD1404900, and Shanghai Municipal Health Commission special project 2020YJZX0125.
Competing interests
The authors declared no known competing financial interests or personal relationships that could have influenced the work.

Study snapshot

DesignPlacebo-controlled, randomized, double-blind, parallel-group human trial embedded in a translational human/dog molecular study.
ModelHealthy human participants assessed through PBMC epitranscriptomic profiling.
SampleHuman randomized trial: n=36, with 20 participants receiving NMN and 16 receiving placebo.
InterventionNMN 300 mg/day versus placebo.
Duration2 months.
EndpointsPBMC NAD-capped RNA abundance and distribution; NAD turnover; Blood-derived epitranscriptomic biomarkers

What the study showed, in plain terms

This trial used NMN as a controlled exposure to study a relatively new molecular biomarker: RNAs carrying an NAD cap. Participants were randomized to NMN or placebo and PBMCs were profiled at the epitranscriptomic level.

NMN increased NAD turnover while NAD-capped RNAs decreased, suggesting that blood NAD-RNA patterns may be sensitive markers of NMN exposure. The study does not establish a clinical health benefit.

Key findings

  • NMN supplementation increased NAD turnover in the human cohort.
  • NAD-capped RNA abundance was reduced after NMN exposure.
  • The authors proposed blood-derived NAD-RNAs as exposure-sensitive molecular biomarkers.
  • Clinical efficacy outcomes were not the focus of the study.

What this study can and cannot tell us

The human cohort contained 36 participants and focused on molecular epitranscriptomic endpoints rather than clinical outcomes. The paper also includes animal experiments, which should not be conflated with the human intervention. The study can show that NMN exposure changes NAD-related RNA biology, not that those changes improve health.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology