Article Impact Level: HIGH Data Quality: STRONG Summary of Nature Aging https://doi.org/10.1038/s43587-025-00947-6 Dr. Jianying Zhang et al.
Points
- NAD+ and NADP+ are crucial for signaling, epigenetics, and energy, influencing aging and diseases.
- Clinical trials on NAD+-related compounds focus on aging and neurodegenerative conditions.
- Established precursors like nicotinic acid and new ones such as nicotinamide riboside are discussed.
- Technological advances in production and detection are accelerating NAD+ research translation.
- Further large-scale studies are needed to determine optimal dosing, administration, and long-term safety.
Summary
This review synthesizes emerging strategies, applications, and challenges of targeting nicotinamide adenine dinucleotide (NAD+) in clinical settings. Beyond their traditional roles as redox cofactors, NAD+ and nicotinamide adenine dinucleotide phosphate (NADP+) have been increasingly recognized for their diverse functions in cellular signaling, epigenetic regulation, and energy homeostasis. Given their influence on numerous diseases and the aging process, NAD+ and NADP+ are gaining prominence as targets for therapeutic intervention. The paper focuses on summarizing existing safety, bioavailability, and efficacy data from NAD+-related clinical trials, particularly concerning aging and neurodegenerative diseases.
The review discusses both established NAD+ precursors, such as nicotinic acid and nicotinamide, and newer compounds, including nicotinamide riboside and nicotinamide mononucleotide, alongside other emerging precursors. It also highlights critical technological advancements that are accelerating NAD+ research and clinical translation. These include innovations in industrial-scale production and real-time detection methods, which facilitate a more comprehensive understanding and application of NAD+-targeting strategies. The ongoing evolution of these technologies is crucial for moving these interventions from bench to bedside.
Finally, the authors emphasize the necessity for further large-scale clinical studies. These studies are essential to determine optimal dosing regimens, ideal administration routes, and appropriate frequencies of NAD+ precursor supplementation. Furthermore, long-term safety profiles and the extent of interindividual variability in response to these interventions remain critical areas requiring extensive investigation to ensure safe and effective clinical translation. This comprehensive overview underscores the potential of NAD+ targeting while outlining the significant research gaps that must be addressed for its successful clinical implementation.
Link to the article: https://www.nature.com/articles/s43587-025-00947-6
References
Zhang, J., Wang, H.-L., Lautrup, S., Nilsen, H. L., Treebak, J. T., Watne, L. O., Selbæk, G., Wu, L. E., Omland, T., Pirinen, E., Cheung, T. C., Wang, J., Ziegler, M., Tysnes, O.-B., Zapata-Pérez, R., Bruzzone, S., Canto, C., Deleidi, M., Janssens, G. E., … Fang, E. F. (2025). Emerging strategies, applications and challenges of targeting NAD+ in the clinic. Nature Aging, 5(9), 1704–1731. https://doi.org/10.1038/s43587-025-00947-6
