01 Jan
The Prospect of the NAD+ Precursors in Age-related Diseases
1. Introduction
Age-related NAD+ depletion affects physiological functions and contributes to various aging-related diseases. NAD+ precursors can significantly elevate NAD+ level in murine tissues, effectively mitigate metabolic syndrome, enhance cardiovascular health, protect against neurodegeneration, and boost muscular strength, with broad prospect in the anti-aging-related field.
2. The synthesis and metabolism of NAD+ in age-related pathologies
NAD+ is synthesized from NAD+ precursors and amino acids tryptophan via three main pathways: De novo, Preiss-Handler, and Salvage. Supplementation of NAD+ precursors can be advantageous in maintaining normal cellular metabolism regulated by NAD+ and NAD+-dependent enzymes such as Sirtuins, PARP, CD38, and SARM1. NAD+ intermediates require conversion into NA to elevate NAD+ level.
NAD+ and its metabolism-related enzymes have very important roles in biological processes such as cellular metabolic processes, gene expression, apoptosis and carcinogenesis. NAD+ repletion is drawing attention as an anti-aging intervention. NAD+ precursors, such as NA, NAM, NR, and NMN, provide beneficial effects in various preclinical disease models of age-induced deficits, including metabolic disorders, cardiovascular, neurodegenerative diseases, and musculoskeletal diseases.
NAD+ and its metabolism-related enzymes have very important roles in biological processes such as cellular metabolic processes, gene expression, apoptosis and carcinogenesis. NAD+ repletion is drawing attention as an anti-aging intervention. NAD+ precursors, such as NA, NAM, NR, and NMN, provide beneficial effects in various preclinical disease models of age-induced deficits, including metabolic disorders, cardiovascular, neurodegenerative diseases, and musculoskeletal diseases.
3. Comparison on the efficacy of replenishing NAD precursors in pre-clinical studies and clinical studies in age-related pathologies
The downregulation of NAD+ level in cells and tissues is not a universal phenomenon for aging-related pathologies. NAD+ merely decreases with age in certain tissues. The efficacy of NAD+ precursors in clinical studies has been limited in comparison with that in the pre-clinical studies. Noteworthily, this issue can be addressed as long as much attention has been paid to the metabolism of NAD. With regards to the oral supplementation of NAD+ precursors, there is obvious link between NAD metabolism and gut microbes. Specifically, oral consumption of NMN is converted into NAMN through interaction with the gut microbiome. In addition, dietary NAM and NR are converted into NA through gut microbiota.
4. Future research directions regarding the NAD+ metabolism
It is fundamental to consider how the gut microbiome affects NAD+ metabolism, and changes in microbiome composition may affect the availability of NAD+ precursors. Future studies also require the comparative analysis of different precursors, and the role of gut microbiomes regarding various intermediaries needs to be investigated. Assessment of how NAD+ precursors affect microbiota and how their interaction with NAD+ metabolism benefits the physiological condition is essential for future preclinical and clinical studies.
5. Conclusion
Supplementation of suitable NAD+ precursors or intervening in NAD+ metabolism can restore the body's NAD+ level, which is of great practical significance for effectively improving aging-related diseases and prolonging healthy life span is of great practical significance for effectively improving aging-related diseases and prolonging healthy life span. NAD metabolism involves gut microbiome, and in-depth research on their interaction is possibly an important breakthrough in the future to combat aging-related pathologies.
Reference
Iqbal T, Nakagawa T. The therapeutic perspective of NAD+ precursors in age-related diseases. Biochem Biophys Res Commun. Published online February 2, 2024. doi:10.1016/j.bbrc.2024.149590
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