NAD+

NAD+ Peptide Overview

Nicotinamide Adenine Dinucleotide (NAD+) is a vital coenzyme present in every living cell, serving as a cornerstone of cellular energy production and systemic physiological health. As the oxidized counterpart to NADH, NAD+ functions primarily as an electron carrier in redox reactions, which is fundamental for converting nutrients into adenosine triphosphate (ATP). Beyond its role in the mitochondria, NAD+ is a critical substrate for enzymes that govern DNA repair, genomic stability, and cellular aging.

Scientific literature suggests that NAD+ levels naturally decline with age, a phenomenon associated with various metabolic and neurodegenerative shifts. By facilitating communication between the cell nucleus and the mitochondria, NAD+ maintains the metabolic bridge required for organelle health. In extracellular environments, it serves as a signaling molecule released by neurons to influence the vascular system, the large intestine, and the bladder.

Critical NAD+-Dependent Biological Pathways

Pathway Class

Primary Enzyme

Physiological Influence

Sirtuins (SIRTs)

SIRT1 - SIRT7

Regulates gene expression, energy balance, and mitochondrial biogenesis.

DNA Repair

PARP Enzymes

Detects genomic damage and recruits repair proteins to prevent mutations.

Calcium Signaling

cADPRS (CD38)

Manages intracellular calcium release for muscle and hormone regulation.

NAD+ Peptide Structure

The molecular architecture of NAD+ consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base, while the other contains nicotinamide. This unique dinucleotide structure enables the molecule to act as a versatile redox cofactor, shuttling electrons between metabolic pathways to maintain cellular homeostasis.

Structure Solution Formula: C21H27N7O14P2

NAD+ Peptide Research

Scientific Evidence on NAD+-Dependent Interactions

Current research focuses on three enzymatic pathways where NAD+ availability is the rate-limiting factor for cellular health:

• Sirtuins (SIRTs): These enzymes are high-affinity consumers of NAD+ and are vital for protecting mitochondria from oxidative stress. They promote stem cell longevity and facilitate tissue regeneration.
• Poly(ADP-ribose) Polymerases (PARPs): The PARP family uses NAD+ to signal DNA damage. While essential for genomic stability, excessive PARP activation due to chronic stress can deplete NAD+ reserves, leading to energy failure.
• Cyclic ADP Ribose Synthetases (cADPRS): This group includes CD38 and CD157, which influence calcium signaling and immune system coordination, linking NAD+ metabolism to regenerative processes.

DNA Repair and Ischemic Stress

In laboratory models, restoring NAD+ levels has shown a significant ability to enhance DNA base-excision repair following ischemic stress (oxygen deprivation). Whether administered before or after a stress event, NAD+ supports the recruitment of repair proteins, helping to counteract cellular energy depletion and support neuronal survival.

Organ Protection and Metabolic Homeostasis

Animal studies demonstrate that increasing circulating NAD+ concentrations provides systemic benefits. In models of obesity, NAD+ elevation led to improved glucose regulation and mitochondrial efficiency. In renal studies, it was shown to boost sirtuin activity and protect kidney cells from hypertrophy and drug-induced toxicity. Furthermore, maintaining adequate NAD+ is vital for cardiac resilience, protecting the heart from tissue damage during periods of aortic constriction or ischemic injury.

Article Author

This literature review was compiled and organized by Dr. Shin-Ichiro Imai, M.D., Ph.D. Dr. Imai is a distinguished molecular biologist and longevity researcher known for his pioneering work on NAD+ metabolism. As a Professor at Washington University School of Medicine, his research has provided the framework for understanding how NAD+ biosynthesis influences aging and mitochondrial health.

Scientific Journal Author

Dr. Imai has led extensive investigations into the molecular regulation of sirtuin activity. His findings, along with those of noted collaborators such as Dr. David A. Sinclair and Dr. Charles Brenner, have advanced the global understanding of neuroprotection and age-related disease prevention.

Reference Citations

1. Schultz, Michael B, and David A Sinclair. "Why NAD(+) Declines during Aging: It's Destroyed." Cell metabolism vol. 23,6 (2016): 965-966.12
2. Braidy N, Liu Y. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. Exp Gerontol. 2020 Apr;132:110831.34
3. Johnson, Sean, and Shin-Ichir5o Imai6. "NAD+ biosynthesis, aging, and disease." F1000Research vol. 7 132. 1 Feb 2018.7
4. Bieganowski P, Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes. Cell. 2004 May 14;117(4):495-502.8
5. F9ang, E. F., et al. (2017). NAD+ in Aging: Molecular Mechanisms and Translational Implications. Trends in molecular medicine, 23(10), 899-916.
6. Harden, A; Young, WJ (1906). "The alcoholic ferment of yeast-juice Part II." Proceedings of the Royal Society of London. 78 (526): 369-375.
7. Mills KF, et al. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016 Dec 13;24(6):795-806.
8. Long AN, et al. Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits. BMC Neurol. 2015 Mar 1;15:19.
9. Safety and Efficacy of Nicotinamide Riboside Supplementation. clinicaltrials.gov Identifier: NCT02921659.
10. Wang S, et al. Cellular NAD replenishment confers marked neuroprotection against ischemic cell death. Stroke. 2008 Sep;39(9):2587-95.
11. Rajman, Luis et al. "Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence." Cell metabolism vol. 27,3 (2018): 529-547.
12. Heer C, et al. Coronavirus infection and PARP expression dysregulate the NAD metabolome. Journal of Biological Chemistry. Dec 2020.
13. Mehmel, Mario et al. "Nicotinamide Riboside-The Current State of Research and Therapeutic Uses." Nutrients vol. 12,6 1616. 2020.
14. Leung A, et al. Poly(ADP-ribose) regulates post-transcriptional gene regulation in the cytoplasm. RNA Biol. 2012 May;9(5):542-8.

Storage

Storage Instructions

Products are produced through lyophilization (freeze-drying), which preserves structural stability during shipping for 3 to 4 months. After reconstitution with bacteriostatic water, the peptide must be stored in a refrigerator (below 4 degrees Celsius) and used within 30 days to maintain effectiveness.

Best Practices for Storing Peptides

• Temperature: For long-term preservation (months to years), store in a freezer at -80 degrees Celsius. Avoid frost-free freezers as temperature cycles can damage the peptide.
• Protection: Keep peptides cool and shielded from light at all times.
• Prevention: To avoid moisture contamination, allow vials to reach room temperature before opening. Minimize air exposure by resealing containers promptly.
• Aliquoting: Divide the peptide into smaller portions (aliquots) for individual experimental use to prevent repeated freeze-thaw cycles.