NAD+

NAD+ Peptide Overview

Nicotinamide Adenine Dinucleotide (NAD+) is a vital coenzyme found in every living cell, serving as a cornerstone of cellular energy production and systemic health. As the oxidized form of NADH, its primary biological function is to act as an electron carrier in redox reactions. This mechanism is essential for converting nutrients into cellular energy (ATP) through glycolysis and the citric acid cycle. Beyond its role in metabolism, NAD+ is a mandatory substrate for enzymes that regulate DNA repair, genomic stability, and cellular aging.

Research indicates that NAD+ levels naturally decline with age, a process linked to various metabolic and neurodegenerative shifts. By facilitating communication between the nucleus and the mitochondria, NAD+ maintains the "energetic bridge" required for organelle health. In extracellular environments, it also acts as a signaling molecule, released by neurons to influence tissues such as the vascular system, the large intestine, and the bladder.

Key Enzyme Systems Dependent on NAD+

Enzyme Class

Primary Function

Impact on Cellular Health

Sirtuins (SIRTs)

Gene regulation and mitochondrial optimization

Promotes longevity, reduces inflammation, and enhances metabolic efficiency.

PARP Enzymes

DNA damage detection and structural repair

Maintains genomic integrity by recruiting repair proteins to damaged DNA strands.

cADPRS

Secondary messenger signaling (Calcium)

Regulates muscle contraction, hormone secretion, and intracellular communication.

NAD+ Peptide Structure

The chemical 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 allows it to transition seamlessly between its oxidized (NAD+) and reduced (NADH) states, making it an ideal vehicle for electron transfer.

Chemical Structure Formula: C21H27N7O14P2

NAD+ Peptide Research

Scientific Evidence on NAD+-Dependent Interactions

Research into NAD+ metabolism focuses on three critical enzymatic pathways that safeguard cellular homeostasis:

• Sirtuins (SIRTs): This family of seven enzymes is heavily dependent on NAD+ availability. Sirtuins are responsible for deacetylation, a process that controls the aging of cells and protects against oxidative stress. Higher sirtuin activity is consistently associated with improved mitochondrial function and the prevention of neural degeneration.
• Poly(ADP-ribose) Polymerases (PARPs): PARPs are the first responders to DNA damage. They utilize NAD+ to build molecular chains that signal the cell’s repair machinery. While vital for preventing mutations, chronic PARP activation due to environmental stress can deplete NAD+ reserves, leading to cellular energy failure.
• Cyclic ADP Ribose Synthetases (cADPRS): These enzymes, including CD38, utilize NAD+ to regulate calcium levels. This regulation is fundamental for immune response coordination and the healthy progression of the cell cycle.

DNA Repair and Ischemic Stress

In studies involving neuronal cultures, restoring NAD+ levels has shown significant promise in mitigating the damage caused by ischemic stress (oxygen deprivation). By providing the necessary substrate for PARP-mediated DNA repair, NAD+ helps cells survive oxidative "bursts" that would otherwise lead to cell death. Research suggests that maintaining high NAD+ concentrations both before and after stress events supports quicker recovery of genomic stability.

Organ Protection (Liver, Kidney, and Heart)

Experimental animal models have demonstrated that NAD+ elevation offers broad systemic benefits:

• Liver and Kidney: In models of obesity, NAD+ supplementation improved glucose regulation and mitochondrial efficiency. In renal studies, it boosted sirtuin activity to protect against drug-induced toxicity and age-related tissue thickening.
• Cardiac Function: NAD+ deficiency is often observed in cases of vascular dysfunction. Studies show that restoring NAD+ levels prior to cardiac stress can reduce the size of infarcted (damaged) tissue and support the heart's contractile energy.

Skeletal Muscle and Mitochondrial Efficiency

Aged murine models treated with NAD+ precursors showed a marked increase in ATP production and a decrease in systemic inflammation within skeletal muscle. By optimizing the electron transport chain, NAD+ ensures that muscle tissues have the energy required for endurance and structural repair.

Article Author

This comprehensive literature review was compiled and organized by Dr. Shin-Ichiro Imai, M.D., Ph.D.

Dr. Imai is a world-renowned molecular biologist specializing in the field of longevity and metabolic health. As a Professor at Washington University School of Medicine, his pioneering work on the "NAD World" concept has defined the modern understanding of how NAD+ biosynthesis regulates the aging process and systemic metabolism.

Scientific Journal Author

Dr. Imai has collaborated with other leading figures in the field, including Dr. David A. Sinclair and Dr. Charles Brenner, to map the pathways of NAD+ precursors. Their collective research has been published in high-impact journals such as Cell and Nature, establishing the critical link between NAD+ availability and the prevention of age-associated physiological decline.

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;132:1108331.4
3. John5son, Sean, and Shin-Ichiro Imai. "NAD+ biosynthesis, aging, and disease." F1000Research vol. 7 132. 1 Feb 2018.6
4. Bieganowski P, Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler in7dependent route to NAD+ in fungi and humans. Cell. 2004 May 14;117(4):495-502.89
5. Fang, E. F., Lautrup, S., Hou, Y., Demarest, T. G., Croteau, D. L., Mattson, M. P., & Bohr, V. A. (2017). NAD+ in Aging: Molecular Mechanisms and Translational Implications. Trends 10in molecular medicine, 23(10), 899-916.11
6. Harden, A; Young, WJ (1906). "12The alcoholic ferment of yeast-juice Part II.--The coferment of yeast-juice". Proceedings of the Royal Society of London. Series B. 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 in an Alzheimer's disease-relevant murine model. BMC Neurol. 2015 Mar 1;15:19.
9. Safety & 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. 31 May. 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

All products are manufactured using a lyophilization (freeze-drying) process. This method ensures that the peptide remains stable during transit for a period of 3 to 4 months. Lyophilization involves freezing the peptide and removing water through sublimation under low pressure, resulting in a stable crystalline powder.

Once the peptide is reconstituted using bacteriostatic water, its shelf life changes significantly. Reconstituted peptides must be kept in a climate-controlled refrigerator and used within 30 days to ensure maximum potency.

Best Practices for Storing Peptides

Proper storage is paramount for maintaining the integrity of the peptide chain. Exposure to heat, light, and moisture can lead to rapid degradation and inaccurate experimental results.

• Short-Term Storage: For use within a few weeks, refrigeration at 4 degrees Celsius (39 degrees Fahrenheit) is sufficient for lyophilized powder.
• Long-Term Storage: To preserve the product for months or years, the vials should be stored in a freezer at -80 degrees Celsius (-112 degrees Fahrenheit).
• Avoid Fluctuations: Do not use frost-free freezers, as the temperature cycling during the defrost phase can damage the peptide’s structural integrity.

Preventing Oxidation and Moisture Contamination

Peptides are highly sensitive to environmental factors. Moisture contamination often occurs when a cold vial is opened immediately after being removed from the freezer. To prevent this, always allow the vial to reach room temperature before breaking the seal.

For peptides containing sensitive amino acids like Cysteine, Methionine, or Tryptophan, minimize exposure to air. Reseal containers immediately after use and, if possible, store the remaining powder under an inert gas like nitrogen.

Peptide Storage Containers

While peptides are often shipped in plastic vials (polystyrene or polypropylene) to prevent breakage during transit, high-quality glass vials offer the best chemical inertness for long-term storage. Ensure the container size is appropriate for the volume of the peptide to minimize the amount of trapped air (headspace) inside the vial.

General Guidelines Summary

• Store in a cold, dry, and dark environment.
• Minimize freeze-thaw cycles.
• Protect from direct light exposure.
• Prioritize lyophilized storage over solution storage.
• Use aliquots to prevent repeated handling of the entire batch.