NAD+

NAD+ Peptide

NAD+, or nicotinamide adenine dinucleotide, is the oxidized form of NADH. This molecule is fundamental to cellular life, primarily serving to facilitate the transfer of electrons between biochemical reactions, which is essential for governing the flow of energy within cells and, in some contexts, to the extracellular environment. In addition to its role in energy production, NAD+ is deeply involved in regulating enzyme activity, mediating posttranslational protein modifications, and enabling essential intercellular communication. Research has observed NAD+ being released as an extracellular signaling molecule by neurons in various tissues, including specific regions of the brain, the large intestine, the bladder, and blood vessels.

NAD+ Peptide Overview

Scientific studies confirm that Nicotinamide Adenine Dinucleotide (NAD+) is an indispensable coenzyme for several enzyme families that orchestrate crucial cellular processes, including metabolism, cell signaling, and DNA repair.

Enzyme Class

Primary Focus

Role in NAD+ Metabolism

Sirtuin Deacetylases

Cellular health and Aging

Utilizes NAD+ to remove acetyl groups from histones and proteins, regulating gene silencing.

Poly(ADP-ribose) Polymerases

DNA integrity and Repair

Consumes NAD+ to generate long poly(ADP-ribose) chains, initiating damage response.

Cyclic ADP Ribose Synthetases

Intracellular communication

Hydrolyzes NAD+ to produce cyclic ADP-ribose, a key regulator of calcium flux.

Sirtuin (SIRT) Deacetylase Enzymes: These enzymes are powerful regulators of energy metabolism, gene expression, and cellular resilience against stress. Their NAD+-dependent deacetylation of target proteins influences aging, inflammation, and mitochondrial function. Increased sirtuin activity is associated with improved metabolic efficiency, enhanced longevity, and protection against oxidative damage.

Poly(ADP-ribose) Polymerase (PARP) Enzymes: PARPs are essential for maintaining genomic stability. They detect DNA breaks and consume NAD+ to form poly(ADP-ribose) chains, which act as signals to recruit DNA repair machinery. However, overactivation of PARPs can rapidly deplete NAD+ reserves, severely compromising cellular energy balance—a scenario linked to certain neurodegenerative and metabolic diseases.

Cyclic ADP Ribose Synthetase (cADPRS): This group of enzymes synthesizes cyclic ADP-ribose, a potent secondary messenger that controls intracellular calcium signaling. This regulated calcium release is necessary for fundamental physiological processes like neurotransmission, muscle contraction, and hormone secretion, demonstrating NAD+’s vital, albeit indirect, regulatory role.

Researchers note that because these crucial enzymatic systems rely so heavily on NAD+, excessive metabolic demand or the overactivation of these pathways can quickly diminish NAD+ availability. This potential depletion can limit the cell's capacity for energy production and repair, highlighting the necessity of maintaining an optimal equilibrium between NAD+ synthesis and utilization.

NAD+ Peptide Structure

NAD+ Peptide Research

Scientific Evidence on NAD+-Dependent Interactions

Ongoing research highlights several critical biological interactions involving Nicotinamide Adenine Dinucleotide (NAD+) that are pivotal for maintaining cellular health, metabolic regulation, and supporting crucial repair mechanisms:

• Sirtuins (SIRTs): As NAD+-dependent enzymes, SIRTs are fundamental for robust mitochondrial function, regulating cellular energy balance, and promoting stem cell longevity and regeneration. They also confer protection against oxidative stress and neural degeneration, pointing to their potential in neuroprotection and age-related disease prevention.
• Poly(ADP-ribose) Polymerases (PARPs): The PARP enzyme family (17 known members) utilizes NAD+ to construct poly(ADP-ribose) chains, a mechanism vital for DNA damage detection and preserving genomic stability. By activating DNA repair pathways, PARPs safeguard cells from genotoxic stress, but over-activation can dangerously deplete NAD+ levels, compromising cellular metabolism.
• Cyclic ADP Ribose Synthetases (cADPRS): This group, which includes the immunoregulatory enzymes CD38 and CD157, catalyzes NAD+ hydrolysis. These reactions influence calcium signaling and may support DNA repair, stem cell renewal, and proper cell cycle progression, linking NAD+ metabolism to immune responses and regenerative biology.

NAD+ Peptide and DNA Repair Following Ischemic Stress

Studies using neuronal culture models demonstrate that restoring NAD+ levels following ischemic stress significantly enhances DNA base-excision repair, boosts cell survival, and mitigates oxidative DNA damage. These beneficial effects are observed whether NAD+ is provided before or after the insult. The mechanism involves PARP enzymes consuming NAD+ to catalyze ADP-ribosylation (PARylation), which activates and recruits DNA repair proteins vital for genomic stability. Research suggests that providing NAD+ during extreme DNA damage, which causes PARP overactivation and rapid NAD+ consumption, can help mitigate this depletion, restoring energy balance and supporting effective DNA repair and neuronal survival.

NAD+ Peptide in Liver and Kidney Protection

Experimental evidence from animal models shows that elevating circulating NAD+ concentrations provides both metabolic and organ-specific protective effects. In models of alcoholic liver disease and obesity, increased NAD+ levels were associated with improved glucose regulation, enhanced mitochondrial efficiency, and better overall liver function. Furthermore, NAD+ supplementation in aged kidney cells was shown to amplify sirtuin (SIRT) enzyme activity and reduce glucocorticoid-induced hypertrophy, supporting renal cellular resilience. Administration of NAD+ precursors, such as nicotinamide mononucleotide (NMN), has produced similar results, including protection against cisplatin-induced nephrotoxicity and a reduction in oxidative stress. These findings indicate NAD+’s broad potential in promoting metabolic homeostasis and organ repair.

NAD+ Peptide and Skeletal Function

In aged mice studies, a seven-day regimen of nicotinamide mononucleotide (NMN) led to higher ATP production, reduced inflammation, and improved mitochondrial efficiency in skeletal tissue. This is consistent with the established role of NAD+ as a redox cofactor in energy metabolism. During the citric acid cycle and glycolysis, NAD+ accepts electrons to generate NADH. NADH then transfers these electrons via the mitochondrial respiratory chain to drive oxidative phosphorylation, which is the process that ensures the continuous production of ATP necessary for muscular endurance and energy.

NAD+ Peptide and Cardiac Function

A deficiency in NAD+ is correlated with reduced sirtuin (SIRT) activity, contributing to compromised mitochondrial energy generation and vascular dysfunction, including aortic constriction. Preclinical mouse studies demonstrated that administering NMN approximately 30 minutes before induced ischemic injury provided substantial cardioprotective effects, reducing tissue damage and supporting cardiac recovery. These results highlight that maintaining optimal NAD+ availability is crucial for healthy heart energy metabolism and its ability to withstand ischemic stress.

Article Author

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

Dr. Imai is a distinguished molecular biologist and longevity researcher renowned for his groundbreaking work on NAD+ metabolism and sirtuin biology. As a Professor at Washington University School of Medicine in St. Louis, his contributions have provided a critical understanding of how NAD+ biosynthesis and signaling pathways fundamentally influence aging, metabolic balance, and mitochondrial health. His research forms a cornerstone for the scientific development of compounds aimed at enhancing cellular resilience and supporting healthy aging.

Scientific Journal Author

Dr. Shin-Ichiro Imai has spear-headed extensive research into the molecular control of NAD+ synthesis and sirtuin activity, illuminating their essential functions in energy metabolism, DNA repair, and mitochondrial integrity. His findings, along with those of celebrated collaborators, including Dr. David A. Sinclair, Dr. Nady Braidy, Dr. Charles Brenner, Dr. Eric F. Fang, and Dr. Vilhelm A. Bohr, have significantly expanded the current scientific knowledge of NAD+’s role in neuroprotection, metabolic regulation, and prevention of age-related disease.

Dr. Imai and his collaborators are recognized as leading experts whose work forms the scientific foundation of modern NAD+ research. This citation is intended solely to acknowledge their academic contributions and is not an endorsement or promotion of this product. Montreal Peptides Canada maintains no professional affiliation, sponsorship, or collaboration with Dr. Imai or any of the researchers referenced herein.

Reference Citations

• Schultz, Michael B, and David A Sinclair. "Why NAD+ Declines during Aging: It's Destroyed." Cell metabolism vol. 23,6 (2016): 965- 966. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088772/
• Braidy N, Liu Y. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. Exp Gerontol. 2020 Apr;132:110831. doi: 10.1016/j.exger.2020.110831. https://pubmed.ncbi.nlm.nih.gov/31917996/
• Johnson, Sean, and Shin-Ichiro Imai. "NAD+ biosynthesis, aging, and disease." F1000Research vol. 7 132. 1 Feb 2018. https://www.ncbi. nlm.nih.gov/pmc/articles/PMC5795269/
• Bieganowski P, Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler in- dependent route to NAD+ in fungi and humans. Cell. 2004 May 14;117(4):495-502. https://pubmed.ncbi.nlm.nih.gov/15137942/
• 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 in molecular medicine, 23(10), 899-916. https://www.ncbi.nlm.nih.gov/pmc/articles/P MC7494058/
• Harden, A; Young, WJ (24 October 1906). "The alcoholic ferment of yeast-juice Part II.--The coferment of yeast-juice". Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character. 78 (526): 369-375. https://royalsocietypublishing.or g/doi/10.1098/rspb.1906.0070
• Mills KF, Yoshida S, Stein LR, Grozio A, Kubota S, Sasaki Y, Redpath P, Migaud ME, Apte RS, Uchida K, Yoshino J, Imai SI. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab. 2016 Dec 13;24(6):795-806. https://pubmed.ncbi.nlm.nih.gov/28068222/
• Long AN, Owens K, Schlappal AE, Kristian T, Fishman PS, Schuh RA. Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer's disease-relevant murine model. BMC Neurol. 2015 Mar 1;15:19. https://pubmed.ncbi.nlm.nih.gov/25 884176/
• Safety & Efficacy of Nicotinamide Riboside Supplementation for Improving Physiological Function in Middle-Aged and Older Adults. h ttps://clinicaltrials.gov/ct2/show/NCT02921659
• Braidy N, Liu Y. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. Exp Gerontol. 2020 Apr;132:110831. https:// pubmed.ncbi.nlm.nih.gov/31917996/
• Wang S, Xing Z, Vosler PS, Yin H, Li W, Zhang F, Signore AP, Stetler RA, Gao Y, Chen J. Cellular NAD replenishment confers marked neuroprotection against ischemic cell death: role of enhanced DNA repair. Stroke. 2008 Sep;39(9):2587-95. https://pubmed.ncbi.nlm.ni h.gov/18617666/
• Rajman, Luis et al. "Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence." Cell metabolism vol. 27,3 (2018): 529- 547. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342515/
• Heer C, et al, Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate im- munity. Journal of Biological Chemistry. Volume 295, Issue 52, Dec 2020. https://www.jbc.org/article/S0021-9258(17)50676-6/fulltext
• Mehmel, Mario et al. "Nicotinamide Riboside-The Current State of Research and Therapeutic Uses." Nutrients vol. 12,6 1616. 31 May. 2020, doi:10.3390/nu12061616 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352172/
• Leung A, Todorova T, Chang P. Poly(ADP-ribose) regulates post-transcriptional gene regulation in the cytoplasm. RNA Biol. 2012 May;9(5):542-8. doi: 10.4161/rna.19899. Epub 2012 May 1. PMID: 22531498; PMCID: PMC3495734.

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STORAGE

Storage Instructions

All products are manufactured via lyophilization (freeze-drying), which ensures stability during shipping for approximately 3-4 months.

After reconstitution with bacteriostatic water, peptides must be stored in a refrigerator to maintain their effectiveness and will remain stable for up to 30 days.

Lyophilization, also known as cryodesiccation, is a specialized dehydration method involving freezing peptides and exposing them to low pressure. This causes the water to undergo sublimation (direct transition from solid to gas), resulting in a stable, white crystalline structure—the lyophilized peptide. The resulting powder is safe for room temperature storage until it is reconstituted.

For extended storage lasting several months to years, storage in a freezer at -80°C (-112°F) is recommended. This deep-freezing condition is optimal for maintaining the peptide’s structural integrity and ensuring long-term stability.

Upon receipt, peptides should be kept cool and protected from light. For short-term use (a few days, weeks, or months), refrigeration below 4°C (39°F) is sufficient. Lyophilized peptides generally remain stable at room temperature for several weeks, which is acceptable for shorter storage durations before use.

Best Practices For Storing Peptides

Correct storage is crucial for preserving the accuracy and reliability of laboratory results. Following proper procedures helps prevent contamination, oxidation, and degradation, ensuring that peptides remain effective and stable over extended periods.

• Upon receipt, peptides should be kept cool and shielded from light.
• Short-term storage (days to several months): Refrigeration below 4°C (39°F) is suitable. Lyophilized peptides are generally stable at room temperature for several weeks, acceptable for shorter storage periods.
• Long-term storage (several months or years): Store in a freezer at -80°C (-112°F) for optimal stability and to prevent structural degradation.

It is essential to minimize freeze-thaw cycles, as repeated temperature fluctuations accelerate degradation. Frost-free freezers must be avoided because their defrosting cycles cause temperature variations that can compromise peptide stability.

Preventing Oxidation and Moisture Contamination

Protecting peptides from air and moisture exposure is paramount for maintaining stability. Moisture contamination is a significant risk when removing cold peptides from the freezer. To prevent condensation from forming on the cold peptide or inside the container, always allow the vial to reach room temperature before opening.

Minimizing air exposure is also vital. The peptide container should be kept closed as much as possible, and promptly resealed after removing the necessary amount. Storing the remaining peptide under a dry, inert gas atmosphere (such as argon or nitrogen) can provide further protection against oxidation. Peptides containing cysteine (C), methionine (M), or tryptophan (W) residues are particularly vulnerable to air oxidation and require extra caution.

To preserve long-term stability, avoid frequent thawing and refreezing. A practical method is to divide the total peptide quantity into smaller aliquots for individual experimental use. This approach minimizes repeated exposure to air and temperature changes, thereby maintaining peptide integrity over time.

Storing Peptides In Solution

Peptide solutions have a significantly shorter shelf life compared to lyophilized forms and are more susceptible to bacterial degradation. Peptides containing cysteine (Cys), methionine (Met), tryptophan (Trp), aspartic acid (Asp), glutamine (Gln), or N-terminal glutamic acid (Glu) residues tend to degrade more rapidly when stored in solution.

If storage in solution is unavoidable, it is recommended to use sterile buffers with a pH between 5 and 6. Aliquoting the solution is essential to minimize freeze-thaw cycles. Under refrigerated conditions at 4°C (39°F), most peptide solutions remain stable for up to 30 days. However, peptides known to be less stable should be kept frozen when not in immediate use.

Peptide Storage Containers

Storage containers for peptides must be clean, clear, durable, and chemically resistant, and sized appropriately to minimize excess air space. Both glass and plastic vials are suitable:

• Polystyrene vials are clear but have limited chemical resistance.
• Polypropylene vials are more chemically resistant though usually translucent.
• High-quality glass vials offer the best combination of clarity, stability, and chemical inertness.

While peptides are often shipped in plastic vials to prevent breakage, they can be safely transferred between glass and plastic vials to suit specific storage or handling requirements.

Peptide Storage Guidelines: General Tips

When storing peptides, follow these best practices to maintain stability and prevent degradation:

• Store peptides in a cold, dry, and dark environment.
• Avoid repeated freeze-thaw cycles.
• Minimize exposure to air to reduce oxidation risk.
• Protect peptides from light.
• Do not store peptides in solution long term; keep them lyophilized whenever possible.
• Aliquot peptides based on experimental needs to prevent unnecessary handling.