The oxidized form of NADH, or nicotinamide adenine dinucleotide hydroxide, is known as nicotinamide adenine dinucleotide (NAD+). Studies suggest that NAD+ may transport electrons produced in biological processes due to its involvement in the ETC. Research suggests that it may serve as a conduit for transferring energy between the inside and outside of the cell. Post-translational modification of proteins and the activation/deactivation of certain enzymes are only two examples of the many biological processes it has been speculated to mediate. It may play an important role in cell communication.

Findings imply that NAD+ is likely released from neurons in the vascular system, the gastrointestinal tract, and the bladder, where it seems to operate as an extracellular signaling molecule that may control several biological processes. Investigations purport that several biological activities may require its presence, including immunological defense, DNA repair, circadian regulation, and energy expediture. However, like other naturally occurring mediators, its level typically decreases with age. Researchers are exploring the possibility that restoring NAD+ levels may possibly contribute to slow or stop the progression of certain age-related diseases. 

NAD+ Peptide Research and Investigations

Researchers are interested in NAD+ because of its alleged central role in many biological processes. The following fields of study have proposed roles for NAD+:

NAD+ Peptide and Age-Related Processes

The mitochondria are the cells’ primary source of energy. Intracellular signaling and the control of innate immunity are two examples of their key metabolic roles. Mitochondrial aging directly impacts these facets, eventually influencing cellular metabolism, inflammation, and stem cell function changes.[i] Together, they slow recovery time after an injury. This shows how crucial mitochondria are to losing tissue and organ function with aging. The aging process may be slowed, stopped, or even reversed by manipulating mitochondrial function. 

Researchers speculate that a lack of NAD+ in the cell may cause a pseudo-hypoxic state, which disrupts nucleus-based signaling. Supplemental NAD+ has been suggested to show promise in studies for slowing or correcting age-related declines in mitochondrial activity.[ii] Scientists hypothesize that “raising NAD+ levels in old mice may restore mitochondrial function to that of a young mouse in a SIRT1-dependent manner.” The activation of the SIRT 1 function, encoded by the gene for the enzyme Sirtuin-1 (NAD+ dependent Deacetylase Sirtuin-1), seems to be the mechanism inducing this characteristic. Thus, Sirtuin-1 may possibly control metabolic, inflammatory, cellular lifespan, and stress-related factors.[iii]

NAD+ Peptide and Muscle Function

Mitochondrial aging is linked to the age-related reduction in muscular function. It’s a two-stage process. Decreased expression of mitochondrial genes is the initial, reversible stage. Oxidative phosphorylation, the mechanism through which mitochondria generate energy, is regulated by these genes. Second, and more permanently, the number of oxidative phosphorylation-related genes in the nucleus decreases. Studies suggest that NAD+ may exhibit some potential to reverse step 1 before the cell moves to step 2; this outcome was suggested in research studies with mice.[iv]

Peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1-alpha) stabilization may be the mechanism underpinning this intervention in mitochondrial aging. Some research suggests that exercise’s impact on the mitochondria of skeletal muscles is comparable to the effect described above.[v]

NAD+ Peptide and the Nervous System

NAD+ is a co-factor that researchers have suggested exhibits substantial neuroprotective potential.[vi] This potential stems through lowering ROS generation and enhancing mitochondrial activity. Inflammatory responses to injury and degenerative changes with age are triggered by reactive oxygen species (ROS). Existing forms of mitigating neurodegenerative disorders, including Alzheimer’s, Huntington’s, and Parkinson’s, relies on this connection. NAD+ has shown promise in protecting against motor impairment progression and substantia nigra dopamine cell death in animal models.[vii] Outcomes “add credence to the positive role of NAD against parkinsonian neurodegeneration in rodent models of PD,” the authors write. “These results provide data for the potential of NAD for the prevention of PD and speculate that NAD may prevent pathological changes in PD via decreasing mitochondrial dysfunctions.” Although NAD+ was not documented to improve symptoms, it was suggested that it might decrease the advancement of Parkinson’s disease or perhaps prevent its onset by the study’s results.

NAD+ Peptide and Inflammation

The enzyme NAMPT has been linked to inflammatory processes. Some forms of cancer seem to have an overexpression of this. Findings imply that NAD+ increases when NAMPT levels rise, and vice versa.[viii] Cancers, obesity, type 2 diabetes, and nonalcoholic fatty liver illness all seem linked to inflammation in the NAMPT pathway. NAMPT may be a powerful inflammatory stimulator, yet its levels may drop significantly after receiving NAD+.

NAD+ for sale is available at Core Peptides only for scientists or licensed professionals purchasing academic studies and experiments. None of the substances mentioned above have been approved for human consumption.

References

[i] Sun N, Youle RJ, Finkel T. The Mitochondrial Basis of Aging. Mol Cell. 2016 Mar 3;61(5):654-666. doi: 10.1016/j.molcel.2016.01.028. PMID: 26942670; PMCID: PMC4779179.

[ii] Gomes AP, Price NL, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, Mercken EM, Palmeira CM, de Cabo R, Rolo AP, Turner N, Bell EL, Sinclair DA. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 2013 Dec 19;155(7):1624-38. doi: 10.1016/j.cell.2013.11.037. PMID: 24360282; PMCID: PMC4076149.

[iii] Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014 Aug;24(8):464-71. doi: 10.1016/j.tcb.2014.04.002. Epub 2014 Apr 29. PMID: 24786309; PMCID: PMC4112140.

[iv] Mendelsohn AR, Larrick JW. Partial reversal of skeletal muscle aging by restoration of normal NAD⁺ levels. Rejuvenation Res. 2014 Feb;17(1):62-9. doi: 10.1089/rej.2014.1546. PMID: 24410488.

[v] Kang C, Chung E, Diffee G, Ji LL. Exercise training attenuates aging-associated mitochondrial dysfunction in rat skeletal muscle: role of PGC-1α. Exp Gerontol. 2013 Nov;48(11):1343-50. doi: 10.1016/j.exger.2013.08.004. Epub 2013 Aug 30. PMID: 23994518.

[vi] Matthews RT, Yang L, Browne S, Baik M, Beal MF. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8892-7. doi: 10.1073/pnas.95.15.8892. PMID: 9671775; PMCID: PMC21173.

[vii] Shan C, Gong YL, Zhuang QQ, Hou YF, Wang SM, Zhu Q, Huang GR, Tao B, Sun LH, Zhao HY, Li ST, Liu JM. Protective effects of β- nicotinamide adenine dinucleotide against motor deficits and dopaminergic neuronal damage in a mouse model of Parkinson’s disease. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Aug 30;94:109670. doi: 10.1016/j.pnpbp.2019.109670. Epub 2019 Jun 17. PMID: 31220519.

[viii] Garten A, Schuster S, Penke M, Gorski T, de Giorgis T, Kiess W. Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol. 2015 Sep;11(9):535-46. doi: 10.1038/nrendo.2015.117. Epub 2015 Jul 28. PMID: 26215259.