NAD+

What is NAD⁺?

NAD⁺ is a critical redox coenzyme involved in metabolic pathways such as glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. It also serves as a substrate for enzymes like sirtuins and poly(ADP-ribose) polymerases (PARPs), which regulate aging, inflammation, and DNA repair. NAD⁺ levels are known to decline with age and in certain disease states, highlighting its importance in aging-related research [2].

Molecular Formula and Structure

• Molecular Formula: C₂₁H₂₇N₇O₁₄P₂
• Molecular Weight: 663.43 g/mol

NAD⁺ is composed of two nucleotides joined by phosphate groups: one containing an adenine base and the other a nicotinamide moiety. This structure is essential for its function in electron transfer and enzymatic activation [3].

NAD⁺ Research

1. Cellular Energy Metabolism

NAD⁺ plays a vital role in cellular energy production by accepting and donating electrons during metabolic reactions. It is a central coenzyme in glycolysis, the TCA cycle, and mitochondrial oxidative phosphorylation, making it essential in studies on cellular bioenergetics [1].

2. DNA Repair and Genomic Stability

NAD⁺ acts as a substrate for PARP enzymes involved in the base excision repair pathway. Research shows that depleted NAD⁺ levels impair DNA repair capacity, potentially accelerating genomic instability and aging [2][4].

3. Age-Related NAD⁺ Decline

Multiple studies have observed a significant decrease in NAD⁺ levels during aging, obesity, and chronic inflammation. This reduction impairs mitochondrial function, sirtuin activity, and stress resistance, making NAD⁺ a key target in aging and longevity research [2][5].

4. Cardiovascular Function

Preclinical studies suggest that NAD⁺ repletion improves cardiac function by enhancing mitochondrial efficiency, reducing oxidative stress, and supporting endothelial function. It has shown promise in experimental models of heart failure and hypertension [1][5].

5. Neuroprotection and Brain Health

NAD⁺ has been linked to neuronal survival and cognitive function. Its role in activating sirtuins and preserving mitochondrial health makes it a promising molecule in neurodegenerative disease models, such as Alzheimer’s and Parkinson’s [4][6].

Referenced Citations

1. Trammell SAJ, et al. NAD⁺ metabolism in aging and disease. Circ Res. 2022;130(3):486–508. PMID: 35077429
2. Verdin E. NAD⁺ in aging, metabolism, and neurodegeneration. Science. 2015;350(6265):1208–1213. PMID: 26785480
3. PubChem. NAD⁺ – Compound Summary. CID 5892
4. Belenky P, et al. NAD⁺ metabolism in health and disease. Trends Biochem Sci. 2007;32(1):12–19. PMID: 17161604
5. Gariani K, et al. Pharmacological stimulation of NAD⁺ improves mitochondrial and stem cell function in muscle. Cell Metab. 2016;24(4):529–541. PMID: 27693237
6. Huang YY, et al. NAD⁺ in neurodegenerative disease models. Brain Res Bull. 2021;168:124–132. PMID: 33647380

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