NAD+ (Nicotinamide Adenine Dinucleotide)

What Is NAD+?

Nicotinamide Adenine Dinucleotide (NAD+) is a coenzyme found in all living cells. It is the obligate electron carrier in oxidative phosphorylation and the essential substrate for three longevity-regulating enzyme families: sirtuins (SIRT1–7), PARPs, and CD38. NAD+ levels decline ~50% between ages 40–60 — a decline now considered a primary molecular driver of biological aging.

Key Mechanisms

• Sirtuin activation (SIRT1–7) — deacetylases that regulate mitochondrial biogenesis, DNA repair, and metabolic homeostasis
• PARP-mediated DNA repair — repairs up to 70,000 single-strand DNA breaks per cell per day
• Complex I electron transport — NADH donates electrons to the mitochondrial ETC — rate-limiting for ATP production
• Circadian clock regulation — SIRT1 deacetylates core clock proteins BMAL1 and PER2
• AMPK cross-talk — via SIRT1→LKB1→AMPK axis, drives catabolic/repair longevity states

Research Applications

• Mitochondrial rejuvenation and age-related muscle decline
• DNA damage and repair kinetics in aging models
• Metabolic health and insulin sensitivity
• Neurodegeneration (Alzheimer's, Parkinson's preclinical models)
• Circadian biology research

Key References

1. Gomes AP et al. “Declining NAD+ induces a pseudohypoxic state during aging.” Cell, 2013;155(7):1624–1638.
2. Verdin E. “NAD+ in aging, metabolism, and neurodegeneration.” Science, 2015;350(6265):1208–1213.
3. Yoshino M et al. “NMN increases muscle insulin sensitivity in prediabetic women.” Science, 2021;372:1224–1229.