What Is NAD+?

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme found in all living cells. It cycles between oxidized (NAD+) and reduced (NADH) forms, shuttling electrons during cellular reactions. Because it is required for energy production and enzyme activity, NAD+ is considered a central molecule in cellular metabolism.

(Reference: Verdin, 2015)

How Has NAD+ Been Studied?

NAD+ has been examined across multiple levels of research:

• In vitro assays have explored how NAD+ interacts with enzymes, such as sirtuins and PARPs.

• Animal models have investigated how NAD+ levels change in tissues during aging, stress, or nutrient shifts.

• Human studies often measure circulating NAD+ or related metabolites, sometimes in the context of supplementation with precursors like nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN).

(Reference: Covarrubias et al., 2021)

Key Roles of NAD+ in Cells

Research has identified several fundamental roles for NAD+:

• Energy Production – Serves as a cofactor in glycolysis, the TCA cycle, and oxidative phosphorylation.

• DNA Repair – Consumed by PARP enzymes during repair of damaged DNA strands.

• Gene Regulation – Provides substrate for sirtuins, which influence chromatin structure and gene expression.

• Stress Response – Helps regulate cellular defense systems during oxidative and metabolic stress.

(Reference: Canto et al., 2015)

What Researchers Have Observed

Studies over the last two decades have highlighted consistent patterns:

• Decline With Age – NAD+ levels are reported to decrease in tissues of animals and humans over time.

• Tissue Variability – NAD+ concentrations differ between organs, with high demand in energy-intensive tissues such as muscle, brain, and liver.

• Precursor Response – Trials with NR or NMN supplementation in humans have measured increases in NAD+ metabolites, though results vary by dose and duration.

• Dynamic Regulation – Environmental stress, diet, and exercise all influence NAD+ turnover, making it a sensitive indicator of metabolic state.

(Reference: Yoshino et al., 2018)

References

• Verdin, E. (2015). NAD+ in aging, metabolism, and neurodegeneration. Science, 350(6265), 1208–1213.

• Covarrubias, A.J., et al. (2021). NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology, 22, 119–141.

• Canto, C., et al. (2015). NAD+ metabolism and the control of energy homeostasis: a balancing act. Cell Metabolism, 22(1), 31–53.

• Yoshino, J., et al. (2018). NAD+ intermediates: The biology of NMN and NR. Science, 362(6412), eaat8289.

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