NAD+ is usually introduced as the electron carrier of central metabolism. That description is correct and incomplete, and the missing half is the reason NAD+ appears in the longevity literature at all.
Job one: the redox carrier
NAD+ cycles between its oxidised and reduced forms to shuttle electrons through glycolysis, the TCA cycle and oxidative phosphorylation. In this role it is recycled, not consumed — the pool turns over but is not depleted. If this were its only function, cellular NAD+ would be effectively self-sustaining.
Job two: the consumed substrate
NAD+ is also an obligate co-substrate for three enzyme families that cleave it and therefore consume it:
- Sirtuins (SIRT1-7) — NAD+-dependent deacetylases, the link to metabolic and chromatin regulation.
- PARPs — DNA-repair enzymes; heavy DNA damage means heavy PARP activity means measurable NAD+ drawdown.
- CD38 — an NAD+ glycohydrolase whose activity rises with age in published work, a major consumer of the pool.
Because these consume rather than recycle, NAD+ availability becomes a genuine limiting resource — and that is the mechanistic bridge between mitochondrial function and the DNA-damage response.
Measurement notes
- Measure the ratio, not just the total. NAD+/NADH tells you about redox state; total NAD+ tells you about pool size. They answer different questions.
- Extraction chemistry matters. NAD+ and NADH are differentially stable in acid and alkali; a single extraction protocol will bias one form.
- Control for CD38 if you are studying pool depletion, since it can dominate consumption.
- NAD+ is a coenzyme, not a peptide — the reconstitution and handling conventions used for lyophilized peptides mostly transfer, but it does not belong in a peptide-purity comparison.
Selected literature
- Verdin E. NAD+ in aging, metabolism, and neurodegeneration. Science. 2015;350(6265):1208-1213.
- Katsyuba E et al. NAD+ homeostasis in health and disease. Nat Metab. 2020;2(1):9-31.
Stocked as a 500 mg lyophilized reference standard: NAD+ 500 mg · background in the peptide library. For laboratory research use only.