NAD+ has two jobs, and most protocols account for one
It is the central redox carrier of metabolism and separately the consumed substrate for sirtuins, PARPs and CD38. The second role is why NAD+ pools deplete.
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.
For laboratory research use only. Reference information, not medical advice or human-use guidance.
