Biology & Longevity
What Is NAD+ and Why Does It Decline?
A redox cofactor, a sirtuin substrate and a PARP substrate at once. Why one molecule sits at the centre of so much metabolic research.
August 15, 2026 · 6 min read · Novanta Research
Two jobs, one molecule
NAD+ shuttles electrons in metabolism, cycling between NAD+ and NADH in glycolysis, the TCA cycle and oxidative phosphorylation. In that role it is recycled continuously and not consumed.
Its second role is different: sirtuins, PARPs and CD38 consume NAD+ as a substrate, breaking it apart in the process. That consumption is why the pool has to be continuously resynthesised.
Salvage and synthesis
Most NAD+ is regenerated through the salvage pathway from nicotinamide, with NAMPT as the rate-limiting enzyme. Smaller contributions come from nicotinic acid and from de novo synthesis out of tryptophan.
Precursor compounds studied in this space — nicotinamide riboside and nicotinamide mononucleotide — feed into these pathways at different points.
Why levels fall with age
Two mechanisms are described: reduced synthesis through declining NAMPT activity, and increased consumption by CD38 and by PARP enzymes responding to accumulated DNA damage. The two are not mutually exclusive and probably operate together.
Open questions
Raising circulating precursor levels is well demonstrated in humans. Whether that reliably raises tissue NAD+ in the tissues that matter, and whether raising it produces functional benefit, is a much less settled question than marketing in this space suggests.
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For laboratory and research use only. Not for human or veterinary consumption. Novanta Research is not a compounding pharmacy and nothing in this article is medical advice or a claim that any compound diagnoses, treats, cures or prevents any condition.