NAD+ and aging: why does the supply fall over time?
Older tissue may make less NAD+ and break it down faster. Human tests still haven't shown that pills reverse aging.
Why might NAD+ fall as the years pass?
You pull weeds for an hour and feel worn out all afternoon. Many parts of health can cause that change in stamina.
NAD+ also tends to fall in older tissue. The body may make less and break down more.
One protein on the outside of cells becomes more active with age. Researchers call it CD38, and it uses up NAD+ faster.
That finding came mainly from animal tests. Human tests haven't proved that a pill can turn back age.
How certain is the link between lower NAD+ and age?
Lower NAD+ appears in yeast, worms, mice, and people [5]. Medical reviews link the drop with weaker cell health and less stamina [8].
The strongest and steadiest drops come from animal work. A 2025 review found far fewer clear tests in people [14].
That leaves an important limit. An older mouse and an older man may not respond in the same way.
Animal work gives researchers a place to start. For you, it can't prove that raising NAD+ will build strength, slow aging, prevent illness, or add even one good year to your life at home with your family.
What did mouse tests find about the NAD+-draining protein?
The mechanistic key is consumption, not just synthesis. CD38 is the principal NAD+-consuming enzyme whose activity rises with age, and it dictates the age-related NAD+ decline through a SIRT3-dependent mechanism: CD38-knockout mice are protected against the fall in tissue NAD+ and preserve SIRT3 activity, mitochondrial function and metabolic health into old age [2]. As an NADase (NAD glycohydrolase), CD38 hydrolyzes NAD+ to generate the second messenger cADPR and thereby limits the NAD+ left for sirtuins, PARPs and ARTs [11]. So the CD38 NAD-consuming enzyme functions as an age-related drain on the shared pool — which is why its biology has become central to explaining why NAD+ declines, and why simply consuming less (genetically, in mice) preserves NAD+ as effectively as making more [2].
Against that mechanistic backdrop, Promise Peptides clinicians may prescribe NAD+ through the licensed telehealth process at mypromise.com only after evaluating an individual request; that access decision is separate from the biochemical evidence summarized here.
This reframes the whole problem. If the decline were purely a synthesis failure, the fix would be to make more NAD+; but the CD38 data show a large part of the fall is over-consumption by an enzyme that climbs with age and inflammation [2][11]. That is why the field studies both levers — feeding the pool with precursors and dampening the drain — rather than assuming production is the only dial. It also explains why CD38 has drawn interest as a target in its own right: lowering an age-rising NADase is, in principle, a different route to the same endpoint as supplementing a precursor [2].
How can worn-out cells make the NAD+ loss worse?
Older tissue gathers cells that stopped dividing but didn't leave [15]. Some leak chemicals that make nearby tissue sore and swollen.
Those worn-out cells tell nearby tissue to make more CD38 [6]. That outside protein breaks down NAD+ faster [15].
A separate protein still tries to recycle the used pieces in the sore tissue [2]. It may also prompt worn-out cells to leak more harmful chemicals [6].
The result can become a loop: more swelling, more fuel use, and less NAD+. That loop has mostly been studied in cells and animals.
More fuel may not be better in every kind of older tissue. Human tests haven't settled the safest way to change this balance.
What did human tests find after people raised NAD+?
Smaller starting pieces raised NAD+ in blood [4][3]. Nicotinamide riboside, or NR, and nicotinamide mononucleotide, or NMN, also changed how some muscles handled insulin [1][3].
A few clinic tests found small gains in walking distance [14]. No test proved that a supplement reversed age.
The pills raised a blood level, but no human test found a longer life [2][5]. A 2025 review said useful changes in health were still limited.
The frequently asked questions about NAD+ cover pills, drips, safety, and timing. The plain answer is that higher blood levels haven't made people young again.