NAD+ participates in energy production, DNA repair, and cellular signaling. This is precisely why it has become one of the most intriguing molecules in aging research — but the science is more complex than the simple idea that “more NAD+ means slower aging.”

In recent years, NAD+ has almost become synonymous with longevity.

There is talk of energy, mitochondria, sirtuins, DNA repair, and “cellular rejuvenation.” Behind some of these claims, there is indeed some very interesting biology.

But between the questions “is NAD+ important for the cell?” and “can we slow down human aging by increasing NAD+?” there is a major scientific difference.

The answer to the first question is very clear.

The answer to the second is not yet known.

What exactly is NAD+?

NAD+ is an abbreviation for nicotinamide adenine dinucleotide.

It is found in virtually all living cells and belongs to the molecules without which normal cellular metabolism could not function.

One of its fundamental functions is electron transport.

NAD+ can accept electrons and convert into its reduced form:

NAD+ ⇄ NADH

This seemingly simple exchange enables a large number of reactions in which the cell converts energy from nutrients into a form it can utilize. PubMed

That is why NAD+ is not a classic “energy ingredient.”

It is part of the chemical system by which the cell produces energy.

NAD+ and energy production

When we consume carbohydrates, fats, or proteins, the energy from them does not transfer directly to our muscles or brain.

Nutrients first pass through a series of metabolic reactions.

During processes like glycolysis, the citric acid cycle, and fatty acid oxidation, NAD+ accepts electrons and turns into NADH.

NADH then transfers them toward the mitochondrial electron transport chain.

There, their energy helps create the proton gradient that powers ATP synthase, the enzyme responsible for producing ATP.

ATP is the cell’s basic energy currency.

In other words:

nutrients → NADH → mitochondria → ATP

Without constant cycling between NAD+ and NADH, this system could not function normally. Nature

But NAD+ is not important just for energy

This is where the story gets particularly interesting.

NAD+ is not just a molecule that carries electrons.

Certain enzymes consume it as a substrate in order to perform their functions.

Among the most important are:

sirtuins

PARP enzymes

CD38

and other enzyme systems involved in cellular signaling, stress response, and metabolism. PubMed

Because of this, the amount and availability of NAD+ link several processes that are currently at the very center of the biology of aging.

Sirtuins: why are they mentioned so much in longevity?

Sirtuins are a family of enzymes designated as SIRT1 through SIRT7.

They require NAD+ for their work.

They participate in the regulation of proteins related to metabolism, mitochondrial function, cellular stress response, gene expression, and the maintenance of cellular homeostasis. PubMed

It is precisely because of the connection between NAD+, sirtuins, and the aging process that a very attractive idea emerged:

more NAD+ → more sirtuin activity → healthier aging

Biology, however, is not that linear.

Sirtuin activity depends on many more factors than just the concentration of NAD+, and different sirtuins operate in different parts of the cell and have different functions.

Therefore, from the fact that sirtuins use NAD+, one cannot automatically conclude that simply increasing NAD+ in a healthy person must lead to an “anti-aging” effect. Nature

NAD+ and DNA repair

Our DNA is not a static structure.

Every day, it is exposed to a large number of chemical and physical influences that can cause damage.

Cells therefore possess a series of sophisticated systems to recognize and repair them.

One important group of enzymes in this process are PARP enzymes, especially PARP1.

When they recognize certain types of DNA damage, they use NAD+ as a substrate to create poly(ADP-ribose) chains, which helps organize the cell's response to the damage.

This means that increased activation of certain PARP enzymes can simultaneously increase NAD+ consumption. PubMed

This is where one of the more interesting hypotheses about aging arises.

If the amount of cellular damage and inflammatory burden increases with age, the increased activity of enzymes that use NAD+ could contribute to changes in its cellular status.

But that is not the only mechanism.

CD38: another major NAD+ consumer

CD38 is an enzyme present on various cells and is particularly interesting due to its link to the immune system and inflammation.

It also breaks down NAD+.

Preclinical research suggests that age- and chronic inflammation-related changes in CD38 activity may be one of the reasons for the decreased availability of NAD+ in certain tissues.

That is why today NAD+ is not viewed in isolation.

The question is not just:

“How much do we create?”

but also:

“How much do we consume?” PubMed

Does NAD+ really drop with age?

This is one of the most frequently repeated claims in the longevity industry:

“NAD+ drops drastically with age.”

There is data supporting age-related changes in NAD+ metabolism.

In some human tissues, lower concentrations of NAD+ have been recorded in older individuals. One study of human skin, for example, found a negative correlation between NAD+ levels and age. PubMed

But a modern review of human research published in Nature Metabolism in 2025 highlights an important point:

evidence of a universal drop in NAD+ in all human tissues is still limited.

Results depend on the tissue, the method of measurement, health status, and other factors. The amount of data from human tissues is still relatively small compared to the vast amount of data from animal models. PubMed

Therefore, it is more accurate to say:

aging is associated with changes in NAD+ metabolism and a decrease in NAD+ in some tissues, but it is not scientifically justified to assume an equal drop in every cell and in every person.

Why would NAD+ decrease at all?

There are several possible reasons.

One is reduced biosynthesis.

Another is increased consumption.

The third is altered metabolism associated with chronic inflammation, oxidative stress, DNA damage, and mitochondrial dysfunction.

PARP enzymes, CD38, and sirtuins all use the same cellular NAD+ pool for different functions.

Because of this, we can imagine NAD+ as a metabolic resource used by multiple systems simultaneously. PubMed

But even that analogy is simplified.

The cell does not have just one NAD+ reservoir

One of the more important discoveries of modern NAD+ biology is that the cell does not simply have one large shared pool of that molecule.

There are different NAD+ pools in the:

cytosol

nucleus

mitochondria

and other cellular compartments.

Their concentration, regulation, and interconnectedness can differ. Nature

This further complicates the question of supplementation.

Even if an intervention increases the concentration of NAD-related metabolites in the blood, it does not automatically mean that it has equally increased NAD+ in muscle mitochondria, neurons, or some other target tissue.

Increasing a number in the blood and changing the biology of a specific cell are not necessarily the same thing.

How does the body create NAD+?

The organism can create NAD+ through several metabolic pathways.

It uses compounds related to vitamin B3 as precursors, including:

nicotinamide (NAM)

nicotinic acid (NA)

nicotinamide riboside (NR)

and nicotinamide mononucleotide (NMN) also enters NAD+ metabolism. Nature

Particularly important is the so-called salvage pathway, by which cells recycle nicotinamide and recreate NAD+.

This shows how economical the system is.

The cell constantly uses, breaks down, and recreates NAD+.

Can we simply increase NAD+?

That is the question that started the entire field of NAD+ supplementation.

In animal models, the results are very interesting.

Increasing NAD+ via precursors like NR or NMN has been linked in various experimental models to improvements in some metabolic, mitochondrial, and functional parameters.

In some models, effects related to healthy aging were also recorded. PubMed

This is one of the main reasons why the field has become so popular.

But then comes the most important question:

What happens in humans?

Here the picture is significantly less spectacular.

What does research on humans show?

Clinical studies have shown that oral precursors like NR and NMN can increase certain NAD+-related metabolites in the blood or certain cells. PubMed

So, there is a clear biochemical effect.

But:

an increase in biomarkers is not the same as proof of life extension or the slowing of aging.

The latest systematic review of preclinical and clinical evidence concludes that NR and NMN in humans show biological activity and were generally well-tolerated during shorter studies, but the results for functional, metabolic, and other health outcomes remain heterogeneous and often without significant effect. PubMed

A review published in Nature Metabolism in 2025 also concludes that current clinical effects of NAD+ precursors on healthy aging are limited and that higher-quality and longer studies are needed. Nature

And what about “life extension”?

For now, we have no quality evidence that NAD+ supplementation extends human life.

This is a particularly important difference.

An experiment on a mouse can show changes in metabolism, function, or even lifespan.

But humans live for decades and have completely different physiology, nutrition, environment, and health factors.

That is why results from laboratory and animal models cannot simply be translated into the claim:

“NAD+ slows down human aging.”

Current human evidence does not confirm this. PubMed

NAD+ and NAD+ precursors are not the same

This is another important difference that often gets lost in marketing.

Most modern clinical research on increasing NAD+ does not necessarily use the NAD+ molecule itself.

They often investigate its precursors, especially:

NR

and

NMN

The organism then metabolizes these molecules through its own pathways.

Because of this, the result of research on one precursor cannot be automatically attributed to every product labeled “NAD+”.

The same applies to oral NAD+, intravenous NAD+, NR, and NMN.

These are different interventions with different pharmacology. Nature

Currently, there is a particular lack of quality clinical outcomes for direct intravenous or oral administration of NAD+ itself in the context of “anti-aging.” The latest systematic review did not find adequate controlled studies of intravenous or intramuscular NAD+ that would prove an anti-aging or wellness effect. PubMed

Why is NAD+ then so interesting?

Because it is located precisely at the intersection of several processes associated with aging.

Energy.

NAD+/NADH enables the electron transport required for metabolism and ATP production.

DNA.

NAD+ is used by PARP enzymes involved in the response to certain DNA damage.

Cellular regulation.

Sirtuins use NAD+ and participate in the regulation of metabolism and stress response.

Mitochondria.

Changes in NAD+ metabolism can affect mitochondrial function.

Inflammation.

Enzymes like CD38 link NAD+ metabolism with immune and inflammatory processes. PubMed

Therefore, NAD+ is not interesting because some simple “molecular switch for youth” has been discovered.

It is interesting precisely because it connects so many fundamental cellular systems.

Aging is not a deficiency of one molecule

Perhaps the biggest mistake of longevity marketing is the idea that we can reduce an extremely complex process to a single value.

Aging involves changes in the genome, epigenetics, mitochondria, proteins, the immune system, metabolism, stem cells, and intercellular communication.

NAD+ overlaps with many of those systems.

But that does not mean that aging is simply “a lack of NAD+”.

Reviews of current literature for this reason warn that we still do not fully understand how NAD+ metabolism differs among tissues, how it changes during normal human aging, and which people — if any — might benefit the most from its pharmacological increase. Nature

Between biology and longevity hype

We can say two things about NAD+ simultaneously.

First:

NAD+ is one of the fundamental molecules of human metabolism and an extremely interesting area of research in the biology of aging.

Second:

we still have no proof that simply increasing NAD+ in humans means slower aging or a longer life.

These two sentences are not a contradiction.

They are exactly what science is currently showing. PubMed

And perhaps that is exactly the best way to look at NAD+.

Not as a “molecule of youth.”

But as one of the molecules through which we can better understand how the cell connects energy, repair, stress, and time.

References and sources

[1] Lautrup S, Hou Y, Fang EF, Bohr VA. Roles of NAD+ in Health and Aging. Cold Spring Harbor Perspectives in Medicine. 2024;14(1):a041193. A review of the role of NAD+ in metabolism, energy, DNA repair, mitophagy, and aging. PubMed

[2] Migaud ME, Ziegler M, Baur JA. Regulation of and challenges in targeting NAD+ metabolism. Nature Reviews Molecular Cell Biology. 2024;25:822–840. A review of NAD+ metabolism, cellular NAD+ pools, and the limitations and open questions related to NAD+ supplementation. Nature

[3] NAD+ precursor supplementation in human ageing: clinical evidence and challenges. Nature Metabolism. 2025;7:1974–1990. A critical review of human evidence on NAD+ changes during aging and the results of precursor supplementation. Nature

[4] Covarrubias AJ et al. / review of NAD+ clinical pharmacology. Nicotinamide Adenine Dinucleotide in Aging Biology: Potential Applications and Many Unknowns. Endocrine Reviews. A review of preclinical and early clinical data and the limitations of their translation to humans. PubMed

[5] Massudi H et al. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLOS ONE. 2012. A study of human tissue that found an association between age, DNA damage, PARP activity, and lower NAD+ levels. PubMed

[6] NAD metabolism: Role in senescence regulation and aging. A review of the relationship between NAD+, cellular senescence and aging, and the limitations of existing NR and NMN clinical research. PubMed Central (PMC)

[7] The therapeutic perspective of NAD+ precursors in age-related diseases. Biochemical and Biophysical Research Communications. 2024;702:149590. A review of the potential role of NAD+ precursors and the fact that their clinical effects are still under investigation. PubMed

[8] NAD+ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence. 2026. A systematic review concludes that NR and NMN can increase NAD-related biomarkers, but that clinical efficacy for anti-aging and wellness outcomes remains unproven. PubMed

[9] The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update. A review of human NMN research and the differences between increasing NAD+ in the blood and the effect in individual tissues. PubMed Central (PMC)

[10] Preclinical and clinical evidence of NAD+ precursors in health, disease, and ageing. A review of NR, NMN, and other NAD+ precursors and the differences between results obtained in animal models and in humans.