NAD+ Levels by Age: Why They Fall and What the Research Shows

“NAD levels by age” is one of the most searched questions in longevity science, often followed by a hopeful request for a chart. Many people have heard somewhere online that NAD+ halves by middle age or falls steadily from birth, and that the decline explains everything from low energy to ageing itself. The real research is more nuanced, and in some ways more interesting. NAD+ does decline with age in several human tissues, researchers have identified some of the reasons why, and they have learned that the decline differs between tissues, between people and even between the sexes. What does not yet exist is a reliable, universal chart.

This guide explains what NAD+ is, what the human evidence on age-related decline actually shows, why levels fall, why they differ between tissues and individuals, how NAD+ is measured, and what research has found about restoring it. It is an educational overview of research findings, not medical advice. Crown Peptides supplies NAD+ for laboratory research use only.

The Short Answer

Research has found that NAD+ levels decline with age in several human and animal tissues, including skin, muscle, liver and brain, though the size of the decline varies between tissues, studies and measurement methods. Two major drivers have been identified: increasing consumption of NAD+ by enzymes that respond to DNA damage and inflammation, particularly PARP and CD38, and changes in how efficiently cells recycle it. There is no standardised chart of “normal” NAD+ levels by age, because levels depend heavily on the tissue measured and the method used.

What NAD+ Does, in Brief

NAD+, nicotinamide adenine dinucleotide, is a coenzyme found in every cell. It carries electrons from the breakdown of food to the mitochondria, where energy is produced. It is also consumed as fuel by sirtuins, enzymes that regulate metabolism and stress responses, and by PARPs, enzymes that repair DNA. Because so many essential processes depend on it, a decline in NAD+ could affect energy, repair and regulation all at once, which is why its age-related fall attracts so much attention. Our NAD+ guide covers its biology in depth.

How the NAD+ Ageing Idea Emerged

For most of the twentieth century, NAD+ was seen as a stable housekeeping molecule of metabolism, and nobody expected its levels to change much with age. That began to change in 2000, when Shin-ichiro Imai, Leonard Guarente and colleagues showed that the yeast longevity protein Sir2 depends on NAD+, linking the molecule directly to lifespan (PMID: 10693811). Researchers then began measuring NAD+ in ageing tissues. Through the 2010s, studies in worms, mice and human tissue reported declines, the enzymes responsible were identified, and precursors such as NMN and NR were tested for their ability to restore it. In little more than a decade, NAD+ went from an overlooked cofactor to one of the most studied molecules in ageing research.

What the Human Evidence Shows

The Sydney skin study

One of the most cited human studies was published in PLoS One in 2012 by Massudi, Guillemin and colleagues in Sydney (PMID: 22848760, PMC3407129). They analysed human skin samples from people aged 15 to 77, along with newborns, measuring NAD+, oxidative DNA damage and the activity of PARP and sirtuins. Oxidative DNA damage increased with age. PARP activity rose strongly with age in males and was inversely correlated with NAD+ levels. NAD+ levels fell with age, and sirtuin activity fell with them in males. The authors concluded that accumulating oxidative DNA damage may drive increased NAD+ consumption with age, and that the resulting depletion may play a major role in ageing.

A sex difference

An intriguing detail of the Sydney study was that several of the age-related changes were stronger or only significant in males. That is a reminder that NAD+ ageing may not follow the same path in everyone, and that studies need to consider both sexes.

Other tissues

Research in other human tissues, including muscle, brain, liver and blood, has also reported lower NAD+ with age, though not every study has found a decline in every tissue. A 2021 review in Nature Reviews Molecular Cell Biology by Covarrubias, Verdin and colleagues summarised the evidence for NAD+ decline across tissues and its roles in ageing (PMID: 33353981, PMC7963035).

Why NAD+ Falls: The Main Drivers

More consumption by PARPs

PARP enzymes use NAD+ to repair damaged DNA. As DNA damage accumulates with age, PARPs work harder and use more NAD+. The Sydney study’s finding that PARP activity rose with age and correlated with lower NAD+ supports this idea.

More consumption by CD38

CD38 is an enzyme on immune cells and other cells that breaks down NAD+. In a 2016 study in Cell Metabolism, Camacho-Pereira, Chini and colleagues at the Mayo Clinic found that CD38 levels and activity increase with age in mice, that mice lacking CD38 were protected from age-related NAD+ decline, and that CD38 acted partly by reducing the activity of the mitochondrial sirtuin SIRT3 (PMID: 27304511, PMC4911708). Because CD38 is linked to inflammation, the chronic low-grade inflammation that accompanies ageing may be one reason NAD+ falls.

Less efficient recycling

Most NAD+ is recycled through the salvage pathway, controlled by the enzyme NAMPT. Research in animals suggests NAMPT activity can decline with age in some tissues, reducing the cell’s ability to rebuild NAD+ as fast as it is consumed.

The “Achilles’ heel” idea

A 2014 review in Trends in Cell Biology by Imai and Guarente brought these threads together, describing NAD+ decline as a possible “Achilles’ heel” of ageing and summarising research in which restoring NAD+ improved age-associated defects in animal models (PMID: 24786309, PMC4112140).

NAD+ Decline in Specific Tissues

Muscle

Muscle is one of the most studied tissues. Research has linked lower muscle NAD+ and NAMPT to ageing and inactivity, and exercise to higher NAMPT. Because muscle is a major consumer of energy and blood sugar, NAD+ here is closely tied to metabolic health, which is why the 2021 NMN trial measured muscle insulin sensitivity.

Brain

Neurons use enormous amounts of energy and depend on NAD+ for DNA repair. Animal research has linked NAD+ decline to brain ageing, and NAD+ has been measured in human brain and cerebrospinal fluid in ageing studies. See our brain research guide.

Liver

The liver is central to NAD+ production from tryptophan and to clearing excess nicotinamide. Animal studies have found lower liver NAD+ with age and with high-fat diets.

Skin

Skin was the tissue studied in the Sydney research, and it is exposed to constant oxidative stress from sunlight, which may increase DNA damage and PARP activity.

Ovaries and eggs

Animal research has linked NAD+ decline to the ageing of eggs and the fall in fertility with maternal age, and precursors have been studied in those models. This is why “NAD levels and fertility” has become a common search, although human evidence remains limited.

Why There Is No Reliable NAD+ Chart by Age

Search for “NAD levels by age chart” and you will find graphics showing neat, steadily falling lines. The research does not support that level of precision, for several reasons.

Tissues differ

NAD+ levels vary widely between tissues, and they decline at different rates. A figure for skin tells you little about muscle or brain.

Blood is not the whole story

Blood is the easiest sample to take, but blood NAD+ levels do not necessarily reflect levels inside tissues.

Methods differ

Different laboratory methods, from enzyme-based assays to mass spectrometry, can give different numbers, and NAD+ breaks down quickly after samples are taken, so handling affects results.

People differ

Sex, health, activity, diet, sleep and the time of day all influence NAD+. Studies of different groups therefore produce different figures.

What can be said

What can be said with reasonable confidence is that, on average, NAD+ tends to be lower in older tissue than in younger tissue in the studies that have measured it. Any chart claiming exact percentages at each age goes beyond what the evidence supports.

How NAD+ Is Measured

In research laboratories

Researchers measure NAD+ in tissue samples and blood using enzyme cycling assays or, increasingly, liquid chromatography coupled with mass spectrometry, which can measure NAD+ alongside related molecules such as NADH, NMN, nicotinamide and their breakdown products. Samples must be processed quickly and kept cold to prevent breakdown.

Commercial tests

Commercial NAD+ tests, usually based on a blood sample, have become available. Because blood levels may not reflect tissue levels, and because reference ranges are not standardised, their results should be interpreted cautiously.

What Influences NAD+ Besides Age

Exercise

Endurance exercise increases NAMPT in muscle, boosting NAD+ recycling. Studies have found that physically active people tend to have higher muscle NAMPT than sedentary people.

Diet and calorie restriction

Calorie restriction and fasting activate sirtuins and influence NAD+ metabolism in animal research. Vitamin B3 intake provides the raw materials.

The body clock

NAMPT is controlled by the circadian clock, so NAD+ rises and falls through the day. Disrupted sleep and rhythms may therefore influence NAD+.

Metabolic health

Obesity and high-fat diets have been associated with lower NAD+ in several animal tissues.

Inflammation

Because CD38 is linked to inflammation, conditions with chronic inflammation may accelerate NAD+ consumption.

NAD+ Through the Whole Lifespan

It is sometimes assumed that NAD+ is highest in childhood and falls steadily from then on. The picture from research is less simple. The Sydney study included newborn skin as well as adult samples, and tissue NAD+ patterns early in life are influenced by rapid growth and development as well as by damage. In adulthood, the balance between NAD+ production and consumption shifts gradually, with consumption tending to rise as DNA damage and inflammation accumulate. Later in life, the combined effects of increased consumption and, in some tissues, reduced recycling become more pronounced. Rather than a single straight line, NAD+ across the lifespan is better thought of as a balance that tips gradually, and at different rates in different tissues and people.

Using NAD+ in Laboratory Research on Ageing

In the laboratory, NAD+ itself is used to test what happens when cells or enzymes have more NAD+ available, to study how extracellular NAD+ is broken down and taken up, and as a reference standard for measurement. Precursors, CD38 inhibitors and NNMT inhibitors are used to study how different parts of the NAD+ budget respond. Combining these tools lets researchers separate the effects of supply, recycling and consumption, which is essential for understanding age-related decline.

What Research Has Found About Restoring NAD+

In mice

In a 2016 study in Cell Metabolism, Mills, Imai and colleagues gave ageing mice the NAD+ precursor NMN for a year and found it mitigated several age-associated changes, including weight gain, reduced energy metabolism and declining insulin sensitivity (PMID: 28068222, PMC5668137).

In people

Human trials of precursors have been smaller and shorter. A 2018 trial found nicotinamide riboside raised NAD+ metabolism in middle-aged and older adults (PMID: 29599478, PMC5876407), and a 2021 trial found NMN improved muscle insulin sensitivity in women with prediabetes (PMID: 33888596, PMC8550608). Whether restoring NAD+ slows ageing in people has not been shown.

Other approaches

Researchers also study reducing NAD+ consumption, for example by inhibiting CD38, and protecting the supply of precursors. 5-Amino-1MQ inhibits NNMT, an enzyme that removes nicotinamide from the recycling loop. Our article NAD+ vs NMN compares the approaches, and NAD+ side effects covers what is known about tolerability.

What Lower NAD+ Might Mean

If NAD+ falls, several processes that depend on it could be affected at once. Energy production in mitochondria could become less efficient. DNA repair could fall behind. Sirtuins, which help regulate metabolism, inflammation and stress responses, could become less active. Research in animals has linked these changes to many features of ageing, from reduced muscle function to metabolic decline. Whether the NAD+ decline is a cause of ageing, a consequence of it or both is still debated. The PARP finding suggests it is at least partly a consequence of accumulating damage, while the benefits of restoring NAD+ in animals suggest it may also drive further decline, a possible vicious circle.

Inflammageing and NAD+

Ageing is accompanied by a persistent, low level of inflammation, sometimes called inflammageing. Because CD38 rises with inflammation and consumes NAD+, inflammageing may be one of the most important drivers of NAD+ decline. Senescent cells, which accumulate with age and release inflammatory signals, may encourage immune cells to increase CD38. This link between inflammation, the immune system and NAD+ is one of the most active areas of current research, and it ties NAD+ to our immune research guide.

Common Misconceptions About NAD+ and Age

“NAD+ halves by a certain age”

Specific figures like this are often quoted but are not supported by consistent evidence across tissues and methods.

“Blood tests show your true NAD+ level”

Blood levels may not reflect levels in muscle, brain or other tissues.

“The decline is the same for everyone”

Sex, activity, health and diet all influence NAD+, and the Sydney study found clear differences between males and females.

“Raising NAD+ reverses ageing”

Restoring NAD+ improved several age-related measures in mice, but human trials have found more modest, specific effects, and there is no evidence that it reverses ageing in people.

How Researchers Study NAD+ Decline in Animals

Much of what is known about why NAD+ falls comes from animal research, because animals can be studied across their whole lifespan under controlled conditions. Researchers compare young, middle-aged and old mice, measure NAD+ in many tissues at once, and use genetic models, such as mice lacking CD38 or with altered NAMPT, to test which enzymes drive the decline. The CD38 study is a good example: mice lacking the enzyme kept their NAD+ levels as they aged, strong evidence that CD38 is a major cause of the decline. These approaches cannot be used in people, which is why animal and human research complement each other.

Can NAD+ Decline Be Slowed?

Research points to several influences on NAD+ beyond supplying precursors. Regular endurance exercise increases the recycling enzyme NAMPT in muscle. Calorie restriction and fasting activate sirtuins and influence NAD+ metabolism in animals. Good sleep and stable daily rhythms support the circadian control of NAMPT. Reducing chronic inflammation may limit CD38 activity. None of these has been shown to prevent NAD+ decline entirely, and much of the evidence comes from animals, but together they suggest that NAD+ levels are shaped by how an organism lives as well as by its age.

What the Research Still Needs

Several gaps remain. Large human studies measuring NAD+ in multiple tissues across the full adult lifespan, using standardised methods, would finally establish how much it declines, where and in whom. Standardised reference ranges for blood tests would make commercial testing meaningful. And long-term trials would show whether restoring NAD+ changes the course of ageing in people, as it appears to in mice. Each of these is an active area of research.

Designing Research on NAD+ and Age

Compare ages directly

The clearest studies compare young and old animals, or younger and older people, under identical conditions, measuring NAD+ in the same tissues with the same methods.

Measure the drivers

Measuring PARP activity, CD38 levels, NAMPT and markers of DNA damage and inflammation, as the Sydney study did, helps explain why NAD+ changed, not just whether it did.

Include both sexes

Given the sex differences seen in human skin, both sexes should be included and analysed separately.

Control timing

Because NAD+ follows a daily rhythm, samples should be taken at consistent times.

NAD+ Inside the Mitochondria

Mitochondria hold their own pool of NAD+, which is essential for the reactions that turn fuel into energy. The mitochondrial sirtuin SIRT3 depends on it to keep the energy machinery running efficiently. The CD38 study found that age-related NAD+ decline reduced SIRT3 activity and impaired mitochondrial function in mice, linking the NAD+ budget directly to the mitochondrial decline seen in ageing. This is also where NAD+ research meets research on compounds that act directly on mitochondria, such as SS-31, which protects the inner mitochondrial membrane, and MOTS-c, a peptide encoded by the mitochondria themselves.

Why the Topic Attracts So Much Attention

NAD+ decline appeals to researchers because it offers something rare in ageing science: a measurable molecular change, with identifiable causes, that may be possible to reverse. Many hallmarks of ageing, such as accumulated DNA damage or mitochondrial dysfunction, are difficult to target directly. NAD+, by contrast, can be measured, its consumers can be inhibited and its supply can be topped up. That tractability, combined with the striking results in ageing mice, is why NAD+ has become one of the central molecules of modern longevity research.

The Technical Breakdown: The NAD+ Budget

It can help to think of NAD+ as a budget. Income comes from making new NAD+ from tryptophan or vitamin B3, and above all from recycling nicotinamide through NAMPT. Spending comes from sirtuins, PARPs and CD38, each of which breaks NAD+ into nicotinamide and another fragment. With age, spending rises, as PARPs respond to accumulating DNA damage and CD38 rises with inflammation, while income may fall if NAMPT activity declines. The balance tips, and NAD+ falls.

Why the sirtuins suffer

Sirtuins have a relatively low affinity for NAD+ compared with PARPs, so when NAD+ becomes scarce, PARPs tend to win the competition and sirtuin activity drops first. That may explain why the Sydney study found falling sirtuin activity alongside rising PARP activity.

Compartments

NAD+ exists in separate pools in the nucleus, cytoplasm and mitochondria, which are partly independent. A decline in one compartment may not be reflected in the others, adding another layer of complexity to measurement.

Related Compounds and Reading

Related compounds include MOTS-c, SS-31, Epitalon and Methylene Blue. Read best peptides for longevity research, Epitalon vs NAD+ and NAD+ vs MOTS-c, and browse the ageing and cellular research peptides category.

NAD+ Levels by Age: Questions, Answered

Do NAD+ levels decline with age?

Research has found lower NAD+ with age in several human and animal tissues, though the size of the decline varies between tissues and studies.

Is there a chart of NAD+ levels by age?

Not a reliable, standardised one. Levels depend on the tissue, the measurement method and the individual.

Why does NAD+ fall as we get older?

Mainly because consumption rises, as PARP enzymes respond to DNA damage and CD38 increases with inflammation, while recycling through NAMPT may become less efficient.

Can NAD+ levels be tested accurately?

Research laboratories measure NAD+ in tissues and blood. Commercial blood tests exist, but blood levels may not reflect tissue levels and reference ranges are not standardised.

Is NAD+ always highest in early childhood?

Not simply. Early-life levels are shaped by growth and development as well as damage, and the research is better described as a gradual shift in the balance between production and consumption through adulthood.

Do NAD+ precursors restore levels in older people?

Small human trials found that NR and NMN raised NAD+ metabolism, but whether this changes the course of ageing in people has not been shown.

What is the difference between NAD+ and NADH?

NAD+ is the form that accepts electrons; NADH is the form that carries them to the mitochondria. The ratio between them reflects the cell’s metabolic state.

Where can I read the studies?

Every study in this guide is linked to its PubMed record.

Does NAD+ decline the same way in men and women?

Not necessarily. The 2012 Sydney skin study found several age-related changes were stronger or only significant in males.

What is NAMPT?

The enzyme that controls the main NAD+ recycling pathway. Its activity follows the body clock and increases with exercise.

Why is NAD+ linked to fertility?

Animal research has linked NAD+ decline to the ageing of eggs, and precursors have been studied in those models. Human evidence is limited.

Is NAD+ decline a cause or a result of ageing?

Probably both. Accumulating DNA damage increases NAD+ consumption, and lower NAD+ may then impair repair and metabolism further.

What is inflammageing?

The persistent low-grade inflammation that accompanies ageing, which may drive NAD+ decline through the enzyme CD38.

Does regular exercise help raise NAD+?

Research indicates endurance exercise increases NAMPT in muscle, supporting NAD+ recycling.

A Budget Under Pressure

NAD+ does not simply run out with age. It is spent faster, as the body responds to accumulating damage and inflammation, and in some tissues it may be rebuilt more slowly. The research tells a consistent story about that shifting balance, while also warning against neat charts and one-size-fits-all numbers. For researchers, the most useful questions are not just how much NAD+ falls, but where it falls, why it falls, in whom it falls fastest and whether that fall can be slowed or reversed in ways that genuinely matter for health.

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