NAD+ is an enzyme aid that supports cellular nutrition and energy production for every living cell in your body. NAD+ primarily functions in our cell’s mitochondria, often nicknamed ”the powerhouse of the cell,” but it’s importance in our bodies was further highlighted by a group of scientists in Australia.
Hassina Massudi and a team of researchers from the University of New South Wales discovered that maintaining levels of NAD+ may play a role in aging.⁽¹⁾
The team's conclusions were based on studying NAD’s role in fueling the mechanisms needed to combat oxidative stress, which is a significant contributor to age-associated changes in the body.
Keep reading to learn more about NAD aging research, how NAD+ levels change throughout life, and what that means for healthy aging. In this article, we’ll explore groundbreaking findings, examine the latest research developments, and discuss practical ways to maintain NAD+ levels as you age.
Key Takeaways
- NAD+ levels naturally decline with age in both males and females, which can significantly impact cellular health.
- The Massudi NAD aging study found that NAD+ depletion affects both genders differently, with males showing more pronounced changes in oxidative stress and enzyme activity.
- Mitochondria are crucial in regulating cellular NAD+ levels, acting as "rheostats" to maintain balance when NAD+ levels drop.
- Multiple approaches can be used to maintain NAD+ levels, including supplementation, diet, exercise, and clinical treatments like IV therapy.
- Recent research suggests the gut microbiome plays an unexpected role in how effectively our bodies process NAD+ supplements and maintain NAD+ levels.
What Is NAD?
NAD (nicotinamide adenine dinucleotide) is a molecule found in every cell of your body. It’s a cellular multitool that helps convert the food you eat into cellular energy, repairs damaged DNA, and supports hundreds of important biological processes that keep you healthy.
When we talk about NAD+, we’re referring to NAD in its oxidized form. NAD+ helps your cells use produce energy, maintain healthy DNA, and regulate important proteins that influence aging.
Your body produces NAD+ naturally, but its levels tend to decrease as you age. This decline may contribute to various signs of aging and age-related health challenges.
What Is Oxidative Stress?
Our mitochondria convert food into cellular energy but produce a terrible byproduct in its manufacturing process called free radicals. Free radicals can cause cellular damage, wreaking havoc on our cellular function.
Usually, our bodies have a healthy amount of antioxidants to combat the problem, keeping a delicate equilibrium of free radicals and antioxidants.
However, sometimes, we demand a little more energy from our bodies. We may overexert ourselves, kicking our mitochondria into overdrive. This overproduction of energy shifts the balance of our free radicals to an unmanageable level, known as oxidative stress.
Factors like overtraining (intensive exercise), lack of exercise or a sedentary lifestyle, sleep deprivation, poor diet, drinking, smoking, and viral infections can all lead to oxidative stress.
How Does Oxidative Stress Connect to Aging?
In 1954, biochemist Dr. Denham Harman proposed the “Free Radical Theory of Aging,” hypothesizing that people age because of the imbalance of free radicals due to their role in damaging proteins, cell membranes, and DNA.⁽²⁾
But later, in 2018, physiologist Dr. José Viña and his colleagues unveiled “A Free Radical Theory of Frailty,” arguing that free radicals do not necessarily dictate how long we live. Instead, Viña hypothesized the excess of free radicals causes frailty in older people, leading to a decline in their overall quality of life.⁽³⁾
Whichever theory posits our understanding in the future, scientists universally agree that an excess of free radicals is a detriment to one’s health, and perhaps, Viña’s approach more so questions how we define aging. Maintaining our well-being as we age is just as much a human desire as lengthening our lifespan.
Excitingly, the research from Massudi and the team in New South Wales shows a strong connection between the presence of NAD+ and oxidative stress, thus underlining NAD’s importance in how we age.
The NAD Aging Study Design
The NAD aging study obtained human skin samples from consenting patients scheduled for surgery at the Sydney Adventist Hospital in Australia. Participants included patients aged 15-77 and newborn babies.
Researchers removed skin tissue from non-sun-exposed areas of the pelvic region to study the least environmentally affected samples from their subjects.
The study monitored the following in correspondence with NAD+ to assess if NAD+ levels are linked to age-associated changes in our body:⁽¹⁾
1. Lipid peroxidation
Lipid peroxidation is a form of oxidative stress that specifically targets and breaks down the lipids (fats) that make up our cell membranes. This process is one of the earliest signs of oxidative stress in our bodies. When lipid peroxidation occurs, it creates compounds called malondialdehyde (MDA), which can damage cell membranes and other important cellular components.
2. Oxidative DNA damage
DNA is highly vulnerable to oxidative stress. The study used phosphorylated H2AX as a marker to measure DNA damage, showing significant increases with age in both males and females. When left unrepaired, this damage can lead to serious consequences, either triggering cell death or causing mutations that alter our genetic information.
3. PARP activity
PARPs (Poly ADP-ribose polymerases) are crucial proteins that activate in response to DNA damage. They play essential roles in DNA repair, maintaining genomic stability, and regulating programmed cell death. The study found that PARP activity significantly increased with age in adult subjects compared to newborns, with males showing a particularly strong correlation with age. Importantly, increased PARP activity was found to deplete cellular NAD+ levels.
4. Sirtuin 1 activity
SIRT1 regulates important cellular processes through NAD+-dependent reactions. The study found that SIRT1 activity declined with age in males but, interestingly, not in females. SIRT1 plays a vital role in regulating cell metabolism, stress responses, and aging processes by modifying the activity of other proteins.
The NAD Aging Research Results
- NAD+ levels declined with age in both males and females.
- Lipid oxidation increased with age in males.
- DNA damage correlated strongly with age in both males and females.
- PARP activity significantly increased with age in males but was less evident in females.
- SIRT1 activity negatively correlated with age in males.
The Latest NAD Aging Research
Since Massudi and the team's groundbreaking work in New South Wales, research has continued to deepen our understanding of NAD+'s critical role in aging and health. Recent NAD and reverse aging studies have revealed fascinating new insights about how NAD+ levels affect our cells and overall health as we age.
Mitochondrial NAD+ management and aging
A 2024 study published provided a crucial breakthrough in understanding how cells manage NAD+ levels. The researchers discovered that mitochondria act as cellular "rheostats" for NAD+, helping maintain balance when NAD+ levels drop. This explains why cells can often tolerate age-related NAD+ decline, but only if the mitochondrial NAD+ pool remains protected. This finding may help explain why some tissues are more vulnerable to aging than others.⁽⁴⁾
NAD+ therapeutic applications
New research explored NAD+'s therapeutic potential across different age-related diseases. The study found that NAD+ precursors showed promising results in treating various conditions, from metabolic disorders to cardiovascular issues. However, the researchers also highlighted an important discovery: the gut microbiome plays a previously unknown role in how effectively our bodies process NAD+ boosters, also known as NAD+ precursors, in food-grade supplement form.
Enzyme regulation and NAD+
Perhaps most intriguingly, a comprehensive review revealed that NAD+ levels don't just passively decline with age—they're actively regulated by several enzymes that either produce or consume NAD+. The study found that targeting these enzymes, particularly CD38 and PARP1, might be just as important as NAD+ supplementation in maintaining healthy aging.⁽⁶⁾
These recent findings suggest that while Massudi's original insights about NAD+'s role in aging were correct, the picture is more complex than initially thought. The interplay between NAD+ levels, mitochondrial function, and enzyme activity creates a sophisticated network that influences how we age and how we might intervene in that process.
How to Maintain or Increase NAD+ Levels to Promote Healthy Aging
Scientific research has identified multiple effective ways to maintain and boost NAD+ levels in our bodies. From targeted supplements to lifestyle changes, these approaches can help support NAD+ production and utilization, potentially slowing age-related decline and promoting better cellular health.
- NAD supplementation: Direct supplementation with NAD+ precursors like nicotinamide riboside (NR) has shown promising results in clinical studies. Tru Niagen supplements contain a research-backed, patented form of NR that's been clinically proven to increase NAD+ levels safely and effectively. These supplements represent one of the most direct ways to boost NAD+ levels.
- IVs and injectables: Premier wellness clinics now offer NAD+ therapy through intravenous delivery and injectable treatments using NiagenPlus, a pharmaceutical-grade Niagen to boost NAD+ levels. These clinical treatments provide a more direct route to increase NAD+ levels and may offer faster results than oral supplements.
- Diet: Several foods naturally support NAD+ production, including fish, mushrooms, and whole grains.
- Exercise: Regular exercise naturally increases NAD+ levels by activating NAMPT, a key enzyme in NAD+ production. Even moderate physical activity can help maintain healthy NAD+ levels.
What Are Additional Benefits of Maintaining NAD+ Levels?
While NAD+'s role in aging is well documented, scientists have found that maintaining healthy NAD+ levels supports multiple aspects of health throughout the body. This molecule works at the cellular level to influence everything from energy production to brain health, making it fundamental to overall wellness.
- Increased cellular energy and mitochondrial function: NAD+ is a crucial component in energy production, helping mitochondria efficiently convert food into fuel (ATP). When NAD+ levels are boosted, cells can efficiently produce energy, potentially leading to more efficient cellular function throughout the body.
- Enhanced DNA repair and reduced cellular damage: NAD+ powers enzymes called PARPs that are essential for repairing damaged DNA strands. Increased NAD+ levels help ensure these repair mechanisms can work efficiently, helping protect cells from accumulating damage over time.
- Support for brain health: NAD+ supports brain health by maintaining proper neuron function and energy metabolism.
- Support for skin health and aging: NAD+ may help maintain skin cell vitality by supporting energy production and repair processes at the cellular level. Higher NAD+ levels may enable skin cells to better defend against environmental damage and maintain their natural renewal processes.
NAD+ and Aging FAQs
Can NAD+ help support healthy aging?
Research into NAD+ has uncovered promising potential to support healthy aging and healthspan. Clinical studies examining NAD+ supplementation and its effects on various conditions have provided compelling evidence for its therapeutic potential. However, more research is needed to confirm these findings.
- Cardiovascular health: Clinical studies have shown that NAD+ may support heart health, by supporting heart cell energy production, cardiovascular function as we age.
- Muscle health and recovery: NAD+ plays a vital role in muscle health by supporting energy production and repair processes. Maintaining adequate NAD+ levels may help preserve muscle health with age while potentially supporting recovery after activity.
At what age does NAD+ start to decline?
NAD+ levels begin to decline naturally as early as our thirties, with research showing a dramatic drop of up to 65% by the time we reach age 70. This significant decrease happens gradually over time and affects multiple aspects of cellular function and health. Fortunately, through NAD+ supplementation and healthy lifestyle habits, you can combat age-related decline.
Can boosting NAD+ levels slow down aging?
NAD aging research is showing promising results about NAD+'s role in slowing down or mitigating age-related effects. Studies have demonstrated that boosting NAD+ levels can help support cellular health and improve various age-related functions, including cellular energy production, DNA repair, and metabolic efficiency.
However, scientists are still conducting research to fully understand how NAD+ supplementation affects human longevity. Current evidence suggests that while NAD+ plays an important role in healthy aging, it's likely one piece of a larger puzzle.
NAD Aging Study: Unlocking the Science Behind Longevity
The study developed by Massudi and the team provides quantitative evidence that the depletion of NAD+ may play a significant role in the aging process by limiting energy production, DNA repair, and genomic signaling.
Further study into the potential of boosting NAD+ with supplements or by natural means could unlock more curious findings. Already paving the road, a paper published in the Translational Medicine of Aging shows the therapeutic potential of boosting NAD+ as we age.⁽⁷⁾
Whether solving the puzzle of oxidative stress will lead to a longer lifespan or a better quality of life as we age, continued NAD+ research may redefine the boundaries of the aging process.
References:
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Massudi, Hassina, et al. “Age-Associated Changes in Oxidative Stress and NAD+ Metabolism in Human Tissue.” PLOS ONE, Public Library of Science, journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0042357
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Gladyshev, Vadim N. “The Free Radical Theory of Aging Is Dead. Long Live the Damage Theory!” Antioxidants & Redox Signaling, U.S. National Library of Medicine, 1 Feb. 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC3901353/.
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Viña, Jose, et al. “A Free Radical Theory of Frailty.” Free Radical Biology & Medicine, U.S. National Library of Medicine, 20 Aug. 2018, www.ncbi.nlm.nih.gov/pubmed/29958933.
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Høyland, Lena E et al. “Subcellular NAD+ pools are interconnected and buffered by mitochondrial NAD.” Nature metabolism vol. 6,12 (2024): 2319-2337. doi:10.1038/s42255-024-01174-w
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Iqbal, Tooba, and Takashi Nakagawa. “The Therapeutic Perspective of NAD+ Precursors in Age-Related Diseases.” Biochemical and Biophysical Research Communications, Academic Press, 2 Feb. 2024, www.sciencedirect.com/science/article/pii/S0006291X24001256.
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Poljšak, Borut, et al. “The Central Role of the NAD+ Molecule in the Development of Aging and the Prevention of Chronic Age-Related Diseases: Strategies for NAD+ Modulation.” MDPI, Multidisciplinary Digital Publishing Institute, 3 Feb. 2023, www.mdpi.com/1422-0067/24/3/2959.
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Arman, Yahyah, et al. “Therapeutic Potential of Boosting NAD+ in Aging and Age-Related Diseases.” Translational Medicine of Aging, Elsevier, 18 Aug. 2018, www.sciencedirect.com/science/article/pii/S2468501118300063?via%3Dihub