What is NMN?

What is NMN?

The Science Behind NMN

Delving into the science behind NMN, or Nicotinamide Mononucleotide, reveals a fascinating world of cellular processes and potential health benefits. This compound, a derivative of vitamin B3, plays a crucial role in our bodies, particularly in the realm of aging.

Our first stop on this scientific journey is the body itself. Here, we'll explore how NMN is produced and its role in our cells, as well as its relationship with NAD+ metabolism. This understanding lays the foundation for our exploration of the potential health benefits of NMN, from improving vascular health to boosting memory in elderly mice and reducing DNA damage.

The benefits of NMN aren't limited to humans. Animal models, particularly mice, have shown promising results when their NAD+ metabolism is boosted with NMN. These studies have paved the way for preclinical and clinical testing of NMN in humans, with potential effects of supplementation being closely monitored.

Beyond internal health, NMN also shows promise in the realm of skin treatments. The potential of NMN for skin health and its role in anti-aging skin products is an exciting area of research.

As we look to the road ahead, the future of NMN research and its potential in anti-aging medicine is bright. Join us as we delve deeper into the science behind NMN, exploring the studies and research that are shaping our understanding of this fascinating compound.

How Is NMN Made in the Body?

Nicotinamide Mononucleotide (NMN) is a crucial molecule that plays a significant role in our body's metabolic processes. It's primarily synthesised from a form of vitamin B3, known as nicotinamide (NAM), through the action of an enzyme called NAMPT (nicotinamide phosphoribosyltransferase). This enzyme is the key player in the conversion of NAM into NMN, a process that occurs within our cells.

Interestingly, our fat tissue also contributes to the synthesis of NAD+, another vital molecule, by secreting sacs filled with NAMPT or NMN. These sacs, known as extracellular vesicles, circulate in the bloodstream, delivering NAMPT and NMN to cells, thus providing them with the necessary tools and materials to produce NAD+.

In addition to this, NMN can also be converted from an NAD+ precursor called nicotinamide riboside (NR) by an enzyme named NRK (nicotinamide riboside kinase). This process, along with the direct movement of NMN into cells through a transporter named Slc12a8, further underscores the importance of NMN in our body's metabolism and overall health.

The Role of NMN in Cells

NMN, or nicotinamide mononucleotide, plays a crucial role in the cells of our bodies. It's a key component in the creation of NAD+, a molecule that's essential for various cellular functions. Without NMN, the production of NAD+ would be significantly hindered, leading to potential issues with cell health and function.

Interestingly, our cells have a unique way of transporting NMN. They use extracellular vesicles, which are essentially tiny sacs that can carry substances like NMN around the body. These vesicles can unload NMN directly into cells, providing them with the necessary materials to produce NAD+. This process is a natural and efficient way of ensuring that our cells have access to the NMN they need.

However, as we age, the levels of NMN, NAD+, and the enzyme NAMPT, which is involved in NMN synthesis, all decline. This decline can have a significant impact on our cells' ability to function properly, contributing to the ageing process and potentially leading to various age-related diseases. Therefore, understanding the role of NMN in cells and how it's transported and utilised is crucial in the field of anti-ageing research.

NMN and NAD+ Metabolism

NMN plays a pivotal role in the metabolism of NAD+, a molecule that is essential for energy production and cellular health. The process begins with the conversion of nicotinamide (NAM), a form of vitamin B3, into NMN by an enzyme called NAMPT. This conversion is a crucial step in the NAD+ metabolic pathway, as NMN is a direct precursor to NAD+.

As we age, the levels of NAD+, NMN, and NAMPT in our bodies decline, which can lead to a variety of age-related health issues. This is where NMN steps in, acting as a supplement to boost NAD+ levels and potentially counteract these effects. When NMN is introduced into the body, it can be converted into NAD+ in cells, thereby replenishing the body's NAD+ levels.

Interestingly, our fat tissue may also play a role in regulating NAD+ synthesis. It secretes membrane-bound sacs filled with NAMPT or NMN, which circulate in the bloodstream and can deliver these essential components into cells. This process provides cells with the necessary tools and materials to produce NAD+, further highlighting the interconnectedness of NMN and NAD+ metabolism.

The Anti-Aging and Health Benefits of NMN

The anti-aging and health benefits of NMN are a topic of growing interest in the scientific community. This compound, a precursor to the essential enzyme NAD+, has shown promising results in various studies, particularly in relation to aging and age-related conditions. The potential of NMN to improve vascular health, boost memory in elderly mice, and reduce DNA damage has been explored, with findings suggesting it could be a key player in promoting longevity and overall health.

In the following sections, we delve into the specifics of these benefits, examining the role of NMN in vascular health, memory enhancement in elderly mice, and DNA damage reduction. We'll explore the science behind these effects, shedding light on how NMN could potentially revolutionise our approach to aging and health.

NMN Improves Vascular Health

The health of our blood vessels is a critical factor in the aging process, and NMN has shown promising results in improving vascular health. In studies involving elderly mice, oral administration of NMN led to a significant enhancement in their vascular system. This was evidenced by an increase in the number of capillaries, small blood vessels crucial for efficient blood flow. The mice also exhibited improved endurance, indicating increased blood flow to their muscles.

Two key indicators of vascular health are Endothelium-dependent dilation (EDD) and vascular stiffness. EDD is a measure of the health of the endothelium, the cells lining the blood vessels. A healthy endothelium is less prone to atherosclerosis, a condition where the blood vessels become clogged. Vascular stiffness, on the other hand, increases with age due to various aging processes and an unhealthy lifestyle. NMN has been shown to improve both EDD and vascular stiffness, reducing oxidative stress in the blood vessel walls. This suggests that NMN can play a significant role in maintaining vascular health, thereby slowing down the aging process.

NMN Boosts Memory in Elderly Mice

The cognitive prowess of elderly mice has been shown to significantly improve with NMN supplementation. In a fascinating study, the working memory of aged mice receiving NMN was not only enhanced compared to their counterparts not receiving NMN, but these elderly NMN mice performed on par with their younger counterparts. This is a remarkable finding, suggesting that NMN has the potential to reverse age-related cognitive decline.

In the context of neurodegenerative diseases, NMN has demonstrated promising results in treating Alzheimer’s disease in mice. The compound slows cognitive decline by promoting the survival of neurons, which are the building blocks of the nervous system. This suggests that NMN could potentially be used as a therapeutic agent in the treatment of Alzheimer's disease and other neurodegenerative conditions. The ability of NMN to maintain the integrity of the blood-brain barrier further underscores its potential in preserving brain health.

NMN Reduces DNA Damage

The ability of NMN to reduce DNA damage is a significant aspect of its anti-aging and health benefits. As we age, our DNA becomes increasingly damaged, leading to a host of health issues and contributing to the aging process. This damage, even when repaired, can leave behind 'epigenetic scratches' that contribute to epigenetic dysfunction, a key factor in aging. NMN, however, has been shown to reduce this DNA damage in cells, thereby potentially slowing down the aging process and improving health.

In a study involving mice, it was found that old mice treated with NMN had significantly less severe DNA damage, as indicated by lower levels of y-H2AX, compared to untreated old mice. This suggests that NMN can effectively reduce DNA damage, which is a crucial factor in aging and health. Another study showed that mice given NMN before being exposed to radiation had significantly higher red blood cell levels, indicating less DNA damage, compared to irradiated mice that didn't receive NMN. These studies highlight the potential of NMN in reducing DNA damage, thereby contributing to its anti-aging and health benefits.

Benefits of Boosting NAD+ Metabolism in Animal Models

The potential of Nicotinamide Mononucleotide (NMN) in slowing down the ageing process has been a subject of extensive research in recent years. NMN, a precursor of Nicotinamide Adenine Dinucleotide (NAD+), has shown promising results in animal models, particularly in mice, where it has been observed to extend healthspan and mitigate premature ageing diseases. The role of NMN in enhancing energy metabolism, improving insulin sensitivity, and preventing age-linked changes in gene expression is noteworthy. This section delves into the benefits of boosting NAD+ metabolism in animal models, focusing on the effects of NMN on ageing and metabolism in mice.

NMN and Aging in Mice

The potential of NMN in slowing down the aging process has been extensively studied in mice. In these animal models, NMN has shown promising results in treating age-related conditions such as Alzheimer's disease. It has been observed that NMN supplementation can slow cognitive decline by promoting the survival of neurons, thereby maintaining the integrity of the blood-brain barrier.

In addition to this, NMN has also been found to restore the muscles of aged mice, reducing age-associated weight gain and improving physical activity. At a cellular level, NMN boosts energy metabolism, combats oxidative stress, and reduces inflammation, all of which are crucial in promoting overall health and longevity.

Furthermore, NMN has been found to be safe and well-tolerated in mice, even after over a year of supplementation. This suggests that long-term NMN supplementation could potentially be a viable strategy for slowing down the aging process in humans. However, more research is needed to fully understand the 'good' and 'bad' effects of NMN in neurons and to determine its potential clinical benefits.

NMN and Metabolism

In the realm of animal models, NMN has shown promising results in boosting metabolism, particularly in mice. A series of studies have demonstrated that NMN supplementation can significantly enhance metabolic health in these creatures. The key to this lies in the role of NMN in the production of NAD+, a crucial molecule that fuels cellular functions.

In one study, mice were given NMN, and the results were remarkable. The mice exhibited improved energy metabolism, which led to enhanced physical performance. This was attributed to the increased levels of NAD+ in their cells, which boosted their metabolic functions. The study also noted that the mice had improved insulin sensitivity, a critical factor in maintaining metabolic health.

In another study, NMN was found to reduce age-associated weight gain in mice. This was linked to the role of NMN in enhancing NAD+ levels, which in turn improved the metabolic functions of the mice. The study concluded that NMN could potentially be used as a strategy to combat metabolic disorders associated with aging. These findings underscore the potential of NMN in boosting metabolism, not just in mice, but possibly in humans as well. However, more research is needed to fully understand the implications of these findings.

From Preclinical to Clinical Testing of NMN

The journey of NMN from preclinical studies to clinical trials is a fascinating one, filled with both promise and challenges. The potential of NMN, a precursor of the essential enzyme NAD+, to reverse age-related decline in the body has been demonstrated in cell and animal studies. However, the translation of these findings to humans has been a complex process. This section delves into the progression of NMN from laboratory studies to human trials, exploring the potential effects of NMN supplementation and the hurdles encountered along the way. As we navigate through this scientific journey, we'll uncover the rigorous process of bringing a promising compound from the lab bench to the bedside.

NMN in Human Trials

The journey of NMN from preclinical to clinical trials has been a fascinating one. The first human trial of NMN was conducted by researchers at Keio University School of Medicine in 2016. They administered NMN to ten healthy Japanese men and found it to be safe and effectively metabolised, with no significant adverse effects. This was a significant milestone in the research of NMN, as it demonstrated its potential for human use.

The study was followed by another trial led by Klein and his team, who evaluated the metabolic effects of NMN in postmenopausal women over 55 years of age. The women were given 250 mg of NMN orally daily for 10 weeks. The results were mixed; while NMN improved glucose uptake by muscles in response to insulin, other expected effects such as lower blood glucose or blood pressure were not observed. This suggested that the dose or duration of treatment may not have been adequate.

Despite these initial trials, the effects of NMN in humans are still not fully understood. More clinical trials are needed to establish therapeutic and toxic dose ranges of NMN. These trials should include both males and females and be conducted in healthy and disease states. As Klein points out, "NMN needs to be tested in more people and for longer periods of time to determine if it has anti-ageing effects in humans." The journey of NMN from preclinical to clinical trials continues, with the hope of unlocking its full potential.

Potential Effects of NMN Supplementation

While the potential benefits of NMN supplementation have been extensively studied in animal models, the translation of these effects to humans is still in its early stages. In rodent studies, NMN has shown promising results in treating age-related conditions such as Alzheimer's disease, diabetes, and obesity. It has been found to improve insulin secretion, enhance insulin sensitivity, reduce weight gain, improve eye function, and boost energy metabolism. Furthermore, NMN has demonstrated its ability to combat oxidative stress, reduce inflammation, promote mitochondrial health, and even restore the muscles of aged mice.

However, the effects observed in humans have been less pronounced. In a small clinical trial involving postmenopausal women with prediabetes, NMN supplementation improved insulin muscle sensitivity but did not translate into other metabolic benefits observed in rodent models. This could be due to several factors, including intrinsic differences between rodents and humans, or the dose or duration of treatment may not have been adequate.

Despite these initial findings, researchers remain optimistic about the potential of NMN supplementation in humans. Ongoing clinical trials are investigating the long-term effects of NMN on glucose metabolism and hormone levels in healthy adults. The results of these studies will provide valuable insights into the potential of NMN as a therapeutic agent for age-related conditions. However, it is important to note that more extensive research is needed to establish the therapeutic and toxic dose ranges of NMN in humans.

NMN and Skin Treatments

The potential of NMN (Nicotinamide Mononucleotide) in skin treatments is a rapidly growing area of interest in the scientific community. Recent studies have shown that NMN, when combined with certain bacteria, can protect the skin from damage caused by ultraviolet B irradiation, a leading cause of premature skin ageing. This has led to the development of innovative skin-penetration technologies that allow NMN to enter human skin cells, potentially suppressing cell ageing and boosting cell division, mitochondrial activity, and hyaluronic acid production.

The use of NMN in anti-aging skin products is also gaining traction. A cream containing NMN and a proprietary system designed to stimulate autophagy, the process of eliminating damaged or unnecessary cellular components, is currently being tested for its effectiveness on middle-aged individuals.

However, while the potential benefits of NMN for skin health are promising, it's important to note that further research is needed to fully understand its effects and establish safe and effective dosage ranges. As the global NMN market continues to grow, the need for rigorous scientific investigation into NMN and skin treatments becomes increasingly crucial.

The Potential of NMN for Skin Health

The potential of NMN for skin health is a burgeoning area of research, with scientists exploring its ability to combat the effects of ageing on the skin. A key study demonstrated that NMN, when combined with the intestinal bacteria Lactobacillus fermentum TKSN041, could protect mouse skin from damage caused by ultraviolet B irradiation, a primary cause of premature skin ageing. This effect was observed even though NMN was delivered intragastrically, as its high water solubility prevents it from passing through the skin barrier.

Yoshihiro Uto, a researcher at Tokushima University in Japan, has been developing a skin-penetration technology that allows NMN to enter human skin cells. His team is investigating whether administering NMN to skin cells using this particle delivery system can suppress cell ageing and stimulate cell division, mitochondrial activity, and hyaluronic acid production. Hyaluronic acid, a naturally occurring sugar molecule found in the skin, eyes, and joints, binds water, helping to retain moisture and improve skin elasticity and firmness.

Uto and his colleagues have developed a cream containing NMN and a proprietary system designed to stimulate autophagy, the process that eliminates damaged or unnecessary cellular components. They are currently testing its effectiveness on middle-aged individuals. This research underscores the potential of NMN in skin health, particularly in the context of anti-ageing treatments.

NMN and Anti-Aging Skin Products

NMN's potential as an anti-aging solution has led to its incorporation in various skin products. Researchers, like Yoshihiro Uto at Tokushima University, have been developing innovative ways to deliver NMN to skin cells. They've created a cream containing NMN and a proprietary system designed to stimulate autophagy, a process that eliminates damaged or unnecessary cellular components. This cream is currently being tested on middle-aged individuals to assess its effectiveness.

The inclusion of NMN in skincare products is based on its ability to boost the production of hyaluronic acid, a sugar molecule that helps retain moisture and improve skin elasticity. By enhancing hyaluronic acid production, NMN could potentially slow down the skin aging process, leading to firmer, more youthful-looking skin.

However, it's important to note that while NMN shows promise, more research is needed to fully understand its effects on human skin. As the global NMN market continues to grow, it's crucial to ensure that the science supports the claims made by these anti-aging skin products.

The Road Ahead

As we delve deeper into the realm of anti-aging medicine, the potential of Nicotinamide mononucleotide (NMN) continues to pique the interest of scientists and health enthusiasts alike. The journey of NMN from being a compound derived from natural sources to a commercially available anti-aging product has been intriguing, but the road ahead is even more promising.

The future research on NMN is set to focus on its effectiveness and safety, with more clinical trials being planned. These trials are crucial in establishing therapeutic and toxic dose ranges of NMN, and in understanding its long-term effects on healthy individuals. The challenges that lie ahead include the development and delivery of NMN-containing products, and the potential interference of the gut microbiome with NMN metabolism.

The potential of NMN in anti-aging medicine is vast. As the body ages, the levels of Nicotinamide adenine dinucleotide (NAD), a compound that supplies energy to cells, deplete. NMN, being a precursor to NAD, aids in its absorption, thereby potentially slowing down the aging process. However, the effectiveness and safety of NMN supplements need to be further validated through rigorous clinical trials. The results of these trials will not only deepen our understanding of NAD+-boosting therapies but also pave the way for expanding healthy longevity.

Future Research on NMN

The path forward for NMN research is laden with both challenges and opportunities. The need for more comprehensive studies on NMN's impact on human health is clear. This includes understanding its effects on the epigenome, transcriptome, proteome, and metabolome, as well as its interaction with the gut microbiome.

Clinical trials are also crucial to establish therapeutic and toxic dose ranges of NMN. These trials should be inclusive, involving both genders and a range of health conditions. However, the current status of NMN as a food product rather than a regulated therapeutic drug presents a hurdle. The financial burden of these studies is significant, requiring funding from government grants, foundations, or industry.

Despite these challenges, the scientific community remains committed to exploring the potential of NMN. Ongoing trials, such as those led by Keio University School of Medicine and Hiroshima University, are expected to provide valuable insights into the long-term effects of NMN. The results of these studies will be instrumental in shaping the future of NMN research and its potential role in anti-aging medicine.

The Potential of NMN in Anti-Aging Medicine

The potential of NMN in anti-aging medicine is vast, with promising results already seen in animal studies. The ability of NMN to suppress age-associated weight gain, enhance energy metabolism, and improve insulin sensitivity, among other benefits, has sparked interest in its potential application in humans.

However, the journey from animal studies to human application is not straightforward. The effects of NMN in neurons, for instance, are complex and require further investigation. An increased intracellular NMN/NAD+ ratio could activate SARM1, an executor of axon degeneration, which could potentially counteract the benefits of NMN.

Despite these challenges, the potential of NMN in anti-aging medicine remains high. With further research and a better understanding of its effects, NMN could become a key player in the fight against aging and age-related diseases. The journey is long, but the destination could be revolutionary.

Are You Maximizing Your Lifespan Potential?

The science behind NMN is compelling, with numerous studies demonstrating its potential to slow down and even reverse certain symptoms of aging. By boosting NAD+ metabolism, NMN can improve various aspects of health, from vascular function to memory in elderly mice. It's also shown promise in reducing DNA damage, a key factor in aging.

The potential of NMN extends beyond just internal health. It's also being explored for its potential in skin treatments, with early research suggesting it could play a role in anti-aging skin products. However, it's important to remember that while NMN shows promise, it's not a magic bullet for aging. Aging is a complex process influenced by many factors, and NMN is just one piece of the puzzle.

Clinical trials are underway to further explore the effects of NMN supplementation in humans. These studies will provide valuable insights into the potential of NMN in anti-aging medicine. As we continue to understand more about NMN and its role in the body, we can better harness its potential to improve health and extend lifespan.

In conclusion, NMN holds significant potential for enhancing health and slowing the aging process. However, it's important to approach it as part of a broader strategy for health and longevity, rather than a standalone solution. As research continues, we can look forward to a future where NMN plays a key role in maximizing our lifespan potential.

 

Researched and reviewed by Dr Elena Seranova, Ph.D.

Dr Seranova holds an M.Sc in Translational Neuroscience from the University of Sheffield, UK, and a Ph.D in Stem Cell Biology and Autophagy from the University of Birmingham, UK. She is a published author in multiple peer-reviewed journals, including Cell Reports and Developmental Cell.