Why NAD+ Matters

NAD+ is essential for over 500 cellular processes, from powering mitochondria to activating sirtuins, proteins that regulate aging and health. As we age, NAD+ declines due to increased consumption (e.g., DNA repair) and reduced synthesis, contributing to fatigue, metabolic issues, and disease vulnerability. Boosting NAD+ through precursors—molecules the body converts into NAD+—is a hot topic in longevity circles, promising to restore cellular resilience.

Harvard longevity expert David Sinclair is a vocal proponent of NAD+ boosting. He argues that NAD+ decline accelerates aging by impairing sirtuins, which maintain cellular health. His groundbreaking mouse studies show that nicotinamide mononucleotide (NMN) restores NAD+ levels, reversing mitochondrial aging and boosting vascular health and lifespan. Sinclair himself takes 1g of NMN daily, paired with resveratrol to enhance sirtuin activity. However, he acknowledges human evidence is still emerging, and his commercial ties to NAD+-related ventures have sparked debate. More human trials are needed to confirm his findings.

How NAD+ Precursors Work

NAD+ precursors feed into the body’s salvage pathway, efficiently replenishing NAD+. Here’s a quick look at the key players:

• Nicotinamide Riboside (NR): Converts to NMN via NRK enzymes, then to NAD+. It boosts muscle NAD+ by ~60%, enhancing energy and reducing inflammation.
• Nicotinamide Mononucleotide (NMN): One step from NAD+, NMN rapidly raises levels in the liver and brain, improving insulin sensitivity. It may convert to NR for cell entry.
• Nicotinamide (NAM) & Nicotinic Acid (NA): NAM recycles to NMN, but high doses may inhibit sirtuins. NA forms NaMN but causes flushing.
• Reduced Precursors (NRH/NMNH): These bypass rate-limiting enzymes for faster NAD+ production but may increase inflammation in some cells.

Precursors restore NAD+ to support metabolism and repair, though excessive doses risk methylation strain or other side effects.

The Science So Far

Mouse studies, including Sinclair’s, show NMN and NR extend lifespan and improve health metrics like endurance and vascular function. Human trials, however, are smaller and less conclusive. NMN (250–500 mg/day) has improved sleep in older adults and insulin sensitivity in prediabetic women, while NR reduces inflammation. Experts like Daniel Craighead and Jonas Thue Treebak caution that evidence for human lifespan extension is thin, with stronger benefits seen in conditions like prediabetes or age-related diseases.

Longevity Supplementation Trends

• Popular Choices: NMN (250–1,000 mg/day) or NR (e.g., Tru Niagen, 250–500 mg/day), often paired with resveratrol, metformin, or senolytics like fisetin.
• Methods: Oral capsules are most common, with sublingual forms for faster absorption. IV infusions ($200–$500/session) are pricier and less studied.
• Lifestyle Boosts: Fasting, exercise, and low-carb diets enhance NAD+ via NAMPT enzyme activity. X users (e.g., @BiohackerX, July 2025) report mixed results, with some feeling energized and others noticing little change.

Risks and Considerations

NAD+ precursors are sold as supplements, often unregulated by the FDA, leading to inconsistent dosages and unverified claims. NMN’s supplement status was questioned in 2022, reclassified as a drug. While short-term use is safe, long-term risks like liver strain or potential cancer promotion (in mice) remain unclear. Side effects include headaches or nausea. Researchers like Eduardo Chini and Joseph Baur suggest NAD+ therapies may better target diseases (e.g., Parkinson’s, heart disease) than general aging, urging caution against overhyped commercial products.

The NOMIX Take

At NOMIX, we’re excited about NAD+’s potential but grounded in science. Precursors like NMN and NR show promise, especially for metabolic and cognitive health, but they’re not a magic bullet. Pairing supplementation with healthy habits—exercise, fasting, and a balanced diet—maximizes benefits. Stay curious and cautious: consult your biocoach or doctor, choose reputable brands, and start with low doses.

The post Boosting Longevity with NAD+: Insights, Science, and Recommendations appeared first on NOMIX.

These misunderstandings not only hinder a deeper understanding of the concept of longevity but also perpetuate misconceptions that can lead to an inaccurate perception of what it truly entails. In this blog post, we will delve into these misconceptions and provide clarity on the true nature of the longevity lifestyle.

Misconception #1: Longevity means living as long as possible, but not necessarily in good health.

This misconception stems from the assumption that the goal of longevity is to simply live longer, regardless of one’s health status. However, the true objective of longevity is to achieve not only a longer lifespan but also a healthier and more vibrant one. – in other words: longevity aims to match lifespan with healthspan. The idea that longevity is solely about living longer, without considering the quality of life during those additional years, is a common misperception that needs to be addressed.

In reality, longevity is about optimizing both the quantity and quality of life. It’s about enjoying a longer and healthier existence, free from chronic diseases, and maintaining a high level of physical and mental well-being. This is why proponents of longevity advocate for a holistic approach that encompasses a healthy diet, regular exercise, stress management, and a strong social support network.

Misconception #2: The longevity lifestyle involves giving up everything nice in life, sacrificing pleasure for the sake of longevity.

This misconception is rooted in the belief that adopting a longevity lifestyle means abandoning all the pleasures and indulgences of life, such as fine dining, travel, and socializing. This could not be further from the truth. The longevity lifestyle is not about denying oneself the things that bring joy and fulfillment; rather, it’s about finding a healthy balance between pleasure and well-being.

A true longevity lifestyle involves making informed choices that support overall health and longevity, while still allowing for the occasional indulgence. This means savoring a delicious meal or a glass of wine in moderation, engaging in activities that bring happiness and contentment, and cultivating meaningful relationships. The key is to strike a balance between pleasure and well-being, recognizing that a fulfilling life includes both.

In conclusion, the misconceptions surrounding longevity are not simply different perspectives on the same topic; they represent misunderstandings that can hinder our understanding of what it truly means to live a long and healthy life. By debunking these myths, we can shed light on the true nature of the longevity lifestyle, which is about optimizing both the quantity and quality of life, and finding a balance between pleasure and well-being. By embracing this approach, we can take a significant step towards achieving our ultimate goal: a longer, healthier, and more fulfilling life.

The post The Elusive Quest for Longevity: Debunking Two Common Misconceptions appeared first on NOMIX.

In a groundbreaking study, a team of researchers used single-cell and single-nucleus RNA sequencing to analyze over 90,000 muscle cells and nuclei from 17 human donors. This innovative approach allowed the researchers to characterize muscle aging at the cellular and subcellular level, providing valuable insights into the processes that contribute to age-related decline in muscle function.

The study revealed several important insights into the mechanisms underlying muscle ageing. One important observation is the degeneration of neuromuscular junctions, which are crucial for proper muscle function. With increasing age, these connections deteriorate, resulting in reduced muscle activation and strength.

Another important finding is the reduced activation of muscle stem cells, which play a critical role in maintaining muscle health and regeneration. As we age, these stem cells become less active, contributing to loss of muscle mass and function.
The study also identified an increase in muscle inflammation as a relevant factor contributing to age-related muscle loss. Chronic inflammation is known to have detrimental effects on various tissues and organs, and it appears to play a similar role in aging muscle.

To facilitate further progress in this area, the researchers have developed an online atlas that makes the data obtained in their study publicly available. This valuable resource will allow researchers worldwide to access and analyze the data, which could lead to new discoveries and breakthroughs in our understanding of muscle aging.

The implications of this study are far-reaching and have the potential to significantly impact the lives of millions of people worldwide. By shedding light on the cellular and molecular mechanisms underlying muscle aging, this research opens new avenues for the development of interventions and therapies aimed at preserving muscle function and preventing age-related decline.
As we age, it is important to understand the complex processes that contribute to the degradation of our bodies. This study is an important step towards this goal, and its findings will undoubtedly stimulate further research and innovation in the field of muscle ageing. By working together and harnessing the power of cutting-edge technology, we can unlock the secrets of ageing and improve the quality of life of older people around the world.

In our BIOCOACH program, we analyze the muscle aging of our participants by measuring grip strength. This is done with the help of a hand dynamometer, a handy device that can be used very easily at home on a daily basis to measure muscle strength.

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What is a BIOCOACH?

A BIOCOACH is a certified expert in Longevity Health who helps its clients lead a longer, healthier, and more active life. Unlike traditional personal trainers who mainly focus on fitness, the BIOCOACH provides holistic counseling based on clinical diagnostics. This includes areas such as nutrition, fitness, sleep, stress management, and lifestyle.

Why is the BIOCOACH important?

Modern medicine has made great strides in treating diseases, but the focus on prevention and healthy aging is often lost. That’s where the BIOCOACH comes in. By providing tailored recommendations and individual guidance, the BIOCOACH supports their clients in developing and maintaining healthy habits. This not only leads to a higher quality of life but can also significantly reduce the risk of chronic diseases.

The connection between individual and doctor

The BIOCOACH acts as a bridge between the individual and the doctor. While doctors are primarily responsible for diagnosing and treating illnesses, BIOCOACHES focus on preventive measures. With the help of AI-supported analysis of health data continuously collected through the BIOCOACH App, personalized recommendations are developed to help customers stay healthy and slow down their biological age. This means that a doctor’s visit is often no longer necessary or only needed in cases of acute illness.

The advantages of the BIOCOACH

• Personalized health counseling: Each person is unique, just like their health conditions (DNA) and lifestyle. A BIOCOACH offers customized recommendations tailored to the individual’s current health status and lifestyle.
• Holistic approach: A BIOCOACH considers all aspects of life – from nutrition to fitness to mental health and sleep. This holistic approach maximizes Healthspan, which is the time spent living a healthy and active life.
• Long-term guidance: Health is a lifelong process. A BIOCOACH supports their clients over an extended period and helps them achieve and maintain their health goals while slowing down their biological age.
• Reduced disease risks: Through preventive measures and a healthy lifestyle, many chronic diseases can be avoided. This not only reduces the need for doctor visits but also improves quality of life.

Conclusion

The BIOCOACH is a valuable addition to modern healthcare systems. By taking a preventive and holistic approach, they help their clients lead a longer and healthier life. In an era where prevention is becoming increasingly important, the BIOCOACH offers an innovative solution that combines the best of two worlds: personalized guidance from a trainer and the scientific foundation of a Longevity expert who works together with their clients to maximize a healthy lifespan.

The post The Revolution in the Healthcare System: The Role of BIOCOACH appeared first on NOMIX.

The anticipated demographic shift to an exponentially growing elderly population with increased morbidity poses the greatest challenge to society in history. This challenge raises a key scientific research question: Can we enhance human health span with the ever-increasing life expectancy resulting from advances in healthcare to prevent premature mortality? Aging is now the dominant risk factor for many degenerative disorders, for which mechanisms and dietary or environmental modulators remain poorly studied. The progressive increase in healthcare costs for non-communicable conditions and the rise in morbidity and mortality with advanced age is promoted by the cumulative bioenergetic burden upon the target population by the Western diet rich in sugar, fat, and salt. An imbalance between NO and SOR has been demonstrated in metabolic diseases such as diabetes and obesity. Antioxidant protection can determine health. Nutrition is decisive in determining health and healthcare costs. Precision nutrition, specific food, and biomatrix supplementation have been proposed to improve health by supplying sufficient macro and micronutrients. Adaptation and aging can be the opposite outcomes of dynamic developmental plasticity. The discovery and development of effective supplements containing amino acids and antioxidants that can restore and improve health even at an advanced age is a rapidly developing field of applied biosciences. Aging can be seen as a process of internal desynchronization induced by stress and aberrant-signaling-induced senescence and the concurrent loss of bioenergetic potential with a depletion of resources to prevent degenerative changes. Supplementation can maintain or even improve human health.

1. Adaptation and Aging

Lifetime exposure to high glucose and free fatty acid levels induces cumulative toxicity that limits adaptational and developmental plasticity. Premature aging and disease can result from nutrition rich in calories but poor in nutrients and natural agents. Supplementation rich in certain amino acids switches the metabolism to enhanced activity, efficacy, and oxidative phosphorylation capacity that improves mitochondrial redox regulation, inducing antioxidant adaptation by retrograde trophic pro-survival signaling. Since caloric restriction is often associated with malnutrition in humans, only bioenergetic agents such as the mitogenic and mitotrophic amino acids glutamine, proline, and arginine, which are abundantly present in proteins and peptides from pulses, grains, or collagen, can significantly improve the metabolism of mitochondria and stimulate their signaling. These amino acids are a real option to extend the human health span substantially. L-arginine and L-arginine-rich proteins or peptides can supply the necessary nutrients to reduce glycemic load, insulin resistance, and lipotoxicity by facilitating and enhancing fat oxidation and reducing glucose accumulation. Bioenergetic agents such as L-arginine and related amino acids have positive health effects, as demonstrated in the target population. These supplements induce bioenergetic stimulation, antioxidant protection, and ubiquitous regeneration that improve, restore, and maintain gut, skin, and joint health. The synergistic effects of this unique L-arginine-rich blend with antioxidant agents of high bioenergetic potency are discussed in the context of easy-to-handle approaches in supplementation aimed at improving, regaining, or maintaining health by improving the diet of the target population.

2. Nutrition and Health

Food and supplementation can be a decisive factor in maintaining health during aging and stress or enhanced demand for protective nutrients. Recent research indicates that a high intake of soy, pea, and pumpkin, rich in arginine, proline, and glutamine, can limit carbohydrate and fat toxicity associated with the Western diet and its predominant arginine-poor animal protein content. The use of amino acids like L-arginine together with the synergistically acting B vitamins, folate, vitamin B6, and vitamin B12, in preparations of premium quality and natural origin, opens up new perspectives in establishing a molecular, metabolic medicine that enables prevention, therapy, and rehabilitation for improving, maintaining, and restoring the health of older adults. Antioxidant protection and health-span extension seem to be possible through such an innovative approach as using amino acids and vitamins to enhance trophic retrograde NO signaling and thus life- and health-span. This review reveals how a holistic strategy employing amino acids like arginine combined with other nutrients can reverse chronic degenerative changes and trigger adaptive reactions and repair processes that restore regeneration via redox regulation and antioxidant protection. Novel, innovative approaches using highly sophisticated supplementation protocols have revealed the molecular mechanisms and physiological mediators of viability and survival that enable the organism to cope with internal and external stressors. All molecular mediators that induce such adaptive plasticity act as mitochondrial metabolism modifiers to increase trophic support through the enhanced supply and more efficient use of bioenergetic resources. The aim and goal of these approaches are to promote human fitness and health. The universal bioenergetic decline as a hallmark of stress and senescence can be corrected through supplementation-dependent mitochondrial support that restores metabolic control mechanisms essential to regeneration and repair.

3. Say NO to Aging

Aging is often associated with increased adiposity and altered reduced muscle mass or sarcopenia, including increased ectopic fat stores such as visceral, hepatic, and intermuscular fat, The age-dependent increase in asymmetric dimethylarginine (ADMA) levels and the upregulation of L-arginine depletion through enhanced arginase activity are the primary factors contributing to the alteration of the L-arginine/nitric oxide (NO) pathway associated with insulin resistance and endothelial dysfunction. These findings help explain the profound effects of precision supplementation, which involves an enhanced supply of L-arginine and other bioenergetic agents, in restoring metabolic control and reducing insulin resistance and lipotoxicity associated with enhanced superoxide anion radical and peroxynitrite formation in older adults. Currently, numerous clinical studies are being conducted to ensure that L-arginine supplementation and L-arginine-rich food can restore redox regulation in the elderly target population. Aging leads to decreased arginine: ADMA ratio and the nitric oxide: superoxide ratio, resulting in oxidative stress, inflammation, and degenerative changes that harm development and health. Supplementation with amino acids such as L-arginine and L-arginine-rich food through certain peptides and proteins can restore a healthy arginine: ADMA ratio.

Recent research confirms the crucial roles of metabolic pathways in regulating and determining human health. The ultimate goal is to explore new avenues that enable active living and healthy aging by preserving fitness throughout life. Upregulating nitric oxide bioavailability can prevent premature aging and neurodegeneration. Boosting the nitrate-nitrite-nitric oxide pathway improves gastrointestinal, cardiovascular, metabolic, and cognitive performance. Vegetables rich in nitrate, like spinach and beetroot, are a good source of nitric oxide, with beneficial effects on cardiovascular health and a lower risk of cardiovascular disease.

L-arginine has potent health-protecting effects, and its beneficial cardiovascular effects are well-established. The age-dependent decline of tryptophan in the brain is associated with toxic kynurenine formation, which impairs nitric oxide formation and leads to insulin resistance and metabolic syndrome.

Supplementation with L-arginine and B vitamins can stop the vicious cycle of oxidative stress and damage. Selectively increasing tryptophan levels through L-arginine or L-arginine-rich food can boost nitric oxide bioactivity and bioavailability. This approach can target elevated blood pressure and improve cardiovascular health. Nitric oxide (NO) can be cytotoxic at high concentrations, but its antioxidant effects typically prevail. Moderate consumption of vegan L-arginine-rich proteins may be beneficial for individuals with kidney problems. Older adults and those with cardiovascular and cardiometabolic diseases have an enhanced need for L-arginine and L-arginine-rich proteins to restore and sustain a healthy NO supply.

L-arginine plays a decisive role in preserving brain health, preventing cognitive impairment, and maintaining high NO levels for healthy aging. Aging and age-related cardiovascular diseases lead to arginine and tryptophan depletion, impairing neurovascular coupling. L-arginine and L-tryptophan determine disease development and progression. Supplementation with L-arginine and L-arginine-rich food assures sufficient NO synthesis, neutralizing the age-dependent accumulation of ADMA and the enhanced formation of superoxide anion radicals.

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Let’s dive deeper into the role of NAD+ in our bodies, its decline with age and health issues, and the challenges of oral supplementation.

Role of NAD+ in the body:
NAD+ is a crucial molecule that acts as a cofactor and substrate for various cellular processes, including:

1. DNA repair: NAD+ is essential for repairing damaged DNA, which helps maintain the stability of our genetic information.
2. Epigenetic regulation: NAD+ plays a role in controlling the expression of genes by modifying their structure. This process is crucial for normal development and cellular function.
3. Energy production: NAD+ is a key player in the process of oxidative phosphorylation, which generates ATP (the energy currency of our cells).
4. Intracellular calcium signaling: NAD+ helps regulate calcium levels within our cells, which is important for cellular communication and function.
5. Immune function: NAD+ is involved in the activation of immune cells, which helps our bodies fight off infections.

Decline of NAD+ with age and health issues:
As we age, our NAD+ levels tend to decrease, which can contribute to various age-related issues. Low NAD+ levels have been linked to:

1. Aging: Reduced NAD+ levels may play a role in the aging process itself.
2. Cellular senescence: Senescent cells, which are cells that have stopped dividing and are no longer functional, accumulate with age and contribute to tissue dysfunction. Low NAD+ levels may promote cellular senescence.
3. Inflammation: Decreased NAD+ levels can lead to chronic inflammation, which is a major contributor to various age-related diseases.
4. Metabolic dysfunction: Low NAD+ levels have been implicated in insulin resistance, type 2 diabetes, and other metabolic disorders.

Challenges of oral NAD+ supplementation:
Despite the potential benefits of boosting NAD+ levels, taking NAD+ orally is not a straightforward solution. This is because:

1. Poor bioavailability: Oral NAD+ supplementation has poor bioavailability, meaning that only a small fraction of the ingested NAD+ is absorbed into the bloodstream.
2. Gut metabolism: NAD+ is metabolized by enzymes in the gut, which further reduces its availability to the body.
3. Inefficient conversion: When NAD+ is absorbed, it may be converted back to its inactive form, NAM, by the enzyme NADase.

Alternative NAD+ precursors:
Researchers are exploring alternative precursors of NAD+ that might be more effective in boosting NAD+ levels. These precursors include:

1. Nicotinic acid (NA): NA is a direct precursor of NAD+ and has been shown to increase NAD+ levels in certain tissues.
2. Nicotinamide riboside (NR): NR is a precursor of NAD+ that is more stable than NAD+ itself and has been shown to increase NAD+ levels in mice.
3. Nicotinamide mononucleotide (NMN): NMN is another precursor of NAD+ that has been shown to increase NAD+ levels in mice and is currently being studied for its potential benefits in humans.
4. Nicotinamide adenine dinucleotide ribose (NAR): NAR is a form of NAD+ that contains ribose instead of deoxyribose. It has been shown to increase NAD+ levels in certain tissues.

These alternative precursors are being investigated for their potential to improve NAD+ levels and provide therapeutic benefits. However, more research is needed to understand their efficacy and safety in humans fully. Intravenous infusion of NAD+ remains the most effective way to boost NAD+ levels, but alternative precursors may offer a more convenient and effective option.

The discovery of Sirtuins, a group of enzymes that depend on NAD and are linked to longevity, has opened up a new frontier in aging research. Recently, there has been a surge of interest in using the NAD/Sirtuin pathway to combat brain aging, and therapies based on this principle are expected to become available in the future.

A breakthrough in this field is the identification of nicotinamide riboside (NR) as a vitamin precursor of NAD with excellent oral bioavailability in both mice and humans. Studies have shown that a single daily dose of NR (1000 mg) can increase blood NAD+ levels by 270% within seven days. Additionally, NMN, another NAD+ precursor, is metabolized into NR, which is then converted into NAD+ inside cells.

In mice with metabolic impairments, NR supplementation has been linked to increased SIRT1 expression, reduced oxidative stress, and enhanced mitochondrial function. In a fly model of Parkinson’s disease, NR supplementation has been shown to reduce the loss of dopaminergic neurons and improve motor skills. Furthermore, NR supplementation has been found to reduce tau phosphorylation and enhance cognitive function in a mouse model of Alzheimer’s disease with DNA repair defects.

Another study demonstrated that NMN supplementation promoted mitogenesis in nematode neurons and improved cognitive decline caused by Alzheimer’s disease. In a rat model of Alzheimer’s disease, NMN reduced Aβ aggregation, enhanced spatial memory, and increased neuronal survival, partly by reducing reactive oxygen species (ROS). These findings suggest that NAD+ precursors like NR and NMN may hold promise in treating age-related brain diseases and improving cognitive function.

The post The Impact of NMN, NAD+, and NR, on Longevity appeared first on NOMIX.

The TCA cycle is a central hub for cellular metabolism, and AKG is an important intermediate in this process. It’s generated during the breakdown of carbohydrates, fats, and proteins, and is used to produce energy in the form of adenosine triphosphate (ATP).

AKG also has other important functions in the cell, including:

1. Nitrogen metabolism: AKG is involved in the metabolism of nitrogen-containing compounds, such as amino acids, which are the building blocks of proteins.
2. Gene expression: AKG can act as a signaling molecule, influencing gene expression and the production of proteins within the cell.
3. Stress response: AKG can help regulate the cell’s response to stress, such as oxidative stress caused by the accumulation of reactive oxygen species (ROS).

As we age, the levels of AKG in our blood plasma tend to decrease. This decline may be associated with various age-related changes and diseases, such as:

1. Reduced energy production: Lower levels of AKG may impair the TCA cycle’s ability to generate energy, leading to cellular dysfunction.
2. Altered gene expression: Changes in AKG levels may affect gene expression, leading to the production of abnormal proteins or the loss of normal protein function.
3. Increased oxidative stress: Lower levels of AKG may compromise the cell’s ability to neutralize ROS, leading to increased oxidative stress and damage to cellular components.

Supplementing with AKG has been shown to have various health benefits in animal models, including:

1. Extended lifespan: AKG supplementation has been found to increase the lifespan of certain organisms, such as worms and fruit flies.
2. Improved metabolic health: AKG supplementation has been shown to improve glucose tolerance, insulin sensitivity, and lipid metabolism in animal models.
3. Reduced oxidative stress: AKG supplementation has been found to decrease oxidative stress and increase the activity of antioxidant enzymes in animal models.

While more research is needed to fully understand the effects of AKG supplementation in humans, it appears to have potential as a dietary supplement for maintaining metabolic health and overall well-being.

The post Alpha-Ketoglutarate AKG May Extend Human Healthspan appeared first on NOMIX.

Several genetic pathways have been identified as key regulators of aging and lifespan, making them potential targets for anti-aging therapies. Currently, research is focused on developing compounds that mimic calorie restriction, induce autophagy, and enhance cell regeneration, as well as epigenetically modulating gene activity. These anti-aging agents offer exciting opportunities for the healthcare and pharmaceutical industries. Here, we explain the aging process and introduce some bioactive compounds that could benefit healthy aging and the potential role of lifespan extension.

In this blog post, we will delve into the properties of slow aging and healthy lifespan extension found in natural products derived from diverse biological sources, endogenous substances, pharmaceuticals, and synthetic compounds. We will explore the mechanisms of targets for anti-aging assessment and discuss bioactive compounds that offer benefits in the context of healthy aging, as well as their potential role in extending life span.

What is Aging?

Aging is a universal, evolutionarily conserved process that affects almost all living organisms, characterized by multisystem tissue dysfunction and the development of age-related diseases. However, aging is a modifiable process, with interventions available to extend life, improve health, and treat diseases in various organisms. These findings hold immense significance in biomedicine, as they offer the potential for groundbreaking improvements in health.  

Aging can be viewed as the progressive reduction of hemodynamic space, with survival being a continuous struggle between biochemical damage and repair. Various molecular, cellular, and biochemical pathways and networks determine an organism’s survival and lifespan. Age-related changes, such as hormonal declines and immune system remodeling, may not necessarily be detrimental and could be adaptive responses. Stress can also have both beneficial and detrimental effects, depending on factors like frequency, intensity, and duration, as well as energy expenditure and metabolic disorders.

Anti-Aging vs Healthy Aging – or: Lifespan vs Healthspan

This understanding of aging has shifted the focus from “anti-aging” interventions to “healthy aging.” We must move away from disease-oriented research and adopt health-oriented prevention strategies to achieve healthy aging aka longevity. Contrary to the notion that aging is an inevitable part of human nature, numerous interventions have shown promise in slowing aging and increasing healthy lifespan across various organisms, from yeast to non-human primates. Interventions can be categorized into lifestyle changes, such as caloric restriction and exercise, and pharmaceutical/genetic regulation, encompassing a wide range of molecules, including natural products, endogenous substances, approved drugs, and synthetic compounds. There is substantial evidence suggesting that aging interventions can delay and prevent the onset of chronic diseases in adults and older adults, and may safely and effectively extend the healthy lifespan of humans.

Aging Mechanisms

Over the past two decades, several genetic pathways have been identified as key regulators of the aging process and lifespan. As a result, genes within these pathways have emerged as attractive and potential targets for anti-aging therapies. Currently, numerous anti-aging drugs are being developed, targeting various aging mechanisms, including calorie restriction mimics, autophagy inducers, putative cell regeneration enhancers, and epigenetic regulators such as DNA methyltransferase and histone deacetylase inhibitors. While evidence on the overall health benefits of these compounds remains limited, epidemiological studies have begun to explore the long-term consequences of exposure to these compounds on human health. Although not yet ready for human trials, further research is warranted, particularly in the context of age-related diseases and conditions. Initial trials should focus on safety and tolerability, using a small number of subjects and a short duration, to provide early insights into promising compounds and potential candidates for more extensive aging studies.

The Aging Industry

For centuries, the pursuit of rejuvenation and youth maintenance has been a topic of scientific interest. In recent decades, this interest has accelerated the emergence of the anti-aging industry. This area of biomedical research remains a subject of debate. According to estimates, the economic impact of delayed aging and increased healthspan in the United States is projected to be around $7 trillion over the next 50 years. China’s health industry, including anti-aging products, has grown significantly, with a market size exceeding $1.3 trillion annually and an average annual growth rate of over 10%. By 2050, it is projected that the annual size of the health industry will surpass that of the United States, reaching $3.5 trillion, with the anti-aging industry also growing considerably. This presents a massive opportunity for the healthcare and pharmaceutical industries to discover new drug targets based on biogerontology.

Evaluating Aging

Conducting clinical trials to evaluate the anti-aging potential of conventional drugs is a challenging task. Older patients often have multiple diseases and are taking multiple medications, leading to drug-drug interactions and comorbidities that make it difficult to assess the full range of effects of these drugs, whether beneficial or adverse. Additionally, the lack of reliable and detectable biomarkers to measure the effectiveness of anti-aging interventions is another significant challenge. To overcome these obstacles, initial trials should be designed to treat age-related diseases and conditions, with a small cohort, short duration, and primary focus on safety and tolerability. Once promising candidates are identified, longer or more detailed studies can be conducted to focus on anti-aging outcomes.

The criteria for evaluating potential anti-aging drugs include:

1. A drug that extends the lifespan of a model organism, preferably a mammal.
2. A drug that delays or prevents age-related diseases in mammals.
3. A drug that inhibits the senescence transition of cells from quiescence to senescence.

These criteria may overlap, and if an intervention aims to extend lifespan, it must also retard diseases associated with aging.

Slow Down, Stop, Reverse Aging

Many plants and fungi, consumed as food, beverages, and spices, contain natural anti-aging compounds that can extend the lifespan of model organisms. These active molecules regulate cellular and physiological pathways affected by calorie restriction (CR) and exercise, mimicking the effects of CR by reducing insulin/IGF-1 signaling and activating autophagy and other stress-resistance mechanisms. These natural products not only increase lifespan but also improve health and quality of life by reducing the development of chronic diseases, including cancer, diabetes, cardiovascular disease, and neurodegeneration.

Anti-Agent Agents

In the table below you find natural products, endogenous substances, drugs, and synthetic compounds that could provide benefits in the aspect of healthy aging and the potential role of healthspn extension. We will discuss their specific benefits in our upcoming posts.

Natural products
Astaxanthin, Curcumin, Morphine, Nordihydroguaiaretic Acid NDGA, Rapamycin, Resveratrol, Sappanone A, Spermidine, Tambulin, Urolithins, Ursolic Acid, Coenzyme Q10, Vitamin A, Vitamin D, Vitamin K2, Quercetin, Caffeic Acid, Rosmarinic Acid, Genistein, EGCG, Protandim, Chicoric Acid, Tyrosol, Fisetin, TA-65, Procyanidins

Endogenous Substances
Alpha-ketoglutarate, Oxaloacetic Acid, Dehydroepiandrosterone DHEA, 17α-Estradiol, S-Linolenoyl Glutathione, Melatonin, Nicotinamide Adenine Dinucleotide NAD+, Nicotinamide Riboside NR, Nicotinamide Mononucleotide NMN

Drugs
Acarbose, Aspirin, (−)Deprenyl, Metformin, Minocycline, Statins, Celecoxib, Doxycycline, Enalapril, Metoprolol, Nebivolol

Synthetic Compounds
Nitrons, Pyridoperimidine Derivatives

Various strategies exist for using these anti-aging agents, including dietary supplements, increasing the intake of foods rich in these molecules, and consuming probiotics and prebiotics to raise blood levels of these molecules. Several nutrients and natural compounds have been linked to increased lifespan in humans, suggesting that these strategies may be feasible for slowing aging and increasing healthspan. Plant and fungal molecules with anti-aging properties in model organisms may also lead to the discovery and identification of new bioactive compounds for the development of improved CR mimetics to slow human aging. 

In addition to those mentioned above, many other compounds have been reported to show anti-aging activity, such as acetic acid, allicin, apigenin, aspalathin, berberine, capsaicin, catalpol, celastrol, garcinol, huperzine, hydroxycitrate, inositol, naringin, piceatannol, and piperlongumine. 

These natural products, endogenous substances, drugs, and synthetic compounds are being evaluated and many of them should find their way to consumers as micronutrition. We will discuss their specific benefits in our upcoming posts.

The post Interventions for Slowing, Stopping, or Reversing Aging and Extending Healthspan appeared first on NOMIX.

The study recruited 25 healthy young men who intended to fast for the entire month of Ramadan from dawn to dusk. The researchers measured gene expression levels one week before Ramadan, in the middle of Ramadan, in the last days of Ramadan, and one week after Ramadan.

The study found that intermittent fasting activated autophagy, a cellular process that breaks down components within cells. Autophagy has been linked to longevity, and the researchers observed an increase in ULK1, a gene involved in autophagy, two weeks and one month after starting the fasting period. Another gene, ATG5, involved in autophagy induction, also showed a similar pattern. However, BECN1, a gene essential for autophagy, exhibited a different pattern, with an increase in expression two weeks after the start of fasting and a subsequent reduction in its levels.

The researchers also measured inflammation and senescence markers, including the inflammasome and senescence mediator p16INK4a. They found that NLRP3 and IL-1β expression increased two weeks and one month after the start of fasting, but ASC levels were lower than basal levels one month after the start of fasting, suggesting that the inflammasome was not activated. The senescence marker p16INK4a did not show statistically significant changes until the end of the observation period, but p21 levels decreased during and after fasting.

The study’s limitations include a lack of data on food intake, physical activity, and sleeping patterns, which could impact gene expression patterns. Additionally, only young males were included in the study, making the results questionable for other demographic groups. The authors emphasize the need for further research to confirm or refute their findings and to assess the levels of actual proteins rather than just gene expression levels.

Overall, the study provides valuable insights into the molecular effects of prolonged intermittent fasting on human health and longevity markers. While more research is needed to understand the complex interplay between autophagy, the inflammasome, and senescence, the findings suggest that fasting may contribute to delaying the onset of age-related diseases and promoting overall health and longevity.

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The Relevant Eight Lifestyle Factors

The study identified eight key lifestyle factors that collectively contribute to a longer lifespan: never smoking, regular physical activity, moderate alcohol consumption, restorative sleep, a nutrient-rich diet emphasizing plant-based whole foods, effective stress management, strong social connections, and the absence of opioid use disorder. By analyzing mortality rates and life expectancy estimates across varying combinations of these factors, the researchers unveiled a striking pattern.

A Continuous Decline in Mortality Risk

Remarkably, the study found that the more of these eight lifestyle factors an individual adhered to, the lower their mortality risk became – a continuous and incremental effect. Those who exhibited none of the eight factors faced a staggering mortality rate of 70.2 deaths per 1,000 person-years. In contrast, those who embraced all eight factors experienced a mere 6.8 deaths per 1,000 person-years, more than a tenfold decrease in mortality risk.

The Power of Physical Activity

Among the eight lifestyle factors, regular physical activity emerged as the most potent determinant of longevity, associated with a remarkable 50% decrease in mortality risk for men and 46% for women. This finding underscores the paramount importance of an active lifestyle in promoting long-term health and well-being.

Substantial Life Expectancy Gains

The study’s findings are particularly striking when translated into life expectancy estimates. At age 40, individuals who exhibited none of the eight lifestyle factors had a remaining life expectancy of 23 years for males and 27 years for females. In stark contrast, those who embraced all eight factors could expect to live an additional 24 years for males and 20.5 years for females, extending their life expectancy to an impressive 47 years and 47.5 years, respectively.

A Call to Embrace a Comprehensive Lifestyle Overhaul

While the study acknowledges certain limitations, such as the binary categorization of lifestyle factors and the potential for confounding factors, its overarching message is clear: adopting a holistic approach to lifestyle optimization can profoundly impact longevity. By embracing a constellation of healthy habits, individuals can significantly reduce their mortality risk and potentially gain decades of additional life expectancy.

This pioneering research not only quantifies the remarkable benefits of a healthy lifestyle but also serves as a powerful motivator for individuals to prioritize their overall well-being through conscious lifestyle choices. As the field of geroscience continues to advance, studies like this underscore the immense potential of preventative measures in promoting longevity and quality of life.​​​​​​​​​​​​​​​​

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