Read the research. Understand the context.

The DoNotAge^® Routine is one drink a day with 15 longevity ingredients in it. You mix the powder with water and drink it once a day. It is Informed Sport certified.

The 15 ingredients, per daily serving:

•Glycine, 2000mg

•SIRT6Activator®, 1600mg

•Pure NMN, 1000mg

•TMG, 1000mg

•Ca-AKG, 800mg

•Trans-Resveratrol, 500mg

•Nitralis®, 400mg

•Quercetin, 400mg

•SulforaBoost®, 230mg

•Magnesium (as magnesium bisglycinate), 250mg

•Vitamin K2 (MK-7), 120µg

•Vitamin D3 (vegan), 125µg

•High Molecular Weight Hyaluronic Acid, 200mg

•CoQ10, 200mg

•Spermidine, 8mg

Contains no artificial ingredients, wheat, gluten, yeast, soy, corn, milk or preservatives.

The DoNotAge^® Routine has been tested as a finished product, the exact product you receive, in randomized, double-blind, placebo-controlled human trials.

In a 60 day trial in Dubai, 30 healthy adults aged 30 to 65 took the DoNotAge^® Routine or a matched placebo once a day. Neither they nor the researchers knew who had which. After 60 days, wellbeing scores in the DoNotAge^® Routine group had more than doubled, going from “low” to “good” on the World Health Organization’s wellbeing scale. Fatigue dropped by 19%. Every person taking the DoNotAge^® Routine improved on both measures. There were no side effects. 93% said they felt better or much better, and 100% said they wanted to keep taking it. The placebo group barely moved.

In a 28 day trial at LifeLab1 in Lithuania, 24 healthy adults aged 40 to 60 took the DoNotAge^® Routine or a placebo once a day. After 28 days, whole blood NAD+ levels in the DoNotAge^® Routine group had risen by 76% on average, from 16.4 to 27.9 micromol per liter. The placebo group showed no change.

There are several more trials of the DoNotAge^® Routine under way.

A biological age trial: 128 people are taking the DoNotAge^® Routine or a placebo at home, with their biological age measured by epigenetic clocks with the Clock Foundation. This trial is overseen by Professor Steve Horvath.

A Crohn’s disease trial: a 6 week, double-blind, placebo-controlled trial of the DoNotAge^® Routine in 64 people with mild to moderate Crohn’s disease, at the University of Central Lancashire and the University of Hertfordshire, with quality of life as the main measure.

A menopause trial: a double-blind, placebo-controlled trial of the DoNotAge^® Routine in 62 perimenopausal women, at the same two universities, with the Menopause Rating Scale as the main measure.

DoNotAge^® RoutineView product

Long term effects of DoNotAge® Routine supplementation on biological age, cognitive function and inflammation (human trial on the DoNotAge® Routine, under way)

Crohn's disease quality of life trial (human trial on the DoNotAge® Routine, under way)

PERI-QoL perimenopause trial (human trial on the DoNotAge® Routine, under way)

DoNotAge^® Performance is a daily drink for anyone who exercises. You mix one serving with water and drink it once a day. Each 13g serving provides 7g of creatine monohydrate, 4g of Nitralis® and 2g of NAC (N-acetylcysteine). It is Informed Sport certified.

DoNotAge^® Performance is currently in a human clinical trial. Professor Sergej Ostojić, who has over 500 published papers on creatine, as well as two patents, has joined the DoNotAge.org Advisory Board and is running this trial. It is a randomized, double-blind, placebo-controlled trial in older adults. Participants will take DoNotAge^® Performance or a placebo every day for 6 months. The main measure is handgrip strength, but the trial will also measure other physical functions (including walking speed), brain function, body composition, inflammation, telomere length and the activity of aging-related genes. It will be completed by the end of 2027.

The three ingredients in DoNotAge^® Performance have their own research too.

Nitralis®: a randomized, placebo-controlled trial in 85 people showed Nitralis® raised nitric oxide levels by 226% compared to placebo, with no side effects (see the Nitralis® section).

Creatine: the CREAM trial at the University of Central Lancashire is testing DoNotAge.org Creatine Monohydrate on brain processing speed in 64 adults aged 40 to 60 (see the Creatine Monohydrate section).

In a pilot study in people with Alzheimer’s disease, creatine raised creatine levels in the brain and improved brain function and memory, and a meta-analysis found creatine helps protect muscle mass more than exercise alone.

NAC: NAC (N-acetylcysteine) is what your body uses to make glutathione, its main antioxidant. A systematic review of controlled trials in men found that most trials showed benefits from NAC: better exercise performance, higher antioxidant capacity and better glutathione balance, with no serious side effects. In a study of endurance-trained athletes, NAC raised glutathione in the muscles and delayed fatigue by 26% during hard exercise.

The Effects of 24-Week DoNotAge® Performance Supplementation on Functional Muscle and Brain Performance, Body Composition and Molecular Aging Biomarkers in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial (human trial on DoNotAge® Performance)

Effects of DoNotAge.org Creatine Monohydrate on Cognitive Function in Healthy Middle-Aged Adults: The CREAM Trial (human trial on DoNotAge.org Creatine Monohydrate, under way)

Nitralis® is a nitric oxide supplement. It helps your body naturally restore Nitric Oxide levels, supporting circulation, oxygen delivery, and vascular health.

Nitralis® is vegan and filler-free. The only ingredients are Nitralis® and a plant-based cellulose capsule.

We put Nitralis® to the test in a randomized, placebo-controlled trial. 85 people took part. One group took Nitralis® every day for 30 days and the other group took a placebo. At the end of the 30 days, nitric oxide levels in the Nitralis® group had risen by 226% compared to the placebo group. There were no side effects.

Other research backs this up. A study of 12 people showed that plant nitrate taken by mouth is absorbed into the blood and moved along the pathway the body uses to make nitric oxide. This is the same pathway Nitralis® works through. A review of the research on dietary nitrates, like those found in beetroot, found they help the body carry oxygen to where it is needed, which supports heart health and exercise capacity.

Key benefits:

•Boosts circulation and vascular health

•Improves oxygen efficiency, stamina, and recovery for better physical performance

•Supports cognitive function by increasing brain blood flow.

•Promotes heart health by balancing blood pressure and supporting endothelial function.

•Aids sexual performance in men and women by enhancing nitric oxide signaling involved in arousal and blood flow.

•Supports longevity by increasing vitality and cardiovascular resilience.

Who should take Nitralis®?

Anyone looking to increase heart and CV health, endurance, focus, and vascular health.

Sirtuins are a family of proteins that keep your cells healthy and promote DNA repair. Sirtuin activity decreases as you age, so by increasing that sirtuin activity we can increase your lifespan.

Our cells are protected by sirtuins in the following ways:

•React to damage and repair.

•Encourage strong DNA.

•Associated with the advantages of exercise and fasting.

•Collaborate with other genes and react to cellular harm.

•Create enzymes that regulate the epigenome.

•May slow down the rate of cell division.

•One of the reasons they can live longer is because of this.

As we age, these remarkable enzymes help keep us free from inflammatory disorders and are crucial for proper cellular metabolism. Sirtuins slow down the rate at which cells divide through a variety of biological processes.

The fuel that Sirtuins use is NAD, so to boost NAD levels we provide NMN. To activate the Sirtuins we provide resveratrol, a potent Sirtuin activator that has been shown to extend a healthy lifespan.

Sirtuin 6, also called the “longevity sirtuin”. SIRT6 enhances DNA double-strand break repair under oxidative stress. Oxidative stress can damage all components of the cell, including DNA. SIRT6 is the only sirtuin that can bind NAD without first having to bind an acylated substrate. SIRT6 recruits PARP1 to facilitate DNA repair and is also instrumental in energy creation as it increases the efficiency of ATP production. SIRT6 has been shown to be closely related to a number of metabolic pathways and genome maintenance, as well as telomere stability.

SIRT6 is neuroprotective, and patients with Alzheimer’s disease have low levels of SIRT6. Activating SIRT6 may provide broad tumor suppressant and health-promoting benefits.

SIRT6Activator® is a seaweed compound especially tested to confirm SIRT6 activation properties, similar to what is seen in centenarians. Seaweed compounds can also have:

•Anti-oxidant effects.

•Anti-tumor effects.

•Anti-coagulant effects.

•Anti-thrombotic effects.

•Immunoregulatory effects.

•Anti-viral effects.

•Anti-inflammatory effects.

•Recently they were shown to give a better immune response after a vaccine.

SIRT6Activator® is a complex polysaccharide derived from seaweed. Laboratory studies suggest that it can prevent the growth of cancer cells and has antiviral, neuroprotective, and immune-modulating effects.

Sirtuin 6, or SIRT6, is a longevity gene. Increased levels of SIRT6 extend lifespan in mammals. Furthermore, long-lived animal species have more active SIRT6. Remarkably, countries with the highest consumption of seaweed, Japan and South Korea, have the longest life expectancies. These ingredients were shown to have multiple health benefits, consistent with pro-longevity function. They improved the immune response to the flu vaccine in the elderly, reduced inflammation, and improved the survival of cancer patients undergoing chemotherapy. There are many varieties of seaweed available on the market, and the end product they produce differs in their chemical formulas. Importantly, SIRT6Activator® has been verified to activate SIRT6.

Boosting NAD levels is another strategy to increase the activity of Sirtuins. However, of all sirtuins, Sirtuin 6 is the least sensitive to NAD concentration. Therefore, to activate Sirtuin 6, it is important to use supplements that activate this enzyme directly.

SIRT6Activator® is being tested in people right now. Professor Andrea Maier at the National University of Singapore is running a randomized controlled trial in middle-aged people. The main question is whether SIRT6Activator® reverses biological age, measured by the GrimAge clock. The trial is also looking at inflammation, frailty, quality of life, sleep, brain function, body composition, heart health and reproductive health. L’Oréal approached us and asked to partner on this study, so the trial now also looks at skin aging and wrinkles. The trial is due to complete in 2027.

Professor Maier is also running PROMETHEUS, an 8 week study in adults aged 50 to 80. It combines lifestyle changes with targeted supplements, including SIRT6Activator®, and measures the effect on biological and clinical markers of aging. This study is Professor Maier’s XPRIZE entry, to prove that we can reduce human aging by over 10 years.

Professor Vera Gorbunova’s lab at the University of Rochester showed that SIRT6Activator® extended lifespan in old mice and reduced frailty, so the mice lived longer and were healthier while they were alive. It worked by activating SIRT6, which lowered inflammation. Blood from the treated mice had lower levels of inflammatory cytokines, the molecules that signal inflammation and that rise with age and disease. In a related cell and mouse study, fucoidan from seaweed boosted SIRT6 activity, which increased DNA repair, lowered markers of senescence and inflammation, and improved healthy lifespan in old mice. Professor Gorbunova’s team also found that most fucoidan did NOT activate SIRT6, so it was very important to test each batch, which is what she does with SIRT6Activator®.

Quercetin is a flavonoid that the human body cannot produce. Quercetin increases the half-life of resveratrol and has been shown to work in conjunction with resveratrol to reduce the hallmarks of aging, as well as reduce inflammation, fat cells, blood pressure, body weight and the risk of heart disease.

Quercetin is commonly used to alleviate allergy symptoms and its effects have been proven in many studies. Quercetin has also been studied for its great anti-cancer potential, across many different types of cancer.

Quercetin has been shown to significantly reduce early morning stiffness, morning pain, and after-activity pain in those with arthritis. Quercetin can protect your brain from dementia and has even reversed Alzheimer’s disease.

Finally, quercetin is an anti-diabetic and has been shown to help reduce blood sugar.

Pure Quercetin from DoNotAge.org has been tested in two human trials. At Ulster University, Dr Ciara Juan studied healthy men doing intense exercise. Pure Quercetin activated the body’s repair pathways during the exercise, protected DNA, kept repair capacity up and kept inflammation down. This points to more efficient, energy-saving DNA repair under stress. It was a small study, but the findings are a big deal.

The second trial has now reported. Dr Jonathan Sinclair at the University of Central Lancashire, with Professor Lindsay Bottoms at the University of Hertfordshire, ran a double-blind, placebo-controlled trial in 40 healthy adults. Half took 400mg of Pure Quercetin a day for 20 days and half took a placebo. After 20 days, systolic blood pressure (the top number) was 6.92 mmHg lower in the quercetin group than in the placebo group. Triglycerides, a type of fat in the blood, were lower too. Daytime sleepiness also improved. There were no side effects, and people took 98.7% of their doses. Dr Sinclair presented the results at DoNotAge^® Conference 2026.

In other human studies, they found quercetin improves blood pressure, which means less chance of stroke or heart disease.

In a double-blind, placebo-controlled trial of 80 healthy adults, quercetin improved reaction time and blood flow to the brain, and reduced the build-up of waste in the brain.

In a trial of 50 people with rheumatoid arthritis, quercetin reduced pain and stiffness and lowered inflammation in the joints.

In people with chronic fatigue syndrome, daily quercetin gave them more energy and better sleep.

In human skin cells, quercetin prevented the breakdown of collagen and shielded the cells from UV damage.

Can DoNotAge.org Pure Quercetin improve cardiometabolic health? A double-blind, placebo-randomised controlled trial in healthy adults (human trial on Pure Quercetin from DoNotAge.org)

Autophagy literally means “self-eating”. This natural bodily process helps us to get rid of old and damaged cells and create new healthy ones. A lack of autophagy is heavily linked to cancer, as the body does not remove those cancerous cells as it should. Autophagy can be activated by performing extended fasts (over 48 hours) or supplementing with ingredients such as spermidine.

The anti-aging properties of autophagy appear to be its primary advantage. In fact, it’s best recognized as the body’s method of producing younger cells.

When our cells are under stress, autophagy levels increase to assist and protect us, lengthening our lifespan.

Additionally, autophagy can maintain the body’s functioning during times of deprivation by disassembling cells and repurposing them for essential functions.

Naturally, this requires energy and cannot go on indefinitely, but it provides us more time to acquire food.

The advantages of autophagy at the cellular level include:

•Eliminating the harmful proteins from cells that are linked to neurodegenerative illnesses including Parkinson’s and Alzheimer’s

•Recycling leftover proteins promotes regeneration and healthy cells by giving energy and building blocks to cells that could still use extensive repair.

•The potential role autophagy may play in preventing or treating cancer is also attracting a lot of attention.

According to Keatley, “autophagy declines with age, which implies that cells that no longer function or may cause harm are permitted to grow, which is the MO of cancer cells.”

While all malignancies originate from damaged cells of some kind, the body should be able to identify and eliminate those cells, frequently through autophagic processes. Some scholars are considering the idea that autophagy may decrease the risk of cancer.

Spermidine has been shown to delay aging in humans. It is known as a geroprotector, with most benefits coming via autophagy. Spermidine is shown to:

•Extend lifespan.

•Improve resistance to stress.

•Decrease the occurrence of age-related diseases.

•Prevent the loss of movement.

•Protect the heart.

•Protect the cardiovascular system.

•Protect the immune system.

Spermidine has also been shown to upregulate sirtuin 1, prevent liver damage and cancer, act as an anti-inflammatory and even promote human hair growth. It may also protect telomere length.

Spermidine may slow down human aging, prevent age-related disorders, increase sirtuin 1, defend against liver damage, have anti-inflammatory effects, and improve cognition, all while warding off diseases of the brain including dementia and Parkinson’s, according to studies.

One of spermidine’s most prominent benefits is its effect on the brain. Spermidine can protect your memory, boost your cognitive abilities and stop neurodegeneration.

Levels of spermidine decrease as we age, and a higher spermidine intake reduces the chance of dying.

A large trial in Denmark has tested Pure Spermidine from DoNotAge.org in older people with heart disease. It is led by Professor Henrik Wiggers at Aarhus University Hospital. The trial measured the heart and other muscles by MRI, fitness (VO2), inflammation, blood sugar (HbA1c), spermidine levels in the blood and in muscle, the immune system, metabolism, the gut microbiome and autophagy. The trial has finished and we are waiting for the results.

A second human trial of Pure Spermidine from DoNotAge.org is under way at Aarhus University Hospital in Denmark, led by Associate Professor Jean Farup. Muscle stem cells drive muscle repair, but they respond more slowly to injury as we get older, and spermidine levels fall with age too. In this trial, older adults take Pure Spermidine every day for 58 days. On day 28 they have a controlled muscle injury, and muscle biopsies are then taken to measure how well their muscle stem cells respond.

In people, a higher spermidine intake is linked to a longer and healthier life, with lower rates of cancer and less heart disease. A review in the journal Science found the same: spermidine levels drop as we get older, and people who get more of it live longer and are healthier, with less cancer and less heart disease. This works through autophagy. In a one year study, daily spermidine helped improve the memory of older adults with dementia.

In mice, spermidine helped old mice live longer and have healthier hearts.

Spermidine and muscle regeneration in older adults (human trial on Pure Spermidine from DoNotAge.org, under way)

NAD or nicotinamide adenine dinucleotide is so vital that without it, you would die within seconds. Your mitochondria, which are responsible for energy production, use NAD as fuel. NAD is also the fuel for your Sirtuins, (you can find out more about Sirtuins above). NAD is crucial for telomeres. They are the caps on your DNA strands that protect your chromosomes, and shortened telomeres are linked to a shorter lifespan.

NAD is a wonderful discovery and extremely important for aging. Finding ways to boost your NAD levels has become central to longevity.

Some of the benefits of NAD include:

•Higher amounts of physical energy.

•An improvement in mental performance.

•Reduced sleep deprivation significantly.

•Increased anti-aging initiatives.

•Reduced effects of jet lag.

•Short-term memory is enhanced.

•Improved mental capacity.

There are two main issues with NAD. The first is that as we age, our natural levels of NAD decline, and it is believed that this is the reason for many age-related diseases.

The other problem with NAD is that it is too large to enter your body. This is why we provide NMN, or nicotinamide mononucleotide, to raise your NAD levels. NMN is a direct precursor to NAD and is proven to raise NAD levels.

Nicotinamide mononucleotide, or NMN for short, is a derivative of Vitamin B3. In the body, it is a precursor to NAD. If you’re unsure what NAD is, see above. Taking NMN as a supplement is safe, and it raises your NAD levels.

NMN reverses vascular aging, stimulates blood vessel growth and boosts stamina and endurance. NMN reduces the physical and neurological decline associated with aging.

NMN has many other possible benefits when it comes to health including:

•Improving longevity.

•Reducing the effects of diabetes.

•Reversing the effects of liver conditions.

•Improving brain health.

•Improving heart health.

•Aiding in exercise training

•Improving sleep quality

Studies have suggested that NMN and NAD levels may be reduced in patients with a variety of age-related ailments, such as diabetes and liver disorders.

Animal and test-tube research also suggest that NMN may be involved in other facets of aging, such as heart and brain function.

Pure NMN from DoNotAge.org is being tested in a clinical trial led by Dr Martin Gnoni at TriHealth in the USA. The trial is in people living with HIV whose immune systems have not recovered even though the virus is under control. The question is whether NMN helps their CD4+ T cells, a key type of immune cell, to recover. The theory is that if NMN helps restore immune function in these patients, it may help everyone’s immune function. Results are expected in 2027.

In people, NMN is safe and raises NAD levels. A review of 12 human studies found this, and a placebo-controlled trial found that even very high doses are safe and raise NAD. A study comparing three NAD boosters found that NMN and NR raise NAD levels equally well, while cheaper alternatives such as nicotinamide do not. In a double-blind, placebo-controlled trial in older adults, NMN raised blood NAD levels, maintained walking speed and improved sleep quality. In prediabetic women, NMN improved insulin sensitivity, which is how well the muscles use sugar. In middle-aged and older adults, a form of NMN reduced body fat, blood pressure and cholesterol. A review of 10 years of trials found NMN quickly converts to NAD+ in the body, supporting energy, DNA repair, inflammation control and cell health. Another review of animal and human studies found NMN helped improve liver function, reduce gut inflammation, strengthen the gut barrier and support a healthy microbiome.

In mice, NMN given from middle age extended lifespan, reduced frailty and improved healthspan, in a study from Dr David Sinclair’s lab. The same long-term study found no increase in cancer across the lifespan of the mice. Other animal and cell studies point the same way on cancer: mice treated with NMN had less bowel cancer, high doses of NMN slowed lung cancer growth, NMN-boosted immune cells suppressed tumors and prolonged survival, NMN reduced breast cancer cells in the lab, and mice having chemotherapy were healthier when given NMN.

In mouse models of MS, raising NAD levels improved symptoms and reduced brain inflammation and nerve damage, and NAD precursors reduced the loss of myelin, the coating around nerves. NMN also eased depression-like behavior in mice. In pregnancy, NMN reduced the harmful effects of obesity in pregnant mice, and in pigs it improved mitochondrial function in the placenta, raised NAD and helped the babies grow better.

NR (nicotinamide riboside) is a form of vitamin B3 and, like NMN, a precursor to NAD.

In humans, NR raises NAD+ levels and is safe. A study comparing three NAD boosters found NMN and NR raise NAD equally well, while cheaper alternatives such as nicotinamide do not. In older adults, NR raised NAD+ in muscle tissue as well as in blood, and reduced inflammation. In the NICE trial, people with peripheral artery disease who took NR for six months improved their walking capacity.

We recommend TMG, particularly for those that take NMN. TMG, or trimethylglycine, acts as a methyl donor to ensure you get the full benefit from your NMN.

TMG has anti-inflammatory properties, can boost your exercise performance and protects both your liver and your heart.

Studies have shown that TMG can also:

•Reduce fatigue.

•Boost your body’s production of proteins.

•Increase the synthesis of creatine.

Creatine is a compound that helps to provide more energy to the muscle cells in your body. By increasing the production of this compound, you will be able to reduce physical exhaustion and help support your muscle growth.

In a double-blind, placebo-controlled trial in college-age women, taking TMG (betaine) over time drastically reduced body fat. A review of the human trials on TMG found it reduces inflammation, protects the liver and improves homocysteine levels. Another review, covering cell, animal and human data, explains how: TMG is a methyl donor, it protects cells when they are under pressure, and it reduces oxidative stress.

Resveratrol supplementation has been shown to increase lifespan. Resveratrol is a potent Sirtuin activator.

Resveratrol has similar effects on your body as a calorie-restricted diet. Resveratrol reduces your blood pressure, protects your brain, protects your arteries and even has anti-cancer potential.

It would be beneficial to supplement resveratrol alongside NMN and Quercetin. This is because, in order for your sirtuins to perform their beneficial work, we want to activate them with resveratrol and increase their fuel with NMN. Regarding Pure Quercetin, in addition to offering a plethora of health advantages of its own, it also lengthens the half-life of resveratrol and should be taken as part of the same supplement regimen.

Resveratrol has been tested in many human trials. A review of 40 of them, covering more than 2,500 people, found resveratrol improved insulin resistance, cholesterol, blood pressure and inflammation. A review of all the human trials from the past 10 years found that when it is taken correctly, resveratrol is well absorbed, and it works for inflammation, heart health, blood sugar control and brain function. A meta-analysis of trials in people with heart disease, more than 400 people in all, found resveratrol drastically reduced inflammation, and the longer people took it, the better the results. In a randomized trial of 50 healthy people, 500mg of resveratrol activated SIRT1 and also reduced stress.

For women going through menopause, resveratrol reduced hot flushes, making them fewer and less severe. In a long-term study of postmenopausal women, daily resveratrol reduced pain, cut menopausal symptoms and improved overall wellbeing.

In animal studies, activating SIRT1, which is what resveratrol does, prevented nerve damage in a model of MS. In pregnant mice fed a high fat diet, resveratrol improved the metabolism of their offspring and prevented obesity in the male offspring.

Sulforaphane is a compound found in cruciferous vegetables (when they are raw) such as broccoli and cabbage. The compound is not stable, so to create a supplement, sulforaphane glucosinolate and an enzyme called myrosinase must be mixed together. SulforaBoost® is the most effective sulforaphane product available.

Sulforaphane has been shown to relieve oxidative stress, reduce cancers, protect against UV damage and sunburn, protect the liver and reduce viral load. This can help with both the body’s internal and external health.

Dr Rhonda Patrick says:

“There’s tons and tons of studies showing that taking these products increases levels of glutathione in blood and also in the human brain. If you don’t know what glutathione is, it’s the major, major antioxidant, particularly in the brain. It’s not only increasing the antioxidant systems it’s decreasing DNA damage, quite significantly by 30%, and this is in humans. Very important.”

Sulforaphane has been shown to protect the heart, conserve the brain and protect from pollution.

The two main avenues that sulforaphane’s benefits come from are the activation of the Nrf2 pathway and increasing glutathione levels. For this reason, sulforaphane is often referred to as the “cell defender”.

Sulforaphane has been tested in people many times. In a 12 week trial in healthy older adults, those taking sulforaphane got faster at processing information and had less negative mood than those taking a placebo. In a trial of 81 people with type 2 diabetes, broccoli sprout powder cut inflammatory markers by more than 20%. In a six week trial in people who had been through heart procedures, sulforaphane eased mild to moderate depression better than a placebo. More people responded to it, more went into remission, and there were no extra side effects. In a trial of 29 young men with autism, more than half showed better behavior on sulforaphane. A large review of the research on sulforaphane and hormones found it helps relieve hot flushes, improves mood and sleep, and relieves vaginal dryness in menopausal women.

Animal studies point the same way. Sulforaphane extended the life of mice, working through the Nrf2 pathway. The mice had healthier mitochondria, hearts and muscles, better exercise capacity and a stronger grip. In mice with an MS-like disease, sulforaphane slowed the disease and made it less severe. In a lab study on microglia, the immune cells of the brain, sulforaphane reduced inflammation.

Sulforaphane is also being studied in pregnancy. In rats, broccoli sprouts taken during pregnancy protected the newborn’s brain when the placenta was not working well. In another animal study, sulforaphane taken in pregnancy improved heart health in the offspring. A placebo-controlled trial of broccoli sprout extract in women with early onset preeclampsia has been set up.

AMP-activated protein kinase, or AMPK, is an enzyme that is known to boost energy and balance hormones. It is often called the master regulator of metabolism.

Cells activate AMPK when they are running low on energy. AMPK is activated in tissues throughout the body following exercise or fasting. In response, AMPK alters the activity of many other genes and proteins, helping keep cells alive and functioning even when they’re running low on fuel.

AMPK assists with autophagy, fat burning and turning nutrients into energy. Activating AMPK is key to longevity.

Activating AMPK can be achieved via both lifestyle, for example, high-intensity exercise, and via supplementation of berberine.

A variety of plants, including the barberry, Oregon grape, and tree turmeric, contain the alkaloid berberine in their barks, leaves, twigs, roots, and/or stems. Berberine has long been utilized in Ayurvedic and traditional Chinese medicine as an antibacterial, antiprotozoal, and antidiarrheal drug.

The majority of human studies have looked at how berberine affects anthropometric factors, blood lipids, liver function markers, and markers of glycemic management in persons with metabolic diseases.

In addition to this, berberine has:

•Anti-cancer properties.

•Anti-inflammatory properties.

•Antibacterial properties.

•Decreases insulin resistance.

•Helps your body break down sugar.

•Increases the number of good gut bacteria.

•Activates your sirtuins.

Berberine activates AMPK, one of the key longevity pathways. Berberine plays an important role in your metabolism, lowering your LDL cholesterol and triglycerides, and protecting you from heart disease.

We are funding a trial of Pure Berberine, called BEST, which is under way at the University of Central Lancashire and the University of Hertfordshire, run by Dr Jonathan Sinclair. It is a 20 day, double-blind, placebo-controlled trial in 40 healthy adults aged 18 to 64. Half take 2000mg of Pure Berberine a day with meals and half take a placebo. The main measure is triglycerides, a type of fat in the blood. It also looks at cholesterol, blood sugar, blood pressure, heart rate, body composition, wellbeing and sleep.

In a human trial, berberine was better than metformin (a diabetes drug) at controlling blood sugar. In women with polycystic ovary syndrome (PCOS), berberine also beat metformin on blood sugar control and also improved triglycerides, cholesterol and waist to hip ratio. An umbrella review, which is a review of reviews covering a very large amount of human data, found berberine lowered fasting blood sugar, lowered HbA1c (your three month average blood sugar), lowered insulin resistance and insulin levels, and even lowered the inflammation markers CRP, IL-6 and TNF-α.

Effects of DoNotAge.org Pure Berberine on Cardiometabolic and Other Health-Related Outcomes: The BEST Trial (human trial on Pure Berberine from DoNotAge.org, under way)

Creatine is involved in making energy for muscles.

Creatine is stored as phosphocreatine in the body and helps to regenerate energy in our cells in the form of Adenosine Triphosphate (ATP)

Creatine promotes the transmission of energy within the cell structure in the form of creatine phosphate. This improves performance during periods of intense muscle use, which results in increased muscle growth and greater strength. The larger creatine phosphate pool also leads to a faster regeneration of ATP (the source of energy for use and storage at the cellular level) and therefore helps recovery after intensive exercise.

Many studies have confirmed that creatine monohydrate is safe to consume. There is far more safety information for this form of creatine than any other form.

There is also evidence to suggest that creatine supplementation aids cognition in the elderly.

There is evidence to support the use of creatine to help with the symptoms of depression.

We are funding a trial of DoNotAge.org Creatine Monohydrate, called CREAM, which is under way at the University of Central Lancashire and the University of Hertfordshire, run by Dr Jonathan Sinclair. It is a 6 week, double-blind, placebo-controlled trial in 64 healthy adults aged 40 to 60. Half take 10g of creatine monohydrate a day and half take a placebo. The main measure is processing speed, which is how fast the brain handles information. It also looks at memory, attention, grip strength, body composition, wellbeing, sleep and physical activity.

In a pilot study in people with Alzheimer’s disease, creatine monohydrate raised creatine levels in the brain and improved brain function and memory. A meta-analysis of human studies found creatine helps protect muscle mass in older adults more than exercise alone.

Effects of DoNotAge.org Creatine Monohydrate on Cognitive Function in Healthy Middle-Aged Adults: The CREAM Trial (human trial on DoNotAge.org Creatine Monohydrate, under way)

Sleep is a vital part of staying healthy, but the majority of adults struggle with it. Your body shuts off from the outside world and begins its daily clean-up. Your brain uses sleep to check its hormones and enzymes are in balance. The cells contract and waste are washed away. If this does not happen, then the brain ages much faster and can lead to diseases such as dementia.

Sleep is important for mental well-being as well as physical. Those lacking in sleep are more likely to:

•Be overweight.

•Have disrupted appetites.

•Lose empathy.

•Have more inflammation.

•Have a low immune system.

•Be depressed.

•Be suicidal

•Have impaired brain function.

•Are more at risk for heart problems.

•Those sleeping for less than 7 hours per night have up to a 26% higher risk of death.

Ultimately, sleep is paramount to having a long and healthy life. Some tips to have quality sleep include:

•Drinking enough water.

•Having enough melatonin.

•Reducing blue light in the evening.

•Stick to a sleep schedule.

•Avoid caffeine and alcohol

•Sleep in a restful environment.

•Increase physical activity in the day.

Everybody experiences nights when it’s difficult to go to sleep or when we wake up during the night. Sleep issues are common, but if our suggestions don’t help or if you’ve been having trouble sleeping for months and it’s making it difficult for you to cope, you might benefit from further treatment from a medical professional.

In 2026, an independent research platform called BioStackr approached us and asked to run a real-world study of SureSleep®. We did not commission it, we did not pay for it, and we did not provide any free product. BioStackr designed the study, collected the data and ran the analysis. We had no access to the raw data and no say over the results.

They tracked 51 DoNotAge.org members in 13 countries, taking SureSleep® for 21 days, with 1,472 daily check-ins. Each person was compared against their own sleep before they started. Here is what our members reported:

•88% reported better sleep quality, with an average of 31% improvement in sleep quality.

•94% reported better daytime energy.

•76% fell asleep more easily.

•53% woke less during the night.

•55% felt a benefit within the first week.

•70% rated it among the best sleep products they had used.

•45% said nothing had worked well for them before SureSleep®.

This is a record of what real members reported during normal life. You can read the full study in the useful links below.

SureSleep® is a mix of ingredients that help get you to sleep, stay asleep, and feel better the next day: tart cherry (Prunus cerasus), magnesium glycinate, magnesium citrate, L-tryptophan and L-theanine.

When it senses that it is time to go to bed, your body releases melatonin, which is primarily dependent on exposure to light. Our melatonin production is impacted by the fact that we are all exposed to artificial light late into the evening, which in turn impacts the quality of our sleep. The generation of melatonin is also impacted by aging, so as you become older, your sleep quality declines even more.

Prunus cerasus, sometimes called tart or sour cherry, is traditionally known as a powerful antioxidant. However, on top of this, prunus cerasus has now been shown to significantly elevate natural levels of melatonin, the sleep hormone. It significantly increases time in bed, total sleep time and sleep efficiency.

A meta-analysis of the trials on tart cherry found it improves how long people sleep and how well they sleep.

Magnesium: in a double-blind, placebo-controlled trial, a high dose of magnesium improved insomnia.

L-tryptophan is an amino acid. Your body uses it to make serotonin and melatonin.

L-theanine: in a randomized trial, L-theanine reduced stress and supported relaxation and sleep.

Long-term direct melatonin supplementation can stop your body from producing its own melatonin, which is not what we want. DoNotAge.org has worked very hard to develop the ideal product that will help you get a restful night’s sleep and wake up feeling rejuvenated.

Senescence is the loss of a cell’s power of division and growth. Once a cell becomes senescent, it remains active and can release harmful substances that may cause inflammation and damage to nearby healthy cells. This is why they are often called “zombie” cells. Senescent cells accumulate as we age. Senescent cells may play a role in the development of cancer and other diseases.

Removing senescent cells is important for health as we age. Something that removes senescent cells is called a “senolytic”. The most potent senolytic we know of is fisetin.

It can be challenging to consume enough fisetin from diet alone. Strawberries contain the highest concentration in natural foods which is less than 2 mg of fisetin in one strawberry. This indicates that you would need to consume 400 strawberries as a minimum in order to obtain the same amount of fisetin from your diet as you would from a single serving of DoNotAge.org Pure Fisetin.

Fisetin is the most potent senolytic and can increase lifespan. Fisetin has also shown the potential to:

•Fight multiple cancers.

•Protect the brain from strokes.

•Reduce inflammation.

•Reduce seizures.

•Support the immune system.

•Fight other diseases.

Whilst more often used for the above reasons, fisetin has also been shown to reduce depression, boost serotonin levels and boost hair growth.

In a double-blind, placebo-controlled trial of 192 people who had had a stroke, fisetin dramatically improved recovery by reducing inflammation.

In mice, fisetin removed senescent “zombie” cells, and the mice were healthier and lived longer. A review of senolytics found fisetin kills senescent cells without harming healthy cells. In liver cancer cells and in mice, fisetin reduced inflammation and helped to fight the cancer.

Alpha Ketoglutarate is a molecule found naturally in the human body. As we age, its levels decrease. It is vital in the KREBS cycle (energy) and it aids the mitochondria (power packs of the cell). It has shown promise in inhibiting MTOR, activating AMPK, protecting stem cells, protecting healthy bones and even helping with collagen production.

Calcium Alpha Ketoglutarate has been shown to reduce age-related inflammation, maintain DNA structure, detoxify the body, boost glutathione levels, reverse grays and most impressively, extend healthspan by 41%.

Ca-AKG has also been shown to:

•Help with weight loss.

•Extend your healthy lifespan.

•Convert white fat into brown fat.

•Reduce the inflammation from senescent cells.

•Strengthen bones.

•Change the color of hair/fur

In a human study, people taking Ca-AKG reduced their biological age by 8 years, measured by an epigenetic clock. Professor Andrea Maier is now running the ABLE trial, a placebo-controlled trial asking whether Ca-AKG reverses biological age. Results are expected in 2027.

The average house mouse lives just 3 years. The naked mole rat lives on average until around 30 years old, the longest-lived rodent by far. DoNotAge.org Advisory Board member Professor Vera Gorbunova concludes that this may be because of their abundance of high molecular weight hyaluronic acid. Naked mole rats very rarely get cancer, and Vera and her team found that removing the high molecular weight hyaluronic acid from naked mole rats makes them more prone to cancer, similarly to their other rodent cousins. Thus it seems the more high molecular weight hyaluronic acid a creature has, the less likely the cancer risk. Hyaluronic acid has also been shown to have cancer-fighting abilities in humans. Interestingly, high molecular weight hyaluronic acid promotes bodily repair over other molecular weight hyaluronic acid.

Skin aging is associated with a loss of skin moisture. The key molecule involved in skin moisture is hyaluronic acid, as it has a unique capacity to bind and retain water molecules. In layman’s terms, the theory is that the higher your hyaluronic acid, the more moisture your skin will retain and therefore less aging of the skin. Functions of hyaluronic acid include hydration, lubrication of joints and the framework for blood vessel formation. The size of hyaluronic acid is of critical importance for its various functions described above. Hyaluronic acid of high molecular size is present in intact tissues and has the potential to stop tumors from growing as well as prevent your immune system from overreacting. Smaller polymers of hyaluronic acid are distress signals and potent inducers of inflammation and angiogenesis, so not what we want. The reduction of hyaluronic acid in the skin by aging, sun exposure and air pollutants can induce dryness in the skin. However, daily hyaluronic acid supplementation moisturizes your skin and makes it healthy. Taking hyaluronic acid alleviates dry skin. It has been proven that oral supplementation of hyaluronic acid reduces wrinkles. Hyaluronic acid counteracts the aging processes with its anti-inflammatory and radical scavenging properties. It also causes significant improvements in skin hydration, wrinkles and elasticity.

Hyaluronic acid may also:

•Protect against respiratory diseases.

•Assist with wound healing.

•Alleviate dry eyes.

•Protect bone density.

•Reduce painful joints.

Hyaluronic acid is also vital for brain health. A lack of hyaluronic acid has led to seizures and diminished brain activity. Hyaluronic acid has a remarkable hydration capacity, and a lack of it causes reduced extracellular space volume in the brain. This space is vital for brain function.

Head trauma, stroke, and other brain injuries that initiate epilepsy are known to be associated with an early decrease in high-molecular-weight hyaluronic acid.

When taken as a supplement, high-molecular-weight hyaluronic acid has a high bioavailability and reaches peripheral tissues, including joints and skin. These findings support reports of biological actions seen after oral administration of high-molecular-weight hyaluronic acid in both animal and human studies. This means that supplementing with high molecular weight hyaluronic acid is beneficial for your joint and skin health.

A review of 7 human trials found that taking hyaluronic acid by mouth improves wrinkles, skin hydration and skin elasticity.

In a randomized, double-blind, placebo-controlled trial of 150 healthy adults, high molecular weight hyaluronic acid improved wrinkles, oiliness and skin hydration, and made skin look younger.

Taken together, animal and human studies suggest that optimal concentrations of both vitamin D and vitamin K are beneficial for bone and cardiovascular health. Vitamin D3 and magnesium are also vital for your bone health. Without magnesium, Vitamin D is neither useful nor safe. Low vitamin D and low magnesium levels are associated with chronic diseases. Magnesium intake is low in populations who consume modern, processed-food diets.

79% of us do not get enough magnesium, and magnesium deficiency can induce a wide range of clinical complications, including:

•Painful muscle spasms.

•Osteoporosis.

•Fibromyalgia.

•Irregular heartbeats.

•Headaches.

People eating a contemporary diet typically consume little magnesium. Your risk of not getting enough vitamin D is greatly reduced by a high magnesium intake. Vitamin D is neither safe nor helpful without magnesium.

Magnesium slows dementia and reduces your chances of cancer. A high intake of magnesium is significantly associated with a reduced risk of vitamin D deficiency. Vitamin D and magnesium deficiency can also lead to mental health issues & depression. Without magnesium, Vitamin D cannot be metabolized.

In a trial of 244 healthy older women, vitamin K2 (as MK-7) reduced the stiffness of their arteries, which is good for the heart and blood vessels.

In a 12 week study, menopausal women taking a supplement with vitamin D3, K2 and magnesium had better immune function, better metabolic health and less body fat.

A review of all research on vitamins D and K found that when they are taken together they are far more effective, and people have stronger bones and less risk of fractures. A review of all the data on magnesium and vitamin D found that most people do not get enough of either of them.

CoQ10 (coenzyme Q10) is made in your body and is needed by your mitochondria to make energy. Levels fall as you get older.

A meta-analysis of randomized trials found CoQ10 relieves fatigue and tiredness, and that it works best at a proper dose (200mg) taken over a longer period.

A meta-analysis of 45 randomized controlled trials, covering thousands of adults, found CoQ10 improves blood pressure.

In women having fertility treatment, a meta-analysis of 5 studies and 450 women found CoQ10 doubled the chance of pregnancy, whatever the cause of infertility.

In people with juvenile idiopathic arthritis, three months of CoQ10 cut arthritis severity by 50%, improved quality of life by 60% and lowered inflammatory markers by 30%, with no side effects.

In diabetic patients on dialysis, CoQ10 reduced inflammation and boosted antioxidants.

Collagen is the main structural protein found in the body. It is vital for healthy skin, muscles, ligaments and tendons. It also enables the body to have stronger bones.

Collagen is especially useful for reducing wrinkles, promoting skin elasticity, and increasing skin moisture.

Studies have shown that consuming 10 grams of collagen per day improves osteoarthritis symptoms.

Collagen can also prevent bone loss, reduce fat mass and prevent muscle wastage.

Collagen provides structure to your arteries, the blood vessels that carry blood from your heart to the rest of your body. Without enough collagen, arteries become less flexible and elastic.

In a randomized, double-blind, placebo-controlled trial in people with knee osteoarthritis, those taking collagen peptides every day had less joint pain and better physical function. In another randomized, double-blind, placebo-controlled trial, daily collagen peptides left skin more hydrated, less flaky and more elastic, with fewer wrinkles.

Omega 3 fats (EPA and DHA) are found in oily fish. Your body cannot make enough of them on its own.

In a large trial of more than 8,000 people, those taking a high dose omega 3 had 25% fewer heart attacks and strokes.

In one study on 174 people with mild to moderate Alzheimer’s disease, omega 3 helped slow the disease and protect the brain.

A global review found that 76% of people do not get enough omega 3.

Our probiotic combines live good bacteria with inulin, a prebiotic fiber that feeds them.

In a double-blind, placebo-controlled study in healthy people, inulin significantly increased the good bacteria in the gut, which is what a prebiotic is meant to do. A review of many trials found that probiotics, especially Lactobacillus and Bifidobacterium, support gut health and help with immunity and digestive problems, and that taking them with a prebiotic helps them survive and work better.

Just as NAD decreases with age, CD38 increases as we age. To compound these issues, CD38 is a NADase, which means it reduces our NAD levels. This means that boosting NAD levels is less effective when CD38 is too high. CD38 is inhibited by both Quercetin and Apigenin.

There are three main applications that use NAD. One relates to sirtuins. Many other genes involved in longevity and health can be activated and deactivated by these genes. Another is an enzyme family known as PARPs that is involved in cellular DNA repair. The third is CD38, a second messenger employed by cells to signal the calcium ion. The most important thing to keep in mind is that there is a limited supply of NAD (if one consuming use is excessively active, it may starve the others).

NAD levels decrease as people age. NAD levels may be roughly half of youthful levels by the time we are in our middle years. As they age, they may plummet much farther. Why do NAD levels decline as we age? While there are several causes, CD38 is a key offender.

As you’ll see in this article, CD38 activity and expression rise with age; by advanced age, it may be several-fold greater in various tissues and cells. Sirtuins, PARPs, and CD38 compete with one another for a limited supply of NAD, so when CD38 uses up too much of it, there is less NAD left over for Sirtuins and PARPs to use. The critical work they conduct suffers as a result. This can be changed by slowing CD38, which increases NAD indirectly and makes more of it available for utilization by sirtuins and PARPs.

Apigenin is the most potent known inhibitor of CD38, and when administered, NAD levels increase. It reduces CD38 by around two-thirds, which leads to a doubling in NAD levels.

Apigenin can reduce anxiety without negative effects, as well as protect the brain from decline. Apigenin is anti-inflammatory as well as anti-diabetic. Other benefits include:

•Works as an antioxidant.

•Has antimicrobial effects

•Reduces pain.

•Supports heart health

•Boosts brain function

•Reduces anxiety

•Reduces depression

•Works as an anticancer agent.

•Can increase testosterone levels.

Many apigenin products available on the market don’t store well and quickly lose their efficacy. Pure Apigenin from DoNotAge.org is derived from nature and thoroughly stabilized to maintain potency over time. It is coupled to beta glycosides.

In a mouse and cell study, apigenin blocked CD38, the enzyme that uses up NAD, and NAD levels went up. In rats, apigenin protected the brain from damage, and the rats learned and remembered better.

Caloric restriction is often referred to as the most proven way to extend life, with some studies showing an 83% increase in lifespan. Cutting your calorie intake by 15% whilst also using supplements can protect against cancer, diabetes and dementia.

Fasting is something that is done by many cultures around the world. Some do it as part of a religious holiday or ritual, while others choose to do it for the fantastic health benefits. While it is something that can work incredibly well when it comes to losing weight and improving your health and longevity, it also depends on the food that you eat. A person who chooses to eat a small McDonald’s meal every day would have a lesser result than someone who eats healthily.

Intermittent fasting is thought to reduce age-related diseases, such as cancer. It has also been shown to improve heart health, cholesterol, blood pressure, brain health, oxidative stress, immunity and insulin sensitivity, without leaving you hungry. Additionally, fasting has been proven to be a good way to lose weight, whilst keeping your muscle mass.

Blood pressure, resting heart rates, and other heart-related issues can all be improved by intermittent fasting. 16-hour fasting young men demonstrated fat reduction while retaining muscle mass. Studies have shown that mice that were fed on different days displayed greater running endurance than those fed every day.

Regular exercise reduces the chance of early death. Exercise helps with quality of life too, preventing chronic diseases, depression and frailty.

We’ve always had exercise as a miracle treatment, but we’ve been neglecting it for far too long. As a result, health is currently deteriorating.

Whatever your age, there is compelling scientific evidence that leading an active lifestyle can improve your overall health and happiness.

Regular exercisers are less likely to suffer from chronic diseases, including:

•Heart disease

•Type 2 diabetes

•Stroke

•Some types of malignancies

According to research, physical activity also lowers your chances of stress, clinical depression, dementia, and Alzheimer’s disease while boosting self-esteem, mood, sleep quality, and energy.

Exercise can boost your NAD levels, increase the size of your brain and in turn, boost your memory. It seems that interval training has superior health benefits to other types of exercise.