Science - DoNotAge.org

FASTING

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. physical activity. 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.

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EXERCISE

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.

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SULFORABOOST®

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”.

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AUTOPHAGY

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-ageing properties of autophagy appear to be its primary advantage. In fact, it’s best recognised 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.

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SPERMIDINE

Spermidine has been shown to delay ageing 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 ageing, 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.

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SLEEP

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:

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.

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SURESLEEP®

SureSleep® contains 3 active ingredients to help get you to sleep, stay asleep, and benefit from the lack of fatigue afterwards.

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 ageing, so as you become older, your sleep quality declines even more.

Rhodiola Rosea is an adaptogen that is a natural substance that stimulates the body’s resistance to stressors. It is commonly used to fight fatigue, anxiety, depression and stress. An extract from the plant has also been shown to kill cancer cells in humans.

Valerian root has long been used to induce sleep, and for good reason. It has been shown to improve sleep significantly, as well as reduce anxiety.

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.

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

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NAD

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 below). 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 ageing. 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-ageing 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.

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C D 38

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 utilisation by sirtuins and PARPs.

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SIRTUINS

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.

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S I R T 6 ACTIVATOR®

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 tumour 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-tumour 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.

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APIGENIN

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:

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

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NMN

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

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 ageing, such as heart and brain function.

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TMG

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.

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RESVERATROL

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.

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QUERCETIN

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 ageing, 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.

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AMPK

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.

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.

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CA-AKG

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 greys 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 colour of hair/fur

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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 utilised 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.

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HYALURONIC ACID

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. Do Not Age Advisory Board member Dr 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 ageing 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 ageing 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 tumours 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 ageing, sun exposure and air pollutants can induce dryness in the skin. However, daily hyaluronic acid supplementation moisturises 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 ageing 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.

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VITAMIN D3, K2 & MAGNESIUM

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.

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SENESCENT CELLS

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.

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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 Do Not Age Pure Fisetin.

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

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

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COLLAGEN

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.

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CREATINE MONOHYDRATE

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.

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WHAT IS THE SCIENCE BEHIND IT ALL?

THE SCIENCE