What are the best anti-aging supplements?

Most “anti-aging” supplements that many popular websites and books recommend do not slow aging.

These are substances like vitamin A, vitamin E, coenzyme Q10, lipoic acid, B-vitamins, calcium, omega-3 fatty acids, zinc, multivitamins, curcumin, EGCG, nicotinamide riboside (NR), mushroom extracts and many more.

All these substances have failed in well-conducted studies to extend lifespan in organisms (we explain here why this is the case).

Also, many touted “anti-aging” supplements are antioxidants, like vitamin A, vitamin E, coenzyme Q10, lipoic acid and so on. However, most antioxidants don’t slow down aging. Some antioxidants can even accelerate aging, like lipoic acid or vitamin A and vitamin E.

Luckily, there are far better, more science-based anti-aging supplements. We compiled a list below.

1. Fisetin

Fisetin is a natural ingredient found in vegetables and fruits, especially in strawberries. Fisetin is mostly known for its senolytic activity, meaning it can clear away senescent cells, and increase lifespan in various organisms (R,R,R,R).

Senescent cells accumulate everywhere in our body during aging. Senescent cells were previously normal cells that turned into “zombie cells”: senescent cells are cells that cannot divide anymore, but refuse to die, and secrete all kinds of substances that damage healthy surrounding cells.

Senescent cells in the skin contribute to wrinkles, senescent cells in the blood vessels make them more stiff, and senescent cells in the liver impair its proper functioning.

There are various natural substances that can have senolytic activity. One of them is quercetin. In fact, quercetin and fisetin look very similar. However, fisetin seems to be the most potent natural senolytic (R):

Researchers concluded that “fisetin had the most potent senotherapeutic effects in several cell types in vitro and showed strong anti-geronic effects in vivo.”

Besides clearing senescent cells, fisetin reduces inflammation (R,R), inhibits mTOR (an important aging switch) (R), reduces glycation (which also contributes to aging) (R), increases the production of cell protective substances, and has many more beneficial effects.  

Various studies show the lifespan extending effects of fisetin (R,R,R). For example, one study found that fisetin extends median and maximum lifespan in mice, even when taken late in a mouse’s life (equivalent to 50 or 60 years old for a human) (R):

Learn more about the anti-aging effects of fisetin here.

2. Alpha-ketoglutarate (the calcium form)

Alpha-ketoglutarate (AKG) is a substance that naturally occurs in our bodies. When we get older, the levels of AKG decline.

Various studies show that AKG extends lifespan (R,R,R,R,R). In one study, mice that received AKG lived on average 14 percent longer (R). 

But even more interestingly, the mice stayed healthy for much longer: The mice that received AKG had less aging-related diseases and symptoms, including a fur that became grey at a slower rate.

This probably has to do with alpha-ketoglutarate improving the stem cell function of the stem cells surrounding the hair shaft.

How can alpha-ketoglutarate extend healthspan and lifespan?

AKG has many functions in the body. For example, it is involved in mitochondrial health. Mitochondria are the power plants of our cells, which create energy so cells can go about their daily business. When we get older, our mitochondria function less and less well. Alpha-ketoglutarate provides energy for the mitochondria, among many other functions (R).

AKG also helps to maintain the epigenome (R). The epigenome determines which genes are active or not. The older we get, the more the epigenome gets dysregulated. Substances like AKG can slow down this decline. Alpha-ketoglutarate is also involved in stem cell maintenance (R). Interestingly, AKG also improves synthesis of collagen (R), which could improve skin appearance (R).  

It’s important that the right form of alpha-ketoglutarate is used, namely calcium alpha-ketoglutarate. Most supplements contain alpha-ketoglutarate, not the calcium form.

Alpha-ketoglutarate needs vitamin C to function properly, especially for its epigenetic functioning (R). So ideally, a good anti-aging supplement would contain both AKG and vitamin C to enable synergistic effects. Interestingly, vitamin C also has epigenetic effects (R).  

Learn more about the anti-aging effects of alpha-ketoglutarate here.

3. Microdosed lithium

Lithium is a mineral found in nature. It seeps from rocks into water, including drinking water. 

Various studies showed links between the amount of lithium in the drinking water and mortality rates (R,R), while other studies showed that people living in regions with more lithium in the drinking water had less neurodegenerative diseases like Alzheimer’s (R) and have lower suicide rates.

Of course, correlation is not causation. However, many studies in animals show that lithium can reduce the risk of Alzheimer’s disease and various other neurodegenerative diseases (R,R,R).

A systematic review and meta-analysis demonstrated that lithium may have beneficial effects on cognitive performance in people with mild cognitive impairment (often the precursor to Alzheimer’s disease) and Alzheimer’s disease (R).

Also, many studies show that lithium can extend lifespan in organisms (R,R,R).

Lithium also has been used for many decades as a medicine to treat psychiatric diseases, especially to stabilize mood disorders, such as bipolar disorder.

However, the amounts of lithium given to psychiatric patients are hundreds to thousands of times higher compared to the amounts of lithium in drinking water, dosages given in trials to reduce dementia, and amounts in longevity supplements like NOVOS. We see that very low or micro doses of lithium (in the range of 0.3 milligram to a few milligrams) can have lifespan effects and protect the brain against neurodegenerative diseases like Alzheimer’s (R,R,R).

There are many ways by which lithium can impact the aging process. Lithium has been shown to increase autophagy (the digestion of proteins that would otherwise accumulate in the cells, a process that contributes to aging) (R,R), enhance the generation of pluripotent stem cells demonstrating its epigenetic effects (R), and improve neurogenesis (R), the formation of new neurons.

Learn more about the anti-aging effects of microdosed lithium here.

4. Glycine

Glycine is an amino acid that occurs naturally in our body. When we age, glycine levels decline.

Low glycine levels also have been associated with various aging-related diseases like cardiovascular disease and with type 2 diabetes.

Glycine extends lifespan in different species (R,R,R,R).  

Glycine has many functions in the body. It improves the epigenome (the machinery that determines which genes are switched on or off, a process that goes increasingly awry when we get older). Glycine especially improves the epigenome of mitochondria, the power plants of our cells (R).

Glycine also functions as a chaperone. Chaperones are small molecules that gently stick to and protect the proteins. That is important, because one of the reasons why we age is due to proteins accumulating everywhere inside and outside our cells, eventually hampering the proper functioning of our cells.

Glycine also reduces inflammation (R) and has many other beneficial effects, especially for the cardiovascular system. People with higher glycine levels in the blood had less risk of a heart attack (R), and glycine can protect the blood vessels (R).  

Learn more about the anti-aging effects of glycine here.

5. Pterostilbene

Pterostilbene is the better brother of the famous anti-aging substance resveratrol.

Resveratrol has long been hyped as a longevity substance. However, it unfortunately did not live up to that hype. Studies showed disappointing results when it came to resveratrol extending lifespan.

One reason for this is that resveratrol has a very short half-life: most of it is broken down in less than an hour. Also, resveratrol, when taken orally, is not very well absorbed.

Pterostilbene, on the other hand, has a far longer half-life and better absorption, so that higher levels reach the blood and stay around for longer in the body.

We see in studies that pterostilbene performs better than resveratrol (R).

Pterostilbene has been associated with longer lifespans (R,R), and could reduce various aging symptoms and mitigate aging-related diseases, including Alzheimer’s disease (R,R,R).

Learn more about the anti-aging effects of pterostilbene here.

6. Malate or malic acid

Malate, also called malic acid, is found in apples, and in our own bodies.

Malate is an important substance in the mitochondria. In fact, malate is a component of the Krebs cycle, which consists of various substances that are chemically modified to provide the energy that keeps all cells going.

Studies show that malate can extend lifespan in simple organisms (R).

In humans, malate can confirm various health benefits. For example, malate is given to provide energy, increase stamina and cognition, especially in combination with magnesium (R). 

That’s why the best form of magnesium for anti-aging purposes is magnesium malate (and not magnesium oxide, magnesium citrate and other forms of magnesium).

Learn more about the anti-aging effects of malate here.

7. Magnesium

Magnesium is an indispensable mineral for the body to function properly.

Magnesium helps innumerable enzymes in our body to function properly. Cells shuttle magnesium in and out to propagate nerve signals and to generate muscle impulses, including the beatings of our heart.

Magnesium also sticks to our DNA, stabilizing our DNA, protecting it against damage (R). Increasing DNA damage is one of the reasons why we get older.

Low intakes of magnesium are associated with increased inflammation, increased blood pressure, increased risk of heart disease, neurodegenerative diseases, insulin resistance, osteoporosis and even development of cancers (R).

Magnesium also provides energy, and can help people to deal with stress. Magnesium especially teams up well with malate, another substance that can provide energy.  

Learn more about the anti-aging effects of magnesium here.

8. Glucosamine (the sulfate form)

Most people know glucosamine as a substance to reduce wear and tear of cartilage and to improve joint health.

Few people know that glucosamine can also extend lifespan in different organisms, including mice (R,R).

Interestingly, studies show that glucosamine is one of the few supplements associated with reduced mortality in humans (R,R), and also reduced risk of cardiovascular disease in humans (R). There are also associations between people taking glucosamine and reduced inflammation (R).

Various animal studies showed that glucosamine reduces atherosclerosis (R,R) and inhibits platelet aggregation (R), making the blood less clotty.

This should not be surprising, given the many effects glucosamine has on the body. It does much more than protect cartilage.

Glucosamine can improve mitochondrial health, thus enabling the mitochondria (the power plants of our cells) to function better. One way of doing this is by increasing “mitochondrial biogenesis”, which means that glucosamine induces the formation (genesis) of extra mitochondria.

Glucosamine also reduces inflammation (R,R,R), which is a good thing given inflammation increases during aging. This low-grade inflammation is called “inflammaging”.

The best form of glucosamine is glucosamine sulfate. Many supplements contain only glucosamine, not the sulfate form.

Learn more about the anti-aging effects of glucosamine here.

9. Hyaluronic acid

Hyaluronic acid is an important component of the skin. But hyaluronic acid (HA) surrounds and embeds many other cells in the body than just the skin cells.

The older we get, the less hyaluronic acid there is in the body. A 70-year-old has only about 19 percent of the amount of hyaluronic acid of a young person.

Studies show that hyaluronic acid, taken orally, can improve skin appearance by reducing wrinkles, improving moisturization of the skin and increasing skin radiance (R,R). It can also improve osteoarthritis (R,R,R), which makes sense given joints and cartilage contain a lot of hyaluronic acid.  

Interestingly, hyaluronic acid is made up of acetyl-glucosamine (do not confuse with glucosamine).

Acetyl-glucosamine has been shown to extend lifespan in mice (R).

Acetyl-glucosamine could do this by inducing the “unfolded protein response”, which is a defense mechanism that kicks into action when the cell senses that there are too many improperly folded proteins accumulating in the cell (R).

Protein accumulation is one of the reasons why we age. When you consume hyaluronic acid, parts of the molecule are broken down in the gut into acetyl-glucosamine, which can be absorbed by the gut cells and end up in the bloodstream.

Learn more about the anti-aging effects of hyaluronic acid and its component acetylglucosamine here.

10. Ginger

Ginger is a well-known spice. But it’s not just any spice.

Many scientific studies demonstrated multiple beneficial health effects of ginger, like reducing inflammation (R) and protecting cells against damage (R).  

Ginger has been found to extend lifespan in simple organisms, like fruit flies (R).

Ginger can improve type 2 diabetes (R,R) and inflammation in humans (R,R).

Studies show that ginger can protect mice against lethal doses of radiation, which is quite impressive (R). The mice that received ginger before they got exposed to a high dose of radiation lived considerably longer. High-energy radiation is very damaging to cells, as the radiation oxidizes (damages) many components of the cells, rips molecules, including DNA apart, and induces strong inflammation.

However, ginger seems to be able to mitigate this molecular onslaught.

Learn more about the anti-aging effects of ginger here.

11. Rhodiola rosea

Rhodiola rosea is a very interesting plant that grows in the northern regions of Europa and Asia.

Rhodiola rosea has been used for centuries as an adaptogen, a substance that can improve resilience against both physiological stress and mental stress.

Rhodiola rosea extends lifespan in various organisms, for reasons that scientists have not completely understood yet (R,R,R,R).

Interestingly, Rhodiola can also improve nerve regeneration; specific substances in Rhodiola, like salidroside could be responsible for this very interesting effect (R,R). This could be one of the several reasons demonstrating neuroprotective effects of Rhodiola rosea (R,R,R).

Studies in humans show that Rhodiola rosea can improve memory, concentration and can reduce fatigue (R). Students and people with demanding jobs take Rhodiola rosea to improve their productivity and energy levels (R,R,R).

Learn more about the anti-aging effects of Rhodiola rosea here.

12. L-theanine

Theanine is a substance found in green tea, and is one of the reasons why green tea is healthy.

Theanine has been shown to extend lifespan in simple organisms (R,R,R).

Theanine has been associated with healthier blood vessels, and could reduce blood pressure and even obesity (R).

Theanine has shown to reduce neurodegeneration and protect neurons (R,R,R). It could also perhaps improve neuronal stem cell health and neurogenesis (the creation of new neurons in the brain) (R,R,R).

In humans, theanine can improve concentration, while also improving relaxation.

Learn more about the anti-aging effects of theanine here.

13. Nicotinamide mononucleotide (NMN)

Nicotinamide mononucleotide (NMN) is needed to make NAD+.

NAD+ is a very important substance in the cells. It provides energy for cells and is also a cofactor for proteins that repair and maintain our epigenome and our DNA.

The epigenome is the intricate machinery that surrounds the DNA and that determines which genes are active. During aging, the epigenome becomes more and more dysregulated.

NMN also improves the functioning of our mitochondria, the power plants of our cells.

NMN improves metabolism and reduces inflammation.

The older we get, the less NAD+ is present in our cells. Taking in NMN can increase NAD+ levels.

Various studies show that NMN has beneficial effects on aging diseases and symptoms (R,R,R,R).

For example, long term administration of NMN mitigated age-associated decline in mice: NMN reduced the typical age-associated increase in body weight, improved energy metabolism, improved lipids in the blood and insulin sensitivity and ameliorated eye function (R).

NMN can also improve aging-related decline in fertility (R), improve bone health (R) and vascular health (R,R,R).

For more information on NMN and aging, click here. For a comparison between NMN and NR (nicotinamide riboside), click here.

The importance of synergy in anti-aging supplements

In conclusion, many anti-aging supplements are based on outdated insights and don’t have any or just very little science backing up their claims.

Also, they do not contain substances that have been shown to act on aging mechanisms (the “hallmarks of aging”).

A good anti-aging supplement is one that contains substances that are based on science and that acts on aging mechanisms. This also enables these supplements to have an additional important benefit: synergy.

After all, aging is a complex process caused by various different mechanisms, such as epigenetic dysregulation, mitochondrial dysfunction, and accumulation of proteins.

If you have an anti-aging supplement that only focuses on “improving mitochondrial health”, you are not addressing other important aging mechanisms, like epigenetic dysregulation or accumulation of proteins.

Therefore, this supplement, even if it could improve mitochondrial health, will have little impact on extending lifespan given it only tackles one facet of the aging process.

As such, it’s very important for a good anti-aging supplement to contain substances that act on different aging mechanisms and this in a synergistic way.

For example, alpha-ketoglutarate (AKG) can maintain the epigenome and improve mitochondrial health. AKG can work together with other substances that improve mitochondrial health, like fisetin and malate, or that improve the epigenome, like NMN and glycine.

But addressing the aging epigenome and mitochondria is not enough. You also need to tackle many other aging mechanisms, like protein accumulation and DNA damage.

For this, other anti-aging substances need to be added, like lithium (which can reduce accumulation of proteins by stimulating autophagy – the digestion of proteins) or acetyl-glucosamine which can also reduce protein accumulation, or magnesium that can help stabilize the DNA.

So the ideal anti-aging supplement contains not just one or two substances that focus on one aging mechanism (like mitochondrial health or the NAD+ metabolism), but contains many substances that act on many aging pathways, and this in a synergistic way.

No such supplement existed, which is why we created NOVOS Core, a pioneering nutraceutical that contains no less than 12 science-based, synergistic ingredients to slow down aging (NOVOS Core contains all the ingredients described in this blog post, except NMN), and NOVOS Boost, which contains NMN. 

Learn more about the anti-aging supplement NOVOS Core

Further reads:

• How to create the best, science-based anti-aging supplement?
• Why antioxidants don’t slow down aging
• What is the best anti-aging supplement?
• Why combinations of longevity drugs are the future
• What anti-aging supplements does Harvard scientist David Sinclair take?
• Why have science-based anti-aging supplements not been developed sooner?
• The 4 best supplements to reduce wrinkles and slow down skin aging, based on science
• What makes the best anti-aging supplement?
• Is NOVOS the best anti-aging supplement?