10 Best Supplements for Longevity and to Live Longer 2023

Aging can be defined as the time-related deterioration of the physiological functions necessary for survival and fertility. The characteristics of aging—as distinguished from diseases of aging (such as cancer and heart disease)—affect all the individuals of a species.

This article compiles more than 100 references and supporting studies related to the anti-aging or slowing the aging process. This article will also reveal exciting new information about a variety of immune-enhancing natural products and nutrients that may help you maintain youthful immune system function into advancing age.

anti-aging supplements

Methodology: The selection or short-listing of the list below is based on the available scientific evidence retrieved from scientific database such as PubMed and scientific search engine such as Google Scholar. The article will also be updated as and when there is a newly discovered major research publication related to anti-aging.

Here are the best supplements with anti-aging properties. Not all the supplements below are required. You are advised to consult with your trusted healthcare provider before taking these supplements.

1. Nicotinamide mononucleotide (NMN)

Nicotinamide mononucleotide (NMN) is a precursor to 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 animal and lab 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).

NMN can also improve and protect stem cells such as mesenchymal stem cells that form bone and fat tissue (R,R).


2. Omega-3 fatty acids

Omega-3 fatty acids reduce inflammation, enable the immune system to carry out its tasks, and help the brain and eyes to function properly.

The Framingham study group is one of the longest-running longitudinal health data sets in existence. Since 1971, the residents of this small Massachusetts town have given us everything from heart health data to their knee annual MRI images. That’s where the data for this new Omega-3 research originates.

The study, published in The American Journal of Clinical Nutrition (Oct 2021), used data from a long-term study group, the Framingham Offspring Cohort, which has been monitoring residents of this Massachusetts town, in the United States, since 1971.

The research looked at 2,200 people who were monitored for 11 years for their blood fatty acid levels. The researchers found that omega-3 levels in red blood cells are very good mortality risk predictors. That means that higher levels of Omega-3 in the blood from regularly eating oily fish, increased life expectancy by almost five years.

This research comes a few months after a meta-analysis of 17 prospective cohort studies was published in Nature Communications. The analysis linked higher circulating omega-3 fatty acid levels to longevity. In a pooled analysis of the studies, participants in the highest fifth of combined blood DHA and EPA were 15 to 18 percent less likely to die from any cause over the follow-up period (median follow-up time is 16 years in these studies). Higher blood omega-3s were also associated with a reduced risk for death from cardiovascular disease and cancer.

According to a review (Nutrients, September 2022), data from scientific literature 'overwhelmingly' supports beneficial effects of omega-3 fatty acids on the length of telomeres, reported to be a marker of biological age.

Many governments recommend eating omega-3 containing fatty fish, two times per week. But that is often not enough. Ideally, people would need to eat fatty fish four times per week, while also supplementing with omega-3 fatty acids, at least 1,000 mg of pure omega-3 (DHA and EPA) per day.

Make sure you buy high-quality omega-3 fatty acid supplements, meaning that the omega-3 fatty acids are pure and have not oxidized much (having low “TOTOX” value).

TOTOX value stands for total oxidation value. The omega 3 fatty acids EPA and DHA from fish oil are highly sensitive to oxidation. This means that they are rapidly affected by contact with oxygen. Oxidised fatty acids are not beneficial to our health. For this reason, a good fish oil supplement has a low TOTOX value. The maximum TOTOX value is set at 26 by the Global Organization for EPA and DHA omega-3.

3. Resveratrol and Pterostilbene

Resveratrol is a polyphenol in grapes, berries, peanuts, and red wine that may promote longevity by activating certain genes called sirtuins. It has been shown to increase the lifespan of fruit flies, yeasts, and nematodes (Source).

It displays powerful antioxidant, anti-inflammatory, and antitumor properties in clinical trials. Resveratrol also enhances sirtuin function (R).

Nearly two decades ago, it was discovered that resveratrol slowed the process of cellular aging in yeast. In 2003, Harvard Medical School Professor David Sinclair, PhD, found that resveratrol activated a longevity gene called SIRT1 and the resultant class of sirtuin proteins.

Then, the same mechanism was studied and found to be true in mice. Investigations into resveratrol then turned toward its effects on human health. Resveratrol was found to support cardiovascular health, antioxidant defenses, glucose metabolism, healthy inflammatory balance, and more. As results of these reported studies, people became more interested in drinking resveratrol-rich red wine and taking resveratrol supplements.

Pterostilbene vs Resveratrol

Some of the biggest hurdles for reaping the benefits of resveratrol in humans appear to be its limited bioavailability and rapid elimination from the body. But those hurdles might be overcome by a compound that has more recently gained some notice.

PubMed has indexed more than 12,000 research studies on resveratrol, but only 500 on pterostilbene. However, the sheer number of scientific studies on a compound doesn’t necessarily mean the compound is superior. It’s also important to note that pterostilbene research lags about 10 years behind resveratrol research.

The slight difference in molecular structure between resveratrol and pterostilbene provides a sound rationale for the superiority of pterostilbene. Pterostilbene should be more stable and bioavailable in theory, and preclinical studies so far validate the assumption.

Buy on Amazon > Resveratrol Supplement

4. Quercetin and Fisetin

Fisetin is a naturally occurring substance found in fruits and vegetables, such as strawberries, apples, grapes, onions, and cucumbers. Fisetin is also a molecular cousin to quercetin.

Fisetin is a flavonoid. Flavonoids are substances that give fruits and vegetables their bright colors (like yellow, orange and blue) and play a major role in conferring the health benefits that we get from eating more vegetables and fruits.

Fisetin is probably most known for its impact on senescent cells: studies showed that this substance can reduce the accumulation of senescent cells (R). Fisetin is a senolytic, a compound that can clear away senescent cells.

Senescent cells accumulate everywhere in the body during aging. Senescent cells were previously normal cells that became too damaged. Normally, when a cell is too damaged, it kills itself, but senescent cells don’t do that.

Instead of dying, they keep lingering around in the body.

Senescent cells secrete all kinds of substances that damage the healthy surrounding cells, like inflammatory substances (cytokines and chemokines), substances that break down the glue that holds the cells together (matrix metalloproteinases), and growth factors that accelerate aging (R). Not only do senescent cells damage healthy surrounding cells, but they also damage stem cells, which are the foundational cells that create new cells, which build up and repair our organs and tissues.

Reducing the senescent cell burden can lead to reduced inflammaging (low-grade inflammation that increases during aging) and enhanced function of stem cells.

Substances that can eliminate senescent cells are called “senolytics”. Fisetin is a well-studied senolytic substance.

Fisetin versus quercetin

Besides fisetin, another senolytic is quercetin. Quercetin and fisetin look very similar. However, fisetin seems to be the most potent and safest of natural senolytics (R):

Fisetin is far better in destroying senescent cells (red bar) than other substances, such as quercetin or curcumin or EGCG. Source image: Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine, 2018

The conclusion of the researchers was the following:

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

More than a senolytic: other anti-aging effects of fisetin

Fisetin has many other beneficial effects on the aging process besides eliminating senescent cells.

For example, fisetin inhibits the mTOR pathway (R), which plays an important role in aging and is where many of the health benefits behind fasting are derived. Fisetin can also reduce oxidative stress (R).

Fisetin can reduce inflammaging (aging-related low-grade inflammation) by inhibiting pro-inflammatory enzymes and substances, like lipoxygenases and NF-kB (RR).

Interestingly, fisetin can also have various beneficial effects on the skin. For example, fisetin can reduce the formation of skin wrinkles and appearance of skin aging.

One way it can achieve this is by reducing the amount of matrix metalloproteinases (MMPs) (RR). MMPs are enzymes that break down the extracellular matrix that surrounds our cells. The extracellular matrix consists of collagen, elastin, hyaluronic acid, glycosaminoglycans (GAGs), and many other molecules that glue the cells together, so that they can firm tissues (like the skin) and organs. An overactivity or overproduction of matrix metalloproteinases plays a role in wrinkle formation.

Fisetin also has a positive impact on brain functioning and brain aging (R). For example, fisetin can improve memory formation in mice (RR).

5. Vitamin D3 and K2

Vitamin D can extend lifespan. Higher levels of vitamin D are associated with less risk of heart disease, auto-immune diseases, improved brain health and a better functioning immune system.

Many governments advise 400 to 800 IU of vitamin D per day, while many vitamin D researchers claim you need at least 2000 to 4000 units per day.

We would recommend to take at 2000 units per day. The risk of excess accumulation of vitamin D is negligible with this amount. Make sure it’s vitamin D3, and not vitamin D2 – the vitamin D3 variant works better.

“We [in the medical community] are beginning to realize the anti-inflammatory effects of vitamin D,” says Amanda Frick, a licensed naturopathic doctor and acupuncturist in Santa Monica, California. It builds bone, boosts immunity, guards against chronic ailments, and is responsible for increasing absorption of calcium and magnesium. If you’re still not sold on vitamin D as one of the anti-aging supplements to add to your regimen, Frick says it can also assist with weight loss when combined with lifestyle intervention.

Theoretically, we should get enough vitamin D through our diet and from the sun, but for many of us, that’s not the case. In the United States, 35% of adults and 61% of people over the age of 65 are deficient in vitamin D. Vitamin D deficiency is associated with an increased risk of osteoporosis, weakness, and bone fractures in the elderly, among other things. Recent studies also show a link between vitamin D deficiency and cardiovascular disease, diabetes, and cancer (Sizar, 2020).

Some studies have shown links between vitamin D supplements and lower blood pressure, decreased symptoms of depression, better cognitive function, and stronger muscles (Nair, 2012).

Vitamin D ensures that your blood levels of calcium are high enough to meet your body’s demands. However, vitamin D does not fully control where the calcium in your body ends up. That’s where vitamin K steps in. Vitamin K2 supplements have been proven to be more effective than vitamin K1. That's why most of the top vitamin D supplement brands do combine their vitamin D3 with K2.

6. 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).

7. Molecular Hydrogen

Molecular hydrogen is the smallest anti-oxidant. The ability of molecular hydrogen (H2) to protect the DNA and the mitochondria from oxidative damage may have beneficial effects on chronic diseases and cancer. But perhaps it could help slow down or reverse the aging process itself. A couple of cellular studies give us some interesting clues [R, R].

It was already discovered that hydrogen can prolong the life of stem cells by reducing oxidative stress
(Biochem Biophys Res Commun. 2010).

A hydrogen-rich environment reduced both oxidative stress and aging in cells. Some scientists think
that drinking hydrogen water could increase longevity in humans (Circ J. 2016).

8. Calcium Alpha-KetoGlutarate (AKG) 

Alpha-ketoglutarate (AKG) is a small molecule naturally present in our body. During aging, levels of AKG decline.

Alpha-ketoglutarate is used by the mitochondria, which convert this substance into energy, but alpha-ketoglutarate has various other functions in the body.

Numerous studies show that alpha-ketoglutarate can extend lifespan in various organisms. AKG extended lifespan in C elegans worms (R) and fruit flies (R,R,R) and mice.

C elegans fed AKG (red) live longer than the control group (black). Source: Chin et al, Nature.
A study in mice, conducted at the Buck Institute, one of the world-leading aging research institutes, found that alpha-ketoglutarate extended lifespan in old mice by 12 percent (R).

Very interestingly, alpha-ketoglutarate extended health span by an impressive 41 percent: the mice didn’t only live longer, they stayed healthier and disease-free for considerably longer.

Alpha-ketoglutarate also siginificantly reduced hair graying in elderly animals (R).

How alpha-ketoglutarate extends lifespan? Alpha-ketoglutarate impacts the aging process in various ways.

First, alpha-ketoglutarate has epigenetic effects. The epigenome is the intricate molecular machinery surrounding the DNA that decides which genes are switched on or off. The older we get, the more the epigenome becomes dysregulated: some genes that should be silent are switched on, and some genes that should be active (like cancer protection genes) are switched off. This epigenetic dysregulation is one of the reasons why we age.

An important enzyme that regulates the epigenome is TET (ten eleven translocation). This enzyme can reprogram the epigenome to a more youthful state. TET needs alpha-ketoglutarate to function properly. TET also needs vitamin C to carry out its work properly.

Alpha-ketoglutarate is also at the nexus of carbohydrate and amino acid metabolism. The older we get, the less flexible cells become at switching between carbohydrates and amino acids to produce energy. Alpha-ketoglutarate, however, can help cells to maintain this metabolic flexibility for longer.

Alpha-ketoglutarate also improves mitochondrial health, which makes sense, given this substance also an energy source for the mitochondria. Alpha-ketoglutarate activates AMPK, an important metabolic and longevity switch (R). 

Besides that, we see that alpha-ketoglutarate can help the body to detoxify: alpha-ketoglutarate helps the body to get rid of ammonia. Ammonia is a waste product from the protein metabolism that tends to accumulate in the body (the more protein you eat, the more ammonium you produce). When we get older, the body has more difficulty getting rid of the ammonia. Too much ammonia is toxic, and alpha-ketoglutarate helps to detoxify the body from ammonium.

Also, given alpha-ketoglutarate serves as a fuel for the mitochondria, it could provide more energy and endurance. That is why athletes and bodybuilders have been taking alpha-ketoglutarate for decades. However, some studies show that alpha-ketoglutarate does not provide substantially extra energy (R). In these studies, however, the arginine-alpha-ketoglutarate form is taken, while ideally, the AKG form without arginine, but with calcium is taken, at least for longevity purposes.

Alpha-ketoglutarate also plays a role in maintaining stem cell health (R), and in bone and gut metabolism (R).

Calcium alpha-ketoglutarate is also involved in collagen production, can reduce fibrosis, and can thus play a role in maintaining healthy, youthful skin (R,R).

Regular alpha-ketoglutarate vs calcium alpha-ketoglutarate

Most alpha-ketoglutarate supplements contain plain alpha-ketoglutarate.

However, scientists believe that the calcium form of alpha-ketoglutarate, namely calcium alpha-ketoglutarate (calcium AKG or CAKG), is significantly better than regular alpha-ketoglutarate, in which the alpha ketoglutarate molecule is not linked to a calcium atom.

Calcium alpha-ketoglutarate can have additional beneficial effects compared to alpha-ketoglutarate. One reason for this is that calcium alpha-ketoglutarate is more slowly absorbed in the gut and released into the bloodstream, so it can work for longer in the body. This makes sense, given alpha-ketoglutarate is an important metabolite and ideally it is present in our body at sufficiently high levels for as long as possible.

Most supplements contain only alpha-ketoglutarate, not calcium alpha-ketoglutarate. Also, their dose of alpha-ketoglutarate is often too low.

Alpha-ketoglutarate ticks all the boxes of an ideal longevity molecule: there is substantial scientific evidence showing it extends lifespan in various organisms (C elegans, fruit flies and mice).

Alpha-ketoglutarate works beneficially on various aging mechanisms (such as epigenetic and mitochondrial dysfunction).

It is a natural substance that occurs in our body, but of which the levels decrease as we get older.

It has been taken by humans for many decades with the only significant side effects seeming to be increased lifespan and healthspan.

9. Collagen

Collagen is promoted as a fountain of youth for its potential to reduce the appearance of skin aging.

It’s an integral component of your skin that helps maintain skin structure. As you age, collagen production slows, leading to collagen loss in the skin that accelerates signs of aging like wrinkles.

Some research suggests that supplementing with collagen may reduce signs of aging, including wrinkles and dry skin.

For example, a 2019 study in 72 women demonstrated that taking a supplement that contained 2.5 grams of collagen — along with several other ingredients, including biotin — per day for 12 weeks significantly improved skin hydration, roughness, and elasticity (R).

Another study in 114 women found that treatment with 2.5 grams of collagen peptides for 8 weeks significantly reduced eye wrinkles and increased collagen levels in the skin (R).

Though these results are promising, keep in mind that many collagen studies are funded by companies that manufacture collagen products, which may influence study results.

Many types of collagen supplements are on the market, including powders and capsules.

Buy on Amazon > Collagen Supplement

10. EGCG (Green Tea Extract)

Epigallocatechin gallate (EGCG) is a well-known polyphenol compound concentrated in green tea. 

Studies have confirmed numerous health benefits of green tea including prevention of cancer (RR) and cardiovascular disease, as well as anti-inflammatory, antioxidant, antiarthritic, antibacterial, and antiviral effects. (RRRR). Plus, animal studies have shown that it can protect against skin aging and wrinkles caused by ultraviolet (UV) light (Source).

Among EGCG’s diverse array of potential health-promoting properties is its ability to promote longevity and protect against age-related disease development.

EGCG may slow aging by restoring mitochondrial function in cells and acting on pathways involved in aging, including the AMP-activated protein kinase signaling pathway (AMPK). It also induces autophagy, the process by which your body removes damaged cellular material (Source).

Green tea may protect against EMF exposure as well. A 2011 study published in Neurotoxicity Research reported that green tea can protect neurons in the brain against cell phone radiation. Cell phone exposure for 24 hours resulted in neuronal cell death in cultured rat cells. Green tea, however, prevented cell death.

The Minnesota Green Tea Trial (MGTT) is the largest and longest double-blind, placebo-controlled, randomized intervention study that specifically evaluated the effects of oral GTE (green tea extract) containing defined quantities of EGCG on established biomarkers of breast cancer risk.

They randomized and stratified 1075 healthy postmenopausal women at high risk of breast cancer according to their breast tissue density and catechol-O-methyltransferase genotypes and divided them into two groups: 537 placebo and 538 green tea groups. Green tea group participants took 4 capsules that contained 843 mg EGCG, whereas the placebo group took capsules without green tea extracts.

Researchers measured changes in percent mammographic density, circulating endogenous sex hormones, and proteins of the insulin-like growth factor axis. Their results showed that supplementation with green tea extract could modify and reduce mammographic density (MD) and protect against breast cancer, even though it was only significant in younger women (50–55 years) and had no effect in older women (R), an age-dependent effect similar to those of tamoxifen.

EGCG can be consumed by drinking green tea or taking concentrated supplements.

Buy on Amazon > EGCG supplement 

Conclusion

It is important to note that supplements should not be used as a substitute for a healthy diet and lifestyle. Eating a balanced diet, exercising regularly, managing stress, and getting enough sleep are all important factors in promoting longevity and overall health. It's always best to talk to your doctor before starting any new supplement program.

Certain supplements may help slow the aging process and promote a long, healthy life. 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 a single dimension such as “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 stack or combination to contain substances that act on different aging mechanisms 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.

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 in a synergistic way.

In real medicine, results are not guaranteed and there are no cure-alls. Real research is published in peer-reviewed journals, and you can search the journals via PubMed or Google Scholar.


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