18 Best Longevity Supplements Proven to Increase Lifespan 2025: Scientifically Proven

Contents

• Introduction
• Best Longevity Supplements

1. Vitamin D3, K2 and Omega-3 fatty acids
2. B Vitamins, Nicotinamide mononucleotide (NMN) and NAD Boosting Supplements
3. Magnesium and Molecular Hydrogen
4. Glycine, NAC and Taurine
5. Vitamin C and Alpha-KetoGlutarate (AKG)
6. Fisetin 
7. EGCG (Green Tea)
8. CoQ10
9. Curcumin (Turmeric)
10. Resveratrol and Pterostilbene
11. Zinc
12. L-Citrulline and L-Arginine (Nitric Oxide Boosters)
13. Lutein and Zeaxanthin
14. Glucosamine and Chondroitin
15. Collagen
16. Spermidine
17. Crocin (Saffron)

• Conclusion and Key Takeaways

Introduction

What are the best anti-aging supplements? Are they the Elixir of Youth? This practical guide on anti aging supplements has more than 250 references and supporting studies that represent the best of science-backed strategies for nutritional interventions in longevity and anti-aging.

Aging is a natural process that everyone goes through, and while there is no magic potion to stop the clock, the use of anti-aging supplements has been a focus of scientific research for decades. However, it's essential to note that there is no one-size-fits-all answer when it comes to the effectiveness of anti-aging supplements, as they can vary depending on individual health, age, and other factors.

NAD, stem cells, nitric oxide, CoQ10, glutathione, glycine and taurine decline as we age. Vitamin and mineral deficiencies are also common in older individuals.

The 2022 Hallmarks of Aging study identified fourteen factors that contribute to health decline in advancing age: 

1. genomic instability, 
2. telomere attrition, 
3. epigenetic alterations, 
4. loss of proteostasis, 
5. deregulated nutrient-sensing, 
6. mitochondrial dysfunction, 
7. cellular senescence, 
8. stem cell exhaustion
9. altered intercellular communication
10. compromised autophagy, 
11. microbiome disturbance, 
12. altered mechanical properties, 
13. splicing dysregulation, and 
14. inflammation.

While aging is inevitable, increasing the human lifespan and slowing the aging process has been a focus of scientific research for decades. If aging is reversible, then maybe heart disease, cancer, diabetes, Alzheimer's or other chronic disorders are reversible as well.

Although many main-stream media channels may state that there is no scientific evidence to support the effectiveness of any specific supplements, it's definitely not true. There are countless anti-aging supplements that are supported by overwhelming scientific evidence out there. However, most of them are based on outdated science, not supported by well-conducted scientific studies or not scientifically proven, focus on aging process that are less relevant, contain doses that are too low, and are not verified in humans.

When interpreting scientific studies, let’s remember that not all studies are created equal. Below is a list of study types ranked in descending order based on their evidence quality:

1. Umbrella review, Meta-analysis and Randomised controlled trials (RCTs)
2. Large clinical trials (phase 3)
3. Small clinical trials (phase 2) and Case studies
4. Mouse results and animal studies
5. In Vitro, cell culture, commentary, review, expert opinions and anecdotal evidence

It's crucial to understand the limitations of conventional medicine when exploring the subject of anti-aging supplements. Most doctors may not have much to offer in the anti-aging space, as the focus of conventional medicine involves treating diseases reactively with drugs and surgery. However, recent scientific studies have proven the effectiveness of many anti-aging supplements, but it's essential to choose the ones that are scientifically proven, based on up-to-date science, and verified in humans.

In this article, using a scientifically-based approach, we delve into the latest research on anti-aging supplements and gero-protectors to provide you with a comprehensive guide to anti-aging strategies.

Longevity Medicine will become the New Primary Care

Most “anti-aging” supplements that many popular websites and books recommend do not slow aging. Probably the biggest problem is that most supplements are based on outdated ideas about aging, such as the over-simplified idea that aging is mainly driven by oxidative damage, caused by free radicals which antioxidants can neutralize. 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. 

Unfortunately, large studies, sometimes even with hundreds of thousands of participants, have shown that antioxidants do not extend lifespan (R,R,R).

Some antioxidants can even accelerate aging, like lipoic acid or vitamin A and vitamin E or increase the risk of cancer (R).

We know now that aging is a far more complex process than just oxidative damage. There are many other and more important reasons why we age, like epigenetic dysregulation, protein accumulation, mitochondrial dysfunction, and so on.

Image credit: Longevity.technology

Which are some examples of these popular “anti-aging supplements” that in fact will do little to slow down aging? Vitamin A, vitamin E, alpha lipoic acid, copper, and potassium are not going to slow down aging.

They can be useful if you have deficiencies in these vitamins or minerals, but taking additional amounts of these substances is not going to address aging at its root causes.

Luckily, there are far better, more science-based anti-aging supplements. We have compiled a list below. Note that this list is not exhaustive, and many other supplements may also offer anti-aging effects.

Methodology: The selection or short-listing of the list below is based on the available scientific evidence retrieved from medical scientific database such as PubMed and scientific search engine such as Google Scholar.

Best Longevity Supplements

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

1. Vitamin D3, Omega-3 and K2

Vitamin D3 and K2

Can Vitamin D 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.

A 2024 paper published in Nutrients by Italian scientists summarized the current knowledge of how vitamin D might modulate some of the hallmarks of aging.

Best Meta-analysis Evidence: A meta-analysis of 18 randomized controlled trials (RCT) including over 57,000 subjects found that intake of daily doses of vitamin D supplements decreased total mortality rates (Autier 2007).

The DO-HEALTH trial, published in Frontiers in Aging 2022. The first randomized-controlled trial (DO-HEALTH) trial to investigate the combination of three complementary treatments for the prevention of cancer and suggest that the combination of daily vitamin D3, supplemental marine omega-3s, and a simple home exercise program may be effective in the prevention of invasive cancer among generally healthy and active adults aged 70 and older. Findings from this 3 year Randomized Controlled Trial with more than 2,000 participants observed a 61% reduction in the risk of invasive cancer among patients who completed a home exercise program and took vitamin D3 and omega-3 fatty acids daily.

Optimizing your vitamin D level is one strategy that can boost your health in myriad ways. A deficiency in vitamin D has been implicated in such problems as multiple sclerosis (R) and Parkinson’s disease (R), for instance. The link between Parkinson’s and vitamin D is so strong that one study found people with high vitamin D levels had a 65% lower risk of Parkinson’s compared to those with low vitamin D levels (R).

In addition, optimizing your vitamin D levels is one of the absolute best affordable strategies to slash your cancer risk.

Previous research found that a vitamin D level of 47 ng/ml was associated with a 50% lower risk of breast cancer (R). Further, researchers at University of California, San Diego School of Medicine reported that raising your vitamin D level to at least 40 ng/ml can slash your risk of all invasive cancers by 67% (R).

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 least 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).

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.

Make sure to take 500 mg to 1000 mg of magnesium and 150 mcg of vitamin K2, (not K1) which are important cofactors for optimizing vitamin D function. 

Data from nearly 3,000 individuals reveal you need 244% more oral vitamin D if you're not also taking magnesium and vitamin K2. What this means in practical terms is that if you take all three supplements in combination, you need far less oral vitamin D in order to achieve a healthy vitamin D level.

And, remember the only way you know what your vitamin D level is, is to test it. Vitamin D level should be in a therapeutic range of 50 to 70 ng/ml for treatment of rheumatoid arthritis. Most people are shocked how low their level is when they finally get around to testing it.

 

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.

Best Evidence: A 2021 report (Nature Communications) suggest that higher levels of omega 3 fatty acids in circulation correlate with lower risk of premature death from age-associated diseases such as cardiovascular disease and cancer.

The analysis was conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42,466 individuals. The researchers found that, after adjustment for relevant risk factors, risk for death from all causes was significantly lower (by 15-18%, at least p < 0.003) in the highest vs the lowest quintile for circulating long chain (20-22 carbon) omega-3 fatty acids (eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids). Similar relationships were seen for death from cardiovascular disease, cancer and other causes. 

According to another 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.

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 (above). 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.

Published in 2022, the Cognitive impAiRmEnt Study (CARES Trial 2), was designed to examine the potential synergistic effects of a combination of omega-3 fatty acids (namely DHA and eicosapentaenoic acid [EPA]), xanthophyll carotenoids (specifically lutein, zeaxanthin and meso-zeaxanthin) and vitamin E (d-α-tocopherol) on the cognitive performance of cognitively healthy older adults. 

In conclusion, the CARES research has shown improvements in working memory following 24-month supplementation with omega-3 fatty acids, xanthophyll carotenoids (lutein and zeaxanthin) and vitamin E in cognitively healthy older adults. This study provides Class II evidence that 24-month supplementation with 430 mg DHA, 90 mg EPA, 10 mg lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthin and 15 mg vitamin E (d-α-tocopherol) is effective in improving cognitive performance, namely working memory, in cognitively healthy older adults.

These results support a biologically plausible rationale whereby these nutrients work synergistically, and in a dose-dependent manner, to improve cognitive performance. These findings illustrate the importance of nutritional enrichment in improving cognition and enabling older adults to continue to function independently, and highlight how a combination of omega-3 fatty acids and xanthophyll carotenoids may prove beneficial in reducing cognitive decline and/or delaying Alzheimer's disease onset in later life. (Power 2022).

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.

Vitamin K2

In a 2022 study, researchers even revealed vitamin K2 modulates mitochondrial dysfunction caused by neurotoxins. Vitamin K2 also inhibited the accumulation of reactive oxygen species (ROS) and promoted mitophagy, which is the removal of damaged mitochondria via autophagy — an essential function to maintain cellular health. Writing in the journal Nutrients, the scientists explained:

“… [V]itamin K2 can reduces mitochondrial damage, and … this effect is related to the participation of vitamin K2 in the regulation of the mitochondrial quality-control loop, through the maintenance of the mitochondrial quality-control system, and repair mitochondrial dysfunction, thereby alleviating neuronal cell death mediated by mitochondrial damage.”

2. B Vitamins and NAD Boosting Supplements

B vitamins are necessary for proper brain function, research suggests. People with low levels of vitamins B6 and B12 can develop anemia as well. Older adults are often low in vitamin B12, and as we age, it’s harder for us to absorb it and even use it because it’s not as bioavailable.

B vitamins include:

• B1 (thiamine)
• B2 (riboflavin)
• B3 (niacin)
• B5 (pantothenic acid)
• B6
• B7 (biotin)
• B12
• Folic acid

B vitamins are commonly found in meat, eggs, fish and leafy greens. 

NAD+ Precursors 

Nicotinamide adenine dinucleotide (NAD+) is a vital molecule for most, if not all, forms of life. The last decade has seen a strong proliferation of therapeutic strategies for the treatment of metabolic and age-related diseases based on increasing cellular NAD+ bioavailability. Among them, the dietary supplementation with NAD+ precursors—classically known as vitamin B3—has received most of the attention. Multiple molecules can act as NAD+ precursors through independent biosynthetic routes.

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 and not. During aging, the epigenome becomes more and more dysregulated.

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).

NMN (Nicotinamide MonoNucleotide) is a molecule found in various foods such as broccoli, cabbage, avocado, mushrooms, meat, and shrimp. However, obtaining sufficient amounts through diet alone can be challenging. 

Studies suggest that daily dosages of NMN range from 50mg to 250mg, and a 150-pound (68kg) person would require approximately 560mg per day. Unfortunately, obtaining these amounts solely through diet would be impractical. For example, you would need to consume about 100 pounds of edamame, 1,800 pounds of broccoli, or unrealistic amounts of cucumber, cabbage, avocado, tomato, mushrooms, raw beef, or shrimp to achieve the required intake. Therefore, taking NMN supplements may be a more practical approach to ensure adequate daily intake.

A study in 2022 suggests that taking 250 mg/day of NMN can significantly increase and sustain the levels of NAD+ in the blood, without adverse side effects.

Related: Best NMN Supplements

Vitamin B12

Vitamin B12 is needed to form red blood cells and DNA. It is also a key player in the function and development of brain and nerve cells. However, we believe the most important function it provides is methylation. If you don’t know what methylation is, allow us to briefly explain. Methylation is a biochemical process which is involved in a wide range of bodily functions, and is essential to our overall well-being. When methylation is out of balance, many different health problems may arise.

3. Glycine, NAC and Taurine

Both Glycine and Taurine levels decline as we age.

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).

In addition to supporting brain function, supplemental glycine may be useful for the "prevention and control of atherosclerosis, heart failure, angiogenesis associated with cancer or retinal disorders and a range of inflammation-driven syndromes, including metabolic syndrome."(McCarty 2019)

People with higher glycine levels in the blood had less risk of a heart attack (Ding 2016), and glycine can protect the blood vessels (DiNicolantonio 2014).

Glycine can also help counteract adverse effects of Glyphosate. When glyphosate enters your system, it can take the place of the glycine molecule. While similar, (the "gly" in glyphosate stands for glycine) it's not identical and does not work the same way as glycine. Hence, this replacement causes all sorts of trouble.

Note: Glyphosate is the active ingredient in Roundup and other common weed killer formulations.

By taking a glycine supplement, you can counteract this chain of events by making sure there's enough glycine present to fill up those glycine slots. As noted by Stephanie Seneff, Ph.D., (a senior research scientist at MIT for over five decades), "If there's lots of glycine, you're going to be much less likely to pick up glyphosate." 

To gain all of glycine's healing potential, doses of 10, 15, or 20 grams a day may be necessary. Land suggests you need at least 12 grams of glycine daily for optimal collagen turnover, plus another 3 grams per day to form glutathione and other compounds (YouTube):

"Your body only makes 3 grams of glycine per day, and if you only consume around 2 to 3 grams of glycine from foods then it means that almost all of us are in a 10-gram glycine deficit every day," he says.

"… I think most people would benefit for at least 5 to 10 grams of glycine a day, which is, uh kind of a moderate amount … if you are eating a lot of muscle meat … or you're just interested in getting more of the benefits of glycine then you can take even up to 20 grams a day."

Doses of 3 to 5 grams have been shown to improve sleep (R). One study estimated that most people are about 10 grams short of what their bodies need for all metabolic uses on a daily basis, and in a study of people with metabolic syndrome, 15 grams of glycine a day for three months reduced oxidative stress and improved systolic blood pressure.

NAC

Marios Kyriazis, M.D., a gerontologist nominated for the 2017 Nobel Prize in Medicine and main contributor at For the Ageless, told Healthnews,

"NAC, the acetylated form of the amino acid cysteine, protects our brain by stimulating the activity of glutathione, which is a potent antioxidant that protects our mitochondria from free radical damage. NAC is also effective against viruses and it is used both for the prevention and treatment of some viral infections, including brain infections."

He added, "Conventional doctors use NAC to counteract the consequences of paracetamol overdose because it protects the liver from damage."

Kyriazis suggests the conventional dose is around 1000 mg to 1500 mg per day and says some doctors recommend taking NAC with vitamin C to prevent it from being destroyed in the body prematurely.

"500mg of NAC every morning is an effective dose for adults looking to use it daily as a longevity supplement," he explained. "It has an excellent safety profile and can be taken with any other supplements, including glutathione."

Glycine and NAC (GlyNAC)
 
Researchers at Baylor College of Medicine also looked into supplementation with a combination of glycine and N-acetylcysteine (NAC), two glutathione precursors known as GlyNAC when taken together.

A pilot trial in older humans (Kumar 2021) with GlyNAC supplementation for 24 weeks corrected glutathione deficiency and improved multiple measures of health, including:

• Mitochondrial dysfunction
• Oxidative stress
• Inflammation
• Endothelial dysfunction
• Insulin resistance
• Genomic damage
• Cognition
• Strength
• Gait speed
• Exercise capacity
• Body fat levels
• Waist circumference

Further, GlyNAC supplementation improved four of nine hallmarks of aging associated with most age-related disorders — mitochondrial dysfunction, inflammation, insulin resistance and genomic damage (Kumar 2021). Glycine, the team noted, is an important methyl-group donor. "Methyl groups are abundant in DNA and are important components of multiple cellular reactions. Glycine is also important for normal brain function."

Related: Best NAC Supplements 2024

Taurine

This semi-essential amino acid is our latest addition and update to our list of 'Best 10 Anti Aging Supplements'. When we age, taurine levels decline as well.

According to research published in the June 2023 issue of the journal Science, the semi-essential amino acid taurine appears to play an important role in longevity and healthy aging.

This isn’t just another ordinary experiment and a report, but a series of experiments at various levels of detail showing that taurine may be the real deal and promote anti-aging.

Animals given supplemental taurine didn’t just live longer, they were also healthier overall. In mice, taurine improved: 

• Strength, coordination and endurance
• Bone mass and bone quality
• Glucose homeostasis and glucose tolerance
• Age-related inflammation
• Immune function
• Gut health
• Memory
• Function of all organs
• Mitochondrial function and health 

Interestingly, according to the authors, taurine “cured” osteoporosis. It’s not often you see the word “cure” being used in medical literature. Taurine also “suppressed ovariectomy-induced body-weight gain in a rodent model of menopause,” and reduced anxiety and depression-like behavior in the mice.

Treated mice also had less body fat (approximately 10% less at 1,000 milligrams of taurine per day) and higher energy levels. According to the authors, “Fat-pad weight divided by body weight percentage was dose-dependently reduced in taurine-treated mice.” Taurine supplementation also improved several markers of aging, including Senescence, Intercellular communication, Telomere length, Epigenetic changes, Genomic stability, Mitochondrial function, Stem cell populations and Nutrient sensing.

Taurine Dosage: Most of the existing research used 1-3 grams daily, which is the amount most bodybuilders use.

Read More: Taurine May Be Key for Anti Aging and Healthier Lifespan

4. Molecular Hydrogen and Magnesium

Molecular hydrogen is the smallest anti-oxidant. This paper (Mar 2022) reviews the basic research and recent application of hydrogen in order to support hydrogen use in medicine for ageing prevention and ageing-related disease therapy.

Molecular hydrogen has therapeutic and preventive effects on various organs. It has antioxidative properties as it directly neutralizes hydroxyl radicals and reduces peroxynitrite level. It also activates Nrf2 and HO-1, which regulate many antioxidant enzymes and proteasomes. Through its antioxidative effect, hydrogen maintains genomic stability, mitigates cellular senescence, and takes part in histone modification, telomere maintenance, and proteostasis. In addition, hydrogen may prevent inflammation and regulate the nutrient-sensing mTOR system, autophagy, apoptosis, and mitochondria, which are all factors related to ageing. Hydrogen can also be used for prevention and treatment of various ageing-related diseases, such as neurodegenerative disorders, cardiovascular disease, pulmonary disease, diabetes, and cancer. 

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

According to a review paper published in BioMedicines 2022:

Maintaining cells in low-oxygen conditions or in the presence of hydrogen gas, matrix modification, and supplying the culture medium with growth factors and antioxidants capable of attenuating ROS (Reactive Oxygen Species) accumulation can slow done the telomere shortening and proliferative senescence.

Related: Best Molecular Hydrogen Tablets

Note: Most Molecular Hydrogen tablets uses pure elemental magnesium as its carrier and provides you with approximately 80 mg of magnesium per tablet. So, you receive also highly bioavailable magnesium for a healthy brain, muscles, cells, kidneys, and heart.

Magnesium

Magnesium is a very important mineral in the human body.

Magnesium functions as a cofactor to hundreds of different enzymes, which need magnesium to function properly.

Magnesium also regulates the excitation and inhibition of cells, and plays an important role in muscle relaxation, including of the heart muscle.

Given the role of magnesium in a myriad of cellular processes, it should not be surprising that magnesium deficiency leads to accelerated aging (R).

There are many ways in which magnesium deficiency can lead to accelerated aging. Magnesium is needed to build, maintain and repair DNA.

Magnesium reduces DNA damage and stabilizes the genome (R,R). For example, magnesium sticks to the DNA strand and stabilizes it, and it is also an essential cofactor for DNA repair proteins which need magnesium to function properly (R).

Magnesium can reduce inflammaging (low-grade inflammation that increases during aging). Low levels of magnesium have been linked to chronic low-grade inflammation, which is one of the drivers of aging (R).

Besides magnesium’s many effects on maintaining our cells, the mineral has various immediately noticeable effects. Athletes take magnesium to improve their physical performance, even when they are not magnesium deficient (R).

Magnesium supplements also improve sleep, and feelings of relaxation and wellbeing.

This is not surprising, given the important role of magnesium in the functioning of brain cells, such as excitation and neuronal metabolism.

Malate is often used in combination with magnesium to bring about health benefits, especially for improving energy and reducing fatigue.

5. CoQ10

Coenzyme Q10 (CoQ10) is an antioxidant that your body produces. It plays an essential role in energy production and protects against cellular damage (Source).

Research suggests that levels of CoQ10 decline as you age. Supplementing with it has been shown to improve certain aspects of health in older individuals.

For instance, a 4-year study in 443 older adults demonstrated that supplementing with CoQ10 and selenium improved overall quality of life, reduced hospital visits, and slowed physical and mental deterioration (Source).

CoQ10 supplements may work by reducing oxidative stress, a condition characterized by an accumulation of free radicals that accelerates the aging process and the onset of age-related disease (Trusted Source).

Additionally, CoQ10 supplements may benefit heart health by reducing stiffness in your arteries, lowering blood pressure, and preventing the buildup of oxidized cholesterol in your arteries (Trusted Source).

CoQ10 is also part of Dr. David Sinclair’s supplement list.

However, various studies show that coenzyme Q10 does not extend lifespan (R,R,R,R). Some studies show that coenzyme Q10 can actually shorten lifespan (R).

There are of course also some studies showing that co-enzyme Q10 can extend lifespan, but often these studies have not been well conducted, or they use organisms that are not ideal representation of normal aging, like using co-enzyme Q10 deficient mice.

Lastly, the interventions testing program (ITP) tested a similar compound, MitoQ (a better absorbable nutrient based on coQ10), and didn’t find a life extension effect (R).

That said, CoQ10 decline as you age and it plays an essential role in energy production and protects against cellular damage. Supplementing with CoQ10 might allow for more physical activity and therefore more likely to have a protective effect than a negative one.

Related: Best CoQ10 Supplements

6. Vitamin C and Calcium Alpha-KetoGlutarate (AKG)

Vitamin C can help to maintain a proper epigenome, especially in combination with another longevity ingredient, alpha- ketoglutarate.

An umbrella review* (Xu 2022) to assess the existing systematic reviews and meta-analyses for the association between vitamin C intake and multiple health outcomes; showed that vitamin C intake was associated with reduced risk of all-cause mortality, cardiovascular disease (CVD), oesophageal cancer, gastric cancer, cervical cancer and lung cancer with an increment of 50–100 mg per day. Beneficial associations were also identified for respiratory, neurological, ophthalmologic, musculoskeletal, renal and dental outcomes. A total of 76 meta-analyses (51 papers) of randomised controlled trials and observational studies with 63 unique health outcomes were identified. Harmful associations were found for breast cancer and kidney stones for vitamin C supplement intake. 

*Umbrella review: An umbrella review, or a review of reviews, is a systematic review that only considers other systematic reviews as an eligible study type for inclusion.

Alpha-ketoglutarate (AKG) extends lifespan and healthspan in different species. In humans, alpha-ketoglutarate has shown to protect cells against damage and stressors. Alpha-ketoglutarate supports a healthy metabolism and a healthy epigenome.

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.

Alpha-ketoglutarate also plays a role in maintaining stem cell health (Nature 2015), 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).

Ascorbic acid vs whole food vitamin C: What's the Difference?

Synthetic Ascorbic acid is NOT the same as whole food vitamin C. If you were to compare the two to a car, vitamin C would be the whole car, fully functional, and the engine is an enzyme called tyrosinase, while ascorbic acid is the car frame, with no moving parts.

Whole food vitamin C can also boost your copper level, as vitamin C contains an enzyme called tyrosinase, which has 2 atoms of copper in it. Ascorbic acid is prooxidant, while vitamin C complex is actually an antioxidant. Anything that has copper is going to be antioxidant.

7. Fisetin

Quercetin and Fisetin have been grouped together due to their similar molecular structure, with only minor differences. Both are flavonoids and senolytics.

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

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 (Lancet 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”.

Quercetin reduces glutathione and inhibits sirtuin-6 and NRF-2. All of these will hurt your longevity (see this clip, 2:30).

Lifespan extension effects of fisetin 

Scientists demonstrated that fisetin can extend 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).

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 (R, R).

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.

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

8. EGCG (Green Tea Extract)

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

Best Evidence: The Minnesota Green Tea Trial (MGTT 2015) 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.

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

As human clinical evidence is still limited, future research needs to define the actual magnitude of health benefits, establishes the safe range of tea consumption associated with these benefits, and elucidates the mechanisms of action.

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.

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

Because scientists aren’t sure how much EGCG is safe to take in pill form, the best way to incorporate it into the diet is by drinking green tea. One cup of green tea usually contains about 50 to 100 mg of EGCG.

Buy on Amazon > EGCG supplement 

9. Resveratrol and Pterostilbene

Resveratrol and pterostilbene have been grouped together due to their similar molecular structure, with only minor differences. 

A 2021 research review suggests that resveratrol supplements may help protect against age-related cardiovascular, neurodegenerative, and diabetic disorders. Unfortunately, confirmation of the therapeutic efficacy of Resveratrol concentration in humans is still needed to mitigate the research.

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 class of sirtuin proteins called SIRT1.

Note: You might have heard of “skinny genes” — genetic components that can help us stay thin, age well, and live longer. Sirtuins are a family of proteins that might do just that. Sirtuins aren’t genes at all, they’re proteins. Humans have seven of them, called SIRT1, SIRT2, SIRT3, and so on. 

Then, the same mechanism was studied and found to be true in mice. An animal study published in 2013 found that resveratrol does extend the life of obese mice, but not of mice that maintain a healthy weight. Not even if they’re give more resveratrol from a very young age. That suggests that resveratrol can help reduce the damage caused by lifestyle factors like diet and fitness levels, but it doesn’t add any extra benefit you can’t already get from leading a healthy lifestyle in the first place.

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.

The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing (Pratap Singh 2019). Resveratrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis.

The polyphenol is reported to be safe at doses up to 5 g/d, when used either alone or as a combination therapy. Although the clinical utility of resveratrol is well documented, the rapid metabolism and poor bioavailability have limited its therapeutic use. In this regard, the recently produced micronized resveratrol formulation called SRT501, shows promise (Pratap Singh 2019).

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.

Related: David Sinclair $720 Million Train Wreck!

10. Curcumin (Turmeric)

Curcumin — the main active compound in turmeric — has been shown to possess powerful anti-aging properties, which are attributed to its potent antioxidant potential.

One 2020 research review in PharmaNutrition concluded that curcumin does have anti-inflammatory effects in the body, and a 2019 research review in the International Journal of Molecular Sciences concluded that curcumin appears to both reduce inflammation and suppress cancer cells.

As published in the European Journal of Pharmacology (Nov 2022), Abe and colleagues focused on testing the effects of the curcumin prodrug TBP1901. They found that TBP1901 metabolized to its active form most greatly in bone marrow, leading them to use the drug on a multiple myeloma mouse model — a model for age-related bone marrow cancer. The researchers found that TBP1901 had significant anti-tumor effects, effectively shrinking tumors in mice. However, TBP1901 did not have strong effects in preventing cancer cell growth in a dish (in vitro). Still, regular curcumin had anti-tumor effects in vitro.

Cellular senescence occurs when cells stop dividing. As you age, senescent cells accumulate, which is believed to accelerate aging and disease progression (Source, Source).

Research demonstrates that curcumin activates certain proteins, including sirtuins and AMP-activated protein kinase (AMPK), which helps delay cellular senescence and promotes longevity (Source, Source).

Plus, curcumin has been shown to combat cellular damage and significantly increase the lifespan of fruit flies, roundworms, and mice. This compound has been shown to postpone age-related disease and alleviate age-related symptoms as well (Source, Source).

This may be why turmeric intake has been associated with a reduced risk of age-related mental decline in humans (Source). You can increase your curcumin intake by using turmeric in recipes or taking curcumin supplements.

Recent studies have come forward that in addition to its anti-aging and anti-inflammatory properties, it may also have anti-tumor properties. However, the bioavailability — ability to be used in the body — of curcumin may not be ideal. Thus, to help enhance its known positive benefits, researchers out of Kyoto University in Japan modified curcumin into a prodrug – an inactive compound that requires metabolism by the body before becoming biologically active.

11. Zinc

Zinc is an essential trace mineral that is critical to healthy immune function. Zinc is an important mineral for proper immune system function, brain health and skin health, among many other effects. Ideally, one takes 10 to 15 mg of zinc per day.

Zinc deficiency is common in older individuals, and causes changes in immune function that resemble those seen in immune senescence (Cabrera 2015; Maywald 2015). Immunological alterations associated with zinc deficiency include diminished thymus function, decreased antibody response to vaccines, and impaired function of phagocytic and NK cells (Haase 2009; Cabrera 2015).

In a study in healthy older volunteers, daily intake of 45 mg zinc for one year resulted in a 67% reduction versus placebo in incidence of infections. Levels of tumor necrosis factor-alpha, an inflammatory cytokine, were also greatly reduced in those taking zinc (Prasad 2007). In a study of older individuals in nursing homes, residents with normal zinc levels had a significantly lower incidence of pneumonia compared with zinc-deficient individuals. Zinc-replete individuals also had shorter pneumonia duration and 50% lower usage of antibiotics, as well as lower all-cause mortality (Meydani 2007). A controlled clinical trial in aged individuals showed supplementation with 45 mg zinc per day for six months decreased plasma markers of inflammation, including IL-6 and C-reactive protein (Bao 2010).

Combining zinc with other important vitamins and minerals may also aid immune function. In a randomized controlled trial that enrolled 42 subjects between 55 and 75 years of age, those who took a multivitamin/mineral supplement containing 10 mg zinc and 1,000 mg vitamin C, along with other vitamins and minerals, for 12 weeks experienced fewer self-reported sick days and less severe symptoms than those who took placebo. The number of sick days decreased by nearly 65% with supplement use (Fantacone 2020).

Be careful, too much zinc can have negative effects. Also, if you take zinc supplements, make sure you take copper, given zinc inhibits the absorption of copper.

More and more studies show the importance of copper to reduce the risk of heart disease and diabetes. Copper also plays an important role in collagen production, skin health and skin appearance.

Ideally, one takes 2 mg of copper per day. 

12. Garlic

Garlic, well known for its ability to improve cardiovascular risk factors, also has immune-modulating and immunostimulatory properties, as well as anti-tumor effects (Ebrahimi 2013; Purev 2012; Kyo 2001).

A detailed review of data from published clinical trials found garlic supplements significantly reduce the number, duration, and severity of upper respiratory tract infections. This review also found garlic supplements stimulate immune function by increasing macrophage activity, numbers of NK cells, and production of T and B cells (Ried 2016). In a clinical trial, 120 healthy participants, 21–50 years old, were assigned to use 2.56 g aged garlic extract or placebo daily for 90 days during cold and flu season. Garlic supplementation was associated with reduced cold and flu severity, as well as increased cytotoxic T-cell and NK-cell proliferation and activity (Percival 2016). In animal research, garlic has been shown to increase antibody production and enhance the cell-killing activity of macrophages, cytotoxic T cells, and NK cells (Ghazanfari 2000). Other animal research suggests aged garlic extract may prevent immune suppression associated with psychological stress (Kyo 1999).

Interestingly, garlic has also been demonstrated to suppress the overactive immune response associated with allergic reactions. Data from experimental studies indicate aged garlic extract may reduce histamine release and modify the function of immune cells involved in allergic reactions (Kyo 2001).

Test-tube and rodent studies have also shown that supplementing with garlic may prevent UV-light-induced skin aging and wrinkles (Trusted Source).

13. L-Citrulline and L-Arginine (Nitric Oxide Boosters)

Nitric oxide deficiency is a primary driver of hypertension (Biochemical Pharmacology 2022).

L-citrulline is a naturally occurring amino acid found in some foods like watermelons and is also produced naturally by the body. Citrulline can promote heart health by widening your blood vessels. It can also improve your exercise performance and may play a role in muscle building (Curr Opin Clin Nutr Metab Care. 2017). After citrulline is consumed, some is converted to another amino acid called arginine. Arginine is converted into a molecule called nitric oxide, which causes vasodilation of blood vessels by relaxing the smooth muscle cells that constrict them (Nitric Oxide. 2015). 

Though research has found both arginine and citrulline to boost levels of nitric oxide (NO) in the body, research—like this The Journal of Nutrition study—shows that citrulline actually delivers the most benefit. The body use arginine for a variety of functions, so it doesn’t use all of the arginine it absorbs to produce Nitric Oxide. Plus, unlike citrulline, higher doses of arginine have been linked to gastrointestinal problems. Because it tends to be poorly absorbed, arginine can even lead to diarrhea when consumed in large amounts.

Related: Best Nitric Oxide Supplements

14. Lutein and Zeaxanthin

Known as the “eye vitamin,” lutein is one of two carotenoids thought to help filter light and protect the eye from sun damage. Oral supplements containing lutein can help prevent age-related macular degeneration. Dietary lutein might help prevent cataracts, but research has yet to confirm whether supplements can have the same effect as food.

Lutein works hand in hand with another antioxidant [called] zeaxanthin. Both of those [nutrients] are usually found together [in the same supplement].

Published in 2022, the Cognitive impAiRmEnt Study (CARES Trial 2), was designed to examine the potential synergistic effects of a combination of omega-3 fatty acids (namely DHA and eicosapentaenoic acid [EPA]), xanthophyll carotenoids (specifically lutein, zeaxanthin and meso-zeaxanthin) and vitamin E (d-α-tocopherol) on the cognitive performance of cognitively healthy older adults. 

In conclusion, the CARES research has shown improvements in working memory following 24-month supplementation with omega-3 fatty acids, xanthophyll carotenoids (lutein and zeaxanthin) and vitamin E in cognitively healthy older adults. This study provides Class II evidence that 24-month supplementation with 430 mg DHA, 90 mg EPA, 10 mg lutein, 2 mg zeaxanthin, 10 mg meso-zeaxanthin and 15 mg vitamin E (d-α-tocopherol) is effective in improving cognitive performance, namely working memory, in cognitively healthy older adults.

A diet rich in fruits and vegetables should provide enough lutein for healthy adults, but there are no known side effects from supplementing for those who choose to do so. However, consuming lutein alongside beta carotene specifically might reduce the body’s absorption of both vitamins, and when taken with vitamin E, lutein can reduce the amount of vitamin E the body can absorb. Food sources of lutein include egg yolks, spinach and kale. It’s also important to consume lutein along with foods high in fat to facilitate better absorption.

15. Glucosamine and Chondroitin

Large studies found that people who take glucosamine live longer. Glucosamine intake was also associated with better heart health. In animals, glucosamine extends lifespan. Glucosamine targets inflammaging at the cellular level, and helps the body to manage oxidative stress and support autophagy.

An encouraging 2020 study shows that glucosamine and chondroitin, commonly used to treat the pain and inflammation of arthritis, can also do “double duty” in reducing the risk of heart disease and the risk of death from cardiovascular disease conditions. 

The study, conducted by researchers at West Virginia University (WVU) and published in the Journal of the American Board of Family Medicine, involved over 16,000 adults over age 40. After adjusting for age, sex, race, education, smoking status, and physical activity, the researchers came to a stunning conclusion.

They found that participants who took glucosamine and chondroitin daily for a year reduced the risk of death from any cause—by an astounding 39 percent. The supplementation also reduced cardiovascular deaths—including death from coronary artery disease, stroke, and other forms of heart disease—by 65 percent. In fact, glucosamine/chondroitin supplementation worked about as well as regular exercise in reducing the risk of death (although the researchers do not recommend that people forego exercising in favor of glucosamine).

Dr. King, the lead author of the WVU study not only strongly recommends glucosamine and chondroitin, but goes a step further, acknowledging that he regularly takes the supplement himself.

In one 2019 study published in the British Medical Journal, the scientists noted that glucosamine/chondroitin given for arthritis pain also significantly lowered the risk of heart disease and stroke. Specifically, the supplementation lowered the risk of adverse cardiovascular events by 15 percent, cardiovascular-related deaths by 22 percent, and coronary heart disease by 18 percent. For the WVU study, researchers took things a step further by setting out to further explore the link between regular consumption and mortality from cardiovascular conditions.

Glucosamine and chondroitin supplements are made from chitin, a compound found in shellfish. Natural healers typically recommend supplementation with 1,500 mg a day of glucosamine and 1,200 mg a day of chondroitin (many products conveniently feature these two compounds together). Note: Most experts feel that glucosamine sulfate is superior to other formulations, such as glucosamine hydrochloride and N-acetyl glucosamine. Of course, check first with your integrative doctor before supplementing. And, if you are allergic to shellfish, don’t use glucosamine or chondroitin.

You can also increase your dietary intake of glucosamine and chondroitin with nourishing bone broth.

Remember, long-term, regular use of these supplements seems to yield the most benefits. Be aware that it may take eight to twelve weeks before improvements begin to appear. 

16. Collagen

Research suggests that collagen supplements may help increase skin elasticity, hydration and dermal collagen density. Collagen is also an outstanding source of glycine. Preferably, use a less denatured (unhydrolyzed) organic collagen supplement, as it has a more balanced amino acid profile or, better yet, simply boost your collagen intake by making homemade bone broth using bones and connective tissue from grass fed, organically raised animals.

A small 2021 randomized, placebo-controlled, double-blind trial with 99 Japanese women between the ages of 35 and 50 concluded that oral collagen supplements helped increase skin hydration.

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).

A 2019 research review in the Journal of Drugs in Dermatology also found oral collagen supplements to be helpful in increasing skin density, hydration and elasticity.

There are no known interactions between collagen supplements and medications, foods or other supplements.

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.

Collagen is the glue that holds us together. It’s great for skin, bones, joints and muscles. The majority of people don’t eat enough collagen foods, such as the skin of poultry and fish, organ meats and bone broth. Therefore, older adults can benefit from a daily supplement of 10 to 15 grams of collagen peptides.

17. Spermidine

While spermidine was first found in semen, it has various metabolic functions in many types of cells and is naturally found in all living organisms. It’s also found in common foods, including aged cheese and fermented soy products, as well as mushrooms, pears and potatoes. A review published in the journal Autophagy details some of spermidine’s benefits:

“This chemical affects numerous biological processes, including cell growth and proliferation, tissue regeneration, DNA and RNA stabilization, enzymatic modulation, and regulation of translation, among others. Furthermore, spermidine exhibits anti-inflammatory and antioxidant properties, enhances mitochondrial metabolic function and respiration, promotes chaperone activity and improves proteostasis.”

Consuming spermidine-rich food lowers mortality associated with cardiovascular diseases and cancer. Further, a study published in The American Journal of Clinical Nutrition found a diet rich in spermidine, at levels commonly found in the Western diet, lowers the risk of all-cause mortality:

“Spermidine showed the strongest inverse relation with mortality among 146 nutrients studied. The reduction in mortality risk related to a diet rich in spermidine (top compared with bottom third of spermidine intake) was comparable to that associated with a 5.7-y younger age. All of the findings apply to spermidine from dietary sources and to amounts characteristically found in the Western diet …”

In humans, higher dietary intake of spermidine is also linked with a reduced risk of cognitive impairment.

A research team with Manipal College of Pharmaceutical Sciences in India further suggested spermidine could be a useful therapeutic strategy for neurological disorders due to its autophagy-inducing properties. They noted that a healthy brain is dependent on its concentration of polyamines:

“Polyamines interact with the opioid system, glutamatergic signaling and neuroinflammation in the neuronal and glial compartments. Among the polyamines, spermidine is found highest in the human brain. Age-linked fluctuations in the spermidine levels may possibly contribute to the impairments in neural network and neurogenesis.”

In humans, a diet high in spermidine is associated with reduced blood pressure and lower incidence of cardiovascular disease (Nature Medicine 2016). It also reverses arterial aging, which is characterized by stiffening of large arteries and the development of arterial endothelial dysfunction, which increases the risk of cardiovascular disease (CVD).

This benefit may be due to its interactions with nitric oxide (NO) and other factors, according to researchers with the University of Colorado, Boulder:

“Our results indicate that spermidine exerts a potent anti-aging influence on arteries by increasing NO bioavailability, reducing oxidative stress, modifying structural factors and enhancing autophagy. Spermidine may be a promising nutraceutical treatment for arterial aging and prevention of age-associated CVD.”

According to The American Journal of Clinical Nutrition study:

“Spermidine is the polyamine most readily absorbed from the human gut. A broad and diverse palette of foods contain high amounts of spermidine, such as fresh green pepper, wheat germ, cauliflower, broccoli, mushrooms, and a variety of cheeses, whereas even higher amounts are found in soybean products such as natto, shitake mushrooms, amaranth grain, and durian.”

Polyamines like spermidine are also present in aged (fermented) cheese, including blue cheese, Brie, cheddar, Swiss, Gouda, Gruyere, Manchego and Parmesan. Intake of spermidine-rich foods is important at any age but may be particularly useful as you get older, when spermidine levels tend to decline.

18. Crocin (Saffron)

Crocin is a yellow carotenoid pigment in saffron, a popular, pricey spice that’s commonly used in Indian and Spanish cuisine.

Saffron is the most expensive spice in the world — with 1 pound (450 grams) costing between 500 and 5,000 U.S. dollars. Saffron contains an impressive variety of plant compounds that act as antioxidants — molecules that protect your cells against free radicals and oxidative stress.

Human and animal studies have shown that crocin offers many health benefits, including anticancer, anti-inflammatory, anti-anxiety, and antidiabetic effects (Source).

Aside from the properties listed above, crocin has been researched for its potential to act as an anti-aging compound and protect against age-related mental decline (Source).

Crocin has also been shown to help prevent aging in human skin cells by reducing inflammation and protecting against UV-light-induced cellular damage (Source, Source).

Given that saffron is the most expensive spice in the world, a more cost-effective way to boost your crocin intake is by taking a concentrated saffron supplement.

Most officially recommended daily doses are too low

You should know that the official recommended dietary allowances of vitamins and minerals, as defined by government agencies, are often just the bare minimum you need to take in to not become sick. They do not tell you what are the best amounts for a long, optimal, healthy life.

Most of these official recommendations are also based on old studies in which volunteers were deprived of a specific vitamin or mineral. Scientists then waited a while until people became sick, and then determined the minimum dose you would need to prevent this.

So these recommended daily intakes are what you need to take on a daily basis in order not to become sick after a number of months (the duration of the study). They do not tell you the ideal amounts you need to stay healthy and slow down aging for decades to come.

Take for example vitamin B12. The recommended dietary allowance is around 2.4 mcg in many countries. But that’s in fact the “minimum” amount you need to not become sick after a few months or years, getting serious complications, like anemia, fatigue or cognitive problems. This doesn’t mean this is the optimal amount for a long, healthy life.

For example, we see in studies that you need at least 20 mcg of vitamin B12 to optimally protect the DNA against DNA strand breaks – more than 8 times greater than the recommendation!

Also, many people do not take up vitamin B12 well, especially as we get older. For example, atrophic gastritis affects at least 10 to 30 percent of people older than 60, leading to malabsorption of vitamin B12. So, they would need far more vitamin B12 than advised by governments.

In fact, The Linus Pauling Institute at Oregon State University recommends that all people older than 50 take at least 100 to 400 ug/day of supplemental vitamin B12 (R). That’s considerably more than the 2.4 mcg many governments advise.

It’s interesting to see that many foods rich in vitamin B12 (clams, mussels, crab, and fish like mackerel and salmon) are water-borne foods. Scientists speculate that people evolved for tens of thousands of years living close to shorelines and rivers and lakes and consumed high amounts of sea food and thus vitamin B12 (R), probably reaching daily intake levels far more than a meagre 2.4 mcg per day.

These are just a few examples demonstrating that yes, we need to take supplements for optimal aging. And this for the rest of our lives, and even more when we are older and suffer from age-related malabsorption issues and changes that hinder us to properly use these important vitamins and minerals.

Conclusion and Key Takeaways

It's important to remember that supplements are not a replacement for a healthy diet and lifestyle, engaging in regular exercise, and reducing stress. 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.

This can increase lifespan by 29%

Online Shopping Guide

Before adding a new supplement to your routine, discuss its use with your healthcare provider, especially if you have an underlying health condition or are taking medication.

• NMN
• Resveratrol
• Turmeric (curcumin) supplement
• EGCG supplement 
• Collagen
• CoQ10
• Saffron supplement
• Garlic supplement
• Calcium AKG Supplement

This article is part of the Anti Aging series.

Related: 

Anti Aging 101: Evidence Review

Best Natural Supplements for Dementia

15 anti aging supplements worth buying

Glutathione vs NAC

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