Early 2015, doctor and investor Joon Yun launched the Palo Alto Longevity prize, a one million dollar award for any scientist who could “hack the code of life” and find a way to keep humans from aging. In the past year, there has been a surge of new research into longevity enhancement in an attempt to win this illustrious prize. This article will explore the science to uncover the various supplements and drugs that can help you tap into the elusive fountain of youth.

longevity grandad

1) Aspirin

Age-related diseases and general aging are often caused by chronic inflammation. In animal studies, using aspirin to quell inflammation resulted in extended lifespans, more physical capability and increased stress resistance (R1 R2). 

Aspirin increased lifespan of mice by 18-21% at doses of 400mg/kg (R).

One study surprisingly found that aspirin was more effective at increasing maximum life span than metformin (see below) (R).

The high doses used in these studies might lead to serious intestinal problems (R).

2) C60

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French biologists found that rats given C60 (a fullerene molecule), dissolved in olive oil at doses of 1.7 mg/kg of body weight, lived nearly twice as long as control groups and had a reduction of age-related diseases, even though the rats were middle age at the start of the study. Rats have never lived as long in any study (R).

None of the rats treated with C60 got cancer, so studies looking at C60 and cancer prevention are currently underway (R).

The longevity mechanisms of C60 are currently not fully understood, but C60 is known to be bioactive in a number of ways, such as affecting DNA expression and protein folding (R).

C60 easily crosses the blood brain barrier. It concentrates itself in the mitochondria where it functions as a free radical scavenger i.e. it detoxifies the bi-products from the cell’s energy metabolism (R).

C60 molecules have the potential to block the replication of the HIV-1 virus so could prove to be an important weapon against AIDs (R).

C60 has never been tested on humans.

3) Lithium

Many people think that the most effective anti-aging strategies start by addressing the mitochondria.  Lithium treatment on worms increased both lifespan and health span and improved mitochondrial energy output (R).

Lithium might improve mitochondrial function by increasing the turnover of dysfunctional mitochondria (R).

However, a recent study of flies found the opposite outcome: lithium exposure did not extend lifespan and actually reduced the female fly’s lifespan advantage (R).

A correlation was found when researches measured the longevity of people and lithium in their water.  There was a decreased risk for all-causes of death in Japanese neighborhoods with higher lithium levels.

The study concluded that “long-term low-dose exposure to lithium may exert anti-aging capabilities and unambiguously decreases mortality in evolutionary distinct species.” (R)

One mechanism might be that lithium should theoretically increase NAD+, which is associated with longevity.

(Lithium inhibits mir-34a, which in turn inhibits NAMPT, the enzyme that makes NAD+ (R, R2). Therefore, lithium probably increases NAD+.)

See my lithium post.

4) Curcumin

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Curcumin increased the median and maximum lifespan of flies by up to 25.8%. The optimal dose of curcumin for male flies (0.5mg/g of  diet) was lower than for females (1mg/g of diet) (R).

Lifespan extension with curcumin has been attributed to its ability to decrease expression of age-related genes (including mTOR).

Curcumin supplementation also acts as a potent antioxidant in the cell (R1, R2).

The increase in life spans did not change if the flies were also calorie restricted, suggesting that curcumin and caloric restriction act on the same biological pathways (R).

I find that curcumin is the most multifunctional supplement available. But not all curcumin supplements are created equal. Many are not bioavailable and do not reach the brain.

See here for full info on benefits of curcumin and which types to buy.

5) Oxaloacetate

Oxaloacetate supplementation increased lifespan in worms by stimulating the same longevity pathways as calorie restriction (R).

Accumulation of proteins is a common cause of aging. Oxaloacetate might increase lifespan by reducing the build up of methylglyoxal (MG) – an important source of protein toxicity and general biological dysfunction (R).

A build up of glutamate can be toxic to cells. It causes serious brain damage after a concussion or stroke and is the favorite energy source for many cancers (R1, R2).

Consumption of oxaloacetate can lower blood glutamate levels by 40%. Rats given oxaloacetate had a 237% increase in brain tumour survival rates (R).

Oxaloacetate also increases NAD+.

Oxaloacetate is a cellular metabolite and so is not available from a dietary source. It must be taken in supplement form.

I find this work well: 

I recommend taking it in the morning or afternoon with meals.  For me to notice a benefit, I need to take 3 pills a day, but since it’s expensive, I take one daily.

6) Rhodiola

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Rhodiola rosea is an adaptogenic herb commonly used to improve stress resilience.

R. rosea can extend lifespan in flies, worms, and yeast (R).

Rhodiola was shown to extend lifespan in both sexes regardless of diet, suggesting that it works on different longevity pathways to caloric restriction (R).

Rhodiola is a supplement that I like to take frequently.  There are many options, but I do better when the rhodiola’s that have a higher salidroside percentage.

Here are the best options:

7) Carnitine

Mitochondrial decay is a significant factor in aging, caused, in part, by the release of reactive oxygen species (ROS) as by-products of mitochondrial electron transport.

Supplementing with carnitine can improve mitochondrial health and efficiency by enhancing electron flow (R).

In one study supplemental carnitine prolonged the aging of yeast cells (R).

The increased electron flow from carnitine also increases the formation of reactive oxygen species. It might be wise idea to take an antioxidant, such as lipoic acid, along with carnitine (R).

8) NAC

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N-acetylcysteine (NAC) is a modified sulfur-containing amino acid that acts as a potent cellular antioxidant (R).

NAC extended the lives of flies. Flies fed NAC lived 26.6% longer than normal (R).

Similarly the lifespan of worms was extended by up to 30.5% with supplemental NAC. The same study showed that NAC significantly increased resistance to a variety of environmental stressors (R).

Because NAC is an antioxidant it may slow the aging process by protecting the organism against free radical-induced damage (R).

NAC effects on longevity might also involve its impact on the expression of specific mRNA genes (R).

NAC is widely available in supplemental form. I suggest capsules as loose crystals taste disgusting.

  • I recommend  NAC

9) Carnosine

Carnosine is an antioxidant and has been shown to reduce the brain damage from oxidative stress (R).

Male flies that were given carnosine lived on average 20% longer than normal. No increase in lifespan was noted in female flies taking carnosine (R1, R2).

I recommend taking this right upon awakening or a half hour before food.  Carnosine binds to divalent metals like magnesium and calcium and others, so you don’t want to take this with meals.

10) Melatonin

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Melatonin is an important regulator of circadian rhythms and is a potent anti-inflammatory compound (R).

Increases in the longevity of fruit flies, mice and rats have been observed when melatonin was given supplementally or added to their food (R1, R2, R3).

In both mice and rats, melatonin acts as a potent antioxidant and inhibits free radical damage (R).

Melatonin has effects on the expression of genes that govern the cell cycle, cell/organism defence, protein expression and transport, and mitochondrial function. It might also activate the same sirtuin pathways as caloric restriction (SIRT1) (R).

One of the best ways to increase melatonin is to minimize exposure to artificial light after sunset (R).

There are many types of melatonin, and people will differ in which kind works for them.  Here are some interesting types of melatonin.

11) Lactic acid 

Feeding lactic acid to fruit flies increased median life span by 12-15% depending on what stage of life supplementation began (R).

It is proposed that lactic acid increases life span by removing hydroxyl radicals (R).

See here for the best ways to increase lactic acid.

12) Gluconic Acid

L-Carnitine

Gluconic acid increased lifespan of flies by 12-22% depending on what stage of life supplementation began (R).

In another study dietary gluconic acid slowed the normal age-related accumulation of copper in adult flies and lead to an increased lifespan of 21.6% (R).

Like lactic acid, gluconic acid increases life span by removing hydroxyl radicals (R).

Kombucha is a good source of gluconic acid.

Potassium gluconate is a good form of potassium and gluconic acid.

13) NAD+

Supplemental NAD led to an extension of lifespan in yeast by activating SIRT1 (R).

Niagen is a good way to increase NAD levels:

This is a relatively new supplement, but my guess is it’s going to become more popular because of its noticeably powerful effect on improving energy and mitochondria.  Its only downside is its expense.

14) Malate

Malate was found to extend the lifespan and stress tolerance in worms through activation of gene pathways that code for longevity (DAF-16 and SIRT1) (R).

Malate did not extend the lifespan of worms that were also calorie restricted (R).

Malate can be synthesized from fumarate. Hence, taking fumarate also extends lifespan (R).

Buy:

Malic acid is also good for chelating heavy metals and to increase energy production.

16) Acetate

Acetic acid increases lifespan of worms (by increasing DAF-16). This extension of lifespan was 30-40% greater when acetic acid  was combined with Reishi extract (R).

Vinegar is a good source of acetic acid.

17) Pyruvate

Worms with the slcf-1 gene mutation had increased blood pyruvate levels and a 40% increase in life span (R).

There are Pyruvate supplements that you can take.

18) Activated charcoal

Activated charcoal is able to absorb substances from the digestive tract. It can be used to eliminate toxic substances and can alter the fat and protein content of the gut.

Rats given an activated carbon compound live an average of 37-60% longer. By absorbing toxic substances in the digestive tract carbon was found to delay age-related structural changes in the organs and tissues (R1, R2).

Here are the source I often recommend:

19) Lutein

Lutein is an abundant carotenoid in fruits and vegetables.

Lutein prolonged the average lifespan of fruit flies by 63% (R).

Lutein extends lifespan by increasing antioxidant enzyme activity and up-regulating the expression of certain genes that correspond to longevity (SOD1, SOD2 & CAT) (R).

You can get lutein by eating lots of fruits and veg, but I also like to supplement.

20) Theaflavins

Lifespan of flies was extended by approximately 10% when given a supplemental black tea extract rich in theaflavins. The flies given BTE also showed an increased resistance to the negative effects of a high fat diet (R).

The longevity enhancing effects of BTE are likely controlled, at least in partly, by its impact on the gene expression of SOD and CAT (R).

I find this one by Life Extension to be effective:

21) Inositol 

D-chiro-inositol slowed the aging process and enhanced longevity in flies (R).

High levels of blood glucose inhibit cell growth and encourage cell aging. Myoinositol protects against the damage done by high glucose levels (R).

D-chiro-inositol/Pinitol is found in carob.

I use 5g per a day of inositol.  These are good options:

22) Metformin

Metformin belongs to a family of drugs called biguanides that have been shown to increase lifespan. For example, Metformin extended the lifespan of worms by 40% (median) and significantly increased the lifespan of mice (R).

Like many other life extending drugs, metformin induces many of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced LDL and cholesterol levels without actual calorie restriction (R).

Metformin might extend lifespan by behaving as a metabolic stressor that activates an oxidative stress and detoxification response (involving AMPK) (R1, R2, R3).

In animal models, deactivation of IGF-1 genes increases life span. Metformin decreases IGF-1 (R).

As already mentioned, blood sugar regulation is an important factor in aging. Metformin lowers blood sugar by increasing insulin sensitivity in liver and muscles. It might also work by suppressing glucose production in the liver (R). 

Metformin mitigates the high risk of diabetics getting cardiovascular disease and brain issues.

Diabetics who take metformin are at decreased risk of developing a range of cancers. It is unclear whether these cancer prevention properties would apply to non-diabetics (R1, R2). 

Metformin changes the microbiome in a way that promotes health and longevity, possibly by altering microbial Folate and Methionine Metabolism (R1, R2).

Metformin promotes mobility in old age, decreases fat build up,  and increases stress resilience in response to oxygen deprivation (R). 

Metformin is a prescription drug, so speak with your doctor before you take it.

23) Deprenyl – MAOBI

Deprenyl’s positive effects on longevity have been tested in at least five different animal species by independent research groups.

Rats treated with .25mg/kg of deprenyl lived and average of 30% longer than the control groups  (R1, R2).

Deprenyl given at 1 mg/kg significantly prolonged the lifespan of middle aged dogs when taken for a minimum of six months (R).

Deprenyl might increase longevity by raising antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) in certain brain regions (R).

24) Butyrate

Butyrate is a short chain fatty acid produced during fermentation by the gut microbiota.

Feeding a form of butyrate to flies increased their maximum lifespan by 30-50% (R).

Similar life extension properties of butyrate have been observed in worms (R).

One of the primary mechanisms by which Butyrate extends lifespan is by altering the copying of genes that code for longevity (e.g  glutathione S-transferase & superoxide dismutase) (R).

Internal Butyrate levels can be increased via supplementation, or by eating more resistant starch and non-digestible fibers that encourage colonic fermentation. 

I recommend: 

  • Butyrate
  • Hi-Maize resistant starch at 50g/day to start

25) Glucosamine

In worm and mouse studies, glucosamine has extended lifespan through creating new mitochondria (R).

In people, glucosamine supplements were associated with a lower risk of dying (R).

Glucosamine has an inhibitory effect on tumors (R).

26) Resveratrol

Resveratrol has been found to increase lifespan in yeast, worms, flies, bees, fish and rodents (R).

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9 COMMENTS

  • CAROL CLOSE

    Delaying the Chronological Aging of the Yeast Saccharomyces cerevisiae by Six Plant Extracts

  • CAROL CLOSE

    28 plant extracts (tea, astragalus, rhodiola, polygonum, mik thistle, chocolate, ashwagandha, ginseng, strawberry, apple, olive leaf, black currant, Chinese yam, cinnamon, soy, calendula, bugbane, ginger, skullcap, acai, kudzu, Echinacea, more) greatly delayed aging, but 6 supplements significantly extended lifespan- Black cohosh, Valerian, Celery seed, Passion Flower, Gingko and White Willow bark which white willow increased the mean and maximum chronological lifespan of yeast by 475% and 369%, respectively.  White Willow bark represents a much greater effect than rapamycin and metformin, the two best drugs known for their anti-aging effects.Yeast were chosen in this study because aging progresses similarly in both yeast and humans. The budding yeast Saccharomyces cerevisiae is a beneficial model organism for the discovery of genes, signaling pathways and chemical compounds that slow cellular and organismal aging in eukaryotes across phyla.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941334/ Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes

    [biofoundations] Delaying the Chronological Aging of the Yeast Saccharomyces cerevisiae by Six Plant Extracts

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5239441/#R3 Six plant extracts delay yeast chronological aging through different signaling pathways

  • Biowolle20vuh

    Bio Baumwolle Neugeborene Handschuhe – Bio Baumwolle Neugeborene Handschuhe

  • john nemes

    You forgotten: vitamin K2

  • Brian

    Hi Joe
    came here looking for info on pyruvate after yesterday’s video from Ron Davis on his latest research breakthrough into CFS [Youtube]
    Would be great if you could do a more focused look into pyruvate.

  • Kyung

    Curcumin is actually early acting life span mediator. Feeding from early age to mid-life would be life-enhancing and after mid-life feeding may be opposite.
    Also, C60 study is too preliminary to draw the life-span-enhancing effects. It seems to mimic hormesis like response while damaging to DNA strands and mitochondria in a genomic level. Net outcomes of pro-oxidant and anti-oxidant effects are also unknown. Its effect also depends on other characteristics of C60 such as lipophilic, hydrophilic properties, and purity factors of other components(C70 content) etc… In other words, there have been concerns regarding to the right form and dosage which yields the beneficial effects.
    Carnosine is also a problematic supplement, which oral supplementation is not effective as carnosinase intervenes. Some people try to decrease this enzyme to maximize the plasma serum, but its safety and plausibility are unknown.
    Yet too early to draw conclusions of life-extension.

  • john seville

    You omitted the Real # 1, D-Glucosamine, the dietary supplement marketed for cartilage degradation,which incidentally it really is in effective for. Study after study has shown its ability to mimic a low carbohydrate diet. In worm and mouse studies it has shown to extend lifespan through mitochondrial biogenesis. Because of it’s safety, dosing is NOT an issue as with most other substances. It’s anti-inflammatory properties has been proven in humans by substantial reduction in cancer across the board, including a substantial 35% decrease in the infamous Lung cancer, with just basically 1500mg 4 times weekly, according to studies. The number of studies indicating the long list of its attributes is quite long and can easily be found in Pubmed, but I will include just a few for your perusal.

    http://ajcn.nutrition.org/content/91/6/1791

    http://www.sciencedirect.com/science/article/pii/S0006291X07014064

    http://www.ncbi.nlm.nih.gov/pubmed/24714520

    1. Joseph M. Cohen

      Thanks.

    2. fred

      also….

      The bottom line is that glucosamine supplementation lowers human mortality

      Glucosamine and Chondroitin Sulfate have already been shown in a large epidemiological study to lower overall mortality and reduce cancer risks – a 5-year study of 77,719 elderly residents of Washington State. We found several publications based on different analyses of data based on this population.

      Conclusions:

      For most of the supplements we examined, there was no association with total mortality. Use of glucosamine and use of chondroitin were each associated with decreased mortality.”

      Both of these papers were done on the same group of 77,719 people. We note that this is as great an effect as combining vegan diet and fish consumption! We find this quite surprising. Glucosamine appears to have a comparable or greater effect on mortality reduction and lifespan extension than Metformin, Rapamycin, 2DG, Veganism, and Resveratrol in nematodes and rodents.

      RESULTS: Persons reporting use of glucosamine + chondroitin on 4+ days/week for 3+ years had a non-statistically significant 45 % lower Colorectal Cancer risk than non-users

      Epidemiological evidence exists that glucosamine and chondroitin supplementation reduces inflammatory biomarkers.

      Glucosamine supplementation may be protective against lung cancer.

      * A 2010 publication suggests that taking high doses of glucosamine or prolonged use it glucosamine reduces levels of SIRT1, leads to apoptosis of pancreatic cells and could increase the risk of developing diabetes.

      * keep dosage under 750 mg?

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