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20 Longevity & Lifespan Increasing Supplements

Written by Mathew Eng, PharmD | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by Mathew Eng, PharmD | Last updated:

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Note that each number in parentheses [1, 2, 3, etc.] is a clickable link to peer-reviewed scientific studies. A plus sign next to the number “[1+, 2+, etc...]” means that the information is found within the full scientific study rather than the abstract.

In 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. Since then, there has been a surge of new research into longevity enhancement in an attempt to win this prize. This article will explore some of the longevity research that has gone into various supplements.

Supplements Associated with Longevity and Lifespan

Animal and Cell Research

The following supplements have only been studied in animals or cells. None of these supplements have been studied in clinical trials. The safety and effectiveness of these supplements in humans are unclear.

It’s also important to let your doctor know of all the supplements you are currently taking, in case of potential interactions. These supplements should not be used to replace medical treatment.

1) C60

C60 is a molecule made up of 60 carbon atoms. It is sold as a dietary supplement that is usually dissolved in olive oil.

A study in rats suggests that C60 dissolved in olive oil may improve longevity. In the study, rats that received oral administration of C60 lived nearly twice as long. The researchers theorize that this life-extending effect may be due to a reduction in oxidative stress [1].

However, there is evidence that C60 may also cause DNA damage, according to animal studies [2]. For more information, check out our C60 article here.

2) Curcumin

In a study looking at flies, curcumin increased the median and maximum lifespan of flies by up to 25.8% [3].

According to some researchers, the potential life-extending effects of curcumin may be due to its ability to decrease the expression of age-related genes (including mTOR). There’s also evidence that curcumin has antioxidant effects [4, 5].

Find out more about the potential benefits of curcumin here.

3) Oxaloacetate

According to a study in worms, supplementation with oxaloacetate may be associated with a longer lifespan [6].

According to some researchers, oxaloacetate may be associated with longevity because it can potentially reduce the build-up of methylglyoxal, which is linked to protein toxicity and cellular dysfunction [7].

There’s also some evidence that oxaloacetate may lower levels of glutamate in rats. A build-up of glutamate may also be toxic to cells [8, 9, 10].

4) Rhodiola

Rhodiola rosea is an adaptogenic herb that is purported to help improve stress resilience.

Research suggests that R. rosea may increase longevity according to several animal models, including flies, worms, and yeast. This effect was seen in both sexes and was independent of dietary restriction [11].

5) Carnitine

A study performed in yeast cells found that carnitine may be associated with lifespan. According to researchers, supplementation with carnitine may improve mitochondrial health, which may play a role in aging [12, 13].

6) NAC

N-acetylcysteine (NAC) is a modified sulfur-containing amino acid that may act as a cellular antioxidant, potentially protecting against free radical-induced damage [14, 15].

In one fly study, flies fed NAC lived 26.6% longer compared to flies that were not treated with NAC [16].

Another study found that supplementation with NAC increased the lifespan of worms by up to 30.5% [17].

The association between NAC and longevity may also involve NAC’s effect on the expression of specific mRNA genes [16].

7) Carnosine

Research in flies has revealed that male flies that were given carnosine lived on average 20% longer than normal. However, no increase in lifespan was noted in female flies taking carnosine [18, 19].

8) Melatonin

Melatonin is an important regulator of circadian rhythms and may have anti-inflammatory effects [20].

Increases in the longevity of fruit flies, mice and rats have been observed when melatonin was given supplementally or added to their food [21].

Research in both mice and rats also suggests that melatonin may act as an antioxidant that can potentially inhibit free radical damage [21].

According to cell studies, melatonin may affect the expression of genes that govern the cell cycle, cell/organism defense, protein expression and transport, and mitochondrial function. It might also activate the same sirtuin pathways as caloric restriction (SIRT1) [21].

9) Lactic acid

A study in fruit flies suggests that lactic acid may increase the median lifespan of flies by 12-15% depending on what stage of life supplementation began [22].

According to some researchers, lactic acid may increase lifespan by removing hydroxyl radicals [22].

10) Gluconic Acid

In a fruit fly study, gluconic acid increased the lifespan of flies by 12-22% depending on what stage of life supplementation began [22].

Like lactic acid, gluconic acid may increase lifespan by removing hydroxyl radicals [22].

11) NAD+

A study in yeast cells suggests that supplemental NAD may extend yeast cell lifespan, potentially by activating SIRT1 [23].

12) Malate

A study in worms found that malate may increase lifespan and stress tolerance in worms, possibly through activation of gene pathways that code for longevity (DAF-16 and SIRT1) [24].

However, malate did not extend the lifespan of worms that were also calorie restricted.

13) Acetate

According to a study in worms, acetic acid may help increase the lifespan of worms by increasing DAF-16. This extension of lifespan was 30-40% greater when acetic acid was combined with Reishi extract [25].

14) Activated charcoal

Activated charcoal is able to absorb substances from the digestive tract and is sometimes used to help eliminate toxic substances from the stomach.

A study in male rats suggests that activated charcoal may help increase longevity. According to researchers, activated charcoal may delay age-related structural changes by absorbing toxic compounds [26].

15) Lutein

Lutein is an abundant carotenoid in fruits and vegetables.

In a study looking at fruit flies, lutein prolonged the average lifespan of flies by 63% [27].

This life-extending effect may be due to increases in antioxidant enzyme activity and up-regulation of certain genes that correspond to longevity (SOD1, SOD2 & CAT) [27].

16) Theaflavins

According to a fly study, supplementation with black tea extract rich in theaflavins may extend the lifespan of flies by approximately 10%. The study also suggests that this extract may increase resistance to the negative effects of a high-fat diet [28].

Research suggests that the longevity-enhancing effects of theaflavins are potentially controlled, at least in part, by its impact on the gene expression of SOD and CAT [28].

17) Inositol

Research in flies suggests that D-chiro-inositol may slow the aging process and enhance longevity [29].

18) 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%, according to one fly study [30].

This life-extending effect may be due to changes in the genes that code for longevity (e.g glutathione S-transferase & superoxide dismutase) [30].

19) Glucosamine

In worm and mouse studies, glucosamine has shown potential life-extending effects, possibly through the creation of new mitochondria [31].

20) Resveratrol

Multiple animal studies suggest that resveratrol may increase lifespan in yeast, worms, flies, bees, fish, and rodents [32].

About the Author

Mathew Eng

Mathew Eng

PharmD
Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.
Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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