20 Best Anti Aging Vitamins and Supplements that Work (2025): 1000+ Studies Analyzed and Ranked
In this Article:
- Vitamin D3, K2 and Omega-3 fatty acids
- B Vitamins, Nicotinamide mononucleotide (NMN) and NAD Boosting Supplements
- Magnesium and Molecular Hydrogen
- Glycine, NAC and Taurine
- Curcumin (Turmeric)
- Vitamin C
- EGCG (Green Tea)
- CoQ10
- Zinc
- Fisetin
- Resveratrol and Pterostilbene
- L-Citrulline and L-Arginine (Nitric Oxide Boosters)
- Lutein and Zeaxanthin
- Glucosamine and Chondroitin
- Collagen and Protein Powder
- Spermidine
- Crocin (Saffron)
- Acetyl-L-Carnitine
- Creatine
- Alpha-KetoGlutarate (AKG)
Can supplements reverse your age? Can you supplement your way out of aging? Dive into 1,000+ research studies to find out.
Current AI tools like ChatGPT, Gemini from Google and Copilot from Microsoft might return generic answers to your questions. While these can be a starting point, they often lack the depth and updated references you might crave for your research.
This practical guide will help you to understand aging, longevity, and all that is involved to “turn back the clock” and to reduce your confusion from reading only ChatGPT answers. We are providing you with science, knowledge, and best of all possibilities.
Wanting it and knowing how to get it are two different things. We know how you can get it, now you need to want it!
The global anti-aging & longevity market size was estimated at USD 63.60 billion in 2023 and is expected to grow at a compound annual growth rate (CAGR) of 21.5% from 2024 to 2030. (R)
Contents
- What is Aging?
- Our Methodology
- Best Anti Aging Supplements
- Vitamin D3, K2 and Omega-3 fatty acids
-
B Vitamins, Nicotinamide mononucleotide (NMN) and NAD Boosting
Supplements
- Magnesium and Molecular Hydrogen
- Glycine, NAC and Taurine
- Curcumin (Turmeric)
- Vitamin C
- EGCG (Green Tea)
- CoQ10
- Zinc
- Fisetin
- Resveratrol and Pterostilbene
- L-Citrulline and L-Arginine (Nitric Oxide Boosters)
- Lutein and Zeaxanthin
- Glucosamine and Chondroitin
- Collagen and Protein Powder
- Spermidine
- Crocin (Saffron)
- Acetyl-L-Carnitine
- Creatine
- Alpha-KetoGlutarate (AKG)
- Conclusion
- What is Aging?
- Our Methodology
- Best Anti Aging Supplements
- Vitamin D3, K2 and Omega-3 fatty acids
- B Vitamins, Nicotinamide mononucleotide (NMN) and NAD Boosting Supplements
- Magnesium and Molecular Hydrogen
- Glycine, NAC and Taurine
- Curcumin (Turmeric)
- Vitamin C
- EGCG (Green Tea)
- CoQ10
- Zinc
- Fisetin
- Resveratrol and Pterostilbene
- L-Citrulline and L-Arginine (Nitric Oxide Boosters)
- Lutein and Zeaxanthin
- Glucosamine and Chondroitin
- Collagen and Protein Powder
- Spermidine
- Crocin (Saffron)
- Acetyl-L-Carnitine
- Creatine
- Alpha-KetoGlutarate (AKG)
- Conclusion
What is Aging?
The process of human aging is a complex and multifactorial process. NAD, stem cells, nitric oxide, glutathione, vitamin B12, CoQ10, glycine, taurine and testosterone decline as we age. Vitamin and mineral deficiencies are also common in older individuals.
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| Longevity Medicine will become the New Primary Care |
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| Credit: ACS Chem. Neurosci. 2024 |
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| Credit: ACS Chem. Neurosci. 2024 |
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| Connecting the dots between Antiaging nutrients and drugs and (A) hallmarks of aging, and (B) antiaging strategies. Credit: ACS Chem. Neurosci. 2024 |
Methodology
- Systematic Review*, Meta-analysis*, Umbrella Review and Randomised Controlled Trials (RCTs)
- Large clinical trials (phase 3)
- Small clinical trials (phase 2) and Case studies
- Mouse results and animal studies
- In Vitro, cell culture, commentary, review, expert opinions and anecdotal evidence
Case studies and preliminary results from small-scale human trials hold less significance than outcomes from umbrella reviews, systematic reviews and meta-analysis*, randomised controlled trials (RCTs), and more extensive, long-term human trials.
Best Anti-Aging Supplements, According to Scientific Evidence
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.
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| Image credit: Longevity.technology |
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.
1. Vitamin D3, Omega-3 and K2
"Those who took 2,000 IU of vitamin D3 daily had almost three years less biological aging compared to those who took a placebo. Omega-3 supplements, which some participants also took, did not show the same benefit."
Experts say this adds to earlier research showing that vitamin D can reduce inflammation and support immune health. While more studies are needed, vitamin D may be a simple way to support healthy aging.
The Intermountain study, called the TARGET-D trial, ran from April 2017 to May 2023 and included 630 patients who had suffered a heart attack within a month of enrolling. Participants were followed until March 2025 to monitor cardiovascular outcomes.
Patients were randomly assigned to one of two groups: one received no vitamin D management, and the other underwent active, targeted vitamin D3 treatment.
The goal for the treatment group was to raise blood vitamin D levels to above 40 nanograms per milliliter (ng/mL). At the start, 85% of participants had vitamin D3 levels below that threshold (<40 ng/mL).
More than half of the patients receiving targeted therapy required an initial dose of 5,000 international units (IU) of vitamin D3, compared to typical supplement recommendations of 600-800 IU.
Participants in the TARGET-D study were randomized to two groups: The standard of care group did not receive management of their vitamin D levels, and the treatment group received tailored vitamin D supplementation, with doses adjusted every three months until their vitamin D blood levels were above 40 ng/mL. Once the vitamin D level was above 40 ng/mL, levels were checked annually and doses adjusted if levels dropped below that target.
Researchers monitored both vitamin D and calcium levels for the participants in the treatment group throughout the study to prevent vitamin D toxicity. Doses were reduced or stopped if vitamin D levels rose above 80 ng/mL. Excessive vitamin D can lead to hypercalcemia (higher-than-normal levels of calcium in the blood), kidney failure and abnormal heart rhythm.
In a 2023 study, 80 RCTs (randomised controlled trials) were analyzed. The meta-analysis concluded that vitamin D supplementation appears to decrease the risk of ACM (all cause mortality i.e. death from all causes) (especially convincing in the fair- and good-quality RCTs), while not showing a decrease in the specific cardiovascular morbidity and death risk.
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.
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.
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). To ensure you're taking the correct dose and type of omega-3, test your blood levels rather than guessing.
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.
2. B Vitamins and NAD Boosting Supplements
B vitamins include:
- B1 (thiamine)
- B2 (riboflavin)
- B3 (niacin)
- B5 (pantothenic acid)
- B6
- B7 (biotin)
- B12
- Folic acid
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).
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. Magnesium and Molecular Hydrogen
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.
It was also already discovered that hydrogen can prolong the life of stem cells by reducing oxidative stress (Biochem Biophys Res Commun. 2010).
4. Glycine, NAC and Taurine
Low glycine levels also have been associated with various aging-related diseases like cardiovascular disease and with type 2 diabetes.
“Most studies (42 over 50) were randomized controlled trials (RCT), of which half were parallel-group trials. The majority of studies (41 over 50) reported oral glycine ingestion as the mode of delivery. Eighteen out of 50 studies were in healthy populations, 34 [out of] 50 in diseased populations and 2 [out of] 50 contained both healthy and diseased populations.
The mean or median age ranged from 21.5 to 41.4 years for healthy populations and 29.5 to 67 years for diseased populations. Glycine was administered for a period of one day (single bolus) to 14 days in healthy populations and up to 4 months in diseased populations.”
Their findings showed that glycine had the most pronounced effect on the nervous system, particularly in patients with psychiatric conditions. For instance, schizophrenic patients experienced notable improvements in psychiatric symptoms, cognition and sleep after long-term glycine supplementation.
This is largely attributed to glycine’s role as a co-agonist at the N-methyl-D-aspartate (NMDA) receptor, which is vital for neural communication and plasticity. The activation of NMDA receptors by glycine has been shown to enhance cognitive and neurological functions.
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."
"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."
Dr Leonid Kim, a physician, board-certified in Internal and Obesity Medicine, reviewed the evidence behind Glycine and how it affects your sleep, your metabolism, and your aging; dosing and when to consider GlyNAC vs Glycine. (YouTube Nov 2025)
"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."
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.
- Mitochondrial dysfunction
- Oxidative stress
- Inflammation
- Endothelial dysfunction
- Insulin resistance
- Genomic damage
- Cognition
- Strength
- Gait speed
- Exercise capacity
- Body fat levels
- Waist circumference
- 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
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.
5. CoQ10 (Best for Mitochondrial Support and Heart Health)
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).
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. An umbrella review
compiles evidence from multiple existing reviews and is one of the
highest levels of evidence.
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.
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).
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. 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.
A 2022 review paper, analysed 21 human studies. Sixteen out of 21 clinical trials were
associated with the effectiveness of curcumin or turmeric on various
types of cancer, and the other five clinical trials were related to the
evaluation of the efficacy of curcumin or turmeric in relieving the side
effects of cancer chemotherapy and radiotherapy. The emerging data from
the clinical trials confirm that curcumin has the potential for cancer
prevention and intervention. Interestingly, curcumin appears to be
universally useful for just about every type of cancer (Arslan 2022), which is really odd since cancer consists of a wide variety of
different molecular pathologies.
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.
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.
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.
8. 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 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
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.
9. 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
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.
10. 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.
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).
Ideally, one takes 2 mg of copper per day.
11. 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!
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.
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).
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).
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.
Lutein works hand in hand with another antioxidant [called] zeaxanthin. Both of those [nutrients] are usually found together [in the same supplement].
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. Collagen and Protein Powder
Protein Powder
Muscle mass optimizes you for longevity, and dietary protein,
especially animal-based protein, is essential for muscle
maintenance and muscle building. The greater your muscle mass,
the higher your survivability against all diseases, including
cancer. Cachexia, for example — the loss of muscle mass —
accounts for 20% of all cancer deaths. (source)
One of the
reasons for this is because muscle acts as a reservoir for amino
acids, which are crucial during illness when your body’s demand
for them increases. Additionally, muscle regulates metabolism and
is integral for glucose disposal, which helps you manage
conditions like diabetes and cardiovascular disease. Your muscle
also interfaces with your immune system.
It’s not only protein quantity that’s important but also its
quality and amino acid balance. Glycine and collagen, which are
often overlooked, are among the most important. Siim Land,
author of "The Collagen Cure" explains:
"Glycine is conditionally essential, not essential, but
that's because your body makes 3 grams of glycine per day. But
those 3 grams would be used for things, like creatine
synthesis. But then you have 12 grams of glycine for collagen
turnover, like optimal collagen turnover." (source)
Most people are deficient, as they’re likely only consuming 0 to 1
gram of collagen protein daily. About one-third of total body
protein is collagen, so it's crucial to consume adequate collagen,
from foods like bone broth or grass fed ground beef, which
contains connective tissue, or glycine to support connective
tissue health.
Collagen and Skin Anti-Aging
Collagen is the king of anti-aging, which is why so many youth
rejuvenation treatments focus on renewing or revitalizing collagen
production in the body — but you can kick start this process without
needles, simply by supplementing collagen into your diet.
Collagen is also 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.
As
we age we produce less of it, leading to skin wrinkles and sagging.
It’s believed that collagen production begins slowing as early as
our early twenties. However, when our bodies start to slow the
production of collagen, we can make sure our levels remain high by
supplementing it.
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 2023 meta-analysis of 26 RCTs (randomized controlled trials), showed that
Hydrolyzed Collagen supplementation significantly improved skin
hydration and elasticity compared to the placebo group.
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 12-week study (RCT 2019) of 72 women showed that regularly taking a
supplement that contained 2.5 grams of collagen (along with several
other ingredients) significantly improved the appearance of skin
elasticity and softness.
Collagen supplements have scientifically been shown to improve skin
elasticity and reduce wrinkles in a 2020 study.
Another 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.
One of the reasons for this is because muscle acts as a reservoir for amino acids, which are crucial during illness when your body’s demand for them increases. Additionally, muscle regulates metabolism and is integral for glucose disposal, which helps you manage conditions like diabetes and cardiovascular disease. Your muscle also interfaces with your immune system.
As we age we produce less of it, leading to skin wrinkles and sagging. It’s believed that collagen production begins slowing as early as our early twenties. However, when our bodies start to slow the production of collagen, we can make sure our levels remain high by supplementing it.
Many types of collagen supplements are on the market, including powders and capsules.
16. 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.
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).
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.
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 2018 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.
“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.”
“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 …”
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.”
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.”
“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.
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.
19. Acetyl-L-Carnitine
Acetyl-l-carnitine is a naturally occurring fatty acid transporting amino
acids. L-carnitine supplementation has long been studied and then used in
many mitochondrial dysfunction disorders. These disorders are also
characterized by low concentrations of serum l-carnitine levels such as
heart disease, diabetes, kidney disease, and overwhelming infections.
An
important cellular longevity function of l-carnitine has been to increase
the rate of mitochondrial oxidative phosphorylation (ATP production) that
declines with age. A study where old rats were fed acetyl-l-carnitine
resulted in the reversal of age-related decreases in l-carnitine levels,
an increase in fatty acid metabolism, and an increase in mitochondrial
activity. Acetyl-l-carnitine also reverses the age-related decline in
muscle mitochondria.
Clinical studies show that L-carnitine
supplementation may also be useful in alleviating fatigue symptoms in
hypothyroid patients, especially in those younger than 50 years and those
who have hypothyroidism after thyroidectomy for thyroid cancer. Note:
L-carnitine is the nomenclature used for many clinical studies, but due to
l-carnitine’s ability to increase TMAO, experts suggest that all human supplementation be done with
acetyl-l-carnitine.
An important cellular longevity function of l-carnitine has been to increase the rate of mitochondrial oxidative phosphorylation (ATP production) that declines with age. A study where old rats were fed acetyl-l-carnitine resulted in the reversal of age-related decreases in l-carnitine levels, an increase in fatty acid metabolism, and an increase in mitochondrial activity. Acetyl-l-carnitine also reverses the age-related decline in muscle mitochondria.
Clinical studies show that L-carnitine supplementation may also be useful in alleviating fatigue symptoms in hypothyroid patients, especially in those younger than 50 years and those who have hypothyroidism after thyroidectomy for thyroid cancer. Note: L-carnitine is the nomenclature used for many clinical studies, but due to l-carnitine’s ability to increase TMAO, experts suggest that all human supplementation be done with acetyl-l-carnitine.
20. Creatine
What is creatine? Creatine, a nitrogenous organic acid naturally
occurring in vertebrates, plays a critical role in the energy metabolism
of brain cells. Synthesized primarily from arginine, glycine, and
methionine, creatine is produced endogenously and obtained through
dietary intake.
A 2024 meta-analysis of 16 randomised controlled trials (RCTs), suggests that creatine monohydrate supplementation may
confer beneficial effects on cognitive function in adults, particularly in
the domains of memory, attention time, and information processing speed.
In a 2023 research, published in Nutrition Reviews, found creatine supplementation enhanced memory performance in healthy
adults, particularly those aged 66 to 76 years. The study concluded:
“These beneficial effects from creatine supplementation on memory
performance may be related to creatine’s ability to influence brain
bioenergetics. For example, creatine elevates phosphocreatine and ATP
levels and increases oxidative phosphorylation in synaptosomes and
isolated brain mitochondria. In hippocampal neuron cultures, creatine
stimulates mitochondrial activity.”
“These beneficial effects from creatine supplementation on memory performance may be related to creatine’s ability to influence brain bioenergetics. For example, creatine elevates phosphocreatine and ATP levels and increases oxidative phosphorylation in synaptosomes and isolated brain mitochondria. In hippocampal neuron cultures, creatine stimulates mitochondrial activity.”
Conclusion and Take Home Messages
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.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.
- I-LONGEVITY Protocol: Comprehensive Anti Aging Guide to Help People Prevent and Reverse Aging
- Longevity and Anti-Aging: Exploring the Most Promising Interventions and Strategies
- Biological Age vs Chronological Age
- David Sinclair recommended supplements
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