I-LONGEVITY Protocol: Anti Aging Guide to Help People Prevent and Reverse Aging (2024)

Introduction

Can diet, lifestyle and supplements reverse your age? 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.

If you are in the anti aging, longevity or biohacking space, chances are you have heard about Dr David Sinclair and Bryan Johnson. Although both of them do share many longevity related strategies, their recommendations might be too overwhelming for an average layperson. You should also consult your doctor before starting any new diet and supplement program to ensure safety and suitability for your individual needs.

That's where this guide is all about. We've delved into the research to provide you with more than just basic advice. We've done the research, so that you don't have to. We'll not only share supporting evidence, but also explain our methodology for selecting the most valuable information.

The process of human aging is a complex and multifactorial process. NAD, stem cells, nitric oxide, glutathione, vitamin B12, CoQ10, glycine, taurine, Alpha-KetoGlutarate (AKG), spermidine and testosterone decline as we age. Vitamin and mineral deficiencies are also common in older individuals.

We are pleased to introduce the I-Longevity protocol, designed to help people to prevent and reverse aging.

Note: This article here is developed as a consumer guide and is not meant to share the various technical theories related to anti aging and longevity but to share practical preventive strategies that we could put into action immediately.  The goal of this article is to summarize the relevant, updated and practical points so that you could have your personal blue-print.

We'll also analyse relevant studies, keeping in mind that new research emerges constantly. We have filtered out all those unproven ‘internet noise’ out there in the virtual world and have summarised the overwhelming information out there into the following list of ‘actionable’ strategies.

In September of 2019, the MIT Technology Review published “The Longevity Issue” with a MASSIVE black heading on a snow-white cover and announced, “OLD AGE IS OVER!” and in a font much smaller underneath are the following words: “IF YOU WANT IT.”

In this comprehensive guide you will learn about many aspects of aging, longevity and age-reversal strategies. 

Contents

1. Methodology
2. What is Aging?
3. Biological Age vs Chronological Age
4. Causes of Aging and Hallmarks of Aging
5. What is Cell Senescence?
6. What is Epigenetics?
7. Diet and Lifestyle for Anti Aging
1. Avoiding Sugar and Ultra-processed Foods
2. Mediterranean Diet and Vegetables
3. Avoiding Smoking and Alcohol
4. Stress Management
5. Avoiding Linoleic Acid (Omega-6 Fatty Acids) and Vegetable Oil
6. Exercise, Resistance Training and Walking
7. Sleep
8. Social Support
9. Caloric Restriction, Intermittent fasting (Time Restricted Eating) and Fasting
8. Best Scientifically Proven Anti Aging Supplements
1. Vitamin D3 and K2
2. Glycine, NAC and Taurine
3. B Vitamins, Nicotinamide mononucleotide (NMN) and NAD Boosting Supplements
4. Omega-3 fatty acids
5. Magnesium and Molecular Hydrogen
6. Curcumin (Turmeric)
7. Vitamin C
8. CoQ10
9. Zinc
10. EGCG (Green Tea)
11. Lutein and Zeaxanthin
12. Glucosamine and Chondroitin
13. Protein Powder and Collagen
14. Spermidine
15. Crocin (Saffron)
16. Cocoa
17. Creatine
18. Melatonin
9. Other Promising Interventions for Longevity
1. Stem Cell Therapy for Anti-Aging
2. Exosomes for Anti Aging
3. Does Metformin Increase Life Expectancy?
4. Metabolic Manipulation (mTOR Inhibitors) and Rapamycin
5. Hyperbaric oxygen therapy (HBOT)
10. Conclusion and Key Takeaways

Time (Jan 2023)

Methodology

We’ve combed the internet, find the best references and reviewed over 1,000 studies so that you don’t have to. The selection or short-listing of the recommendations below is based on the available scientific evidence retrieved from scientific database such as PubMed and scientific search engine such as Google Scholar. 

When interpreting and filtering scientific research, it’s crucial to consider the hierarchy and quality of evidence. Not all evidence is equal.

Cell culture findings carry less weight than results from studies conducted on mice. Similarly, conclusions drawn from mouse studies are surpassed by findings from human studies.

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.

*A systematic review is a review that collects, critically appraises, and synthesizes all the available evidence to answer a specifically formulated research question. A meta-analysis, on the other hand, is a statistical method that is used to pool results from various independent studies, to generate an overall estimate of the studied phenomenon.

It would be impossible to review all the studies on the internet; rather, we have focused on, curated and evaluated the information that appear to have the greatest clinical utility. The article will also be updated as and when there is a newly discovered major research publication related to anti-aging and longevity.

 

What is Aging?

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)
 

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

Longevity Medicine will become the New Primary Care

Biological Age vs Chronological Age

When asked how old you are, you likely answer based on the number of years that have passed since you were born. That would be your chronological age.

But maybe your doctor says you have the physical conditioning of a 21-year-old. This would be considered your biological age, regardless of how many years ago you were born.

Your chronological age will always be an easy-to-determine number, while your biological age depends on a number of variables that can change on a continuing basis.

The difference between the two can be surprising and definitely worthy of further exploration.

What is chronological aging?

Your chronological age is the amount of time that has passed from your birth to the given date. It’s your age in terms of years, months, days, etc. This is the primary way people define their age.

It’s also a primary risk factor for chronic diseases, mortality, and any impairments to bodily functions, such as hearing and memory.

What is biological aging?

The basic idea behind biological aging is that aging occurs as you gradually accumulate damage to various cells and tissues in the body.

Also known as physiological or functional age, biological age differs from chronological age because it takes into consideration a number of factors other than just the day you were born.

The actual number comes down to different biological and physiological development factors. Some of these include:

• chronological age
• genetics (for example, how quickly your body’s antioxidant defenses kick in)
• lifestyle
• nutrition
• diseases and other conditions

Using these guidelines along with various mathematical models, medical professionals can figure out what age your body “acts” like it is.

While chronological age is a factor, you may not end up having the same biological age as your chronological age. For example, if you’re a 28-year-old male who doesn’t exercise, only eats high-fat foods, and has smoked five packs of cigarettes per day for the last 10 years, it’s likely you would have a biological age of greater than 28 years.

We are interested in your 'biological age' and in Healthspan rather than Lifespan, which means that you LIVE - HEALTHIER - LONGER. This is better than chronologic age and Longevity because it just means a long life with no regard to your quality and function.

Image credit: Longevity.technology

Causes of Aging

The process of aging is not a simple single dimensional change. In order to guide and provide a framework for ageing research and discussion, the landmark 2013 Hallmarks of Aging study identified 9 factors that contribute to health decline in advancing age: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. 

The review was updated (Cell 2023) by the same authors in 2023 to include 12 hallmarks of aging: 

1. genomic instability, 
2. telomere attrition, 
3. epigenetic alterations, 
4. loss of proteostasis, 
5. deregulated nutrient-sensing, 
6. mitochondrial dysfunction, 
7. cellular senescence, 
8. stem cell exhaustion, 
9. altered intercellular communication, 
10. disabled macroautophagy, (new)
11. chronic inflammation, and (new)
12. dysbiosis. (new)

While aging is inevitable, increasing the human lifespan and slowing the aging process has been a focus of scientific research for decades. If aging is reversible, then maybe heart disease, cancer, diabetes, Alzheimer's or other chronic disorders are reversible as well. A comparison of the Hallmarks of 'Aging' vs the Hallmarks of 'Cancer' (Cancer Discov 2022) reveals significant overlap between the two hallmarks.

Source: Cell 2023

While mainstream media often portrays a lack of scientific evidence to substantiate the efficacy of diet, lifestyle and specific supplements, this narrative is not entirely accurate. 

Credit: ACS Chem. Neurosci. 2024

Credit: ACS Chem. Neurosci. 2024

What is Cell Senescence? 

Senescence is defined as biological aging and the gradual deterioration of functional characteristics in a living organism. There is a loss of the cell’s power to divide and grow. This may seem like a natural life cycle pattern, however, the problem is these cells are not alive, nor dead. They are providing no benefit to your body, in fact, they are creating destruction of healthy cells leading to inflammation, the precursor to all dysfunction and disease. For this reason, these cells are also referred to as “zombie cells’’.

Below are a few examples of the damage these “zombie cells” cause to your body: 

• Interfere with organ function (heart, brain, liver, kidney, skin…) 
• Create age related diseases (cardiovascular, kidney, diabetes…) 
• Shorten healthy lifespan (decrease function and create disease) 
• Accelerate degeneration (damage causes breakdown) 
• Damage organs (colon, blood vessels, nervous system…) 
• Triggers inflammation causing problems (high blood pressure, elevated cholesterol, elevated blood sugar….)

You have probably heard that inflammation is a precursor to all diseases. In a nutshell, all healthy aging and longevity strategies focus on countering chronic latent inflammation. Chronic inflammation and an impaired immune system accelerate cell death, which can be proven by measuring biomarkers such as telomeres, inflammatory markers, hormones, neurotransmitters, and many others. 

Senescent cells can be eliminated with a combination of diet, specialized nutraceuticals, peptides, medications and exosomes, since eliminating senescent cells is critical to any effective longevity strategy when the goal is to improve healthy lifespan, and quality of life.

The medications that are the key players in the clearing of senescent cells are called SENOLYTICS. Senolytics, also called geroprotectors, are substances that are used to halt or reverse cellular aging. Researchers identified a novel class of (senolytic) drugs that delay several age-related symptoms in mice. The results demonstrate the ability of compounds with potential to extend healthy life. (NATIONAL Health Institute, September 12, 2017)

Studies published as early as 2018 ” reveal that just a few senescent cells transplanted into young mice result in persistent physical decline, a characteristic of aging. There was an obvious acceleration of aging in these mice just by inoculating them with “old” senescent cells.

When these mice were given senolytic compounds to remove the senescent cells, there was an obvious alleviation of physical decline and an extended lifespan, which equated to living 36% longer. Imagine the opportunity to add 36% more productive years to your life! 

Let’s do the math. Say the average US lifespan is 76 years old; that means we could potentially add another 27 productive years? Now this is what we mean by elongating your “HEALTHSPAN”!

What is Epigenetics?

Now science has learned genetics are responsible for only 10% of all human disease, while the remaining 90% are triggered by environmental factors (Exposome and Exposomics, CDC).

The term epi means above or in addition to and epigenetics describes the study of gene expression regulation that cannot be directly attributed to changes in the DNA sequence. Epigenetics (the study of epigenomes) describes the way our specific behaviors (e.g., lifestyle choices including how much alcohol we drink, or whether we use a water filter) and environmental factors (e.g., air pollution) can alter the way our genes work. Epigenetic changes can be extremely impactful, often passed on from generation to generation, yet they are reversible, and do not alter the DNA sequence (although they do change how our bodies READ a DNA sequence). A bit confusing?

Think of it this way: The way our epigenomes are affected by our external environment represents the interaction between our environment and the process of adaptation that all living systems use to adapt and thrive. Still confused, let us describe it to you in this way: Smokers have lower DNA methylation than non-smokers (in the AHRR gene, which mediates toxicity, and epigenetic adaptation). However, this epigenetically-altered DNA response is often reversed after a smoker kicks the habit.

The epigenetic marks, or modifications, that we each pick up in life, do not cause any adaptations to DNA itself. Though sometimes temporary, epigenetic marks can still be inherited from cell to cell, as cells divide and reproduce, and that is then passed down through generations, possibly to the detriment of our offspring, depending on what those epigenetic adaptations might be. Here is an example: a famed epigenetic study conducted in the Netherlands studied children born during “The Hunger Winter” of 1944-1945, where food was severely rationed. Parents suffered a vastly decreased caloric intake, which impacted their children, notably. Children became significantly more likely to develop cardiovascular disease, diabetes, and obesity, partly a result of the epigenetic adaptations made to the fetus’s intrauterine environment, because of these environmental stressors.

Did you know that six months of aerobic exercise, can positively alter whole-genome DNA methylation in skeletal muscle, and adipose (fat) tissue, directly influencing more effective lipogenesis (fat loss). A body of evidence also supports the idea that a clean diet can: Reverse abnormal gene activation or gene silencing, using bioactive dietary compounds (e.g., garlic, soy products, herbs, and cruciferous vegetables), with clear indicators that many nutritional compounds have epigenetic targets in cancer cells. Ultimately, epigenetics represents one of the most fascinating and exciting areas of modern medical research. 
 

Diet and Lifestyle for Anti Aging

Nutrition, exercise, proper sleep and stress reduction are also very important methods to extend lifespan. 

A 2024 review aims to summarize recent findings on the dietary factors influencing chronic diseases and longevity, primarily from large cohort studies. 

• First, maintaining a healthy weight throughout life is pivotal for healthy aging and longevity, mirroring the benefits of lifelong, moderate calorie restriction in today's obesogenic food environment. 
• Second, the specific types or food sources of dietary fat, protein, and carbohydrates are more important in influencing chronic disease risk and mortality than their quantity. 
• Third, some traditional diets (e.g., the Mediterranean, Nordic, and Okinawa) and contemporary dietary patterns, such as healthy plant-based diet index, the DASH (dietary approaches to stop hypertension) diet, and alternate healthy eating index, have been associated with lower mortality and healthy longevity. These patterns share many common components (e.g., a predominance of nutrient-rich plant foods; limited red and processed meats; culinary herbs and spices prevalent in global cuisines) while embracing distinct elements from different cultures. 
• Fourth, combining a healthy diet with other lifestyle factors could extend disease-free life expectancies by 8-10 years.

Another research presented in July 2023 at the American Society for Nutrition’s annual conference in Boston (SciTechDaily). Researchers examined the data of nearly 720,000 military veterans ages 40–99, who were followed over time. Those who adopted eight healthy habits saw a 13% reduction in mortality compared to those who did not. The eight habits are: being physically active, being free from opioid addiction, not smoking, managing stress, having a good diet, not regularly binge drinking, having good sleep hygiene, and having positive social relationships.

Studies showed the critical role of diet in cardiovascular health. An analysis by the Institute for Health Metrics and Evaluation attributed 30 percent of cardiovascular disease deaths in 2021 to poor diet. This finding aligns with broader research suggesting that more than two-thirds of heart disease-related deaths worldwide are linked to food choices, according to the European Society of Cardiology.

A 2019 study found that healthy lifestyle choices could reduce the risk of stroke—a cardiovascular event when blood supply to the brain is cut off or when a blood vessel in the brain bursts—by 80 percent, with diet identified as the most influential factor.

1. Avoiding Ultra-processed Foods and Sugar

At this point, there is simply no question that processed foods that are high in sugar and low in fiber are unhealthy.

Avoid ultra-processed foods

A 2024 umbrella review* (BMJ) of the literature confirmed what multiple studies have shown — the higher your intake of ultraprocessed food, the higher your risk of adverse health outcomes. The analysis, which included 14 meta-analysis studies, 45 unique pooled analyses and 9,888,373 participants, found direct associations between 32 health parameters and exposure to ultra processed food, including metabolic dysfunction, cancer, mental, respiratory, cardiovascular and gastrointestinal issues, as well as all-cause mortality.

*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 strongest and highest levels of evidence.

Another 2024 study, Fang and colleagues (BMJ 2024) evaluated the relation between ultra-processed food consumption and mortality in two large US cohort studies with up to 34 years of follow-up.

The study found an increase in the risk of total mortality with higher ultra-processed food consumption. The positive associations were mainly driven by meat/poultry/seafood based ready-to-eat products, sugar and artificially sweetened beverages, dairy based desserts, and ultra-processed breakfast foods.

Avoid Sugar

Evidence from a 2023 umbrella review (BMJ 2023) of more than 8,000 studies supports the limiting dietary sugar recommendation.

An article by the New York Times (2016) titled "How the Sugar Industry Shifted Blame to Fat" suggested that the sugar industry paid scientists in the 1960s to play down the link between sugar and heart disease and promote saturated fat as the culprit instead, newly released historical documents show. This article was based on the internal sugar industry documents, discovered by a researcher at the University of California, San Francisco, and published in JAMA Internal Medicine (2016) that suggested that five decades of research into the role of nutrition and heart disease, including many of today’s dietary recommendations, may have been largely shaped by the sugar industry.

Think Twice About Plant-Based Foods: Some Types Could Heighten Cardiovascular Risks and Mortality

In June 2024, The Lancet Regional Health–Europe published a study indicating a positive association between the intake of ultra-processed plant-based foods and the risk of CVD and mortality. Conversely, consuming non-ultra-processed plant-based foods was negatively associated with these risks.

The study, which analyzed data from nearly 127,000 individuals aged 40 to 69 in the UK Biobank with a median follow-up of nine years, found that each 10 percent increase in the proportion of total energy intake from ultra-processed plant-based foods was associated with a 5 percent increase in the risk of CVD and a 6 percent increase in the risk of coronary heart disease. Moreover, the risk of mortality from CVD increased by 12 percent.

Related: Carnivore Diet vs Plant Based Diet

2. Best Anti Aging Diet: Mediterranean Diet and Vegetables

A heart-healthy diet such as a Mediterranean based diet or the DASH diet is recommended in order to reduce risk and decrease inflammation in the body.

A high adherence to well-known anti-inflammatory dietary patterns (e.g., Mediterranean Diet and DASH) was associated with delayed biological aging (Clinical Nutrition 2022) and dietary polyphenols consumption was also associated with delayed biological aging (Nutrients 2021).

The Mediterranean diet (MedDiet) is one of the most consistent dietary patterns analyzed in relation to the prevention of cardiovascular disease (CVD) and other health outcomes, including reduction of overall mortality and increased likelihood of healthy aging (Silvia Canudas 2020). In a this review of 8 original studies, the meta-analysis demonstrates that higher MedDiet adherence is associated with longer Telomere Length (TL). 

A 2022 umbrella review* of 41 systematic reviews and meta-analyses of 303 observational studies

revealed that CV (cruciferous vegetable intake might be associated with beneficial effects on several health-related outcomes (gastric cancer, lung cancer, endometrial cancer, and all-cause mortality).

Another 2018 study, eating just one serving of green leafy vegetables a day may help to slow cognitive decline associated with aging, helping you to be 11 years younger, cognitively speaking, than your non-leafy green-eating peers. They’re a rich source of brain-protective nutrients like folate, vitamins E and K, lutein and beta-carotene (source). Cruciferous vegetables, like broccoli and cauliflower, are equally impressive, in part because they’re good sources of choline, a B vitamin known for its role in brain development.

Caution: What are the nutrients of concern for vegetarians and vegans? Vitamin B12 and K2. Anybody who is eating a vegan diet or a vegetarian diet or just a mostly plant-based diet should be taking vitamin B12 and K2 supplements. Vitamin B12 is only found in significant amounts in animal products and fortified foods, and a deficiency can cause anemia, mood changes, or permanent neurological damage. Plant-based diets may also be low in vitamin D, omega-3 fatty acids, and minerals like iodine, selenium, iron, and zinc.

3. Avoiding Smoking and Alcohol

Avoid Smoking

“Smoking is one of the strongest risk-factors for every chronic disease, including heart disease and cancer,” says Susan Lakoski, M.D., associate professor of cancer prevention at MD Anderson Cancer Center.

Smoking and secondhand smoke introduce harmful toxins to the body. There’s no such thing as a healthy smoker - especially when it comes to cancer prevention.

“The biggest myth I hear is that if someone exercises they can offset the negative effects from smoking, but that’s absolutely not the case,” says Susan Lakoski, M.D.

Smoking has been linked to many types of cancer, including cancer of the lung, mouth, throat, voice box, pancreas, bladder, cervix and kidney. Even being around secondhand smoke might increase the risk of lung cancer.

But it's not only smoking that's harmful. Chewing tobacco has been linked to cancer of the mouth, throat and pancreas.

Staying away from tobacco — or deciding to stop using it — is an important way to help prevent cancer. For help quitting tobacco, ask a health care provider about stop-smoking products and other ways of quitting.

Avoid Alcohol

According to a study from the UK Biobank that examined brain scans of 36,678 middle-aged and older adults (Nature 2022), even just one to two alcoholic drinks per day is associated with negative changes in brain structure, including reductions in overall brain volume, gray matter and white matter integrity.

Drink alcohol only in moderation, if at all. Alcohol increases the risk of various types of cancer, including cancer of the breast, colon, lung, kidney and liver. Drinking more increases the risk.

4. Avoiding Linoleic Acid and Vegetable Oil

Advice to substitute polyunsaturated fats for saturated fats is a key component of worldwide dietary guidelines for coronary heart disease risk reduction. However, clinical benefits of the most abundant polyunsaturated fatty acid, omega 6 linoleic acid, have not been established. 

In this cohort (BMJ 2013), substituting dietary linoleic acid in place of saturated fats increased the rates of death from all causes, coronary heart disease, and cardiovascular disease. An updated meta-analysis of linoleic acid intervention trials showed no evidence of cardiovascular benefit. These findings could have important implications for worldwide dietary advice to substitute omega 6 linoleic acid, or polyunsaturated fats in general, for saturated fats.

Another study (Women's Health Initiative Study), a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits, and grains did not significantly reduce the risk of CHD, stroke, or CVD in postmenopausal women.

The Minnesota Coronary Experiment (MCE), a randomized controlled trial conducted in 1968-73, was the largest (n=9570) and perhaps the most rigorously executed dietary trial of cholesterol lowering by replacement of saturated fat with vegetable oil rich in linoleic acid. A re-evaluation of the trial data (published in BMJ 2016), add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid. Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. 

While most have heard about the health risks of eating processed sugars, net carbs and trans fats, seed oils far surpass all of these in the damage they cause to your health. If you were to make one change today to lower your risk of chronic diseases, eliminating all seed oils from your diet would be the highest priority.

Over the last century, thanks to fatally flawed research suggesting saturated animal fat caused heart disease, the LA in the human diet has dramatically increased, from about 2 to 3 grams a day 150 years ago, to 30 or 40 grams a day. 

On a side note, do not confuse LA with conjugated linoleic acid (CLA). While most think CLA and LA are interchangeable, they're not. CLA has many potent health benefits and will not cause the problems that LA does.

Another study builds on existing evidence linking ultra-processed food consumption to chronic disease and premature death. The study published in the American Journal of Preventive Medicine (Nov 2022) found that increased consumption of ultra-processed foods (UPF) was associated with a significant increase in all-cause premature, preventable deaths in Brazil in 2019.

Like other nutrition experts, study author Nilson agreed that a healthy, balanced diet should be based on fresh and minimally processed foods, when possible, in addition to avoiding ultra-processed foods.

“The continuity of the current trends with gradual increases in ultra-processed food consumption will increase premature deaths,” Nilson said, adding that his research highlights a need for a shift in policy around ultra-processed foods.

5. Enough Quality Sleep

This is one of the most under-rated anti-aging strategies. Research has demonstrated sleep is a crucial component of a healthy lifestyle.

In a 2023 study (The Lancet), scientists looked at how the relationship between sleep and exercise might impact cognitive decline. Researchers from University College London examined the association between physical activity and sleep duration in 8,958 participants over 10 years. The data were collected from the English Longitudinal Study of Aging, during which participants were interviewed every two years.

The researchers evaluated episodic memory using recall tasks and verbal fluency using animal naming tasks. They found that participants with lower levels of physical activity and suboptimal sleep had worse performance on the cognitive tests and those who slept the least exhibited faster cognitive decline. Interestingly, the participants who had higher levels of physical activity and shorter sleep times also had faster rates of cognitive decline. 

Those who had higher levels of physical activity and slept an optimal number of hours had the slowest cognitive decline. Overall, the data suggested that higher-intensity physical activity was not enough to mitigate the rapid cognitive decline that is associated with insufficient sleep.

Lack of quality sleep can also weaken immune function and increase susceptibility to respiratory infections, including the common cold, and chronic lack of sleep may be associated with an increased risk of death (Prather 2015; Ibarra-Coronado 2015; Wilder-Smith 2013; Aldabal 2011). 

Sleep deprivation is associated with elevated cortisol levels, as well as higher daytime levels of inflammatory cytokines including IL-1, IL-6, and tumor necrosis factor-alpha (Aldabal 2011; Hirotsu 2015). A study in individuals aged 61‒86 found even a single night of partial sleep deprivation induced patterns of gene activation associated with biological aging (Carroll 2016).

6. Exercise, Resistance Training and Walking

In combination with a healthy diet, exercise is one of the most cost effective, long term, and preventative measures you can take.

Physical exercise has been well validated as an effective antiaging intervention. Regular physical activity of the elderly plays a vital role at a multi-system level, avoiding muscle atrophy, mending or sustaining cardiorespiratory health and cognitive performance, and enhancing metabolic activity. Recommendations predicated on the most recent American College of Sports Medicine Guidelines advise that physical exercises for elderly need to involve aerobic exercise, muscle strengthening, and endurance training, as well as flexibility and neuromotor exercises. (ACS Chem. Neurosci. 2024)

Physical exercise is also the most studied anti-aging strategy as shown below.

Connecting the dots between Antiaging nutrients and drugs and (A) hallmarks of aging, and (B) antiaging strategies. Credit: ACS Chem. Neurosci. 2024

A 2024 meta-analysis from the European Society of Cardiology found that people who chose to take the stairs saw a 39 percent lower likelihood of death from heart disease, compared to those who always take the elevator or escalator.

It has also been evidenced recently that one of the best strategies for healthy brain aging is regular aerobic exercise. It is suggested that exercise likely remains the most effective intervention for healthy brain aging because it stimulates strategic energy-sensing pathways that modulate multiple hallmarks of aging. (Exerc Sport Sci Rev 2021)

Related: Muscle Mass - The Key to Longevity

That said, if you're eating very small amounts of food, you are becoming very frail and skinny. Exercise without proper nutrition is counter-productive. In the actual world, we're starting to see right now that frailty is a huge risk factor for early death and mortality. And malnutrition itself also increases the risk of a lot of different diseases, all-cause mortality and neuro-degeneration and heart disease events.

Walking Is a Simple, Powerful Key to Longevity

A 2023 review published in GeroScience highlights the crucial role of regular physical activity, particularly walking, in promoting healthy aging and longevity.14 The researchers emphasize that walking is not just a basic exercise but a potent antiaging intervention. It has been shown to lower the risk of age-related chronic diseases such as heart disease, high blood pressure, Type 2 diabetes and cancer. Moreover, walking can alleviate pain and enhance function in musculoskeletal conditions.

VO2 max: Longevity biomarker

Many longevity biohackers especially those in the fitness niche do measure their VO2 max on a regular basis. In a study (Front Biosci (Landmark Ed) 2018), VO2 max is related to functional capacity and human performance and has been shown to be a strong and independent predictor of all-cause and disease-specific mortality.

7. Stress Management

A big component of the longevity equation is the management of stress.

A June 2022 study supports what immunologists have long suspected: A key stressor to our immune system as we age may be stress itself.

“Immune aging may help explain why older people tend to benefit less from vaccines and why they have more serious complications associated with infections like COVID-19,” Erik Klopack, Ph.D., a lead author of the study and a postdoctoral scholar at the Leonard Davis School of Gerontology at the University of Southern California. “Our study suggests that social stress may accelerate immune aging,” he said.

8. Social Support

As part of the Cardiovascular Health Study, 5,749 adults aged 65 years and older from 4 US field centers for 25 years were followed. In older adults, higher social network scores are significantly associated with longer life expectancy and disability-free life expectancy. (Bhatia 2023)

This prospective cohort study included 6,670 women from the Women's Health Initiative Memory Study who were cognitively unimpaired at enrollment; showed that improving social support may reduce risk of MCI (mild cognitive impairment) and dementia in older women. (Posis 2023)

9. Intermittent fasting, time restricted eating (TRE) and Calorie Restriction

Intermittent fasting is currently one of the most popular nutrition programs around. Unlike diets that tell you what to eat, intermittent fasting focuses on when to eat.

Limiting the hours you eat each day may help you consume fewer calories. It may also provide health benefits, including weight loss and improved heart health and blood sugar levels.

There are several forms of intermittent fasting, including a common form called time-restricted eating. 

Fasting, or reducing your calorie intake is also an excellent method for indirectly boosting the body’s NAD levels. Fasting has been shown to increase the levels of NAD+ and surtuins; the proteins which have been found to slow the aging process. 

While fasting is effective in increasing NAD+ levels, drastic reduction in calorie intake or fasting can have a counterproductive effect. There is also some speculation that intermittent fasting or adopting a low carb-ketogenic diet may also provide similar positive results.

Research also suggests that caloric restriction and fasting might be helpful to give your existing so-called endogenous stem cells a boost. 

Additionally, fasting reduces insulin levels. Elevated insulin levels are linked to an increased risk of breast, prostate, and colorectal cancers.

Caution: Historically, many mistakes have been made in longevity research, particularly the focus on extreme calorie, carbohydrate and protein restriction. If you're eating very small amounts of food, you are becoming very frail and skinny. In the actual world, we're starting to see right now that frailty is a huge risk factor for early death and mortality. And malnutrition itself also increases the risk of a lot of different diseases, all-cause mortality and neuro-degeneration and heart disease events.

Best Anti-Aging Supplements

There are a lot of options out there, and we know it can be overwhelming.

Food for Thought: Scurvy, pellagra, and beriberi were once thought to be infectious and were finally recognized as nutritionally linked. Scurvy is a deficiency of vitamin C, Pellagra is a deficiency of niacin, more commonly known as vitamin B3, and Beriberi is a deficiency of thiamine, more commonly known as vitamin B1.

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

1. Vitamin D3 and K2

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

Food for thought: The Sun powers photosynthesis, the process by which plants convert sunlight into energy, fueling the entire ecosystem. Additionally, the sun’s rays also enable our bodies to produce vitamin D, essential for immune system, bone health and overall well-being.

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

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

Another 2024 study in older adults, low vitamin D and inflammation (high hs-CRP*), both independently and jointly, increase mortality risk in Chinese community-dwelling older adults. Thus, priority should be given to early detection and appropriate intervention in older individuals with combined vitamin D deficiency and systemic inflammation. 

*hs-CRP: High-sensitivity C-reactive protein (hs-CRP) is widely used to reflect the degree of systemic inflammation (source).

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.

Another 2023 study, 116 randomised controlled trials were analysed. The meta-analysis concluded that vitamin D reduces lung cancer mortality. All-cause mortality is decreased in patients with COVID-19  and liver diseases, especially in liver cirrhosis.

The DO-HEALTH trial (ClinicalTrials.gov identifier NCT01745263), were published in Frontiers in Aging 2022. The first randomized-controlled trial (DO-HEALTH) trial to investigate the combination of three complementary treatments for the prevention of cancer and suggest that the combination of daily vitamin D3, supplemental marine omega-3s, and a simple home exercise program may be effective in the prevention of invasive cancer among generally healthy and active adults aged 70 and older. Findings from this 3 year Randomized Controlled Trial with more than 2,000 participants observed a 61% reduction in the risk of invasive cancer among patients who completed a home exercise program and took vitamin D3 and omega-3 fatty acids daily.

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 1,000 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.

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

Make sure to take 500 mg to 1000 mg of magnesium and 150 mcg of vitamin K2, (not K1) which are important cofactors for optimizing vitamin D function. And, remember the only way you know what your vitamin D level is, is to test it. Most people are shocked how low their level is when they finally get around to testing it.

Vitamin K2

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

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

Vitamin D3 and K2

Rosu et al (Nutrients 2024) performed a systematic review of 31 trials of vitamin D plus K2 on a variety of outcomes including bone mineral density, other physiologic measures, and when provided, risk of fractures.

“The randomized controlled studies performed on menopausal women of various ethnicities and health statuses suggest that combined vitamin D and vitamin K supplementation may be more beneficial for the prevention and potential treatment of age-associated diseases including CVD and osteoporosis than either supplementation alone. This approach may be part of a multifaceted strategy, which could include nutrition counseling and diet changing, addressing sedentary behavior and physical activity, avoiding tobacco exposure, and preventing or minimizing long-term glucocorticoid therapy, all holistic concepts needed to support the health of postmenopausal women.”

2. Omega-3 fatty acids

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

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

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

The study, published in The American Journal of Clinical Nutrition (Oct 2021), used data from a long-term study group, the Framingham Offspring Cohort, which has been monitoring residents of this Massachusetts town, in the United States, since 1971. The research looked at 2,200 people who were monitored for 11 years for their blood fatty acid levels. The researchers found that omega-3 levels in red blood cells are very good mortality risk predictors. That means that higher levels of Omega-3 in the blood from regularly eating oily fish, increased life expectancy by almost five years.

This research comes a few months after a meta-analysis of 17 prospective cohort studies was published in Nature Communications (2021). The analysis linked higher circulating omega-3 fatty acid levels to longevity. In a pooled analysis of the studies, participants in the highest fifth of combined blood DHA and EPA were 15 to 18 percent less likely to die from any cause over the follow-up period (median follow-up time is 16 years in these studies). Higher blood omega-3s were also associated with a reduced risk for death from cardiovascular disease and cancer.

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

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

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

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

Make sure you buy high-quality omega-3 fatty acid supplements, meaning that the omega-3 fatty acids are pure and have not oxidized much (having low “TOTOX” value). TOTOX value stands for total oxidation value. The omega 3 fatty acids EPA and DHA from fish oil are highly sensitive to oxidation. This means that they are rapidly affected by contact with oxygen. Oxidised fatty acids are not beneficial to our health. For this reason, a good fish oil supplement has a low TOTOX value. The maximum TOTOX value is set at 26 by the Global Organization for EPA and DHA omega-3.

3. B Vitamins and NAD Boosting Supplements

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

B vitamins include:

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

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

NAD+ Precursors

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

Nicotinamide mononucleotide (NMN)

Nicotinamide mononucleotide (NMN) is a precursor to NAD+. NAD+ is a very important substance in the cells. It provides energy for cells and is also a cofactor for proteins that repair and maintain our epigenome and our DNA.

The epigenome is the intricate machinery that surrounds the DNA and that determines which genes are active and not. During aging, the epigenome becomes more and more dysregulated.

The older we get, the less NAD+ is present in our cells. Taking in NMN can increase NAD+ levels.

Various animal and lab studies show that NMN has beneficial effects on aging diseases and symptoms (R,R,R,R).

For example, long term administration of NMN mitigated age-associated decline in mice: NMN reduced the typical age-associated increase in body weight, improved energy metabolism, improved lipids in the blood and insulin sensitivity and ameliorated eye function (R).

NMN can also improve aging-related decline in fertility (R), improve bone health (R) and vascular health (R,R,R).

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

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

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

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

Related: Best NMN Supplements

NMN with TMG

Some brands have created a liposomal NMN formula with TMG* to speed up NAD+ production. Combining NMN and TMG is proposed as one of the potential ways to promote longevity.

*Trimethylglycine (TMG) is a form of the amino acid glycine with three methyl groups that are attached to it. TMG is also commonly known as betaine or betaine anhydrous. TMG functions as a methyl donor. TMG methylates homocysteine, an amino acid that can build up in the blood and raise the risk of heart disease, and converts it into methionine.

Nicotinamide Riboside (NR)

The Interventions Testing Program (ITP) tested NR and didn’t find a life extension effect (Aging Cell 2021).

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.

4. Glycine, NAC and Taurine

Both Glycine and Taurine levels decline as we age.

Glycine

Glycine is an amino acid that occurs naturally in our body. When we age, glycine levels decline.

The Interventions Testing Program (ITP) tested Glycine and found a life extension effect on both male and female mice (Aging Cell 2019).

Low glycine levels also have been associated with various aging-related diseases like cardiovascular disease and with type 2 diabetes.

Glycine has many functions in the body. It improves the epigenome (the machinery that determines which genes are switched on or off, a process that goes increasingly awry when we get older). Glycine especially improves the epigenome of mitochondria, the power plants of our cells (R).

Glycine also functions as a chaperone. Chaperones are small molecules that gently stick to and protect the proteins. That is important, because one of the reasons why we age is due to proteins accumulating everywhere inside and outside our cells, eventually hampering the proper functioning of our cells.

Glycine also reduces inflammation (R) and has many other beneficial effects, especially for the cardiovascular system. People with higher glycine levels in the blood had less risk of a heart attack (R), and glycine can protect the blood vessels (R).

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

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

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

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

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

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

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

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

NAC

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

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

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

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

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

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

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

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

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

How to get GlyNAC supplement > Buy on Amazon

Taurine

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

In a 2024 meta-analysis of 25 RCTs (randomized controlled trials), researchers from Taiwan (Nature 2024) concluded that taurine supplementation exhibits positive effects on multiple Metabolic Syndrome related factors, making it a potential dietary addition for individuals at risk of or already experiencing Metabolic Syndrome.

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

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

The key to remember is that it's best to get taurine and other nutrients from whole foods and, if necessary, via high-quality supplements — not synthetic energy drinks. Energy drinks are not a safe source of taurine.

Taurine is found in animal foods such as seafood, red meat, poultry and dairy products. If you're a vegan, however, you may want to consider a high-quality taurine supplement, as you're not getting any from the foods you eat. While your body can synthesize some taurine, it's not going to be sufficient in the long run, especially as you get older and your body's ability to synthesize it diminishes.

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

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

5. Magnesium and Molecular Hydrogen

Magnesium

Magnesium is a very important mineral in the human body.

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

In a 2024 study published in Nutrients, researchers dove deep into the effects of magnesium on the 12 Hallmarks of Aging. This is an important undertaking, as they noted that magnesium deficiency becomes more common as you age. According to the authors:

We show in this review evidence of the relationship of magnesium with all the hallmarks of aging (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, disabled autophagy, dysbiosis, and chronic inflammation), which may positively affect the human healthspan. It is feasible to hypothesize that maintaining an optimal balance of magnesium during one’s life course may turn out to be a safe and economical strategy contributing to the promotion of healthy aging.

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.

Molecular Hydrogen

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

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

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

Related: Best Molecular Hydrogen Tablets

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

6. Curcumin (Turmeric)

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

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

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-cancer 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.

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.

Click here to buy Bioavailable Curcumin.

7. Vitamin C

Vitamin C can help to maintain a proper epigenome.

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.

The Interventions Testing Program (ITP) tested AKG and didn’t find a life extension effect (GeroScience 2024).

8. CoQ10 

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

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

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

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

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

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

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

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

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

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

Related: Best CoQ10 Supplements

9. 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. 

10. EGCG (Green Tea Extract)

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

Studies have confirmed numerous health benefits of green tea including prevention of cancer (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).

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

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

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

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

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

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

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

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 

11. 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.

Source: Ancestral Diet Could Prevent Most Diseases Including Blindness

12. 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 healthcare providers 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. 

13. Protein Powder and Collagen

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

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

A 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.

 

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

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

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

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

14. Spermidine

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

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

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

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

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

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 (2018):

“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, 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.

15. Cocoa

Howard Sesso et al conducted a large randomized double blind, placebo-controlled trial of cocoa extract supplementation for prevention of CVD and cancer that involved 21,442 older US adults (12,66 women) between 2015 and 2020. Participants were randomly assigned to cocoa extracts [500 mg flavanols/d, including 80 mg (-)-epicatechin] or placebo.

Although the cocoa extract did not achieve statistical significance in reducing total cardiovascular events among these older adults, it did reduce CVD death by 27%. That should still encourage most adults to consume a bit more cocoa.

Source: Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. (2022)

16. Garlic supplements

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). 

17. Melatonin

At 45 years old, melatonin production drops close to zero.

In a 2022 study:

To highlight, a 10-fold decrease in pineal melatonin production in octogenarians compared to teenagers was observed, which results in a significant attenuation of the antioxidant, anti-inflammatory, and mitochondrial optimizing effects of melatonin. This has important consequences for the immune changes common over the course of aging, including immune senescence and inflammaging (inflammation associated with aging), which may be mediated by the effects of night-time pineal melatonin in resetting and resynchronizing immune cell mitochondrial function...

Hence, a vicious circle between melatonin production levels and aging seems to exist, since melatonin synthesis decreases with the age and, at the same time, the aging is worsened as a consequence of the melatonin deficiency.

18. 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.”

Most officially recommended daily doses are too low

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

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

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

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

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

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

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

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

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

Other Promising Interventions for Longevity

If you are an anti aging, longevity or biohacking space enthusiast, chances are you have heard about many more advanced and emerging anti aging interventions mentioned below. We will review few of the popular ones below. However, do note that some of them might be too overwhelming for an average layperson and will require medical supervision to proceed.

Stem Cell Therapy for Anti-Aging

Stem cell therapy for anti aging is an ongoing topic for cutting edge life-science research and is considered experimental by the medical community at the moment. Is there any evidence that stem cell therapy for anti aging is effective and safe?

The global stem cells market size was valued at USD 15.07 billion in 2023 and is projected to grow from USD 17.02 billion in 2024 to USD 56.15 billion by 2032, exhibiting a CAGR (compound annual growth rate) of 16.1% during the forecast 2024-2032. (Source) 

As of October 2024, there are more than 300 scientific publications related to stem cell and anti-aging on PubMed.gov.

Despite the fact that there are many published studies on stem cell therapy for anti-aging, major media has been slow to report the findings.

Read More: Best Stem Cell Supplements

Exosome Therapy for Anti Aging

Exosomes are small vesicles released by all the cells, but especially by stem cells. They are, essentially, little messengers carrying important signaling proteins and genetic information from cell to cell. Or in other words, a fat bubble with a message. 

The exosomes market size was valued at USD 250.8 million in 2022 and is expected to reach USD 3.2 billion in 2032 with a CAGR of 29.9% from 2023 to 2032 (source). 

Exosomes' primary job is to act as a connection between all our cells, facilitating communication whether cells are near or far to one another. The information they carry tells our cells to turn on or off certain functions or to react in a certain way. Exosomes are being heralded as the next frontier of cell therapy. While not being cells at all, they play a vital role in the communication and rejuvenation of all the cells in our body. Science has shown that the cell-to cell communication is important in maintaining a healthy cellular terrain.

Exosomes therapy is responsible, among other things, for assisting both the T-cells and NK cells in our immune system. T-cells are responsible for calming an immune response, while NK cells are responsible for ramping up that response. We need both, but when NK cells aren’t “turned off” or T-cells aren’t “turned on,” pain and inflammation are often the result.

Generally speaking, exosomes carry healthy and lost information and insert this into target cells. Exosomes released by young stem cells have been shown to be very powerful in regulating regenerative processes in the body and assisting in rejuvenation. You may be wondering the difference between exosomes and stem cells. The number one difference is that exosome therapy DOES cross the blood brain barrier and get to places whole stem cells cannot. 

Few of the important benefits of Exosomes:

• Manage degenerative conditions 
• Repair degenerated and damaged tissue 
• Powerful anti-inflammatory effects 
• Promising anti-aging capabilities 
• Improve pain control 
• Decrease brain inflammation 

MTOR and Rapamycin

Mechanistic (previously referred to as mammalian) Target Of Rapamycin (mTOR) is a protein kinase that regulates protein synthesis and cell growth in response to growth factors, nutrients, energy levels, and stress (Marin et al., 2011).

Why is mTOR important? mTOR is responsible for both intracellular and extracellular signals and serves as a central regulator of cell metabolism, growth, proliferation and survival. In simple words mTOR activation causes cells to age faster. The good news is that there are ways that you can slow your and even inhibit mTOR. We ALL know that severe caloric restriction is one of the ways to inhibit mTOR but this is not sustainable, nor is it good for your body long-term. Luckily, pioneers in lifespan and longevity have made an amazing discovery called Rapamycin. The following background information is from an organization that studies human lifespan.

We found it interesting enough to share, verbatim: 

Rapamycin was first discovered in 1972 in the soil of Easter Island, produced by a bacterium called Streptomyces hygroscopicus. It takes its name from Rapa Nui, the indigenous name for the island. In the early 2000s, researchers discovered its potential to increase lifespan. In low doses, rapamycin reliably increases the lifespan of worms, yeast, flies, and mice. In one study, researchers gave a group of 20-month-old mice (roughly equivalent to that of 60-year-old humans) rapamycin in small doses over three months. They then simply observed the mice until they died naturally. 

They were astonished at what they observed! Normally, these 20-month-old mice would have died of agerelated diseases around the 30-month mark. But they didn’t! They lived another 2-months on average, which would be equal to a human living to 140 years old! There are many other research examples in multiple species of increased lifespan resulting from rapamycin periodic dosing. In October 2021, Steve Hill published a review of the Rapamycin literature in a popular Longevity Medicine Journal. 

Related: Rapamycin: Benefits, Side Effects, and Research (2024)

In his Summary of Rapamycin he found the following:

Late-life mice treated with Rapamycin for three months showed: 

• Significant benefits in cardiovascular function with reversal or attenuation of age-related changes in the heart 
• Beneficial behavioral, skeletal and motor changes compared with mice fed a control diet 
• Reduced indicators of inflammatory, metabolic, and hypertrophic expression of cardiac tissues

From these findings, we propose that late-life rapamycin therapy not only extends the lifespan of mammals, but also confers functional benefits to a number of tissues. In July 2013, James M Flynn published in the journal, Aging Cell reporting that Late-life Rapamycin Treatment Reverses Age-related Heart Dysfunction. Much has been learned about Rapamycin since the mouse study mentioned here. The important news? All signs pointed to increased lifespan in humans.

Some of the benefits of periodic dosing of Rapamycin found through scientific exploration are: 

• A decrease in cancer incidence 
• Improvement of cardiac function (heart function) 
• Improvement in bone marrow function (immune system) 
• Metabolizes cellular fat stores (weight and body composition) 
• Increases lifespan by inhibiting mTOR (slows down rate of aging) 

Matt Kaeberlein’ research gives us information on the benefits of Targeting mTOR Signaling to promote Healthy longevity. He reports that Rapamycin is a viable option, especially when combined with: 

• A highly-optimized diet 
• Individualized power supplements 
• A healthy sleep routine 
• Stress management techniques

Notes: 

• There are more than 2,900 search results on rapamycin and aging on PubMed. 
• Rapamycin have demonstrated in the Interventions Testing Program (ITP) an increase in the total lifespan of the longest-lived mice by 9-14% as well as an overall increase in median survival (Nature 2009).
• Other tested interventions in the Interventions Testing Program (ITP): https://www.nia.nih.gov/research/dab/interventions-testing-program-itp/supported-interventions

Does Metformin Increase Life Expectancy?

Metformin, a biguanide that combats age-related disorders and improves health span, is the first drug to be tested for its age-targeting effects in the large clinical trial—TAME (targeting aging by metformin). A 2020 review (Cell 2020) focuses on metformin’s mechanisms in attenuating hallmarks of aging and their interconnectivity, by improving nutrient sensing, enhancing autophagy and intercellular communication, protecting against macromolecular damage, delaying stem cell aging, modulating mitochondrial function, regulating transcription, and lowering telomere attrition and senescence. These characteristics make metformin an attractive gerotherapeutic to translate to human trials.

Metformin is arguably the most well-known, and the most common prescription drug that life-extension enthusiasts take in an effort to slow down aging and extend lifespan.

In humans, metformin has been in clinical use for over 60 years, studied extensively, has a high safety profile, and is uniquely positioned to intervene several crucial pathways responsible for aging and age-related diseases (Barzilai et al., 2016). As recommended by the American Diabetes Association, due to its glucose-lowering effects, metformin monotherapy is the preferred first-line pharmacological action against type 2 diabetes (American Diabetes Association, 2019).

Metformin is a prescription drug that has been used for decades to treat type 2 diabetes. It’s mechanism of action is different from most diabetes drugs, given it improves insulin sensitivity (or reduces insulin resistance).

In a 2024 study, published in Cell, gero-protective effects of metformin on monkeys were evaluated in a rigorous 40-month study. The results highlighted a significant slowing of aging indicators, notably a roughly 6-year regression in brain aging. Metformin exerts a substantial neuroprotective effect, preserving brain structure and enhancing cognitive ability. This research pioneers the systemic reduction of multi-dimensional biological age in primates through metformin, paving the way for advancing pharmaceutical strategies against human aging.

Conclusion and Key Takeaways

Our best bet to promote longevity and overall health is to engage in healthy practices like consuming a nutritious diet, engaging in regular exercise, improving your sleep, reducing stress and being social.

While some research suggests potential benefits from supplements, hormone therapy, or even stem cells in slowing aging, these shouldn't replace core healthy practices. A well-rounded approach is key for optimal well-being.

Focus on Fundamentals:

•  Nutritious Diet: Prioritize a balanced diet rich in fruits, vegetables, and whole grains.
• Regular Exercise: Aim for consistent physical activity, incorporating different types like cardio and strength training.
• Quality Sleep: Get enough restful sleep for optimal body and brain function.
• Stress Management: Find healthy ways to manage stress, such as meditation or spending time in nature.

Supplements: A Supportive Role

Remember, supplements are not magic bullets. They should complement, not replace, a healthy lifestyle. Consult your doctor before starting any new supplement program to ensure safety and suitability for your individual needs.

Multi-Faceted Aging Solutions

Aging is a complex process with various contributing factors. Ideally, an anti-aging supplement should address these factors synergistically, meaning the components work together for a stronger effect.

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.

A Holistic Approach

There's no magic bullet for aging. It's unlikely a single strategy will address all the complexities involved. The best approach for most people likely involves a personalized menu of strategies that combines a healthy diet and lifestyle with potential benefits from evidence-based supplements.

Reliable Research

Always prioritize credible sources for information. Look for research published in peer-reviewed journals, searchable through platforms like PubMed or Google Scholar.

Related: 

I-Prevent Cancer Protocol

Best Natural Supplements for Dementia

Best Stem Cell Supplements

Best Antioxidant Supplements 2024

Glutathione vs NAC

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