Longevity and Anti Aging: A Comprehensive Guide (2024 Edition)

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.”

Wanting it and knowing how to get it are two different things. We know how you can get it, now you need to want it!

This practical guide will help you to understand aging, longevity, and all that is involved to “turn back the clock”. We are providing you with science, knowledge, and best of all possibilities. 

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.

This guide is based on a comprehensive review of over 500 scientific references and supporting studies. It explores the latest science-backed interventions for promoting longevity and healthy aging.

This long form article compiles research related to the anti-aging space. This article will also reveal exciting new information about a variety of immune-enhancing natural products and nutrients that may help you maintain youthful immune system function into advancing age.

Methodology: The selection or short-listing of the topics below is based on the available scientific evidence retrieved from scientific database such as PubMed and scientific search engine such as Google Scholar. The article will also be updated as and when there is a newly discovered major research publication related to anti-aging and longevity.

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

Contents
  • What is Aging?
  • Biological Age vs Chronological Age
  • Causes of Aging
  • What is Cell Senescence?
  • What is Epigenetics?
  • Diet and Lifestyle for Anti Aging
    1. Healthy Lifestyle
    2. Mediterranean Diet
    3. Exercise and Resistance Training
    4. Stress Management
    5. Caloric Restriction, Intermittent fasting (Time Restricted Eating) and Fasting
    6. Avoiding Linoleic Acid (Omega-6 Fatty Acids) and Vegetable Oil
    7. Avoiding Ultra-Processed Foods
    8. Sleep
    9. Social Support
  • Best Scientifically Proven Anti Aging Supplements
    1. Vitamin D3 and Omega-3 fatty acids
    2. B Vitamins, Nicotinamide mononucleotide (NMN) and NAD Boosting Supplements
    3. Glycine, NAC and Taurine
    4. Magnesium and Molecular Hydrogen
    5. Curcumin (Turmeric)
    6. Fisetin 
    7. Vitamin C and Alpha-KetoGlutarate (AKG)
    8. CoQ10
    9. Resveratrol and Pterostilbene
    10. Zinc
    11. EGCG (Green Tea)
    12. L-Citrulline and L-Arginine (Nitric Oxide Boosters)
    13. Lutein and Zeaxanthin
    14. Glucosamine and Chondroitin
    15. Collagen
    16. Spermidine
    17. Crocin (Saffron)
  • Stem Cell Therapy for Anti-Aging
  • Hormone Replacement Therapy
  • Peptide Therapy for Anti Aging
  • Exosomes for Anti Aging
  • What is mTOR (Mammalian Target of Rapamycin)?
  • Conclusion and Key Takeaways
Time (Jan 2023)

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.

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

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

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)
These hallmarks are grouped into three categories: primary, antagonistic, and integrative.

Source: Cell 2023

When interpreting scientific studies, let’s remember that not all studies are created equal. Below is a list of study types ranked in descending order based on their level of evidence quality:
  1. Meta-analysis and Randomised controlled trials (RCTs)
  2. Large clinical trials (phase 3)
  3. Small clinical trials (phase 2) and Case studies
  4. Mouse results and animal studies
  5. In Vitro, cell culture, commentary, review, expert opinions and anecdotal evidence
Credit: ACS Chem. Neurosci. 2024

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. There are numerous anti-aging supplements backed by compelling scientific research. 

Credit: ACS Chem. Neurosci. 2024

Connecting the dots between Antiaging nutrients and drugs and (A) hallmarks of aging, and (B) antiaging strategies. 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?

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. 

Healthy habits like exercising, getting good sleep, and drinking in moderation could pay off not just in quality of life, but in length of life too.

That's according to 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.

@dr.kevin.reese

Everything has a root cause…

♬ original sound - Dr. Kevin Reese, PhD, PAS, DS

1. Diet and Healthy Lifestyle studies

In this study (Sakaniva 2022), 45,021 people were studied from 1988 to 1990 and the subjects continued to be monitored until 2009. Each healthy lifestyle factor like diet, exercise, smoking, sleep, and BMI (body mass index) was given a point.

According to this pilot randomized controlled trial (Fitzgerald 2021):

This is the first randomized controlled study to suggest that specific diet and lifestyle interventions may reverse Horvath DNAmAge (2013) epigenetic aging in healthy adult males.

2. Diet

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.

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 2020 review of 8 original studies, the meta-analysis demonstrates that higher MedDiet adherence is associated with longer Telomere Length (TL). 

In a 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.

@lewis Biochemist Jessie Inchauspé aka @glucosegoddess_ shares incredible hacks in this episode to minimize glucose spikes without cutting sugar out of your diet - have you listened yet? #sugar #sciencetok #aging #reverseaging #glucose #glucosegoddess #jessieinchauspe #jessieinchauspé #biochemistry #nutrition #nutritiontips #healing #healingjourney #wellness #wellnesstips #healthandwellness #healthandwellnesstips #food #glycation #ageinreverse #nutritionhacks #biohack #biohackingsecrets ♬ Adventurer - Lux-Inspira


3. Avoiding Linoleic Acid, Vegetable Oil and Ultra-Processed Foods

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.

4. Avoiding 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.

5. Avoiding Alcohol

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.

6. 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).

7. Stress Management

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

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. Exercise and Resistance Training

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 antiaging strategy as shown below.

Credit: ACS Chem. Neurosci. 2024

Researchers have also analyzed 13 studies of sitting time and activity levels. They found that those who sat for more than eight hours a day with no physical activity had a risk of dying similar to that posed by obesity and smoking. However, unlike some other studies, this analysis of data from more than 1 million people found that 60 to 75 minutes of moderately intense physical activity a day countered the effects of too much sitting. Other studies have found that for people who are most active, sitting time contributes little to their risk of death (Mayo Clinic).

In another 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.

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)

According to Dr Murtaza Ahmed:

The most important way to negate the effects of sarcopenia is through resistance exercise. Exercises such as walking are great for cardiovascular fitness but they do very little to help with sarcopenia. Resistance exercise means exercising against resistance, such as with weights or resistance machines that you find in your local gym. Everybody is capable of doing some form of resistance exercise and this is something you should not be intimidated by.

Another important factors in slowing sarcopenia is diet. As we age our appetite declines, so as we eat less we naturally reduce the amount of protein that we consume. To slow sarcopenia we need to keep our protein intake high, and as we are eating less this means that a higher proportion of the food we eat needs to be protein. It is also important to spread this protein out through the day over three or meals as this produces more muscle protein synthesis when compared to one or two high protein meals.

It is also important to get your vitamin D levels checked as you age since deficiency is common due to reduced sun exposure. As well as weakening our bones, low vitamin D results in weaker muscles and accelerated sarcopenia. A low vitamin D level can be easily rectified with supplementation. When was the last time you had your vitamin D level checked?

Being aware that sarcopaenia affects us all is the first step in combating its effects. The earlier you commence resistance exercise, the greater the benefits, but it is never too late to start. If you are new to resistance exercise or intimidated by the gym environment, talk to your local gym about some personal training to help you learn.


9. 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)

Okinawa in Japan, Sardinia in Italy, Roseto in Pennsylvania, Loma Linda in California, Icaria in Greece and Nicoya in Costa Rica are some of the places with the highest proportions of people who live to be 100 years old.

All these places have the same thing in common. What is it?

In the 1950s, Roseto, Pennsylvania, shocked the medical community. From 1954 to 1961, Roseto had nearly no heart attacks for men ages 55 to 64. And for men over 65, the death rate was half of that of the U.S. average.

Dr. Robert J. Waldinger, a Clinical Professor of Psychiatry at Harvard Medical School, conducted the longest scientific study on health and happiness in history, the Harvard Study of Adult Development

According to Prof. Waldinger:

We had more than 40 years of data. We began to find that when we looked at our 80 year olds, and we looked back at what we knew about them when they were 50, that the strongest predictor of who was going to be happy and healthy at age 80, was the quality of their relationships at age 50.


10. 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. 

Research overwhelmingly supports the notion that ditching the three square meals a day approach in favor of time-restricted feeding — can do wonders for your health. Contrary to modern belief, your body isn't designed to be fed throughout the day, and the near-continuous grazing that most engage in can have serious health consequences.

Time-restricted eating is just what it sounds like. It's a form of intermittent fasting where you eat all of your meals for the day within a restricted window of time, ranging from two to eight hours. That means you're avoiding food (fasting) for 16 to 22 consecutive hours. Eating within a four- to six-hour window is likely close to metabolic ideal for most. As noted in the paper "A Time to Fast," published in the November 2018 issue of Science:

"Adjustment of meal size and frequency have emerged as powerful tools to ameliorate and postpone the onset of disease and delay aging, whereas periods of fasting, with or without energy intake, can have profound health benefits.

The underlying physiological processes involve periodic shifts of metabolic fuel sources, promotion of repair mechanisms, and the optimization of energy utilization for cellular and organismal health …

In general, both prolonged reduction in daily caloric intake and periodic fasting cycles have the power to delay the onset of disease and increase longevity."

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. 

Fasting may also help reduce obesity-associated cancers. “There’s a lot of obesity-associated cancers,” said Dr. Jason Fung, a nephrologist and fasting expert. “There’s about 13 cancers that are well accepted that they are associated with obesity; fasting might help decrease that.”

Fasting can potentially starve cancer cells. When fasting, the body uses fats and produces ketones for energy. Cancer cells rely heavily on glucose, making them less efficient at using ketones.

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

Caloric Restriction

The goal of caloric restriction is to reduce total caloric intake while maintaining optimal nutrition. This may be best accomplished by eating a diet primarily composed of low-calorie, nutrient-dense foods such as vegetables, fruits, legumes, nuts and seeds, and whole grains; limiting intake of animal products; and avoiding calorie-dense, nutrient-poor foods (Rizza 2014). Caloric restriction in animals has been shown to prolong lifespan and delay aging, and to confer a more youthful profile of T cells (Ahmed 2009; Fernandes 1997; Michan 2014).

Best Anti-Aging Supplements

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

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, Omega-3 and K2

Vitamin D3 and K2

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

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

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

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

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 2000 units per day. The risk of excess accumulation of vitamin D is negligible with this amount. Make sure it’s vitamin D3, and not vitamin D2 – the vitamin D3 variant works better.

“We [in the medical community] are beginning to realize the anti-inflammatory effects of vitamin D,” says Amanda Frick, a licensed naturopathic doctor and acupuncturist in Santa Monica, California. It builds bone, boosts immunity, guards against chronic ailments, and is responsible for increasing absorption of calcium and magnesium. If you’re still not sold on vitamin D as one of the anti-aging supplements to add to your regimen, Frick says it can also assist with weight loss when combined with lifestyle intervention.

Theoretically, we should get enough vitamin D through our diet and from the sun, but for many of us, that’s not the case. In the United States, 35% of adults and 61% of people over the age of 65 are deficient in vitamin D. Vitamin D deficiency is associated with an increased risk of osteoporosis, weakness, and bone fractures in the elderly, among other things. Recent studies also show a link between vitamin D deficiency and cardiovascular disease, diabetes, and cancer (Sizar, 2020).

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

Make sure to take 500 mg to 1000 mg of magnesium and 150 mcg of vitamin K2, (not K1) which are important cofactors for optimizing vitamin D function. 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.
 
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 knee annual MRI images. That’s where the data for this new Omega-3 research originates.

The study, published in The American Journal of Clinical Nutrition (Oct 2021), used data from a long-term study group, the Framingham Offspring Cohort, which has been monitoring residents of this Massachusetts town, in the United States, since 1971.

The research looked at 2,200 people who were monitored for 11 years for their blood fatty acid levels. The researchers found that omega-3 levels in red blood cells are very good mortality risk predictors. That means that higher levels of Omega-3 in the blood from regularly eating oily fish, increased life expectancy by almost five years.

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

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

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

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

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

Make sure you buy high-quality omega-3 fatty acid supplements, meaning that the omega-3 fatty acids are pure and have not oxidized much (having low “TOTOX” value).

TOTOX value stands for total oxidation value. The omega 3 fatty acids EPA and DHA from fish oil are highly sensitive to oxidation. This means that they are rapidly affected by contact with oxygen. Oxidised fatty acids are not beneficial to our health. For this reason, a good fish oil supplement has a low TOTOX value. The maximum TOTOX value is set at 26 by the Global Organization for EPA and DHA omega-3.

Vitamin K2

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

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

2. B Vitamins and NAD Boosting Supplements

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

B vitamins include:
  • B1 (thiamine)
  • B2 (riboflavin)
  • B3 (niacin)
  • B5 (pantothenic acid)
  • B6
  • B7 (biotin)
  • B12
  • Folic acid
B vitamins are commonly found in meat, eggs, fish and leafy greens. 

NAD+ Precursors

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

Nicotinamide mononucleotide (NMN)

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

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

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

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

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

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

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

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

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

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

Vitamin B12

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

3. Glycine, NAC and Taurine

Both Glycine and Taurine levels decline as we age.

Glycine 

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

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

Glycine extends lifespan in different species (R,R,R,R).

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

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

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

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

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

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

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

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

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

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

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

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

NAC

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

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

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

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

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

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

A pilot trial in older humans (Kumar 2021) with GlyNAC supplementation for 24 weeks corrected glutathione deficiency and improved multiple measures of health, including:
  • Mitochondrial dysfunction
  • Oxidative stress
  • Inflammation
  • Endothelial dysfunction
  • Insulin resistance
  • Genomic damage
  • Cognition
  • Strength
  • Gait speed
  • Exercise capacity
  • Body fat levels
  • Waist circumference
Further, GlyNAC supplementation improved four of nine hallmarks of aging associated with most age-related disorders — mitochondrial dysfunction, inflammation, insulin resistance and genomic damage (Kumar 2021). Glycine, the team noted, is an important methyl-group donor. "Methyl groups are abundant in DNA and are important components of multiple cellular reactions. Glycine is also important for normal brain function."


Taurine

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

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

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

Animals given supplemental taurine didn’t just live longer, they were also healthier overall. In mice, taurine improved: 
  • Strength, coordination and endurance
  • Bone mass and bone quality
  • Glucose homeostasis and glucose tolerance
  • Age-related inflammation
  • Immune function
  • Gut health
  • Memory
  • Function of all organs
  • Mitochondrial function and health 
Interestingly, according to the authors, taurine “cured” osteoporosis. It’s not often you see the word “cure” being used in medical literature. Taurine also “suppressed ovariectomy-induced body-weight gain in a rodent model of menopause,” and reduced anxiety and depression-like behavior in the mice.

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

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

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

4. Molecular Hydrogen and Magnesium

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

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

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

According to a review paper published in BioMedicines 2022:

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


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

Magnesium

Magnesium is a very important mineral in the human body.

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

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

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

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

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

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

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

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

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

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

5. Curcumin (Turmeric)

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

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

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

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

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

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 (SourceSource).

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

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

6. CoQ10 

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

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

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

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

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

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

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

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

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

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

Related: Best CoQ10 Supplements

7. Fisetin

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

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

Fisetin is a flavonoid. Flavonoids are substances that give fruits and vegetables their bright colors (like yellow, orange and blue) and play a major role in conferring the health benefits that we get from eating more vegetables and fruits.

Fisetin is probably most known for its impact on senescent cells: studies showed that this substance can reduce the accumulation of senescent cells (R). Fisetin is a senolytic, a compound that can clear away senescent cells.

Senescent cells accumulate everywhere in the body during aging. Senescent cells were previously normal cells that became too damaged. Normally, when a cell is too damaged, it kills itself, but senescent cells don’t do that.

Instead of dying, they keep lingering around in the body.

Senescent cells secrete all kinds of substances that damage the healthy surrounding cells, like inflammatory substances (cytokines and chemokines), substances that break down the glue that holds the cells together (matrix metalloproteinases), and growth factors that accelerate aging (R). Not only do senescent cells damage healthy surrounding cells, but they also damage stem cells, which are the foundational cells that create new cells, which build up and repair our organs and tissues.

Reducing the senescent cell burden can lead to reduced inflammaging (low-grade inflammation that increases during aging) and enhanced function of stem cells.

Substances that can eliminate senescent cells are called “senolytics”. Fisetin is a well-studied senolytic substance.

Fisetin versus quercetin 

Besides fisetin, another senolytic is quercetin. Quercetin and fisetin look very similar. However, fisetin seems to be the most potent and safest of natural senolytics (Lancet 2018).

The conclusion of the researchers was the following:

“Fisetin had the most potent senotherapeutic effects in several cell types in vitro and showed strong anti-geronic effects in vivo”.

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

Lifespan extension effects of fisetin 

Scientists demonstrated that fisetin can extend median and maximum lifespan in mice, even when taken late in a mouse’s life (equivalent to 50 or 60 years old for a human) (R).

More than a senolytic: other anti-aging effects of fisetin 

Fisetin has many other beneficial effects on the aging process besides eliminating senescent cells.

For example, fisetin inhibits the mTOR pathway (R), which plays an important role in aging and is where many of the health benefits behind fasting are derived. Fisetin can also reduce oxidative stress (R).

Fisetin can reduce inflammaging (aging-related low-grade inflammation) by inhibiting pro-inflammatory enzymes and substances, like lipoxygenases and NF-kB (RR).

Interestingly, fisetin can also have various beneficial effects on the skin. For example, fisetin can reduce the formation of skin wrinkles and appearance of skin aging.

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

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

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

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

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

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

Alpha-ketoglutarate (AKG) is a small molecule naturally present in our body. During aging, levels of AKG decline.

Alpha-ketoglutarate is used by the mitochondria, which convert this substance into energy, but alpha-ketoglutarate has various other functions in the body.

Numerous studies show that alpha-ketoglutarate can extend lifespan in various organisms. AKG extended lifespan in C elegans worms (R) and fruit flies (R,R,R) and mice.

Alpha-ketoglutarate also plays a role in maintaining stem cell health (Nature 2015), and in bone and gut metabolism (R).

Calcium alpha-ketoglutarate is also involved in collagen production, can reduce fibrosis, and can thus play a role in maintaining healthy, youthful skin (R,R).

9. Resveratrol and Pterostilbene

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

2021 research review suggests that resveratrol supplements may help protect against age-related cardiovascular, neurodegenerative, and diabetic disorders.

Resveratrol is a polyphenol in grapes, berries, peanuts, and red wine that may promote longevity by activating certain genes called sirtuins. It has been shown to increase the lifespan of fruit flies, yeasts, and nematodes (Source).

It displays powerful antioxidant, anti-inflammatory, and antitumor properties in clinical trials. Resveratrol also enhances sirtuin function (R).

Nearly two decades ago, it was discovered that resveratrol slowed the process of cellular aging in yeast. In 2003, Harvard Medical School Professor David Sinclair, PhD, found that resveratrol activated a class of sirtuin proteins called SIRT1.

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

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

Investigations into resveratrol then turned toward its effects on human health. Resveratrol was found to support cardiovascular health, antioxidant defenses, glucose metabolism, healthy inflammatory balance, and more. As results of these reported studies, people became more interested in drinking resveratrol-rich red wine and taking resveratrol supplements.

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

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

Pterostilbene vs Resveratrol

Some of the biggest hurdles for reaping the benefits of resveratrol in humans appear to be its limited bioavailability and rapid elimination from the body. But those hurdles might be overcome by a compound that has more recently gained some notice.

PubMed has indexed more than 12,000 research studies on resveratrol, but only 500 on pterostilbene. However, the sheer number of scientific studies on a compound doesn’t necessarily mean the compound is superior. It’s also important to note that pterostilbene research lags about 10 years behind resveratrol research.

The slight difference in molecular structure between resveratrol and pterostilbene provides a sound rationale for the superiority of pterostilbene. Pterostilbene should be more stable and bioavailable in theory, and preclinical studies so far validate the assumption.

Related: David Sinclair $720 Million Train Wreck!

10. 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. 

11. 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 (RR) and cardiovascular disease, as well as anti-inflammatory, antioxidant, antiarthritic, antibacterial, and antiviral effects. (RRRR). 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 

12. Garlic

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

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

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

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

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

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

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

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


14. Lutein and Zeaxanthin 

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

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

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

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

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

15. Glucosamine and Chondroitin

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

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

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

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

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

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

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

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

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

16. Collagen

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

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

A 2019 study in 72 women demonstrated that taking a supplement that contained 2.5 grams of collagen — along with several other ingredients, including biotin — per day for 12 weeks significantly improved skin hydration, roughness, and elasticity (R).

Another study in 114 women found that treatment with 2.5 grams of collagen peptides for 8 weeks significantly reduced eye wrinkles and increased collagen levels in the skin (R).

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

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

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

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

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

17. Spermidine

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

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

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

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

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

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

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

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

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

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

According to The American Journal of Clinical Nutrition study:

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

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

18. Crocin (Saffron)

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

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

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

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

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

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

Most officially recommended daily doses are too low

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

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

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

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

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

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

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

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

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


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?

As of May 2024, there are more than 200 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.

Stem cell therapies are widely used in the regenerative medicine due to their intrinsic biological characteristics, including plasticity, self-renewal, and multiway differentiation ability. Stem cell treatment includes human autograft or allograft cultured stem cells locally injected into specific parts of the body or administered by intravenous infusion. Bringing active stem cells into the body can rejuvenate existing cells and allow the body to age more gently and even reverse some impacts of aging. Currently, neural stem cells, bone marrow mesenchymal stem cells, umbilical cord mesenchymal stem cells, adipose stem cells, embryonic stem cells, and human induced pluripotent stem cells are the most closely related antiaging agents. (ACS Chem. Neurosci. 2024)

Stem cell transplantation has shown promising results in clinical trials for aging-related conditions (ACS Chem. Neurosci. 2024). Longeveron studied the use of allogeneic mesenchymal stem cells (allo-MSCs) for the condition of frailty in a successful clinical trial (NCT02065245). Thirty patients with a mean age of 75.5 years received either a 100-million or 200-million cell dose infusion. Significant reduction of inflammatory marker TNF-α and early and late-stage T-cells activation occurred. B cell intracellular TNF-α and physical performance among participants was also improved in both treatment groups. Longeveron also explored the use of MSCs through its biotherapeutic candidate Lomecel-B for the treatment of Alzheimer’s disease (AD) in phase I clinical trial NCT02600130. Thirty participants were enrolled with low and high dose infusion groups of 30 and 100 million cells. 

Significant improvement was seen for inflammatory and AD biomarkers along with neurocognitive assessments. Due to these encouraging results, Alzheimer’s disease treatment with Lomecel-B is further researched in phase II trial NCT05233774 currently recruiting participants.

The Vinmec Research Institute of Stem Cell and Gene Technology are exploring the use of MSC for male sexual dysfunction in a phase I/II clinical trial (NCT05345418). They are currently recruiting male subjects aged 50–70 years old with sexual functional deficiency. Treatment groups will receive two iv doses of 1.5 million cells/kg body weight spaced out by 3 months. Various biomarkers, testosterone levels, and sexual life quality information will be measured. The First Affiliated Hospital with Nanjing Medical University has an upcoming phase I clinical trial (NCT04706312) researching the use of amniotic mesenchymal stem cells (AMSCs) for the treatment of infertility is people with diminished ovarian response. Subjects will receive an iv injection of AMSCs and measurements recorded for ovarian function and in vitro fertilization such as stimulated follicles, number of oocyte retrieval, fertilization rate, etc. (ACS Chem. Neurosci. 2024)


Hormone Replacement Therapy

HRT for Women

The media has been slow to report the findings which indicate that not only is hormone replacement therapy not an identifiable causative agent of breast cancer, but that when begun early, hormone therapy actually has a collective mortality risk reduction of 40%. [BMJ 2012]

Hormone replacement therapy (HRT) for women has been a topic of much debate in recent decades. This is due largely to the fact that the Women’s Health Initiative (WHI) study in 2002 was halted prematurely because of a reported increase in the instance of breast cancer in women participating in the hormone replacement arm of the study. Thereafter, thousands of women were taken off or stopped taking HRT unnecessarily, despite the fact that many studies have debunked the WHI conclusions.

HRT for women has indeed developed a bad reputation, but any fears surrounding the treatment are unfounded. Here, we examine the relationship among HRT and breast cancer, colon cancer, cardiovascular disease, osteoporosis, and brain health to dispel the myths once and for all. Discover how this powerful treatment helps, rather than harms, postmenopausal women in tremendous ways below.

HRT & Breast Cancer: What’s the Connection?

One of the major flaws of the WHI was the confusion and fear it spread by projecting its results to all women receiving HRT. In the original study, more women who took estrogen plus progestin (E+P) developed breast cancer than those taking placebos. 

Further research published in a 2013 article in The Journal of Clinical Endocrinology and Metabolism shows that breast cancer rates were actually found to decrease significantly with estrogen alone. Moreover, the article goes on to say that even though there isn’t a significant increase with E+P used together versus estrogen alone, for illustrative purposes, any increased risk of breast cancer associated with E+P originally publicized with the WHI trial is less than the risk conferred by obesity, being a flight attendant, and many other common exposures.

Another noteworthy difference which can play a role in breast cancer risk is the use of synthetic progestins versus bioidentical progesterone. Synthetic progestins, which were used in the WHI, are hormones which are synthetically produced, and thus different in structure from bioidentical progesterone. Bioidentical progesterone, while produced from a plant source, is structurally and chemically identical to the progesterone produced by the ovaries. Synthetic progestins mimic some effects of the natural hormone, but react differently with progesterone receptors within the body and are felt to be responsible for the increase in breast cancer seen in WHI. On the other hand, bioidentical progesterone does not increase, and may actually reduce the risk of breast cancer

For many women, HRT is a powerful means of regaining quality of life and maintaining optimal wellness through the postmenopausal years. In fact, avoiding estrogen therapy can actually have serious implications. One article published in the American Journal of Public Health indicates that as many as 91,610 postmenopausal women died prematurely because of the avoidance of hormone therapy. Estrogen therapy, especially when used in younger postmenopausal women (aged 50-59), is linked to a decisive reduction in all-cause mortality.

Yet the use of HRT in this group continues to fall. If the potential for reducing breast cancer risk isn’t compelling enough to take another look at hormone therapy, consider how it could also combat colon cancer, below.

Can HRT Help Prevent Cardiovascular Disease in Women?

Cardiovascular disease is responsible for 1 in every 4 deaths in the U.S. It’s the leading cause of death in both men and women, and leads to more than 600,000 deaths across the country annually (CDC). It’s therefore critical that as the risk for cardiovascular disease increases with age, individuals find ways to optimize heart health.

HRT may not be prescribed for women primarily as a means for improving cardiovascular health, but this is indeed a powerful byproduct of the treatment. According to research published in the BMJ, women receiving HRT early after experiencing menopause had a significantly reduced rate of heart failure, myocardial infarction, and mortality overall. At the start of treatment, women on average were aged 50 and had been postmenopausal for seven months. Roughly half as many women using HRT experienced cardiovascular events compared to those in the control group. Additionally, these results did not correlate with an increased risk in any cancer [BMJ 2012]. 

Moreover, evidence shows that there is a clear benefit in using estrogen alone, with coronary calcium scores significantly reduced. This measures the buildup of calcium and other substances which can narrow or close the arteries, leading to cardiovascular issues. In particular, women under 60 who receive hormone therapy have a statistically significant reduction in coronary disease (Lobo 2013).

Women who were given hormone therapy during early menopause also experienced reduced atherosclerosis progression (buildup of fats and cholesterol in the artery walls) (Sriprasert 2019). 

These aren’t the only positive outcomes of HRT, however. Hormone therapy has been commonly used as an osteoporosis preventative, which brings us to our next segment.

Testosterone Replacement Therapy (TRT) for Men

Testosterone is a male steroid hormone that does a lot more for men than just promote a healthy sex drive. The hormone affects several other factors in your health, including body fat, muscle mass, bone density, red blood cell count, and mood.

In a multicenter, randomized, double-blind, placebo-controlled (NEJM 2023), 5246 men 45 to 80 years of age who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels of less than 300 ng per deciliter were enrolled. The study concluded that testosterone-replacement therapy was non inferior to placebo with respect to the incidence of major adverse cardiac events.

meta-analysis (Lancet 2022) of 35 published studies that tracked heart attacks and heart disease in men taking testosterone found no association between testosterone and heart attacks and in fact in most studies, men on testosterone had fewer heart attacks.

Normal testosterone levels are between 300 and 1,000 ng/dL. If a blood test shows that your levels are far below the norm, your doctor may suggest testosterone injections. These are a form treatment called testosterone replacement therapy (TRT).

Testosterone injections are most often given by your doctor. The injection site is typically in the gluteal muscles in the buttocks. 

TRT is an acronym for testosterone replacement therapy, sometimes called androgen replacement therapy. It’s primarily used to treat low testosterone (T) levels, which can occur with age or as a result of a medical condition.

But it’s becoming increasingly popular for non-medical uses, including: 
  • enhancing sexual performance
  • achieving higher energy levels
  • building muscle mass for bodybuilding
Your body naturally produces less T as you age. According to an article in American Family Physician, the average male’s T production goes down by about 1 to 2 percent each year.

This is all part of a completely natural process that starts in your late 20s or early 30s.

This gradual decrease in Testosterone often doesn’t cause any noticeable symptoms. But a significant drop in T levels may cause: 
  • low sex drive
  • fewer spontaneous erections
  • erectile dysfunction
  • lowered sperm count or volume
  • trouble sleeping
  • unusual loss of muscle and bone density
  • unexplained weight gain
Your body can transform DHEA (Dehydroepiandrosterone) into testosterone. Taking a DHEA may increase your testosterone levels. A 2013 study found that taking 50 milligrams (mg) of DHEA per day raised the free testosterone levels of middle-aged adults undergoing high-intensity interval training.

Dehydroepiandrosterone (DHEA) is a steroid hormone that plays a major role in healthy immune system functioning (Buford 2008; Weksler 1993). DHEA levels decline markedly with age. By age 80, DHEA levels fall to 10‒20% of their peak values (Kroll 2015; UMMC 2014).

DHEA plays a critical role by serving as a counterweight to cortisol. Cortisol is an adrenal hormone with immunosuppressive properties, while DHEA may have direct immunostimulating properties: in a laboratory study of white blood cells from donors who were at least 65 years old, DHEA treatment reversed the age-related reduction of specific receptors on immune cells and increased immune cell responsiveness (Corsini 2005). Although DHEA levels decline dramatically with age, cortisol levels remain relatively constant, leading to an imbalance of these two hormones that is believed to contribute to immune senescence (Buford 2008; Buoso 2011).

Cautionary Note: Don't use DHEA with testosterone. Combining DHEA and testosterone might cause symptoms such as low sperm count and enlarged breasts in men (gynecomastia) and the development of typically male characteristics in women.

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. Their 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 


Peptide Therapy for Anti Aging

We promised you peptide therapy, and we always deliver. Peptide therapy has become quite a familiar term with those who are on a quest for health and wellness. However, knowing what peptide to use and for a specific outcome is quite confusing. This is where you need an expert in the field to guide you. Lucky for you, the practitioners at Doctors Studio, have years of experience and expertise in this space. There are over 7,000 known peptides within the human body and though some may be similar, each is responsible for facilitating a different response and action within the body. All are very important to the health and wellness of your body. In fact, there are so many peptides that we have decided to dedicate an entire eBook to just peptide therapy. However, for the purposes of longevity, we will review 3 essential peptides that we believe are paramount in one’s quest to live longer, at optimal function:
  • BPC-157 
  • CJC-1295 with Ipamorelin 
  • Epithalon (Epitalon) 
Before we go into the amazing benefits these 3 peptides have, let’s first define what a peptide actually is. Pep·tide - / ’peptīde/noun a compound consisting of two or more amino acids linked in a chain, the carboxyl group of each acid being joined to the amino group of the next by a bond of the type -OC-NH-. Put simply, a small group of small chain amino acids (protein building blocks) that when linked together target a specific function in the body. Now that you have a very basic understanding of what a peptide chain is, let’s get into the specifics.

BPC-157, The body protection compound (BPC), is a very versatile peptide. (This happens to be one of our favorite ones as well) Not only is it used for overall gastrointestinal (GI) health or to heal your leaky gut, it also has additional properties to promote the health of your connective tissue. When used for gut health, BPC-157, is amazing at balancing your flora, and protecting the very vulnerable lining of the intestine. When the gut is not the focus, BPC157 is prescribed to help protect active individuals from injuries or to accelerate the overall healing process. Few of the important benefits of BPC-157:
  • Alleviate aches and pain 
  • Promoting tissue healing 
  • Heal and unhealthy gut 
  • Maintain a newly healed healthy gut 
CJC-1295 with Ipamorelin is used to stimulate your growth hormone to help build muscle, lean out, improve sleep, and improve recovery time. CJC-1295 can increase serum growth hormone (GH) levels by 200-1000%, by stimulating your body’s own natural production. The elevated growth hormone production and release continue for up to 6 days because CJC-1295 has a half-life of about 6-8 days. Ipamorelin has an added effect because of its own ability to facilitates the release of growth hormone (GH). This dynamic duo boosts the amount of circulating GH in your body, making you feel and look younger. The combination is just fantastic.

Some of the amazing benefits of CJC 1295 with Ipamorelin: 
  • Increase in lean muscle mass 
  • Decrease in body fat percentage 
  • Increased collagen, elastin, and fibrin production for younger skin 
  • Increase in restful sleep 
  • Increase in energy levels 
  • Improved cardiovascular function 
  • Stronger immunity 
  • Decreased joint and muscle pain
  • Enhanced healing after injury
EPITHALON has a primary role to increase the natural production of telomerase, a natural enzyme that helps cells reproduce telomeres, which are the protective parts of our DNA. In essence, this allows the replication of our DNA so the body can grow new cells and rejuvenate old ones. In addition, it is used to improve specific aging mechanisms like gene expression and autophagy. Short peptides like EPITHALON regulate different cellular levels by embedding themselves into the DNA chain. By being part of the DNA, Epithalon expands gene expression. Epithalon also increases energy levels through autophagy, the body’s mechanism of cleaning worn-out and damaged cells, regenerating newer and healthier ones. Some of the show-stopping benefits of Epithalon: 
  • Increases telomerase 
  • Improving telomere health 
  • Cellular regeneration 
  • Improves autophagy 
  • Expands gene expression

What is mTOR?

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. 


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

Conclusion and Key Takeaways

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

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.

  • Epigenetics: Look for substances supporting a healthy epigenome, like alpha-ketoglutarate (AKG) and NMN.
  • Mitochondrial Health: Consider ingredients like AKG, fisetin, and malate to support healthy mitochondrial function.

A Holistic Approach

Remember, there's no one-size-fits-all solution to aging. A well-rounded approach that combines a healthy lifestyle with potential benefits from evidence-based supplements might be the best strategy.

Reliable Research:

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

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