Anti Aging 101: An Evidence Review (2022 Edition)

Consumers spent hundreds of billions every year on supplements and various “anti-aging” treatments. The search engine results for 'anti aging' are dominated by skin care related products and guides. However, anti aging science is 'more than meets the skin'. 

best anti aging supplements

Aging, which can be defined as the “time-related deterioration of the physiological functions necessary for survival and fertility,” is a process that most people would like to slow (Source). While aging is inevitable, increasing the human lifespan and slowing the aging process has been a focus of scientific research for decades.

This long form article compiles research related to the anti-aging or slowing the aging process. 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 list 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.

In this Article

  • Causes of Aging
  • Diet and Lifestyle
    • Healthy Lifestyle
    • Mediterranean Diet
    • Sleep
    • Exercise
    • Stress Management
    • Caloric Restriction
    • Avoiding Linoleic Acid
    • Intermittent fasting
  • Nutrients and Supplements
    1. Curcumin (Turmeric)
    2. Nicotinamide mononucleotide (NMN)
    3. EGCG (Green Tea)
    4. Pu-erh Tea Extract
    5. CoQ10
    6. Collagen
    7. Zinc
    8. NAC (N-Acetyl Cysteine)
    9. Crocin (Saffron)
    10. Resveratrol
    11. Garlic
    12. Molecular Hydrogen
    13. Glycine
    14. L-Theanine
    15. Magnesium Malate
    16. Ginger 
    17. Micro-Dosed Lithium
    18. Fisetin 
    19. Pterostilbene (blueberries)
    20. Vitamin C 
    21. Glucosamine
    22. Alpha-ketoglutarate (AKG)
    23. L-Citrulline
    24. Olive Leaf Extract
    25. Whey Protein
  • Hormone Replacement Therapy
  • Stem Cell Therapy for Anti-Aging
  • Conclusion

What Causes Aging?

The human ageing process is a complex and multifactor process. We have uncovered top 10 key mechanisms based on our research and review on the scientific literature.

1. Mitochondrial Dysfunction: During aging, mitochondria – the power plants of our cells – become dysfunctional.

2. Dysfunctional and lack of stem cells: With age, stem cells become dysfunctional or die off, leading to our tissues being less replenished & maintained.

3. Loss of Proteostasis: Over time, more and more proteins accumulate inside and outside our cells, interfering with their proper functioning.

4. Altered Cellular Communication: When we get older, our cells become increasingly exposed to a hostile environment, characterized by inflammation, senescent cells, dysfunctional stem cells, and deleterious substances.

5. Genomic Changes: During aging, our DNA becomes damaged, and telomeres become shorter and dysfunctional, especially in stem cells and fast-dividing cells.

6. Epigenetic Changes: During aging, the epigenome – the molecular machinery that regulates our genes’ activity – becomes disorganized.

7. Telomere Shortening: As we age, the ends of DNA, known as telomeres, get shorter and cannot protect DNA any longer.

8. Dysregulated Nutrient Sensing: During aging, our cells become less tuned to nutrient signals, which disrupts a cell’s ability to produce energy.

9. Cellular Senescence: Senescent cells are former healthy cells that stopped dividing and secrete substances that damage healthy surrounding cells.

10. Crosslinking: As we grow older, sugar-derived bonds, or crosslinks, are formed between the proteins that make up our tissues, making tissues more stiff.

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

Diet and Lifestyle

Healthy Lifestyle study (Sakaniva 2022)

In this study, 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 the study:

Adopting modifiable healthy lifestyles was associated with lifetime gain, even in individuals aged 80 years or more, regardless of the presence of any major co-morbidities in each life stage since middle age. The findings imply the importance of improving the one’s lifestyle for an increased lifespan, even among older patients and/or those with multi-morbidity.

Mediterranean Diet


The Mediterranean diet is a dietary pattern based on foods and drinks traditionally consumed by people in the region surrounding the Mediterranean Sea (Oldways 2016). The Mediterranean diet has been shown to protect against several age- and inflammation-related conditions including diabetes, atherosclerosis, obesity, cancers, and neurodegenerative diseases. The Mediterranean diet is primarily characterized by inclusion of olive oil, fruits, vegetables, legumes, whole grains, nuts, and seeds; with moderate amounts of fish, poultry, cheese, yogurt, and eggs; limited inclusion of red meat, cured meat products, and foods rich in refined sugars; and low-to-moderate alcohol intake, usually in the form of red wine consumed with meals (Casas 2014; Estruch 2010).

In a 2014 review of 17 clinical trials, greater adherence to a Mediterranean dietary pattern was associated with significantly reduced levels of interleukin (IL)-6 and high-sensitivity C-reactive protein, two important markers of inflammation (Schwingshackl 2014; Coventry 2009; Ershler 2000; US Department of Health and Human Services 2015).

Exercise

Regular moderate-intensity exercise can strengthen resistance to infection and improve immune system function. Single bouts of moderate-intensity exercise have even been used to improve response to vaccines. On the other hand, prolonged, excessive high-intensity exercise (ie, over-training) temporarily suppresses immune function and increases vulnerability to infection (Simpson 2015; Gleeson 2013; Zheng 2015).

Several human studies have indicated that moderate exercise may combat immune senescence (de Araujo 2013; Simpson 2011; Simpson 2010; Spielmann 2011; Woods 2009). In a study in sedentary older adults, participants randomized to 10 months of moderate cardiovascular exercise exhibited improvements in antibody responses to influenza vaccine compared with elderly individuals who only engaged in flexibility and balance exercises (Woods 2009).

In a study in elderly women, two years of regular physical activity increased production of IL-2—an important regulator of immune response that ordinarily decreases with age (Drela 2004). A 2011 study demonstrated that aerobic fitness is associated with reduced accumulation of senescent T cells (Spielmann 2011).

The effects of high levels of physical activity were evaluated in an observational cohort study of 125 adults aged 55 to 79 years who are master cyclists. Compared with 75 age-matched older adults who do not routinely exercise, the cyclists were shown to have more markers of a robust immune system. Older, physically active adults had significantly lower levels of immune senescence markers, including lower Th17 cell polarization and higher proportions of regulatory B cells. Lower levels of Th17 cells, which are T cells that have been shown to suppress the immune system, together with higher levels of regulatory B cells, may help decrease the risk of age-associated inflammatory autoimmune disease. Older adult cyclists also had cytokine signatures that promote thymus health—the key organ in which T cells mature. Furthermore, T-cell levels in the cyclists were comparable with those of much younger adults (aged 20 to 39 years). In contrast, inactive older adults had lower levels of T cells compared with both older adult cyclists and younger adults. Taken together, these results suggest that maintaining physical activity may delay immune senescence (Duggal 2018).

Stress Management

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

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

“Our study suggests that social stress may accelerate immune aging,” he said.

Those who study immunity and aging – called immunosenescence – have long known that as people age, many see a decrease in immune protection.

Chronic stress causes dysregulation of innate and adaptive immune responses by promoting persistent systemic inflammation and suppressing immune cells (Morey 2015; Dhabhar 2014). When sustained stress diminishes immune function, it can allow latent viruses such as cytomegalovirus to escape immune system control. Frequent reactivation of latent viruses can then further strain the immune system (Morey 2015). Chronic stress, and the accompanying chronic elevation of the stress-induced adrenal hormone, cortisol, appear to contribute to immune senescence (Bosch 2009; Bauer 2015). In fact, the ratio of cortisol to another adrenal hormone, dehydroepiandrosterone (DHEA), may be an important determinant of immune senescence (Bauer 2008).

In studies on patients with early-stage breast cancer, stress management interventions have been shown to improve cellular immune function and reverse pro-inflammatory gene expression in circulating immune cells (Antoni 2012; McGregor 2004). Stress management training in patients with rheumatoid arthritis resulted in decreased levels of stress-induced IL-8—an inflammatory cytokine (de Brouwer 2013). 

Sleep

Lack of sleep can 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).

The adverse effects of poor sleep include functional changes in regulatory T cells and other cells of the adaptive immune system, as well as reduced numbers of NK cells and T and B cells (Zuppa 2015; Bollinger 2009).

Reduced sleep has been shown to alter the balance between antibody-mediated and cell-mediated immunity (Ganz 2012). In one study, participants allowed regular sleep the night after vaccines had markedly superior long-term antibody responses compared with those who stayed awake that night. Another study showed sleep-deprived individuals had a significantly lower antibody response 10 days after immunization than those who had normal sleep (Lange 2003; Spiegel 2002). 

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).

In humans, long-term caloric restriction results in metabolic changes that reduce the risk of a number of age-related diseases including type 2 diabetes, cardiovascular disease, and cancer (Steven 2015; Rizza 2014; Bales 2013; Lefevre 2009; Meyer 2006; Fontana 2004; Stein 2012). In a clinical study, six months of caloric restriction significantly improved the ability of T cells to reproduce in response to foreign antigens (Ahmed 2009).

Studies in animal models have demonstrated that caloric restriction can improve multiple aspects of immune activity, particularly T-cell function (Jolly 2004; Messaoudi 2006; Nikolich-Zugich 2005). In a study in mice, caloric restriction was shown to maintain youthful function of the thymus gland and reduce immune senescence during aging. Compared with mice fed freely, calorie-restricted mice had greater proliferation and diversity of T cells (Yang 2009).

Avoiding Linoleic Acid

While considered an essential fat, when consumed in excessive amounts, which over 99% of people do, Linoleic Acid (an omega-6 polyunsaturated fat or PUFA) acts as a metabolic poison.

Most clinicians who value nutritional interventions to optimize health understand that vegetable oils, which are loaded with omega-6 PUFA, are something to be avoided. What most fail to appreciate is that even if you eliminate the vegetable oils and avoid them like the plague, you may still be missing the mark.

Chances are you're still getting too much of this dangerous fat from supposedly healthy food sources such as olive oil and chicken (which are fed LA-rich grains). Another common mistake is to simply increase the amount of omega-3 that you eat. Many are now aware that the omega-3 to omega-6 ratio is very important, and should be about equal, but simply increasing omega-3 can be a dangerous strategy.

When we talk about omega-6, we're really referring to LA. They're largely synonymous, as LA makes up the bulk — about 60% to 80% — of omega-6 and is the primary contributor to disease. Broadly speaking, there are three types of fats:
  • Saturated fats, which have a full complement of hydrogen atoms
  • Monounsaturated fats, which are missing a single hydrogen atom
  • PUFAs, which are missing multiple hydrogen atoms
The missing hydrogen atoms make PUFAs highly susceptible to oxidation, which means the fat breaks down into harmful metabolites. OXLAMS (oxidized LA metabolites) are what have a profoundly negative impact on human health. While excess sugar is certainly bad for your health and should be limited to 25 grams per day or less, it doesn't oxidize like LA does so it's nowhere near as damaging.

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.

Intermittent fasting

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."

Nutrients and Supplements

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.

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

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

Plus, curcumin has been shown to combat cellular damage and significantly increase the lifespan of fruit flies, roundworms, and mice. This compound has been shown to postpone age-related disease and alleviate age-related symptoms as well (Trusted SourceTrusted Source).

This may be why turmeric intake has been associated with a reduced risk of age-related mental decline in humans (R).

You can increase your curcumin intake by using turmeric in recipes or taking curcumin supplements.

Nicotinamide mononucleotide (NMN)

Nicotinamide mononucleotide (NMN) is a one of the precursors of NAD+. In humans, nicotinamide mononucleotide (NMN) increases levels of NAD+, which is needed for proper DNA repair and to maintain the epigenome. NMN has shown to support a healthy metabolism in humans, and improve muscle strength and performance in the elderly. In animals, NMN slows down various aging processes.

The older we get, the less NAD+ is present in our cells. Various 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).


EGCG (Green Tea)

Epigallocatechin gallate (EGCG) is a well-known polyphenol compound concentrated in green tea. It offers impressive health benefits, with research supporting its use to reduce the risk of certain cancers, as well as other health conditions like heart disease (Trusted SourceTrusted SourceTrusted 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 (Trusted Source).

Green tea intake has been associated with a reduced risk of all-cause mortality, diabetes, stroke, and heart-disease-related death. Plus, animal studies have shown that it can protect against skin aging and wrinkles caused by ultraviolet (UV) light (Trusted SourceTrusted SourceTrusted Source).

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

Pu-erh Tea Extract

Pu-erh tea, made from select leaves of Camellia sinensis, has a long history of use in ancient Chinese medicine for anti-aging and preventing infections (Lv 2014; Zhang 2012; Chu 2011). Pu-erh tea is rich in polyphenols and other bioactive molecules, including theabrownins, a unique group of compounds developed during the post-fermentation process (Lee 2013). Laboratory, animal, and clinical studies have demonstrated the ability of Pu-erh tea extract to help improve multiple features of immune senescence.

In senescence-accelerated mice (a model for aging), supplementation with Pu-erh tea extract markedly increased fractions of naïve T cells, cytotoxic T cells, and NK cells. In addition, elevated levels of the inflammatory cytokine IL-6 fell by 43%. Based on these results, the authors concluded that long-term consumption of Pu-erh tea may increase resistance to infection and cancer in aging individuals (Zhang 2012).

In a randomized controlled trial in 90 individuals with increased susceptibility to chronic low-level inflammation due to metabolic syndrome, Pu-erh tea extract supplementation plus diet and lifestyle advice was compared with diet and lifestyle advice alone. In the pu-erh tea extract group, levels of the inflammatory markers C-reactive protein, tumor necrosis factor-alpha, and IL-6 significantly decreased, while levels of IL-10, an anti-inflammatory molecule, increased; there were no significant changes in levels of these markers in the group receiving only diet and lifestyle advice (Chu 2011; Moore 2001).

In a laboratory study, Pu-erh tea inhibited proliferation and induced programmed cell death (apoptosis) in cancer cells. In an animal component of this study, mice treated with Pu-erh tea had reduced tumor volumes and fewer lymph node metastases than untreated mice. In addition, levels of IL-6, IL-12, and tumor necrosis factor-alpha were lower in Pu-erh-treated mice than in control mice. In this study, higher doses of pu-erh tea produced greater anti-cancer effects (Zhao 2014).

CoQ10 

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

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

For example, a study in 443 older adults demonstrated that supplementing with CoQ10 and selenium over 4 years improved their overall quality of life, reduced hospital visits, and slowed the deterioration of physical and mental performance (Trusted Source).

CoQ10 supplements help reduce oxidative stress, a condition characterized by an accumulation of free radicals and other reactive molecules that accelerates the aging process and onset of age-related disease (Trusted SourceTrusted Source).

Though CoQ10 shows promise as an anti-aging supplement, more evidence is needed before it can be recommended as a natural way to delay aging.

Be sure to consult a trusted healthcare professional before giving it a try.

Collagen 

Collagen is promoted as a fountain of youth for its potential to reduce the appearance of skin aging.

It’s an integral component of your skin that helps maintain skin structure. As you age, collagen production slows, leading to collagen loss in the skin that accelerates signs of aging like wrinkles.

Some research suggests that supplementing with collagen may reduce signs of aging, including wrinkles and dry skin.

For example, 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 (Trusted Source).

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 (Trusted Source).

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.

Zinc

Zinc is an essential trace mineral that is critical to healthy immune function. 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).

NAC (N-Acetyl Cysteine)

Cysteine is a semi-essential amino acid. It’s considered semi-essential because your body can produce it from other amino acids, namely methionine and serine. It becomes essential only when the dietary intake of methionine and serine is low.

Cysteine is found in most high-protein foods, such as chicken, turkey, yogurt, cheese, eggs, sunflower seeds and legumes.

N-acetyl cysteine (NAC) is a supplement form of cysteine.

Consuming adequate cysteine and NAC is important for a variety of health reasons — including replenishing the most powerful antioxidant in your body, glutathione. These amino acids also help with chronic respiratory conditions, fertility and brain health.

NAC is valued primarily for its role in antioxidant production. Along with two other amino acids — glutamine and glycine — NAC is needed to make and replenish glutathione.

Glutathione is one of the body’s most important antioxidants, which helps neutralize free radicals that can damage cells and tissues in your body.

It’s essential for immune health and fighting cellular damage. Some researchers believe it may even contribute to longevity (Trusted Source).

Its antioxidant properties are also important for combatting numerous other ailments caused by oxidative stress, such as heart disease, infertility and some psychiatric conditions (Trusted Source).

In a controlled clinical trial in 262 individuals at high risk of influenza (flu) and flu-like illness, NAC supplementation at a dosage of 600 mg twice daily for six months resulted in a significant decrease in frequency and severity of flu and flu symptoms, such as cough, sore throat, headache, and muscle and joint pain. NAC’s ability to protect against flu symptoms was especially evident during the winter season. Of those who tested positive for influenza virus infection during the study, only 25% in the NAC group developed symptomatic illness compared with 79% in the placebo group (De Flora 1997). 

This same NAC dosage in dialysis patients, over eight weeks, resulted in marked reductions in levels of inflammatory markers, including C-reactive protein, tumor necrosis factor-alpha, and IL-6 (Purwanto 2012).

NAC is likely safe for adults when provided as a prescription medication. However, high amounts may cause nausea, vomiting, diarrhea and constipation (Trusted Source).

When inhaled, it can cause swelling in the mouth, runny nose, drowsiness and chest tightness.

People with bleeding disorders or taking blood thinning medications should not take NAC, as it may slow blood clotting (Trusted Source).

NAC has an unpleasant smell that makes it hard to consume. If you choose to take it, consult with your doctor first.

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 (Trusted 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 (Trusted Source).

Test-tube and rodent studies have demonstrated that crocin helps prevent age-related nerve damage by inhibiting the production of advanced glycation end products (AGEs) and reactive oxygen species (ROS), which are compounds that contribute to the aging process (Trusted SourceTrusted 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 (Trusted SourceTrusted Source).

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

Resveratrol

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 (Trusted Source).

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).

Molecular Hydrogen

According to a review paper published in Oxidative Medicine and Cellular Longevity (Oxid Med Cell Longev. 2022):

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.

The ability of molecular hydrogen (H2) to protect the DNA and the mitochondria from oxidative damage may have beneficial effects on chronic diseases and cancer. But perhaps it could help slow down or reverse the aging process itself. A couple of cellular studies give us some interesting clues [Ref, R].

It was already discovered that hydrogen can prolong the life of stem cells by reducing oxidative stress [Ref].

A hydrogen-rich environment reduced both oxidative stress and aging in cells. Some scientists think
that drinking hydrogen water could increase longevity in humans (Circ J. 2016).

Glycine

Glycine has shown to extend lifespan in different species. In humans, higher glycine levels are associated with heart health, combating inflammaging at the cellular level, and supporting glucose metabolism.

Alpha-ketoglutarate (AKG)

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.

Glucosamine

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.

Vitamin C 

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

Pterostilbene (blueberries)

Pterostilbene, a natural substance found in blueberries, is better absorbable and lasts longer in the body than resveratrol, a compound that has shown to extend lifespan in different species. Pterostilbene can target inflammaging at a cellular level and contribute to a healthy epigenome and DNA stability.

Fisetin 

Fisetin has shown to extend lifespan in animals. Fisetin helps the body to manage senescent cells, and can combat inflammaging at the cellular level.

Micro-Dosed Lithium

Various studies found that people who take micro doses of lithium live longer. In human studies, supplementing with microdosed lithium supports healthy brain aging. Micro doses of lithium extend lifespan in multiple species.

Ginger 

Ginger can protect cells against damage and has various longevity-promoting effects. In humans, ginger can target inflammaging at a cellular level, can help to maintain proper glucose levels and support a healthy metabolism, and help to mitigate oxidative damage in cells.

Magnesium Malate

Malate is a natural substance found in apples which has shown to extend lifespan in organisms. Malate can support healthy energy levels in humans.

People who supplement with magnesium have shown to have less DNA damage. Magnesium supports a healthy metabolism and targets inflammation at the cellular level.

L-Theanine

Theanine is one of the substances responsible for the healthy effects of green tea. Theanine can extend lifespan in different organisms. It can upregulate aging-protective proteins, like FOXO1 and antioxidative enzymes and can help the body to manage crosslinks.

L-Citrulline 

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, most recent 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 NO. 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.

Olive Leaf Extract

Olive leaf extract is a natural source of wellness with therapeutic properties that are:
  • gastroprotective (protects digestive system)
  • neuroprotective (protects central nervous system)
  • antimicrobial (inhibits microorganism growth)
  • anticancer (reduces risk of cancer)
  • anti-inflammatory (reduces risk of inflammation)
  • antinociceptive (reduces pain stimuli)
  • antioxidant (prevents oxidation or cell damage)
Whey Protein

Whey is the liquid separated from the curds during the cheese making process. Products derived from whey have demonstrated immune-modulating properties (Krissansen 2007; Rusu 2009). Whey protein is especially rich in precursor amino acids involved in the synthesis of glutathione, a powerful free radical scavenger with anti-inflammatory properties. Glutathione is essential for both innate and adaptive immunity (Krissansen 2007; Kloek 2011; Kent 2003; Micke 2001). (N-acetylcysteine, described earlier, is also a glutathione precursor.)

A pilot study compared the effects of whey protein and soy protein on vaccine responsiveness in 17 healthy senior citizens (Freeman 2010). The participants were randomly assigned to consume either whey protein or soy protein for four weeks. They then received the pneumococcal vaccine and continued protein supplementation for four weeks after vaccination. Compared with those who received soy protein, people who received whey protein exhibited a more robust antibody response to 12 of 14 types of pneumococcal bacteria, including the four most harmful bacterial types. The investigators concluded, “ Whey protein supplementation is a promising supplement to stimulate the immune response to vaccine in senior citizens and possibly to counteract [immune senescence] while larger studies are warranted.”

In another clinical trial in 12 healthy volunteers, a single dose of a whey extract was a more effective immune activator than placebo, rapidly increasing phagocytic (microbe-engulfing) activity of certain immune cells and mobilizing new NK cells into circulation (Jensen 2012). In a study in cultured neutrophils, whey protein extract had no immediate effect but instead had a priming effect, heightening neutrophil activity 24 hours later (Rusu 2009).

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.

How Does HRT Influence Colon Cancer Risk?

In the United States, colorectal cancer is the third leading cause of cancer-related deaths in men and in women, and the second most common cause of cancer deaths when men and women are combined. It's expected to cause about 52,980 deaths during 2021, according to the American Cancer Society.

As with many types of cancer and serious illness, the risk for colorectal cancer increases with age. While screenings have helped to reduce the death rate of the disease, taking preventive steps to minimize risk remains the most powerful approach in combatting the disease.

One especially effective tool for reducing risk in women is HRT. After adjustment for other known risk factors, the use of HRT indicated a 63% relative reduction of colorectal cancer risk in postmenopausal women. Aspirin users and women who participated in sports regularly did not receive the same benefits. While the mechanism of this protective effect remains unknown, it’s suspected that HRT use contributes to lower rates of colonic adenomas, and that duration of use, medication type, and age could all factor in to individual prevention rates (Rennet 2009). 

Cancer isn’t the only thing HRT may help prevent, however. Research also indicates it could play a role in boosting overall cardiovascular health – find out how in the next section.

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.

HRT: Good or Bad for Osteoporosis?

The most pronounced symptoms associated with a sudden drop in estrogen include hot flashes, mood swings, and other readily noticeable physical or psychological impacts. Yet, it isn’t until much later that the ways in which hormonal changes affect the bones become realized. When estrogen levels dip, special cells called osteoblasts are no longer able to produce bone as effectively. For this reason, estrogen replacement is a common and effective treatment for conserving bone mass.

Menopausal Hormone Therapy (MHT), also known as Hormone Replacement Therapy (HRT), may consist of oestrogens alone or in combination with progestin. With MHT a slowing bone turnover and an increase in bone mineral density (BMD) at all skeletal sites in early and late postmenopausal women has been observed (JAMA 2001).

Women who discontinued hormone therapy had an increased rate of hip fractures compared to those who remained on it (Menopause 2009). Even in women who do not have established osteoporosis or are not at a significant risk for fracture, HRT can still improve bone health and reduce fracture (Villiers 2012). 

Next, let’s take a look at a lesser-known way HRT influences health by examining its impact on brain health.

How Does HRT Affect Women’s Brain Health?

Several studies and meta-analysis have suggested that estrogen prescribed to younger women can decrease the risk of Alzheimer’s disease or delay onset (Lobo 2013).

As with the benefits of HRT for cardiovascular disease, timing is critical when it comes to realizing the advantages of HRT for brain health. Specifically, HRT used past age 65 could reduce Alzheimer’s risk if begun during the critical window when menopause first develops, and taken continuously over a decade (Neurology 2017). This could be a result of the fact that, according to a study published in Neurology, HRT may preserve areas of the brain responsible for memory and thinking, while also reducing beta-amyloid plaques which contribute to cell death in Alzheimer’s (Neurology 2018). 

Two randomized controlled trials addressed some of the issues with WHIMS by enrolling women closer to the onset of menopause and examining synthetic versus bioidentical hormones. The KEEPS trial included 662 women with an average age of 52.6 years. It found that neither type of hormone benefited cognitive function (KEEPS 2015), though in women who carried the APOE4 gene, bioidentical hormones were associated with lower levels of beta-amyloid plaques (i.e., a hallmark of Alzheimer's) in the brain compared with synthetic hormones or placebo (J Alzheimers Dis 2016). The ELITE trial compared healthy women within 6 years versus those over 10 years after menopause taking bioidentical hormones. It also found no evidence of cognitive benefit or harm in either group (Neurology 2016). These studies only lasted four to five years, which isn't long enough to assess Alzheimer's risk.

As with any medication, there are some risks with HRT. It has been associated with small increased risks of heart attack, stroke, deep vein thrombosis, and breast cancer. The North American Menopause Society states: "Provided that the woman has been advised of the increase in risks associated with continuing hormone therapy beyond age 60 and has clinical supervision, extending hormone therapy use with the lowest effective dose is acceptable under some circumstances". If you do choose HRT, see your physician regularly and consider bioidentical rather than synthetic hormones.

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.

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).

A clinical trial in men with an average age of 63 and low serum DHEA-sulfate (DHEA-S) levels found that DHEA status was rapidly corrected with oral supplementation. Compared with placebo, DHEA treatment resulted in improved immune parameters, including monocyte levels, B- and T-cell function, and NK-cell levels (Khorram 1997). In a small observational study of 38 participants, salivary DHEA levels were positively correlated with salivary bactericidal activity, a measure of innate immune function (Prall 2015). Another observational study noted an association between low levels of DHEA and high levels of IL-6, an inflammatory cytokine implicated in immune senescence. Furthermore, DHEA inhibited IL-6 production by immune cells taken from study participants (Straub 1998; Varadhan 2014). According to a study in aged mice, DHEA may also enhance the immune response to influenza vaccine (Danenberg 1995).

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.

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?

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.

The results of 2 clinical studies, published in The Journals of Gerontology, showed how a type of adult stem cell called mesenchymal stem cells (MSCs) could reverse the effects of aging.

The first trial involved 15 frail patients, each received single MSC infusion of stem cells collected from adult bone marrow donors aged between 20 and 45 years old. The patients exhibited improved overall quality of life and fitness, as well as diminished tumor necrosis factor levels. The second trial was a double-blind, randomized study involving a placebo group. Aside from noting no adverse effects, the research team found the improvements to be “remarkable.”

Other related published studies include:
  • Yu Y. Application of Stem Cell Technology in Antiaging and Aging-Related Diseases. Adv Exp Med Biol. 2018;1086:255-265
  • Ivonne Hernandez Schulman, Wayne Balkan and Joshua M. Hare. Mesenchymal Stem Cell Therapy for Aging Frailty. Front Nutr. 2018; 5: 108.
  • Juan Antonio Fafián-Labora, Miriam Morente-López, and María C Arufe. Effect of aging on behaviour of mesenchymal stem cells. World J Stem Cells. 2019 Jun 26; 11(6): 337–346.

Conclusion

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

While some studies suggest that taking certain supplements, hormone replacement or even stem cells may help slow aging, you can't do away with healthy practices as mentioned above. Strategies that are implemented as a combination are better than a single strategy alone.

In real medicine, results are not guaranteed and there are no cure-alls. Real research is published in peer-reviewed journals, and you can search the journals via PubMed or Google Scholar.

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Online Shopping Guide

Before adding a new supplement to your routine, discuss its use with your healthcare provider, especially if you have an underlying health condition or are taking medication.

While many of the anti-aging supplements may be available in your local stores, it may be more convenient or affordable to shop for them online on Amazon (US):
 

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