Anti Aging and Longevity Medicine: Advanced Guide (2023 Edition)
This practical guide on anti aging has more than 150 references and supporting studies that represent the best of science-backed strategies for interventions in longevity and anti-aging.
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.
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 and Resistance Training
- Stress Management
- Caloric Restriction
- Avoiding Linoleic Acid (Omega-6 Fatty Acids)
- Intermittent fasting (Time Restricted Eating)
- Avoiding Ultra-Processed Foods
- Anti-oxidant supplements and Aging
- Nutrients and Supplements
- Nicotinamide mononucleotide (NMN) (NAD Boosting Supplement)
- Omega-3 fatty acids
- Collagen
- Resveratrol and Pterostilbene (blueberries)
- Zinc
- Crocin (Saffron)
- Garlic and Ginger
- Curcumin (Turmeric)
- EGCG (Green Tea) and Pu-erh Tea Extract
- Molecular Hydrogen
- Glycine
- L-Theanine
- Magnesium Malate
- Fisetin
- Vitamin C and Alpha-ketoglutarate (AKG)
- Glucosamine
- CoQ10
- L-Citrulline
- Olive Leaf Extract
- 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.
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.
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.
In a 2020 review of 8 original studies, the meta-analysis demonstrates that higher MedDiet adherence is associated with longer Telomere Length (TL).
A Mediterranean diet rich in virgin olive oil is also effective in boosting stem cells. A 4-week control study published in The American Journal of Clinical Nutrition showed that compared to those on a diet high in saturated fat or a diet low in fat but high in carbohydrates, those on a Mediterranean diet rich in virgin olive oil showed a significant doubling in their endothelial progenitor cell count in the blood.
Dietary patterns containing fish and seafood are consistently associated with lower CVD risk. Systematic reviews of prospective observational studies have concluded that 2 to 3 servings of fish per week is associated with a lower incidence of all-cause mortality, CVD, CHD, myocardial infarction, stroke, and heart failure than lesser intakes of fish (R). This finding has been attributed to the omega-3 fatty acid content and substitution effect when fish and seafood replaces other sources of animal protein (eg, red and processed meat or full-fat dairy products) (R). Current data support dietary patterns that contain at least 2 fish meals per week (R). The greatest benefits occur when seafood replaces foods rich in saturated fat.
Based on consistent evidence from prospective cohort studies, systematic reviews and meta-analyses, the 2020 Dietary Guidelines Advisory Committee concluded that dietary patterns that included low-fat dairy are associated with a lower risk of all-cause mortality, CVD, overweight, and obesity (R). Nonfat and low-fat dairy products are 1 component of the DASH dietary pattern (R).
Avoiding Saturated Fat
A comprehensive systematic review and meta-analysis documented the detrimental effects of saturated fat relative to unsaturated fat on CVD outcomes and risk factors (R). Major dietary sources of saturated fats are meats, full-fat dairy products, and tropical oils (coconut, palm, and palm kernel). A meta-analysis that included only high-quality randomized clinical trials concluded modification lowered CVD by ≈30%, similar to the effect of statin drugs (R). When all randomized trials were combined, regardless of quality, the reduction in CVD was diminished but still significant.
Diet and Lifestyle
Healthy Lifestyle study (Sakaniva 2022)
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.
Dietary Patterns
Dietary patterns encompass the balance, variety, and combination of foods and beverages habitually consumed.
In general, heart-healthy dietary patterns, those patterns associated with low CVD risk, contain primarily fruits and vegetables, foods made with whole grains, healthy sources of protein (mostly plants, fish and seafood, low-fat or fat-free dairy products, and if meat or poultry are desired, lean cuts and unprocessed forms), liquid plant oils, and minimally processed foods. These dietary patterns are also low in beverages and foods with added sugars and salt. (R)
Some heart-healthy dietary patterns emphasized in the Dietary Guidelines for Americans include the Mediterranean style, Dietary Approaches to Stop Hypertension (DASH) style, Healthy US-Style, and healthy vegetarian diets. Research on dietary patterns that used data from 3 large cohorts of US adults, the Dietary Patterns Methods Project, found a 14% to 28% lower CVD mortality among adults with high compared with low adherence to high-quality dietary patterns. (R)
Mediterranean Diet
Mediterranean Diet
The Mediterranean diet (MedDiet) is 1 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).
Telomeres —the protective ends of linear chromosomes—shorten throughout an individual's lifetime. Accumulation of critically short telomeres is proposed to be a primary molecular cause of aging and age-associated diseases such as CVD, type 2 diabetes, neurodegenerative diseases, and decreased life expectancy. TL is considered to be a biomarker of aging. In this regard, positive relations were established between different pathological conditions modulated by oxidative stress and inflammation and the accelerated shortening of telomeres. Indeed, nutrition, oxidative damage, telomere shortening, and cell senescence represent a sequence of processes, which may play an important role in in vivo aging and longevity, with TL being the potential mediator between lifestyle and risk of disease. One of the mechanisms in which diet can reduce the risk of disease is with regards to its impact on telomeres (R).
Related: The Best Diet for Healthy Aging
Choose Healthy Sources of Protein
Soybeans (including edamame and tofu), other beans, lentils, chickpeas, and split peas are common types of legumes. These plant foods are not only rich in protein, but they are also good sources of fiber.
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).
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).
Soybeans (including edamame and tofu), other beans, lentils, chickpeas, and split peas are common types of legumes. These plant foods are not only rich in protein, but they are also good sources of fiber.
A recent systematic review that compared high and low intake of legumes concluded that higher intake was associated with lower CVD risk (R). Higher nut intake was associated with lower risk of Cardio Vascular Disease, Coronary Heart Disease, and stroke mortality and incidence (R).
The rapid emergence of plant-based meat alternatives requires some caution, because, at this time, many are ultra-processed and contain added sugar, saturated fat, salt, stabilizers, and preservatives (R).
The rapid emergence of plant-based meat alternatives requires some caution, because, at this time, many are ultra-processed and contain added sugar, saturated fat, salt, stabilizers, and preservatives (R).
Dietary patterns containing fish and seafood are consistently associated with lower CVD risk. Systematic reviews of prospective observational studies have concluded that 2 to 3 servings of fish per week is associated with a lower incidence of all-cause mortality, CVD, CHD, myocardial infarction, stroke, and heart failure than lesser intakes of fish (R). This finding has been attributed to the omega-3 fatty acid content and substitution effect when fish and seafood replaces other sources of animal protein (eg, red and processed meat or full-fat dairy products) (R). Current data support dietary patterns that contain at least 2 fish meals per week (R). The greatest benefits occur when seafood replaces foods rich in saturated fat.
Based on consistent evidence from prospective cohort studies, systematic reviews and meta-analyses, the 2020 Dietary Guidelines Advisory Committee concluded that dietary patterns that included low-fat dairy are associated with a lower risk of all-cause mortality, CVD, overweight, and obesity (R). Nonfat and low-fat dairy products are 1 component of the DASH dietary pattern (R).
Over 40 years, the population-wide diet and lifestyle changes were associated with significant reductions in serum cholesterol concentrations and CHD mortality. It was estimated that about half of the benefit was derived from reductions in serum cholesterol (R), with additional favorable dietary changes including increased fruits, vegetables, and fish, decreased sugar and salt, and a shift from fatty to lean meats contributing to the lower CHD mortality (R).
It is important to note that the benefits of low-fat and fat-free dairy products compared with full-fat dairy products is not without controversy and continues to be debated (R). Taken together, replacing full-fat dairy products with nonfat and low-fat dairy products and other sources of unsaturated fat shifts the composition of dietary patterns toward higher unsaturated to saturated fat ratios that are associated with better cardiovascular health.
Several systematic reviews and meta-analyses have documented a direct association between red meat intake and CVD incidence and mortality, although the magnitude of the association is less strong than that for processed meat (R). Substitution analyses based on large cohort studies found that the replacement of red and processed meat with alternative foods such as unprocessed poultry, fish, nuts, and legumes was associated with a lower risk of total and CVD mortality (R). The potential adverse effect of red meat on CVD risk has been attributed to a combination of factors, including saturated fat and heme iron content, and gut microbiota metabolism of l-carnitine and phosphatidylcholine (R).
The term “processed meats” includes meat, poultry, or seafood products preserved by smoking, curing, or salting or the addition of chemical preservatives. Common examples include bacon, sausage, hot dogs, deli meat (eg, turkey, ham), pepperoni, and salami. Ingredients used to make these foods include sodium and nitrites. Many processed meats are high in salt, saturated fat, cholesterol, heme iron, and polycyclic aromatic hydrocarbons, and heterocyclic amines (depending on the heating method), as well. Substitution analyses indicate that the replacement of processed meats with other protein sources is associated with lower mortality rates (R).
Several systematic reviews and meta-analyses have documented a direct association between red meat intake and CVD incidence and mortality, although the magnitude of the association is less strong than that for processed meat (R). Substitution analyses based on large cohort studies found that the replacement of red and processed meat with alternative foods such as unprocessed poultry, fish, nuts, and legumes was associated with a lower risk of total and CVD mortality (R). The potential adverse effect of red meat on CVD risk has been attributed to a combination of factors, including saturated fat and heme iron content, and gut microbiota metabolism of l-carnitine and phosphatidylcholine (R).
The term “processed meats” includes meat, poultry, or seafood products preserved by smoking, curing, or salting or the addition of chemical preservatives. Common examples include bacon, sausage, hot dogs, deli meat (eg, turkey, ham), pepperoni, and salami. Ingredients used to make these foods include sodium and nitrites. Many processed meats are high in salt, saturated fat, cholesterol, heme iron, and polycyclic aromatic hydrocarbons, and heterocyclic amines (depending on the heating method), as well. Substitution analyses indicate that the replacement of processed meats with other protein sources is associated with lower mortality rates (R).
Use Liquid Plant Oils Rather Than Tropical Oils (Coconut, Palm, and Palm Kernel), Animal Fats (Butter and Lard), and Partially Hydrogenated Fats
The cardio-protective effects of unsaturated fat, including reducing low-density lipoprotein (LDL) cholesterol concentrations and CVD risk, are somewhat stronger for polyunsaturated than for monounsaturated fats (R). This difference between the 2 major classes of unsaturated fatty acids may be related, in part, to the 2 primary food sources. Polyunsaturated fat comes primarily from plant oils, whereas monounsaturated fat comes from both meat fat and plant oils.
The cardio-protective effects of unsaturated fat, including reducing low-density lipoprotein (LDL) cholesterol concentrations and CVD risk, are somewhat stronger for polyunsaturated than for monounsaturated fats (R). This difference between the 2 major classes of unsaturated fatty acids may be related, in part, to the 2 primary food sources. Polyunsaturated fat comes primarily from plant oils, whereas monounsaturated fat comes from both meat fat and plant oils.
Major dietary sources of polyunsaturated fat include plant oils such as soybean, corn, safflower and sunflower oils, walnuts, and flax seeds. Major plant sources of monounsaturated fat include canola and olive oils, and nuts; high oleic acid safflower and sunflower oils; and peanuts and most tree nuts and their butters. In addition, fish with a high fat content are a good source of omega-3 fatty acids. To achieve a healthy dietary pattern, saturated and trans fats (animal and dairy fats, and partially hydrogenated fat) should be replaced with nontropical liquid plant oils.
Avoiding Saturated Fat
A comprehensive systematic review and meta-analysis documented the detrimental effects of saturated fat relative to unsaturated fat on CVD outcomes and risk factors (R). Major dietary sources of saturated fats are meats, full-fat dairy products, and tropical oils (coconut, palm, and palm kernel). A meta-analysis that included only high-quality randomized clinical trials concluded modification lowered CVD by ≈30%, similar to the effect of statin drugs (R). When all randomized trials were combined, regardless of quality, the reduction in CVD was diminished but still significant.
Many population studies in which research participants are followed for years showed that diets low in saturated fats and rich in unsaturated fat were associated with lower risk of CVD, diabetes, and other causes of death (R). Over the past several years, the use of coconut oil has become increasingly prevalent despite its high saturated fat content. These oils raise LDL cholesterol, with little evidence of positive healthy benefits (R).
The 2020 Dietary Guidelines Advisory Committee report noted that current intakes should not be increased (R). Assessing the independent effect of dietary cholesterol on CVD risk is complicated by the lack of evidence at plausible, rather than extremely high intakes, and the difficulty in isolating the effects of eggs from those of frequently paired foods such as bacon and sausage. Adhering to a dietary pattern consistent with the guidance in this document will result in relatively low dietary cholesterol intakes. An in-depth analysis of the topic can be found in the AHA scientific statement on dietary cholesterol and cardiovascular risk (R).
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).
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.
“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).
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
This is one of the most under-rated anti-aging strategy. Lack of quality 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
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.
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.
Related: The Shocking Truth About How Milk Accelerates Aging
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.
Other studies show that taking antioxidants after exercise blunts the beneficial effects of exercise (R).
In some cases, antioxidants can even increase the risk of cancer, and help cancer cells to spread around the body (to metastasize) (R,R,R,R,R). This also makes sense, because cancer cells focus mainly on dividing and multiplying, and don’t have good antioxidant defenses. Therefore, taking extra antioxidants might actually help cancer cells to protect themselves against free radicals.
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).
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.
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).
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 (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 Source, Trusted 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 Source, Trusted 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
A meta-analysis (Lancet 2022) of 35 published studies that tracked heart attacks and heart disease in men taking testosterone (2) found no association between testosterone and heart attacks and in fact in most studies, men on testosterone had fewer heart attacks.
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.
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.
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
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.
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.
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."
"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."
Avoiding Ultra-Processed Foods
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.
Antioxidant supplements
It’s still a widespread, popular belief that antioxidants slow down aging. Unfortunately, most antioxidants do not slow down aging.
Numerous large studies have shown that people who take antioxidants do not live longer, and in some cases even have shorter lifespans (R,R,R).
This makes sense, because when one takes antioxidants via a food supplement, the cells won’t make their own antioxidant proteins, which are in fact many times more effective than orally taken antioxidants.
Food supplement-based, external antioxidants lower the antioxidant defense and repair mechanisms of cells.
Numerous large studies have shown that people who take antioxidants do not live longer, and in some cases even have shorter lifespans (R,R,R).
This makes sense, because when one takes antioxidants via a food supplement, the cells won’t make their own antioxidant proteins, which are in fact many times more effective than orally taken antioxidants.
Food supplement-based, external antioxidants lower the antioxidant defense and repair mechanisms of cells.
Other studies show that taking antioxidants after exercise blunts the beneficial effects of exercise (R).
In some cases, antioxidants can even increase the risk of cancer, and help cancer cells to spread around the body (to metastasize) (R,R,R,R,R). This also makes sense, because cancer cells focus mainly on dividing and multiplying, and don’t have good antioxidant defenses. Therefore, taking extra antioxidants might actually help cancer cells to protect themselves against free radicals.
Nutrients and 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).
Related: Best NMN Supplement
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 new 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.
According to a new 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.
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.
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 (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 (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.
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 (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 (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).
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 (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 Source, Trusted 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 Source, Trusted 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 (Source).
Garlic
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).
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).
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 (Source, Source, Source). 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 (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 Source, Trusted Source, Trusted Source).
EGCG can be consumed by drinking green tea or taking concentrated supplements.
CoQ10 is also part of Dr. David Sinclair’s supplement list.
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).
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.
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).
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.
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.
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).
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).
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 (Source, Source, Source). 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 (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 Source, Trusted Source, Trusted Source).
EGCG can be consumed by drinking green tea or taking concentrated 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 Source, Trusted 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 Source, Trusted 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 Source, Trusted 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.
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 Source, Trusted 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 Source, Trusted 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 Source, Trusted 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.
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).
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).
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.
Vitamin C and Alpha-ketoglutarate (AKG)
Vitamin C can help to maintain a proper epigenome, especially in combination with another longevity ingredient, alpha- ketoglutarate.
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.
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.
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).
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).
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.
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.
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.
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:
Whey ProteinOlive 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 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).
Related: Best whey protein powders
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.
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.
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.
How Does HRT Influence Colon Cancer Risk?
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).
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).
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.
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).
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.
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.
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:
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:
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.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.
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
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
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).
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.
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:
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.
Related: What Can You Do to Prevent Cancer (2023 Edition)
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):
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 March 2023, 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.
The results of 2 salient 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.
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 salient 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.”
- 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 MarÃa C Arufe. Effect of aging on behaviour of mesenchymal stem cells. World J Stem Cells. 2019 Jun 26; 11(6): 337–346.
Related: Anti aging stem cell treatments
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.
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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