Guide to Anti Aging and Longevity 101: The Science (2023 Edition)

By Dr Frank Yap, MD August 24, 2023

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

Causes of Aging

In order to guide and provide a framework for ageing research and discussion, the landmark 2013 Hallmarks of Aging study identified 9 factors that contribute to health decline in advancing age: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. The review was updated (Cell 2023) by the same authors in 2023 to include 12 hallmarks of aging:

genomic instability,
telomere attrition,
epigenetic alterations,
loss of proteostasis,
deregulated nutrient-sensing,
mitochondrial dysfunction,
cellular senescence,
stem cell exhaustion,
altered intercellular communication,
disabled macroautophagy, (new)
chronic inflammation, and (new)
dysbiosis. (new)

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

Source: Cell 2023

When interpreting scientific studies, let’s remember that not all studies are created equal. Below is a list of study types ranked in descending order based on their level of evidence quality:

Meta-analysis and Randomised controlled trials (RCTs)
Large clinical trials (phase 3)
Small clinical trials (phase 2) and Case studies
Mouse results and animal studies
In Vitro, cell culture, commentary, review, expert opinions and anecdotal evidence

In this practical guide, we have covered anti aging with more than 200 references and supporting studies that represent the best of science-backed information on anti-aging and longevity.

While aging is inevitable, increasing the human lifespan and slowing the aging process has been a focus of scientific research for decades. If aging is reversible, then maybe heart disease, cancer, diabetes, Alzheimer's or other chronic disorders are reversible as well.

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

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

Diet and Lifestyle

Healthy Lifestyle study

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

According to 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.

Reversal of epigenetic age using a diet and lifestyle intervention (Dr Kara Fitzgerald protocol)

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

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

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

The Mediterranean diet (MedDiet) is one of the most consistent dietary patterns analyzed in relation to the prevention of cardiovascular disease (CVD) and other health outcomes, including reduction of overall mortality and increased likelihood of healthy aging (Silvia Canudas 2020).

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

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 (2011) 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.

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).

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).

Related: The Best Diet for Healthy Aging

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.

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).

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).

Related: The Shocking Truth About How Milk Accelerates Aging

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.

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).

Dietary Cholesterol

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).

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

Related: Muscle Mass - The Key to Longevity

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 and Vegetable Oil

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

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

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

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

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

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

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

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

When we talk about omega-6, we're really referring to LA. They're largely synonymous, as LA makes up the bulk — about 60% to 80% — of omega-6 and is the primary contributor to disease. Broadly speaking, there are three types of fats:

Saturated fats, which have a full complement of hydrogen atoms
Monounsaturated fats, which are missing a single hydrogen atom
PUFAs, which are missing multiple hydrogen atoms

The missing hydrogen atoms make PUFAs highly susceptible to oxidation, which means the fat breaks down into harmful metabolites. OXLAMS (oxidized LA metabolites) are what have a profoundly negative impact on human health. While excess sugar is certainly bad for your health and should be limited to 25 grams per day or less, it doesn't oxidize like LA does so it's nowhere near as damaging.

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

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

Intermittent fasting

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

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

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

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

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

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

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

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

Avoiding Ultra-Processed Foods

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.

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).

Stress Management

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

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

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

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

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

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

Social Support

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

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

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

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

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

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

According to Prof. Waldinger:

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

Nutrients and Supplements

What are the best anti-aging supplements? Are they the Elixir of Youth?

Although many main-stream media channels may state that there is no scientific evidence to support the effectiveness of any specific supplements, it's definitely not true. There are countless anti-aging supplements that are supported by overwhelming scientific evidence out there. However, most of them are based on outdated science, not supported by well-conducted scientific studies or not scientifically proven, focus on aging process that are less relevant, contain doses that are too low, and are not verified in humans.

It's crucial to understand the limitations of conventional medicine when exploring the subject of anti-aging supplements. Most doctors may not have much to offer in the anti-aging space, as the focus of conventional medicine involves treating diseases reactively with drugs and surgery. However, recent scientific studies have proven the effectiveness of many anti-aging supplements, but it's essential to choose the ones that are scientifically proven, based on up-to-date science, and verified in humans.

To delve into the latest research on anti-aging supplements and gero-protectors, check out "Best Anti Aging Supplements" (2023 Edition).

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.

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.

Hormone Replacement Therapy

HRT for Women

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

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

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

HRT & Breast Cancer: What’s the Connection?

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

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

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

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

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

How Does HRT Influence Colon Cancer Risk?

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

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

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

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

Can HRT Help Prevent Cardiovascular Disease in Women?

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

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

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

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

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

HRT: Good or Bad for Osteoporosis?

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

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

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

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

How Does HRT Affect Women’s Brain Health?

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

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

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

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

Testosterone Replacement Therapy (TRT) for Men

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

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

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

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

But it’s becoming increasingly popular for non-medical uses, including:

enhancing sexual performance
achieving higher energy levels
building muscle mass for bodybuilding

Your body naturally produces less T as you age. According to an article in American Family Physician, the average male’s T production goes down by about 1 to 2 percent each year.

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

This gradual decrease in Testosterone often doesn’t cause any noticeable symptoms. But a significant drop in T levels may cause:

low sex drive
fewer spontaneous erections
erectile dysfunction
lowered sperm count or volume
trouble sleeping
unusual loss of muscle and bone density
unexplained weight gain

Your body can transform DHEA (Dehydroepiandrosterone) into testosterone. Taking a DHEA may increase your testosterone levels. A 2013 study found that taking 50 milligrams (mg) of DHEA per day raised the free testosterone levels of middle-aged adults undergoing high-intensity interval training.

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

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).

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

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

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

Stem Cell Therapy for Anti-Aging

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

As of August 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.

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.

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

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

Related:

What Can You Do to Prevent Cancer (2023 Edition)

Best Stem Cell Supplements

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