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THYMUS GLAND AND AGING
The older a person gets, the higher their risk of dying from cancer or even a common cold. One reason is age-related changes in the thymus86 (thymus gland). This immune organ plays an essential role in preserving life by blocking the development of dangerous mutations and destroying dangerous microbes. However, as we age, the gland cells of the thymus are replaced by adipose tissue, and organ function declines. Therefore, one of the most important tasks of modern medicine is to find measures to rejuvenate the thymus gland and restore its protective functions.
As thymus function declines, the number of T lymphocytes capable of learning (recognizing foreign aggressors), decreases.
Researchers from the University of Copenhagen have published the results of a large-scale study, in which they traced the connection between a decrease in the level of lymphocytes in the blood (lymphopenia) and the risk of death from all causes87.
The study involved more than 108,000 people between the ages of 20 and 100 (the average age is 68), which were followed for 12 years (2003–2015). 10,372 people died during this period. It turned out that people with lymphopenia had 1.6 times increased risk of dying from all causes, and mortality from heart disease, cancer, and respiratory infections was 2.8 times higher than in subjects with normal lymphocyte levels.
Experts explain this by the fact that a decrease in the number of lymphocytes indicates a reduced immunity readiness to respond to invading factors, leading to disease and death. Characteristically, lymphopenia develops with age in most people. It is associated with a decline in thymus function. Restoring the thymus gland potential will help manage many age-related problems, prevent cancer development, and probability of death from infections.
IS IT POSSIBLE TO TRANSPLANT THE THYMUS GLAND?
Transplantation of the thymus gland or its fragments to an adult could solve the problem of age-related decline in thymus function. It is possible, but to date, thymus transplants have only been performed on infants. Scientists from the Institute of Child Health (UK) 2017 published a paper on the results of thymus transplantation in children with Di George's syndrome, a genetic disease in which the thymus gland does not develop and there is a pronounced deficit of T lymphocytes88.
Between 2009 and 2014, 12 children were transplanted, with an average age of 10 months. Immunosuppressive therapy was performed to suppress the reject phenomena. One patient had a rejection of a donor organ and underwent a second thymus transplant. Three patients died (two weeks, eight months, and two years after transplantation) from infectious complications caused by immunodeficiency.
9 of the 12 operated, at the time of publishing, were alive. Five to six months after transplantation, the recipients start to show their T lymphocytes, indicating the proper functioning of the transplanted organ. As a result, eight patients were taken off permanent antibiotic treatment, and five patients no longer needed supportive immunoreplacement drugs.
Doctors concluded that thymus transplantation is a method that allows us to establish the production of our T lymphocytes, but the chance of autoimmune reactions is still quite high.
Perhaps, as this practice improves, it will be possible to raise the issue of thymus transplantation not only for newborn children but also for elderly people with age-related decline of thymus gland function.
FUN FACT
"COCKTAIL" FOR THYMUS RECOVERY LED TO LIFE PROLONGATION
Experts from Stanford University, working on a medicine restoring the thymus gland, created the "elixir of life." Studies have shown that a cocktail of several substances "moved" the epigenetic clock back, giving subjects 2.5 additional years of life.
The initial objective of the study, which involved nine men between the ages of 52 and 65, was to stimulate the multiplication of active immune cells in the thymus gland. Previous studies have shown that injecting somatotropin (growth hormone) into the body helps reverse age-related changes in the thymus gland, but simultaneously with the positive effect it provokes diabetes.
In a new experiment, scientists decided to use a cocktail that included, in addition to growth hormone, substances that prevent diabetes development: metformin89 and dehydroepiandrosterone90. Specialists were able to achieve the desired result – the replacement of fat cells of the thymus with immune cells, avoiding diabetes development.
It turned out that the cocktail not only "strengthened" immunity, but also rejuvenated the body.
Specialists learned this by analyzing methyl tags that appear on the surface of DNA sites as they age, indicating a change in genomic activity. The cocktail of growth hormone and antidiabetic medications helped move the "hands of the epigenetic clock" by 2.5 years, and this effect was maintained in participants six months after the study.
It is not necessary to transplant the whole thymus – the donor gland scaffold can be enough91.
American scientists have found that one of the causes of age-related involution of the thymus gland is a microenvironment change. As a result, stem progenitor cells stop transforming into mature T lymphocytes. The proposed method consists in creating a new organ scaffold with a microenvironment suitable for lymphocyte multiplication.
The experiment was performed on mice: thymus was removed from donor animals and decellularized (cells were removed by freezing and thawing cycles followed by washing). As a result, a connective scaffold was left, which was transplanted to recipient mice with the thymus removed. The creation of an extracellular 3D matrix helped to form conditions for the transformation of stem progenitor cells into full-fledged T lymphocytes.
The study showed that the use of bioengineering technologies, helping to restore the proper cell microenvironment, contributes to thymus function restoration and can be used to rejuvenate the gland. Perhaps after the completion of preclinical trials conducted on laboratory animals, scientists will be able to perform thymus scaffold transplantation for humans as well.
EXERCISE AND NUTRITIONAL SUPPLEMENTS CAN IMPROVE THYMUS FUNCTION
The experiment conducted by specialists from the University of Birmingham (UK) showed that to rejuvenate the thymus, we need to move more92. A total of 125 amateur cyclists participated in the experiment: 75 between the ages of 55 and 79 and 55 between the ages of 20 and 36.
Subjects participated in a 100-kilometer race in 6.5 hours for men and a 50-kilometer race in 5.5 hours for women. In preparation for the competition, they trained regularly. The comparison group was people of similar age who are not into sports. Studies have shown that regular exercise helps the thymus of older people to remain as active as it was when they were young: the number of T lymphocytes in the "young" and "old" groups was almost identical.
A gentle method of thymus restoration was also proposed by scientists from the Singapore Immunology Network93. Experts found that the formation of T killer cells in the thymus, the "first line of defense" cells during the invasion of foreign agents, is activated under the influence of lipid molecules. These fat molecules are produced by pathogenic bacteria and are synthesized in the thymus itself.
Scientists managed to decipher the structure of these signal substances and artificially synthesize their analogs. It turned out that administration of these molecules into the body leads to increased formation of T killers, which can be used to fight against infectious diseases, especially in people with a reduced thymus gland function due to age.
In Chinese medicine, there is a practice aimed at stimulating the immune system – thymus massage ("happiness point" massage). To find the "happiness point," you need to feel the sensitive area on the breastbone, located two fingers (about 2 centimeters) below the sternal notch (notch between collar bones). Affect "happiness point" with massage: nine times to one side and nine times to the other. Another way to affect is percussion – tapping the "happiness point." The frequency and intensity do not matter: what is important is that it does not cause discomfort. It is believed that these practices increase blood supply to the thymus gland, which is beneficial for thymus function.
Among the methods of alternative medicine aimed at rejuvenating the thymus is the chanting of mantras. It is believed that sound vibration occurring during the chanting of the Om mantra enhances blood flow to the thymus gland and helps to improve its function.
CONCLUSION: HOW TO MAINTAIN IMMUNITY?
Today we see the development of high technology, which with high probability will help soon to solve problems of age imbalance of the immune system, to slow down or to prevent the development of diseases associated with the aging of the body's defenses. However, even today we can support our immune system with a healthy lifestyle.
Good sleep is an important condition for the full functioning of the immune system. A study conducted at the University of Tübingen (Germany) showed that during sleep, T lymphocytes are "reprogrammed" and start to fight infection more actively94. Scientists from the University of Texas Southwestern Medical Center (USA) and their colleagues from Australia found in a series of experiments that muscle exercise not only strengthens bones but also activates the formation of stem cells – lymphocyte precursors in the bone marrow, which affects the immune system95.
However, it's important to understand that it's not just working on the physical aspects of our lifestyle, such as nutrition, movement, and sleep, important for maintaining a fully functioning immune system. Taking care of mental well-being also has a powerful effect on the body's defenses: techniques such as meditation, mindfulness, and relaxation will have a positive effect on immune function.
Thus, it is an integrated approach considering both the physical aspects of a healthy lifestyle and methods that promote stress resistance, as well as social interactions, that help to maintain the correct immune balance in the body, allowing you to stay young and healthy for a long time.
CHAPTER 9
METABOLISM
METABOLISM – THIS CONCEPT IS PORTRAYED WITH MANY MYTHS, WHICH SPREAD ACROSS THE GLOBAL NETWORK AT THE SPEED OF LIGHT. IN MOST PUBLICATIONS AND VIDEOS, "FAST METABOLISM" IS DECLARED A PREREQUISITE FOR STAYING SLIM AND YOUNG.
"Ten ways to boost your metabolism without dieting," "Lifehacks to increase your metabolic rate," "Top 10 foods to speed up your metabolism" – the Internet is full of such headlines. Various types of exercise, diets, supplements, teas, exposure to cold or heat, etc. are presented as levers to control the metabolism.
At the same time, there are also adepts of "slow metabolism," who consider the metabolism as something like a battery: the more actively it is used, the faster the charge runs out and the inevitable end comes. So, which is better for our metabolism – burn bright or just barely glow? How can we affect the speed of our metabolic processes, and what it will bring?
WHAT IS METABOLISM?
Every cell in our body needs energy to function properly, which comes with food. Energy release occurs during a huge number of chemical reactions involving the processes of the breakdown of molecules (catabolism) and the synthesis of new substances (anabolism). The totality of all these processes is called metabolism.
What body functions use the energy produced and in what quantity?
● Life processes support. There is an indicator called basal metabolism, which is the energy needed to sustain the body's vital functions. It is consumed to provide the processes of breathing, heartbeat, digestion, maintaining body temperature, regulation of the nervous and hormonal systems, tissue repair, and much more. All these processes take place every second of our lives, both during periods of activity and during sleep. Basal metabolism takes the lion's share of energy produced, 60 % to 75 % of calories that enter the body with food. At the same time, with age, the basal metabolic rate decreases by an average of 12 % every decade after a person reaches the age of 2096. Scientists attribute this to a decrease in muscle mass, whose cells consume more energy even at rest, and an increase in the adipose tissue percentage, which is more inert in energy expenditure. It is generally believed that it is difficult to influence basal metabolism with any measures. It is also known that the rate of basal metabolism in men is 10 % higher than in women: males with normal build burn an average of 1 kcal/hour for each kilogram of body weight, while women burn 0.9 kcal/hour97.
● Energy expenditure in digestion. The digestion itself requires energy: it is necessary to break down the food in the gastrointestinal tract, absorb the obtained molecules into the blood, and deliver them to the place of use or storage. Energy expenditure for digestion is called diet-induced thermogenesis and accounts for 5-10 % of calories consumed. However, different types of food take different amounts of energy to digest. For example, the rate of diet-induced thermogenesis for porridge based on various kinds of cereal (millet, oats, buckwheat) is about 18–19 %, for cottage cheese – 30–31 %, for butter – 1415 % of the caloric value of food products themselves98. It was found that immediately after a meal the basal metabolism level increases, and the amount of energy absorbed also depends on the chemical composition of food: consumption of proteins increases the basal metabolic rate by 30–40 %, fats by 4-14 %, carbs by 4–7 %. This means that a person whose diet is dominated by protein products (cottage cheese, meat, etc.) will burn more energy per day than a person who eats a lot of fats and carbs99.
● Total metabolism is the energy a person expends on physical and mental activity. Separately distinguish energy expenditures for daily physical activity: going to work, to the store, cleaning, cooking, etc., and the energy expenditures for special physical activity: sports, walking, and hard work that is not part of daily activity. Mental work also makes the body expend energy: the brain is a very energy-consuming organ, and with intense mental activity it can absorb up to one-third of the body's energy.
● Facultative thermogenesis – energy expenditure in stressful situations is isolated as a separate category. For example, with hypothermia, heat-regulating centers in the brain cause the body to expend more heat to maintain optimal body temperature.
IS IT POSSIBLE TO SPEED UP THE METABOLISM?
Searching for recommendations to speed up the metabolism is associated primarily with the desire to get rid of excess weight, with an attempt to shift metabolic processes towards the burning of ingested energy and to create a calorie deficit. However, if we consider the components of our metabolism, it becomes obvious that most of the energy during the day is spent on basal metabolism, i.e., on vital processes. This energy is spent no matter what kind of lifestyle we lead – devoting most of our time to physical and mental activity or lying passively on the couch.
Thus, the basic "energy capital" that can be disposed of in one way, or another is the calories we spend on total metabolism, that is, on physical and mental activity. The amount of energy expended for total metabolism is 30–40 % of the total amount of kilocalories consumed in metabolic processes. Therefore, one of the key recommendations for people who want to speed up their metabolism and lose weight is to lead a more active lifestyle. The importance of exercise in activating metabolic processes has been shown in several studies.
Physical activity is known to improve metabolic processes in the body, helping to convert food into energy and eliminate "waste." Substances formed during digestion, are called metabolites, which can be used to track how a person's metabolic profile changes in response to exercise.
Researchers from Australia measured about 200 metabolites in the blood of 52 soldiers before and after an 80-day program of weight and aerobic exercise and associated them with changes in fitness100. It turned out that physical activity significantly changed the composition of metabolites in the soldiers' bodies: exercised muscles used much more "fuel" (e.g., fat), than before. They also recorded major changes in intestinal processes, in factors related to blood clotting, protein breakdown, and vasodilation to improve blood flow.
Therefore, scientists have concluded that exercise is the key to speeding up the metabolism in addition to having positive effects on blood pressure, heart rate, body weight, and fitness. The study confirms the central role of physical activity in the prevention of cardiovascular disease.
NEW INSIGHTS INTO THE METABOLISM (WHY DOESN'T MOVEMENT ALWAYS HELP?)
As some studies show, the principle of "eat less, move more" does not always lead to desired results – increased metabolism and weight loss. This paradigm was questioned in a study conducted by Herman Pontzer, professor of evolutionary anthropology at Duke University101.
For 10 years, Pontzer and his colleagues analyzed the metabolism of U.S. and European residents: they focused on both professional athletes, whose lifestyle is accompanied by significant energy expenditure, and office workers, who consume minimal calories for physical activity.
At the same time, experts were studying the characteristics of metabolic processes and energy expenditures among the members of the Hadza tribe. These are the inhabitants of Tanzania who led a "primitive" way of life, engage in hunting and gathering, and do not have access to such fruits of civilization as water supply and electricity.
It is logical to assume that tribal members, who walk at least 16,000 steps every day in search of food, expend significantly more energy than office workers who suffer from physical inactivity. However, Professor Pontzer's and his colleagues' research appeared to show otherwise. Scientists found that despite their high activity levels, the Hadza do not burn more energy per day than sedentary people in the U.S. and Europe.
According to scientists, this and other studies change views on the relationship between energy expenditure, physical activity, and diet. The study authors state that our metabolism is much more complex than it seems, and our actual energy expenditure cannot be measured by calculating the difference between "eaten" and expended calories.
"Our metabolic engines were not crafted by millions of years of evolution to guarantee a beach-ready bikini body," Herman Pontzer says. But rather, our metabolism has been primed "to pack on more fat than any other ape." What is more, our metabolism responds to changes in exercise and diet in ways that thwart our efforts to shed pounds."
At the same time, as the study authors claim, despite the equal energy expenditures of office workers and Tanzanian hunter-gatherers, the daily activity provides the members of the Hadza tribe with great bonuses. First, it's about strong health even in old age: at 60 and 70, the Hadza people rarely experience cardiovascular diseases, diabetes, obesity, hypertension, or osteoporosis.
"All those adjustments our bodies make responding to exercise are important for our health," emphasizes Professor Pontzer. "When we burn more calories on exercise, our bodies spend less energy on inflammation, stress reactivity (like cortisol), and other things that make us sick."
According to Pontzer and his colleagues, it is important for modern individuals living in industrialized countries to be active to keep up healthy. However, we should not rely too much on exercise to make our bodies burn calories more intensively in combating obesity. This new understanding of metabolism helps to realize that the body quickly adapts to additional physical activity by starting to burn energy in a more "narrow range."
Scientists from Baylor University (USA) obtained similar results in a study examining the energy expenditure patterns of children from Ecuador.102 The young subjects (they were from 5 to 12 years old when the study began) lived with their families in the Amazon rainforest. Like members of the Hadza tribe, they had no access to modern technology to make life easier, and they were subsistence farmers, devoting their time to hunting, fishing, gathering, and gardening. Experts analyzed not only the level of energy consumption of children from Ecuador but also used modern technology to understand exactly what the experiment participants spent their calories on during the day.
It turned out that the total energy expenditure of the young subjects did not differ from the energy expenditure of their peers from industrialized countries, although children from South America were more active (by at least 25 %) than children from the USA. At the same time, the basal metabolic rate (the amount of energy to support basic needs) of children from Ecuador was 20 % higher than that of their "civilized" peers, while their physical activity, in contrast, took less energy than that of the much less mobile children from North America.
Scientists found that the excess energy of basal metabolism in young inhabitants of the Amazon was spent on maintaining the tone of the immune system: children were less susceptible to colds and almost did not suffer from obesity, unlike their peers from the United States. Experts believe that despite similar daily energy consumption in both study groups, children from the United States are much more likely to be obese and to have a significantly higher risk of developing heart disease, diabetes, and other diseases than their peers from Ecuador.
This study updated the data obtained by Professor Pontzer and showed that children's metabolism has the same flexibility as adults' metabolic processes and can adjust to different levels of activity, including energy-saving mode.
Today, several studies show that physical activity plays an essential role in maintaining health, but it has a very limited efficiency potential when it comes to weight loss. The fight against obesity should be based primarily on reducing caloric intake. However, does a calorie deficit help to speed up metabolism? On the contrary! Studies show, that reducing the amount of dietary energy often leads to a slower metabolism. This point lies behind experiments about the effect of metabolic rate on longevity.
