Enemies of Youth
7 main elements of aging: the view of Dave Asprey
At the age of 26, successful programmer Dave Asprey was already a multimillionaire and almost disabled: weight – 136 kg, prediabetes, arthritis, head fog, high risk of heart attack and stroke. From such a starting point, his path to biohacking began. Now he is 45, he weighs 90 kg, with a fat content of only 9.6%, feels better than in his youth, and seriously plans to live up to 180 years. To win the fight against aging, Esprit believes, you first need to determine who you are fighting with.
Reminder publishes a chapter from his book "Superman" dedicated to the seven main elements of aging.
Many of my friends working in the field of anti-aging technologies (and I am friends with strange, but outstanding personalities) are primarily interested in special types of cell damage that accelerate the aging of the human body. I call these types of damage the seven main elements of aging. The influence of this seven on our body is manifested at the cellular level. Understanding how this happens is the most important task. Let's take a look at which paths old age is coming to us and how exactly it affects the body.
1. Reduction of tissue volume
In youth, there are a lot of stem cells in the body. Being universal, they are able to renew themselves, which leads to the appearance of new cells of the same kind. After division, they turn into different types of cells, that is, into cells of different tissues and organs. When some cells are destroyed during apoptosis, stem cells immediately get down to business, taking the places of the dead. But as you get older, a lot of things change. The stock of stem cells is gradually decreasing. In addition, mitochondria stop stimulating apoptosis when it is really necessary. Some cells die before the due date, and the body is not immediately able to find a suitable replacement for others.
What is usually associated with the concept of "old age"? You probably immediately imagined a weak, thin man with a wrinkled face and shaking hands? Typical signs of aging are essentially external manifestations of the process of reducing the number of cells and disrupting the mechanism of replacing dead cells with new ones. The destruction of muscle tissue in old age is such a common problem that it was even given a special name: sarcopenia (age–related atrophic degenerative change in skeletal muscles, leading to a gradual loss of muscle mass and strength). A person in this state often begins to fall, often breaking bones, and, even sadder, the body after such injuries (or, for example, surgical operations) ceases to fully recover.
When the neurons of the brain die and the body cannot find a replacement for them, conditions are created for the deterioration of mental abilities and the development of dementia. Atrophy of the hippocampus tissues – the area of the brain responsible for emotions, memory and the work of the nervous system – is even considered the main indicator by which it is possible to determine how old the human body is.
2. Mitochondrial mutations
The phrase "mitochondrial mutations" means that damage occurs in the mitochondria. This is another loophole that allows old age to gradually come into its own, and it is impossible to overestimate the degree of this danger. With undesirable changes in the "power plants" of your cells, that is, in the organelles that supply you with energy and, therefore, help you stay alive, the whole body soon begins to suffer, and not individual organs and systems.
The genetic code can be represented in the form of a plan, according to which "construction works" are taking place in your body and will continue to take place. But you need to understand: an organism that lacks energy is good for nothing. Do not forget that the DNA of mitochondria exists separately from human DNA: these tiny organoids originate from ancient bacteria and have their own heredity. The latter performs a very significant role: it regulates the production of energy in your body. Unfortunately, mitochondrial DNA is much less resistant to mutations than human DNA: in the former, the ability to repair itself after any violations is limited. That is why you need to protect your small "power plants" in good faith from the effects of undesirable factors.
Let's reconnect the imagination. Suppose our genes are a blueprint for understanding what the "building" (body) will become: tall or not, with a lot of rooms and windows, or with a small one, with one kind of roof or another. The DNA of organelles-"power plants" makes it possible to determine exactly how wiring, heating, lighting and ventilation will be arranged in this "building". When serious failures suddenly begin in these systems, the entire structure of flesh and blood, which, however, can be quite resistant to external influences by itself until a certain period of time, will become completely unusable. Mitochondrial DNA "breaks" and "deteriorates" very easily, so monitoring its condition is one of your top priorities.
The DNA of mitochondria is damaged due to the harmful effects of free radicals, which leads to the loss of parts of the genetic material possessed by organelles. After such violations, microscopic "power plants" cease to produce enough energy and, accordingly, do not provide us with forces. In addition, due to "wounded" mitochondria, inflammation occurs in the body, and it begins to age prematurely. But the first stage of this chain is the appearance of an excess of free radicals resulting from the deteriorated work of mitochondria. The more effectively mitochondria cope with their main task, the less their DNA will be damaged, regardless of which genes were passed on to you from your parents.
3. Zombie cells
Modern specialists in the field of anti-aging technologies focus primarily on the study of non-dying (senescent) cells, that is, those that, even being "worn out", continue to exist. They do not divide, do not fulfill the tasks inherent in them by nature and become literally a dead weight – however, not functioning properly, they continue to secrete proteins that contribute to inflammation, as a result of which it turns into a chronic form and many problems arise. In addition, mitochondria in senescent cells stop working properly and produce a lot of reactive oxygen species. This condition is called mitochondrial dysfunction. It is associated with the effects of aging cells, and causes the body to become decrepit very, very quickly.
Over time, the number of zombie cells increases, and the more and more tangible damage they cause to the body becomes the main cause of rapid aging and various ailments. When too many useless, but undying cells appear in the tissues, the body stops responding correctly to insulin. This is how insulin resistance develops – a harbinger of type 2 diabetes mellitus. Due to zombie cells, the amount of visceral fat also increases. The larger its volume, the higher the probability that you will acquire a whole bunch of diseases. Especially often in such cases, type 2 diabetes mellitus develops.
In addition, infinitely senile cells contribute to the appearance of many symptoms of aging, which will not shorten your life expectancy, but in old age will significantly weaken your health. For example, doctors have long known that patients in need of knee joint transplantation have too many zombie cells in the cartilage of this joint. By the way, studies show that if even a small number of such cells are injected into the knee joint, arthritis can develop.
Senescent cells, as some experts believe, can be destroyed by metformin, a drug used in the treatment of diabetes mellitus. Judging by the results of research, thanks to its use in both animals and humans, the risk of disorders and diseases that usually accompany aging is reduced. These are, for example, metabolic disorders, cardiovascular diseases, cancer and cognitive impairment. In elderly and elderly people, after taking metformin, life expectancy increased by five years. To achieve such an effect, according to the conclusions of researchers who conducted experiments on mice, it is possible under two main conditions: if the aging of cells slows down and the number of free radicals decreases.
Rapamycin also seems to help in the fight against zombie cells. It has a depressing effect on one of the signaling pathways called the mammalian rapamycin target (mTOR) and is responsible for the proper course of the most important processes directly related to the life and functioning of cells, namely growth, death, division and autophagy. As a result of research, it turned out that when the mTOR is suppressed, the number of "eternally senile" ceases to increase. In mice, thanks to rapamycin, life expectancy increases, the immune response improves, tissue destruction slows down and, in general, the body does not become noticeably weaker during aging, in addition, the risk of heart failure, cancer and cognitive impairment decreases. Not bad, right? But since there are no proven facts at our disposal that indicate that rapamycin is more safe for health than dangerous, it is better to wait a little until the results of in-depth studies appear.
4. Extracellular matrix changes
In the space between the cells there is an extracellular matrix – a set of proteins that protect the tissues of the body from stress, injury and even the effects of gravity. The extracellular matrix allows the tissues to fully perform their functions, without it the cell would look like a very liquid jelly spreading in different directions.
The extracellular matrix literally holds cells next to each other; in addition, thanks to it, tissue elasticity is ensured. This fact is important, especially if we are talking about tissues of a certain type, of which, for example, arteries consist. If such cell systems lose elasticity and become rigid, then the body, driving blood through the circulatory system, will be forced to spend an excessive amount of energy, which can lead to an increase in blood pressure and the development of cardiovascular diseases. But over the years, the extracellular matrix can become too rigid. What is the reason?
Sugar, moving in the circulatory system, continuously reacts compounds with proteins, forming the end products of glycation, or CNG (advanced glycation end products, or AGEs), contributing to inflammation. Glycation is a process in which glucose is "attached" to proteins. If you eat a product containing sugar, glucose molecules begin to move through all the vessels and systems of the body, trying to find proteins with which to connect. When such a connection is realized, proteins under the influence of glucose will acquire a brown color. Exactly the same chemical reaction will occur, for example, if you slowly fry the onion: thanks to the sugars contained in it, caramelization will begin.
In order to maintain the elasticity of the extracellular matrix, first of all it is necessary to reduce the level of sugar in the blood, or rather, to prevent its sharp increase after eating. According to the results of the study, in which special attention was paid to the amount of glucosepane in the body, the level of this CNG increases over the years in almost every person. The control group consisted of volunteers who did not suffer from diabetes, but for a long time they had high blood sugar levels; it turned out that the content of glucosepane in the body of these subjects doubled compared to the values at normal glucose levels. So, if you want to live longer, it is necessary to reduce the amount of sugar in the diet.
The number of proteins with transverse molecular bonds ("crosslinking") also increases with the development of inflammation in the body, and it does not matter what type. It is quite a logical thought, because the increased sugar level stimulates inflammatory processes and promotes the formation of cross-links. In addition to performing actions that help regulate blood glucose, it's a good idea to take time to analyze your nutrition system and exclude all dishes under the influence of which inflammatory processes begin in the body. With high sensitivity to certain foods, when they are consumed, an immune reaction is triggered each time, leading to the development of inflammation. And if this happens regularly, then the inflammation becomes chronic, and the level of CNG is too high. To find out which kind of food your body is most sensitive to, you can conduct testing at home. Viome and Everywell companies offer very effective ways.
5. Extracellular "garbage"
Over the years, waste products – extracellular aggregates – accumulate both inside and outside the cell. Of those that gather outside, poorly functioning proteins with an irregular three-dimensional structure, commonly called amyloids, cause the greatest harm to health. When their number increases, they stick together and form deposits that disrupt the normal interaction of cells, accelerating the aging process and causing the development of diseases.
People suffering from Alzheimer's disease have deposits of a certain type in the brain (consisting of beta-amyloids – proteins belonging to the number of extracellular aggregates). But long before the onset of the disease, due to accumulations of beta-amyloids, cognitive deterioration may begin. In type 2 diabetes mellitus, the level of extracellular amylin aggregate, which disrupts insulin secretion, increases. The amount of substances released by cells as waste, increasing, accumulates – including in the heart, as a result, amyloidosis develops, creating the most favorable soil for the development of heart failure.
What makes proteins stick together in the first place? The fact is that amyloids accumulate in tissues for various reasons, but scientists cannot yet clearly determine for what reasons. At the moment, it is known that an autoimmune reaction definitely leads to negative consequences, that is, the process during which the body attacks its own healthy cells. Alas, about 30% of the population suffers from autoimmune diseases in one form or another. But even if there are no signs of an autoimmune reaction in the body, inflammation caused by excessive sensitivity to certain products or constant emotional stress can lead to the formation of a significant amount of amyloids (in addition to the end products of glycation that are already being produced).
6. Intracellular "garbage"
Almost every cell has its own built–in waste treatment system - the lysosome. This organelle promptly destroys any substances unnecessary for the body's work, helping the cell not to experience their harmful effects and function as expected.
There is one "but" here: if the lysosome cannot break down and process certain substances, they accumulate inside the cell, filling the space provided to them until the cell ceases to work fully. This is how intracellular protein deposits are formed. If this happens with a very large number of cells, then the main element of aging number 1 begins to negatively affect your health: a decrease in tissue volume.
Lysosomes lose their ability to recycle "garbage" for one of the following reasons. Firstly, these organoids are sometimes damaged and cease to function fully. In order to decompose everything unnecessary that occurs during the vital activity of cells, lysosomes need about 60 types of enzymes; and since mutations can occur in the genes responsible for their work, then, of course, these organelles cease to perform their work correctly due to such changes. In addition, lysosomes are damaged under the influence of reactive oxygen species or free radicals when mitochondria malfunction.
But, most likely, the main reason why cells are filled with "garbage" is that you consume a lot of foods with food that cannot be fully processed by lysosomes, even if the latter function properly.
In 2019, the results of a study were published in the journal BMJ, in which experts for several years studied the eating style of more than 100 thousand women aged 50 to 75 years. Factors such as: a) lifestyle; b) the total amount of nutrients consumed daily with food; c) the level of education and income of each individual subject were taken into account. It turned out that regular consumption of fried food (it also includes CNG, since the preparation of such food is essentially similar to the process that results in meat with a crust) correlates with an increased risk of dying from a number of ailments, and especially from cardiovascular diseases. Compared with the subjects who did not eat fried food at all, the risk mentioned above was 8% higher in women who ate at least one serving of such food every day.
7. Telomere shortening
Imagine laced shoes with plastic caps attached to the ends of the laces so that they do not get disheveled. Telomeres perform a similar function in the body: these are the "caps" of our DNA, thanks to which the chromosomes do not wear out as much over time (that is, during aging) as they could without such protection. The work of telomeres is regulated by the enzyme telomerase, but over the years they naturally break down, shortening with each cell division. The "caps" of DNA become smaller as the body ages, until finally their ability to protect the cell is completely lost. Then either the growth of the cell stops, or its programmed death begins – apoptosis.
Telomere shortening is associated with a weakening of the immune system, the development of chronic and degenerative diseases, such as cardiovascular diseases and heart failure, as well as the development of cancer, diabetes mellitus and osteoporosis. The rate of shortening of the "caps" of chromosomes significantly depends on the rate of your aging. According to scientists, the length of telomeres can accurately determine the biological age of a person (not always coinciding with the number of years lived). If we compare people whose sizes of the mentioned "caps" are quite normal for their age with those who have them less than normal, then the risk of serious illness and death from it is higher for the latter. According to the results of one study involving volunteers over 60 years of age, subjects with telomere sizes less than normal values, compared with the average person of this age, the probability of dying from cardiovascular diseases and from any infection was three and eight times higher, respectively, than volunteers with telomere length, normal for their age category.
Some researchers have managed to find ways to lengthen telomeres, but there is still not enough evidence to say that there is a suitable way for each individual case. But still, we already know something about why telomeres shorten and how to prevent this process. It is curious that, most likely, this is directly related to stress. In one study, it turned out that in terms of telomere length, women experiencing severe stress are ten years older than their biological age. This is not surprising, because both psychological and physical stress are ideal conditions for increasing oxidative stress.
Another effective way to prevent premature shortening of telomeres is physical exercise. German researchers studied the length of chromosomal "caps" in four groups of subjects: the first consisted of young people who lead a sedentary lifestyle; the second – young, but devoted a lot of time to motor activity; the third – middle-aged volunteers, who, like participants from the first group, moved very little throughout the day; in the fourth was the subjects of the same age, but active, that is, physical activity occupied a significant place in their daily life. There were few differences between the representatives of the first and second groups, but when they began to be compared with the subjects from the third and fourth groups, and then also decided to compare the participants of the last two groups with each other, it was possible to identify a significant difference. In middle-aged volunteers who were used to sitting all day, telomeres were 40% shorter than in young subjects, while in energetic participants from the fourth group, the sizes of chromosomal "caps" were only 10% smaller than in young representatives of the first two groups. In other words, telomere shortening was slowed down by 75% in active volunteers. This can most likely be explained by the fact that thanks to physical exercise, a person's resistance to stress increases and inflammatory processes slow down.
There are several promising areas in the field of telomere elongation research. For example, the study of the synthetic peptide epithalon – an analogue of epithalamine produced by the epiphysis. During the experiments, epithalon was injected into mice, and it turned out that their life expectancy increased by 13.3%, because, firstly, telomerase was activated, and secondly, apoptosis began and tumor growth slowed down. Telomerase is also being activated with the help of a biologically active supplement TA-65. This trademark hides cycloastragenol, a highly concentrated extract of the astragalus plant used in Ayurvedic medicine.
We do not yet know the results of studies with which we can get a complete picture of the ways to lengthen telomeres, so to begin with, it makes sense to do at least the following: avoid the influence of dangerous external factors, try not to stay in a state of emotional stress for a long time and ensure that sleep becomes strong – it is the latter that allows you to properly restore the energy consumed by the body for strong and sometimes not very pleasant feelings and emotions.
The book is provided by the publishing house Mann, Ivanov and Ferber. You can buy it here.
Portal "Eternal youth" http://vechnayamolodost.ru