We are aging for a reason, but as a result of a special biological program. But in the world there is an African naked mole rat, a mouse-like animal unable to grow old.
Scientists have figured out why people age, but excavators do not.
Here is what Jared Sluyter writes about it:
The life of a separate individual, a separate individual of some biological species, is a very valuable thing, but there are things that are even more important. Namely, the view itself. That is, in fact, the complete set of genes (this is called a genome) that is contained in each individual of this species and, in fact, determines what it is.
It is more correct to consider any living creatures simply as a temporary receptacle for genes that they received from their parents and pass on to their children. For the first time, in an explicit form such an idea was formulated, probably, by Richard Dawkins in his famous book "The Selfish Gene".
As a rule, the interests of the genome and its temporary carrier (living creature) coincide. But sometimes it doesn't. And then it instantly becomes clear who is the boss - of course the genome.
If the genome of a species is in danger or the species just needs to develop, then the carrier can be safely sacrificed - the next generations will “give birth to new”.
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As a result, I am sure that the genomes of most (if not all) living things contain special harmful programs. From which the creatures themselves do not have anything good, but which are necessary for the development of the species. First of all, death programs that ensure the change of generations and, accordingly, evolution. And sometimes they are arranged in a "fast" way - for example, in annual plants, which die, killed by their own seeds after they ripen, and sometimes - in a "slow" way. And the nastiest slow suicide program is the aging program. Which makes many species, including you and me, “deteriorate” with age and, ultimately, die.
The fact that we are aging for a reason, but as a result of the activity of a special biological program, is not an obvious thing and requires proof. I tried to build it "by contradiction", showing you an example of an animal that turned off the aging program for itself. Because he no longer needs to accelerate his own evolution so much - he is already good! This, like you and me, is a mammal, a fairly close relative of an ordinary mouse - an African rodent, a naked mole rat! If a mouse lives for 2-3 years, manages to become completely old during this time and dies of old age, then a mole rat lives for more than 30 years, and if he sometimes shows some signs of aging, then they are usually not fatal. Most biologists agree that the naked mole rat is an ageless animal (well,or more scientifically, an animal with negligible aging).
And now, in our series, the time has come to answer the main "question about the diggers": how did he do it? How did he turn off his aging ??!
A couple of years ago I would have had nothing to say on this topic. But in 2017, in one of the most prestigious scientific journals in the world, Physiological Reviews, we managed to publish a theoretical work explaining the phenomenon of naked mole rat non-aging. At the end of 2017, a Russian version was released.
It all started, as always, with mitochondria. These are such small power plants that are in every cell and with which we breathe. I hope that there will be a separate episode of our series about them. The study of mitochondria is the main specialty of Academician Vladimir Petrovich Skulachev. Actually, in his laboratory at the end of the 60s it was found out how they work. For the last 20 years, the academician, in addition to mitochondria, has been interested in the problems of aging and, of course, made titanic efforts to conduct an experiment with the mitochondria of the naked mole rat. I should note that mitochondria are very strongly associated with aging, but more on that in the next series.
Research into the mitochondria of the naked mole rat has been crowned with success. At the institute at the Berlin Zoo, experiments were carried out on mole rats, and an employee of Vladimir Skulachev, the famous biologist Mikhail Vysokikh, who had specially arrived from Moscow for this, managed to obtain a sample of the tissue of a mole rat and measure various parameters of the mitochondria in this tissue. There was nothing particularly interesting in them, except for a slightly strange curve showing the rate of oxygen absorption by mitochondria (they also breathe) under certain conditions.
Returning to Moscow, Mikhail showed this curve to the leader, whom she also reminded something, but what exactly - they could not remember. So biologists racked their brains until they showed the graph to another colleague, the head of the cell bioenergy laboratory Boris Chernyak, who is known for never forgetting anything (well, at least if it is connected with mitochondria, respiration and living cells). He looked and immediately said - exactly the same curve can be obtained by registering the respiration of the mitochondria of newborn rat pups!
And here Vladimir Petrovich had one idea. Capturing him so much that he packed up and went to Berlin to personally look at the naked mole rat.
What did he find? That he (the mole rat) is naked. And do you know who he looks like because of this?
Look at the photo of a naked mole rat. And nearby - not diggers at all. These are newborn rats. See how similar they are? In a few days, the pups will grow up, dress with fur and turn into normal rats. And the diggers are not. He will remain so for life and will remain, as it were, a newborn.
Further investigation showed that the mole rats have more than 40 signs of such a "newborn" or "childishness" compared to rats. Here are some of them:
- Low weight compared to other species of the family.
- Lack of hair (rodents always have it).
- Lack of auricles.
- Limited ability to maintain a constant body temperature (as in newborn mammals).
- High cognitive abilities (curiosity).
- Low susceptibility to pain.
- The ability of neurons to regenerate and increase the lifespan of neurons.
- No decline with age in the level of insulin-like growth factor 2 (IGF2).
- No decrease with age in the levels of superoxide dismutases 1 and 2, as well as catalase.
- And also a few dozen more external, physiological and biochemical signs.
That is, it turns out that the mole rat stopped the program of his individual development at the stage of a newborn rodent. A similar phenomenon has been described earlier for, for example, amphibians, and it is called neoteny. For the sake of fairness, it must be said that Vladimir Skulachev was not the first to draw attention to the fact that the mole rat is a neotenic animal. Before him, this was noticed by Richard Alexander in 1991 and some other scientists. But they did not at all connect this phenomenon with longevity (Alexander simply did not know about the life span of these animals).
Stuck in childhood
Academician Skulachev formulated a very simple idea: if the mole rat stopped at the cub stage, then his program of individual development simply does not reach the point when it is time to start aging. Children don't grow old! Thus, we get the most important proof: aging is part of the program for the development and life of the body. The same as birth, growth, maturation. And if this whole program is stopped, then aging too!
This is what happened to the diggers. If this happened to an ordinary species, it would disappear very soon, because in the absence of aging, its evolution would slow down greatly. And the digger saved his eusociality. Life in the "anthill mode" turned out to be so much more stable that he could afford to turn off aging as an evolutionary tool.
And it seems that in the evolution of the most interesting species of biological creatures for us - Homo sapiens - exactly the same story began that happened with the naked mole rat. Have you ever noticed that people are most like … baby monkeys?
Is it possible to prolong life and stay young for a long time? Everything is real, scientists say, because over five hundred years, the life expectancy of people has almost tripled. Still, why are we getting old?
What is aging?
Aging is usually called the biological process of gradual decrease or complete shutdown of the vital functions of the body. Due to aging, the body adapts worse to the environment, the ability to regenerate tissues decreases, diseases and metabolic disorders are acquired.
The external result of aging is muscle sagging, wrinkles, and gray hair.
Of course, you can do plastic surgery, use makeup and have a good doctor, but you can't cheat your age. However, you need to know - everyone ages differently, and this is the merit of the person himself. There are men and women in their fifties who look gorgeous, and there are forty-year-olds who seem to be "well over fifty."
Aging theories and hypotheses
Nobody knows the exact reason why we are aging, and hence hypotheses and speculations are born - more or less supported by scientific data. Each of them has supporters, but, most likely, the true reasons will be in the merging of theories.
First of all, the body is aging due to the fact that each cell of the body has its own program - how and how many times to share it, replacing "oldies" with "new recruits". In each of the cells, on average, these replacements occur about seventy times.
How soon these seventy times will occur in each of the cells depends on the body and metabolism, on your attitude to your body. If you do not monitor your health, do not eat well and are exposed to harmful environmental factors, the body cells have to renew themselves more often, their resource is depleted faster.
For example, the skin ages much faster from frequent and intense sunburn, when it acquires a chocolate hue, and especially when sunburned sharply and with burns.
Another reason for aging is considered to be the launch of a program of self-destruction of cells due to their active damage by environmental factors and internal disorders. A damaged cell is potentially dangerous for the body by degeneration into a tumor, therefore, the slightest defects in cells are a start to launching a "cleaning system", and sometimes this is carried out with very drastic measures, with the capture of all neighboring cells and the death of entire areas in tissues or organs.
According to this principle, liver damage occurs with excessive libation, damage to the bronchi and lungs when smoking, damage to blood vessels in atherosclerosis. A similar principle of cell death works during heart attacks or strokes - this is the death of non-viable cells.
Could it be genes?
The gene theory of aging is gaining popularity among the scientific world today, it would explain a lot - both the launch of a certain number of divisions, and the death of cells when damaged, and even a change in metabolism with age.
If we can isolate the aging gene, now that we can combine and change genes, we can cancel old age. True, the abolition of death threatens to overpopulate the planet and its destruction in several years. But nobody wants to die!
Why are we getting old?
Until the genes are found, we propose to consider the reasons that bring closer acquaintance with it. Most of them are created by ourselves.
Look closely at your life - this is a series of stresses with an overexertion of the nervous system, problems at home and at work, children with lessons and bruises, broken knees - all this adds to our gray hair. Stress undermines immunity and health, disrupts sleep - and chronic lack of sleep significantly shortens life expectancy. Therefore, if you want to live a long time, learn how to properly rest and relax.
Other causes of premature aging are decreased physical activity and extra pounds. They deposit fat in the region of the heart and blood vessels, the kidneys and intestines float with fat - will this add to your health and long years? It's time, probably, to reconsider your eating habits, eat less, go on a diet, walk more often and play sports.
Addictions that shorten our already short life are also cigarettes and alcohol, even weak ones. It is believed that from one cigarette, life becomes eight minutes shorter. Calculate how much time from your life have you already put in the smoke? And taking more than one glass of dry wine a day is minus 24 hours of your life and minus a thousand liver cells, is the dubious pleasure of your health worth it?
Another "killer" of your body is … sugar, this sweet crystalline powder is as harmful as cigarettes. After all, we consume it much more than it is physiologically required. However, you shouldn't replace it with sweeteners - they are even more harmful.
Of course, solar radiation, ultraviolet rays, polluted air and heavy metals in it and water also affect, however, all this influence is negligible in comparison with our own "experiments" on the body. You need to think about it - most of the causes of aging mainly depend on us.
Occasionally there are people to whom ordinary laws and regulations do not apply - they can do without sleep, do not become infected with dangerous infections during the most terrible epidemics. However, there is no person who is not subject to aging. All living things grow old, destroyed and perish. And even inanimate nature: buildings, stones, bridges and roads - also gradually decay and fall into disrepair. Obviously, aging is a certain obligatory process, common for living and inanimate nature.
In 1865, the German physicist R. Clausis shed light for the first time on the underlying causes of this phenomenon. He postulated that all processes in nature proceed asymmetrically, unidirectionally. Destruction happens by itself, and creation requires the expenditure of energy. Due to this, entropy is constantly growing in the world - energy depreciation and chaos increase. This fundamental law of natural science is also called the second law of thermodynamics. According to him, for the creation and existence of any structure, an influx of energy from the outside is required, since energy itself tends to dissipate in space (this process is more likely than the creation of ordered structures). Living organisms belong to open thermodynamic systems: plants absorb solar energy and convert it into organic and inorganic compounds,animal organisms decompose these compounds and thus provide themselves with energy. At the same time, living beings are in thermodynamic equilibrium with the environment, gradually give or dissipate energy, supplying entropy to the world space.
It turned out, however, that the existence of living organisms is not completely exhausted by the second law of thermodynamics. The patterns of their development are explained by the third law of thermodynamics, substantiated by the outstanding Belgian scientist I. Prigozhin, a native of Russia: the excess of free energy absorbed by an open system can lead to self-complication of the system. There is a certain level of complexity, below which the system cannot reproduce its own kind.
Living organisms, in a sense, resist the growth of entropy and chaos in the Universe, forming more and more complex structures and accumulating information. This process is the opposite of the aging process. Such a struggle with entropy is possible, apparently, due to the existence of a timeless genetic program, which is repeatedly rewritten and passed on to future generations. A living organism can be compared to a book that is constantly being reprinted. The paper on which the book is written may wear out and deteriorate, but its content is eternal.
Immortal bacteria
When we talked about the fact that all living things are subject to aging, we made an inaccuracy: there are situations to which this rule does not apply. For example, what happens when a living cell or bacterium divides in half during reproduction? It gives rise to two other cells, which in turn divide again, and so on ad infinitum. The cell that gave rise to all the rest did not have time to grow old; in fact, it remained immortal. The question of aging in unicellular organisms and continuously dividing cells, such as reproductive or tumor cells, remains open. A. Weisman at the end of the nineteenth century created a theory that postulated the immortality of bacteria and the absence of aging in them. many scholars agree with it today, while others question it. There is enough evidence for both.
What about multicellular organisms? After all, most of their cells cannot constantly divide, they must perform some other tasks - to provide movement, nutrition, regulation of internal processes. This contradiction between the need for specialization of cells and the preservation of their immortality has been resolved by nature by dividing cells into two types. Somatic cells support vital processes in the body, and germ cells divide, ensuring the continuation of the genus. Somatic cells age and die, while sex cells are practically eternal. The existence of huge and complex multicellular organisms containing trillions of somatic cells, in essence, is aimed at ensuring the immortality of the germ cells.
How does aging of somatic cells take place? The American researcher L. Hayflick established that there are mechanisms limiting the number of divisions: on average, each somatic cell is capable of no more than 50 divisions, and then it grows old and dies. The gradual aging of the whole organism is due to the fact that all its somatic cells have exhausted the number of divisions allocated to them. After this, the cells age, break down and die.
If somatic cells violate this law, they divide continuously, reproducing their new copies many times. This does not lead to anything good - after all, this is how a tumor appears in the body. The cells become "immortal", but this imaginary immortality is ultimately bought at the cost of the death of the whole organism.
From mouse to elephant
The problem of aging is directly related to the issue of different life expectancy in different organisms. The German physiologist M. Rubner in 1908 was the first to draw the attention of scientists to the fact that large mammals live longer than small ones. For example, a mouse lives 3.5 years, a dog - 20 years, a horse - 46, an elephant - 70. Rubner explained this by different metabolic rates.
The total expenditure of energy in different mammals during life is approximately the same - 200 kcal per 1 gram of mass. According to Rubner, each species is able to process only a certain amount of energy - having exhausted it, it dies. The metabolic rate and total oxygen consumption depend on the size of the animal and the surface area of the body. The mass increases in proportion to the linear dimensions of the body, taken in a cube, and the area, in a square. An elephant needs much less energy to maintain its body temperature than an equal number of mice by weight - the total body surface of all these mice will be significantly larger than that of an elephant. Therefore, an elephant can "afford" a much lower metabolic rate than a mouse. This high energy expenditure in the mouse leads to the fact that it depletes the energy reserves allocated to it faster,than an elephant, and its lifespan is much shorter.
Thus, there is an inverse relationship between the metabolic rate of the animal and the duration of its life. Low body weight and high metabolism result in a short lifespan. This pattern was called the Rubner surface energy rule.
Despite the convincing simplicity of the rule discovered by Rubner, many scientists did not agree with him. They doubted that the rule explains the reasons for the aging of all living organisms - there are many exceptions to it. For example, a person does not obey this law: his total energy expenditure is very high, and his life expectancy is four times longer than it should be with such an exchange. What is the reason for this? The reason has only recently become clear.
Oxygen must be handled with care
There is another factor that determines lifespan - this is the partial pressure of oxygen. The oxygen concentration in the air is 20.8 percent. A decrease or an increase in this figure is possible only within narrow limits, otherwise living organisms die. It is well known that the lack of oxygen is fatal to the living. But few are aware of the danger of its excess. Pure oxygen kills laboratory animals within a few days, and at a pressure of 2-5 atmospheres, this period is reduced to hours and minutes. So this gas is not only necessary for life, it can also be a terrible universal poison that kills all living things. Many scientists believe that the Earth's atmosphere in the early period of its development did not contain oxygen, and it was this circumstance that contributed to the emergence of life on our planet. According to rough estimates of experts,The oxygen-rich atmosphere of the Earth was formed about 1.4 billion years ago as a result of the vital activity of primitive organisms capable of photosynthesis. They absorbed solar energy and carbon dioxide and gave off oxygen. Their existence created the preconditions for the emergence of other types of living organisms - those consuming oxygen for breathing. However, living beings had to take care to neutralize the toxicity of this substance.to neutralize the toxicity of this substance.to neutralize the toxicity of this substance.
The oxygen molecule itself and the product of its complete reduction with hydrogen - water - are not toxic. However, oxygen reduction proceeds in such a way that products that damage cells are formed at almost all stages of the process: superoxide anion radical, hydrogen peroxide and hydroxyl radical. They are called reactive oxygen species. Organisms that use oxygen for respiration, using enzymes and protein catalysts, prevent the production of these substances or reduce their harmful effects on cells.
American biochemists J. McCord and I. Fridovich in 1969 discovered that the main role in this protection is played by the enzyme superoxide dismutase. This enzyme converts superoxide anion radicals into more harmless hydrogen peroxide and molecular oxygen. Hydrogen peroxide is immediately destroyed by other enzymes - catalase and peroxidases.
The discovery of the mechanism of neutralization of reactive oxygen species provided a key to other researchers to understand the problems of radiobiology, oncology, immunology, and gerontology. The English researcher D. Harman put forward the so-called free radical theory of aging. He suggested that age-related changes in cells are due to the accumulation of damage caused by free radicals - fragments of molecules that have an unpaired electron and therefore have increased chemical activity. Such free radicals can form in cells under the influence of radiation, certain chemical reactions and temperature changes. But the main source of free radicals in the body is the reduction of the oxygen molecule. Therefore, we can say that aging in general is a consequence of the destructive, toxic effect of oxygen on the body,which gradually increases with age.
Biochemistry of aging
After it became clear that superoxide dismutase plays the role of an “antiaging enzyme” in the cell, the researchers wondered if the activity of this enzyme is the key cause of age-related changes and differences in lifespan? It was expected that with age, the enzyme activity decreases, and the destructive effect of oxygen increases. It turned out, however, that the activity of superoxide dismutase in most cases changes very little with age.
The accumulation of age-related changes in cells depends on the ratio of two processes: the formation of free radicals and their neutralization. The "factories" of free radicals are small elongated bodies inside the cell - mitochondria, its energy stations. D. Harman called these structures the molecular clock of the cell: the faster the production of radicals goes in them, the faster the hands on the clock spin and the less time the cell has to live. In species with a short lifespan, mitochondria work very actively, more radicals are formed and damage to cell structures accumulates faster, leading to its premature aging. For example, in a house fly, mitochondria produce radicals 24 times more intensively than in a cow. The researchers conducted the experiment:houseflies were kept in an atmosphere of pure oxygen (this significantly accelerates aging) and observed what happens to the mitochondria. The system of protection against reactive oxygen species works quite reliably, but individual radicals, which did not have time to interact with antioxidant enzymes, constantly slip through it. The reason for this problem is apparently the second law of thermodynamics, which excludes one hundred percent efficiency of energy processes. Once formed in the cell, radicals damage its internal structures, as well as the membranes of the mitochondria themselves, which increases leakage. As a result, there are more and more reactive oxygen species, and they gradually destroy the cell. What we call aging is happening. The system of protection against reactive oxygen species works quite reliably, but individual radicals, which did not have time to interact with antioxidant enzymes, constantly slip through it. The reason for this problem is apparently the second law of thermodynamics, which excludes one hundred percent efficiency of energy processes. Once formed in the cell, radicals damage its internal structures, as well as the membranes of the mitochondria themselves, which increases leakage. As a result, there are more and more reactive oxygen species, and they gradually destroy the cell. What we call aging is happening. The system of protection against reactive oxygen species works quite reliably, but still separate radicals constantly slip through it, which did not have time to interact with antioxidant enzymes. The reason for this problem is apparently the second law of thermodynamics, which excludes one hundred percent efficiency of energy processes. Once formed in the cell, radicals damage its internal structures, as well as the membranes of the mitochondria themselves, which increases leakage. As a result, there are more and more reactive oxygen species, and they gradually destroy the cell. What we call aging is happening.the second law of thermodynamics, which excludes one hundred percent efficiency of energy processes. Once formed in the cell, radicals damage its internal structures, as well as the membranes of the mitochondria themselves, which increases leakage. As a result, there are more and more reactive oxygen species, and they gradually destroy the cell. What we call aging is happening.the second law of thermodynamics, which excludes one hundred percent efficiency of energy processes. Once formed in the cell, radicals damage its internal structures, as well as the membranes of the mitochondria themselves, which increases leakage. As a result, there are more and more reactive oxygen species, and they gradually destroy the cell. What we call aging is happening.
The rate of “delivery” of radicals into the cell also increases in various mammalian organs as the organism ages. The amount of free radicals formed in the cell, apparently, the greater, the higher the level of oxygen consumption, or the intensity of metabolism. The American gerontologist R. Cutler and his collaborators showed that the life span of animals and humans is determined by the ratio of superoxide dismutase activity to metabolic rate. It became clear why in some species with a high level of energy expenditure, including humans, the lifespan does not fit into the energy rule of the Rubner surface. The high level of activity of superoxide dismutase protects humans and animals with an intensive metabolism from premature aging.
Answers on questions
The new theory of aging made it possible to find an explanation for some facts that are well known to gerontologists, but remained incomprehensible. For example, why do animals fed a low-calorie but balanced diet live longer than those fed enough? The answer was obvious - because limited nutrition reduces the intensity of metabolism and, accordingly, slows down the accumulation of damage in cells. The dependence of the aging rate on the ambient temperature in animals that are unable to regulate body temperature has also become clear. The high temperature keeps their metabolic rate high. So, the fruit fly of Drosophila hatches from the larva at a temperature of 10 degrees and develops into an adult insect, grows old and dies within 177 days, and at a temperature of 20 degrees - within 15 days. In an earthworm, when its body temperature rises from 15 degrees to 30 degrees, oxygen consumption increases 2.5 times. At the same time, the activity of superoxide dismutase increases by 28 percent, but the life of the worm is still shortened.
The longer life expectancy of women compared to men (on average by 10 years) was associated with a lower metabolic rate in the beautiful half of humanity. The phenomenon of longevity in mountainous regions is also well explained by the lower metabolic rate in people living in thin air: the oxygen content there is less than in the plains.
It turned out that the cells within the same human body also have different periods of time: the more superoxide dismutase in the cells, the less the degree of cell damage by reactive oxygen species, the longer the cells live. Therefore, some blood cells, for example, live for several hours, others for several years.
It was also possible to explain a curious phenomenon that researchers discovered long ago: changes in the body during natural aging are similar to the action of ionizing radiation. The reason became obvious: after all, when exposed to radiation, water decomposes with the formation of reactive oxygen species, which begin to damage cells.
All this made it possible to develop a strategy for the search for anti-aging agents. For example, it was possible to increase the life of laboratory animals by one and a half times by introducing strong antioxidants into their diet. Antioxidants such as superoxide dismutase, which are enzymes, should be especially effective. The introduction of superoxide dismutase into the body of animals protected them from the toxic effects of oxygen and increased their lifespan. This gives hope that antioxidants can be used in the fight against human aging. Perhaps, after a while, older people will take them in the same way as vitamins to improve their well-being and slow down the aging process.
