Physics, not biology, makes aging inevitable.
Hi, Habr! I present to you the translation of the article Physics Makes Aging Inevitable, Not Biology . By Peter Hoffmann .
The insides of every cell of our body are like an overpopulated city filled with paths, vehicles, libraries, factories, power stations, and garbage chutes. The workers of this city are protein machines that digest food, take out garbage or restore DNA. Loads are moved from one place to another with the help of molecular machines moving on two legs along protein ropes. While these machines do their work, the thousands of water molecules surrounding them randomly crash into them millions of times a second. This phenomenon, which physicists euphemistically call "thermal motion", and which is more appropriate to call the monstrous thermal chaos.
It is puzzling how these molecular machines can do their job well in such unbearable conditions. Part of the answer is that protein machines in cells, like tiny ratchets , transform the energy of randomly bombarding water molecules into directional movement that causes cells to work. Turn chaos in order.
')
Four years ago, I published a book called “Ratchet Life” that explains how molecular machines create order in our cells. My main task was to show how life avoids diving into chaos. To my great surprise, soon after the book was published, researchers studying biological aging contacted me. At first, I did not see the connection between the theme of the book and aging, because I knew nothing about it except what I knew from observations of the aging of my body.
Then, from understanding the important role of thermal chaos in the work of molecular machines, enlightenment arose, and I encouraged aging researchers to think of this as the driving force of aging. Thermal movement may be useful in the short term, as an engine of molecular machines, but can it be harmful in the long run? Indeed, in the absence of external energy consumption, the random thermal motion tends to destroy order.
This trend is described by the second law of thermodynamics , which states that everything is aging and falling apart: buildings and roads are crumbling; ships and rails rust; the mountains are washed away into the sea. Inanimate structures are helpless against the destructive force of thermal motion. But life is different: protein machines constantly repair and renew cells.
This is the meaning of the opposition of life, as a biological form, to physics, in a battle with death. So why do living things die? Is aging the ultimate triumph of physics over biology? Or is aging part of biology itself?
If you look for the basic document for the modern level of research on aging, then it may be the “Unsolved problem of biology” by Sir Peter Medawar . Medawar, a Nobel Prize winner in biology, as well as a witty and sometimes caustic author of essays and books. In his book, Medawar put forward two opposing explanations of aging: on the one hand, “congenital aging", or aging as a biological necessity . On the other, the theory of "wear and tear," aging due to "accumulation of the effects of constant stress." The first is biology, the second is physics. Congenital aging implies that aging and death are products of evolution designed to free up space for new generations.
The idea of ​​innate aging suggests that within us there are major clocks counting the time of our life. Such watches are really available. The most famous are telomeres - small DNA fragments that shorten each time a cell divides. The results of the study of telomeres are contradictory, it is unclear whether telomere shortening is a cause or a consequence of aging. Telomeres are not reduced by a constant amount. There is a minimum value that falls on each cell division, and a faster shortening if the cell has been damaged in any way. Many researchers believe that telomere shortening is more a sign of aging than its cause.
Medawar himself advocated the theory of "wear" - the point of view of physics on aging. He stated that, firstly, it is difficult to explain how natural selection can act in old age, when people stop reproducing offspring, and natural selection is associated with the rate of reproduction. Secondly, there is no need to deliberately kill the elderly in order to reduce their number. Chance can do it yourself.
Medawar argued that the biological clock for aging is not needed. To illustrate why, he gave an example not from biology: test tubes in the laboratory. Suppose the tubes occasionally break from time to time, and are discarded. To keep the stock of tubes constant, we buy new ones every week. How many old and new tubes will there be in a few months? If we assume that the probability of accidental breakage does not depend on age (reasonable assumption), and plot the number of tubes depending on the age of each tube, we will get a falling exponential curve resembling a children's slide.
Death without aging. Computer simulation of the survival curve for randomly broken test tubes and its exponential approximation (in red). The vertical axis is the number of tubes in each age group, the horizontal axis is the age of tubes in weeks.
Although test tubes do not age (old test tubes do not break more easily than new ones), the constant probability of breakage significantly reduces the number of old test tubes. Suppose that people, like test tubes, are equally likely to die at any age. Then the number of older people will also be small. Probability will do the trick.
The trouble is that the survival curves constructed for human populations do not resemble the survival curve of the Medavar test tubes. They are almost horizontal at the beginning, with a small number of losses at a young age (except for newborns). Then, starting at a certain age, the curve begins to fall sharply. To get such a curve into the model of the Medavar tubes, one more assumption needs to be added: over time, the tubes must accumulate tiny cracks that increase the likelihood of their breaking. In other words, they must grow old. If the probability of failure increases exponentially, we get the curve described by the Gompertz-Meijheim law . This law describes well the human survival curve. As with test tubes, the law includes a constant and exponentially increasing probability of breakage. For humans, exponential growth is observed when the likelihood of death begins to double every seven years, after reaching 30 years.
What is the reason for this exponential growth? Thermal movement is not the only source of damage in our cells. Some regular processes, especially metabolism in our mitochondria, are not ideal , and tend to produce free radicals — highly reactive compounds that can damage DNA . Together, thermal noise and the formation of free radicals create a background risk of cell damage. Usually the damage is restored , if the cell is not subject to recovery, then it starts the process of suicide - apoptosis , and stem cells replace them.
However, damage accumulates over time. DNA can only be recovered when there is an intact copy to copy. Damaged proteins unfold and begin to stick together, forming aggregates . Cell protection and the mechanism of apoptosis are violated. "Aging cells" begin to accumulate in the organs, which leads to inflammation . Stem cells are not activated, or depleted. Mitochondria are damaged by reducing the energy supply that is necessary for the operation of molecular DNA repair machines. This is a vicious circle , which in technical language is called a chain of positive feedback. Mathematically, the presence of positive feedback leads to an exponential increase in risk, which can explain the shape of a person’s survival curve.
There are many explanations for aging in the scientific literature: protein aggregation, DNA damage, inflammation, and telomeres. But these are biological reactions to the root cause, which is the accumulation of damage due to thermal and chemical degradation. To prove that thermal effects do cause aging, it is necessary to observe people with different internal temperatures. This is impossible, but there are organisms that can be exposed to different temperatures without immediate consequences. In a recent article in Nature, a team at Harvard Medical School conducted a study on the temperature dependence of aging in the C. elegans roundworm, a simple and well-studied species. They found that the shape of the survival curve remains almost unchanged, but stretches or shrinks depending on temperature changes. Individuals living at lower temperatures had longer stretched survival curves, while worms living at higher temperatures had a shorter lifespan.
Moreover, the coefficient of stretching of the survival curve depended on temperature according to a scheme familiar to every scientist: the same dependence of the rate of breaking of chemical bonds on the temperature of thermal motion.
I saw a potential connection between breaking ties and aging people, even in my laboratory. When I first encountered the law of Gompertz-Meckheim, it seemed strangely familiar to me. In the laboratory, we use the atomic force microscope to study the probability of maintaining single molecular bonds. This microscope allows you to measure weak forces acting between two molecules. In a typical experiment, we attach one protein to a flat surface, and another to the end of a small spring. Allow the two proteins to bind to each other, then slowly pull the spring to apply force to the molecules. In the end, the bond between the two molecules is broken, and we measure the force applied for this.
This is a random process associated with thermal movement, each time the strength of the gap is different. But the graph of the dependence of the probability of maintaining a connection on the magnitude of the applied force looks the same as a graph of human survival with age. There is a particularly strong resemblance to the results for C. elegans, which suggest a possible link between protein breaks and aging, as well as between aging and thermal movement.
Common death Left: a survival plot for a person with an approximation by the Gompertz-Meijheim law. Right: a graph of the preservation of single protein bonds, depending on the applied force. Mathematically, the shape of the two curves is identical.
The research community on aging is actively discussing whether aging should be classified as a disease. Many researchers studying specific diseases, cellular systems, or molecular components would like their favorite subject matter to be clothed in the mantle of the cause of aging. But the very number of reasons put forward refutes this possibility. Leonard Hayflick, the discoverer of cellular aging, noted in his provocatively entitled article "Biological aging is no longer an unsolved problem," that "the common denominator that underlies all modern theories of aging is the change in molecular structure, and therefore function." The ultimate cause, according to Hayflick, "is a growing loss of molecular precision or an increase in molecular disturbances." This loss of accuracy and an increase in violations will manifest, by their very nature, in a random way, and, therefore, in different ways for different people. But the main reason remains the same.
If this interpretation of the data is correct, then aging is a natural process that can be reduced to nanoscale thermal physics, and not to disease. Up until the 1950s, the great successes achieved in increasing human longevity were almost entirely associated with the eradication of infectious diseases, a permanent risk factor that does not particularly depend on age. As a result, life expectancy has increased dramatically (average age at death), but the maximum human lifespan has not changed. An exponentially growing risk ultimately surpasses any reduction in persistent risk. Doing constant risk is useful, but up to a certain limit: permanent risk is environmental (accidents, infectious diseases), much of the exponentially growing risk is associated with internal wear and tear. The elimination of cancer or Alzheimer's disease would improve life, but that would not make us immortal or even prevent us from living much longer.
This does not mean that we can not do anything. More research is needed on specific molecular changes in the aging process. This can show us whether there are key molecular components that are first violated, and whether these violations lead to a subsequent cascade of failures. If such key components are available, then we will have clear goals for intervention and recovery, perhaps with the help of nanotechnology, stem cell research or gene editing. It is worth a try. But we must clearly understand: we will never defeat the laws of physics.
Nanoscale thermal physics guarantees our extinction, no matter how many diseases we cure.
The insides of every cell of our body are like an overpopulated city filled with paths, vehicles, libraries, factories, power stations, and garbage chutes. The workers of this city are protein machines that digest food, take out garbage or restore DNA. Loads are moved from one place to another with the help of molecular machines moving on two legs along protein ropes. While these machines do their work, the thousands of water molecules surrounding them randomly crash into them millions of times a second. This phenomenon, which physicists euphemistically call "thermal motion", and which is more appropriate to call the monstrous thermal chaos.
It is puzzling how these molecular machines can do their job well in such unbearable conditions. Part of the answer is that protein machines in cells, like tiny ratchets , transform the energy of randomly bombarding water molecules into directional movement that causes cells to work. Turn chaos in order.
')
Four years ago, I published a book called “Ratchet Life” that explains how molecular machines create order in our cells. My main task was to show how life avoids diving into chaos. To my great surprise, soon after the book was published, researchers studying biological aging contacted me. At first, I did not see the connection between the theme of the book and aging, because I knew nothing about it except what I knew from observations of the aging of my body.
Then, from understanding the important role of thermal chaos in the work of molecular machines, enlightenment arose, and I encouraged aging researchers to think of this as the driving force of aging. Thermal movement may be useful in the short term, as an engine of molecular machines, but can it be harmful in the long run? Indeed, in the absence of external energy consumption, the random thermal motion tends to destroy order.
This trend is described by the second law of thermodynamics , which states that everything is aging and falling apart: buildings and roads are crumbling; ships and rails rust; the mountains are washed away into the sea. Inanimate structures are helpless against the destructive force of thermal motion. But life is different: protein machines constantly repair and renew cells.
This is the meaning of the opposition of life, as a biological form, to physics, in a battle with death. So why do living things die? Is aging the ultimate triumph of physics over biology? Or is aging part of biology itself?
If you look for the basic document for the modern level of research on aging, then it may be the “Unsolved problem of biology” by Sir Peter Medawar . Medawar, a Nobel Prize winner in biology, as well as a witty and sometimes caustic author of essays and books. In his book, Medawar put forward two opposing explanations of aging: on the one hand, “congenital aging", or aging as a biological necessity . On the other, the theory of "wear and tear," aging due to "accumulation of the effects of constant stress." The first is biology, the second is physics. Congenital aging implies that aging and death are products of evolution designed to free up space for new generations.
The idea of ​​innate aging suggests that within us there are major clocks counting the time of our life. Such watches are really available. The most famous are telomeres - small DNA fragments that shorten each time a cell divides. The results of the study of telomeres are contradictory, it is unclear whether telomere shortening is a cause or a consequence of aging. Telomeres are not reduced by a constant amount. There is a minimum value that falls on each cell division, and a faster shortening if the cell has been damaged in any way. Many researchers believe that telomere shortening is more a sign of aging than its cause.
Life contrasts biology with physics in a deadly battle
Medawar himself advocated the theory of "wear" - the point of view of physics on aging. He stated that, firstly, it is difficult to explain how natural selection can act in old age, when people stop reproducing offspring, and natural selection is associated with the rate of reproduction. Secondly, there is no need to deliberately kill the elderly in order to reduce their number. Chance can do it yourself.
Medawar argued that the biological clock for aging is not needed. To illustrate why, he gave an example not from biology: test tubes in the laboratory. Suppose the tubes occasionally break from time to time, and are discarded. To keep the stock of tubes constant, we buy new ones every week. How many old and new tubes will there be in a few months? If we assume that the probability of accidental breakage does not depend on age (reasonable assumption), and plot the number of tubes depending on the age of each tube, we will get a falling exponential curve resembling a children's slide.
Death without aging. Computer simulation of the survival curve for randomly broken test tubes and its exponential approximation (in red). The vertical axis is the number of tubes in each age group, the horizontal axis is the age of tubes in weeks.Although test tubes do not age (old test tubes do not break more easily than new ones), the constant probability of breakage significantly reduces the number of old test tubes. Suppose that people, like test tubes, are equally likely to die at any age. Then the number of older people will also be small. Probability will do the trick.
The trouble is that the survival curves constructed for human populations do not resemble the survival curve of the Medavar test tubes. They are almost horizontal at the beginning, with a small number of losses at a young age (except for newborns). Then, starting at a certain age, the curve begins to fall sharply. To get such a curve into the model of the Medavar tubes, one more assumption needs to be added: over time, the tubes must accumulate tiny cracks that increase the likelihood of their breaking. In other words, they must grow old. If the probability of failure increases exponentially, we get the curve described by the Gompertz-Meijheim law . This law describes well the human survival curve. As with test tubes, the law includes a constant and exponentially increasing probability of breakage. For humans, exponential growth is observed when the likelihood of death begins to double every seven years, after reaching 30 years.
What is the reason for this exponential growth? Thermal movement is not the only source of damage in our cells. Some regular processes, especially metabolism in our mitochondria, are not ideal , and tend to produce free radicals — highly reactive compounds that can damage DNA . Together, thermal noise and the formation of free radicals create a background risk of cell damage. Usually the damage is restored , if the cell is not subject to recovery, then it starts the process of suicide - apoptosis , and stem cells replace them.
Elimination of cancer or Alzheimer's disease would improve life, but that would not make us immortal or even allow us to live much longer.
However, damage accumulates over time. DNA can only be recovered when there is an intact copy to copy. Damaged proteins unfold and begin to stick together, forming aggregates . Cell protection and the mechanism of apoptosis are violated. "Aging cells" begin to accumulate in the organs, which leads to inflammation . Stem cells are not activated, or depleted. Mitochondria are damaged by reducing the energy supply that is necessary for the operation of molecular DNA repair machines. This is a vicious circle , which in technical language is called a chain of positive feedback. Mathematically, the presence of positive feedback leads to an exponential increase in risk, which can explain the shape of a person’s survival curve.
There are many explanations for aging in the scientific literature: protein aggregation, DNA damage, inflammation, and telomeres. But these are biological reactions to the root cause, which is the accumulation of damage due to thermal and chemical degradation. To prove that thermal effects do cause aging, it is necessary to observe people with different internal temperatures. This is impossible, but there are organisms that can be exposed to different temperatures without immediate consequences. In a recent article in Nature, a team at Harvard Medical School conducted a study on the temperature dependence of aging in the C. elegans roundworm, a simple and well-studied species. They found that the shape of the survival curve remains almost unchanged, but stretches or shrinks depending on temperature changes. Individuals living at lower temperatures had longer stretched survival curves, while worms living at higher temperatures had a shorter lifespan.
Moreover, the coefficient of stretching of the survival curve depended on temperature according to a scheme familiar to every scientist: the same dependence of the rate of breaking of chemical bonds on the temperature of thermal motion.
I saw a potential connection between breaking ties and aging people, even in my laboratory. When I first encountered the law of Gompertz-Meckheim, it seemed strangely familiar to me. In the laboratory, we use the atomic force microscope to study the probability of maintaining single molecular bonds. This microscope allows you to measure weak forces acting between two molecules. In a typical experiment, we attach one protein to a flat surface, and another to the end of a small spring. Allow the two proteins to bind to each other, then slowly pull the spring to apply force to the molecules. In the end, the bond between the two molecules is broken, and we measure the force applied for this.
This is a random process associated with thermal movement, each time the strength of the gap is different. But the graph of the dependence of the probability of maintaining a connection on the magnitude of the applied force looks the same as a graph of human survival with age. There is a particularly strong resemblance to the results for C. elegans, which suggest a possible link between protein breaks and aging, as well as between aging and thermal movement.
Common death Left: a survival plot for a person with an approximation by the Gompertz-Meijheim law. Right: a graph of the preservation of single protein bonds, depending on the applied force. Mathematically, the shape of the two curves is identical.The research community on aging is actively discussing whether aging should be classified as a disease. Many researchers studying specific diseases, cellular systems, or molecular components would like their favorite subject matter to be clothed in the mantle of the cause of aging. But the very number of reasons put forward refutes this possibility. Leonard Hayflick, the discoverer of cellular aging, noted in his provocatively entitled article "Biological aging is no longer an unsolved problem," that "the common denominator that underlies all modern theories of aging is the change in molecular structure, and therefore function." The ultimate cause, according to Hayflick, "is a growing loss of molecular precision or an increase in molecular disturbances." This loss of accuracy and an increase in violations will manifest, by their very nature, in a random way, and, therefore, in different ways for different people. But the main reason remains the same.
If this interpretation of the data is correct, then aging is a natural process that can be reduced to nanoscale thermal physics, and not to disease. Up until the 1950s, the great successes achieved in increasing human longevity were almost entirely associated with the eradication of infectious diseases, a permanent risk factor that does not particularly depend on age. As a result, life expectancy has increased dramatically (average age at death), but the maximum human lifespan has not changed. An exponentially growing risk ultimately surpasses any reduction in persistent risk. Doing constant risk is useful, but up to a certain limit: permanent risk is environmental (accidents, infectious diseases), much of the exponentially growing risk is associated with internal wear and tear. The elimination of cancer or Alzheimer's disease would improve life, but that would not make us immortal or even prevent us from living much longer.
This does not mean that we can not do anything. More research is needed on specific molecular changes in the aging process. This can show us whether there are key molecular components that are first violated, and whether these violations lead to a subsequent cascade of failures. If such key components are available, then we will have clear goals for intervention and recovery, perhaps with the help of nanotechnology, stem cell research or gene editing. It is worth a try. But we must clearly understand: we will never defeat the laws of physics.
Postscript author translation.
1. An article under such a provocative title provoked heated discussions on several Internet sites, and forced the author to write a response to the comments of readers. I found it advisable to add a translation of this response (in the text of a blog post) to the article.
2. With the accumulation of damage in the body, it is possible to fight with different methods, which the users of Batin and arielf in their publications cheerfully tell us in their publications :) The most consistent approach to dealing with damage at all levels of the body is declared by the SENS research foundation.
3. The article focuses on the thermal movement of molecules and the formation of free radicals, as the basic causes of destructive changes in the body, leading ultimately to its aging and death. But little attention is paid to the macroscopic thermodynamic characteristics of this process, in particular, related to the basal metabolism , as an indicator of the level of metabolism, and its connection with other characteristics of organisms such as mass, growth time, maximum life expectancy, etc. With a favorable set of circumstances, I plan to fill this space by writing a separate article on this topic.
4. The article is limited in size, the author does not go into details, so added links for more information on the topics covered. The work of cellular molecular machines is clearly shown in the film The Secret Cell Life . However, the quality of video and sound leaves much to be desired.
Physics, Aging and Immortality
When I published The Ratchet of Life 2 years ago, I focused on how life can create and maintain highly ordered systems in the surrounding molecular chaos — in particular, how molecular machines “take order out of chaos.” To my surprise, the book aroused great interest in the field of research on aging. Aging, says Ed Lakatta, head of the Laboratory for Cardiology at the Institute of Aging NIH, takes "chaos out of order."
Given this interest, I was invited to write an article for the popular science magazine Nautilus (which I can only recommend). My article on aging appeared yesterday on the Internet under the provocative (not chosen by me) heading "Physics, but not biology, makes aging inevitable." My headline was "Aging: Where Physics Meets Biology." Which is probably more boring, but less provocative.
Since it was impossible to expand on this issue in 2000 words in the article, I will share a few additional thoughts about it here in my blog.
First, I looked at the comments on the article. Some recurring topics in the comments are that (1) a person is an open thermodynamic system, and therefore not subject to an increase in entropy (since we can always lower the entropy by getting energy from the environment), (2) that our cells have regenerative systems that can eliminate any disturbances that may occur, and (3) there are “immortal” cells and organisms that refute my assertion that aging is inevitable.
(1) and (2) have almost the same answer:
It is absolutely true that man is an open system. This is what I described in detail in my book. The consumption of low-entropic energy (food and oxygen, approx. Translator) is the reason that our cellular machinery can clean up the molecular chaos. However, molecular chaos is always present, the molecules in our cells are permanently damaged. Unlike other thermodynamically open self-organizing systems, such as a hurricane, living systems are tightly controlled systems consisting of complexly interconnected feedback circuits and control loops . These feedback loops rely on perfectly adapted and engineered molecular machines, intact DNA to carry out the program, as well as timely and accurate regulation and signaling. These systems interact through a hierarchy of molecules, organelles, cells, cell-cell interactions, tissues, organs, and at the level of the whole organism. They have many backup, backup and recovery systems.
However, some of these systems are subject to subtle damage. The energy supply slows down, signal chains are disturbed, synchronization of the feedback loop is upset, damaged molecules are not removed from the cells and accumulate over time, molecular machines do not function or are not activated. This loss of function can cause a loss of function in other systems, due to the interdependence of all systems in the body. This leads to an increasing cascade of failures. The beginning of this process is a matter of probability in a huge number of cells and functions. You can try to prevent one system from failing, but there are many others that will fail.
The recovery systems in our cells are excellent - they allow us to live up to 80+ years. We live longer than any mammal of comparable size and heart rate. Can we live even longer? In principle, restoration systems could be improved, but their complexity postpones this perspective for many years. Therefore, we will always be subject to a game of probabilities, which we will eventually lose.
3) Some readers point out that there are “immortal” organisms. One feature that can be seen in all these immortal organisms is that they are all very simple, usually single-celled or at least slightly differentiated. Examples are bacteria, but and such creatures as the so-called "immortal jellyfish" . The immortal jellyfish passes a stage in which it reverses the process of its development, returning from the adult to the larval stage, which can then develop into a new adult. This is in It may continue indefinitely, making the jellyfish “immortal.” At first glance, this seems surprising. However, in a sense, people do the same thing! Our embryonic lines are also “immortal.” But this differs from the aging of a complex adult. In comparison maintaining order at the molecular and systemic level in a complex organism for many years, maintaining DNA in the egg is a relatively easy task, but even there degradation occurs over time. This is the main reason why we multiply mainly at a young age, since birth defects are more common in aging mothers and fathers. As for jellyfish, as separate adults, they are clearly not immortal, as they must “die” in order to return to the larval stage. In addition, probably not all jellyfish do this transformation successfully, so the “immortality” is at the population level, and not at the individual level. But if this definition of "immortality", then people are immortal. But we usually do not use this definition!
Regular (somatic) human cells can also become immortal, this is called cancer . Cancer and aging are two sides of the same coin of molecular impairment. If our cells did not die at some point, molecular damage and DNA damage would continuously increase the likelihood of the cells becoming cancerous. The fee for maintaining our cells in the ranks is a tight regulation of cell division, growth and differentiation. The price for this tight regulation, which is facing the onslaught of thermal and chemical damage, is aging.
Given this interest, I was invited to write an article for the popular science magazine Nautilus (which I can only recommend). My article on aging appeared yesterday on the Internet under the provocative (not chosen by me) heading "Physics, but not biology, makes aging inevitable." My headline was "Aging: Where Physics Meets Biology." Which is probably more boring, but less provocative.
Since it was impossible to expand on this issue in 2000 words in the article, I will share a few additional thoughts about it here in my blog.
First, I looked at the comments on the article. Some recurring topics in the comments are that (1) a person is an open thermodynamic system, and therefore not subject to an increase in entropy (since we can always lower the entropy by getting energy from the environment), (2) that our cells have regenerative systems that can eliminate any disturbances that may occur, and (3) there are “immortal” cells and organisms that refute my assertion that aging is inevitable.
(1) and (2) have almost the same answer:
It is absolutely true that man is an open system. This is what I described in detail in my book. The consumption of low-entropic energy (food and oxygen, approx. Translator) is the reason that our cellular machinery can clean up the molecular chaos. However, molecular chaos is always present, the molecules in our cells are permanently damaged. Unlike other thermodynamically open self-organizing systems, such as a hurricane, living systems are tightly controlled systems consisting of complexly interconnected feedback circuits and control loops . These feedback loops rely on perfectly adapted and engineered molecular machines, intact DNA to carry out the program, as well as timely and accurate regulation and signaling. These systems interact through a hierarchy of molecules, organelles, cells, cell-cell interactions, tissues, organs, and at the level of the whole organism. They have many backup, backup and recovery systems.
However, some of these systems are subject to subtle damage. The energy supply slows down, signal chains are disturbed, synchronization of the feedback loop is upset, damaged molecules are not removed from the cells and accumulate over time, molecular machines do not function or are not activated. This loss of function can cause a loss of function in other systems, due to the interdependence of all systems in the body. This leads to an increasing cascade of failures. The beginning of this process is a matter of probability in a huge number of cells and functions. You can try to prevent one system from failing, but there are many others that will fail.
The recovery systems in our cells are excellent - they allow us to live up to 80+ years. We live longer than any mammal of comparable size and heart rate. Can we live even longer? In principle, restoration systems could be improved, but their complexity postpones this perspective for many years. Therefore, we will always be subject to a game of probabilities, which we will eventually lose.
3) Some readers point out that there are “immortal” organisms. One feature that can be seen in all these immortal organisms is that they are all very simple, usually single-celled or at least slightly differentiated. Examples are bacteria, but and such creatures as the so-called "immortal jellyfish" . The immortal jellyfish passes a stage in which it reverses the process of its development, returning from the adult to the larval stage, which can then develop into a new adult. This is in It may continue indefinitely, making the jellyfish “immortal.” At first glance, this seems surprising. However, in a sense, people do the same thing! Our embryonic lines are also “immortal.” But this differs from the aging of a complex adult. In comparison maintaining order at the molecular and systemic level in a complex organism for many years, maintaining DNA in the egg is a relatively easy task, but even there degradation occurs over time. This is the main reason why we multiply mainly at a young age, since birth defects are more common in aging mothers and fathers. As for jellyfish, as separate adults, they are clearly not immortal, as they must “die” in order to return to the larval stage. In addition, probably not all jellyfish do this transformation successfully, so the “immortality” is at the population level, and not at the individual level. But if this definition of "immortality", then people are immortal. But we usually do not use this definition!
Regular (somatic) human cells can also become immortal, this is called cancer . Cancer and aging are two sides of the same coin of molecular impairment. If our cells did not die at some point, molecular damage and DNA damage would continuously increase the likelihood of the cells becoming cancerous. The fee for maintaining our cells in the ranks is a tight regulation of cell division, growth and differentiation. The price for this tight regulation, which is facing the onslaught of thermal and chemical damage, is aging.
2. With the accumulation of damage in the body, it is possible to fight with different methods, which the users of Batin and arielf in their publications cheerfully tell us in their publications :) The most consistent approach to dealing with damage at all levels of the body is declared by the SENS research foundation.
3. The article focuses on the thermal movement of molecules and the formation of free radicals, as the basic causes of destructive changes in the body, leading ultimately to its aging and death. But little attention is paid to the macroscopic thermodynamic characteristics of this process, in particular, related to the basal metabolism , as an indicator of the level of metabolism, and its connection with other characteristics of organisms such as mass, growth time, maximum life expectancy, etc. With a favorable set of circumstances, I plan to fill this space by writing a separate article on this topic.
4. The article is limited in size, the author does not go into details, so added links for more information on the topics covered. The work of cellular molecular machines is clearly shown in the film The Secret Cell Life . However, the quality of video and sound leaves much to be desired.
Source: https://habr.com/ru/post/429056/
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