The cause of aging is life
What is aging?
Vadim Gladyshev, Post-science
Chronic human diseases have a characteristic age structure: they are practically absent in youth, but the older a person is, the more they appear. Age is the main risk factor for chronic diseases. If we find a mechanism of influence on this process, then chronic diseases can be "pushed aside". In this formulation, aging becomes the most important issue of biology, but how to define it? Oddly enough, it still remains unclear.
A couple of months ago I was at a conference on the topic of aging in Canada, they conducted a survey there. Experts from the conference were asked: "What is aging?" 35 people answered, it turned out 35 different definitions.
On an intuitive level, we understand that aging is associated with the passage of time of the body's life, with loss of functions, with the accumulation of damage and with the probability of mortality. But all these features of aging vary greatly in different situations. For example, time may flow and mortality may not increase, or damage may accumulate, but this will not lead to loss of function.
Programmed aging
In the XIX century . German scientist August Weissmann suggested that aging is a programmed process: there is a special program that leads to aging and death of organisms in order to free up space and resources for the next generations. Such a program will definitely be genetic, which means that there are genes on which selection is so strong that they are found in all complex organisms on Earth.
For example, this idea can be compared with the development process – this is a specific program that has many genes, and each gene can be "cut down", confused. If you delete specific genes, the program will be disrupted, and the body will stop developing. But in the case of the program theory of aging, there is not a single case where the process of cutting down genes worked according to the same scheme.
The evolutionary theory of aging
There are other ideas about aging, such as evolutionary theories of aging. One such theory was proposed by Nobel laureate Peter Medawar. He suggested that aging is associated with the accumulation of mutations that have a harmful effect on the old organism. When an organism has already left offspring, it becomes unimportant for procreation, the power of selection decreases, and it is easier for mutations to leak out. At a young age, these mutations have no effect, so the body does not remove them, and when the effect begins to manifest, it will be too late.
A concept similar to the evolutionary idea was proposed by George Williams. He came up with the theory of antagonistic pleiotropy. Williams suggested that mutations are harmful in old age, but give an advantage at a young age. For example, there is a new gene that allows us to be stronger or see better, think better. This gene will be fixed during evolution, even if it has a pronounced harmful effect at the end of life, so it is impossible to get rid of such genes. The theories of Medawar and Williams were proposed almost sixty years ago, but so far nothing is specifically known about mutations, their number, the number of genes that are antagonistically pleiotropic, so there are many questions.
Harmful functions of oxygen
The next idea proposed for the definition of aging is the free radical theory of aging. It is associated with the harmful function of oxygen. Oxygen is a necessary molecule that we inhale. But oxygen is still reactive and leads to damage to other molecules. For example, DNA, carbohydrates, and proteins can be damaged by oxygen. American physician Denham Harman suggested that these injuries accumulate and the body dies from them in old age. But in this theory it remains unclear why oxidative damage is the most harmful. There are other injuries in the body, so this theory has been criticized, and now it is unpopular.
Another theory was proposed by the British chemist Leslie Orgel. He began to look at the damages that are associated with the most important processes, for example, the process of creating proteins. But, despite the importance of these processes, they do not cover the whole biology, so the choice of processes remains unclear.
The theory of the expenditure amount
The next idea is the theory of the expenditure amount, which was proposed by the British scientist Tom Kirkwood. He said that organisms live in conditions of limited resources, so they always have to fight for them. If resources are limited, and they need to be partially spent on reproductive function, then the maintenance of the body cannot be one hundred percent effective, therefore damage accumulates, and the body dies.
There are questions to this theory related to the fact that all organisms always exist in conditions of limited resources. It is possible to imagine a situation when an organism has been living in conditions of full abundance of resources for several generations, but even such an organism will show aging.
Theory of hyperfunction of aging
The last and one of the main theories was proposed by the Russian oncologist Mikhail Blagosklonny. He presented the theory of hyperfunction, which is related to the ongoing development. A person reaches puberty, finishes development, but this trajectory continues further, it cannot be stopped, because there is not one hundred percent selection. As a result, the damage still accumulates, and the body dies. Regarding the aspect with damages, the theory of the Benevolent is partially related to the evolutionary theory.
Useful and harmful functions of protein
There are many different lines of thought, but all these theories only partially describe aging, so there is still no common understanding in terms of the definition and essence of aging.
In order to understand the main idea of aging yourself, it is necessary to study protein. Let's take a protein that supports some kind of biological function of the body. It is encoded by a gene, so this function has a genetic program. But this protein is not perfect, because there is nothing perfect in biology. Protein is built from only 20 types of amino acids. This is a kind of polymer that sometimes interacts with the wrong thing, or produces the wrong product. In other words, there is a non-zero probability that a protein that supports a specific function will produce some kind of damage, it will have a harmful function. This means that the protein has a positive function encoded in the genome, and there is a harmful function that is a consequence of the positive function, and it is also indirectly programmed in the genome.
If we extend this idea to other biological molecules, then we can say that all the damage and other harmful effects of life come from biological functions. Let's imagine tens of thousands of functions that are associated with different genes and with the integration of these processes. If you add up the harmful functions of molecules and external damage, then there will always be more damage than functions.
It is very difficult to detect all these injuries, so it is impossible to say exactly how the body copes with all the damage. On the one hand, we have many protective systems: enzymes that remove damage, transporters, kidneys, lymphatic system, stem cells. But even such a number of protective systems cannot cover all the variety of damages.
It is important to understand that there is no major damage. Aging is not only associated with mitochondria, or telomeres, or DNA damage. It is associated with all the consequences of all the functions in the body that exist. Aging happens because we live. The main cause of aging is life. Aging is a more complex process than life, than metabolism. But this complexity is important for us, because we understand who our enemy is, and having understood this, we can come up with experiments that will allow us to fight this process, push it aside.
About the author: Vadim Gladyshev is a professor at Harvard Medical School.
Portal "Eternal youth" http://vechnayamolodost.ru