You can 't forbid living for a long time

How the human body ages

Daria Stepanenko, Newspaper.Roo

Why do people start to age at 20-25, at what age the body loses the ability to cope with new diseases, and also what progress scientists have made in the fight against old age, says the science department of the newspaper.Ru».

Old age is just around the corner

With age, the signs of old age manifest themselves more and more: bones become more fragile, muscle tone decreases, gray hair appears, the efficiency of the cardiovascular system decreases, antibodies are produced worse in the immune system, diseases "stick" more often, and it is more difficult to cure them, memory disorders are observed and the activity of the nervous system is disrupted. At the same time, there is no unified theory of the appearance of causes and effects of old age today. Moreover, old age is not considered a disease at all.

It is well known that aging is very closely related to the development of the mature state (the state of the body before reaching reproductive age). If a representative of a certain species grows and develops quickly, then his life expectancy will be small. If you understand exactly how the rate of development of the body is regulated, then it will be possible to influence the aging processes, scientists believe. For example, a person can live up to 100 years, and the age of a macaque is limited to 30 years, although "only" 30 million years ago, the ancestors of humans and macaques were one species. What is the reason for such global differences in the life expectancy of different species, scientists are still unclear.

In general, aging is a process caused by many factors, the effect of which accumulates throughout life and leads to increased vulnerability of the body. Scientists do not always manage to unambiguously trace the causal relationship "old age - disease" or "disease – old age", but they certainly agree on one thing: it is necessary to fight old age on all fronts. What fronts do scientists distinguish?

"Leukocyte Factory"

The body begins to age in 20-25 years. At this age, we begin to get sick more often, and it becomes more difficult to be treated. The thing is that the obstacle to diseases in the body is immunity, whose main function is the recognition and destruction of "foreign" cells among "their own". Immune cells – lymphocytes – fall from the bone marrow into the thymus gland of the body, which is also called the thymus (translated from Greek – "life force"). These cells are able to fight infectious microorganisms, viruses and other foreign elements. They regularly enter the bloodstream in large numbers and "patrol" the blood vessels.

The problem is that the thymus gland develops only until puberty, that is, until about 20 years, after which the process of its degradation begins. Lymphocytes are formed less and less, the level of protection of the body is greatly reduced. By the age of 40, the body can still fight with diseases known to it, but against new, newly arisen diseases it becomes practically powerless. Therefore, with age, people begin to get sick more often.

Is thymus wilting a process programmed by evolution or the result of the accumulation of errors? Rather the first than the second. But scientists are still working on this problem. For example, it has been shown that a change in just one gene in the roundworm nematode C. elegans leads to a doubling of its lifespan. A person has a much more complex organization than a worm, but it can still be considered a small victory.

A person is made up of organs, organs are made up of tissues, and tissues are made up of trillions of cells. Accordingly, the aging of a person is the aging of his cells, or rather, their information-hereditary system stored in the nuclei. In fact, cells are the "koshcheev egg" of our body.

Imagine that each cell is a small cube, and a person is a self–assembling constructor. This constructor is so complex that inside each cube there is an assembly instruction (its role is performed by the hereditary information of the cell – DNA), and each detail itself knows where its place is, and moves to it in small steps. The realization of hereditary information and the movement of the cell in the right direction is carried out thanks to internal molecular machines, which, unfortunately, do not work with impeccable accuracy at all.

And even the presence of reparative mechanical machines aimed at correcting the flaws of assembly machines cannot guarantee that the hereditary instruction will be executed without distortion. There are many reasons for this. When the time comes, the cell divides into two identical parts. This is preceded by doubling all the internal components of the cell so that each daughter cell gets the same complete set. The most difficult thing in this process is to make an exact copy of the instructions for the subsequent assembly.

A molecular machine called DNA polymerase, which copies hereditary information, makes mistakes with a frequency of once per million nucleotides it reads. Excellent accuracy, as it may seem. But there are about 10 ⁴ nucleotides in one gene, the number of genes in the genome is 3*10 ⁴, and the total number of cells that need to be shared in the human body is 10 ¹³. It turns out that a lot of errors are allowed in the sum and over time they accumulate in the genome. The more often a cell divides, the more errors accumulate. Thus, the cell always seems to be faced with a choice: either to divide frequently, thereby increasing the risks of mutations, or to reduce its activity and divide less frequently, thereby reducing the growth rate of the cell population, which can be critical if the cells live in an aggressive environment. The second strategy is chosen by neurons that are practically incapable of dividing. Human stem cells also try to divide as little as possible so as not to accidentally cause a mutation.

But not all cells can afford a static existence, because if they do not divide, then there will simply be no one to work in the body.

It turns out that time is working against us. The older a person is, the more mutations there are in his cells, and when there are too many of them, the cell stops dividing altogether and dies – goes into a state of apoptosis. Attempts to strengthen the cell repair apparatus can bring victory on this battlefield. But the artificial cancellation of apoptosis is a contradictory idea. This can be done by making cells immortal, but an endless life with a set of all kinds of diseases caused by mutations is not what people dream of.

Division limit

In 1961, Leonard Hayflick, a professor of anatomy at the University of California, established that human skin cells in laboratory conditions have a limit of division – no more than 50 times, after which they will die. The phenomenon was called the "Hayflick limit", but the reason for this behavior of the cell became clear later.

At each cell division, the end sections of the hereditary "instruction" (DNA), called telomeres, cannot be copied completely, which is due to the specifics of the copying mechanism. Consequently, with each cell division, the ends of telomeres are slightly shortened. At some point, the "edges" of DNA are shortened so much that the cell can no longer divide at all. This, according to the telomeric theory, is the essence of the aging process of cells.

This theory was simultaneously developed by American scientists Elizabeth Blackburn, Carol Greider, Jack Shostak and Soviet scientist Alexey Olovnikov. Later it turned out that a special enzyme – telomerase – can protect the ends of chromosomes from under-replication and stabilize them. In 2009, the Nobel Prize in Medicine was awarded for this discovery.

At first, the scientific community believed in the discovery of the key to prolonging life, and telomerase became a candidate for the title of a kind of philosopher's stone.

But then Russian scientists again entered the research ring, who in experiments on mice showed that an increase in the amount of telomerase does not lead to a significant increase in life expectancy. All mice – both wild (with short telomeres) and laboratory (with long telomeres) – live about the same period. And now the situation on this front has not changed yet, and scientists do not yet understand whether telomere lengthening somehow affects the aging of the body or not.

Neighborhood friendship

There are bonds between the cells, which are called membrane proteins. Thanks to these couplings, cells know everything about their "neighbors", receive signals from them, and their connections do not fall apart. But the bonds weaken over time, the cells stop sticking together and cannot find out what is happening to their "neighbors". They become loners, lose all connections with the outside world, and the "constructor" crumbles.

If you imagine an organism's cell in the form of a room, then the membrane protein will be the handle from the front door. In this case, part of the handle is located outside the room and penetrates into the adjacent room, and part is located inside the room. Once the "neighbor" pulls the handle, the door opens, and then you can enter the cage room.

This is how large and small biomolecules get into the cell, which, by transmitting information, start or stop, accelerate or slow down vital processes.

But if the pen breaks, then nothing can get into the room, and information – for example, from the senses – can remain on the threshold of damaged cells, without reaching the brain for processing. This is how signaling pathways in cells are disrupted, which leads to neurodegenerative diseases – another companion of aging.

Life expectancy vs quality of life

We all grow old and sooner or later we will die – such is the merciless nature of man. But each of us wants to live longer, and to extend the period of life when the body is healthy, active and strong. Therefore, the forces of scientists are thrown not at increasing life expectancy (lifespan), but at prolonging the active period of life – healthspan.

A long healthspan is guaranteed if you reduce the likelihood of illness or increase the likelihood of recovery. In any of these scenarios, age-dependent diseases should be minimized. Now researchers are paying special attention to diseases such as cancer, cataracts, type II diabetes, cardiovascular diseases, Alzheimer's disease, etc. In Russia, many research institutes and centers deal with issues of healthy longevity at different levels. One of these is the recently established MIPT "Center for Research on the Molecular Mechanisms of Aging and Age-related Diseases", in which pathologies are investigated at the level of membrane proteins. In particular, in the laboratory of advanced research of membrane proteins, together with foreign colleagues, a big breakthrough was made in the study of Alzheimer's disease.

For a long time it was believed that the cause of the disease was amyloid plaques. In the human brain, with age, a substance – the beta-amyloid monomer - can accumulate in excessive amounts. This is a byproduct of the improper breakdown of the membrane protein responsible for the growth and maturation of nerve cells. Deposits of beta-amyloids are called plaques. Plaques, clinging to the cell, lead to the launch of apoptosis mechanisms.

But scientists from MIPT managed to find out that plaques are not the cause of the disease. All the most terrible things happen inside the cell, at its power stations.

Beta-amyloid from the cell membrane gets inside, attaches to the mitochondrial membrane and thereby knocks down all the energy and signaling processes of the cell, only after that the damaged cell goes into apoptosis. The death of neurons, which practically do not recover, adversely affects all brain processes, neural connections are disrupted, a person ceases to remember something and is unable to learn new things. Now scientists are working to prevent beta-amyloid from entering the mitochondria.

Scientists are also making progress in studying the processes of old age. So, more recently, researchers have found out that cells of different organs of the body age at different rates, for example, the liver ages faster than the brain. This is explained by the fact that cells of different organs have different properties: for example, liver cells are updated quite often and accumulate mutations. At the same time, most of the neurons of the brain "live" in it from the birth of the organism to its death, which means that the neurons must have an "innate" ability to resist time.

Another group of scientists, thanks to the study of telomeres, found out that the body of some people ages at a triple rate, "overcoming" three years in 12 months (this means that the biological age of their organs and tissues exceeds the actual age by three times). There are, however, some people who age more slowly, their biological clock measures a year in 16.5 calendar months. In the course of 12 years of work, scientists came to the conclusion: genetics is responsible for the rate of aging of the body by only 20%, the remaining 80% is the contribution of our lifestyle (sports, nutrition, ecology, and so on).

Despite all the successes of scientists, it is still very early to talk about the victory over old age. Nevertheless, the discoveries already made give hope that someday a "cure for old age" - or at least a slowing down of old age – will still be created.

Portal "Eternal youth" http://vechnayamolodost.ru  31.05.2016