"Flexible interface between the genome and the environment": Russian biologist - about the epigenetic regulation of the organism

- Sergey Lvovich, British scientists have been able to improve the regeneration of the spinal cord in mice using epigenetic treatment.

The researchers used a special molecule TTK21 to activate a gene responsible for regenerating axons in neurons.

The experiment was successful: in mice that had suffered a spinal cord injury, regeneration really began to be more active than in animals from the control group.

Recently, Russian scientists also published work on a similar topic - they managed to create a molecule for targeted activation of certain genes.

How close has science come to epigenetic regulation in humans?

And what is epigenetics?

Let's start with the basic concepts.

In every cell of the human body there is a genome that we inherit from our parents.

It remains unchanged throughout life.

The genome can be compared to a monolithic rock that does not move or change.

At the same time, we know that each person develops from a single cell, which was formed as a result of the fusion of parental genomes.

An adult organism consists of trillions of different cells: cells of the nervous tissue, blood, skin, etc. Each of these various cells contains the same DNA, but this does not prevent them from performing different functions, because there is a so-called epigenetic regulation of the genome.

For example, in blood cells, genes that are responsible for a different specialization, say, neurons, are silent, and only those genes that allow blood cells to function work.

Sometimes one of the genes can be silenced.

Then comes the functional insufficiency of the cell.

In general, in the process of development of an organism, some genes work first, then they fall silent and others begin to work.

However, all these genes still remain in the genome.

For example, the growth of neurons is very important at the early stage of body growth - as they grow, new tissues appear that need to be innervated.

Therefore, during this period, the corresponding genes are actively working.

And upon reaching the stage when all the organs are already formed, the genes responsible for the growth of the nervous tissue become silent.

• Gettyimages.ru

This regulation occurs through epigenetic mechanisms that are associated with the chemical modification of DNA.

Attaching a methyl group to a certain part of the genome (methyl group is a compound consisting of one carbon atom and three hydrogen atoms.

) leads to the fact that a certain gene will not be read, and vice versa.

In epigenetic processes, the three-dimensional structure of chromatin itself also plays an important role (the nucleoprotein threads that make up chromosomes.

), simply put, the way the genome is packaged inside the cell.

Each cell contains almost two meters of DNA strands.

On the one hand, chromatin must be compactly packed, and on the other hand, the necessary genes must be outside, on the surface, so that they can be read.

Those genes that are not needed at the moment are wrapped inside this tangle.

In fact, all epigenetic mechanisms are chemical mechanisms.

Therefore, scientists are now looking for molecules that affect the genome so that silent genes can be activated, a number of chemical formulas have already been discovered.

The experience of British scientists with improving the regeneration of the spinal cord in mice is based on this principle: the authors of the work managed to restart those processes in the body that are characteristic of the early period of development, to activate the necessary genes.

However, the use of such technologies in humans is still very far away.

The fact is that it is still difficult to achieve a point and directed chemical effect on DNA only in a certain tissue, simply by introducing molecules into the body.

A directed effect can be obtained by a mechanical method if we introduce this molecule into the damaged tissue of the body.

Then the cells in this area can change their functions.

For example, the function of a gene that is responsible for the proliferation of neurons may change (proliferation - an increase in the number of cells.

).

In this case, we will get a certain effect.

In fact, I think that the effect of about a third of the drugs already used is due to the effect on epigenetics.

Another thing is that only recently science was able to look inside this mechanism, descending to the submolecular level.

• Gettyimages.ru

- In 2003, American scientists conducted an experiment with agouti mice, which had a predisposition to obesity.

They gave rodents folic acid, vitamin B12, choline and methionine, donors of methyl groups that can attach to DNA regions and block their activity.

As a result, the obesity gene was blocked, and the mice recovered and produced healthy offspring.

At the same time, there are already scientific works that say that stress suffered at an early age leads to methylation - blocking the cortisol receptor gene, which greatly affects the human psyche and behavior in the future.

That is, in some cases, epigenetics blocks harmful genes, and in others, beneficial ones.

Are there any patterns in this process?

- Nature is arranged in such a way that if we want to influence a particular gene, we must do it very precisely.

This is now possible thanks to the CRISPR/Cas9 gene editing system, for which the Nobel Prize was awarded.

And chemical methods of exposure have serious side effects.

If an excess of sources of methyl groups enters the body with food, each cell of the body will be oversaturated with them and any DNA region may be methylated, which, in turn, can lead to negative consequences.

In general, you should never get too carried away with broad-spectrum drugs and chemicals, as this can be harmful in the long run.

In no case is it necessary, after reading about successful experiments on mice, to begin an excessive intake of B vitamins or folic acid.

Even if it does not harm you, it is impossible to predict how an excess of these substances will affect your descendants.

Fortunately, a person is so arranged that he usually begins to think about his longevity and take various supplements after the childbearing age has passed.

So offspring, as a rule, are insured against the consequences of such self-treatment.

— When scientists studied the consequences of the famine that the inhabitants of Amsterdam experienced during the Second World War, it turned out that this affected the health of the children and grandchildren of these people.

What is currently known about epigenetic inheritance, what mechanisms are responsible for it?

— Yes, the story of people who survived the famine in 1945 in Amsterdam is a very famous example of epigenetic inheritance.

Children who were born or lived there during this period had later health problems: an increased incidence of diabetes, obesity and various neuropsychological disorders.

Moreover, these deviations were transmitted even to the grandchildren of these people, although there were no changes at the genome level.

In fact, obesity and diabetes are an attempt by the body to resist hunger, an adaptive response to it, when cells begin to accumulate nutrients in excess.

• Two Hungry Hikers in the Hungry Winter in Amsterdam

• © Wikimedia Commons / CC BY-SA 3.0

We can say that epigenetics is needed by the body so that it can adapt to environmental conditions, although the genome remains unchanged.

It is through these mechanisms that the genome is able to respond to current challenges.

For example, there is a hypothesis according to which the ability of cells to accumulate sugar (which today leads to the disease - diabetes) arose during the Ice Age as a mechanism for human adaptation to cold.

Since the freezing temperature of the liquid in the cells became lower due to increased sugar, respectively, the tissues of the body after frostbite were not destroyed, but were quickly restored.

And at first, such an adaptive mechanism could have arisen at the epigenetic level, and only then be fixed in the genome.

- But if the situation returns to normal before these adaptive changes in the body are finally fixed, will they disappear?

- Of course.

Because epigenetics is essentially a flexible interface between the genome and the environment.

• Gettyimages.ru

- There are suggestions that epigenetics can influence the mental state of a person, for example, epigenetic factors can explain the tendency to suicide.

How researched is this area, how can DNA methylation be related to the psyche and, maybe, psychology?

Yes, such studies are underway and there is definitely a connection between epigenetics and mental manifestations.

However, the regularities and mechanisms of such links have yet to be established.

Is it possible to treat genetic diseases with epigenetic methods in the future?

Not to cut, but to turn off harmful genes?

— This scientific direction is developing now.

For example, oncology is the result of genetic changes in cells.

And after genetic transformation, epigenetic changes also occur in such tissues.

With the help of various substances - epigenetic activators or inhibitors - it is possible to kill tumor cells.

- Are there diseases caused solely by epigenetic failures?

- Yes, they are associated with gene imprinting (a non-inherited epigenetic process in which the expression of some genes depends on which parent their allele came from - form.

), so the genome is also involved in this case.

For example, it happens that the genomes of both the father and the mother contain a certain mutation, but it does not manifest itself in them, since each of the parents has such a gene only on one chromosome and is in an inactive state.

And the second chromosome contains a healthy copy of this gene.

However, in a child with a certain combination of chromosomes, a mutated gene can appear, and a healthy copy, on the contrary, “fall asleep”.

For example, a serious illness, Angelman's syndrome, is associated with such failures.

This disease has not yet been cured.

However, like another manifestation of epigenetics - aging.

• Gettyimages.ru

-

“To put it simply, Steve Horvath found 350 epigenetic marks on DNA that somehow correlate with age.

The technique for determining the age of cells using these marks is called the "epigenetic clock".

Based on DNA methylation, several such "clocks" have been developed - they allow you to analyze DNA isolated from different types of cells.

Yes, this technique allows you to accurately determine the current biological age of the tissue, the error is four to five years.

For example, if you take the tissue of a corpse for analysis, you can determine with such accuracy at what age a person died.

However, it is impossible to find out with the help of “epigenetic clocks” how much a person has left to live, because the environment affects DNA methylation and changes in external conditions can also change epigenetic indicators.

— What happens to the human epidemiological system with age?

- Its functioning is disrupted, because the activity of genes decreases, and methylation increases - this is due to the accumulation of errors and failures.

With age, the functions of biological tissues begin to decline, because the genes begin to "silence".

And if we try to indiscriminately activate them by chemical methods, this will lead to a tumor process.

It is difficult to find tools for selective epigenetic influence, although scientists are working in this direction.