Epigenetic changes. Epigenetics: genes and something above. Epigenetics: Lifestyle changes are the key to changing genes

Epigenetics is a branch of genetics that has relatively recently emerged as an independent field of research. But today this young dynamic science offers a revolutionary insight into the molecular mechanisms of development of living systems.

One of the most daring and inspiring epigenetic hypotheses, that the activity of many genes is subject to external influence, is now being confirmed in many experiments in animal models. The researchers cautiously comment on their results, but do not rule out that Homo sapiens does not fully depend on heredity, which means it can purposefully influence it.

In the future, if scientists turn out to be right and they manage to find the keys to the mechanisms of gene control, humans will be able to control physical processes occurring in the body. Aging may well be one of them.

In Fig. mechanism of RNA interference.

dsRNA molecules can be a hairpin RNA or two paired complementary strands of RNA.
Long dsRNA molecules are cut (processed) in the cell into short ones by the Dicer enzyme: one of its domains specifically binds the end of the dsRNA molecule (marked with an asterisk), while the other produces breaks (marked with white arrows) in both dsRNA strands.

As a result, a double-stranded RNA of 20-25 nucleotides in length (siRNA) is formed, and Dicer proceeds to the next cycle of cutting the dsRNA, binding to its newly formed end.

These siRNAs can be incorporated into a complex containing the Argonaute protein (AGO). One of the siRNA chains, in complex with the AGO protein, finds complementary messenger RNA (mRNA) molecules in the cell. AGO cuts target mRNA molecules, causing the mRNA to degrade, or stops translation of the mRNA on the ribosome. Short RNAs can also suppress transcription (RNA synthesis) of a gene homologous to them in nucleotide sequence in the nucleus.
(drawing, diagram and comment / Nature magazine No. 1, 2007)

Other, as yet unknown, mechanisms are also possible.
The difference between epigenetic and genetic mechanisms of inheritance is their stability and reproducibility of effects. Genetically determined traits can be reproduced indefinitely until a certain change (mutation) occurs in the corresponding gene.
Epigenetic changes induced by certain stimuli are usually reproduced over a series of cell generations within the life of one organism. When they are transmitted to subsequent generations, they can reproduce for no more than 3-4 generations, and then, if the stimulus that induced them disappears, they gradually disappear.

What does this look like at the molecular level? Epigenetic markers, as these chemical complexes are usually called, are not located in the nucleotides that form the structural sequence of the DNA molecule, but they directly pick up certain signals?

Absolutely right. Epigenetic markers are indeed not IN the nucleotides, but ON them (methylation) or OUTSIDE them (acetylation of chromatin histones, microRNAs).
What happens when these markers are passed on to subsequent generations is best explained using the analogy christmas tree. Passing from generation to generation, “toys” (epigenetic markers) are completely removed from it during the formation of a blastocyst (8-cell embryo), and then, during the process of implantation, they are “put on” in the same places where they were before. This has been known for a long time. But what has become known recently, and which has completely revolutionized our understanding of biology, has to do with epigenetic modifications acquired during the life of a given organism.

For example, if the body is under the influence of a certain influence (heat shock, fasting, etc.), a stable induction of epigenetic changes occurs (“buying a new toy”). As previously assumed, such epigenetic markers are completely erased during fertilization and embryo formation and, thus, are not passed on to offspring. It turned out that this was not the case. In a large number of studies in recent years, epigenetic changes induced by environmental stress in representatives of one generation were detected in representatives of 3-4 subsequent generations. This indicates the possibility of inheritance of acquired characteristics, which until recently was considered absolutely impossible.

What are the most important factors causing epigenetic changes?

These are all factors that operate during sensitive stages of development. In humans, this is the entire period of intrauterine development and the first three months after birth. The most important are nutrition, viral infections, maternal smoking during pregnancy, insufficient production of vitamin D (due to sun exposure), maternal stress.
That is, they increase the body’s adaptation to changing conditions. What “messengers” exist between factors? environment and epigenetic processes - no one knows yet.

But, in addition, there is evidence that the most “sensitive” period during which major epigenetic modifications are possible is periconceptual (the first two months after conception). It is possible that attempts at targeted intervention in epigenetic processes even before conception, that is, on germ cells even before the formation of a zygote, may be effective. However, the epigenome remains quite plastic even after the end of the stage embryonic development, some researchers are trying to correct it in adults.

For example, Min Ju Fan ( Ming Zhu Fang) and her colleagues from Rutgers University in New Jersey (USA) found that in adults, using a certain component of green tea (the antioxidant epigallocatechin gallate (EGCG)) can activate tumor suppressor genes through DNA demethylation.

Currently, about a dozen drugs are already under development in the United States and Germany, the creation of which was based on the results of recent studies of epigenetics in the diagnosis of cancer.
What are the key questions in epigenetics now? How can their solution advance the study of the mechanisms (process) of aging?

I believe that the aging process is inherently epigenetic (“like a stage of ontogeny”). Research in this area began only in last years, but if they are successful, perhaps humanity will receive a new powerful tool to fight disease and prolong life.
The key issues now are the epigenetic nature of diseases (for example, cancer) and the development of new approaches to their prevention and treatment.
If we can study the molecular epigenetic mechanisms of age-related diseases, it will be possible to successfully counteract their development.

After all, for example, a worker bee lives 6 weeks, and a queen bee lives 6 years.
With complete genetic identity, they differ only in that the future queen bee is fed royal jelly for several days more during development than an ordinary worker bee.

As a result, representatives of these bee castes develop slightly different epigenotypes. And, despite the external and biochemical similarity, their life expectancy differs by 50 times!

During research in the 60s, it was shown that it decreases with age. But have scientists made any progress in answering the question: why is this happening?

There is a lot of work indicating that the characteristics and rate of aging depend on the conditions of early ontogenesis. Most associate this with the correction of epigenetic processes.

DNA methylation does indeed decrease with age; why this happens is not yet known. One version is that this is a consequence of adaptation, an attempt by the body to adapt to both external stress and internal “super stress” - aging.

It is possible that DNA “turned on” during age-related demethylation is an additional adaptive resource, one of the manifestations of the vitaukta process (as it was called by the outstanding gerontologist Vladimir Veniaminovich Frolkis) - a physiological process that counteracts aging.

To make changes at the gene level, it is necessary to identify and replace the mutated “letter” of DNA, maybe a section of genes. So far, the most promising way to carry out such operations is biotechnological. But this is still an experimental direction and there are no major breakthroughs in it yet. Methylation is a more flexible process; it is easier to change, including with the help of pharmacological drugs. Is it possible to learn to control selectively? What else remains to be done for this?

Methylation is unlikely. It is non-specific, it affects everything “wholesale”. You can teach a monkey to hit the keys of a piano, and it will extract loud sounds, but he is unlikely to perform the “Moonlight Sonata”. Although there are examples where, with the help of methylation, it was possible to change the phenotype of an organism. The most famous example is with mice - carriers of the mutant agouti gene (I have already cited it). The reversion to normal coat color occurred in these mice because the “defective” gene was “turned off” due to methylation.

But it is possible to selectively influence gene expression, and interfering RNAs, which act highly specifically, only on “their own” ones, are excellent for this. Such work is already being carried out.

For example, American researchers recently transplanted human tumor cells into mice whose immune system was suppressed, which could freely multiply and metastasize in immunodeficient mice. Scientists were able to identify those expressed in metastasizing cells and, by synthesizing the corresponding interfering RNA and injecting it into mice, block the synthesis of “cancer” messenger RNA and, accordingly, suppress tumor growth and metastasis.

That is, based on modern research, we can say that epigenetic signals underlie various processes occurring in living organisms. What are they? What factors influence their formation? Are scientists able to decipher these signals?

Signals can be very different. During development and stress, these are signals primarily of a hormonal nature, but there is evidence that even the influence of low-frequency radiation can lead to the expression of heat shock protein genes (HSP70) in cell culture. electromagnetic field certain frequency, the intensity of which is a million (!) times less than the natural electromagnetic field. IN in this case this field, of course, does not act “energetically”, but is a kind of signal “trigger” that “launches” gene expression. There is still a lot of mystery here.

For example, recently opened bystander effect(“bystander effect”).
Briefly, its essence is this. When we irradiate a cell culture, they experience a wide range of reactions, from chromosomal aberrations to radioadaptive reactions (the ability to withstand high doses of radiation). But if we remove all the irradiated cells and transfer other, non-irradiated cells into the remaining nutrient medium, they will show the same reactions, although no one has irradiated them.

It is assumed that irradiated cells release certain epigenetic “signaling” factors into the environment, which cause similar changes in non-irradiated cells. No one knows yet what the nature of these factors is.

Great expectations for improving quality of life and life expectancy are associated with scientific achievements in the field of stem cell research. Will epigenetics be able to live up to its promise of reprogramming cells? Are there serious prerequisites for this?

If a reliable technique for “epigenetic reprogramming” of somatic cells into stem cells is developed, this will certainly be a revolution in biology and medicine. So far, only the first steps have been taken in this direction, but they are encouraging.

A well-known maxim: a person is what he eats. What effect does food have on our lives? For example, geneticists from the University of Melbourne, who studied the mechanisms of cellular memory, discovered that after receiving a one-time dose of sugar, the cell stores the corresponding chemical marker for several weeks.

There is even a special section on epigenetics - Nutritional Epigenetics, dealing specifically with the issue of the dependence of epigenetic processes on nutritional characteristics. These features are especially important for early stages development of the body. For example, when a baby is fed not with mother's milk, but with dry formulas based on cow's milk, epigenetic changes occur in the cells of his body, which, fixed by the imprinting mechanism, lead over time to the onset of an autoimmune process in the beta cells of the pancreas and , as a consequence, type I diabetes.

In Fig. development of diabetes (the figure enlarges when clicked with the cursor). In autoimmune diseases such as type 1 diabetes, a person's immune system attacks his own organs and tissues.
Some autoantibodies begin to be produced in the body long before the first symptoms of the disease appear. Their identification can help in assessing the risk of developing the disease.
(drawing from the magazine “IN THE WORLD OF SCIENCE”, July 2007 No. 7)

And inadequate (limited in the number of calories) nutrition during fetal development is a direct path to obesity in adulthood and type II diabetes.

Does this mean that a person is still responsible not only for himself, but also for his descendants: children, grandchildren, great-grandchildren?

Yes, of course, and to a much greater extent than was previously believed.

What is the epigenetic component in the so-called genomic imprinting?

With genomic imprinting, the same gene appears phenotypically differently depending on whether it is passed on to the offspring from the father or mother. That is, if a gene is inherited from the mother, then it is already methylated and is not expressed, whereas a gene inherited from the father is not methylated and is expressed.

The most actively studied is genomic imprinting in the development of various hereditary diseases that are transmitted only from ancestors of a certain sex. For example, the juvenile form of Huntington's disease manifests itself only when the mutant allele is inherited from the father, and atrophic myotonia - from the mother.
And this despite the fact that the diseases themselves that cause these diseases are absolutely the same, regardless of whether they are inherited from the father or mother. The differences lie in the “epigenetic prehistory” caused by their presence in the maternal or, conversely, paternal organisms. In other words, they carry the "epigenetic imprint" of the parent's sex. When present in the body of an ancestor of a certain sex, they are methylated (functionally repressed), and of another - demethylated (respectively, expressed), and in the same state are inherited by descendants, leading (or not leading) to the occurrence of certain diseases.

You have been studying the effects of radiation on the body. It is known that low doses of radiation have a positive effect on the lifespan of fruit flies fruit flies. Is it possible to train the human body with low doses of radiation? Alexander Mikhailovich Kuzin, expressed by him back in the 70s of the last century, doses that are approximately an order of magnitude larger than the background ones lead to a stimulating effect.

In Kerala, for example, the background level is not 2, but 7.5 times higher than the “average Indian” level, but neither the incidence of cancer nor the mortality rate from it differs from the general Indian population.

(See, for example, the latest on this topic: Nair RR, Rajan B, Akiba S, Jayalekshmi P, Nair MK, Gangadharan P, Koga T, Morishima H, Nakamura S, Sugahara T. Background radiation and cancer incidence in Kerala, India-Karanagappally cohort study. Health Phys. 2009 Jan;96(1):55-66)

In one of your studies, you analyzed data on the dates of birth and death of 105 thousand Kiev residents who died between 1990 and 2000. What conclusions were drawn?

The life expectancy of people born at the end of the year (especially in December) turned out to be the longest, and the shortest for those born in April-July. The differences between the minimum and maximum monthly averages turned out to be very large and reached 2.6 years for men and 2.3 years for women. Our results suggest that how long a person will live largely depends on the season of the year in which he was born.

Is it possible to apply the information obtained?

What could be the recommendations? For example, should children be conceived in the spring (preferably in March) so that they are potentially long-lived? But this is absurd. Nature does not give everything to some and nothing to others. So it is with “seasonal programming.” For example, in studies carried out in many countries (Italy, Portugal, Japan), it was revealed that schoolchildren and students born in late spring - early summer (according to our data - “short-lived”) have the highest intellectual capabilities. These studies demonstrate the futility of “applied” recommendations for having children during certain months of the year. But these works, of course, are a serious reason for further scientific research into the mechanisms that determine “programming,” as well as the search for means of targeted correction of these mechanisms in order to prolong life in the future.

One of the pioneers of epigenetics in Russia, Moscow State University professor Boris Vanyushin, in his work “Materialization of epigenetics or Small changes with big consequences,” wrote that the last century was the century of genetics, and the current one is the century of epigenetics.

What allows us to evaluate the position of epiginetics so optimistically?

After the completion of the Human Genome program, the scientific community was shocked: it turned out that information about the structure and functioning of a person is contained in approximately 30 thousand genes (according to various estimates, this is only about 8-10 megabytes of information). Experts who work in the field of epigenetics call it the “second information system” and believe that deciphering the epigenetic mechanisms that control the development and functioning of the body will lead to a revolution in biology and medicine.

For example, a number of studies have already been able to identify typical patterns in such drawings. Based on them, doctors can diagnose the formation of cancer at an early stage.
But is such a project feasible?

Yes, of course, although it is very expensive and can hardly be implemented during a crisis. But in the long term - quite.

Back in 1970, Vanyushin’s group in the magazine "Nature" published data on what regulates cell differentiation, leading to differences in gene expression. And you talked about this. But if every cell of an organism contains the same genome, then each type of cell has its own epigenome, and accordingly the DNA is methylated differently. Considering that the cell types in human body about two hundred and fifty - the volume of information can be colossal.

This is why the Human Epigenome project is very difficult (although not hopeless) to implement.

He believes that the smallest phenomena can have a huge impact on a person’s life: “If the environment plays such a role in changing our genome, then we must build a bridge between biological and social processes. It will absolutely change the way we look at things.”

Is it all that serious?

Certainly. Now, in connection with the latest discoveries in the field of epigenetics, many scientists are talking about the need for a critical rethinking of many provisions that seemed either unshakable or forever rejected, and even about the need to change the fundamental paradigms in biology. Such a revolution in thinking can certainly have a significant impact on all aspects of people’s lives, from their worldview and lifestyle to an explosion of discoveries in biology and medicine.

Information about the phenotype is contained not only in the genome, but also in the epigenome, which is plastic and can, changing under the influence of certain environmental stimuli, influence the expression of genes - A CONTRADICTION TO THE CENTRAL DOGMA OF MOLECULAR BIOLOGY, ACCORDING TO WHICH THE FLOW OF INFORMATION CAN ONLY GO FROM DNA TO PROTEINS, BUT NOT THE OVERSEAS.
Epigenetic changes induced in early ontogenesis can be recorded by the imprinting mechanism and change the entire subsequent fate of a person (including psychotype, metabolism, predisposition to diseases, etc.) - ZODIACAL ASTROLOGY.
The reason for evolution, in addition to random changes (mutations) selected natural selection, are directed, adaptive changes (epimutations) - THE CONCEPT OF CREATIVE EVOLUTION by the French philosopher (Nobel laureate in literature, 1927) Henri BERGSON.
Epimutations can be transmitted from ancestors to descendants - INHERITANCE OF ACQUIRED CHARACTERISTICS, LAMARCHISM.

What pressing questions will need to be answered in the near future?

How does the development of a multicellular organism occur, what is the nature of the signals that so accurately determine the time of occurrence, structure and functions of various organs of the body?

Is it possible to change organisms in the desired direction by influencing epigenetic processes?

Is it possible to prevent the development of epigenetically determined diseases, such as diabetes and cancer, by correcting epigenetic processes?

What is the role of epigenetic mechanisms in the aging process, is it possible to prolong life with their help?

Is it possible that the currently incomprehensible patterns of evolution of living systems (non-Darwinian evolution) are explained by the involvement of epigenetic processes?

Naturally, this is only my personal list; it may differ for other researchers.

Perhaps the most comprehensive and at the same time accurate definition of epigenetics belongs to the outstanding English biologist, Nobel laureate Peter Medawar: “Genetics suggests, but epigenetics disposes.”

Did you know that our cells have memory? They remember not only what you usually eat for breakfast, but also what your mother and grandmother ate during pregnancy. Your cells remember well whether you exercise and how often you drink alcohol. Cellular memory stores your encounters with viruses and how much you were loved as a child. Cellular memory decides whether you are prone to obesity and depression. Thanks largely to cellular memory, we are not like chimpanzees, although we have approximately the same genome composition. And the science of epigenetics helped us understand this amazing feature of our cells.

Epigenetics is a fairly young field modern science, and while she is not as widely known as her “sister” genetics. Translated from Greek, the preposition “epi-” means “above”, “above”, “above”. If genetics studies the processes that lead to changes in our genes, in DNA, then epigenetics studies changes in gene activity in which the DNA structure remains the same. One can imagine that a certain “commander” in response to external stimuli, such as nutrition, emotional stress, physical exercise, gives orders to our genes to strengthen or, conversely, weaken their activity.

Mutation Control

Development of epigenetics as a separate area molecular biology started in the 1940s. Then the English geneticist Conrad Waddington formulated the concept of an “epigenetic landscape,” which explains the process of organism formation. For a long time it was believed that epigenetic transformations are characteristic only of initial stage development of the body and are not observed in adulthood. However, in recent years, a whole series of experimental evidence has been obtained that has produced the effect of a bomb exploding in biology and genetics.

A revolution in the genetic worldview occurred at the very end of the last century. A number of experimental data were obtained in several laboratories at once, which made geneticists think very hard. Thus, in 1998, Swiss researchers led by Renato Paro from the University of Basel conducted experiments with Drosophila flies, which, due to mutations, had yellow eye. It was discovered that, under the influence of increased temperature, mutant Drosophila offspring were born not with yellow, but with red (as normal) eyes. One chromosomal element was activated in them, which changed their eye color.

To the surprise of the researchers, the red eye color remained in the descendants of these flies for another four generations, although they were no longer exposed to heat. That is, inheritance of acquired characteristics occurred. Scientists were forced to make a sensational conclusion: stress-induced epigenetic changes that do not affect the genome itself can be fixed and transmitted to future generations.

But maybe this only happens in fruit flies? Not only. Later it turned out that in humans the influence of epigenetic mechanisms also plays a very important role. For example, a pattern has been identified that the susceptibility of adults to type 2 diabetes may largely depend on the month of their birth. And this despite the fact that 50-60 years pass between the influence of certain factors associated with the time of year and the onset of the disease itself. This is a clear example of so-called epigenetic programming.

What can connect predisposition to diabetes and date of birth? New Zealand scientists Peter Gluckman and Mark Hanson managed to formulate a logical explanation for this paradox. They proposed the “mismatch hypothesis,” according to which “predictive” adaptation to the environmental conditions expected after birth can occur in a developing organism. If the prediction is confirmed, this increases the organism's chances of survival in the world where it will live. If not, adaptation becomes maladaptation, that is, a disease.

For example, if during intrauterine development the fetus receives an insufficient amount of food, metabolic changes occur in it, aimed at storing food resources for future use, “for a rainy day.” If there is really little food after birth, this helps the body survive. If the world into which a person finds himself after birth turns out to be more prosperous than predicted, this “thrifty” nature of metabolism can lead to obesity and type 2 diabetes later in life.

The experiments conducted in 2003 by American scientists from Duke University Randy Jirtle and Robert Waterland have already become textbook. A few years earlier, Jirtl managed to insert an artificial gene into ordinary mice, which is why they were born yellow, fat and sickly. Having created such mice, Jirtle and his colleagues decided to check: is it possible to make them normal without removing the defective gene? It turned out that it was possible: they added folic acid, vitamin B 12, choline and methionine to the food of pregnant agouti mice (as they began to call yellow mouse “monsters”), and as a result, normal offspring appeared. Nutritional factors were able to neutralize mutations in genes. Moreover, the effect of the diet persisted in several subsequent generations: baby agouti mice, born normal thanks to nutritional supplements, themselves gave birth to normal mice, although they already had a normal diet.

We can confidently say that the period of pregnancy and the first months of life is the most important in the life of all mammals, including humans. As German neuroscientist Peter Sporck aptly put it, “In old age, our health is sometimes much more influenced by our mother’s diet during pregnancy than by food at the current moment in life.”

Destiny by inheritance

The most studied mechanism of epigenetic regulation of gene activity is the process of methylation, which involves the addition of a methyl group (one carbon atom and three hydrogen atoms) to the cytosine bases of DNA. Methylation can influence gene activity in several ways. In particular, methyl groups can physically prevent the contact of a transcription factor (a protein that controls the process of messenger RNA synthesis on a DNA template) with specific DNA regions. On the other hand, they work in conjunction with methylcytosine-binding proteins, participating in the process of remodeling chromatin - the substance that makes up chromosomes, the repository of hereditary information.

DNA methylation
Methyl groups attach to cytosine bases without destroying or changing DNA, but affecting the activity of the corresponding genes. There is also a reverse process - demethylation, in which methyl groups are removed and the original activity of genes is restored" border="0">

Methylation is involved in many processes associated with the development and formation of all organs and systems in humans. One of them is the inactivation of X chromosomes in the embryo. As is known, female mammals have two copies of sex chromosomes, designated as the X chromosome, and males are content with one X and one Y chromosome, which is much smaller in size and in the amount of genetic information. To equalize males and females in the amount of gene products (RNA and proteins) produced, most of the genes on one of the X chromosomes in females are turned off.

The culmination of this process occurs at the blastocyst stage, when the embryo consists of 50−100 cells. In each cell, the chromosome to be inactivated (paternal or maternal) is randomly selected and remains inactive in all subsequent generations of that cell. Associated with this process of “mixing” the paternal and maternal chromosomes is the fact that women are much less likely to suffer from diseases associated with the X chromosome.

Methylation plays an important role in cell differentiation, the process by which “generalist” embryonic cells develop into specialized cells of tissues and organs. Muscle fibers, bone tissue, nerve cells - they all appear due to the activity of a strictly defined part of the genome. It is also known that methylation plays a leading role in the suppression of most types of oncogenes, as well as some viruses.

DNA methylation has the greatest practical significance of all epigenetic mechanisms, since it is directly related to diet, emotional status, brain activity and other external factors.

Data well supporting this conclusion were obtained at the beginning of this century by American and European researchers. Scientists examined elderly Dutch people born immediately after the war. The pregnancy period of their mothers coincided with a very difficult time, when there was a real famine in Holland in the winter of 1944-1945. Scientists were able to establish: severe emotional stress and a half-starved diet of mothers had the most negative impact on the health of future children. Born at low birth weight, they were several times more likely to have heart disease, obesity, and diabetes in adulthood than their compatriots born a year or two later (or earlier).

An analysis of their genome showed the absence of DNA methylation in precisely those areas where it ensures the preservation of good health. Thus, in elderly Dutch men whose mothers survived the famine, the methylation of the insulin-like growth factor (IGF) gene was noticeably reduced, which is why the amount of IGF in the blood increased. And this factor, as scientists well know, has an inverse relationship with life expectancy: the higher the level of IGF in the body, the shorter life.

Later, the American scientist Lambert Lumet discovered that in the next generation, children born into the families of these Dutch people were also born with abnormally low weight and more often than others suffered from all age-related diseases, although their parents lived quite prosperously and ate well. The genes remembered information about the hungry period of pregnancy of grandmothers and passed it on even through a generation, to their grandchildren.

The many faces of epigenetics

Epigenetic processes occur at several levels. Methylation operates at the level of individual nucleotides. The next level is the modification of histones, proteins involved in the packaging of DNA strands. The processes of DNA transcription and replication also depend on this packaging. A separate scientific branch - RNA epigenetics - studies epigenetic processes associated with RNA, including methylation of messenger RNA.

Genes are not a death sentence

In addition to stress and malnutrition, fetal health can be affected by numerous substances that interfere with normal hormonal regulation. They are called “endocrine disruptors” (destroyers). These substances, as a rule, are of an artificial nature: humanity obtains them industrially for their needs.

The most striking and negative example is, perhaps, bisphenol-A, which has been used for many years as a hardener in the manufacture of plastic products. It is found in some types of plastic containers - water and drink bottles, food containers.

The negative effect of bisphenol-A on the body is its ability to “destroy” free methyl groups necessary for methylation and inhibit the enzymes that attach these groups to DNA. Biologists from Harvard Medical School have discovered the ability of bisphenol-A to inhibit egg maturation and thereby lead to infertility. Their colleagues from Columbia University discovered the ability of bisphenol-A to erase differences between the sexes and stimulate the birth of offspring with homosexual tendencies. Under the influence of bisphenol, the normal methylation of genes encoding receptors for estrogen and female sex hormones was disrupted. Because of this, male mice were born with a “feminine” character, docile and calm.

Fortunately, there are foods that have a positive effect on the epigenome. For example, regular consumption of green tea may reduce the risk of cancer because it contains a certain substance (epigallocatechin-3-gallate), which can activate tumor suppressor genes (suppressors) by demethylating their DNA. In recent years, the modulator of epigenetic processes genistein, contained in soy products, has become popular. Many researchers associate the content of soy in the diet of residents of Asian countries with their lower susceptibility to certain age-related diseases.

The study of epigenetic mechanisms has helped us understand an important truth: so much in life depends on ourselves. In contrast to relatively stable genetic information, epigenetic “marks” when certain conditions may be reversible. This fact allows us to count on fundamentally new methods of combating common diseases, based on the elimination of those epigenetic modifications that arose in humans under the influence of unfavorable factors. The use of approaches aimed at correcting the epigenome opens up great prospects for us.

Epigenetics is a relatively new branch of genetics that has been called one of the most important biological discoveries since the discovery of DNA. It used to be that the set of genes we are born with irreversibly determines our lives. However, it is now known that genes can be “turned on” and “turned off”, and also their expression can be increased or decreased under the influence of various factors lifestyle.

the site will tell you what epigenetics is, how it works, and what you can do to increase your chances of winning the “health lottery.”

Epigenetics: Lifestyle changes are the key to changing genes

Epigenetics - a science that studies processes that lead to changes in gene activity without changing the DNA sequence. Simply put, epigenetics studies the effects of external factors on gene activity.

The Human Genome Project identified 25,000 genes in human DNA. DNA can be called the code that an organism uses to build and rebuild itself. However, the genes themselves need “instructions” by which they determine the necessary actions and the time for their implementation.

Epigenetic modifications are the very instructions.

There are several types of such modifications, but the two main ones are those affecting methyl groups (carbon and hydrogen) and histones (proteins).

To understand how modifications work, imagine that a gene is a light bulb. Methyl groups act as a light switch (i.e., a gene), and histones act as a light regulator (i.e., they regulate the level of gene activity). So, it is believed that a person has four million of these switches, which are activated under the influence of lifestyle and external factors.

The key to understanding the influence of external factors on gene activity was observing the lives of identical twins. Observations have shown how strong changes can be in the genes of such twins who lead different lifestyles in different external conditions.

Identical twins are supposed to have "common" illnesses, but this is often not the case: alcoholism, Alzheimer's disease, bipolar disorder, schizophrenia, diabetes, cancer, Crohn's disease and rheumatoid arthritis can occur in only one twin, depending on various factors. The reason for this is epigenetic drift- age-related changes in gene expression.

The Secrets of Epigenetics: How Lifestyle Factors Affect Genes

Research in epigenetics has shown that only 5% of disease-associated gene mutations are completely deterministic; the remaining 95% can be influenced through nutrition, behavior and other environmental factors. The healthy lifestyle program allows you to change the activity of 4000 to 5000 different genes.

We are not simply the sum of the genes we were born with. It is the person who is the user, it is he who controls his genes. At the same time, it is not so important what “genetic maps” nature has given you - what matters is what you do with them.

Epigenetics is in its infancy and much remains to be learned, but knowledge exists about the major lifestyle factors that influence gene expression.

1. Nutrition, sleep and exercise

It is not surprising that nutrition can influence the state of DNA. A diet rich in processed carbohydrates causes DNA to be attacked by high levels of glucose in the blood. On the other hand, DNA damage can be reversed by:

• sulforaphane (found in broccoli);
• curcumin (found in turmeric);
• epigallocatechin-3-gallate (found in green tea);
• resveratrol (found in grapes and wine).

When it comes to sleep, just a week of sleep deprivation negatively affects the activity of more than 700 genes. Gene expression (117) is positively affected by exercise.

1. Stress, relationships and even thoughts

Epigeneticists argue that it is not only “material” factors such as diet, sleep and exercise that influence genes. As it turns out, stress, relationships with people and your thoughts are also significant factors influencing gene expression. So:

• meditation suppresses the expression of pro-inflammatory genes, helping to fight inflammation, i.e. protect against Alzheimer's disease, cancer, heart disease and diabetes; Moreover, the effect of such practice is visible after 8 hours of training;
• 400 scientific studies have shown that expressing gratitude, kindness, optimism and various techniques that engage the mind and body have a positive effect on gene expression;
• lack of activity, poor nutrition, constant negative emotions, toxins and bad habits, as well as trauma and stress trigger negative epigenetic changes.

Durability of epigenetic changes and the future of epigenetics

One of the most exciting and controversial discoveries is that epigenetic changes are passed on to subsequent generations without changing the gene sequence. Dr. Mitchell Gaynor, author of The Gene Therapy Blueprint: Take Control of Your Genetic Destiny Through Nutrition and Lifestyle, believes that gene expression is also inherited.

Epigenetics, says Dr. Randy Jirtle, shows that we are also responsible for the integrity of our genome. Previously, we believed that everything depended on genes. Epigenetics allows us to understand that our behavior and habits can influence the expression of genes in future generations.

Epigenetics is a complex science that has enormous potential. Experts still have a lot of work to do to determine exactly what environmental factors influence our genes, how we can (and whether) we can reverse diseases or prevent them as effectively as possible.

The DNA sequencing of the human genome and the genomes of many model organisms has generated considerable excitement in the biomedical community and among the general public over the past few years. These genetic blueprints, demonstrating the generally accepted rules of Mendelian inheritance, are now readily available for careful analysis, opening the door to greater understanding of human biology and disease. This knowledge also raises new hopes for new treatment strategies. However, many fundamental questions remain unanswered. For example, how does normal development occur, given that each cell has the same genetic information and yet follows its own specific developmental path with high temporal and spatial precision? How does a cell decide when to divide and differentiate and when to maintain its cellular identity, reacting and expressing itself according to its normal developmental program? Errors that occur in the above processes can lead to disease conditions such as cancer. Are these errors encoded in erroneous blueprints that we inherited from one or both parents, or are there other layers of regulatory information that were not correctly read and decoded?

In humans, genetic information (DNA) is organized into 23 pairs of chromosomes, consisting of approximately 25,000 genes. These chromosomes can be compared to libraries containing different sets of books that together provide instructions for the development of an entire human organism. The DNA nucleotide sequence of our genome consists of approximately (3 x 10 to the power of 9) bases, abbreviated in this sequence by the four letters A, C, G and T, which form certain words (genes), sentences, chapters and books. However, what dictates exactly when and in what order these different books should be read remains far from clear. The answer to this extraordinary challenge likely lies in understanding how cellular events are coordinated during normal and abnormal development.

If you add up all the chromosomes, the DNA molecule in higher eukaryotes is about 2 meters long and, therefore, must be maximally condensed - about 10,000 times - in order to fit into the cell nucleus - the compartment of the cell in which our genetic material is stored. Winding DNA onto spools of proteins, called histone proteins, provides an elegant solution to this packaging problem and gives rise to a polymer of repeating protein:DNA complexes known as chromatin. However, in the process of packaging DNA to better fit a limited space, the task becomes more complex - much in the same way as when arranging too many large number books on library shelves: It becomes more and more difficult to find and read a book of choice, and thus an indexing system becomes necessary.

This indexing is provided by chromatin as a platform for genome organization. Chromatin is not homogeneous in its structure; it appears in a variety of packaging forms, from a fibril of highly condensed chromatin (known as heterochromatin) to a less compacted form where genes are typically expressed (known as euchromatin). Changes can be introduced into the underlying chromatin polymer by the inclusion of unusual histone proteins (known as histone variants), altered chromatin structures (known as chromatin remodeling), and the addition of chemical tags to the histone proteins themselves (known as covalent modifications). Moreover, the addition of a methyl group directly to a cytosine base (C) in the DNA template (known as DNA methylation) can create protein attachment sites to alter the state of chromatin or influence covalent modification of resident histones.

Received in Lately Data suggest that non-coding RNAs can “direct” the transition of specialized regions of the genome into more compact chromatin states. Thus, chromatin should be viewed as a dynamic polymer that can index the genome and amplify signals from the environment, ultimately determining which genes should be expressed and which should not.

Taken together, these regulatory capabilities endow chromatin with a genome-organizing principle known as “epigenetics.” In some cases, epigenetic indexing patterns appear to be inherited during cell division, thereby providing a cellular “memory” that can expand the potential for heritable information contained in the genetic (DNA) code. Thus, in the narrow sense of the word, epigenetics can be defined as changes in gene transcription caused by chromatin modulations that are not the result of changes in the nucleotide sequence of DNA.

This review introduces basic concepts related to chromatin and epigenetics, and discusses how epigenetic control may provide clues to some long-standing mysteries - such as cell identity, tumor growth, stem cell plasticity, regeneration and aging. As readers work their way through subsequent chapters, we encourage them to take note of the wide range of experimental models that, apparently, have an epigenetic (non-DNA) basis. Expressed in mechanistic terms, understanding how epigenetics functions will likely have important and far-reaching implications for human biology and disease in this “post-genomic” era.