DNA is the code that an organism uses to build and rebuild itself. But the genes also need "instructions" to structure the course of work. And the collection of such "instructions" is our other code, the epigenetic program, which tells the body how our genes shall work.
HOW THE EPIGENETIC MECHANISM WORKS
The main ways to control gene activity are histone modification and methylation. Histones are special proteins to which the DNA in the cell nucleus is wound around, like a coil, to form a tight pack, the nucleosome. The tighter this pack, the less DNA is available to the enzymes that conduct transcription synthesis of RNA from the DNA matrix. And since there is less RNA, less protein is produced. This means that the gene in this area will have little or no activity. However, signals from the external environment can contribute to a looser arrangement of these "coils," so that enzymes gain access to this DNA section. This means that RNA, and then proteins, can be synthesized the gene is active.
The second mode of gene regulation is methylation, i.e., the addition of a methyl group CH3 to DNA. As a result, cytosine is transformed into 5-methylcytosine. Once the signal is received, the methyl group attaches to the DNA, which prevents enzymes from binding to it and changes the density of the nucleosome, as with histone modification, making genes inactive. In contrast, the process opposite to methylation, i.e., demethylation, activates previously "silenced" genes, which promotes the formation of new proteins.
Understanding the mechanisms that "turn on" and "turn off" genes can give science and medicine the ability to regulate the aging process, as well as to control and treat various diseases, including those of genetic origin. For example, "uncontrollable" genes are often "guilty" in the development of cancer their "silencing" will stop further growth of the tumor. Therefore, the most prestigious scientific prizes are awarded for research in this field: for example, in 2006, American scientists Andrew Fire and Craig Mello were awarded the Nobel Prize for the discovery of another epigenetic mechanism RNA interference.
FUN FACT
ONLY 5-10 % OF DISEASE DEVELOPMENT DEPENDS ON GENETICS
Canadian scientists at the University of Alberta conducted the largest meta-analysis, summarizing data from 569 genetic studies over two decades, and concluded that the association between most human diseases and genetics is very low only 5-10 %. This means that human life and health are not predetermined by genes, but depend more on lifestyle and environment.
In their work, the researchers studied the relationship between gene mutations known as single-nucleotide polymorphism (SNPs) and various diseases and conditions. Many SNPs are considered risk factors for the development of hundreds of diseases, but the results of a meta-analysis have shown that this relationship is highly questionable.
Experts have found that most diseases, including many cancers, diabetes mellitus type II, and Alzheimer's disease, are only 5-10 % or less dependent on genetic factors. However, there are exceptions: for example, Crohn's disease, gluten-sensitive enteropathy, and age-related macular degeneration, for which the genetic risk is 4050 %.
Despite these rare exceptions, it has become apparent that in most cases the development of disease is related to metabolic disorders, environmental and lifestyle factors, or exposure to dangerous bacteria, viruses, and toxic substances. It can be concluded that we should not blame deviations in health on heredity, and it is better to monitor the ecological security in which people live and work: food, water, air quality, etc., as well as lead a healthy lifestyle.
We can monitor epigenetics in action through the observation of the lives of identical twins who have identical DNA at birth. These observations show how strong the differences in gene expression of twins can be if they live in different conditions and lead different lifestyles. In theory, the disease in twins should develop equally, but it is far from being true: depending on various factors, only one of them may have symptoms.
This finding supports a study conducted in 2005[28]. Scientists studied several dozen pairs of identical twins 374 years old. It turned out that people did have similar gene expression in childhood because they were in about the same conditions: they lived in the same house, went to the same school, and ate similar food. However, the older the twins got, the more differences there were between them. And when the siblings separated as adults, and started to lead different lifestyles, to have some different hobbies, to work in different fields, the number of these differences increased several times.
It is the same with ordinary people: as soon as you change your lifestyle in one way or another, your genes will manifest themselves differently. And this changed methylation profile we pass on to our children! Why don't we then take advantage of this ability to make genes work for better health, slower aging, and longer life? Knowing how the epigenetic mechanism works can enable you to control your genetic code and thereby silence the "bad" genes inherited and activate the "good" ones. So how do we start the chain of beneficial epigenetic changes?
FACTORS THAT MAY AFFECT OUR GENES
Although epigenetics is still in its infancy, much is already known about the ways to change the activity of hundreds or even thousands of genes.
NUTRITION. In 2003, a study at Duke University (USA) showed that nutrition not only changes DNA operation but also causes hereditary transformations[29]. Test objects were so-called agouti mice. They differ from normal mice in the more active special gene responsible for the formation of the agouti signal peptide. This protein makes animals prone to obesity, increases the likelihood of tumor development, and produces a pigment in the follicles, giving the fur a yellow color (instead of brown or black).
In the study, female agouti mice shortly before mating were "put" on a special diet rich in folic acid, vitamin B12, and the amino acids, choline, and methionine. This dietary pattern was maintained throughout pregnancy and the lactation period. Most of the young mice were born with normal color and healthy metabolic processes, with no tendency to become obese as adults. Moreover, several more generations of rodents born from the first offspring of agouti mice also showed no signs of agouti peptide activity, although they adhered to a standard diet.
Such results, experts say, are very applicable to humans as well. They state that folic acid and vitamin B12 deficiency in pregnant women leads to negative changes in methylation, which can lead to pathologies manifesting not only in the child but even in their future children and grandchildren.
A correct diet and healthy lifestyle can help silence the expression of hundreds of genes associated with cancer development. This was shown in a 2008 experiment carried out by scientists from the University of California, San Francisco[30]. For three months, men diagnosed with prostate cancer were on a low-fat plant-based diet and received vitamin and amino acid supplements. In addition, an exercise program was designed for them. As a result, patients were able to change the expression of more than 500 genes: activate 48 genes reducing tumor growth and suppress 453 genes associated with tumor overgrowth.