Methylation is the addition of one carbon and three hydrogen atoms to another molecule. This phenomenon is considered the last word in the field of he alth care. It accompanies almost all body functions.
Functions
Methyl groups (carbon and hydrogen atoms) participate in:
- The body's response to stressful situations.
- Production and processing of glutathione. It acts as a key antioxidant in the body.
- Detoxification of hormones, heavy metals and chemical compounds.
- Control inflammation.
- Repair damaged cells.
- The immune response and its regulation, the fight against viruses and infections, the control of the production of T-elements.
The process of DNA methylation is also important. Let's take a closer look at it.
Epigenetic control of development
DNA methylation promotes the transmission of patterns to the next generation of cells during mitosis. Relatively recently, it was found that the process of joining groups of atoms in the terminaldifferentiated structures has a certain relationship with memory formation and synaptic plasticity. K. Miller and D. Sweet investigated DNA methylation. The study of the phenomenon led them to the conclusion that the activity of deoxyribonucleic acid methylase significantly increases in animals during the memorization of new information. This contributes to a decrease in the expression of genes that suppress memory processes. In addition, the authors point to another phenomenon. The researchers report that activation of the reelin protein gene, which promotes changes in synaptic connections and is involved in the pathological course of schizophrenia, is affected by memory formation. In this case, the determining factor is demitalase-enzymes that provide DNA demethylation (release from methyl groups). The established facts allow us to draw the most important conclusion. DNA methylation as one of the epigenetic mechanisms, as well as its reverse phenomenon, play an essential role in information storage and memorization. This idea is confirmed by the results of a study by E. Costa's group. It has been found that the demylation of the glutamate decarboxylase and reelin genes can be mediated in mice by small molecules that interfere with the installation of DNA in the nucleus. These studies indicate not only the possibility of changing the prevailing ideas about the formation of memory. They also indicate that DNA methylation, previously considered permanent, is dynamic. Moreover, it can be used in therapy.
Features
The idea that memory and DNA methylation are linked is not new. The conditionality of synaptic transmission by histone acetylation has already been established earlier. They form the skeleton around which the DNA winds. Acetylation leads to a decrease in the affinity of histones for nucleic acids. As a result, access to DNA and other proteins associated, among other things, with gene activation is opened. In fact, the histone acetyltransferase activity of CREBBP (a binding protein), which acts as a key neuronal transcription factor, has been associated with the effect of this protein on memory. In addition, an increase in long-term memory was found during the use of histone deacetylase inhibitors. It led to an acceleration of histone acetylation.
Hypotheses
Sweet and Miller asked the following question regarding histone-dependent downregulation of structure expression. If it can play a role in memory regulation, would DNA methylation have a similar effect? This phenomenon was considered primarily as a means of maintaining the activity of structures during mitosis and the formation of systems. However, in the mature mammalian brain, the intensity of methylases was observed, despite the fact that most of its cells are non-dividing. Due to the fact that the phenomenon under consideration contributes to the suppression of gene expression, scientists could not reject the possibility of a connection between methylases and regulatory processes in neurons.
Checking assumptions
Sweet and hisColleagues, studying DNA methylation and the significance of this phenomenon in memory formation, treated sections of the hippocampus with inhibitors of deoxyribonucleic acid methyltransferases. They found that this prevents the onset of long-term potentiation - the strengthening of synaptic connections in response to neuronal activity. This process determines the operation of the mechanisms of learning and memory. The scientists also found that inhibitors reduced the level of methylation in reelin DNA. This indicated his reversibility.
Experiments
Deciding to go further with their research, Sweet and Miller began observing changes in methylation patterns in mice in a model in which animals learn to associate a specific location with unpleasant stimuli, particularly mild shocks. The behavior of subjects treated with inhibitors expressed the possible difficulties of learning. When placed in an environment in which they should have been afraid, they froze significantly less frequently than control animals.
Conclusions
How might methylation affect the memory of mice? Scientists explained this as follows. There are quite a lot of sites in DNA that can be affected by the addition of groups of hydrogen and carbon atoms. In this regard, the researchers decided to turn to the following phenomenon. They first studied the methylation of genes whose role in memory formation had already been established. First, the area where the memory processes of the phosphatase protein are suppressed was considered. Reduced expressioncould cause the opposite. Indeed, after an hour of contextual fear conditioning, methylation levels increased more than a hundredfold. At the same time, mRNA levels in the CA1 hippocampal region underwent a slight but statistically significant decrease. This effect is found in the brain of animals with a combination of minor shock to the limbs and the novelty of the context. Individually, these stimuli provide no effect on methylation. Accordingly, joining groups is carried out exclusively with real training.
DNA methylation and aging
Problems of age and oncological diseases are among the most discussed topics. Over many years of research, scientists have proposed a variety of theories and models. However, no single concept currently answers all questions completely. Meanwhile, the greatest interest in the search for a solution to the problem of aging is the study of changes in gene activity. In particular, Professor Anisimov expressed his opinion on this matter. He points out that expression of genes depends, among other things, on methylation, which can affect the rate of aging. Up to 5% of the cytosine residues of deoxyribonucleic acid underwent the addition of groups of carbon and hydrogen atoms with the formation of 5MC (5-methylcytosine). This base is considered the only constant in the DNA of higher organisms. The joining of groups takes place in both threads symmetrically. The 5mC residues are always covered by guanine residues. At the same time, the structuresperform different functions. However, it is important to note that methylation is involved in the regulation of gene activity. Changes in the course of joining groups are caused by failures in the transcription level.
Reasons
Age-related demethylation was first described in 1973. This revealed a difference in the degree of separation of groups in the tissues of rats. In the brain, demethylation was more active than in the liver. Subsequently, a decrease in 5mC was found with age in the lungs, as well as in fibroblast formations of the skin. The researchers suggested that age-related demethylation predisposes cells to tumor transformation. This phenomenon can be represented in simple terms as follows. An inactive gene is attached to a methyl group. Under the influence of chemical reactions, it is disconnected. Accordingly, the gene is activated. A group of atoms acts as a fuse. The smaller their number, the more the cell will be differentiated and, accordingly, older, the more of them, the younger it will be. A classic example widely used in the literature is the development of certain salmon species. The phenomenon of their exceptionally rapid death immediately after spawning was revealed. Yesterday, young individuals of reproductive age die within a short time. In biological terms, this phenomenon is accelerated aging, which is accompanied by massive demethylation of DNA.
How to help the body?
There are various ways in whichcan improve innate DNA methylation. Among the most popular are:
- Eating fresh greens. Leafy vegetables are especially recommended. They act as a source of folic acid, which is essential for proper methylation.
- Taking vitamins B12 and B6, riboflavin. Their sources are eggs, fish, almonds, walnuts, asparagus, etc.
- Get enough zinc and magnesium. They provide maintenance of methylation.
- Probiotic intake. They contribute to the receipt and absorption of B-group vitamins and folic acid.
It is also important to minimize stressful situations, give up bad habits (drinking, smoking). Care must be taken to ensure that toxic substances do not enter the body. These compounds take methyl groups, load the liver.
