A vicious circle
Why do the diseases of old age progress like an avalanche
Maria Nedyuk, Izvestia
In search of a "cure for old age" Russian scientists have revealed the causes of age-related diseases. Biologists examined the statistics of deaths from atherosclerosis, hypertension, diabetes mellitus of two types, Alzheimer's and Parkinson's diseases, step by step studied the course of these diseases. They also described which cellular processes need to be affected in order to slow down the development of age-related pathologies. To do this, scientists have applied the concept of "vicious circles", based on a large amount of data, showing that such diseases develop in an avalanche.
Avalanche of age-related diseases
According to UN forecasts, by 2050 the number of people aged 60 and older will be more than 2 billion compared to 900 million today. Therefore, the problem of age-related diseases has come to the fore in medical science: scientists around the world are trying to find an effective cure for old age.
Drugs that can increase life expectancy and reduce the risk of aging-related ailments are called geroprotectors. It is assumed that a person, having started taking such medications in his youth, will be able to live longer and get sick less. However, the conclusions made by scientists from the Moscow Institute of Physics and Technology contradict this. The results of their research show that medicines will not be able to rid humanity of senile diseases.
– It is impossible to get rid of age–related diseases completely, - Alexey Belikov, an employee of the laboratory for the development of innovative medicines and agrobiotechnologies at MIPT, told Izvestia. – Having considered the course of development of age-related diseases, it can be concluded that by the time of diagnosis, it is useless to influence the initial, starting factor. The most effective is to suppress chemical reactions that provoke the development of ailments.
Physictech scientists have analyzed modern approaches to the treatment of age-related diseases and data on how they are formed. Then we compared mortality statistics, conducted mathematical and bioinformatic data analysis and found out that during life the risk of irreversible development of such ailments increases exponentially.
In the course of the study, scientists focused on the five most common diseases that are commonly attributed to age. They examined the statistics of deaths from atherosclerosis, hypertension, diabetes mellitus of two types, Alzheimer's and Parkinson's diseases. Then, step by step, we examined the process of occurrence of each of the five ailments and identified molecular and cellular reactions that form closed cycles.
In a detailed analysis of the development of age-related diseases, it turned out that exponential growth is observed when single reactions produce toxic products at the molecular or cellular level. They, in turn, restart the same reactions at first, multiplying themselves many times and contributing to the avalanche-like development of the disease.
Reaction cycle
In human nervous tissue there is a small amount of the protein α-synuclein, which is involved in the transmission of nerve impulses. Sometimes the gene encoding this substance mutates. The changes lead to the formation of an incorrectly folded protein. But mutant α-synuclein by itself does not lead to rapid progress of the disease.
– The avalanche-like progress of Parkinson's disease can be explained by the fact that the mutant protein triggers a cycle of reactions and forms polymers and clusters. They, in turn, initiate the appearance of new molecules of the wrong α-synuclein. Thus, the cycle of reactions is closed. Toxic products stimulate the production of the starting substance, and so on in a circle," said Alexey Belikov.
In the case of Alzheimer's disease, the vicious circles are triggered by the beta-amyloid protein according to a scheme similar to Parkinson's disease. If a genetic mutation occurs in at least one protein molecule, it begins to produce pathogenic beta-amyloid around itself. Then these mutant molecules stick together into plaques, which disrupts the functioning of neurons and synapses in the brain and causes Alzheimer's disease.
In atherosclerosis, the cycle is triggered by oxidized low-density lipoproteins. This so-called "bad cholesterol" is oxidized due to the fact that the walls of blood vessels contain enzymes that produce active oxygen. As a result, substances are formed that attract cells of the immune system – macrophages. They, in turn, tend to absorb the "wrong" lipoproteins, but they themselves produce oxygen.
– These reactive oxygen species oxidize those low-density lipoproteins that have not yet been modified. This is how the cycle of atherosclerosis formation starts," Alexey Belikov noted.
Glucose plays a key role in diabetes. According to the theory put forward by scientists from MIPT, diabetes of both the first (not congenital) and the second type occurs due to the fact that beta cells of the pancreas producing the hormone insulin, which lowers blood glucose levels, are overloaded. Under certain factors, in particular obesity, cells do not have time to process excess monosaccharides and die. As a result of a decrease in their number, the load on the pancreas only increases, which, in turn, leads to the death of even more beta cells. At the same time, the demand for insulin in the body increases again. This leads to the formation of the disease.
There are two ways of occurrence of hypertension – through an increase in average pressure and through the difference between "upper" and "lower" pressure. In the first case, the avalanche-like development of hypertension is provoked by the reactive oxygen species produced in the vessels, which oxidize the nitric oxide necessary for vasodilation. Due to the fact that the vessels cannot expand, a spasm occurs, which provokes general pressure surges.
As for the difference between the "upper" and "lower" pressure, the reason lies in the fact that with age, the artery tissue itself becomes more rigid – it produces more collagen and less elastin. During the contraction of the heart, a pulse wave of blood pressure spreads through the blood vessels. If the artery is not elastic, then when a pressure wave hits its walls, smooth muscle cells change their phenotype and become secretory. That is, they turn into cells that additionally synthesize collagen and destroy elastin. This is how the circle of hypertension formation starts.
The concept of "vicious circles"
The concept of "vicious circles" it has never been associated with age-related diseases. MIPT scientists expect that this theory will help to create drugs for the five listed age-related diseases. Since now, in their opinion, it is clear which biological targets (cells or tissues capable of reacting to certain drugs) need to be affected in order to break the destructive closed cycles.
The level of systematization and generalization of available data is of great interest, says Konstantin Brazovsky, professor at the Research School of Chemical and Biomedical Technologies at Tomsk Polytechnic University.
– To build the structural models given in the article, gigantic efforts are required to collect information from a variety of sources, to verify their consistency, – he stressed.
The vision of the problem proposed by MIPT scientists is one of the first steps in the development of systemic bioinformatics, according to Maria Vedunova, director of the Institute of Biology and Biomedicine of N.I. Lobachevsky National Research University, a university participating in the 5-100 project.
– However, the approaches used to solve this problem from a biological point of view seem rude and do not take into account modern knowledge. For example, about the development of metabolic syndrome as a complex pathology, the separate links of which are hypertension, type II diabetes mellitus and atherosclerosis. Despite this, such work should become the basis for the development of a new direction of research and in the future may be of great importance for the development of medicine and active longevity, – said Maria Vedunova.
The results of the study are published in the international scientific journal Aging Research Reviews.
Portal "Eternal youth" http://vechnayamolodost.ru