In search of Health Genes
Evgeny Rogaev: We are exploring the genomes of centenarians to find "health genes"
Vasilisa Babitskaya, "Snob"
Professor of Moscow State University, nominee for the "Made in Russia" award Evgeny Rogaev discovered the genes responsible for the onset of Alzheimer's disease. In an interview with Snob, he talked about when the scientific community will be able to defeat death and find the long-awaited "pill for old age".
– How can genetic analysis predict the development of Alzheimer's disease?
– Alzheimer's disease is a neuropsychic disease that is studied in neurological clinics. In 1907, Alzheimer discovered that sufferers of this disease have plaques in the brain – accumulations of proteins in the intercellular space – and tangles of protein cells that are located inside neurons. Thus, the scientist proved that physiological lesions are behind the violation, which was considered mental.
Together with colleagues from Toronto, we began to find out how the mechanism of Alzheimer's disease works, and discovered the so-called presenilins. Mutations in presenilins lead to the early development of Alzheimer's disease: if there are changes in these proteins, then it is almost one hundred percent likely that a person will definitely get sick before the age of 60-65.
Out of 100 people with Alzheimer's disease, five to seven people will have such mutations. Although presenilin activity is a necessary component of the development of the disease, there are other genetic mutations of late and most common forms of Alzheimer's disease. Knowing these gene targets, you can look for drugs aimed at them.
– How often are mental illnesses caused genetically?
– Along with the study of Alzheimer's disease genes, we are also looking for genes responsible for the development of schizophrenia. With this disease, everything is more difficult: it is not possible to find some clear sign of organic disorders in the brain that would make it possible to unambiguously determine the presence of this disease. Early assumptions were that schizophrenia appears due to violations of the "chemistry" of the brain and failures in the production of active substances, chemical signals, in particular, dopamine. These assumptions were based on the fact that the drugs used to treat schizophrenia affect the dopamine system of the body. But there is no convincing evidence that this is the cause of the disease. Schizophrenia may be caused by brain development disorders that are influenced by genetic and non–genetic factors, but which ones are still to be determined. It is not yet possible to identify genes whose mutation will necessarily mean that a person will get schizophrenia.
Most likely, schizophrenia is a consequence of genetic variations in several or many genes, each of which does not have a strong pathological effect. But their specific combination in the genome of one person determines the risk of the disease.
– What other factors influence the development of such genetic diseases?
In the process of human development, so-called epigenetic changes occur: the structure of DNA remains the same, but the activity of genes changes. They have a particularly strong effect on the body if they occur at the age of one to three years.
For example, viral infections combined with genetic factors can lead to an increased likelihood of mental illness. The study of such changes is a new scientific field in which it will be possible to study the risk of developing autism, schizophrenia and other diseases affecting the human psyche.
– Is it possible to reverse such epigenetic changes? Reduce the risk of developing mental illness?
– Unlike genetic mutations, epigenetic changes are reversible in principle. During the development and maturation of the organism, the genome of each type of cells, neurons, liver, muscles, and so on acquires its own epigenetic imprint. When culturing skin cells in a Petri dish, such an imprint can be "erased" and the activity of genes can be changed, turning them into another type of cell.
There is one unique example in nature that illustrates that it is possible to reverse the development of an organism. Our Italian colleagues have discovered a jellyfish called Turitopsis – it literally knows how to turn back time. An ordinary jellyfish is first born and remains in a polyp state, after which it multiplies and dies, like all animals. Turitopsis does not die after reproduction, but goes through all these stages backwards, from the adult stage of the jellyfish turning back into a polyp. It is not yet known how many such cycles this creature goes through. One of the possible reasons is that this type of animal reacts to stress in this way and, instead of dying, moves into a safer form of existence for it. We assume that the genome of this animal can be reprogrammed, which includes the reverse process of development. To understand which genes are involved in such a process and how their activity changes, first you need to determine the sequence of the genome and all the genes of this animal, which is what we are doing. This organism can be a natural model of "struggle" with aging.
Why is it important to try to push back aging as much as possible? Because this is the main factor for the occurrence of many common human diseases. If we postpone the programmed aging process, we automatically prevent the risk of getting sick and dying from conditional Alzheimer's, cancer, cardiovascular and other senile diseases. Even if a person has genetic risk factors prescribing such a disease, for what reason does it manifest itself only in adulthood or in old age?
We assume that in old age, epigenetic changes begin in a person, affecting the activity of genes, which, along with genetic factors, lead to the occurrence of diseases. And today we know that with aging, some parts of the human genome in different cell types change their activity. As in the case of Alzheimer's disease, we can potentially influence gene targets, and therefore regulate many diseases of aging in the future.
– How realistic do you think the possibility of overcoming death is?
– The idea that a person can biologically live indefinitely is still groundless. No diet or pills will help us in this. All animals have a specific life span, including humans. The oldest person studied by scientists was 114 years old.
Yes, indeed, the average life expectancy has now increased, primarily due to successful methods of treating many infectious diseases and a sharp decrease in child mortality. But that's not enough. One of the directions of our research is the search for so–called "health genes". We study the genomes of centenarians to understand how they lived to their years without cancer, dementia and other senile diseases. And if such natural genetic mechanisms of the body's defense are found, then this knowledge can be used in the development of ways to treat and prevent "popular" diseases in middle and late age.
Evgeny Rogaev is a Professor at Moscow State University, Head of the Human Genomics Department at the Institute of General Genetics of the Russian Academy of Sciences.
Portal "Eternal youth" http://vechnayamolodost.ru