Scientists spoke about fundamental research into the aging process
Most of us are prevented from living beyond 100 years by the species barrier. According to some unknown program, the longest-living creature on Earth — the Greenland shark — lives up to 400 (!) years, and man — the “crown of creation” — is four times less. Scientists are trying to find an answer to this question, which in the future may move our “barrier” to a more distant period. Russian scientists spoke about basic research in this direction at the RAS Life Sciences Council held on April 17, dedicated to the problem of aging. A MK observer was present at the meeting.
Aging is one of the few human “diseases” for which the mechanism has not yet been unraveled.
– We lack a comprehensive understanding of this mechanism, – clarifies academician of the Russian Academy of Sciences, rector of RNIIMU named after. N.I. Pirogova Sergei LUKYANOV. – But it’s even more interesting, because this is a challenge for scientists all over the world.
Lukyanov, according to him, focused his search for an answer on the complex immune system inherent in higher animals and humans: it is in it that dramatic changes occur, it is in it there is enormous individualization involved.
According to the scientist, at the same time that a person accumulates memory T cells throughout his life, protecting him from all previously suffered diseases, the number of so-called naive T cells in his body, which are actively formed up to 20 years in the thymus gland, decreases in his body ( thymus) and have not previously had contact with pathogens. Naïve T cells have great potential in fighting new viruses and cancer cells. With age, their number decreases, making older people very sensitive to new infections.
But there are exceptions: the peculiarity of those who have crossed the 90 and 100-year mark is, according to Lukyanov, precisely their immune status, which corresponds to the status of middle-aged people who are still generating stronger naive T cells.
“We tried to understand how a similar system works in other animals,” says Lukyanov. – For example, in a mole rat or naked mole rat — rodents that, unlike their counterparts — mice, live 10 times longer, naive cells are generated all the time, but memory cells are absent, and this allows them to exist longer.
Further, according to Lukyanov, scientists deeply studied the composition of those very T-memory cells that accompany both mice and humans throughout their lives. It turned out that they sometimes become poorly controlled!
“Our general concept is this: our complex immunity, which makes decisions to destroy numerous infections and resists oncology, can make not entirely correct decisions (that is, direct its “defensive” reaction in the wrong direction), says the academician. – You can’t call their actions erroneous (that would be autoimmune reactions). But such inaccurate decisions accumulate with age and create the pro-inflammatory environment characteristic of older people. These are nonspecific inflammations (without any obvious pathology) that simply make people more “fragile.” Currently, scientists are looking for ways to isolate such “bad” T cells.
Head of the Department of Genetics, Faculty of Biology, Moscow State University. M.V. Lomonosov, academician Evgeny ROGAEV spoke about genetic studies of the aging process.
“When we talk about life expectancy, we must separate the average and maximum life expectancy,” says Rogaev. – The average life expectancy in our population is constantly growing, but as for the maximum, it is quite obvious that there is a species barrier. It has been observed that organisms with a high metabolism live less, those with a lower metabolism live longer, and animals that reach a large size also live longer. And the latter have individual mechanisms that prolong their life. For example, an elephant has more copies of the gene responsible for resistance to cancer.
But the general genomic mechanism of species limitation of life is still unknown. Genetic factors, according to the scientist, play a rather limited role in human survival to 60 years of age. Then, to reach a later age, the importance of genetics increases. Rogaev's group's research is aimed at studying Russian centenarians and identifying genes and genetic variants that allow them to live to 100 years or more. Moreover, the task is not so much to determine which genes are responsible for the ability to live to 100 years old, but to find the molecular mechanisms responsible for protection against diseases of old age, such as atherosclerosis, cancer, Alzheimer's disease and other dementias.
B Russia has several thousand centenarian citizens. As part of one of the programs, scientists studied the complete genomes of hundreds of such people and suggested that for many, longevity may be associated with rare genetic variants.
“We also paid attention to the ApoE gene,” says Rogaev. This gene encodes a protein responsible for lipid transport. – Most people have the ApoE3 variant in their genome. The frequency of another genetic variant, ApoE4, is about 10% in many European populations, including Russians. It turned out that in the group of 100-year-olds, the frequency of occurrence of ApoE4 is significantly reduced compared to the population, while the third variant, ApoE2, is more common in centenarians than in the population. That is, we conclude that ApoE2 may play a protective role against aging diseases.
Turritopsis dohrnii
By the way, ApoE4 is a risk factor for Alzheimer's disease, and it is believed that the presence of the ApoE2 variant is precisely and protects older people from this disease. Overall, ApoE is a potential target for the development of therapies, including gene therapy for Alzheimer's disease.
In addition, according to the academician, scientists are trying to “find out” the epigenetic mechanism of influence on life expectancy. That is, a mechanism different from mutations that humans can manipulate. How? Increased physical activity, changes in diet, and certain medications.
“We are trying to build a bridge between these methods and the molecular level,” says Evgeniy Rogaev. – For example, it will be interesting to find out what level of physical activity is aerobic or anaerobic, which foods will be more useful for prolonging life and regulating genes beneficial for health and healthy longevity.
The scientist also spoke about another unique project that his laboratory is carrying out — the study of the so-called “immortal” jellyfish Turritopsis dorhnii.
Biologists have long paid attention to this organism, which is reversing its development. Direct development from polyp to jellyfish and back — from jellyfish to polyp. If ordinary living beings are first born, then mature, reproduce and ultimately die, then the “immortal” jellyfish repeats its life cycle again at the end of each complete development cycle. It turns out that this creature has unraveled the mystery of genomic reprogramming!
“It was believed that the Turritopsis dorhnii jellyfish could not be cultivated in the laboratory,” says the project manager. “But this is the first time we have succeeded.” In fact, despite its name — «immortal», the jellyfish is very fragile — in order to preserve it in the laboratory, we have to feed it live shrimp and oyster oil. As a result, several life cycles of this living creature have already been obtained.
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