Vaccination against old age?
Pushchina scientists suggest ways to prolong an active human life
Firyuza Yanchilina, the newspaper "Search" No. 36-2013
How to maintain an active and full-blooded life until old age? The answer to this question was tried to find in ancient times. Today, scientists are throwing the whole arsenal of modern tools to unravel the secret of "ageless aging". Many of them are used in their work by senior researcher at the Institute of Cell Biophysics (IBC) of the Russian Academy of Sciences, Doctor of Biological Sciences Nikolay Vekshin. The researcher admitted that he has been worried about this problem since his school years.
– At some point I suddenly realized that people are doomed to die, - says Nikolai Lazarevich. – I really wanted to invent the "elixir of youth". This aroused interest in biology. After graduating from school, he entered the Department of Biophysics of the Faculty of Medicine and Biology of the 2nd Medical Institute named after N.I.Pirogov.
He began to pay special attention to research methods that made it possible to understand what processes take place in a living cell and what leads to the loss of its viability. It turned out that her aging strongly depends on the functioning of mitochondria. This is a kind of cell battery, the source of its energy, without which it cannot function. This means that life is impossible without it.
I have been studying mitochondria since the very beginning of my scientific career, when I was still an intern at the IBC Bioenergetics laboratory. We have all heard about these intracellular structures one micron in size, which are responsible for the energy, respiration of cells and protect them from oxygen damage, even in biology lessons. Mitochondrial aging is one of the main causes of aging of the body. Scientists have learned, in particular, to isolate the embryos of these organelles with a size of 0.1-0.2 microns and studied their "maturation". Interestingly, the amount of DNA in them increases with development in proportion to the increase in the amount of protein. The process of maturation consists not only in a 100-fold "swelling" of the volume of particles, but also in qualitative changes in the enzyme composition, an increase in the number of cytochromes and flavoproteins – proteins responsible for electron transfer.
In 2000, with the funds of the Dutch-Russian NWO grant and in 2007, under the RFBR grant, we studied damage to NADH dehydrogenase, a key enzyme in the mitochondrial respiratory chain. It turned out that aging is sharply activated when this enzyme loses the flavin mononucleotide (FMN) necessary for electron transfer in NADH dehydrogenase. FMN "falls out" of the mitochondria almost spontaneously, but especially strongly when heated, mechanical damage, the action of detergents (chemical soaps that are contained, for example, in washing powders). It is the FMN that is the weak link of the respiratory chain. Why nature has arranged such an "outrage" is not clear. After all, all other similar enzymes have flavin in their composition, which is firmly bound. In the laboratory, we learned how to prevent FMN from "falling out": we added a number of natural metabolites to a suspension of isolated mitochondria or cells by mixing them in a test tube. One of these metabolites is NADH (nicotinamide adenine dinucleotide). When it binds in NADH-dehydrogenase, it stabilizes it, making the active center of the enzyme hard as a crystal, and as if "plugging" the place from which FMN could "fall out". The respiratory chain begins to work properly, without forming superoxide. This allows you to block dangerous damage and dramatically slow down the aging of cells. Superoxide is oxygen that has taken on one electron. This form of the "element of life" is especially "aggressive", it quickly enters into various reactions: it oxidizes lipids, proteins, DNA, leading to a violation of their functions.
– Tell us about the most important stages of your work.
– First, we studied the physico-chemical mechanisms of cellular aging. A lot was already known about these mechanisms before us. But it was necessary to process and systematize a huge array of experimental disparate information, to establish the main ways of "senile degradation" without getting bogged down in minor details. Then we experimentally discovered a number of new substances that effectively slow down aging and even reverse it. Among them are natural metabolites, antioxidants, cofactors, vitamins, DNA stabilizers. For example, it turned out that NADH dehydrogenase is stabilized by the addition of adenylic nucleotides, which, as it turned out, prevent FMN from "falling out" of the enzyme. We tested a number of substances on isolated mitochondria, cells and mice. Natural substances such as ATP, the antioxidant dehydroquercetin and some others prevent damage to mitochondria and cells by superoxide. After administration of DNA-stabilizing compounds to mice (for example, actinomycin), life expectancy increased by 40%.
For 10 years, the research work was carried out by a large team of researchers, graduate students, undergraduates (only two dozen people). Several dissertations were defended. Unfortunately, only five are working now, the reason is insufficient funding.
– And yet, is the elixir of youth a myth and a dream of alchemists or a very real thing? What did you manage to do?
– It's too early to talk about the elixir, of course. But we managed to develop a complex drug with the working name "Antistarin", which is now being tested on animals (cats and dogs). It consists of 15 natural substances (no "chemistry") with high physiological activity. It is a yellow powder. The drug is obtained by mixing the components in certain proportions and under special conditions. When dissolved in water, nanoparticles are formed that easily penetrate into cells and rejuvenate them. Similar drugs are being developed in our country and abroad, but they all have a narrow spectrum of action and are often not harmless to the human body, since they are products of chemical synthesis. For example, in the laboratory of Academician Vladimir Petrovich Skulachev in Moscow, an analogue of natural ubiquinone, SkQ, was synthesized, which has pronounced beneficial antioxidant properties, but has a rather toxic substance in its composition. This drug makes it possible to treat cataracts in animals and prolongs the life of rapidly aging genetically defective mice, but the possibilities of its use to combat natural aging, especially in humans, are not yet clear.
The prospects for our drug look quite promising, at least in veterinary medicine. "Antistarin" improves the condition of animals with parkinsonism, activates metabolism, restores hair. We conducted research on several old dogs and cats. After a month's course, they became more active, looked noticeably younger. For example, my dog (a West Siberian husky) at the age of 15 passed badly: he could not go hunting, he got tired quickly, his hind legs buckled, his fur fell out in shreds. After using the first trial drug (of eight components), almost all of these problems disappeared. The dog began to jump, stopped getting tired, the condition of the coat improved.
Animal testing is ongoing now. Then, in one of the Pushchina innovative enterprises, we plan to start the production (first experimental, later serial) of "Antistarin" as a veterinary remedy. Well, our research continues. We hope that in the future their results will allow us to start treating people.
Portal "Eternal youth" http://vechnayamolodost.ru06.09.2013