Senior Fellow, Institute of Biochemical Physics, Russian Academy of Sciences Alexei Olovnikov believes that the aging of the organism manages the gravitational field of the Moon. It causes periodic "hot flashes" in the pineal gland that result in hormonal release, shortens the life of the organism
Illustration: Konstantin Batynkov
Black Sicilian night. New Moon. Over the looming volcano erupts from time to time a thick cloud of scarlet, illuminated from inside the crater. Feelings are fantastic — a delight and horror on the power of wildlife. These feelings then remember Alex Olovnikov when will build almost mystical theory of aging, which tied seem unrelated elements — a young moon, the tides, the sand in the brain (in the part called the pineal gland), volcanic emissions hormones acting on the small yet unknown science of DNA that act as biological clock that is ticking, as we left.
Why the organism dies, why is there a certain time of life, why aging occurs, which is the cause? These are questions that scientists have set themselves for hundreds of years. There are dozens of theories of aging. Among them — the theory of gene-related death, or programmed changes in gene expression, telomere shortening, or disruption of genes that lead to the synthesis of excess protein. Some authors believe that aging is associated with mutations, DNA damage and protein depletion as a result of the accumulation of damage.
The most vivid and believable, according to the president of the Gerontological Society of Sciences Prof. Vladimir Anisimov, who are four theories: launched in the fifties D. Harman, The free radical theory, Elevating Dil'man, cellular aging and L. Hayflick's theory Olovnikova.
Our compatriot Vladimir Dilman, who lived the last years in the United States, believed that aging and diseases associated with it — a by-product of the genetic program of development of the organism. He also formulated the idea of the biological clock as a regulatory mechanism that determines the laws of the various homeostatic systems.
The free radical theory of aging Harman says that when external harmful influences on the organism appear in the cytoplasm of free radicals, particularly reactive oxygen species, hydrogen peroxide decomposition products, which can damage any molecules, including DNA. Over time the body is getting worse neutralizes free radicals, aging, and death occurs. Proponents of this theory, Academician Vladimir Skulachev, however, believes that free radicals do not appear by chance and suggests that aging program embedded in the human body. And if so, then this program can try to cancel with antioxidative drugs (see "Do not be stupid salmon" "Expert» № 29-30 in 2005). Theory Hayflick limit associated with the effect of cell division. Having exhausted the limit, the cells die, the body is aging. However, Hayflick has not explained why there is this limit. Alex guessed the riddle Olovnikov. He suggested that the Hayflick limit is associated with a terminal underreplication DNA. Recall how the cell divides: DNA runs on a special enzyme — DNA polymerase to form a copy or replica DNA. However, the polymerase does not read the tips of DNA because it does not capture the most extreme sequence of nucleotides. Schematically the linear DNA consists of the structural genes coding for proteins, and its ends are portions that contain certain genes and regulatory sequences, such as would not carry any useful information. These sequences in the thirties, scientists discovered B. McClintock and H. Muller. They suggested that the tips of DNA likely serve as a protection of the genome from damage. Scientists have named their telomeres. Alexei Olovnikov conjectured that every time a cell divides, these telomeres are shortened, and the opinion that this is the cause of aging. However, at the beginning of the new century, he put forward a new original theory, which he called's redusome. He suggested that aging is associated with telomere shortening is not as redumer. Redumery same — a new type of DNA that are small tabs are arranged on the chromosomal DNA. According to him, they are shortened under the influence of hormones emissions and these emissions peak occurs at new moon.
The idea of Olovnikova redumerah many seemed to be fantastic — because such small DNA were not known to science. More recently, however, scientists discovered in the mitochondria are small single-stranded DNA. It is unclear what the purpose of these short threads of DNA, but the mere fact of their existence gives hope that small double-stranded DNA — redumery Olovnikova — not just a figment of imagination theorist. "Of course, Alexis Olovnikova redusomnaya theory, despite its speculative and science fiction character, even if it is not confirmed as a whole, gives an extraordinary charge and encourages to seek surprising and beautiful world with which we are acquainted the author", — says Vladimir Anisimov theory . Academician Vladimir Skulachev also notes that the theory seems a little crazy, but that all geniuses are a little crazy … Skulachev does not deny that the theory Olovnikova may well be true. Incidentally, Skulachev also reported that Alex Olovnikov have repeatedly put forward a candidate for the Nobel Prize. Give the floor to Alexei Olovnikova.
— Alex Matveyevich, at which point you are interested in the problems of aging?
— Initially I was doing experimental work in the field of immunochemistry. And aging interested in the sixties, when Leonard Hayflick put his remarkable experiments. He showed that cells have a limited mitotic potential — on average, they are divided about 50 times. Previously it was believed that doubling the cells indefinitely. Hayflick showed that the cells sits a sort of "molecular accountant" that counts down the division. And always remember how many times a cell shared. In a series of experiments it was, and such experiments: After twenty, for example, dividing cells were frozen in liquid nitrogen, then taken out — five minutes or year — and they have continued to divide the allotted number of times, about thirty.
— And Hayflick linked this effect with aging?
— Yes. And after him, too. It was assumed that the cells cease to divide, die, body aging begin ages disease and so on. In general, when I first heard about the experiments of Hayflick, I was naturally very interested. Repeatedly heard about them at MSU. A lecture on the work of Hayflick read the discoverer of mesenchymal stem cells Alexander Y. Fridenshtein. Lectures he gave brilliant. I listened, and am stunned by this riddle Hayflick: he did not say where the cage is the limit. I left the university in the state of polutransa. I remember well: fall, the earth is strewn with golden leaves. I walked, and never thought, well, what's working? The answer did not come. So I dobrel to the subway. And when came down, he heard the noise of the approaching train. And then it dawned. I get it. The image was formed. What is the doubling of the cells? This is essentially a doubling of the DNA. DNA — is rails. By doubling the cellular DNA is progressing special enzyme DNA polymerase that makes copies (replicas) of DNA. The polymerase moves like leading a wagon train. But DNA, like the rails, end there. As a leading car, the enzyme DNA polymerase rests to a standstill. Imagine that in the middle of the lead car has a catalytic center, as in a DNA polymerase. That's it for the rails and makes a copy. This catalytic center does not reach the end of the rails. This means that the end of our DNA (speaking of chromosomes, the telomeres piece) is not copied. That's how I found the solution to the problem Hayflick.
— And when you put forth the idea?
— In 1971 I published an article in the Proceedings of the Academy of Sciences and the American Journal Theoretical Biology. Then I thought that telomeres are simply the buffer regions of DNA that are sacrificed, becoming shorter and shorter with each cell division. I ran to molecular biologists with requests to do experiments and test it. A cute so I said, well, you're kind of a fool, what are you talking nonsense — because we all know that the genome is stable, it can not be shortened. By the way, Hayflick and because of this dogma is not linked to the DNA division limit. I insisted — well, tell me, where I have piercings logical, well try it anyway do in the West, let us we will try to forward.
— In general, did the West?
— Yes, all of my predictions experimentally confirmed. First — that the ends of the DNA — a buffer zone, and after each division, they are shortened. Second prediction — nature should devise a compensatory mechanism in the form of special DNA polymerase to keep the ends of chromosomes in the germ cells, or — the end of the living. This mechanism should also work in the immortal tumor cells. Later it turned out that this is a compensatory mechanism in stem cells. This compensatory DNA polymerase is known in the literature the name of telomerase. Another prediction — a ring of DNA in bacteria invented by nature to no end underreplication. Finally, I predicted that there should be a correlation between the size of chromosome ends, or telomeres, and the number of cell divisions of the done. And the thought that this is the cause of aging.
— That is, the cells die, the functions of the body weaken, he grows old and dies?
— Yes, but that last prediction — the role of telomere shortening in aging — I myself later rejected.
— It has not been confirmed in experiments?
— All the predictions were confirmed in experiments. Including correlation between the degree of telomere shortening and the number of cell doublings. But some studies have shown that the cells of the old man even retain the ability to double. They took twenty and ninety-cells, and it turned out that the spread in their ability to divide is not so great. The cells simply do not have time to exhaust your limit doublings before the body will age and even step back into another world. It was also found that lab mice with long telomeres and quite wild with short telomeres are living the same life. And I realized that telomere shortening is not the driving force of aging. When I expressed this thought, friends waving their hands at me: you yourself came up with the theory of telomeric and now you cut under a bough!
— Are you disappointed in telomere theory?
— I began to look for something in a cell that is not a telomere, but just like her, shortening, can be considered. Then I suggested that "accountant" could be another type of DNA molecule.
Senior Fellow, Institute of Biochemical Physics, Russian Academy of Sciences Alexei Olovnikov :: Photo: Mitya Aleshkovsky
Senior Fellow, Institute of Biochemical Physics, Russian Academy of Sciences Alexei Olovnikov
Photo: Mitya Aleshkovsky
— How is that? We know of only one large DNA molecule that is located on chromosome?
— Well, yes. And next to her, I guess, there's so little DNA.
— Draw …
— (Paints and comments.) That's longer than normal chromosomal DNA (see diagram). At the ends of telomeric DNA in her next subtelomeric so-called land and in them — some regulatory genes. So, on some regulatory genes arise, I believe, short of a DNA molecule, which contains copies of regulatory genes.
— This is your "deenkushka" floats somewhere near the large DNA?
— No, do not swim, and anchored at its ends to the body of the chromosome. These small DNA I called redumerami. We redumery, like a big DNA, there are small tips, like telomeres, I called them akromerami. And these akromerami it is attached to the places that limit the scope of the original chromosomal gene. And this little copy of akromerami looks like a parenthesis or a large loop on the DNA. When dividing redumera also replicated, and copies go to the daughter cells, keeping on chromosomes. And when replicating it also shortened the tips of how telomeres in the chromosomal DNA. The term redumera — from reduce, that is reduced. Shortening redumery in a dividing cell is causing cellular senescence. But I hasten to note that the aging of dividing cells — this is not the aging of the body, which is associated with a particular form of redumer — hronomerami.
— Has anyone seen these your redumery?
— So why are you so sure that they're there, why not say that instead redumer there is a plug socket or a parrot with battery. You all came up with!
— Of course invented. One of the famous scholars say that science — a mixture of fantasy and logic. But it seems this whole fantasy fits into the logic. In the logic cells. Because the mechanism of telomere end underreplication I also nafantaziroval.
— What redumery can not see?
— You know what it looks like DNA? The slices — like a tangle with multiple loops. I think these redumery not seen, but not identified them. Someday, I'm sure they will be looking at a student workshop. In principle, they can be identified if the sighting to search, and then separated from the large DNA.
— In one of your scientific article I read that you share on redumery printomery and hronomery
— Yes, redumery — it's common to say, the generic name. They are divided into printomery who work in dividing cells, and hronomery. The participants of the biological clock of the brain critical for understanding aging are just hronomery that are in the hypothalamus.
— Come, come! You told me that redumery decrease in cell division and that leads to aging, but that the brain's neurons do not divide. How, then, they are shortened hronomery?
— And that's the fun part. Shortening hronomer is not on the mechanism of DNA end underreplication like telomeres and printomer. Shortening hronomer due to the effect skraptinga (from the words of transcription and rupture — a break). A small gap hronomernoy DNA is called when a particular form of transcription (ie, the construction of RNA to DNA) carried transcription machinery — RNA polymerase. It is assumed that during a particularly intense transcription hronomer gap is fixed on the body of the chromosome end hronomery. This happens occasionally — against the background of rapidly rising emissions of hormones in the central nervous system.
— Under what circumstances?
— With the assistance of the moon.
— Y-yes …
— Do you think it is time to call the psihovozku? I'll explain. Here we have a little bit let's leave our rushing hronomeru. The famous Soviet scientist Vladimir Dilman has long been assumed that in the hypothalamus of human biological clock is ticking. But he did not explain what is their spring mechanism. He was an endocrinologist and a ticking clock linked to the level of hormones. Hormones perform many functions in the body. The main centers of the brain are hormonal hypothalamus, pituitary and pineal gland. In the endocrine system operates its own system of checks and balances — releases hormones, synergists and antagonists, all in order to secure the system works. But I believe that the nature of this management has used the endocrine system, and more time to think. We do know that in about fifteen years there puberty, about thirty — completely intellectually mature brain, about fifty — menopause in women, and in a certain period of time — andropause in men. Hormones are subject to different rhythms. Man in general is permeated through and through rhythms. Nature, in my view, was to choose a relatively rare rhythm that would affect the shortening hronomer and thus acted as economically spending the length of these hronomer.
— That is the biological clock control hormonal rhythms?
— Yes. This temporal rhythm of what I call the T-rhythm. A hormone (or hormones) at the peak emission to act on shortening hronomer. As I said, at the expense of transcription. Admission to the cells of the hypothalamus (that's where the hronomery) stimulating hormone causes the RNA polymerase to run on hronomere (and, of course, at all on any of the transcribed DNA) faster, creating many copies of RNA. But polymerase run so intense that at the peak of the T-hormonal rhythm mechanically pluck akromer ends at points of anchorage. A little piece of torn akromery destroyed by enzymes and accessory proteins, DNA is constantly sitting on hronomery, fix now shorten akromeru repeatedly on its original site. But now hronomera become shorter. And this is equivalent to one "tick" of the brain hronomernyh hours. The next release of hormones peak, it will be even shorter. But what else is going on? Since the attachment points on the ends of chromosomal DNA are always on the same standard distance from each other, hronomera as a kind of hinge or spring, each time more and more stretched between these points. In hronomere growing so-called torsion (spinning) voltage. This voltage must inevitably affect the work of the RNA polymerase. In experiments with individual DNA molecule, American scientists deliberately badly twisted, stretched, or, conversely, dissolve the DNA, and watched how the rate of movement by DNA polymerases. It was found that too large torsional stress in the DNA may even stop the polymerases. And in the over-stretched hronomere should decrease the productivity of RNA polymerase.
— And why this may affect the aging of the whole organism?
— In the loop-hronomere sit genes that regulate the structural genes in the chromosomal DNA by a conventional regulatory RNA. So, RNA polymerase due to the stress in natyanuvsheysya hronomernoy loop forced to move more slowly, and therefore produce fewer regulatory RNA. And without them, the activity of the structural genes of chromosomes can not be shown in full force. Therefore falls synthesis products of these genes. These products become smaller (or, conversely, more if hronomery shortening causes a decrease in protein synthesis inhibitor). That is, the old man had some kind of cell production may decrease and some increase, and all this leads to a hormonal imbalance, a change in the activity of different cells. And because of this, the entire body is aging.
In general, I postulated that the signal of aging is the failure of productivity hronomernyh regulatory genes. And the number of years lived hypothalamus man remembers shortened akromerami, not telomere DNA large as previously thought. Yes, the telomeres are shortened, too, but they are a kind of innocent bystanders of the aging process. Telomeres can not be said about his shortened cell. A hronomery can. Because of them ultimately depends structural gene activity.
— Well, as, for example, the process is said that it is time to puberty?
— If, for example, in the hypothalamus, shortened hronomera, which regulates the production of large DNA genes responsible for the containment of the process of puberty, then gradually shortening it let those reins. You will ripen.
— And what is the connection with the Moon?
— I think that the T-rhythm — it's the moon 28? Day rhythm. The sun — our pacemaker in daily rhythms, and the Moon is also our pacemaker, only in the rhythms that control the lifespan.
— But then we have to have some kind of antenna or something?
— Gravisensor. You have heard that in our ear is a sensor that allows us to know where we bow? There are hanging on thin hairs like small balls. So here they are, when we cant touch the ear cells, and so we feel which way to bend over.
— And your gravisensor not sitting in your ear?
— No, in the epiphysis. I called him lunosensorom. And the most important component of this is lunosensora sand.
— Sand in the brain? Well, there is something there.
— Do not be surprised is the scientific name — the sand of the brain (brain sand). These are calcium stones that are found in the intercellular space in the epiphysis, or otherwise in the pineal gland of the brain. They are denser and larger cells and under the influence of the moon, is particularly strong in the period of the new moon, putting pressure on the pineal gland cells, and they begin to throw out the answer of this neuropeptide hormones of the endocrine glands that are in special cellular vesicles-vacuoles. Since forming the emission peak of hormones. Epiphyseal attack hypothalamus hormones, stimulate him through it — pituitary, and in total there is a hormonal cocktail that causes cells containing hronomery, particularly in the hard work and progress to shorten them.
— And all this is happening at a given moment?
— Yes, with the participation of the Moon. Moon gravity has little influence on all that is on earth, as it is much smaller than the gravitational force of the earth. But in the new moon, when the Earth, Moon and Sun are aligned, the gravitational force of the moon is added to the sun. And then, for example, occur most powerful ocean tides. And there is a shift of grains of sand in the epiphysis. That's why I called the epiphyseal gravisensor lunosensorom.
— Is it possible to make these your T-rhythms that lead to a shortening of hronomer, ticked to less often?
— Really, would like to see less often. And I think in the future it will be possible. There will be a new branch of pharmacology — search for drugs that control the new postulated me a physiological system in the body — lunosensornoy.
— Yes, the brothers Grimm, just relax. How are you so cleverly tied the moon with sand, hormones and hronomerami?
— At a conference in Stromboli Sicilians we drove around the volcano. Night, the moon, the sea, the volcano … Something in the subconscious settled. And at the conference was a lot of material about the pineal gland. Back in Moscow, I began to read them. And one that I can see — the pineal gland slices, like a field strewn with boulders, and in between cells. Boulders — is a grain of sand. The same sand brain. And then there was, as psychologists like to say, Insight: Stromboli, the moon, the sand in the epiphysis. All lined up and contacted. I frantically began scribbling a new theory. Glad that everything is so logical. But when he wrote, read another small note that the sand-it is, of course, in the epiphysis of an adult, but the embryo is something it is not.
— I can imagine your design has to crumble like a sand castle.
— I was in a terrible disorder. As many as half an hour. My God, but that the embryo is a very necessary hours to build the body over time. And I began to dig all the information about the sand. And then nature holds out his hand. Indeed, the human embryo has no sand in the epiphysis, but it turned out it fully in the embryonic pituitary gland. And he's mechanically affects the endocrine cells. And then, about the birth of the child, this sand is absorbed in the pituitary gland, and first appears in the epiphysis. That's it.
— Pass. And then what? As a theory can be linked to the practice? Academician Skulachev already tried his drops, which make sighted dogs and horses, what do you suggest, anti-gravity helmet?
— No, the helmet does not offer. But as soon as redumery find, and I am sure, it will be possible to use their products. And you can go the other way. We are a Russian project conceived by the experimenter, the meaning of which is to find drugs interrupt signals, leading to brain aging.
«Expert» № 21 (562) / June 4, 2007