Muradyan, Razmik Khachikovich. How long has your group “Life Extension” existed?

“...the problems of rejuvenation and phenomenal longevity are not only solvable in principle, but also long ago resolved, “introduced” into practice and successfully exploited for billions of years. Unfortunately, only nature has the monopoly right to conduct such operations.”
Khachik Muradyan
"Artificial atmosphere, rejuvenation and longevity"

According to gerontologist, Doctor of Biological Sciences Khachik Muradyan, there is no more grandiose scientific idea “than maximizing the active period of human life and longevity.”
For many years, Dr. Muradyan has been studying experimental ways to prolong life. In his new study, together with his colleagues, he tried to answer the question: is the existing environment optimal, or is an atmosphere with a different gas composition necessary for quality life and longevity?

KHACHIK KAZAROVYCH MURADYAN- Doctor of Biological Sciences, researcher at the Laboratory of Physiology
/ Kyiv /. Head of the Life Extension group.

Scientific interests: phylogenetic and ontogenetic correlates and determinants of longevity, search for means of

Interview with Khachik Muradyan

Questions_Elena Vetrova
Kyiv - Moscow
May, 2009

Khachik Kazarovich, in your new article “Artificial atmosphere, rejuvenation and longevity” you write that “aging and rejuvenation are indivisible properties of living systems.” But why is it that in complex multicellular systems, even in the presence of self-repairing DNA in each cell, pronounced aging rather than rejuvenation is observed?

In order for the idea of ​​the unity of aging and rejuvenation not to seem seditious, I wanted to repeat a simple truth: if only aging existed in nature, then all living things would die, barely having time to form. The very existence of life is irrefutable proof of the coexistence and, importantly, the equal effectiveness of aging and rejuvenation of biological objects. All species in which this balance was shifted towards aging, sooner or later had to accumulate a critical mass of disorders and die.

But the question of why a multicellular organism consisting of potentially immortal elements (cells) is mortal does not yet have a satisfactory explanation. Indeed, no credible exception to this rule is known to date. In essence, a multicellular organism is a collection of cells with the same or, more precisely, almost the same genome, but located at different stages of differentiation.

Now there is a real boom in the study of stem cells and the cellular level of organization in general. Maybe we really need to be patient and wait until reliable methods are found for manipulating the cellular populations of the body, opening up the possibility of immortality not only at the level of the species, but also the individual?

In 1988, the Leningrad branch of the Nauka publishing house published the monograph “Experimental Ways to Extend Life,” written by you, together with Vladimir Veniaminovich Frolkis. Today this is a very well-known and sought-after book by biologists.

Yours new job“Artificial atmosphere, rejuvenation and longevity” indicates the existence of another way to extend life. Is this a continuation of the search that began back then?

Absolutely yes. After all, nothing disappears without a trace and nothing appears out of nowhere. By the way, Vladimir Veniaminovich and I have written several more monographs and reviews devoted to the analysis of means of life extension, for example, books published in the USA (Boca Raton: CRC Press, 1991) and Ukraine (Aging, evolution and life extension, Kyiv: Naukova Dumka , 1992).
At the same time, I have always viewed monographs as something like a large literature review. The facts or considerations set out in them should not be considered as dogmas or oaths of allegiance to these ideas, but should help broaden one’s horizons and the right choice next steps forward.

In this work, you posed two questions: “firstly, how is rejuvenation and maintenance of the viability of living systems ensured, for example, through the cell line of the reproductive system; secondly, what are the possibilities of transferring such patterns and approaches to the level of the individual and individual life expectancy.” Is it possible to resolve them in the near future? What is needed for this?

To do this, you first need to believe in this possibility and seriously pursue it. Such studies, if they do not immediately point the way to “immortality,” will at least become a significant contribution towards understanding further steps in this direction. What is needed for this? Of course, I have ideas about what and where to look for first. But I am not ready to discuss them now, especially since almost every gerontologist probably has such thoughts, however, not only them.

You hypothesized that “for successful aging and longevity, an artificial atmosphere with a different gas composition is necessary.” Today there is a device - a hypoxicator, which simulates the conditions of oxygen starvation. Few people dispute its usefulness for humans. It is known that it activates the body’s protective functions, thanks to which a person resists stress more confidently, copes better with physical activity, mobilizes in case of illness, etc.
What might the artificial atmosphere you write about be like in practical terms? What is needed to create it? What is the difficulty of reproducing it?

I'll start with the last part of the question. The fact of the matter is that there are no big and, especially, insurmountable difficulties here. Technically, humanity has been ready to solve this problem for many centuries. It is enough to note that noteworthy attempts to solve this problem were made in ancient times. However, almost all of them were based on intuitive guesses or insufficiently tested ideas and were not brought to truly completion. scientific analysis.

The essence of the problem is that the Earth's atmosphere was constantly subject to quantitative and qualitative changes. Thus, since the emergence of cyanobacteria, the ratio of the two most important gases for biological objects - oxygen (O2) and carbon dioxide (CO2) in the atmosphere has changed by many orders of magnitude. In the beginning, O2/CO2 was practically zero, but in the modern atmosphere it is over 500! Interestingly, inside the cell and in the intercellular space this ratio is close to unity. Moreover, first during the Carboniferous period (approximately 300 million years ago), the content of free oxygen in the atmosphere increased to 35% or more, and then decreased to approximately 21% (today), and according to forecasts will continue to decline rapidly.

On the diagram: composition of dry air.
N2 - nitrogen. In the form of diatomic molecules, N2 makes up most of the atmosphere - 75.6% (by mass) or 78.084% (by volume);

O2 - oxygen. In the atmosphere, the content of free oxygen is 20.95% (by volume); in the air, the mass fraction of oxygen is 23.12%. The element oxygen is part of more than 1,500 compounds in the earth's crust.

CO2 is carbon dioxide. The concentration of carbon dioxide in the Earth's atmosphere is 0.038%.

Ar - argon. The third most common element in the atmosphere - 0.93% by volume.

http://ru.wikipedia.org

Could adaptation to such significant and multidirectional changes in the composition of the atmosphere be complete and painless? Are there any memories of “ better days» evolutionary infancy and youth that could provide greater potential for vitality and longevity? I think that such a possibility cannot be excluded, and it certainly deserves proper verification.

Moreover, if our goal is to create something longer-lived and, therefore, more perfect than has yet been invented by nature, then it is quite justified to use means for this purpose that have not yet been tested. I mean, for example, inert or, as they are now more often called, noble gases. In fact, the idea that it is possible to prolong life with the help of chemical elements that under normal conditions do not react with anything and have never even been “suspected” of participating in any ontogenetic or phylogenetic transformations seems at first glance delusional. However, recent pilot studies conducted in our laboratory indicate the promise of such models.
However, other gases may also be promising in this regard. Our group has recently started doing this intensively. But, I suppose, this is a topic for another discussion.

How long has your group “Life Extension” existed?

The group was created in 1990 on the initiative of academician Vladimir Frolkis. As the name suggests, the main goal is to find means to prolong life. Since then I have been its leader (field marshal without an army).
Currently, the group officially includes 3 employees and one graduate student, but there are “enthusiastic volunteers,” so in reality 5-6 people are involved in the research.

What were the pilot studies you mentioned and what were the encouraging results?

Together with Albert Timchenko, a researcher at our institute, we tried to create a model of either hypoxia or “hypernobility” (just kidding!) by adding the noble gases at our disposal - helium and argon - to the atmospheric air. A relatively small but significant effect on life extension was found. We understand that this is only the beginning of the journey and do not lose hope that the subsequent search for more optimal concentrations and application patterns, as well as the use of other noble gases, in particular xenon and krypton, can provide a more tangible effect of life extension.

Why has the question of the role of the atmosphere in human life expectancy been ignored so far? Or is that not true?

It cannot be said that the role of the atmosphere was completely ignored. It’s just that the “chemical” aspect of this problem has not received due attention and has not entered the phase of necessary scientific analysis. In fact, there is a developed network of meteorological observations and rapid dissemination of information about the state of the atmosphere, including various media.

Moreover, the majority of the population of developed countries has almost completely switched to living in conditions of air-conditioned air, that is, essentially, an artificial atmosphere with optimized physicochemical characteristics (temperature, humidity, charged particles, etc.).

Why they are delaying a much more radical optimization of the atmosphere by changing the gas composition is indeed difficult to explain. There are, of course, unresolved problems and a certain risk here. But there are hardly more of them than, for example, in the development of new medicines, genetically modified products and some other innovations.


In 1953, Stanley Miller, a graduate student Nobel laureate Harold Urey, wondered about the origin of life on Earth and tried to recreate “in vitro” (in a flask) conditions close to those in which it could have originated.
As a result of the experiment, he received a strong broth of amino acids, the so-called “building blocks of life,” sugars, fatty acids, other organic compounds... and even more questions.
What questions do you want to find answers to?

There are indeed many such experiments confirming the possibility of the emergence of life from inanimate matter. Looking into such a distant past, even by evolutionary standards, the most important question for us seems to be: what was the role of the gas composition of the atmosphere in establishing the fundamental principles of the relationship between the processes of aging and rejuvenation?

After all, it is obvious that already the first, most primitive replicators, who managed to survive and lay the foundation for subsequent biological life, inevitably faced the problem of the interaction of aging and rejuvenation, in which the atmosphere of that time could play an important role.

Perhaps modeling such conditions will simplify this problem and make it more accessible for research and analysis. Regardless of the success of such theoretical developments, a practically important question is of independent interest: can full or partial reproduction of those conditions modify the characteristics of aging and increase the life expectancy of modern species?

The so-called endosymbiotic process (the capture of one bacterium by another and the transformation of the one inside into a mitochondrion) is a key event in the creation of multicellular organisms.

As English science journalist Bill Bryson puts it, mitochondria in cells “behave as if they believe that there can be nothing in common between us.” And one more thing: “They don’t even speak the same genetic language as the cell in which they live. In short, they keep their suitcases packed. It’s like you let a stranger into your house, but he’s been here for a billion years.”
How far have scientists progressed in studying the phenomenon of mitochondria? And what is still puzzling about them?

Indeed, the role and behavior of mitochondria in the cell remain largely mysterious, and the images of mitochondria created by different authors are contradictory, not to say multifaceted.

These are altruists, “kamikaze stokers” who, at the cost of their well-being and shortened life (the half-life of mitochondria usually does not exceed several weeks), extract energy for the host cell; then mitochondria are the main sources of uncontrolled free radicals, which many still attribute to a causal role in aging and numerous pathological disorders; then these are “parasites” who receive everything ready-made from the host cell, but at the same time, like “monkeys with a grenade in their hand,” they can destroy it at any moment by apoptosis or necrosis. After all, mitochondria have a full arsenal of means of programmed cell death, and in certain situations, for example, in denucleated (non-nuclear) cells, they can carry out “self-destruction” of the cell without the participation of the nucleus.

In Fig. structure of mitochondria (gr. mitos - thread and chondrion - granule).
The shell consists of two membranes (external and internal). The inner membrane is laid out in cristae (from Latin crista - ridge). It contains respiratory enzymes and ATP synthase enzymes. The semi-liquid matrix contains a concentrated solution of various substances (RNA, DNA, proteins, lipids, carbohydrates, ATP synthase and others), as well as ribosomes. Typically, each mitochondria contains several copies of its genome.

Whatever the true role of mitochondria, one thing is important for us - it is with them that the most powerful correlates of life expectancy are associated. Regardless of whether mitochondria are “executioners”, blindly following someone else’s instructions, or whether they themselves determine the fate of the cell and the lifespan of the organism, in any case, they seem to be the most promising targets in the search for means of extending life.

What is the connection between mitochondrial DNA (mtDNA) and longevity?


In Fig. diagram of the human mitochondrial genome.

We are only getting closer to understanding this issue. But the results that have already been obtained certainly make an impression.

Suffice it to say that in our research, conducted jointly with Professor Vadim Fraifeld from the University of the Negev (Beer Sheva / Israel), the reliability of the correlation coefficients between longevity potential and such a seemingly “rough” indicator as the composition of mtDNA bases, in mammals reaches values ​​that have no analogues among other correlates.
Only the intensity of metabolism, which is largely determined, again, by mitochondria, has a correlation of comparable strength with the species’ lifespan.

Such a strong correlative dependence probably indicates the special role of mitochondria in determining life span, although this, of course, is not yet enough to conclude that there is a causal relationship between longevity and mtDNA.
I think that this issue will be intensively developed, and soon we will learn more, including about the possibilities of extending life by modifying mtDNA and mitochondria in general.

Mitochondrial DNA is particularly sensitive to reactive oxygen species.

The negative role of oxygen in determining (limiting) the finiteness of life of multicellular organisms and in aging in general should not be exaggerated. In any case, uncontrolled oxidative transformations are far from the only processes that are difficult to control, and the proportion of oxygen in the variety of other damaging factors should be small.

You studied the role of nuclear mitochondrial - copies of various sections of mtDNA embedded in the nuclear genome - in determining a species' lifespan and found a positive correlation. Please tell us about this work.

We have collected various characteristics of Newmites from available literature sources. different types animals and compared with their maximum life spans. The highest correlation was found with the number of newmites. We were surprised that the correlation was positive.

That is, the more copies of different sections of mtDNA are introduced into the nuclear genome, the longer the life expectancy?

Yes, we believed that in long-lived species the “purity” of the preservation of nuclear and mitochondrial genomes is more strictly controlled than in short-lived species, therefore, we expected a negative correlation. And so, we had to assume that longevity is associated with the degree of “communication and good neighborly relations” between the nuclear and mitochondrial genomes. Namely, the more persistently the mitochondrial genome strives to introduce its copies into the nuclear genome and the more tolerant the latter is to this, the more long-lived the species is.

Interesting. Why are Newmites, which you figuratively called in your work “a kind of historical archive in the nuclear genome,” still little studied?

I think this is mainly due to the novelty of the question and methodological difficulties. Indeed, for a correct assessment of the number, localization and degree of homology of Newmites with mtDNA, not only highly efficient analytical tools and programs are required, which are constantly being modified, but also a complete decoding of the genome. Judging by the available databases, the number of such species, for example, mammals, does not yet go beyond the top ten. It is expected to grow rapidly in the coming years, so there is reason to hope for rapid progress in knowledge in this area.

In your work, it was suggested that not only mtDNA sequences were integrated into the nuclear genome, but also “mtDNA contains sequences of nuclear origin through which direct control and regulation of the genesis and functioning of mitochondria is carried out.” You proposed to call these executive representatives of the nuclear genome in mtDNA mitonuks (from the English mitochondrial nuclear). Do other researchers share your hypothesis?

The hypothesis about mitonuks was published for the first time in the latest issue of our journal “Problems of Longevity and Aging” for 2008, which is published in a limited edition and has a relatively narrow circle of readers. Whether my colleagues and other readers share this hypothesis, I cannot say anything definite yet. I think, as most often happens, first the majority, unfortunately, will say that this is unnecessary nonsense, and then, if such ideas become popular, “who doesn’t know about it.” Still, a certain part of my colleagues, I hope, will react with understanding and, perhaps, even with interest, and I will have the opportunity to participate in testing this hypothesis.

It is believed that three atmospheres have changed on Earth (primary - about 4 billion years ago, secondary - about 3 billion years ago and to this day, and tertiary).
Environmentalists say that rapid human activity is not in the best possible way is reflected in the current atmosphere: the content of lead and other heavy metals in it increases; the ozone layer is disrupted, etc.

Could these changes lead to the extinction of existing species? Do scientists have any predictions about this?

In general, I share the concerns of ecologists and “greens,” although they often seem prone to exaggeration. At the same time, it should be recognized that there has always been a change in species in nature, and atmospheric changes were one of the main factors of such shifts.

Will the creation of an artificial atmosphere worsen the separation of man from the biosphere? Or is there nothing scary for a person who has “cancelled” natural selection for himself?

We have long since switched to limiting “communication” with nature, replacing it with periodic nostalgia in front of the TV. In the event of the introduction of an atmosphere modified in gas composition, the appearance of additional restrictions, apparently, cannot be excluded. At the same time, as already noted, humanity has already moved on to living in an artificial atmosphere with optimized physicochemical characteristics, so the worst is apparently behind us.


If we succeed in simulating an artificial atmosphere, will this trigger a process of parallel evolution? Or is this an assumption from the realm of fantasy?

I don’t think this can have such drastic consequences, at least in the foreseeable future. But it’s good that someone is thinking about this.

Does the problem of modeling the atmosphere characteristic of critical moments of phylogenesis (the development of biological species over time) intersect with the question of the emergence of the phenomenon of life on Earth?

This is a layer of problems that deserves separate discussion.

Are you going to continue research with modeling hypoxia, hyperoxia and hypercapnia on model objects?

So far, such experiments are carried out mainly on fruit flies. Of course, I wanted to start similar studies on mammalian models, but this is associated with considerable difficulties, including financial ones. How quickly and painlessly the change of objects and level of research occurs depends not only on us, but also on the reaction of possible sponsors and “grant givers.” Taking this opportunity, I would like to thank the management (Moscow), which found it possible to support our research, in particular, with noble gases.

What question did I not ask you, but is it important for understanding the topic raised?

There are so many such questions! But I will still voice one of them.
Why is the search for means to prolong life a priority for us?
I mean researchers from the CIS who have a lot in common not only historically, but also in psychology, methodological equipment, position in society, etc.

It's no secret that our science lags behind the level achieved by Western and overseas colleagues. Such a lag has existed almost always, including during the Soviet era.
However, after the well-known events of recent decades, when our foreign colleagues continued to rapidly move forward, and we moved mainly in the opposite direction, the methodological lag has reached critical proportions. It is especially large in areas that require complex and expensive modern techniques, and it is difficult to believe that such a large gap will be closed in the foreseeable future.

Fortunately, there are scientific disciplines where the level of molecular biological and genetic techniques used is not decisive, and the search for means of life extension is one of them. This is an area where we can compete almost equally with foreign colleagues and, it seems to me, even have some psychological advantages.

According to Rinad Minvaleev, best medicine from stress, and therefore from aging - complete relaxation and good sleep. And the physiologist is also sure that eating at night is not a harmful, but a useful habit, since it also helps with stress. Animals, unlike us, never voluntarily go to bed hungry.

The best conditions for restoring energy, that is, for rest, are precisely created by the parasympathetic tone of the autonomic nervous system, and it is most active at night. Therefore, eating at night is completely physiological from all points of view.

Hydrogen is the most abundant element in the Universe. This chemical element can bring both life and death. It can destroy an entire planet (everyone knows what a hydrogen bomb is). On the other hand, when burned, it releases only heat and water, and therefore hydrogen is called an environmentally friendly fuel. Cars powered by a hydrogen engine have already been created, although this is still too expensive.

Hydrogen has another wonderful property: this gas is perfect for humans to breathe. When life first began on our planet, the atmosphere consisted almost entirely of hydrogen. But today it is generally accepted that we need oxygen to live.

Khachik Muradyan, Doctor of Biological Sciences, head of the “Life Extension” group: “If the body is depicted as a so-called black box, inside of which it is impossible to understand, you can only observe what is at the input and output, and analyze the input and output signals, then it is not difficult to see that at the input we have oxygen, and at the output - carbon dioxide. Thus, by varying these parameters, it is possible to achieve life extension, which, in fact, we succeeded in.”

Gerontologist Khachik Muradyan is sure: oxygen only accelerates aging. To prolong life, an atmosphere with a different composition is needed. Inert gases are best suited for humans - helium, argon, xenon and others, Muradyan believes. The scientist conducts his experiments on fruit flies. By mixing gases in different proportions, he tries to find the best option.

The researcher offers his experimental insects a cocktail of a mixture of hydrogen and helium, with the hydrogen content reaching up to 90%. Flies live in a test tube. The scientist changes the food, counts the dead, and sets the necessary parameters.

The first results have already been received. According to the gerontologist, the life expectancy of fruit flies in such an atmosphere increases by at least one and a half times. And this is just the beginning!

In ancient times, the average life expectancy did not exceed 40 years. In the 19th century, people rarely lived to be 60, and today no one considers an 80-year-old person a long-liver. Is bad ecology really good for us? Maybe when there is no oxygen left on Earth, we will finally become immortal?

According to the forecasts of futurologist Igor Bestuzhev-Lada, the first cyborgs on our planet will appear in 20–30 years. Outwardly they will look like people, but they will be controlled by an internal computer.

Igor Bestuzhev-Lada, honorary president of the International Forecasting Academy: “Imagine that a computer is working inside you all the time, correcting unwanted deviations. You can make it work in heuristic mode, that is, ask it a question and it will give the desired answer. And this is not fantasy at all.”

It turns out that the computer will actually be able to control a person. This means that a person will lose his importance over time.

A person made of flesh and blood turns out to be superfluous, and we come to the “radiant humanity” described by Tsiolkovsky. It should be viewed as a collection of ordered information fields.

The time will come when scientists will erase the boundary separating people and energy substances. Absolutely everything will be available to radiant humanity. Dreams of flying without wings will come true, we will stop fearing the end of the world, and the vast Universe will become our home. We will lose our bodies, but we will finally become immortal!

Conclusion

It is generally accepted that time cannot be scrolled back, like a film, in order to select the right moment and pause it. Go back in time or look into the future. However, it is curious that in physics there are no calculations according to which time cannot stop. And most importantly, there is no law that would deny the possibility of traveling to the past or future. Moreover, discoveries recent years persistently indicate that almost all of our ideas about time are fragmentary and far from final. Moreover, the creator of the hydrogen bomb, laureate Nobel Prize world, academician Andrei Sakharov, back in the 70s, fundamentally substantiated the possibility of traveling not only in time, but also in other spaces. The scientist suggested that galaxies in the Universe are connected by tunnels through which one can penetrate from one cosmic system to another. Moreover, in his diaries, Sakharov even formulated a method for such movement. And here is one of the probable proofs of this. In 1983, Soviet archaeologists discovered a sensational discovery in Turkmenistan. On a huge plateau about 400 meters long, dinosaur tracks were clearly visible. There are a lot of prints, more than three thousand. Prehistoric monsters trampled, stepping on each other's paws, as if on a dance floor. Both old and young danced. The length of the smallest print was 20 centimeters, and the largest was about one meter. These were megalosaurs - the largest predators of the Jurassic period. However, the main sensation awaited scientists later, when, next to the traces of ancient lizards, archaeologists unexpectedly discovered traces that were very similar to human ones. But if this is so, then we have to admit an incredible thing. Either dinosaurs have survived to this day, or, which looks like a miracle, man was born millions of years earlier. True, science says that miracles do not happen. Although, as you have seen after reading this book, history knows many examples when, contrary to all laws, death retreats from the bedside of a terminally ill person. Children are born to those women who, according to the verdict of doctors, should never become mothers, and inevitable catastrophes at the last moment turn away their deadly face. What are these - incredible coincidences, unknown laws of nature? Maybe. And yet, even those who do not believe in miracles, if something happens, secretly only hope and wait for it. And you can't argue with that.

I wish you more miracles, cosmic happiness, universal luck and eternal love.

Sincerely yours

Igor Prokopenko

WITHtop, stop! What if this is the way to solve the problem of “supercentenarians”? To ensure that no centenarian becomes a burden to his loved ones.

So that men and women in their winter, sunset time can move normally, eat, drink, think, engage in one or another type of creativity...

Then we can no longer get an army of powerless and capricious pensioners, but people who can provide for themselves until the Methuselah years, and bring benefit to society! And it will not be weakened, weak-minded paralytics who will overcome the century mark, but full of energy, wise patriarchs.

And their inertia, a consequence of dullness, will not become a brake on progress: no, next to younger people there will appear living accumulators of experience, the most valuable advisers...

Actually, it cannot be otherwise, since science already intends to increase the species-specific, that is, the maximum lifespan allowed by nature. If hundred-year-old senile people are a burden to the world, then what can be said about 200-year-olds, 300-year-olds?!

No, extending life is, first of all, extending its active phase. Otherwise there is no need to fence the garden. Swift's Struldbrugs - feeble-minded elders doomed to immortality from Gulliver's Travels - are an excellent warning...

According to Professor Bezrukov, several ways to possibly overcome the species boundary have been outlined. Some have been tested for decades - they move slowly, but quite confidently. One of the most well-founded theories associates aging with the accumulation of free radicals in the body.

These ominously active molecules wander through our tissues and damage proteins. Many means of combating radicals have been developed, but there is no universal, reliable one yet... There is another way to slow down aging. A healthy body produces sufficient quantities of telomeres - enzymes responsible for the “assembly” and protection of DNA molecules.

For those who have forgotten, let me remind you: this polymer compound, the famous “double helix,” is found in the nuclei of cells and carries the genetic code. When cells divide, the DNA structure must be reproduced exactly; if this is not so, the cellular “offspring” is born defective, destruction and decay of tissues and organs occurs...

As we age, our internal telomere factories begin to work worse and worse. Renewing them means preserving the magic spiral and thereby ensuring its own longevity.

A healthy, active life can be extended, obviously, through diet. Vladislav Viktorovich described it as follows: “qualitatively complete, but quantitatively limited nutrition.”

Five centuries ago, a certain Luigi Cornaro, forty years old, was forced for health reasons to sharply limit himself in food. So what? Cornaro, who was promised only a few days by doctors, recovered and lived... until he was 102 years old!

Of course, this does not mean that everyone who simply starts starving themselves will become a supercentenarian. Everything must be done under the strict supervision of doctors.

It remains undeniable that life can be extended - and perhaps to the greatest extent - by cooling.

The lower the temperature of a body, the longer it can exist without collapsing. The reason for this is a slowdown in metabolism. It has already been calculated that a decrease in temperature by four degrees will allow a person to live on average about 250 years!

But, firstly, so far only experiments on lower animals have been successful; With the current level of knowledge, it will not be possible to “cool” either higher mammals or humans... at least, without harm to them.

Secondly... a little earlier we said that prolonging life is meaningless without preserving its quality, without ensuring that a person remains an actively functioning rational being. And a slow metabolism is half life. Something like bear hibernation.

It’s scary to imagine a country of incredibly long-lived, but equally slow, sluggish and barely moving people. Accordingly, feelings will fade and intellectual abilities will decline...

Of course, my conversation with gerontologists was not complete without mentioning cloning, which is so fashionable now. In principle, you can significantly extend your life by gradually replacing worn-out organs with new ones - either foreign, donor, or grown from our own cells. At least the current level of science and technology does not prohibit this.

Another thing is how accessible and widespread, in specific social conditions, will cloning be? If only the rich and people with power can afford it, our descendants will be present at the birth of such a privileged caste, divorced from the people, which even the ancient eastern monarchies did not know!

A class of people will appear who are by no means the most talented, intelligent or righteous, but who are capable of buying eternity for themselves... The consequences are not difficult to imagine. Therefore, let's hope that organ cloning will become real no sooner than peoples come to a fair, humane social system...
However, these are no longer questions of gerontology.

In a conversation with me, Dr. Muradyan expressed an interesting idea - again, this is something you will only hear from a deep specialist... You can choose one way or another to combat aging - but, most likely, it will be a half-measure. After all, what are we mainly fighting against? With external manifestations of a mysterious hidden process: diseases, disorders of important functions...

Even replacing a diseased organ is only a short delay on the path to destruction. If we defeat cardiovascular diseases and malignant tumors tomorrow, this will increase the average life expectancy by just a few years! As Khachik Kazarovich figuratively put it, we are trying to repel the blows of an ax, without even knowing what kind of killer is wielding it... And the killer is precisely the root cause of aging.

The most interesting thing is that the most courageous and original-minded scientists, not yet really knowing what kind of force forces us to grow old, are already predicting the discovery of an anti-aging mechanism!

In particular, the wonderful Russian gerontologist Vladimir Veniaminovich Frolkis wrote about this. Something inside each of us resists creeping destruction and puts barriers in its path.

Perhaps the antiaging process is controlled by one of the brain centers - the hypothalamus. It is responsible for many things in the body, in particular, for the nature of metabolism. And one small zone in the hypothalamus is somehow connected with... the emergence of positive emotions!

And, oddly enough, it was Frolkis who considered her a likely bulwark against old age. But, on the other hand, what’s strange? It has long been known that fun and laughter prolong youth, that happy people live longer and more active.

Take, for example, the well-known longevity of great scientists, who devoted themselves completely to their favorite work and are therefore happy.

Boris Paton, Platon Kostyuk, the great museum organizer Mikhail Sikorsky, the former director of the Institute of Gerontology Dmitry Chebotarev, who are over 80, still think first-class and work productively... Professor Bezrukov believes that sooner or later a way will be found to activate the “center of joy” in people and thus help them in the battle against inexorable time...

“I am convinced that life extension is possible,” says Dr. Muradyan. - It will definitely be achieved someday. Why? Because any cell is potentially immortal...” The body consists of billions and trillions of essentially eternal elements - cells. Each of them carries a self-rejuvenation program!

After all, during division, “waste” does not reproduce... Why, having once united into a multicellular organism, did the tiny creatures not transfer to it their ability for endless renewal? It's hard to say yet. Many biologists consider this the price to pay for multicellularity, for the “decision” of countless amoebas to become a single whole.

Evolution is not interested in the individual living long; It’s more important to her that he leaves offspring. The more often the change of generations, the more vigorously the species develops... Maybe so. But such conditions of the game are not suitable for an intelligent, creative creature - man, the heir of thousand-year-old wisdom and the eternal discoverer of new things.

With the progress of history, each Homo sapiens becomes more and more valuable, truly a unique microuniverse... Therefore, steps will certainly be taken to return to the cells that make up our flesh the ability to endlessly renew themselves by division. Here we are no longer talking about longevity - about individual physical immortality...

Why not?

“...the problems of rejuvenation and phenomenal longevity are not only solvable in principle, but also long ago resolved, “introduced” into practice and successfully exploited for billions of years. Unfortunately, only nature has the monopoly right to conduct such operations.”
Khachik Muradyan
"Artificial atmosphere, rejuvenation and longevity"

According to gerontologist, Doctor of Biological Sciences Khachik Muradyan, there is no more grandiose scientific idea, “ than the maximum increase in the active period of human life and longevity».
For many years, Dr. Muradyan has been studying experimental ways to prolong life. In his new study, together with his colleagues, he tried to answer the question: is the existing environment optimal, or is an atmosphere with a different gas composition necessary for quality life and longevity?

KHACHIK KAZAROVYCH MURADYAN- Doctor of Biological Sciences, researcher at the Laboratory of Physiology
/ Kyiv /. Head of the Life Extension group.

Scientific interests: phylogenetic and ontogenetic correlates and determinants of longevity, search for means of life extension.

Khachik Kazarovich, in your new article “Artificial Atmosphere, Rejuvenation and Longevity” you write that “ aging and rejuvenation are indivisible properties of living systems" But why is it that in complex multicellular systems, even in the presence of self-repairing DNA in each cell, pronounced aging rather than rejuvenation is observed?

In order for the idea of ​​the unity of aging and rejuvenation not to seem seditious, I wanted to repeat a simple truth: if only aging existed in nature, then all living things would die, barely having time to form. The very existence of life is irrefutable proof of the coexistence and, importantly, the equal effectiveness of aging and rejuvenation of biological objects. All species in which this balance was shifted towards aging, sooner or later had to accumulate a critical mass of disorders and die.

But the question of why a multicellular organism consisting of potentially immortal elements (cells) is mortal does not yet have a satisfactory explanation. Indeed, no credible exception to this rule is known to date. In essence, a multicellular organism is a collection of cells with the same or, more precisely, almost the same genome, but located at different stages of differentiation.

Now there is a real boom in the study of stem cells and the cellular level of organization in general. Maybe we really need to be patient and wait until reliable methods are found for manipulating the cellular populations of the body, opening up the possibility of immortality not only at the level of the species, but also the individual?

In 1988, the Leningrad branch of the Nauka publishing house published the monograph “Experimental Ways to Extend Life,” written by you, together with Vladimir Veniaminovich Frolkis. Today this is a very well-known and sought-after book by biologists.

Your new work, “Artificial Atmosphere, Rejuvenation and Longevity,” indicates the existence of another way to prolong life. Is this a continuation of the search that began back then?

Absolutely yes. After all, nothing disappears without a trace and nothing appears out of nowhere. By the way, Vladimir Veniaminovich and I have written several more monographs and reviews devoted to the analysis of life extension means, for example, books published in the USA (, Boca Raton: CRC Press, 1991) and Ukraine (Aging, evolution and life extension, Kyiv: Naukova Duma, 1992).
At the same time, I have always viewed monographs as something like a large literature review. The facts or considerations presented in them should not be considered as dogmas or oaths of allegiance to these ideas, but should contribute to broadening one’s horizons and the correct choice of next steps forward.

In this work you posed two questions: “ firstly, how is rejuvenation and maintenance of the viability of living systems ensured, for example, through the cell line of the reproductive system; secondly, what are the possibilities of transferring such patterns and approaches to the level of the individual and individual life expectancy" Is it possible to resolve them in the near future? What is needed for this?

To do this, you first need to believe in this possibility and seriously pursue it. Such studies, if they do not immediately point the way to “immortality,” will at least become a significant contribution towards understanding further steps in this direction. What is needed for this? Of course, I have ideas about what and where to look for first. But I am not ready to discuss them now, especially since almost every gerontologist probably has such thoughts, however, not only them.

You hypothesized that “ For successful aging and longevity, an artificial atmosphere with a different gas composition is required" Today there is a device - a hypoxicator, which simulates the conditions of oxygen starvation. Few people dispute its usefulness for humans. It is known that it activates the body’s protective functions, thanks to which a person resists stress more confidently, copes better with physical activity, mobilizes in case of illness, etc.
What might the artificial atmosphere you write about be like in practical terms? What is needed to create it? What is the difficulty of reproducing it?

I'll start with the last part of the question. The fact of the matter is that there are no big and, especially, insurmountable difficulties here. Technically, humanity has been ready to solve this problem for many centuries. It is enough to note that noteworthy attempts to solve this problem were made in ancient times. However, almost all of them were based on intuitions or insufficiently tested ideas and were not brought to a truly complete scientific analysis.

The essence of the problem is that the Earth's atmosphere was constantly subject to quantitative and qualitative changes. Thus, since the emergence of cyanobacteria, the ratio of the two most important gases for biological objects - oxygen (O2) and carbon dioxide (CO2) in the atmosphere has changed by many orders of magnitude. In the beginning, O2/CO2 was practically zero, but in the modern atmosphere it is over 500! Interestingly, inside the cell and in the intercellular space this ratio is close to unity. Moreover, first during the Carboniferous period (approximately 300 million years ago), the content of free oxygen in the atmosphere increased to 35% or more, and then decreased to approximately 21% (today), and according to forecasts will continue to decline rapidly.

On the diagram: composition of dry air.
N2 - nitrogen. In the form of diatomic molecules
N2 makes up most of the atmosphere - 75.6% (by mass) or 78.084% (by volume);

O2 - oxygen. In the atmosphere, the content of free oxygen is 20.95% (by volume); in the air, the mass fraction of oxygen is 23.12%. The element oxygen is part of more than 1,500 compounds in the earth's crust.

CO2 is carbon dioxide. The concentration of carbon dioxide in the Earth's atmosphere is 0.038%.

Ar - argon. The third most common element in the atmosphere - 0.93% by volume.

http://ru.wikipedia.org

Could adaptation to such significant and multidirectional changes in the composition of the atmosphere be complete and painless? Are there still genetic memories of the “better days” of evolutionary infancy and youth that could provide greater potential for vitality and longevity? I think that such a possibility cannot be excluded, and it certainly deserves proper verification.

Moreover, if our goal is to create something longer-lived and, therefore, more perfect than has yet been invented by nature, then it is quite justified to use means for this purpose that have not yet been tested. I mean, for example, inert or, as they are now more often called, noble gases. In fact, the idea that it is possible to prolong life with the help of chemical elements that under normal conditions do not react with anything and have never even been “suspected” of participating in any ontogenetic or phylogenetic transformations seems at first glance delusional. However, recent pilot studies conducted in our laboratory indicate the promise of such models.
However, other gases may also be promising in this regard. Our group has recently started doing this intensively. But, I suppose, this is a topic for another discussion.

How long has your group “Life Extension” existed?

The group was created in 1990 on the initiative of academician Vladimir Frolkis. As the name suggests, the main goal is to find means to prolong life. Since then I have been its leader (field marshal without an army).
Currently, the group officially includes 3 employees and one graduate student, but there are “enthusiastic volunteers,” so in reality 5-6 people are involved in the research.

What were the pilot studies you mentioned and what were the encouraging results?

Together with Albert Timchenko, a researcher at our institute, we tried to create a model of either hypoxia or “hypernobility” (just kidding!) by adding the noble gases at our disposal - helium and argon - to the atmospheric air. A relatively small but significant effect on life extension was found. We understand that this is only the beginning of the journey and do not lose hope that the subsequent search for more optimal concentrations and application patterns, as well as the use of other noble gases, in particular xenon and krypton, can provide a more tangible effect of life extension.

Why has the question of the role of the atmosphere in human life expectancy been ignored so far? Or is that not true?

It cannot be said that the role of the atmosphere was completely ignored. It’s just that the “chemical” aspect of this problem has not received due attention and has not entered the phase of necessary scientific analysis. In fact, there is a developed network of meteorological observations and rapid dissemination of information about the state of the atmosphere, including various media.

Moreover, the majority of the population of developed countries has almost completely switched to living in conditions of air-conditioned air, that is, essentially, an artificial atmosphere with optimized physicochemical characteristics (temperature, humidity, charged particles, etc.).

Why they are delaying a much more radical optimization of the atmosphere by changing the gas composition is indeed difficult to explain. There are, of course, unresolved problems and a certain risk here. But there are hardly more of them than, for example, in the development of new medicines, genetically modified products and some other innovations.


In 1953 Stanley Miller
(Stanley Miller ), graduate student of Nobel laureate Harold Urey (Harold Urey ), wondered about the origin of life on Earth and tried to recreate " in vitro"(in the flask) conditions close to those in which it could originate.
As a result of the experiment, he received a strong broth of amino acids, the so-called “building blocks of life”
, sugars, fatty acids, other organic compounds... and even more questions.
What questions do you want to find answers to?

There are indeed many such experiments confirming the possibility of the emergence of life from inanimate matter. Looking into a past so distant even by evolutionary standards, the most important question for us seems to be: what was the role of the gas composition of the atmosphere in establishing the fundamental principles of the relationship between the processes of aging and rejuvenation?

After all, it is obvious that already the first, most primitive replicators, who managed to survive and lay the foundation for subsequent biological life, inevitably faced the problem of the interaction of aging and rejuvenation, in which the atmosphere of that time could play an important role.

Perhaps modeling such conditions will simplify this problem and make it more accessible for research and analysis. Regardless of the success of such theoretical developments, a practically important question is of independent interest: can full or partial reproduction of those conditions modify the characteristics of aging and increase the lifespan of modern species?

The so-called endosymbiotic process (the capture of one bacterium by another and the transformation of the one inside into a mitochondrion) is a key event in the creation of multicellular organisms.

In the words of the English science journalist Bill Bryson (Bill Bryson) mitochondria in cells " act as if they believe that there can be nothing in common between us" And one more thing: “ They don't even speak the same genetic language as the cell in which they live. In short, they keep their suitcases packed. It’s like you let a stranger into your house, but he’s been here for a billion years.”.
How far have scientists progressed in studying the phenomenon of mitochondria? And what is still puzzling about them?

Indeed, the role and behavior of mitochondria in the cell remain largely mysterious, and the images of mitochondria created by different authors are contradictory, not to say multifaceted.

These are altruists, “kamikaze stokers” who, at the cost of their well-being and shortened life (the half-life of mitochondria usually does not exceed several weeks), extract energy for the host cell; then mitochondria are the main sources of uncontrolled free radicals, which many still attribute to a causal role in aging and numerous pathological disorders; then these are “parasites” who receive everything ready-made from the host cell, but at the same time, like “monkeys with a grenade in their hand,” they can destroy it at any moment by apoptosis or necrosis. After all, mitochondria have a full arsenal of means of programmed cell death, and in certain situations, for example, in denucleated (non-nuclear) cells, they can carry out “self-destruction” of the cell without the participation of the nucleus.


In Fig. mitochondrial structure(gr. mitos - thread and chondrion - granule) .
The shell consists of two membranes (external and internal).
The inner membrane is laid out in cristae(from lat. crista- crest ). It contains respiratory enzymes and ATP synthase enzymes. The semi-liquid matrix contains a concentrated solution of various substances (RNA, DNA, squirrels, lipids, carbohydrates, ATP synthase and others), as well asribosomes.Typically, each mitochondrion contains several copies of its genome.

Whatever the true role of mitochondria, one thing is important to us: they are the ones that are associated with the most powerful correlates of lifespan. Regardless of whether mitochondria are “executioners”, blindly following someone else’s instructions, or whether they themselves determine the fate of the cell and the lifespan of the organism, in any case, they seem to be the most promising targets in the search for means of extending life.

What is the connection between mitochondrial DNA (mtDNA) and longevity?



In Fig. diagram of the human mitochondrial genome.

We are only getting closer to understanding this issue. But the results that have already been obtained certainly make an impression.

Suffice it to say that in our research, conducted jointly with Professor Vadim Freifeld ( Vadim Fraifeld) from the University of the Negev (Beer Sheva/Israel), the reliability of the correlation coefficients between longevity potential and such a seemingly “rough” indicator as the composition of mtDNA bases in mammals reaches values ​​that have no analogues among other correlates.
Only the intensity of metabolism, which is largely determined, again, by mitochondria, has a correlation of comparable strength with the species’ lifespan.

Such a strong correlative dependence probably indicates the special role of mitochondria in determining life span, although this, of course, is not yet enough to conclude that there is a causal relationship between longevity and mtDNA.
I think that this issue will be intensively developed, and soon we will learn more, including about the possibilities of extending life by modifying mtDNA and mitochondria in general.

Mitochondrial DNA is particularly sensitive to reactive oxygen species.

The negative role of oxygen in determining (limiting) the finiteness of life of multicellular organisms and in aging in general should not be exaggerated. In any case, uncontrolled oxidative transformations are far from the only processes that are difficult to control, and the proportion of oxygen in the variety of other damaging factors should be small.

Have you studied the role of Newmites? nuclear mitochondrial) - copies of various sections of mtDNA embedded in the nuclear genome - in determining the species' life span and found a positive correlation. Please tell us about this work.

We collected from available literary sources various characteristics of newmites in different animal species and compared them with their maximum life spans. The highest correlation was found with the number of newmites. We were surprised that the correlation was positive.

That is, the more copies of different sections of mtDNA are introduced into the nuclear genome, the longer the life expectancy?

Yes, we believed that in long-lived species the “purity” of the preservation of nuclear and mitochondrial genomes is more strictly controlled than in short-lived species, therefore, we expected a negative correlation. And so, we had to assume that longevity is associated with the degree of “communication and good neighborly relations” between the nuclear and mitochondrial genomes. Namely, the more persistently the mitochondrial genome strives to introduce its copies into the nuclear genome and the more tolerant the latter is to this, the more long-lived the species is.

Interesting. Why the newmites, which you figuratively called in your work “ a kind of historical archive in the nuclear genome", are still little studied?

I think this is mainly due to the novelty of the question and methodological difficulties. Indeed, for a correct assessment of the number, localization and degree of homology of Newmites with mtDNA, not only highly efficient analytical tools and programs are required, which are constantly being modified, but also a complete decoding of the genome. Judging by the available databases, the number of such species, for example, mammals, does not yet go beyond the top ten. It is expected to grow rapidly in the coming years, so there is reason to hope for rapid progress in knowledge in this area.

Your work suggested that not only mtDNA sequences were integrated into the nuclear genome, but also into “mtDNA contains sequences of nuclear origin through which direct control and regulation of the genesis and functioning of mitochondria is carried out”. You proposed to call these executive representatives of the nuclear genome in mtDNA Maitonukami(from English mitochondrial nuclear). Do other researchers share your hypothesis?

The hypothesis about mitonuks was published for the first time in the latest issue of our journal “Problems of Longevity and Aging” for 2008, which is published in a limited edition and has a relatively narrow circle of readers. Whether my colleagues and other readers share this hypothesis, I cannot say anything definite yet. I think, as most often happens, at first the majority, unfortunately, will say that this is not useless nonsense, and then if such ideas are popular “who doesn’t know about this”. Still, a certain part of my colleagues, I hope, will react with understanding and, perhaps, even with interest, and I will have the opportunity to participate in testing this hypothesis.

It is believed that three atmospheres have changed on Earth ( primary- about 4 billion years ago , secondary- about 3 billion liters n. and to this day,And tertiary).
Environmentalists argue that rapid human activity does not have the best effect on the current atmosphere: the content of lead and other heavy metals in it increases; the ozone layer is disrupted, etc.

Could these changes lead to the extinction of existing species? Do scientists have any predictions about this?

In general, I share the concerns of ecologists and “greens,” although they often seem prone to exaggeration. At the same time, it should be recognized that there has always been a change in species in nature, and atmospheric changes were one of the main factors of such shifts.

Will the creation of an artificial atmosphere worsen the separation of man from the biosphere? Or is there nothing scary for a person who has “cancelled” natural selection for himself?

We have long since switched to limiting “communication” with nature, replacing it with periodic nostalgia in front of the TV. In the event of the introduction of an atmosphere modified in gas composition, the appearance of additional restrictions, apparently, cannot be excluded. At the same time, as already noted, humanity has already moved on to living in an artificial atmosphere with optimized physicochemical characteristics, so the worst is apparently behind us.


If we succeed in simulating an artificial atmosphere, will this trigger a process of parallel evolution? Or is this an assumption from the realm of fantasy?

I don’t think this can have such drastic consequences, at least in the foreseeable future. But it’s good that someone is thinking about this.

Does the problem of modeling the atmosphere characteristic of critical moments of phylogenesis (the development of biological species over time) intersect? ) with the question of the origin of the phenomenon of life on Earth?

This is a layer of problems that deserves separate discussion.

Are you going to continue research with modeling hypoxia, hyperoxia and hypercapnia on model objects?

So far, such experiments are carried out mainly on fruit flies. Of course, I wanted to start similar studies on mammalian models, but this is associated with considerable difficulties, including financial ones. How quickly and painlessly the change of objects and level of research occurs depends not only on us, but also on the reaction of possible sponsors and “grant givers.” Taking this opportunity, I would like to thank the management (Moscow), which found it possible to support our research, in particular, with noble gases.

What question did I not ask you, but is it important for understanding the topic raised?

There are so many such questions! But I will still voice one of them.
Why is the search for means to prolong life a priority for us?
I mean researchers from the CIS who have a lot in common not only historically, but also in psychology, methodological equipment, position in society, etc.

It's no secret that our science lags behind the level achieved by Western and overseas colleagues. Such a lag has existed almost always, including during the Soviet era.
However, after the well-known events of recent decades, when our foreign colleagues continued to rapidly move forward, and we moved mainly in the opposite direction, the methodological lag has reached critical proportions. It is especially large in areas that require complex and expensive modern techniques, and it is difficult to believe that such a large gap will be closed in the foreseeable future.

Fortunately, there are scientific disciplines where the level of molecular biological and genetic techniques used is not decisive, and the search for means of life extension is one of them. This is an area where we can compete almost equally with foreign colleagues and, it seems to me, even have some psychological advantages.

In fact, here it is more important to believe in the beauty and greatness of the idea and try to realize it, often not thanks to comfortable conditions, but despite difficulties, in a word, everything that has always distinguished our people. And what could be more grandiose than maximizing the active period of human life and longevity?

You're right! It would only be useful for the common cause if not only scientists understood this. In the end, this directly affects every person.
Thank you for taking the time to answer the questions.

Thank you for selecting the most important issues raised in the article, as well as for your interesting interpretations and comments.