03 December 2008

Evolution according to Skulachev: a reasonable and ageless man

Elena Kokurina, "In the World of Science" No. 11-2008

Old age is a "relic of the past" inherited from animals, according to the director of the Research Institute of Physico—Chemical Biology of the Moscow State University named after A.N. Belozersky, academician V.P. Skulachev. A few years ago, an ambitious project "Jonah Skulachev" was born within the walls of his institute, the purpose of which is to fight aging and prolong life. However, its results can be considered not only from a practical point of view — they provide the basis for the emergence of new hypotheses related to human evolutionTHEY LIVE FOR A LONG TIME AND "BREAK DOWN"

— Vladimir Petrovich, you have completed a five-year stage of experiments.

Have your expectations been met?— Of course, although in many ways the results were unexpected.

Starting the experiments, we assumed that the substance we synthesized, which "fights" with toxic forms of oxygen in the cell, can dramatically increase life expectancy. However, the effect turned out to be somewhat different: life expectancy increases, but not very much, but the aging process slows down sharply or even stops. The animals we gave the drug to lived to a very old age in a healthy and active state, and then suddenly died in a matter of days or even hours. You know, it's like the fulfillment of a prayer for an easy death.

The results are amazing, and I wouldn't talk about them if they hadn't already been repeated in other places, in particular in Sweden, in the laboratory of Vice-President of the Swedish Academy of Sciences Barbara Cannon, on a very interesting model — rapidly aging mice. They live three times less than usual, about nine months, but go through a full life cycle, including old age with all the signs of aging.

So, it has been proven that our substance, firstly, prolongs the life of mice (by an average of 50%), and secondly, relieves animals of many signs of old age - osteoporosis, baldness, graying, retinal dystrophy, cataracts, falling immunity and others. For example, old mice are characterized by stupor at the end of life — they sit, tremble, they are not interested in anything, and the experimental animals were active until the very last day.

But at the very beginning of your work, as I remember, you had other hopes. Have you abandoned the idea of radical life extension?— You don't understand that we actually got more than we expected!

These journalists basically presented everything in such a way that we are fighting for immortality. But our main task was to prolong not so much life as youth. We are struggling with the humiliating state of aging, when various functions of the body begin to fail one after another. We, as they say, were "agreed" to any option, but we did not expect such an amazing result — the abolition of multiple senile diseases.

WHERE NATURE LOOKS— Well, how does nature "look" at all this?

Is it possible to find natural analogues to the action of your drug?— Such cases are known in nature: for example, there are large ocean birds that live up to 50 years without aging, and then suddenly die.

In mammals, such a property has been observed: life expectancy is inversely proportional to the formation of toxic oxygen forms in mitochondria. The weaker this process, the longer the animals live. This has been widely researched in the world, but the best work was done in England two years ago by Lambert and co—workers, who tested 12 different species of animals - from baboons to mice and from quails to pigeons. 11 fulfilled the rule mentioned above, but there was one exception that scientists pointed out when publishing.

This is the so-called naked digger, a mouse-sized rodent discovered in the middle of the XIX century in equatorial Africa. These creatures have a strict hierarchy: at the head is a female, who has from one to three husbands, and all the others are workers and soldiers who protect her from snakes, the main enemy. Soldiers live no more than three years, dying in the fight against snakes, and the "queen" — ten times longer. And it "with impunity" forms poisonous forms of oxygen, which do not cause, as in all other animals, cell suicide and, apparently, do not shorten life expectancy.

This is a wonderful confirmation of my hypothesis that aging is a mechanism that accelerates evolution, and if a creature has no enemies, aging simply becomes meaningless. I always give an example with a fox and two hares, "smart" and "stupid". While the hares are young, they can both easily escape from the fox. With age, it becomes more and more difficult, because the number of cells in the muscles decreases, and then the "smart" hare will find a way out of the situation, and the "stupid" fox will eat. Thus, the hare breed gets a chance to "get smarter" within one generation. But if it were not for the fox, hares would not need these new properties, and with them aging, because it is aging, decrepitude that forces the body to look for new ways of survival.

What will this "evolutionary hypothesis" look like in relation to humans?— Man is not interested in his evolution at all — if we need to fly, we build an airplane, and do not wait for wings to grow behind our backs.

We adapt the environment to ourselves, not adapt to it ourselves. Therefore, the biological evolution of man has practically stopped. And this means that the need for specialized mechanisms of evolution in humans has disappeared. Aging as a mechanism that accelerates evolution is not just unnecessary for us, but also harmful. All this worked while primitive man lived in the forest, before he began to adapt the environment to himself. Now aging is an atavism, a counterproductive program that would be beneficial for the Homo sapiens species if it were still evolving, but is extremely unprofitable for the individual. Our task is to bring a person into the category of ageless animals, and there are such. In addition to diggers, these are giant crabs and turtles, which have almost no enemies, this is a pearl oyster that sits at the bottom of the river, and no one touches it, large whales and some others. Nature has a firm rule: if there are no enemies, aging disappears.

Our substance removes precisely the enemies of man — poisonous forms of oxygen, which accelerate the aging process. In the first approximation, this is one of the key points affecting aging. Toxic forms of oxygen oxidize lipids, proteins and DNA in the same way as the bottom of a car rushes. Only here the effect is more sophisticated: a little on the heart, a little on the liver, a little on the kidneys… God forbid to attack one thing too sharply - the body will immediately die, and aging is a gradual process. In our animals that have received the SkQ drug, it seems to proceed differently. One of their main functions suddenly becomes unusable.

"You're probably going to find out what's going on with them.— Of course, but we are approaching another issue in this regard — the problem of sudden death.

I have a hypothesis why this happens, which I call the "Bakhis principle". If you remember, Bakhis is one of the characters in Moliere's comedy "Love is a Healer". Moliere, as you know, ridiculed doctors all his life and in this play gave them various mocking Greek names — "killing", "blood—sucking", etc., and Bakhis - translated into Russian as "barking". So, Bakhis said: "It's better to die by all the rules than to survive against the rules." An amazing phrase! If we talk about the genome of a particular species, then it is much safer to preserve it for centuries if individuals "die according to the rules". Because an individual can get over some serious disease, allow damage to the genome, and then recover and multiply, spoiling the breed.

It is believed that sudden death occurs "out of the blue", in healthy people. That's not so. Either they are sick, but do not know about it, and sudden death "saves" their genome from consequences dangerous to the species, or it is the result of a disease that a person has coped with, but could not guarantee the safety of his genome. The "Bakhis principle" works completely mercilessly and, apparently, is activated by the same mechanism as aging, but acting much faster.

So sudden death syndrome is an evolutionary problem?

— At least in some cases, it is a mechanism invented by evolution in order not to risk the genome in a series of generations.

So, you are trying to cancel this useless mechanism called aging. And what happens next? — I would proclaim such a slogan: "From Nomo sapiens to Homo sapiens discatenatus."

Catena means "fetters" in Latin. A person should be not only intelligent, but also uninhibited, having thrown off the shackles put on him by evolution. By the way, for the first time this idea was proclaimed by I.I. Mechnikov. He was a very brave scientist for whom there were no barriers. He believed that humans have many traits that we inherited from animals, and which are not only useless, but also harmful.

And what do you think about the hypothesis of a specifically human path of evolution — it is also called "cognitive"?— There is no reason to believe that biological evolution has been replaced by cognitive evolution in humans.

After all, we invented computers that do calculations and think for us, and did not improve our brains! A lot of tasks that were inaccessible to our mind have now been solved. We have followed the path not of our own evolution, but of the evolution of external carriers.

And what will your Homo sapiens discatenatus be like?— Such as that ocean bird that lives for a long time and suddenly dies.

A NEW PARADIGM— Ideal option: people live up to 120 years, feel healthy until something takes them out of action almost instantly.

So?— Yes, and we are going to find out what exactly is "disabling" in the near future, and perhaps a new generation of scientists will do it.

And if in the end there really is some one reason that puts the body out of order, then I think humanity will cope with it. But we have not been able to achieve this yet. We have stopped many "diseases of old age" in our mice, but cancer has not yet been canceled. Our wards have stopped dying from pneumonia, hepatitis, nephritis, but they are dying from cancer. Although the course of some cancers is slowed down by SkQ.

Perhaps a study of the genome of a naked digger would help us: he does not suffer from cancer, does not suffer from atherosclerosis, he does not have immunodeficiency.

We collected signatures of 80 scientists from different countries and applied with this proposal to the National Institutes of Health of the USA, but they refused us, deciding that this was an uninteresting topic. You see, there's such a different paradigm, as if we speak different languages. People who think like me are probably five people in the world.

You chose one method that worked. But perhaps there are others?— In my opinion, there are very few such methods and directions.

There are a lot of theories of aging that lead nowhere.

And yet this is a complex problem? From your point of view, is there a need for a joint program of fundamental research aimed at increasing life expectancy?— Personally, I have never been able to reduce everything we know in other areas to some real experiment that can be set up.

My qualification is mitochondria, and here it coincided with one of the solutions to the problem. There are probably others.

But it's better to have a program than not to have one. I am for any action in this direction. Research needs to be initiated, and I have no ambitions here. However, to do this, we need to radically change the approach, the paradigm in gerontology. In this regard, I will quote the response of the Italian gerontologist J. Libertini to our work: "The new paradigm that considers aging as a specific biological function is ahead of the position of those who consider the weakening of the body with age as something that has a maladaptive character and can only be partially delayed. However, a paradigm shift is always a scientific revolution and requires, as a rule, a generational change."

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