Defeat aging
Russian scientists have found a way to defeat aging "News of Science"
Why does evolution need aging? How does it work at the biochemical level? What substances slow it down in animals? The correspondents of the "Week" Natalia Kienya and Ekaterina Pryakhina tried to understand the intricacies of the process.
Maxim Skulachev, Scientific director of the SkQ project: "We already have 300 volunteers"
Question: Why does evolution need aging?
answer: Pacific salmon, bamboo, and octopus have a biochemical suicide program after reproduction. But mammals age before death. From the point of view of evolution, this is true. My father, Vladimir Skulachev, has a theorem about two birds with one stone: smart and stupid. Exaggerating, let's assume that the main factor of the external environment is a fox. As long as both hares are young and strong, they run away equally efficiently, and the mind is not important. But then we gradually make them thinner muscles, a bigger heart, so that it works worse, weaken the immune system. Now you can escape from the fox only if you notice it early and understand who it is. A smart one will do it. And the stupid one will be stupid, and they will eat him. The result is an increase in the population in one generation. This is natural selection. Aging is an evolutionary program, and its basis is oxygen superoxide radicals. They play a key role in the development of certain types of cancer, eye and heart diseases.
Q: How do they work?
a: Oxygen can exist in two forms: O2 molecules that we breathe and burn nutrients. And the poisonous form is when the molecule grabs electrons and turns into a free radical, superoxide. It's a scary thing, reacts with everything around. It turns lipids into the same radicals, damages proteins and DNA – the body's systems stop working and heredity suffers.
Q: Why are we allowed to live after the end of the reproductive period?
a: From the point of view of evolution, this is meaningless. You may have huge horns and a gorgeous tail, but if you don't reproduce, you're lost, the genome has disappeared. And man has invented a way to transmit information not genetically, but orally. Evolution shows how nature tried to do this: it would adapt the monkey this way and that, make it stronger, more mature, and in the end everything worked out only when everything was pumped into the brain and speech. Without DNA: you take it and explain. This is how the institute of grandparents appeared. They could tell the youngsters: don't go to that mountain, there are lions there. A strong evolutionary advantage: if you don't go, they won't eat you.
"Primitive people lived up to 35"
Q: And what is the species limit of a person? 100-110 years old?
A: More like 20-30 years. If we destroy the cities now, pour napalm over everything, grow a normal jungle and let us out there, it will be the same. Primitive man at 35 is a toothless, sick wreck. But humanity is pushing back the moment of death step by step. At first, Cro-Magnons died of cold in winter. A fire appeared – and they gained another 5-10 years. They died of hunger, there was not enough game – agriculture arose. Mortality remained high due to infectious diseases – they lived closely, crowded. They managed to cancel it only with the advent of vaccines and antibiotics. The next limitation is cardiovascular diseases and cancer. Maybe targeted antioxidants will cancel it.
Q: How do they work?
a: We send them to the mitochondria, the "powerhouse" of the cell, where nutrients are burned in oxygen and where free radicals arise. In order for the antioxidant to get there, lipophilic ions are needed. They are both fat and charged, walk like ghosts through any bio-shells and at the same time carry a charge. If it is positive, the substance will go to the mitochondria – the only negatively charged place in the cell. Lipophilic ions are electric locomotives, and antioxidants are attached to them.
Q: On which diseases has the effect been proven?
A: It is difficult to prove something completely in biology. That's why the project is so big – 300 people, several countries and 40 laboratories. If there is an interesting model of a heart attack, stroke or eye diseases somewhere, we order this work. However, we noticed the influence on the latter by accident. In Novosibirsk, Professor Kolosova has an excellent line of rapidly aging rats – Oxys. She offered to try SkQ on them. They began to look at the eyes – they did not expect anything, it was just convenient to look at them, the animal did not need to be killed for this. But they found that for some reason there are no cataracts and retinal dystrophy, which have been observed in these mice since three months. In older sick rats, as Natalia said, "the results were indecent": there was a disease, but it disappeared somewhere. In general, if there is a degeneration of the retina, it has nothing to recover from. Maybe we don't know something about the physiology of rats, but during the electrical test, there was no retinal response to light at first - and then it appeared. Next, we made eye drops for animals based on SkQ. While under testing, they are already available in veterinary clinics for dogs and cats.
"We don't have a culture of drug development"
Q: Does SkQ have side effects?
A: Haven't noticed yet. The substance is used in tiny doses. Nevertheless, the safety of eye drops has been proven for years. Now we are just completing one experiment. We have submitted documents to the Ministry of Health, maybe they will allow us to start clinical trials on humans.
Q: Are there any results in oncology and cardiovascular diseases?
A: In oncology, we are not very happy with the results so far. Against the background of SkQ, the frequency of cancers decreases slightly, but there is no direct antitumor effect. The drug only improves the condition of the body by all signs, maybe it can be used after chemotherapy.
Q: Is the government investing money in your project now?
A: No. Everything was done with the money of Oleg Deripaska's private investment company. The project is commercial: we want to make a set of medicines that will be sold. The market for them is huge, especially abroad.
Q: Why abroad and not here?
A: The drug market in the USA is 50 times larger than in Russia.
Q: But will we produce medicines?
A: Yes. Here we know who is a sharomyzhnik, and who can be trusted. Besides, we are not interested in creating jobs for Americans. All capacities in Russia meet our tasks.
Q: Really? Do we have enough production culture?
A: We don't have a culture of drug development. But many drugs, for example, from Bayer are made by her here for export to the West. The quality of our chemists' work is excellent. You just need to know the places.
"SkQ is a slightly improved Q10"
Q: Will there be no SkQ in age cosmetics?
A: It will. In fact, the SkQ is an improved Q10, popular now in Europe. Quinone is used as an antioxidant in it. The only "trick" is that we attached the mitochondria address to it. The body does not resist quinones because these substances have no natural analogues. They are synthesized. They were invented out of my head. That's why we are delaying clinical trials: we need to make sure that the chemical reaction in the human body will not go.
Q: Will SkQ be in cream or in microcells?
A: In the cream. The substance penetrates perfectly through the skin and loves an oily environment very much. We already have permission to use SkQ in cosmetics. In principle, we could start selling it now, but we don't play like that. We need large-scale research and proof of effectiveness. We have already agreed with the 1st Medical Institute. We will test the SkQ solution in water – so that there are no effects from glycerin, vaseline and other substances useful for the skin. However, now we have problems with money due to the financial crisis. If we find the money for testing, the product will be able to enter the market in the fall of 2009.
Q: How stable is the substance itself?
A: Stable enough. It is stored in solution for six months. It is excreted from the body quite quickly – in a day.
Q: Do you not cooperate with the Science against Aging Foundation?
A: No. We know each other, and its creators are engaged in a noble cause. But it is hardly possible to make a "road map" on aging yet. We know too little. Even based on our positive data, it is virtually impossible to answer the final question: will SkQs be effective for humans?
Q: When will the first human trials be conducted?
A: It depends on when we get permission. We are not speeding up anything in this difficult procedure. Our substance was invented out of my head a few years ago, and you just can't give it to people. And it also depends on finances. We have never turned to the state for help before, but now it seems that we will finally have to do it.
Q: After all, this is nanotechnology...
A: Yes. On November 19, Anatoly Chubais came to Moscow State University, we made a presentation, and told him that we had not had a penny for several months. We are counting very much on Rusnano, because ideologically they should support exactly such projects. Of course, you still need to pass their expertise. However, if all the stars add up correctly and we get the money and permission, we hope to start testing in the spring of 2009. We already have a group of 300 volunteers with cataracts and retinal dystrophy
The head of the laboratory "Geron Lab" Evgeny Nudler: "Pills are already being invented"
Question: You live in the USA, but why do you conduct many studies in Russia?
answer: In America, our laboratory did not deal with the problem of aging at all. We discovered some interesting things there, but this is more "condor" molecular biology. And here, in Russia, we are researching the mechanisms of aging. We are starting from the "radical" theory of aging: in the process of vital activity, free radicals are released in the cell, which cause significant damage to it. But there is a special mechanism in the cell that can reduce their number. That's just it turns on only in certain, "stressful" conditions. We want to learn how to keep this system activated all the time.
q: But won't it "burn out" then?
A: Not at all. Most of the systems in the cell work constantly. For example, the genes are housewives, obliged to work continuously. We want to make the so-called "emergency care" genes work in the same mode.
Q: In what way?
A: We are working with a heat shock response system. Back in the 60s, they noticed that if you heat a cell to 42 degrees, proteins of a certain type instantly begin to be synthesized in it. And the synthesis of many other proteins is turned off. The genes that are turned on are responsible for the synthesis of shepherd proteins. Chaperon is a French word, it is... how's Russian? When an elderly woman is assigned to a young woman to make sure that she does not enter into unwanted relationships... Chaperone. Exactly this is what shepherd proteins do: they bind to other proteins and do not allow them to enter into undesirable connections.
How to stop the process of dying? One of the ideas is heat shock proteins, which will prevent the accumulation of other damaged proteins.
We train on nematodes
Q: Why does the body age at all?
A: A lot of senile diseases are associated with improper folding of proteins. Alzheimer's, Parkinson's. "Shepherons" can prevent this. And if we learn to activate this system ourselves, it will definitely postpone the onset of old age.
Q: Do you already know how to do this?
A: Yes. We are experimenting with nematodes. These are tiny worms – they are so beautiful, transparent, that's why they are called C.elegance. So, our worms elegance already live much longer. We have discovered regulators that activate shepherons. One of them is an RNA thermometer. It can turn on and off its functions depending on the temperature. We want to come up with a small molecule with it that would turn it on without stress. Pills could be made with these molecules. The invention of new medicines for senile diseases is a real tool for prolonging life. In 10-20 years, science will achieve that a person will live 120 years.
Q: Provided that medicines are invented?
A: They are already being invented, but not everything has reached the clinic yet. These are medicines for diseases that are directly related to aging. Actually, these diseases are aging, the result of aging. Cardiovascular diseases – strokes, heart attacks. To treat these diseases means to prolong life. Effective medicines already exist. In America, doctors are very flexible, they constantly monitor the literature, they are legally obliged to do this. And, as soon as a new medicine appears, it is immediately used – everywhere.
Antibiotics are also an intervention in God's providence
Q: Strangely enough, the life extension program causes contradictory reactions in society. Are you not accused of interfering with God's providence?
A: I have a negative attitude to this position. After all, antibiotics are also an intervention in God's providence. I know respected scientists, however, there are very few of them who are religious. But they somehow get along very well in their heads.
Q: Demographers are among the critics of the program. Prolonging life, in their opinion, means prolonging old age. A person can live longer, but he will not be useful to society, because he will still not be able to fully maintain his working capacity.
a: Although the brain gets smaller over the years, this does not mean that a person becomes stupid. Or rather, some – yes. And some don't. We are not prolonging old age, but youth. Yes, it will immediately increase the number of people on earth. For one or two generations. But then everything will be balanced again. In the end, you know, these people will die anyway. And civilization will develop faster, because a person will be able to gain much more experience and knowledge. And I believe that the country that achieves this first will have huge advantages. Russia has such a chance
Political scientist Igor Panarin: "It may take 4-7 years to make a breakthrough in this area"
"We have two powerful research centers: The Brain Institute and the Natalia Bekhtereva Institute, where a huge number of unique world technologies have been accumulated. There are Dubna, Korolev, Novosibirsk Akademgorodok, scientific centers near Krasnoyarsk. And it is these sites that should become centers for the development of breakthrough scientific technologies that would make it possible to make an innovative breakthrough.
I think such projects already exist now and are even funded by business structures, but the task of the state is to make sure that all discoveries in this direction do not become the property of one company, even a large one. It is necessary to connect the Russian Academy of Sciences (RAS), institutes of biotechnology and psychology. It makes sense to create a special section in the Russian Academy of Sciences, to use nanotechnology...
I would set aside 4-7 years for a breakthrough in the field of creating technologies for the continuation of people's lives, after which the active phase of the project will begin. If, for example, it is launched today, then it will be implemented in 2012-2015.
Of course, cooperation with foreign countries is possible within the framework of such a project, but very carefully. I would name only two countries with which such work is possible here – Italy and Germany, no more. These are our strategic partners, and in Europe they will be able to become our allies in the dissemination of new technologies.
Who can use the received technologies? I think that the initial preferences should be with the developers and those who have invested resources in this project. At the same time, the access and use of such discoveries should be strictly regulated by special legislation. The results of this work today should become a national treasure."
Portal "Eternal youth" www.vechnayamolodost.ru09.12.2008