Why was dry eye syndrome chosen for the first clinical trials?

There are two answers. Firstly, this is an incurable disease, and any success in treating an incurable disease is impressive: if it helps, it helps. And according to our concept, many incurable diseases are not diseases at all, but the fulfillment of the aging program. And the second answer: for dry eye syndrome there is only symptomatic treatment. Usually they drip something that moisturizes the eye, for example the drug “Natural Tear”. There is nothing natural there, but there are high-molecular compounds and something else. But it does not eliminate the causes of the disease; first you have to drip once a day, then two, three... then fifty.

And what did the drug trials show?

The decisive moment is when, after three weeks, patients are asked if they have any complaints. With our drug, 60% answered no, but with tears - only 20%. I think that if the tests had continued longer, our percentage would have been even higher. But according to the conditions of the Ministry of Health, we had to drip for no more than three weeks. They were afraid of adverse events, as they affectionately call them, AEs. We only had one case of NEA, although not in this series, but with glaucoma, when a tree fell on the patient, but, God knows, we are not to blame. We have been treating glaucoma and cataracts for six months now, and so far there have not been a single adverse event in dozens of people. By the way, we didn’t choose dry eye syndrome, it was suggested to us by the Ministry of Health.

Are there any results on cataracts and glaucoma?

It is impossible to say until the end of the tests. This is a double-blind experience - and in the case of almost blind people, it turns out to be triple-blind. Neither the doctor nor the patient knows which drug is being given - a “dummy” or our medicine. But the experiments on cataracts have ended, and so far I can say that the effect is good. It is determined by how many lines in the table a person can read. And for glaucoma, we just can't get enough people to complete the trial.

Why?

A person must drip into himself who knows what for six months, without receiving a penny. And he must sign a document stating that he will not be held accountable if he becomes blind as a result of the experiments. There is standard paper: when a leg is cut off and when drops are put in, the document is the same.

They say you cured your eye with your medicine...

Yes, my eyes generally have bad heredity. Senile cataracts have set in. Both eyes were affected, the right one more severely. I feel like I can no longer read with my right eye. The doctor prescribed me an operation to replace the lens. And I took a break for a month and a half and began to drip our drug. Then I came to the appointment, and the doctor still prescribed surgery for one eye. The thing is that our drug no longer works on very old rats. I decided that I was an old rat. But then God punished me for not believing in my strength. We did not cut the second eye right away; it was the very end of 2008 - the beginning of 2009, the crisis, there was no time for surgery. But I continued to drip. And he came to the doctor only eight months later. And the doctor says: “Where did you put your cataract? She's gone. You don't need surgery." Four years have passed since that time, I continue to drip, cataracts have not appeared.

Moreover, my myopia has dropped: it was seven units, and became three. And visual acuity is now one in one eye, and 0.9 in the other. So we will expand the list of indications for our drops.

The main goal of the project is “pills of youth”, turning off the body’s aging program. You should start clinical trials in the coming years. When?

We aim to begin testing next year.

How will it look like? A person is not a rat, he lives a long time - how can you determine that the drug is working?

This will look like therapy for individual diseases of old age. You can try the same eye diseases - do not put drops in the eye, but take a pill. There are several options. We are doing very well in treating wounds. It is known that old people have a painful healing process: any scratch can lead to gangrene. And we showed in rats that such senile processes do not appear if the rat is fed our substance.

What about any heart diseases? These are also all diseases of aging, arrhythmias for example.

Yes. This is next on the list. Moreover, we modeled several types of arrhythmias in rats, all of them are perfectly treatable. We also have amazing results on behavior. There is such an experiment - an elevated cross-shaped maze (an installation of two open and two closed paths, raised above the floor; with its help, the level of anxiety and activity in rats is studied. - “RR”). Old animals usually spend all their time in a closed area and generally prefer to sit in one place. And our rats behave in such a maze as if they were young. It’s not very clear how to find an analogue for a person, but I think psychologists will advise something.

We have three rats living in our editorial office. They are old in age, but act like young people. We, however, try to limit their diet...

It's right. The second way to slow down the aging program, besides our drug, is to fast. Eat 30% less, and most importantly, don’t eat meat.

And what is the mechanism?

My hypothesis is that when the amount of food decreases, some receptors in the body register this in the blood. And they perceive it as a threat of hunger. And for a population, the only thing worse than hunger is an epidemic. The body is faced with a choice: either mobilize all resources and find food, or die. In such a situation, all optional programs are canceled. The aging program is also optional, it is needed only for future generations. The body turns off aging for a while. For several months or even a year. The symptoms are the same as when taking our substance: osteoporosis, muscle atrophy, baldness, graying do not develop, menstruation does not disappear, attraction of males to females... But, unfortunately, anxiety appears when there is a signal of hunger. This can be measured: usually a mouse in a wheel runs no more than a kilometer in a day, and when there is a signal of hunger - up to eight, and sometimes it even dies from exhaustion and falls dead. She tries to run away and find food. If you use our drug, there are no such effects, because the receptors signal that everything is in order.

It is known that the active substance in eye drops is the same as in the “youth pill”. Didn't you think that these drops would be bought up and simply taken orally?

There's very little substance there. There are two nanograms in a droplet. So you need to buy thousands of our bottles, pour them into a glass and then drink them instead of water for the rest of your life. If there is some kind of millionaire, perhaps...

Will there be more for oral administration?

Certainly. We will recalculate in kilograms of live weight... I’m now thinking about what to call this drug. You see, a medicine is some substance that makes it easier for the body to fight an illness. And here we are trying to prevent the body from doing bad things itself. This is actually the fight against suicide. Our logic is this: there is some kind of center that sends aging signals to cells, signals of slow suicide. The center operates according to a genetic program. And we interrupt signal transmission at the cellular level. If this is all true, then the drug must be taken all the time: as soon as you stop, the signal begins to flow again, because the genes have not gone away.

Aren't you afraid that the “youth pill” will become an analogue of the atomic bomb in biology? Will it completely change social life?

If it turns around, it will be for the better.

You can imagine the following consequences, for example: social elevators will stop working. The boss will be the boss for a hundred years. Forever young.

Well why? Everything is decided politically. Rigid rotation, for example. I'm not a politician, I'm a biologist. Our job is to offer. After all, this has already happened: people now live on average twice as long as they did in the 19th century.

Yes, we have already experienced one such revolution - antibiotics.

We survived. And no one, not a single person complained about it. By the way, I’m not saying that people will live 800 years. There is an example: whales. They do not age, but mature with age. And they live about 200 years. They apparently do not have an aging program, but this does not mean that nothing bad happens to the body. Parts of the body do wear out. There are real diseases of aging, and I think people will not live 800 years. By the way, there is still cancer that our pill cannot treat, which means that everyone will live to see their cancer. So it is unknown how many years we can extend life, and that is not the main thing. The main thing will be that the layer of unfortunate people who have fallen into childhood, if not because of their mental abilities, then because of their physical capabilities, will disappear. We managed to do this in animals. There is hope that it will work on humans.

With the development of scientific and technological progress, our ideas about aging have changed significantly. Today it has ceased to be an insurmountable law of nature and is regarded as a completely curable disease. Thanks to breakthroughs in biology and medicine, we now well understand many aspects of the “machine” of the human body, have learned to effectively protect it from external threats and even “repair” various breakdowns. All this contributed to a significant extension of human life. Within just one generation, the concept of “very an old man» shifted on the time scale by 20 years - from 70 to 90.

However, the impressive increase in average life expectancy has had little effect on its maximum life expectancy, which remains around 120 years. The fact is that the increase in the risk of death with age consists of two components: the first is the accumulation of random breakdowns of various components of the human “machine”, each of which is technically correctable; the second is the result of the work of an as yet unexplored “clock mechanism”, including inevitable decrepitude, which limits the ceiling of life expectancy to 120 years.

So even when we defeat cancer, Alzheimer's disease, type 2 diabetes, cardiovascular disease and other metabolic diseases, we will "only" improve the quality of life of older people, but we will not increase its duration or relieve the body from non-stop wear and tear.

In solving this problem, society places great hopes on pharmacology, namely on the development of drugs that can prevent, stop, or even reverse the aging process. We, as a rule, cannot develop a drug that would be able to replace a lost function, but we can quite count on success if it is necessary to suppress an active pathological process, neutralize toxic factors, or push the system to reprogram, in which it is able to perform a suppressed function illness. This is precisely what the efforts of leading research organizations are focused on today.

Longevity market

The potential size of the market for anti-aging drugs can be estimated by the number of consumers: it is close to 100% of people in the category over 50 years old - this is exactly the age when anti-aging drugs become necessary for everyone. By the way, in the US alone, insurance company expenses related to aging today amount to at least $18 billion a year. Growing confidence in the very possibility of finding a cure for old age caused a “gold rush” and forced many companies to join the race for a new market of unprecedented size.

Probably the largest project in terms of investment in this area belongs to Google: this is the company Calico, which has not yet presented its own developments, but at the beginning of 2017 announced a strategic partnership with C4 Therapeutics, which is developing drugs aimed at targets associated with protein degradation . Another trend is related to the positioning of drugs already on the market in a new capacity - as anti-aging drugs. For example, the University of Texas Health Science Center at San Antonio is conducting a study of metformin in this context (now used in the treatment of type 2 diabetes). By the way, this study became landmark, since the authoritative American agency FDA first approved it specifically for the indication “Frailty” (senility, senile infirmity). A number of scientific developments aimed at treating aging are being carried out in many laboratories around the world, but they are still far from clinical implementation. According to our estimates, closest to others practical solution The American company UNITY Biotechnology approached the problem and entered the market, with which Everon Biosciences (our portfolio company) is fighting for the right to be the first in this area.

The first generation of anti-aging drugs is expected to hit the market in 2024-2025. It is already approximately clear what the next generation of drugs may be, the development and launch of which will take another 8-12 years. Modern tendencies indicate that during this period the market will be partially formed, and a number of currently existing regulatory problems will be resolved.

Finding a “target” for treatment

Telomerase. Lessons from tumor immortality

One of the first scientifically based attempts to find an approach to the treatment of aging was the study of the phenomenon of immortality of malignant tumors. By the mid-90s, this phenomenon could be explained thanks to the discovery of telomeres - special structures formed around repeating sections of DNA at the ends of all chromosomes and acting as a kind of thimbles that protect the chromosome ends from sticking together. With each new division cycle, the sections with telomeres gradually shorten. As a result, at some point the ends of the chromosomes become so short that telomeres can no longer form, the stuck chromosomes break down, and the cell cycle stops.

A common feature of tumor cells is the presence of telomerase, a special enzyme that allows the lengthening of telomeric sections of DNA. It is this property that determines the ability of tumor cells to divide unlimitedly, in other words, to immortality.

The discovery of telomerase led to a bold practical hypothesis: activating telomerase in normal cells was expected to be a way to prevent aging. However, in practice, the restoration of telomerase activity, although it contributed to the appearance of endlessly dividing cells, did not lead to the immortality of the entire organism. Thus, the activation of telomerase, which initially attracted attention as a solution to the problem of combating aging, did not live up to expectations.

Genes of youth. Lessons from centenarians

Another direction in the search for a cure for old age was genome research. Well-documented examples of long-lived families are widely known, the very existence of which demonstrates the fundamental possibility of extending human life with the help of a certain set of genes. In addition, there are mammals that live 10 times longer than expected of their species, do not develop cancer, and do not show signs of developing senility as they age. But, unfortunately, at this stage we are not able to translate the obtained observations about genetic properties into a prescription for a pill for old age.

There is great hope that it will be possible to translate observations made on such centenarians to those individuals who are deprived of natural mechanisms to combat aging. However, there are still not enough pieces of knowledge to fully compile this puzzle, and the path to the creation of therapeutic approaches on this basis is still very far.

Senescent cells. Common denominator for age-related diseases?

The fact that the risk of developing a whole host of seemingly unrelated diseases increases sharply after a certain age has led scientists to assume that they all have a common cause. Today, more and more specialists in the field of aging are coming to this conclusion.

The most likely common cause of the development of cardiovascular, metabolic, autoimmune, malignant and degenerative diseases is systemic chronic inflammation that develops with age (“inflammaging”). However, for a long time the cause of the development of this inflammation remained unclear. Among the numerous candidates for the role of the causative agent of chronic inflammation, the theory of senescent cells (SC) has received the greatest scientific support. In 2011, a breakthrough was made in this field when a team led by James Kirkland and Jan van Deursen from the Mayo Clinic showed that removing cells carrying one of the markers of KS (p16-positive cells that accumulate with age) in mice leads to partial rejuvenation individuals.

The results of subsequent studies strengthened the belief that SCs are the main cause of aging, and set a clear direction for the search for anti-aging drugs among “senolytics” that can selectively remove SCs, which are considered the source of senility and senile poisoning of the body. It was this development that formed the basis for the products of UNITY Biotechnology and Everon Biosciences.

Macrophages associated with aging

Subsequently, a more detailed study of the problem of “senolytics” showed that while SCs carry the p16 marker, not all p16+ cells are senescent. Most of them are cells of the immune system responsible for the removal of SC. Thus, with age, not only the accumulation of SC occurs, but also a disruption of the immune system, which is capable of at a young age independently remove SC, preventing the development of inflammation. The main “actors” of this restructuring turned out to be macrophages associated with aging, which, as it turned out, have many of the properties of SCs. This discovery was made by a group led by Professor Andrey Gudkov, scientific director of Everon Biosciences, and set the direction for the company’s developments.

The fact that at least some of the cells thought to be SCs turned out to be macrophages does not contradict the theory of “chronic inflammation” and does not discredit the importance of the results of previous studies. New data have only adjusted the course of development of anti-aging drugs towards a better characterized target and a better understanding of the processes occurring in the aging body.

Thus, the definition of “chronic inflammation” as the “connecting thread” of all diseases associated with age was a major breakthrough in the process of developing a cure for old age. For the first time in the history of gerontology, the majority of specialists representing various fields of aging science are in agreement. This concept has extremely important consequences not only because it allows us to name the common cause of all aging ailments, but also because it allows us to identify a target for therapy - cells that accumulate with age - sources of inflammatory factors.

Today, the most important events are unfolding around the precise definition of the nature of these cells: the original focus on SCs has turned towards innate immune cells before our eyes. All these prerequisites give confidence that an anti-aging drug will be created in the near future and will be on the market within 5-10 years.

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It is difficult to imagine that our distant ancestors had a short life and rarely any of them lived to be 40 years old. By modern standards, the most active period of a person’s life occurs at this age, when knowledge and life experience. The phenomenon of centenarians who have exceeded 90 years of age is being studied by doctors, biologists, geneticists, biochemists and demographers who are trying to find factors influencing life expectancy. With the development of technology and various branches of science such as genetic engineering and biochemistry, humanity is learning more and more and moving forward in finding ways to extend human life.

What is associated with aging of the body?

The aging process is primarily associated with natural breakdowns and mutations in gene regions that lead to incurable diseases. Numerous studies have proven that free radicals produced in mitochondrial cells play a key role in the aging process. Mitochondria play a dual role in the human body. On the one hand, they produce the necessary energy for the life of the body by oxidizing substances entering the cell, and on the other hand, they lead to the appearance of free radicals, which have a detrimental effect on intracellular processes and lead to cell death. Various studies have proven that disruption of mitochondrial processes can lead to various diseases of the heart, blood vessels, weakened immunity and the occurrence of cancer.

The Research Institute of Mitoengineering of Moscow State University has been working for many years on a drug that prolongs youth, and which is already in the stage of clinical trials. The principle of operation of the drug is based on the effect of free radicals in the mitochondria of the body's cells. A group of researchers from this institute, led by Academician V.P. Skulachev developed a two-component composition of the substance SkQ1, which affects the functioning of mitochondria. With the help of the first component, a positively charged ion, the second component, an antioxidant that neutralizes free radicals, is delivered to the mitochondria. With the help of this " medicines for old age“You can influence the amount of free radicals and reduce them accordingly. Eye drops for the treatment of cataracts and dry eye syndrome based on the SkQ1 composition are already available in pharmacies.

Cell Process Research

It is clear that the first developments can still be used narrowly for the treatment of certain diseases, and much remains to be done in creating a universal cure for aging. There are obvious successes of Russian and foreign scientists working in areas related to aging and the emergence of diseases. The mechanisms of formation of lipid mediators and, accordingly, ways of influencing metabolic processes in mitochondria were determined. Another direction is related to the study of mechanisms associated with caspases, enzymes of the protein complex that are directly related to the processes of cell functioning or death.

Many scientists are conducting genetic research to study aging processes. American scientists are experimenting with making changes to the structure of DNA, rewriting a damaged chain into a healthy one, thereby eliminating gene mutations and renewing the body. In the future, changes in genes may overcome hereditary diseases (blindness, diabetes, heart disease), the number of which is increasing every year.

What will increase life expectancy lead to?

Research that helps find ways to treat diseases and prolong life raises debate in society about what increasing people's life expectancy will lead to. What ethical, economic and social consequences might arise if people, using anti-aging drugs, were able to live 150 or 200 years? It is obvious that, with 150 years to spare, people will be able to realize their full potential and live fully. On the other hand, the question arises of how much longevity will be available to each person, and by what criteria will people become centenarians. How will humanity solve the issue of overpopulation and resource provision? Questions arise constantly, but progress definitely leads to scientists making discoveries that help every person overcome illnesses and enjoy life.

Our expert is an employee of the Oncology Research Institute named after. N. N. Petrova, President of the Gerontological Society at the Russian Academy of Sciences, Doctor of Medical Sciences, Corresponding Member of the Russian Academy of Sciences Vladimir Anisimov.

In fact, “pills for old age” have already been invented, and the day is not far when doctors will prescribe them to us.

Against diabetes and more

In the 70s of the last century, our scientists put forward the idea that drugs from the biguanide group, which are prescribed to patients with diabetes, can prolong life. Studies were conducted on laboratory rats, and it turned out that the drug has another effect - it inhibits the development of tumors.

A quarter of a century later, employees of the N. N. Petrov Oncology Research Institute found that a drug from this group, metformin, increases the life expectancy of mice and inhibits the development of breast cancer in them. At the same time, American and English scientists announced the results of their research. They analyzed the health status and life expectancy of 70 thousand patients with diabetes who took metformin. Their risk of developing cancer was 35-40% lower than those who did not take this drug, and they lived 15% longer.

Recently, American scientists announced plans to study how metformin affects older people without diabetes, but with other diseases: atherosclerosis, cancer... Observation will take place over 3 thousand volunteers over 70 years of age in 15 medical centers. But metformin is already recognized by the US FDA medicines(analogue of our Pharmaceutical Committee) geroprotector. And in the USA it is already prescribed as a medicine that delays aging.

Who's next?

Another substance - melatonin - can be called a geroprotector. It was opened in 1958. This is a hormone that is produced in our body at night, in the dark, and is a regulator of sleep and biorhythms. In the 70s of the last century, our scientists found that melatonin, administered as a drug to rats and mice, prolongs their life.

Melatonin is already prescribed in the United States as an anti-aging agent. In Russia, it, like metformin, is already used in the treatment of cancer. And the use of melatonin as a geroprotector that delays aging is a matter of the near future.

St. Petersburg scientists are now testing a number of drugs that can prolong our lives. Among them are aspirin in small doses, resveratrol - a polyphenol found in grape seeds and red wine... The same studies are underway in the USA and other countries. People now live longer, and it is necessary to extend their working period, and push old age to the very edge of life.