It's great to get old
Russian scientist knows how to prolong the quality of life
Yuri Medvedev, Rossiyskaya Gazeta
The results of a unique study by Professor Alexey Ryazanov of Rutgers University of America will become the basis for the development of the principles of "healthy aging". The scientist told the correspondent of "RG" about this.
Alexey Ryazanov defended himself at the age of 28 and became the youngest doctor of biological sciences in the USSR. Photo from the archive of Alexey Ryazanov.
Although aging has probably been studied for as long as modern man exists, but its causes remain a mystery behind seven seals. I remember at a major international conference, 35 scientists gave different answers to the question of what aging is. This is reminiscent of the situation from the famous parable about the sages, who, studying an elephant, answered differently what kind of animal it was. And you are a supporter of what hypothesis of aging?
Alexey Ryazanov: You may be surprised, but none. My approach to aging basically contradicts the generally accepted ones. How is it traditionally studied? One scientist says, I think the main thing is the telomeres that have already become famous, let's study them, another blames antioxidants, the third blames protein crosslinking and further down the list. That is, first they put forward a hypothesis, propose some mechanism of action, and then they look for confirmation of the hypothesis in the laboratory. And here it is necessary to emphasize the most important thing: all these works are overwhelmingly carried out on cells, yeast, flies, they look at what is happening in the genes. Using your analogy, with this approach, we will never understand what an elephant is. We will not understand the causes of aging, because it needs to be studied in the whole body, and an animal in many ways very similar to a person. Therefore, I suggested: let's discard all these endless hypotheses, and test all pharmacology and many known compounds on animals. How they affect aging.
But such studies have been conducted on mice for a long time ...
Alexey Ryazanov: Yes, they are, but what is the scale? For example, the Intervention Testing Program in the USA has tested only 30 substances on mice since 2004. In fact, nothing, because there are several thousand medicines alone. So we will not deal with the "pharmacological" elephant. We need a fundamentally different approach. When I told about it at a scientific seminar ten years ago, one of our businessmen became interested in the idea and offered to implement it. Which we did.
Ten whole years to pump pharmacology through mice? I understand that your approach was unexpected, contradicted the traditional one, but the science itself in this case, it seems to me, is not so complicated: feed the drug and see how long the mice will live.
Alexey Ryazanov: I think it doesn't make sense to go into all the details of studies that are difficult for the mass reader. Let me just remind you of the example I just gave: 30 substances have been tested in the USA since 2004, and we have tested more than 1000 in one experiment! It lasted almost 4 years, it used about 20 thousand special long-lived mice. Our research is very expensive, more than $10 million has been invested in it.
What are the results? Did you manage to find "rejuvenating apples"?
Alexey Ryazanov: 1033 drugs and compounds, including vitamins, dietary supplements and natural compounds, have been studied. We found 60 compounds that prolong life by 10% or more, and 5 of them – by 16-20%. But it took several more years of work after the experiment to unravel two mechanisms of life extension based on the data obtained.
Specifically, what are these substances?
Alexey Ryazanov: They belong to two pharmacological classes. The first is chelators, but they are special, the second is certain activators of xenobiotic metabolism. Both are responsible for cleaning "garbage" from the body, that is, various toxins. These "wipers" work in different ways. Chelators capture garbage, bind it and remove it, and activators stimulate the detoxification system in the body, and it already removes all kinds of toxins and "garbage" better. As a result, on large statistics, on large groups of mice, we saw that the animals receiving these substances became long-lived compared to their usual relatives.
Alexey Georgievich, in our science you are a historical person in your own way. They defended their dissertation at the age of 28 and became the youngest doctor of biological Sciences in the USSR. What kind of research was it? Also related to aging?
Alexey Ryazanov: This is a separate story. At that time I was not even a candidate of sciences, moreover, I did not write a traditional doctoral dissertation. In defense of his work, he made a scientific report, which, in fact, was an abstract of 10 pages. It was about a new enzyme, eEF2 kinase, that I discovered in the late 80s at the Institute of Protein of the Russian Academy of Sciences. It turned out that it has many different properties, for example, it helps to remove defective germ cells. Its shutdown can be used in the treatment of oncology. In addition, this enzyme can be used to create drugs that protect against radiation. But it took many years to figure it out, to understand how it works. And then we published an article in the journal Nature about the fact of the discovery of a hitherto unknown enzyme.
An article in this journal is a dream for any scientist. It is believed that if you are published in Nature, it means that you have done something very worthy in science. And you published without even being a candidate of sciences. And then who was listed first in the list of authors?
Alexey Ryazanov: There were three authors. My name came first. I was still a graduate student then. And two interns. And my scientific supervisor was the largest Russian biologist Alexander Sergeyevich Spirin. Although we worked in the same room with him, we discussed everything every day, but he believed that this was not enough to become a co-author. We need to make a specific scientific contribution. He was a man of the highest ethical standards. He had a huge influence on me. And having already worked for many years in the USA, I came to Pushchino every year, met with Alexander Sergeevich, we discussed the situation in world and domestic science. Unfortunately, he recently passed away. This is a huge loss not only for the entire scientific community, but also for me personally.
After that publication in Nature, you were probably inundated with offers from foreign scientific centers. That's when you left Russia. Moreover, the hardest times have come for Russian science, tens of thousands of our scientists have flocked to the West.
Alexey Ryazanov: I have not left anywhere, I am still a citizen of Russia. And until 2017, he was listed as a leading researcher at the Belka Institute, it was believed that he was on a business trip. And I had to quit under the terms of the megagrant, but that's another story.
I didn't go to the USA because I was going to emigrate. The fact is that our famous scientist Israel Moiseevich Gelfand wanted to organize a biological laboratory at Rutgers University and invited me to help. That's how I ended up in the USA. We've been doing this for two years, but it didn't work out, but I was offered to stay. So since 1991 I have been living here, but in my heart I remain an employee of my institute in Pushchino. I really love this place, I come here several times a year.
Alexey Georgievich, do you have a hobby besides science?
Alexey Ryazanov: Of course there is. For example, I am very fond of cycling, and also camping.
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