How to treat old age with genes

Vladimir Borovoy, "Snob", with the participation of Alexey Aleksenko

Gene therapy can extend human life to at least 110 years. Biologist Ilya Dukhovlinov, founder of the Pharma Gen company, probably knows how to do this

Ilya Dukhovlinov. Photo from the personal archive

Old age and death await us all, and science, unfortunately, does not yet know why this is so and what to do about it. Nevertheless, many medical companies around the world offer a wealthy consumer different therapies designed to delay the onset of old age. If you just type "life extension" in the search engine, you will get a huge list of clinics and techniques. And of course, two–thirds, or even more, is pure or slightly diluted by science quackery, sometimes dangerous, sometimes with no real consequences. As a result, the consumer seems to be even a little tired of this industry, where the effectiveness is not obvious, but the desire to exploit the human thirst for eternal youth is obvious and undisguised.

Meanwhile, modern medicine has really learned something and is able to delay the onset of some signs of old age. It is easy to see that effective methods exist by looking at the faces of 70-year-old world stars: how good they are! No, it's not just healthy lifestyle and a healthy climate. This is the result of anti-aging therapies.

The only question is whether you need such a result and whether you are ready to pay the appropriate price, and not only in monetary terms. Most of the methods of anti–aging clinics are based on spurring the body to do what it – due to old age and decrepitude - does reluctantly. It is possible, for example, to stimulate tissue regeneration. As you know, our cells do not divide indefinitely: there is a "Hayflick limit", the maximum possible number of divisions. It can be overcome with the help of various means, on which many therapies are based.

The most popular option today is hormone therapy. With age, the sensitivity of cells to their own hormones decreases, and they begin to be lacking. If you add hormones, it should get better, and judging by the results, by the same smooth faces of the stars, it works. However, both this method and the previous one are based on stimulation – forcing the body to do what it does not really want. And with age, the body lends itself to stimulation worse and worse. We are getting old, and it is impossible to endlessly squeeze out of us the potency for cell division and hormone assimilation.

"I undertake to predict that the current 70-year–old stars, whose beautiful form we admire, will live a fairly standard period for developed countries – 80-90 years – and will die in the same perfect shape, having visited the gym the day before their death," says Ilya Dukhovlinov (who, in fact, told us everything that's where we started this article). He does not say this out of malice, although one might suspect him of wanting to sink competitors. Since Ilya is the founder of several biotech companies, which are also engaged in gerontology. Only his gerontology is different. Genetic.

In the early 2000s, Ilya, as a research biologist, participated in the development of an interesting technique. Here's the thing: let's say you need to increase the tissue's ability to regenerate. You can, for example, pump it with growth factors. You can do a little more subtle: introduce into the tissue not the growth factors themselves, but their genes, so that they start working and producing goods... but only then will the need for them disappear, and then how can these genes be picked out back if they are already firmly embedded in the chromosome?!

Dukhovlinov did this: he simply injected a piece of DNA into the tissue, on which the necessary genes, for example human ones, were suspended from a special motor borrowed from the virus. The motor (they are called "promoters") made the genes work. As it turned out, such pieces of DNA, even if they are simply introduced into the bloodstream, with a certain probability penetrate into the cell, into the nucleus itself and remain there for some time without being embedded in the chromosomes and without spoiling the genome given to us by God. At the same time, the viral motor does not work indefinitely in the cell: after 8-9 days it turns off, and the whole structure fails. Everything is going back to how it was. Except that all this time the cell was stimulated to divide, and the wound that we wanted to heal had time to grow.

In those years, Dukhovlinov healed wounds in mice, not in humans. But things have progressed a lot since then. The drugs developed by Dukhovlinov at Pharma Gen are currently undergoing clinical trials. And one of them is just a drug for old age.

What is it? Again, a simple circular DNA molecule without any special tricks, on which there is a viral motor. And behind it are the genes of receptor proteins, the very ones that make the cell respond to hormones. The genes turn on, and for nine days the cell becomes very susceptible to hormonal signals. At the same time, it is not necessary to accustom her to high levels of hormones: everything comes back to normal as soon as the deadline expires and the genetic design turns off.

And what kind of receptors we will build into the cell in this way depends on what we want to achieve. Maybe it will be insulin receptors for liver cells. Insulin resistance is a key factor in aging, and a handful of new receptors won't hurt you at all. Or maybe you are an athlete and you want to spur the growth of muscle mass with testosterone. Just add testosterone receptors – without any, mind you, banned drugs. Finally, it is possible to force cells to produce endorphins and achieve the highest bliss... well, or at least a strong analgesic effect.

That's about all this and the scientist Ilya Dukhovlinov intends to offer humanity. And we received more detailed explanations from him.

"Snob": Ilya, how can I make sure that your methods work? The beauty of anti-aging as a business is that a dead patient will not demand money back...

– Perhaps the main achievement of modern genetic gerontology is that it has absolutely specific methods that allow assessing the benefits of certain drugs at the genetic level. This is one time. And secondly, there are fairly clear criteria for longevity – now it has become noticeably more measurable than before. There are specific enzymes, specific sections of chromosomes, by which it is possible to determine whether aging is going on or not. There is enough knowledge to establish whether certain anti-aging agents work, and this is very important.

– Have you tested your medications according to these criteria?

– We have tested our development on two generations of rodents. I have spent eight years of my life on this experiment. It's good that laboratory mice live on average 2-2.5 years, and not longer – you know, the experience is in real time. Our experimental animals both times reached the 3.8 year mark. In such work, of course, it is important to choose a model in order to live to the final and present the result.

But now, thanks to the very markers of aging, it has become easier to demonstrate the results of the experiment. Now I can take animals, puncture them with a drug, remove the markers of aging after a year and say: yes, this group ages more slowly.

– God be with them, with mice – what about people?

– The next stage of testing – based on these markers – will take place already in humans. Clinical trials will start in about a month. We will take a group of volunteers – not elderly, because aging prevention needs to be done in advance – we will remove their current markers, start giving them the drug, and they will take markers every three weeks. If the indicators decrease, this will be the main proof of the effectiveness of the drug.

– What is the probability that this will happen?

– So that you understand, such clinical tests are very expensive and troublesome. If I start this process, invest tens of millions of rubles in it and get a negative result, I must understand that I am losing this money. Therefore, in this case, I am confident of success.

– Will you test the final "pharmacy" version of the drug on yourself?

– Yes, of course, I will use the final version of the drug. As a professional, I also know which markers of aging will need to be checked first.

– How is your method fundamentally better than traditional hormone therapy?

– We start from the fact that with age our tissues and organs gradually lose the ability to absorb hormones – insulin, somatotropin, sex hormones. The cells in the tissues do not feel them. We can just flood them with hormones, make them consume the right amount. But the ability to assimilate them will continue to fall, and by the age of 90 it will completely disappear. And then a person will die, despite the fact that he will have a synthetic cocktail of all the substances necessary for life in his blood. Therefore, we have taken the path of restoring tissue sensitivity to hormones.

– Is there a big gap between Russian and foreign genetic companies?

– For a long time we were lagging behind: if you look at the picture of a decade ago, the United States was very seriously ahead of us. Now, in my opinion, our laboratories can adequately compete with foreign ones.

– What is the task of life extension for you – a business or a mission?

– It seems that the business component plays a secondary role in this. Although, who disputes, the money earned is the most important measure of the effectiveness of the project. For me, the possibility of knowing the world and how everything works in it is very important. And of course, the search for scientific answers to the questions "What is the meaning of aging?" and "Why should we die?". Working in the field of genetic gerontology, you somehow find them.

For example, studying the human body, I came to the conclusion that initially it has a service life of 130 years. On very specific grounds. But the conditions of our life are such that at first, in prehistoric times, we barely reached 35, and now 80 years is the limit for most.

– There is an opinion that the hope for science in the fight against old age is a new form of religious consciousness. Instead of believing in God, there is a belief that science will allow you to live forever. Do you think maybe it is?

– I do not find a religious feeling in myself for this problem. I don't aim to extend life to 1000 years. Here some kind of religious faith is already required, here it is already possible to talk about playing God – the scale is suitable. I solve the issue of aging through the possibilities of matter. My goal is to give us back power over the entirety of our body's resources. If you can live 130 years, who will refuse? I am sure that an additional 50 years of active life will not hurt anyone. And think what a plus it will be for the development of civilization! At the age of 80, having accumulated a unique life experience, we will not die, but fully use it for the benefit of ourselves and others.

– There are fears that all these technologies will be usurped by the rich so that the "golden billion" will live for 130-150 years, and the rest will feed them and break down in their 50s. Aren't you afraid of that?

– Of course, there are such risks with any such technology. But here it is important not to hide this topic, to give relevant information on it. To make this prospect real, not fantastic. Now we will talk, our conversation will be published – we will make it a little more real, we will make our small contribution.

– How soon will all these drugs become commonplace? Those who are now forty, will they find this time? Will they have time to use it?

– They'll catch you and have time.

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