Digger's Recipe
How to live 130 years and become younger
Yuri Medvedev, Rossiyskaya Gazeta
When does aging begin? How did nature learn to slow it down? Which method of rejuvenation is preferable? The correspondent of "RG" talks about this with one of the world's leading experts in the field of gerontology, Professor of Harvard Medical School Vadim Gladyshev. His lecture caused a lot of responses on the online forum "Science of the Future - the science of the young", where leading scientists, including Nobel laureates, presented the latest achievements in various fields of science.
From the first words of your lecture, you immediately intrigued the audience by saying that science still does not know what aging is. But a person has probably been thinking about its causes since he began to realize himself.
Vadim Gladyshev: Recently, at a conference, 35 well-known experts gave different answers to the question of what aging is. Today, there is no theory of aging that most would lean towards. Some believe that this is a programmed process, the purpose of which is to give resources to the next generations. There is also a theory that the cause of aging is the accumulation of mutations. The bottom line is that some gene variants behave neutrally in the younger years of the body, and by old age, damage accumulates because of them. There are supporters of the theory of free radicals, because of which molecules are damaged. But none of them fully describes the entire aging process.
Isn't it possible that science is looking for ways to neutralize the enemy without understanding what he is? You can recall the famous parable about the wise men who tried to understand what an elephant is. Everyone studied some separate organ of the animal and gave their own answer. But everyone was far from right. But then everyone is hoeing their own garden?
Vadim Gladyshev: Of course, there is unity in some issues. For example, that by influencing the body, you can change the life span. For example, if you remove a certain gene, the body will age more slowly. But aging has many faces, it manifests itself in different ways, so there is no one definition for it yet. That does not prevent you from studying it. As the research progresses, its essence will be clarified and, in the end, a generally accepted opinion will be formed. This happened with many theories that are considered classics today.
What theory do you support?
Vadim Gladyshev: I believe that this is the accumulation of damage and other harmful changes with age. It is important to emphasize that when the body ages, there is no one major damage. Or the main gene that is involved in this. On the contrary, the whole body is involved. And since there is no main culprit, that is why it is so difficult to fight aging.
But there are known phenomena in nature that do not actually age, for example, the naked digger, which has already become famous. Maybe we should use his secret?
Vadim Gladyshev: Science has already found several such amazing creatures. This is also a digger who lives 10 times longer than rodents of the same size related to him, practically does not suffer from anything, including cancer. Or, for example, hydra, which probably does not age at all, since the probability of her death does not increase with age. It would seem, why? After all, the digger, like all other mammals, increases the number of injuries with age. Of course, the body can remove some of them, but others remain. Therefore, the digger still ages, but much slower than other rodents.
But if the accumulation of damage is inevitable, even they got a digger, then how did hydra manage not to age?
Vadim Gladyshev: In hydra, damage dilution appears to be taking place. How? Let me explain with a simple example. Let's say there were two damages in some cell, and after its division, there was one damage in each new one. The cells continue to live, and two damages accumulate in each one again. Then the cells divide again, and there is one in each new one. This is dilution. If the whole organism can exist like this, then it may not age.
And if the rate of damage accumulation is not greater than the rate of dilution, does the cell continue to live? And old age will not come? Or at least it will be much pushed back?
Vadim Gladyshev: That's right. Perhaps this strategy was key for life on Earth to arise and be maintained at all. From the very first protocells, the damage had to be diluted by cell division. But in some organisms there are cells that do not divide after the end of development, for example, neurons, some cells of the eye, heart and others. The dilution mechanism does not work with them. This applies to all mammals, including humans. For them, aging is inevitable. But it can be slowed down, life expectancy can be increased.
And the digger demonstrated that this is real. So, nature has such tools. Why don't we use them?
Vadim Gladyshev: This is what science is doing today. Of course, nature is amazing in everything, including the diversity in life expectancy. For example, a shrew lives only one year, a bowhead whale is 200 years old, and their set of genes is approximately the same. Nature uses a variety of strategies for life expectancy. We studied 30 species of animals with a life span of 3 to 50 years and on three organs – the liver, kidneys and brain, looked at how their metabolism changes, how nature acted to increase the life span. It turned out that, say, in the liver, the activity of genes that are responsible for metabolism is strongly suppressed. And in the kidneys, their activity is weakened, but not so much. In the brain, the same effect is practically absent. And at the same time, other processes are activated in these three organs, for example, different protective functions, etc. Conclusion? To increase the life span, nature works very carefully, it has changed the same processes in different ways in different organs. But if we know how nature works, we can try, at least to some extent, to repeat it.
There is another approach. To do this, we used 17 already known ways to increase the lifespan of mice – calorie restriction, knockout of the growth hormone receptor, etc. Analyzing these methods, we understood the general patterns and tested 3000 compounds – various drugs, as well as natural chemical compounds. We have identified those that are most effective. You can combine them, look for optimal combinations. We hope that, in the end, this knowledge will help a person to push back old age, prolong life.
Reassuring. And if you dream up? How realistic is it not just to live up to 120-130 years, but to get younger?
Vadim Gladyshev: This is a new field of science that has been very little studied so far. In principle, it is known that it is possible to rejuvenate certain cells of the body. For these works, Shinyi Yamanaki received the Nobel Prize. He managed to transfer ordinary adult cells to a younger, embryonic state. How this happens is completely unclear. For example, not all cells are rejuvenated during this procedure, but some of them die altogether. Research in this area is in its infancy, we do not fully understand much yet, but we know for sure that it is possible to rejuvenate cells. It is unlikely that such a trick will work with the whole body, because some cells of the adult body no longer divide and they will not be able to return to a young state. But individual organs can be rejuvenated. However, other questions will immediately arise. For example, what is the age of an organism whose half of the cells are younger than the rest?
In your lecture, you said that an unexpected connection was found between aging and covid. Please explain in more detail.
Vadim Gladyshev: It is now known that the probability of mortality increases with age, and doubles every eight years. There is a similar pattern with mortality from covid. That is, it behaves like an aging disease. In addition, the same genetic variants that increase the life span protect against mortality in the case of covid. This means that covid can be affected not only by antiviral drugs and vaccines, but also by those that slow down aging.
The key question
When do we even begin to age? Does science have a common opinion? Or, as with the definition of aging, is there a "general" disagreement here?
Vadim Gladyshev: The situation is about the same. There are several versions: aging begins during the period of fertilization; after birth; after nine years; upon reaching puberty; after 20 years, when the end of the development of the body ends, or even further, when obvious signs of aging are visible, such as baldness or wrinkles.
It would seem that the closer to birth, the lower the probability of death.
Vadim Gladyshev: By simple logic, indeed, the picture should be like this. And then in the very first months and years of life, mortality would be close to zero. But everything is much more complicated. As you know, at the beginning of life, especially in newborns, it is high. Gradually falls by the age of 9, then begins to grow again.
Why is it at the age of nine that the mortality rate is the lowest? Apparently, a failure of 9 years is obtained at the intersection of two curves. One is mortality due to natural aging, which is small in children, but gradually increases over the years. But there is another, early mortality, it is not associated with aging, but with developmental errors. In addition, each of us is already born with some harmful mutations that he receives from his parents. Mutations that we get in life are also added to them. They accumulate and contribute to mortality. As I said, at the intersection of these two curves is the failure of mortality in nine years.
The most prosperous age for a person. And why is there a high mortality rate at an early age? After all, harmful mutations have not yet accumulated, and the figure is the same as in 20 years.
Vadim Gladyshev: This is due to development errors. In addition, the child receives some harmful mutations from the parents. And in each generation, an average of 50-100 new mutations are added. It seems that because of this, the gene pool of the population should get worse with each generation, but this does not happen, since natural selection works. Although now it is quite weak, as medicine and society help the sick and weak. But at the beginning of life, the selection mechanism works more strongly, which allows you to remove such mutations from the population. All this explains the high mortality rate in very young years.
By the way
Biologically, life can be extended. But how is a person going to spend those extra 40 years? What will he do when his children, grandchildren, great-grandchildren have grown up? The point is not that there should be some biological substrate, but that this life should be active and meaningful, so that there should be some purpose in it. This was discussed at the round table "Live to 150. And why?"
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