From the very first words of your lecture, you immediately intrigued the audience by saying that science still does not know what aging is. But the person has been thinking about its causes, probably, since he began to realize himself.
Vadim Gladyshev: Recently, at one conference, 35 well-known experts gave different answers to the question of what aging is. Today, there is no theory of aging to which the majority would be inclined. Someone thinks 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 variants of genes in the young years of the body behave neutral, and by old age, damage accumulates because of them. There are supporters of the theory of free radicals, due to which molecules are damaged. But none of them fully describe the entire aging process.
Isn't it so that science is looking for ways to neutralize the enemy, not understanding what he is? You can recall the famous parable about the wise men who tried to understand what an elephant is. Each studied some separate organ of the animal and gave his own answer. But each was far from correct. But then everyone spuds their own garden?
Vadim Gladyshev: Of course, there is unity in some issues. For example, that by acting on the body, you can change the lifespan. 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 single definition for it yet. Which does not prevent you from studying it. As research progresses, its essence will be clarified and, in the end, a generally accepted opinion will be formed. This was the case with many theories that are considered classics today.
Which 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 as the body ages, there is no one major damage. Or the main gene that is involved in this. On the contrary, the whole organism is involved. And since there is no main culprit, that is why it is so difficult to fight aging.
But in nature, phenomena are known that do not actually age, for example, the already famous naked mole rat. Maybe we can use his secret?
Vadim Gladyshev: Science has already found several such amazing creatures. This is a mole rat, which lives 10 times longer than related rodents of the same size, practically does not get sick, including cancer. Or, for example, the hydra, which may not age at all, since the likelihood of its death does not increase with age. It would seem why? Indeed, in a mole rat, like in all other mammals, the number of injuries increases with age. Of course, the body can remove some of them, but others remain. Therefore, the mole rat does age, but much slower than other rodents.
Vadim Gladyshev: Today science does not have a unified theory of aging. Photo: Evgeniya Frolova, Department of Photojournalism and Media Technologies, Moscow State University
But if the accumulation of damage is inevitable, they even got the digger, then how did the hydra manage not to age?
Vadim Gladyshev: The damage seems to be diluting in the hydra. How? Let me explain with a simple example. Let's say, in a cell, two injuries have occurred, and after its division, each new one has one damage. The cells continue to live, and each of them again accumulates two damage. Then the cells divide again, and each new cell contains one. This is dilution. If the whole organism can exist in this way, then it may not age.
And if the rate of accumulation of damage is not greater than the rate of dilution, the cell continues to live? And old age will not come? Or at least it will be much pushed back?
Vadim Gladyshev: Quite right. Perhaps this strategy was key for life on Earth to emerge and sustain at all. From the earliest protocells, damage had to be diluted by cell division. But in some organisms there are cells that, after the end of development, do not divide, 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, the life span can be increased.
And the excavator has demonstrated that this is real. This means that nature has such tools. Why don't we use them?
Vadim Gladyshev: This is what science is doing today. Of course, nature is striking 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 lifespan of 3 to 50 years and on three organs - liver, kidney and brain, looked at how their metabolism changes, how nature acted to increase the lifespan. It turned out that, say, in the liver, the activity of genes that are responsible for metabolism is greatly 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. Output? To increase the lifespan, nature works very skillfully; 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 also another approach. To do this, we used 17 already known ways to increase the lifespan on mice - calorie restriction, knockout of the growth hormone receptor, etc. Analyzing these methods, we understood the general laws and tested 3000 compounds - various drugs, as well as natural chemical compounds. Highlighted those that are most effective. They can be combined, looking for optimal combinations. We hope that, in the end, this knowledge will help a person to postpone old age, prolong life.
It is encouraging. And if you dream up? How realistic is it not just to live up to 120-130 years, but to look younger?
Vadim Gladyshev: This is a new area of science, which is still very little studied. In principle, it is known that it is possible to rejuvenate certain cells in the body. For these works, Shinyi Yamanaki received the Nobel Prize. He was able to transfer ordinary adult cells into a younger, embryonic state. How this happens is not fully understood. For example, during this procedure, not all cells are rejuvenated, but some part of them dies altogether. Research in this area is in its infancy, we still do not fully understand a lot, but we know for sure that it is possible to rejuvenate cells. It is unlikely that such a trick will work with the entire body, because some cells of the adult body no longer divide and they cannot be returned to a young state. But individual organs can be rejuvenated. True, other questions will immediately arise. For example, how old is an organism in which half of its cells are younger than the rest?
Covid behaves like an aging disease. This means that it can be influenced by drugs that slow down aging.
You said in your lecture that you found an unexpected link 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. A similar picture is with mortality from covid. That is, it behaves like an aging disease. In addition, the same genetic variants that extend lifespan 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.
When do we start getting old at all? Does science have a consensus? Or as with the definition of aging, is there a "general" disagreement?
Vadim Gladyshev: The situation is about the same. There are several versions: aging begins during fertilization; after birth; after nine years; upon reaching puberty; after 20 years, when the end of the body's development ends, or even further, when obvious signs of aging are visible, such as bald spots 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, the mortality rate 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 nine years of age that the mortality rate is lowest? Apparently, a dip 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 errors in development. In addition, each of us is already born with some harmful mutations that we receive from our parents. To them are also added mutations that we receive in life. They accumulate and contribute to mortality. As I said, at the intersection of these two curves, there is a nine-year mortality dip.
The most prosperous age for a person. 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 at 20 years old.
Vadim Gladyshev: This is due to developmental errors. In addition, the child receives some harmful mutations from the parents. And in each generation, on average, 50-100 new mutations are added. It seems that because of this, with each generation, the gene pool of the population should become worse and worse, but this does not happen, since natural selection is at work. Although now it is rather weak, since medicine and society help the sick and the weak. But at the beginning of life, the selection mechanism works stronger, which allows you to remove such mutations from the population. All this explains the high mortality rate in very young years.
By the way
Life can be prolonged biologically. But how is a person going to spend those additional 40 years? What will he do when the children, grandchildren, great-grandchildren have grown up? The point is not that there is a biological substrate, but that this life is active and meaningful, so that it has some kind of purpose. This was discussed at the round table "Live to 150. Why?" (2019-23-01).
Centenarians from the Guinness Book of Records
Woman Jeanne Louise Calment (France) - 122 years 164 days;
Male Shigetiino Izumi (Japan) - 120 years 237 days;
Bowhead whale - 200 years old
Galapagos tortoise - 175 years old;
Elephant Ling-Wong - 86 years old;
Cat Cream Poof (USA) - 38 years old;
Rabbit Flopsy (Australia) - 18 years 10 months 3 days.