The secret of eternal youth. What are the causes of human aging and death?

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We age for a reason, but as a result of a special biological program. But there is an African naked mole rat in the world, an animal that looks like a mouse and is incapable of aging. Scientists have figured out why humans age, but mole rats don'tThis article is the fourth in a small biological series about youth, aging, death, and genetic programs.

Death for Life
In case you are too lazy to read the previous three articles (1, 2 and 3) or in the constant turmoil of our lives you have forgotten what was about them, here is a "summary of the previous series".

I am of the opinion that the life of an individual, a single individual of a biological species, is a very valuable thing, but there are more important things. Namely, the species itself. That is, in fact, the complete set of genes (this is called a gene) that is contained in each individual of this species and, in fact, determines what it is. In our view, it is more correct to think of all living things simply as temporary receptacles for genes that they have inherited from their parents and will pass on to their children. For the first time, such an idea was probably formulated explicitly by Richard Dawkins in his famous book The Selfish Gene.

As a rule, the interests of the genome and its temporary carrier (a living being) coincide. But sometimes they don't. And then it immediately becomes clear who is the boss in the house: the genome, of course. If the genome of a species is threatened, or if the species simply needs to evolve, then the host can be safely sacrificed — the next generations of "new generations" will give birth.

As a result, I believe that the genomes of most (if not all) living things contain special harmful programs. From which nothing good happens to the creatures themselves, but which are necessary for the development of the species. First of all, death programs that ensure the change of generations and, accordingly, evolution. And sometimes they are arranged in a "fast" way, for example, in annual plants that die when killed by their own seeds after they ripen, and sometimes in a "slow" way. And the most disgusting program of slow suicide is the aging program. Which causes many species, including us, to "deteriorate" with age and eventually die.

 
The Wrong Mouse
The fact that we age for a reason, but as a result of the activity of a special biological program, is not an obvious thing and requires proof. I tried to build it "from the opposite" by showing you an example of an animal that turned off its aging program. Because he doesn't have to speed up his own evolution so much anymore – he's already good! It is, like you and me, a mammal, a fairly close relative of the common mouse – the African rodent naked mole rat! If a mouse lives for 2-3 years, manages to age completely during this time and dies of old age, then a mole rat lives more than 30 years and, if it sometimes shows any signs of aging, they are usually not fatal. Most biologists agree that the naked mole rat is an ageless animal (or, to put it more scientifically, an animal with negligible aging).

A couple of years ago, I wouldn't have had much to say on this subject. But in 2017, in one of the most prestigious scientific journals in the world, Physiological Reviews, we managed to publish a theoretical work explaining the phenomenon of non-aging of the naked mole rat.

It all started, as always, with mitochondria. These are small power plants that are in every cell and with the help of which we breathe. I hope that there will be a separate episode of our series about them. The study of mitochondria is the main specialty of Academician Vladimir Petrovich Skulachev. In fact, in his laboratory in the late 60s, it was found out how they work. For the last 20 years, the academician, in addition to mitochondria, has been interested in the problems of aging and, of course, has made titanic efforts to conduct an experiment with the mitochondria of the naked mole rat. I should note that mitochondria are very much associated with aging, but more on that in the next episode.

Studies of naked mole rat mitochondria have been successful. At the institute at the Berlin Zoo, experiments were conducted on mole rats, and Vladimir Skulachev's employee, the famous biologist Mikhail Vysokikh, who came specially from Moscow for this purpose, managed to obtain a sample of mole rat tissue and measure various parameters of mitochondria in this tissue. There was nothing particularly interesting about them, except for a slightly strange curve showing the rate of oxygen uptake by mitochondria (they also breathe) under certain conditions.

Returning to Moscow, Mikhail showed this crooked remark to the leader, to whom it also reminded something, but they could not remember what exactly. So the biologists racked their brains until they showed the graph to another colleague, the head of the Laboratory of Cell Bioenergetics, Boris Chernyak, who is known for never forgetting anything (well, at least if it has to do with mitochondria, respiration, and living cells). He looked at it and immediately said: exactly the same curve can be obtained by recording the respiration of the mitochondria of newborn rats!

And that's when Vladimir Petrovich had an idea. It captivated him so much that he packed up and went to Berlin to personally see the naked mole rat (the photo above is "The Academician and the Digger"). What did he find? That he (the digger) is naked. And you know who he looks like because of that?

Look, the photo above shows naked mole rats. And there are no diggers nearby. These are newborn rats. See how similar they are? In a few days, the baby rats will grow up, dress in fur and turn into normal rats. And the diggers don't. They will remain like newborns for the rest of their lives.

Further investigation revealed that mole rats had more than 40 signs of such "newbornness," or "babyness," compared to rats. Here are some of them:

Low weight compared to other species of the family.
Lack of hair (rodents always have it).
Absence of auricles.
Limited ability to maintain a constant body temperature (as in newborn mammals).
High cognitive abilities (curiosity).
Low sensitivity to pain.
The ability of neurons to regenerate and increase the lifespan of neurons.
No decrease in insulin-like growth factor 2 (IGF2) levels with age.
No age-related decline in superoxide dismutase 1 and 2 levels, as well as catalase.
As well as several dozen more external, physiological and biochemical signs.
That is, it turns out that the mole rat stopped the program of his individual development at the stage of a newborn rodent. A similar phenomenon has been described before for, for example, amphibians, and it is called neoteny.

For the sake of fairness, it should be said that Vladimir Skulachev was not the first to draw attention to the fact that the mole rat is a neotenic animal. Before him, this was noticed by Richard Alexander in 1991 and some other scientists. But they didn't associate this phenomenon with longevity at all (Alexander simply didn't know about the lifespan of these animals).

Stuck in childhood
Academician Skulachev formulated a very simple idea: if a mole rat stops at the baby stage, then his individual development program simply does not reach the point where it is time to start aging. Children don't get old! Thus, we get the most important proof: aging is part of the program of development and life of the body. Same as birth, growth, maturation. And if this whole program is stopped, so is aging!

That's what happened to the diggers. If this were to happen to the normal species, it would disappear very soon, because in the absence of aging, its evolution would be greatly slowed down. And the digger was saved by his eusociality. Life in "anthill mode" proved to be so much more resilient that he could afford to turn off aging as an evolutionary tool.

And it seems that in the evolution of the most interesting species of biological creatures for us, Homo sapiens, exactly the same story began that happened with the naked mole rat. Have you ever paid attention to the fact that people are most like... baby monkeys?

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