“You can’t delay aging just by taking a pill”: Russian scientist on the mechanisms of longevity

— Nikolai Sergeevich, tell us what science knows about the mechanisms of aging of the human body today?

What happens as cells age?

Any complex task can be divided into simpler ones.

There are signs of aging at the cellular and molecular level that can be fixed.

The first is the breakdown of the cell's DNA.

Such a cell must be destroyed by the body, otherwise it will become alien, there will be a danger of its cancerous degeneration.

The second sign is the shortening of telomeres (portions of the chromosome that decrease as the cell divides).

The following are epigenetic changes.

The fact is that although all the cells of the body have the same DNA, it is read differently, so we have different types of cells.

These settings can go astray, causing cells to lose their function and age quickly.

In addition, normally, homeostasis (self-regulation. -

) of proteins must be maintained in the cell, synchronous processes must go on: proteins must be expressed in time and degraded in time.

Usually it does, it's a very reliable system.

However, for example, severe or prolonged stress can upset it.

As a result, incorrectly stacked chains of amino acids, the so-called protein aggregates, accumulate in the cell.

And this is a sign of aging.

Another sign is a violation of the cell's susceptibility to nutrients.

Each cell has sensors that regulate its vital activity.

There is a program, the cell cycle, which consists of nutrition, growth and division.

If a cell is fed in a normal amount, but periods of feeding are punctuated by slight starvation, then the cell can grow.

If the cell is chronically lacking in nutrients, then it stops its growth.

And if, as in cases of overeating, the cells constantly receive a signal about the presence of food, their susceptibility to nutrients begins to decrease.

There is, for example, glucose resistance, diabetes.

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“So the cells need small dosed periods of starvation between the intake of nutrients?”

Yes, because cells have circadian rhythms.

During the day we eat, and at night it is worth abstaining from food so that the body has time to digest everything eaten, clean up the garbage.

This will help the body stay healthy.

Returning to the topic of molecular signs of aging, I would like to note one more - a disorder in the work of mitochondria.

These are cell organelles in which ATP (adenosine triphosphate) is synthesized - a substance that, when broken down, releases energy.

Thus, one of the functions of mitochondria is the supply of energy for the body.

Oxygen is needed to produce ATP.

When mitochondria malfunction, free radicals can be released, which leads to oxidative stress and has a detrimental effect on cells.

At the same time, normally, oxidative stress even helps the body, it signals problems in the cell.

This can be compared to how, by lighting torches on the wall, people transmitted a signal of danger.

However, if the fire turns into a fire, it must be extinguished.

With age, mitochondria begin to work less well, as “broken” organelles accumulate.

In general, the system for cleaning cells from non-functional elements, debris - autophagy - weakens with age.

This is a common problem, but mitochondria are especially dangerous in this regard, since their improper work leads to increased production of free radicals that damage DNA, lipids, and proteins.

You can improve the functioning of mitochondria with the help of sports training.

This way we can prepare mitochondria for the situation of hypoxia and reoxygenation.

This is exactly what happens to the body during a heart attack and stroke - when the mitochondria first stop receiving oxygen, and then the blood supply is restored abruptly.

This results in a surge of free radicals that damage cells.

And physical activity allows mitochondria to prepare for such a scenario, since during sports, jogging, a person usually experiences a slight hypoxia.

In this way, we can prepare the cell for a situation where it does not have enough oxygen due to blockage of blood vessels, for example.

I have listed the basic signs and causes of cell aging at the molecular level.

At the same time, you need to understand that in our body there are different types of cells and each has its own specific problems.

For example, somatic cells that make up most of the tissues - "mortal" have their own limit of divisions.

After its exhaustion, they should go into a senescent state and signal the body that they need to be replaced.

Senescent, old cells have a lot of problems, they accumulate damage.

• Chromosomes

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Normally, the immune system removes such a cell, and instead of it, stem cells create a new somatic cell.

This is how the self-renewal mechanism of the body works.

And somatic cells act as a kind of consumable components that need to be changed often.

But if the immune system does not have time to do it in time, as it happens in old age, senescent cells accumulate in the body, which leads to chronic inflammation, to the risk of oncology.

Another type of cells is stem cells, which are responsible for repairing damage and renewing cells.

These cells are immortal and also very resistant to various stress factors.

However, each stem cell is located in a so-called niche surrounded by somatic cells.

And if the latter gain breakdowns, begin to function incorrectly, then stem cells also begin to work incorrectly, their reserves are depleted and their quality decreases.

Normally, one somatic and one new stem cell should be formed from one stem cell.

And with aging, this mechanism can break down and only one cell will appear. 

In addition, intercellular interaction plays an important role in the mechanisms of aging.

The fact is that for the proper functioning of the whole organism, it is important that the cells do not interfere with each other's work.

There are different levels of coordination of this interaction, the highest is tied to brain signals.

They activate the production of certain hormones that regulate the functioning of tissues and organs.

Therefore, the emotional state of a person, a positive attitude really play an important role in maintaining health and longevity.

The role of microbiota is also great: beneficial microflora enhances immunity, protects against pathogenic bacteria that harm the intestines.

Violation of tight contacts between intestinal cells leads to uncontrolled entry of substances from the intestine into the blood, which can lead to allergies.

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- It is known that the p53 protein protects cells from mutations, triggers the destruction of cells with damaged parts of the genome.

At the same time, this protein is involved in the mechanisms of aging.

It turns out that if it is “turned off”, aging can slow down, but this will not do much, since oncological tumors will quickly begin to appear in the body.

Is it possible that this dual mechanism, which even has the scientific name "antagonistic pleiotropy", makes it impossible to find remedies for aging?

Can a way out of this impasse be found?

— The question is to the point.

Indeed, when scientists in their research press, figuratively speaking, on various mechanisms of aging, trying to stop the process, they invariably begin to encounter the problem of cancer in their work.

And it is already clear that if the body's aging mechanisms are completely turned off, then everything will go according to a very negative scenario: oncology will inevitably begin.

However, there is an idea that you can try to turn off these mechanisms only partially: not enough to provoke cancer, but enough to still prolong life.

It is believed that adaptation to some stress factor or partial shutdown of aging-controlling regulators can delay aging.

True, in this case, the question will inevitably arise: what will you have to pay for this?

For example, if you partially turn off the expression of the p53 protein, then old, so-called senescent cells will begin to accumulate in the body.

The fact is that this protein is one of the regulators that reacts to breakdowns in DNA and causes cells to go into a senescent state, after which they are destroyed.

If the intensity of its work decreases, then the cell will be able to live a little longer, this will allow us to extend the potential of using the cells of our body.

But then not only will the risk of cells degenerate into cancer cells increase, but additional energy costs for the body will also arise, since destroying a very old cell,

However, there is also good news.

Nobel laureate Shinya Yamanaka discovered that almost any cell can be turned into a stem cell by activating four specific genes.

These genes are called Yanamaki factors.

• Nobel laureate Shinya Yamanaka

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However, for a long time it was not clear how this knowledge could be applied in practice.

After all, if a laboratory mouse activates these genes in all cells, then it will simply return to the state of the embryo, which consists of stem cells alone.

Then the scientists realized that it was possible to activate the expression of these genes in a very dosed, temporary way.

And as a result, it was really possible to achieve a noticeable rejuvenation of experimental animals.

This is a positive example, which indicates that aging can be slowed down a little.

However, the question still remains at what cost.

This science has yet to find out. 

One thing is for sure: aging is a complex process.

And you can’t delay it just by taking some pill.

Because even if you stop the aging of some body systems, others will still fail.

Therefore, the main thing that we can do for our body is to comprehensively monitor its condition and lead a healthy lifestyle: observe sleep, diet, exercise, control stress, etc. If each of us starts at least with this, already it will be possible to speak about serious chances for longevity.

As our teacher, President of the Gerontological Society at the Russian Academy of Sciences, Vladimir Nikolayevich Anisimov, noted, demographic studies show that family people live longer than single people.

And also that the profession also plays a significant role: for example, the maximum average life expectancy is noted among representatives of those professions that combine mental and physical activity.

In general, longevity depends on a whole range of factors.

- Probably the most famous theory of aging and death is connected with telomeres.

According to this approach, as the cell's DNA replicates, its special sections - telomeres - become shorter and shorter, and the cells lose their ability to divide.

Everyone is familiar with the experiment of Elizabeth Parrish, who made changes in her body to express telomerase, an enzyme that can lengthen telomeres.

What are the pitfalls of this theory?

— Shortening of telomeres is the first scientifically proven mechanism of aging of somatic cells.

However, now this mechanism is no longer considered the only explanation for aging, because in the body there are, for example, neurons that do not divide, there are stem cells in which telomerase is already always active.

And even if we manage to make them immortal with the help of artificial expression of telomerase in somatic cells, this will not be enough.

You will not solve other problems with this: with mitochondria, with autophagy of proteins, etc. This will be an extension of the life of non-viable cells - as they say, a dead poultice.

— You have listed a number of signs and mechanisms of aging.

Is there any common cause of aging, which caused all these processes?

- There are a number of studies, and quite successful ones, that give hope that aging can be at least slightly delayed.

These are experiments with Yamanaka factors, and, for example, blood transfusion from young individuals to old ones - this also works, and now scientists are looking for which blood protein is responsible for this effect in order to introduce not blood, but simply a working component.

But there is still no general, fundamental theory of aging that would describe the initial cause of aging and death.

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- Does science know why different animal species have such a wide difference in life expectancy?

“There is a correlation between animal size and lifespan.

Large animals develop for a long time, and also give a few offspring - one or two cubs.

Such species have their own survival strategy: in their case, nature is invested in quality, not quantity.

And there are, for example, small rodents that give very numerous offspring, because in their case the emphasis is on quantity, not quality.

Simply because, due to their small size, they are very quickly eaten by predators.

So the lifespan of species is largely tied to the strategy of their species survival.

In addition, there is a theory of the so-called retrotransposons - these are mobile elements of the genome that can change their position and create their own copies.

It was believed that they do not perform useful functions and simply litter DNA, but now there is evidence in favor of the regulatory function of the genome that does not code for proteins.

Retrotransposons are remnants of viruses embedded in DNA.

Their activity is normally suppressed by the immune system, but with age, the latter begins to weaken.

And as a result, transposons get the opportunity to make breakages in DNA, integrating into the genes necessary for the cell and making it impossible to synthesize useful proteins, which can ultimately lead to the death of the organism.

It is believed that the activity and representation of transposons differ in different animal species.

And this may partly determine the average life expectancy of each of the species.

There is a hypothesis that if we learn to take control of transposons, we will be able to increase the maximum possible duration of human life, which is 120 years.

— Tell us, what research is being conducted at the Center for Research on Molecular Mechanisms of Aging and Age-Related Diseases at Moscow Institute of Physics and Technology?

— Now we are engaged in the application of biophysical approaches to cellular systems.

In the 2010s, light-sensitive proteins were discovered in lake bacteria that allow you to regulate the ionic composition of the cell.

It is known that the activation of autophagy (self-cleaning of cells) can slow down aging.

The essence of our work is to introduce into the cell we need DNA that will produce such a light-sensitive protein.

Under the action of light, it will change the ionic composition of cells, which will become a signal for the activation of autophagy in them.

This will be a selective, specific effect, unlike chemicals or changing the DNA of the cell itself with the help of genetic engineering, controlling gene expression, which can lead to many side effects.

The idea is that perhaps