Turning age: details

The midlife crisis is in your genes

Alexey Aleksenko, "Snob"

Usually human life goes like this: you live for yourself, you live, and suddenly once! – divorced, married, bought a motorcycle. Midlife crisis, – knowledgeable people say. This, of course, does not explain anything, but there is nothing to explain here: a person just suddenly realized that life was heading towards the end, and he did not have time to do anything in his life. Well, is it okay? At least a motorcycle and this brunette. So, stop working hard for the future, we will live in the present.

To think such a banal thought once, you don't even need to be a reasonable being. At some point, it is useful for any biological object to stop working for the future (since its prospects have come to an end) and give all its strength to the last breakthrough. Therefore, one may suspect that evolution has forged a tool for making such a decision: a kind of genetic switch that one day clicks and starts a countdown, changing the entire survival strategy. No more investments, we spend what we have.

Does a person have such a mechanism or not? This is a terribly important question of the science of gerontology, and there are two possible answers to it.

The first option: there is no mechanism, but there is just a gradual deterioration of everything in the world over time. The organism is born, then gradually deteriorates and dies. In order not to die longer, it is necessary to take care of it and pass the service in a timely manner.

The second option: there is a mechanism. There is a genetic program in a person that triggers old age at a certain moment. Let's imagine that for the time being our body somehow resists the accumulation of small defects, and then, after consulting the calendar, says: "That's it, it's more expensive to fix such junk. Now let him live as long as he can, and fuck it." This is the start of the aging process, which is fundamentally different from the simple accumulation of breakdowns: here, as in the life of a car owner, the moment of deciding that you should no longer spend money on repairs is important.

The work of scientists from the University of Miami, which will be discussed, speaks in favor of the second answer.

Legends of Easter Island

The researchers dealt with human nervous and muscular tissue: they isolated RNA from it (what is read from genes when they work) and looked at which of them could be associated with aging processes.

Here a small digression is necessary – like half a century ago, and this will be the most difficult part of our article that you can skip. In the late 1960s, an expedition went to the distant Easter Island, the participants of which intended to discover new natural biologically active substances. One of these substances, isolated from streptomyces bacteria, was named "rapamycin" – in honor of the native name of the island of Rapanui.

Rapamycin had an antifungal effect, since it stopped the division of fungus cells. This would not have been a big sensation if it hadn't turned out later that this rapamycin is capable of doing many other things. For example, in a very similar way to block the division of human T-lymphocytes, thereby stopping the immune response. This was already something: the substance could be used as an immunosuppressor after organ transplantation. And then it went on the rise: rapamycin, it seems, influenced both, so that cell biologists of various directions became interested in it.

It turned out that rapamycin acts like this: it suppresses the activity of a certain protein, which is called the mechanical target of rapamycin, or mTOR. The protein turned out to be a "kinase" – the so-called proteins that are able to attach phosphate to other proteins and thus regulate their activity. Different kinases in cells are responsible for a variety of regulatory chains, and often one kinase phosphorylates another, that one another, and so on, and at the output we have the body's response to this or that time challenge. So, the mTOR kinase stands out vividly in this crowd: if its activity in cells is lowered in some way, different organisms - for example, worms and fruit flies – increase life expectancy. And in mice, life can be extended directly with rapamycin.

That we are attached to this rapamycin and mTOR kinase? It's very simple: if some substances affect the cellular signaling pathways in which mTOR is involved, they may be related to the mechanisms of aging. There are other substances noticed that can affect the life expectancy of some worms or flies. If we add them to human cells and look at the result, this result can tell us what exactly in the cells has to do with aging. For example, if a certain gene begins to work stronger or weaker in response to these substances, this is a clear hint that it may be somehow involved in this fascinating story designed to explain the mystery of the human limb.

Now the most difficult part is over, then everything will be clearer.

Turning point

So, our researchers – using the most modern methods of bioinformatics – followed the fate of all the RNAs that are synthesized in cells. Among this wealth, a group stood apart, including about 800 different molecules – as molecular biologists call them, "transcripts". Their number depended on the age of the fabric – some became smaller, others, on the contrary, more. All this formed, as the authors put it, into a "linear age signature". However, the above behavior did not last forever: in the sixth decade, the "signature" failed.

Further: the "signature" of transcripts responded to the very substances discussed in the previous section (those that affect the lifespan of simple model organisms and, in particular, affect the activity of mTOR). Kinase inhibitors acted in the same direction as the "age signature", and activators – in the opposite direction. This leads to an interesting conclusion: the activity of a whole bunch of human genes is regulated "in the direction of longevity" – the cell is actively engaged in living longer.

Yes, but the trouble is: this pattern can be traced only to the sixth decade. And then – everything. The cell (in this case, the myocyte) seems to lose all interest in delaying the coming old age. What new hobby is replacing a healthy lifestyle? A yellow Porsche? This is still unknown to science.

However, she does not know much else in this story – in fact, almost everything. What are these 800 transcripts, what are they doing? A person, as you know, has a couple of tens of thousands of genes, but by "genes" here we mean pieces of the genome encoding proteins. Meanwhile, there are a huge number of different pieces in the genome, from which RNA is also read, but it does not encode anything, and what it does is not really clear yet. Approximately half of the transcripts involved in the "age signature" belong to this mysterious group of "long non-coding RNAs".

Be that as it may, a completely meaningful hypothesis emerges from all these facts. The cells have a mechanism that protects them from age-related changes. However, it does not work all his life: for some reason, when approaching the 60th anniversary, the mechanism turns off. The linear trend fails. "Molecular pathways associated with longevity in humans are susceptible to shutdown in the middle of life" – this is how the title of the article is roughly translated into Russian, and it was this idea that the researchers wanted to convey to us.

And what should I do now?

Now the question is: how do we live with this knowledge now? That is, not personally for you and me – we can only twist – but for gerontologists. There are two ways, the choice between which depends on why suddenly, in our sixth decade, such a wonderful and useful mechanism of a long life turns off.

Perhaps simply because it is no longer effective. Even the most dear to your heart grandfather's "Lada" can not be repaired indefinitely – sooner or later it will just be money thrown away, and it's better to get yourself some other hobby.

But, perhaps, everything is different, and disabling the mechanism of longevity is a gadget that has arisen on the crooked paths of evolution, which allows you not to waste resources on prolonging old age, but to use them finally for something more useful (from the point of view of evolution). This option does not suit us: from our point of view, there can be nothing more useful than continuing our sinful life, in principle, even if our heirs have a different opinion on this matter. In this case, you can try this: somehow influence the said mechanism so that it does not turn off for a longer time. A set of transcripts, characterized by researchers from Miami, is already something to start with, and the set of drugs to which they react is also a good start.

In conclusion, it remains for us to wish all readers long years of active life, and for scientists to unravel this whole fascinating story one day. It must be terribly exciting. If you reveal such a secret, it's not a pity to die.

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