Shock, awe and suicide
How the genetic program drives people to the grave
Maxim Skulachev, Forbes, 25.12.2017
The biggest threat to humans is biological aging, that is, a slow weakening of the body's functions, inexorably increasing the likelihood of death. There is every reason to consider aging the result of the activity of the genetic program
In the previous issue of my heartbreaking, I hope, series about love, death and the tyranny of the genome, I tried to draw the attention of dear readers that for all the greatness of Man and Humanity, we are nothing more than biological machines. Our parents uploaded a program into us – our genome, our life – in fact, the execution of this program. What is it? That we need to develop as an embryo, be born, grow up and, if the copy of the genome loaded into us was successful, pass this copy to our children. But the program does not end there. Because there is also a final stage in it – it is necessary to make room in the cave for the next generation, that is, to die.
If everyone agrees with the first stages of the program, then they don't really like to think about the last part. And not only ordinary people, but also professional scientists. Probably, this is because most biologists are terribly fond of life, in all its manifestations. Actually, that's why we became biologists. It is always much more interesting for us to study where something comes from than where it then goes, how it is destroyed.
In this regard, the history of studying proteins is very instructive (their other name is proteins, this is exactly what is encoded in our genes, the most important part of any living system). The process of protein synthesis in cells began to be closely studied in the 50s and pretty quickly figured out how it happens. In all textbooks since the 70s, the corresponding mechanism has been described, which works perfectly and constantly produces all the proteins we need. Question: and then where do they go? They don't live forever. The cell would simply burst from constantly synthesized proteins. But for some reason, biologists somehow "didn't bother with this question." And they overlooked a huge and complex system of protein degradation. It occupies more than 10% of all our genes, and which determines exactly how long a particular protein should live, depending on its function. Some of them live only a few hours, others remain in the cage for years. This was thought about only in the late 80s, and the Nobel Prize was awarded for the discovery of a system for the targeted destruction of proteins.
Mess up the program
And did the same story happen with the programmed death of the organism? Maybe biologists just didn't want to think about it? And in vain! Because if our passing away is also programmed, as well as our birth, then it gives us a huge chance to live longer and better. The fact is that with all its achievements, biology is a very young science. We still know very roughly how wildlife works and are not yet able to create any new biological systems that we might need to prolong our lives. But if our death is due to the action of the program, then nothing needs to be built. It is necessary on the contrary – to break. To break the last stage of the work of this program, which is fatal for us. Moreover, you can not even completely break it (it can be dangerous, and it is certainly not yet possible), it's enough to just somehow prevent it, to put sticks in the wheels of this mechanism. With all the youth of biology and biological engineering, we are already able to break at least. And then the mechanism will work worse, which means we will live longer.
And yet, is such a mechanism of programmed suicide embedded in the human body? Maybe scientists overlooked it, simply because it is not there, and not because they did not want to look for it? With all due respect to my colleagues, I don't think so. And then I will try to prove, as far as it is possible in such a non-strict science as biology, that yes, we have this program. And it is quite possible to start fighting with it. But to find out what it's about, you'll have to finish reading my bioengineering series to the end.
So, what kind of program can we talk about? There are several options and, perhaps, let's start with the simplest one. There is such an unpleasant and deadly thing – sepsis. It usually occurs when the blood is infected with bacteria. That is, if enough microbes get into the blood, it is extremely dangerous. A person's temperature jumps, so–called systemic inflammation develops, the process most likely ends in the saddest way - the patient dies. By the way, it also works on other animals – mice, rats, any animals.
Why is this happening? It would seem that everything is clear. Bacteria began to multiply in the blood, the immune system cannot cope with them and they "eat" the human body from the inside. And what, the question is, can we not be satisfied with such a direct and understandable explanation?
Lethal immunity
But here's the problem. At some point, it turned out that the same effect can be achieved (not on a person, of course, but in an experiment on mice) if dead (!) bacteria are injected into the blood. They can neither reproduce nor "eat" anything. And the symptoms are the same – fever, inflammation, death from multiple organ failure. Yeah! – the scientists who were interested thought, – it means that bacteria are scary not by themselves, but because they have some very poisonous substance for humans (or mice)! It causes septic shock. They began to understand and really isolated such a substance from bacteria, or rather from their shells. If it is cleaned and injected into the blood of an animal, then the unfortunate creature also dies from septic shock. What is this substance? What is this terrible bacterial poison, which was immediately called endotoxin – that is, the internal poison of bacteria?
It turned out that this is a simple polymer consisting of residues of sugars and lipids – lipopolysaccharide (English abbreviation – LPS). In its chemical essence, the substance is completely harmless, it is just a building material that makes up the cell wall of bacteria. How can LPS be poisonous to mammals? They began to understand further and found out that mammals have special proteins – LPS receptors, which constantly monitor the blood for the appearance of this substance. And if they detect a certain amount of LPS, they trigger a terrible cascade of biological reactions, which we call septic shock. If you make a mutant mouse that has a broken gene for this receptor, then for such a GMO mouse, the most lethal dose of LPS will be absolutely harmless.
Her body simply will not notice the "endotoxin" and will continue to live safely on. You can break this suicidal program in another way. The terrible inflammatory cascade in response to LPS is part of the work of the body's immune system. We know of substances, such as corticosteroids, like dexamethasone, which suppress the immune system well. Accordingly, if you inject LPS into a mouse together with dexamethosone, then the mouse LPS receptors, of course, will detect and transmit a signal "up" to the immune system. But it won't lead to anything terrible, because it will be disabled. And the mouse will survive.
In general, if we omit all these terrible details, the conclusion is the following: death from septic shock occurs as a result of the work of a special suicide program. The body kills itself if it finds a sufficiently large number of pathogenic bacteria inside itself. By now, a lot is known about this program: how it is launched, which parts of the immune system it activates, how and when the process enters an irreversible phase.
Sacrifice for the sake of others
A reasonable, but very unloved by biologists question arises: why? Why did mammals have this deadly system? An individual organism definitely does not need it. Without the septic shock system, he would have at least some chance of "crushing" the infection and surviving. But nature does not give this chance, finishing off the unfortunate, and even if the bacteria that infected him are already dead. Why?
Of course, it is impossible to give an exact answer to this question, because the ways of evolution are inscrutable ... well, or the one who directs it there. But, actually, this whole story looks very reasonable and practical. However, not from the point of view of an individual, as the crown of nature, but from the point of view of his Majesty the Genome of Homo sapiens.
In primitive times, which by evolutionary standards were only a few seconds ago, an infected individual was extremely dangerous to the rest of his species. Because he could transmit an infection to them, infect the entire population and... what if this is the last population of this species? Then he (the species) will disappear, and with him his genome. Worse, even if the disease is not fatal, it is still very dangerous. The fact is that in the initial stages the body fights infection by synthesizing very toxic substances – free radicals (I will tell you about them in one of the following columns).
These substances have mutagenic activity. And if the infection was severe, then a lot of radicals are synthesized, and this is a direct threat to the appearance of too many mutations in the genome. But how will the diseased individual survive and, with all its mutations, give birth to children with don't-understand-what genomes? Dangerous! From the point of view of the species and, most importantly, its genome, it is much preferable if the infected individual does not run anywhere, lies down quietly under the nearest bush and ... dies without infecting relatives and not participating in reproduction anymore. This is the task of the septic shock program.
That's just in the modern world, a person does not need such a program at all. Because we have antiseptics and antibiotics.
And about old age
Well, the valiant reader who has lasted up to these lines will say, let's say sepsis is a program. But, fortunately, septic shock is far from the main cause of death of people. There are others, much more common. And what do they have to do with programs, genomes and the rise of biological machines?
We answer: do you know what is the most common cause of death? Threatening 100% of people over, say, 20 years old? This is biological aging! That is, a slow and consistent weakening of the body's functions with age, inexorably increasing the likelihood of death. So, the author refers to those biologists who believe that we have every reason to consider aging the result of such a genetic program. And in the next issue of our bio-series, I will try to present you with evidence of this bold hypothesis, and naked evolutionary champions will help me in this.
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