Promising technologies in the fight against aging
In the "Point of View" format, Post-Science introduces readers to the opinions of our experts on current problems of society, education and science. In the new issue, we asked our authors to express their point of view about when life extension developments can be created and where they can be applied.
Evgeny Berezikov
PhD in molecular biology, Professor, Hubrecht Institute, Group Leader of the Laboratory of Stem Cell Regulation and Mechanisms of Regeneration at ERIBA
It was considered unfashionable to work on aging for quite a long time, because there was an idea that a lot of different factors were involved in aging and that aging was a natural process in which nothing could be studied.
A breakthrough in understanding aging occurred when the C.elegans model showed for the first time that there was a genetic component when certain genes were knocked out and worms (C.elegans) began to live longer. Then the next phase in the study of the biology of aging started, when they began to study more seriously different molecular pathways and how exactly this can be regulated.
Now we know quite a lot about regulation at the level of metabolism, energy, and so on. One of the interesting areas is aging, which is associated with the aging of stem cells. Aging is a very complex process, and stem cells are one of such factors of the process. According to the theory of stem cell aging, the number of such cells does not decrease with age, but their activity decreases. Due to a decrease in this activity, tissue aging occurs. The practical question is whether these old stem cells can be reactivated in some way so that they start working again as young ones. There are a number of experiments that show that this is really possible.
One of the principal experiments is an experiment with parabiosis in mice, when during the experiment scientists connected the circulatory systems of an old and a young mouse and then watched how the muscles regenerate in an old mouse. And it turned out that in such an experiment, muscle rejuvenation occurs in an old mouse. This suggests that there are some circulating factors in the blood that affect the activity of the aging process. Such experiments justify the need to study aging. In principle, in the future, progress will be made in identifying some regulatory pathways, and then in the development of drugs that will allow the rejuvenation of stem cells.
As far as I know, at the moment there are no commercial products in this area yet, but at the same time, various stem cell therapies are very popular "among the people". The only problem is that all of them have nothing to do with science yet. Basically, this is done by various charlatans, whose actions usually end badly. Although the idea of using stem cells for medical purposes is clear and relevant, there is still too much research to be done before commercial products are created.
Fazli AtaullakhanovDoctor of Biological Sciences, Professor of Lomonosov Moscow State University, Director of the Center for Theoretical Problems of Physico-Chemical Pharmacology of the Russian Academy of Sciences, Head of the Laboratory of Physical Biochemistry of the Hematology Research Center of the Russian Academy of Medical Sciences, Head of the Laboratory of Biophysics at the Children's Center of Hematology, Oncology and Immunology named after Dm.
Rogachev
The most important thing that has been happening over the past 100 years is the prolongation of life by combating the causes that shorten life abnormally. Such causes include, first of all, infectious diseases, injuries, oncological diseases, in which very great successes have been achieved over the past 20 years.
But if we take the natural life of a person and our understanding of how to prolong it, then we have no great achievements in this area. We want to make sure that people live up to 100 and remain 40-year-olds, 30-year-olds, that is, remain in the prime of life. But such a goal contains a biological problem. Nature has arranged us in such a way that we must be able to develop up to some point, we must maintain plasticity, we must grow bones, increase the skull. These changes cannot happen indefinitely, maturation must occur at some point. When a person becomes an adult, mature, he largely loses plasticity. And if we don't really care about physical plasticity, then mental plasticity is extremely important. Starting from the age of 20-25, we begin to lose the ability to learn, which means the ability to adapt to new conditions.
As a result, the question arises, at what age should we stop: at 40-50 years old, when we have already lost the ability to change plastically, or at 15-20 years old, when we are still able to study very well, but still almost do not know how to do anything?
There are many scientific groups that are trying to understand the mechanisms of why a person loses certain abilities with age. But most of all we know about these processes in the field of immunology. The immune system is a system that is practically lost over the years, since, apparently, the reserves of stem cells are being exhausted. But I cannot say that there are directly established facts that changes in the immune system are the mechanism of aging. We know dozens of causes of aging, including the exhaustion of stem cells – precursors of cells of other tissues, but we can't say about any of them that it is definitely the leading one. The fight against tumors has been very successful in recent decades. It turned out that in fact the variety of tumors is fantastic. Every year we learn more and more that leukemia is not one disease, but several hundred very different blood diseases. And the main progress of today's oncology is that we have begun to understand that different leukemias need to be treated differently. And as a result of this understanding, today the probability of curing this disease can be about 90%. We continue to use medicines that were invented relatively long ago, but now we are doing it more effectively: we know the diagnosis more accurately and are able to treat more accurately. The sooner we know the nature of the breakdown that occurred in our native cells, the more likely we will learn to live more efficiently.
The answer to the question posed in the title, in my opinion, looks like this: the greatest success in the fight against aging is provided by developments that eliminate the causes of interruption of the natural aging process. Firstly, we can try to greatly reduce the number of various accidents (automobile accidents are probably leading) and other man-made disasters, and this will be a great success in prolonging life. Secondly, we can defeat many infectious diseases that are rampant mainly in underdeveloped countries, and this will also be a great success in prolonging life. Thirdly, we can greatly reduce mortality from cancer, which will also make a great contribution to prolonging life. All these successes will not affect the natural aging process. In highly developed countries, such as Japan, Western European countries, life expectancy reaches 80 years or more. Many began to live up to 100. One might think that this is the approximate natural life expectancy of a person. Are there any ways today to move this border much? I don't know anyone like that. And is it necessary to shift it? The question is controversial.
Konstantin Agladze
Candidate of Physical and Mathematical Sciences, Professor at MIPT
One direction is the extension of a healthy life and getting rid of the so–called diseases of old age. It's no secret that, in addition to the general senile withering of the body, there is a whole bouquet that is characteristic of older people: diabetes, high blood pressure, various kinds of cardiac arrhythmias. And there are a lot of opportunities in these areas. In fact, many diseases of retirement age are not solved at all by medication and not with the help of medical technologies, but simply by preventing a healthy lifestyle. In addition, there are now very serious tools for reprogramming the cell, which make it possible to restore individual organs and all body systems, in particular the liver or kidneys.
However, these technologies are not used in clinics, and all kinds of procedures for using stem cells are not currently allowed by the Food and Drug Administration of the United States, which is a very important criterion. As for medical tests, recently experiments on retinal implantation were done in Japan, and a positive result was officially given. But here we must understand that relatively simple things were used in this experiment: only a layer of one cell thick was planted there, which is globally simpler than creating a three-dimensional, highly structured organ. But if we take into account that research is very intensive in many countries now, for example, at the Research Institute (CIRA) in Kyoto, headed by Professor Yamanaka, at Johns Hopkins University (USA), UCLA (USA) and others, then I think that kidney and liver tissue transplantation will soon be possible. Highly structured organs, such as the heart, will, of course, be made later. Most likely, in the near future we will be able to update a person "in parts", but this will not remove the fundamental problem of cell death as a result of the inherent mechanism of death.
And here we come to the second direction. Recently, there have been periodic reports that a gene or group of genes responsible for longevity has been found. However, later it turns out that this is not the case. Attempts to find and eliminate the genetic predestination of death is an unsuccessful task so far. To the physiological natural threshold of a little over a hundred years, which at the beginning of the XX century was designated by I.I. Mechnikov ("Studies of Optimism", Paris, February 7, 1907), I think humanity will approach quickly enough. But what will happen next is unclear. Separately, we will be able to replace organs, but in order to preserve consciousness and nervous tissue, in order to leave the personality, we have not yet come up with mechanisms.
Philip Haitovich
PhD in Biology, Head of the Comparative Biology Group at the Institute of Computational Biology in Shanghai, Professor at the Skolkovo Institute of Science and Technology (SkolTech)
The most promising works are those that study the difference in life expectancy between closely related species. As part of these studies, scientists are trying to answer the question: why do people get cancer or heart disease and die after 60-70 years, monkeys after 20, and mice after 1 year? Why do mice live for a maximum of 3 years, while bats live for more than 40 years? If we were monkeys, we would all study humans to understand why they live so long.
It is important that the difference in maximum life expectancy evolves very quickly: over the last 30 million years of primate evolution, the maximum life expectancy has tripled. So, if we allow our species, man, to continue this evolutionary development, then in another 30 million years, the maximum human life expectancy will increase three times more – up to 300 years! But why wait 30 million years? If we unravel the evolutionary mechanism controlling this process, we will be able to live up to 300 years or more tomorrow.
Since the 50s of the XX century, it was considered proven that the mechanism of aging is oxidation. In each cell, mitochondria produce free radicals that oxidize and destroy our DNA, thereby causing aging. But, as it turned out 60 years later, this hypothesis was untenable.
Experiments were conducted on mice to block this oxidation process, and it turned out that this mechanism does not work. Nevertheless, oxidation is really going on. Experiments were done, increasing the oxidation level of mice by 500 times. It would seem that mice should die after such a dose, but, to the surprise of scientists, it did not affect the aging of mice in any way.
That is, it became obvious that oxidation exists, but it is not the main process. If we remove the rest of the processes, then in the end, maybe in a million years, oxidation will kill us. But this is a very slow process, it has little effect on aging, at least in mice. Nevertheless, even now researchers are trying to figure out how to reduce the oxidation of our body, although it is unclear whether this will have an effect or not.
There are researchers who believe that the hormonal composition of the body changes with age, so we can deceive our body by introducing hormones corresponding to a young age into it. They think that then our body will recover. This idea has a basis: already about a hundred years ago it was shown that if you connect the circulatory systems of two mice – an old and a young one, then the old mouse will rejuvenate.
This work was forgotten, but about 10 years ago this experiment was repeated at Stanford University, and it turned out that, indeed, judging by the molecular markers of aging, the old mouse rejuvenates. If you take the plasma of a young person and pour it into the plasma of an older person, then, most likely, the second person will really rejuvenate. I do not know if this is used in practice, but such work is being carried out in America.
However, what is the active component in this process is still not known, so experiments use the same technology as a thousand years ago – plasma transfusion. Plasma transfusion does not require any permission, since, in fact, plasma or blood transfusion is a traditional medical practice. But if you isolate the molecule that is responsible for this process, then in order to use it, you will need to get permission. That is, it will need to be tested, do a lot of different experiments. And then such a process will no longer be a blood transfusion, but it can be taken as a pill, injected into your blood and rejuvenated. But so far, no one knows the essence of this mechanism.
Portal "Eternal youth" http://vechnayamolodost.ru02.12.2014