How evolution has built into us the limitation of life expectancy
Evolution is not interested in us
Sergey Sumlyonny, "Expert" – Country Reviews No. 4-2013
The European Institute for the Biology of Aging (ERIBA) in Groningen, the Netherlands, is one of the world's largest centers dedicated to the study of aging mechanisms. The head of ERIBA agreed to answer the questions of the "Expert". Professor Peter Lansdorp spoke about why some cells die and others live forever, how evolution has built in a limitation of life expectancy in us and how cooperation with the Skolkovo project is conducted.
– How did it happen that one of the world's centers for the study of aging appeared in Groningen?
– It's a long story. The University of Groningen decided several decades ago to actively work on the problems of aging, including healthy aging. It was a strategic decision – the university chose which types of research to make its business card. And it was a very right choice, which is now bearing fruit.
– What is your research?
– The research I am doing is devoted to the study of aging at the molecular level. The fact is that aging is a very complex, complex process. When I was still a very young scientist, I was actively interested in immunology and stem cells. I spent a lot of time isolating stem cells from the bone marrow, which give rise to various blood cells. At some point, it was discovered that the characteristics of stem cells isolated from the bone marrow change over time, during the development of the body – old stem cells are not identical to young ones.
– So stem cells also age?
– Yes, and it was a surprise for us. Because it was assumed that stem cells can regenerate and that they can reproduce without suffering from changes. And then it turned out that in the process of division, their abilities for further division change. The second surprise was that we found that after each cell division, its chromosomes become shorter. It turned out that inside the cell there is a kind of clock that ticks and limits the number of its divisions.
– Is this what is the basis for most studies of aging today?
– Let's just say: for many. This is an important aspect of aging, necessary for understanding the mechanisms of hematopoietic stem cells or for immune system research. We know, for example, that when people get old, their immune system often begins to malfunction. Today we believe that one of the reasons is the reduction in the length of chromosomes in the blood cells responsible for the immune system. In any case, these were very interesting studies.
– And you were invited to return from Canada, where you were engaged in them, to the Netherlands to continue working here?
– Yes, it was a chance that could not be refused. Although it was a pity to leave Vancouver, but look: we are opening a new center here, we are hiring staff, this is a very large active project. The official opening of our center will take place only in autumn. In this we are similar to Skoltech, where the construction of the building has not yet been completed.
– You work together with Skoltech. What exactly is this cooperation?
– A stem cell research center is being created at Skoltech, and we are cooperating with them in educational projects. Their students can come to us, we send our scientists to Moscow. We also help Skoltech in the arrangement of laboratories, facilitate the participation of students in international projects. Our interest lies in the selection of gifted students and their involvement in international projects. You know us scientists: international relations and the exchange of ideas are very important for us. If money suddenly appears for research, for the creation of international cooperation centers, it is always extremely interesting.
– How many students from Russia do you expect next year?
– The center is still under construction, but I believe that every year, starting in September, about 20 students studying aging will come to the centers cooperating with Skoltech. I think it's a great idea to create a university, not just by hiring a permanent staff of professors, but by involving other universities in project cooperation. The cooperation agreement itself was signed during Vladimir Putin's visit to the Netherlands. And the stem cell research center is one of the fifteen centers that are proposed to be created.
– If we go back from organizational problems to scientific ones: what was the biggest discovery in the field of aging research in recent years – and what could be the next breakthrough?
– It is now quite clear that if you reduce the body's calorie intake – this applies to both animals and humans – then you increase life expectancy. That is, there is a clear inverse relationship between the number of calories consumed and life expectancy. Active metabolism causes aging.
– So the diet is a good thing?
– In the laboratory – definitely. If you do not feed animals as abundantly as they would like, if you keep them on a diet, then they live longer and show better results in any tests, including intelligence tests. Of course, the question arises: how does it work? Why does reducing the amount of food increase life expectancy? We believe that the fact is that under the conditions of a diet, food begins to be processed more efficiently and as a result, DNA gets less damage during reproduction. That is why sport is useful – because the body learns to burn fuel more efficiently. But, of course, it would be extremely interesting to study this mechanism in detail.
– I will return to my question: what could be the next comparable discovery?
– A new breakthrough can happen in a variety of research areas. For example, the mechanisms of worm regeneration are being actively studied now. You can cut them in half – and they recover. Stem cells are responsible for this process, they somehow receive a signal that a part of the body is missing, and begin to divide and restore it. We see the same process in lizards. The question arises: why can animals do this, but people can't? Yes, we see that even in human stem cells there are "ticking clocks" that limit their lifespan. But these clocks are not present in the cells responsible for the formation of spermatozoa, for example. Apparently, in biology there is a difference between the cells responsible for the continuation of the life of a species and the cells responsible for the life of a particular organism. The problem is that for biology, for evolution, the life of an organism is not so important. Evolution doesn't care about a particular person or animal, it cares about molecules, about DNA, which must survive. But in order to prolong a person's life, we need to understand how these mechanisms work. In general, there are a lot of riddles that we have to solve, because only now we have the tools to solve many puzzles.
– What role does the environment play in aging and in DNA breakdowns?
– DNA breakdowns and the accumulation of these breakdowns is a natural process. Life itself leads to the fact that breakdowns accumulate in the DNA. The more active your metabolism is, the more damage accumulates in the reproducible DNA. Of course, serious damage is caused by radiation – both natural and arising from human activity. Certain chemical effects can severely damage DNA. The question is where exactly the breakdown occurs. Each time, the cell is forced to choose whether to die or continue to live damaged and possibly accumulate new errors. There are DNA repair mechanisms in cells, without which their life is impossible, but every time the question arises whether these restoration works are worth the effort. I repeat: from the point of view of evolution, the carrier of genetic material, DNA, should only pass it on, and he himself may well die.
– What is the most intriguing mystery for you?
– Look, enzymes work in chromosomes that maintain the integrity of the endings of chromosomes. These enzymes are responsible for ensuring that the ends of chromosomes do not become shorter. In the so-called primary germ cells, gonocytes, which are responsible for the production of sperm and eggs, these enzymes are always in abundance, and the chromosomes have a constant length, so these cells are practically immortal. But in somatic cells, that is, in all other adult cells of the body, the level of these enzymes is not high enough, and they cannot maintain the chromosomes in the right state, although they continue to partially protect them. I am extremely interested in how the amount of these enzymes is regulated. Because if we can manage them, it will open up fantastic prospects. I really want to know why this enzyme does not work with chromosomes in somatic cells, although it works fine in gonocytes.
– You can often hear that aging and death are a natural process that protects us from diseases. For example, that an increase in life expectancy leads to a sharp increase in cancer.
– Well, some people live a very long time. Of course, we can say that the reduction of the length of chromosomes is in some sense a protective mechanism against unlimited cell division, which, in turn, can be considered as a mechanism of protection against cancer. If you remove this brake, then yes, an easier way for the cells to turn into cancerous ones will be opened. The cells will be immortal at the cellular level, but the body can die from cancer. However, we are not inclined today to consider the link between cancer and age as a direct link. Everything is more complicated here.
– However, a long life does not mean a healthy and active life.
– Only if for some lucky ones. Of course, there is a risk that with age, cells accumulate errors that occurred during division. However, today we can look at the level of each cell, which errors have accumulated in it. It wasn't possible before. In general, now the issues of studying aging are of great economic importance. A large generation of baby boomers is starting to age. In the USA and Canada, up to half of GDP may begin to go to medical purposes. Therefore, today it is more important than ever for us to invest at least some of this money in the study of aging in order to understand what exactly we are dealing with. Perhaps if we delve into the subject, we will be able to develop individual diet strategies that help certain people cope with aging, increase the duration of productive life.
– Excuse me for a somewhat cynical question: how economically justified is an attempt to prolong a person's life, if every additional year of life means a sharp increase in medical costs?
– I am not an economist, the value of human life is much more important to me. Perhaps, for some of the economists, the optimal solution would be if people did not live at all. This is the question of which parameter is the key for you. I am convinced that humanity is driven by a thirst for knowledge. And the study of aging is one of the most fundamental medical research. I am sure that if, thanks to research, we get the opportunity to extend the active phase of life, it will be great. People will probably not live much longer, but the active phase of their life will be much longer. The biggest contribution to the increase in life expectancy was made by hygienic measures such as centralized water supply, as well as antibiotics. It was an instant and fantastic increase in life expectancy. However, until now, life expectancy is slowly increasing, and the duration of active life is also growing. If the trend continues, the average life expectancy is unlikely to exceed 100 years, although there will continue to be individuals who live to 110 or 120 years. As for the active period of life, I think it will last on average up to seventy-something years, although here everything will depend on the individual. But I would not pay too much attention to such forecasts – so far it all looks like fortune-telling.
Portal "Eternal youth" http://vechnayamolodost.ru17.06.2013