Aging, cancer, life expectancy – and again a naked digger
Let's meet old age
On the 20th of April, an international conference "Genetics of aging and life expectancy" was held in Moscow. I catch myself thinking that ten years ago I might not have been interested in this… Now age is already making itself felt – I attended the conference. I listened to the speeches in the hall, and during the break I took two gerontologists to a secluded corner (their reports were to take place later). For forty minutes we talked about the current state and prospects of the fight against aging. It turned out a decent amount of interviews. My interlocutors are Vera Gorbunova and Andrey Seluyanov from the University of Rochester (USA), where they directly study the processes of aging and cancer development on human and rodent tissues. Their laboratory stands out because it is closely engaged in a naked digger (an animal, strange in many ways), which interested scientists, first of all, by the fact that it lives up to 30 years. For a rodent the size of a mouse, this is a phenomenal indicator.
Reference:
Vera Gorbunova (PhD, Associate Professor) heads a biological laboratory at the Department of Biology of the University of Rochester (USA), where age-related changes in the repair systems of double-stranded DNA breaks on human and transgenic mice cell material are investigated. The laboratory is also engaged in the study of DNA repair in cancer cells and the analysis of anticancer mechanisms in short- and long-lived rodents.
In 2010 Vera Gorbunova and Andrey Seluyanov (PhD, Assistant Professor) became laureates of the Cozzarelli Prize, an award presented by PNAS magazine for articles distinguished by "outstanding scientific quality and originality".
In their work, the authors showed that the cells of the naked digger have an unusual mechanism of regulation of the p16 gene, which prevents the rapid growth of the cell population. The actual absence of cancer in rodents of this species may be directly related to the open mechanism.
About the choice of the object of researchV.G. Our approach differs from what most specialists in this field do.
Scientists are trying to focus on mutants, for example, they study mice that live shorter than usual and have one gene changed. Or on mutant mice that live 10-20 percent longer. We thought, why not look at rodents that live 10 times longer, and understand what works differently for them. It is unlikely to be a single gene. We decided to study long-lived animals, but which at the same time have relatives with a much shorter life cycle, which allows them to compare with each other. This is what is called an unbiased approach, an unbiased approach. We are not studying a separate process, but choosing an organism and studying everything in it that may be related to aging.
A.S. I think there is a fundamental difference here, because most laboratories focus on one process. For example, if I am interested in DNA repair, I will look for something related to DNA repair. This may be important, but in my opinion it is fundamental to investigate what processes are selected by evolution and allow you to live for a long time. Instead of dwelling on some one process, about which for some reason we begin to think that it is important, we rather ask the question of how evolution went, which processes allowed themselves to be selected so that the animal lived longer. In this sense, the result is completely unpredictable. And sometimes we go into other topics that we haven't dealt with before, but that's just the beauty of science.
V.G. Before the naked digger was investigated by several laboratories, which mainly dealt with environmental aspects, behavior issues, but from the point of view of gerontology, only in recent years there has been a surge of interest. In 2011, several laboratories literally simultaneously completed sequencing of his genome. This information was not enough for us. We can't say that we understood everything right away, but this is a tool with which it will be much easier for us to move.
I will note the performance of Judith Campisi. Most of the speakers stuck to the chair and actually voiced their slides. Judy didn't really need slides, she spoke with inspiration, understandable language and addressing the audience directly. She suggests that aging is a consequence of the body's attempts to protect itself from cancer. Here is an interesting and detailed conversation with Campisi, I recommend
Why has the problem of aging turned out to be so difficultA.S.: The problem is that aging is not a single process, when, for example, one indicator decreases or some fats accumulate in the blood vessels.
This is a complex phenomenon, which is why it is, in general, so difficult to study. Because there are so many ways that lead to aging. It can be caused by the accumulation of free radicals, mutations in DNA and proteins. True, the body is being updated, but proteins, which, for example, in the lens, are practically not updated. There are proteins that are constantly present in the body. This problem is difficult to solve in one blow. In this case, it is fundamental to consider the general complex of causes, see what is changing, and try to regulate everything, instead of following one gene.
VG: Yes, another additional consideration is why, having deciphered the genome, we did not immediately answer everything. We don't know enough pairs of related animals, one of which is long-lived. Comparing the genome of a mouse and an elephant, we will find a lot of differences in addition to those related to life expectancy. In this case, it is difficult to draw the right conclusion. The study of rodents that live a long time, in our opinion, will help solve this problem, because they need to be compared with short–lived rodents - mice and rats. So far, the genome of the naked digger has just been deciphered, but I think that in the end there will be breakthroughs.
About the link between aging and cancerA.S. We started as a gerontological laboratory, and aging is the main issue that we solved.
We took twenty different species of animals, began to compare them, and every time we looked for something related to aging, we found anti-cancer mechanisms all the time. Just by virtue of the fact that we used an unbiased approach, we ran into this wall of cancer. To solve the problem of aging, you need to first solve the problem of cancer – from our data it turns out so. It is difficult to say what is really the cause and what is the effect, but these two processes are very tightly connected.
V.G. The most interesting thing is that a naked digger, besides living for 30 years, does not suffer from cancer. On the one hand, with age there are more molecular damages, the frequency of mutations increases. On the other hand, in order to live long, an animal needs to develop some kind of protection against cancer in the process of evolution.
A.S. Tried to induce cancer in him and failed. If we use the same parameters at which an experimental population of mice develops cancer, and they die out after 11-12 weeks, then the population of diggers lives up to 24 weeks – then it simply did not make sense to continue the experiment. It's not very clear how they do it, although we know something.
V.G. We did a similar experiment in vitro – we grew cells of a naked digger and treated them with certain oncogenes. If mouse cells are treated with oncogenes, they begin to form tumors in a test tube. And the cells of the naked digger do not start. And we were able to isolate such a substance that the cells of a naked digger produce – if we remove this substance, they also begin to form tumors.
A.S. So far we have done this on cells: if hyaluronic acid is removed, they become cancerous, if they continue to secrete, they are resistant to cancer. We are now trying to make a mouse that will produce the same long hyaluronic acid as a naked digger, and we assume that the mouse will stop getting cancer and will live longer.
V.G. We can use genetic engineering on a mouse, and it is possible to develop some way for a person to take it in tablets. In principle, it is sold in tablets, but we think that what is being sold now is not optimal, because it is produced from bacteria. Acid from the cells of a naked digger is much more active. In the human body, there is also hyaluronic acid under the skin, in the joints, but in a naked digger it is more high-molecular, and this, apparently, is exactly what determines its anti-cancer property.
About the growth of life expectancy in the worldA.S. You are talking about the average life expectancy.
The maximum is preserved somewhere in the region of 120 years. It is assumed that earlier the life expectancy curve was flat, now it is more square, that is, almost everyone lives to a certain age and dies. Thus, the reserve for prolonging life remains for 30-40 years, then we will run into a barrier, and then only genetics will be able to push it away.
V.G. I think by improving living conditions, curing diseases, you can approach 120 years. To live longer, you will need something fundamentally different. Now genetic engineering is developing, maybe it will overcome the barrier. But it seems to me that a more likely approach is to develop some chemicals that can specifically affect proteins, enzymes of those pathways that regulate aging. That is, without changing the human genome itself, but armed with knowledge about how these pathways work, you can specifically manage these processes.
A.S. Rodents and humans have a very similar genome. There are slight differences in how similar genes are regulated. Both we and the naked digger have an enzyme that synthesizes hyaluronic acid, but in the rodent it is more stable, which ensures the production of longer molecules. So, it is necessary to stabilize it in a person to the same level. We are not going to make genetically engineered people, we are talking about drugs that will affect certain genes, cascades of reactions that will lead to the same effects that we observe in a naked digger. It will most likely be possible to use such drugs after puberty.
Portal "Eternal youth" http://vechnayamolodost.ru29.05.2012