Alexey Moskalev – how to overcome aging

"120 years of life is just the beginning"

Alexey Moskalev, "Newspaper.Ru"

What can a person take from a naked digger to live 100 years, and what role genes play in longevity, "the newspaper.Ru" said Alexey Moskalev, Doctor of Biological Sciences, Head of the Laboratory of Molecular Radiobiology and Gerontology of the Institute of Biology of Komi NC Ural Branch of the Russian Academy of Sciences, author of the book "120 years of life is just the beginning. How to defeat aging?".

– Next Friday, you and your colleagues are publishing an article on aging. While there is a strict embargo on this publication, let's start with general things. Is aging inevitable? It seems to us that it is inevitable, since all the surrounding people are aging, who is faster, who is slower. In your book, you cite species of animals that practically do not age. What is the difference between us and them?

– Indeed, there are several groups of living beings in nature that do not fall under the classical definitions of aging: their mortality rate does not increase with age, and fertility and other physiological functions do not decrease. This does not mean, of course, that they are immortal.

Some types of coniferous trees, such as sequoias, are distinguished by the greatest longevity. What are the mechanisms of their longevity? I will make a few assumptions. Firstly, polyploidization of the genome: they have many copies of the same genes, this is a kind of backup of genetic information, protection from "data loss" – mutations. They are distinguished by high stress resistance: plants have nowhere to run from adverse environmental conditions, they need to be able to adapt to the environment at all costs.

Finally, permanent growth is the constant death of defective cells and their replacement with new cells. If we talk about the famous rodent naked digger, according to Rochelle Baffenstein, important physiological indicators characteristic of youth and maturity do not decrease with age: basic metabolism, the ability to vascular relaxation, bone density, the condition of articular cartilage, glucose tolerance, antioxidant activity. The digger does not increase the formation of glycated hemoglobin, free radicals with age, and oxidative damage does not accumulate. But these age–related changes are biomarkers of aging in humans.

A similar mechanism of "non–aging" was observed in another species with negligible aging - the sea urchin Strongylocentrotus franciscanus. The reasons for this constancy may lie in the yet undisclosed features of the epigenetics of these species.

Another probable cause of minor aging is the unlimited ability to regenerate. At least some signs of aging (for example, an increase in mortality with age) are not found in simple multicellular animals, including combworms, sponges, placozoa, cnidarians (hydra, jellyfish, corals and anemones), mixozoa, flatworms. The key factor determining clonal immortality in most of these simple animals is the large number of pluripotent stem cells in adults that underlie the ability of these animals to regenerate. What turned out to be fundamentally possible for individual species of living beings can become a reality for humans.

– You stand on the position that aging is a disease. What is the evidence?

– While aging is considered as a normal physiological phenomenon, it is not necessary to expect any breakthrough in the fight against it. At the time, I noticed that no definition of aging practically distinguishes this phenomenon from the disease. For example, according to the outstanding Soviet gerontologist V.V. Frolkis, aging is "a multi–causal destructive process caused by a complex of regulatory and stochastic factors and determined by the genetically determined biological organization of a living system." In my opinion, this is a very beautiful definition that reflects the role of genetic, epigenetic, environmental and stochastic factors. However, a cold will also fit the same definition.

If we look at the graph of the dependence of various causes of death on age (cardiovascular diseases, tumors, strokes, pneumonia, type 2 diabetes, kidney disease, Alzheimer's disease), we will see that mortality from these causes is constantly increasing from the age of 15-25. That is, they do not arise spontaneously and from scratch. There are internal reasons for their occurrence – aging – which constantly increase the probability of mortality with age.

The number of chronic diseases per person by the age of 70 years, compared with 50 years, doubles, reaching an average of 7 diseases. Even deaths from accidents after the age of 65 begin to increase. The latter, apparently, is associated with progressive aging of the neuromuscular system, impaired vision, hearing, balance, and coordination of movements.

Why does aging occur in all people? From the point of view of evolution, there is a high probability of accumulation of mutations that have a delayed harmful effect falling on the period of life following a decrease in the peak of reproduction. Simply put, natural selection sweeps away only those mutations that interfere with growth, puberty and the abandonment of offspring. Mutations that contribute to our aging fall under the influence of selection to a lesser extent. Therefore, they accumulated in evolution and spread among all individuals of our species.

And only those species of living creatures that, due to their lifestyle, have lost the need for early abandonment of offspring, living underground (like a naked digger), deep under water (Aleutian sea bass), who have acquired the ability to fly (bats, birds), have received negligible aging. Due to the protection of their habitats from the pressure of predators, they could afford to dramatically increase their reproductive lifespan, evenly leave offspring throughout their lives.

– Please list the main pathological changes at different levels, from molecular to organismal. If there are so many changes, then a potential anti-aging remedy should have a lot of application points, is it real?

– As for the general picture of aging, it is really complicated and it is not possible to present it in a brief interview. About seven years ago, I displayed the pathological changes known at that time during aging from the molecular to the organismic level on a large diagram. Currently, this project has resulted in the creation of more than 100 interconnected schemes, and several people are already helping me in its implementation.

Therefore, it is obvious that there can be many application points for combating aging and the solution must be comprehensive. Most likely, there will not be the only pill for old age, which was so dreamed of. There will be a whole set of geroprotectors aimed at different molecular targets and aging processes, as well as complex gene therapy, cell therapy taking into account the knowledge of the device of stem niches, transplantation of organs grown from the patient's cells. Nature has examples of species whose life expectancy is several times higher than the maximum human lifespan. There are even mammalian species that do not have cancer, osteoporosis or diabetes. Therefore, there is nothing unrealistic in the fight against aging. It's all about the speed of accumulation of scientific knowledge and the effectiveness of their implementation in medical practice.

– What have the studies of centenarians shown? To what extent does longevity depend on genes, and to what extent on lifestyle?

– In centenarians, unlike the average individual, the contribution of lifestyle and genes to longevity is completely different. In an ordinary person, genes affect life expectancy by 25%, and lifestyle by 75%. But even the most correct way of life on average allows you to live only 86 years. Centenarians do not differ in lifestyle from the rest, but they live more than 90, 100, and sometimes 110 years. Therefore, the contribution of heredity to their longevity can reach 50%.

The ability to live that long is usually inherited. Genetic studies of centenarians have not revealed anything fundamentally new. As it turned out, they have all the same genes, but some of them are modified, which affects their function. For example, long–livers have mutations of the following genes - LRP5 (responsible for bone condition), GHR and GH (carcinogenesis), MSTN (muscle condition), SCN9A (insensitivity to pain), CCR5 and FUT2 (immunity to viruses), PCSK9 and APOC (cardiovascular diseases), APP (Alzheimer's disease), SLC3 OA8 (diabetes).

– Thank you, and we hope to continue our conversation.

Nadezhda Markina was talking.

Portal "Eternal youth" http://vechnayamolodost.ru 17.12.2014