Anti-aging terpenoids?

The cure for aging

Anastasia Penzina, "Scientific Russia"

In 2016 Ekaterina Proshkina, a young scientist from the Institute of Biology of the Komi Scientific Center of the Ural Branch of the Russian Academy of Sciences, received the prize of the President of Russia in the field of science and innovation "for her contribution to the development of genetics of life expectancy and aging." Today, Ekaterina continues to study the mechanisms that will help slow down the aging of the body. It is believed that the aging process is largely associated with DNA damage in cells. The more genetic breakdowns accumulate in the body, the more noticeable the results of its degradation become. Ekaterina, together with colleagues from the laboratory of Molecular Radiobiology and gerontology, is looking for special substances that protect DNA from accidental damage. One of the contenders can be considered terpenoids – an amazing group of secondary metabolites of higher plants, which has no analogues in the variety of structural types and biological role in regulating the processes of vital activity of living organisms. These substances protect plants from diseases and pests, as well as many adverse environmental factors (overheating, cooling, damage, etc.). Perhaps their properties have a beneficial effect on human health, and hence on life expectancy. Learn more about unique enzymes and their benefits in our conversation with a young scientist.

– What is known about the mechanisms of aging today? In what areas are scientific research conducted?

– Aging is a multifaceted process. It represents a gradual deterioration of the functional abilities of the body, its adaptive capabilities. All this ultimately leads to death.

There are a huge number of scientific directions in the field of gerontology (the science of aging). In particular, I am engaged in the molecular mechanisms of aging. Some scientists study aging at the tissue level or at the systemic level. In addition, the direction of mathematical modeling of the aging process is actively developing. And, of course, specialists work in an applied way, for example, they study certain substances, on the basis of which they develop pharmacological drugs that affect certain mechanisms and slow down the aging process.

– How is aging related to genetics?

– Aging is caused by a number of factors. It depends on the set of genes that are present in the cells of our body, and on how these genes are implemented (this is the epigenetic level). The second component is the effect of external factors, including environmental factors, a person's lifestyle, eating habits, and the presence of bad habits.

Genetics plays an important role, but it is not limited to the impact on life expectancy. For example, there are polymorphisms, in other words, point changes in genes that allow their owners to live exceptionally long. But in the human population, they are not so common, and in general, the stability of the functioning of our body's cells depends on the work of genes and how effectively the body will respond to external stimuli and cope with the negative effects of the environment.

– Before we go directly to your latest research, I would like to know if you have been engaged in similar topics before? Or has this scientific task turned out to be new for you?

– Our laboratory was formed in 2012. From the very beginning, we have been researching the molecular foundations of aging and looking for ways to influence them to increase the lifespan of the body. We conduct research on model animals, mainly fruit flies and fruit flies. And we influence the aging process either with the help of genetic manipulations, when we work with drosophila lines with different genotypes, or with the help of pharmacological preparations and biologically active substances. Previously, we have already conducted both experimental and review work on the analysis of the geroprotective properties of anti-inflammatory drugs, flavonoids, carotenoids (which belong to terpenoids) and some other compounds. That is, this task was already familiar to us.

– Tell us more about these substances – terpenoids. How did the idea to study them come about, since when did the search for such substances to affect the mechanisms of aging begin? How do these substances affect life expectancy?

– Terpenoids are a very common class of substances. This is a group of secondary metabolites of plants with a huge variety of structural types and functions in the regulation of vital processes of organisms. The scientific community has several tens of thousands of such compounds. And it has been known for a long time that terpenoids can have a beneficial effect on human health. For example, some of the substances can prevent the development of cancer, cardiovascular and inflammatory diseases, nervous disorders, improve the condition of the musculoskeletal system. There are terpenoids that exhibit antibacterial and antiviral activity. They can be used as antidepressants and painkillers. But, nevertheless, despite the fact that there are a lot of them in nature and they exhibit a wide range of biological activities, from the point of view of slowing down aging, they were almost not considered. Therefore, in our work we tried to find representatives of terpenoids that could be effective in terms of slowing down the aging process and increasing life expectancy. We analyzed various terpenoids according to the criteria of geroprotectors, identified almost two dozen compounds that could slow down aging and improve health.

In general, we started studying terpenoids in 2013. But at that time we were limited only to the properties of carotenoids. Gradually, this direction is expanding. We include other groups of terpenoids in the research, and new experimental methods for a deeper analysis of the features of their action, and new model objects. To do this, we cooperate with other organizations, for example, with the V.A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences and with Initium-Pharm. As part of this collaboration, we studied the geroprotective properties and the ability to improve the health of preparations based on Siberian fir terpenoids. It has been found that they are able to have a positive effect on health, for example, to weaken inflammatory reactions in the body, and have a good potential for the treatment of various age-related diseases.

– How do these substances affect the health of the body?

– Terpenoids have a wide range of biological activities. It is known that terpenoids are quite strong antioxidants and stimulants of the protective systems of the cell and the body. They reduce the level of reactive oxygen species, the level of DNA and protein damage in cells. At the same time, they can affect the mechanisms that contribute to the elimination of such damage. Terpenoids reduce inflammation in tissues and in the body. This is exactly the property that is used when using terpenes as medicines for certain diseases. These natural substances improve metabolism, for example, normalize the balance of carbohydrates and lipids. In addition, terpenoids have additional activities: immunostimulating, antiviral, antibacterial and antiparasitic actions.

– At what stage is your research? Have clinical trials started?

– Our task was to identify the main terpenes and terpenoids, which are worth paying attention to for further, deeper study of them as geroprotectors. In the study, we pointed out those representatives of the terpenoid class who are able to slow down the processes associated with aging, stimulate defense mechanisms and slow down the development of age-related diseases. Screening and preclinical tests are currently being conducted for most of these compounds. On various model organisms and cell cultures, scientists analyze what useful properties these substances have, and what action can be expected from them. Nevertheless, for the already mentioned preparations based on Siberian fir, there are also clinical studies where they show their effectiveness, including for the treatment of age-related disorders. As far as I know, there are several terpenes for which clinical studies have also been conducted, and which are recommended for use as an additional therapy, for example, in the treatment of cancer.

– So all the substances that you have studied can potentially become medicines in the future? 

- of course. But it is important to understand that before using new substances for people, it is necessary to study very carefully and in detail what side effects can lead to the use of the drug for the treatment of certain diseases and to increase life expectancy. With geroprotective therapy, it will be necessary to take terpenoids (as well as any other potential geroprotector) for a long time. Therefore, there may be some side effects that we will not notice with short-term use of drugs based on them.

– What are you working on today?

– One of the directions of our laboratory is connected with the study of the geroprotective properties of various drugs. We study both natural compounds and synthetic pharmacological preparations. In addition to expanding research on terpenoids, we consider the effects of various polyphenolic compounds, polyamines, fatty acids and some other compounds. We study the geroprotective effects of various plant extracts, for example, from berries that grow in our northwestern region of Russia. In addition, laboratory specialists analyze which synthetic drugs can be used to increase life expectancy. Previously, we studied the geroprotective properties of nonsteroidal anti-inflammatory drugs, which include, for example, ibuprofen and aspirin. Last year we managed to get an RNF grant. One of the tasks of the supported project is devoted to the study of the ability of synthetic drugs that stimulate the mechanisms of DNA damage repair to increase life expectancy.

The interview was conducted with the support of the Ministry of Science and Higher Education and the Russian Academy of Sciences.

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