Will a couple of glasses of red wine be enough to manifest the effects of resveratrol?
A new mechanism of action of the "elixir of youth"
NanoNewsNet based on TSRI materials:
Scripps Research Institute Scientists Uncover New, Fundamental Mechanism for How Resveratrol Provides Health BenefitsScientists of The Scripps Research Institute (TSRI) have found that the ingredient of red wine resveratrol, often extolled as the "elixir of youth", powerfully activates the evolutionarily ancient response of cells to stress.
The results of the experiments should help to dispel much of the mystery surrounding this compound and resolve disputes about what the mechanism of its action really is.
"This stress response is a largely unexplored area of biology, and resveratrol appears to activate it at much lower concentrations than those used in previous studies," says Professor Paul Schimmel, PhD, researcher at the Skaggs Institute of Chemical Biology (The Skaggs Institute for Chemical Biology) TSRI.
"Based on this, we propose a new fundamental mechanism of action of resveratrol, explaining its known beneficial effects," the lead author of the article on the study (Mathew Sajish, Paul Schimmel) continues the thought of his supervisor. A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol), published online in the journal Nature, by Mathew Sajish, senior researcher at the Schimmel Laboratory.
Resveratrol is a compound formed in grapes, cocoa beans, Japanese knotweed and some other plants in response to stress infection, drought, and ultraviolet radiation. Over the past decade, this compound has aroused the interest of both scientists and ordinary people, since, according to scientific research, it is able to increase life expectancy, prevent the development of diabetes in obese mice and significantly increase the physical endurance of ordinary mice.
However, more recently, scientists have disagreed about the signaling pathways activated by resveratrol and questioned the presence of some of its supposed health benefits, based, in particular, on unrealistically high doses used in some experiments.
Professor Schimmel's laboratory is known for its work not on resveratrol, but on the ancient family of tRNA synthetase enzymes. The first and main function of these enzymes is to help translate genetic material into amino acid building blocks that make up proteins. But, as Schimmel and others showed in the late 1990s, in mammals, tRNA synthetases perform many other functions.
tRNA synthetases (shown in green and purple) are involved in the translation of genetic material
the amino acid building blocks that make up proteins.
They bind amino acids to their transport RNAs.
(Fig. Art For Science)
Earlier, Xiang-Lei Yang, professor of the Department of Chemical Physiology and Cellular and Molecular Biology at TSRI, obtained data that the tRNA synthetase TyrRS, which binds the amino acid tyrosine to the genetic material encoding it, can move into the cell nucleus under stressful conditions, apparently taking over the function activation of a protective anti-stress reaction. Sajish noticed that resveratrol in general has similar properties (the ability to cause a stress response), and is also structurally close to the normal binding partner of TyrRS – the amino acid tyrosine.
"I began to consider TyrRS as a potential target of resveratrol," says the scientist.
In their new study, Sajish and Schimmel compared TyrRS and resveratrol and, using, inter alia, X-ray crystallography, showed that resveratrol is indeed so close to tyrosine that it can tightly interact with the tyrosine-binding pocket of TyrRS. The binding of resveratrol, scientists have found, "distracts" TyrRS from the translational function and directs it to perform a function in the cell nucleus (fig. from an article in Nature).
By tracking the TyrRS associated with resveratrol in the nucleus, the researchers determined that the enzyme captures and activates the protein PARP-1 – the main factor of stress response and DNA repair, which is believed to have a great impact on life expectancy. This interaction was confirmed in mice injected with resveratrol. Activation of the PARP-1 protein by the TyrRS enzyme, in turn, led to the activation of a number of protective genes, including the tumor suppressor p53 and the longevity genes FOXO3A and SIRT6.
In the early 2000s, based on the results of the first work on resveratrol, scientists came to the conclusion that it has some of its positive health effects by activating SIRT1, also considered a longevity gene. But recently, the role of SIRT1 in mediating resveratrol in its health effects has been questioned in terms of the exclusivity of this gene.
Thus, the experiments of Schimmel's group showed that the TyrRS-PARP-1 pathway can be powerfully activated by much lower (1000 times) doses of resveratrol than were used in some of the most well-known previous studies, including those in which scientists' attention was focused on SIRT1.
"Based on these results, it can be assumed that a couple of glasses of red wine (rich in resveratrol) will give a person enough resveratrol to trigger a protective effect through this pathway," concludes Sajish.
In his opinion, the effects of resveratrol, manifested only at extremely high doses, could lead to an incorrect interpretation of some earlier results.
Why does resveratrol, a protein produced by plants, have such a powerful and specific effect on the activation of the main stress response pathway in human cells? Probably because it does almost the same thing in plant cells. And it must have been with the help of the same TyrRS protein, so important for life due to its interaction with one of the amino acids that for hundreds of millions of years, since plants and animals have gone their own evolutionary paths, it has hardly changed.
"We believe that, as TyrRS evolved, it began to function as a higher switch or activator of a fundamental cellular defense mechanism that works in almost all forms of life," says Sajish.
Whatever activity resveratrol has in natural conditions in mammals, its effects can be an example of hormesis – a mild, health-enhancing activation of a natural reaction to stress.
"If resveratrol brought significant benefits to mammals, they could develop a symbiotic relationship with plants producing resveratrol," Sajish believes.
"In our opinion, this is just the tip of the iceberg. We assume that there are many more amino acid-mimicking compounds that can have the same beneficial effect on the human body. And now we are working on it," Professor Schimmel shares his thoughts and plans.
In addition, he and his laboratory are searching for molecules that can activate the TyrRS pathway responsible for the stress response even more powerfully than resveratrol.
Portal "Eternal youth" http://vechnayamolodost.ru29.12.2014