Oxidants slow down aging
Cell aging can be slowed down by oxidants
Anna Yudina, "Scientific Russia"
Scientists have found that reducing the level of oxidants slows down the aging process, according to a press release from Chalmers University of Technology Cell aging can be slowed by oxidants.
Article by Roger et al. Peroxiredoxin promotes longevity and H 2 O 2-resistance in yeast through redox-modulation of protein kinase A is published in the journal eLife – VM.
In high concentrations, reactive oxygen species, known as oxidants, are harmful to the cells of all organisms and are associated with aging. But a study by Chalmers University of Technology (Sweden) has now shown that low levels of the oxidant hydrogen peroxide can stimulate an enzyme that helps slow down the aging of yeast cells.
One of the benefits of antioxidants, such as vitamins C and E, is that they neutralize reactive oxygen species known as oxidants, which otherwise may react with important molecules in the body and disrupt their biological functions. For example, large amounts of oxidants can cause serious damage to DNA, cell membranes and proteins. Therefore, our cells have developed powerful defense mechanisms to get rid of these oxidants that are formed in our normal metabolism.
It used to be thought that oxidants were exceptionally harmful, but recently we have begun to realize that they also have positive functions. A new study by Chalmers University of Technology shows that the well-known oxidizer hydrogen peroxide can actually slow down the aging of yeast cells. Hydrogen peroxide is a chemical used, among other things, to whiten hair and teeth. It is also one of the oxidizing agents formed as a result of metabolism, which is harmful at higher concentrations.
Chalmers researchers studied the Tsa1 enzyme, which is part of a group of antioxidants called peroxyredoxins.
"Previous studies of these enzymes have shown that they are involved in protecting yeast cells from harmful oxidants," says Mikael Molin, who heads the research group at Chalmers Department of Biology and Biological Engineering. – But peroxiredoxins also help prolong the life of cells when they are subjected to calorie restriction. The mechanisms underlying these functions are not yet fully understood."
It is already known that reducing calorie intake can significantly prolong the life of a variety of organisms, from yeast to monkeys. Several research groups, including Mikael Molin, have also shown that stimulating the activity of peroxiredoxin, in particular, slows down cell aging in organisms such as yeast, flies and worms when they receive fewer calories from food than usual.
"Now we have discovered a new function of Tsa1," says Cecilia Picazo, a researcher in the Department of Systems and Synthetic Biology at Chalmers. – Previously, we thought that this enzyme simply neutralizes reactive oxygen species. But now we have shown that Tsa1 does require a certain amount of hydrogen peroxide to activate in order to participate in the process of slowing down the aging of yeast cells."
Surprisingly, the study shows that Tsa1 does not affect the level of hydrogen peroxide in old yeast cells. In contrast, Tsa1 uses small amounts of hydrogen peroxide to reduce the activity of the central signaling pathway when cells receive fewer calories. The consequences of this eventually lead to a slowdown in cell division and the processes associated with the formation of cell building blocks. It also stimulates the protection of cells from stress, which causes them to age more slowly.
"The signaling pathways affected by calorie intake may play a central role in aging by sensing the state of many cellular processes and controlling them," says Mikael Molin. "By studying this, we hope to understand the molecular reasons why the occurrence of many common diseases, such as cancer, Alzheimer's disease and diabetes, increases dramatically with age."
The fact that researchers have come a step closer to understanding the mechanisms underlying how oxidants can actually slow down the aging process may lead to new research, for example, searching for drugs that stimulate peroxiredoxin, or checking whether it is possible to slow down the development of age-related diseases with other drugs that enhance the positive effect of oxidants in the body.
Chalmers researchers have shown the mechanism of how the enzyme peroxyredoxin Tsa1 directly controls the central signaling pathway. It slows down aging due to the oxidation of the amino acid of another enzyme, protein kinase A, which is important for the regulation of metabolism. Oxidation reduces the activity of protein kinase A, destabilizing the part of the enzyme that binds to other molecules. Thus, the transmission of nutrient signals through protein kinase A is reduced, which, in turn, suppresses cell division and stimulates their protection from stress.
Other studies have also shown that low levels of reactive oxygen species may be associated with several positive health effects. These oxidants are formed in the mitochondria – the "powerhouses" of the cell, and a process called mitohormesis can be observed in many organisms, from yeast to mice. In mice, tumor growth is slowed down by mitohormesis, whereas in roundworms it was possible to link both peroxiredoxins and mitohormesis with the ability of metformin, a type 2 diabetes drug, to slow cellular aging.
(Hormesis, from the Greek hórmēsis rapid movement, aspiration, is the stimulating effect of doses of stressors having a force insufficient for the manifestation of harmful effects of stress – VM).
Metformin is also important for finding drugs that can reduce the risk of serious damage to the elderly Covid-19. Studies in China and the United States have yielded promising results, and one theory is that metformin may counteract the deterioration of the immune system caused by aging.
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