In high concentrations, reactive oxygen species – so-called oxidizing agents – are harmful to cells in all organisms and have been linked to aging. A study by the Swedish Chalmers University of Technology has now shown that low concentrations of the oxidizing agent hydrogen peroxide can stimulate an enzyme that slows down the aging of yeast cells.
One advantage of antioxidants like vitamins C and E is that they neutralize reactive oxygen species – so-called oxidizing agents – that can otherwise react with important molecules in the body and destroy their biological functions.
Larger amounts of oxidizing agents can seriously damage DNA, cell membranes, and proteins, for example. Our cells have therefore developed strong defense mechanisms to get rid of these oxidants that are made in our normal metabolism.
It used to be thought that oxidizers were only harmful, but we have recently come to understand that they also have positive functions. New research from Chalmers University of Technology now shows that the well-known oxidizing agent hydrogen peroxide can actually slow down the aging of yeast cells. Hydrogen peroxide is a chemical that is used for hair and teeth whitening, among other things.
It is also one of the oxidizing agents formed in our metabolism that is harmful at higher concentrations.
The Chalmers researchers studied the enzyme Tsa1, which is part of a group of antioxidants called peroxiredoxins.
Previous studies of these enzymes have shown that they are involved in yeast cells’ defense against harmful oxidizing agents. The peroxiredoxins also extend the life of cells if they are subject to a calorie restriction. The mechanisms behind these functions are not yet fully understood. ”
Mikael Molin, Head of Studies, Institute for Biology and Biotechnology, Chalmers University of Technology
It is already known that reduced caloric intake can significantly extend the lifespan of a wide variety of organisms, from yeasts to monkeys. Several research groups, including Mikael Molin, have also shown that stimulating peroxiredoxin activity in particular slows the aging of cells in organisms such as yeast, flies, and worms when they receive fewer calories than normal from their diet.
“Now we have found a new function for Tsa1,” says Cecilia Picazo, postdoctoral fellow at the Department of Systems and Synthetic Biology in Chalmers. “We used to think that this enzyme simply neutralized reactive oxygen species. Now we have shown that Tsa1 actually has to trigger a certain amount of hydrogen peroxide in order to participate in slowing down the aging of yeast cells. ”
Surprisingly, the study shows that Tsa1 does not affect hydrogen peroxide levels in aged yeast cells. On the contrary, Tsa1 uses small amounts of hydrogen peroxide to decrease the activity of a central signaling pathway when cells are receiving fewer calories.
The effects ultimately lead to a slowdown in cell division and the processes that are associated with the formation of the cell building blocks. The cells’ defenses against stress are also stimulated – which means that they age more slowly.
“Signaling pathways that are influenced by calorie intake can play a central role in aging by recording and controlling the status of many cellular processes,” says Mikael Molin. “By investigating this, we hope to understand the molecular causes behind why the incidence of many common diseases such as cancer, Alzheimer’s and diabetes increases sharply with age.”
The fact that researchers are now closer to understanding the mechanisms behind how oxidants can actually slow down the aging process could lead to new studies, such as finding peroxiredoxin-stimulating drugs or testing whether age-related diseases slow down can be caused by other drugs that increase the beneficial effects of oxidants in the body.
More on the topic: The mechanism of slowed aging by the enzyme Tsa1:
The Chalmers researchers have shown a mechanism by which the peroxiredoxin enzyme Tsa1 directly controls a central signaling pathway. It slows aging by oxidizing an amino acid in another enzyme, protein kinase A, which is important for metabolic regulation.
Oxidation reduces protein kinase A activity by destabilizing part of the enzyme that binds to other molecules. This reduces the nutrient signaling via protein kinase A, which in turn downregulates cell division and stimulates their defense against stress.
More on the topic: Related results from other research groups:
Other studies have also shown that low levels of reactive oxygen species can be linked to several positive health effects. These oxidants are made in the mitochondria, the “powerhouse” of a cell, and the process known as mitohormesis can be seen in many organisms, from yeasts to mice.
In mice, mitohormesis slows tumor growth, while in roundworms, both peroxiredoxins and mitohormesis have been linked to the ability of the type 2 diabetes drug metformin to slow down cell aging.
Metformin is also relevant in the search for drugs that can reduce the risk of the elderly being severely affected by Covid-19. Studies in China and the United States have shown some promising results, and one theory suggests that metformin may counteract the deterioration in the immune system caused by aging.
Chalmers University of Technology
Roger, F., et al. (2020) Peroxiredoxin promotes longevity and H2O2 resistance in yeasts through redox modulation of protein kinase A. eLife. doi.org/10.7554/eLife.60346.
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