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Oxidants, i.e. reactive oxygen species, can damage the cells of all organisms and are linked to aging. A study from Chalmers University of Technology, Sweden, has now indicated that low levels of oxidizing hydrogen peroxide can stimulate an enzyme that slows the aging of yeast cells.
Despite neutralizing oxidants, antioxidants could otherwise react with the body’s essential molecules and destroy their biological functions. Large amounts of oxidants can cause severe damage to DNA, particularly cell membranes and proteins. Our cells have thus developed powerful defense mechanisms to get rid of these oxidants.
Previously, oxidants were only considered harmful, but now scientists have begun to understand the positive functions of oxidants. In a new study, scientists show that the well-known oxidizing hydrogen peroxide can slow the aging of yeast cells.
Scientists studied the Tsa1 enzyme, which is part of a group of antioxidants called peroxyroxins. Peroxyroxins are enzymes that eliminate H2O2 that also perform H2O2 signaling and chaperone functions. In yeast, the major cytosolic peroxyroxin, Tsa1, is required to promote resistance to H2O2 and extend lifespan on calorie restriction.
Mikael Molin, who leads the research team at Chalmers Department of Biology and Biological Engineering, said: “Previous studies on these enzymes have shown that they participate in the defenses of yeast cells against harmful oxidants. But peroxyroxins also help extend the lifespan of cells when they are subject to calorie restriction. The mechanisms underlying these functions are not yet fully understood. “
Several research groups, including that of Mikael Molin, have also shown that stimulating peroxyroxin activity specifically slows down the aging of cells in organisms such as yeasts, flies, and worms when they receive fewer calories than normal through their food.
Cecilia Picazo, postdoctoral researcher at Chalmers Division of Systems and Synthetic Biology, said: “Now we have found a new function of Tsa1. Previously, this enzyme was thought to neutralize reactive oxygen species. But we have now shown that Tsa1 requires the activation of a certain amount of hydrogen peroxide to participate in the slowing process of the aging of yeast cells. “
Surprisingly, the investigation shows that Tsa1 does not affect buhyperoxide levels in aged yeast cells. In fact, Tsa1 uses limited amounts of hydrogen peroxide to reduce central signaling pathway activity when cells are consuming fewer calories. This ultimately leads to a slowdown in cell division and processes related to the development of cell building blocks. It also stimulates the defecation of the cells against stress, which makes them age more and more slowly.
Mikael Molin said, “Signal pathways that are affected by calorie intake can play a central role in aging by detecting the state of many cellular processes and controlling them. By studying this, we hope to understand the molecular causes behind why the onset of many common diseases such as cancer, Alzheimer’s and diabetes show a steep increase with age. “
Scientists have now come close to understanding the mechanisms behind how oxidants can slow down the aging process. This could lead to further studies, such as researching peroxyroxin-stimulating drugs or testing whether age-related diseases can be slowed by other drugs that increase the positive effects of oxidants in the body.
Chalmers analysts have pointed to a mechanism for how the peroxiredoxin enzyme Tsa1 legitimately controls a central signaling pathway. It hinders aging by oxidizing an amino acid into another enzyme, protein kinase A, which is significant for metabolic regulation. Oxidation decreases the activity of protein kinase A by destabilizing a portion of the enzyme that binds to different atoms. As a result, nutrient signaling is reduced using protein kinase A, which downregulates cell division and stimulates their defense against stress.
Other studies have also shown that low levels of reactive oxygen species can be linked to several positive health effects. These oxidants are formed in mitochondria, they can be observed in many organisms, from yeast to mice. In mice, tumor growth is slowed by mitormesis. At the same time, in nematodes, it was possible to link both peroxyroxins and mitormesis to the ability of metformin, a drug for type 2 diabetes, to slow down cellular aging.
Journal reference:
- Friederike Roger et al. Peroxiredoxin promotes longevity and resistance to H2O2 in yeast through redox modulation of protein kinase A. DOI: 10.7554 / eLife.60346
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