Tsa1 in the Hormetic Response to Mild Oxidative Stress

Stressing cells a little leads to overall benefits, as maintenance mechanisms such as autophagy are upregulated to more than compensate for any damage. This is known as hormesis, and it is one of the reasons why exercise, calorie restriction, radiation, and heat can produce health benefits at appropriate dose levels. Researchers here explore one of the links between oxidative damage and the beneficial responses to that damage. In theory, a better view of these linking mechanisms may lead to better ways to mimic the effects of mild stress in order to improve long term health.

Researchers studied the enzyme Tsa1, which is part of a group of antioxidants called peroxiredoxins. Previous studies of these enzymes have shown that they participate in yeast cells' defences against harmful oxidants. But the peroxiredoxins also help extend the life span of cells when they are subjected to calorie restriction. The mechanisms behind these functions have not yet been fully understood.

It is already known that reduced calorie intake can significantly extend the life span of a variety of organisms, from yeast to monkeys. Several research groups have also shown that stimulation of peroxiredoxin activity in particular is what slows down the ageing of cells, in organisms such as yeast, flies, and worms, when they receive fewer calories than normal through their food. "Now we have found a new function of Tsa. Previously, we thought that this enzyme simply neutralises reactive oxygen species. But now we have shown that Tsa1 actually requires a certain amount of hydrogen peroxide to be triggered to participate in the process of slowing down the ageing of yeast cells."

Surprisingly, the study shows that Tsa1 does not affect the levels of hydrogen peroxide in aged yeast cells. On the contrary, Tsa1 uses small amounts of hydrogen peroxide to reduce the activity of a central signalling pathway when cells are getting fewer calories. The effects of this ultimately lead to a slowdown in cell division and processes linked to the formation of the cells' building blocks. The cells' defences against stress are also stimulated - which causes them to age more slowly.

Link: https://www.chalmers.se/en/departments/bio/news/Pages/Cell-ageing-can-be-slowed-by-oxidants.aspx

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