02 June 2009

Do free radicals slow down aging?

A little stress won't hurtNadezhda Markina, Infox.ru
Everyone has heard about harmful oxidants and beneficial antioxidants.

Oxidative stress, which is caused by reactive oxygen species, is associated with the mechanism of many diseases and, according to the most popular theory, causes the aging of the body. But it turns out that in small doses, oxidative stress is useful because it trains the body and helps to cope with a lot of stress, the staff of the University of California found out.

Oxidative stress is caused by reactive oxygen species, which actually appear in the body constantly as byproducts of metabolism involving oxygen (or aerobic respiration). But when there are too many of them, and this happens under the action of external damaging chemical or physical agents (ultraviolet radiation, temperature, etc.), they damage proteins, DNA, components of cell membranes. When cells cannot cope with this, various diseases arise.

For example, the oxidation of low-density lipoproteins causes damage to the heart vessels. Oxidative stress also contributes to age-related diseases such as Parkinsonism and Alzheimer's disease.

A little stress won't hurt For a long time it was believed that free oxygen forms are extremely evil, but recently scientists have come across the fact that they are useful in small doses.

With them, the body receives a kind of vaccination and copes better with subsequent high doses. However, the mechanism of this phenomenon remained unclear.

Professor of Bioengineering and Head of the Genetics Department at the University of California, San Diego School of Medicine (Division of Genetics in the Department of Medicine at UC San Diego's School of Medicine) Trey Ideker and his colleague Ryan Kelley studied this phenomenon by yeast.

The researchers exposed yeast cells to a moderate dose of peroxide (0.1 mM H 2 O 2 for 45 minutes), followed by a high dose (0.4 mM H 2 O 2 for 1 hour). In the control experiment, only a high dose of hydrogen peroxide was tested on cells without prior "training". Hydrogen peroxide is one of the most important damaging agents in oxidative stress. It easily decomposes into atomic oxygen and water. Surrounded by organic molecules, atomic oxygen almost instantly breaks the first bond that comes along, thereby destroying any molecule that turns up to it. And although in reality the process is much more complicated, its essence does not change from this.

Yeast was sorted by genes

To detect the genes responsible for adaptation, scientists used 4831 genetic lines of yeast, in each of which one gene did not work. The scientists were helped to work with so many genetic varieties of yeast by the method of biological microchips, in which thousands of samples can be placed in cells on one die and analyzed in parallel.

After the cells were exposed to hydrogen peroxide, the scientists estimated their number in the samples. To determine the number of cells, the optical density index OD600 was used (if OD600 = 1, then a milliliter contains a billion cells). In the experiment, all crops were grown to a value of OD600 equal to 0.6. The control, untreated group grew to the specified density in 400 minutes. Yeast treated with a high dose – in 700 minutes. And if the cells were pre-trained with a low dose of peroxide, they grew to the specified density in 470 minutes. That is, a high dose slowed down cell growth (since almost half of the culture died during processing), and preliminary adaptation to a low dose significantly reduced this damaging effect.

After analyzing the results in all mutant yeast lines, the scientists found many genes that were involved in the cellular response to a high dose of peroxide (108 genes) and in adaptation to it (156 genes). Of these, 88 genes worked both ways.

At the next stage, scientists began to look for regulatory factors that include these genes, if necessary. They found three such factors – proteins YAP1, SKN7 and MGA2, and the first two were previously candidates for resistance to oxidative stress, and the MGA2 protein was previously associated with resistance to hypoxia.

And then they showed that yeast cells in which one of these three genes – YAP1, SKN7 or MGA2 - does not work, cannot adapt to peroxide. In these cultures, almost the same number of cells die, either without adaptation or with adaptation. MGA2 turned out to be the most interesting for scientists, since it included genes at the very first stage of adaptation.

Why Food Restriction Slows down Aging

This work is directly related to another one, in which the influence of caloric intake on life expectancy was studied. Trying to explain this phenomenon, scientists first decided that calorie restriction slows down the rate of aerobic respiration, which serves as a source of reactive oxygen species. But then it turned out that breathing increases with calorie restriction, which means that the level of reactive oxygen species also increases.

The adaptation hypothesis explains the paradox. Moderate oxidative stress resulting from calorie restriction adapts the body to the subsequent action of a high dose. That is, when there are a lot of reactive oxygen species with age, the body trained on small doses can cope with them more easily.

"Perhaps it is adaptation to oxidative stress that underlies the fact that calorie restriction prolongs life," says Idecker. "This mechanism can be applied to models of disease and aging."

In the future, scientists are going to test the data obtained on higher organisms.

The article was published in the journal PLoS Genetics.

Portal "Eternal youth" http://vechnayamolodost.ru/02.06.2009

Found a typo? Select it and press ctrl + enter Print version