Nursing care

One mutation has weaned flies to benefit from physical education

Polina Loseva, N+1

Proteins have been found in animal muscles that are responsible for the body's response to exercise – muscle growth and metabolic restructuring. They are called sisters. Their knockout reduces the effect of physical education to nothing. Adding sestrins to cells, on the contrary, helps prevent muscle atrophy, even if the animal does not train them. Two complementary papers on the sisters have been published in the journal Nature Communications.

Exercise is the easiest way to maintain health in old age and prevent muscles from atrophy. However, not all people are able to use it, work interferes with someone, health interferes with someone, and someone simply cannot get together. Therefore, it would be convenient to find some kind of medical substitute for physical education, which would allow avoiding age-related muscle atrophy even for those who cannot do exercises. But to do this, you must first find out what mechanism connects physical education and the health of muscle tissue.

Two groups of researchers – from University of Michigan and Pompeu Fabra University in Barcelona – proposed to consider sestrina proteins as such a link. Mammals have three types of them, flies and worms have one each. Sestrins work mainly in muscles, accumulate in cells under stress and are responsible for regulating metabolism: they reduce the level of oxidative stress, suppress protein synthesis (blocking the TOR protein complex) and trigger autophagy – digestion and renewal of individual parts of the cell.

To check whether the sisters are really responsible for the effect of exercise, scientists from The University of Michigan has developed a physical education complex for fruit flies. They periodically shook the flies to the bottom of the test tube, from where they, obeying their negative geotaxis, crawled up, where they were shaken off again. After three weeks of such training, the experimental flies really became stronger: for example, they could run tirelessly for 500 minutes instead of the usual 400. However, the training did not have any effect on the knockout flies: animals whose sestrin gene was turned off tired as quickly after classes as before.

Then the researchers confirmed that sestrin works precisely in the muscles. To do this, they selectively blocked its expression in healthy animals – and they turned out to be just as insensitive to training as knockout flies. And vice versa: if the working gene of sestrin was added to the muscles of knockout flies, physical education began to bear fruit, despite the fact that sestrin did not work in all other cells of the body.

Then the scientists switched to mice and found out that out of the three sisters they had, sestrin-1 was responsible for the effect of physical education: only his knockout made the mice insensitive to training. After studying the physiology of the sestrin-1 knockout mice in more detail, the researchers noticed that after training, not only the speed with which they get tired remains unchanged, but also insulin sensitivity, respiratory intensity and the number of mitochondria. Thus, sestrin came to the role of a protein that changes the metabolism in muscles, thereby affecting other organ systems.

At the same time , researchers from Barcelona only worked with mice and tested how their sisters are involved in different types of muscular atrophy. They found that in all cases of atrophy – caused by immobility, death of muscle nerves or age – overexpression of sestrins reduces losses in muscle tissue. They confirmed that this is due to autophagy: as a rule, its level decreases in the degrading muscle, and the sisters, on the contrary, stimulate it and maintain the viability of muscle fibers.

Thus, the sisters could be used as molecular analogues of physical exercises. However, since these are large molecules, it is quite difficult to deliver them selectively into the muscle tissue of an adult. Therefore, in order to create a tablet-a "simulator of physical education" – just as fasting simulators appeared, we will have to find small molecules that are able to start the work of sestrins in the muscles.

Scientists now and then find the most unexpected effects of physical exercise. For example, physical education helps not only to reduce the risk of death from all causes, but also to reduce the number of mutations in mitochondria, prevent depression and "pump up" memory.

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