Myostatin inhibitor helped mice preserve bones and muscles in space

The mouse has the myostatin gene "off" in the foreground, so it has more muscle mass. In the background is a wild-type mouse, in which muscle growth is limited by the action of myostatin

The loss of bone and muscle mass caused by prolonged exposure to microgravity can be prevented by introducing a myostatin protein inhibitor — a decoy receptor (a modification of the activin II receptor, ACVR2B), according to the Proceedings of the National Academy of Sciences. This was shown by experiments on mice, some of which spent 33 days on the International space station, and some spent the same time in a laboratory on Earth. Normally, myostatin restricts muscle growth.

Reduced gravity on the ISS and in similar conditions leads to the fact that some of the muscle mass and the bone matter is lost, which makes a person weaker and his bones become more fragile. Although they try to combat this with physical exercise (astronauts on the ISS devote an average of two hours to it almost every day), they cannot completely prevent the loss.

Probably, pharmacological methods can help in this, namely, the suppression of the protein myostatin. It is known to inhibit muscle growth: animals with the "switched Off" mstn gene have significantly more muscle mass than wild-type individuals, while the proportion of adipose tissue is very low. Blocking myostatin is already used in cattle breeding (cows of at least one breed initially have a mutation in the Mstn gene) and is discussed in bodybuilding (although effective and permitted for human use of myostatin blockers are not yet available). Researchers led by Emily L. Germain-Leeg of the University of Connecticut School of Medicine have tested how neutralization of myostatin affects changes in bone and muscle mass resulting from prolonged exposure to microgravity. Experiments were conducted on mice that were injected with a myostatin blocker — a molecule based on the receptor for myostatin and acvr2b activin, in which the real "body" of ACVR2B was attached to the sites of binding to these proteins, but a crystallizing fragment of immunoglobulin Fc Thus, myostatin, binding to the decoy receptor, did not trigger the cascade of reactions in the cell that it normally should cause.

In addition to these rodents, scientists used mice that had the Mstn gene knocked out, and wild-type individuals acted as controls. Some individuals (40 females) lived on the ISS, and the main experiment with them lasted 33 days. Some of them returned to Earth, the rest were killed. Another 24 females were tested in parallel with them during the same period in the laboratory. In all ISS groups, biologists measured muscle and bone mass before, during, and after microgravity.

During the 33 days spent in orbit, wild-type mice lost 8-18 per cent of the mass of most major muscles: the triceps of the shoulder, quadriceps of the hip, calves, and others (comparison with the control group). In mice with the non-functioning myostatin gene, muscle mass increased over the same time, but in those who were exposed to microgravity, muscle growth was weaker.

A similar effect was observed in the case of rodents that received a decoy receptor. In addition, the mice that were given modified ACVR2B did not suffer much from bone loss due to microgravity (and their musculoskeletal system recovered faster after returning from the ISS), since this receptor affects metabolism not only in the muscles but also in the bones. It turns out that inhibitors of cascades of reactions triggered in cells by myostatin and activin can theoretically be used to reduce the loss of bone and muscle tissue in microgravity and accelerate the recovery of these tissues after a flight into space. The authors of the paper suggest that the use of "deceptive" ACVR2B and similar molecules is not limited to this. It is necessary to prevent the degradation of muscles and bones not only in cosmonauts but also in everyone who has been left without movement for a long time (people chained to a wheelchair or bed), as well as in the elderly.

Recently, we wrote that many changes in the human brain caused by a six-month stay in microgravity are reversible and pass after seven months from the moment of return to Earth. And Escherichia coli benefits from microgravity: under it, they form colonies per unit of time 2-2. 5 times more than under" full " earth's gravity. Their descendants, who have grown up already under normal conditions, retain this feature: although their rate of colony formation slightly decreases, it is still twice as high as that of the bacteria in the control group.

Photo: Se-Jin Lee

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