The ability of grizzly bears to hibernate for up to four months without ill effects may be the key to helping prevent astronauts and medical patients from suffering debilitating muscle atrophy. An international team led by Michael Gotthardt of the Max Delbrück Center for Molecular Medicine (MDC) in Berlin is looking for genetic clues to learn more about the secrets of the sleeping bears.

If a human being was to try imitating a hibernating grizzly bear, the results would be devastating to their health, if not fatal. When a bear hibernates after gorging itself on food to build up its body fat, it can go for months sleeping or in a state of torpor without ill effects and wake up in the spring much thinner, but otherwise healthy. But a human under similar conditions would be suffering from circulatory and psychological problems as well as bone loss and muscle atrophy.

One reason why the grizzly does so well is that its metabolism shifts gears completely. The heart rate drops, the animal becomes resistant to insulin, it stops excreting body wastes, reabsorbs amino acids from its urine, and blood nitrogen levels skyrocket. But the way it preserves its muscles almost intact is of particular interest.

To understand the muscle-preserving mechanism, Gotthardt's team sought to uncover the genes in the bear's muscle cells that are transcribed and converted into proteins – which is difficult because not all the proteins of the grizzly bear, called the proteome, nor its full genome, are known.

For the study, the team took samples from grizzly bears during and between hibernations. These were then compared to observations of elderly or bedridden human patients, mice, and nematodes. Nematodes were particularly useful because their genes can be switched off relatively easily to see their effect on muscle growth, which helped to narrow down candidate genes.

Grizzly bears’ muscles manage to survive hibernation virtually unharmed Michael Gotthardt

"By combining cutting-edge sequencing techniques with mass spectrometry, we wanted to determine which genes and proteins are up-regulated or shut down both during and between the times of hibernation," says Gotthardt.

One thing that the team found was that Non-Essential Amino Acids (NEAAs), which are amino acids produced by the body instead of from food, have an important role in preventing muscle atrophy by altering the bear's metabolism.

"In experiments with isolated muscle cells of humans and mice that exhibit muscle atrophy, cell growth could also be stimulated by NEAAs," says Gotthardt. "It is known, however, from earlier clinical studies that the administration of amino acids in the form of pills or powders is not enough to prevent muscle atrophy in elderly or bedridden people. Obviously, it is important for the muscle to produce these amino acids itself – otherwise, the amino acids might not reach the places where they are needed."

The team is currently studying a set of genes in mice that control circadian rhythms for better insights into how to develop what they've learned into an effective therapy.

"We will now examine the effects of deactivating these genes," says Gotthardt. “After all, they are only suitable as therapeutic targets if there are either limited side effects or none at all."

The research was published in Scientific Reports.

Source: MDC