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Microgravity is quite dangerous for us, the inhabitants of the soil: bodies no longer act constantly against gravity, muscle mass and bone density disappear. Even with two hours of exercise a day, it can take months for astronauts to regain their muscle density after a six-month stint on the International Space Station. Bone density can take years to recover.
Therefore, the effect of microgravity on the bodies of astronauts on longer missions – say, a three-year round trip to Mars – is of great concern. Now, it seems that genetically modified space mice may bring us closer to a solution.
These so-called “Mighty Mice” spent 33 days aboard the ISS and retained significantly more muscle and bone density than control mice that had not been manipulated.
“These findings,” the researchers wrote in their paper, “have implications for therapeutic strategies to combat the concomitant loss of muscle and bone that occurs in people affected by disuse atrophy on Earth, as well as in astronauts in space. especially during long missions. “
The engineering target was a protein called myostatin, which plays an important role in regulating muscle growth. Mutations in the myostatin gene can produce something called myostatin-related muscle hypertrophy, resulting in large meat cake musculature – this has been observed in some cattle and in this viral whippet.
A normal mouse (left) and a Mighty Mouse. (Se-Jin Lee, PLOS One, 2007)
To create their Mighty Mice, molecular geneticist Se-Jin Lee of the Jackson Laboratory and endocrinologist Emily Germain-Lee of the University of Connecticut and Connecticut Children’s deleted the myostatin gene. Previously, this had been found to increase skeletal muscle mass and strength and inhibit the growth of adipose (fat) tissue.
But Lee and Germain-Lee wanted to see what would happen to these Mighty Mice in microgravity. So in December of last year, they sent 40 female mice to the ISS.
These mice were divided into five groups of eight mice each. Three of these groups were completely untreated wild-type mice; served as a control for the experiment.
The fourth group were wild-type mice that were injected with ACVR2B / Fc, a protein that inhibits myostatin and activin A signaling, and therefore can induce muscle growth. The fifth and final group were the genetically modified Mighty Mice.
At the same time that the mice were aboard the ISS, similar groups were kept here on the ground, in the same environmental conditions as the space station: everything was the same except for microgravity.
Wild mice untreated in space yielded results that were expected: In their 33-day excursion, they lost 8 to 18 percent of their muscle mass and 8 to 11 percent of their bone mineral density.
The Mighty Mice, by contrast, with about twice the initial muscle mass of the wild mice, didn’t lose much muscle mass at all. As the researchers wrote in their paper, “These data show that the muscle gain due to myostatin loss is largely (if not entirely) maintained after exposure to microgravity.”
The results become even more interesting with ACVR2B / Fc mice. During a 22-day period aboard the ISS, the muscle mass of these mice increased by 27 percent and their body fat levels dropped. Meanwhile, the muscle mass of terrestrial ACVR2B / Fc mice only increased by 18 percent.
The bone mineral density of ACVR2B / Fc mice aboard the ISS also increased, although slightly less than ACVR2B / Fc terrestrial mice, in contrast to muscle mass. And, upon returning to Earth, ACVR2B / Fc mice recovered more quickly than control mice, which continued to lose bone density for a time even after re-entering Earth’s gravity.
“Thus,” the researchers wrote, “blocking myostatin / activin A signaling by treatment with the decoy receptor ACVR2B / Fc can dramatically increase bone mass even in microgravity situations and, in addition, may protect against bone loss caused by microgravity. “
It is far from a silver bullet, of course. To begin with, we are a long way from human trials. And deleting the myostatin gene is not harmless either: Previous research shows that the tendons of these mice tend to be brittle and weak, and their overall strength is reduced.
But these Mighty Mice show us that there could be a potential way to mitigate the effects of long-term space travel. And it could even help develop new treatments for diseases like osteoporosis, the gradual breakdown of bone tissue, and spinal muscular atrophy here on Earth.
The research has been published in the procedures of the National Academy of Sciences.
