Engineered "Mighty Mice" sent to space retain their mass in low gravity

The short- and long-term impacts of the space environment on the human body is still a great unknown, and one that a number of research groups are trying to get to the bottom of. The results of an interesting experiment in which muscled-up mice were sent into space has shed some new light on the matter, revealing that these brawny rodents could retain their muscle mass in low-gravity when engineered to lack a certain protein.

While there is a lot we don’t know about human physiology and space, we do know that weightlessness can cause bones to lose calcium and muscles to lose mass as they atrophy. We’ve seen a few inventive approaches to counteract this process and ensure the health of astronauts, including skin-tight body suits and human centrifuges, but the authors of the new study have instead sought answers by diving into genetics.

The team was led by Professor Se-Jin Lee at The Jackson Laboratory, who more than two decades ago discovered a protein called myostatin that limits muscle growth in mice and which could be turned off to allow for considerable muscle gains. As it turns out, this protein plays the same role in a number of species including humans, spawning a number of research projects geared towards developing a form of “exercise pill” to tackle obesity and other health problems.

Last December, Lee and his team launched 40 mice into space for a 33-day stint living aboard the International Space Station (ISS). This included a group of regular mice, a group of so-called "Mighty Mice" engineered to be missing the myostatin gene, and another group that were given a compound called ACVR2B/Fc that inhibits not just myostatin, but a protein that complements it called activin A.

These were compared to similar groups of mice kept on Earth in conditions replicating those on the ISS, but without microgravity. Unsurprisingly, the regular mice lost considerable mass during their stay on the ISS, between eight and 18 percent of weight in individual muscles and 11 percent of their bone density, compared to the regular mice on Earth.

Meanwhile, the group engineered to lack myostatin maintained their muscle mass and the group receiving the ACVR2B/Fc compound actually gained muscle mass and exhibited an increase in lean body weight of 27 percent, compared to the same group on the ground which gained 18 percent lean body weight. Both of these groups of mice also showed an increase in bone mineral density.

Using molecular analysis, the researchers also delved into the differences between these groups of mice, revealing large differences in protein levels, expression of dozens of genes and signaling pathways linked to muscle and bone maintenance.

The team hopes improving our understanding of muscle mass and bone density in this way, along with the different factors that influence them, can guide the development of specialized exercise programs for astronauts traveling into deep space. Additionally, this kind of research could lead to new therapies for people with limited mobility on Earth who suffer from ailments like muscle atrophy and bone fragility.

The research was published in the journal Proceedings of the National Academy of Sciences.

Source: The Jackson Laboratory