Flying into space is a dream for many — but it also comes with many risks and problems. And staying healthy is one of the key problems. We’ve known for a while that muscle atrophy is a problem for astronauts, but now, researchers have shown that simply being in outer space can make muscles get “older”.

But there’s some good news as well: we know the genes responsible for this.

Muscle on a chip — now in space

Skeletal muscle constitutes about 40% of human body weight and plays a crucial role in movement and stability. These muscles are constantly being regenerated, a process primarily driven by satellite cells, a type of muscle stem cell that activates upon injury or disease. These cells fuse to form new muscle fibers, a process essential for muscle repair and growth. However, exposure to microgravity, as experienced during space travel, significantly hinders this regenerative capacity.

Basically, researchers found that human cells sent to space experience something that resembles accelerated aging.

To investigate the challenges posed by microgravity (what most people would refer to as weightlessness experienced in space), scientists have developed a muscle-on-a-chip platform. This technology involves creating engineered human muscle tissue on a micro-scale device that can simulate muscle function and regeneration. In this study, human skeletal muscle cells were first cultured in an ideal environment.

What we see in astronauts fits with what we see in cells

The engineered muscle constructs were then sent to the International Space Station National Laboratory (ISSNL) to study the effects of microgravity. These muscle-on-a-chip devices were housed in custom-made bioreactors that maintained optimal conditions for cell growth during space travel and experiments.

After seven days in microgravity, the muscle-on-a-chip constructs displayed significant changes compared to those kept in normal gravity conditions on Earth. First, there was a metabolic shift towards lipid and fatty acid metabolism in the microgravity samples. Additionally, there was an increase in the expression of some genes. This led to a higher rate of programmed cell death, which negatively impacts muscle regeneration.

Another notable finding was that microgravity induces mitochondrial stress. Proper mitochondrial function is essential for muscle regeneration, as it supports the energy needs of repairing and forming new muscle fibers. This stress also leads to reduced regenerative capacity.

Overall, the study found that muscle-on-a-chip constructs exposed to microgravity showed similarities to sarcopenia, a condition of age-related muscle loss.

Most of our information about what happens to the human body in outer space comes from, well, human bodies. Astronauts who go on missions are thoroughly investigated, showing a muscular degradation associated with microgravity environments. This degradation was also confirmed in studies on animals sent into space. This new research further confirms the findings — now on a cellular level.

But there’s more.

A promising method

The muscle-on-a-chip platform also offers a promising avenue for drug screening to counteract the adverse effects of microgravity. In this study, two drugs were tested: insulin-like growth factor-1 (IGF-1) and a 15-hydroxyprostaglandin dehydrogenase inhibitor (15-PGDH-i). Both drugs have shown potential in promoting muscle growth and regeneration.

The addition of these drugs to the microgravity-exposed muscle constructs partially inhibited the negative effects of microgravity. Specifically, IGF-1 and 15-PGDH-i helped maintain normal gene expression levels associated with muscle regeneration, lipid metabolism, and cell survival pathways. This finding suggests that these drugs could mitigate the detrimental impacts of microgravity on muscle tissue.

So in addition to confirming a problem and suggesting some solutions for it, the researchers also showed the benefits of this muscle-on-a-chip framework for sacropenia-type conditions. By replicating the muscle environment in a controlled, scalable platform, researchers can gain deeper insights into muscle biology and develop targeted therapies.

As for astronauts, the implications of this study are profound. The successful modeling of sarcopenia-like conditions using muscle-on-a-chip technology in space underscores the potential for advanced research and drug screening in microgravity. And we absolutely need better solutions to keep their muscles strong. Who knows? If we’re lucky, the same solutions that keep astronauts kicking could translate into medical advancements that can benefit millions suffering from muscle degeneration here on Earth.

Journal Reference: Kim, S., Ayan, B., Shayan, M., Rando, T.A., Huang, N.F. (2024). Skeletal muscle-on-a-chip in microgravity as a platform for regeneration modeling and drug screening. Stem Cell Reports. doi:10.1016/j.stemcr.2024.06.010