One biological molecule may explain how space affects astronauts' health

For more than 50 years, humans have been fascinated by the idea of exploring the cosmos, sending astronauts to the Moon and the International Space Station in low-Earth orbit.

But all those space journeys come at a cost. The microgravity environment appears to take a toll on the human body, affecting astronauts' brains, hearts, muscle and bone mass, and vision. But because so few people have been to space, little is known about the true extent of these worrying symptoms or what drives them in the body.

To try and tease out what exactly is going on in astronauts' bodies, more than 200 scientists pooled their efforts and their data to generate the largest set of space-related biological data ever produced. Together, they identified one common thread behind all the changes taking place in the human body as a result of time in space — mitochondrial dysfunction.

Their work was published in a series of papers on Wednesday in the journal Cell and in affiliated journals.

Afshin Beheshti is co-author on the work and a researcher and bioinformatician at NASA for the GeneLab Project. He tells Inverse part of why he was so curious about the biological effects of space is because there are so many unknowns.

Studying the effects of spaceflight on the human body is challenging: Few people have ventured out into space, so there's a limited pool of people to participate in research, and sending out samples to space for future analysis is also difficult and costly. That's why the scientists turned to one another for help.

The researchers used data from experiments which involved sending mice up to the International Space Station and observing any changes in their health compared to control mice on Earth. They also used data collected during NASA's infamous Twin Study, in which NASA astronaut Scott Kelly spent nearly a year on the space station, while his identical twin Mark Kelly remained on the ground.

They also took physiological data from 59 astronauts, as well as data from blood and urine samples collected from dozens of other astronauts over the years as part of NASA's GeneLab.

The question Besheti and his colleagues sought to answer: "Is there a master switch that could be changing your entire body in space?"

From the amassed data, the scientists noticed a common thread: changes in mitochondrial activity. Mitochondria are a kind of molecule which act like the powerhouses for the cells in our body. They are essentially a digestive system for cells, and break down nutrients to produce energy. It was not what the scientists had expected, Beheshti says, but it does jibe with past research.

"As we kept analyzing, certain biological patterns kept popping up," Beheshti says. "The mitochondria was surprising because that wasn’t really on my radar, but it connects a lot of these things together."

The study suggests mitochondrial stress — affecting how cells get energy — leads to changes in gene regulation, metabolism, and the immune system in both mice and humans after time spent in space. It may be the root cause of symptoms so diverse as bone problems, vision issues, and muscle wasting, the study suggests. There is also some indication the changes in mitochondria are linked to increased oxidative stress, too, according to the study.

But the scientists behind the research are still not sure whether the changes occur as the result of another process — a kind of domino effect — or if mitochondria themselves set off all the other changes to the body. Beheshti has his own suspicions.

"In my opinion, it's an effect," Beheshti says. "You go through a hyper-gravity effect, you get the stress that happens and once it stabilizes, something might change right away."

"This mitochondrial dysfunction I imagine is a cumulative effect due to all the changes," he adds.

Now that scientists have identified mitochondria as a common theme, the next step is to find ways to mitigate mitochondrial changes to protect the health of astronauts in space.

Abstract: Spaceflight is known to impose changes on human physiology with unknown molecular etiologies. To reveal these causes, we used a multi-omics, systems biology analytical approach using biomedical profiles from fifty-nine astronauts and data from NASA’s GeneLab derived from hundreds of samples flown in space to determine transcriptomic, proteomic, metabolomic, and epigenetic responses to spaceflight. Overall pathway analyses on the multi-omics datasets showed significant enrichment for mitochondrial processes, as well as innate immunity, chronic inflammation, cell cycle, circadian rhythm, and olfactory functions. Importantly, NASA’s Twin Study provided a platform to confirm several of our principal findings. Evidence of altered mitochondrial function and DNA damage was also found in the urine and blood metabolic data compiled from the astronaut cohort and NASA Twin Study data, indicating mitochondrial stress as a consistent phenotype of spaceflight.