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Defects in mitochondria may clarify many health issues observed during space travel


For space travel to be effective, it’s necessary to understand and find methods to address fundamental reasons for the health issues that have been seen in astronauts who have spent extended periods of time in outer space.

These issues include deficiency of bone and muscle mass, immune dysfunction, and heart and liver issues. Utilizing data collected from various resources, a multidisciplinary group is reporting the discovery of a common thread that drives this harm: mitochondrial dysfunction.

The scientists used a systems method to look at widespread alterations affecting biological function. The findings are published on 25, November in the journal Cell.

“We started by asking whether there is some kind of universal mechanism happening in the body in space that could explain what we have observed,” says Afshin Beheshti, a principal investigator and bioinformatician at KBR in the Space Biosciences Division of the NASA at Ames Research Center in California’s Silicon Valley and a visiting scientist at the Broad Institute.

“What we found over and over was that something is happening with the mitochondria regulation that throws everything out of whack.”

The investigators analyzed data acquired from NASA’s GeneLab platform, a comprehensive data set that includes data from animal studies, the NASA Twin Study, and samples collected from 59 astronauts over many years of space travel.

Huge numbers of researchers who participated in this study are engaged with GeneLab’s Analysis Working teams, which draw from institutions all over the world. The platform contains a range of “omics” data related to changes in tissues and cells that occur because of the combined effects of space radiation and microgravity, including proteomic, metabolomic, transcriptomic, and epigenomic data.

The scientists used an unbiased method to look for correlations that could clarify the widespread changes observed. Beheshti says, “We compared all these different tissues from mice that were flown in space on two different missions, and we saw that mitochondrial dysfunction kept popping up.”

“We looked at problems in the liver and saw they were caused by pathways related to the mitochondria. Then we looked at problems in the eyes and saw the same pathways. This is when we became interested in taking a deeper look.”

He clarifies that mitochondrial suppression, just as overcompensation that can once in a while happen because of that suppression, can lead to numerous systemic organ responses. They can also clarify huge numbers of the common changes found in the immune system.

Utilizing their discoveries from mice as a beginning point, the scientists then looked at whether the same mechanisms could be involved with humans in space. Analyzing data from the NASA Twins Study, in which identical twins Scott and Mark Kelly were followed over time, the former on the International Space Station and the latter on the ground, they saw numerous changes in mitochondrial activity.

Some of these changes could explain modifications in the distribution of immune cells that occurred in Scott during his year in space. They also used physiological data and blood and urine samples that had been collected from dozens of many different astronauts to confirm that mitochondria activity in different cell types had been altered.

Beheshti says, “I was completely amazed to see that mitochondria are so important because they weren’t on our radar.”

“We were focusing on all the downstream components but hadn’t made this connection.”

He adds that mitochondrial dysfunction can also help explain another common problem with extended space travel: disrupted circadian rhythms. Since the team first reported their findings within NASA, other NASA scientists have begun making connections between mitochondrial changes and common space-related cardiovascular problems as well.

The hope is that now those mitochondrial issues have been identified as a cause of so many health risks related to space travel, countermeasures could be developed to address them. “There are already many approved drugs for various mitochondrial disorders, which would make it easier to move them toward this application,” Beheshti notes. “The low-hanging fruit now would be to test some of these drugs with animal and cell models in space.”

Reference: Cell, da Silveira et al.: “Multi-Omics Analysis Reveals Mitochondrial Stress as a Central Hub for Spaceflight Biological Impact”

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