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Critical parts of a cell’s energy-producing mechanism, the mitochondria, may be dysfunctional due to changes in gravity, radiation exposure, and other factors, according to new research.
Spaceflight is known to impose changes to human physiology with unknown molecular etiologies. To reveal these causes, da Silveira et al. used a multi-omics and systems biology analytical approach using biomedical profiles of 59 astronauts and data from NASA’s GeneLab derived from hundreds of samples flown into space to determine transcriptomic, proteomic, metabolomic and epigenetic responses to space flight. Image credit: da Silveira et al., doi: 10.1016 / j.cell.2020.11.002.
Humanity is on the brink of a new era in space exploration, with NASA and international partners committed to returning to the moon and planned manned missions to Mars.
Exposure to space radiation and microgravity are primary health risks for astronauts on long-duration space missions.
In addition to the known increased risk of cancer due to chronic low doses of radiation exposure, astronauts who returned from missions on the International Space Station experienced health problems similar to geriatric stress, including bone and muscle loss, central nervous system, immune dysfunction, and cardiovascular health risks.
Future success in long-term space exploration requires a thorough understanding of the impact of space flight on human biology, and that knowledge could be used to design efficient countermeasures that benefit astronauts and the health of people on Earth.
“We started by wondering if there is some kind of universal mechanism happening in the body in space that could explain what we observed,” said Dr. Afshin Beheshti, a lead investigator of the Space Biosciences Division at the Ames Research Center of the NASA and the Broad Institute.
“What we’ve discovered over and over is that something is happening with the regulation of mitochondria that knocks everything out.”
Dr Beheshti and colleagues analyzed data obtained from NASA’s GeneLab platform, the agency’s twin study, and samples collected from 59 astronauts over decades of space travel.
The GeneLab platform contains a series of “omics” data relating to changes in tissues and cells that occur due to the combined effects of spatial radiation and microgravity, including proteomics, metabolomics, transcriptomics and epigenomics.
The researchers used an unbiased approach to look for correlations that could explain the diffuse changes observed.
“We compared all these different tissues from mice that had flown into space on two different missions and we saw that mitochondrial dysfunction kept popping up,” said Dr Beheshti.
“We looked at the liver problems and saw that they were caused by pathways related to mitochondria.”
“Then we looked the problems in the eye and saw the same paths. That’s when we got interested in taking a deeper look.
Mitochondrial suppression, as well as the overcompensation that can sometimes occur due to such suppression, can lead to many systemic organic responses.
They can also explain many of the common changes seen in the immune system.
Using the findings from mice as a starting point, the scientists then examined whether the same mechanisms could be involved with humans in space.
Looking at data from the Twins Study, in which identical twins Scott and Mark Kelly were tracked over time, the first on the International Space Station and the second on the ground, they saw many changes in mitochondrial activity.
Some of these changes could explain the alterations in the distribution of immune cells that occurred in Scott during his year in space.
The team also used physiological data and blood and urine samples collected from dozens of other astronauts to confirm that the activity of mitochondria in different cell types had been altered.
“I was completely surprised to see that mitochondria are so important because they weren’t on our radar,” said Dr Beheshti.
“We were focusing on all the downstream components but we hadn’t established this link.”
“Mitochondrial dysfunction may also help explain another common problem with extended space travel: disrupted circadian rhythms.”
“The launch of SpaceX earlier this month was very exciting,” said Dr. Evagelia Laiakis, a researcher at Georgetown University Medical Center.
“From this and other planned initiatives on the Moon, and ultimately on Mars, we hope to learn much more about the effects spaceflight can have on metabolism and how to potentially mitigate the negative effects for future space travelers.”
The findings were published in the November 25, 2020 issue of the journal Cell.
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Willian A. da Silveira et al. 2020. Comprehensive multi-omics analysis reveals mitochondrial stress is a central biological hub for the impact of space flights. Cell 183 (5): 1185-1201; doi: 10.1016 / j.cell.2020.11.002
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