Critical parts of a cell’s energy production machinery, the mitochondria, can be made dysfunctional due to changes in gravity, radiation exposure and other factors, according to new research.
Spaceflight is known to impose changes on human physiology with unknown molecular etiologies. To reveal these causes, da Silveira et al. used a multi-omics, systems biology analytical approach using biomedical profiles from 59 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. 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 hazards to astronauts’ health in long-duration space missions.
In addition to the known increased cancer risk from chronic low doses of radiation exposure, astronauts that returned from missions on the International Space Station presented with health issues similar to geriatric stress, including bone and muscle mass loss, central nervous system issues, immune dysfunction, and cardiovascular health risks.
Future success in long-duration space exploration requires a comprehensive understanding of the impact of spaceflight on human biology, and such knowledge could be used to design efficient countermeasures that would benefit astronauts and the health of people on Earth.
“We started by asking whether there is some kind of universal mechanism happening in the body in space that could explain what we’ve observed,” said Dr. Afshin Beheshti, a principal investigator in the Space Biosciences Division at NASA’s Ames Research Center and the Broad Institute.
“What we found over and over was that something is happening with the mitochondria regulation that throws everything out of whack.”
Dr. Beheshti and colleagues analyzed data obtained from NASA’s GeneLab platform, the agency’s Twins Study, and samples collected from 59 astronauts over decades of space travel.
The GeneLab platform contains a range of ‘omics’ data related to changes in tissues and cells that occur due to the combined effects of space radiation and microgravity, including proteomic, metabolomic, transcriptomic, and epigenomic data.
The researchers used an unbiased approach to look for correlations that could explain the widespread changes observed.
“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,” Dr. Beheshti said.
“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.”
Mitochondrial suppression, as well as overcompensation that can sometimes occur because of that suppression, can lead to many systemic organ responses.
They can also explain many of the common changes seen in the immune system.
Using the discoveries from mice as a starting point, the scientists then looked at whether the same mechanisms could be involved with humans in space.
Examining data from the 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 many changes in mitochondrial activity.
Some of these changes could explain 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 that had been collected from dozens of other astronauts to confirm that mitochondria activity 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,” Dr. Beheshti said.
“We were focusing on all the downstream components but hadn’t made this connection.”
“Mitochondrial dysfunction can 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 in the Georgetown University Medical Center.
“From this, and other planned ventures to the Moon, and eventually Mars, we hope to learn much more about the effects that spaceflight can have on metabolism and how to potentially mitigate adverse 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 as a Central Biological Hub for Spaceflight Impact. Cell 183 (5): 1185-1201; doi: 10.1016/j.cell.2020.11.002
