Twins study reveals how the human body changes in space

Results from NASA’s landmark Twins Study, which took place from 2015–2016, have finally been published in the journal Science.

The findings represent 27 months of data collection, supported by 84 researchers at 12 locations across eight states, providing the most comprehensive and integrated molecular view to date of how the human body responds to — and recovers from — the extreme environment of space.

Retired astronaut Scott Kelly and his identical twin brother Mark participated in the investigation, conducted by NASA’s Human Research Program. Mark provided a baseline for observation on Earth, and Scott provided a comparable test case during the 340 days he spent in space aboard the International Space Station. This is the first time ever that scientists have studied one twin in spaceflight and one on the ground, with Scott becoming the first American astronaut to spend nearly a year in space.

The record-setting mission saw Scott participate in a number of biomedical studies, including research into how the human body adjusts to known hazards, such as weightlessness and space radiation. Meanwhile, Mark participated in parallel studies on Earth to help scientists compare the effects of space on a body down to the cellular level.

Key results from the study include findings related to gene expression changes, immune system response and telomere dynamics. Other changes include broken chromosomes rearranging themselves in chromosomal inversions, and a change in cognitive function. Many of the findings are consistent with data collected in previous studies and other research in progress.

“We observed thousands and thousands of changes at the molecular and genetic level when Scott Kelly was in space,” said study co-author Christopher Mason from Weill Cornell Medicine. “We observed changes in the small molecules in the bloodstream; changes in how genes go up and go down; changes in how DNA was packaged. The telomeres got longer, the microbiome in the gut changed; we saw stresses in the body, changes in his vision. And also, we’ve been looking intensely at immune cells, which are notoriously adaptive.”
 

The telomeres in Scott’s white blood cells, which are biomarkers of ageing at the end of chromosomes, were unexpectedly longer in space then shorter after his return to Earth, with average telomere length returning to normal six months later. In contrast, his brother’s telomeres remained stable throughout the entire period. Because telomeres are important for cellular genomic stability, additional studies on telomere dynamics are planned for future one-year missions to see whether results are repeatable for long-duration missions.

A second key finding is that Scott’s immune system responded appropriately in space. For example, the flu vaccine administered in space worked exactly as it does on Earth. A fully functioning immune system during long-duration space missions is critical to protecting astronauts from opportunistic microbes in the spacecraft environment.

A third significant finding is the variability in gene expression, which reflects how a body reacts to its environment and will help inform how gene expression is related to health risks associated with spaceflight. While in space, researchers observed changes in the expression of Scott’s genes, with the majority returning to normal after six months on Earth. However, a small percentage of genes related to the immune system and DNA repair did not return to baseline after his return to Earth. Further, the results identified key genes to target for use in monitoring the health of future astronauts and potentially developing personalised countermeasures.

“The gene expression in Scott’s white blood cells changed in flight,” said Craig Kundrot, Director, Space Life and Physical Sciences Research and Application (SUPSRA) Division at NASA Headquarters. “7% of the gene expression persisted six months after his flight. So genes are not on or off — they’re throttled, like your automobile engine. 7% of them were throttled in a different position even six months after flight.”

Bearing in mind that Scott’s mission was less than a year in duration, Mason speculated, “The really big question is, what about three years? Should we expect to see three times the number of changes, 10 times the number of changes? Really, we don’t know at this point, ‘cause this is the first study of its kind.”

“We have only scratched the surface of knowledge about the body in space,” admitted Jennifer Fogarty, Chief Scientist of the Human Research Program at NASA’s Johnson Space Center. “The Twins Study gave us the first integrated molecular view into genetic changes, and demonstrated how a human body adapts and remains robust and resilient even after spending nearly a year aboard the International Space Station.”

According to Mason, the study results provide far more than just raw data — they also foresee a future where the genetic code of astronauts could be optimised for long-term missions.

“So this could be physical changes to how they do exercise, and also even just how they take vitamins, and how they manage their microbiome,” Mason said. “Really, every molecule is fair game for making sure it’s customised for each astronaut.”

“The Twins Study has been an important step toward understanding epigenetics and gene expression in human spaceflight,” said JD Polk, Chief Health and Medical Officer at NASA Headquarters. “Thanks to the twin brothers and a cadre of investigators who worked tirelessly together, the valuable data gathered from the Twins Study has helped inform the need for personalised medicine and its role in keeping astronauts healthy during deep space exploration, as NASA goes forward to the Moon and journeys onward to Mars.”

Image caption: Astronaut Scott Kelly (right) along with his brother, former astronaut Mark Kelly (left), at the Johnson Space Center. Photographer: Robert Markowitz. Image courtesy of NASA Johnson under CC BY-NC 2.0

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