International Space Station astronauts show temporary effects in their white blood cells during long-duration missions, but more study is required to understand the extent.
A new study in Frontiers of Immunology published June 22 shows alterations to the gene expression – or how the body reacts under stress – of (mainly) protein-coding genes during long-duration missions on the orbiting complex of between 4.5 months and 6.5 months.
That said, levels return to normal often within a few weeks – and if not, by about a year after return. Astronauts were not tracked for this study beyond 12 months post-flight. The study suggests – but does not conclusively show – that gravity may have a critical role in immune system response, and may explain why astronauts appear to be more prone to illnesses like shingles, herpes sores and other viruses while in orbit.
“My interest has been trying to understand the biology of immobility, and that has relevance for clinics, in particular for bedridden people,” participating author Odette Laneuville, an associate professor at the department of biology at the University of Ottawa, told SpaceQ. The research was funded by the Canadian Space Agency and the first author listed in the new paper is the University of Ottawa’s Daniel Stratis.
Astronauts are not bedridden, but there are numerous “bed studies” of volunteers who spend weeks lying down that show analogies between those conditions and the microgravity conditions one faces in spaceflight. Like astronauts returning from space, patients need an extensive rehab program to recover from being in bed for long periods of time – and some of those patients struggle with recovery, Laneuville said.
The new study was sparked by a conversation, she added: “I was approached by a physician who works with those patients, which [have] what we call severe deconditioning. He said, ‘Why do you think that some patients respond to therapy, and some don’t?’ “
This conversation took place roughly 10 years ago, as Laneuville remembers almost in parallel watching a video of CSA astronaut Chris Hadfield’s deconditioning in Kazakhstan in the moments after he landed from his last, half-year mission in space in 2012-13. (Hadfield has fully recovered, as is the typical case with astronauts.)
In the intervening years, Laneuville and her team have picked up extensive space experience at DLR (the German space agency) and in studies in Toulouse, France. Laneuville was then named as a co-investigator on MARROW, a CSA-backed study (led by fellow University of Ottawa researcher Guy Trudel) that collected samples from astronauts in 2015-20 to study blood marrow. One participant was CSA astronaut David Saint-Jacques, who voluntarily disclosed his identity, although not all astronauts chose to do so. It was from the MARROW samples that this study’s samples also came.
The new study examined 14 astronauts (3 women and 11 men) who lived on the ISS for long-duration missions on 2015 and 2019; notably, one-year missions were not included, but only a minority of astronauts have done so on the ISS and most of those flights took place after the study period.
Laneuville’s team, however, did look at the data from the so-called “Twins Study,” which involved NASA astronaut Scott Kelly during a year in space in 2015-16. Among many other items, his gene expression was compared with twin brother (and NASA astronaut) Mark Kelly, who remained on the ground during the same period.
While Scott Kelly did see small differences in gene expression compared to his twin, most returned to normal roughly six months after spaceflight, with the exception of 7 percent – a “very minimal” amount, according to a NASA statement.
Laneuville called the Twins Study “remarkable because of the extent of the analyses they conducted,” as they did not consider all the same parameters. But there were forced limitations in terms of personnel, and the collection periods were different as well.
Notably, only two people participated in the Twins Study, instead of 14 in Laneuville’s – and they were both men. Only one person flew in space during the survey period of the Twins Study, too. Laneuville also said that although her study group was small, there was more immune variability between individuals due to the different exposure that people have in childhood.
The participating astronauts in Laneuville’s study had their blood drawn 10 times during the study period: once before flight, four times in flight, and five times after flight. The samples were particularly analyzed for leukocytes, which are part of the body’s immune system.
A tiny fraction of the leukocytes’ 15,410 genes were expressed differently during the study timeline, particularly in two clusters with 247 and 29 genes respectively. The first cluster, relating to immunity, saw gene expression decreasing in space and increasing on Earth. The second cluster, relating to cellular structures and functions, had the opposite effect: gene expression increased in orbit and decreased back on-planet.
Together, the two results for this study suggest that gene expression changes during orbit can decrease the strength of the immune system. That said, only 14 astronauts were analyzed for a limited time, so drawing broader implications will require more cohorts. Researchers also say when immune resistance comes back will depend on factors such as age, sex, genetic differences between individuals and how the individuals were exposed to pathogens in childhood.
The gene expression may be induced by the famous “fluid shift” that happens in astronauts during microgravity, when blood plasma moves more to the upper parts of the body (which includes the lymphatic system) and reduces by roughly 10 percent to 15 percent in the first days of spaceflight.
“The future direction is really to apply this finding, or this list of genes, to design some countermeasures to mitigate that negative effect in space,” Laneuville said. She suggested some directions could include identifying biomarkers, or looking into viruses that may be activated while latent (like shingles), to create countermeasures for patients and astronauts alike.