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Photo: NASA

Scott Kelly’s year in space highlights risks to DNA and brains

‘One of the best examples of human plasticity and adaptability that we’ve ever seen’

After years of processing data, the official release of a study comparing twin astronauts Scott and Mark Kelly is finally here. One clear trend emerged in the findings, which were published today in the journal Science: a year in space changed Scott Kelly’s body, but many of those changes were only temporary and vanished after time back on the ground.

The exceptions — like damage to Scott’s DNA and drops in his mental performance — give NASA a starting point for research into the effects of extended spaceflight on the human body. With his 340 days aboard the International Space Station, Scott has had the longest stay in space of any American. As Scott has said, space is hard: radiation, weightlessness, the restrictive diet, a screwed-up sleep schedule, and confinement can take a toll on the body. NASA needs to know what to be on the lookout for as the space agency makes plans to send people first to a lunar station and then, maybe, to Mars.

Over the 25 months surrounding Scott’s trip to space, research labs across the country measured his mind and body and collected his blood, pee, and poop. They made the same measurements and collected the same samples from an almost perfect control subject: Scott Kelly’s identical twin brother Mark Kelly, a former astronaut and current Senate candidate who spent that year on the ground.

The findings, overall, are good news, says Christopher Mason, an associate professor at Weill Cornell Medicine and one of the authors on the study. “The really dramatic response of the human body in flight is only matched by how quickly it reverted back to the preflight stage when it got back to Earth,” Mason says. “Scott really showed one of the best examples of human plasticity and adaptability that we’ve ever seen.” For the most part, the results line up with the preliminary results that were released in 2017.

There are some major caveats to the research. For one thing, the researchers examined only two genetically identical people, which means they can’t generalize the findings to other astronauts. They also can’t tell whether spaceflight caused any of the changes that Scott experienced during or after his time on the International Space Station. And they don’t know for certain whether any of the changes they identified will cause health problems for him long term. “You can’t really draw any big conclusions,” says Petra Illig, a doctor specializing in aerospace medicine who was not involved in the research. “But you can get some ideas of what some of the issues may be.”

During his 340 days on the space station, Scott lost weight (his brother Mark gained weight), peed less frequently, and showed signs of dehydration. The makeup of his microbiome changed, but it bounced back after spending time on the ground. Changes in the pattern of chemical tags that tell cells whether to turn certain genes on or off didn’t change much overall. And while his immune system showed some big shifts while he was in space, the flu vaccine worked just fine for him, which suggests that his immune system was still capable of doing its job.

More worrying, the blood supply to the back of his eye swelled, and parts of his retina thickened, which can cause vision problems. Scott’s carotid artery thickened as well, which could be a sign of cardiovascular disease or stroke in the future. Of all the results described in the study, four, in particular, stood out to us.

Gene behavior

Scott Kelly’s gene activity changed in space, which means his cells were turning certain genes on or off in different patterns than they did on Earth. When Scott got to the space station, about 1,400 genes started behaving differently, which was possibly the result of changing demands on his body. But the big shifts happened in the latter half of the trip, particularly for the genes that are involved in immune responses and DNA damage. That could be a big deal for longer space trips because it suggests bigger changes to Scott’s body the longer he was up in space.

Those changes didn’t stop once he landed: shortly after touching down on Earth, Scott experienced a massive spike in inflammation. “Space is hard, landing is harder, and you could just see it in his body,” says Mason, who led the gene expression investigation. Six months out, however, the activity of more than 91 percent of the genes that changed during flight were back to normal. As for the genes that didn’t bounce back, it’s hard to know what to make of them, Mason says. “Does that mean the immune system is still freaking out on Earth?” Mason says. “No, it could just mean that’s what it does for a while after a stressful experience. Maybe that’s a good thing.” They won’t know until they see similar changes in more astronauts.

Shrinking telomeres

Susan Bailey, a professor of radiation cancer biology at Colorado State University-Fort Collins, took an even closer look at the DNA. Bailey’s team wanted to know what a year in space would do to the structures at the ends of Scott Kelly’s chromosomes, called telomeres. These help keep chromosomes stable, Bailey explains. “Like the thing on the end of your shoestring, it helps it keep from fraying,” she says.

Telomeres usually get shorter as we age and with stress, and shortened telomeres have been linked to age-related diseases like cardiovascular disease. So in the stressful environment of spaceflight, you’d expect telomeres to shrink. Instead, Bailey’s team found that Scott Kelly’s telomeres lengthened. “It’s exactly the opposite of what we thought, it was in every sample, every time point,” Bailey says. Weirder still, Scott’s telomeres shrank as soon as he landed. By nine months out, the team saw more missing or seriously shortened telomeres than they did before. “So, not a fountain of youth,” Bailey says.

DNA damage

During Scott’s time on the ISS, he experienced about 146 millisieverts of ionizing space radiation, which is about equivalent to 10 to 15 abdominal CT scans, Bailey says. So her team also analyzed the Kellys’ DNA for damage linked to radiation. They found that before the flight, Scott and Mark Kelly had similar levels of a form of damage where the DNA breaks out of a chromosome, flips around, and gets stuck back in. But during his time in space, this damage started increasing for Scott and continued climbing in the months after he landed. “And that could put him at increased risk of genomic instability, and that’s one of the things associated with cancer,” she says.

Dan Arking, a professor at Johns Hopkins Medicine who was not involved in the study, agreed that the finding is concerning. “Mutation’s generally not good for you,” he says. “You really have to worry about the risk of cancer and things like that that are going to be associated with these kinds of mutations.” But he cautions that there was a lot of variability baked into the measurements, and we won’t know if this trend holds true unless we see it in another study.

Photo: NASA


DNA damage and altered gene activity weren’t the only changes that persisted after Scott landed: he also didn’t perform as well on cognitive tests as he did before and during the flight (nor did he perform as well as his brother). These tests measured things like memory, attention, emotion recognition, risk-taking, and they’re specifically designed for astronauts, according to Mathias Basner, a professor at the University of Pennsylvania’s Perelman School of Medicine who led the cognitive testing effort. “Taking an off-the-shelf test geared toward the general population doesn’t really work for astronauts because many of these tests aren’t really difficult enough for them,” he says.

For the six months after he landed, Scott was slower and less accurate on most of the tests, Basner’s team found. The decreases weren’t huge, according to Basner. “It is a relevant cognitive decline, but it’s not to a degree where he would stop functioning,” he says. The team can’t explain what’s going on. It could be Earth’s gravity, long-term changes to the brain from spaceflight, or that Scott had just retired and had a busy schedule after landing, Basner says. “We will never be able to say for sure because we only have one subject.”

Despite all of the caveats and the need for more research, it’s an important study as NASA continues looking toward the future and longer spaceflights. “It’s probably the most comprehensive study that has ever been performed on an astronaut,” says Markus Löbrich, a professor at the Technical University of Darmstadt who wrote a commentary about today’s paper. He thinks the research will be important for designing future space missions. Illig agrees: “There’s a ton of stuff happening on a very, very microscopic, molecular basis that we need to understand before we send humans out to colonize off planet.”


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