NASA/Robert Markowitz

For 340 days, NASA astronaut Scott Kelly lived and worked inside the International Space Station while his identical twin brother Mark, a former astronaut, was going about life down on Earth. In that time, the brother's bodies -- their genes, guts, immune systems, blood and brains -- were part of an elaborate, multifaceted study designed to teach us how spaceflight might affect human bodies.

Over the course of a year, the Kelly brothers were put under the proverbial microscope, subjected to a bit of prodding and pushing, and provided blood, saliva and urine samples to a host of research teams. The idea being that Mark, down on Earth, would provide a valuable control subject to compare with Scott as he spent a year in orbit. Every few weeks, Scott's frozen biological samples were ferried between the space station and Earth by Soyuz resupply rockets.

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The results of the "Twin Study," which featured researchers from 12 different universities working across 10 different projects, are set to be published in the April 12 issue of Science. The findings demonstrate how the human body responds to time spent in space, unraveling the complex changes that take place when it's exposed to the wholly alien experience of living in microgravity.

Space vs. staycation

The research team studied a wide variety of human physiological processes, including gene expression, gut health, immunity and cognition, allowing them to pin down just how much space might change Scott while his brother stayed at home.

Preliminary results had already filtered out since the experiment's completion in 2016, such as those pointing to the idea that space lengthens telomeres, the protective caps on chromosomes that generally shorten the older we get. Surprisingly, it seems that space is somehow protective against telomere shortening, which could help determine the risks and benefits of long-duration spaceflight.

But the scope of the new study went far beyond just aging.

"It is likely that these two astronauts have been studied at greater depth than any other person in history," said Chris Mason, a lead researcher studying the gene expression of the Kelly brothers, in a press release.

"They give us a really in-depth view of cellular, molecular and physiological changes that can help us learn what is in the range of what a human can endure."

DNA duo

Mason and his team analyzed the genes of Scott and Mark across six months before Scott's trip, during his time aboard the station and nine months after his return. They found dramatic shifts in gene expression, particularly during the final six months of the mission where Kelly's genes showed marked changes.

For the most part, Scott's expression returned to normal once he had two feet back on Earth, but some changes remained, leading to DNA damage, cognitive deficits and impairment of the immune system. While that sounds ominous, Mason states that he's not sure whether those changes are actually good or bad yet -- and further study is required to untangle that mystery a little more.

A second team at Johns Hopkins University, lead by Andy Feinberg, studied the "epigenetic" effects -- chemical changes in gene expression unrelated to DNA changes. Feinberg's team also collected blood samples and looked at "DNA methylation", a process that can change how genes are expressed. Nine months into the mission, they saw a 4% decrease in methylation of Scott's DNA compared to Mark's.

"It was encouraging to see that there was no massive disruption of the epigenome in either Mark or Scott," said Lindsay Rizzardi, who worked on Feinberg's team, in a press release. "The findings give us clues to what we should examine more closely in future studies of astronauts."

A bellyful of space

Researchers at Northwestern University put the Kelly brothers gut health under the microscope and found that Scott, up on the ISS, experienced a change to his "microbiome" -- the world of microbes that call his gut home.

To understand how the invisible world inside Scott's gastrointestinal tract was changing, the researchers took fecal samples from before, during and after Scott's space station visit. In this particular case, it was more interesting to compare across time, rather than with his brother on Earth, to understand how a year in space changes the community of gut bacteria he harbored. They found that the ratio between two particularly prominent kinds of gut bacteria dramatically shifted during spaceflight, but returned to normal once he was back on Earth.

"We think that microgravity has an effect on the bacteria," said Fred Turek, who led the microbiome study, in a press release. However, the Northwestern team noted that it is a little hard to definitively say microgravity was wholly responsible, because there are other factors, such as diet, sleep and stress, that may contribute to the changes the team saw.

The reason the results are so powerful is because identical twins like the Kelly brothers not only look the same (although Mark has, in the past, cultivated a wispy, brown mustache which differentiates the two) but have similar genetic profiles. Their genes aren't exactly the same, but they're about as close as we can get without a direct Kelly clone, providing a way to understand how space changes the very stuff that makes us up: DNA.

Some of the researchers caution the study, by its nature, is limited in scope. Only one set of astronaut twins were studied. If we had hundreds of identical twins, would we see that same result? And how much did being in space actually contribute to the changes seen in Scott?

Those are just some of the lingering question that researchers will hope to answer in the future. But we do know one thing for sure: Space has no regard for human life. The good news is the investigators suggest that human health can be "sustained" during a year in space. Scott Kelly was certainly affected by the stresses of space but once he got back to Earth, many of the changes his body underwent reversed as if he wasn't in space at all.

With NASA's sights set on getting back to the moon in the next five years and an eye to long-term missions to Mars, it will be increasingly important to determine how space might change us.

Originally published April 11, 2 p.m. PT

Updated 4:50 p.m. PT: Additional video added,