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NASA Twins Study Finds Space-Linked Changes to Gene Expression, Telomere Length

NEW YORK (GenomeWeb) – While spaceflight leads to changes in gene expression, telomere length, and other physiological measures, most of these alterations return to normal upon return to Earth, according to a new analysis from the NASA Twins Study.

The NASA Twins Study began when astronaut Scott Kelly spent a year at the International Space Station between March 2015 and March 2016, and the agency took the opportunity to study the effects of that time in space on Scott Kelly, as compared to his twin brother Mark Kelly, a retired astronaut, who remained on Earth. This way, the researchers said, they could begin to tease out what the effect of longer spaceflights, such as ones to Mars, might have on the human body.

Using blood, stool, and urine samples collected from the Kellys, both before Scott Kelly's spaceflight, during the flight, and after it, the researchers investigated what changes being in space wrought on Scott Kelly's epigenome, transcriptome, and more. In their analysis, appearing today in Science, the researchers reported that his telomeres lengthened, his gene expression — particularly of immune-related genes — changed, and his genomic instability was heightened while in orbit. Most, though not all, of these changes went back to baseline upon his return.

"When Scott goes into space, there are dramatic changes, there are thousands of genes and molecular changes that occur as someone goes in space," co-corresponding author Michael Snyder from Stanford University said during a press briefing. "And somewhat reassuring, of course, is that when he comes back … virtually all of those returned to normal by six months."

Prior to Scott Kelly's extended stay in space, he and his brother had similar average telomere lengths, as gauged by a qRT-PCR analysis of DNA isolated from their peripheral blood mononuclear cells. While the average length of Mark Kelly's telomeres remained the same throughout the study, Scott Kelly's telomeres lengthened. This, co-author Susan Bailey from Colorado State University said, seems to be corroborated by other epigenetic and gene expression changes.

"We're seeking correlations between some of these things to get a little more mechanistic insight into how those shifts in telomere length could be happening during space flight," she added during the briefing.

After his return to Earth, Scott Kelly's telomeres quickly shortened, with his average telomere length returning to baseline.

The researchers similarly compared DNA methylation patterns within the twins' CD4 and CD8 lymphocytes. While they noted differences between the brothers as well as between Scott Kelly's inflight and other samples, these alterations also returned to normal after his return to Earth.

Nearly 1,000 of Scott Kelly's genes had altered expression levels while he was in space, according to Weill Cornell Medicine's Christopher Mason. These changes largely affected genes involved in the immune system, which he noted was expected, as spaceflight stresses the body.

Despite this, the researchers reported that Kelly's immune system still functioned as it should. Partway through his time in space, he received a flu vaccine and his immune system responded appropriately.

The researchers also noted a number of chromosomal aberrations among the twins' samples. Inversions, they reported, were more frequent among Scott Kelly's samples, which the researchers said was consistent with his increased radiation exposure. These inversions, however, were among the changes that persisted after Scott Kelly returned to Earth

"[This is] giving us some indication of ongoing genomic instability following space flight," Bailey said.

The researchers likewise reported that the expression of some immune genes remained high after Kelly's return and that while his average telomere length returned to baseline, his genome harbored some telomeres that were shorter than they were at baseline.

These and other findings suggested to the researchers that there could be longer-term effects of spaceflight.

"What this [study] really does is open a door to the kind of analysis you could never do before that's going to be important for astronauts when they go on a long duration space flight to Mars," author Andy Feinberg from Johns Hopkins University said, adding that as their missions take them further from Earth, astronauts are "going to have be progressively independent from the resources that are on the ground."

Indeed, in 2016, NASA astronauts, scientists, and outside collaborators reported that it was possible to sequence DNA while in space.

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