Scientists have found no long-lasting, major epigenetic differences in astronaut Scott Kelly, who spent a year in space aboard the International Space Station (ISS), and his twin brother, Mark Kelly, who remained on Earth.
Epigenetic changes involve chemical "tweaks" to DNA that can influence gene activity, but the changes don't affect the underlying genetic code itself.
The changes affect when and how a gene is read, or expressed, for its protein-encoding instructions.
"This is the dawn of human genomics in space," said Andrew Feinberg from the Johns Hopkins University in the US.
"We developed the methods for doing these types of human genomic studies, and we should be doing more research to draw conclusions about what happens to humans in space," Feinberg said in a statement.
Scientists have long monitored and studied the physiological effects of space travel on astronauts.
However, most of these astronauts travel on spaceflight missions of six months or less, not the longer missions required to travel to Mars or elsewhere.
Feinberg noted that studying identical twins -- who, by nature, have the same genetic material -- was an important and rare opportunity to compare physiological and genomic changes when one twin went into space and the other remained on Earth.
"However, since we only have two people in our study, we can't say that these changes are due to space travel itself. We need more studies of astronauts to draw such conclusions," said Feinberg.
For the study, published in the journal Science, scientists collected blood samples, physiological data and cognitive measurements from Scott and Mark at various time points over 27 months before, during and after Scott's one-year space mission.
The samples from Scott during the flight were collected on the space station when shipments from Earth arrived on a Soyuz rocket and, that same day, shipped back to Earth on the rocket so that the samples could be processed within 48 hours.
Feinberg and former postdoctoral student Lindsay Rizzardi, now a senior scientist at the HudsonAlpha Institute for Biotechnology in the US, focused on epigenetic changes to Scott and Mark's genomes.
Specifically, researchers examined two types of white blood cells (CD4+ and CD8+) isolated from Mark and Scott's blood.
They focused on epigenetic marks consisting of chemical modifications called methyl groups that are added onto the DNA in a process called methylation.
Overall, they found that about just as many epigenetic changes occurred in earthbound Mark's DNA as in his space-flying twin.
There was a less than five per cent difference in overall methylation between the twins during the mission.
The largest difference occurred nine months into the mission when 79 per cent of Scott's DNA was methylated, compared with 83 per cent of Mark's.
The locations of methylation changes in the genome were different for each twin.
For example, the scientists found methylation changes near genes involved in immune system responses in Scott during his time in space, but not in Mark.
This correlated with data from other researchers involved in the current study who found increases in certain biochemical markers associated with inflammation in Scott but not Mark.
"It was encouraging to see that there was no massive disruption of the epigenome in either Mark or Scott," said Rizzardi.
"However, with only two people in the study, we're limited in the conclusions we can draw about the effect of space travel on the genome. But the findings give us clues to what we should examine more closely in future studies of astronauts," she said.
Some of the notable results included Scott's in-flight lengthening of telomeres, the protective endcaps on chromosomes. The telomere lengthening, as previously reported, returned to normal when Scott returned to Earth.
In addition, more than 90 per cent of genes that changed activity levels during Scott's flight returned to normal six months after the flight.
Feinberg noted these changes are not indicative of space flight alone, nor do they differ from what might occur normally.
The scientists also found that the shape of Scott's eyeball changed over the course of the flight, including a thicker retinal nerve and folds in the choroid layer that surrounds the eye.
These changes typically affect visual acuity and have occurred in other male astronauts but not females, said Feinberg.
The scientists also observed cognitive changes and increased stress levels in Scott during the flight, which, again, may not be attributed to space flight alone.
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