Nearly a year in space put astronaut Scott Kelly's immune system on high alert and changed the activity of some of his genes compared to his Earth-bound identical twin, researchers have found.

Scientists don't know if the changes were good or bad but results from a unique Nasa twins study are raising new questions for doctors as the space agency aims to send people to Mars.

Tests of the genetic doubles gave scientists the first opportunity to track details of human biology, such as how an astronaut's genes turn on and off in space differently. One puzzling change that was announced at a science conference: Kelly's immune system was hyperactivated.

"It's as if the body is reacting to this alien environment sort of like you would a mysterious organism being inside you," said geneticist Christopher Mason of New York's Weill Cornell Medicine, who helped lead the study. He said doctors were now looking for that in other astronauts.

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Since the beginning of space exploration, Nasa has studied the toll on astronauts' bodies, such as bone loss that requires exercise to counter. Typically they're in space about six months at a time. Kelly, who lived on the International Space Station, spent 340 days in space and set a US record.

"I've never felt completely normal in space," the now-retired Kelly said in an email to AP, citing the usual congestion from shifting fluid, headaches and difficulty concentrating from extra carbon dioxide, and digestive complaints from microgravity.

But this study was a unique dive into the molecular level, with former astronaut Mark Kelly, Scott's twin, on the ground for comparison. Full results haven't yet been published, but researchers presented some findings at a meeting of the American Association for the Advancement of Science.

A number of genes connected to the immune system became hyperactive, Mason said. Mason also spotted a spike in the bloodstream of another marker that primed the immune system. Yet Kelly's blood showed fewer of another cell type that was an early defence against viruses.

It's no surprise gene activity changes in space — it does in response to all kinds of stress.

"You can see the body adapting to the change in its environment," Mason said.

The good news: Most everything returned to normal shortly after Kelly got back on Earth in March 2016. Those immune-related genes, however, "seemed to have this memory or this need to almost be on high alert" even six months later, Mason said.

"On the whole it's encouraging," said Craig Kundrot, who heads space life and science research for Nasa. "There are no major new warning signs. We are seeing changes that we didn't necessarily anticipate but don't know if those changes matter."

From four Russians living in space for more than a year, Nasa already knew prolonged time off Earth was possible, Kundrot said, adding, "We also aim for more than just possible. We want our astronauts to do more than just survive."

Immune issues sound familiar to Jerry Linenger, a US astronaut who spent more than four months on the Russian space station Mir. He said he was never sick in orbit, but once back on Earth, "I was probably more sick than I was in my life".

Astronauts got exposed to their crewmates' germs, then after a week with nothing else new in the sterile environment of a space station, "your immune system is really not challenged," Linenger said.

- AP