The historic NASA Twins Study investigated identical twin astronauts Scott and Mark Kelly and provided new information on the health effects of spending time in space.

More than 80 scientists across 12 universities who conducted research on the textbook experiment; Mark remained on Earth while Scott orbited high above for nearly one year. The massive effort was coordinated by NASA's Human Research Program.and published in the journal Cell.

The research - including an over-arching paper that covers what the investigators have learned about the fundamental features of space flight - represents the largest set of space biology and astronaut health effects data ever produced.

"We now have a foundation to build on - things we know to look for in future astronauts, including telomere length changes and DNA damage responses," the author said. "Going forward, our goal is to get a better idea of underlying mechanisms, of what's going on during long-duration space flight in the human body and how it varies between people. Not everybody responds the same way. That was one of the good things about having the larger cohort of astronauts in these studies."
. In the previous study, the team found that Scott's telomeres in his white blood cells got longer while in space, and subsequently returned to near normal length after he was back on Earth.

Telomeres are protective "caps" on the ends of chromosomes that shorten as a person ages. Large changes in telomere length could mean a person is at risk for accelerated aging or the diseases that come along with getting older, cardiovascular disease and cancer for example.

In the latest research, the team studied a group of 10 unrelated astronauts, including CSU alum Dr. Kjell Lindgren, comparing the results with findings from the Kelly twins. The researchers did not have access to in-flight blood and other samples for all of the crewmembers, but Bailey said they did have blood samples before and after space flight for everyone.

The investigations involved astronauts who spent approximately six months on the International Space Station in low-Earth orbit, which is protected from some space radiation. Despite the protection, scientists found evidence of DNA damage that could be warning signs of potential health effects.

Among the new findings, the research team found that chronic oxidative stress during spaceflight contributed to the telomere elongation they observed. They also found that astronauts in general had shorter telomeres after spaceflight than they did before. The team also observed individual differences in responses.

To gain more insight on these findings, the  team also studied twin mountain climbers who scaled Mt. Everest, an extreme environment on Earth. The non-climbing twins remained at lower altitude, including in Boulder, Colorado. Remarkably, the team found similar evidence of oxidative stress and changes in telomere length in the climbers.

The authors performed gene expression analyses on the Mt. Everest climbers. They found evidence of a telomerase-independent, recombination-based pathway of telomere length maintenance known to result in longer telomeres.

The author said that when chronic oxidative stress occurs, it damages telomeres.

"Normal blood cells are dying and trying to survive," the author said. "They're adapting to their new environment. Some cells will activate an alternative pathway to keep their telomeres going. It's similar to what happens with some tumors. Some of the cells emerge from that process. That's what we think we're seeing during spaceflight as well."

Another said the mechanism described above - known as alternative lengthening of telomeres, or ALT - was an unexpected finding.

Similar to conclusions from the Twins Study, the author said the new findings have implications for future space travelers establishing a base on the Moon or traveling to Mars, or even as a space tourist. Long-duration exploration missions will involve increased time and distance outside of the protection of the Earth.

Although longer telomeres in space might seem like a good thing, perhaps even a "fountain of youth," the scientist said she suspects a somewhat different ending to the story.

"Extended lifespan, or immortality, of cells that have suffered space radiation-induced DNA damage, such as chromosomal inversions, is a recipe for increased cancer risk," the author said.

The team observed increased frequencies of inversions in all crewmembers, during and after spaceflight.

"Telomeres really are reflective of our lifestyles - whether on or off the planet," said the author. "Our choices do make a difference in how quickly or how well we are aging. It's important to take care of your telomeres."

https://www.cell.com/cell/fulltext/S0092-8674(20)31461-6

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