Spaceflight activates ‘dark genome’ in human cells, researcher says

Research on the effects of spaceflight on stem cells was performed during four International Space Station resupply missions Space X operated from late 2021 to early 2023. (Thomas Marshburn/NASA via CNN Newsource)

Spaceflight makes certain human stem cells age faster, a new study has found, furthering scientists’ understanding of the potential effects of space exploration on the human body.

Stem cells are found throughout the body, and they can make more of themselves or turn into other specialized cells — including blood, brain or bone cells — for maintenance and repair.

“In space, stem cells decline in function,” said lead study author Catriona Jamieson, director of the Sanford Stem Cell Institute and professor of medicine at the University of California, San Diego School of Medicine. “They actually reduce their ability to renew themselves or regenerate, and that’s an important thing to be able to know for long-term space missions.”

The study, which NASA funded in part, was performed during four International Space Station resupply missions that SpaceX operated from late 2021 to early 2023. The research published Thursday in the journal Cell Stem Cell.

“This is the first study that looks at how stem cells behave in space, in low Earth orbit, in real time,” Jamieson added, noting that this kind of research could have a direct impact on health management for astronauts poised to go to space.

“It’s important to study stem cell health and see who’s likely to be able to withstand the rigors of space — it’s stressful to get up, it’s stressful to come down, and it’s stressful to be up there.”

Sleepless in orbit

NASA conducted one of the first experiments on the effects of spaceflight on stem cells in 2010 using the space shuttle Discovery. Called the Stem Cell Regeneration Experiment, it investigated how microgravity affected the ability of mice’s embryonic stem cells to make other types of cells.

In the new study, researchers examined bone marrow stem cells donated by patients undergoing hip replacement surgery. The stem cells, which are directly connected to the health of the immune system and the blood, were placed on a sterile sponge matrix, housed in specially developed bioreactors the size of a cell phone. On board the International Space Station, the cells were constantly monitored by an artificial intelligence system, which could detect their state in real time.

“Our stem cells should be asleep (inactive) 80 per cent of the time to retain their full function,” Jamieson said. However, that wasn’t the case in space, where microgravity and cosmic radiation had an influence on their well-being.

“The stem cells woke up, and they didn’t go back to sleep, and they became functionally exhausted,” she added. “If our stem cells become exhausted under conditions of stress like microgravity, then they won’t function to make a proper immune system.”

Some of the cells in the study sustained up to 45 days of spaceflight, and because they were more active than normal, they burned through their energy reserves and showed signs of accelerated aging. Their ability to generate new cells was also reduced, and, according to Jamieson, they began activating normally hidden sections of DNA called repetitive elements or the “dark genome.”

“Under conditions of stress, really strong stress, we activate these repetitive elements,” Jamieson said. “These are retroviruses that invaded our genomes thousands and thousands of years ago and represent 55 per cent of our DNA. They send the stem cells into a death spiral. The cells just feel overstressed. They have a crisis. They age too quickly.”

This is similar to the stem cell stress that Jamieson, who is also a medical doctor, observes in the cells of patients with preleukemic disorders. Jamieson tries to stop these cells in their tracks before they turn into full-blown leukemia, a type of blood cancer.

Jamieson, a veteran of space stem cell research who has worked on nine missions so far, is planning future studies that will look at practical countermeasures for the aging process.

“We can actually use these bioreactors, or avatars for stem cell health, to predict who’s likely to do well and who’s likely to do extremely badly in space … and develop countermeasures,” she added, noting some upcoming clinical trials for potential medications to counteract the effects of this dark genome activity.

The good news is that stem cells can recover from the accelerated aging once an astronaut returns to Earth, according to preliminary results from a separate, upcoming study, although the recovery takes about a year.

The research can also have a beneficial impact for cancer patients as their stem cells exhibit some of the same stress-related damage that the new study has detected in the stem cells in space. “I think this is an important tool for us to accelerate the pace of (cancer) research,” Jamieson said.

Clear evidence of aging

For astronauts, these findings mean that long missions could weaken the blood and immune systems, potentially raising health risks, said Arun Sharma, a stem cell biologist and an associate professor of biomedical sciences at Cedars-Sinai Medical Center in California. Sharma, who was not involved with the study, agreed with Jamieson that the findings may help scientists understand the aging process and develop new therapies that slow or reverse it.

The study provides strong evidence of the potential damage that radiation exposure and microgravity can have on stem cells, highlighting the possible health risks associated with long-range space expeditions, said Luis Villa-Diaz, an assistant professor in the biological sciences and bioengineering departments at Oakland University in Michigan. Villa-Diaz was also not involved in the research.

“The good news is that knowing the potential negative effects that low Earth orbit has on (stem cell) aging and function gives us directions to address these issues and develop strategies to prevent or counteract these effects, and support future space exploration,” he added. “This often translates into biomedical advances that can be applied to patients on Earth.”

While earlier space research on stem cells suggested vulnerabilities in more indirect or limited ways, this study provides much clearer evidence of aging, said Elena Kozlova, a professor in the department of immunology, genetics and pathology at Sweden’s University of Uppsala.

Kozlova, who was also not part of the new research, noted that not all studies on stem cells in space point in the same direction. Her own research with early developmental stem cells on microgravity research rockets — operated by the Swedish Space Corporation — showed an increase in growth-associated genes.

That finding, she added, suggests that under certain conditions spaceflight may even promote a more youthful state in some stem cell populations.

By Jacopo Prisco, CNN