The 2019 NASA Twins Study provided an all-encompassing look at the effects of spending nearly a year in space on the human body when NASA astronaut Scott Kelly spent 340 days on the International Space Station while his identical twin Mark (now a US Senator-elect from Arizona) was on Earth.
Now, scientists have gathered the largest set of data about space biology to date based on astronauts including the Kelly twins, mice and insects that have flown on the space station.
The 30 studies, authored by more than 200 researchers from around the world, represent the largest body of information on the risks of space flight to the human body.
The studies identify six key molecular changes that may have a significant impact on astronaut health. Understanding these changes is key for preparing for long-term spaceflight missions to the moon and Mars in the future.
The Biology of Spaceflight collection of 30 studies published Wednesday in the journals Cell, Cell Reports, Cell Systems, Patterns and iScience.
Risks of deep space missions
The six molecular changes that occur during spaceflight include DNA damage, oxidative stress, alterations of telomere length, shifts in the microbiome, mitochondrial dysfunction and gene regulation.
Oxidative stress happens when free radicals overwhelm antioxidants in a cell, encouraged by the space environment. This type of stress was found to be largely connected to the other molecular changes the researchers observed.
These changes on a cellular and molecular level can have a significant impact on astronaut health, both during and after their missions. These impacts have been observed on the cardiovascular, central nervous, musculoskeletal, immune and gastrointestinal systems, as well as causing disruptions to circadian rhythms and changes in vision.
Increased cancer risks have also been associated with these changes.
One of the new studies also identified clonal hematopoiesis, when blood cells carrying mutations spread more quickly than others, as a potential risk among astronauts for cardiovascular disease, lymphoma and leukemia. Clonal hematopoiesis was identified in blood samples from astronauts 20 years before the average age when it is normally detected at age 70, compared to 157 cancer patients.
So far, missions to the space station have not exceeded a year, but deep space missions to Mars could last up to five years.
"Understanding the health implications from the (6) features and developing effective countermeasures and health systems are key steps in enabling humanity to reach the next stage of space exploration," the authors wrote at the conclusion of their study spanning the effects of spaceflight.
DNA damage
Telomeres act like caps at the ends of chromosomes to protect them and they shorten as people age.
During the Twins Study, the telomeres in Scott's white blood cells actually grew longer in space and returned to a normal length after he returned to Earth.
In a new study, the blood samples of 10 astronauts collected before and after spaceflight were studied and compared with the results of the Twins Study.
Although these astronauts were shielded from some space radiation during their six-month stays on the space station since it's in low-Earth orbit, the researchers still spotted evidence of damage to their DNA.
The astronauts' telomeres elongated in space due to chronic oxidative stress sustained during spaceflight. Once they returned to Earth, their telomeres were shorter than before spaceflight.
"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," said Susan Bailey, author on three of the studies and Colorado State University professor, said in a statement.
"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."
Bailey, an expert on radiation damage to DNA and telomeres, was also an investigator for the Twins Study.
While longer telomeres may sound like an advantage of space travel, Bailey suspects this effect could lead to other risks rather than serving as a fountain of youth.
"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," Bailey said. "Telomeres really are reflective of our lifestyles - whether on or off the planet. Our choices do make a difference in how quickly or how well we are aging. It's important to take care of your telomeres."
It's all in the mitochondria
Health issues specific to astronauts include muscle and bone loss, heart and liver problems and immune system dysfunction.
Now, researchers believe these issues are rooted in a broader issue called mitochondrial dysfunction.
Mitochondria are the powerhouses that generate chemical energy required for cells. And when they're exposed to altered gravity or radiation, they essentially malfunction.
"We started by asking whether there is some kind of universal mechanism happening in the body in space that could explain what we've observed," said Afshin Beheshti, senior study author and a principal investigator and bioinformatician at NASA's Ames Research Center in California, in a statement.
"What we found over and over was that something is happening with the mitochondria regulation that throws everything out of whack."
Their study included data from the Twins Study, animal studies and samples from 59 astronauts.
When the mitochondria are suppressed, ripple effects can be observed across the liver, other organs and in the immune system. The researchers believe this dysfunction could also explain the issues astronauts have with disrupted circadian rhythms (body clock) and even cardiovascular issues.
Understanding the root of the problem could help researchers target it.
"There are already many approved drugs for various mitochondrial disorders, which would make it easier to move them toward this application," Beheshti said. "The low-hanging fruit now would be to test some of these drugs with animal and cell models in space."
Heart stress in space
A study using fruit flies born on the space station, which means they spent half of their lives in space, showed that their hearts were smaller and less efficient at pumping blood. And if astronauts live on the moon or the surface of Mars for a lengthy mission, they may experience something similar.
"For the first time, we can see the cellular and molecular changes that may underlie the heart conditions seen in astronaut studies," said Karen Ocorr, co-senior author of the study and assistant professor in the Development, Aging and Regeneration Program at Sanford Burnham Prebys Medical Discovery Institute, in a statement.
"We initiated this study to understand the effects of microgravity on the heart, and now we have a roadmap we can use to start to develop strategies to keep astronaut hearts strong and healthy."
Fruit fly hearts are similar to those of humans when we're in the womb. The flies were returned to Earth and had their heart function tested by seeing how they fared when climbing up the side of a test tube.
"In the normal fly heart, the muscle fibers work like your fingers when they squeeze a tube of toothpaste. In the space flies, the contraction was like trying to get toothpaste out by pressing down instead of squeezing," Ocorr said. "For humans, this could become a big problem."
The benefits of understanding how the human heart functions in space could help those with heart issues on Earth -- and those planning on future space missions.
"As we continue our work to establish a colony on the moon and send the first astronauts to Mars, understanding the effects of extended time in microgravity on the human body is imperative," said Sharmila Bhattacharya, study author and senior scientist at NASA, in a statement.
"Today's results show that microgravity can have dramatic effects on the heart, suggesting that medical intervention may be needed for long-duration space travel, and point to several directions for therapeutic development."
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