NASA’s Twins Study brought ten teams of researchers from around the country together to observe what physiological, molecular and cognitive changes could happen to a human from exposure to spaceflight hazards. Retired NASA astronauts Scott Kelly and his identical twin brother Mark, participated in the investigation, conducted by NASA’s Human Research Program. Scott was monitored before, during, and after a 340-day mission onboard the International Space Station; his twin, Mark, served as a genetically matched ground control. The results, published in the journal Science, reveal some interesting, surprising and positively assuring data of how a single human body adapted to the extreme environment of space.
“The Twins Study has been an important step toward understanding epigenetics and gene expression in human spaceflight,” said Dr. J.D. Polk, chief health and medical officer at NASA Headquarters.
“Thanks to the twin brothers and a cadre of investigators who worked tirelessly together, the valuable data gathered from the Twins Study has helped inform the need for personalized medicine and its role in keeping astronauts healthy during deep space exploration, as NASA goes forward to the Moon and journeys onward to Mars.”
Key results from the study are summarized below. They include findings related to gene expression changes, immune system response, and telomere dynamics. Other changes include broken chromosomes rearranging themselves in chromosomal inversions, and a change in cognitive function.
The ends of each strand of DNA have special features called telomeres, which protect our chromosomes, as plastic handles protect jump ropes. Telomere lengths tend to get shorter as we age; however, lifestyle factors, stresses and environmental exposures can also affect the rate at which this shortening occurs. One of the most striking discoveries from the Twins Study is that Scott experienced a change in telomere length dynamics during spaceflight and within days of landing. The results may help to evaluate general health and identify potential long-term risks.
Scott received three flu vaccines, each one year apart; first on Earth, second in space (the first time an astronaut was given a vaccine while in space), and third back on Earth. The study found that Scott’s body reacted appropriately to the vaccine. This is a significant finding because it allows NASA to have greater confidence that the immune system responds appropriately in space, should a vaccine ever be needed, during long-duration missions.
Samples taken before, during and after Scott’s mission revealed some changes in gene expression. Mark also experienced normal-range changes in gene expression on Earth, but not the same changes as Scott. Changes Scott experienced may have been associated with his lengthy stay in space. Most of these changes (about 91.3%) reverted to baseline after he returned to Earth; however, a small subset persisted after six months. Some observed DNA damage is believed to be a result of radiation exposure. Gene expression data corroborated and supported other findings in the Twins Study, including the body’s response to DNA damage, telomere regulation, bone formation and immune system stress. These findings help demonstrate how a human body was able to adapt to the extreme environment of space and help researchers better understand how environmental stressors influence the activity of different genes, leading to a better understanding of physiological processes in space.
With few exceptions, Scott’s cognitive performance (such as mental alertness, spatial orientation, recognition of emotions) remained largely unchanged during his time in space, and relative to Mark on the ground. This is important as it suggests that astronauts can maintain high levels of cognitive performance for longer durations in space. However, a more pronounced decrease in speed and accuracy was observed after he landed and persisted for six-months. The changes observed just after landing are possibly due to re-exposure and adjustment to Earth’s gravity, and the busy schedule that enveloped Scott after his mission.
Studying various elements in Scott found that his body mass decreased by seven percent during flight. This is likely due to increased exercise and controlled nutrition while on his mission, but he also consumed about 30% fewer calories than researchers anticipated. His bone breakdown and bone reformation cycle occurred at a faster rate during the first six months he was in space, but slowed down in the second half when his exercise volume was lower. His chemistry of blood and urine samples indicated that his folate status (vitamin B9) was low before flight but went up during flight, likely due to better food choices from the space food system. Folate has many important functions in the body, including support of DNA synthesis. In fact, there is a correlation between Scott’s folate status and telomere dynamics. These data support the fact that nutrition plays an important role in all aspects of health in space and on Earth.
A highly diverse gut microbiome is generally associated with good health. Scott’s gut flora was found to be profoundly different during flight from preflight. This could be due to the food he consumed while on the space station (mainly freeze-dried or thermo-stabilized prepackaged food) although other space-specific environmental factors may have also contributed. When he landed back on Earth, Scott’s microbiome returned to preflight state. Observing how much Scott’s gut bacteria returned to normal was reassuring. The findings may provide researchers with a better understanding of how to help improve overall health, such as adjusting astronauts’ diets to help beneficial bacteria thrive.
This study looked at how the twins’ environments influenced changes in DNA methylation, which has a significant impact on many biochemical reactions in the body. The scientists found Scott experienced epigenetic changes inflight, but the degree of changes was no greater than Mark’s on Earth. Furthermore, most of Scott’s epigenetic changes took place during the second six-months of the mission and would not have been observed in a shorter mission. Scott’s white blood cells revealed genes, or regions of the genome, where DNA methylation was altered in flight but returned to baseline upon his return. These regions were different than those identified in Mark, helping the researchers identify genes that appear most responsive to the space environment. These results open the door to epigenetic measurements of astronauts on long-duration space missions and may help determine whether spaceflight-associated changes are transient or long-lived. They could also help identify which preventative countermeasures might better protect astronauts’ health.
The metabolomics study looked for signs of atherosclerosis (narrowing of the inside of an artery wall due to plaque buildup) which may be caused by inflammation and oxidative stress during spaceflight. By imaging the carotid artery using ultrasound and from sampling blood and urine, the researchers found indications of inflammation and carotid artery wall thickening in Scott during and immediately after his mission, but no such changes were observed in Mark. Whether this adaptation is reversible remains to be determined. The results help scientists understand better the effects of long duration spaceflight on the cardiovascular system.
The proteomics team studied fluid shifts in the body, the structure of the eye, and proteins in urine to see if changes in protein pathways in response to fluid shifts might contribute to some astronauts’ vision problems. The researchers found that a protein, AQP2, was elevated in Scott in space as compared to Mark on the ground. AQP2 regulates water reabsorption in the body and is a useful indicator of hydration or dehydration status. These results are helping to piece together the puzzle of vision problems during spaceflight.
Finally, the longitudinal integrated multi-omics analysis team examined all of the biomedical and molecular data collected from the other nine research teams to produce the single most comprehensive view of how the human body responds to spaceflight. The scientists found three strong indications of inflammation in Scott in space. Interestingly, some of these markers were elevated in Mark as well.
“To our knowledge, this team of teams has conducted a study unprecedented in its scope across levels of human biology: from molecular analyses of human cells and the microbiome to human physiology to cognition,” said Dr. Craig Kundrot, director of Space Life And Physical Sciences Research And Application Division at NASA Headquarters.
“This paper is the first report of this highly integrated study that began five years ago when the investigators first gathered. We look forward to the publication of additional analyses and follow-up studies with future crew members as we continue to improve our ability to live and work in space and venture forward to the Moon and on to Mars.”
Francine E. Garrett-Bakelman et al. 2019. The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight. Science 364 (6436); doi: 10.1126/science.aau8650