NASA’s Twins Study Explores Gene Expression Scott Kelly and Mark Kelly are identical twins; both are retired astronauts, but with two different sets of DNA. We know that identical twins have identical sets of DNA, so how did this happen? NASA astronaut Scott Kelly returned home last March after nearly one year in space living on the International Space Station. His identical twin brother, Mark Kelly, remained on Earth. NASA used this opportunity to study the impact of space travel and zero gravity at the molecular, genetic, or DNA level. In fact, it was a great opportunity to test Nature versus Nurture. Thus the Twins Study was formed. Using Mark, a retired NASA astronaut, as a ground-based control subject, ten researchers are sharing biological samples taken from each twin before, during and after Scott’s mission. From these samples, knowledge is gained as to how the body is affected by living in space for extended times. These studies are far from complete. Additional research analysis is in progress, but recently NASA released some preliminary findings. The Twin Study propelled NASA into the genomics era of space travel. It was a ground-breaking study comparing what happened to astronaut Scott Kelly, in space, to his identical twin brother, Mark, who remained on Earth. The perfect nature versus nurture study was born. The Twins Study brought ten research teams from around the country together to accomplish one goal: discover what happens to the human body after spending one year in space. NASA has a grasp on what happens to the body after the standard-duration six-month missions aboard the International Space Station but Scott Kelly’s one-year mission is a stepping stone to a three-year mission to Mars. Biochemical Profile Another team found that Scott Kelly’s body mass dropped during flight. His folate status was low before flight, but his folate went up while in space, perhaps due to better food choices from the space food system. Kelly’s body mass decline and folate increase agree with the findings of telomere lengthening: the healthier lifestyle could have resulted in lengthening telomeres. Inflammation Another study reported that altered levels of a lipid panel (lipids are fats) in Scott indicated inflammation while in space. On the ground, Mark’s data indicated similar but lesser inflammation. They also measured the levels of cytokines, which are proteins that have an effect on well-known blood markers that indicate inflammation. There was an increase in groups of cytokines both durning and after Scott's mission. There was also an increase of some proteins which help maintain normal insulin activity to regulate blood sugar after meals. Effect of vaccines Both brothers were given flu vaccines, on the ground and in space. There were similar immune responses in each twin, leading to the conclusion that the flu vaccine given aboard the space station is as effective as it is on the ground. Hardening of arteries Hardening and thickening of the arteries tell how inflammation and stress during spaceflight influences the structure and function of blood vessels. The twins’ arteries were examined with ultrasound and they provided blood and urine samples throughout the duration of the mission. The carotid artery wall was thickened in Scott during and immediately after his mission, but no changes were observed in Mark. It is not clear yet whether this change is permanent. or reversible. Gut bacteria Many thousands of types of bacteria (entire communities) live in the gastrointestinal tract and play a major role in human health. Scott’s microbial species while in space were different than pre-flight, but became similar after he returned to Earth. Study on Telomeres Telomeres are a protective “cap” on the ends of chromosomes, which are made of DNA and carry genetic information. Telomeres usually decrease in length as a person ages. However, one team reported that Scott’s telomeres significantly increased in average length while he was in space. Once he returned to Earth, his telomeres shortened in length within about 48 hours of landing, then stabilized to nearly the same levels as before his space stay. The reasons for the lengthening of Scott’s telomeres in space are still under investigation, but may be from his rigorous exercise regime and restricted caloric intake while on the space station. Genetic changes Identical twins are genetically indentical, so they have identical DNA. The entire genome of both twins was sequenced. It showed that each twin has hundreds of unique mutations in their genome, more than expected, and some were found only after spaceflight, circulating in the blood as “cell-free DNA”. This is thought to be from the stresses of space travel, which can cause changes in a cell’s biological pathways and ejection of DNA and RNA. Such actions can trigger the assembly of new molecules, like a fat or protein. It can also turn genes on and off, which change cellular function. Significant responses were found for at least five biological pathways in Scott during his time in space. These responses are important for future missions: hypoxia (likely from lack of oxygen and high CO2 levels); mitochondrial stress and increased levels of mitochondria in the blood (indicating damage to the “power houses of cells”); telomere length, DNA damage, and DNA repair (likely from radiation and caloric restriction); collagen, blood clotting, and bone formation (likely from fluid shifts and zero gravity); and hyperactive immune activity (from the new environment). Although 93% of genes’ expression returned to normal postflight, a subset of several hundred “space genes” were still disrupted after return to Earth. Hence, space travel has altered Scott's genes due to mutation. While most returned to normal after landing, the remaining 7% point to possible longer term changes in genes related to his immune system, DNA repair, bone formation networks, hypoxia, etc. Summary findings By measuring large numbers of metabolites, cytokines, and proteins, researchers learned that spaceflight is associated with oxygen deprivation stress, increased inflammation, and dramatic nutrient shifts that affect gene expression. After returning to Earth, Scott started the process of readapting to Earth’s gravity. Most of the biological changes he experienced in space quickly returned to nearly his preflight status. Some changes returned to baseline within hours or days of landing, while a few persisted after six months. The Twins Study was an amazing opportunity to understand potential risks to the human body in space. This will help realise various possiblilities for long-term space travel, such as a journey to Mars (where the one-way outward journey itself lasts six to eight months), or even farther. Source: NASA