A few days ago, results from the landmark NASA’s “Twin Study” were published in the scientific journal Science (April 12, 2019). The study was carried out in 2015/2016 to understand the health impact of long-duration spaceflight, and centered around astronauts Scott and Mark Kelly, who are identical twins. One of the twins, Scott Kelly, was monitored before, during, and after a 1-year mission onboard the International Space Station, whereas his twin, Mark Kelly, stayed on Earth and served as a genetically matched control subject. The study results help to understand how the human body responds to the spaceflight environment, and how to maintain crew health during human expeditions to the Moon and Mars.
The published paper (The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight) details the integrated work of 10 research teams on the effects of the spaceflight environment on human health and performance, physiology, and cellular and molecular processes. The paper points out that “The space environment is made harsh and challenging by multiple factors, including confinement, isolation, and exposure to environmental stressors such as microgravity, radiation, and noise.” Therefore, during and after the year in space, the researchers collected physiological, telomeric, transcriptomic, epigenetic, proteomic, metabolomic, immune, microbiomic, cardiovascular, vision-related, and cognitive data. The researchers observed significant changes in multiple data types in association with the spaceflight period. However, most observed changes eventually returned to the preflight state, showing the human body’s resilience.
Jennifer Fogarty, chief scientist of the Human Research Program at NASA’s Johnson Space Center in Houston, said: “A number of physiological and cellular changes take place during spaceflight. We have only scratched the surface of knowledge about the body in space. The Twins Study gave us the first integrated molecular view into genetic changes, and demonstrated how a human body adapts and remains robust and resilient even after spending nearly a year aboard the International Space Station. The data captured from integrated investigations like the NASA Twins Study will be explored for years to come.”
The researchers found changes in telomere length, gene regulation measured in both epigenetic and transcriptional data, gut microbiome composition, body weight, carotid artery dimensions, subfoveal choroidal thickness and peripapillary total retinal thickness, and serum metabolites. Cognitive performance was significantly affected by the stress of returning to Earth. For a few measures, persistent changes were observed even after 6 months on Earth, including the expression levels of some genes, increased DNA damage from chromosomal inversions, increased numbers of short telomeres, and attenuated cognitive function.
What about the immune system? The researchers found that many immune-related pathways were significantly changed inflight across all cell types. Adaptive immune system, innate immune response, and natural killer cell-mediated immunity were all affected. Notably, inflammatory cytokines and immune response gene networks were significantly influenced by the stress of returning to Earth. However, the researchers also found that the flu vaccine administered in space worked exactly as it does on Earth. A fully functioning immune system during long-duration space missions is critical to protecting astronaut health from opportunistic microbes in the spacecraft environment.
In the published paper, the researchers conclude that astronauts conducting exploration-class missions could experience risks from mitochondrial dysfunction, immunological stress, vascular changes and fluid shifts, cognitive performance decline, as well as alterations in telomere length, gene regulation, and genome integrity. However, the researchers point out that given the limitations related to the analysis of a single spaceflight individual, further studies are needed, including studies of additional astronauts on long-duration (≥12 month) missions.
When reading about the spaceflight experiments, one question I kept thinking about is how exactly the zero gravity changes the mechanism of genetic activities in the body. Reading the article, the issue of radiation was brought up as a possible hurdle for extended spaceflight, however since the ISS is inside the Van Allen belts of radiation that orbit the earth outside of LEO, Scott Kelly won’t be susceptible to any of the solar radiation that can cause harm to the genetic code, like the Apollo astronauts had to deal with. Reading further, it seems that the article places great interest in the stress of returning to earth through the tumultuous reentry procedure rather than the stress of space travel itself. Physiological Stress appears to be the reason for the majority of genetic complications measured in the Twins experiment. Due to this, I believe that a possible solution to the genetic complications is a focus on making space travel less stressful and more like an airline flight rather than a spaceflight. Additionally using rotating space stations to simulate gravity could also reduce the stress of having blood pooling in the head and upper torso due to the habituation the blood vessels in the legs have from gravity which results in squeezing blood to the upper body. Since genes are the parts of the cell that code for proteins, all lymphocytes will be affected by genetic abnormalities. I chose
https://www.ncbi.nlm.nih.gov/pubmed/10352154
I also noticed that the article focused more on the physical changes than the immunological ones. I’m reading that the innate immune response was enhanced in a study I found. In one case it talked about being in a stressful environment with fellow astronauts and not being able to retreat to their own quarters and the innate immune response in increased. There are already well known studies on how stress can influence health. In another case it mentions that the crew members studied had no inflammation but they did have deregulation of lymphocytes. It seems as though the isolation part and the returning to Earth played a more extreme role on the immune system in the article I found and on this one.
https://www.ncbi.nlm.nih.gov/pubmed/26846554
The ISS has about the interior volume of a 747, so I don’t think that the stress is caused by a lack of space, however, I think that the stress is caused by an increased and very busy work schedule. For this reason, i think that having a similar stress study on immunological response should be done with other professions which have constant stress and a rigidly scheduled day just like an astronaut. Arctic sailors, soldiers on the front line or oil well workers would be good options in my opinion. I linked this study since it gives a broad overview of stress and it’s effects on the human body.
https://www.ncbi.nlm.nih.gov/pubmed/8416086
These findings are remarkable, yet they make much sense. Humans are like animals, we adapt to changes in our environments, but what’s more incredible is the fact that the body can return to its original state after a short period. We know that stress alone can lower the immune systems ability to respond when needed. In this case, traveling from earth to space I imagine would put a lot of stress on the immune system, yet the body reacts by altering genes and once returned to earth only takes 6 months to revert to its original state. It raises the question, would longer time in space slowly suppress the immune systems resilience? With such a huge change in environment, we expect the body to react quickly, but this reaction must take a lot of energy. They forget to take into consideration the fact that immunity and psychology share a relationship, maybe the changes were not all dependent upon genetic alterations, but a strong and resilient mindset might have supported these alterations.
https://www.ncbi.nlm.nih.gov/pubmed/30102966
I found it interesting that in your paper it talks about psychoneuroimmunology. Which I never really read or heard about it. But that resilience only becomes an issue when the stress reaches a level where it lowers our immune system and makes it more challenging to respond to infection.
I found it cool that stress can affect specific parts of the immune system according to the papers cells such as natural killer cells, lymphocyte proliferation or even antibody production to vaccines and biomarkers for inflammation (IL6) were all affected. I had no idea that stress could cause the immune system to be suppressed in both cellular and humoral immunity. The article I found about this topic was fascinating in making individuals have chronic stress for 150 days on Earth. This is more of a study of what can happen here on earth and other stress factors that could affect us and possible stress-related disorders. It also brings up cytokines such as (IL-7) which in the study showed a dramatic decrease IL-7 and would not return to normal after 150 days after the chronic stress was removed. I attached the paper if you want to read more about it!
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464898/
When I read the blog, I thought Resilience means our immune system is OK with the space environment because of some reactions in our body. Now I realized that resilience is linked to spaceflight period and prefight period.
In the post, you mentioned like inflammatory cytokines being influenced by the stress of returning to Earth. Here I saw a article that describes dendritic cells and hydraulic resistance(HR). I think hydraulic(stress) maybe one major stress that our immune system faced when during spaceflight. According to the article, immature rearrange actomyosin to form macropinosomes and mature DCs instead decrease micropinocytosis. Besides, HR may lead to DCs to lymph node as the article states and DCs are bridge between innate and adaptive immune response, it is related to what I have learned.
Here is the link:
https://www.ncbi.nlm.nih.gov/pubmed/30982662
This article was thoroughly intriguing. I’d never thought about different environments (outside of our planet) and their effects on normal bodily functions. Seeing the resilience of the human body as it returned to relatively normal levels after returning to earth has me questioning how much time would be needed before we see irreversible effects. This lead me to an article that found the normally dormant virus, herpes, became active during/after time in space. It discusses how the extended time in space and the constant environmental/social stresses, paired with decreased cell-mediated immunity could have contributed to the reactivation of the normally latent herpes virus. It’s common knowledge that consistently high levels of stress have significant adverse effects on the body, especially on the immune system. This weakening of the immune system brings up the question of whether other opportunistic viruses/pathogens could essentially ‘awaken’ and take advantage of the deteriorated state of the immune system during/after time in space.
https://www.ncbi.nlm.nih.gov/pubmed/30792698
I chose this article because it seemed quite different from the others, as it introduces the changing immune system caused by space exploration of humans. After reading this article I asked the question: what exactly changes, specifically which parts of the immune system, and are all the space explorers affected the same way?
This experiment from the link below portrays the differentiation of the immune system after a 6 month expedition. According to the authors, there is a significant down regulation of T/NK cells and an increase in inflammatory cytokines. Diminished cell-mediated response was detected by the increased latent herpes virus activation. The inflammatory cytokines were said to be caused by pressure changes along with pre-exposure to antihistamines that the crew members were taking on earth: suggesting that the body wasn’t producing enough anti-inflammation to down regulate the cytokines caused by pressure changes.
The article also signifies the importance of how each crew members were affected differently, as some did not show any immunological differences at all. Comparing to the article above, I believe that although the use of twins was a good way to control the experiment, more than one subject is necessary to fully understand the extent of changes or why the changes occur. In addition, the article suggests that life of earth prior to their expeditions had a significant effect on how the crew members perform in space, thus providing yet another variable to the changes seen in their immunity. This is further supported by the changes the human body goes through just by changing the altitude or the temperature of their environment; concurrent with the stress factors mentioned above.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038331/
I suppose the question that major space agencies are asking now is since we know that the change in habitat causes the plethora of problems we face in space today, how can we make sure that the astronauts don’t face issues. Even during the age of exploration, many travelers, immigrants, and armies faced problems such as Malaria or West Nile Virus, which decimated entire groups of newcomers to an area. Unlike that previous time, the ISS can control what the climate, and microbiome is inside the vessel to such a degree that the only problem facing people in space is just microgravity. For this reason, I am convinced that the best way to solve this issue is to introduce gravity in space in spinning spaceships or space stations. The paper I chose talked about how the immune system is dysregulated when in space. If gravity is introduced, all the major causes of problems are eliminated (sans radiation). If this issue can be solved, then most immunological problems that face astronauts (which are caused by physiological stress of microgravity) are greatly reduced or solved.
https://www.ncbi.nlm.nih.gov/pubmed/30018614
I find the suppression of the immune system due to space flight very interesting. The findings in the report show that many bodily functions are affected by the lack of gravity experienced by the astronauts. DNA damage has been shown to actually trigger an immune response since there is a DNA damage response in cells which react to abnormalities in gene expression. However, the astronauts are in space so conditions are changed for their bodily function. There are a number of factors which may affect the immune system although DNA damage does not seem to be included. Some factors which may have impeded the function of the immune system can include the different bodily fluid circulation in space,
altered gut microbiome, or even the mitochondrial misfunction. While there are many unknown effects of spaceflight on the human body, they seem to be working in tandem to inhibit many bodily functions, not just the immune system. There are most likely several causes for the weakness in the immune system during and after spaceflight.
https://www.ncbi.nlm.nih.gov/pubmed/16914325