ISS Resident “Mousetronauts” Experience Liver Lipid Dysregulation: Challenges To Prolonged Space Exploration Deep Within Your DNA

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ISS Resident “Mousetronauts” Experience Liver Lipid Dysregulation: Challenges To Prolonged Space Exploration Deep Within Your DNA

Life on Earth is the achievement of 4.5 billion years of selective pressure and responsive fine-tuning. Evolution demands survival of the fittest, that is, such individuals best adapted to their environment will outcompete less viable contenders and live long enough to pass down their genes through successive generations. Like all other life on Earth, we Humans have only ever experienced the environmental rigors of our biosphere, and therefore have never weathered the ambient stressors that would drive adaptations suitable for life beyond the confines of the Earth. Mammalian adaptation to earthly amenities such as gravity, a protective atmosphere and 24-hour circadian rhythm, constitute the potential for a variety of metabolic and physiological dysregulations in the absence of such conditions.1


It is hypothesized that the pathologies experienced by astronauts may be attributed to a wide array of metabolic and physiological perturbations, that are of direct consequence from prolonged trips to space. Previous studies have characterized a variety of metabolic and physiological abnormalities in mice and humans, including immune system dysregulation2, insulin suppression3, muscle atrophy4 and abnormal stem cell differentiation5, however, the extent of such disruptions in the liver are under-explored, and only recently have attempts been made to link astronaut experienced pathologies to the effects of space flight on mammalian metabolism through biochemical approaches. 


The liver is considered the most metabolically active organ in the body, thus, it is a seductive target for understanding a wide range of metabolic processes and the effects that microgravity, ionizing radiation, and disruption of circadian rhythm may have on metabolism.7,8 A previous study found that mice flown on the ISS for a duration of only thirteen days had significant accumulations of hepatic lipid droplets, the buildup of abnormal triglycerides in the liver, which correlated with liver damage and activation of peroxisome proliferator-activated receptor alpha (PPARα), a molecular regulator of fatty acid transport and beta-oxidation.6 These findings suggest that even short-term space expedition have detrimental effects on mammalian physiology, specifically through dysregulation of lipid metabolism in the liver.   


The Circadian rhythm is understood to play an important role in metabolic regulation. It has been demonstrated that the molecular basis of circadian rhythm lies in gene transcription and rhythmic DNA binding proteins that dynamically activate and suppress transcription like tiny molecular stopwatches. Therefore, it is understandable that the disruption of the biological clock has significant epigenetic consequences and may be linked to the downstream accumulation of lipids in the liver.9


In considerations of the findings by Jonscher et al. the liver has once again been explored as a site of metabolic lipid dysregulation in mice living aboard the ISS (International Space Station). A recent study by Beheshti et al. (Sci. Rep. 2019, 9 (1), 19195. https://doi.org/10.1038/s41598-019-55869-2) expands on a prior study involving liver lipid metabolism in ISS resident mice by identifying differential gene and protein expression in harvested liver tissues.1 In their exploration, the authors identify metabolic dysregulation typically associated with pathologies such as nonalcoholic steatohepatitis, liver fibrosis, and nonalcoholic fatty liver disease through omics analysis.1,6  Omics are an extremely powerful approach to understanding the relationships between biochemical cause and physiological effect. In their approach, the authors use transcriptomic and proteomic analysis as a means of monitoring metabolic pathway regulation in mice, so that they may better understand the long-term detriments of extended spaceflight in Humans to be better prepared for future efforts to explore the far reaches of space.1


 Transcriptomics and proteomics are two similar tactics that inform on two entirely different aspects of a systems biology. While transcriptomics speaks to the “motivations” of the cell, that is, what is the cell being told to do by environmental stimuli, proteomics speaks to the capabilities of the cell, that is, what functions can the cell perform given certain conditions. The key difference between these two approaches is that the transcriptome is not necessarily predictive of the proteome, just as the genome is not descriptive of the transcriptome. Each layer has a plethora of regulation and profiling the individual layers allow us to better understand the biology of these highly regulated systems. Being that this research was done by NASA, a well funder national organization, and the fact that this research required the sending of mice to space; an extremely costly effort, the authors were not selective in which genes and proteins they chose to profile and therefore assayed several thousand regardless of their involvement in previous literature.

Figure 3. Liver pathway activation based on RNA-seq data interpreted through Gene Set Enrichment Analysis and GO (gene ontology) analysis. Nodes are cut into four segments descriptive of four independent missions (STS-135, RR1, RR3, and CASIS RR1). The size of the individual nodes are descriptive of the number of genes described in an individual node. Blue nodes describe downregulation, whereas red nodes describe upregulation (Beheshti et. al. 2019).1

In their transcriptomics analysis, the authors used RNA-seq combined with Gene Set Enrichment Analysis to determine the activity of a variety of metabolic pathways in the liver based on the amount of RNA recoverable from processed liver tissue. Across three experimental groups, from various orbital missions, the authors found that pathways responsible for lipid localization, lipid catabolism, fatty acid metabolism, and circadian rhythm maintenance were all upregulated in space flight mice, with z-scores representative of two standard deviations outside of mean values.1 Two particular pathways of interest, the GCG (Glucagon production pathway) and INS (insulin production pathway) were observed to be down-regulated and up-regulated respectively, which could signal for a low energy state in the liver. The authors argue, that despite these pathways typically having greater involvement in the pancreas, that the dysregulation observed in their transcriptomic analysis has been previously associated with non-alcoholic fatty liver disease due to the accumulation of lipids in the liver.1


In their analysis of the liver proteome, the authors found significant downregulation of Apolipoproteins such as ApoC1, ApoA2, and ApoA5, proteins commonly associated with lipid transport and cellular internalization of lipids.1 Analysis of their proteomic data in the gene ontology database revealed associations with lipid, sterol, and cholesterol metabolism. The authors use the proteomic data to further support that (PPARα) signaling is involved in lipid disruptions, as the aforementioned proteins are directly linked to (PPARα) metabolism.1


These two main experiments, taken together, suggest the involvement of key regulatory proteins and differential gene transcription in the disruptions observed in the liver. The up-regulation of metabolic clock genes, in association with the up-regulation of lipid metabolism pathways taken in light with knowledge that metabolism is intrinsically tied to circadian rhythm, suggests that restoration of normal circadian rhythm will restore the liver to its natural metabolic state. In the future, the authors should seek to isolate their variables and perform their experiments in an environment that produces a 90-minute circadian rhythm, such as that on the ISS, but does not possess attributes such as microgravity. The authors must also profile their proteome and transcriptome data to identify which proteins of the CLOCK and BMAL1 pathways are specifically disrupted. These efforts would allow the authors to isolate disruptions of the circadian clock as the causal agent of lipid accumulation in the liver and would aid them in developing a drug treatment that restores proper metabolic function as well as eliminates all circadian derived metabolic disruptions at their roots. This work would be salient in maintaining the health of astronauts on long expositions to space as we move forward as a society bent on colonizing far off worlds.


References

(1)        Beheshti, A.; Chakravarty, K.; Fogle, H.; Fazelinia, H.; Silveira, W. A. da; Boyko, V.; Polo, S.-H. L.; Saravia-Butler, A. M.; Hardiman, G.; Taylor, D.; et al. Multi-Omics Analysis of Multiple Missions to Space Reveal a Theme of Lipid Dysregulation in Mouse Liver. Sci. Rep. 20199 (1), 19195. https://doi.org/10.1038/s41598-019-55869-2.

(2)        Crucian, B. E.; Choukèr, A.; Simpson, R. J.; Mehta, S.; Marshall, G.; Smith, S. M.; Zwart, S. R.; Heer, M.; Ponomarev, S.; Whitmire, A.; et al. Immune System Dysregulation During Spaceflight: Potential Countermeasures for Deep Space Exploration Missions. Front. Immunol. 20189, 1437. https://doi.org/10.3389/fimmu.2018.01437.

(3)        Tobin, B. W.; Uchakin, P. N.; Leeper-Woodford, S. K. Insulin Secretion and Sensitivity in Space Flight. Nutrition. 200218 (10), 842–848. https://doi.org/10.1016/S0899-9007(02)00940-1.

(4)        Droppert, P. M. A Review of Muscle Atrophy in Microgravity and during Prolonged Bed Rest. J. Br. Interplanet. Soc.199346 (3), 83–86.

(5)        Microgravity Directs Stem Cell Differentiation. Histol. Histopathol. 2016, No. 32, 99–106. https://doi.org/10.14670/HH-11-810.

(6)        Jonscher, K. R.; Alfonso-Garcia, A.; Suhalim, J. L.; Orlicky, D. J.; Potma, E. O.; Ferguson, V. L.; Bouxsein, M. L.; Bateman, T. A.; Stodieck, L. S.; Levi, M.; et al. Spaceflight Activates Lipotoxic Pathways in Mouse Liver. PLOS ONE 201611(4), e0152877. https://doi.org/10.1371/journal.pone.0152877.

(7)        Guo, J.-H.; Qu, W.-M.; Chen, S.-G.; Chen, X.-P.; Lv, K.; Huang, Z.-L.; Wu, Y.-L. Keeping the Right Time in Space: Importance of Circadian Clock and Sleep for Physiology and Performance of Astronauts. Mil. Med. Res. 20141 (1), 23. https://doi.org/10.1186/2054-9369-1-23.

(8)        Flynn-Evans, E. E.; Barger, L. K.; Kubey, A. A.; Sullivan, J. P.; Czeisler, C. A. Circadian Misalignment Affects Sleep and Medication Use before and during Spaceflight. Npj Microgravity 20162 (1), 15019. https://doi.org/10.1038/npjmgrav.2015.19.

(9)        Khan, S.; Nabi, G.; Yao, L.; Siddique, R.; Sajjad, W.; Kumar, S.; Duan, P.; Hou, H. Health Risks Associated with Genetic Alterations in Internal Clock System by External Factors. Int. J. Biol. Sci. 201814 (7), 791–798. https://doi.org/10.7150/ijbs.23744.

Comments: 17

  1. Em Panetta says:

    Hi Jake! Thanks for such an entertaining review of the Beheshti et al. paper; the background information you provided at the start was an especially helpful framework for the new findings to follow. One quick question: you mention PPARα in parentheticals a few times, but I’m a bit unclear about how this type of signaling/metabolism works in conversation with Beheshti et al.’s discussion of Apolipoproteins. Other than that, I really enjoyed how you broke down the paper into systems of up and down regulation, and how these function under environmental pressures like microgravity and altered circadian rhythm. In addition to the suggested further work involving controlling for gravitational conditions and focusing closely on a few pathways-of-interest, I also think it may be interesting for research to follow up on an aside you mentioned, wherein the authors likened their findings to that of non-alcoholic fatty liver disease. Perhaps further clinical research will also work from this commonplace of liver metabolism to increase care for those experiencing this medical condition.

    • admin says:

      Hi Em, thank you so much! I’m glad you enjoyed the article. Ah yes, the involvement of PPARα. The authors don’t focus a whole lot on how this gene is being differentially regulated in this particular paper, however, it was in their previous study where they found that PPARα had heightened activation in mice flown aboard the ISS for 13 days. PPARα or (Peroxisome proliferator-activated receptor alpha) is a transcription factor whose presence is associated with beta-oxidation, fatty acid transport and glucose metabolism in the liver. It was found in a previous study that high levels of PPARα transcript correlated with non-alcoholic fatty liver disease. In terms of PPARα’s involvement with the current study, they do not elevate their claim as to say that PPARa is the culprit, they only say that there are a multitude of pathways that are affected and that this is one of the downstream players involved in the dysregulation seen in space-flight mice. The take away from this article is that because the circadian rhythm is being disrupted, nearly all of metabolism suffers. It really brings to light how interconnected the pathways; that we typically look at in isolation, really are. To reiterate, the link between PPARα and the apolipoproteins is that they all suffer dysregulation and the mediator of such dysregulation has yet to be discerned.

      I am curious as to what pathways you have in mind? I think that the CLOCK pathway would be a good place to start. I feel that an understanding of how circadian rhythm is maintained will be useful in advancing this study.

  2. Delsin Mayne says:

    Hey Jake, this was a great review on an interesting topic. Space travel and the ability to colonize other planets is definitely an interest of society but there are many issues with being in a different environment for a prolonged period of time. I am particularly interested in how well this study translates to humans because astronauts knowingly go into space and prepare their bodies for extreme conditions. I’m curious if this has any impact on the stress placed on the body and if it potentially reduces the dysregulation observed through the transcriptomics analysis. During my reading, I also wondered the possible implications these findings could have for individuals on Earth. I think there is potential for it to be applied to non-alcoholic fatty liver disease and maybe even other liver conditions. Would disrupting your circadian rhythm increase your risk of developing liver disease to a significant degree? This could be a concern for people who work odd hours or don’t get adequate sleep on a regular basis. Future studies focused on the specific impact of circadian rhythm would be exciting to read. I think your suggestion of isolating specific variables is perfect and would allow us to see whether one of these conditions of living in space is the primary culprit of this observed dysregulation.

    • admin says:

      Hi Delsin, thank you! From what I’ve gathered in the articles that I read astronauts do experience the same symptoms as seen in the mice, all though, they don’t have the abundant biochemical data that they have for the mice. One of the articles that I read mentioned that the lipids in human astronauts return to normal upon reclamation to the earth and the reestablishment of a proper sleep cycle. The current concern is what could happen to these astronauts while they are suffering from this dysregulation, and will it get worse as their missions to space get longer. Astronauts also suffer from a host of other ill effects such as muscle atrophy due to microgravity as well as weakened immune systems due to disruptions in hematopoiesis. As far as I have seen there have not yet been any efforts at a translational study, they simply don’t know enough to find suitable targets at this time.

      I like your idea about individuals with disrupted sleep schedules. Take a look at this paper I found. DOI: 10.1016/j.metabol.2018.02.010 It is well documented that sleep disruptions do correlate with a statistically significant increase in BMI. This could perhaps be due to disruptions of certain metabolic pathways. I would be interested in performing an analysis of the transcriptomics of sleep-deprived mice versus control to see what genes of the circadian clock pathways are dysregulated and potentially design a study in which certain mediators are knocked out and constitutively turned on to see how they individually affect metabolism.

  3. Thanks for reviewing such a cutting-edge, 21st-century paper. The effects of spaceflight on life have always fascinated me, since so much about the body is impacted by the increasing radiation exposure or removing the Earthly factors we take for granted. You said spaceflight downregulated GCG and upregulated INS, which should have a net effect of reducing glucose levels in the blood. I would expect a foreign environment (i.e. microgravity) to increase blood glucose since the organism needs to be ready for unexpected circumstances. I’m wondering what you think, or if my way of looking at it is even applicable. More Omics experiments in the future should help elucidate a better explanation of these data.

    • admin says:

      No problem Brian, I really enjoyed writing about this paper! I think that the body’s “choice” to downregulate GCG and upregulated INS was not necessarily the easiest to predict. I think that the activation of gluconeogenesis pathways is mainly due to lipid accumulation in the body. From what I can tell the body is trying to counter the lipid accumulation by deconstructing lipids and storing them as glycogen. The paper doesn’t necessarily explore this route, however, this is a potential option for where the fats may end up. It is also possible that the body simply isn’t responding to the lipid accumulation in the liver and that this change in regulation is a result of the fatty liver itself. I agree that more Omics experiments will be useful in explaining their observations. I think that one particular route that they should explore is metabolomics as this would allow us to see not what genes are being transcribed and not what proteins are being made, but the actual activities of the proteins themselves by looking at what products are being produced. This, however, for obvious reasons, ie. the mice are in space and would require frequent assaying as we are literally looking at metabolism in the works, would require a massive study to retrieve any meaningful data about the molecular composition of the mouse liver at any given moment.

  4. Ethan Forrer says:

    These sorts of experiments involving a system in a completely unnatural state are fascinating and, I agree, definitely help uncover more information about the intricacies of a pathway that we may not have thought of otherwise. The points you make on the results of this research are really interesting and I am also interested in knowing why you chose to focus on the circadian dysregulation as being the primarily instigator of the initially observed phenomena. Was that the conclusion the Authors focused on too or was that a decision you made on your own? I wonder mostly because if the symptoms really were primarily circadian based then there should be far more effective ways to test that than sending mice to space, unless I’m putting together the order of events in the wrong way.

    • admin says:

      I love this question. I chose to focus on the circadian dysregulation as the primary instigator of the observed phenomenon because it appeared to me to be the causal link. In all the papers that I read about metabolic disruptions in astronauts and mice in space, there was at least one log paragraph that would suggest circadian clock involvement. The only other option that made any real sense was the presence of microgravity, however it appears that circadian disruptions are believed to be caused by a combination of microgravity and the fact that a day on the ISS is equivalent to 92 minutes which not only prevents the normal 24-hour circadian rhythm but fails to facilitate a 92-minute circadian rhythm. We just aren’t evolved to modulate our metabolism that rapidly. The proteins, which are described as molecular timers are finely adjusted to operate on a ~24-hour cycle. I think that you’re on to something with your conclusion. I agree it should be relatively straight forward to perform these experiments on earth. The authors suggest that the microgravity simply disrupts sleep, therefore we should be able to see the same effects on mice kept in a dark room on earth in which the lights are cycled every 46 minutes and the mice are disturbed at such levels that lead to the same wakeness (activity) as mice on the ISS.

  5. WOW! What a cool paper! These authors hit so many interesting aspects of lipid metabolism (in outer space!). This was truly one of those reads that makes your mind jump to a million different places in a matter of seconds. Metabolic dysregulation of lipid profiles in particular has been demonstrated to have severe impacts on human health (especially with respect to the things that are of the most immediate effect to those in developed nations: diabetes, hyperlipidemia, metabolic syndrome, etc.). These authors did a particularly good job at elucidating potential confounding factors at every step along the way, which is eerily easy to neglect if one is not diligent. Still I have so many questions with regard to mechanism. Given the broad range of potential factors that physiologically impact mammals in outer space (e.g. microgravity, radiation exposure, stress, disruption of circadian rhythms, etc.), it still seems there is probably a more poignant answer to be had on this front. I understand the authors briefly address some of these elements in their discussion, but it seems as though there is some hand-waving going on here. I am curious, Jake, as to what your thoughts are (since the authors provide little in the way of additional speculation) for why these particular aspects of metabolism are upregulated in the context of space flight. Which features of mammalian lipid homeostasis are disrupted in such a way that the bodies of these mice (and humans as well) respond this way? Do you have any further thoughts on potential mechanism/adaptive functionality of these changes? These metabolic impacts appear to be very directed, so it seems to me there is something deeper going on here than simply an adjustment to the change in effective gravity. Why would insult to our circadian rhythms cause this transcriptomic cascade as it seems to?

    • admin says:

      Thanks Eli, I’m glad you enjoyed the paper! As to your question, I don’t think that there are any physiological reasons as to why particular pathways are upregulated in space. The key thing that I kept having to remind myself was that these mice are in an environment that mice have never had to endure. There is zero pressure on the evolution of mice to be adapted to live in space (ie, microgravity, radiation, and a 92 minute day). I think that an important experiment that the authors should perform is the knocking out of individual CLOCK genes as well as the entire CLOCK: BMAL1 pathway. I think that what is occurring is metabolism returning to its steady (unregulated state) in the absence of direction by the proteins of the circadian clock. To explore this further, I would suggest that we identify genes that are differentially activated at night and day and then compare them to the genes that are activated in space-flight mice over the course of 24 hours. Essentially see how the transcriptome of ground vs flight mice changes in a 24 hour period and then correlate that to day and night cycles. My theory is that the mice or at least their bodies think that its always night, or possibly always day, and I think that identifying how transcription changes over time are the best way to elucidate how their bodies are responding to the lack of a biological clock.

      As for your other question, the insult to the circadian rhythm seems to be multifactorial as there are many down-stream pathways that stem from key mediators of the CLOCK pathway. I think that the effects go far beyond the liver and that this paper did a great job of hiding everything else so that we can appreciate what is going on specifically with lipid metabolism.

      In terms of mechanism, I haven’t a clue as to what is going on. I do however think that all the proteins that the authors identified are effects of the dysregulation rather than the root cause. I think that they focussed too specifically on the liver and may have missed the molecular mediators responsible for the dysregulation.

  6. Iffat Imran says:

    Hi Jake! This paper is a change from the usual biochemical papers we are used to reading, in terms of the angle that is taken to explain biochemical concepts, and I think you did a great job explaining the important aspects and goals of the authors.

    So, I am gathering that the gist of the information that you have summarized is that PPARα is involved in lipid destruction because its presence usually results in liver damage.. Is the up-regulation of PPARα what directly leads to a disruption in the Circadian rhythm or is it just the excess lipid metabolism that leads to this (where overproduction can occur in other ways as well)? I think I am just confused as to how significant PPARα is in all of this, if at all..

    Do you think it is possible that these destructive effects on metabolism occur simply because of the pressure differences that are present between the Earth and ISS?

    Thanks for picking such a fun article, it was so interesting to read!

    • admin says:

      Thanks Iffat! In regards to PPARα, it is comparable to any of the genes in Fig. 3, all that matters is that they see it upregulated in space-flight mice and that it is known to have involvement in beta-oxidation of fats by mitochondria and is also associated with fatty acid transport to the liver. Rather than being the cause of the circadian rhythm disruption, the authors believe it to be an effect. PPARα while important, was just a catalyst for this larger study as in a prior study they found this highly interconnected pathway to be disrupted. The disruption of lipid metabolism is also an effect of the circadian disruptions, not a cause, at least from what the authors and primary literature suggest. I totally agree with you that pressure in space could be a potential cause for the differential phenotypes observed on the ISS versus earth. One of the main effects of atmospheric pressure on the ISS is the buildup of spinal fluid in the skull which exerts pressure on the brain. This opens up questioning to things such as the potential for hormonal effects on gene transcription due to the influence that low pressure and the absence of gravity has on the brain.

  7. Ryan Johnson says:

    This paper had a particularly interesting context, Jake. Biochemistry and space travel don’t have the most obvious overlap between disciplines, so it’s fascinating that the authors chose this. An in depth understanding of how life works in space is critical, as Humans begin to delve further into space travel and exploration. I agree with the consensus that more needs to be done in light of the tremendous potential for follow-up research of this paper. The paper discusses the suppression of glucagon and increase of insulin, and therefore a notable decrease in blood glucose levels. This in turn would mean less glucose for energy and macromolecule synthesis, which might explain why such conditions as muscle atrophy are frequent side-effects of space travel. The authors do seem vague in some places overall, however. As you said, it would have been helpful if they had identified exactly which proteins were disrupted in the affected pathways, and perhaps provided a cause or mechanism for how (or at the very least their speculation). There are a number of conditions in space that differ greatly from the environment in which we are meant to live here on Earth, but the authors only briefly mention these and to my knowledge, don’t provide much information or speculation as to which factor(s) affect what and how. It is understandable that some of these areas are more vague, given that this is relatively new breakthrough involving complex multi-omics, and the additional complication of necessitating spaceflight data.

  8. Miranda Robinson says:

    Hi Jake!

    Wow, what a crazy paper! I had no idea that environmental changes (albeit, drastic environmental changes in this case) could have such profound effects on metabolic processes. This paper really made me think about the classic nature-nurture debate. While extreme, I think this is a fantastic illustration of not only differential expression, but differential function and regulation of metabolic pathways in response to environmental factors. It seems that (especially because this was funded by NASA) the authors were truly interested here in the metabolic effects of long-term space travel, but do you think that these findings could be applicable to the more average human systems at all? I am particularly interested in this question with regards to circadian rhythms. The authors first introduce the possibility of this effect in the discussion after explaining the possible disruption to the sleep cycles of the mice by microgravity. I think a lot of people (especially students) have somewhat irregular sleep cycles, and I feel like I hear about sleep-health associations all the time, so do you know if sleep or other circadian disruption has been associated with metabolic pathologies like NAFLD in non-astronauts? You mention in your background information for the paper that circadian rhythm has known metabolic links, which I suppose is not surprising, but I would be interested in knowing if you came across any specifics established here.

  9. Lauren Stover says:

    This was a really interesting paper to read because, like other people said, the idea of taking biochemistry and seeing what happens when we change the environment (like going to space) affects the body, especially because this is something people have dreamed and written about for decades. This presents another complication as to why humans can’t live in space indefinitely on top of all of the other logistical challenges, and in some ways this is more serious due to the medical issues which could arise due to being in space. I think it’s also interesting to think about how this in a way explains why when astronauts return to Earth after being in space they often develop medical issues like muscle atrophy and weaker bones. However, that’s almost too easy to diagnose and complications with the liver, I think would be harder to know about ahead of time because the symptoms might not be as obvious or could be blamed on other things, so this paper is definitely an interesting and necessary paper if humans do want to travel in space. The one question I have is about what you believe the next step of the authors should be and perhaps you could expand on what you were getting at. I understand the 90 minute circadian rhythm and isolating specific genes and proteins to study in more detail, but you mention not doing this in microgravity. Since this paper is looking specifically at mice in microgravity environments like space to better understand the effects on the body, I question why you think they should not be studied under this condition. Would this be to simplify factors and to then build up to an environment that mimics space or would this be to better understand particular steps in the pathway and perhaps better understand the diseases you mentioned (like nonalcoholic fatty liver disease). Do you propose another environment that would be interesting to test in instead and how those results could be applied

  10. Alex Goldberg says:

    I have what may be a dumb question concerning the article, but I will ask it any way. It seems that the authors are concerned about the effects that stress may have on the animals as they are sent back from the ISS, and used new methods of sacrificing the animals while they are on the ISS. Maybe I am misunderstanding, but the article says that these mice were flown to the ISS. Does this not cause the same stressors that they are trying to eliminate by killing the mice on the ISS? Would it not be better to just raise the mice exclusively on the ISS so that they can just focus on the effects of the microgravity environment? Again, maybe I am misunderstanding something, but this is a question that I had about the methodology. Thanks!

  11. Matt Hager says:

    Hi Jake, great job breaking down this very complex and exciting article. There is a lot of data and findings within this article that could be integral in our research into how to better withstand the conditions of space, especially as space travel becomes more and more prevalent. One question I had while reading through the article and your summary, was regarding the recovery of the accumulation of lipid droplets within the liver. From what I read, it seems as though all of the mice that were flown to space in this experiment were off the earth from around 13 to ~40 days. I’m curious as to whether or not after this time, perhaps the circadian rhythm could be better adjusted, and the accumulation of lipid droplets could be reduced. With that being said, further research would need to be done about the direct effects of microgravity more specifically, as this could be more of a problem compared to the disruption of circadian rhythm.

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