During missions into outer space, galactic cosmic radiation (GCR) will penetrate current spacecraft shielding and thus pose a significant risk to human health. Previous studies have shown that GCR can cause short-term cognitive deficits in male rodents. Now a study published in the Journal of Neurochemistry reveals that GCR exposure can also cause long-lasting learning deficits in female rodents.
The impact of GCR on cognition was lessened when mice were fed an antioxidant and anti-inflammatory compound called CDDO-EA.
Beyond its immediate implications for space exploration, the findings contribute to a broader understanding of radiation’s long-term impact on cognitive health.
“Our study lays the groundwork for future causal delineation of how the brain responds to complex GCR exposure and how these brain adaptations result in altered behaviours,” said co-corresponding author Sanghee Yun, PhD, of the Children’s Hospital of Philadelphia Research Institute and the University of Pennsylvania Perelman School of Medicine.
As space travel becomes more frequent, a new biomarker tool was developed by an international team of researchers to help improve the growing field of aerospace medicine and the health of astronauts.
Dr Guy Trudel (Professor in the Faculty of Medicine), Odette Laneuville (Associate Professor, Faculty of Science, and Director of the Biomedical Sciences) and Dr Martin Pelchat (Associate Professor in the Department of Biochemistry, Microbiology and Immunology) are among the contributors to an international study led by Eliah Overbey of Weill Cornell Medicine and the University of Austin. Published today in Nature it introduces the Space Omics and Medical Atlas (SOMA), a database of integrated data and sample repository from a diverse range of space missions, including from SpaceX and NASA.
Space travel creates cellular, molecular, and physiological shifts in astronauts. SOMA is expected to provide a much necessary biomedical profiling that can help tease out the short and long-term health impacts of spaceflight. This will bring needed health monitoring, risk mitigation, and countermeasures baseline data for upcoming lunar, Mars, and exploration-class missions. It is meant to help keep astronauts and space travellers alive and healthy.
It may also have some intended use here on Earth.
“This represents a breakthrough in the study of human adaptation and life in space. Since many of the changes in astronaut in space resemble those of people who are immobile in bed, these studies can be clinically relevant. The data are therefore important for future space exploration while also providing a correlation to people on Earth with limited mobility or who are bedridden before their rehabilitation,” says Dr Trudel, a rehabilitation physician and researcher at The Ottawa Hospital who has focused on space travel and its effects on the human immune system.
Highlights of the study, include:
The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiome data sets, which reveal some consistent features across missions.
Samples were taken pre-flight, during, post-flight and throughout the recovery period.
Comprehensive profile of the physiological changes of the I4 crew (ages 29, 38, 42, 51) and 13 unique biospecimen sample types were collected and processed.
2911 samples were banked with over 1000 samples processed for sequencing, imaging, and biochemical analysis creating the first-ever aerospace medicine biobank.
The SOMA resource represents an over 10-fold increase in total publicly available human space omics data.
“The University of Ottawa’s Faculty of Medicine, its Faculty of Science, and The Ottawa Hospital’s Bone and Joint Research laboratory have a long history of contributions and successes in studying human adaptation to space. They also involve students from different programs, providing a unique learning experience in both bone and joint health, and in the rapidly developing field of aerospace medicine,” adds Dr Trudel.
Space travel and zero gravity can take a toll on the body. A new study has found that astronauts with no prior history of headaches may experience migraine and tension-type headaches during long-haul space flight, which includes more than 10 days in space. Studying this type of headache may provide new insights into the mechanisms behind headaches on Earth. The study was published in Neurology.
“Changes in gravity caused by space flight affect the function of many parts of the body, including the brain,” said study author W. P. J. van Oosterhout, MD, PhD, of Leiden University Medical Center in the Netherlands.
“The vestibular system, which affects balance and posture, has to adapt to the conflict between the signals it is expecting to receive and the actual signals it receives in the absence of normal gravity. This can lead to space motion sickness in the first week, of which headache is the most frequently reported symptom. Our study shows that headaches also occur later in space flight and could be related to an increase in pressure within the skull.”
The study involved 24 astronauts from the European Space Agency, the U.S. National Aeronautics and Space Administration (NASA) and the Japan Aerospace Exploration Agency. They were assigned to International Space Station expeditions for up to 26 weeks from November 2011 to June 2018.
Prior to the study, nine astronauts reported never having any headaches and three had a headache that interfered with daily activities in the last year.
None of them had a history of recurrent headaches or had ever been diagnosed with migraine.
Of the total participants, 22 astronauts experienced one or more episode of headache during a total of 3596 days in space for all participants. Astronauts completed health screenings and a questionnaire about their headache history before the flight.
During space flight, astronauts filled out a daily questionnaire for the first seven days and a weekly questionnaire each following week throughout their stay in the space station.
The astronauts reported 378 headaches in flight. Researchers found that 92% of astronauts experienced headaches during flight compared to just 38% of them experiencing headaches prior to flight.
Of the total headaches, 170, or 90%, were tension-type headache and 19, or 10%, were migraine. Researchers also found that headaches were of a higher intensity and more likely to be migraine-like during the first week of space flight.
During this time, 21 astronauts had one or more headaches for a total of 51 headaches – of which 39 were considered tension-type headaches and 12 were migraine-like or probable migraine.
In the three months after return to Earth, none of the astronauts reported any headaches.
“Further research is needed to unravel the underlying causes of space headache and explore how such discoveries may provide insights into headaches occurring on Earth,” said Van Oosterhout.
“Also, more effective therapies need to be developed to combat space headaches as for many astronauts this a major problem during space flights.”
This research does not prove that going into space causes headaches; it only shows an association.
A limitation of the study was that astronauts reported their own symptoms, so they may not have remembered all the information accurately.
By using a bioreactor aboard a flight that simulated zero gravity, researchers have found that the reason why women have a greater risk of developing knee osteoarthritis is down to genetic differences in knee meniscus tissue.
Better tests, prevention and treatments could be developed for knee osteoarthritis in women here on Earth, based on this research.
Though knee osteoarthritis is more common in females than in males, the difference cannot be explained solely by hormones. The researchers have pinpointed a genetic difference in the meniscus that makes about 50% of females more vulnerable to developing osteoarthritis than males or other females. Exposure to zero gravity is known to mimic the ageing process, as muscles atrophy and bones lose density. The zero gravity environment of space has greatly contributed to medical research.
Researchers ran the experiment aboard an aircraft flying in parabolic arcs to specially simulate zero gravity conditions, to mimic the damage that can happen to the meniscus due to lack of exercise.
“Some of the genes that were found in the females that responded more to simulated space microgravity were also associated with the development of knee osteoarthritis,” said principal investigator Adetola Adesida, professor of surgery in the Faculty of Medicine & Dentistry.
The results suggest that a blood test could screen for the high-risk gene, allowing for early interventions such as physiotherapy, and eventually even drug therapy. It might also allow women to stay in space longer.
“We’ve uncovered the mechanisms that lead to this higher response, and we are hoping to develop drugs to target those pathways and block those responses,” Adesida said.
Previously thought to be rather unimportant, meniscus acts as a load distributor for the body’s full weight. However, it is now known that just a small tear in the meniscus, often from a sports injury, increases the risk of later osteoarthritis, even if the damaged tissue has been removed. On the other hand, lack of use can also lead to deconditioning of the meniscus and increase arthritis risk.
Knee osteoarthritis is the most common joint problem, affecting an estimated 250 million people worldwide, including 14% of females older than 60 and 10% of males in the same age group.
Prof Adesida’s team has developed bioengineered meniscus tissue grown from cells that have been removed from the damaged menisci of otherwise healthy individuals. The hope is one day to be able to replace damaged tissue through transplant, preventing the development of knee osteoarthritis.
For their experiment on sex differences, the team studied how the bioengineered tissue functioned while at rest and under mechanical loading and unloading conditions. For the loading, they used a device that exerted hydrostatic pressure on the cells. For the unloading, they put the cells into a bioreactor designed by NASA to fly aboard the zero-gravity aircraft.
“Our loading and unloading experiment mimics what we actually see in a clinical situation where the development of spaceflight microgravity-induced knee osteoarthritic changes is possible,” he said.
“This will help us to have human relevant models to study knee osteoarthritis in the future. And our research has both Earth benefits and space benefits.”
Astronaut Raja Chari sequences DNA from bacteria samples to understand the microbial environment on the International Space Station. Credit: NASA
The lack of gravity in outer space could be the key to the efficient production of large quantities of stem cells. Scientists at Cedars-Sinai have found that the microgravity environment in space stations can potentially aid life-saving advances on Earth by facilitating the rapid mass production of stem cells.
A new paper in Stem Cell Reports outlines key opportunities discussed at a space biomanufacturing symposium to expand the manufacture of stem cells in space.
With new rocket technology, the cost of access to space has plummeted, opening up new opportunities for research and industry, as well as spaceflight by private citizens. Biomanufacturing of therapeutic and research biomaterials can be more productive in microgravity conditions.
“We are finding that spaceflight and microgravity is a desirable place for biomanufacturing because it confers a number of very special properties to biological tissues and biological processes that can help mass produce cells or other products in a way that you wouldn’t be able to do on Earth,” said stem cell biologist Arun Sharma, PhD, head of a new Cedars-Sinai research laboratory.
“The last two decades have seen remarkable advances in regenerative medicine and exponential advancement in space technologies enabling new opportunities to access and commercialise space,” he said.
Attendees at the virtual space symposium in December identified more than 50 potential commercial opportunities for conducting biomanufacturing work in space, according to the Cedars-Sinai paper. The most promising fell into three categories: Disease modelling, biofabrication, and stem-cell-derived products.
Scientists use disease modelling, to study diseases and possible treatments by replicating full-function structures – whether using stem cells, organoids or other tissues.
Decades of spaceflight experience has shown that when the body is exposed to low-gravity conditions for extended periods of time, it experiences accelerated bone loss and ageing. By developing disease models based on this accelerated ageing process, research scientists can better understand the mechanisms of the ageing process and disease progression.
“Not only can this work help astronauts, but it can also lead to us manufacturing bone constructs or skeletal muscle constructs that could be applied to diseases like osteoporosis and other forms of accelerated bone ageing and muscle wasting that people experience on Earth,” explained Dr Sharma.
Biofabrication, another major topic of discussion at the symposium, produces materials like tissues and organs with 3D printing a core technology.
A major issue with biofabrication on Earth involves gravity-induced density, which makes it hard for cells to expand and grow. This requires the use of scaffolding structures, but it generally cannot support the small, complex shapes found in vascular and lymphatic pathways. With the lack of gravity in space, scientists are hopeful that they can use 3D printing to print unique shapes and products, like organoids or cardiac tissues, in a way that can’t be replicated on Earth. This technology is being tested on the International Space Station.
The third category has to do with the production of stem cells and understanding how some of their fundamental properties are influenced by microgravity. Some of these properties include potency, or the ability of a stem cell to renew itself, and differentiation, the ability for stem cells to turn into other cell types.
Understanding some of the effects of spaceflight on stem cells can potentially lead to better ways to manufacture large numbers of cells in the absence of gravity. In coming months, Cedars-Sinai scientists will send stem cells into space to test whether it is possible to produce large batches in a low gravity environment.
“While we are still in the exploratory phase of some of this research, this is no longer in the realm of science fiction,” Dr Sharma said. “Within the next five years we may see a scenario where we find cells or tissues that can be made in a way that is simply not possible here on Earth. And I think that’s extremely exciting.”
ESA astronaut Matthias Maurer is shown during preflight training for the BioPrint First Aid investigation, which tests a bioprinted tissue patch for enhanced wound healing. Credit: ESA
A suitably advanced piece of wound care technology will be sent into orbit to the space station in the next few days: a prototype for portable bioprinter that can cover a wound area on the skin by applying a tissue-forming bio-ink that acts like a patch, and accelerates the healing process.
While the aim is to provide a effective wound treatment for astronauts millions of kilometres from the nearest hospital, such a personalised wound healing patch would also have a great benefit on Earth. Since the cultured cells are taken from the patient, immune system rejection is unlikely, allowing a safe regenerative and personalised therapy. Other advantages are the possibilities of treatment and greater flexibility regarding wound size and position. In addition, due to its small size and portability, physicians could take the device anywhere to an immobile patient if their cells were cultivated in advance.
“On human space exploration missions, skin injuries need to be treated quickly and effectively,” said project manager Michael Becker from the German Space Agency. “Mobile bioprinting could significantly accelerate the healing process. The personalised and individual bioprinting-based wound treatment could have a great benefit and is an important step for further personalised medicine in space and on Earth.”
The use of bioprinting for skin reconstruction following burns is one growing application for the technology. However, it presently requires large bioprinters that first print the tissue, allow it to mature, before it is implanted onto the patient. By testing it in the gravity-free environment of space, Bioprint FirstAid will help optimise of bioprinting materials and processes. Microgravity-based 3D tissue models are important for greater understanding of the bioengineering and bio-fabrication requirements that are essential to achieve highly viable and functional tissues. Under microgravity conditions, the pressure of different layers containing cells is absent, as well as the potential sedimentation effect of living cell simulants. The stability of the 3D printed tissue patch, and the potentially gravity-dependent (electrolyte to membrane interface) crosslinking process, can be analysed for future applications.
The Bioprint FirstAid prototype contains no cells at this point. The surprisingly simple prototype is a robust, purely mechanical handheld bioprinter consisting of a dosing device in the handle, a print head, support wheels, and an ink cartridge. The cartridge contains a substitution (in total two different substitutions, both without skin cells) and a crosslinker, which serves as a stabilising matrix. To test it out, the simulant will be applied to the arm or leg of a crew member wrapped in foil, or alternatively at any other surface wrapped in foil. On Earth, a printed sample with human cells will be tested, and the distribution pattern will be compared to the cell-free sample that was printed in space.
A study of five Russian cosmonauts who had stayed on the International Space Station (ISS) reveals that extended time in space causes signs of brain injury. The study is published in the scientific journal JAMA Neurology.
Scientists followed five male Russian cosmonauts working on the permanently manned International Space Station (ISS), in an orbit 400km above the surface of the Earth.
Early on in spaceflight history, extended time in zero gravity was found to result in muscle atrophy and bone loss. More recently, changes in vision were discovered during long flights, a potentially serious hazard. The vision changes were ascribed to increased cerebral pressurecaused by the lack of gravity no longer pulling fluid into the lower extremities. On Earth this is similar to lying with a head-down tilt, causing fluids to pool in the upper body and head.
Blood samples were taken from the cosmonauts, whose mean age was 49, 20 days before their departure to the ISS, where they had an average stay of 169 days.
After landing on Earth, follow-up blood samples were taken one day, one week, and about three weeks after landing. Concentrations of three of the biomarkers analysed – NFL, GFAP and the amyloid beta protein Aβ40 – were increased after their stay in space. The peak readings did not occur simultaneously after the men’s return to Earth, but their biomarker trends nonetheless broadly tallied over time.
“This is the first time that concrete proof of brain-cell damage has been documented in blood tests following space flights. This must be explored further and prevented if space travel is to become more common in the future,” said Henrik Zetterberg, professor of neuroscience and one of the study’s two senior coauthors.
”To get there, we must help one another to find out why the damage arises. Is it being weightless, changes in brain fluid, or stressors associated with launch and landing, or is it caused by something else? Here, loads of exciting experimental studies on humans can be done on Earth,” he continued.
Changes also seen in magnetic resonance imaging (MRI) of the brain after space travel add evidence to the notion of spaceflight causing brain injurt. Clinical tests of the men’s brain function that show deviations linked to their assignments in space further support this, but the present study was too small to investigate these associations in detail.
Prof Zetterberg and his coauthors are currently discussing follow-up studies.
“If we can sort out what causes the damage, the biomarkers we’ve developed may help us find out how best to remedy the problem,” Prof Zetterberg said.
Hayley Arcenaux, seated furthest left, is the Medical Officer for the Inspiration4 flight. She is a survivor of childhood cancer and works as a physician assistant at St Jude’s Children’s Hospital, for which the flight is raising funds and awareness.
The first chartered spaceflight into orbit, scheduled for launch on September 15, will have a crewmember who is both a childhood cancer survivor and physician assistant as part of the crew.
The three-day long mission aboard a SpaceX Dragon spacecraft was chartered by entrepreneur Jared Isaacman. Dubbed Inspiration4, the flight is in fact also raising money and awareness for St Jude Children’s Hospital, which was given two of the four seats on the spacecraft. The funds raised for the hospital are believed to have exceeded the cost of the flight.
Isaacman offered the first seatto 29 year-old Hayley Arceneux, who works as a physician assistant at St Jude’s and will be the medical officer for the flight. She was also a patient at the very same hospital. At age 10, she was diagnosed with osteosarcoma, the most common primary paediatric bone malignancy. In addition to a dozen rounds of chemotherapy, she had a limb-sparing operation which replaced her knee and inserted a titanium reinforcing rod in her femur. This will make her the first person with a prosthetic in space. Such a medical history would have immediately disqualified her for astronaut selection with any of the government-run space agencies like NASA.
In an interview with The Cut, she described her work as a physician assistant at St Jude’s: “I work inpatient… with leukaemia and lymphoma patients specifically. The majority of them received their cancer diagnoses pretty recently, so a big part of my role is helping to educate and support families through the beginning of treatment. I help them understand, What is cancer? What does the treatment process look like? What should I expect?
“We also manage the kids while they are in treatment. If they get an infection or if they get a fever, we take that really seriously. So I’ll manage their IV antibiotics or other treatment-related complications that can occur.. I check on patients, assess labs, order tests, update families on the results, order meds for outpatients. It is a lot of coordinating and educating. It’s hard, but it’s the greatest job in the world.”
St Jude’s held an auction for the other crew seat that Isaacman offered. The winning bidder declined the seat and gifted it to data engineer Christopher Sembroski. The final seat was won in an entrepreneurial competition by Dr Sian Proctor, a geologist and pilot who narrowly missed out on being chosen as a NASA astronaut.
Speaking about the auction, Richard C. Shadyac Jr, president and chief executive of American Lebanese Syrian Associated Charities, which raised fund for St Jude’s, said: “The impact of the Inspiration4 mission has been immeasurable, serving as an incredible platform to educate and engage millions in the movement to find cures and deliver care for childhood cancer and other catastrophic diseases through accelerated research and treatment. The auction is a critical component of the overall campaign as it enables us to reach new audiences and supporters as we work to fulfill our mission.”
So far, $100 million has been raised for St Jude’s.
While in space, the crew will conduct experiments such as examining fluid shifts in zero gravity using ultrasound, as well as other medical experiments including measuring blood glucose levels — in order to help expand space travel to those with diabetes.
A documentary has been made of the crew’s training, and is available to stream on Netflix.
Researchers from the University of Tsukuba have found a new gene involved in muscle atrophy when they sent mice into space to explore effects of weightlessness on skeletal muscles.
Extended periods of skeletal muscle inactivity or mechanical unloading (bed rest, immobilisation, spaceflight and reduced step) can result in a significant loss of muscle mass and strength which ultimately lead to muscle atrophy. Spaceflight is one of the leading models of understanding muscle atrophy from disuse.
As the molecular and cellular mechanisms involved in disuse skeletal muscle atrophy have been studied, several different signaling pathways have been studied to understand their regulatory role in this process. However, large gaps exist in the understanding of the regulatory mechanisms involved, as well as their functional significance.
Prior studies examining the effects of reduced gravity on muscle mass and function have used a ground control group which cannot be directly compared to the space experimental group. Researchers from the University of Tsukuba set out to explore the effects of gravity in mice subjected to the same housing conditions, such as the stresses of launch, landing and cosmic radiation. “In humans, spaceflight causes muscle atrophy and can lead to serious medical problems after return to Earth” says senior author Professor Satoru Takahashi. “This study was designed based on the critical need to understand the molecular mechanisms through which muscle atrophy occurs in conditions of microgravity and artificial gravity.”
Two groups of six mice each were housed onboard the International Space Station for 35 days. One group was subjected to artificial gravity (1g) and the other was left in microgravity. All mice were returned to Earth aboard a Dragon capsule and the team compared the effects of the different onboard environments on skeletal muscles. “To understand what was happening inside the muscles and cells, at the molecular level, we examined the muscle fibers. Our results show that artificial gravity prevents the changes observed in mice subjected to microgravity, including muscle atrophy and changes in gene expression,” explained Prof Takahashi.
Transcriptional analysis of gene expression showed that the artificial gravity environment prevented altered expression of atrophy-related genes, and also identified other genes possibly associated with atrophy. Specifically, a gene called Cacng1 was identified as possibly having a functional role in myotube atrophy, which previously had no known function, and was shown to have increased activity when muscle atrophy was present.
When muscle fibres were cultured in vitro, ones which had Cacng1 expression upregulated were decreased in diameter by 27.5%. A similar effect was seen in newborn mice with upregulated Cacng1.
This work validated the use of 1g artificial gravity environments in spaceflight for examining the effects of microgravity in muscles. These studies add to the body of knowledge surrounding the mechanisms of muscle atrophy, possibly improving the treatment of related diseases.
Journal information: Okada, R., et al. (2021) Transcriptome analysis of gravitational effects on mouse skeletal muscles under microgravity and artificial 1 g onboard environment. Scientific Reports. doi.org/10.1038/s41598-021-88392-4.
SpaceX, an aerospace manufacturing company currently providing satellite launch services as well as transport of crew to the International Space Station, collaborated with researchers from MIT to monitor the spread of COVID amongst its employees.
Unusually, the paper included SpaceX CEO Elon Musk as a byline author. The technology entrepreneur is known to be quite hands-on in his company’s projects. However, he has also courted controversy by openly questioning COVID tests and saying he and his family would not take COVID vaccines, saying that achieving herd immunity naturally was a better strategy.
SpaceX was seeking data-driven methods to safeguard its essential workforce. The collaboration allowed the researchers to track the emergence of mild and asymptomatic cases in a cohort of adults as early as April, when data for such cases were rare.
“Essentially, this study indicates that it’s not simply the presence or absence of antibodies that matter; rather, the amount and type of antibodies may play a defining role in the development of a protective immune response,” said Professor Galit Alter, Harvard Medical School and Immunologist, Division of Infectious Diseases, Massachusetts General Hospital.
The study was originally aimed at measuring antibody levels over time, but when reinfections began to be reported, the team realised their samples had some valuable information.
“In early spring, we weren’t sure if asymptomatic infection could drive long-lived antibodies,” said Prof Alter, “nor whether they possessed the capability to neutralise or kill the virus.”
The researchers knew that 120 participants had mild or asymptomatic COVID infections, resulting in their bodies producing antibodies. Using sophisticated techniques to analyse those antibodies, they found that individuals with stronger symptoms in mild COVID, had a larger number of antibodies and developed immune functions associated with natural immune protection.
The study found that although the presence of antibodies was sufficient to determine whether an individual had experienced a COVID infection, they did not automatically mean that individual is protected against the virus in the long term.
Antibody effector functions (on the ‘long arm’ of the antibody) linked to long-term protection, such as T cell activation and virus neutralisation were only seen in certain immune responses. These involved high levels of antibodies targetting a part of the virus known as the receptor binding domain.
“Once you hit a certain threshold of these antibodies, it’s like a switch turns on and we can observe antibody effector functions,” said first author Yannic Bartsch, PhD. “These functions were not observed in individuals with lower antibody binding titers, and the level of protection from reinfections is uncertain in these individuals.”
