Even intense physical activity by astronauts cannot compensate for the muscle atrophy caused by microgravity. This atrophy occurs, in part, due to the mechanism regulating calcium absorption. Recent studies have shown that spaceflight alters calcium absorption by muscles. However, the molecular mechanisms underlying these changes are poorly understood.
Researchers at the Ames Research Center investigated these mechanisms by using machine learning (ML) to identify patterns in datasets obtained from mice exposed to microgravity. ML methods are particularly effective at identifying patterns in complex biological data and are suitable for space biology research, where small datasets are often combined to increase statistical power. This was reported in the study “Explainable Machine Learning Reveals Multi-omics Signatures of Muscle Response to Spaceflight in Mice,” Microgravity, December 2023.
ISS032-E-011701 (August 4, 2012) – NASA astronaut Sunita Williams, Expedition 32 flight engineer, equipped with an elastic harness, performs exercises on the Combined Workload External Resistance Treadmill (COLBERT) in the International Space Station’s Tranquility Node. NASA
This image shows NASA astronaut Sunita Williams, a flight engineer for Expedition 32, exercising on a weight-bearing treadmill on the ISS. Strength training can counteract the negative effects of microgravity on muscle atrophy, but a new study from NASA’s Ames Research Center aims to understand the physiological mechanisms involved in this process and identify biomarkers that could form the basis for innovative countermeasures. The study was a project of NASA’s Space Life Sciences Training Program at NASA’s Ames Research Center, which provided the funding.
Machine learning analysis identifies molecular drivers of physiological changes in the sarcoplasmic/endoplasmic reticulum calcium channel (SERCA) pump that lead to changes and loss of muscle mass in rodents during spaceflight. Machine learning models were created to identify proteins capable of predicting microgravity tolerance in terms of muscle calcium uptake. Specific proteins, Acyp1 and Rps7, were found to be the most predictive biomarkers associated with increased calcium uptake in fast-twitch muscles.
This study presented the first investigation of the effects of ML on muscle calcium uptake in microgravity. It demonstrated the role of NASA’s Open Science initiative in accelerating the development of space biology through its use within the Open Science Data Repository (OSDR) and ARC Analysis Working Groups, as well as through the participation of an international research team from the United States, Canada, Denmark, and Australia. Notably, the paper’s first author was a UC Berkeley student, demonstrating the boundless potential of NASA-Berkeley collaboration in life sciences research, particularly within the future Berkeley Space Center at NASA’s Research Park.
Scientists have discovered that heart cells “don’t fare well in space.” Scientists from Johns Hopkins University sent 48 samples of bioengineered heart tissue to the International Space Station, where they were monitored for 30 days and compared with identical samples on Earth.
A team of scientists studied how low gravity affects measures such as the force of cell contraction, known as contractile force, and any irregular beating patterns.
The results were alarming: the scientists found that the heart cells “really did poorly in space,” contracting with about half the force of control samples on Earth—but that wasn’t unexpected.
Previous studies have shown that after returning to Earth, astronauts experience decreased heart muscle function and irregular heart rhythms known as arrhythmias. While some of these effects of space travel fade over time, not all of them do, and this will have serious implications for long-term space missions.
Kim Duk-Ho, professor of biomedical engineering and medicine at the Johns Hopkins University School of Medicine, led the project to send cardiac tissue to the space station. He and his graduate student, Jonathan Tsui, created bioengineered cardiac tissue from human induced pluripotent stem cells (iPSCs).
The cells were grown in “organ-on-a-chip” devices—miniature models of various organs in which artificial or natural tissues and cells are grown inside microfluidic chips. In this case, the 3D chip was designed to mimic an adult human heart in a chamber half the size of a standard mobile phone.
“An incredible amount of advanced technology in stem cell and tissue engineering, biosensors and bioelectronics, and microfabrication has been used to ensure the viability of these tissues in space,” Kim said in a statement.
The scientists found that the confined tissue showed increased levels of inflammation and oxidative damage; proteins called sarcomeres, which help heart cells contract, also became shorter and more disordered. These changes are comparable to those observed in people with cardiovascular disease.
Furthermore, the cells’ mitochondria, their powerhouses, became larger, rounder, and lost their characteristic shape. This further suggests that the heart cells experienced significant stress or dysfunction in space, likely resulting in disrupted energy production. This could have contributed to the weakened contractions of the heart cells and the overall deterioration of the cells observed during the experiment. Such damage could also have impacted the cells’ overall ability to function normally.
“Many of these markers of oxidative damage and inflammation are routinely detected in post-flight examinations of astronauts,” said Mayr Eun Hyun Ahn, an associate professor in the Department of Biomedical Engineering, in a statement.
The researchers intend to continue refining their “heart-on-a-chip” to collect more data that will allow them to pinpoint exactly how this damage occurs at the molecular level, and thus find ways to keep astronauts safe during the long-duration spaceflights that may soon become a reality.
Assessing PFO in relation to DCS in spaceflight conditions and during ground testing. Decompression sickness (DCS) is a condition that results from the formation of bubbles of dissolved gases (primarily nitrogen) in the bloodstream and tissues.
It typically occurs when there is a rapid drop in ambient pressure, such as in scuba diving, high-altitude aviation, or other high-pressure conditions. The released gas bubbles have various physiological effects and can clog blood vessels, cause inflammation, and damage tissue, leading to the symptoms of DCS.
NASA currently classifies DCS into two categories: Type I DCS, which is less severe, typically results in musculoskeletal symptoms, including joint or muscle pain and skin rash. Type II DCS is more severe and typically results in neurological, inner ear, and cardiopulmonary symptoms. The risk of DCS in spaceflight arises during extravehicular activity (EVA), when astronauts perform mission tasks outside the spacecraft while in a pressurized spacesuit at a pressure lower than cabin pressure.
DCS mitigation protocols based on strategies to reduce systemic nitrogen load are implemented through a combination of environmental parameters, suit pressure, and breathing gas preparation procedures (preconditioning protocols) to ensure safe and effective operations. The pathophysiology of DCS remains poorly understood, as cases are observed despite the absence of detectable gas bubbles. However, it involves right-to-left venous gas embolism (VGE) shunting through several potential mechanisms, one of which is a patent foramen ovale (PFO).
A patent foramen ovale (PFO)—the opening between the left and right atria of the heart—is known to be a cause of stroke in young people. S. Mazzucco, L. Lee, L. Binnie, P. M. Rothwell. Nuffield Department of Clinical Neurosciences
A patent foramen ovale (PFO) is a shunt between the right and left atria of the heart, a surviving remnant of the physiological connection that existed in the fetal heart. Increased left atrial pressure during the postnatal period typically compresses the interseptal valve against the septum secundum, and within the first two years of life, the septa finally fuse due to the development of fibrous adhesions. Thus, all people are born with a PFO, and in approximately 75% of cases, they fuse after birth. Of the 25% of people in whom a PFO does not fuse, approximately 6% have what some consider a large PFO (>2 mm). The diameter of the PFO can increase with age.
The problem with patent foramen ovale (PFO) is that, when a right-to-left atrial shunt occurs, venous embolic gas can flow from the right atrium (venous) to the left atrium (arterial) (the “shunt”), bypassing the normal pulmonary filtration of venous emboli, which prevents them from entering the arterial system. Without filtration, bubbles in the arterial system can lead to a neurological event such as a stroke. Any activity that increases right atrial/venous pressure relative to left atrial/arterial pressure (e.g., Valsalva maneuver, abdominal compression) can further facilitate the passage of blood and/or emboli through the PFO/shunt.
The goal of the working group was to review and analyze the status and progress of research and clinical interventions aimed at reducing the risk of PFO and DCS problems during spaceflight. Cases of DCS identified during NASA’s ground-based atmospheric testing in pressurized chambers led to the prioritization of this topic for external review.
The working group met for two days at NASA’s Johnson Space Center and included NASA subject matter experts and stakeholders, as well as invited external reviewers from fields such as cardiology, hypobaric medicine, spaceflight medicine, and military health. During the working group, participants were asked to review previous reports and evidence related to PFO and DCS risk, materials and information related to NASA’s current experience and practices, as well as case studies and subsequent decision-making processes. The working group concluded its deliberations in an open forum, where recommendations for current and future practices were made, which were subsequently summarized in a final summary report available on the NASA OCHMO standards group’s public website.
Decompression sickness (DCS): Bubbles form in the blood and tissues, causing localized damage. Arterial gas embolism (AGE) occurs when bubbles enter the bloodstream and block blood flow, which can lead to tissue damage. Peter N. Shochet, MD, and Hau S. Lee, MD, Dr. Shochet and Dr. Lee, pediatric pulmonologists
In extreme/high-risk settings, excluding individuals with a patent foramen ovale (PFO) and treating the PFO does not necessarily reduce the risk of developing DCS or create a “safe” environment. It may lead to additional differences and slightly reduce the overall risk, but it does not eliminate the risk. Other physiological factors also contribute to the risk of developing DCS and may have a more significant impact.
Based on current data and the risk of ongoing decompression exposures (as per current NASA protocols and NASA-STD-3001 requirements for mitigating the risk of DCS), screening for oval foramen defects in spaceflight or ground test participants is not recommended. The best strategy for mitigating the risk of DCS is to create the safest possible environment in any situation, including effective pre-decompression protocols, ensuring safety, and ensuring prompt treatment of DCS should symptoms develop.
Experts believe that no specific studies are currently needed to further characterize PFO with DCS and altitude exposure due to the low risk and the preference for implementing adequate safety protocols and ensuring the availability of treatment both on Earth and in spaceflight.
When conducting engineering protocols on the ground, it is necessary to ensure the same level of treatment capabilities (a treatment chamber in close proximity to the test site) as during research protocols. The ability to immediately treat patients with DCS is critical to ensuring the safety of test subjects.
Risk of Venous Thromboembolism During Spaceflight. In October 2024, the NASA Office of the Chief Medical Officer (OCHMO) initiated a working group to review the status and progress of research and clinical interventions aimed at reducing the risk of venous thromboembolism (VTE) during spaceflight. The working group met for two days at NASA’s Johnson Space Center; a second meeting on this topic was held in December 2024 at the European Space Agency (ESA) headquarters in Cologne, Germany.
The working group was formed from internal NASA subject matter experts (SMEs), the NASA OCHMO standards group, NASA and ESA stakeholders, and external SMEs, including physicians and medical professionals from leading universities and medical centers in the United States and Canada.
Spaceflight-associated venous thrombosis (SVT) is a phenomenon occurring during spaceflight in which a thrombus (blood clot) forms in the internal jugular vein (and/or associated vascular system). The thrombus may be symptomatic (a thrombus accompanied by, among other things, visible swelling of the internal jugular vein, facial swelling exceeding the “nominal” degree of adaptation to spaceflight, eyelid edema, and/or headache) or asymptomatic. Obstructive thrombi have been detected in a very small number of crew members.
This drawing is for illustrative purposes only; locations are approximate and dimensions are not to scale. Approximate locations of identified blood clots in crew members. Adapted from “Cerebral Sinus Venous Thrombosis” – University of Colorado at Denver
Thanks to treatment, the crew members were able to complete their mission, and anticoagulants were discontinued several days before landing to minimize the risk of bleeding in the event of injury. Some thromboses resolved completely after landing, while others required additional treatment.
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The proposed pathogenesis of VTE is called Virchow’s triad and suggests that VTE results from:
– Alterations in blood flow (i.e., congestion),
– Damage/changes to the vascular endothelium, and/or
– Changes in blood composition leading to hypercoagulability (i.e., hereditary predisposition or acquired hypercoagulability).
Virchow’s triad of risk factors for venous thrombosis. Bushnitsa, 2017
Venous stasis, or venous congestion, is a condition in which blood flow in the veins slows, leading to stagnation. Slow blood flow can be caused by damaged or weakened venous valves, immobility, and/or lack of muscle contraction. Associated symptoms include swelling, skin changes, varicose veins, and slow-healing ulcers. In terrestrial medicine, venous thrombosis is usually caused by damaged or weakened venous valves, which can be due to many factors, including aging, blood clots, varicose veins, obesity, pregnancy, a sedentary lifestyle, estrogen use, and a family history.
In addition to terrestrial risk factors for venous thromboembolism, there are physiological changes associated with spaceflight that are thought to potentially play a role in the development of venous thromboembolism in microgravity. Specifically, researchers have studied the effects of microgravity conditions and the subsequent observed shift in circulating fluid in the brain, as well as its potential impact on blood flow. Crew members aboard the International Space Station (ISS) experience weightlessness due to microgravity, which leads to a prolonged redistribution of circulating fluid from the legs to the head. This prolonged shift in circulating fluid in the brain during microgravity leads to facial swelling, decreased leg volume, increased cardiac stroke volume, and decreased plasma volume.
Crew members also experienced blood flow changes during spaceflight, including retrograde venous flow (RVF) (reverse flow of venous blood toward the brain) and stasis (stopping or slowing of blood flow). Although the causes of observed stasis and retrograde blood flow in spaceflight participants are poorly understood, the potential clinical significance of this role in the development of thrombosis requires further study.
Other physiological problems associated with fluid shifts are also being studied to determine whether there is any association with venous thromboembolism (VTE).
Doppler study of retrograde blood flow in the left internal jugular vein. Yang and Seow, 2009
Chronic weightlessness can cause bodily fluids, such as blood and cerebrospinal fluid, to shift toward the head, which can lead to optic nerve swelling, retinal folds, flattening of the back of the eye, and cerebral edema. This set of eye and brain changes is called spaceflight-associated neuroocular syndrome, or SANS. Some astronauts experience only minor changes in space, while others have clinically significant effects. The long-term health effects of these changes are unknown but are being actively studied. The risk of developing SANS is higher during long-duration missions.
Based on expert opinion and an assessment of thrombosis risk factors, an algorithm was developed to facilitate the diagnosis and treatment of thrombotic events in zero-gravity conditions during flight. The algorithm is based on early in-flight ultrasound imaging to determine blood flow characteristics in the left internal jugular vein and adjacent vessels.
Five years after space travel, astronauts are in good cardiovascular health. Living in microgravity changes the human body, usually for the worse. Bone density decreases, muscles atrophy, and eyes swell—these are just some of the physical side effects of long-term spaceflight. However, according to a new study, there’s good news for astronauts: long-term stays on the International Space Station (ISS) pose no risk to their arteries.
An illustration of the PULSE project platform, which uses magnetic and acoustic levitation to biologically print a model of the human heart. IN society
Researchers studied 13 NASA astronaut volunteers, aged 30 to 50, who spent between four months and a year on the ISS. They performed ultrasound examinations of the participants’ carotid and brachial arteries before, during, and immediately after spaceflight, as well as one, three, and five years later. Remarkably, everyone’s arteries looked healthy. A paper on the study was published on June 10, 2025, in the Journal of Applied Physiology.
“Long-duration spaceflight on the ISS did not result in carotid artery wall thickening, increased common artery stiffness, endothelial dysfunction, or the development of new symptoms or signs of cardiovascular disease during the first 5 years after long-duration spaceflight,” the researchers wrote in their study. They also noted that any risk of cardiovascular disease was likely due to natural aging, not spaceflight.
Levitating particles, controlled by magnetic and acoustic fields, come together to form a model of the human heart. IN Society
However, the study found oxidative stress and inflammation in the astronauts’ blood and urine samples—signs of cardiovascular problems. These signs disappeared within a week of returning to Earth. Ultimately, the cardiovascular system appears to be quite resilient to the effects of microgravity.
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