NASA Research Mitigates Microgravity Effects, Creates Better Treatments for Muscle, Bone Deterioration

By now, researchers are familiar with the effects of microgravity on bone tissue. Astronauts witness a monthly reduction of approximately 1% in the density of their weight-bearing bones during space sojourns, unless precautionary measures are taken to counteract this decline.

Bone cells recalibrate their functions; those engaged in building new bone decelerate, while their counterparts breaking down old or damaged bone tissue persist at their customary pace. The outcome is a delicate equilibrium where breakdown outpaces growth, giving rise to bones that are not only weaker but also more brittle.

Muscles also go through a similiar deterioration when exposed to low gravity. This simultaneous loss of bone and muscle, aptly termed atrophy, emerges as a formidable concern for astronaut health. Strikingly, the parallels between space-induced atrophy and terrestrial health issues arising from aging, sedentary lifestyles, and illnesses underscore the far-reaching implications of microgravity research.

Unraveling the Microgravity Enigma: A Continuing Quest

Scientists already understand most of the basics of microgravity’s impact on bone and muscle deterioration. However, they still routinely conduct research to understand specific causes and machinations of this deterioration and how to mitigate it. This research can have practical applications on Earth through new therapies and treatments.

Exercise remains the most common way to try to mitigate atrophy in both bone and muscle for astronauts on long-duration missions like a 5- to 6-month rotation on the International Space Station. A pivotal focus for researchers lies in deciphering the optimal combination of diet, exercise, and medication that ensures the well-being of astronauts during their missions and upon their return to Earth, the Moon, or Mars.

Some of this research has already had practical applications for treating the symptoms of conditions that can cause bone and muscle loss. For instance, NASA has previously partnered with the biotechnology company AMGEN to develop a treatment that blocks the bone formation inhibiting protein sclerostin.

Cosmic Exercise Regimens: Engaging Forces in Space

Astronauts aboard the International Space Station (ISS) spend an average of two hours daily to engage their muscles, bones, and connective tissues comprising their musculoskeletal systems. The stalwart companions in this cosmic endeavor include stationary bicycles, treadmills, and the Advanced Resistive Exercise Device (ARED), a specialized apparatus enabling astronauts to simulate weightlifting in microgravity.

The logistical challenge arises from the sheer size of these exercise machines, rendering them impractical for extended space flights where space is at a premium. Mission planners may prefer to use the space for other important cargo like supplies, equipment, spare parts, or ways to mitigate radiation exposure.

A tantalizing question captivates researchers: Can exercises with minimal or no equipment offer sufficient physical activity while conserving valuable space? The Zero T2 experiment stands as a beacon in this quest, exploring aerobic and resistance exercises without a treadmill, potentially revolutionizing exercise routines for astronauts and paving the way for space-efficient workout strategies.

(Yes, exercise equipment that doesn’t take up much space already exists. That’s great for people who can’t justify the expense of a gym membership or an expensive treadmill that might just take up limited space in their homes. However, this equipment hasn’t always been rated for long-duration space missions or as much as two hours per day of exercise, every day.)

Virtual Reality: Transforming Cosmic Workouts into an Odyssey

Convincing astronauts to dedicate two hours or more to daily exercise poses a significant challenge. Enter Virtual Reality (VR) for Exercise, an innovative approach aiming to develop virtual reality environments that astronauts can traverse while cycling on the station’s exercise bicycle. More than a change in scenery, this immersive experience seeks to inject an element of enjoyment into exercise routines, bridging the gap between monotony and enthusiasm.

This idea likely was not unique to NASA. Bicyclists have often been frustrated by the monotony of having to make do with a stationary bike during harsh winter months. Many of them get around this by buying an inexpensive virtual reality headset and finding apps that can provide the same interesting landscapes that they’d get during more pleasant cycling weather.

This approach can also make astronauts on long-duration missions more enthusiastic about an otherwise boring workout. It also gives researchers a chance to get better results in their studies of the physiological realm of how the body perceives exercise in microgravity. Companies like ARED Kinematics can have their R&D departments analyze muscle strain, bone stress, and internal factors to develop more effective workouts and products to improve fitness, both in space and on Earth. The insights gleaned aim to guide scientists in adapting exercises to microgravity, preserving astronaut health during prolonged space missions, and facilitating safe and swift recovery post-flight.

Vertebral Strength and the Overlapping Odyssey

Experiments such as Vertebral Strength extend their gaze beyond the cosmos, capturing detailed scans of astronauts’ bones and muscles supporting the vertebral column before and after spaceflight. This wealth of information becomes a linchpin in understanding overall musculoskeletal strength, mirroring research on Earth related to osteoporosis. The synchronicity of symptoms between bone loss in microgravity and osteoporosis on Earth ignites a beacon of hope. Drugs designed to counteract bone loss on Earth, including myostatin inhibitors, emerge as potential saviors for astronauts and terrestrial beings grappling with bone and muscle loss.

Bridging the Gulf: Rodent Research 19 (RR-19)

In the quest for solutions, Rodent Research 19 (RR-19) takes center stage, testing myostatin inhibitors during spaceflight. The findings, encapsulated in the research paper “Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight,” illuminate a promising path.

Amidst the significant health challenges confronted by astronauts on extended space journeys lies the issue of losing muscle and bone mass. The focus of the investigation was on the impact of directing attention to the signaling pathway mediated by secreted signaling molecules, myostatin, and activin A, in mice sent to the International Space Station (ISS). The outcomes demonstrate that targeting this signaling pathway yields notable beneficial effects in safeguarding against both muscle and bone loss in microgravity. This suggests the potential effectiveness of this strategy in preventing or treating muscle and bone loss not only in astronauts on prolonged missions but also in individuals on Earth experiencing disuse atrophy, such as older adults or those immobilized due to illness.

Extended spaceflight brings about physiological consequences, including the loss of skeletal muscle and bone mass. A crucial signaling pathway involved in maintaining muscle and bone homeostasis is regulated by secreted signaling proteins, myostatin (MSTN), and activin A.

Myostatin, also known as growth differentiation factor 8 (GDF-8), is a protein that plays a crucial role in regulating muscle growth and development. It can inhibit muscular development by limiting muscle cells’ ability to differentiate and grow.

Activin A is a protein in the same superfamily, transforming growth factor-beta (TGF-β), and plays a role in embryonic development and cellular differentiation. Like myostatin, it helps regulate muscle growth. It also plays a role in bone metabolism, which makes it capable of influencing bone density and remodeling.

This scientific study’s approach involved utilizing genetic and pharmacological methods to investigate the impact of targeting MSTN and activin A signaling in mice transported to the International Space Station (ISS). Wild type mice experienced substantial muscle and bone mass loss during the 33 days in microgravity. In contrast, genetically modified mice that lack the expression of the gene that produces myostatin, with approximately twice the muscle weights of wild type mice, maintained their mass more effectively during spaceflight. The systemic inhibition of MSTN and activin A signaling, achieved through a soluble form of the activin type IIB receptor (ACVR2B) capable of binding both ligands, resulted in significant increases in muscle and bone mass. Notably, these effects were comparable between ground and flight mice.

Exposure to microgravity and treatment with the soluble receptor induced alterations in numerous signaling pathways. These changes were evident in the levels of key signaling components in the blood, as well as their RNA expression levels in muscle and bone. The implications of these findings extend to therapeutic strategies aimed at addressing concurrent muscle and bone loss in individuals affected by disuse atrophy on Earth and astronauts in space, particularly during prolonged missions.

Tissue Chips: Microscopic Marvels in Space Research

Downsizing the quest for solutions, tissue chips emerge as miniature marvels imitating the complex functions of specific tissues and organs. A departure from studying whole organs in space, researchers employ handheld devices to send small tissue samples into microgravity. The Human Muscle-on-Chip experiment, utilizing a 3D model of muscle fibers from various age groups, becomes a beacon of insight into muscle function changes in microgravity. Electric pulses induce tissue contraction, mirroring the intricate dance of muscles in the human body. Notably, decreased gene expression related to muscle growth and metabolism surfaces in muscle cells exposed to space, with age-dependent variations.

Navigating the Celestial Odyssey: CIPHER’s Comprehensive Insights

As NASA sets its sights on missions to the Moon and Mars, researchers grapple with the prospect of astronauts engaging in strenuous activity in partial gravity after prolonged exposure to weightlessness. The Comprehensive Physiological Investigation of Human Response to Spaceflight (CIPHER) is an integrated experiment measuring psychological and physiological changes, including bone and muscle loss, in crew members on missions spanning a few weeks to a year.

The crucial questions unfold: Do extended missions induce more profound changes in astronauts’ physical bodies? Do changes to certain systems plateau after a specific duration in space? Do these changes reverberate across different biological systems?

Spearheaded by project scientist Cherie Oubre, the study aims to unravel the intricate adjustments within various bodily systems, encompassing the heart, muscles, bones, and eyes, in the face of prolonged spaceflight.

CIPHER incorporates 14 research studies sponsored by NASA and international partners, with a focus on three mission-length categories for approximately 30 astronauts: Short (less than 3.5 months in space), Standard (3.5 to eight months), and Extended (over eight months). Much of the Extended category of studies build on Scott Kelly’s famous Year in Space mission, which produced a considerable amount of data on the effects of extended space space flight on the human body. His twin, now-Senator Mark Kelly, served as a control on the ground.

These studies diligently monitor astronauts’ health before, during, and after missions, exploring key themes across different physiological aspects.

1. Bone and Joint Health:
   • Evaluation of bone density, skeletal health, and muscle quality via scans.
   • Collection of blood and urine samples to understand the impact of space on the skeletal system.
   • Examination of the rate of bone and muscle loss during and after missions, assessing associated health risks.
2. Brain and Behavior:
   • Cognitive tests and spatial cognition tasks using virtual reality.
   • Proficiency assessments in controlling a robotic arm through computer interfaces.
   • MRI scans during cognitive tests to understand alterations in brain structure and function.
3. Cardiovascular:
   • Imaging of the heart, organs, muscles, and blood vessels using CT, MRI, and ultrasound.
   • Continuous monitoring of heart rate and respiration through wearable technology.
   • Periodic blood pressure measurements to decipher cardiovascular health indicators.
4. Exercise:
   • Assessment of muscle strength and endurance using the space station’s exercise equipment.
   • Tracking of nutrition and sleep habits.
   • Post-mission obstacle course navigation, sometimes in spacesuits simulating Martian gravity.
5. Sensorimotor:
   • Recording of eye, head, and body movements to analyze factors influencing balance.
   • Surveys on the perception of motion to understand the adaptation to different gravity levels.
6. Vision:
   • MRI and eye imaging scans to examine structural changes.
   • Vision tests, eye pressure assessments, and evaluation of retinal responses to light.
7. Biomarkers:
   • Collection of blood and urine samples to explore potential health indicators.
   • Questionnaires on health and exercise habits.
   • Examination of biomarkers for changes in cartilage health, inflammation, immune function, kidney health, brain structure, and cardiovascular risk.

CIPHER incorporates the Spaceflight Standard Measures, gathering essential data on sleep, cognition, biomarkers, immune function, and the microbiome. The study employs an integrated approach, analyzing data collectively to identify patterns and deepen the understanding of the human body’s response to prolonged space travel. Key questions revolve around whether changes plateau uniformly across bodily systems after specific durations in space and if alterations in one system correlate with changes in another.

NASA relies on CIPHER to provide insights crucial for preparing astronauts for agency exploration goals.

Bridging the Gulf Between Worlds: A Cosmic Odyssey

In the vast cosmic tapestry, the exploration of bone and muscle loss aboard the ISS not only amplifies our comprehension of space-related challenges but also serves as a crucible for developing strategies safeguarding space travelers. Simultaneously, these endeavors contribute to treatments for Earth-bound individuals grappling with disease-related and age-related bone and muscle atrophy. As humanity strides further into the cosmic expanse, each venture in microgravity research becomes a beacon illuminating the intricate dance between human physiology and the cosmos, propelling us toward a future where the mysteries of space are not merely challenges but gateways to profound understanding and transformative solutions.