D

Complementarity of NASA’s Division of Biological and Physical Sciences and Human Research Program

This appendix references the scope of Chapter 4, and specifically the recognition that some biological/life science research in the NASA Science Mission Directorate (SMD) Division of Biological and Physical Sciences (BPS Division) that enables space exploration has natural connections to the separate Human Research Program (HRP) that has focused on astronaut health and safety.

The biological and physical sciences (BPS) research community perceives a natural, beneficial overlap between the applied, human, risk mitigation–focused research that is the focus of HRP and the fundamental, discovery-focused research that is the focus of the BPS Division and extends beyond humans. That said, this decadal survey comes at a time of adjustment within NASA as a funding agency, especially with the move of the BPS Division from the Human Exploration and Operations (HEO) Mission Directorate to SMD. To emphasize, NASA’s BPS Division rests within the Science Mission Directorate and sponsors scientific research to answer fundamental questions requiring access to space, among other important roles in science-focused missions. Separately, the HRP is a NASA program within the Human Exploration and Operations Mission Directorate, focused on discovering the best methods and technologies to support safe, productive human space travel. HRP is headquartered and administered at Johnson Space Center in Houston, Texas, and includes other elements at other NASA centers.

These foci are complementary; new methods and technologies for safe and impactful human space travel can benefit from the underlying science of mechanisms conferring or avoiding risks—in natural or engineered systems. The BPS research community’s perspective and preference inferred from input papers, panel discussions, and committee discussions is that the BPS Division maintains a strong, positive interaction with the biological sciences at the HRP within NASA. That relationship continues to evolve, with HRP focusing ever more directly on the science of human health in space, with the BPS Division focusing more on the fundamental biology of model systems to inform the basic science that impacts human health and the biology of all systems that are part of traveling in space.

In identifying priority key scientific questions (KSQs) for the BPS decadal survey, it was necessary for the BPS research community to reflect on commonalities and distinctions of research areas supported by two different parts of NASA, the BPS Division and HRP. To be clear, several other government agencies and some companies fund research related to human health and safety, and the BPS Division’s research focus is much broader than fundamental science related to mechanism associated with health or countermeasures in space environments. But NASA’s unique focus on space science is key to momentum in BPS research and is of finite resources well below

that of the National Institutes of Health (NIH). Thus, concerns about delineation between BPS Division priorities and HRP priorities draws attention of the BPS research community. This decadal survey is not tasked with advising NASA on its own internal organization and budget lines. However, from the BPS researcher community, the sense built over this decadal survey is that these are viewed appropriate as a Venn diagram of overlapping scientific interests buttressed by distinct missions to apply that understanding.

Recommendation 4-1 emphasized scientific exchange (e.g., of plans and data) and coordination (including of sponsoring scientific research of complementary benefit) between these two NASA units. This recommendation stems from strong preference by the science community that artificial siloes of funding and information exchange are minimized so that answers to critical scientific questions and U.S. leadership in finding and using those answers are not stalled by U.S. agency-internal administrative details. When the primary beneficiary of the answer is the astronaut of the coming decade, this is HRP-leaning research; when the primary beneficiary of the answer is the Earth-based population now and in the distant future, this is BPS-leaning research. But rather than debates about whether the scientific question falls into a BPS or HRP bucket, debates among research administrators and planners and peer reviewers can be focused on the relative importance of the question and impact of answering it for society. One way (among others) to consider the Venn diagram position of the research plan could be: If not for humans traveling to and exploring space safely and productively, would answering this research question, achieving this research aim, or testing this research hypothesis be prioritized? Or, If not for access to the more resource-intensive laboratory of the space environment, would less precise or accurate answers to this research question be a societal detriment on Earth?

Consider the following two science questions where one grapples with this real or perceived overlap, given awareness of finite resources (including both available funding and researchers’ time):

1. How does reduced gravity affect aging processes in the brain?
2. How does fluid flow in reduced gravity through narrow channels?

Clearly, addressing either of these science questions can aid fundamental understanding and discovery unrelated to human health and safety, and can also aid astronaut human health and safety. A proposed research plan would inform the balance of each. In broad question 1, research project plans could be focused on durations and conditions and countermeasure technologies relevant to cognition during astronaut missions (HRP-leaning), or they could be focused on leveraging the space environment because accelerated effects of aging facilitate organoid-based assays of demyelination that would take decades on Earth but help address untreatable neurodegenerative diseases if understood (BPS-leaning). In broad question 2, research project plans could be focused on experiments that could improve fire safety associated with transfer of specific combustible liquids in the space environment for refueling (HRP-leaning), or they could be a computational modeling effort requiring validation of semi-empirical constants with potential applications of that validated general model to blood flow in astronauts on the way to Mars, to water flow in LEO-located plants, and to improved spatial tolerance when three-dimensional (3D) printing with complex fluids on Earth’s moon or on Earth (BPS-leaning).

These examples show that while one can map the relative position of a research project plan on a Venn diagram, the more important exercise during finite resource allocation is understanding the relative impact of the knowledge gained from the research—including the impact of fundamental knowledge that may have no immediate utility in space or on Earth—and the relative quality of the research project plan. The “so what?” of the research outcomes should be compelling but need not be immediately useful to astronauts or to Earth-based communities to be compelling.

With this context specific to NASA organization, the research areas below are those that were discussed within the BPS decadal survey, with thoughtful input across the BPS research community. These research areas are not an exhaustive list of complementary research areas between HRP and the BPS Division, but they are those developed in the process of considering potential scientific questions of interest to the BPS community. These research areas were not included among the KSQs for BPS in the coming decade, not because they are not important avenues of study in the coming decade, but because they represent areas much closer to the HRP side of synergistic overlap in NASA between HRP and the BPS Division.

IMPACT OF THE SPACEFLIGHT ENVIRONMENT ON THE MUSCULOSKELETAL SYSTEM AND ITS FUNCTION

The response of the musculo-skeletal system to microgravity includes significant muscle wasting and bone loss (Backup et al. 1994; Fitts et al. 2001; Radugina et al. 2018; Shenkman et al. 2003; Trappe et al. 2009). Astronauts are estimated to lose ~1–3 percent of bone mass per month while in space. Over the course of an exploration class mission, this rate of bone loss will increase fracture risk for any astronaut transitioning to a partial or full gravity environment. Such an event could be mission-critical and potentially life threatening, depending on any complications. Indeed, post-flight fractures have occurred in long-duration astronauts, although not yet during space missions. There is also significant muscle loss in arms and hands of astronauts in response to long-duration spaceflight (Puglia et al. 2018), despite the fact that arms and hands are continuously engaged in daily activities. This has prompted the implementation of daily exercise to counteract muscle and bone remodeling. Despite such measures, astronauts still experience muscle weakness and bone loss when returned to Earth’s gravity (Fitts et al. 2010; Gopalakrishnan et al. 2010; LeBlanc et al. 2000), suggesting that other factors, in addition to reduced activity, play roles in musculoskeletal remodeling.

Potential Research Areas

The main mechanosensory cells in bone are osteocytes. Osteocytes normally play an essential role in modulating bone formation and resorption by recruiting osteoblast (bone-forming) or osteoclast (bone-resorbing) cells. Bones exposed to microgravity have greater numbers of empty osteocyte lacunae than control bones, indicating the death of osteocytes. It has been proposed that this loss of viable osteocytes dramatically alters bone mechanosensation during spaceflight. Numerous studies have further shown altered expression in osteoclasts (Backup et al. 1994), which has relevance for bone loss in astronauts. Several studies have suggested that one factor is a decline in protein synthesis (Allen et al. 1996; Caiozzo et al. 1994; Esser and Hardeman 1995; Fitts et al. 2000; Gambara et al. 2017; Martin 1988). Following exposure to microgravity, osteocyte apoptosis occurs, which leads to further osteoclast recruitment. If decreases in viable osteocytes alter the mechanosensory systems of bone, this may also impact nearby skeletal muscle, given the degree of biochemical crosstalk between these two tissues. Understanding how to best mitigate these effects remains an open question.

Impact of the Spaceflight Environment on Aging

The cause of aging, an inevitable biological process that affects almost all living organisms, is still an area of significant controversy. Although numerous hypotheses, including increased oxidative stress, accumulation of damaged DNA molecules and mutations, and telomere shortening (da Costa et al. 2016; Horvath and Raj 2018), have been proposed, none of these hypotheses completely explains aging phenotypes or processes. Thus, it is difficult to determine if the space/planetary environment affects aging or not. However, all the hypothetical drivers of aging listed above have been shown to occur in response to the space environment, indicating the likelihood that accelerated aging does indeed occur. One unifying factor that supports the idea that space travel increases aging is the level of stress experienced. Exposure to chronic adverse conditions, and the resultant activation of the neurobiological stress response cascade, has been associated with an increased risk of early-onset, age-related disease as well as an older biological age. This body of research has led to the hypothesis that exposure to stressful life experiences, when occurring repeatedly or over a prolonged period, may accelerate the rate at which the body ages (Polsky et al. 2022). Astronauts undoubtedly experience chronic adverse conditions, whether in a spacecraft or on a planetary base, and are therefore likely to experience psychological and physiological stress leading to accelerated aging.

To address the premise that exposure to the spaceflight environment represents an environment of accelerated aging study, 3D cell models have recently been explored on the International Space Station (ISS) as part of an NIH initiative.¹ This initiative comprised nine separate projects that explored the effects of spaceflight on a spectrum of

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¹ National Institutes of Health, “Tissue Chip for Drug Screening,” updated May 10, 2023, https://ncats.nih.gov/tissuechip.

disease states and organ functions, including immune responses, kidney and cardiac function, osteoarthritis, and biological barrier responses. But, given the recency of these studies, results are yet to be published. In this context, it is noteworthy that the bone loss and muscle atrophy are hallmark aging phenotypes (Bettis et al. 2018). In addition, simulated microgravity has been shown to accelerate aging of cultured human skeletal muscle myoblasts, with these effects remaining upon return to Earth’s gravity (Takahashi et al. 2021). Given these similarities, it is highly likely that studies of organisms and tissue interactions in altered gravities will shed light on fundamental aging processes occurring in humans on Earth.

What Are the Mechanisms and Impact of Spaceflight-Induced Changes in Telomere Length?

A key age-related marker is telomere length, which has been assessed in astronauts (Bailey et al. 2022). In the majority of human cells, telomeres shorten with time until reaching a critically short length, at which point a permanent cell cycle arrest, known as replicative senescence, is entered. This underlies a major theory of aging. Surprisingly, spaceflight-specific telomere elongation was confirmed in three unrelated astronauts during 1-year and 6-month missions aboard the ISS using multiple assays. For example, telomere length in humans was altered in the Twin study; although in this case, telomeres lengthened in space but returned to normal upon return to Earth (Garrett-Bakelman et al. 2019). However, on returning to Earth, astronauts showed a rapid shortening to a length below that seen before flight, indicating that increased telomere shortening, and therefore accelerated aging, is a feature of spaceflight.

What is the impact of spaceflight-induced changes in known hallmarks of aging (genomic instability, epigenetic alterations, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication)? Many changes in accepted hallmarks of aging have been shown to occur after exposure to space radiation, suggesting that aging is accelerated in the space environment. A caveat to this view is that the dose rates of charged-particle radiation in the extraterrestrial environments accessed to date are too low to affect these biological responses significantly. However, the nature of aging and age-related degenerative diseases (e.g., age-related Alzheimer’s) is that they develop gradually; the process is incremental and cumulative, meaning that small amounts of insults over time can eventually lead to an overall large impact. This point is particularly relevant for future long-term missions in space where such cumulative damage could be expedited. To effectively answer these questions, future studies focused on improving long-term monitoring of aging markers in current and former space travelers are required.

Is it possible to alter and/or leverage the regenerative capacity of stem cells to develop targeted countermeasures for the physiological stress induced by space exploration? Stem cells are critically important for regeneration of muscle cells, bone cells, and nervous system and immune system function, but understanding of the effects of altered gravity is limited. A number of different studies have sent eukaryotic stem cell models to the ISS, including, but not limited to, iPSC-derived cardiomyocytes (iPSC-CM) (Acharya et al. 2022; Wnorowski et al. 2019). Experiments to date suggest that the ability of stem cells to differentiate along multiple phenotypic lineages is negatively affected by spaceflight, although cells returned to Earth’s gravity subsequently exhibited increased stemness and ability to differentiate into (e.g., myocardial [Blaber et al. 2015]) cells. Similarly, human mesenchymal stem cells were reported to show an increased capacity to secrete cytokines and growth factors and were more potent in their immunosuppressive capacity compared to ground controls in one study (Huang et al. 2020), although other studies found no significant change (Ludtka et al. 2021). Nevertheless, the current literature suggests that individual stem cells have intrinsic gravity-sensing mechanisms and that understanding the cellular basis of these effects could unlock the regenerative capacity of stem cells to develop targeted countermeasures.

IMPACT OF THE SPACEFLIGHT ENVIRONMENT ON THE NERVOUS SYSTEM AND ITS FUNCTION

The abrupt transition to a reduced gravity environment during spaceflight, as well as the abrupt reappearance of gravity experiences during landing, has a marked impact on the nervous system. Astronauts experience significant impairments regarding their perceptual and motor performance. This is because the reduced gravity environment

of space unloads the vestibular otolith organs of the inner ear, which normally detect the orientation of the head relative to gravity (Carriot et al. 2021). As a result, the otolith organs are no longer stimulated as they would be on Earth. This also affects vestibular nuclei and cortical projection, where different sensory inputs are integrated (Morita et al. 2016). There is emerging evidence that the brain uses two main strategies to adapt to such changes. The first involves the rapid updating of a cerebellum-based internal model of the sensory consequences of gravity (Mackrous et al. 2019). The second involves the reweighting of extra-vestibular information (Jamali et al. 2019) as the vestibular system becomes less (i.e., entering microgravity) and then again more reliable (i.e., return to Earth). Research in animal models and humans exposed to analogs of spaceflight have revealed substantial reorganization of the peripheral and central nervous systems. However, knowledge of environmentally induced changes remains largely based on ground-based studies that have focused on the influence of altered gravity (Carriot et al. 2021; Clément et al. 2020). Space-based experiments are required to advance knowledge of the neural mechanisms that mediate neural adaptation to the space environment, as well as establish how to best optimize these mechanisms to improve behavioral and cognitive performance.

In addition, although the central nervous system (CNS) is not traditionally considered to be the most radio-sensitive organ, any damage to it can be particularly devastating to health and quality of life, and it is difficult to repair. Because all body systems are regulated to some degree by neural input, impaired CNS and/or neural damage can result in a cascade of negative functional outcomes. Recent research has revealed significant neural damage and concomitant cognitive deficits induced by simulated galactic cosmic radiation on Earth. For example, new functional dentate granule cells deriving from adult neural stem cells are formed during adult hippocampal neurogenesis and then integrated into the existing neural circuits. These cells are particularly vulnerable to galactic cosmic radiation. Damage to their structure will impact cognitive ability to perform pattern separation, specifically the brain’s ability to temporally distinguish information in order to store memories independently of each other. Galactic cosmic radiation also decreases dendrite complexity and density, which has been shown to negatively impact decision-making and critical thinking functions. Epigenetic effects have been demonstrated in mouse retina, which is likely relevant to spaceflight-associated neuro-ocular syndrome (SANS). CNS responses to radiation, including repair potential, can be analyzed and mitigated at different levels—from molecular (DNA damage, reactive oxygen species), to cellular (cell membrane damage, cell death), to vascular leakage and disrupted electrochemical connections between neurons, to tissue and organ damage that eventually culminates in behavioral deficits (Greene-Schloesser et al. 2012). It is important to understand the impact of galactic cosmic radiation in the actual space environment at low Earth orbit (LEO) and interplanetary regions.

Potential Research Areas

How Do the Environmental Challenges Experienced During Space Exploration Alter the Peripheral and Central Nervous Systems?

Microgravity and radiation can alter and ultimately damage sensitive sensory organs, neurons, and the connectivity between structures. Additionally, ground-based studies have shown that central neural pathways are highly plastic and display rapid reorganization in response to altered environmental constraints. Importantly, there is now emerging evidence that central neural pathways likewise display significant reorganization following exposure to microgravity that produces anatomical and structural changes across multiple regions (e.g., brain stem, hippocampus, and sensorimotor cortex) (Carriot et al. 2021; Clément et al. 2020). Thus, research is required to establish the mechanisms underlying changes within the CNS during space exploration, as well as to understand the long-term functional consequences of the resulting central neural pathway reorganization.

How Does the Space Environment Impact the Blood-Brain Barrier and Lymphatic Vessels, and Do These Changes Impair Function?

The blood-brain barrier plays an important role in protecting the brain from many compounds circulating in blood supply and in preventing edema in the brain compartment. There is evidence that blood-brain barrier

integrity is compromised after combined hindlimb unloading and chronic low-dose, low-dose-rate gamma radiation, which could lead to brain edema and cognitive impacts (Bellone et al. 2016). Similarly, lymphatic vessels form a network in parallel to the cardiovascular system and are important to the regulation of tissue fluid volume and immune responses. Lymph flow is enabled by local tissue deformation and by gravity-induced tissue fluid pressures, and hence is disrupted in the absence of gravity. Impaired drainage of cerebrospinal fluid (CSF) from the brain via lymphatics may contribute to elevated intracranial pressure and possibly blurring of vision while in LEO (Rasmussen et al. 2020). There is evidence that elements of the spaceflight environment impact the lymphatics in other systems. For example, combined proton radiation and hindlimb unloading in rodents reduces lymphocyte counts in the spleen (Mao et al. 2018) and impairs clearance of bacterial infections (Li et al. 2014), which implicates altered lymphatics given their important role in normal spleen and immune function. These data on blood-brain barrier integrity and lymphatics alterations suggest that a more thorough understanding of both is needed, especially with longer-term sojourns in the space environment.

How Does the Space Environment Modify Risks of Preexisting Abnormal Heart Rhythms (e.g., Atrial Fibrillation) and Progression of Underlying Atherosclerosis (Most Common Form of Heart Disease)?

Atrial fibrillation has been detected in ~5 percent of astronauts, similar to the rate in non-astronauts but presenting at an earlier age. Six months of spaceflight has induced transient changes in atrial electrophysiology; if this chronic condition is preexisting prior to spaceflight, longer-term complications may be possible. Sex-specific differences in atrial fibrillation and stroke put men at increased risk of serious complications in terrestrial environments; further, men may be asymptomatic in early stages. Any induction or aggravation of ventricular arrythymias can be life-threatening. Further, there is growing evidence that space-relevant radiation doses in mammals may induce (Vernice et al. 2020) and/or accelerate growth of preexisting atherosclerotic plaque (Boerma et al. 2015) and impair small arteries’ dilation capabilities (Delp et al. 2016). Functional consequences of these effects and rate of progression could be better defined.

How Does Prevention of Pregnancy and Menstrual Suppression via Oral Contraceptives Used by Women Crew Interact with Risk of In-Flight Blood Clot (Thrombus) Formation and Cancer Risks?

Many hormonal-based oral contraceptives increase risks of venous thromboembolisms (Reyes et al. 2022); this is of increased relevance given recent documentation of jugular vein thrombi in crew members.

IMPACT OF THE SPACEFLIGHT ENVIRONMENT ON IMMUNE FUNCTION

Virtually all immune cell populations are reduced after spaceflight (Baqai et al. 2009). Studies in both animal models and humans have shown that the spaceflight environment can influence mitogen-induced proliferation, cytokine production and reactivity (Baqai et al. 2009; Chapes et al. 1999; Crucian et al. 2011, 2013; Hwang et al. 2015), and leukocyte subpopulation distributions (Crucian et al. 2008, 2013; Hwang et al. 2015; Pecaut et al. 2000; Stowe et al. 2011). The overall development of macrophage subpopulations is affected both in vivo (Ortega et al. 2009) and in vitro (Armstrong et al. 1995; Ortega et al. 2012). Blood monocyte counts increased in astronauts after 9 days and decreased after 16 days in space (Stowe et al. 2003). There also appear to be functional deficits in these populations. For example, monocytes isolated from astronauts exposed to the spaceflight environment had a diminished capacity to generate an oxidative burst and phagocytize E. coli (Kaur et al. 2005). Similar changes were noted in neutrophils (Kaur et al. 2004). However, the functional consequences of these changes are not well understood.

Potential Research Areas

Potential areas of research may seek to answer the following questions: Given impacts of the space environment on the immune system and exposure of humans on Earth to circulating viral infections, will reactivation of latent viruses become problematic during exploration missions? Will immune memory developed from vaccinations

be effective in space? A review of ISS medical records indicates that prolonged rashes, allergies, and cold sores are linked to viral reactivation and immune system dysregulation (Crucian et al. 2016). What countermeasures (like those currently used aboard the ISS to mitigate reactivation of Epstein-Barr virus, cytomegalovirus, and varicella-zoster virus) (Crucian et al. 2020) will be needed to protect future space travelers, given the endemic nature of commonly circulating viruses like HIV and SARS-CoV-2, the virus causing the COVID-19 pandemic? Reactivation of either of these viruses during long-term space travel warrants consideration.

What Are the Negative Impacts of Lunar or Martian Dust on Inflammatory Processes in the Lung?

Once astronauts arrive and live on the surface, they will be exposed to elevated levels of fine dust generated from the surrounding regolith. On Earth, chronic exposure to fine particles or dust results in alveolitis, emphysema, and chronic obstructive pulmonary disease. In the Apollo era, astronauts coming back from the Moon complained about the pernicious dust from their moonwalks; it was fine and electrostatic, and it posed a respiratory hazard in a low gravity environment. Little is known about how martian or Moon dust will impact astronaut physiology, but it is likely that pulmonary function will be one of the first physiological systems to respond to extraterrestrial dust.

Will Asymptomatic, Preclinical Cancers (and Which Ones) Be Accelerated in the Space Environment and How Rapidly?

Ionizing radiation of the space environment increases risks of cancer generation, with a higher incidence in women. Sex-specific cancers such as breast, ovary, and uterus are highest risks terrestrially that could be monitored during spaceflight. During over-winter Antarctic missions, diagnoses of breast, lung, and testicular cancers have occurred, despite precautions and screening (Reyes et al. 2022).

From BPS Theme 1: Adapting to Space; Fluid Shifts

How Do Fluid Shifts Affect Vascular and Cardiac Remodeling, Baroreceptor Function, and Cardiovascular Subsystem Function?

Microgravity causes adaptive changes in cardiovascular physiology that pose deleterious consequences for astronauts. Fluid shifts alter the shape, size, and contractility of the heart. Increased cardiac filling and diuresis results in reduced blood volume and diastolic pressure. Microgravity also increases cytosolic calcium concentrations in cardiomyocytes, which enables Ca²⁺/calmodulin remodeling. Transcriptomic analysis in Drosophila hearts demonstrated a reduction in extracellular matrix proteins and an increase in proteases owing to microgravity. Thus, remodeling of heart tissue is significant following exposure to microgravity, which plays a role in pathology. For example, orthostatic intolerance is a consequence to long-term exposure to microgravity. Identifying remodeling pathways may pinpoint therapeutic targets for prophylaxis.

Fluid Shift Impacts on Visual Acuity

SANS—a condition characterized by a loss of visual acuity—has been observed in human crew members. For example, exposure to microgravity reduces intraocular—intracranial pressure gradients and has been linked to impaired visual acuity (Eklund et al. 2016; Lawley et al. 2017; Mader et al. 2011). Notably, SANS generally does not resolve after return to 1 g. Furthermore, it is more prevalent in those exposed to the space environment for longer periods of time (e.g., >6 months). There is accumulating evidence that headward fluid shifts (and perhaps reduced lymphatic drainage from the cranial compartment) contributes to increased intracranial pressure, resulting in impaired function of the optic nerve and retinal ischemia (Ly et al. 2022). Future work is required to establish whether reversing headward fluid shifts for brief periods each day (e.g., by lower body negative pressure [LBNP] countermeasures) can effectively mitigate these visual deficits and if radiation exposure exacerbates these vision changes.

From BPS Theme 1, Question 4: Multigenerational Effects

If Sperm Development and/or Ovarian Function (and Related Hormonal Factors) in Sexually Mature Mammals Is Altered by the Space Environment, Does This Result in Functional Impacts on Fertility?

This question is of immediate concern to current crew members who spend at least several months in space, and it is also critically important to long-term settlement of planetary surfaces.

How Are Conception and Pregnancy (Including Implantation in the Placenta) Initiated in the Space Environment Affected?

There is nearly zero information on this in mammalian systems, and the impact on the next generation needs to be understood.

How Is Fetal Organ Development, Particularly the Ovaries and Testes, Affected by the Independent or Combined Factors of Microgravity and GCR Exposure?

Gonadal development and any impacts on the germline will be particularly important to understanding the impact on a second generation produced by adults conceived and raised in the space environment.

Theme 3, Question 8: Probing Phenomena Hidden by Gravity or Terrestrial Limitations

Bone Growth and Remodeling

Bone loss in response to microgravity is well documented (Moosavi et al. 2021). Osteocytes show intrinsic ability to sense changes in applied stress, specifically although not uniquely among tissue cell types (Yang et al. 2018). Apoptosis plays a critical role in bone and muscle loss in response to both real and simulated microgravity (Hughes-Fulford 2003; Prasad et al. 2020). The deleterious effects of microgravity on muscle structure and function are well documented (Moosavi et al. 2021). These effects can be highly specific; for example, changes in expression of oxidative enzymes differ depending on the specific muscle fiber type being analyzed within a muscle (Thomason et al. 1992). Apoptosis plays a critical role in bone and muscle loss in response to both real and simulated microgravity (Prasad et al. 2020).

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