Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration

Abstract

Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.

Keywords: DNA damage; aerospace medicine; epigenetic; microbiome; mitochondria; multi-omics; oxidative stress; space biology; spaceflight; telomere.

Figure 1.. Information Flow from the Space Environment.

The space environment introduces several different hazards (distance, confinement, hostile/closed environments, radiation, and microgravity) that have health risks and consequences that span multiple organ systems. Monitoring of the space environment and astronauts help inform ground simulations and flight tests. These summative analyses and experimentation lead to the development of countermeasures precisely targeted towards addressing the results from risk models and predictions to mitigate the risks and health consequences posed by the hazards of the space environment. This information flow is a closed loop with feedback throughout multiple levels, for example, models may reveal new risks and the implementation of countermeasures may shift the models.

Figure 2.. Biological Features of Spaceflight.

Experiments and analyses have been designed both on Earth and in space to study the impacts spaceflight has on human biology and physiology. Subjects vary from plants, cell cultures, non-human animals, and humans. In space the hazards outlined in Figure 1 are highlighted here as they pose health risks and drive many physiological changes seen during spaceflight. On Earth, these hazards are simulated in different experiments and milieus. For example, bed studies, radiation of cancer patients, and climbers help to mimic some of the hazards experienced in the extreme environment of space and provide some insights on their impacts on human physiology. These experiments involve several analyses across multiple systems including cognition, vision, waste, blood, fluid, and post-mortem tissue measurements. Collectively, these experiments and analyses reveal significant recurrent molecular and cellular features of spaceflight including DNA damage, oxidative stress, mitochondrial dysregulation, microbiome shifts, epigenetic changes and telomere length dynamics. These features help to understand what drives some of the systemic and physiological impacts of spaceflight.

Figure 3.. Astronaut Mission or Long-Term Health Risks.

(A) Health risks are outlined based on mission types as well as over the long-term. The mission types include Low Earth Orbit, Deep Space Sortie and Journey, Lunar and Planetary visits. These missions are defined by their characteristics including mission duration, return duration, radiation exposure and gravity. Astronaut health risks spanning multiple organ systems are included with color scale to denote the NASA defined overall safety risk scores (low to high, green to red, respectively) for mission risk and long-term risk. The risks are further defined as follows: Aerobic = Risk of Reduced Physical Performance Capabilities Due to Reduced Aerobic Capacity, Arrhythmia = Risk of Cardiac Rhythm Problems, ARS = Risk of Acute Radiation Syndromes Due to Solar Particle Events (SPEs), BMed = Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders, Cancer = Risk of Radiation Carcinogenesis, CNS = Risk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure, DCS = Risk of Decompression Sickness, Degen = Risk of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure and Secondary Spaceflight Stressors, Dust = Risk of Adverse Health & Performance Effects of Celestial Dust Exposure, EVA = Risk of Injury and Compromised Performance Due to EVA Operations, Hypobaric Hypoxia = Risk of Reduced Crew Health and Performance Due to Hypobaric Hypoxia, Immune = Risk of Adverse Health Event Due to Altered Immune Response, Medical = Risk of Adverse Health Outcomes & Decrements in Performance due to Inflight Medical Conditions, Microhost = Risk of Adverse Health Effects Due to Host-Microorganism Interactions, Muscle = Risk of Impaired Performance Due to Reduced Muscle Mass, Strength & Endurance, Occupant Protection = Risk of Injury from Dynamic Loads, OI = Risk of Orthostatic Intolerance During Re-Exposure to Gravity, Renal = Risk of Renal Stone Formation, SANS = Risk of Spaceflight Associated Neuro-ocular Syndrome (SANS), Sensorimotor = Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight, Sleep = Risk of Performance Decrements and Adverse Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, and Work Overload, Stability = Risk of Ineffective or Toxic Medications Due to Long Term Storage, Team = Risk of Performance and Behavioral Health Decrements Due to Inadequate Cooperation, Coordination, Communication, and Psychosocial Adaptation within a Team. B) Future planned human missions to Low Earth Orbit (LEO), the Moon, and Mars over the next decade until 2030. ISS missions are planned throughout all years in LEO.

Figure 4.. Multi-Omics Monitoring Platform.

Schematic of a multi-omics approach to monitor astronauts. Each -omic data has its own level of localization (extracellular, intracellular, physiological, systemic, or external) and provides a unique insight that can be utilized for regular monitoring and follow-up. However, the molecular interactions highlighted in-between the different -omic data demonstrates the need to integrate all these measurements into one platform for the most comprehensive characterization and precise monitoring of an astronaut’s health.