Weightlessness and gravitational physiology.

Physiologic responses to the weightless environment have been documented in Skylab astronauts. Significant changes in cardiovascular responses, calcium metabolism, fluid distribution, and red blood cell mass are described. Although the data are limited and the sample size small, several hypotheses can be formulated. Future studies in a space laboratory setting offer the potential for understanding the effects of weightlessness on human physiology and the implications to medicine.     

REGULATION OF HAEMOPOIESIS IN ALTERED GRAVITY

(1) The aetiology of one of the most striking physiological changes occurring during space-flight, the loss of red blood cells, remains unknown, and its precise time-pattern in flight has not yet been studied. (2) It is suggested that the changes during space-flight responsible for loss of red blood cells in man are (a) loss of plasma volume resulting from disappearance of hydrostatic pressure in the circulation during weightlessness and (b) reduced energy expended in maintenance of form, posture and locomotion resulting from elimination of the usual gravitational load on the muscles. Quadrupeds, like rats, would be expected to suffer minimal blood shifts in weightlessness and therefore have an unchanged plasma volume. However, since in weightlessness the activity-related energy expenditure by the muscles is reduced, the accompanying reduced oxygen demand by the tissues would cause a reduction in erythropoietin levels and so in the production of red blood cells, and a progressive lowering of the total red blood cell mass toward a new steady-state level. (3) Loss of plasma volume alone does not explain the observed loss of red blood cells in astronauts because, in the three manned Skylab missions, as the duration of the missions increased, loss of red blood cell mass decreased, whereas loss of plasma volume increased. This discrepancy is, however, well accounted for by the above hypothesis by taking into consideration the increased level of exercise of the astronauts as the duration of the mission increased. (4) Though water submersion of human subjects does mimic the effects of weightlessness, such effects were overriden in sea mammals because of adaptation to other factors associated with a life in the sea. (5) From the presented analysis of haemopoietic changes observed in spaceflight, an experiment can be designed for a future flight to uncover the causes and mechanisms of these changes and provide a basis for developing protective measures. Thus, the space environment can be used as an investigative tool to enhance the knowledge of the function of the haemopoietic system, which is a major homeostatic system of man and other vertebrates.     

Effects of a Closed Space Environment on Gene Expression in Hair Follicles of Astronauts in the International Space Station

Adaptation to the space environment can sometimes pose physiological problems to International Space Station (ISS) astronauts after their return to earth. Therefore, it is important to develop healthcare technologies for astronauts. In this study, we examined the feasibility of using hair follicles, a readily obtained sample, to assess gene expression changes in response to spaceflight adaptation. In order to investigate the gene expression changes in human hair follicles during spaceflight, hair follicles of 10 astronauts were analyzed by microarray and real time qPCR analyses. We found that spaceflight alters human hair follicle gene expression. The degree of changes in gene expression was found to vary among individuals. In some astronauts, genes related to hair growth such as FGF18, ANGPTL7 and COMP were upregulated during flight, suggesting that spaceflight inhibits cell proliferation in hair follicles.     

The effects of weightlessness on the human organism and mammalian cells

It has always been a desire of mankind to conquest Space. A major step in realizing this dream was the completion of the International Space Station (ISS). Living there for several months confirmed early observations of short-term spaceflights that a loss of gravity affects the health of astronauts. Space medicine tries to understand the mechanism of microgravity-induced health problems and to conceive potent countermeasures. There are four different aspects which make space medicine appealing: i) finding better strategies for adapting astronauts to weightlessness; ii) identification of microgravity-induced diseases (e.g. osteoporosis, muscle atrophy, cardiac problems and others); iii) defining new therapies to conquer these diseases which will benefit astronauts as well as people on Earth in the end; and iv) on top of that, unveiling the mechanisms of weightlessness-dependent molecular and cellular changes is a requirement for improving space medicine. In mammalian cells, microgravity induces apoptosis and alters the cytoskeleton and affects signal transduction pathways, cell differentiation, growth, proliferation, migration and adhesion. This review focused on gravi-sensitive signal transduction elements and pathways as well as molecular mechanisms in human cells, aiming to understand the cellular changes in altered gravity. Moreover, the latest information on how these changes lead to clinically relevant health problems and current strategies of countermeasures are reviewed.     

Bone markers during a 6-month space flight: effects of vitamin K supplementation

Rapid bone loss is a serious health problem for astronauts during long lasting missions in space. We have recorded the changes of biochemical markers for bone metabolism in one of the astronauts during the 6-month space flight of the EUROMIR-95 mission. Immediately after launch both bone resorption markers and urinary calcium excretion increased about two fold, whereas bone formation markers remained unchanged. After 12 1/2 weeks the astronaut received vitamin K1 (10 mg/day for 6 weeks). Vitamin K is known to be involved in the formation of gamma-carboxyglutamate (Gla) in proteins, such as the calcium-binding bone Gla-proteins osteocalcin and matrix Gla-protein. Concomitant with the start of vitamin K treatment, the calcium-binding capacity of osteocalcin increased, and so did the urinary excretion of free Gla. This is suggestive for a subclinical vitamin K-deficiency in the astronaut before vitamin K-supplementation. During periods of high vitamin K status markers for bone formation (osteocalcin and bone alkaline phosphatase) had increased as compared to the first part of the flight. The mean increases were 14 and 23%, respectively. Our data suggest that increased intake of vitamin K may contribute to counteracting microgravity-induced loss of bone mass during long lasting space missions, but need confirmation in more astronauts.     

Decreased non-MHC-restricted (CD56+) killer cell cytotoxicity after spaceflight.

Cytotoxic activity of non-major histocompatibility complex-restricted (CD56+) (NMHC) killer cells and cell surface marker expression of peripheral blood mononuclear cells were determined before and after spaceflight. Ten astronauts (9 men, 1 woman) from two space shuttle missions (9- and 10-day duration) participated in the study. Blood samples were collected 10 days before launch, within 3 h after landing, and 3 days after landing. All peripheral blood mononuclear cell preparations were cryopreserved and analyzed simultaneously in a 4-h cytotoxicity (51)Cr release assay using K562 target cells. NMHC killer cell lytic activity was normalized per 1,000 CD56+ cells. When all 10 subjects were considered as one study group, NMHC killer cell numbers did not change significantly during the three sampling periods, but at landing lytic activity had decreased by approximately 40% (P < 0.05) from preflight values. Nine of ten astronauts had decreased lytic activity immediately after flight. NMHC killer cell cytotoxicity of only three astronauts returned toward preflight values by 3 days after landing. Consistent with decreased NMHC killer cell cytotoxicity, urinary cortisol significantly increased after landing compared with preflight levels. Plasma cortisol and ACTH levels at landing were not significantly different from preflight values. No correlation of changes in NMHC killer cell function or hormone levels with factors such as age, gender, mission, or spaceflight experience was found. After landing, expression of the major lymphocyte surface markers (CD3, CD4, CD8, CD14, CD16, CD56), as determined by flow cytometric analysis, did not show any consistent changes from measurements made before flight.     

Circadian regulation in aging: Implications for spaceflight and life on earth

Alterations in the circadian system are characteristic of aging on Earth. With the decline in physiological processes due to aging, several health concerns including vision loss, cardiovascular disorders, cognitive impairments, and muscle mass loss arise in elderly populations. Similar health risks are reported as “red flag” risks among astronauts during and after a long-term Space exploration journey. However, little is known about the common molecular alterations underlying terrestrial aging and space-related aging in astronauts, and controversial conclusions have been recently reported. In light of the regulatory role of the circadian clock in the maintenance of human health, we review here the overlapping role of the circadian clock both on aging on Earth and spaceflight with a focus on the four most affected systems: visual, cardiovascular, central nervous, and musculoskeletal systems. In this review, we briefly introduce the regulatory role of the circadian clock in specific cellular processes followed by alterations in those processes due to aging. We next summarize the known molecular alterations associated with spaceflight, highlighting involved clock-regulated genes in space flown Drosophila, nematodes, small mammals, and astronauts. Finally, we discuss common genes that are altered in terms of their expression due to aging on Earth and spaceflight. Altogether, the data elaborated in this review strengthen our hypothesis regarding the timely need to include circadian dysregulation as an emerging hallmark of aging on Earth and beyond.     

Lipid peroxidation rate and the antioxidant protection system during the readaptation period after long-term space flights on board the International Space Station

The content of lipid peroxidation (LPO) products (diene conjugates (DC), malondialdehyde (MDA), Schiff bases (SB), and tocopherol (TP, a main lipid antioxidant) were measured in blood serum of 17 astronauts taking part in long-term (125–217 days) missions on board the International Space Station (ISS) during the preflight period, on the day of the landing, and on the 7th and 14th days after landing (the rehabilitation period, RP). A decrease in the DC and MDA levels against a background of an increase in TP has been found in a group of eight astronauts after landing on board the Space Shuttle spacecraft and a group of eight astronauts after a space flight on board the Soyuz TM in the course of RP. The changes in measured indices were more pronounced in the group of astronauts after the space flight on board the Space Shuttle spacecraft. Inhibition of LPO during RP was regarded as an adequate response to readaptation stress to the conditions on earth. The possible mechanisms of differences in the efficiency of LPO inhibition between groups are discussed: the changes in the biomembrane phase state under the conditions of deceleration load during disorbiting and the stressful reaction to landing on board different spacecrafts.     

How and why does the proteome respond to microgravity?

For medical and biotechnological reasons, it is important to study mammalian cells, animals, bacteria and plants exposed to simulated and real microgravity. It is necessary to detect the cellular changes that cause the medical problems often observed in astronauts, cosmonauts or animals returning from prolonged space missions. In order for in vitro tissue engineering under microgravity conditions to succeed, the features of the cell that change need to be known. In this article, we summarize current knowledge about the effects of microgravity on the proteome in different cell types. Many studies suggest that the effects of microgravity on major cell functions depend on the responding cell type. Here, we discuss and speculate how and why the proteome responds to microgravity, focusing on proteomic discoveries and their future potential.     

Influence of space flight on red blood cells

Losses of red blood cell mass (RCM) averaging 10-15% have been observed consistently in astronauts after space flight; postflight recovery of RCM requires 4-6 wk. Although apparently not harmful to the health and effectiveness of crews during uncomplicated flights, decreased RCM could compromise health and performance in the event of illness, injury, or partial malfunction of the life support system. Whether the loss of RCM would worsen or stabilize in missions longer than 7 months is unknown. As a biological response, it is a significant, predictable reaction whose etiology, biological mechanisms, and potential operational significance are inadequately defined. Weightlessness is probably the primary cause; however, contributory factors may include hypokinesia/hypodynamia, bone loss, muscle atrophy, altered hemodynamics, stress, and metabolic disturbances. Space medical specialists consider other possible influences such as hypoxia, hypobaria, radiation, toxic contaminants, and launch and reentry accelerations as less likely factors. Because the data base on loss of RCM is insufficient for the National Aeronautics and Space Administration's space medical responsibilities, the Life Sciences Research Office ad hoc Working Group on Space Anemia suggested research approaches ranging form fundamental topics such as utilization of erythropoietin and oxygen in target organs and cell-cell interactions, through possible splenic and vascular dysfunctions, metabolic disturbances, and inhibitors of erythropoiesis, to methodology and models.     

亚磁场及其生物响应机制

根据亚磁生物学的研究历史和空间亚磁环境的实际情况,本文定义磁感应强度总量在“0<|B|≤5 μT”区间内的静态弱磁场为亚磁场．亚磁场能对生命活动的多个方面,特别是中枢神经系统产生负面影响．随着月球与火星航天计划的开展,航天员将长期暴露于亚磁空间中．这可能对宇航员的身心健康带来潜在的危害．亚磁场生物学效应及其机制的研究,将为相关载人航天的空间防护提供理论基础,已成为空间生物科学以及航天医学等相关领域的新热点．     

The theory and application of space microbiology: China's experiences in space experiments and beyond

Microorganisms exhibit high adaptability to extreme environments of outer space via phenotypic and genetic changes. These changes may affect astronauts in the space environment as well as on Earth because mutant microbes will inevitably return with the spacecraft. However, the role and significance of these phenotypic changes and the underlying mechanisms are important unresolved questions in the field of space biology. By reviewing, especially the Chinese studies, we propose a space microbial molecular effect theory, that is, the space environment affects the nature of genes and the molecular structure of microorganisms to produce phenotypic changes. In this review, we discussed three basic theories for the research of space microbiology, including (1) space microbial pathogenicity and virulence mutations and the human mutualism theory; (2) space microbial drug‐resistance mutations and metabolism associated with space pharmaceuticals theory; (3) space corrosion, microbial decontamination, and new materials technology theory.     

Changes of insulin in plasma and receptor for insulin in various tissues after the exposure of rats to space flights and hypokinesia

The explanation of the mechanism of the response to gravity changes is of great importance for the determination of the capacity of human subjects to adapt to the load of gravitational stress. Therefore several studies were performed to investigate the activity of endocrine system, since the hormones are involved in the regulation of physiological functions and metabolic processes. However the studies of endocrine system activity during altered gravity conditions, especially during the weightlessness are influenced by the several interventions in biomedical observations due to operational program of astronauts, wide variability in individual response and tolerance, use of extensive countermeasures, differences in the type of space missions and in the studies after landing also a hypergravity effect at landing and variability in postflight readaptation process. The significant changes of plasma insulin and glucose levels were observed in astronauts during space flights and in the first days of recovery period. In the first inflight period plasma insulin levels were increased, unchanged or decreased however after 4-5 weeks of exposure to weightlessness a decrease of insulin plasma levels were noted. After space flights an increase of plasma insulin levels were demonstrated in experimental animals and in human subjects. Since plasma insulin level is considered as most important factor involved in the regulation for insulin receptors in target tissues, an investigation of insulin receptors in various tissues was performed in rats exposed to space flight or to hypokinesia (model used for simulation of some effects of microgravity).     

UBC researcher's back-pain studies focus on space travel.

Researchers at the University of British Columbia have been studying back pain that develops in astronauts in space. Their findings not only may help astronauts cope with future space travel, but also lead to new treatments for Earth-bound patients who experience back pain.     

A sustained hyper-g load as a tool to simulate space sickness

In April 1989 the three European scientist astronauts of the D1 Spacelab Mission were exposed to a 1.5 hours +3G centrifuge run in supine position, resulting in a linear acceleration along the subjects' x-axis. Afterwards, severe motion sickness symptoms were provoked by head movements (Sickness Induced by Centrifugation: SIC). The astronauts mentioned close similarities with what they experienced in space during the D1-Spacelab Mission in 1985, where head movements also provoked motion sickness symptoms (Space Adaptation Syndrome: SAS). Moreover, the astronauts agreed that the rank order of their susceptibility to SAS was the same as for SIC. It was therefore postulated that with this method SAS could be simulated on earth. Additionally, in otolith function tests following the centrifuge run, changes in visual-vestibular interaction were observed, which replicated objective findings obtained with the same astronauts immediately after the D1 Spacelab Mission. During the last couple of years a series of experiments has been carried out to determine the nature of the stimulus causing SIC, the incidence of SIC, and the underlying cardio-vascular and/or vestibular mechanisms. These experiments were carried out on several astronauts and some 50 'normal' healthy subjects. In the next sections the main findings of all these experiments and the implications are summarized.     

Space radiation does not induce a significant increase of intrachromosomal exchanges in astronauts’ lymphocytes

Chromosome aberration analysis in astronauts has been used to provide direct, biologically motivated estimates of equivalent doses and risk associated to cosmic radiation exposure during space flight. However, the past studies concentrated on measurements of dicentrics and translocations, while chromosome intrachanges (inversions) have never been measured in astronauts’ samples. Recent data reported in the literature suggest that densely ionizing radiation can induce a large fraction of intrachanges, thus leading to the suspicion that interchanges grossly underestimate the cosmic radiation-induced cytogenetic damage in astronauts. We have analyzed peripheral blood lymphocytes from 11 astronauts involved in short- or long-term space flights in low-Earth orbit using high-resolution multicolor banding to assess the frequency of intrachromosomal exchanges in both pre- and post-flight samples. We did not detect any inversions in chromosome 5 from a total of 2800 cells in astronauts’ blood. In addition, no complex type exchanges were found in a total of 3590 astronauts’ lymphocytes analyzed by multifluor fluorescence in situ hybridisation. We conclude that, within the statistical power of this study, the analysis of interchanges for biological dosimetry in astronauts does not significantly underestimate the space radiation-induced cytogenetic damage, and complex-type exchanges or intrachanges have limited practical use for biodosimetry at very low doses.     

Effects of long-term microgravity exposure in space on circadian rhythms of heart rate variability

We evaluated their circadian rhythms using data from electrocardiographic records and examined the change in circadian period related to normal RR intervals for astronauts who completed a long-term (≥6-month) mission in space. The examinees were seven astronauts, five men and two women, from 2009 to 2010. Their mean?±?SD age was 52.0?±?4.2 years (47–59?yr). Each stayed in space for more than 160 days; their average length of stay was 172.6?±?14.6 days (163–199 days). We conducted a 24-h Holter electrocardiography before launch (Pre), at one month after launch (DF1), at two months after launch (DF2), at two weeks before return (DF3), and at three months after landing (Post), comparing each index of frequency-domain analysis and 24-h biological rhythms of the NN intervals (normal RR intervals). Results show that the mean period of Normal Sinus (NN) intervals was within 24?±?4?h at each examination. Inter-individual variability differed among the stages, being significantly smaller at DF3 (Pre versus DF1 versus DF3 versus Post?=?22.36?±?2.50 versus 25.46?±?4.37 versus 22.46?±?1.75 versus 26.16?±?7.18?h, p?<?0.0001). The HF component increased in 2 of 7 astronauts, whereas it decreased in 3 of 7 astronauts and 1 was remained almost unchanged at DF1. During DF3, about 6 months after their stay in space, the HF component of 5 of 7 astronauts recovered from the decrease after launch, with prominent improvement to over 20% in 3 astronauts. Although autonomic nervous functions and circadian rhythms were disturbed until one month had passed in space, well-scheduled sleep and wake rhythms and meal times served as synchronizers.     

Is Autonomic Modulation Different between European and Chinese Astronauts?

Purpose

The objective was to investigate autonomic control in groups of European and Chinese astronauts and to identify similarities and differences.

Methods

Beat-to-beat heart rate and finger blood pressure, brachial blood pressure, and respiratory frequency were measured from 10 astronauts (five European taking part in three different space missions and five Chinese astronauts taking part in two different space missions). Data recording was performed in the supine and standing positions at least 10 days before launch, and 1, 3, and 10 days after return. Cross-correlation analysis of heart rate and systolic pressure was used to assess cardiac baroreflex modulation. A fixed breathing protocol was performed to measure respiratory sinus arrhythmia and low-frequency power of systolic blood pressure variability.

Results

Although baseline cardiovascular parameters before spaceflight were similar in all astronauts in the supine position, a significant increase in sympathetic activity and a decrease in vagal modulation occurred in the European astronauts when standing; spaceflight resulted in a remarkable vagal decrease in European astronauts only. Similar baseline supine and standing values for heart rate, mean arterial pressure, and respiratory frequency were shown in both groups. Standing autonomic control was based on a balance of higher vagal and sympathetic modulation in European astronauts.

Conclusion

Post-spaceflight orthostatic tachycardia was observed in all European astronauts, whereas post-spaceflight orthostatic tachycardia was significantly reduced in Chinese astronauts. The basis for orthostatic intolerance is not apparent; however, many possibilities can be considered and need to be further investigated, such as genetic diversities between races, astronaut selection, training, and nutrition, etc.