Effects Of Long-term Spaceflight Research Articles

Sensory organization of postural control after long term space flight.

Alterations in motor control systems is an inevitable consequence of space flights of any duration. After the flight, the crew-members have significant difficulties with maintaining upright balance and locomotion, which last several days following landing. At the same time, the specific mechanisms of these effects remain unclear. The aim of the study was to assess effects of long-term space flight on postural control and to define the changes of sensory organization caused by microgravity. 33 cosmonauts of Russian Space Agency, the members of International Space Station (ISS) flights of duration between 166 and 196 days took part in this study. Computerized Dynamic Posturography (CDP) tests, which include assessment of visual, proprioceptive and vestibular function in postural stability, was performed twice before the flight and on the 3rd, 7th, and 10th days after landing. The video analysis of ankle and hip joints fluctuations was performed to investigate the basis of postural changes. Exposure to long-term space flight was followed by considerable changes of postural stability (-27% of Equilibrium Score value in the most complicated test, SOT5m). Changes in postural strategies to maintain balance were observed in the tests which provide the challenge for vestibular system. In particular, increased hip joint involvement (+100% in median value and +135% in 3rd quartile of hip angle fluctuation RMS in SOT5m) into postural control process was revealed. Decrease of postural stability after long-term space flight was associated with alterations in vestibular system and biomechanically was revealed by increased hip strategy which is less accurate, but simpler in terms of the central control.

Long-term spaceflight and the cardiovascular system.

While early investigations into the physiological effects of spaceflight suggest the body's ability to reversibly adapt, the corresponding effects of long-term spaceflight (>6 months) are much less conclusive. Prolonged exposure to microgravity and radiation yields profound effects on the cardiovascular system, including a massive cephalad fluid translocation and altered arterial pressure, which attenuate blood pressure regulatory mechanisms and increase cardiac output. Also, central venous pressure decreases as a result of the loss of venous compression. The stimulation of baroreceptors by the cephalad shift results in an approximately 10%–15% reduction in plasma volume, with fluid translocating from the vascular lumen to the interstitium. Despite possible increases in cardiac workload, myocyte atrophy and notable, yet unexplained, alterations in hematocrit have been observed. Atrophy is postulated to result from shunting of protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated action. While data are scarce regarding their causative agents, arrhythmias have been frequently reported, albeit sublethal, during both Russian and American expeditions, with QT interval prolongation observed in long, but not short duration, spaceflight. Exposure of the heart to the proton and heavy ion radiation of deep space has also been shown to result in coronary artery degeneration, aortic stiffness, carotid intima thickening via collagen-mediated action, accelerated atherosclerosis, and induction of a pro-inflammatory state. Upon return, long-term spaceflight frequently results in orthostatic intolerance and altered sympathetic responses, which can prove hazardous should any rapid mobilization or evacuation be required, and indicates that these cardiac risks should be especially monitored for future missions.

Influence of Long-Term Space Flight on Mechanical Properties of the Human Triceps Surae Muscle: Electro Mechanical Delay and Musculo-Tendinous Stiffness

The effects of long-term space flight on human triceps surae (TS) muscle function and electromechanical delay (EMD) have been investigated. Voluntary and electrically evoked contractions of the TS were obtained from 7 male cosmonauts 30 days before and 3 days after landing. For all cosmonauts the isometric maximal voluntary contraction was reduced by 41.7 % (p < 0.01), whereas the electrically evoked maximal tetanic contraction force (Po) was found to decrease by 25.6 % (p < 0.05). Force deficit increased by 50 % (p < 0.001). This suggests that most of the force loss is due to a reduction in motor drive (motor control). The decrease in Po was associated with a significant increase of the corresponding maximal rates of tension development (43.7 %). The twitch tension (Pt) was not significantly changed and the Pt/Po ratio was increased by 46.7 % (p < 0.05) after space mission. The twitch time-to-peak tension of the TS increased by 7.7 %, but half-relaxation time decreased by 20.6 %. Force-velocity properties of the TS calculated according to a relative scale of voluntary contraction development significantly decreased. The calculations of the same properties of electrically evoked contraction development did not differ substantially from the initial physiological state. Total reaction time (TRT), pre-motor time (PMR) and motor time or EMD were determined. In response to a supramaximal single electrical pulses applied to the tibial nerve, the latent period between the M-wave and Рt beginning was determined. The voluntary contraction EMD increased by 34.1 %; but PMR and TRT decreased by 19.0 and 14.1 %, respectively. The EMD of electrically evoked contraction did not significantly change. Thus, the comparison of the mechanical alterations recorded during voluntary contractions and in contractions evoked by electrical stimulation of the motor nerve, suggests that weightlessness not only modifies the peripheral processes associated with contractions, but also changes central and/or neural command of the contraction.

Influence of muscle activity on musculotendinous stiffness quantification in stunted, prepubertal children

The quick-release technique to estimate musculotendinous (MT) stiffness has been extensively used over the last years, in both animals and humans, to gain insights in the adaptive process of the series elastic component (SEC). Recently, MT stiffness quantification, i.e., SEC behavior, has been revisited for subjects not able to fully activate their muscles (effects of long-term spaceflight or non-mature muscles). Such a phenomenon can also be encountered in stunted children. So, the aim of the present study was to analyze the effect of stunting on MT stiffness taking into account possible defect in muscle activation. For this study, 20 eutrophic children (EU) with an average age of 9years±4months were compared to 11age matched stunted children (S) evaluated by the height-to-age index. The MT stiffness index was obtained with regard to stiffness–torque and stiffness–soleus EMG relationships. The children of the S group presented a significantly lower Maximal Voluntary Contraction (MVC) in plantar flexion in comparison with children of the EU group (−37.8%). The significantly lower MT stiffness index for S children (−42.6%) was evidenced only when quantified with regard to the stiffness–soleus EMG relationship (66.5±42.8 vs. 38.2±19.9 Nmrad−1%−1). Possible delay in fiber type differentiation or tendinous structure maturation can account for the lower MT stiffness index in S children. In conclusion, stunting during early childhood delays the differentiation and maturation processes of musculotendinous structures as shown by the lower MT stiffness quantified with regards to muscle activity, also altered for stunted prepubertal children.

Spaceflight Influences both Mucosal and Peripheral Cytokine Production in PTN-Tg and Wild Type Mice

Spaceflight is associated with several health issues including diminished immune efficiency. Effects of long-term spaceflight on selected immune parameters of wild type (Wt) and transgenic mice over-expressing pleiotrophin under the human bone-specific osteocalcin promoter (PTN-Tg) were examined using the novel Mouse Drawer System (MDS) aboard the International Space Station (ISS) over a 91 day period. Effects of this long duration flight on PTN-Tg and Wt mice were determined in comparison to ground controls and vivarium-housed PTN-Tg and Wt mice. Levels of interleukin-2 (IL-2) and transforming growth factor-beta1 (TGF-β1) were measured in mucosal and systemic tissues of Wt and PTN-Tg mice. Colonic contents were also analyzed to assess potential effects on the gut microbiota, although no firm conclusions could be made due to constraints imposed by the MDS payload and the time of sampling. Spaceflight-associated differences were observed in colonic tissue and systemic lymph node levels of IL-2 and TGF-β1 relative to ground controls. Total colonic TGF-β1 levels were lower in Wt and PTN-Tg flight mice in comparison to ground controls. The Wt flight mouse had lower levels of IL-2 and TGF-β1 compared to the Wt ground control in both the inguinal and brachial lymph nodes, however this pattern was not consistently observed in PTN-Tg mice. Vivarium-housed Wt controls had higher levels of active TGF-β1 and IL-2 in inguinal lymph nodes relative to PTN-Tg mice. The results of this study suggest compartmentalized effects of spaceflight and on immune parameters in mice.

Genetic analysis of the human hair roots as a tool for spaceflight experiments

The use of hair roots as experimental samples has been a research focus for understanding the effects of spaceflight on astronauts, because it has many advantages, one of which is the fact that hair matrix cells actively divide in a hair follicle and sensitively reflect the physical conditions of the human body. In 2009, a research program focusing on the analysis of astronauts’ hairs was initiated to examine the effects of long-term spaceflight on the gene expression and mineral metabolism in the human body. Since the number of samples per astronaut is limited to 5 strands of hairs at each sampling point, due to the ethical viewpoint of astronauts or limited resources in space, it is important to develop an effective method for the molecular analysis of small amounts of hair roots. In this study, mRNA successfully extracted from 1, 5, and 10 hair follicles was amplified and subjected to the DNA microarray analysis to compare the gene expression within subjects. The results indicated that (1) it was possible to perform the genetic analysis on hair samples stored at -80℃, even without a fixation buffer and (2) the newly modified method of mRNA extraction and analysis was effective in detecting differential gene expression in samples containing only 5 hairs. In conclusion, RNA was efficiently extracted from 5 hair roots, which is the same number of hair roots used in the space experiment; therefore, this method can be applied to genetically analyze astronauts’ hair samples.

Effects of Long-Term Space Flight on Erythrocytes and Oxidative Stress of Rodents

Erythrocyte and hemoglobin losses have been frequently observed in humans during space missions; these observations have been designated as “space anemia”. Erythrocytes exposed to microgravity have a modified rheology and undergo hemolysis to a greater extent. Cell membrane composition plays an important role in determining erythrocyte resistance to mechanical stress and it is well known that membrane composition might be influenced by external events, such as hypothermia, hypoxia or gravitational strength variations. Moreover, an altered cell membrane composition, in particular in fatty acids, can cause a greater sensitivity to peroxidative stress, with increase in membrane fragility. Solar radiation or low wavelength electromagnetic radiations (such as gamma rays) from the Earth or the space environment can split water to generate the hydroxyl radical, very reactive at the site of its formation, which can initiate chain reactions leading to lipid peroxidation. These reactive free radicals can react with the non-radical molecules, leading to oxidative damage of lipids, proteins and DNA, etiologically associated with various diseases and morbidities such as cancer, cell degeneration, and inflammation. Indeed, radiation constitutes on of the most important hazard for humans during long-term space flights. With this background, we participated to the MDS tissue-sharing program performing analyses on mice erythrocytes flown on the ISS from August to November 2009. Our results indicate that space flight induced modifications in cell membrane composition and increase of lipid peroxidation products, in mouse erythrocytes. Moreover, antioxidant defenses in the flight erythrocytes were induced, with a significant increase of glutathione content as compared to both vivarium and ground control erythrocytes. Nonetheless, this induction was not sufficient to prevent damages caused by oxidative stress. Future experiments should provide information helpful to reduce the effects of oxidative stress exposure and space anemia, possibly by integrating appropriate dietary elements and natural compounds that could act as antioxidants.

Biomedical analysis of rat body hair after hindlimb suspension for 14 days

The levels of 26 minerals in rat body hair were analyzed in control and hindlimb-suspended Wistar Hannover rats (n=5 each). We quantified the levels of 22 minerals in this experiment. However, we were unable to measure the levels of 4 minerals (Be, V, Cd, and Hg) quantitatively because they were below the limit of detection. Of the 22 quantified, the levels of 19 minerals were not significantly different between control and hindlimb-suspended groups. The levels of 3 minerals (Pb, Cr, and Al) tended to be higher in the hindlimb-suspended group than in the control group; however, this difference was not significant. The concentrations of 3 other minerals (I, K, and Mg) were significantly different between the 2 groups. The iodine (I) level was 58.2% higher in the hindlimb-suspended group than in the control group (P<0.05). Potassium (K) and magnesium (Mg) levels were 55.2% and 20.4% lower, respectively, in the experimental group (P<0.05 in both cases).These results indicate that a physiological change in mineral metabolism resulting from physical or mental stress, such as hindlimb suspension, is reflected in body hair. The Japan Aerospace Exploration Agency (JAXA) has initiated a human research study to investigate the effects of long-term space flight on gene expression and mineral metabolism by analyzing hair samples of astronauts who stayed in the International Space Station (ISS) for 6 months. We believe that hindlimb suspension for 14 days can simulate the effects of an extremely severe environment, such as space flight, because the hindlimb suspension model elicits a rapid physiological change in skeletal muscle, bone, and fluid shift even in the short term. These results also suggest that we can detect various effects on the body by analyzing the human scalp hair shaft.

Mutation frequency of plasmid DNA and Escherichia coli following long-term space flight on Mir.

To elucidate the biological influence of space radiation, we studied the effects of long-term space flight on mutation of the bacterial ribosomal protein L gene (rpsL). We prepared dried samples of plasmid DNA and repair-deficient and wild type cells of Escherichia (E.) coli. After a 40-day space flight on board the Russian space station Mir, the mutation frequencies of the rpsL gene were estimated by transformation of E. coli and by assessment of conversion of rpsL wild type phenotype (SmS) to its mutant phenotype (SmR). The experimental findings indicate that mutation frequencies of space samples were not significantly different from those of ground control samples in plasmid DNA and both E. coli strains. It may suggest that space radiation did not influence mutation frequency.

Effects of long-term spaceflight on mechanical properties of muscles in humans.

The effects of long-term spaceflight (90-180 days) on the contractile and elastic characteristics of the human plantarflexor muscles were studied in 14 cosmonauts before and 2-3 days after landing. Despite countermeasures practiced aboard, spaceflight was found to induce a decrease in maximal isometric torque (17%), whereas an index of maximal shortening velocity was found to increase (31%). In addition, maximal muscle activation evaluated during isokinetic tests decreased by 39%. Changes in musculotendinous stiffness and whole joint stiffness were characterized by means of quick-release movements and sinusoidal perturbations. Musculotendinous stiffness was found to be increased by 25%. Whole joint stiffness decreased under passive conditions (21%), whereas whole joint stiffness under active conditions remained unchanged after spaceflight (-1%). This invariance suggests an adaptive mechanism to counterbalance the decrease in stiffness of passive structures by an increased active stiffness. Changes in neural drive could participate in this equilibrium.

Analysis of deletion mutations of the rpsL gene in the yeast Saccharomyces cerevisiae detected after long-term flight on the Russian space station Mir

Using the yeast Saccharomyces cerevisiae on board the Russian space station Mir, we studied the effects of long-term space flight on mutation of the bacterial ribosomal protein L gene ( rpsL) cloned in a yeast- Escherichia coli shuttle vector. The mutation frequencies of the cloned rpsL gene on the Mir and the ground (control) yeast samples were estimated by transformation of E. coli with the plasmid DNAs recovered from yeast and by assessment of the conversion of the rpsL wild-type phenotype (Sm S) to its mutant phenotype (Sm R). After a 40-day space flight, some part of space samples gave mutation frequencies two to three times higher than those of the ground samples. Nucleotide sequence analysis showed no apparent difference in point mutation rates between the space and the ground mutant samples. However, the greater part of the Mir mutant samples were found to have a total or large deletion in the rpsL sequence, suggesting that space radiation containing high-linear energy transfer (LET) might have caused deletion-type mutations.