Delta efficiency(DE) at mild-moderate (31%-56% of maximum oxygen uptake) bicycle exercise in the upright sitting and in the supine position was measured in 10 young males and 5 females before and after 20 days bed rest (BR). Total muscle mass in the both legs(TMML) were measured by dual-energy x-ray absorptiometry. After BR, oxygen uptake decreased at all intensities during upright exercise and at 100 W during supine exercise (p<0.05) in the males but cardiac output (acetylene rebreathing) was almost unchanged. As defined as increase in work over the corresponding increase in energy liberation, DE significantly increased by 20.1% during upright exercise and 18.4% during supine exercise in males, but unchanged in females. TMML was decreased in both males and females. The differences in DE between males and females could not be explained in the present study. One possibility might be that the decreased DE was due to a simultaneous decrease in slow twitch muscle fiber content which might be responsible for the decreased TMML induced by BR in the males.
Abstract Epigenetic changes during long-term spaceflight are beginning to be studied by NASA’s twin astronauts and other model organisms. Here, we evaluate the epigenetic regulation of gene expression in space-flown C. elegans by comparing wild type and histone deacetylase ( hda ) -4 mutants. Expression levels of 39 genes were consistently upregulated in all four generations of adult hda-4 mutants grown under microgravity compared with artificial Earth-like gravity (1 G ). In contrast, in the wild type, microgravity-induced upregulation of these genes occurred a little. Among these genes, 11 contain the domain of unknown function 19 (DUF-19) and are located in a cluster on chromosome V. When compared with the 1 G condition, histone H3 trimethylation at lysine 27 (H3K27me3) increased under microgravity in the DUF-19 containing genes T20D4.12 to 4.10 locus in wild-type adults. On the other hand, this increase was also observed in the hda-4 mutant, but the level was significantly reduced. The body length of wild-type adults decreased slightly but significantly when grown under microgravity. This decrease was even more pronounced with the hda-4 mutant. In ground-based experiments, one of the T20D4.11 overexpressing strains significantly reduced body length and also caused larval growth retardation and arrest. These results indicate that under microgravity, C. elegans activates histone deacetylase HDA-4 to suppress overregulation of several genes, including the DUF-19 family. In other words, the expression of certain genes, including negative regulators of growth and development, is epigenetically fine-tuned to adapt to the space microgravity.
Our previous spaceflight experiment CERISE showed that gene and protein expression levels of muscular components, cytoskeleton, and mitochondrial enzymes are altered in space flown wild-type C. elegans.To confirm and clarify whether the C. elegans muscle fibers and mitochondrial network are physically altered in response to microgravity, this Nematode Muscles project was designed with wild-type and several mutant lines with GFP expression.This investigation also studied whether microgravity could affect the insulin/ IGF-1 (Insulin-like growth factor -1) and/or TGF-β signaling by imaging DAF-16::GFP fusion protein.Wild-type and several mutants were grown in a culture bag kept under microgravity or 1G centrifuge conditions on board ISS for 4 days starting from L1 larva.All samples were fixed on board and recovered, to be analyzed on the earth.The worms did not grow well in the μG culture bag probably due to unexpected air bubbles.Therefore, DAF-16 activation observed in larval worms in μG and not in 1G may be attributed to starvation instead of μG response.In 1G samples, we could successfully find normal mitochondrial network.We also found that chemical fixation using CFA is an effective method for preservation of GFP containing C. elegans in space environment.
Delta efficiency defined as increase in work over the corresponding increase in energy liberation (delta work/delta energy) may be used to express the efficiency of working muscles under standard conditions where work is performed with similar changes in muscle length, identical pedal revolution frequencies, and contraction-to-relaxation ratios. The Delta efficiency is probably the most valid measure of the efficiency of muscular work, so it may be influenced by the difference in distribution and/or density of muscle fiber types in exercising muscles. It has been reported that after bed rest of 7-14 days, not only maximum oxygen uptake (VO2 max) but also oxygen uptake (VO2) at 3-min submaximal upright exercise decreased. However, the decrease might be apparent, and the mechanical efficiency might be unchanged. On the other hand, muscle mass of bicycling legs was decreased after continuous horizontal bed rest of 10 days and 20 days. Because the decreased muscle mass is probably related to decrease in the density of the slow twitch muscle fibers (ST-fiber), the decrease in submaximal VO2 during bicycle exercises after bed rest may result from a decrease in ST-fiber mass. Therefore, it could be hypothesized that the mechanical efficiency should increase during upright exercise because of the relative increase in amount of more efficient fast twitch muscle fibers (FT-fiber) than ST fibers in exercising muscles. The purpose of the present study was to investigate whether delta efficiency in working muscle is influenced by the decrease in muscle mass after 20 days horizontal bed rest in young males.
How microgravitational space environments affect aging is not well understood. We observed that, in Caenorhabditis elegans, spaceflight suppressed the formation of transgenically expressed polyglutamine aggregates, which normally accumulate with increasing age. Moreover, the inactivation of each of seven genes that were down-regulated in space extended lifespan on the ground. These genes encode proteins that are likely related to neuronal or endocrine signaling: acetylcholine receptor, acetylcholine transporter, choline acetyltransferase, rhodopsin-like receptor, glutamate-gated chloride channel, shaker family of potassium channel and insulin-like peptide. Most of them mediated lifespan control through the key longevity-regulating transcription factors DAF-16 or SKN-1 or through dietary-restriction signaling, singly or in combination. These results suggest that aging in C. elegans is slowed through neuronal and endocrine response to space environmental cues.
Reduced orthostatic tolerance is commonly observed after spaceflight, occasionally causing presyncopal symptoms which may be due to low cerebral blood flow (CBF). It has been suggested that CBF decreases in early stages of exposure to orthostatic stress. The purpose of this study was to investigate cerebrovascular responses during presyncope induced by lower body negative pressure (LBNP).Although CBF decreases during LBNP exposure, blood pressure (BP) or heart rate (HR) contributes more to induce presyncopal conditions.Eight healthy male volunteers were exposed to LBNP in steps of 10 mm Hg every 3 min until presyncopal symptoms were detected. Electrocardiogram (ECG) was monitored continuously and arterial BP was measured by arterial tonometry. CBF velocity at the middle cerebral artery was measured by transcranial Doppler sonography (TCD). Cerebral tissue oxygenation was detected using near-infrared spectroscopy (NIRS). We focused our investigation on the data obtained during the final 2 min before the presyncopal endpoint.BP gradually decreased from 2 min to 10 s before the endpoint, and fell more rapidly during the final 10 s. HR did not change significantly during presyncope. CBF velocity did not change significantly, while cerebral tissue oxygenation decreased prior to the presyncopal endpoint in concert with BP. Our results suggest that CBF is maintained in the middle cerebral artery during presyncope, while BP decreases rapidly.Cerebrovascular hemodynamics are relatively well maintained while arterial hypotension occurs just prior to syncope.
To assess if propranolol influences orthostatic intolerance induced by prolonged bed rest (BR), a lower body negative pressure test (LBNP) and left ventricular (LV) echocardiography before and during -40mmHg of LBNP were performed with and without intravenous propranolol administration (0.04mg/kg) in 9 healthy volunteers (mean age: 21 years) before and after 20 days BR. LBNP tolerance time (LBNP-T), endpoint heart rate(HR), and percentage changes from 0 to -40mmHg LBNP in HR, LV diastolic dimension(LVDd), stroke volume (SV), cardiac output (CO), and systemic vascular resistance(SVR) were measured. After BR, percentage changes in CO during LBNP was not altered by propranolol (-12+/-21% vs. -24+/-24%; with and without propranolol; p>0.05) because the effect on percentage changes in HR (18+/-11% vs. 26+/-12%; p<0.05) cancelled out the effects of percentage changes in LVDd (-9+/-6% vs. -15+/-10%; p<0.05) and percentage changes in SV (-26+/-16% vs. -39+/-22%; p<0.05). In addition, propranolol decreased end-point HR (85+/-15bpm vs. 119+/-l4bpm; p<0.05) and percentage changes in SVR (25+/-32% vs. 53+/-57%; p<0.05). As a result, LBNP-T after BR was unchanged by propranolol (8.8+/-3.3min vs. 10.8+/-5.0min; p>0.05). In conclusion, propranolol failed to change orthostatic intolerance induced by BR.
