Release of CD36-associated cell-free mitochondrial DNA and RNA as a hallmark of space environment response.

A detailed understanding of how spaceflight affects human health is essential for long-term space exploration. Liquid biopsies allow for minimally-invasive multi-omics assessments that can resolve the molecular heterogeneity of internal tissues. Here, we report initial results from the JAXA Cell-Free Epigenome Study, a liquid biopsy study with six astronauts who resided on the International Space Station (ISS) for more than 120 days. Analysis of plasma cell-free RNA (cfRNA) collected before, during, and after spaceflight confirms previously reported mitochondrial dysregulation in space. Screening with 361 cell surface marker antibodies identifies a mitochondrial DNA-enriched fraction associated with the scavenger receptor CD36. RNA-sequencing of the CD36 fraction reveals tissue-enriched RNA species, suggesting the plasma mitochondrial components originated from various tissues. We compare our plasma cfRNA data to mouse plasma cfRNA data from a previous JAXA mission, which had used on-board artificial gravity, and discover a link between microgravity and the observed mitochondrial responses.

Changes in the astronaut serum proteome during prolonged spaceflight.

The molecular mechanisms associated with spaceflight-induced biological adaptations that may affect many healthy tissue functions remain poorly understood. In this study, we analyzed temporal changes in the serum proteome of six astronauts during prolonged spaceflight missions using quantitative comprehensive proteome analysis performed with the data-independent acquisition method of mass spectrometry (DIA-MS). All six astronauts participated in a spaceflight mission for approximately 6 months and showed a decreasing trend in T-scores at almost all sites where dual-energy X-ray absorptiometry scans were performed. DIA-MS successfully identified 624 nonredundant proteins in sera and further quantitative analysis for each sampling point provided information on serum protein profiles closely related to several time points before (pre-), during (in-), and after (post-) spaceflight. Changes in serum protein levels between spaceflight and on the ground suggest that abnormalities in bone metabolism are induced in astronauts during spaceflight. Furthermore, changes in the proteomic profile occurring during spaceflight suggest that serum levels of bone metabolism-related proteins, namely ALPL, COL1A1, SPP1, and POSTN, could serve as highly responsive indicators of bone metabolism status in spaceflight missions. This study will allow us to accelerate research to improve our understanding of the molecular mechanisms of biological adaptations associated with prolonged spaceflight.

Methods for assessing change in brain plasticity at night and psychological resilience during daytime between repeated long-duration space missions.

This study was designed to examine the feasibility of analyzing heart rate variability (HRV) data from repeat-flier astronauts at matching days on two separate missions to assess any effect of repeated missions on brain plasticity and psychological resilience, as conjectured by Demertzi. As an example, on the second mission of a healthy astronaut studied about 20 days after launch, sleep duration lengthened, sleep quality improved, and spectral power (ms2) co-varying with activity of the salience network (SN) increased at night. HF-component (0.15-0.50 Hz) increased by 61.55%, and HF-band (0.30-0.40 Hz) by 92.60%. Spectral power of HRV indices during daytime, which correlate negatively with psychological resilience, decreased, HF-component by 22.18% and HF-band by 37.26%. LF-component and LF-band, reflecting activity of the default mode network, did not change significantly. During the second mission, 24-h acrophases of HRV endpoints did not change but the 12-h acrophase of TF-HRV did (P < 0.0001), perhaps consolidating the circadian system to help adapt to space by taking advantage of brain plasticity at night and psychological resilience during daytime. While this N-of-1 study prevents drawing definitive conclusions, the methodology used herein to monitor markers of brain plasticity could pave the way for further studies that could add to the present results.

Lunar gravity prevents skeletal muscle atrophy but not myofiber type shift in mice.

Skeletal muscle is sensitive to gravitational alterations. We recently developed a multiple artificial-gravity research system (MARS), which can generate gravity ranging from microgravity to Earth gravity (1 g) in space. Using the MARS, we studied the effects of three different gravitational levels (microgravity, lunar gravity [1/6 g], and 1 g) on the skeletal muscle mass and myofiber constitution in mice. All mice survived and returned to Earth, and skeletal muscle was collected two days after landing. We observed that microgravity-induced soleus muscle atrophy was prevented by lunar gravity. However, lunar gravity failed to prevent the slow-to-fast myofiber transition in the soleus muscle in space. These results suggest that lunar gravity is enough to maintain proteostasis, but a greater gravitational force is required to prevent the myofiber type transition. Our study proposes that different gravitational thresholds may be required for skeletal muscle adaptation.

Unconscious mind activates central cardiovascular network and promotes adaptation to microgravity possibly anti-aging during 1-year-long spaceflight.

The intrinsic cardiovascular regulatory system (ß, 0.00013-0.02 Hz) did not adapt to microgravity after a 6-month spaceflight. The infraslow oscillation (ISO, 0.01-0.10 Hz) coordinating brain dynamics via thalamic astrocytes plays a key role in the adaptation to novel environments. We investigate the adaptive process of a healthy astronaut during a 12-month-long spaceflight by analyzing heart rate variability (HRV) in the LF (0.01-0.05 Hz) and MF1 (0.05-0.10 Hz) bands for two consecutive days on four occasions: before launch, at 1-month (ISS01) and 11-month (ISS02) in space, and after return to Earth. Alteration of ß during ISS01 improved during ISS02 (P = 0.0167). During ISS01, LF and MF1 bands, reflecting default mode network (DMN) activity, started to increase at night (by 43.1% and 32.0%, respectively), when suprachiasmatic astrocytes are most active, followed by a 25.9% increase in MF1-band throughout the entire day during ISS02, larger at night (47.4%) than during daytime. Magnetic declination correlated positively with ß during ISS01 (r = 0.6706, P < 0.0001) and ISS02 (r = 0.3958, P = 0.0095). Magnetic fluctuations may affect suprachiasmatic astrocytes, and the DMN involving ISOs and thalamic astrocytes may then be activated, first at night, then during the entire day, a mechanism that could perhaps promote an anti-aging effect noted in other investigations.

Sleep patterns among shift-working flight controllers of the International Space Station: an observational study on the JAXA Flight Control Team.

BACKGROUND: Flight controllers of the International Space Station (ISS) are engaged in shift work to provide 24-h coverage to support ISS systems. The purpose of this study was to investigate the prevalence and associated factors of shift work sleep disorder (SWSD) among Japanese ISS flight controllers. METHODS: A questionnaire study was conducted using the Standard Shiftwork Index to evaluate sleep-related problems and possible associated variables. Among 52 respondents out of 73 flight controllers, 30 subjects were identified as night shift workers who worked 3 or more night shifts per month. Those night shift workers who answered "almost always" to questions about experiencing insomnia or excessive sleepiness in any case of work shifts and days off were classified as having SWSD. Additionally, 7 night shift workers participated in supplemental wrist actigraphy data collection for 7 to 8 days including 3 to 4 days of consecutive night shifts. RESULTS: Fourteen of 30 night shift workers were classified as having SWSD. Significant group differences were observed where the SWSD group felt that night shift work was harder and reported more frequent insomniac symptoms after a night shift. However, no other variables demonstrated remarkable differences between groups. Actigraphy results characterized 5 subjects reporting better perceived adaptation as having regular daytime sleep, for 6 to 9 h in total, between consecutive night shifts. On the other hand, 2 subjects reporting perceived maladaptation revealed different sleep patterns, with longer daytime sleep and large day-to-day variation in daytime sleep between consecutive night shifts, respectively. CONCLUSIONS: As the tasks for flight control require high levels of alertness and cognitive function, several characteristics, namely shift-working schedule (2 to 4 consecutive night shifts), very short break time (5 to 10 min/h) during work shifts, and cooperative work with onboard astronauts during the evening/night shift, accounted for increasing workloads especially in the case of night shifts, resulting in higher or equal prevalence of SWSD to that among other shift-working populations. Further studies are required to collect more actigraphy data and examine the possibility of interventions to improve SWSD.

Long-term exposure to space's microgravity alters the time structure of heart rate variability of astronauts.

BACKGROUND: Spaceflight alters human cardiovascular dynamics. The less negative slope of the fractal scaling of heart rate variability (HRV) of astronauts exposed long-term to microgravity reflects cardiovascular deconditioning. We here focus on specific frequency regions of HRV. METHODS: Ten healthy astronauts (8 men, 49.1 ± 4.2 years) provided five 24-hour electrocardiographic (ECG) records: before launch, 20.8 ± 2.9 (ISS01), 72.5 ± 3.9 (ISS02) and 152.8 ± 16.1 (ISS03) days after launch, and after return to Earth. HRV endpoints, determined from normal-to-normal (NN) intervals in 180-min intervals progressively displaced by 5 min, were compared in space versus Earth. They were fitted with a model including 4 major anticipated components with periods of 24 (circadian), 12 (circasemidian), 8 (circaoctohoran), and 1.5 (Basic Rest-Activity Cycle; BRAC) hours. FINDINGS: The 24-, 12-, and 8-hour components of HRV persisted during long-term spaceflight. The 90-min amplitude became about three times larger in space (ISS03) than on Earth, notably in a subgroup of 7 astronauts who presented with a different HRV profile before flight. The total spectral power (TF; p < 0.05) and that in the ultra-low frequency range (ULF, 0.0001-0.003 Hz; p < 0.01) increased from 154.9 ± 105.0 and 117.9 ± 57.5 msec2 (before flight) to 532.7 ± 301.3 and 442.4 ± 202.9 msec2 (ISS03), respectively. The power-law fractal scaling ß was altered in space, changing from -1.087 ± 0.130 (before flight) to -0.977 ± 0.098 (ISS01), -0.910 ± 0.130 (ISS02), and -0.924 ± 0.095 (ISS03) (invariably p < 0.05). INTERPRETATION: Most HRV changes observed in space relate to a frequency window centered around one cycle in about 90 min. Since the BRAC component is amplified in space for only specific HRV endpoints, it is likely to represent a physiologic response rather than an artifact from the International Space Station (ISS) orbit. If so, it may offer a way to help adaptation to microgravity during long-duration spaceflight.

Walking can be more effective than balance training in fall prevention among community-dwelling older adults.

AIM: To examine the effects of walking on falls among community-dwelling older adults while accounting for exposures. METHODS: A total of 90 older adults, ranging in age from 65 to 79 years, were allocated into either the walking (brisk walking, n = 50) or the balance (balance and strength training, n = 40) group to participate in a 3-month supervised and 13-month unsupervised fall-prevention program held from 2012 to 2014 in Japan. Falls and trips that occurred during the 16-month period were monitored with a monthly fall calendar. The risk of falls and trips was evaluated by person-year, physically active person-day and person-step. RESULTS: The walking group showed a significant reduction in the fall risk when evaluated by the falls per physically active person-day (rate ratio 0.38, 95% confidence interval 0.19-0.77) and falls per person-step (rate ratio 0.47, 95% confidence interval 0.26-0.85) compared with the balance group. In contrast, the number of trips significantly increased with walking, even when evaluated as trips per physically active person-day (rate ratio 1.50, 95% confidence interval 1.12-2.00). CONCLUSION: The present findings suggest that walking among community-dwelling older adults can be more effective for fall prevention than balance training. However, because walking can induce more trips, walking should not be recommended for older adults who are susceptible to falling or frailty.

Erratum: Intrinsic cardiovascular autonomic regulatory system of astronauts exposed long-term to microgravity in space: observational study.

[This corrects the article DOI: 10.1038/npjmgrav.2015.18.].

Intrinsic cardiovascular autonomic regulatory system of astronauts exposed long-term to microgravity in space: observational study.

The fractal scaling of the long-term heart rate variability (HRV) reflects the 'intrinsic' autonomic regulatory system. Herein, we examine how microgravity on the ISS affected the power-law scaling ß (beta) of astronauts during a long-duration (about 6 months) spaceflight. Ambulatory electrocardiographic (ECG) monitoring was performed on seven healthy astronauts (5 men, 52.0±4.2 years of age) five times: before launch, 24±5 (F01) and 73±5 (F02) days after launch, 15±5 days before return (F03), and after return to Earth. The power-law scaling ß was calculated as the slope of the regression line of the power density of the MEM spectrum versus frequency plotted on a log10-log10 scale in the range of 0.0001-0.01 Hz (corresponding to periods of 2.8 h to 1.6 min). ß was less negative in space (-0.949±0.061) than on Earth (-1.163±0.075; P<0.025). The difference was more pronounced during the awake than during the rest/sleep span. The circadian amplitude and acrophase (phase of maximum) of ß did not differ in space as compared with Earth. An effect of microgravity was detected within 1 month (F01) in space and continued throughout the spaceflight. The intrinsic autonomic regulatory system that protects life under serious environmental conditions on Earth is altered in the microgravity environment, with no change over the 6-month spaceflight. It is thus important to find a way to improve conditions in space and/or in terms of human physiology, not to compromise the intrinsic autonomic regulatory system now that plans are being made to inhabit another planet in the near future.

Effects of whole-body vibration exercise on muscular strength and power, functional mobility and self-reported knee function in middle-aged and older Japanese women with knee pain.

BACKGROUND: Whole-body vibration training using vertical-vibration machines is called "acceleration training" (AT). The purpose of this study was to elucidate the effect of AT on lower-limb muscular strength and power, functional mobility and self-reported knee function in middle-aged and older Japanese women with knee pain. METHODS: Thirty-eight middle-aged and older Japanese women (aged 50-73 years) with knee pain were divided into two groups: (1) the AT group (n=29) engaged in AT three times per week for eight weeks, and (2) the control group (C group, n=9). The AT program consisted of flexibility training, strength training of mainly the quadriceps and surrounding muscles and cool-down exercises. The C group was encouraged to perform the same or similar exercises at home without vibratory stimulus. We evaluated knee strength and power, functional mobility (timed up and go: TUG) and self-reported knee function (Japanese Knee Osteoarthritis Measure: JKOM). RESULTS: No one in the AT group dropped out during the program. All JKOM categories except degree of pain improved significantly post intervention indicating improved knee function, and TUG was significantly shorter in these participants. All knee strength and power parameters except isometric knee extension peak torque improved significantly. The degree of change in JKOM total score and TUG was significantly different between the two groups. CONCLUSION: Vibratory stimulus during an eight week AT programme can promote participation and safely improve functional mobility and self-reported knee function better than exercise without vibratory stimulus in middle-aged and older Japanese women with knee pain. LEVEL OF EVIDENCE: level 2.