Recovery from 6‐month spaceflight at the International Space Station: muscle‐related stress into a proinflammatory setting

Abstract

The Sarcolab pilot study of 2 crewmembers, investigated before and after a 6-mo International Space Station mission, has demonstrated the substantial muscle wasting and weakness, along with disruption of muscle’s oxidative metabolism. The present work aimed at evaluating the pro/anti-inflammatory status in the same 2 crewmembers (A, B). Blood circulating (c-)microRNAs (miRs), c-proteasome, c-mitochondrial DNA, and cytokines were assessed by real-time quantitative PCR or ELISA tests. Time series analysis was performed ( i.e. , before flight and after landing) at 1 and 15 d of recovery (R+1 and R+15, respectively). C-biomarkers were compared with an age-matched control population and with 2-dimensional proteomic analysis of the 2 crewmembers’ muscle biopsies. Striking differences were observed between the 2 crewmembers at R+1, in terms of inflamma-miRs (c-miRs-21-5p, -126-3p, and -146a-5p), muscle specific (myo)-miR-206, c-proteasome, and IL-6/leptin, thus making the 2 astronauts dissimilar to each other. Final recovery levels of c-proteasome, c-inflamma-miRs, and c-myo-miR-206 were not reverted to the baseline values in crewmember A. In both crewmembers, myo-miR-206 changed significantly after recovery. Muscle biopsy of astronaut A showed an impressive 80% increase of α-1-antitrypsin, a target of miR-126-3p. These results point to a strong stress response induced by spaceflight involving muscle tissue and the proinflammatory setting, where inflamma-miRs and myo-miR-206 mediate the systemic recovery phase after landing.—Capri, M., Morsiani, C., Santoro, A., Moriggi, M., Conte, M., Martucci, M., Bellavista, E., Fabbri, C., Giampieri, E., Albracht, K., Flück, M., Ruoss, S., Brocca, L., Canepari, M., Longa, E., Di Giulio, I., Bottinelli, R., Cerretelli, P., Salvioli, S., Gelfi, C., Franceschi, C., Narici, M., Rittweger, J. Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting.

Endoplasmic reticulum stress‐dependent activation of iNOS/NO‐NF‐κB signaling and NLRP3 inflammasome contributes to endothelial inflammation and apoptosis associated with microgravity

“…Endothelial inflammation was assessed by increased levels of the adhesion molecules E‐selectin and VCAM‐1, and the cytokine monocyte chemoattractant protein‐1 (MCP‐1) in HU rat cerebral arteries 42,43 . A pro‐inflammatory state was observed in astronauts after space travel of a long duration 1,29,30 . Chronic activation of the innate immune system and enhanced circulating levels of pro‐inflammatory mediators were observed in 28 astronauts during a long‐duration spaceflight in the International Space Station 30 and this was validated in other recent studies 29,31 .…”

“…42,43 A pro-inflammatory state was observed in astronauts after space travel of a long duration. 1,29,30 Chronic activation of the innate immune system and enhanced circulating levels of F I G U R E 4 Blocking iNOS inhibited inflammation and apoptosis in HUVECs under simulated microgravity. Under condition of simulated microgravity and ER stress inhibition, the 1400 W was administered to block iNOS in HUVECs.…”

Immunological and hematological outcomes following protracted low dose/low dose rate ionizing radiation and simulated microgravity

“…There are several consequences to living in low-Earth orbit. These include edema due to fluid and cardiovascular deconditioning 1 , myelin degeneration 2 , disorientation and motor control deficits 3 , 4 , visual deficits 5 , endocrine and hormonal alterations 6 , muscle tone wasting 7 , and bone loss due to lack of mechanical loading 8 . Upon return to Earth, there is a period of readaptation that includes acute motion sickness, unsteadiness, imbalance due to gravity-induced vestibular fluid shifts 9 , and blood pressure changes 10 – 12 .…”

Potential Application of Whole Body Vibration Exercise for Improving the Clinical Conditions of COVID-19 Infected Individuals: A Narrative Review from the World Association of Vibration Exercise Experts (WAVex) Panel

“…Ample evidence demonstrates the benefits of early rehabilitation in ICU-bound patients [68]. In fact, given the profound homeostatic and neuro-inflammatory processes involved during (bed-ridden) immobilization [69], one can conclude that musculoskeletal depletion is a highly detrimental side-effect of critical illness, not only with respect to successful rehabilitation after critical illness, but also for the clinical management during the active disease state. We therefore propose that ICU-bound patients are in greater need of adequate medical exercise therapy compared to ambulatory patients.…”