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Albracht Kirsten - One of the best experts on this subject based on the ideXlab platform.

  • Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting
    'FASEB', 2019
    Co-Authors: Capri Miriam, Morsiani Cristina, Santoro Aurelia, Moriggi Manuela, Conte Maria, Martucci Morena, Bellavista Elena, Fabbri Cristina, Giampieri Enrico, Albracht Kirsten
    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 alpha-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

  • Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a pro-inflammatory setting
    'FASEB', 2019
    Co-Authors: Capri Miriam, Morsiani Cristina, Santoro Aurelia, Moriggi Manuela, Conte Maria, Martucci Morena, Bellavista Elena, Fabbri Cristina, Giampieri Enrico, Albracht Kirsten
    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. It is known that short- and long-term spaceflights are associated with physiologic and biologic changes of the human body (1–3). Currently, long-term orbiting flights are regularly performed to serve the International Space Station (ISS) missions, and deep space missions (e.g., to the moon or Mars) are thought to be feasible soon (4). Among the many bodily effects, those related to the skeletal-muscle apparatus and brain appear to be particularly relevant in terms of possible health risks and difficulty to revert the changes after landing (5). Many of the space-related changes are detrimental to the body, and it has been suggested that microgravity could be seen as a model of ageing (6). Access to astronauts is quite limited, which is a considerable impediment to the generation of knowledge in space medicine. Luckily, the possibility of measuring advanced blood biomarkers, such as microRNAs (miRs), and pro- and anti-inflammatory cytokines offer the intriguing opportunity of easily monitoring crew health concerning the physiologic and stress-associated challenges of spaceflight. In addition, circulating (c-)markers are promising tools for the evaluation of healthy and unhealthy ageing trajectories (7). Thus, blood is an informative tissue in which the presence and the concentration of markers may indicate not only tissue/organ injuries or suffering status but also epigenetic changes that may propagate in all the body, especially in the case of c-miRs. In fact, many of these molecules are able to modulate inflammatory signaling pathways, in particular the inflamma-miRs (miR-21-5p, -126-3p, -146a-5p), which were found to be increased or dysregulated in the blood with ageing or pathologic conditions (8). The Sarcolab pilot study has studied the neuromuscular adaptations to long-term space flight in 2 Crewmembers before and after a 6-mo ISS mission and has demonstrated substantial muscle wasting and weakness, along with disruption of muscle’s oxidative metabolism, as a result of spaceflight (9). The muscle atrophy observed with spaceflight has some analogy with the age-associated loss of muscle mass (sarcopenia) (10). In both conditions, the loss of muscle mass could contribute to the increase of c-markers networking with the stress response and proinflammatory status as well as inflammageing along with life span (11–13). Further support for such a view is provided by the recent observation that body core temperature is increased in space in a way that is independent of impeded heat dissipation and which seems to be linked with an inflammatory response (14). The driving hypothesis is that spaceflight, as a prolonged stressor, and recovery may favor a proinflammatory status, increasing the molecular “garbage,” such as misplaced molecules (15), which in turn may favor the inflammatory stress conditions. To this purpose, the present work attempts to evaluate the pro- and anti-inflammatory status in the 2 Crewmembers (A and B) who spent ∼6 mo in space. Blood c-miRs, c-proteasome, c-mitochondrial DNA (mtDNA), and cytokines were evaluated before flight and after 1 and 15 d of recovery and correlated with muscle proteomic analysis. All data were acquired taking into account the main question: How similar are the 2 Crewmembers’ responses to spaceflight and recovery after 1 and 15 d from landing

Capri Miriam - One of the best experts on this subject based on the ideXlab platform.

  • Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting
    'FASEB', 2019
    Co-Authors: Capri Miriam, Morsiani Cristina, Santoro Aurelia, Moriggi Manuela, Conte Maria, Martucci Morena, Bellavista Elena, Fabbri Cristina, Giampieri Enrico, Albracht Kirsten
    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 alpha-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

  • Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a pro-inflammatory setting
    'FASEB', 2019
    Co-Authors: Capri Miriam, Morsiani Cristina, Santoro Aurelia, Moriggi Manuela, Conte Maria, Martucci Morena, Bellavista Elena, Fabbri Cristina, Giampieri Enrico, Albracht Kirsten
    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. It is known that short- and long-term spaceflights are associated with physiologic and biologic changes of the human body (1–3). Currently, long-term orbiting flights are regularly performed to serve the International Space Station (ISS) missions, and deep space missions (e.g., to the moon or Mars) are thought to be feasible soon (4). Among the many bodily effects, those related to the skeletal-muscle apparatus and brain appear to be particularly relevant in terms of possible health risks and difficulty to revert the changes after landing (5). Many of the space-related changes are detrimental to the body, and it has been suggested that microgravity could be seen as a model of ageing (6). Access to astronauts is quite limited, which is a considerable impediment to the generation of knowledge in space medicine. Luckily, the possibility of measuring advanced blood biomarkers, such as microRNAs (miRs), and pro- and anti-inflammatory cytokines offer the intriguing opportunity of easily monitoring crew health concerning the physiologic and stress-associated challenges of spaceflight. In addition, circulating (c-)markers are promising tools for the evaluation of healthy and unhealthy ageing trajectories (7). Thus, blood is an informative tissue in which the presence and the concentration of markers may indicate not only tissue/organ injuries or suffering status but also epigenetic changes that may propagate in all the body, especially in the case of c-miRs. In fact, many of these molecules are able to modulate inflammatory signaling pathways, in particular the inflamma-miRs (miR-21-5p, -126-3p, -146a-5p), which were found to be increased or dysregulated in the blood with ageing or pathologic conditions (8). The Sarcolab pilot study has studied the neuromuscular adaptations to long-term space flight in 2 Crewmembers before and after a 6-mo ISS mission and has demonstrated substantial muscle wasting and weakness, along with disruption of muscle’s oxidative metabolism, as a result of spaceflight (9). The muscle atrophy observed with spaceflight has some analogy with the age-associated loss of muscle mass (sarcopenia) (10). In both conditions, the loss of muscle mass could contribute to the increase of c-markers networking with the stress response and proinflammatory status as well as inflammageing along with life span (11–13). Further support for such a view is provided by the recent observation that body core temperature is increased in space in a way that is independent of impeded heat dissipation and which seems to be linked with an inflammatory response (14). The driving hypothesis is that spaceflight, as a prolonged stressor, and recovery may favor a proinflammatory status, increasing the molecular “garbage,” such as misplaced molecules (15), which in turn may favor the inflammatory stress conditions. To this purpose, the present work attempts to evaluate the pro- and anti-inflammatory status in the 2 Crewmembers (A and B) who spent ∼6 mo in space. Blood c-miRs, c-proteasome, c-mitochondrial DNA (mtDNA), and cytokines were evaluated before flight and after 1 and 15 d of recovery and correlated with muscle proteomic analysis. All data were acquired taking into account the main question: How similar are the 2 Crewmembers’ responses to spaceflight and recovery after 1 and 15 d from landing

Clarence Sams - One of the best experts on this subject based on the ideXlab platform.

  • immune dysregulation following short versus long duration space flight
    2018
    Co-Authors: Clarence Sams, Duane L Pierson, Raymond P Stowe, Brian Crucian
    Abstract:

    Immune system dysregulation has been demonstrated to occur during spaceflight and has the potential to cause serious health risks to Crewmembers participating in exploration-class missions. A comprehensive immune assessment was recently performed on 13 short duration Space Shuttle Crewmembers and 8 long duration International Space Station (ISS) Crewmembers. Statistically significant post-flight phenotype alterations (as compared to pre-flight baseline) for the Shuttle Crewmembers included: granulocytosis, increased percentage of B cells, reduced percentage of NK cells, elevated CD4/CD8 ratio, elevated levels of memory CD4+ T cells, and a CD8+ T cell shift to a less differentiated state. For the Shuttle Crewmembers, T cell function was surprisingly elevated post-flight, among both the CD4+ and CD8+ subsets. This is likely an acute stress response in less-deconditioned Crewmembers. The percentage of CD4+/IL-2+, CD4+/IFNg+ and CD8+/IFNg+ T cells were all decreased at landing. Culture secreted IFNg production was significantly decreased at landing, whereas production of Th2 cytokines was largely unchanged. It was found that the IFNg:IL-10 ratio was obviously declined in the Shuttle Crewmembers immediately post-flight. A similar pattern of alterations were observed for the long duration ISS Crewmembers. In contrast to Shuttle Crewmembers, the ISS Crewmembers demonstrated a dramatic reduction in T cell function immediately post-flight. This may be related to the effect of acute landing stress in conjunction with prolonged deconditioning associated with extended flight. The reduction in IFNg:IL-10 ratio (Th2 shift) was also observed post-flight in the ISS Crewmembers to a much higher degree. These data indicate consistent peripheral phenotype changes and altered cytokine production profiles occur following space travel of both short and long duration.

  • immune system dysregulation following short vs long duration spaceflight
    Aviation Space and Environmental Medicine, 2008
    Co-Authors: Brian Crucian, Raymond P Stowe, Duane L Pierson, Clarence Sams
    Abstract:

    INTRODUCTION: Immune system dysregulation has been demonstrated to occur during and immediately following spaceflight. If found to persist during lengthy flights, this phenomenon could be a serious health risk to Crewmembers participating in lunar or Mars missions. METHODS: A comprehensive postflight immune assessment was performed on 17 short-duration Space Shuttle Crewmembers and 8 long-duration International Space Station (ISS) Crewmembers. Testing consisted of peripheral leukocyte subset analysis, early T cell activation potential, and intracellular/secreted cytokine profiles. RESULTS: For Shuttle Crewmembers, the distribution of the peripheral leukocyte subsets was found to be altered postflight. Early T cell activation was elevated postflight; however, the percentage of T cell subsets capable of being stimulated to produce IL-2 and IFN gamma was decreased. The ratio of secreted IFN gamma:IL-10 following T cell stimulation declined after landing, indicating a Th2 shift. For the ISS Crewmembers, some alterations in peripheral leukocyte distribution were also detected after landing. In contrast to Shuttle Crewmembers, the ISS Crewmembers demonstrated a statistically significant reduction in early T cell activation potential immediately postflight. The percentage of T cells capable of producing IL-2 was reduced, but IFN gamma percentages were unchanged. A reduction in the secreted IFN gamma:IL-10 ratio (Th2 shift) was also observed postflight in the ISS Crewmembers. CONCLUSION: These data indicate that consistent peripheral phenotype changes and altered cytokine production profiles occur following spaceflight of both short and long duration; however, functional immune dysregulation may vary related to mission duration. In addition, a detectable Th2 cytokine shift appears to be associated with spaceflight.

  • the risk of renal stone formation during and after long duration space flight
    Nephron, 2001
    Co-Authors: Peggy A Whitson, Robert A Pietrzyk, Boris Morukov, Clarence Sams
    Abstract:

    Background: The formation of a renal stone during space flight may have serious negative effects on the health of the crewmember and the success of the mission. Urinary biochemical factors and the influence of dietary factors associated with renal stone development were assessed during long duration Mir Space Station missions. Methods: Twenty-four-hour urine samples were collected prior to, during and following long duration space flight. The relative urinary supersaturation of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were determined. Results: Changes in the urinary biochemistry of Crewmembers during long duration spaceflight demonstrated increases in the supersaturation of the stone-forming salts. In-flight hypercalciuria was evident in a number of individual Crewmembers and 24-hour dietary fluid intake and urine volume were significantly lower. During flight, there was a significant increase in brushite supersaturation. Conclusions: These data suggest acute effects of space flight and postflight changes in the urinary biochemistry favoring increased crystallization in the urine. The effects of dietary intake, especially fluid intake, may have a significant impact on the potential for renal stone formation. Efforts are now underway to assess the efficacy of a countermeasure to mitigate the increased risk.

Albracht K. - One of the best experts on this subject based on the ideXlab platform.

  • Recovery from 6-month spaceflight at the International Space Station: Muscle-related stress into a proinflammatory setting
    'FASEB', 2019
    Co-Authors: Capri M., Morsiani C., Santoro A., Moriggi M., Conte M., Martucci M., Bellavista E., Fabbri C., Giampieri E., Albracht K.
    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 \u3b1-1-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., Fl\ufcck, 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

Morsiani Cristina - One of the best experts on this subject based on the ideXlab platform.

  • Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting
    'FASEB', 2019
    Co-Authors: Capri Miriam, Morsiani Cristina, Santoro Aurelia, Moriggi Manuela, Conte Maria, Martucci Morena, Bellavista Elena, Fabbri Cristina, Giampieri Enrico, Albracht Kirsten
    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 alpha-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

  • Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a pro-inflammatory setting
    'FASEB', 2019
    Co-Authors: Capri Miriam, Morsiani Cristina, Santoro Aurelia, Moriggi Manuela, Conte Maria, Martucci Morena, Bellavista Elena, Fabbri Cristina, Giampieri Enrico, Albracht Kirsten
    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. It is known that short- and long-term spaceflights are associated with physiologic and biologic changes of the human body (1–3). Currently, long-term orbiting flights are regularly performed to serve the International Space Station (ISS) missions, and deep space missions (e.g., to the moon or Mars) are thought to be feasible soon (4). Among the many bodily effects, those related to the skeletal-muscle apparatus and brain appear to be particularly relevant in terms of possible health risks and difficulty to revert the changes after landing (5). Many of the space-related changes are detrimental to the body, and it has been suggested that microgravity could be seen as a model of ageing (6). Access to astronauts is quite limited, which is a considerable impediment to the generation of knowledge in space medicine. Luckily, the possibility of measuring advanced blood biomarkers, such as microRNAs (miRs), and pro- and anti-inflammatory cytokines offer the intriguing opportunity of easily monitoring crew health concerning the physiologic and stress-associated challenges of spaceflight. In addition, circulating (c-)markers are promising tools for the evaluation of healthy and unhealthy ageing trajectories (7). Thus, blood is an informative tissue in which the presence and the concentration of markers may indicate not only tissue/organ injuries or suffering status but also epigenetic changes that may propagate in all the body, especially in the case of c-miRs. In fact, many of these molecules are able to modulate inflammatory signaling pathways, in particular the inflamma-miRs (miR-21-5p, -126-3p, -146a-5p), which were found to be increased or dysregulated in the blood with ageing or pathologic conditions (8). The Sarcolab pilot study has studied the neuromuscular adaptations to long-term space flight in 2 Crewmembers before and after a 6-mo ISS mission and has demonstrated substantial muscle wasting and weakness, along with disruption of muscle’s oxidative metabolism, as a result of spaceflight (9). The muscle atrophy observed with spaceflight has some analogy with the age-associated loss of muscle mass (sarcopenia) (10). In both conditions, the loss of muscle mass could contribute to the increase of c-markers networking with the stress response and proinflammatory status as well as inflammageing along with life span (11–13). Further support for such a view is provided by the recent observation that body core temperature is increased in space in a way that is independent of impeded heat dissipation and which seems to be linked with an inflammatory response (14). The driving hypothesis is that spaceflight, as a prolonged stressor, and recovery may favor a proinflammatory status, increasing the molecular “garbage,” such as misplaced molecules (15), which in turn may favor the inflammatory stress conditions. To this purpose, the present work attempts to evaluate the pro- and anti-inflammatory status in the 2 Crewmembers (A and B) who spent ∼6 mo in space. Blood c-miRs, c-proteasome, c-mitochondrial DNA (mtDNA), and cytokines were evaluated before flight and after 1 and 15 d of recovery and correlated with muscle proteomic analysis. All data were acquired taking into account the main question: How similar are the 2 Crewmembers’ responses to spaceflight and recovery after 1 and 15 d from landing