{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:58:24Z","timestamp":1791644304051,"version":"4.3.4"},"reference-count":72,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Federal Department of Economy and Energy (BMWi), German Aerospace Board, Deutsches Zentrum f\u00fcr Luft und Raumfahrt e.V. (DLR), Bonn-Oberkassel, Germany","award":["50WB0521-0821-1121"],"award-info":[{"award-number":["50WB0521-0821-1121"]}]},{"name":"German Federal Department of Economy and Energy (BMWi), German Aerospace Board, Deutsches Zentrum f\u00fcr Luft und Raumfahrt e.V. (DLR), Bonn-Oberkassel, Germany","award":["2021-21-U.O ASTRONEMUS"],"award-info":[{"award-number":["2021-21-U.O ASTRONEMUS"]}]},{"name":"Agenzia Spaziale Italiana (ASI)","award":["50WB0521-0821-1121"],"award-info":[{"award-number":["50WB0521-0821-1121"]}]},{"name":"Agenzia Spaziale Italiana (ASI)","award":["2021-21-U.O ASTRONEMUS"],"award-info":[{"award-number":["2021-21-U.O ASTRONEMUS"]}]},{"name":"authors\u2019 institutions","award":["50WB0521-0821-1121"],"award-info":[{"award-number":["50WB0521-0821-1121"]}]},{"name":"authors\u2019 institutions","award":["2021-21-U.O ASTRONEMUS"],"award-info":[{"award-number":["2021-21-U.O ASTRONEMUS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The molecular mechanisms of skeletal muscle adaptation to spaceflight are as yet not fully investigated and well understood. The MUSCLE BIOPSY study analyzed pre and postflight deep calf muscle biopsies (m. soleus) obtained from five male International Space Station (ISS) astronauts. Moderate rates of myofiber atrophy were found in long-duration mission (LDM) astronauts (~180 days in space) performing routine inflight exercise as countermeasure (CM) compared to a short-duration mission (SDM) astronaut (11 days in space, little or no inflight CM) for reference control. Conventional H&amp;E scout histology showed enlarged intramuscular connective tissue gaps between myofiber groups in LDM post vs. preflight. Immunoexpression signals of extracellular matrix (ECM) molecules, collagen 4 and 6, COL4 and 6, and perlecan were reduced while matrix-metalloproteinase, MMP2, biomarker remained unchanged in LDM post vs. preflight suggesting connective tissue remodeling. Large scale proteomics (space omics) identified two canonical protein pathways associated to muscle weakness (necroptosis, GP6 signaling\/COL6) in SDM and four key pathways (Fatty acid \u03b2-oxidation, integrin-linked kinase ILK, Rho A GTPase RHO, dilated cardiomyopathy signaling) explicitly in LDM. The levels of structural ECM organization proteins COL6A1\/A3, fibrillin 1, FBN1, and lumican, LUM, increased in postflight SDM vs. LDM. Proteins from tricarboxylic acid, TCA cycle, mitochondrial respiratory chain, and lipid metabolism mostly recovered in LDM vs. SDM. High levels of calcium signaling proteins, ryanodine receptor 1, RyR1, calsequestrin 1\/2, CASQ1\/2, annexin A2, ANXA2, and sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) pump, ATP2A, were signatures of SDM, and decreased levels of oxidative stress peroxiredoxin 1, PRDX1, thioredoxin-dependent peroxide reductase, PRDX3, or superoxide dismutase [Mn] 2, SOD2, signatures of LDM postflight. Results help to better understand the spatiotemporal molecular adaptation of skeletal muscle and provide a large scale database of skeletal muscle from human spaceflight for the better design of effective CM protocols in future human deep space exploration.<\/jats:p>","DOI":"10.3390\/ijms24044095","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T03:56:07Z","timestamp":1676865367000},"page":"4095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Space Omics and Tissue Response in Astronaut Skeletal Muscle after Short and Long Duration Missions"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0355-3340","authenticated-orcid":false,"given":"Dieter","family":"Blottner","sequence":"first","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10115 Berlin, Germany"},{"name":"NeuroMuscular System & Signaling Group, Center of Space Medicine and Extreme Environments, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4718-0307","authenticated-orcid":false,"given":"Manuela","family":"Moriggi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8917-2962","authenticated-orcid":false,"given":"Gabor","family":"Trautmann","sequence":"additional","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Hastermann","sequence":"additional","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10115 Berlin, Germany"},{"name":"NeuroMuscular System & Signaling Group, Center of Space Medicine and Extreme Environments, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7701-728X","authenticated-orcid":false,"given":"Daniele","family":"Capitanio","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6374-3325","authenticated-orcid":false,"given":"Enrica","family":"Torretta","sequence":"additional","affiliation":[{"name":"IRCCS Orthopedic Institute Galeazzi, 20161 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2752-5232","authenticated-orcid":false,"given":"Katharina","family":"Block","sequence":"additional","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2223-8963","authenticated-orcid":false,"given":"Joern","family":"Rittweger","sequence":"additional","affiliation":[{"name":"Institute of Aerospace Medicine, German Aerospace Center (DLR), 51147 Cologne, Germany"},{"name":"Department of Pediatrics and Adolescence Medicine, University Hospital Cologne, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9927-4180","authenticated-orcid":false,"given":"Ulrich","family":"Limper","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care Medicine, Merheim Medical Center, Witten\/Herdecke University, 51109 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2996-6912","authenticated-orcid":false,"given":"Cecilia","family":"Gelfi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy"},{"name":"IRCCS Orthopedic Institute Galeazzi, 20161 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7066-3876","authenticated-orcid":false,"given":"Michele","family":"Salanova","sequence":"additional","affiliation":[{"name":"Institute of Integrative Neuroanatomy, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10115 Berlin, Germany"},{"name":"NeuroMuscular System & Signaling Group, Center of Space Medicine and Extreme Environments, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"547","DOI":"10.3389\/fphys.2017.00547","article-title":"Human Pathophysiological Adaptations to the Space Environment","volume":"8","author":"Demontis","year":"2017","journal-title":"Front. 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