Effects of the space environment and re-adaptation to Earth's gravity on astronauts' plasma proteome

We performed a label-free quantitative plasma proteomic analysis on samples from eight astronauts who completed a 6-month mission aboard the International Space Station, using an Orbitrap Fusion Lumos mass spectrometer (MS). Blood samples were collected from each astronaut at different times, i.e., pre-flight, in-flight, and post-flight. We found that the abundance levels of 16 proteins were significantly altered ( p ≤ 0.05), particularly in the in-flight samples. The functions of these 16 proteins are associated with four major pathways that pose health risks to astronauts: impairment of the immune system, reorganization of the cytoskeleton, coagulation disorders, and abnormal metabolism. Following the spaceflight, the levels of certain proteins, such as Apolipoprotein L1 (APOL1) and inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2), returned to or close to their preflight levels. While the abundance levels of some proteins involved in the actin cytoskeleton ( e.g., pleckstrin or PLEK) and coagulation ( e.g., platelet glycoprotein 1b alpha chain or GP1BA) decreased, others such as Brain acid soluble protein 1 (BASP1) and Insulin-like growth factor-binding protein 4 (IGFBP4) increased postflight. Although the mechanisms underlying the upregulation or downregulation of these proteins are not yet fully understood, they may play functional roles in response to spaceflight or in re-adjusting to Earth. This may impact cellular and tissue integrity as well as homeostasis, potentially leading to long-term health risks. Our findings have important implications for developing strategies to mitigate the adverse effects of spaceflight on human health.