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.