Multi-omic, Single-Cell, and Biochemical Profiles of Astronauts Guide Pharmacological Strategies for Returning to Gravity

Abstract

Highlights d IL-6, IL-10, IL-1ra, CCL2, and CRP rose significantly on landing after a year in space d IL-6 and IL-1ra are potential targets for pharmacological intervention in astronauts d These cytokines are also associated with muscle regeneration in response to gravity d Muscle-generated IL-6 drives classic signaling cascades in an anti-inflammatory role

Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development

“…Therefore, there is a need for a more comprehensive and unbiased assessment of all miRNA through miRNA-seq in a wide range of tissues from each of the experimental models investigated here. In addition, scRNA-seq has indicated major changes in miRNA-associated gene expression among different blood immune cell types in the human blood from the NASA Twins Study (Gertz et al, 2020). CD14 + monocytes are particularly likely to express and respond to miRNAs, suggesting a potential regulatory role of miRNAs on the innate immune response that is known to be dysregulated in spaceflight (Crucian et al, 2011).…”

Spaceflight Modulates the Expression of Key Oxidative Stress and Cell Cycle Related Genes in Heart

“…In addition, human T cell cultures on the International Space Station (ISS) show a 15-fold decrement in expression of Tnf in T cells and its downstream effectors in microgravity as compared to cells centrifuged at 1g [68]. During a very long duration spaceflight, TNFα expression in the blood of astronauts is elevated [24] but after return to Earth (between days 0 and 5) as skeletal muscle enters a recovery phase, Tnfα expression rapidly declines along with other cytokines in the Il6 pathway [69]. Together, these findings implicate a biomechanical, gravity-dependent mechanism for regulating Tnf-related pathways.…”

Clonal Hematopoiesis Before, During, and After Human Spaceflight

“…Here, the two astronauts were found to have mutations in DNMT3A and TET2 consistent with the presence of CH. People with CH progress to hematologic malignancies at a rate of 0.5%-1% per year, similar to the rate of progression of frank neoplasia observed in monoclonal gammopathy of uncertain significance (MGUS) or monoclonal B cell lymphocytosis (MBL) (Gertz et al, 2020). However, CH has the potential to give rise to a broader range of blood cancers than either MGUS or MBL because it usually arises in earlier, less committed hematopoietic stem or progenitor cells.…”