Comparative Transcriptomics Identifies Neuronal and Metabolic Adaptations to Hypergravity and Microgravity in .

Deep space exploration is firmly within reach, but health decline during extended spaceflight remains a key challenge. In this study, we performed comparative transcriptomic analysis of responses to varying degrees of hypergravity and to two spaceflight experiments (ICE-FIRST and CERISE). We found that progressive hypergravitational load concomitantly increases the extent of differential gene regulation and that subtle changes in ∼1,000 genes are reproducibly observed during spaceflight-induced microgravity. Consequently, we deduce those genes that are concordantly regulated by altered gravity or that display inverted expression profiles during hypergravity versus microgravity. Through doing so, we identify several candidate targets with terrestrial roles in neuronal function and/or cellular metabolism, which are linked to regulation by /FOXO signaling. These data offer a strong foundation from which to expedite mechanistic understanding of spaceflight-induced maladaptation in higher organisms and, ultimately, promote future targeted therapeutic development.