Comparative Transcriptomics Identifies Neuronal and Metabolic Adaptations to Hypergravity and Microgravity in Caenorhabditis elegans
Craig R.G. Willis,
Nathaniel J. Szewczyk,
Sylvain V. Costes,
Ingrid A. Udranszky,
Sigrid S. Reinsch,
Timothy Etheridge,
Catharine A. Conley
Affiliations
Craig R.G. Willis
Department of Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, Exeter, EX1 2LU, UK
Nathaniel J. Szewczyk
MRC-ARUK Centre for Musculoskeletal Ageing Research and National Institute of Health Research, Biomedical Research Centre, School of Medicine, Royal Derby Hospital, University of Nottingham, Derby, DE22 3DT, UK; Ohio Musculoskeletal and Neurological Institute (OMNI) and Department of Biomedical Sciences, Ohio University, Athens, OH 43147, USA
Sylvain V. Costes
Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA
Ingrid A. Udranszky
Lockheed Martin Space Operations, Moffett Field, CA 94035, USA
Sigrid S. Reinsch
Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA
Timothy Etheridge
Department of Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, Exeter, EX1 2LU, UK; Corresponding author
Catharine A. Conley
Space Science and Astrobiology Division, NASA Ames Research Center, Moffett Field, CA 94035, USA
Summary: 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 Caenorhabditis elegans 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 per se 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 daf-16/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.
