Microgravity elicits reproducible alterations in cytoskeletal and metabolic gene and protein expression in space-flown Caenorhabditis elegans

Although muscle atrophy is a serious problem during spaceflight, little is known about the sequence of molecular events leading to atrophy in response to microgravity. We carried out a spaceflight experiment using Caenorhabditis elegans onboard the Japanese Experiment Module of the International Space Station. Worms were synchronously cultured in liquid media with bacterial food for 4 days under microgravity or on a 1-G centrifuge. Worms were visually observed for health and movement and then frozen. Upon return, we analyzed global gene and protein expression using DNA microarrays and mass spectrometry. Body length and fat accumulation were also analyzed. We found that in worms grown from the L1 larval stage to adulthood under microgravity, both gene and protein expression levels for muscular thick filaments, cytoskeletal elements, and mitochondrial metabolic enzymes decreased relative to parallel cultures on the 1-G centrifuge (95% confidence interval (P⩽0.05)). In addition, altered movement and decreased body length and fat accumulation were observed in the microgravity-cultured worms relative to the 1-G cultured worms. These results suggest protein expression changes that may account for the progressive muscular atrophy observed in astronauts. Researchers in Japan have uncovered the molecular genetic changes that lead to the loss of muscle mass after lengthy periods in space. Atsushi Higashitani at Tohoku University and colleagues in Japan and the UK sent nematode worms into orbit on the International Space Station and observed changes in their gene and protein expression. Compared with worms grown in a centrifuge in space that kept them at normal Earth gravity, worms grown in microgravity showed down-regulation of genes coding for proteins that make up internal cell scaffolding and attach muscle cells to the cuticle. In addition, genes controlling mitochondrial metabolism were switched to “energysaving” mode. Both changes likely contribute to the loss of muscle mass in orbit, and the same proteins are believed to be associated with muscle atrophy in human astronauts.