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

Abstract

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.

Regulation of the Response of Caenorhabditis elegans to Simulated Microgravity by p38 Mitogen-Activated Protein Kinase Signaling

“…Caenorhabditis elegans is a classic model animal for the study in the field of life sciences due to the properties of at least short life-cycle, short lifespan, and ease of culture 8 . Meanwhile, C. elegans is an ideal animal model for the study of physiological effects of simulated microgravity because of its common use on Earth as a model organism for human medical pathologies and its sensitivity to environmental toxicants or stresses 9 – 11 . In “the first International C. elegans Experiment in Space” (ICE-First) experiments, C. elegans has been employed to evaluate the potential different aspects of effects of spaceflight on animals 12 – 15 .…”

Nematode Muscles Project in Spaceflight Experiment

“…Gene expression studies reveal that the transcriptional response is consistent with the physiological and biological effects of spaceflight. Downregulation of cytoskeletal proteins, mitochondrial proteins and muscle proteins have also been observed in our last spaceflight experiment CERISE (Higashibata et al, 2016).…”

Molecular Muscle Experiment: Hardware and Operational Lessons for Future Astrobiology Space Experiments

“…Our current experiment, the Molecular Muscle Experiment (MME), uses the model organism, Caenorhabditis elegans, to explore the molecular mechanisms of spaceflight-induced muscle atrophy. C. elegans is an established model organism for studies on Earth (Kaletta and Hengartner, 2006;Corsi et al, 2015;Shen et al, 2018) and in space (Szewczyk et al, 2008;Higashitani et al, 2009;Honda et al, 2012Honda et al, , 2014Higashibata et al, 2016).…”