Multigenerational Study Of Spaceflight-Responsive Gene Networks

As the interest in human missions to Mars has elevated drastically, understanding the genome-wide responses to the space environment has become an urgent task. To address this, we investigated the transcriptomic responses for spaceflight-like microgravity conditions on C. elegans. Multigenerational effects of simulated spaceflight conditions were examined by exposing the animals to the altered conditions and observing the continuing effects for two to four generations after return to the ground control environment. Bioinformatics analyses were conducted to identify the spaceflight-specific gene networks. Our results depicted that approximately 88% of the gene networks are significantly enriched in previously found protein-protein interactions (P<0.01). Moreover, the networks predict 19% - 98% more interactions than the previously reported. A high correlation was found between the function of the gene networks and the observed phenotype. For example, our fluorescence microscopy results demonstrated that the animals experience a change in muscle mass under microgravity. The microgravity-related gene networks also showed an enrichment for tissue development and muscle fiber development Gene Ontology terms. Interestingly, up to 78% of the differentially expressed genes (compared to control) maintained these expression patterns for approximately three generations. In particular, Longevity Regulating Pathway genes were differentially expressed and the Sphingolipid Metabolism Pathway was downregulated under microgravity. Given that inhibition of this pathway increases lifespan, our data suggests an extended lifespan under microgravity. Surprisingly, these pathways maintained the differential expression patterns for two more subsequent generations on the ground conditions. We further investigated the epigenome and regulatory non-coding RNA elements and identified the controlling switches of these networks.