Organismal adaptations to spaceflight have been characterized at the molecular level in model organisms, including Drosophila and C. elegans. Here we extend molecular work to energy metabolism and sex hormone signaling in mice and humans. We found spaceflight-induced changes in insulin and estrogen signaling in rodents and humans. Murine changes were most prominent in the liver, where we observed inhibition of insulin and estrogen receptor signaling with concomitant hepatic insulin resistance and steatosis. Based on the metabolic demand, metabolic pathways mediated by insulin and estrogen vary among muscles, specifically between the soleus and extensor digitorum longus. In humans, spaceflight induced changes in insulin and estrogen related genes and pathways. Pathway analysis demonstrated spaceflight-induced changes in insulin resistance, estrogen signaling, stress response, and viral infection. These data strongly suggest the need for further research on the metabolic and reproductive endocrinologic effects of space travel, if we are to become a successful interplanetary species

Human space exploration is hazardous, causing molecular changes that can alter astronauts' health. This can include genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and epigenomic changes. These alterations are similar to changes during aging on Earth. However, little is known about the link between these changes and disease development in space. Frailty syndrome is a robust predictor associated with biological aging, however its existence during spaceflight has not been examined. We used murine data from NASA’s GeneLab and astronaut data from JAXA and Inspiration4 missions to evaluate the presence of biological markers and pathways related to frailty, aging and sarcopenia. We identified changes in gene expression that could be related to the development of a frailty-like condition. These results suggest that the parallels between spaceflight and aging may extend to frailty as well. Future studies examining the utility of a frailty index in monitoring astronaut health appear warranted.