Fig. 3. Effects of space missions and ROS on general physiology.

A High levels of ROS can damage hepatocytes. The damage results in increased lipid droplets in the liver, increased triglycerides, and loss of retinoids from lipid droplets in stellate cells, PPAR-ɑ dysregulation, and diabetic changes that can cause NAFLD. B Space radiation damages skeletal lipids and increases the activity of NRF2. ROS acts as a second messenger during RANKL activation and differentiation. This increases bone resorption and osteoclastogenesis. C Microgravity and radiation can cause red blood cell destruction, which releases iron. The iron then acts as a cofactor in excess ROS production to accelerate oxidative damage and ultimately cause muscle atrophy. D Increased production of ROS and NOX leads to endothelial dysfunction and promotes myocardial necrosis. E Oxidative damage causes neurodegeneration that can alter neurotransmitters, induce psychiatric disorders, and dementia. F The innate immune system requires the production of ROS in the defense of microorganisms within the phagocytic process and the inflammatory response. However, a dysregulation in the production of ROS induces a lower lymphocyte response, impairing phagocytosis and increasing susceptibility to latent infections such as HSV. Created with BioRender.com.