Study of metabolic changes in human erythrocytes and plasma under simulated microgravity conditions

The absence of gravity is considered as an extreme biological stressor and the human body's adaptive response to microgravity conditions triggers a series of metabolic changes that are often associated with bone density loss, skeletal muscle atrophy, nervous system dysfunction, and anaemia. To understand the biological mechanisms underlying aerospace anaemia we investigated the structural and/or metabolic changes that occur in the erythrocytes under low gravity, as well as we compared the profile of human plasma polar metabolite under normal- and micro-g conditions. Erythrocytes exposed to simulated microgravity showed morphological changes, a constant increase in reactive oxygen species (ROS), a significant reduction in total antioxidant capacity (TAC), a remarkable and constant decrease in total glutathione (GSH) concentration, and an increase of malondialdehyde (MDA) levels. In this PhD work, experiments were also performed to evaluate the lipid profile of erythrocyte membranes changes under microgravity conditions. Lipidomics results showed an upregulation of the levels of complex lipids such as phosphocholines and sphingomyelins. Alterations in the lipid composition of the membrane determine membrane rigidity and fluidity, and plays a crucial role in membrane organization, dynamics, and function. No less important is the role that lipids have in the signalling of programmed cell death. In conjunction with these results, the metabolomics analysis revealed that microgravity in human plasma induced an increase of glycolysis, Krebs cycle and fatty acids β-oxidation perturbations, and lactic acid production. These findings indicate an evident damage of circulating mitochondria causing a defective respiratory chain, oxidative environment, and incomplete β-oxidation of fatty acids with consequent accumulation of carnitines, in particular propionyl carnitine.