Extreme physical inactivity alters iron metabolism: mechanisms and health issues for astronauts and bedridden...

Iron is a biologically indispensable yet potentially harmful element: essential for numerous metabolic processes but toxic in excess, potentially leading to organ damage. Under conditions of extreme physical inactivity, such as microgravity or prolonged bed-rest, physical deconditioning occurs, adversely affecting functional capacities and health. Anaemia and muscle atrophy may contribute to systemic iron redistribution, as red blood cells and skeletal muscle collectively concentrate most body iron. Here we summarize a decade of research conducted in rodent and human ground-based models to investigate how extreme physical inactivity alters systemic and cellular iron homeostasis, and explore the underlying mechanisms. During the first days an increase in plasma iron availability occurs in both men and premenopausal women, likely due to accelerated erythrophagocytosis in spleen and redistribution of iron from degraded erythrocytes. Despite the rapid onset of muscle fibre atrophy under these conditions, skeletal muscle appears to accumulate iron rather than release it and therefore may not necessarily contribute to the systemic redistribution of iron. Increased circulating hepcidin levels observed during this early phase could contribute to both redistribution and tissue iron sequestration. After several weeks of exposure plasma iron availability remains elevated in men exposed to extreme physical inactivity, potentially exposing to chronic tissue iron accumulation. In contrast a return to baseline seems to occur in premenopausal women. These findings point to a broad and persistent redistribution of iron metabolism in men in response to extreme physical inactivity. However the long-term effects on iron metabolism in women remain poorly understood and warrant further investigation.