The space environment chiefly includes microgravity and radiation, which seriously threatens the health of astronauts. Bone loss and muscle atrophy are the two most significant changes in mammals after long-term residency in space. In this review, we summarized current understanding of the effects of microgravity and radiation on the musculoskeletal system and discussed the corresponding mechanisms that are related to iron overload and oxidative damage. Furthermore, we enumerated some countermeasures that have a therapeutic potential for bone loss and muscle atrophy through using iron chelators and antioxidants. Future studies for better understanding the mechanism of iron and redox homeostasis imbalance induced by the space environment and developing the countermeasures against iron overload and oxidative damage consequently may facilitate human to travel more safely in space.
Iron is an essential micronutrient in mammalian cells for basic processes such as DNA synthesis, cell cycle progression, and mitochondrial activity. Macrophages play a vital role in iron metabolism, which is tightly linked to their phagocytosis of senescent and death erythrocytes. It is now recognized that the polarization process of macrophages determines the expression profile of genes associated with iron metabolism. Although iron metabolism is strictly controlled by physiology, cancer has recently been connected with disordered iron metabolism. Moreover, in the environment of cancer, tumor‐associated macrophages (TAMs) exhibit an iron release phenotype, which stimulates tumor cell survival and growth. Usually, the abundance of TAMs in the tumor is implicated in poor disease prognosis. Therefore, important attention has been drawn toward the development of tumor immunotherapies targeting these TAMs focussing on iron metabolism and reprogramming polarized phenotypes. Although further systematic research is still required, these efforts are almost certainly valuable in the search for new and effective cancer treatments.
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