Abstract
Spaceflight entails exposure to numerous environmental challenges with the potential to contribute to both musculoskeletal and vascular dysfunction. The purpose of this review is to describe current understanding of microgravity and radiation impacts on the mammalian skeleton and associated vasculature at the level of the whole organism. Recent experiments from spaceflight and ground-based models have provided fresh insights into how these environmental stresses influence mechanisms that are related to redox signaling, oxidative stress, and tissue dysfunction. Emerging mechanistic knowledge on cellular defenses to radiation and other environmental stressors, including microgravity, are useful for both screening and developing interventions against spaceflight-induced deficits in bone and vascular function.
Highlights
Microgravity and radiation are two unique elements of the spaceflight environment that pose challenges to the health of an organism
The downregulation of antioxidant defenses as a potential mechanism for the increased levels of oxidative damage post-flight is supported by the observation that hair follicle samples from International Space Station (ISS) crew members at post-flight display decreased expression of endogenous antioxidant genes, including Mn superoxide dismutase (MnSOD), CuZnSOD, glutathione peroxidase 4 (GPX4) and kelch-like ECH-associated protein 1 (KEAP1), the regulator of nuclear factor erythroid 2-related factor 2
Studies overwhelmingly demonstrate a link between oxidative damage and tissue dysfunction that ensues from exposure to spaceflight factors (Figure 1)
Summary
Microgravity and radiation are two unique elements of the spaceflight environment that pose challenges to the health of an organism. In rodent models of weightlessness such as hindlimb unloading (HU), the onset of osteopenia correlates with reductions in skeletal perfusion, vascular density (rarefication), and vasodilation responses similar to that observed in aging [5,6,7]. These are serious risks for long-duration, exploration-class missions when astronauts will face the challenges of increased exposure to space radiation and abrupt transitions between different gravitational states upon return to Earth. Other responses to ionizing radiation include oxidative stress, damage to proteins, lipids, and DNA, adversely affecting functions of membranes, the extracellular matrix, cell cycle and survival [15,16,17]
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