A limitation of simulated space radiation studies is that radiation exposure is not the only environmental challenge astronauts face during missions. Therefore, we characterized behavioral and cognitive performance of male WAG/Rij rats 3 months after sham-irradiation or total body irradiation with a simplified 5-ion mixed beam exposure in the absence or presence of simulated weightlessness using hindlimb unloading (HU) alone. Six months following behavioral and cognitive testing or 9 months following sham-irradiation or total body irradiation, plasma and brain tissues (hippocampus and cortex) were processed to determine whether the behavioral and cognitive effects were associated with long-term alterations in metabolic pathways in plasma and brain. Sham HU, but not irradiated HU, rats were impaired in spatial habituation learning. Rats irradiated with 1.5 Gy showed increased depressive-like behaviors. This was seen in the absence but not presence of HU. Thus, HU has differential effects in sham-irradiated and irradiated animals and specific behavioral measures are associated with plasma levels of distinct metabolites 6 months later. The combined effects of HU and radiation on metabolic pathways in plasma and brain illustrate the complex interaction of environmental stressors and highlights the importance of assessing these interactions.

Ionizing radiation is a critical aspect of current cancer therapy. While classically mature bone was thought to be relatively radio-resistant, more recent data have shown this to not be the case. Radiation therapy (RT)-induced bone loss leading to fracture is a source of substantial morbidity. The mechanisms of RT likely involve multiple pathways, including changes in angiogenesis and bone vasculature, osteoblast damage/suppression, and increased osteoclast activity. The majority of bone loss appears to occur rapidly after exposure to ionizing RT, with significant changes in cortical thickness being detectable on computed tomography (CT) within three to four months. Additionally, there is a dose–response relationship. Cortical thinning is especially notable in areas of bone that receive >40 gray (Gy). Methods to mitigate toxicity due to RT-induced bone loss is an area of active investigation. There is an accruing clinical trial investigating the use of risderonate, a bisphosphonate, to prevent rib bone loss in patients undergoing lung stereotactic body radiation therapy (SBRT). Additionally, several other promising therapeutic/preventative approaches are being explored in preclinical studies, including parathyroid hormone (PTH), amifostine, and mechanical loading of irradiated bones.

A primary objective of the National Aeronautics and Space Administration (NASA) is expansion of humankind’s presence outside low-Earth orbit, culminating in permanent interplanetary travel and habitation. Having no inherent means of physiological detection or protection against ionizing radiation, humans incur capricious risk when journeying beyond low-Earth orbit for long periods. NASA has made large investments to analyze pathologies from space radiation exposure, emphasizing the importance of characterizing radiation’s physiological effects. Because natural evolution would require many generations to confer resistance against space radiation, immediately pragmatic approaches should be considered. Volitional evolution, defined as humans steering their own heredity, may inevitably retrofit the genome to mitigate resultant pathologies from space radiation exposure. Recently, uniquely radioprotective genes have been identified, conferring local or systemic radiotolerance when overexpressed in vitro and in vivo. Aiding in this process, the CRISPR/Cas9 technique is an inexpensive and reproducible instrument capable of making limited additions and deletions to the genome. Although cohorts can be identified and engineered to protect against radiation, alternative and supplemental strategies should be seriously considered. Advanced propulsion and mild synthetic torpor are perhaps the most likely to be integrated. Interfacing artificial intelligence with genetic engineering using predefined boundary conditions may enable the computational modeling of otherwise overly complex biological networks. The ethical context and boundaries of introducing genetically pioneered humans are considered.