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.

Space radiation and microgravity pose significant health risks for astronauts conducting deep space exploration. The impact of galactic cosmic radiation (GCR) and weightlessness alone, and their combined effects on cardiac disease, the immune system, cytokines and calcium dynamics should be understood before undertaking such missions. Male WAG/RijCmcr rats, Rattus norvegicus, 8–9 months old were hind limb unloaded (HLU) to simulate exposure to microgravity for 5 days before, during, and 25 days after whole-body exposure to a simplified GCR simulation (simGCRsim) dose of 1.5 Gy that was administered rapidly. Other rats maintained normal weight-bearing. Exposure to 1.5 Gy of simGCRsim with or without HLU increased cardiac perivascular collagen content, the primary endpoint, compared to sham-irradiated no HLU rats after 270 days. The extent of cardiac fibrosis present in the two irradiated groups could not be distinguished, indicating no interaction between the two space flight stressors. A series of secondary endpoints were also measured. Sham irradiation with HLU increased blood lymphocytes but not myeloid cells compared with non-HLU, an outcome that was inhibited by simGCRsim with HLU, indicating an interaction between spaceflight stressors at this high dose-rate. HLU alone decreased multiple circulating cytokines and depleted CD56 ⁺ cells in the spleen. Notably, simGCRsim and HLU alone and in combination did not disrupt calcium homeostasis. An exposure to 1.5 Gy simGCRsim no HLU revealed distinct genomic alterations in circulating nucleated blood cells as compared with sham-irradiated subjects no HLU, and identified mutations, frameshifts, and deletions in genes that contribute to human disease in the irradiated cohort. A limited follow-on study involved exposure to 0.75 Gy simGCRsim with no HLU with appropriate controls. This radiation dose, a dose relevant to human missions to Mars, caused cardiac perivascular fibrosis at an extended follow up period of after 360 days. Taken together, our findings show exposure to simGCRsim, representing the composition of GCR behind spacecraft shielding, caused cardiac perivascular fibrosis and gene variants. Simulated microgravity (HLU) alone engaged the immune system and decreased cytokine production. We conclude that exposure of rats to simGCRsim and/or HLU results in persistent health effects with limited interactions between the two spaceflight stressors.