Synthetic torpor protects rats from exposure to accelerated heavy ions

Abstract

Hibernation or torpor is considered a possible tool to protect astronauts from the deleterious effects of space radiation that contains high-energy heavy ions. We induced synthetic torpor in rats by injecting adenosine 5′-monophosphate monohydrate (5′-AMP) i.p. and maintaining in low ambient temperature room (+ 16 °C) for 6 h immediately after total body irradiation (TBI) with accelerated carbon ions (C-ions). The 5′-AMP treatment in combination with low ambient temperature reduced skin temperature and increased survival following 8 Gy C-ion irradiation compared to saline-injected animals. Analysis of the histology of the brain, liver and lungs showed that 5′-AMP treatment following 2 Gy TBI reduced activated microglia, Iba1 positive cells in the brain, apoptotic cells in the liver, and damage to the lungs, suggesting that synthetic torpor spares tissues from energetic ion radiation. The application of 5′-AMP in combination with either hypoxia or low temperature environment for six hours following irradiation of rat retinal pigment epithelial cells delays DNA repair and suppresses the radiation-induced mitotic catastrophe compared to control cells. We conclude that synthetic torpor protects animals from cosmic ray-simulated radiation and the mechanism involves both hypothermia and hypoxia.

Towards sustainable human space exploration—priorities for radiation research to quantify and mitigate radiation risks

“… Selection campaigns—genome-wide association studies—radioprotective pharmaceuticals—hibernation (synthetic torpor) 49 —food supplements—genome editing. Illustration created by the authors for this manuscript.…”

Transcriptome Profiling Reveals Enhanced Mitochondrial Activity as a Cold Adaptive Strategy to Hypothermia in Zebrafish Muscle

“…Additionally, shielding and minimising time spent in spaceflight remain the only two effective countermeasures for radiation exposure. When it comes to long-term interplanetary space travel, the idea of induced torpor as a countermeasure to the effects of spaceflight has been the topic of much discussion given the evidence that it can provide radio-protective effects [19]; furthermore, while undergoing long periods of inactivity and fasting, muscles of hibernating animals are more resistant to atrophy [20]. The bear represents an excellent model for long-term torpor, due to modest reductions in basal metabolic rate, comparable body mass, and its utilisation of torpor for 5-7 months at a time, comparable to a journey to Mars.…”