Synthetic Torpor Research Articles

Hibernation and Radioprotection: Gene Expression in the Liver and Testicle of Rats Irradiated under Synthetic Torpor.

Hibernation has been proposed as a tool for human space travel. In recent years, a procedure to induce a metabolic state known as “synthetic torpor” in non-hibernating mammals was successfully developed. Synthetic torpor may not only be an efficient method to spare resources and reduce psychological problems in long-term exploratory-class missions, but may also represent a countermeasure against cosmic rays. Here we show the preliminary results from an experiment in rats exposed to ionizing radiation in normothermic conditions or synthetic torpor. Animals were irradiated with 3 Gy X-rays and organs were collected 4 h after exposure. Histological analysis of liver and testicle showed a reduced toxicity in animals irradiated in torpor compared to controls irradiated at normal temperature and metabolic activity. The expression of ataxia telangiectasia mutated (ATM) in the liver was significantly downregulated in the group of animal in synthetic torpor. In the testicle, more genes involved in the DNA damage signaling were downregulated during synthetic torpor. These data show for the first time that synthetic torpor is a radioprotector in non-hibernators, similarly to natural torpor in hibernating animals. Synthetic torpor can be an effective strategy to protect humans during long term space exploration of the solar system.

A pharmacological composition for induction of a reversible torpor-like state and hypothermia in rats

AimsTo initiate a state of artificial torpor we suggested a pharmacological multi-targeting strategy for simulation of the physiological pattern of natural hibernation including a significant reduction in heart rate, respiratory rate, body temperature and oxygen consumption as well as a decline in brain activity known as torpor. Materials and methodsWe have developed a composition which initiates a pharmacologically induced torpor-like state (PITS-composition), made up of eight therapeutic agents, inert gas xenon and lipid emulsion served as a drug vehicle. Key findingsAfter a single intravenous injection to rats, PITS-composition causes a rapid decline in heart rate followed by a steady decrease in body temperature from about 38.5 °C to 31.5 °C, at ambient temperature of 22 °C–23 °C. The hypothermic state may continue on average for 16–17 h with the subsequent spontaneous return of heart rate and body temperature to the initial values. In the open field test at torpor the motility, rearing and grooming were suppressed but 4–8 days later they were restored. SignificanceSuspended animation states, including natural hibernation or pharmacologically induced synthetic torpor are of special attention of medicine, since it may improve survival rate after cardiac arrest, brain hemorrhage and ischemia, and during long-term space traveling. The suggested here multi-targeting strategy made possible to develop the pharmacological composition able, after a single intravenous injection, to initiate long, stable and reversible hypothermia and torpor at room temperature. After the torpor, animals were able to spontaneously restore both physiological parameters, and behavioral reactions.

Consciousness in hibernation and synthetic torpor.

While human hibernation would provide many advantages for medical applications and space exploration, the intrinsic risks of the procedure itself, as well as those involved if the procedure were to be misused, need to be assessed. Moreover, the distinctive brain state that is present during a hibernation-like state raises questions regarding the state of consciousness of the subject. Since, in animal studies, the cortical activity of this state differs from that of sleep, coma, or even general anesthesia, and resembles a sort of "slowed wakefulness", it is uncertain whether residual consciousness may still be present. In this review, I will present a brief summary of the literature on hibernation and of the current state of the art in inducing a state of artificial hibernation (synthetic torpor); I will then focus on the brain changes that are observed during hibernation, on how these could modify the neural substrate of consciousness, and on the possible use of hibernation as a model for quantum biology. Finally, some ethical considerations on the use of synthetic torpor technology will be presented.

Potential role of the gut microbiota in synthetic torpor and therapeutic hypothermia.

Therapeutic hypothermia is today used in several clinical settings, among them the gut related diseases that are influenced by ischemia/reperfusion injury. This perspective paved the way to the study of hibernation physiology, in natural hibernators, highlighting an unexpected importance of the gut microbial ecosystem in hibernation and torpor. In natural hibernators, intestinal microbes adaptively reorganize their structural configuration during torpor, and maintain a mutualistic configuration regardless of long periods of fasting and cold temperatures. This allows the gut microbiome to provide the host with metabolites, which are essential to keep the host immunological and metabolic homeostasis during hibernation. The emerging role of the gut microbiota in the hibernation process suggests the importance of maintaining a mutualistic gut microbiota configuration in the application of therapeutic hypothermia as well as in the development of new strategy such as the use of synthetic torpor in humans. The possible utilization of tailored probiotics to mold the gut ecosystem during therapeutic hypothermia can also be taken into consideration as new therapeutic strategy.

The Central Control of Energy Expenditure: Exploiting Torpor for Medical Applications.

Autonomic thermoregulation is a recently acquired function, as it appears for the first time in mammals and provides the brain with the ability to control energy expenditure. The importance of such control can easily be highlighted by the ability of a heterogeneous group of mammals to actively reduce metabolic rate and enter a condition of regulated hypometabolism known as torpor. The central neural circuits of thermoregulatory cold defense have been recently unraveled and could in theory be exploited to reduce energy expenditure in species that do not normally use torpor, inducing a state called synthetic torpor. This approach may represent the first steps toward the development of a technology to induce a safe and reversible state of hypometabolism in humans, unlocking many applications ranging from new medical procedures to deep space travel.