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

Tinganelli, Walter; Hitrec, Timna; Romani, F.; Simoniello, Palma; Squarcio, Fabio; Stanzani, Agnese; Piscitiello, Emiliana; Marchesano, Valentina; Luppi, Marco; Sioli, M.; Helm, Alexander; Compagnone, G.; Morganti, Alessio Giuseppe; Amici, Roberto; Negrini, M.; Zoccoli, À.; Durante, Marco; Cerri, Matteo

doi:10.3390/ijms20020352

Cited by 26 publications

(23 citation statements)

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“…The first artificial method capable of bringing a non-hibernator (rat) into what is now called synthetic torpor was developed ( Figure 1 and Figure 2 ) using microinjections of the GABA-A agonist muscimol into the brainstem region of the raphe pallidus (RPa) of a rat [ 19 ]. This synthetic torpor was shown to increase the radioprotection of organs such as the liver and testis four hours after X-ray irradiation [ 18 ]. Here, we discuss the possible mechanisms underlying this fascinating physiological process.…”

Section: What Are Torpor and Hibernation?mentioning

confidence: 99%

“…These adaptations include upregulated genomic protective measures, specifically proteins involved in the detection and response to double-strand breaks (e.g., RAD50, NBN, and ATM) [ 32 ], which are important for ATM activation by DNA damage [ 33 ]. Interestingly, when the synthetic torpor rats were acutely exposed to 3 Gy of X-rays, ATM-related genes were downregulated in the testis and the liver [ 18 ]. ATM primarily initiates cellular responses to radiation-induced double-strand breaks [ 34 ], and this finding is crucial for the response to radiation-induced DNA damage.…”

Section: Hibernation and Survival In Extreme Environmentsmentioning

confidence: 99%

“…During the hibernation period, animals go through a series of extreme physiological adaptations. Among these is a reduction in food intake, and the most important adaptation, as shown by several studies on acute high-dose low-linear energy transfer (LET) irradiation, is that animals increase their radioresistance, one of the main advantages of hibernation [ 15 , 16 , 17 , 18 ]. In 2013, the first successful procedure to induce a reversible state mimicking natural hibernation in a non-hibernating animal (rat) was discovered (Figures 1 and 2) [ 19 ], which was proposed to be called synthetic torpor [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Hibernation as a Tool for Radiation Protection in Space Exploration

Puspitasari

Cerri

Takahashi

et al. 2021

Life

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With new and advanced technology, human exploration has reached outside of the Earth’s boundaries. There are plans for reaching Mars and the satellites of Jupiter and Saturn, and even to build a permanent base on the Moon. However, human beings have evolved on Earth with levels of gravity and radiation that are very different from those that we have to face in space. These issues seem to pose a significant limitation on exploration. Although there are plausible solutions for problems related to the lack of gravity, it is still unclear how to address the radiation problem. Several solutions have been proposed, such as passive or active shielding or the use of specific drugs that could reduce the effects of radiation. Recently, a method that reproduces a mechanism similar to hibernation or torpor, known as synthetic torpor, has started to become possible. Several studies show that hibernators are resistant to acute high-dose-rate radiation exposure. However, the underlying mechanism of how this occurs remains unclear, and further investigation is needed. Whether synthetic hibernation will also protect from the deleterious effects of chronic low-dose-rate radiation exposure is currently unknown. Hibernators can modulate their neuronal firing, adjust their cardiovascular function, regulate their body temperature, preserve their muscles during prolonged inactivity, regulate their immune system, and most importantly, increase their radioresistance during the inactive period. According to recent studies, synthetic hibernation, just like natural hibernation, could mitigate radiation-induced toxicity. In this review, we see what artificial hibernation is and how it could help the next generation of astronauts in future interplanetary missions.

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Section: What Are Torpor and Hibernation?mentioning

confidence: 99%

Section: Hibernation and Survival In Extreme Environmentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hibernation as a Tool for Radiation Protection in Space Exploration

Puspitasari

Cerri

Takahashi

et al. 2021

Life

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“…The idea of hibernation has been proposed as a possible approach for use in human space travel. Recently, a procedure to induce a metabolic state known as “synthetic torpor” in non-hibernating mammals was successfully developed; this could be an efficient means of conserving resources, reducing the incidence of mental disorders related with long-term missions and mitigating or preventing radiation-induced acute effects [ 90 ]. However, GCR-induced long-term or chronic health risks for humans, such as cancer, heart failure, and dementia, during hibernation or synthetic torpor are still unclear.…”

Section: Possible Issues Related To Human Space Exploration and Thmentioning

confidence: 99%

The Effect of Low Temperatures on Environmental Radiation Damage in Living Systems: Does Hypothermia Show Promise for Space Travel?

Fukunaga

2020

IJMS

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Low-temperature treatments (i.e., hypothermia) may be one way of regulating environmental radiation damage in living systems. With this in mind, hibernation under hypothermic conditions has been proposed as a useful approach for long-term human space flight. However, the underlying mechanisms of hypothermia-induced radioresistance are as yet undetermined, and the conventional risk assessment of radiation exposure during hibernation remains insufficient for estimating the effects of chronic exposure to galactic cosmic rays (GCRs). To promote scientific discussions on the application of hibernation in space travel, this literature review provides an overview of the progress to date in the interdisciplinary research field of radiation biology and hypothermia and addresses possible issues related to hypothermic treatments as countermeasures against GCRs. At present, there are concerns about the potential effects of chronic radiation exposure on neurological disorders, carcinogenesis, ischemia heat failures, and infertility in astronauts; these require further study. These concerns may be resolved by comparing and integrating data gleaned from experimental and epidemiological studies.

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“…(Ghosh.S et al, 2017). Radioprotection during synthetic torpor has also been shown in irradiated rats (Tinganelli. W et al, 2019).…”

Section: Introductionmentioning

confidence: 95%

Radioprotective effects of induced astronaut torpor and advanced propulsion systems during deep space travel

Squire

Ryan

Bernard

2020

Life Sciences in Space Research

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relatively lower radioprotection in cells with a weak clock during normothermia. We were also able to demonstrate that if torpor weakened the circadian clock, a protective effect could be partially restored by an external drive such as lighting schedules to aid entrainment i.e: Blue light exposure for periods of awake and no light for rest times For the propulsion simulation, estimated transit times from Earth to Mars were 258 days for chemical propulsion with 165.9mSv received, 209 days for nuclear propulsion with 134.4mSv received and 80 days for electrical propulsion with 51.4mSv received. Conclusion A state of torpor for astronauts on deep space missions may not only improve weight, fuel and storage requirements but also provide a potential biological radiation protection strategy. Moreover, maintaining a controlled circadian rhythm during torpor conditions may aid radioprotection. In the not too distant future, propulsion techniques will be improved to limit transit time and hence decrease radiation dose to astronauts. Limiting exposure time and enhancing physiological radioprotection during transit could provide superior radioprotection benefits compared with active and passive radiation shielding strategies alone.

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

Cited by 26 publications

References 32 publications

Hibernation as a Tool for Radiation Protection in Space Exploration

Hibernation as a Tool for Radiation Protection in Space Exploration

The Effect of Low Temperatures on Environmental Radiation Damage in Living Systems: Does Hypothermia Show Promise for Space Travel?

Radioprotective effects of induced astronaut torpor and advanced propulsion systems during deep space travel

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