During hibernation, certain mammals can undergo a physiological state analogous to reversible? suspended animation, with severe hypothermia and a core body temperature (CBT) close to 0 degrees C. In? non-hibernators including the human, this degree of hypothermia is fatal. It is well established that cells? under hypoxia survive longer in hypothermic conditions due to slowing of metabolism, a feature with? many clinical applications. Due to the risk of organ failure, clinical application of hypothermia is limited? to a CBT of 32-34 degrees C. Even at this temperature, the beneficial effect of controlled hypothermia is? significant. The laboratory mouse is a non-hibernator but under caloric restriction it can undergo torpor? (hibernating-like) behavior with a CBT of 31 degrees C or below. Primates such as Malagasy lemurs can? undergo torpor, suggesting that the basic mechanism for such behavior may be preserved in humans.? We have recently identified endogenous 5?-adenosine monophosphate (5?-AMP) as a mediator of torpor? behavior in mice. Our studies revealed that torpor behavior is linked to the regulation of blood glucose? by 5?-AMP, an important allosteric regulator of several rate-limiting enzymes involved in glucose? homeostasis. Our finding raised the possibility that non-hibernators can also achieve a state of? suspended animation observed only in hibernating mammals. Using the physiological variables, 5?-? AMP, environmental temperature and glucose, we can induce, sustain and rescue mice in suspended? animation. Shivering, a sign of thermo-regulatory defense, is blocked by 5?-AMP, allowing rapid cooling? of CBT to 17 degrees C or below, causing the animal to enter suspended animation. Recovery from a? suspended animation state of up to 10 hours is spontaneous but was enhanced by glucose. Our goal is? to bring this technology into two areas. 1) To explore the physiological limits of suspended animation in? non-hibernating mammals. 2) To extend findings from the laboratory mouse to other non-hibernating? mammals along the evolutionary chain.
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