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core temperature dropped from the normal 37 degrees Celsius to as low as 11 C, depending on the controlled ambient temperature within the chamber.

"We have, on demand, reversibly demonstrated the widest range of metabolic flexibility that anyone has ever seen in a non-hibernating animal," Roth said.

"The cool thing about this gas we're using, hydrogen sulfide, is that it isn't something manufactured that we're taking down from a shelf ?it isn't 'better living through chemistry' ?it's simply an agent that all of us make in our bodies all the time to buffer our metabolic flexibility. It's what allows our core temperature to stay at 98.6 degrees, regardless of whether we're in Alaska or Tahiti," Roth said.

In addition to mice, Roth and colleagues in previously published work have demonstrated the ability to metabolically arrest ?and subsequently re-animate ?such model organisms as yeast and worms, as well as the embryos of fruit flies and zebrafish.

In each case they achieved metabolic suspension through oxygen deprivation caused by exposure to gases such as hydrogen sulfide and carbon monoxide. Known as oxygen mimetics, these chemicals are very similar to oxygen at the molecular level and so bind to many of the same receptor sites. As a result, they compete for and interfere with the body's ability to use oxygen for energy production - a process within the cell's power-generating machinery called oxidative phosphorylation. The inhibition of this function, in turn, is what the researchers believe causes the organism to shut down metabolically and enter a hibernation-like state. In each case, upon re-exposure to normal room air, the organisms quickly regained normal function and metabolic activity with no long-term negative effects.

If Roth and colleagues are able to replicate these findings in larger animal models, they foresee the first clinical use of this technology in humans could involve treating people suffering from severe
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Source:FHCRC


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