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Lowering Body Temperature Extends Life Spans of Mice

Results were attained without dietary restriction, but some question study's conclusions

THURSDAY, Nov. 2, 2006 (HealthDay News) -- Lowering the core body temperature of mice let them live an average of 15 percent longer, researchers report.

The study may help resolve a debate about the role of lower body temperature in the life-extending effect of calorie restriction, said study lead author Bruno Conti, an associate professor at the Scripps Research Institute in La Jolla, Calif.

Previous research has shown that restricting caloric intake prolongs life in a variety of organisms, including mammals. The reasons why are unknown, but lowering core body temperature has been suggested as one possible explanation, Conti said.

"It was known in animals that calorie restriction is associated with reduction of the core body temperature," he said. "It was not known if temperature reduction was a consequence of calorie restriction or also contributed to its beneficial effects."

The new study, published in the Nov. 3 issue of the journal Science, shows the latter to be true because the cooled-down mice lived longer even when they were allowed to eat as much as they wanted, Conti said.

An American expert on calorie restriction, Dr. John O. Holloszy, begged to differ.

While the study was "very ingenious and original," it had some flaws, said Holloszy, a professor of medicine at Washington University in St. Louis.

Most notably, the study showed that "lowering body temperature does not prolong life span," Holloszy said. "It allows more mice to reach old age." Calorie restriction, by contrast, does extend life span, he said.

In addition, "the paper gave no information about what the animals died from, so there is no way of knowing what aspect of aging is affected by lower body temperature," he said.

Conti said that lowering human body temperature, while feasible in terms of technology, is not something to be done lightly. "The mice appear fine and normal, but there is much more that we need to investigate," he said.

Lowering the core body temperature of a mammal such as a mouse or a human is not easily done. In this study, it required tinkering with the hypothalamus, the brain structure that acts as the body's thermostat. The mice were "bioengineered" to produce large quantities of a molecule called uncoupling protein 2, which had the effect of making the hypothalamus believe the outside temperature was high. So the rodents' core body temperature was reduced by 0.3 to 0.5 degrees Celsius.

Compared to mice that hadn't been bioengineered, the average life span was longer for the low-temperature mice -- 20 percent longer for females and 12 percent longer for males.

All the mice were allowed to eat as much as they wanted. The weights of the female normal and experimental mice were about the same. Male experimental mice weighed about 10 percent more, probably because they needed less energy to maintain body temperature, the researchers said.

"Our model addresses something more basic than the amount of food," Tamas Bartfai, chairman of molecular and integrative neurosciences at Scripps and a co-author of the paper, said in a prepared statement. The mechanism used in the study "will be a good target for pharmacological manipulation or heating," he said.

Conti said researchers should proceed carefully. "This study is showing a way of life extension that is independent of calorie restriction," he said. "It has not elucidated the actual methods of body temperature control. The reduction [in temperature] was very small, so we do not know what the effect would be if it were larger."

Some strains of mice in calorie-restriction studies reduced their body temperatures several degrees and were found to be unusually lethargic, Conti said.

"How cool can we get?" he asked.

More information

Learn about U.S. government work on varying aspects of aging from the National Institute on Aging.

SOURCES: Bruno Conti, Ph.D., associate professor, Scripps Research Institute, La Jolla, Calif.; John O. Holloszy, M.D., professor of medicine, Washington University, St. Louis; Nov. 3, 2006, Science
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