"Cooler" Mice Live Longer, Study Finds

Sean Markey
for National Geographic News
November 2, 2006
Scientists say they've made a cool discovery about living longer.

Mice genetically engineered to have lower body temperatures live substantially longer than normal mice, researchers report in tomorrow's issue of the journal Science.

The newfangled mice are only slightly cooler than standard—just 0.5 to 0.9 degree Fahrenheit (0.3 to 0.5 degree Celsius), an effect that occurs only during waking hours.

But the temperature drop significantly increases the rodents' life spans, scientists say. Altered male mice live 12 percent longer on average, while females live 20 percent longer than regular mice.

"We've demonstrated that a modest but prolonged reduction of core body temperature can contribute to increased longevity," said lead study author Bruno Conti, a biologist and neuroscientist at the Scripps Research Institute in La Jolla, California.

(See a National Geographic magazine feature on "The Secrets of Longevity.")

Genetic Engineering

To create the "cool mice," investigators used genetic engineering to fool the rodents' central thermostat, which is found in the hypothalamus region of the brain.

By targeting a specific protein, the scientists caused a small cluster of neurons to heat up, duping the nearby thermostat to turn down the rodents' body heat.

Despite lower body temperatures, the mice appear to be as physically active as, and eat the same amount of food as, normal mice.

Precisely why these cool mice live longer remains unclear, investigators say. But they suspect the rodents produce fewer free radicals over time.

The chemical by-products of metabolism, free radicals damage DNA and other cell structures, an erosion linked to disease and aging.

Calories Versus Birthdays

Prior to the new findings, the only reliable way to prolong life in several mammal species has been a calorie-restricted diet, Conti says.

In 1935 scientists discovered that mice fed 40 percent fewer calories lived up to 50 percent longer than mice on full-calorie diets.

Such calorie-restricted diets not only increase life expectancy but also produce lower body temperatures.

Severe calorie-restriction can also delay the onset of age-related diseases, research has found.

But such diets are hardly practical, Conti says.

"Maybe there is a way that we can improve life span and health span without necessarily undergoing a strict diet," he said.

His study doesn't offer any immediate ways to extend the human life span, he adds, but the findings do provide a new model for understanding how aging works.

Future Therapies

Clifford Saper, a Harvard Medical School neuroscientist, says the new study is the first to test the hypothesis that lowering body temperature prolongs life.

The finding yields some tantalizing prospects, he notes.

"The substantial increase of life span raises the question of whether mild hypothermia … might be easier to tolerate than a lifetime of starvation as a way to increase longevity," he writes in any accompanying Science perspective.

Gene therapy—possibly delivered by a virus to the same temperature-regulating area of the brain that was altered in the mice—may be available in the future, Saper says.

In the meantime another recent mouse study published yesterday in the journal Nature suggests a more low-tech option currently available at the local liquor store.

Large daily doses of resveratrol, a substance found in red wine, appears to not only offset the ill effects of a high-calorie diet, but can significantly extend life span, the study suggests.

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