Calorie Restriction Linked to Body Temperature and Healthspan

Reducing calories significantly may be challenging for most people, but it is linked to a number of health benefits ranging from longer lifespan to a much lower possibility of developing cancer, heart diseases, diabetes, and neurodegenerative conditions such as Alzheimer’s.

New research from teams of scientists led by Scripps Research Professors Bruno Conti, Ph.D., and Gary Siuzdak, Ph.D., details on the vital role that body temperature plays in realizing these diet-induced health benefits.

Through their findings, the team paves the way toward developing a medical compound that mimics the impacts of reduced body temperature. The research was published in Science Signaling.

Making the Correlation

​Conti has spent years analyzing how and why calorie limitation leads to better health, with the ultimate aim to translate the discoveries into drugs that can imitate what takes place naturally in a human body when a person eats less.

One steady observation is that when mammals eat less food, their body temperature drops. It’s nature’s way of helping the body preserve energy until food is available again, the researcher explains. This is rather logical, taking into consideration that up to half of what we consume every day is turned into energy only in order to maintain our core body temperature.

Conti’s prior research showed that temperature decrease can enhance lifespan independently of calorie restriction and that these impacts involve activation of specific cellular processes, most of which are still not identified.

On the other hand, studies have shown that preventing body temperature from going down can actually neutralize the positive effects of calorie restriction. In addition, in an experiment on calorie-reduced mice, anti-cancer benefits were decreased when core body temperature remained the same.

“It’s not easy to discern what’s driving the beneficial changes of calorie restriction,” Conti says. “Is it the reduced calories on their own, or the change in body temperature that typically happens when one consumes fewer calories? Or is it a combination of both?”

Metabolites are the Key

In the new study, Conti and his colleagues created an experiment that would enable them to independently analyze the impacts of reduced nutrients and those of body temperature.

They compared one group of calorie-limited mice housed at room temperature (about 68 degrees Fahrenheit, or 22 degrees Celsius), to another group housed at 86 degrees Fahrenheit (30 degrees Celsius). The warmer setting triggered ‘thermoneutrality,’ a state at which the majority of animals cannot easily decrease their body temperature.

The Siuzdak team then used a technology they developed, known as metabolomics, to analyze the mice by measuring their metabolites, or chemicals produced by their metabolism. The team was able to look for molecules in the bloodstream and in the brain that are adjusted by the reduction of either nutrients or body temperature.

“The data we collected showed that temperature has an equal or greater effect than nutrients on metabolism during calorie restriction,” Conti says.

In addition, the team of researchers came up with the first detailed profiling of the metabolites that are changed by temperature decrease. Via a computing assay of results from both groups of mice, the researchers could prioritize which metabolites were most accountable for producing the changes to the core body temperature.

Conti says that further research to validate the changes created by temperature during calorie restriction should offer new targets for future drugs he calls ‘temperature mimetics.’

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