Calorie restriction lowers body temperature in mammals, but most research on how reduced calorie intake produces benefits to long-term health and longevity has focused on nutrient sensing as the primary trigger for the upregulation of stress responses and other helpful changes to cellular metabolism. Here, researchers demonstrate that reduced body temperature is in fact an important trigger mechanism, possible more so than nutrient sensing, as keeping calorie restricted mice warm eliminates much of the beneficial metabolic adaptation to reduced nutrient levels.

Cutting calories significantly may not be an easy task for most, but it’s tied to a host of health benefits ranging from longer lifespan to a much lower chance of developing cancer, heart disease, diabetes, and neurodegenerative conditions such as Alzheimer’s. One consistent observation is that when mammals consume less food, their body temperature drops. It’s evolution’s way of helping us conserve energy until food is available again. It makes sense, considering that up to half of what we eat every day is turned into energy simply to maintain our core body temperature.

Previous work showed that temperature reduction can increase lifespan independently of calorie restriction – and that these effects involve activation of certain cellular processes, most of which remain to be identified. On the flip side, studies have shown that preventing body temperature from dropping can actually counteract positive effects of calorie restriction. Notably, in an experiment involving calorie-restricted mice, anti-cancer benefits were diminished when core body temperature remained the same. “It’s not easy to discern what’s driving the beneficial changes of calorie restriction. 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?”

In the new research, scientists compared one group of calorie-restricted mice housed at room temperature, about 68 degrees Fahrenheit (22 degrees Celsius), to another group housed at 86 degrees (30 degrees Celsius). The warmer environment invoked “thermoneutrality,” a state at which most animals cannot easily reduce their body temperature. The team evaluated the mice by measuring their metabolites, or chemicals released by the animals’ metabolism. Through this, they were able to look for molecules in the bloodstream and in the brain that are changed 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.”