Be cool, live long

I had earlier written about Calorific restriction (eating less) and living longer. This wasn’t about starvation, but just by eating less in terms of calories (but still getting enough essential nutrients) led to substantially longer and healthier life spans (in everything from the humble yeast to mammals, and likely, us). Now, the New York Times has an article chronicling the same story, but perhaps written in a more entertaining style.

But that is not what this post is about. That’s old news. This one is cool.

Literally.

It is widely believed that body temperature acts in concert with calorific restriction in increasing life span, as calorific restriction does seem to lower body temperature.

The normal body temperature is 98.6 F (or 37 degrees Centigrade). That’s what we all know. We also believe that this temperature is the optimal temperature for survival and life. This body temperature is controlled by a region of the brain, the hypothalamus, where a complex network of different types of neurons interact to maintain and control body temperature. By directing blood flow to shift to cutaneous blood vessels (that reach the skin), heat can be spent, while directing blood flow to deep blood vessels retains heat.

Researchers decided to test the cool-body temperature- long lifespan theory, and to do that they made use of this central temperature controlling system. Cells have a certain organelle, the mitochondria, which convert organic material in to energy (in the form of ATP) that the body uses. Now, mitochondria also have a protein called UCP (with two forms, 1 and 2) that uses up this energy and results in the release of heat. In this study, the researchers cleverly decided to take advantage of the central temperature controlling region of the hypothalamus to modify the core body temperature itself.

What they did was to engineer mice to over express this UCP protein (UCP-2) exclusively in the hypocretin region of the hypothalamus. This excess of UCP-2 slightly increased the heat in that small region alone. This effectively fooled the hypothalamus in to thinking that the entire body was too hot, and resulted in a lowering of the core body temperature of the mice, resulting in a lowering of temperature by 0.3-0.5 degrees centigrade.

The engineered “cool” mice were then fed the same amount of food as wild-type (normal) mice, and were monitored. Due to their lowered body temperature, these engineered mice ended up gaining more weight (compared to the normal mice), even though they ate the same amount of food. This was somewhat expected, since maintaining a lower body temperature would require less energy.

One would imagine that this weight gain (which is normally known to adversely affect lifespan) would result in a lowered life span. But surprisingly, what the researchers observed was exactly the opposite.

What they saw was that the engineered mice with slightly lower body temperature on average increased their life span by about 8% (in human terms that would be an increase in lifespan of about 8 years!). To push the question further, both the normal as well as the lower body temperature mice were fed on a fat diet. The engineered mice ate normally, and ended up surviving longer than the normal mice.

Now, what was earlier known was that calorific restriction would result in lower body temperature as well as longer lifespan. But here, the results suggested that lower body temperatures actually increase lifespan, independent of calorific restriction.

This study raises some really interesting questions. Would it be desirable to decrease body temperature slightly, and therefore live longer? Body temperatures are tightly regulated, and have evolved over millions of years to be where they are today. So, even if a slightly lower body temperature results in a longer lifespan, could there be other adverse side effects on behavior, or psychology or reproduction or something else? Calorific restriction appears to lead to healthier longer lives. Will just lowering of the body temperature do the same?

As always, more questions, each as fascinating as the other.

(You can read the complete article here (Science Vol. 314. no. 5800, pp. 825 – 828), or a short comment here)