Fight Aging!

A review paper I noticed today reminded me of the relationship between body temperature and longevity. Calorie restriction leads to lowered body temperature - as well as extended healthy life - in mice, but unrelated methods of lowering body temperature over the long run also seem to extend longevity to some degree. For example, see this research from a couple of years ago:

Was calorie restriction itself responsible for longer lifespan, with reduced body temperature simply a consequence? Or was the reduction of core body temperature a key contributor to the beneficial effects of calorie restriction? Conti and colleagues wanted to find out. To tackle the problem, the scientists decided to try to lower core body temperature directly, without restricting food intake.

...

Conti and colleagues decided to focus their efforts on the preoptic area of the hypothalamus, a structure in the brain that acts as the body’s thermostat and is crucial to temperature regulation. Just as holding something warm near the thermostat in a room can fool it into thinking that the entire room is hotter so that the air conditioning turns on, the Scripps Research team reasoned that they could reset the brain’s thermostat by producing heat nearby.

To do so, they created a mouse model that produced large quantities of uncoupling protein 2 in hypocretin neurons in the lateral hypothalamus, which is near the preoptic area. The action of uncoupling protein 2 produced heat, which diffused to other brain structures, including the preoptic area. And, indeed, the extra heat worked to induce a continuous reduction of the core body temperature of the mice, lowering it from 0.3 to 0.5 degrees Celsius.

The scientists were then able to measure the effect of lowered core body temperature on lifespan, finding that the mice with lowered core body temperature had significantly longer median lifespan than those that didn’t. While this effect was observed in both males and females, in this study the change was more pronounced in females - median lifespan was extended about 20 percent in females and about 12 percent in males.

Some researchers would like to pin temperature-dependent longevity on the rate of chemical reactions in the body (reaction speeds generally being proportional to temperature), but I suspect that's too simplistic. An alteration in the rate at which mitochondrial processes generate damaging free radicals sounds more plausible, driven by some temperature-sensitive signaling and control process.

The interesting question with regard to this is what proportion of calorie restriction benefits stem from this mechanism - as opposed to, say, the loss of visceral fat, changes in metabolic control pathways, increased autophagy, other regulatory changes in cells, and so forth. None? A tenth? A third? What? As we look at ongoing work to produce calorie restriction mimetic drugs, based on manipulating the biochemical pathways researchers discovered through research into calorie restriction, how much benefit will these mimetics provide for people who still have visceral fat and a high body temperature?