Relationship between calorie restriction and the biological clock: lessons from long-lived transgenic mice

The master clock located in the brain regulates circadian rhythms in mammals. Similar clocks are found in peripheral tissues. Life span has been independently increased by reset circadian rhythms and caloric restriction (CR). The mechanisms by which CR extends life span are not well understood. We found that alphaMUPA transgenic mice that exhibit reduced eating and live longer show high amplitude, appropriately reset circadian rhythms in clock gene expression, and clock-controlled output systems, such as feeding time and body temperature. As CR resets circadian rhythms, and the circadian clock controls many physiological and biochemical systems, we suggest that the biological clock could be an important mediator of longevity in calorically restricted animals.