The interrelations among feeding, circadian rhythms and ageing.

The master clock located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus in the brain regulates circadian rhythms in mammals. Similar circadian oscillators have been found in peripheral tissues, such as the liver, intestine and retina. Life span has been previously linked independently to both circadian rhythms and caloric restriction (CR). The mechanisms by which CR attenuates ageing and extends life span are virtually unknown. It has recently been found that the alphaMUPA mice, transgenic mice that exhibit spontaneously reduced eating and live longer compared to their FVB/N wild-type control mice, show high amplitude, appropriately reset circadian rhythms. These pronounced rhythms were found both in clock gene expression in the liver and clock-controlled output systems, such as feeding time and body temperature. Furthermore, it was previously shown that CR could reset the central biological clock in the SCN. As the circadian clock in the SCN controls many physiological and biochemical systems, we suggest that appropriately reset peripheral rhythms could constitute an important mediator of longevity in calorically restricted animals. Thus, we suggest that three parameters, i.e., caloric restriction, circadian rhythms and life span, are interconnected. This surmise is novel, and we provide evidence to support it. Furthermore, we discuss other feeding regimens and their effects on circadian rhythms and/or life span.