The daily rhythms of genes, cells and organs

Abstract

All living organisms have time‐measuring devices that affect their development, generation time, lifespan and lifestyle. These biological timers can be categorized into hourglasses and oscillators; the latter can be further classified as ultradian, circadian and infradian. Most physiological processes in mammals are influenced by a complex circadian timing system in which the master pacemaker in the brain synchronizes numerous subsidiary oscillators in peripheral cells. The phase of the master clock—located in the suprachiasmatic nucleus (SCN) of the ventral hypothalamus—must be readjusted every day by light cues to stay tuned to the actual geophysical time. In both SCN neurons and peripheral cells, the circadian clockwork is constructed from interconnected feedback loops in gene expression that function in a cell‐autonomous fashion. A variety of output pathways translate these gene‐expression cycles into physiological and behavioural rhythms. Experiments on a variety of organisms have shown that their maximal lifespan is determined by an hourglass timer (Fig 1, left panel), which measures different timespans in each species and is further modulated by the genetic makeup and lifestyle of the individual. Species‐specific hourglass clocks also determine the duration of embryonic development, the timespan required to reach sexual maturity and the time at which a woman reaches menopause. Hourglass mechanisms thus determine the timing of biological events that happen only once in a lifetime—unless the hourglass is flipped around by a mystical force, a process that adherents of the Hindu religion believe occurs after death. Figure 1. Two types of biological clock. Biological clocks that determine the duration of unique events for an organism or populations of organisms are termed hourglass timers. Examples of such processes are indicated below the hourglass. Oscillators are designed to drive reiterative processes, of which a few examples are listed below the picture. Yeast respiration is controlled by an oscillator that generates 40‐min …