Circadian Clocks: The past, present and future of telling the time.

Abstract

The world completes a 360 degree spin every 24 hours and by doing so, creates a regular circadian rhythm of light. All living creatures have adapted to this reliable rhythm, allowing them to predict and prepare for upcoming events. The adaptation was discovered by extensive behavioural studies across the taxonomic groups, which simultaneously uncovered the biological circadian clock. This endogenous timepiece produces an autonomous, self-sustaining circadian rhythm and can be entrained by external light time cues to keep the animal in synchrony with its environment. The next step in chronobiology was to determine the molecular mechanisms driving the endogenous clock. Early on a transcription-translation (TT) feedback looping system was postulated. The TT model is still widely accepted today even though there is mounting evidence contrary to the models predictions. The supporting and contrary findings are discussed and the direction of future work is suggested. In mammals, including humans, the suprachiasmatic nucleus (SCN) is well established as the master clock, synchronising the peripheral clocks and entraining the body to the external light signals it receives. However, SCN lesions do not stop all circadian behaviour, and peripheral clocks are often entrained by more local signals more relative to their function. Moreover, newer studies are looking at other brain areas and extra-SCN areas are potential clock candidates. The literature in support of the SCN as master clock and studies revealing other potential clockwork circuitry is discussed. The importance of accuracy in chronobiology is essential as the role of functioning circadian rhythms in health is becoming more and more apparent.