Decoding the function and regulation of the mammalian 12-h clock

Both Eastern and Western ancient philosophies posited that a harmony exists between the universe and the human beings (and by extension, all life forms on earth). For example, the Chinese is strongly influenced by the Taoism doctrine of the Unity of Man and Heaven (Raz, 2012), while the great Greek mathematician Pythagoras raised the concept of ‘musica universalis’, which claims the movements of celestial bodies follow mathematical equations and resonate to produce an inaudible harmony of music, of which the harmonious sounds that men make were mere an approximation (Koff and Fiveisky, 1975). The best example of the harmony between the natural world and living organisms probably lies in the well-characterized 24-h circadian rhythm, which is synchronized to the diurnal natural cycles of temperature and light coinciding with the 24-h cycle of the Earth self-rotation. Unbeknownst to many, in addition to the circadian rhythms, 12-h rhythms also exist in living organisms, with the prominent example of circatidal rhythms found in coastal and estuarine animals that modulate their behavior in tune to the 12.4-h ebb and flow of the tides (Wilcockson and Zhang, 2008). Intriguingly, the circatidal rhythms are also evolutionarily conserved in in-land animals that are no longer exposed to tidal cues, including mammals (Zhu et al., 2017, 2018; Pan et al., 2020). In this perspective, I will focus on the mammalian 12-h rhythms and discuss our current understandings of their prevalence, physiological function, and regulation.