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Creatine accelerates the circadian clock in a unicellular alga

Abstract

The circadian clock is considered to be a universal feature of eucaryotic organisms, controlling the occurrence and rates of many different aspects of life, ranging from single enzymatic reactions and metabolism to complex behaviours such as activity and rest1. Although the nature of the underlying cellular/biochemical oscillator is still unknown2, many substances are known to influence either phase or period of circadian rhythms in different organisms. These include D2O3,4, electrolytes5 and ion channel inhibitors5,6, small organic molecules such as alcohols7,8 and aldehydes9, inhibitors of protein synthesis10–12 and ammo-acid analogues13,14. Certain transmitter15 and neurochemical drugs16,17 also influence the circadian clock in higher animals. We report here that the period of free-running circadian rhythms in the unicellular marine alga Gonyaulax polyedra is shortened by extracts from mammalian cells. The effect is dose-dependent, accelerating the circadian clock by as much as 4 hours per day. The substance responsible for this effect has been isolated from bovine muscle and identified as creatine. Authentic creatine has identical biological effects at micromolar concentrations and is known in animal systems for its involvement in cellular energy metabolism. A period shortening substance with similar chemical properties is also present in extracts of Gonyaulax itself.

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Roenneberg, T., Nakamura, H. & Hastings, J. Creatine accelerates the circadian clock in a unicellular alga. Nature 334, 432–434 (1988). https://doi.org/10.1038/334432a0

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