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Bert van der Horst

Chronobiology and Health

Like most organisms, we have developed an internal time keeping system that drives daily rhythms in metabolism, physiology and behavior, and allows us to optimally anticipate to the momentum of the day. At the basis of circadian timekeeping lies an intracellular molecular oscillator in which a set of clock genes cyclically regulate their own expression with an approximate (circa) 24-hour (dies) periodicity. The mammalian circadian system consists of a light-entrainable master clock in the neurons of the suprachiasmatic nucleus (SCN) in the brain, and light-irresponsive peripheral clocks in the cells of virtually all other tissues. As the circadian clock drives rhythmic expression of up to 10 % of the active genes (thereby conferring rhythmicity to a wide range of cellular processes such as, but certainly not limited to, energy metabolism, metabolic activation of drugs, detoxification, hormone synthesis, DNA repair and cell cycle control), it may not come as a surprise that disruption of the circadian system is associated with disease. Indeed, genetic disruption of the circadian system in rodent models by inactivation of clock genes has been found to increase tumor growth, accelerate aging, and disrupt metabolism. On the other hand, our 24/7 economy requires many people to work at “non-standard” times. Recently, epidemiological and experimental animal studies have revealed a relation between disturbance of our body clock by repeated shift-work and an increased risk for developing pathologies such as cancer, metabolic syndrome and cardiovascular disease.