One of the most intriguing aspects of this is that the mammalian clock is actually composed of many separate clocks that maintain different circadian rhythms specifically adapted to the various tissues of the body.

The liver, the heart, and the kidneys each have their own distinct clocks. The liver, for instance, expresses a number of enzymes that remove toxic substances from the bloodstream during the day, which corresponds with the prime time for food (and toxic compound) intake.

Coordinating the activities of all these different clocks is the job of the master circadian oscillator, or master clock, which in humans and other mammals is the suprachiasmatic nuclei, a small center in the brain's hypothalamus with about 10,000 neurons that sits above the optic chasmthe location where the optic nerves cross each other.

This master clock synchronizes independent clocks that reside in peripheral tissues, and every 24 hours, the master clock cycles. This cycling involves the coordinated expression of many genes involved in feedback loops, in which the expression of one gene turns on the expression of a second gene, which turns off the first gene, which turns off the second gene, which turns the first gene back on, etc., day in and day out.

However, in real life, the situation is not so simple as a loop involving only two genes. Multiple clock genes in mammals are involved in overlapping feedback loops. The clock also keeps time dynamically, constantly shifting to stay in time with environmental changes. And these adjustments vary from tissue to tissue. Different tissues respond to the clock in their own way, and they all reset their own clocks independently of one another.

The heart, for instance, is like an obsessive-compulsive clock watcher. It monitors the master clock closely and trains its circadian rhythms to change
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
18-Aug-2004