Resetting the clock of life


We know that the circadian clock keeps time in every living cell, controlling biological processes such as metabolism, cell division, and DNA repair, but we don’t understand how.

Night shifts. Jet lag. Disturbed sleep. Far from causing just drowsiness, these have a more profound effect. That’s because they disrupt our circadian clock, so called because it synchronizes biological processes to the earth’s 24-hour rotation and, in turn, governs the basic chemical mechanisms of our body. The clock controls when thousands of genes turn on and off, and these in turn synthesize proteins that operate the machinery of a cell. Every cell has its own clock, and the clocks control different genes in different cell types. Life is, in effect, a marvelously intricate clockwork process—in bacteria, in fungi, in plants, in insects, and in animals. In humans and likely in other animals, there is a central clock in the brain which is influenced by light and which synchronizes all the other clocks throughout the body. So when the clock is disrupted or when it doesn’t work right, we feel the effects in every tissue and organ.

It may seem strange that such a fundamental biological process still lies outside our understanding, but that’s the case. Research in bacteria, fruit flies, plants, and mice has shed some light on the clock. We know that in mammals it has four central components, four clock proteins and the genes that synthesize them, which are interconnected in a feedback loop with a “positive” arm and a “negative” arm: The proteins turn the genes on and off, which in turn dictate the levels of the clock proteins, such that the levels of the clock proteins fluctuate in an intricate dance. Think of it as the biochemical equivalent of a two-pendulum grandfather clock. Only in this case, each swing of the pendulum influences a whole swath of other genes and sets in motion other essential processes, such as the process—which takes exactly 24 hours—by which mammalian cells divide and replicate themselves, or by which photosynthesis occurs in plants. The clock seems to be as old as life itself. Even ancient bacteria have a clock. The specific clock proteins found in people are also found in all animals—from bees to lizards to whales—showing how closely conserved the mechanism has been throughout hundreds of millions of years of evolution and thus how central it is to all living things.

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