The tick of the biological clock

Before I had a baby daughter to keep me sleep-deprived, I almost always woke up a few minutes before the alarm went off. It’s a common phenomenon, and it’s only possible because we each have an additional clock, not on our bedside tables, but in our heads.  These clocks regulate a number of bodily functions, of which sleep is only the most obvious.

Although we can’t speed up or slow down our internal clock, we can reset it, because it’s light-sensitive–and that light doesn’t have to shine in our eyes;  we have light detectors in cells throughout our bodies, so that even shining a light on the back of someone’s knees can affect his or her internal clock.

We also know the part of the brain that coordinates the bodily functions that make use of the clock–it’s called the superchiasmatic nucleus.  But what we haven’t known, until now, is the biological basis of the clock–the tick-tock, like the swinging pendulum of a grandfather clock, on which all our internal measurement of time is based.

Last month the husband-and-wife research team of D. James and Dorothy Morré at Purdue University announced they have discovered a single protein in cells that keeps our internal clocks ticking.

Back in the 1960s, James Morré, now a professor of medicinal chemistry in Purdue’s School of Pharmacy and Pharmacal Sciences, first set out to find the source of the biological clock when he was a student in 1962. There was a hint that there must be a biochemical basis to the biological clock in experiments that showed that cells fed heavy water would run on a 27-hour day instead of a 24-hour day.

Recently, the Morrés noticed that cells grow at a periodic rate:  they enlarge for 12 minutes, rest for 12, enlarge for 12, and so on.  The Morrés theorized that some undiscovered proteins must be behind this cycle; it turned out to be a single, cylinder-shaped protein with which acts as a catalyst for cell growth for 12 minutes, switches over to other activities for 12 minutes, then promotes cell growth again, and so on. The protein’s 24-minute cycle is, of course, exactly one-60th of a 24-hour day.

By altering the protein, the Morrés discovered they could produce protein clocks with cycles of anywhere from 22 to 42 minutes (and, correspondingly, cells with 22 to 42-hour “days”).  And sure enough, heavy water altered the protein’s cycle to 27 minutes.

Further research on the protein could lead to new therapies for seasonal-affective disorder, jet lag and sleep problems in shift workers and people living in artificial environments like Antarctic research stations or the space station, where day-night cycles may be absent or confused.

There might be additional medical benefits, because it’s not just sleep that’s governed by our internal clock. Our entire body undergoes significant internal changes as day turns to night and back to day again. Blood pressure is a good example. It isn’t constant: it normally rises in the morning (in expectation of increased physical activity), remains elevated during the day and early evening, and then decreases to its lowest level during sleep. Various diseases and conditions, from asthma to arthritis to angina, are worst at specific times of the day.

That means our internal clocks can influence the results of medical tests, and the resulting diagnosis and treatment.  Many doctors now try to monitor symptoms over a 24-hour period or to run tests at several different times to get a truer picture of the condition they’re diagnosing.

This kind of thinking applies to drug therapy, as well. If the symptoms of your asthma are worse at night, then maybe you should be taking your pill just before bedtime instead of first thing in the morning. Since osteoarthritis tends to worsen in the afternoon and evening, some doctors recommend taking medication for it at mid-day. Antihistamines, anticancer drugs, corticosteroids–the effective of many drugs can be enhanced if they’re taken at a specific time of the day, a time that may vary from patient to patient.

The more we understand about our internal clocks, the better we may eventually be able to treat a whole host of diseases and conditions, enhancing the lives of many people.

Maybe we’ll even figure out a way to keep our internal clocks from ringing alarms in our head on the weekend, waking us up at 6 a.m. on the one day we get to sleep in.

Now that would be a scientific breakthrough worth celebrating!

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