September 1, 2009

Scientists extend circadian clock cycle

Japanese and U.S. scientists say they've identified an enzyme that can be inhibited to extend the circadian 24-hour metabolic cycle to more than 48 hours.

The scientists said the circadian clock has long been known to play a central role in regulating the daily activities of living organisms. But its detailed biochemical mechanisms have largely remained unidentified.

Researchers at the Riken Center for Developmental Biology in Tokyo, led by Hiroki Ueda and Northwestern University Professor Joseph Takahashi, analyzed 1,260 pharmacologically active compounds in mouse and human clock cell lines. They identified 10 that exerted the greatest impact on the clock cycle.

The scientists said they were surprised to find all but one targets a single enzyme -- casein kinase -- the inhibition of which, researchers showed, dramatically extends the circadian cycle from 24 hours to more than 48 hours.

The researchers, who said that finding overturns conventional thinking on the topic, also discovered the inhibition process is insensitive to changes of as much as 10 degrees Celsius, further hinting at how circadian clocks maintain constant periodicity over a broad range of temperatures.

The scientists said their findings suggest the need to revise models of the mammalian circadian clock.

The study is reported in the Proceedings of the National Academy of Sciences.