8 August 1998

Cool Research Into Body Clock

Biological clocks are the cellular basis of the circadian rhythm, the 24-hour light-dark cycle that times behavior and metabolism for most organisms from plants to people. In humans, delayed resetting by the clock is an underlying cause of jet lag, and clock malfunction has been linked to seasonal affective disorder and various sleep and mental disorders.

Light had previously been thought to be the dominant signal controlling our body clocks but new research from Dartmouth Medical School (DMS) indicates that temperature may be even more influential than light in regulating the clockwork components that cells use to pace themselves. The study, reported in the August 7 issue of Science, advances understanding of how internal clocks keep time over the wide range of environmental conditions living things encounter.

DMS Researchers, Jay Dunlap, Ph.D., Jennifer Loros, Ph.D., Yi Liu and Martha Merrow monitored production of the Frequency (FRQ) protein and its related components in the bread mold Neurospora. Investigations involved the intricate feedback loop that determines how circadian clocks operate. The loop relies on levels of the FRQ clock protein that feeds back to shut off activity of the gene that produces it. Visible light and high ambient temperatures, interpreted as dusk (going from light to dark) trigger a delay that lengthens the circadian cycle; low temperature and darkness, dawn for example, drive the clock rhythms in the opposite direction, advancing the clock and shortening the cycle.

To determine the relative strength of the two factors, the investigators forced light and temperature to compete with each other in conditions of cool light and warm darkness. They measured the levels and ratios of the FRQ protein and its related gene components and discovered that contrary to previous assumptions, temperature was more effective than light in triggering the clock rhythms.

Given the parallels between the bread mold and mammalian systems (studies on the Neurospora clock mechanisms have predicted and presaged subsequent work in mammals), the findings have implications for humans, the researchers note. They suggest that in the human brain, a low point for key timekeeper proteins could be just before dawn, corresponding to the temperature nadir for healthy adults. Moreover, the asynchrony between light and temperature cycles may be significant for organisms in temperate regions, particularly in spring or fall when environmental temperature touches the lower boundary of the range the clock to keep running.