New understanding of jet lag

A new study demonstrates that the brain’s central timekeeper - the biological clock that regulates waking and sleeping cycles - has two parts that fall out of synchrony during light schedule shifts of six hours, the time it takes to fly across the Atlantic.

The finding may explain, at least in part, why transmeridian travelers suffer from jet lag, the malaise experienced after crossing several time zones. The new understanding could eventually lead to the development of medicines that would “reset” the biological clock so travelers could adjust much more quickly to rapid time zone changes. Most people require about two-and-a-half days to adjust to a six-hour flight from Europe to the United States, and even longer after an eastbound trans-Atlantic flight. The study also has implications for ways to treat shift workers - health care providers, factory employees, truck drivers, etc. - who encounter alertness problems, and those with sleep disorders.

A team of researchers at the University of Virginia and at Leiden University Medical Center in the Netherlands published their findings in the May 24 - June 6, 2005 issue of the journal Current Biology.

The investigators found that the dorsal and ventral sections of the suprachiasmatic nucleus (SCN), the brain’s central timekeeper, adjust to shifts in light schedules at vastly different rates, potentially causing the difficult period of adjustment that most people experience after air travel across several time zones.

The researchers found that the ventral part of the SCN, which is directly connected by a nerve to the light-sensing retina, synchronizes rapidly with a new light schedule, even a radically shifted schedule. But the dorsal part of the clock requires several additional days to adjust. This results in complex signaling patterns that may adversely affect the functioning of tissues and organs throughout the body for a period of several days.

Importantly, the study identifies the neurotransmitter GABA (gamma-aminobutyric acid) as the link between the two clock parts that eventually pulls them back into synchronization, according to co-investigator Gene D. Block, professor of biology at the University of Virginia.

Block likens GABA to a weak rubber band linking pendulums swinging at different rates. If the “rubber band” could be made stronger, such as using a drug to enhance GABA, the ventral and dorsal parts of the central timekeeper could more quickly move back into harmony. The symptoms of jet lag would then be reduced or eliminated.

“The key here is, we now know what the ‘rubber band’ is: the neurotransmitter GABA that ultimately brings the clock back into synch,” Block said. “This could lead to future therapies for jet lag. This is the first time that we have a mechanistic understanding of the systematic coupling of the different parts of the clock. We are now on our way to suggesting strategies for shifting the clock more quickly in response to unnatural light cycle changes.”

Block said that future therapies, using this new knowledge, might also benefit shift workers and older people who suffer from sleep disorders.

In nature, day and night cycles shift slowly as the seasons change. The body is able to adjust to the slow changes and is in fact adapted to these seasonal cycles. But transmeridian flight is an unnatural manipulation of the light cycles, forcing the body to try to rapidly adjust to abrupt light cycle shifts. This sudden disruption in the normal pattern can compromise the normal function of organs. The result often is sleeplessness or sleepiness, reduced alertness, indigestion, fatigue and possibly ulcers.

“This new finding adds support to the emerging view that the central timekeeper, the SCN, is more complex than previously thought, and in fact adjusts to light cycle shifts at a different rate within its own structure,” Block said. “Most importantly, the new research identifies the mechanism that couples the two parts of the SCN clock.”

He suggested that the differing rates of synchronization that occurs in the central clock may be part of a complex evolutionary adaptation to seasonal light changes, but the mechanism, in effect, becomes confused when confronted with unnatural and dramatic shifts in light schedules.

The research is part of a long-term international collaboration between the Center for Biological Timing at the University of Virginia and the Department of Neurophysiology at Leiden University Medical Center in the Netherlands. Block’s co-authors at Leiden are Henk Albus, Mariska J. Vansteensel, Stephan Michel and Johanna H. Meijer.