JET LAG

What physiological processes lie behind the many disagreeable symptoms that people experience when they take an airplane flight across several time zones? Today’s scientific understanding of the cause of these symptoms, collectively known as jet lag, is based on the fact that the human body contains not one but several biological clocks distributed throughout its various tissues.

All of these clocks contain genes that produce proteins that form negative feedback loops affecting their own production, thus creating an endogenous oscillating rhythm, or cycle. These endogenous cycles last approximately 24 hours, which is why they are also called circadian rhythms (from the Latin circa and dies, meaning “about or around a day”). These cycles normally follow the alternating pattern of day and night and are entrained (regulated) by a variety of factors, the most important of which is daylight.

In humans, the intensity of the ambient light directly affects the brain’s suprachiasmatic nuclei (SCNs) through certain specialized ganglion cells in the retinas. The SCNs are thus directly entrained by daylight and act as the central biological clock with which all of the body’s other, peripheral clocks are synchronized. This synchronization is achieved in various ways, depending on the tissue involved. Sometimes it is achieved very quickly, through the autonomic nervous system. Other times it is achieved much more slowly, through the secretion of hormones, such as glucocorticoids or ACTH, into the bloodstream.

One of the proposed explanations for jet lag is that it occurs when the body’s various biological clocks get out of phase with one another, because they take differing amounts of time to become synchronized with the ambient light levels in the destination time zone. The central clock in the SCNs does resynchronize very quickly after a sudden change in the light cycle. But the peripheral clocks seem to adjust much more slowly. Part of the reason for this slower adjustment and the resultant dephasing may be the time it takes for the signals from the SCNs to reach the peripheral clocks. Experiments with mice have confirmed this decoupling of the peripheral clocks from the central clock when a sudden change occurs in the regularity of an entraining factor such as eating or daylight.

Studies with rats suggest another possible source of lag that causes the body’s clocks to become desynchronized. Like many other structures in the brain, the suprachiasmatic nuclei have now been shown to be composed of several different regions. The ventral region of each SCN receives afferences directly from the ganglion cells of the retina. Researchers have shown that in rats, the ventral SCNs seem to be reset much more quickly by a sudden change in light than the dorsal SCNs.

Thus, a time lag may be created within the central clock itself, between the ventral SCNs and the dorsal SCNs. In practical terms, this means that for several days after someone flies across several time zones, the peripheral clocks that receive signals from his or her SCNs will be exposed to more complex patterns of electrical activity than they are used to. These structures may then in turn cause other physiological functions to go out of phase, thus contributing to the symptoms of jet lag.

Thus, whereas scientists once thought the body’s biological rhythms were driven by a single, central biological clock located in the suprachiasmatic nuclei, they now embrace a model in which the SCNs act like the conductor of an orchestra, and all of the body’s peripheral clocks act like the musicians. And studies of jet lag have further revealed that the SCNs themselves may be seen as systems composed of several distinct but interconnected functional units.

The biological clock is thus much more like a network of multiple oscillators, some of which adjust to changes in light levels quickly, others of which do so more slowly, and still others of which are regulated less by light than by other factors such as food.