Demonstrates That Internal Body Clocks Become Desynchronized Under
Conditions Simulating Jet-Lag
27, 2000 -- A new study demonstrates that internal
time clocks in mammals, involving multiple organs, reset at different
rates following changes in light cycles. This disruption of the
normal relationships among circadian rhythms throughout the body
may explain why air travelers experience malaise after crossing
several time zones.
findings will be reported in the April 28 issue of the journal Science.
The research was conducted at the University of Virginia, the home
site of the National Science Foundation Center
for Biological Timing.
are finding that an organism is a conglomeration of oscillators,"
says Michael Menaker, Commonwealth Professor of Biology
at the University of Virginia. "When the primary oscillator in the
brain shifts to follow an abrupt shift in the light cycle, the clocks
controlling several other organs become desynchronized. It likely
takes some time before these clocks adjust back to synchrony."
says the findings have health implications for air travelers who
must frequently cross multiple time zones, and for shift workers
who regularly rotate shift cycles.
researchers used brain, skeletal muscle, liver and lung tissue from
transgenic rats to collect their data. The rat tissue included a
known clock gene indicator from a mouse that is spliced with a glowing
"tag" (a fire fly enzyme). The tag is activated when the clock gene
responds, or is transcribed, during changing light cycles. Menaker
and his team were able to "reset" the brain and organ clocks --
the circadian rhythms -- forward by six hours or back by six hours,
mimicking the effects of trans-Atlantic travel.
question was, what is the physiology that explains the malaise people
experience after flying across several time zones?" Menaker says.
"We wanted to know how many circadian clocks there are, how the
individual tissues respond when the organism is subjected to light
cycle changes, and how the various biological clocks operate together
as a system.
demonstrated clearly that both brain and peripheral tissues are
rhythmic when they are removed from the animal and held in culture
conditions. This is new information, but was suspected. What is
surprising is that while the central oscillator in the brain keeps
cycling for up to one month, the peripheral tissues rapidly lose
their rhythmicity in culture. We now believe the central oscillator
in the brain is the key timer that synchronizes the peripheral clock
cycles. This helps us understand biologically what happens in an
organism when its light cycle is suddenly shifted.
nature, light shifts occur slowly as the seasons change," Menaker
says. "Organisms, therefore, have several months to adjust to the
changes. But transmeridian flight is an unnatural event for the
body. It causes very abrupt light cycle shifts. The body is not
naturally prepared for this sudden change. Once the relationships
between the various oscillators are disrupted, the normal function
of the organs may be compromised."
says that while the symptoms of occasional jetlag may be annoying,
the new findings may imply that the physiological effects of rotating
shift work could be more serious.
percent of the U.S. workforce are shift workers," Menaker says.
"Our findings suggest that frequent irregular light cycle shifts
may have biological repercussions. Shift workers, for example, often
experience reduced alertness, fatigue, ulcers and poor digestion.
We do not know yet the full extent of the health issues that may
result from regular disruption of circadian rhythm synchrony."
to Menaker, most catastrophic accidents -- such as the Exxon Valdez
grounding, and the Three Mile Island and Chernoble incidents --
are the result of human error, commonly occurring among shift workers
late at night.
people are trying to adjust to abnormal sleep and wake cycles, they
tend to lose focus, become fatigued more easily, and generally don't
feel as healthy as they normally would," he says. "We are showing
that a physiological change is occurring. The ramifications for
health and performance are real and potentially serious."
researchers who conducted the study include Shin Yamazaki, the principal
investigator, Michikazu Abe, Gene Block, and Menaker. Six researchers
from the University of Tokyo and the New Technology Institute in
Japan also participated.
Fariss Samarrai, (804) 924-3778