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Saturday, August 11, 2007

Mars' Sleep Cycle Study May Help Earthlings

By synchronizing people to the Martian day, U.S. researchers are demonstrating the flexibility of the human biological clock.

The study might help further research into sleep woes, said researchers in the division of sleep medicine at Brigham and Women's Hospital in Boston.

"Understanding how our biological clock can be adjusted is a critical step in developing therapy for circadian rhythm sleep disorders, which disturb sleep at night and compromise daytime cognitive functioning," lead author Frank A. J. L. Scheer, associate director of the Medical Chronobiology Program at BWH, said in a prepared statement.

His team was able to synchronized volunteers' biological clocks to the 24.65-hour day of Mars and to the 23.5-hour day often experienced by astronauts in low orbit around the Earth.

The researchers also found that synchronizing with the Martian clock resulted in long-term changes to the circadian period of the volunteers' biological clock. This showed, for the first time, flexibility in the this system in humans, the study authors said.

For this study, seven young men spent 73 days in a controlled environment without any time cues, other than controlled light/dark conditions.

According to the researchers, the findings could prove important in treating circadian rhythm sleep disorders (such as those caused by jet lag and shift work) and in preparing humans for space exploration.

Anyone who has traveled has experienced jet lag-that groggy realization that while your day is beginning in Washington, D.C., the night you just left in San Francisco is hardly over. Jet lag is an inconvenient reminder that the body is set to a 24-hour clock, known by scientists as circadian rhythms, from the Latin circa dies, "about one day." An internal biological clock is fundamental to all living organisms, influencing hormones that play a role in sleep and wakefulness, metabolic rate, and body temperature.

Disruption of circadian rhythms not only affects sleep patterns but also has been found to precipitate mania in people with bipolar disorder (manic-depressive illness).1 Other types of illnesses also are affected by circadian rhythms; for example, heart attacks occur more frequently in the morning while asthma attacks occur more often at night.2,3

Although biological clocks have been the focus of intensive research over the past four decades, only recently have the tools needed to examine the molecular basis of circadian rhythms become available. Early studies pointed to an area of the brain, the hypothalamus, as the location of the circadian pacemaker in mammals.4 More recent findings show proteins called cryptochromes, located throughout the body, are also involved in detecting changes in light and setting the body's clock.5

Genes that code for the clock protein, PER, glow in the head and other body parts of a fruit fly. Researchers made the clocks glow by engineering transgenic strains of flies in which the same genes that illuminate a jellyfish and a firefly's tail are attached to PER. The gene for luciferase, the enzyme that glows intermittently in fireflies, was expressed along with PER to reveal when the clock protein was being produced. Flies were also molecularly altered to brightly mark the clock sites with Green Fluorescent Protein, which glows constantly in jellyfish. Source: Jeffrey Plautz, Ph.D., Stanford University; Steve Kay, Ph.D., The Scripps Research Institute.6

The first circadian gene was discovered in 1971 in the fruit fly;7 a second circadian gene was detected 13 years later.8,9 Following these discoveries, however, the search for clock genes in other organisms faltered. Not until 1997 was the first circadian gene found in a mammalian model, the mouse.10 This discovery immediately accelerated the search for other clock genes, and findings in higher order animals are yielding a consistent picture of the role and function of circadian rhythms in organisms from bacteria to plants to mammals.11

Today, we know the most about the workings of the biological clock in the fruit fly and a peek inside its mechanisms illustrates the complex elegance of the rhythms of life.12 The fly's clock consists of a core system of four regulatory proteins that interact to give the clock periodicity. The cycle begins when two of these proteins, CLOCK and CYCLE, bind together and increase the production of two other proteins, PER and TIM, the levels of which slowly accumulate over time. When enough PER and TIM are made, they inactivate the CLOCK-CYCLE complex, slowing their own production and signaling the end of the cycle.

Fruit fly clock cycle-Interaction of four regulatory proteins, entrained by light, creates the daily rhythm of the fruit fly's clock. The binding of CYCLE and CLOCK turns on genes that make PER and TIM, which accumulate over several hours until they reach levels that turn off CYCLE and CLOCK. This, in turn, slows down the production of PER and TIM, which begins the cycle all over again. Source: Steve Kay, Ph.D., and Karen Wager-Smith, Ph.D., The Scripps Research Institute.12

Although parts of the puzzle still are missing, discoveries stimulated by this progress are yielding intriguing findings. Proteins such as DBT ("Double-Time") that act to fine tune the mechanism have been identified.13 Recently, variations have been found in the human Clock gene, which may predispose people to be "early birds" or "night owls."14 Other research has linked academic and behavior problems in adolescents to irregular sleep patterns.15

Researchers have found that imposing too early school start times on children requires unrealistic bedtimes to allow adequate time for sleeping.16 Early school start times for adolescents are frequently associated with significant sleep deprivation, which can lead to academic, behavioral, and psychological problems, as well as increased risk for accidents and injuries, especially for teenage drivers. Completing our understanding of biological clockworks will lead to better treatments for diseases affected by circadian rhythm, as well as to methods of coping with disrupted sleep patterns.

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