Bad Night's Sleep? The Moon Could Be to Blame

Bad Night's Sleep? The Moon Could Be to Blame

  7:26:00 PM    Science Lover

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Many people complain about poor sleep around the full moon, and now a report appearing in Current Biology, a Cell Press publication, on July 25 offers some of the first convincing scientific evidence to suggest that this really is true. The findings add to evidence that humans -- despite the comforts of our civilized world -- still respond to the geophysical rhythms of the moon, driven by a circalunar clock.

Many people complain about poor sleep around the full moon, and now a report appearing in Current Biology, a Cell Press publication, on July 25 offers some of the first convincing scientific evidence to suggest that this really is true. The findings add to evidence that humans -- despite the comforts of our civilized world -- still respond to the geophysical rhythms of the moon, driven by a circalunar clock. (Credit: Current Biology, Cajochen et al.)

"The lunar cycle seems to influence human sleep, even when one does not 'see' the moon and is not aware of the actual moon phase," says Christian Cajochen of the Psychiatric Hospital of the University of Basel.

In the new study, the researchers studied 33 volunteers in two age groups in the lab while they slept. Their brain patterns were monitored while sleeping, along with eye movements and hormone secretions.

The data show that around the full moon, brain activity related to deep sleep dropped by 30 percent. People also took five minutes longer to fall asleep, and they slept for twenty minutes less time overall. Study participants felt as though their sleep was poorer when the moon was full, and they showed diminished levels of melatonin, a hormone known to regulate sleep and wake cycles.

"This is the first reliable evidence that a lunar rhythm can modulate sleep structure in humans when measured under the highly controlled conditions of a circadian laboratory study protocol without time cues," the researchers say.

Cajochen adds that this circalunar rhythm might be a relic from a past in which the moon could have synchronized human behaviors for reproductive or other purposes, much as it does in other animals. Today, the moon's hold over us is usually masked by the influence of electrical lighting and other aspects of modern life.

The researchers say it would be interesting to look more deeply into the anatomical location of the circalunar clock and its molecular and neuronal underpinnings. And, they say, it could turn out that the moon has power over other aspects of our behavior as well, such as our cognitive performance and our moods.

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The Link Between Circadian Rhythms and Aging: Gene Associated With Longevity Also Regulates the Body's Circadian Clock

The Link Between Circadian Rhythms and Aging: Gene Associated With Longevity Also Regulates the Body's Circadian Clock

  12:39:00 AM    Science Lover

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Human sleeping and waking patterns are largely governed by an internal circadian clock that corresponds closely with the 24-hour cycle of light and darkness. This circadian clock also controls other body functions, such as metabolism and temperature regulation.

A new study finds that a gene associated with longevity also regulates the body’s circadian clock. (Credit: iStockphoto)

Studies in animals have found that when that rhythm gets thrown off, health problems including obesity and metabolic disorders such as diabetes can arise. Studies of people who work night shifts have also revealed an increased susceptibility to diabetes.

A new study from MIT shows that a gene called SIRT1, previously shown to protect against diseases of aging, plays a key role in controlling these circadian rhythms. The researchers found that circadian function decays with aging in normal mice, and that boosting their SIRT1 levels in the brain could prevent this decay. Conversely, loss of SIRT1 function impairs circadian control in young mice, mimicking what happens in normal aging.

Since the SIRT1 protein itself was found to decline with aging in the normal mice, the findings suggest that drugs that enhance SIRT1 activity in humans could have widespread health benefits, says Leonard Guarente, the Novartis Professor of Biology at MIT and senior author of a paper describing the findings in the June 20 issue of Cell.

"If we could keep SIRT1 as active as possible as we get older, then we'd be able to retard aging in the central clock in the brain, and health benefits would radiate from that," Guarente says.

Staying on schedule

In humans and animals, circadian patterns follow a roughly 24-hour cycle, directed by the circadian control center of the brain, called the suprachiasmatic nucleus (SCN), located in the hypothalamus.

"Just about everything that takes place physiologically is really staged along the circadian cycle," Guarente says. "What's now emerging is the idea that maintaining the circadian cycle is quite important in health maintenance, and if it gets broken, there's a penalty to be paid in health and perhaps in aging."

Last year, Guarente found that a robust circadian period correlated with longer lifespan in mice. That got him wondering what role SIRT1, which has been shown to prolong lifespan in many animals, might play in that phenomenon. SIRT1, which Guarente first linked with aging more than 15 years ago, is a master regulator of cell responses to stress, coordinating a variety of hormone networks, proteins and genes to help keep cells alive and healthy.

To investigate SIRT1's role in circadian control, Guarente and his colleagues created genetically engineered mice that produce different amounts of SIRT1 in the brain. One group of mice had normal SIRT1 levels, another had no SIRT1, and two groups had extra SIRT1 -- either twice or 10 times as much as normal.

Mice lacking SIRT1 had slightly longer circadian cycles (23.9 hours) than normal mice (23.6 hours), and mice with a 10-fold increase in SIRT1 had shorter cycles (23.1 hours).

In mice with normal SIRT1 levels, the researchers confirmed previous findings that when the 12-hour light/dark cycle is interrupted, younger mice readjust their circadian cycles much more easily than older ones. However, they showed for the first time that mice with extra SIRT1 do not suffer the same decline in circadian control as they age.

The researchers also found that SIRT1 exerts this control by regulating the genes BMAL and CLOCK, the two major keepers of the central circadian clock.

Enhancing circadian function

A growing body of evidence suggests that being able to respond to large or small disruptions of the light/dark cycle is important to maintaining healthy metabolic function, Guarente says.

"Essentially we experience a mini jet lag every day because the light cycle is constantly changing. The critical thing for us is to be able to adapt smoothly to these jolts," Guarente says. "Many studies in mice say that while young mice do this perfectly well, it's the old mice that have the problem. So that could well be true in humans."

If so, it could be possible to treat or prevent diseases of aging by enhancing circadian function -- either by delivering SIRT1 activators in the brain or developing drugs that enhance another part of the circadian control system, Guarente says.

"I think we should look at every aspect of the machinery of the circadian clock in the brain, and any intervention that can maintain that machinery with aging ought to be good," he says. "One entry point would be SIRT1, because we've shown in mice that genetic maintenance of SIRT1 helps maintain circadian function."

Some SIRT1 activators are now being tested against diabetes, inflammation and other diseases, but they are not designed to cross the blood-brain barrier and would likely not be able to reach the SCN. However, Guarente believes it could be possible to design SIRT1 activators that can get into the brain.

Roman Kondratov, an associate professor of biology at Cleveland State University, says the study raises several exciting questions regarding the potential to delay or reverse age-related changes in the brain through rejuvenation of the circadian clock with SIRT1 enhancement.

"The importance of this study is that it has both basic and potentially translational applications, taking into account the fact that pharmacological modulators of SIRT1 are currently under active study," Kondratov says.

Researchers in Guarente's lab are now investigating the relationship between health, circadian function and diet. They suspect that high-fat diets might throw the circadian clock out of whack, which could be counteracted by increased SIRT1 activation.

The research was funded by the National Institutes of Health and the Glenn Foundation for Medical Research.

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Scientists Redraw the Blueprint of the Body's Biological Clock

Scientists Redraw the Blueprint of the Body's Biological Clock

  7:52:00 PM    Science Lover

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The discovery of a major gear in the biological clock that tells the body when to sleep and metabolize food may lead to new drugs to treat sleep problems and metabolic disorders, including diabetes.

The discovery of a major gear in the
biological clock that tells the body when
to sleep and metabolize food may lead
to new drugs to treat sleep problems and
metabolic disorders, including diabetes.
(Credit: © nicobatista / Fotolia)

Scientists at the Salk Institute for Biological Studies, led by Ronald M. Evans, a professor in Salk's Gene Expression Laboratory, showed that two cellular switches found on the nucleus of mouse cells, known as REV-ERBα and REV-ERBβ, are essential for maintaining normal sleeping and eating cycles and for metabolism of nutrients from food.

The findings, reported March 29 in Nature, describe a powerful link between circadian rhythms and metabolism and suggest a new avenue for treating disorders of both systems, including jet lag, sleep disorders, obesity and diabetes.

"This fundamentally changes our knowledge about the workings of the circadian clock and how it orchestrates our sleep-wake cycles, when we eat and even the times our bodies metabolize nutrients," says Evans. "Nuclear receptors can be targeted with drugs, which suggests we might be able to target REV-ERBα and β to treat disorders of sleep and metabolism."

Nurses, emergency personnel and others who work shifts that alter the normal 24-hour cycle of waking and sleeping are at much higher risk for a number of diseases, including metabolic disorders such as diabetes. To address this, scientists are trying to understand precisely how the biological clock works and uncover possible targets for drugs that could adjust the circadian rhythm in people with sleep disorders and circadian-associated metabolic disorders.

In mammals, the circadian timing system is orchestrated by a central clock in the brain and subsidiary clocks in most other organs. The master clock in the brain is set by light and determines the overall diurnal or nocturnal preference of an animal, including sleep-wake cycles and feeding behavior.

Scientists knew that two genes, BMAL1 and CLOCK, worked together at the core of the clock's molecular machinery to activate the network of circadian genes. In this way, BMAL1 acts like the accelerator on a car, activating genes to rev up our physiology each morning so that we are alert, hungry and physically active.

Prior to this work REV-ERBα and β were thought to play only a minor role in these cycles, possibly working together to slow CLOCK-BMAL1 activity to make minor adjustments to keep the clock running on time.

However, genetic studies of two genes with similar functions can be very difficult and thus the real importance of REV-ERBα and β remained mysterious.

The Salk scientists got around this hurdle by developing mice in which both genes could be turned off in the liver at any point by giving them an estrogen derivative called tamoxifen. Now mice could develop normally to adulthood, at which point the scientists could turn off REV-ERBα and REV-ERBβ in their livers -- -- an organ crucial to maintaining the correct balance of sugar and fat in blood -- -- to see what effects it had on circadian rhythms and metabolism.

"When we turned off both receptors, the animal's biological clocks went haywire," says Han Cho, first author on the paper and a postdoctoral researcher in Evan's laboratory. "The mice started running on their exercise wheels when they should have been resting. This suggested REV-ERBα and REV-ERBβ aren't an auxiliary system that makes minor adjustments, but an integral part of the clock's core mechanism. Without them, the clock can't function properly."

Digging more deeply into the clockworks, the Salk scientists mapped out the genes that the REV-ERBs control to keep the body operating on the right schedule, finding that they overlap with hundreds of the same genes controlled by CLOCK and BMAL1. This and other findings suggested that the REV-ERBs, act as a break on the genes BMAL1 activates.

"We thought that the core of the clock was an accelerator, and that all REV-ERBα and REV-ERBβ did was to pull the foot off that pedal," says Evans. "What we've shown is that these receptors act directly as a break to slow clock activity. Now we've got a accelerator and a break, each equally important in creating the daily rhythm of the clock."

The scientists also found that the REV-ERBs control the activity of hundreds of genes involved metabolism, including those responsible for controlling levels of fats and bile. The mice in which REV-ERBα and REV-ERBβ were turned off had high levels of fat and sugar in their blood -- -- common problems in people with metabolic disorders.

"This explains how our cellular metabolism is tied to daylight cycles determined by the movements of the sun and the earth," says Satchidananda Panda, an associate professor in Salk's Regulatory Biology Laboratory and co-author on the paper. "Now we want to find ways of leveraging this mechanism to fix a person's metabolic rhythms when they are disrupted by travel, shift work or sleep disorders."

Other researchers on the study were Xuan Zhao, Megumi Hatori, Ruth T. Yu, Grant D. Barish, Michael T. Lam, Ling-Wa Chong, Luciano DiTacchio, Annette R. Atkins and Michael Downes, from the Salk Institute; Christopher K. Glass, of University of California San Diego; Christopher Liddle, of University of Sydney, Australia; and Johan Auwerx, of Ecole Polytechnique Fédérale, Switzerland.

The research was supported by the National Institutes of Health, the National Health and Medical Research Council of Australia, the Leona M. and Harry B. Helmsley Charitable Trust, the Glenn Foundation for Medical Research and the Howard Hughes Medical Institute.

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