Our Body Clock Regulates Our Metabolism

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Scientists have discovered that your circadian rhythms regulate the energy levels in your cells. In addition, the proteins involved with circadian rhythms and metabolism are intrinsically linked and dependent upon each other. This finding has far-reaching implications, which could include new ways to treat cancer, diabetes, obesity and a host of related diseases.

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24-hour circadian rhythms govern fundamental physiological functions in almost all organisms. These circadian clocks are the essential time-tracking systems in your body. Disruption of these rhythms can profoundly influence human health.

In a new study, researchers showed that an enzyme protein which is an essential molecular gear of the circadian machinery interacts with a protein that senses cell energy levels and modulates aging and metabolism.

This suggests that proper sleep and diet may help maintain or rebuild the balance between your circadian clock and your metabolism, and could also help explain why lack of rest or disruption of normal sleep patterns can increase hunger, leading to obesity-related illnesses and accelerated aging.

Sources: Science Daily March 19, 2009

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Jet Lag to be History

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Scripps Research scientists say that they have determined the molecular structure of a plant photolyase protein, which is very similar  to the two proteins that control the circadian clock in humans and other mammals, moving a step closer to making jet lag history.


The researchers claim that their study has even enabled them to test how structural changes affect the function of such proteins.

“The plant photolyase structure provides a much better model to use to study how the cryptochrome proteins in the human clock function than we have ever had before,” says Dr. Kenichi Hitomi, a postdoctoral research fellow at Scripps Research.

“It’s like knowing for the first time where the engine is in a car. When you know what the most important parts of the protein are, then you can begin to figure out how it functions,” the researchers added.

Dr. Elizabeth Getzoff, professor in the Department of Molecular Biology and member of The Skaggs Institute for Chemical Biology at Scripps Research, says that understanding how these proteins work may be helpful in fixing the clock when needed.

“In addition to decoding how the clock works, a long-term goal is to develop a drug to help people who can’t reset their clock when they need to, like people who work night shifts or travel long distances. Having the three-dimensional protein is a great step forward in both of those pursuits,” she says.

Working in collaboration with researchers from Scripps Research and from other institutions, including two universities in Japan, Hitomi studied Arabidopsis thaliana, a plant native to Europe and Asia that has one of the smallest genomes of all plants.

The researchers point out that just like all other plants, this plant also contains proteins known as photolyases, which use blue light to repair DNA damage induced by ultraviolet light.

They say that humans and mammals possess a homologous protein known as cryptochrome that modulates the circadian clock.

Getzoff says: “This is an amazing, and very puzzling, family of proteins, because they do one thing in plants and quite a different thing in mammals, yet these cousins all have the same structure and need the same cofactor, or chemical compound, to become activated.”

Hitomi adds: “All of these proteins were probably originally responses to sunlight. Sunlight causes DNA damage, so plants need to repair this damage, and they also need to respond to sunlight and seasons for growth and flowering. The human clock is set by exposure to sunlight, but also by when we eat, sleep and exercise.”

Hitomi and his colleagues set about producing proteins from the Arabidopsis thaliana genes that produce two related photolyase enzymes. These genes had been cloned earlier in the laboratory of co-author Dr Takeshi Todo of Kyoto University.

The researchers moved the gene from the plant into E coli bacteria to produce a lot of the protein, and later crystallized it to determine the atomic structure by using X-ray diffraction.

The researchers then produced a variety of mutant proteins in order to test the functional structure of the enzymes.

“We can now look at things that are the same and different between human and mouse cryptochromes and plant photolyases. Our results provide a detailed, comparative framework for biological investigations of both of these proteins and their functions,” says Hitomi.

He believes that his team’s findings may form the basis of drugs that can ease jet lag and regulate drug metabolism, as well as help better understand some fascinating circadian clock disorders that have been found in mice and man.

The study has been published in The Proceedings of the National Academy of Sciences.

Sources:The Times Of India

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Going gray? Hair ‘Bleaches Itself as People Age’

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Why people turn gray is no longer a gray area, for scientists have finally solved the mystery by discovering that hair bleaches itself as  people age.


A team in Europe has found that going gray is caused by a massive build up of hydrogen peroxide due to wear and tear of our hair follicles. The peroxide winds up blocking the normal synthesis of melanin, our hair’s natural pigment.

According to Gerald Weissmann, the Editor-in-Chief of the ‘FASEB Journal‘, which published the study, “All of our hair cells make a tiny bit of hydrogen peroxide, but as we get older, this little bit becomes a lot.

“We bleach our hair pigment from within, and our hair turns gray and then white. This research, however, is an important first step to get at the root of the problem, so to speak.”

In fact, the scientists made this discovery by examining cell cultures of human hair follicles. They found the build up of hydrogen peroxide was caused by a reduction of an enzyme that breaks up hydrogen peroxide into water and oxygen (catalase).

They also discovered that hair follicles could not repair the damage caused by the hydrogen peroxide because of low levels of enzymes that normally serve this function (MSR A and B).

Sources: The Times Of India

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New Drug May Put Jet Lag to Rest

The experimental medication, called tasimelteon, works like melatonin and restores normal sleep patterns, researchers say.
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An experimental drug that mimics the effects of the hormone melatonin can reset the body’s circadian rhythms, bringing relief to jet-lagged travelers and night-shift workers, researchers reported Monday.

In a study of 450 people who were subjected to simulated jet lag in a sleep laboratory, a team from Brigham and Women’s Hospital in Boston found that the drug restored near normal sleep the first night it was used.

There were no aftereffects from the drug, minimal side effects, and people who took it performed normally the next day, said Dr. Elizabeth B. Klerman, one of the co-authors of the study published online in the journal Lancet.

And unlike conventional sleeping aids such as Ambien or Lunesta, she added, the new drug, called tasimelteon, has no potential for addiction or abuse.

The main limitations of the study were the relatively small size and the researchers’ inability to measure performance and mood after the drug was used, experts said.

The study was designed and funded by Vanda Pharmaceuticals Inc. of Rockville, Md., which developed tasimelteon, and all of the researchers reported receiving funds from Vanda or other pharmaceutical companies.

“This is a very promising first step,” said Dr. Jay Udani, who runs the integrative medicine program at Northridge Hospital Medical Center and who was not involved in the study. But the research “does not prove that it works for jet lag or shift workers,” he added. “That needs controlled studies in the field.”

The body’s sleep-wake cycle is controlled by melatonin, which is produced by the pineal gland in response to patterns of light and darkness. Higher concentrations of melatonin in the blood are associated with greater sleepiness.

Some research has shown that administering melatonin can adjust sleep cycles in travelers and workers, but the results have been mixed.

Because melatonin can’t be patented, drug companies have been interested in developing melatonin mimics, such as tasimelteon, which can be patented.

In the first part of the study, 39 patients’ normal sleep habits were monitored for three nights in the laboratory before they were sent to bed five hours early.

They were then given one of four different doses of tasimelteon or a placebo 30 minutes before bedtime.

Researchers monitored their sleep efficiency — the percentage of time in bed they actually slept — and the amount of time required for them to fall asleep.

Although all the subjects benefited from the drug, those receiving the highest dose had a sleep efficiency of 89% the first night, virtually the same as the 90% efficiency before the trail started. Those receiving a placebo had an efficiency of 71%.

Patients taking the highest doses slept for an average of about 428 minutes, compared with 430 minutes before the trial and 324 minutes for those taking a placebo. It took an average of seven minutes for them to go to sleep, compared with 11 minutes before the trial and 22 minutes for those receiving a placebo.

Blood analysis showed that the melatonin cycle of those receiving the drug was altered to match the new conditions.

“They would be expected to sleep better because their internal clock is on the right time,” Klerman said.

Sources Los Angles Times

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Pine Bark Extract Reduces Jet Lag

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Pycnogenol, a bark extract from the French maritime pine tree, reduces jet lag in passengers by nearly 50%, a study suggests.

A recent two-part study, comprising a brain CT scan and a scoring system, showed Pycnogenol lowered symptoms of jet lag like fatigue, headaches, insomnia and brain oedema (swelling) in both healthy individuals and hypertensive patients.

Jet lag, also called desynchronosis, is a temporary disorder that causes a variety of temporary mental and physical impairments as a result of air travel across time zones.

“This study could not have come at a better time for the upcoming holiday travel season,” said Gianni Belcaro, a co-author of the study of G D’Annunzio University in Pescara, Italy.

Belcaro attributed Pycnogenol’s combined activities for better circulation and antioxidant potency to such remarkable results, said an Annunzio University release.

“Previous Pycnogenol flight studies have shown a reduction in jet lag; however this was the first study to solely focus on the condition.”

The study comprised 133 passengers who took flights that were seven to nine hours in length. Fifty mg of oral Pycnogenol was administered three times daily, for seven days, starting two days prior to the flight.

“I’m encouraged by the results of the study as Pycnogenol was effective in preventing jet lag related effects without any side effects,” said Belcaro.

While more research needs to be conducted on this topic, Pycnogenol is emerging as natural, yet safe option for long distance travellers.

These findings were published in Minerva Cardioangiologica.

Sources: The Times Of India

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