January 27, 2011

Body Clock Helps Keep All Living Things On Time

The mechanism that controls the internal 24-hour clock of all forms of life from human cells to algae has been cracked by researchers.

Not only does the finding provide important insight into health-related issues linked to individuals with disrupted internal clocks -- such as pilots and shift workers -- it also indicates that the 24-hour circadian clock found in human cells is the same as that found in algae and dates back to when the earliest life on Earth was formed.

New research suggests that these internal timepieces may be more complicated than scientists thought.

Scientists have said for years this clock is basically the activity of certain genes. But in a new study, researchers looked at human cells that don't even have genes. They found, in these red blood cells, an enzyme flip-flopping between two forms on a regular 24-hour cycle.

Two new studies published in the journal Nature on Wednesday give insight into the circadian clock which controls patterns of daily and seasonal activity, from sleep cycles to butterfly migrations to even flower opening.

The first study, from the University of Cambridge's Institute of Metabolic Science, has for the first time identified 24-hour rhythms in red blood cells. This is an important find because circadian rhythms have always been assumed to be linked to DNA and gene activity. But, unlike most of the other cells in the human body, red blood cells do not have DNA.

"We know that clocks exist in all our cells; they're hard-wired into the cell. Imagine what we'd be like without a clock to guide us through our days. The cell would be in the same position if it didn't have a clock to coordinate its daily activities," said Akhilesh Reddy, from the University of Cambridge and lead author of the study.

"The implications of this for health are manifold. We already know that disrupted clocks "“ for example, caused by shift-work and jet-lag "“ are associated with metabolic disorders such as diabetes, mental health problems and even cancer. By furthering our knowledge of how the 24-hour clock in cells works, we hope that the links to these disorders "“ and others "“ will be made clearer. This will, in the longer term, lead to new therapies that we couldn't even have thought about a couple of years ago," he said.

For the study, the scientists, funded by the Wellcome Trust, incubated purified red blood cells from healthy volunteers in the dark and at body temperature, and sampled them at regular intervals for several days.

They then examined the levels of biochemical markers "“ proteins called peroxiredoxins "“ that are produced in high levels in blood and found that they underwent a 24-hour cycle. Peroxiredoxins are found in virtually all known organisms.

The second study, conducted by scientists at the Universities of Edinburgh and Cambridge, and the Observatoire Oceanologique in Banyuls, France, found a similar 24-hour cycle in marine algae, indicating that internal body clocks have always been important, even for ancient forms of life.

The researchers conducting this study found the rhythms by sampling peroxiredoxins in algae at regular intervals over several days. When the algae were kept in darkness, their DNA was no longer active, but the algae kept their circadian clocks ticking even without active genes.

"This groundbreaking research shows that body clocks are ancient mechanisms that have stayed with us through a billion years of evolution. They must be far more important and sophisticated than we previously realized. More work is needed to determine how and why these clocks developed in people "“ and most likely all other living things on earth "“ and what role they play in controlling our bodies," said Andrew Millar of the University of Edinburgh's School of Biological Sciences, who led the study.

Joseph Bass of Northwestern University, who co-wrote a Nature commentary on the work, told The Associated Press in an interview that the new findings don't overturn the standard notion of a gene-based clock. Still, he said, "our understanding of the clock is expanding with this work and other work."


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