Monday, March 2, 2015

Our Body many Cellular Clocks

Anyone who has ever flown east or west at 500 knots for more than a few hours has experienced firsthand what happens when the body’s internal clock does not match the timezone in which it finds itself. Up to a week may be needed to get over the resulting jet lag—depending on whether the master clock, which is located deep inside the brain, needs to be advanced or slowed to synchronize when the body and brain want to sleep with when it is dark outside. Over the past several years, however, scientists have learned, much to our surprise, that, in addition to the master clock in the brain, the body depends on multiple regional clocks located in the liver, pancreas and other organs, as well as in the body’s fatty tissue. If any one of these peripheral clocks runs out of sync with the master clock, the disarray can set the stage for obesity, diabetes, depression or other complex disorders.
Studies in the laboratory have focused on mice, but circadian clock genes have been identified in an amazing range of living organisms, from bacteria to fruit flies to humans. Many of these genes appear to be similar in a wide range of species—a sign that they have been central to survival throughout evolution.
The greatest progress so far has come in deciphering the role of clocks in disorders of metabolism, which is the set of processes by which the body converts food into energy and stores fuel for later use. (Among the more surprising finds: when you eat appears to be as important as what you eat in the regulation of weight gain.) Circadian rhythms do not explain every aspect of these complex conditions, of course, but we ignore our body’s various clocks at our peril. Rapidly growing knowledge of these rhythms could radically change the ways diseases are diagnosed and treated in the future and improve people’s ability to maintain their health. 

From the most complex organisms to the simplest ones, all of life on earth is governed by circadian rhythms that match the 24-hour day. Circadian rhythms are found even among the earliest life forms to emerge: cyanobacteria, single-celled blue-green algae now widespread throughout diverse habitats. These organisms derive energy from the sun through photosynthesis, using light to power the production of organic molecules and oxygen from carbon dioxide and water.
An internal clock enables each cyanobacterium to prime its photosynthetic machinery before sunrise, which enables it to start harvesting energy as soon as light starts to shine and gives it a leg up on cellular organisms that merely respond to light.
Similarly, the clock enables the cyanobacteria to turn off photosynthesis when the sun sets. In this manner, they can avoid wasting energy and other resources on systems that do not work at night. Instead resources can be diverted to reactions better suited for darkness, such as DNA replication and repair, which may be compromised by ionizing radiation from the sun’s rays. Bacterial strains carrying mutations in different clock genes may switch from the usual 24-hour cycles for turning genes on and off to periods, or “clock lengths,” of 20, 22 or sometimes even 30 hours. In studies that grouped cells according to their altered cycles, Carl Johnson and his colleagues at Vanderbilt University showed in 1998 that cyanobacteria with a clock length that matched the environmental light cycle outcompeted those with a mismatch. For example, in a 24-hour light-and-dark cycle, normal cyanobacteria grow more quickly and divide more successfully than mutants with a 22-hour clock length. But when Johnson’s team artificially set the light-and-dark cycle to 22 hours, those same mutants survived better than the normal bacteria. These experiments demonstrated clearly, for the first time, that the ability to properly coordinate internal metabolic rhythms to environmental cycles enhances fitness.

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