Molecular ‘timetable’ could aid personalized medicine

Sep 4 2012

By Eleanor McDermid, Senior medwireNews Reporter

Researchers have developed a method, based on analysis of circadian rhythm metabolites in blood samples, which can pinpoint the time of the body's internal "clock" to within 3 hours.

"A minimally invasive internal body-time detection method is essential for facilitating the development of chronotherapy to realize tailored medication regimens as well as for efficient time-restricted feeding to avoid or cure obesity," say Hiroki Ueda (RIKEN Center for Developmental Biology, Kobe, Japan) and team.

The researchers used liquid chromatography mass spectrometry, which they note is not readily available. However, they say that bench-top systems are becoming available and suggest that a simpler antibody-based test could be developed along similar lines. "In any case, our method is more pragmatic than serial time-course sampling because only a few samples are required for body-time estimation and because blood is an easy tissue to sample and analyze."

As reported in the Proceedings of the National Academy of Sciences, Ueda et al analyzed blood samples taken every 1.5 hours from three volunteers to construct a "timetable" of peaks in circadian rhythm metabolites.

Using this timetable, the researchers were able to estimate the body clock time of another three volunteers, from just two blood samples drawn 12 hours apart. The estimated time was correct to within 3 hours according to a conventional method - cortisol rhythm - after allowing for individual variations in the size of difference between time according to the metabolite timetable and cortisol rhythm.

Notably, the metabolite timetable remained accurate for measuring body clock time in all six volunteers after they had undergone a forced desynchronization protocol in a sleep laboratory.

"These results suggest that the molecular timetable method has potential to be a body-time estimation tool for humans in both normal and abnormal environments like enforced sleep-wake cycles," says the team.

The metabolite timetable cannot distinguish between genetic and environmental causes of circadian rhythm disruption, but the researchers note the existence of another test that detects only genetic causes.

"These two methods are therefore complementary for detecting circadian rhythm disorders," they conclude.

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