Like flowers opening and closing with the sun, our bodies have a rhythm that follows the daily turning of the earth. Processes speed up and slow down; hormones rise and fall; we feel wakeful or tired. But our internal clocks aren't always in sync with the day. By finding out what time our bodies think it is, doctors can time their treatments to work better. And now, there might be a simple way to check the time on our inner clocks.
The idea of coordinating medical treatments with the ticking of patients' internal watch hands is called "chronotherapy." Hiroki Ueda, a researcher at the RIKEN Center for Developmental Biology in Kobe, Japan, says that some doctors are already using chronotherapy in treatments such as chemo for colon cancer. Checking a patient's internal schedule before delivering medicine can make a treatment both more effective and less toxic.
But doctors don't have an easy way to check the body clock. "It was labor-intensive and time-consuming for clinical researchers to measure body time using classical methods," Ueda says. One method involves keeping subjects under controlled conditions for more than a day while constantly sampling their blood to check levels of cortisol or melatonin (two hormones with a strong daily cycle). Methods like this aren't exactly practical, which has been an obstacle to chronotherapy. So Ueda and his colleagues have been working on a better technique.
The researchers took inspiration from a hypothetical garden described by 18th-century Swedish botanist Carolus Linnaeus. The Horologium Florae (Latin for "clock of flowers"), as Linnaeus imagined it, would hold a few dozen varieties of flowers that he'd chosen for the precise timing with which they opened and closed each day. By simply looking around the garden, a knowledgeable gardener could tell the time of day.
Instead of flowers, the Japanese researchers used molecules circulating in the bloodstream that wax and wane over the course of the day. They'd previously built this kind of molecular flower clock for mice; now they tried it with humans.
They recruited six healthy volunteers who were willing to pretty seriously jet-lag themselves inside a lab. First, subjects stayed awake and sitting in a chair for a day and a half while researchers fed them and took their blood every two hours.
In these blood samples, the researchers found 58 molecules that cycled over the course of the day. (Since subjects weren't sleeping, moving around, or eating normal meals, they knew these molecular rhythms were intrinsic to their bodies and not a reaction to their environment.) They created a timetable that would predict the time of day based on the levels of all these molecules in the blood.
Next came the jet-lagging. For a week, subjects were put on a 28-hour cycle of sleeping and waking instead of the usual 24. This was to knock their internal rhythms out of alignment with the true time of day. Then subjects sat through the same day and a half of blood sampling as before.
The frequent blood samples let researchers find their subjects' internal body time the old-fashioned way, by closely plotting the rise and fall of one hormone (cortisol). This gave them a cheat sheet against which they could check the answers from their molecular flower clock.
Using the timetable they'd created in the first part of the experiment, Ueda and his team found that any pair of blood samples taken 12 hours apart could accurately tell their subjects' body time to within 2 or 3 hours. If a person's body thought it was 4:00 PM when it was really noon outside, the molecular timetable could detect the difference.
Ueda's subjects for this study were all young adult males. But he says the cycling molecules in the timetable—including steroid hormones, amino acids, and lipids—should apply to females and other age groups as well. One of the researchers' next steps will be to start testing their molecular clock in these other populations. They'd also like to hone the technique so it works with a single blood sample, rather than two.
Even when we're not trapped inside a sleep lab with manipulative researchers, our circadian rhythms can get misaligned. Jet lag or night shifts at work can push people's bodies out of sync with the sun. Genetic mutations can create whole families of extra-early risers who wake up before dawn.
If a simple blood test allows doctors to peek at patients' internal clocks, they could more easily diagnose these disorders. They could also better tailor chemotherapy and other treatments to patients' bodies. And recent research in mice suggested that high-fat foods consumed during the usual sleeping hours contribute more to obesity than the same foods eaten during waking hours. Understanding our individual clocks might keep us not just sleeping and waking well, but blooming with health.
Takeya Kasukawa, Masahiro Sugimoto, Akiko Hida, Yoichi Minami, Masayo Mori, Sato Honma, Ken-ichi Honma, Kazuo Mishima, Tomoyoshi Soga, & Hiroki R. Ueda (2012). Human blood metabolite timetable indicates internal body time. PNAS : 10.1073/pnas.1207768109
Image: Josh Greenberg/Flickr
