Our body clocks don’t get much respect.
Sure, we talk about them all the time: “I’m not a morning person” or “I’m sooooo jetlagged.” Usually, though, it’s just to make conversation, or to play the biology card if we’re feeling especially dysfunctional.
But our internal clock, in fact, seems to be a powerful force in keeping us healthy. And, now that three American circadian rhythm scientists won the Nobel Prize in Physiology or Medicine last year, its impact on how we feel and how we function is being taken more seriously in the medical community.
Those researchers made the point that genes tied to our body clocks play a critical role in everything from our hormone levels and body temperature to our sleep cycles and even our behavior. It’s now thought that between 30 to 50 percent of our genes have activity regulated by circadian rhythms, including those that are part of our immune system.
“There’s a ton of evidence showing that conditions like depression, diabetes, heart disease and Alzheimer’s have a connection to your body clock,” says Rosemary Braun, assistant professor of preventive medicine at Northwestern University’s Feinberg School of Medicine.
“So, what if we could detect a person’s physiological time?”
What time are you?
Braun is part of a research team at Northwestern that has taken a big first step in doing just that. In a study recently published in the Proceedings of the National Academy of Sciences, the scientists reported on the development of a blood test they say can detect what time it is in a person's body.
Braun says the test, called TimeSignature, can come within an hour and a half of assessing a person’s biological time. One likely benefit is that it could help doctors gauge with more precision when medication—whether it’s a blood pressure pill or chemotherapy—would be most effective.
“It may make more sense to take your medicine at one time as opposed to another,” says Ravi Allada, a professor of neurobiology at Northwestern’s Weinberg College of Arts and Sciences and one of the study’s co-authors. “And this test could guide us in determining when you should take that pill.”
By pinpointing the best time to take a drug, lower doses can be used, and that can reduce the risk of side effects.
Allada notes that many aspects of disease are related to our internal clocks, such as when during the day a person may be at greatest risk of suffering a heart attack or an asthma attack. He reiterates Braun’s point about a suspected link between a disrupted body clock and chronic health problems.
“You can think of the clock as the conductor of an orchestra, and everything has to happen at an appropriate time,” Allada says. “But if you disrupt the conductor, you don’t have the music anymore.”
Reading gene patterns
The idea that blood samples can be used to establish a person’s body time is not new. But previously it would have required a person to have blood drawn every hour hours for much of a day, a process that’s both costly and highly impractical.
But with TimeSignature, blood needs to be taken only twice in one day, and the goal is to get that down to one sample. So, how were the researchers able to simplify the process so dramatically?
Specifically, they collected blood samples every two hours from a group of test subjects and augmented that data with measurements from four other studies. Then, they wrote an algorithm directing a computer to analyze 20,000 different genes and look for patterns in the timing of “gene expression”—when DNA is converted into a product, such as protein. Ultimately, the machine was able to narrow the number down to 41 genes that most strongly exhibited gene activity during different times of the day. From that, it was able to correlate a time of day with activity in those 41 gene expression markers.
“We had the idea that we’d be able to use activity in those genes and work backwards and be able to deduce what time of day it is in your body,” Braun says.
So far, TimeSignature has only been used to test healthy subjects. By analyzing blood samples, it was able to deduce the time the blood was drawn.
Braun says future research will focus on determining the biological time of people whose body clocks are out of sync with real time.
Kenneth Wright is director of the Sleep and Chronobiology Laboratory at the University of Colorado, Boulder. He was not involved in the study, but appreciates the test’s potential.
“Being able to accurately and easily determine internal circadian time has important relevance for determining the circadian health of a person and for the optimal timing of treatments,” he says.
“The new technique is an advance,” Wright adds, “but it needs to be tested to see how accurately it can predict actual internal biological timing of people. The findings from the study show the new technique can predict the clock hour that the sample was taken, not the biological time of the person.”
Allada acknowledges that there can be a deviation between body clock time and “wall clock time,” but says that in the healthy subjects they tested, the former was a “close approximation” of the latter.
While Northwestern has applied for a patent for the actual TimeSignature blood test, it has made the algorithm behind it available to other researchers. Braun says it’s promising that the test works in other outside labs, and that it has proven to be “robust”—its estimate of an individual’s internal time doesn’t appear to be thrown off by random events, such as an overseas flight through multiple time zones.
That increases the chances that a body clock blood test could one day become a standard part of an annual checkup.
Allada believes that given the connection between disrupted body clocks and various health conditions, the test could one day be used to predict who might be at a higher risk of developing certain diseases. That could be particularly helpful in treating conditions like Alzheimer’s, where symptoms usually aren’t apparent until the disease has significantly progressed.
“If someone’s body time is way off from what it should be, that may be a predisposing risk factor for a disease,” Allada says. “The major advance here is being able to measure a biological process that we know is important when it comes to diseases, and do it in a way that’s practical, that someone can go into their doctor’s office and get their blood drawn and figure this out.”