As more and more research highlights the role our body's internal clock, known as the circadian rhythm, may have in everything from developing dementia, to driving weight gain to promoting tumor growth, scientists are getting creative in their attempts to unravel its secrets. Studies are starting to demonstrate how one day we might be able to check the time of this body clock through a simple blood test, and a team at the University of Colorado (CU) Boulder has now put forward a new technique that proved highly accurate alongside the current gold-standard approach.
The reason we get sleepy at night and naturally wake in the morning is tied to a central, master clock in the brain, which regulates the 24-hour cycles throughout all cells in the body. This circadian rhythm differs between individuals, however, which is why some people are night owls and others are early risers, or why others enjoy an afternoon nap on the couch.
Research is beginning to link circadian rhythms to a range of health outcomes in humans. This includes how disruptions can increase Alzheimer's risk and tumor growth, along with studies that show how administering specific cancer drugs in the morning might be more effective, or how eating protein at breakfast as opposed to later in the day can lead to better muscle growth. The hope is that these insights can lay the foundation for a new era of personalized medicine, where treatments and wellness regimes are better tailored to individuals.
“If we can understand each individual person’s circadian clock, we can potentially prescribe the optimal time of day for them to be eating or exercising or taking medication,” says senior author Christopher Depner. “From a personalized medicine perspective, it could be groundbreaking.”
As it stands, the gold standard for measuring the body's internal clock, or seeing what time the body "thinks" it is as opposed to what is says on your watch, is known as a dim-light melatonin assessment. To do this, subjects remain in a dark space and provide hourly blood and saliva samples to measure the hormone melatonin, which signals to the body when it is time to sleep and wake up.
“If we want to be able to fix the timing of a person’s circadian rhythm, we need to know what that timing is,” Depner says. “Right now, we do not have an easy way to do that.”
Scientists hope to develop more practical ways of reading a patient's body clock that can be incorporated into routine care, and blood tests are shaping as a promising solution, just as they are used to check cholesterol levels, for example. Researchers have made inroads in this area, by using blood samples to gauge the activity of genes that help regulate the circadian rhythm or measure certain proteins, but the CU Boulder team has taken a different approach referred to as "metabolomics."
For their study, the scientists enlisted 16 volunteers who spent 14 days in a sleep lab and provided hourly blood tests for melatonin assessment. At the same time, the researchers assessed the levels of 4,000 different metabolites in their blood, including amino acids, vitamins and fatty acids. A machine learning algorithm was then used to identify sets of these metabolites that were associated with various phases of the circadian clock. Using this "molecular fingerprint" to predict the circadian phase from a single sample, the team found it was surprisingly accurate.
“It was within about one hour of the gold standard of taking blood every hour around the clock,” says Depner.
The team managed to refine the technique so that it only needs to look for 65 metabolites, but say it would need to be narrowed down further to make it commercially viable. Further, there are other problems to solve before the technology moves beyond the lab, such as the fact it was far more accurate when the subjects were well rested and hadn't eaten recently. Still, the researchers are enthused by the promising early results.
“We are at the very beginning stages of developing these biomarkers for circadian rhythm, but this promising study shows it can be done," says Depner. “This is an important step forward in paving the way for circadian medicine – for providing the right treatment to the right individual at the right time of day."
The research was published in the Journal of Biological Rhythms.
Source: University of Colorado Boulder