The 24-hour internal clock in your brain is known as your circadian rhythm and its personal manifestation is your chronotype—which varies greatly on an individual basis.
For example, night owls tend to have a late chronotype; these individuals have their circadian rhythm delayed by any number of hours, going to bed late and waking up late. In the same manner, those whose internal clock is advanced have an early chronotype, and tend to be early risers.
Recently, scientists have created a blood test that can be used to determine how delayed or advanced one’s internal clock is with respect to the external time.
Three labs have explored techniques to do just this. All have the same basic approach, namely measuring changes in RNA levels in blood cells. This gives us an idea about which genes are being expressed and to what degree, and which are not. This information can then be used to determine where in their 24-hour cycle a person falls at the time they have taken the test, essentially providing their internal, or biological, time.
At Northwestern University Dr. Rosemary Braun developed “TimeSignature”, a test that determines the expression of 40 different genes from two blood samples. Why these 40? During the development of the test, Braun’s team used data from blood samples collected from subjects every 2 hours to find patterns in variation of gene expression throughout the day. They initially measured the expression of about 20,000 different genes. They then ran this data through a machine-learning algorithm to see which genes had patterns of expression that could best predict the time of day, and these 40 genes came up as the result. The method can predict a person’s biological time with reasonable accuracy, within 1.5 hours.
How might this test be useful? Since our internal clock regulates the functioning of all our major organs, each of which has its own circadian rhythm, it may be possible to better determine the best time to give specific medications or treatments. One striking example is that giving patients with gastrointestinal cancer 5-fluorouracil, a type of chemotherapy, in the middle of the night reduces its toxicity fivefold. Another is that open-heart surgery performed in the afternoon instead of the morning halves the risk of complications. One study also found that in individuals with hypertension, angiotensin-2 receptor blockers were found to be more effective at reducing complications of cardiovascular disease if taken at bedtime compared to if taken in the morning. This kind of treatment schedule is known as chronotherapy. Knowing if someone’s internal clock is delayed or advanced can further aid in the precise timing of these and other treatments to maximize its benefit and minimize risk.
In addition, abnormalities in the timing of one’s circadian cycle have been associated with a multitude of conditions, such as depression, diabetes, heart disease, and Alzheimer’s disease. It is important to investigate if this difference in their internal time contributes to the symptoms of these disorders. Knowing whether these patients present with a circadian phase advance or delay in addition to these conditions may, therefore, be of help in treating them.
There is also a class of sleep disorders known as circadian rhythm disorders, which involve disruption of the sleep-wake cycle. Delayed phase sleep disorder and advanced phase sleep disorder are two of these, and occur when significant phase advances or delays begin to affect the quality of one’s life. Also included in this category is shift-work disorder, seen in individuals whose work falls right around the time where their body would be inclined to be asleep. Circadian rhythm disorders can result in excessive sleepiness, insomnia, attention, and mood difficulties, as well as multiple negative long-term effects. This blood test could be ideal in diagnosing and treating such disorders, by knowing the timing of the circadian cycle and how it is altered in these patients.
It is also a well-known fact that sleep changes as we age. With aging, it takes longer to fall asleep and sleep becomes more fragmented. Contributing to the fragmentation of sleep is the increased need for bathroom trips during the night that comes with aging, as well as a general lowering of the threshold for awakening. In addition, sleep architecture, that is, the organization of sleep into distinct stages, exhibits some changes as well. Older individuals tend to spend less time in 2 of these stages, slow-wave sleep, and REM sleep. These and other factors lead to a shorter overall sleep duration at night.
Importantly, there is also a notable phase advance that occurs in aging, meaning that despite one’s best efforts, one will tend to become sleepy much earlier on in the day, and wake up earlier as well, with the inability to sleep past a certain time in the morning. This shift in circadian rhythm can sometimes have undesirable consequences, such as an overall lack of sleep. Knowing the circadian phase of older individuals may provide insight into how to help those whose quality of life has been affected by these changes.
In all, the timing of circadian rhythms varies greatly between individuals. As we work towards creating more personalized treatments, this tool could be crucial in helping us diagnose, understand, and treat a multitude of conditions. All this illustrates that the body’s internal clock may matter just as much as the time you see when you look down at your watch.
Caitlin Bard is completing her Bachelor of Science with a major in neuroscience at McGill University.
