From: University of Colorado Boulder
By
Lisa Marshall
July
27, 2021 – What time is your body clock set on?
The answer, mounting research suggests,
can influence everything from your predisposition to diabetes, heart disease
and depression to the optimal time for you to take medication. But unlike
routine blood tests for cholesterol and hormone levels, there’s no easy way to
precisely measure a person’s individual circadian rhythm.
At least not yet.
New CU Boulder research, published in
the Journal of Biological Rhythms, suggests that day could come in the
not-too-distant future. The study found it’s possible to determine the timing
of a person’s internal circadian or biological clock by analyzing a combination
of molecules in a single blood draw.
“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,” said senior author
Christopher Depner, who conducted the study while an assistant professor of
integrative physiology at CU Boulder. “From a personalized medicine
perspective, it could be groundbreaking.”
Syncing our life with our clock
For decades, researchers have known that
a central ‘master clock’ in a region of the brain called the hypothalamus helps
to regulate the body’s 24-hour cycle, including when we naturally feel sleepy
at night and have the urge to wake up in the morning.
More recently, studies reveal that
nearly every tissue or organ in the body also has an internal timing device,
synced with that master clock, dictating when we secrete certain hormones, how
our heart and lungs function throughout the day, the cadence of our metabolism
of fats and sugars, and more.
As many as 82% of protein-coding genes
that are drug targets show 24-hour time-of-day patterns, suggesting many
medications could work better and yield fewer side effects if administration
was timed appropriately.
And when our internal rhythm is at odds
with our sleep-wake cycle, that can boost risk of an array of diseases, said
study co-author Ken Wright, a professor of integrative physiology and director
of the Sleep and Chronobiology Laboratory at CU Boulder.
“If we want to be able to fix the timing
of a person’s circadian rhythm, we need to know what that timing is,” he said.
“Right now, we do not have an easy way to do that.”
Even among healthy people, sleep-wake
cycles can vary by four to six hours.
Simply asking someone, ‘are you a
morning lark, a night owl or somewhere in-between?’ can provide hints to what a
person’s circadian cycle is.
But the only way to precisely gauge the
timing of an individual’s circadian clock (including where the peaks and
troughs of their daily rhythm) is to perform a dim-light melatonin assessment.
This involves keeping the person in dim light and drawing blood or saliva
hourly for up to 24 hours to measure melatonin––the hormone that naturally
increases in the body to signal bedtime and wanes to help wake us up.
A molecular fingerprint for circadian
rhythm
In pursuit of a more precise and
practical test, Wright and Depner brought 16 volunteers to live in a sleep lab
on the CU Anschutz Medical campus in Aurora for 14 days under tightly
controlled conditions.
In addition to testing their blood for
melatonin hourly, they also used a method called “metabolomics”––assessing
levels of about 4,000 different metabolites (things like amino acids, vitamins
and fatty acids that are byproducts of metabolism) in the blood.
They used a machine learning algorithm
to determine which collection of metabolites were associated with the circadian
clock––creating a sort of molecular fingerprint for individual circadian
phases.
When they tried to predict circadian
phase based on this fingerprint from a single blood draw, their findings were
surprisingly similar to those using the more arduous melatonin test.
“It was within about one hour of the
gold standard of taking blood every hour around the clock,” said Depner, now an
assistant professor of kinesiology at the University of Utah.
He noted the test was significantly more
accurate when people were well rested and hadn’t eaten recently––a requirement
that could make the test challenging outside of a laboratory setting. And to be
feasible and affordable, a commercial test would likely have to narrow down the
number of metabolites it’s looking for (their test narrowed it down to 65).
But the study is a critical first step,
said Wright.
“We are at the very beginning stages of
developing these biomarkers for circadian rhythm, but this promising study
shows it can be done.”
Other research, including some from
Wright’s lab, is exploring proteomics (looking for proteins in blood) or
transcriptomics (measuring the presence of ribonucleic acid, or RNA) to assess
circadian phase.
Ultimately, the researchers imagine a
day when people can, during a routine physical, get a blood test to precisely
determine their circadian phase––so doctors can prescribe not only what to do,
but when.
“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,” said Depner.
https://www.colorado.edu/today/2021/07/27/blood-test-your-body-clock-its-horizon
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