Experimental Maps Circadian Rhythm Via the Hair Cell – Neuroscience News

Summary: Are you a morning owl or a night owl? The answer is written in your hair. Researchers have developed a powerful diagnostic test that determines the chronotype (internal biological clock) using just a few strands of hair. By analyzing the activity of 17 genes in the hair follicle, the team could map circadian rhythms without the need for hours of lab-based saliva analysis.

A study of more than 4,000 participants reveals that although genetics and gender play a role, lifestyle and work conditions change our internal clocks more than we previously thought.

Important Points

  • 17-Gene Signature: The experiment uses machine learning to analyze a pattern of 17 genes in hair cells that act as “molecular sensors” of the body.
  • Genetic way of life: The data showed that employed people have internal clocks that run approx 30 minutes earlier more than the unemployed, proving that society’s “zeitgebers” (time givers) like work schedules are changing our biology dramatically.
  • The Gender Gap: Women’s internal clocks indicate the beginning of “biological night” by six minutes earlier than men—a difference smaller than previously thought, but statistically significant.
  • Age migration: Studies have confirmed that biological rhythms change with age; people in their 20s are almost always alert an hour later than those over 50 years of age.
  • Circadian Medicine: This trial paves the way for “timed” health care, where cancer immunotherapies or blood pressure medications are given at the precise hour that will be most effective for a particular patient.

Source: Charity

A research team at the Charité – Universitätsmedizin Berlin has developed a test that can determine a person’s chronotype based on the roots of their hair. It is intended to lay the foundation for circadian medicine – that is, medicine that is closely aligned with the human body’s internal clock.

Used on almost 4,000 people, this new method also reveals that women and men differ slightly in their natural rhythms, and that lifestyle has a greater influence than previously thought. The results have been published in the journal PNAS.

Clocks have changed, but the body hasn’t: Most people become particularly aware of their internal clock after the time has changed; they experience a kind of jet lag because social time and their internal rhythm are no longer in sync. However, biological rhythms not only affect sleep but also influence metabolism and even the effects of medicine.

For example, studies show that the time of day when certain cancer treatment is given can have a great impact on its success,” says Prof. Achim Kramer, head of the Division of Chronobiology at the Department of Anesthesiology and Intensive Care Medicine Charité.

This is possible because – like most of our body’s organs – the immune system also follows a 24-hour rhythm. And that rhythm varies from person to person.”

The goal of circadian medicine is to systematically take this rhythm of the internal clock into account in diagnosis and treatment.

In the new Joint Research Institute headed by Achim Kramer, scientists from the Charité and the Universität zu Lübeck are working to develop this field of research. Circadian medicine requires techniques that allow natural rhythms to be distinguished as easily as possible.

It has been difficult until now: “The standard method so far measures the ‘dark hormone’ melatonin running under dim light for several hours,” explains Achim Kramer. “This can only be done in a laboratory and is too difficult for widespread use.”

17 genes in hair follicles indicate internal timing

Achim Kramer and his team have now performed a test that determines the rhythm of the body’s internal clock using hair – or, more precisely, using cells from a few hair follicles.

“In these cells, we measure the activity of 17 genes that are part of the molecular clock or are controlled by it,” explains the chronobiologist.

“Using machine learning, this method can be used to calculate where a person is in a daily rhythm. One sample is enough for this.”

In the current study, the researchers showed that the new test identifies circadian rhythms almost as accurately as the original method.

“However, the hair test is very easy to do, which is what makes this method so important,” emphasizes Achim Kramer.

The team has already shown that the test is suitable for widespread use: More than 4,000 people have sent hair samples from home to have their chronotype determined.

Genetic predisposition, age, gender and lifestyle influence the period

The analysis of this sample confirmed for the first time on a large scale, using biological measurements, the findings that research has already produced: For example, that the biological rhythm depends on age, which means that people in their 20s get tired on average an hour later than those over 50 years old.

However, at six minutes, the difference revealed by the current study is smaller than that measured in questionnaire-based studies. “However, we assume that gender affects the internal clock, as sex hormones have also been shown to influence circadian rhythms in other studies,” explains Achim Kramer.

In general, a person’s chronotype is determined by several factors. “Genetics, age, gender and lifestyle all play a role. That’s why people’s internal clocks can vary so much,” says the chronobiologist.

The researchers were surprised by how the lifestyle strongly influences the biological rhythm: As the data shows, the internal clock works about half an hour earlier in people who work than those who do not work.

Next step: circadian medicine

To further develop the new test, the research team is working to validate it for routine use in the laboratory. This will make it even easier to use in medical practice in the future – for example, as a basis for sleep counseling or to examine unusual sleep patterns.

Circadian medicine is also close to becoming a reality. The experiment can now be used to determine whether treatments designed for internal timing are more effective or have fewer side effects than those without such timing adjustments.

About education
The company BodyClock Technologies GmbH was expelled from Charité to sell the new test; Prof. Achim Kramer is one of the shareholders and copyright holders. BodyClock Technologies GmbH collected data on approximately 4,000 samples analyzed in the current study.

Parts of the study were carried out within the framework of the Joint Research Center “Fundamentals of Circadian Medicine” (TRR 418), supported by the German Research Foundation (DFG).

Important Questions Answered:

Q: Why are you using hair instead of asking me if I’m a “morning person”?

A: Studies are voluntary and often triggered by caffeine or stress at work. This test measures real genetic work. As Professor Achim Kramer notes, your body’s “natural night” can start much earlier or later than you do. think it does so. Knowing the exact molecular timing is important for medical treatment, as is knowing exactly when your immune system is working to fight a tumor.

Q: Can I change my chronotype by changing my job?

A: Yes. One of the biggest surprises of the study was the “lifestyle effect.” Working people had changed their clocks 30 minutes earlier than non-working people. This suggests that although we have genes “to begin with,” our daily habits can restore the expression of our genes.

Q: How does this help with “Jet Lag” or jet lag?

A: Many people experience “social flight hesitation”—the gap between what their boss wants and what their cells want. This test allows doctors to diagnose abnormal sleep rhythms and provide “sleep counseling” or light therapy to help you reconnect with your health.

Editor’s Notes:

  • This article was edited by a Neuroscience News editor.
  • The journal paper has been thoroughly reviewed.
  • Additional information has been added by our staff.

About this circadian rhythm research issues

Author: Mark Heggen
Source: Charity
Contact: Markus Heggen – Charity
Image: Image submitted to Neuroscience News

Basic research: Road closed.
“HairTime: A non-invasive test to measure the circadian phase from a single hair sample” by Bert Maier, Luísa K. Pilz, Selin Özcakir, Ali Rahjouei, Ashraf N. Abdo, Jan de Zeeuw, Dieter Kunz, and Achim Kramer. PNAS
DOI:10.1073/pnas.2514928123


Summary

Circadian clocks regulate daily physical and behavioral patterns and are essential for health; obstructions can cause various diseases.

The circadian phase of entrainment—the phase of the internal circadian clock in relation to the external environmental cycle—is influenced by genetics and the environment, varies between individuals, and is reflected in daily behaviors such as sleep-wake patterns, mental activity, and physical activity.

Although the circadian phase can also change within individuals, the strength and magnitude of such variation in daily life remains largely unexplored. The gold standard for the evaluation of the circadian phase, dim-light melatonin onset (DLMO), does not work for large studies, and molecular biomarkers based on blood, although promising, have limited potential.

To solve these problems, we created HairTime, a non-invasive test that estimates the circadian phase from a single daytime hair sample. Developed and tested in two stages—a study and a validation study—HairTime has shown strong predictive power compared to DLMO. Suitable for large studies, it was analyzed using more than 4,000 samples.

Estimates of Circadian phases showed a normal distribution and are associated with age, sex, and especially, the work schedule, in the first period of work days, suggesting that social factors can change the internal rhythm.

Together, these results establish HairTime as a promising tool to assess the circadian role in research and lay the foundation for future applications in personalized chronotherapy.

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