HairTime, a noninvasive assay estimating circadian phase from a single daytime hair sample, demonstrated strong predictive power compared to dim-light melatonin onset (DLMO) and revealed associations between circadian phase and age, sex, and work schedules across over 4,000 samples.
Key Findings
Methods
HairTime was developed as a noninvasive assay that estimates circadian phase from a single daytime hair sample, evaluated through a training study and a validation study.
The assay was developed and evaluated in two steps: a training study and a validation study.
The assay uses gene expression from hair follicle cells, which can be collected noninvasively.
The gold standard comparator used was dim-light melatonin onset (DLMO).
HairTime was designed to be suitable for large-scale studies, overcoming feasibility limitations of blood-based molecular biomarkers and DLMO.
Results
HairTime demonstrated strong predictive power for circadian phase compared to DLMO.
DLMO is described as the gold standard for circadian phase assessment.
HairTime estimates were validated against DLMO measurements in the validation study.
The assay was assessed using over 4,000 samples, establishing its scalability.
The study describes the predictive power of HairTime as 'strong' relative to DLMO.
Results
Circadian phase estimations derived from HairTime showed a normal distribution across the study population.
Circadian phase estimates from over 4,000 samples were analyzed for their distribution.
The distribution of estimated circadian phases was found to be normal across participants.
This distribution pattern supports the validity of the assay for population-level studies.
Results
Circadian phase estimated by HairTime was associated with age and sex.
Both age and sex were identified as significant factors associated with circadian phase estimates.
These associations are consistent with known biological influences on circadian timing.
The large sample size of over 4,000 samples provided statistical power to detect these associations.
Results
Work schedules were associated with circadian phase, with earlier timing observed on workdays, suggesting societal factors can modulate internal rhythms.
Circadian phase was notably associated with work schedules among the factors examined.
Earlier circadian timing was found on workdays compared to non-workdays.
The authors conclude that 'societal factors can modulate internal rhythms.'
This finding was detected across over 4,000 samples collected in a large-scale setting.
Background
The circadian phase of entrainment is influenced by both genetic and environmental factors, varies between individuals, and is reflected in daily behaviors such as sleep-wake patterns, cognitive performance, and physical activity.
Circadian clocks govern daily physiological and behavioral processes and are described as crucial for health.
Disruptions to circadian clocks can lead to various diseases.
Circadian phase may also fluctuate within individuals, and the dynamics of such variation in daily life remain 'largely unexplored' according to the authors.
Behavioral markers including sleep-wake patterns, cognitive performance, and physical activity reflect circadian phase.
Conclusions
The authors establish HairTime as a foundation for future applications in personalized chronotherapy.
The authors describe HairTime as 'a promising tool for assessing circadian phase in research.'
Future applications in personalized chronotherapy are identified as a key translational direction.
The noninvasive, scalable nature of the assay is presented as enabling large-scale chronobiological research previously limited by DLMO impracticality.
What This Means
Every person has an internal biological clock — a circadian clock — that controls when we feel sleepy or alert, when our hormones peak, and many other bodily functions. Knowing the exact timing of a person's internal clock (called circadian phase) is important for health research and for tailoring medical treatments to the right time of day. Currently, the most accurate way to measure this is a test called dim-light melatonin onset (DLMO), which requires people to sit in dim light and give multiple saliva or blood samples over many hours — making it impractical for large studies or routine use. This research introduces HairTime, a new method that estimates a person's circadian phase from just a single hair sample taken during the day. The researchers trained and validated the method against DLMO, then used it to analyze over 4,000 samples, finding that it performed well as a predictor of true circadian phase.
Using HairTime across this large dataset, the researchers found that estimated circadian phase followed a normal (bell-curve) distribution in the population and was linked to age, sex, and — notably — work schedules. People tended to show earlier internal clock timing on workdays compared to non-workdays, suggesting that social obligations like work can shift the timing of a person's biological clock. This aligns with the concept of 'social jetlag,' where people's natural sleep timing is misaligned with societal schedules.
This research suggests that a simple, painless hair sample could one day replace burdensome multi-hour testing protocols for measuring circadian timing, opening the door to large-scale studies on how biological clocks affect health and disease. It also lays groundwork for personalized chronotherapy — the idea of timing medical treatments to match each patient's unique internal clock — which could improve the effectiveness of drugs and other interventions.
Maier B, Pilz L, Özcakir S, Rahjouei A, Abdo A, de Zeeuw J, et al.. (2026). HairTime: A noninvasive assay for estimating circadian phase from a single hair sample.. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.2514928123