Article Impact Level: HIGH Data Quality: STRONG Summary of Proceedings of the National Academy of Sciences https://doi.org/10.1073/pnas.2514928123 Dr. Bert Maier et al.
Points
- Scientists at Charité Berlin developed a noninvasive hair follicle test that measures the activity of seventeen different genes to accurately determine a patient’s internal biological clock and individual chronotype.
- Analysis of four thousand participants revealed that biological rhythms are influenced by age and gender, with younger individuals becoming tired roughly one hour later than those over the age of fifty.
- The study confirmed that lifestyle factors significantly alter internal rhythms, finding that working individuals maintain a biological clock that is approximately thirty minutes earlier than those who are currently unemployed.
- This molecular test demonstrated predictive accuracy nearly identical to the clinical gold standard of measuring melatonin levels while being significantly easier and more cost-effective to perform in various settings.
- Implementing this simple hair-based diagnostic tool allows clinicians to practice circadian medicine by timing immunotherapies and other treatments to coincide with the periods of peak biological effectiveness for each patient.
Summary
This study evaluated the efficacy of a novel noninvasive assay, HairTime, for determining individual circadian phase through the transcriptomic analysis of hair follicles. Given that the existing gold standard, dim-light melatonin onset (DLMO), is clinically impractical for large-scale application due to its requirement for multi-hour serial sampling, researchers sought a simpler molecular biomarker. The study quantified the activity of 17 genes involved in the molecular clock using machine learning to calculate the biological rhythm from a single daytime sample, facilitating the integration of chronobiology into routine clinical diagnostics and personalized therapy.
The research team validated the assay using over 4,000 participants, demonstrating strong predictive power comparable to DLMO measurements. Analysis of the data revealed that biological rhythms are significantly influenced by demographic and lifestyle factors. For instance, participants in their mid-20s displayed a circadian phase approximately one hour later than those over 50. Sex-based differences were also observed, with the internal clock signaling the start of the night an average of six minutes earlier in women than in men. Furthermore, societal factors exerted a measurable impact, as the internal clocks of employed individuals were advanced by approximately 30 minutes compared to those not in the workforce.
The findings suggest that HairTime provides a scalable foundation for circadian medicine, allowing for the optimization of treatment timing based on individual biological rhythms. By accurately identifying an individual’s chronotype, clinicians can potentially enhance the efficacy of chronotherapies, such as cancer immunotherapies, which exhibit time-of-day dependent variations in performance. Future efforts will focus on standardizing the 17-gene expression pattern for routine laboratory use to support sleep counseling and the diagnosis of irregular rhythms. This advancement moves the field closer to a model of personalized medicine that systematically accounts for the 24-hour physiological cycles of the human body.
Link to the article: https://www.pnas.org/doi/10.1073/pnas.2514928123
References
Maier, B., Pilz, L. K., Özcakir, S., Rahjouei, A., Abdo, A. N., De Zeeuw, J., Kunz, D., & Kramer, A. (2026). HairTime: A noninvasive assay for estimating circadian phase from a single hair sample. Proceedings of the National Academy of Sciences, 123(13), e2514928123. https://doi.org/10.1073/pnas.2514928123
