Assessment of circadian rhythms in humans: comparison of real-time fibroblast reporter imaging with plasma melatonin
Open accessAbstract
We compared the period of the rhythm of plasma melatonin, driven by the hypothalamic circadian pacemaker, to in vitro periodicity in cultured peripheral fibroblasts to assess the effects on these rhythms of a polymorphism of PER3 (rs57875989), which is associated with sleep timing. In vitro circadian period was determined using luminometry of cultured fibroblasts, in which the expression of firefly luciferase was driven by the promoter of the circadian gene Arntl (Bmal1). The period of the melatonin rhythm was assessed in a 9‐d forced desynchrony protocol, minimizing confounding effects of sleep‐wake and light‐dark cycles on circadian rhythmicity. In vitro periods (32 participants, 24.61±0.33 h, mean±SD) were longer than in vivo periods (31 participants, 24.16±0.17 h; P > 0.0001) but did not differ between PER3 genotypes ( P >0.4). Analyses of replicate in vitro assessments demonstrated that circadian period was reproducible within individuals (intraclass correlation=0.62), but in vivo and in vitro period assessments did not correlate ( P >0.9). In accordance with circadian entrainment theory, in vivo period correlated with the timing of melatonin ( P >0.05) at baseline and with diurnal preference ( P >0.05). Individual circadian rhythms can be reliably assessed in fibroblasts but may not correlate with physiological rhythms driven by the central circadian pacemaker.—Hasan, S., Santhi, N., Lazar, A.S., Slak, A., Lo, J., von Schantz, M., Archer, S. N., Johnston, J. D., Dijk, D.‐J. Assessment of circadian rhythms in humans: comparison of real‐time fibroblast reporter imaging with plasma melatonin. FASEB J. 26, 2414‐2423 (2012). www.fasebj.org
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Healthy adults show interindividual differences in the free-running circadian period (tau), which shows robust stability within individuals.
“Healthy adults show interindividual differences in the free-running circadian period (tau),94–98 which shows robust stability within individuals.97”
From Circadian rhythms, sleep deprivation, and human performance (2013) · cites this paper as [97]
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References 72 · Cited by 68
- Authors
- Hasan, S., Santhi, N., Lazar, A. S., Slak, A., Lo, J., von Schantz, M., Archer, S. N., Johnston, J. D., & Dijk, D.
- Affiliations
- University of Surrey (GB)
- Surrey Sleep Research Centre University of Surrey Guildford UK
- Corresponding author
- Dijk, Derk‐Jan
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2012-02-27
- Volume
- 26
- Issue
- 6
- Pages
- 2414-2423
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- PMC
- PMC3360144
- OpenAlex
- W2130866419
- Cited by
- 68
- References
- 72
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2022: 4 · 2021: 2 · 2020: 6 · 2019: 2 · 2018: 2 · 2017: 7 · 2016: 10 · 2015: 3 · 2014: 5 · 2013: 11 · 2012: 6
- FWCI
- 3.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The FASEB Journal (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Northumbria Research Link (Northumbria University) (submittedVersion, cc-by-nc)
- Open Research (University of Surrey) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion, cc-by-nc)
- Funders
- University College London
- Universität Zürich
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council (BB/F022883/1)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- circadian rhythm, circadian period, plasma melatonin, Bmal1, forced desynchrony, diurnal preference, circadian entrainment, sleep timing, luciferase reporter
- MeSH terms
- Adult, Cells, Cultured, Circadian Rhythm, Female, Fibroblasts, Humans, Male, Melatonin, Reproducibility of Results, Minisatellite Repeats, ARNTL Transcription Factors, Period Circadian Proteins
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