Assessment of circadian rhythms in humans:Comparison of real-time fibroblast reporter imaging with plasma melatonin

Hasan, Sibah, Santhi, Nayantara, Lazar, Alpar S, Slak, Ana, Lo, June, von Schantz, Malcolm, Archer, Simon N, Johnston, Jonathan D and Dijk, Derk-Jan (2012) Assessment of circadian rhythms in humans:Comparison of real-time fibroblast reporter imaging with plasma melatonin. The FASEB Journal, 26 (6). pp. 2414-2423. ISSN 0892-6638

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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.

Item Type: Article
Additional Information: This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords: arntl transcription factors,adult,cells, cultured,circadian rhythm,female,fibroblasts,humans,male,melatonin,minisatellite repeats,period circadian proteins,reproducibility of results
Faculty \ School: Faculty of Medicine and Health Sciences > School of Health Sciences
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Dementia & Complexity in Later Life
Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
Depositing User: Pure Connector
Date Deposited: 07 Dec 2016 00:07
Last Modified: 19 Oct 2023 01:52
DOI: 10.1096/fj.11-201699

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