The physiological period length of the human circadian clock In Vivo is directly proportional to period in human fibroblasts

Lucia Pagani, Ekaterina A. Semenova, Ermanno Moriggi, Victoria L. Revell, Lisa M. Hack, Steven W. Lockley, Josephine Arendt, Debra J. Skene, Fides Meier, Jan Izakovic, Anna Wirz-Justice, Christian Cajochen, Oksana J. Sergeeva, Sergei V. Cheresiz, Konstantin V. Danilenko, Anne Eckert, Steven A. Brown

Research output: Contribution to journalArticle

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Abstract

Background: Diurnal behavior in humans is governed by the period length of a circadian clock in the suprachiasmatic nuclei of the brain hypothalamus. Nevertheless, the cell-intrinsic mechanism of this clock is present in most cells of the body. We have shown previously that for individuals of extreme chronotype ("larks" and "owls"), clock properties measured in human fibroblasts correlated with extreme diurnal behavior. Methodology/Principal Findings: In this study, we have measured circadian period in human primary fibroblasts taken from normal individuals and, for the first time, compared it directly with physiological period measured in vivo in the same subjects. Human physiological period length was estimated via the secretion pattern of the hormone melatonin in two different groups of sighted subjects and one group of totally blind subjects, each using different methods. Fibroblast period length was measured via cyclical expression of a lentivirally delivered circadian reporter. Within each group, a positive linear correlation was observed between circadian period length in physiology and in fibroblast gene expression. Interestingly, although blind individuals showed on average the same fibroblast clock properties as sighted ones, their physiological periods were significantly longer. Conclusions/Significance: We conclude that the period of human circadian behaviour is mostly driven by cellular clock properties in normal individuals and can be approximated by measurement in peripheral cells such as fibroblasts. Based upon differences among sighted and blind subjects, we also speculate that period can be modified by prolonged unusual conditions such as the total light deprivation of blindness.

Original languageEnglish
Article numbere13376
JournalPLoS One
Volume5
Issue number10
DOIs
StatePublished - Nov 17 2010

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Circadian Clocks
Fibroblasts
circadian rhythm
fibroblasts
Clocks
Strigiformes
Suprachiasmatic Nucleus
blindness
Physiology
melatonin
human behavior
cells
Melatonin
Blindness
hypothalamus
Gene expression
Hypothalamus
Brain
physiology
hormones

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Pagani, L., Semenova, E. A., Moriggi, E., Revell, V. L., Hack, L. M., Lockley, S. W., ... Brown, S. A. (2010). The physiological period length of the human circadian clock In Vivo is directly proportional to period in human fibroblasts. PLoS One, 5(10), [e13376]. https://doi.org/10.1371/journal.pone.0013376

The physiological period length of the human circadian clock In Vivo is directly proportional to period in human fibroblasts. / Pagani, Lucia; Semenova, Ekaterina A.; Moriggi, Ermanno; Revell, Victoria L.; Hack, Lisa M.; Lockley, Steven W.; Arendt, Josephine; Skene, Debra J.; Meier, Fides; Izakovic, Jan; Wirz-Justice, Anna; Cajochen, Christian; Sergeeva, Oksana J.; Cheresiz, Sergei V.; Danilenko, Konstantin V.; Eckert, Anne; Brown, Steven A.

In: PLoS One, Vol. 5, No. 10, e13376, 17.11.2010.

Research output: Contribution to journalArticle

Pagani, L, Semenova, EA, Moriggi, E, Revell, VL, Hack, LM, Lockley, SW, Arendt, J, Skene, DJ, Meier, F, Izakovic, J, Wirz-Justice, A, Cajochen, C, Sergeeva, OJ, Cheresiz, SV, Danilenko, KV, Eckert, A & Brown, SA 2010, 'The physiological period length of the human circadian clock In Vivo is directly proportional to period in human fibroblasts', PLoS One, vol. 5, no. 10, e13376. https://doi.org/10.1371/journal.pone.0013376
Pagani, Lucia ; Semenova, Ekaterina A. ; Moriggi, Ermanno ; Revell, Victoria L. ; Hack, Lisa M. ; Lockley, Steven W. ; Arendt, Josephine ; Skene, Debra J. ; Meier, Fides ; Izakovic, Jan ; Wirz-Justice, Anna ; Cajochen, Christian ; Sergeeva, Oksana J. ; Cheresiz, Sergei V. ; Danilenko, Konstantin V. ; Eckert, Anne ; Brown, Steven A. / The physiological period length of the human circadian clock In Vivo is directly proportional to period in human fibroblasts. In: PLoS One. 2010 ; Vol. 5, No. 10.
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AU - Hack, Lisa M.

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AU - Arendt, Josephine

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AU - Wirz-Justice, Anna

AU - Cajochen, Christian

AU - Sergeeva, Oksana J.

AU - Cheresiz, Sergei V.

AU - Danilenko, Konstantin V.

AU - Eckert, Anne

AU - Brown, Steven A.

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