Cargando…

The Physiological Period Length of the Human Circadian Clock In Vivo Is Directly Proportional to Period in Human Fibroblasts

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 extrem...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958564/
https://www.ncbi.nlm.nih.gov/pubmed/21042402
http://dx.doi.org/10.1371/journal.pone.0013376
_version_ 1782188363753717760
author 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.
author_facet 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.
author_sort Pagani, Lucia
collection PubMed
description 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.
format Text
id pubmed-2958564
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-29585642010-11-01 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. PLoS One Research Article 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. Public Library of Science 2010-10-15 /pmc/articles/PMC2958564/ /pubmed/21042402 http://dx.doi.org/10.1371/journal.pone.0013376 Text en Pagani et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
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
title The Physiological Period Length of the Human Circadian Clock In Vivo Is Directly Proportional to Period in Human Fibroblasts
title_full The Physiological Period Length of the Human Circadian Clock In Vivo Is Directly Proportional to Period in Human Fibroblasts
title_fullStr The Physiological Period Length of the Human Circadian Clock In Vivo Is Directly Proportional to Period in Human Fibroblasts
title_full_unstemmed The Physiological Period Length of the Human Circadian Clock In Vivo Is Directly Proportional to Period in Human Fibroblasts
title_short The Physiological Period Length of the Human Circadian Clock In Vivo Is Directly Proportional to Period in Human Fibroblasts
title_sort physiological period length of the human circadian clock in vivo is directly proportional to period in human fibroblasts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958564/
https://www.ncbi.nlm.nih.gov/pubmed/21042402
http://dx.doi.org/10.1371/journal.pone.0013376
work_keys_str_mv AT paganilucia thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT semenovaekaterinaa thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT moriggiermanno thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT revellvictorial thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT hacklisam thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT lockleystevenw thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT arendtjosephine thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT skenedebraj thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT meierfides thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT izakovicjan thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT wirzjusticeanna thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT cajochenchristian thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT sergeevaoksanaj thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT cheresizsergeiv thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT danilenkokonstantinv thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT eckertanne thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT brownstevena thephysiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT paganilucia physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT semenovaekaterinaa physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT moriggiermanno physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT revellvictorial physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT hacklisam physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT lockleystevenw physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT arendtjosephine physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT skenedebraj physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT meierfides physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT izakovicjan physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT wirzjusticeanna physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT cajochenchristian physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT sergeevaoksanaj physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT cheresizsergeiv physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT danilenkokonstantinv physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT eckertanne physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts
AT brownstevena physiologicalperiodlengthofthehumancircadianclockinvivoisdirectlyproportionaltoperiodinhumanfibroblasts