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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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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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 |
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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 |
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