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 extreme chronotype ("larks" and "owls"), clock properties measured in human fibroblasts correlated with extreme diurnal behavior.


RESULTS
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
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.
Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University Clinics Basel, Basel, Switzerland.
Lucia
L
Pagani
Ekaterina A
EA
Semenova
Ermanno
E
Moriggi
Victoria L
VL
Revell
Lisa M
LM
Hack
Steven W
SW
Lockley
Josephine
J
Arendt
Debra J
DJ
Skene
Fides
F
Meier
Jan
J
Izakovic
Anna
A
Wirz-Justice
Christian
C
Cajochen
Oksana J
OJ
Sergeeva
Sergei V
SV
Cheresiz
Konstantin V
KV
Danilenko
Anne
A
Eckert
Steven A
SA
Brown
D057906:Circadian Clocks; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans