Biology Reference
In-Depth Information
Chapter 21
The Role of the Circadian System
in Homeostasis
Anand Venkataraman, Heather Ballance and John B. Hogenesch
Department of Pharmacology, Penn Center for Bioinformatics, Penn Genome Frontiers Institute, Institute for Translational Medicine and Therapeutics,
University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
Chapter Outline
Introduction
407
Clocks in Energy and Metabolic Homeostasis
415
Evolution of Clocks
407
What are Peripheral Clocks?
415
Role of the clock in neurological functions
408
Understanding Energy Homeostasis with Animal Models of
the Clock
Sleep
409
417
Homeostasis: You Notice It When It's Broken
412
Molecular Integrators of Clock and Metabolism
418
Cognition (Learning and Memory)
412
Conclusion
419
Neuropsychiatric Disorders
414
References
419
INTRODUCTION
In the early 1700s, Jean-Jacques d'Ortous de Mairan
reported that the daily opening and closing of the mimosa
plant's leaves persisted in the complete absence of all
external cues
[1]
. de Mairan inferred that plants have an
endogenous biological clock, and the field of chronobi-
ology was officially born. Since this observation, scientists
have investigated and identified biological rhythms in almost
all living organisms. The termcircadian (Latin circa
machinery on the overall
regulation of our body's
homeostasis.
In the late 19th and 20th centuries the concept of
'homeostasis' was formalized by the likes of Claude Ber-
nard
[5]
and Walter Cannon
[6]
. The word homeostasis,
derived from Greek meaning 'similar' and 'stability',
refers to the properties by which biological systems keep
their physiology at steady-state levels
[7]
. For example,
mammals maintain their body temperature within a precise
and narrow range throughout the day. When this mainte-
nance fails, e.g., during a fever and recovery, homeostatic
mechanisms are in place to return temperature to a normal
working range. Importantly, these mechanisms need to
work in an open system and constantly adapt to environ-
mental changes. In this chapter, we will detail ways in
which the biological clock helps maintain homeostasis
amidst daily changes in the environment, and what can
happen to the organism when clock-enabled homeostasis is
disrupted.
¼
about,
dies
day) was coined by Franz Halberg to describe the
near-24-hour period of these biological rhythms
[2,3]
.
Remarkably, the fundamental molecular machinery driving
these rhythms is conserved between unicellular prokaryotic
cyanobacteria and mammals
[4]
.
Using reductionist approaches, research endeavors from
de Marian's time have increasingly focused on under-
standing the molecular nuts and bolts of the circadian
machine. This approach led researchers to understand the
basic mechanisms of clock function across species, but by
itself this approach could not explain all the complex
properties of circadian clocks. One of the key questions is
why we need clocks at all. Another is how clocks act in the
homeostatic process. Over the past decade integrative or
systems biology approaches have once again allowed us to
step back and appreciate the influence of the circadian
¼
EVOLUTION OF CLOCKS
Early life was faced with a volatile environment, with wild
fluctuations in levels and intensity of light as well as
temperature. To explain how clocks could help these
