Health Consequences of Circadian Disruption in Humans and Animal Models - Progress in Molecular Biology and Translational Science - page 289

LD cycle. 54,55 Lastly, non-24 h LD cycles that do not support entrainment
entail aberrant exposure to light at night, with more light exposure occur-
ring under ultra short LD cycles (e.g., LD cycles of 3.5 h of light and 3.5 h of
darkness). 56,57

3.2.5 Genetic models
Mutations that affect the molecular oscillator can produce deficits ranging
from altered period to a complete lack of circadian coordination. The first
genetic model to be discovered was the tau mutant hamster, which displays a
2 h reduction in period with each copy of the mutated gene, 58 due to a
reduction in the phosphorylation capacity of casein kinase 1 e . 59 With the
advance of molecular tools, a variety of mouse models have been generated
that display altered circadian clock function. 60 In the most extreme, these
mouse models are arrhythmic under constant dark conditions (e.g., the
bmal1 knockout mouse, 61 clock mutant mouse, 62 the the per1 / per2

mouse 64 ) . These mice models
lack self-sustained circadian rhythms but may nevertheless display daily
changes in behavior and physiology when maintained under 24 h LD cycles
because of the masking effects of light and darkness. While deletions of only
one clock gene paralog (e.g., per1 ) are typically insufficient to completely
abolish circadian rhythms, this can produce a change in the free-running
period and species-atypical alignment to the 24 h LD cycle. These latter
models may be of particular interest for addressing the consequences of cir-
cadian disruption because overall clock function remains intact but is altered
in a manner that disrupts the temporal relationship with the environment.

mouse, 63 and the cry1

/ / cry2 /

3.2.6 Surgical models
Brain lesions targeting the SCN have been used historically in rodent models
to understand the consequences of complete loss of circadian rhythmic-
ity. 65,66 However, recent work has focused on environmental and genetic
manipulation of circadian regulation.

4. HEALTH CONSEQUENCES OF CIRCADIAN DISRUPTION
4.1. Longevity and aging
Shift workers display an increased mortality risk. 67,68 That proper alignment
to environmental cycles has benefits for the fitness and longevity of inver-
tebrate species has been suggested for a variety of organisms, including
cyanobacteria, 69 plants, 70 and flies. 71,72 Within these studies, longevity or