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Review
. 2016 Apr;27(4):192-203.
doi: 10.1016/j.tem.2016.02.003. Epub 2016 Mar 3.

Circadian Rhythms, Sleep, and Disorders of Aging

Joanna Mattis  1 , Amita Sehgal  2
Affiliations
Review

Circadian Rhythms, Sleep, and Disorders of Aging

Joanna Mattis et al. Trends Endocrinol Metab. 2016 Apr.

Abstract

Sleep-wake cycles are known to be disrupted in people with neurodegenerative disorders. These findings are now supported by data from animal models for some of these disorders, raising the question of whether the disrupted sleep/circadian regulation contributes to the loss of neural function. As circadian rhythms and sleep consolidation also break down with normal aging, changes in these may be part of what makes aging a risk factor for disorders like Alzheimer's disease (AD). Mechanisms underlying the connection between circadian/sleep dysregulation and neurodegeneration remain unclear, but several recent studies provide interesting possibilities. While mechanistic analysis is under way, it is worth considering treatment of circadian/sleep disruption as a means to alleviate symptoms of neurodegenerative disorders.

Keywords: Alzheimer's; Huntington's; Parkinson's; aging; circadian rhythms; neurodegeneration; sleep.

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Figures

Figure 1
Figure 1. The circadian clock
BMAL1 and CLOCK are transcription factors that heterodimerize and bind to E-box element-containing promoters, including promoters for Per and Cry. PER and CRY form a complex that inhibits BMAL1/CLOCK. In an interlocked loop, BMAL1 and CLOCK target nuclear receptors, REV-ERB and ROR, which feedback to negatively or positively regulate BMAL1 transcription respectively
Figure 2
Figure 2. Sleep and circadian brain circuitry in mammals
The SCN is the central circadian pacemaker, entraining other brain regions as well as peripheral tissues. The SCN projects directly to the wake-promoting LH, which contains hypocretin neurons, and to the DMH. The DMH projects broadly to sleep and arousal centers. Abbreviations: SCN: suprachiasmatic nucleus; DMH: dorsomedial hypothalamus; LH: lateral hypothalamus; LC: locus coeruleus; VLPO: ventrolateral preoptic area
Figure 3
Figure 3. Possible causal links between neurodegenerative disorders and disruptions in sleep and circadian rhythms
Sleep and circadian disruption may lead to oxidative damage, metabolic disruption, and decreased clearance of metabolites such as β-amyloid. These may accelerate neurodegeneration. Neurodegeneration may also impact brain centers that control sleep and circadian behavior.
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