Circadian Disruption Leads to Loss of Homeostasis and Disease

Abstract

The relevance of a synchronized temporal order for adaptation and homeostasis is discussed in this review. We present evidence suggesting that an altered temporal order between the biological clock and external temporal signals leads to disease. Evidence mainly based on a rodent model of “night work” using forced activity during the sleep phase suggests that altered activity and feeding schedules, out of phase from the light/dark cycle, may be the main cause for the loss of circadian synchrony and disease. It is proposed that by avoiding food intake during sleep hours the circadian misalignment and adverse consequences can be prevented. This review does not attempt to present a thorough revision of the literature, but instead it aims to highlight the association between circadian disruption and disease with special emphasis on the contribution of feeding schedules in circadian synchrony.

Circadian clock control of endocrine factors

“…91 Invariably these manipulations negatively impact endocrine-regulated processes, including metabolic homeostasis. 92–97 …”

Major depressive disorder: A loss of circadian synchrony?

“…While this is not a new concept [34, 35], the authors elegantly demonstrate that this desynchronization in MDD could be due to gene expression disruption in extra-SCN brain regions. Understanding the exact nature of this desynchronization in MDD subjects could be a first step in personalizing treatment to resynchronize the internal and external rhythms.…”

The mammalian clock and chronopharmacology

“…In the case of jet-lag, circadian disruption is temporary but often leads to feelings of general discomfort, irritability, depression, gastrointestinal upset, and a decreased mental and physical performance. 49,50 Similar to individuals with jet-lag, shift workers tend to have circadian disruption of the master and peripheral clocks, leading to an increased incidence of gastrointestinal, cardiovascular, and metabolic diseases, as well as menstrual problems in women, and increased cancer risks. 49 It should also be noted that even low-intensity light exposure at night can disrupt the clock in humans, which often alters temperature and hormonal rhythms and may lead to an increased disease propensity.…”

“…49,50 Similar to individuals with jet-lag, shift workers tend to have circadian disruption of the master and peripheral clocks, leading to an increased incidence of gastrointestinal, cardiovascular, and metabolic diseases, as well as menstrual problems in women, and increased cancer risks. 49 It should also be noted that even low-intensity light exposure at night can disrupt the clock in humans, which often alters temperature and hormonal rhythms and may lead to an increased disease propensity. 49,51 An interesting study performed by Cheeseman et al tested the effects of general anesthesia on time perception and circadian rhythm in honeybees.…”

“…49 It should also be noted that even low-intensity light exposure at night can disrupt the clock in humans, which often alters temperature and hormonal rhythms and may lead to an increased disease propensity. 49,51 An interesting study performed by Cheeseman et al tested the effects of general anesthesia on time perception and circadian rhythm in honeybees. 52 Honeybees have a remarkably similar genetic and functional molecular circadian network to mammals and this work demonstrated that isoflurane exposure, a general anesthetic, led to abnormal orienting behavior, alterations in foraging time, atypical circadian rhythms, and severely altered circadian gene expression markers.…”