Abstract
BackgroundCircadian clocks are found in nearly all organisms, from bacteria to mammals, and ensure that behavioral and physiological processes occur at optimal times of day and in the correct temporal order. It is becoming increasingly clear that chronic circadian misalignment (CCM), such as occurs in shift workers or as a result of aberrant sleeping and eating schedules common to modern society, has profound metabolic and cognitive consequences, but the proximate mechanisms connecting CCM with reduced organismal health are unknown. Furthermore, it has been difficult to disentangle whether the health effects are directly induced by misalignment or are secondary to the alterations in sleep and activity levels that commonly occur with CCM. Here, we investigated the consequences of CCM in the powerful model system of the fruit fly, Drosophila melanogaster. We subjected flies to daily 4-h phase delays in the light-dark schedule and used the Drosophila Activity Monitoring (DAM) system to continuously track locomotor activity and sleep while simultaneously monitoring fly lifespan.ResultsConsistent with previous results, we find that exposing flies to CCM leads to a ~ 15% reduction in median lifespan in both male and female flies. Importantly, we demonstrate that the reduced longevity occurs independent of changes in overall sleep or activity. To uncover potential molecular mechanisms of CCM-induced reduction in lifespan, we conducted whole body RNA-sequencing to assess differences in gene transcription between control and misaligned flies. CCM caused progressive, large-scale changes in gene expression characterized by upregulation of genes involved in response to toxic substances, aging and oxidative stress, and downregulation of genes involved in regulation of development and differentiation, gene expression and biosynthesis.ConclusionsMany of these gene expression changes mimic those that occur during natural aging, consistent with the idea that CCM results in premature organismal decline, however, we found that genes involved in lipid metabolism are overrepresented among those that are differentially regulated by CCM and aging. This category of genes is also among the earliest to exhibit CCM-induced changes in expression, thus highlighting altered lipid metabolism as a potentially important mediator of the negative health consequences of CCM.
Highlights
Circadian clocks are found in most organisms, from bacteria to mammals, and ensure that behavioral and physiological processes occur at optimal times of day and in the correct temporal order
It should be noted that all flies were maintained on minimal sucrose-agar food during longevity analysis, resulting in a relatively short lifespan of even control flies in these experiments compared with those performed with standard food
The ~ 15% reduction in median lifespan we observed agrees well with results obtained with flies kept on standard food [10], which demonstrates that the negative health impacts of circadian misalignment (CCM) are similar regardless of diet
Summary
Circadian clocks are found in most organisms, from bacteria to mammals, and ensure that behavioral and physiological processes occur at optimal times of day and in the correct temporal order. The daily rotation of the Earth on its axis produces predictable cycles of light and temperature This has led to the evolution of endogenous circadian clocks, which allow organisms to anticipate and adapt to environmental cycles to ensure that behavioral and physiological processes occur at optimal times of day. More extensive clock resetting is necessary following abrupt shifts in lighting schedules, such as occur with trans-meridian travel, shiftwork, or as a result of the aberrant eating and sleeping schedules that are common in modern society The latter in particular, which has been termed ‘social jetlag’, has led to a situation in which as much as 2/3 of the population live under a state of chronic circadian misalignment (CCM) typified by a behavioral schedule that runs outside the dictates of their endogenous circadian rhythms [5, 6]. These irregular schedules likely result in a misalignment between circadian clocks and external environmental signals as well as internal desynchrony between different clock-containing tissues in the body
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
