Date of Award
Master of Science (MS)
As a result of earth's orientation toward the sun producing day and night, organisms have evolved an endogenous circadian timing system that is responsible for the 24-hour oscillation of most physiological and behavioral processes. This timing system is constantly synchronized to the external environment to adapt to and anticipate changes in light, temperature, food, and mate availability. In modern society, social and work constraints cause people to live schedules that are out of sync with their internal circadian clocks, producing a chronic circadian misalignment (CCM). While epidemiological studies in humans point to potentially damaging metabolic and cognitive consequences of CCM, the full extent of these negative effects is unknown. Furthermore, very little is known about the molecular and cellular mechanisms that lead to the negative effects. Here, we model and investigate the consequences of CCM in the powerful model system of the fruit fly, Drosophila melanogaster, by exposing the flies to a 28-hour day comprised of 14-hours of light and 14-hours of dark (compared to control flies that are exposed to a standard 24-hour day). Consistent with previous results, we demonstrate that exposure of flies to the 28-hour schedule led to a 14.78% reduction in median lifespan in the females and a 14.72% reduction in males. Previously, it was unknown whether the reduced longevity that results from CCM is due to direct effects of circadian misalignment or whether it occurs secondary to changes in overall sleep or activity levels of misaligned flies. To differentiate between these possibilities, we used the Drosophila Activity Monitoring (DAM) system tocontinuously monitor fly locomotor activity and sleep while simultaneously conducting ourlongevity analysis. This allowed us to assess the effect of long-term CCM on aging-associatedchanges in locomotor activity and sleep levels, and to correlate these measures with fly lifespan. While misaligned flies exhibited aberrant patterns of locomotor activity, evidenced by reduced rest:activity rhythm strength, overall sleep and activity levels were largely unchanged. Furthermore, the CCM-induced reduction in longevity persisted when we matched flies for sleep and activity levels, indicating that the reduction in lifespan was independent of these behaviors. 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. Through this analysis, we identified several groups of genes that displayed altered expression under CCM conditions. These include upregulation of genes associated with cellular stress and downregulation of genes involved in the nervous system. This indicates that CCM induces endogenous stress in animals, potentially leading to reduced neuronal function.
Boomgarden, Alex Christ, "Chronic Circadian Misalignment Leads to Reduced Longevity and Largescale Changes in Gene Expression in Drosophila Melanogaster" (2018). Master's Theses. 3981.
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Copyright © 2018 Alex Christ Boomgarden