Effects of Oxidative Stress on Circadian Gene Expression during Aging Public

http://ir.library.oregonstate.edu/concern/honors_college_theses/jh343v42n

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  • All organisms possess circadian clocks, which generate daily oscillations in clock controlled gene expression that regulate many essential biological functions in synchrony with the 24-hour light/dark cycles. When the genes that control the internal clock are weakened, accelerated aging symptoms are observed. Past research in Drosophila demonstrated that aging flies with disrupted clocks have higher levels of reactive oxygen species (ROS) and oxidative damage to proteins than age-matched control flies with normal clock function. To understand how functional clock protects the aging brain, genome-wide gene expression profiles were measured around the clock in heads of young and old flies using RNA-seq. The results revealed that many clock controlled genes lose rhythmicity with age; however, other genes actually become very rhythmic in old flies; we refer to them as late life cyclers (LLCs). The goal of this project was to investigate the mechanisms that induce rhythmic gene expression in old flies. We used hyperoxia to generate oxidative damage in young flies. We measured gene expression levels and determined that these five LLCs exhibited induced rhythmicity in young flies exposed to hyperoxia, suggesting that they may be beneficial for the aging process. We observed LLC expression levels under hyperoxia in mutants with disrupted clock and as well in constant darkness. Our findings revealed a multifaceted regulation of these stress response genes involving both clock and light. Because oxidative stress has been linked to a variety of neurodegenerative diseases and also to cancer, our discovery of the novel role of the circadian system in defense against oxidative damage may help to understand mechanisms regulating healthspan in humans. Key words: oxidative damage, circadian rhythms, reactive oxygen species, late-life cyclers
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