Abstract
Disruption of the circadian clock, which directs rhythmic expression of numerous output genes, accelerates aging. To enquire how the circadian system protects aging organisms, here we compare circadian transcriptomes in heads of young and old Drosophila melanogaster. The core clock and most output genes remained robustly rhythmic in old flies, while others lost rhythmicity with age, resulting in constitutive over- or under-expression. Unexpectedly, we identify a subset of genes that adopted increased or de novo rhythmicity during aging, enriched for stress-response functions. These genes, termed late-life cyclers, were also rhythmically induced in young flies by constant exposure to exogenous oxidative stress, and this upregulation is CLOCK-dependent. We also identify age-onset rhythmicity in several putative primary piRNA transcripts overlapping antisense transposons. Our results suggest that, as organisms age, the circadian system shifts greater regulatory priority to the mitigation of accumulating cellular stress.
Highlights
Disruption of the circadian clock, which directs rhythmic expression of numerous output genes, accelerates aging
Stress-response genes were enriched among transcripts with age-induced rhythmicity, hereafter called ‘late-life cyclers’ (LLCs), and we show that exogenous oxidative stress can induce rhythmic LLC expression in young flies
Using ARSER, we identified 2,036 genes to be rhythmic in young flies, including 67% of genes previously deemed rhythmic at the messenger RNA level in heads of male flies[3]; this overlap is substantial considering differences in sex and periodicity detection methods (Methods)
Summary
Disruption of the circadian clock, which directs rhythmic expression of numerous output genes, accelerates aging. Oscillating clock components impose rhythmic expression on a diverse portfolio of target clock-controlled genes (CCGs) that continues to expand as sensitivity of detection techniques improve[2,3,4,5,6]. These CCGs generate molecular and cellular rhythms, which profoundly influence metabolism and tissue homoeostasis. Despite substantial evidence that circadian disruption shortens healthspan, the mechanisms by which the clock protects aging organisms are not understood To address this question, here we conduct an RNA sequencing (RNA-seq) study and compared diurnal expression of clock genes and CCGs in heads of young and old female flies. Our data suggest that LLC activation is a strategy by which the clock helps organisms adapt to their changing cellular environments during aging
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