Maintenance of robust circadian rhythms is associated with healthy aging and delayed onset of age-related diseases. Disruption of these rhythms in flies increases susceptibility to oxidative stress and neurodegeneration. Loss of core clock gene function in mice similarly accelerates the onset of late life diseases and mental decline, indicating that the links between circadian desynchrony and neuronal aging are conserved from flies to mammals. However, the epigenetic mechanisms underlying this relationship have remained enigmatic. Here, we used RNA sequencing (RNA-seq) to compare gene expression in young and old Drosophila melanogaster heads at 4-hour intervals around the clock. Although attenuations of core clock gene expression were minor, we identified diverse age-induced transcriptional changes among oscillatory genes, including phase shifts and weakened or abolished rhythmicity. Remarkably, we also discovered a subset of mRNAs that adopted synchronous, de novo rhythmicity during aging. These genes were termed “Late Life Cyclers” (LLCs) and include, among others: small heat shock protein Hsp22, cytokine bnl, lactate dehydrogenase ImpL3, and Hsp40-like CG7130. Because the majority of LLCs were known to be upregulated in oxidative stress, we used qRT-PCR to test their expression in heads of young flies challenged with hyperoxia. Interestingly, hyperoxic insult approximately phenocopied the aging effect by inducing rhythmic upregulation of the LLCs, supporting our hypothesis that increased oxidative stress during aging contributes to the LLC phenomenon. We also show that LLC expression was significantly reduced in the heads of Clkout and cyc01 flies compared to controls with functional clocks, implicating the circadian transcription factors CLK and CYC as important regulators of LLC transcription. In addition, novel transcript assembly with our RNA-seq data uncovered many age-induced, unannotated genes, including several that exhibit LLC behavior. Besides providing a genome-wide, round-the-clock expression profile in heads of young and old Drosophila, our data more broadly offer a temporally unbiased measure of age-dependent differential expression. We have developed a web-based database to enable convenient viewing of these RNA-seq results for individual genes and isoforms. In summary, this study demonstrates a novel role for the circadian clock during aging and begins to uncover the mechanistic relationship between the senescent organism’s timekeeper and its changing cellular environment.