Circadian rhythms provide temporal coordination between organisms and their environment, and contribute to healthy aging in animals from flies to humans. Clock genes regulate many biological processes, and a disrupted circadian system increases risk for oxidative damage, neurodegenerative diseases, and metabolic disorders. Expression of many genes appears to be clock-dependent in young flies. However, as aging weakens circadian rhythms and synchrony, it has been unclear how expression of clock-controlled genes may change with age. Using RNA-Seq to obtain a large-scale overview of transcriptome differences around the clock in heads of young and old flies, we found a group of genes that had constitutively low expression in young, but were greatly upregulated and rhythmic in heads of old flies. Genes showing this expression pattern were called “Late Life Cyclers,” or LLCs. Further investigation revealed that many LLCs were involved in stress response, specifically oxidative stress. These included, among others: small heat shock protein Hsp22, cytokine bnl, dehydrogenase ImpL3, and Hsp40-like CG7130. Since the most robustly rhythmic LLCs’ expression peaked at lights-off, or Zeitgeber Time (ZT)12, we tested whether this would be affected by longer or shorter periods of light during a 24h cycle. In flies collected in light:dark (LD) 16:8 or LD 8:16, the peak expression of most LLCs tested by qRT-PCR shifted to follow the time of lights off. In constant darkness (DD), expression was low and arrhythmic, suggesting that light is a factor in regulation of these genes. To mimic oxidative stress known to occur in old flies, we exposed young flies to 100% hyperoxia (HO). We found that LLCs were indeed upregulated and rhythmically expressed upon HO exposure in LD12:12, similar to what was seen in old flies. When flies were exposed to HO in DD, these genes were barely upregulated compared to normoxia controls, again resembling expression in old flies in DD. The inability of these genes to be overexpressed and rhythmic in the absence of light despite strong oxidative insult led us to investigate the role of the photoreceptive protein encoded by the gene cryptochrome (cry). CRY, a flavoprotein, has a key role in circadian regulation by causing degradation of the core clock protein TIM in the presence of blue light. However, other possible roles for cry remain unknown. We tested whether CRY was necessary for LLC upregulation, by measuring their expression profiles in young cry-null mutants, cry01 and cry02 held in LD under HO. We observed a loss of typical LLC rhythms and their reduced overall expression compared to wild type controls. Our data suggest that CRY has a novel role in stimulating expression of neuroprotective genes in response to light and oxidative stress.