• CircRNAs Accumulate with Age: It has been observed across species that circRNA levels tend to increase in older tissues. The Kadener Lab recently provided definitive evidence for this in the fly brain. In Cell Reports 2025 (Kirio et al.), they profiled circRNAs at multiple ages across the fly lifespan and found that circRNAs accumulate linearly with age in the brain. Importantly, this increase was independent of changes in linear mRNA levels – meaning it’s not just because the genes are more active, but because circRNAs are extraordinarily stable molecules. They demonstrated some circRNAs have half-lives exceeding 20 days in vivo, far longer than typical mRNAs. This exceptional stability likely explains why older brains have more circRNA (they stick around), and it suggests circRNAs could serve as lasting molecular “memory” of cellular states.

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• CircRNAs as Markers of Experience and Stress: Fascinatingly, the same 2025 study showed that circRNA levels can record an organism’s exposure to stress. Flies that were exposed to a mild heat stress (10 days at 29°C) and then returned to normal temperature still had elevated levels of certain circRNAs weeks later. In other words, circRNAs served as molecular markers of the flies’ past environmental experience. This finding suggests a paradigm where circRNAs could be an “archive” of life history – for instance, perhaps in humans, specific circRNAs might indicate if a person’s brain experienced certain stressors or conditions over their lifetime. This has intriguing implications: circRNAs might be developed as biomarkers for aging or cumulative stress exposure.

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• Mechanistic Links to Aging Phenotypes: The lab is now investigating if any circRNAs actively influence aging or lifespan. Our data indicates certain circRNAs can modulate lifespan in flies and worms. The Kadener Lab’s work provides the groundwork to ask if reducing or increasing specific circRNAs in an organism can alter the aging process or neurodegenerative progression. This is a forward-looking aspect likely to attract funder interest, as it merges RNA biology with geroscience.