Circular RNAs exhibit exceptional stability in the aging brain and serve as reliable age and experience indicators

Circular RNAs (circRNAs) increase in the brain with age across various animal systems. To elucidate the reasons behind this phenomenon, we profile circRNAs from fly heads at six time points throughout their lifespan. Our results reveal a linear increase in circRNA levels with age, independent of changes in mRNA levels, overall transcription, intron retention, or host gene splicing, demonstrating that the age-related accumulation is due to high stability rather than increased biogenesis. This remarkable stability suggests that circRNAs can serve as markers of environmental experience. Indeed, flies exposed to a 10-day regimen at 29°C exhibit higher levels of specific circRNAs even 6 weeks after returning to standard conditions, indicating that circRNAs can reveal past environmental stimuli. Moreover, half-life measurements show circRNA stability exceeding 20 days, with some displaying virtually no degradation. These findings underscore the remarkable stability of circRNAs in vivo and their potential as markers for stress and life experiences.