Circular RNAs (circRNAs) are a largely unexplored, highly stable class of RNA molecules produced by backsplicing. One intriguing property of circRNAs is their accumulation in the brain with age, which various studies have observed in models such as Drosophila melanogaster, C. elegans, and mice. Work previously performed in the Kadener lab showed that circRNAs are exceptionally stable in biological contexts, displaying little to no degradation in neurons and revealing that they can serve as reliable age and experience markers. Recently, a single circRNA has been shown to be a predictor of apparent aging, establishing a basis for addressing a key question in the field: whether circRNA accumulation reflects chronological age (the time elapsed since birth), or instead apparent aging (biological age). This work aims to answer this question.Here, I hypothesized that circRNAs serve as a marker of the aging process, and that circRNA regulation is correlated with the biological age of the fly through aging pathways. If this is the case, Drosophila strains or mutants displaying different lifespans should exhibit distinct patterns of circRNA accumulation compared to wild-type flies. To test this possibility, I investigated whether circRNA buildup displays divergent kinetics in flies that age faster or slower. I used qRT-PCR to assay circRNA accumulation in the heads of some mutant flies and some fly strains with known altered lifespan at four ages (timepoints). I found that circRNAs accumulate at a rate corresponding to the biological age of the fly, serving as a biomarker of the aging process in wild-type fly strains. I found one circRNA, circSfl, that serves as a marker of aging in insulin mutant flies when previous circRNA accumulation trends invert. These data suggest that while some circRNAs can be used as signatures of biological age in wild-type strains, others can be used in insulin-related contexts, suggesting the involvement of circRNAs in the aging process itself.
Japheth Buchanan Theobald (Sat,) studied this question.