Circular RNAs (circRNAs) are abundant and accumulate with age in neurons of diverse species. However, only few circRNAs have been functionally characterized, and their role during aging has not been addressed. Here, we use transcriptome profiling during aging and find that accumulation of circRNAs is slowed down in long-lived insulin mutant flies. Next, we characterize the in vivo function of a circRNA generated by the sulfateless gene (circSfl), which is consistently upregulated, particularly in the brain and muscle, of diverse long-lived insulin mutants. Strikingly, lifespan extension of insulin mutants is dependent on circSfl, and overexpression of circSfl alone is sufficient to extend the lifespan. Moreover, circSfl is translated into a protein that shares the N terminus and potentially some functions with the full-length Sfl protein encoded by the host gene. Our study demonstrates that insulin signaling affects global circRNA accumulation and reveals an important role of circSfl during aging in vivo.

环状RNA（circRNA）丰富，并且随着年龄的增长在各种物种的神经元中积累。但是，只有少数circRNA具有功能性特征，其在衰老过程中的作用尚未得到解决。在这里，我们使用衰老过程中的转录组分析，发现长寿命胰岛素突变体果蝇中circRNA的积累会减慢。接下来，我们描述了无硫酸盐生成的circRNA的体内功能基因（circSf1），其持续变化，特别是在大脑和肌肉中，是多种长寿胰岛素突变体的上调基因。令人惊讶的是，胰岛素突变体的寿命延长取决于circSf1，而单独的circSf1的过表达足以延长其寿命。而且，circSfl被翻译成与宿主基因编码的全长Sfl蛋白共享N末端并可能具有某些功能的蛋白。我们的研究表明，胰岛素信号传导会影响circRNA的整体积累，并揭示circSfl在体内衰老过程中的重要作用。