CircRNA accumulation: A new hallmark of aging?

Circular RNAs (circRNAs) are a newly appreciated class of RNAs found across phyla that are generated most commonly from back-splicing of protein-coding exons. Recent profiling of circRNAs genome-wide has shown that hundreds of circRNAs dramatically increase in expression during aging in the brains of multiple organisms. No other class of transcripts has been found to show such a strong correlation with aging as circRNAs-could they be playing a role in the aging process? Here, we discuss the different methods used to profile circRNAs and discuss current limitations of these approaches. We argue that age-related increases in global circRNA levels likely result from their high stability. The functions of circRNAs are only beginning to emerge, and it is an open question whether circRNA accumulation impacts the aging brain. We discuss experimental approaches that could illuminate whether age-accumulation of circRNAs are detrimental or protective to the aging brain.