Circular RNA involvement in aging: An emerging player with great potential

Circular RNA (circRNA) is a class of newly discovered noncoding RNA (ncRNA), presenting as a special covalent loop without a 5' cap or 3' tail. Multiple biological properties of circRNA have been revealed during the past decades, such as widespread expression, high conservation, cell-specificity, tissue-specificity and developmental stage-specific expression patterns, as well as resistance to RNase R digestion. CircRNA also exhibits diverse biological functions, including regulation of host genes, alternative splicing, miRNA sponges, protein traps and even protein synthesis. Recently, a global accumulation of circRNAs during aging has been identified across different species, indicating a potential role as a causal factor in aging and age-related disease. The high stability could be one of the mechanisms contributing to this phenomenon. CircRNA could play a role in aging, such as neural aging, muscle aging, reproductive aging, skin aging, immunosenescence, visual aging and age-related diseases like Alzheimer's disease, via interaction with miRNAs, RNA binding proteins, modulation of parental gene transcription, mainly at the transcriptional and posttranscriptional levels. The present study will focus on the advancement of circRNA regarding aging and age-related diseases. We will also discuss the biogenesis, properties, biological functions, and the perspectives of circRNA.