CircRNA in Frailty

This work describes for the first time a different circular RNA (circRNAs) expression pattern between frail and robust individuals. Moreover, the level of some circRNAs is modulated after a physical intervention. These results suggest that they could be used as minimally invasive biomarkers of frailty. Frailty is an intermediate and reversible geriatric syndrome that often precedes dependency. Therefore, its identification is essential to prevent dependency. Diverse molecules have been proposed as biomarkers of frailty, but none of them has reached clinical practice. Recently, circular RNAs have emerged as new non-coding RNAs. Their regulatory role together with their high stability in biofluids makes them good candidates as biomarkers for several processes, but, to date, no studies have characterized circRNA expression in frailty. We studied RNA from leukocytes of 35 frail and 35 robust individuals. After RNA-Sequencing, circRNA detection was performed by CIRI2 and Circexplorer2 and differential expression analysis by DESeq2. Validation was performed by Quantitative-PCR. A Linear Discriminant Analysis was performed to determine the best circRNA combination to discriminate frails from robusts. Besides, CircRNA candidates were studied in 13 additional elder donors before and after a 3-month physical intervention. We found 89 differentially expressed circRNAs (p-value<0.05, FC>|1.5|) with frailty. The upregulation of hsa_circ_0007817, hsa_circ_0101802 and hsa_circ_0060527 in frail individuals was validated. The combination of hsa_circ_0079284, hsa_circ_0007817 and hsa_circ_0075737 levels showed a great biomarker value with a 95.9% probability of correctly classifying frail and robust individuals. Moreover, hsa_circ_0079284 levels decreased after physical intervention in concordance with an improvement in frailty scores. Frail vs Robust pools analysis