Iparraguirre Leire, Alberro Ainhoa, Iñiguez Saioa Gs, Muñoz-Culla Maider, Vergara Itziar, Matheu Ander, Otaegui David
Multiple Sclerosis Unit. Biodonostia Health Research Institute, 20014, San Sebastián, Spain.
CIBERNED, MADRID, Spain.
Immun Ageing. 2023 Jul 11;20(1):33. doi: 10.1186/s12979-023-00356-6.
Frailty is an intermediate and reversible geriatric syndrome that often precedes dependence. Therefore, its identification is essential to prevent dependence. Several molecules have been proposed as biomarkers of frailty, but none of them have 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 various processes, but, to date, no study has characterized the expression of circRNA in frailty.
We studied RNA from leukocytes of 35 frails 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. Linear Discriminant Analysis was performed to determine the best circRNA combination to discriminate frail from robust. In addition, 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. 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.
This work describes for the first time a different expression pattern of circular RNA (circRNAs) 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.
衰弱是一种介于中间且可逆的老年综合征，通常先于失能出现。因此，识别衰弱对于预防失能至关重要。已有多种分子被提议作为衰弱的生物标志物，但均未应用于临床实践。最近，环状RNA作为新型非编码RNA出现。它们的调控作用以及在生物流体中的高稳定性使其成为各种生理过程生物标志物的良好候选者，但迄今为止，尚无研究对衰弱患者体内环状RNA的表达进行表征。
我们研究了35名衰弱个体和35名健康个体白细胞中的RNA。经RNA测序后，使用CIRI2和Circexplorer2进行环状RNA检测，并通过DESeq2进行差异表达分析。通过定量PCR进行验证。进行线性判别分析以确定区分衰弱个体和健康个体的最佳环状RNA组合。此外，在另外13名老年捐赠者进行为期3个月的体育干预前后，对环状RNA候选物进行了研究。我们发现89种环状RNA在衰弱个体中差异表达（p值<0.05，FC> |1.5|）。在衰弱个体中hsa_circ_0007817、hsa_circ_0101802和hsa_circ_0060527的上调得到验证。hsa_circ_0079284、hsa_circ_0007817和hsa_circ_0075737水平的组合显示出很高的生物标志物价值，正确分类衰弱个体和健康个体的概率为95.9%。此外，体育干预后hsa_circ_0079284水平下降，同时衰弱评分有所改善。
这项工作首次描述了衰弱个体和健康个体之间环状RNA（circRNAs）的不同表达模式。此外，一些环状RNA的水平在体育干预后受到调节。这些结果表明，它们可作为衰弱的微创生物标志物。
