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miRNome Profiling Detects miR-101-3p and miR-142-5p as Putative Blood Biomarkers of Frailty Syndrome
Giulia Carini1,2, Jessica Mingardi1, Francesco Bolzetta3
1Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
Abstract:
Frailty is an aging-related pathology, defined as a state of increased vulnerability to stressors, leading to a limited capacity to meet homeostatic demands. Extracellular microRNAs (miRNAs) were proposed as potential biomarkers of various disease conditions, including age-related pathologies. The primary objective of this study was to identify blood miRNAs that could serve as potential biomarkers and candidate mechanisms of frailty. Using the Fried index, we enrolled 22 robust and 19 frail subjects. Blood and urine samples were analysed for several biochemical parameters. We observed that sTNF-R was robustly upregulated in the frail group, indicating the presence of an inflammatory state. Further, by RNA-seq, we profiled 2654 mature miRNAs in the whole blood of the two groups. Expression levels of selected differentially expressed miRNAs were validated by qPCR, and target prediction analyses were performed for the dysregulated miRNAs. We identified 2 miRNAs able to significantly differentiate frail patients from robust subjects. Both miR-101-3p and miR-142-5p were found to be downregulated in the frail vs. robust group. Finally, using bioinformatics targets prediction tools, we explored the potential molecular mechanisms and cellular pathways regulated by the two miRNAs and potentially involved in frailty.
Insights
This study identified two blood microRNAs (miRNAs), miR-101-3p and miR-142-5p, as potential biomarkers for frailty, a condition linked to aging and inflammation.
Area of Science:
- Gerontology and Molecular Biology
- Biomarker Discovery
- Aging Research
Background:
- Frailty is an aging-related condition characterized by increased vulnerability to stressors.
- Extracellular microRNAs (miRNAs) are emerging biomarkers for age-related diseases.
- Identifying specific miRNAs could elucidate frailty mechanisms.
Purpose of the Study:
- To identify blood-based miRNAs as potential biomarkers for frailty.
- To explore candidate molecular mechanisms underlying frailty.
- To differentiate frail individuals from robust controls using miRNA profiles.
Main Methods:
- Frailty assessment using the Fried index in 22 robust and 19 frail subjects.
- RNA sequencing (RNA-seq) to profile 2654 mature miRNAs in whole blood.
- Quantitative PCR (qPCR) for miRNA expression validation and bioinformatics for target prediction.
Main Results:
- Upregulation of soluble tumor necrosis factor receptor (sTNF-R) in frail individuals indicated inflammation.
- Downregulation of miR-101-3p and miR-142-5p in frail subjects compared to robust controls.
- Identification of two specific miRNAs capable of significantly differentiating frail from robust individuals.
Conclusions:
- miR-101-3p and miR-142-5p show potential as blood biomarkers for frailty.
- These miRNAs may play a role in the molecular pathways contributing to frailty.
- Further research can explore therapeutic strategies targeting these miRNA pathways.
