Identifying Exosome-Derived Micrornas as Candidate Biomarkers of Frailty

Abstract

Frailty is a geriatric syndrome associated with progressive physical decline and significantly increases risk for falls, disability, hospitalizations, and death. However, much remains unknown regarding the biological mechanisms that contribute to aging and frailty, and to date, there are no clinically used prognostic or diagnostic molecular biomarkers. The present study profiled exosome-derived microRNAs isolated from the plasma of young, robust older, and frail older individuals and identified eight miRNAs that are uniquely enriched in frailty: miR-10a-3p, miR-92a-3p, miR-185-3p, miR-194-5p, miR-326, miR-532-5p, miR-576-5p, and miR-760. Furthermore, since exosomes can deliver miRNAs to alter cellular activity and behavior, these miRNAs may also provide insights into the biological mechanisms underlying frailty; KEGG analysis of their target genes revealed multiple pathways implicated in aging and age-related processes. Although further validation and research studies are warranted, our study identified eight novel candidate biomarkers of frailty that may help to elucidate the multifactorial pathogenesis of frailty.

Implementing Precision Medicine in Human Frailty through Epigenetic Biomarkers

“…Ipson and co-workers compared the differential expression of exosome-derived miRNAs from young adults by using small RNA sequencing (smallRNA-seq) in robust and frail individuals and identified eight enriched miRNAs associated with frailty: miR-10a-3p, miR-92a-3p, miR-185–3p, miR-194–5p, miR-326, miR-532–5p, miR-576–5p, and miR-760 [ 82 ].…”

Cancer and Aging: Two Tightly Interconnected Biological Processes

“…Dysregulation of specific miRNAs is associated with several disorders (e.g., cancer, cardiovascular diseases, etc.). It is believed that miRNAs also play a role in aging, immunosenescence and inflammation but also frailty [ 64 , 88 , 89 , 90 , 91 , 92 ]. By consequence, miRNA signatures could also be interesting as potential aging/immunosenescence/inflammation markers, especially since plasma miRNAs have recently been recognized as sensitive, specific and extremely stable biomarkers [ 64 , 88 , 89 ].…”

“…The miR-17–92 cluster and miR-155 are highly involved in immunological processes [ 89 , 90 ] and important inflammatory miRNAs are miR-155 and miR-21 [ 64 , 91 ]. Additionally, the expression levels of particular miRNAs seem to correlate with clinical frailty, e.g., miR-92a and miR-326 [ 92 ]. In our own biomarker study six immune-related plasma miRNAs showed different expression levels between different age groups.…”

Blood Immunosenescence Signatures Reflecting Age, Frailty and Tumor Immune Infiltrate in Patients with Early Luminal Breast Cancer

“…Like aging, frailty is associated with profound biological alterations. Increased levels of inflammatory mediators (e.g., interleukin (IL)-6, tumor necrosis factor alpha (TNF-α)) have been observed in the blood [ 16 ], as well as differential expression of circulating microRNAs (miRNAs) (e.g., miR-92a, miR-326,…) [ 17 ], alterations in immune cell populations (e.g., loss of CD28 expression and/or increased expression of CD57 on T-cells) [ 18 ] and increased expression of P16 INK4a in T-cells [ 19 ].…”

“…. ) [17], alterations in immune cell populations (e.g., loss of CD28 expression and/or increased expression of CD57 on T-cells) [18] and increased expression of P16 INK4a in T-cells [19].…”