miR-126-3p and miR-21-5p as Hallmarks of Bio-Positive Ageing; Correlation Analysis and Machine Learning Prediction in Young to Ultra-Centenarian Sicilian Population.
Human ageing can be characterized by a profile of circulating microRNAs (miRNAs), which
are potentially predictors of biological age. They can be used as a biomarker of risk for age-related
inflammatory outcomes, and senescent endothelial cells (ECs) have emerged as a possible source
of circulating miRNAs. In this paper, a panel of four circulating miRNAs including miR-146a-5p,
miR-126-3p, miR-21-5p, and miR-181a-5p, involved in several pathways related to inflammation, and
ECs senescence that seem to be characteristic of the healthy ageing phenotype. The circulating levels
of these miRNAs were determined in 78 healthy subjects aged between 22 to 111 years. Contextually,
extracellular miR-146a-5p, miR-126-3p, miR-21-5p, and miR-181a-5p levels were measured in human
ECs in vitro model, undergoing senescence. We found that the levels of the four miRNAs, using ex
vivo and in vitro models, progressively increase with age, apart from ultra-centenarians that showed
levels comparable to those measured in young individuals. Our results contribute to the development
of knowledge regarding the identification of miRNAs as biomarkers of successful and unsuccessful
ageing. Indeed, they might have diagnostic/prognostic relevance for age-related diseases