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

miR-126-3p 和 miR-21-5p 是生物阳性衰老的标志;西西里岛年轻至百岁老人的相关性分析和机器学习预测

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作者:Giulia Accardi, Filippa Bono, Giuseppe Cammarata, Anna Aiello, Maria Trinidad Herrero, Riccardo Alessandro, Giuseppa Augello, Ciriaco Carru, Paolo Colomba, Maria Assunta Costa, Immaculata De Vivo, Mattia Emanuela Ligotti, Alessia Lo Curto, Rosa Passantino, Simona Taverna, Carmela Zizzo, Giovanni Dur

Abstract

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.

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