Identification of Senomorphic miRNAs in Embryonic Progenitor and Adult Stem Cell-Derived Extracellular Vesicles.

Tianpeng Zhang, Allancer D C Nunes, Jieun Lee, Dana Larocca, Giovanni Camussi, Sai Kiang Lim, Vicky U Bascones, Luise Angelini, Ryan D O'Kelly, Xiao Dong, Laura J Niedernhofer, Paul D Robbins

Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA.Masonic Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, Minnesota, USA. · pubmed

Paper

Abstract

Extracellular vesicles (EVs) are secreted by most cell types, transmitting crucial signaling molecules like proteins, small RNAs, and DNA. We previously demonstrated that EVs from murine and human mesenchymal stem cells (MSCs) functioned as senomorphics to suppress markers of senescence and the inflammatory senescence-associated secretory phenotype (SASP) in cell culture and in aged mice. Here we demonstrate that EVs from additional types of human adult stem cells and embryonic progenitor cells have a senomorphic activity. Based on their miRNA profiles showing prevalence in stem cell EVs versus nonstem cell EVs and the number of age-related genes targeted, we identified eight miRNAs as potential senomorphic miRNAs. Analysis of these miRNAs by transfection into etoposide-induced senescent IMR90 human fibroblasts revealed that each of the miRNAs alone regulated specific senescence and SASP markers, but none had complete senomorphic activity. Evaluation of ~300 combinations of miRNAs for senotherapeutic activity identified a senomorphic cocktail of miR-181a-5p, miR-92a-3p, miR-21-5p, and miR-186-5p that markedly reduced the expression of p16

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Research summary

The paper identifies specific miRNAs in extracellular vesicles that exhibit senomorphic activity, potentially targeting the mechanisms of cellular senescence. This research is relevant as it explores the underlying biological processes of aging and seeks to mitigate senescence, which is a key contributor to age-related decline.

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