Journal
JOURNAL OF EXTRACELLULAR VESICLES
Volume 9, Issue 1, Pages -Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/20013078.2020.1725285
Keywords
Cellular senescence; microRNAs; DNMT1; SIRT1; extracellular vesicles
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Funding
- Marche Region, Italy (POR Marche FESR 2014-2020) [PrInTAGE 10439]
- Universita Politecnica delle Marche
- Universita Politecnica delle Marche (MIR-AGE -Multidisciplinary Innovative Research Actions on AGE)
- Italian Ministry of Health
- European Union [721815]
- Fondazione Umberto Veronesi
- Marie Curie Actions (MSCA) [721815] Funding Source: Marie Curie Actions (MSCA)
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The role of epigenetics in endothelial cell senescence is a cutting-edge topic in ageing research. However, little is known of the relative contribution to pro-senescence signal propagation provided by microRNAs shuttled by extracellular vesicles (EVs) released from senescent cells. Analysis of microRNA and DNA methylation profiles in non-senescent (control) and senescent (SEN) human umbilical vein endothelial cells (HUVECs), and microRNA profiling of their cognate small EVs (sEVs) and large EVs demonstrated that SEN cells released a significantly greater sEV number than control cells. sEVs were enriched in miR-21-5p and miR-217, which target DNMT1 and SIRT1. Treatment of control cells with SEN sEVs induced a miR-21/miR-217-related impairment of DNMT1-SIRT1 expression, the reduction of proliferation markers, the acquisition of a senescent phenotype and a partial demethylation of the locus encoding for miR-21. MicroRNA profiling of sEVs from plasma of healthy subjects aged 40-100 years showed an inverse U-shaped age-related trend for miR-21-5p, consistent with senescence-associated biomarker profiles. Our findings suggest that miR-21-5p/miR-217 carried by SEN sEVs spread pro-senescence signals, affecting DNA methylation and cell replication.
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