Acronimo: VISTA

Titolo: extracellular Vesicles In Slowing down the Ticking clock of Aging

Codice Progetto: 20223FW48B

Responsabile scientifico per il DMM: Prof. Mario Vincenzo Di Iorio
Coordinatore: Università degli Studi di PERUGIA - Prof.ssa Ilaria BELLEZZA

Partner-Unità di ricerca: Università degli Studi di PADOVA

Bando: PRIN 2022 - Decreto Direttoriale n. 104 del 02-02-2022
Durata: 28/09/2023 - 27/09/2025 (24 mesi)

Finanziamento progetto: € 193.803,00 - CUP C53D23003010006

 

Abstract del progetto

Age-associated chronic diseases are placing a tremendous burden on healthcare systems. The dissection of mechanisms driving aging and the development of novel therapeutics are urgent needs. Aging is characterised by the loss of stem cells (SCs) regenerative capacity which impairs the ability to respond to stress. However, physiological aging, which does not always result in age-associated diseases, differs from accelerated aging, which compromise tissue functions later in life. Thus, a cellular model recapitulating accelerated SCs aging will permit to delineate the molecular signature of age-associated diseases. In this scenario, oral mucosa derived epithelial SCs (OMESCs) from patients affected by EEC syndrome, represent a valuable resource since they undergo an accelerated aging process. All cells, including SCs, produce and secrete extracellular vesicles (EVs), membrane-enclosed particles devoted to cell-cell communication. EVs cargo composition is affected by the aging process. Our project aims to analyse EVs derived from SCs at different aging stages and their potential to control the behaviour of immune, endothelial and SCs to identify molecular pathways to be tackled for assuring healthy aging. To reach these goals, the project will be divided in 4 work packages (WP) developed by two research units (RUs) based in University of Perugia and University of Padua. Fondazione Banca degli Occhi del Veneto ONLUS, providing OMESCs cells for functional analyses and their conditioned medium for EVs isolation, will be involved as subunit. In WP1 we will perform the analysis of OMESC at different aged stages and the characterization of their EVs. We will obtain a deep miRNomic and proteomic characterization of EVs from OMESCs at different stages of aging. In WP2 we will elucidate whether OMESC-EVs differentially alter inflammatory responses and endothelial cell fitness. In WP3 we will define the role of OMESC-EVs on corneal keratinocytes fitness. In WP4 we aim to identify molecular candidates for the observed effects, paving the way for the identification EVs-carried molecules that can be recognized as targets for the prevention of aging-associated diseases. This project is expected to give important insights into the involvement of EVs in the mechanisms of aging induced by the accelerated epithelial SC aging. The novelty of this project resides in the molecular and functional characterization of EVs isolated from a model of prematurely aged SCs. The extensive functional portrait of the EVs from our cell models, will contribute to understand the effects on target cells which, together with the deep molecular characterization of the EVs cargo will be fundamental to define the molecular cargo selectively included in EVs during the aging process. The discovery of the EVs molecular signature of aging may allow the identification of druggable pharmacological targets and propose EVs administration as cell-free option to prevent accelerated epithelial aging.