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      Extracellular Vesicles as New Players in Cellular Senescence

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          Abstract

          Cell senescence is associated with the secretion of many factors, the so-called “senescence-associated secretory phenotype”, which may alter tissue microenvironment, stimulating the organism to clean up senescent cells and replace them with newly divided ones. Therefore, although no longer dividing, these cells are still metabolically active and influence the surrounding tissue. Much attention has been recently focused not only on soluble factors released by senescent cells, but also on extracellular vesicles as conveyors of senescence signals outside the cell. Here, we give an overview of the role of extracellular vesicles in biological processes and signaling pathways related to senescence and aging.

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          The Hallmarks of Aging

          Carlos López-Otín, Maria Blasco, Linda Partridge … (2014)
          Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

            Hadi Valadi, Karin Ekström, Apostolos Bossios … (2007)
            Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).
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              Biological properties of extracellular vesicles and their physiological functions

              María Yañez-Mó, Pia Siljander, Zoraida Andreu … (2015)
              In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
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                Author and article information

                Contributors
                Gregor Drummen: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 26 August 2016
                Publication date Collection: September 2016
                Volume: 17
                Issue: 9
                Electronic Location Identifier: 1408
                Affiliations
                [1 ]Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06123 Perugia, Italy; sandra.buratta@ 123456unipg.it (S.B.); krizia.sagini@ 123456studenti.unipg.it (K.S.); brunella.tancini@ 123456unipg.it (B.T.)
                [2 ]Centro di Eccellenza sui Materiali Innovativi Nanostrutturati (CEMIN), University of Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy
                Author notes
                [* ]Correspondence: lorena.urbanelli@ 123456unipg.it (L.U.); carla.emiliani@ 123456unipg.it (C.E.); Tel.: +39-075-585-7440 (L.U.); +39-075-585-7436 (C.E.); Fax: +39-075-585-7436 (L.U. & C.E.)
                Article
                Publisher ID: ijms-17-01408
                DOI: 10.3390/ijms17091408
                PMC ID: 5037688
                PubMed ID: 27571072
                SO-VID: df64c87d-c0cd-4b19-9294-13e37bd2c4cb
                Copyright © © 2016 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 22 July 2016
                Date accepted : 22 August 2016
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: senescence,aging,senescence-associated secretory phenotype (sasp),extracellular vesicles,exosomes,ectosomes,microvesicles
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: senescence, aging, senescence-associated secretory phenotype (sasp), extracellular vesicles, exosomes, ectosomes, microvesicles

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