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Small Extracellular Vesicles Have GST Activity and Ameliorate Senescence-Related Tissue Damage.

Authors
  • Fafián-Labora, Juan Antonio1
  • Rodríguez-Navarro, Jose Antonio2
  • O'Loghlen, Ana3
  • 1 Epigenetics & Cellular Senescence Group, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.
  • 2 Instituto Ramón y Cajal de Investigaciones Sanitarias, Neurobiología-Investigación, Hospital Ramón y Cajal, Ctra Colmenar km 9.1, 28034 Madrid, Spain. Electronic address: [email protected] , (Spain)
  • 3 Epigenetics & Cellular Senescence Group, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK. Electronic address: [email protected]
Type
Published Article
Journal
Cell metabolism
Publication Date
Jul 07, 2020
Volume
32
Issue
1
Identifiers
DOI: 10.1016/j.cmet.2020.06.004
PMID: 32574561
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Aging is a process of cellular and tissue dysfunction characterized by different hallmarks, including cellular senescence. However, there is proof that certain features of aging and senescence can be ameliorated. Here, we provide evidence that small extracellular vesicles (sEVs) isolated from primary fibroblasts of young human donors ameliorate certain biomarkers of senescence in cells derived from old and Hutchinson-Gilford progeria syndrome donors. Importantly, sEVs from young cells ameliorate senescence in a variety of tissues in old mice. Mechanistically, we identified sEVs to have intrinsic glutathione-S-transferase activity partially due to the high levels of expression of the glutathione-related protein (GSTM2). Transfection of recombinant GSTM2 into sEVs derived from old fibroblasts restores their antioxidant capacity. sEVs increase the levels of reduced glutathione and decrease oxidative stress and lipid peroxidation both in vivo and in vitro. Altogether, our data provide an indication of the potential of sEVs as regenerative therapy in aging. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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