Publication:
Age-related oxidative stress compromises endosomal proteostasis

relationships.isAuthorOfPublication
relationships.isSecondaryAuthorOf
relationships.isDirectorOf
Authors
Cannizzo, Elvira S. ; Clement, Cristina C. ; Morozova, Kateryna ; Valdor, Rut ; Kaushik, Susmita ; Almeida, Larissa N. ; Follo, Carlo ; Sahu, Ranjit ; Cuervo, Ana María ; Macian, Fernando ; Santambrogio, Laura
item.page.secondaryauthor
item.page.director
Publisher
publication.page.editor
Description
© 2012 The Authors. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted Manuscript version of a Published Work that appeared in final form in Cell Reports. To access the final edited and published work see https://doi.org/10.1016/j.celrep.2012.06.005
Abstract
A hallmark of aging is an imbalance between production and clearance of reactive oxygen species and increased levels of oxidatively damaged biomolecules. Herein we demonstrate that splenic and nodal antigen presenting cells purified from old mice accumulate oxidatively modified proteins with side chain carbonylation, advanced glycation end products and lipid peroxidation. We show further that the endosomal accumulation of oxidatively modified proteins interferes with the efficient processing of exogenous antigens and degradation of macroautophagy-delivered proteins. In support of a causative role for oxidized products in the inefficient immune response, a decrease in oxidative stress improved the adaptive immune response to immunizing antigens. These findings underscore a previously unrecognized negative effect of age-dependent changes in cellular proteostasis on the immune response.
publication.page.subject
Citation
item.page.embargo
Collections