Publication: Age-related oxidative stress compromises endosomal proteostasis
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
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© 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.
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