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Age-related oxidative stress compromises endosomal proteostasis.

Authors
  • Cannizzo, Elvira S1
  • Clement, Cristina C
  • Morozova, Kateryna
  • Valdor, Rut
  • Kaushik, Susmita
  • Almeida, Larissa N
  • Follo, Carlo
  • Sahu, Ranjit
  • Cuervo, Ana Maria
  • Macian, Fernando
  • Santambrogio, Laura
  • 1 Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Publication Date
Jul 26, 2012
Volume
2
Issue
1
Pages
136–149
Identifiers
DOI: 10.1016/j.celrep.2012.06.005
PMID: 22840404
Source
Medline
License
Unknown

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 aging mice accumulate oxidatively modified proteins with side-chain carbonylation, advanced glycation end products, and lipid peroxidation. Furthermore, we show 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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