Age-related oxidative stress compromises endosomal proteostasis

Elvira S. Cannizzo, Cristina C. Clement, Kateryna Morozova, Rut Valdor, Susmita Kaushik, Larissa N. Almeida, Carlo Follo, Ranjit Sahu, Ana Maria Cuervo, Fernando Macian, Laura Santambrogio

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42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)136-149
Number of pages14
JournalCell Reports
Volume2
Issue number1
DOIs
StatePublished - Jul 26 2012

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cannizzo, E. S., Clement, C. C., Morozova, K., Valdor, R., Kaushik, S., Almeida, L. N., Follo, C., Sahu, R., Cuervo, A. M., Macian, F., & Santambrogio, L. (2012). Age-related oxidative stress compromises endosomal proteostasis. Cell Reports, 2(1), 136-149. https://doi.org/10.1016/j.celrep.2012.06.005