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.

Age-related oxidative stress compromises endosomal proteostasis / E.S. Cannizzo, C.C. Clement, K. Morozova, R. Valdor, S. Kaushik, L.N. Almeida, C. Follo, R. Sahu, A.M. Cuervo, F. Macian, L. Santambrogio. - In: CELL REPORTS. - ISSN 2211-1247. - 2:1(2012), pp. 136-149.

Age-related oxidative stress compromises endosomal proteostasis

E.S. Cannizzo
Primo
;
2012

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.
Aging; Animals; Cells, Cultured; Dendritic Cells; Endosomes; Glycosylation End Products, Advanced; Homeostasis; Lymphatic System; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Models, Biological; Oxidation-Reduction; Oxidative Stress; Protein Processing, Post-Translational; Proteins; Reactive Oxygen Species; Biochemistry, Genetics and Molecular Biology (all)
Settore MED/04 - Patologia Generale
2012
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/483073
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