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-Juan, Laura Santambrogio

Research output: Contribution to journalArticle

42 Citations (Scopus)

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

Fingerprint

Oxidative stress
Oxidative Stress
Aging of materials
Carbonylation
Antigens
Advanced Glycosylation End Products
Proteins
Cell Aging
Autophagy
Antigen Presentation
Biomolecules
Adaptive Immunity
Antigen-Presenting Cells
Lipid Peroxidation
Reactive Oxygen Species
Lipids
Degradation
Processing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Age-related oxidative stress compromises endosomal proteostasis. / Cannizzo, Elvira S.; Clement, Cristina C.; Morozova, Kateryna; Valdor, Rut; Kaushik, Susmita; Almeida, Larissa N.; Follo, Carlo; Sahu, Ranjit; Cuervo, Ana Maria; Macian-Juan, Fernando; Santambrogio, Laura.

In: Cell Reports, Vol. 2, No. 1, 26.07.2012, p. 136-149.

Research output: Contribution to journalArticle

Cannizzo, ES, Clement, CC, Morozova, K, Valdor, R, Kaushik, S, Almeida, LN, Follo, C, Sahu, R, Cuervo, AM, Macian-Juan, F & Santambrogio, L 2012, 'Age-related oxidative stress compromises endosomal proteostasis', Cell Reports, vol. 2, no. 1, pp. 136-149. https://doi.org/10.1016/j.celrep.2012.06.005
Cannizzo ES, Clement CC, Morozova K, Valdor R, Kaushik S, Almeida LN et al. Age-related oxidative stress compromises endosomal proteostasis. Cell Reports. 2012 Jul 26;2(1):136-149. https://doi.org/10.1016/j.celrep.2012.06.005
Cannizzo, Elvira S. ; Clement, Cristina C. ; Morozova, Kateryna ; Valdor, Rut ; Kaushik, Susmita ; Almeida, Larissa N. ; Follo, Carlo ; Sahu, Ranjit ; Cuervo, Ana Maria ; Macian-Juan, Fernando ; Santambrogio, Laura. / Age-related oxidative stress compromises endosomal proteostasis. In: Cell Reports. 2012 ; Vol. 2, No. 1. pp. 136-149.
@article{9b9c7f29f96f401cb7e0021a605eb9c9,
title = "Age-related oxidative stress compromises endosomal proteostasis",
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.",
author = "Cannizzo, {Elvira S.} and Clement, {Cristina C.} and Kateryna Morozova and Rut Valdor and Susmita Kaushik and Almeida, {Larissa N.} and Carlo Follo and Ranjit Sahu and Cuervo, {Ana Maria} and Fernando Macian-Juan and Laura Santambrogio",
year = "2012",
month = "7",
day = "26",
doi = "10.1016/j.celrep.2012.06.005",
language = "English (US)",
volume = "2",
pages = "136--149",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Age-related oxidative stress compromises endosomal proteostasis

AU - Cannizzo, Elvira S.

AU - Clement, Cristina C.

AU - Morozova, Kateryna

AU - Valdor, Rut

AU - Kaushik, Susmita

AU - Almeida, Larissa N.

AU - Follo, Carlo

AU - Sahu, Ranjit

AU - Cuervo, Ana Maria

AU - Macian-Juan, Fernando

AU - Santambrogio, Laura

PY - 2012/7/26

Y1 - 2012/7/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84864319448&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864319448&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2012.06.005

DO - 10.1016/j.celrep.2012.06.005

M3 - Article

VL - 2

SP - 136

EP - 149

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 1

ER -