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

doi:10.1016/j.celrep.2012.06.005

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^*

^*Corresponding author for this work

Institute of Systemic Inflammation Research

Albert Einstein College of Medicine of Yeshiva University

84 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 language	English
Journal	Cell Reports
Volume	2
Issue number	1
Pages (from-to)	136-149
Number of pages	14
ISSN	2211-1247
DOIs	https://doi.org/10.1016/j.celrep.2012.06.005
Publication status	Published - 26.07.2012

Funding

This work was supported by the National Institutes of Health Grants AI48833 to L.S. and AG031782 and DK041918 to A.M.C., F.M., and L.S., and a National Institute on Aging Training Grant to S.K. L.N.A. was supported by the NIH Fogarty Geographic Infectious Diseases Training Grant D43TW007129.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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10.1016/j.celrep.2012.06.005

Cite this

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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 and Laura Santambrogio",

note = "Funding Information: This work was supported by the National Institutes of Health Grants AI48833 to L.S. and AG031782 and DK041918 to A.M.C., F.M., and L.S., and a National Institute on Aging Training Grant to S.K. L.N.A. was supported by the NIH Fogarty Geographic Infectious Diseases Training Grant D43TW007129. ",

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doi = "10.1016/j.celrep.2012.06.005",

language = "English",

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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, Fernando

AU - Santambrogio, Laura

N1 - Funding Information: This work was supported by the National Institutes of Health Grants AI48833 to L.S. and AG031782 and DK041918 to A.M.C., F.M., and L.S., and a National Institute on Aging Training Grant to S.K. L.N.A. was supported by the NIH Fogarty Geographic Infectious Diseases Training Grant D43TW007129.

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 - https://www.scopus.com/pages/publications/84864319448

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DO - 10.1016/j.celrep.2012.06.005

M3 - Journal articles

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AN - SCOPUS:84864319448

SN - 2211-1247

VL - 2

SP - 136

EP - 149

JO - Cell Reports

JF - Cell Reports

IS - 1

ER -

Age-related oxidative stress compromises endosomal proteostasis

Abstract

Funding

UN SDGs

Research Areas and Centers

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