Age-related oxidative stress compromises endosomal proteostasis
Elvira S Cannizzo1, Cristina C Clement, Kateryna Morozova
1Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Cell Reports
|July 31, 2012
Summary
Aging impairs immune function by causing oxidatively damaged proteins to accumulate in antigen-presenting cells. Reducing oxidative stress enhances the adaptive immune response, highlighting a link between aging, proteostasis, and immunity.
Area of Science:
- Immunology
- Cellular Biology
- Aging Research
Background:
- Aging is characterized by an imbalance in reactive oxygen species (ROS) and accumulation of damaged biomolecules.
- Oxidative stress and impaired proteostasis are implicated in age-related functional decline.
Purpose of the Study:
- To investigate the accumulation of oxidatively modified proteins in antigen-presenting cells (APCs) during aging.
- To determine the impact of these modifications on antigen processing and immune response.
Main Methods:
- Purification of splenic and nodal APCs from aging mice.
- Analysis of protein modifications including carbonylation, advanced glycation end products, and lipid peroxidation.
- Assessment of antigen processing and immune response following reduction of oxidative stress.
Main Results:
- Aging APCs accumulate oxidatively modified proteins, including side-chain carbonylation, advanced glycation end products, and lipid peroxidation.
- Endosomal accumulation of these oxidized proteins impairs exogenous antigen processing and macroautophagy-delivered protein degradation.
- Decreasing oxidative stress improved the adaptive immune response to antigens.
Conclusions:
- Age-dependent accumulation of oxidatively modified proteins in APCs negatively impacts immune function.
- Impaired proteostasis in aging APCs contributes to inefficient immune responses.
- Targeting oxidative stress may be a strategy to improve age-related immune dysfunction.
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