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.
authors: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Elvira S
authors: ES
authors: Cannizzo
authors: Cristina C
authors: CC
authors: Clement
authors: Kateryna
authors: K
authors: Morozova
authors: Rut
authors: R
authors: Valdor
authors: Susmita
authors: S
authors: Kaushik
authors: Larissa N
authors: LN
authors: Almeida
authors: Carlo
authors: C
authors: Follo
authors: Ranjit
authors: R
authors: Sahu
authors: Ana Maria
authors: AM
authors: Cuervo
authors: Fernando
authors: F
authors: Macian
authors: Laura
authors: L
authors: Santambrogio
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology; D011992:Endosomes / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D008208:Lymphatic System / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008954:Models, Biological; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D011506:Proteins; D017382:Reactive Oxygen Species