The role of autoantibodies in bridging obesity, aging, and immunosenescence

Abstract Antibodies are essential to immune homeostasis due to their roles in neutralizing pathogenic agents. However, failures in central and peripheral checkpoints that eliminate autoreactive B cells can undermine self-tolerance and generate autoantibodies that mistakenly target self-antigens, lea...

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Main Authors: Taylor R. Valentino, Nan Chen, Priya Makhijani, Saad Khan, Shawn Winer, Xavier S. Revelo, Daniel A. Winer
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Immunity & Ageing
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Online Access:https://doi.org/10.1186/s12979-024-00489-2
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author Taylor R. Valentino
Nan Chen
Priya Makhijani
Saad Khan
Shawn Winer
Xavier S. Revelo
Daniel A. Winer
author_facet Taylor R. Valentino
Nan Chen
Priya Makhijani
Saad Khan
Shawn Winer
Xavier S. Revelo
Daniel A. Winer
author_sort Taylor R. Valentino
collection DOAJ
description Abstract Antibodies are essential to immune homeostasis due to their roles in neutralizing pathogenic agents. However, failures in central and peripheral checkpoints that eliminate autoreactive B cells can undermine self-tolerance and generate autoantibodies that mistakenly target self-antigens, leading to inflammation and autoimmune diseases. While autoantibodies are well-studied in autoimmune and in some communicable diseases, their roles in chronic conditions, such as obesity and aging, are less understood. Obesity and aging share similar aspects of immune dysfunction, such as diminished humoral responses and heightened chronic inflammation, which can disrupt immune tolerance and foster autoantigen production, thus giving rise to autoreactive B cells and autoantibodies. In return, these events may also contribute to the pathophysiology of obesity and aging, to the associated autoimmune disorders linked to these conditions, and to the development of immunosenescence, an age-related decline in immune function that heightens vulnerability to infections, chronic diseases, and loss of self-tolerance. Furthermore, the cumulative exposure to antigens and cellular debris during obesity and aging perpetuates pro-inflammatory pathways, linking immunosenescence with other aging hallmarks, such as proteostasis loss and mitochondrial dysfunction. This review examines the mechanisms driving autoantibody generation during obesity and aging and discusses key putative antigenic targets across these conditions. We also explore the therapeutic potential of emerging approaches, such as CAR-T/CAAR-T therapies, vaccines, and BiTEs, to tackle autoimmune-related conditions in aging and obesity.
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spelling doaj-art-1cdb5fee36fd43eb88ea9741c400c57a2025-08-20T02:49:16ZengBMCImmunity & Ageing1742-49332024-11-0121112510.1186/s12979-024-00489-2The role of autoantibodies in bridging obesity, aging, and immunosenescenceTaylor R. Valentino0Nan Chen1Priya Makhijani2Saad Khan3Shawn Winer4Xavier S. Revelo5Daniel A. Winer6Buck Institute for Research on AgingDepartment of Laboratory Medicine and Pathobiology, University of TorontoBuck Institute for Research on AgingDivision of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health NetworkDepartment of Laboratory Medicine and Pathobiology, University of TorontoDepartment of Integrative Biology & Physiology, University of MinnesotaBuck Institute for Research on AgingAbstract Antibodies are essential to immune homeostasis due to their roles in neutralizing pathogenic agents. However, failures in central and peripheral checkpoints that eliminate autoreactive B cells can undermine self-tolerance and generate autoantibodies that mistakenly target self-antigens, leading to inflammation and autoimmune diseases. While autoantibodies are well-studied in autoimmune and in some communicable diseases, their roles in chronic conditions, such as obesity and aging, are less understood. Obesity and aging share similar aspects of immune dysfunction, such as diminished humoral responses and heightened chronic inflammation, which can disrupt immune tolerance and foster autoantigen production, thus giving rise to autoreactive B cells and autoantibodies. In return, these events may also contribute to the pathophysiology of obesity and aging, to the associated autoimmune disorders linked to these conditions, and to the development of immunosenescence, an age-related decline in immune function that heightens vulnerability to infections, chronic diseases, and loss of self-tolerance. Furthermore, the cumulative exposure to antigens and cellular debris during obesity and aging perpetuates pro-inflammatory pathways, linking immunosenescence with other aging hallmarks, such as proteostasis loss and mitochondrial dysfunction. This review examines the mechanisms driving autoantibody generation during obesity and aging and discusses key putative antigenic targets across these conditions. We also explore the therapeutic potential of emerging approaches, such as CAR-T/CAAR-T therapies, vaccines, and BiTEs, to tackle autoimmune-related conditions in aging and obesity.https://doi.org/10.1186/s12979-024-00489-2AutoantibodiesObesityAgingImmunosenescenceChronic inflammation
spellingShingle Taylor R. Valentino
Nan Chen
Priya Makhijani
Saad Khan
Shawn Winer
Xavier S. Revelo
Daniel A. Winer
The role of autoantibodies in bridging obesity, aging, and immunosenescence
Immunity & Ageing
Autoantibodies
Obesity
Aging
Immunosenescence
Chronic inflammation
title The role of autoantibodies in bridging obesity, aging, and immunosenescence
title_full The role of autoantibodies in bridging obesity, aging, and immunosenescence
title_fullStr The role of autoantibodies in bridging obesity, aging, and immunosenescence
title_full_unstemmed The role of autoantibodies in bridging obesity, aging, and immunosenescence
title_short The role of autoantibodies in bridging obesity, aging, and immunosenescence
title_sort role of autoantibodies in bridging obesity aging and immunosenescence
topic Autoantibodies
Obesity
Aging
Immunosenescence
Chronic inflammation
url https://doi.org/10.1186/s12979-024-00489-2
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