PERSPECTIVE article
Front. Aging
Sec. Aging and the Immune System
Volume 6 - 2025 | doi: 10.3389/fragi.2025.1688060
Inflammasome Activation and Accelerated Immune Aging in Autoimmune Disorders
Provisionally accepted
- 1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, United States
- 2University of Miami Miller School of Medicine, Miami, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Abstract Autoimmune diseases, particularly those with early onset such as systemic lupus erythematosus, juvenile idiopathic arthritis, and type 1 diabetes, are paradoxically characterized by molecular and cellular features typically associated with aging. These include telomere shortening, mitochondrial dysfunction, epigenetic alterations, and skewed immune cell phenotypes, which are considered hallmarks of immunosenescence. This perspective explores the hypothesis that aberrant inflammasome activation, particularly of the NLRP3 complex, serves as a key upstream driver of premature immune aging in autoimmunity. We examine how chronic inflammasome signaling induces senescence through pro-inflammatory cytokine production and oxidative stress, reinforces the senescence-associated secretory phenotype (SASP), and perpetuates immune dysregulation. By reframing autoimmunity as a disorder of accelerated immune aging, we highlight emerging opportunities for therapeutic intervention using senolytics, inflammasome inhibitors, and lifestyle modifications. In addition, incorporating biomarkers of immune aging into clinical assessment may enable precision immunogerontology, particularly in pediatric populations where biological and chronological age may be dissociated. Elucidating the relationship between inflammasome signaling and immune senescence provides a critical framework for understanding autoimmune pathogenesis and for developing interventions that modify disease course by targeting age-associated mechanisms.
Keywords: cellular senescence, senescence-associated secretory phenotype (SASP), Inflammaging, Immune senescence, Autoimmunity
Received: 18 Aug 2025; Accepted: 17 Sep 2025.
Copyright: © 2025 Mittal, Saavedra, Mittal, Lemos and Hirani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rahul Mittal, r.mittal11@med.miami.edu
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.