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Accumulating evidence indicates that LN stromal cells undergo degenerative changes with aging that critically impair LN function, including the generation of protective primary immune responses. The nature of these defects remains incompletely understood. We here demonstrate that age\u2010related LN stromal changes manifest themselves in mitochondrial dysfunction and oxidative stress. Ex\u00a0vivo, all three major stromal cell subsets, fibroblastic reticular cells (FRC), lymphatic endothelial cells (LEC), and blood endothelial cells (BEC) exhibit elevated mitochondrial reactive oxygen species (ROS) stress, reduced mitochondrial potential, and elevated mitochondrial mass with aging. Old FRC also exhibited elevated cytoplasmic ROS production. This was accompanied by the reduced ability of old LN stromal cells to support Tn survival in\u00a0vitro, a defect alleviated by pretreating old LN stroma with the general antioxidant <jats:italic>N<\/jats:italic>\u2010acetyl cysteine (NAC) as well as by mitochondrial ROS\u2010reducing (mitoquinone) and mitophagy\u2010inducing (urolithin A) compounds. Mitochondrial dysfunction and, in particular, reduced mitochondrial potential in old FRC were also seen upon vaccination or infection in\u00a0vivo. Consistent with these results, in\u00a0vivo antioxidant treatment of old mice with NAC restored to adult levels the numbers of antigen\u2010specific CD8<jats:sup>+<\/jats:sup> effector T cells and their production of granzyme B in response to antigenic challenge.<\/jats:p>","DOI":"10.1111\/acel.70100","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T18:39:57Z","timestamp":1747852797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Age\u2010Related Oxidative Stress and Mitochondrial Dysfunction in Lymph Node Stromal Cells Limit the Peripheral T Cell Homeostatic Maintenance and Function"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6193-5529","authenticated-orcid":false,"given":"Sandip Ashok","family":"Sonar","sequence":"first","affiliation":[{"name":"Department of Immunobiology University of Arizona College of Medicine\u2010Tucson  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