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T cells are particularly vulnerable to thymic involution, hematopoietic stem cell aging, repeated homeostatic proliferation, chronic antigenic stimulation, and metabolic and mitochondrial dysfunction. As a result, aged T cells may lose their capacity to combat infection and eliminate senescent cells, while also contributing to inflammaging through the production of inflammatory cytokines. Recent preclinical studies in murine models have demonstrated that modulation of T-cell immunosenescence can ameliorate age-related diseases. These approaches include PD-1\/PD-L1 blockade, senolytic chimeric antigen receptor T (CAR-T) cells, and CXCL4\/platelet factor 4 (PF4). In addition, early-stage human clinical studies of caloric restriction, low-dose mTOR inhibition, thymic regeneration, and mesenchymal stromal\/stem cell (MSC) therapy suggest that interventions targeting immunosenescence may provide health benefits. Moreover, in murine models of Alzheimer\u2019s disease, T cells infiltrating the brain may exert either disease-promoting or protective effects depending on the disease stage, highlighting an important point of intersection between T-cell-mediated immunosenescence and brain aging. This review summarizes the basic concepts of immunosenescence, the molecular basis of immune surveillance of senescent cells, age-associated T-cell subsets, their links to brain aging, and interventional strategies aimed at clinical translation, with particular emphasis on T-cell biology and the transcriptional regulatory network driven by NR4a.<\/jats:p>","DOI":"10.1186\/s41232-026-00419-3","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T07:44:20Z","timestamp":1777016660000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Senescence of T cells and organ aging"],"prefix":"10.1186","volume":"46","author":[{"given":"Masaki","family":"Ohyagi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minako","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"issue":"1","key":"419_CR1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1158\/2767-9764.CRC-21-0034","volume":"1","author":"M Ando","year":"2021","unstructured":"Ando M, Kondo T, Tomisato W, Ito M, Shichino S, Srirat T, et al. 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