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Here, we perform single\u2010cell transcriptomic profiling of bone marrow, spleen, mesenteric lymph nodes, and peripheral blood mononuclear cells from young and naturally aged male rhesus monkeys. Our study revealed extensive transcriptional remodeling across tissues, particularly the marked upregulation of GZMB expression across multiple cell types in aged monkeys, highlighting it as a candidate biomarker of immunosenescence. Gene regulatory network analysis identifies BHLHE40 as a key transcription factor enriched in multiple CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell subtypes during aging, regulating pro\u2010inflammatory and exhaustion\u2010related genes. We also observe an age\u2010associated expansion of CD8\n                    <jats:sup>+<\/jats:sup>\n                    central memory T cells with increased CCL5 and reduced IL7R expression, consistent with a shift toward a dysfunctional state. In the bone marrow, we discover a distinct na\u00efve B cell population with low PDCD4 expression that declines with age, potentially compromising humoral immunity. These findings offer a comprehensive single\u2010cell atlas of immune aging in a non\u2010human primate model, providing novel insights into cell\u2010type\u2010specific and tissue\u2010dependent features of immunosenescence. Our work establishes a valuable resource for future translational studies and biomarker discovery in human aging.\n                  <\/jats:p>","DOI":"10.1002\/advs.202514353","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T11:21:23Z","timestamp":1768908083000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Single\u2010Cell Profiling Across Immune Tissues and Organs Reveals Immunosenescence Signatures in Male Rhesus Monkeys"],"prefix":"10.1002","volume":"13","author":[{"given":"Shengnan","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Primate Biomedical Research Institute of Primate Translational Medicine Kunming University of Science and Technology  Kunming Yunnan China"},{"name":"Yunnan Key Laboratory of Primate Biomedical Research  Kunming Yunnan 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