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However, the underlying mechanisms and organ specificity remain unclear. Utilizing a 12\u2010month unpredictable chronic mild stress (UCMS) mouse model, we revealed chronic stress significantly exacerbates systemic inflammation, causing widespread tissue damage and lifespan shortening. Integrated single\u2010cell RNA sequencing analysis of multiple tissues suggests a common feature of lymphocyte reduction and myeloid cell expansion. The lungs and kidneys exhibited pronounced stress responses, including epigenetic dysregulation and mitochondrial dysfunction. Both \u03b2\u2010nicotinamide mononucleotide (NMN) and compound medicine Bazi Bushen (BZBS) effectively alleviate the UCMS\u2010induced aging phenotypes. BZBS restores immune system homeostasis and reduces stress\/inflammation levels in various tissues. Bioactive compounds from BZBS constituents\n                    <jats:italic>\u2014Schisandra chinensis (Turcz.) Baill. and Cnidium monnieri (L.) Cusson\u2014<\/jats:italic>\n                    improved mitochondrial function via AMPK\u2010SIRT\u2010PGC\u20101\u03b1 signaling activation. The present study underscores the importance of early intervention in chronic stress to prevent or delay age\u2010related diseases, with significant implications for public health strategies aimed at healthy aging.\n                  <\/jats:p>","DOI":"10.1002\/exp2.70235","type":"journal-article","created":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T09:55:47Z","timestamp":1791712547000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reversal of Chronic Stress\u2010Induced Inflammaging by Bazi Bushen Formula Through AMPK\u2010Sirtuins Axis Activation and Myeloid Reset"],"prefix":"10.1002","author":[{"given":"Mengnan","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory For Innovation and Transformation of Luobing Theory  Shijiazhuang China"},{"name":"Hebei Provincial Administration of Traditional Chinese Medicine Anti\u2010Aging Research Key Laboratory  Shijiazhuang China"},{"name":"Hebei Medical University  Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheming","family":"Chen","sequence":"additional","affiliation":[{"name":"LC\u2010BIO Technologies CO., LTD.  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