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Therefore, targeting oxidative stress has emerged as a potential strategy. Pyrroloquinoline quinone (PQQ), a potent antioxidant, has demonstrated significant efficacy in reducing oxidative stress and modulating immune responses, making it a promising therapeutic candidate. In this study, we investigated the effects of aging on the hematopoietic immune system (HIS) through single\u2010cell RNA sequencing (scRNA\u2010seq) of spleen and bone marrow cells in murine models. Our results revealed widespread age\u2010related inflammation and oxidative stress within immune cell populations. Notably, long\u2010term PQQ supplementation improved physiological parameters and reduced blood inflammatory factors levels in aged mice. Subsequent scRNA\u2010seq analysis demonstrated that PQQ supplementation effectively reduced oxidative stress levels across various HIS cell types and reversed aging\u2010related phenotypes, such as inflammatory responses and immunosenescence. Additionally, PQQ reversed aging\u2010induced disrupted signaling and restored immune homeostasis, particularly in B cells and hematopoietic stem cells (HSCs). Importantly, we identified critical molecular targets, including ASPP1, which mediates PQQ's anti\u2010apoptotic effects in B cells, and Yy1 and CD62L, which were upregulated by PQQ to restore HSCs self\u2010renewal and differentiation potential. Furthermore, the machine learning program and experimental validation demonstrated the senolytic and senomorphic effects of PQQ in\u00a0vivo and vitro. These findings underscore PQQ's potential not only in mitigating oxidative stress but also in restoring immune homeostasis and promoting cellular regeneration, highlighting its therapeutic potential in addressing immune aging and improving physiological function.<\/jats:p>","DOI":"10.1111\/acel.70050","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T16:14:07Z","timestamp":1744042447000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pyrroloquinoline Quinone Reprograms the Single\u2010Cell Landscape of Immune Aging in Hematopoietic Immune System"],"prefix":"10.1111","volume":"24","author":[{"given":"Xiuxing","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology West China Hospital, Sichuan University  Chengdu Sichuan China"},{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center, Sun Yat\u2010sen University, Guangdong 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