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Understanding how aging alters the transcriptomic landscape of HSPCs is critical to uncovering the origins of immune system aging. We performed a comprehensive single\u2010cell RNA sequencing analysis integrating over 300,000 bone marrow\u2010derived HSPCs from 50 healthy individuals spanning 19 to 84 years of age. Aging was associated with immune lineage skewing, marked by increased myeloid and decreased lymphoid output in both bone marrow and peripheral blood. Subtle increases in HSCs, MEPs, and myeloid progenitors alongside reductions in lymphoid progenitors were already evident in aged bone marrow, suggesting that lineage bias is encoded at the progenitor level. Age\u2010associated transcriptional changes included extensive upregulation of ribosomal genes encoding small (RPS11, RPS12, RPS23) and large (RPL9, RPL19, RPL24) cytoplasmic ribosomal subunit proteins, as well as pro\u2010inflammatory mediators (IL1B, IL18, TGFB1, S100A8). Enrichment analysis identified mitochondrial function, ribosome biogenesis, chromatin remodeling, and inflammatory signaling as key ontologies disrupted during HSPC aging. Our study identifies molecular signatures of systemic aging rooted in bone marrow HSPCs and suggests that dysregulated ribosomal protein gene expression is an under\u2010appreciated hallmark of hematopoietic stem cell aging.<\/jats:p>","DOI":"10.1002\/adbi.70150","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T07:26:07Z","timestamp":1786692367000},"source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Cell Analyses Reveal Dysregulation of Ribosomal Protein Genes During Hematopoietic Stem and Progenitor Cell Aging"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7644-6326","authenticated-orcid":false,"given":"Roger","family":"Atanga","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology R Ken Coit College of Pharmacy University of Arizona  Tucson Arizona USA"},{"name":"Coit Center For Longevity and Neurotherapeutics R Ken Coit College of Pharmacy University of Arizona 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