Single-cell RNA sequencing analysis combined with bulk RNA sequencing revealed changes in the micro-environment of bone marrow aging

Aging cells in the bone marrow contribute to bone aging and related diseases. By combining single-cell and bulk RNA analysis, we aim to better understand the changes in the bone marrow micro-environment caused by aging. We established single-cell profiles of bone marrow from young and aging mice to identify cell types that exhibited significant aging-related changes. And differential gene enrichment analysis and cell-cell communication analysis were conducted on cells with significant changes. Then, we validated the enrichment analysis results using bulk RNA sequencing. Based on sequencing data and machine learning, we identified key genes involved in cellular aging. And the best anti-aging drugs were screened through molecular docking. Finally, the communication between cells, effectiveness of drugs and key genes were validated through experiments. In the aged bone marrow, the content of mesenchymal stem cells (BMSCs) and macrophages (BMMs) significantly increases. The aging of bone marrow is related to cellular fibrosis, immune inflammatory response, resulting in reduced ossification and enhanced osteoclast differentiation. Aging BMSCs secrete various cytokines to promote the aging of BMMs, such as adiponectin, annexin, and galectin. The effect of aging BMMs on BMSCs is relatively small. CADM1 and FAP may be key targets for BMSCs and BMMs aging. Rapamycin has the highest binding affinity with target gene and can to some extent reverse the aging of bone marrow cells. Aged bone marrow cells can further spread aging, and the interaction between bone marrow cells helps us better understand bone aging.