Glycyrrhizic Acid Inhibits Myeloid Differentiation of Hematopoietic Stem Cells and Improves Cognition in Aged Mice by Binding to the S100 Calcium-Binding Protein A8 [scRNA-seq]

Glycyrrhizic acid (GA) has numerous biological activities, but the mechanism by which it regulates the immune system and improves cognition in aged mice remains unclear. In this study, we analyzed single-cell sequencing data of peripheral blood mononuclear cells from young mice, aged mice, and GA-treated aged mice, and found that GA reduced senescence-induced increases in macrophages and neutrophils, and increased numbers of lymphoid lineage subpopulations specifically reduced by senescence. In vitro, GA significantly promoted differentiation of Lin-CD117+ hematopoietic stem cells toward lymphoid lineages, especially CD8+ T cells. Moreover, GA inhibited differentiation of CD4+ T cells and myeloid (CD11b+) cells by binding to the S100 calcium-binding protein 8 (S100A8). Overexpression of S100A8 in Lin- CD117+ hematopoietic stem cells enhanced cognition in aged mice and in immune reconstited severely immunodeficient B-NDG mice. Collectively, our results suggest that GA exerts anti-aging effects by binding to S100A8 to remodel the immune system of aged mice. We implemented single cell transcriptomic analyses of PBMC from young, aged and aged mice treatment with GA for 1 month .