甘草酸通过结合S100钙结合蛋白A8抑制造血干细胞的髓系分化，从而改善老年小鼠的认知能力。
Glycyrrhizic acid inhibits myeloid differentiation of hematopoietic stem cells by binding S100 calcium binding protein A8 to improve cognition in aged mice.
作者信息
Gong Xue, Shen Haitao, Guo Liuling, Huang Ce, Su Tingting, Wang Hao, Feng Shengyu, Yang Shanshan, Huo Fenjiao, Liu Haifeng, Zhu Jianbo, Zhu Jian-Kang, Li Hongbin, Liu Hailiang
机构信息
Key Laboratory of Xinjiang Phytomedicine Resource and Utilization of Ministry of Education, College of Life Sciences, Shihezi University, Shihezi, 832003, China.
Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China.
出版信息
Immun Ageing. 2023 Mar 11;20(1):12. doi: 10.1186/s12979-023-00337-9.
BACKGROUND
Glycyrrhizic acid (GA), a saponin compound often used as a flavoring agent, can elicit anti-inflammatory and anti-tumor effects, and alleviate aging. However, the specific mechanism by which GA alters immune cell populations to produce these beneficial effects is currently unclear.
RESULTS
In this study, we systematically analyzed single-cell sequencing data of peripheral blood mononuclear cells from young mice, aged mice, and GA-treated aged mice. Our in vivo results show 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 LinCD117 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 S100 calcium-binding protein 8 (S100A8) protein. Overexpression of S100A8 in Lin CD117 hematopoietic stem cells enhanced cognition in aged mice and the immune reconstitution of severely immunodeficient B-NDG (NOD.CB17-Prkdcscid/l2rgtm1/Bcgen) mice.
CONCLUSIONS
Collectively, GA exerts anti-aging effects by binding to S100A8 to remodel the immune system of aged mice.
背景
甘草酸（GA）是一种常用作调味剂的皂苷类化合物，具有抗炎、抗肿瘤作用，并可延缓衰老。然而，GA改变免疫细胞群体以产生这些有益作用的具体机制目前尚不清楚。
结果
在本研究中，我们系统分析了来自年轻小鼠、老年小鼠和GA处理的老年小鼠外周血单个核细胞的单细胞测序数据。我们的体内结果表明，GA减少了衰老诱导的巨噬细胞和中性粒细胞增加，并增加了衰老特异性减少的淋巴谱系亚群数量。在体外，GA显著促进LinCD117造血干细胞向淋巴谱系分化，尤其是CD8 T细胞。此外，GA通过与S100钙结合蛋白8（S100A8）蛋白结合抑制CD4 T细胞和髓样（CD11b）细胞分化。在Lin CD117造血干细胞中过表达S100A8可增强老年小鼠的认知能力，并促进严重免疫缺陷的B-NDG（NOD.CB17-Prkdcscid/l2rgtm1/Bcgen）小鼠的免疫重建。
结论
总体而言，GA通过与S100A8结合重塑老年小鼠免疫系统发挥抗衰老作用。
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