单细胞分析揭示了原花青素C1在造血免疫系统中通过衰老和同源效应的老年保护作用。

IF 4.1 Q2 GERIATRICS & GERONTOLOGY
Xiuxing Liu, Yidan Liu, Yuehan Gao, Chun Zhang, Chenyang Gu, Jianjie Lv, Junying Wu, Wenru Su
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引用次数: 0

摘要

造血和免疫系统(HIS)的老化导致细胞衰老和免疫失调,导致与年龄有关的疾病。在这里,我们发现原花青素C1 (PCC1),一种具有衰老和同形特性的化合物,可以抵消HIS中与衰老相关的变化。通过单细胞RNA测序和验证实验,我们发现衰老导致小鼠骨髓和脾脏组织的细胞衰老、炎症和免疫失调。长期PCC1治疗可改善老年小鼠的主要生理参数,尤其是握力。进一步的单细胞分析显示PCC1对HIS具有广泛的衰老保护作用,包括B细胞(bc)和造血干细胞(hsc)比例的增加,衰老相关标志物的抑制以及正常免疫过程的恢复。具体来说,PCC1通过抑制Cebpb表达和年龄相关的bc来减轻炎症和恢复bc的免疫稳态。此外,PCC1通过上调Nedd4和CD62L-Ca2+轴的表达,逆转了hsc中衰老诱导的改变。最后,我们利用机器学习和基因集富集分析鉴定了衰老细胞(SnCs),揭示了PCC1诱导SnCs凋亡并调节其代谢过程,特别是在粒细胞和髓细胞中。实验验证进一步证实了PCC1在体内和体外的抗衰老和同形作用。总的来说,PCC1有可能作为一种治疗药物,通过抗衰老和促衰老作用来缓解免疫功能障碍和促进健康衰老。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Single-cell profiling unveils a geroprotective role of Procyanidin C1 in hematopoietic immune system via senolytic and senomorphic effects.

Aging of hematopoietic and immune system (HIS) leads to cellular senescence and immune dysregulation, contributing to age-related diseases. Here, we show that Procyanidin C1 (PCC1), a compound with both senolytic and senomorphic properties, can counteract aging-related changes in HIS. Using single-cell RNA sequencing and validation experiments, we found that aging induced cellular senescence, inflammation, and immune dysregulation in the bone marrow and spleen tissues of mice. Long-term PCC1 treatment improved key physiological parameters especially the grip strength of aged mice. Further single-cell analysis revealed PCC1's broad geroprotective effects on HIS, including an increase in the proportion of B cells (BCs) and hematopoietic stem cells (HSCs), suppression of senescence-associated markers, and restoration of normal immune processes. Specifically, PCC1 mitigated inflammation and restored immune homeostasis in BCs by suppressing Cebpb expression and age-associated BCs. Moreover, PCC1 reversed aging-induced alterations in HSCs through upregulating Nedd4 and CD62L-Ca2+ axis expression. Finally, we identified senescent cells (SnCs) using machine learning and gene set enrichment analysis, revealing that PCC1 induced apoptosis of SnCs and regulated their metabolic processes, particularly in granulocytes and myeloid cells. The experimental validation further confirmed the senolytic and senomorphic effects of PCC1 both in vivo and in vitro. Overall, PCC1 holds potential as a therapeutic agent for alleviating immune dysfunction and promoting healthy aging via senolytic and senomorphic effects.

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