Lai Wenpu, Feng Qiuyue, Lei Wen, Xiao Chanchan, Wang Juan, Zhu Yi, Mao Lipeng, Zhu Yue, He Jiacheng, Li Yangqiu, Wang Hao, Li Zhenhua, Chen Guobing, Luo Oscar Junhong
Department of Anesthesiology, The First Affiliated Hospital, Jinan University, Guangzhou, China.
Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.
Aging Cell. 2025 Jul;24(7):e70082. doi: 10.1111/acel.70082. Epub 2025 Apr 26.
Aging induces significant alterations in the immune system, with immunosenescence contributing to age-related diseases. Peripheral blood mononuclear cells (PBMCs) offer a convenient and comprehensive snapshot of the body's immune status. In this study, we performed an integrated analysis of PBMCs using both bulk-cell and single-cell RNA-seq data, spanning from children to frail elderlies, to investigate age-related changes. We observed dynamic changes in the PBMC transcriptome during healthy aging, including dramatic shifts in inflammation, myeloid cells, and lymphocyte features during early life, followed by relative stability in later stages. Conversely, frail elderly individuals exhibited notable disruptions in peripheral immune cells, including an increased senescent phenotype in monocytes with elevated inflammatory cytokine expression, heightened effector activation in regulatory T cells, and functional impairment of cytotoxic lymphocytes. Overall, this study provides valuable insights into the complex dynamics of immunosenescence, elucidating the mechanisms driving abnormal inflammation and immunosuppression in frailty.
衰老会引起免疫系统的显著变化，免疫衰老会导致与年龄相关的疾病。外周血单核细胞（PBMC）能方便且全面地反映身体的免疫状态。在本研究中，我们使用批量细胞和单细胞RNA测序数据，对从儿童到体弱老年人的PBMC进行了综合分析，以研究与年龄相关的变化。我们观察到健康衰老过程中PBMC转录组的动态变化，包括生命早期炎症、髓系细胞和淋巴细胞特征的显著变化，随后在后期相对稳定。相反，体弱的老年人在外周免疫细胞中表现出明显的紊乱，包括单核细胞衰老表型增加，炎症细胞因子表达升高，调节性T细胞效应激活增强，以及细胞毒性淋巴细胞功能受损。总体而言，本研究为免疫衰老的复杂动态提供了有价值的见解，阐明了导致体弱状态下异常炎症和免疫抑制的机制。
