编辑丨王多鱼 排版丨水成文 时间永不停歇地前进……但这对于免疫系统意味着什么？ 近期， Immunity 期刊 特邀来自中国科学院 （ 刘光慧 、 田烨 ） 、斯坦福大学、剑桥大学等机构的一组知名学者， 围绕衰老如何影响免疫反应、免疫细胞如何 参与衰老进程等关键问题展开了深入探讨。这些讨论为 通过调控免疫力以延长健康寿命 提供了新的科学视角。 Christoph A. Thaiss ， Arc 研究所，斯坦福大学， 感知免疫变化 在其 1956 年前瞻性讲座《 心灵与物质 》的开篇，物理学家 埃尔温 · 薛定谔 指出： " 世界是我们感觉、知觉与记忆的建构产物。 " 这一建构基于两大感觉系 统：外感受负责感知外部物理与化学环境，内感受则负责感知机体内在环境。免疫细胞发出的信号极大地拓展了内感受的疆界 —— 例如，响应微生物识别而释放 的细胞因子可激活感觉神经元上的受体，进而将信号传递至大脑，协调适应性反应。 尽管外感受功能随年龄增长而衰退 （日常生活中常通过眼镜或助听器等设备进行补偿） ，但关于内感受如何衰老，我们仍知之甚少。免疫细胞功能在整个生命周 期中发生深刻变化：骨髓造血输出呈现髓系偏倚，记忆性 T 细 ...

Core Viewpoint - The article discusses the advancements in in vivo CAR-T cell therapy, particularly focusing on a new type of lipid nanoparticle (LNP) that does not require antibody modification, which enhances the delivery of circRNA-based CAR-T cells for treating inflammatory aging diseases [1][2][3][5]. Group 1: In Vivo CAR-T Therapy Advantages - In vivo CAR-T therapy, based on mRNA, offers significant advantages over traditional ex vivo CAR-T therapy, especially in treating inflammatory aging diseases [6][14]. - The transient expression of in vivo CAR-T cells may be beneficial for inflammatory aging, contrasting with its potential drawbacks in solid tumor treatments [6][14]. Group 2: Research Innovations - The research team developed a novel type of LNP inspired by cardiolipin, which enhances T cell targeting without the need for antibody modification [8][15]. - The study demonstrated that the CAMP lipid increases the stiffness and phase separation of LNPs, improving T cell uptake [9][15]. Group 3: CircRNA Utilization - The research utilized circRNA to modify CAR mRNA, enhancing its stability and reducing cytotoxicity, which prolongs CAR protein expression in vivo [10][15]. - The encapsulation of CAR mRNA targeting uPAR in PL40-LNP provides a proof of concept for treating liver fibrosis and rheumatoid arthritis [11][12]. Group 4: Clinical Implications - The study highlights the potential of non-antibody targeting strategies in developing in vivo CAR-T therapies for clearing senescent cells associated with inflammatory aging diseases [17].