中国科学院动物研究所的刘光慧等研究人员合作发现，空间转录组学景观揭示免疫球蛋白相关衰老作为衰老的标志。2024年11月4日，国际知名学术期刊《细胞》在线发表了这一成果。
为了系统地表征衰老导致的组织完整性丧失和器官功能障碍，研究人员在雄性小鼠衰老过程中制作了九种组织的深入空间转录组学剖面。研究人员发现衰老敏感点（SSS）与组织结构中的熵升高共定位，并且免疫球蛋白表达细胞的聚集是SSS周围微环境的特征性特征。
免疫球蛋白G（IgG）在雄性和雌性小鼠的衰老组织中均有积累，且在人的组织中也观察到了类似现象，这表明免疫球蛋白异常升高可能作为衰老中进化保守的特征。进一步研究发现，IgG可以诱导巨噬细胞和小胶质细胞进入促衰老状态，从而加剧组织衰老，而靶向减少IgG则减缓了雄性小鼠各个组织的衰老过程。
该研究提供了衰老的高分辨率空间图谱，并指出免疫球蛋白相关衰老在衰老过程中的关键作用。
附：英文原文
Title: Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging
Author: Shuai Ma, Zhejun Ji, Bin Zhang, Lingling Geng, Yusheng Cai, Chao Nie, Jiaming Li, Yuesheng Zuo, Yuzhe Sun, Gang Xu, Beibei Liu, Jiaqi Ai, Feifei Liu, Liyun Zhao, Jiachen Zhang, Hui Zhang, Shuhui Sun, Haoyan Huang, Yiyuan Zhang, Yanxia Ye, Yanling Fan, Fangshuo Zheng, Jinghao Hu, Baohu Zhang, Jingyi Li, Xin Feng, Feng Zhang, Yuan Zhuang, Tianjie Li, Yang Yu, Zhaoshi Bao, Sipei Pan, Concepcion Rodriguez Esteban, Zhili Liu, Haohao Deng, Feng Wen, Moshi Song, Si Wang, Guodong Zhu, Jiayin Yang, Tao Jiang, Weihong Song, Juan Carlos Izpisua Belmonte, Jing Qu, Weiqi Zhang, Ying Gu, Guang-Hui Liu
Issue&Volume: 2024-11-04
Abstract: To systematically characterize the loss of tissue integrity and organ dysfunction resulting from aging, we produced an in-depth spatial transcriptomic profile of nine tissues in male mice during aging. We showed that senescence-sensitive spots (SSSs) colocalized with elevated entropy in organizational structure and that the aggregation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding SSSs. Immunoglobulin G (IgG) accumulated across the aged tissues in both male and female mice, and a similar phenomenon was observed in human tissues, suggesting the potential of the abnormal elevation of immunoglobulins as an evolutionarily conserved feature in aging. Furthermore, we observed that IgG could induce a pro-senescent state in macrophages and microglia, thereby exacerbating tissue aging, and that targeted reduction of IgG mitigated aging across various tissues in male mice. This study provides a high-resolution spatial depiction of aging and indicates the pivotal role of immunoglobulin-associated senescence during the aging process.
DOI: 10.1016/j.cell.2024.10.019
Source: https://www.cell.com/cell/abstract/S0092-8674(24)01201-7