Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China; Aging Biomarker Consortium (ABC), Beijing 100101, China.
Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem Cell and Regeneration, CAS, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China.
Cell. 2024 Nov 27;187(24):7025-7044.e34. doi: 10.1016/j.cell.2024.10.019. Epub 2024 Nov 4.
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.
为了系统地描述衰老导致的组织完整性丧失和器官功能障碍，我们对雄性小鼠衰老过程中的 9 种组织进行了深入的空间转录组学分析。结果表明，衰老敏感点（SSSs）与组织结构熵的升高密切相关，而表达免疫球蛋白的细胞聚集是 SSSs 周围微环境的一个特征。免疫球蛋白 G（IgG）在雄性和雌性小鼠的衰老组织中积累，在人类组织中也观察到了类似的现象，这表明异常升高的免疫球蛋白可能是衰老过程中一种进化上保守的特征。此外，我们发现 IgG 可诱导巨噬细胞和小胶质细胞出现衰老前状态，从而加剧组织衰老，而靶向降低 IgG 可减轻雄性小鼠多种组织的衰老。本研究提供了衰老的高分辨率空间描述，并表明免疫球蛋白相关衰老在衰老过程中起着关键作用。
