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.

中文翻译：

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空间转录组学景观揭示了免疫球蛋白相关衰老是衰老的标志


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，我们制作了雄性小鼠衰老过程中 9 个组织的深入空间转录组学谱。我们表明衰老敏感点 （SSS） 与组织结构中的高熵共定位，并且表达免疫球蛋白的细胞聚集是 SSS 周围微环境的特征。免疫球蛋白 G （IgG） 在雄性和雌性小鼠的衰老组织中积累，在人体组织中观察到类似的现象，表明免疫球蛋白异常升高可能作为进化上保守的特征老化。此外，我们观察到 IgG 可以在巨噬细胞和小胶质细胞中诱导促衰老状态，从而加剧组织衰老，并且靶向减少 IgG 可减轻雄性小鼠各种组织的衰老。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的关键作用。