Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging

IF 5.7 1区化学 Q2 CHEMISTRY, PHYSICAL

Journal of Chemical Theory and Computation Pub Date : 2024-11-04 DOI:10.1016/j.cell.2024.10.019

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, Guang-Hui Liu

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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.

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空间转录组景观揭示了作为衰老标志的免疫球蛋白相关衰老

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九个组织进行了深入的空间转录组分析。我们发现，衰老敏感点（SSSs）与组织结构熵的升高相一致，而免疫球蛋白表达细胞的聚集是 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都有积累，在人类组织中也观察到了类似的现象，这表明免疫球蛋白的异常升高可能是衰老过程中进化保守的特征。此外，我们还观察到，IgG 可诱导巨噬细胞和小胶质细胞的促衰老状态，从而加剧组织衰老，而有针对性地减少 IgG 可减轻雄性小鼠各种组织的衰老。这项研究提供了衰老的高分辨率空间描述，并表明了免疫球蛋白相关衰老在衰老过程中的关键作用。

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来源期刊

Journal of Chemical Theory and Computation 化学-物理：原子、分子和化学物理

CiteScore

9.90

自引率

16.40%

发文量

568

审稿时长

1 months

期刊介绍： The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.