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

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

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 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. · pubmed

Paper

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.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

This paper is relevant to longevity research as it investigates the mechanisms of aging, specifically focusing on immunoglobulin-associated senescence and its role in tissue aging. The findings suggest a potential root cause of aging-related dysfunction, which aligns with the goals of longevity research. The impact score of 5 reflects that while the study presents important findings regarding the relationship between immunoglobulins and senescence, it may not be groundbreaking enough to significantly alter the current understanding of aging or lead to immediate applications in lifespan extension.

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