Transcriptional and epigenetic decoding of the microglial aging process

被引：63

作者：

Li, Xiaoyu ^{[1
]}

Li, Yuxin ^{[1
]}

Jin, Yuxiao ^{[2
]}

Zhang, Yuheng ^{[1
]}

Wu, Jingchuan ^{[3
]}

Xu, Zhen ^{[4
]}

Huang, Yubin ^{[4
]}

Cai, Lin ^{[1
,5
]}

Gao, Shuai ^{[1
]}

Liu, Taohui ^{[1
]}

Zeng, Fanzhuo ^{[1
,6
]}

Wang, Yafei ^{[1
]}

Wang, Wenxu ^{[1
]}

Yuan, Ti-Fei ^{[7
]}

Tian, Hengli ^{[5
]}

Shu, Yousheng ^{[1
]}

Guo, Feifan ^{[1
]}

Lu, Wei ^{[1
]}

Mao, Ying

Mei, Xifan

Rao, Yanxia ^{[2
]}

Peng, Bo ^{[1
,3
,8
]}

机构：

[1] Fudan Univ, Inst Translat Brain Res,Minist Educ, Jinshan Hosp,Innovat Ctr New Drug Dev Immune Infl, Dept Neurosurg,State Key Lab Med Neurobiol,MOE Fr, Shanghai, Peoples R China

[2] Fudan Univ, Zhongshan Hosp, Dept Neurol, Dept Lab Anim Sci,MOE Frontiers Ctr Brain Sci, Shanghai, Peoples R China

[3] Fudan Univ, Huashan Hosp, Dept Neurosurg, Shanghai, Peoples R China

[4] Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen, Peoples R China

[5] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 6, Dept Neurol, Sch Med, Shanghai, Peoples R China

[6] Jinzhou Med Univ, Dept Orthoped, Affiliated Hosp 1, Jinzhou, Peoples R China

[7] Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Shanghai Key Lab Psychot Disorders, Sch Med, Shanghai, Peoples R China

[8] Nantong Univ, Coinnovat Ctr Neurodegenerat, Nantong, Peoples R China

来源：

NATURE AGING | 2023年 / 3卷 / 10期

基金：

中国国家自然科学基金;

关键词：

NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CENTRAL-NERVOUS-SYSTEM; MOUSE MODEL; CELL; ACTIVATION; DISEASE; HETEROGENEITY; MEMORY; BETA; RISK;

D O I：

10.1038/s43587-023-00479-x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

As important immune cells, microglia undergo a series of alterations during aging that increase the susceptibility to brain dysfunctions. However, the longitudinal characteristics of microglia remain poorly understood. In this study, we mapped the transcriptional and epigenetic profiles of microglia from 3-to 24-month-old mice. We first discovered unexpected sex differences and identified age-dependent microglia (ADEM) genes during the aging process. We then compared the features of aging and reactivity in female microglia at single-cell resolution and epigenetic level. To dissect functions of aged microglia excluding the influence from other aged brain cells, we established an accelerated microglial turnover model without directly affecting other brain cells. By this model, we achieved aged-like microglia in non-aged brains and confirmed that aged-like microglia per se contribute to cognitive decline. Collectively, our work provides a comprehensive resource for decoding the aging process of microglia, shedding light on how microglia maintain brain functions.

引用

页码：1288 / +

页数：36

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