生物
衰老
转录组
下调和上调
表型
细胞生物学
肝细胞
细胞
基因表达
基因
遗传学
内科学
医学
作者
Shanshan Yang,Chengyu Liu,Mengmeng Jiang,Xiaoqian Liu,Lingling Geng,Yiyuan Zhang,Shuhui Sun,Kang Wang,Jian Yin,Shuai Ma,Si Wang,Juan Carlos Izpisúa Belmonte,Guang‐Hui Liu,Jing Qu,Weiqi Zhang
出处
期刊:Protein & Cell
[Springer Nature]
日期:2023-06-28
卷期号:15 (2): 98-120
被引量:15
标识
DOI:10.1093/procel/pwad039
摘要
Abstract Aging increases the risk of liver diseases and systemic susceptibility to aging-related diseases. However, cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized. Here, we constructed the first single-nucleus transcriptomic landscape of primate liver aging, in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell–cell interactions between hepatocytes and niche cells. Upon in-depth dissection of this rich dataset, we identified impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging. In particular, hyperactivated sterol regulatory element-binding protein (SREBP) signaling was a hallmark of the aged liver, and consequently, forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes, manifesting as impaired detoxification and accelerated cellular senescence. This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.
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