文章基本信息

标题：Hallmarks of Aging in the Liver
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作者：Nicholas J. Hunt ; Sun Woo (Sophie) Kang ; Glen P. Lockwood 等
期刊名称：Computational and Structural Biotechnology Journal
印刷版ISSN：2001-0370
出版年度：2019
卷号：17
页码：1151-1161
DOI：10.1016/j.csbj.2019.07.021
出版社：Computational and Structural Biotechnology Journal
摘要：While the liver demonstrates remarkable resilience during aging, there is growing evidence that it undergoes all the cellular hallmarks of aging, which increases the risk of liver and systemic disease. The aging process in the liver is driven by alterations of the genome and epigenome that contribute to dysregulation of mitochondrial function and nutrient sensing pathways, leading to cellular senescence and low-grade inflammation. These changes promote multiple phenotypic changes in all liver cells (hepatocytes, liver sinusoidal endothelial, hepatic stellate and Küpffer cells) and impairment of hepatic function. In particular, age-related changes in the liver sinusoidal endothelial cells are a significant but under-recognized risk factor for the development of age-related cardiometabolic disease.
关键词：Endothelial ; Hepatocyte ; Genetic ; Nutrient sensing pathways ; Mitochondrial dysfunction ; Senescence ; αSMA alpha smooth muscle actin ; AMPK 5′ adenosine monophosphate-activated protein kinase ; CR caloric restriction ; FOXO forkhead box O ; HSC hepatic stellate cell ; IGF-1 insulin like growth factor 1 ; IL-6 interleukin 6 ; IL-8 interleukin 8 ; KC Küpffer cell ; LSEC liver sinusoidal endothelial cell ; miR microRNA ; mTOR mammalian target of rapamycin ; NAD nicotinamide adenine dinucleotide ; NAFLD non-alcoholic fatty liver disease ; NO nitric oxide ; PDGF platelet derived growth factor ; PGC-1α peroxisome proliferator-activated receptor gamma coactivator 1-α ; ROS reactive oxygen species ; SIRT1 sirtuin 1 ; TNFα tumor necrosis factor alpha ; VEGF vascular endothelial growth factor