Aging and Aging-Related Senescence in Liver.

IF 3.7 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Souradipta Ganguly, Sadatsugu Sakane, Kanani Hokutan, Vivian Zhang, Charlene Miciano, Allen Wang, David A Brenner, Tatiana Kisseleva
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引用次数: 0

Abstract

Aging is characterized by the progressive deterioration of cell and tissue functions. The liver, which regulates metabolic homeostasis, detoxification, and immune responses, undergoes structural and functional changes with age. These include increasing genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing and intracellular communication, mitochondrial dysfunction, cell senescence, stem cell exhaustion, chronic inflammation, disabled macroautophagy, and dysbiosis. These alterations contribute to hepatocyte dysfunction, impaired regenerative responses, and fibrosis risk, which all exacerbate existing liver diseases. Senescence involves irreversible cell cycle arrest resulting in an inflammatory, senescence-associated secretory cell phenotype. Senescent hepatocytes, liver sinusoidal endothelial cells, hepatic stellate cells, and Kupffer cells accumulate in the aged liver, creating an inflammatory and fibrotic microenvironment that promotes tumorigenesis. As the burden of aging-related liver disease increases, therapeutic strategies targeting hepatic senescence have gained attention. We review these, along with the mechanisms and pathogenic effects of liver aging.

衰老及与衰老相关的肝脏衰老。
衰老的特征是细胞和组织功能的逐渐退化。肝脏调节代谢稳态、解毒和免疫反应,随着年龄的增长,肝脏会经历结构和功能的变化。这些包括基因组不稳定性增加、端粒磨损、表观遗传改变、蛋白质平衡丧失、营养感知和细胞内通讯失调、线粒体功能障碍、细胞衰老、干细胞衰竭、慢性炎症、巨噬功能丧失和生态失调。这些改变导致肝细胞功能障碍、再生反应受损和纤维化风险,这些都加剧了现有的肝脏疾病。衰老涉及不可逆的细胞周期阻滞,导致炎症,衰老相关的分泌细胞表型。衰老的肝细胞、肝窦内皮细胞、肝星状细胞和库普弗细胞在衰老的肝脏中积累,形成促进肿瘤发生的炎症和纤维化微环境。随着衰老相关肝脏疾病负担的增加,针对肝衰老的治疗策略受到关注。我们回顾了这些,以及肝衰老的机制和致病作用。
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来源期刊
Seminars in liver disease
Seminars in liver disease 医学-胃肠肝病学
CiteScore
8.20
自引率
2.40%
发文量
38
期刊介绍: Seminars in Liver Disease is a quarterly review journal that publishes issues related to the specialties of hepatology and gastroenterology. As the premiere review journal in the field, Seminars in Liver Disease provides in-depth coverage with articles and issues focusing on topics such as cirrhosis, transplantation, vascular and coagulation disorders, cytokines, hepatitis B & C, Nonalcoholic Steatosis Syndromes (NASH), pediatric liver diseases, hepatic stem cells, porphyrias as well as a myriad of other diseases related to the liver. Attention is also given to the latest developments in drug therapy along with treatment and current management techniques. Seminars in Liver Disease publishes commissioned reviews. Unsolicited reviews of an exceptional nature or original articles presenting remarkable results will be considered, but case reports will not be published.
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