Division of Gastroenterology, Department of Medicine, Duke University Health System, Durham, North Carolina.
Liver Vascular Biology Research Group, IDIBAPS Biomedical Research Institute, CIBEREHD, Barcelona, Spain.
Semin Liver Dis. 2020 Nov;40(4):373-384. doi: 10.1055/s-0040-1715446. Epub 2020 Nov 20.
Aging increases the incidence of chronic liver disease (CLD), worsens its prognosis, and represents the predominant risk factor for its development at all different stages. The hepatic sinusoid, which is fundamental for maintaining liver homeostasis, is composed by hepatocytes, liver sinusoidal endothelial cells, hepatic stellate cells, and hepatic macrophages. During CLD progression, hepatic cells suffer deregulations in their phenotype, which ultimately lead to disease development. The effects of aging on the hepatic sinusoid phenotype and function are not well understood, nevertheless, studies performed in experimental models of liver diseases and aging demonstrate alterations in all hepatic sinusoidal cells. This review provides an updated description of age-related changes in the hepatic sinusoid and discusses the implications for CLD development and treatment. Lastly, we propose aging as a novel therapeutic target to treat liver diseases and summarize the most promising therapies to prevent or improve CLD and extend healthspan.
衰老增加了慢性肝病（CLD）的发病率，使疾病预后恶化，并成为各个阶段 CLD 发展的主要危险因素。肝脏窦状隙对于维持肝脏内环境稳定至关重要，它由肝细胞、肝窦内皮细胞、肝星状细胞和枯否细胞组成。在 CLD 进展过程中，肝细胞的表型发生失调，最终导致疾病发生。衰老对肝脏窦状隙表型和功能的影响尚不清楚，然而，在肝脏疾病和衰老的实验模型中进行的研究表明，所有的肝窦细胞都发生了改变。本综述提供了对肝脏窦状隙与衰老相关变化的最新描述，并讨论了其对 CLD 发展和治疗的影响。最后，我们提出衰老作为治疗肝脏疾病的一个新的治疗靶点，并总结了最有希望的预防或改善 CLD 和延长健康寿命的治疗方法。
