Impact of Aging on Liver Cells and Liver Disease: Focus on the Biliary and Vascular Compartments

Abstract

The aging process is represented by the time-dependent decay in physiologic functions of living beings. Major interest has been focused in recent years on the determinants of this progressive condition due to its correlative relationship with the onset of diseases. Several hallmark features have been observed in aging, such as genetic alterations, mitochondrial impairment, and telomere shortening. At the cellular level, a senescent phenotype has been identified in response to aging that is characterized by a flat appearance, proliferative arrest, and production of specific molecules. The net effect of these cells in the course of diseases is an argument of debate. In fact, while the onset of a senescent phenotype may prevent tumor spreading, these cells appear to support pathological processes in some conditions. Several studies are now focused on clarifying the specific molecular pathways of aging/senescence in different cells, tissues, or organs. Biliary and vascular components, within the liver, have emerged as important determinants of some form of liver disease. In this review we summarize the most recent achievements on aging/senescence, focusing on the biliary and vascular liver system. Conclusion: Several findings, in both preclinical animal models and on human liver specimens, converge in supporting the presence of specific aging hallmarks in the diseases involving these hepatic compartments.

FIG. 1

Schematic representation of biliary tract and peribiliary vascular plexus assembly. The main functions of peribiliary vascular plexus, in supporting biliary tract activities, are reported in the gray box on the right side. (This figure was made with BioRender.com under a purchased license agreement.)

FIG. 2

The molecular determinants of cholangiocyte senescence, identified in experimental models of cholestasis. (This figure was made with BioRender.com under a purchased license agreement.)

FIG. 3

Major phenotypic modifications due to aging in liver sinusoidal cells. Abbreviation: HMΦ, hepatic macrophage. (This figure was made with BioRender.com under a purchased license agreement.)