Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2019; 25(34): 5069-5081
Published online Sep 14, 2019. doi: 10.3748/wjg.v25.i34.5069
Hepatic senescence, the good and the bad
Nazmul Huda, Gang Liu, Honghai Hong, Shengmin Yan, Bilon Khambu, Xiao-Ming Yin
Nazmul Huda, Gang Liu, Honghai Hong, Shengmin Yan, Bilon Khambu, Xiao-Ming Yin, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, United States
Author contributions: Huda N designed, prepared and edited the manuscript. Liu G, Hong H, Yan S and Khambu B contributed intellectually to this manuscript. Yin XM conceived, edited and finalized the manuscript.
Conflict-of-interest statement: The authors have declared that no conflict of interest exists.
Open-Access: This is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Xiao-Ming Yin, FAASLD, MD, PhD, Full Professor, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 975 W Walnut St, Indianapolis, IN 46202, United States.
Telephone: +1-317-4916096 Fax: +1-317-4916639
Received: June 26, 2019
Peer-review started: June 26, 2019
First decision: July 20, 2019
Revised: July 25, 2019
Accepted: August 7, 2019
Article in press: August 7, 2019
Published online: September 14, 2019

Gradual alterations of cell’s physiology and functions due to age or exposure to various stresses lead to the conversion of normal cells to senescent cells. Once becoming senescent, the cell stops dividing permanently but remains metabolically active. Cellular senescence does not have a single marker but is characterized mainly by a combination of multiple markers, such as, morphological changes, expression of cell cycle inhibitors, senescence associated β-galactosidase activity, and changes in nuclear membrane. When cells in an organ become senescent, the entire organism can be affected. This may occur through the senescence-associated secretory phenotype (SASP). SASP may exert beneficial or harmful effects on the microenvironment of tissues. Research on senescence has become a very exciting field in cell biology since the link between age-related diseases, including cancer, and senescence has been established. The loss of regenerative and homeostatic capacity of the liver over the age is somehow connected to cellular senescence. The major contributors of senescence properties in the liver are hepatocytes and cholangiocytes. Senescent cells in the liver have been implicated in the etiology of chronic liver diseases including cirrhosis and hepatocellular carcinoma and in the interference of liver regeneration. This review summarizes recently reported findings in the understanding of the molecular mechanisms of senescence and its relationship with liver diseases.

Keywords: Senescence, Senescence associated secretory phenotype, Hepatocyte, Cholangiocyte, Hepatic stellate cell, Cell cycle arrest, DNA damage

Core tip: The liver is a vital organ for metabolic regulation and plays a major role in the nutrient utilization of the whole body. Although scientists have paid much attention to hepatic senescence, the precise mechanisms in, and the contribution of cellular senescence to liver diseases have yet to be clearly defined. In this review, we have summarized the mechanism of senescence in general and in the liver. We have also discussed whether hepatocellular senescence is beneficial or harmful to the liver in the light of published findings.