Hepatic senescence, the good and the bad

Abstract

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.