The role of senescence in the development of non-alcoholic fatty liver disease and progression to non-alcoholic steatohepatitis.
The Role of Senescence in the Development of Nonalcoholic Fatty Liver Disease and Progression to Nonalcoholic Steatohepatitis
In recent years cellular senescence has generated a lot of interest among researchers due to its involvement in normal aging process and also in common human diseases. During senescence, cells undergo alterations that include telomere shortening, nuclear area enlargement, genomic and mitochondrial DNA damage, leading to irreversible cell cycle arrest, and secretion of proinflammatory cytokines. Evidence suggests that the complex process of senescence is involved in the development of a plethora of chronic diseases including metabolic and inflammatory disorders and tumorigenesis. Recently, several human and animal studies have emphasized the involvement of senescence in the pathogenesis and development of liver steatosis including the progression to Non-Alcoholic Steatohepatitis (NASH) as characterized by the additional emergence of inflammation, hepatocyte ballooning and liver fibrosis. The development of Non-Alcoholic Fatty Liver Disease (NAFLD) and its progression to NASH are commonly accompanied by several pathophysiological events including metabolic dysregulation and inflammatory phenomena occurring within the liver which may contribute to or derive from cellular senescence, implying that the latter may be both a stimulus and a consequence of the disease. In this review we summarize the current literature on the impact of cellular senescence in NAFLD/NASH, and discuss the effectiveness and safety of novel senolytic drugs and therapeutic options available to delay or treat the disease. Finally we identify the open questions and issues to be addressed in the near future.