Cellular senescence during aging and chronic liver diseases

Cellular senescence is a cell fate characterized by an irreversible cell-cycle arrest, and among various changes, metabolic dysfunction and a proinflammatory secretory phenotype. Senescence has attracted a lot of interest in recent years, particularly, because of its role as a driver of aging and disease. Senescence has been found in different cell types in the liver, including hepatocytes, cholangiocytes, and hepatic stellate cells. Cellular senescence has been associated with several diseases such as nonalcoholic and alcoholic fatty liver disease, chronic hepatitis, liver cancer, chronic biliary liver disorders, and hereditary hemochromatosis. Importantly, studies have shown that clearance of senescent cells improves phenotypes in preclinical models during aging and disease, supporting the hypothesis that senescent cells may be promising targets for interventions to counteract chronic liver diseases. This chapter focuses on senescence in aging and chronic liver disease and explores some of the underlying molecular mechanisms and therapeutic opportunities.