Cellular Senescence in Disease: Chapter 5 - Liver diseases fibrosis and cirrhosis

Elsevier, Cellular Senescence in Disease, 2022, Pages 107-153
Thomas G. Bird and Christos Kiourtis

The liver is the largest solid organ in the body and is responsible for a range of metabolic, synthetic, and detoxification functions which are essential for survival. Due to this role and given its anatomical position, acting as a guardian between the intestine and the systemic circulation, together with its propensity for viral infection the liver is a frequent site of damage. Chronic liver disease is a blight on worldwide human health. Chronic damage results in perpetual turnover of hepatocytes in the liver and is associated with unresolved inflammation, the development of progressive scarring, fibrosis, and eventually cirrhosis. Virtually all forms of liver injury have been associated with a senescentlike response in the organ's various cellular constituents. The role of senescence is key to the regenerative response, deposition of fibrosis, and the formation of cancer in this organ. Here we review recent advances in our appreciation of senescence development in various liver resident cells and how this develops both during physiological aging and various disease states including carcinogenesis. We highlight the recent interest in using senolytic therapies for liver disease as an attractive option for further development.