Cellular senescence limits the extent of fibrosis following liver damage

Cellular senescence is emerging as a mechanism that limits tissue damage. In most tissues of the body, following short-term damage this response aims to ensure the return to the predamaged state. This novel physiological role of cellular senescence is additional to its wellestablished function as a tumor suppressor. In a mouse model of liver fibrosis, cellular senescence limits fibrosis progression by several mechanisms. Cell cycle arrest limits expansion of activated hepatic stellate cells, senescent cells produce less extracellular matrix and more enzymes that degrade it, and the immune system speci fically recognizes and eliminates senescent cells, returning the liver tissue to its normal state. The mechanisms responsible for interaction with the immune system are part of the senescence phenotype and are needed to prevent the long-term destructive effects of senescent cells. Initially cellular senescence is bene ficial, as it limits tumorigenesis and tissue damage, but when senescent cells persist in tissues they contribute to tissue ageing and potentially promote tumorigenesis in their microenvironments. The coordinated molecular pathways governing the induction of senescence followed by elimination of senescent cells seems to be a product of evolutionary selection as a program that protects the organism from a variety of internal and external threats, while also preserving the organism's integrity. Understanding of these molecular pathways might eventually be exploited therapeutically by elimination of senescent cells in order to treat a variety of fibrosis-related conditions, prevent cancer, and delay tissue ageing.