Exploring the double-edged role of cellular senescence in chronic liver disease for new treatment approaches.

Abstract

Cellular senescence is a fundamental yet complex defense mechanism that restricts excessive proliferation, maintains cellular homeostasis under various stress conditions-such as oncogenic activation and inflammation-and serves as a dynamic stress response program involved in development, aging, and immunity. Its reversibility depends on essential maintenance components. Cellular senescence is a "double-edged sword": on one hand, it limits the malignant proliferation of damaged cells, thereby preventing tumor development. However, by retaining secretory functions, senescent cells can also induce persistent changes in the microenvironment and disrupt homeostasis, leading to tissue inflammation, fibrosis, and carcinogenesis. Senescence plays a critical role in the pathogenesis of various chronic liver diseases, including chronic viral hepatitis, liver fibrosis, and hepatocellular carcinoma. It exerts a dual influence by facilitating immune evasion and inflammation in chronic viral hepatitis, modulating hepatic stellate cell activity in fibrosis, and reshaping the tumor microenvironment to accelerate hepatocarcinogenesis. This article reviews the characteristics of cellular senescence and its role in the pathogenesis of these chronic liver diseases while exploring potential treatment and prevention strategies. The aim is to provide a comprehensive reference for future clinical and research investigations into chronic liver disease.