Autophagy and Senescence: The Molecular Mechanisms and Implications in Liver Diseases

作者：Li Qiao, Yan Lin, Guangyu Liang, Nanyin Xiao, Heng Zhang, Xiao Yang, Jiankun Yang, Anding Liu · 发表于：International Journal of Molecular Sciences · 年份：2023 · DOI：10.3390/ijms242316880 · 被引用次数：41 · 研究领域：Autophagy in Disease and Therapy、MicroRNA in disease regulation、Telomeres, Telomerase, and Senescence

The liver is the primary organ accountable for complex physiological functions, including lipid metabolism, toxic chemical degradation, bile acid synthesis, and glucose metabolism. Liver function homeostasis is essential for the stability of bodily functions and is involved in the complex regulation of the balance between cell proliferation and cell death. Cell proliferation-halting mechanisms, including autophagy and senescence, are implicated in the development of several liver diseases, such as cholestasis, viral hepatitis, nonalcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Among various cell death mechanisms, autophagy is a highly conserved and self-degradative cellular process that recycles damaged organelles, cellular debris, and proteins. This process also provides the substrate for further metabolism. A defect in the autophagy machinery can lead to premature diseases, accelerated aging, inflammatory state, tumorigenesis, and cellular senescence. Senescence, another cell death type, is an active player in eliminating premalignant cells. At the same time, senescent cells can affect the function of neighboring cells by secreting the senescence-associated secretory phenotype and induce paracrine senescence. Autophagy can promote and delay cellular senescence under different contexts. This review decodes the roles of autophagy and senescence in multiple liver diseases to achieve a better understanding of the regulatory mechanisms and implicatio...