Gradual alterations of cell’s physiology and functions due to age or exposure to various stresses lead to the conversion of normal cells to senescent cells.Once becoming senescent,the cell stops dividing permanently ...Gradual alterations of cell’s physiology and functions due to age or exposure to various stresses lead to the conversion of normal cells to senescent cells.Once becoming senescent,the cell stops dividing permanently but remains metabolically active.Cellular senescence does not have a single marker but is characterized mainly by a combination of multiple markers,such as,morphological changes,expression of cell cycle inhibitors,senescence associatedβ-galactosidase activity,and changes in nuclear membrane.When cells in an organ become senescent,the entire organism can be affected.This may occur through the senescence-associated secretory phenotype(SASP).SASP may exert beneficial or harmful effects on the microenvironment of tissues.Research on senescence has become a very exciting field in cell biology since the link between age-related diseases,including cancer,and senescence has been established.The loss of regenerative and homeostatic capacity of the liver over the age is somehow connected to cellular senescence.The major contributors of senescence properties in the liver are hepatocytes and cholangiocytes.Senescent cells in the liver have been implicated in the etiology of chronic liver diseases including cirrhosis and hepatocellular carcinoma and in the interference of liver regeneration.This review summarizes recently reported findings in the understanding of the molecular mechanisms of senescence and its relationship with liver diseases.展开更多
Objective:Autophagy is important for cellular homeostasis.It has been well documented that while autophagy can be important for cancer cell survival,it can also be a tumorsuppressing mechanism in normal cells.Mice wit...Objective:Autophagy is important for cellular homeostasis.It has been well documented that while autophagy can be important for cancer cell survival,it can also be a tumorsuppressing mechanism in normal cells.Mice with hepatic autophagy deficiency develop liver tumors,but the mechanisms of tumorigenesis are not known.Methods:Atg7-or Atg5-deficient mice and their counterparts with additional genetic deficiencies in other genes.展开更多
Autophagy is an evolutionarily conserved intracellular degradative function that is important for liver homeostasis.Accumulating evidence suggests that autophagy is deregulated during the progression and development o...Autophagy is an evolutionarily conserved intracellular degradative function that is important for liver homeostasis.Accumulating evidence suggests that autophagy is deregulated during the progression and development of alcoholic and non-alcoholic liver diseases.Impaired autophagy prevents the clearance of excessive lipid droplets(LDs),damaged mitochondria,and toxic protein aggregates,which can be generated during the progression of various liver diseases,thus contributing to the development of steatosis,injury,steatohepatitis,fibrosis,and tumors.In this review,we look at the status of hepatic autophagy during the pathogenesis of alcoholic and non-alcoholic liver diseases.We also examine the mechanisms of defects in autophagy,and the hepato-protective roles of autophagy in non-alcoholic fatty liver disease(NAFLD)and alcoholic liver disease(ALD),focusing mainly on steatosis and liver injury.Finally,we discuss the therapeutic potential of autophagy modulating agents for the treatment of these two common liver diseases.展开更多
文摘Gradual alterations of cell’s physiology and functions due to age or exposure to various stresses lead to the conversion of normal cells to senescent cells.Once becoming senescent,the cell stops dividing permanently but remains metabolically active.Cellular senescence does not have a single marker but is characterized mainly by a combination of multiple markers,such as,morphological changes,expression of cell cycle inhibitors,senescence associatedβ-galactosidase activity,and changes in nuclear membrane.When cells in an organ become senescent,the entire organism can be affected.This may occur through the senescence-associated secretory phenotype(SASP).SASP may exert beneficial or harmful effects on the microenvironment of tissues.Research on senescence has become a very exciting field in cell biology since the link between age-related diseases,including cancer,and senescence has been established.The loss of regenerative and homeostatic capacity of the liver over the age is somehow connected to cellular senescence.The major contributors of senescence properties in the liver are hepatocytes and cholangiocytes.Senescent cells in the liver have been implicated in the etiology of chronic liver diseases including cirrhosis and hepatocellular carcinoma and in the interference of liver regeneration.This review summarizes recently reported findings in the understanding of the molecular mechanisms of senescence and its relationship with liver diseases.
文摘Objective:Autophagy is important for cellular homeostasis.It has been well documented that while autophagy can be important for cancer cell survival,it can also be a tumorsuppressing mechanism in normal cells.Mice with hepatic autophagy deficiency develop liver tumors,but the mechanisms of tumorigenesis are not known.Methods:Atg7-or Atg5-deficient mice and their counterparts with additional genetic deficiencies in other genes.
基金This work was supported in part by the USA National Institutes of Health(NIH)grants R01AA021751 and R21AA021450(to X.-M.Yin).
文摘Autophagy is an evolutionarily conserved intracellular degradative function that is important for liver homeostasis.Accumulating evidence suggests that autophagy is deregulated during the progression and development of alcoholic and non-alcoholic liver diseases.Impaired autophagy prevents the clearance of excessive lipid droplets(LDs),damaged mitochondria,and toxic protein aggregates,which can be generated during the progression of various liver diseases,thus contributing to the development of steatosis,injury,steatohepatitis,fibrosis,and tumors.In this review,we look at the status of hepatic autophagy during the pathogenesis of alcoholic and non-alcoholic liver diseases.We also examine the mechanisms of defects in autophagy,and the hepato-protective roles of autophagy in non-alcoholic fatty liver disease(NAFLD)and alcoholic liver disease(ALD),focusing mainly on steatosis and liver injury.Finally,we discuss the therapeutic potential of autophagy modulating agents for the treatment of these two common liver diseases.
