Hepatic senescence, the good and the bad

Abstract

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 associated β-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.

Creatine Alleviates Doxorubicin-Induced Liver Damage by Inhibiting Liver Fibrosis, Inflammation, Oxidative Stress, and Cellular Senescence

“…Cellular senescence is a protective mechanism to protect potentially damaged cells against mutation; however, when cellular senescence becomes chronic, it causes the tissue to be more susceptible to damage [ 38 , 39 ]. Senescent cells are usually arrested in the G1/S phase and express P16 and P21 cell cycle inhibitors [ 40 ].…”

Nonphagocytic Activation of NOX2 Is Implicated in Progressive Nonalcoholic Steatohepatitis During Aging

“…1C). As senescence has been observed in aging livers in the context of steatosis and alcohol use, (12,13) we examined senescence phenotypes in our models. Middle-aged mice had an increase in p21 Cip1 nuclear signal (Fig.…”

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

“…One way in which TGF-β1 drives immune responses is thorough the establishment of paracrine senescence in hepatic cells. This describes the transmission of senescence properties from senescent cells to otherwise normal cells in acute and chronic liver injuries ( 57 ). Senescence is considered as a multistep, dynamic cellular process in response to endogenous and exogenous stress, such as oncogene activation, DNA damage or other stress-mediated signals, which induces cells to enter a permanent cell cycle arrest.…”

“…In the liver, cellular senescence may cause loss of regenerative capability affecting the function and tissue renewal ( 58 ). The SASP is a dynamic pro-inflammatory response that activates and reinforces the senescent phenotype in the surrounding cells and modulates fibrosis ( 57 ). Most senescent cells express multiple cytokines such as IL-8, chemokine ligand (CCL)-2 (monocyte chemoattractant protein (MCP)-1), CCL7 (MCP-3), CCL8 (MCP-2), CCL13 (MCP-4), CCL3, etc ( 59 , 60 ).…”