Cellular Senescence in Liver Disease and Regeneration

Abstract

Cellular senescence is an irreversible cell cycle arrest implemented by the cell as a result of stressful insults. Characterized by phenotypic alterations, including secretome changes and genomic instability, senescence is capable of exerting both detrimental and beneficial processes. Accumulating evidence has shown that cellular senescence plays a relevant role in the occurrence and development of liver disease, as a mechanism to contain damage and promote regeneration, but also characterizing the onset and correlating with the extent of damage. The evidence of senescent mechanisms acting on the cell populations of the liver will be described including the role of markers to detect cellular senescence. Overall, this review intends to summarize the role of senescence in liver homeostasis, injury, disease, and regeneration.

The Potential Role of Cellular Senescence in Non-Alcoholic Fatty Liver Disease

“…Cellular senescence is a term which generally marks a decline of cell division capacity and ability to proliferate [ 21 ]. In the context of mutations, senescence is considered protective since it prevents the unlimited proliferation and dissemination of potentially malignant cells [ 23 ].…”

“…Cellular senescence may be also linked to hepatic injury. In some cell types such as fibroblast or hepatic stellate cells, senescence may be beneficial as it mitigates scar formation and fibrosis [ 21 ]. In addition, senescence is an essential process during maturation that ensures coordinated and controlled growth [ 24 ].…”

“…Cellular senescence is a term describing cells which are in cell cycle arrest but remain metabolically active [ 21 ]. There is evidence showing that cellular senescence, especially in hepatocytes, may modulate fat accumulation and inflammation in patients with different stages of NAFLD [ 21 , 22 ].…”

“…Cellular senescence is a term describing cells which are in cell cycle arrest but remain metabolically active [ 21 ]. There is evidence showing that cellular senescence, especially in hepatocytes, may modulate fat accumulation and inflammation in patients with different stages of NAFLD [ 21 , 22 ]. Therefore, this review will focus on the current evidence for the role of cellular senescence in NAFLD and its effect on intercellular crosstalk as a central driver of disease progression.…”

Nociceptin/orphanin FQ opioid receptor (NOP) selective ligand MCOPPB links anxiolytic and senolytic effects

“…Based on the RNA-Seq data, the lower SA-B-Gal activity in the livers of MCOPPB-treated animals seems not to be due to lower GLB1 mRNA expression but to a lower number of cells displaying activity of SA-β-galactosidase. The decrease in liver resident macrophages in the liver during infectious and non-infectious stimuli might prime this organ for repair and regeneration [74,75]. Indeed, macrophages are powerful scavengers and are the major cell type involved in phagocytosis of apoptotic cells, but the fate of macrophages once they have ingested apoptotic cells is open to much debate.…”