NFATc4 mediates ethanol-triggered hepatocyte senescence

ZNF281 drives hepatocyte senescence in alcoholic liver disease by reducing HK2‐stabilized PINK1/Parkin‐mediated mitophagy

“…Our previous studies have repeatedly confirmed the rationality and stability of in vivo and in vitro alcoholic liver disease models that we established. 5 , 6 , 19 , 20 Based on the model, this study showed that both mRNA and protein abundance of ZNF281 in murine liver tissues were progressively increased during alcoholic liver disease (Figure 1A,B ). Hepatocytes are the dominant type of liver cells as well as the place for alcohol metabolism wherein metabolic byproducts usually cause hepatocellular damage.…”

“…Senescent cells are also featured by low proliferation capacity, senescence‐associated β‐galactosidase (SA‐β‐gal) positivity, cell cycle arrest, and telomere shortening 5 . Most senescent cells may exhibit a senescence‐associated secretory phenotype (SASP) and overproduce massive proinflammatory cytokines, aggravating inflammation and related pathology 6 . Cellular senescence could be driven by various factors, including genotoxic stress, oxidative stress, inflammatory cytokines, etc 7 .…”

“… 5 Most senescent cells may exhibit a senescence‐associated secretory phenotype (SASP) and overproduce massive proinflammatory cytokines, aggravating inflammation and related pathology. 6 Cellular senescence could be driven by various factors, including genotoxic stress, oxidative stress, inflammatory cytokines, etc. 7 Previous studies have revealed that alcohol as well as its endogenous metabolite acetaldehyde induced cellular oxidative stress and DNA double strand breaks.…”

“… 8 Notably, our studies further specified that hepatocytes under chronic alcohol exposure were manifested with senescence‐like cell appearance and behaviour, which accelerates the progression of alcoholic liver disease. 5 , 6 , 9 However, according to currently available studies, the node factors that comprehensively regulate the process of senescence are far from clear.…”

Curcumol Suppresses CCF-Mediated Hepatocyte Senescence Through Blocking LC3B–Lamin B1 Interaction in Alcoholic Fatty Liver Disease

“…Recently, several studies revealed that hepatocyte senescence participates in the development of alcoholic liver disease and suppression of hepatocyte senescence can effectively alleviate alcohol-induced hepatic steatosis, inflammation, and fibrosis, suggesting a potential strategy for the management of AFLD ( Aravinthan et al, 2013 ; Jiang et al, 2021 ; Wu et al, 2021 ). Cellular senescence, a state of irreversible cell cycle arrest, is characterized by decreased proliferation capacity, increased senescence-associated β-galactosidase (SA-β-gal) activity, and senescence-related markers p16 and p21 expression, and the dysfunction of telomere and telomerase system ( Collado et al, 2007 ; Hernandez-Segura et al, 2018 ).…”