TABLE 1.
Factors associated with cellular senescence in chronic liver disease.
| Chronic liver disease | Cellular mechanism associated with senescence |
|---|---|
| Primary Biliary Cholangitis (PBC) | Telomere shortening, p16 and p21 expression |
| Oxidative stress and ER stress | |
| Increased expression of CXCL11, CCL20, CCL2 and fractalkine | |
| Cholangiocyte autophagy including p62 signaling | |
| Loss of AE2 and the bicarbonate umbrella | |
| Enhanced secretin/SR signaling (early-stage PBC) | |
| Increased Bcl-xL (anti-apoptosis) expression | |
| Reduced Bmi1 (antioxidant) expression | |
| Primary Sclerosing Cholangitis (PSC) | p16, p21, γH2A.X and SA-β-galactosidase expression |
| Cholangiocyte secretion of SASP factors (IL-6, IL-8, CCL2, PAI-1) | |
| N-Ras activation in cholangiocytes | |
| Increased TGF-β1 signaling | |
| Upregulation of biliary secretin/SR signaling | |
| Mast cell-derived TGF-β1 and FXR signaling | |
| Cholangiocyte SCF secretion | |
| Increased biliary H2HR signaling | |
| Reduced biliary expression of FoxA2 | |
| Increased age-related miRs and Twf-1 signaling | |
| Enhanced miR-34a/SIRT1 activity | |
| Increased Bcl-xL (anti-apoptosis) expression | |
| Biliary Atresia | Reduced telomere length in hepatic tissues and peripheral leukocytes |
| Enhanced biliary MHC I and II expression, and secretion of TNFα and TGF-β | |
| p16, p21 and NCAM expression | |
| Enhanced TGF-β1, TGF-β2, decorin and CTGF expression | |
| Increased serum and hepatic H19 levels | |
| Biliary expression of TGF-β, αSMA and Cil-1a | |
| Serum exosome H19, HMGA2 and S1PR2 levels | |
| Increased caspase-3, TGF-β1, PDGF, IL-1β, IL-6, and TNF-α expression in ex vivo ductal organoids | |
| Non-Alcoholic Fatty Liver Disease (NAFLD)/Non-Alcoholic Steatohepatitis (NASH) | Dysregulated histamine/leptin signaling in cholangiocytes |
| Biliary IGF-1 secretion and mast cell miR-144-3p/ALDH1A3 signaling | |
| Age-related M1 macrophage infiltration | |
| Alcoholic Liver Disease (ALD) | Reduced SIRT1 activity |
| Inhibition of ALDH2 and ALDH3A1 | |
| Increased miR-34a |
Table outlining the various signaling mechanisms and phenotypes associated with cellular senescence in chronic liver diseases, as discussed in the review. Senescence-associated factors and mechanisms are divided by disease, including PBC, PSC, NAFLD/NASH, and ALD.