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Updated: Jun 13, 2026

Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
Cellular senescence in livers from children with end stage liver disease
Gabriela Gutierrez-Reyes1, Maria del Carmen Garcia de Leon, Gustavo Varela-Fascinetto
1Department of Experimental Medicine, School of Medicine, Universidad Nacional Autónoma de México, (UNAM), Hospital General de México, [corrected] Mexico City, Mexico.
Insights
Cellular senescence, indicated by SA-betagal, p53, p16INK4a, and p21cip1, is present in children with end-stage liver disease, suggesting it’s linked to liver damage, not age.
Area of Science:
- Hepatology
- Cellular Biology
- Pediatric Gastroenterology
Background:
- Senescent cells are found in adult cirrhotic livers.
- The role of senescence in pediatric end-stage liver disease is unclear.
Purpose of the Study:
- To investigate cellular senescence and cell cycle checkpoint expression in pediatric end-stage liver disease.
- To determine if senescence is age-dependent or associated with liver damage.
Main Methods:
- Analysis of liver explants from five children (≤3 years) with end-stage liver disease (tyrosinemia, biliary atresia, fulminant hepatitis).
- Assessed senescence-associated beta-galactosidase (SA-betagal) activity.
- Evaluated expression of p16INK4a, p21cip1, and p53 cell cycle markers.
Main Results:
- All pediatric liver samples showed positive SA-betagal staining in biliary ducts.
- SA-betagal and p53 staining were prominent in ductular transformations in fulminant hepatitis.
- p16INK4a and p21cip1 expression was observed in various liver cells and ducts in tyrosinemia and fulminant hepatitis cases.
Conclusions:
- Cellular senescence in pediatric end-stage liver disease is associated with liver damage.
- Senescence in this context does not appear to be an age-dependent phenomenon.
- Further research is needed to correlate senescence markers with disease progression.
Background:
Senescent cells occur in adults with cirrhotic livers independent of the etiology.
Aim:
Investigate the presence rate of cellular senescence and expression of cell cycle check points in livers from children with end stage disease.
Methodology/Principal Findings:
Livers of five children aged three years or less undergoing liver transplantation due to tyrosinemia (n = 1), biliary atresia (n = 2), or fulminant hepatitis (n = 2) were analyzed for senescence associated beta-galactosidase (SA-betagal) activity and p16INK4a, p21cip1 and p53. All livers displayed positive cellular staining for SA-betagal in the canals of Hering and interlobular biliary ducts. In the presence of cirrhosis (3/5 cases) SA-betagal was found at the cholangioles and hepatocytes surrounding the regenerative nodules. Children with fulminant hepatic failure without cirrhosis had significant ductular transformation with intense SA-betagal activity. No SA-betagal activity was evident in the fibrous septa. Staining for p53 had a similar distribution to that observed for SA-betagal. Staining for p16(INK4a) and p21(cip1) was positive in the explanted liver of the patient with tyrosinemia, in the hepatocytes, the canals of Hering, cholangioles and interlobular bile ducts. In the livers with fulminant hepatitis, p21(cip1) staining occurred in the areas of ductular transformation and in the interlobular bile ducts.
Conclusions/Significance:
Cellular senescence in livers of children with end stage disease is associated with damage rather than corresponding to an age dependent phenomenon. Further studies are needed to support the hypothesis that these senescence markers correlate with disease progression.
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