AI Article Synopsis
- The study examined the presence of senescent cells in the livers of five young children undergoing liver transplantation due to severe liver diseases like tyrosinemia and biliary atresia.
- Results showed positive indicators of cellular senescence, such as SA-betagal activity, predominantly in the bile ducts and liver cells, especially in cases with cirrhosis and ductular transformations in fulminant hepatitis.
- The findings suggest that cellular senescence in these livers reflects damage from disease rather than being an age-related process, indicating a need for further research on its links to disease progression.
Article Abstract
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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858078 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0010231 | PLOS |
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