title: Cellular senescence in livers from children with end stage liver disease.
abstract: BACKGROUND
  Senescent cells occur in adults with cirrhotic livers independent of the etiology.
  
  
  OBJECTIVE
  Investigate the presence rate of cellular senescence and expression of cell cycle check points in livers from children with end stage disease.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Experimental Medicine, School of Medicine, Universidad Nacional Autónoma de México, (UNAM), Hospital General de México, [corrected] Mexico City, Mexico.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Gutierrez-Reyes
authors.forename: Maria
authors.initials: M
authors.lastname: del Carmen Garcia de Leon
authors.forename: Gustavo
authors.initials: G
authors.lastname: Varela-Fascinetto
authors.forename: Pedro
authors.initials: P
authors.lastname: Valencia
authors.forename: Ruy
authors.initials: R
authors.lastname: Pérez Tamayo
authors.forename: Claudia Gonzalez
authors.initials: CG
authors.lastname: Rosado
authors.forename: Blanca Farfan
authors.initials: BF
authors.lastname: Labonne
authors.forename: Norma Morales
authors.initials: NM
authors.lastname: Rochilin
authors.forename: Rosalinda Martinez
authors.initials: RM
authors.lastname: Garcia
authors.forename: Jonathan Aguirre
authors.initials: JA
authors.lastname: Valadez
authors.forename: Gabriela Togno
authors.initials: GT
authors.lastname: Latour
authors.forename: Dana Lau
authors.initials: DL
authors.lastname: Corona
authors.forename: Guillermo Robles
authors.initials: GR
authors.lastname: Diaz
authors.forename: Albert
authors.initials: A
authors.lastname: Zlotnik
authors.forename: David
authors.initials: D
authors.lastname: Kershenobich
mesh_terms: D001656:Biliary Atresia; D016922:Cellular Senescence; D002648:Child; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology; D017093:Liver Failure / Q000209:etiology* / Q000473:pathology*; D017114:Liver Failure, Acute; D016031:Liver Transplantation; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D020176:Tyrosinemias
chemical_list: C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53