title: Vacuolation in hepatocyte nuclei is a marker of senescence.
abstract: Hepatocyte nuclear vacuolation is considered benign and associated with non-alcohol-related fatty liver disease. Vacuolated hepatocyte nuclei were compared with non-vacuolated hepatocyte nuclei in eight patients with advanced fibrosis and a spectrum of liver disease to explore the hypothesis that such nuclei represent senescence. Age- and sex-matched liver donors served as normal tissue. In normal liver <0.01% hepatocytes showed nuclear vacuolation. In contrast, nuclear vacuolation was present in all patients with liver disease, ranging from 0.1% to 11.7% hepatocytes, irrespective of the aetiology of liver disease and independent of insulin resistance. There was a close association between nuclear vacuolation and increased nuclear area, p21 expression, γ H(2)AX expression and the absence of Mcm-2, consistent with senescence and cell cycle arrest. Nuclear vacuolation in hepatocytes is a marker of senescence and likely to be a consequence of liver injury, unrelated to insulin resistance.
authors.affiliation: Division of Gastroenterology & Hepatology, University Department of Medicine, Cambridge University Hospitals, Cambridge, UK.
authors.forename: Aloysious
authors.initials: A
authors.lastname: Aravinthan
authors.forename: Suman
authors.initials: S
authors.lastname: Verma
authors.forename: Nick
authors.initials: N
authors.lastname: Coleman
authors.forename: Susan
authors.initials: S
authors.lastname: Davies
authors.forename: Michael
authors.initials: M
authors.lastname: Allison
authors.forename: Graeme
authors.initials: G
authors.lastname: Alexander
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D002467:Cell Nucleus / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D022781:Hepatocytes / Q000473:pathology*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014617:Vacuoles / Q000473:pathology*
chemical_list: D015415:Biomarkers; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C468783:H2AX protein, human; D006657:Histones