We thank the members of our research groups and colleagues with the Colorectal Cancer Program. “
“Telomeres, a validated biomarker of aging, comprise multiple nucleotide repeats capping chromosomes that shorten with each cell cycle until a critical length is achieved, precipitating cell senescence. Only two previous studies focused on the effect of aging in “normal” liver tissue, but these studies were compromised by small
sample size, limited age range, tissue derived from individuals with an increased risk of selleck products senescence, and the use of liver homogenates. We developed a robust large-volume, four-color quantitative fluorescent in situ hybridization technique to measure telomere length in large numbers of hepatocytes, Kupffer cells, hepatic stellate cells, CD4-positive and CD8-positive lymphocytes, and cholangiocytes. Following validation against the gold standard (Southern blotting), the technique was applied to normal archived paraffin-embedded liver tissue obtained following reperfusion of implanted donor liver. We studied 73 highly selected donors
Selleckchem GSK458 aged 5-79 years with a short medical illness preceding death and no history of liver disease, reperfusion injury, or steatosis and normal graft function 1-year posttransplantation. Cholangiocytes had significantly longer telomeres compared with all other intrahepatic lineages over a wide age range (P < 0.05). Age-related telomere attrition was restricted to sinusoidal cells (i.e., Kupffer cells [P = 0.0054] and stellate cells [P = 0.0001]). Cholangiocytes and hepatocytes showed no age-related telomere shortening. Conclusion: In normal liver and over a broad age range, cholangiocytes have longer telomeres than all other intrahepatic lineages. Age-related telomere length decline is restricted to Kupffer cells and stellate cells. (HEPATOLOGY 2012) As the median MCE公司 age of populations increases worldwide, so too does that of patients presenting with liver disease. There are many structural and functional changes in all organs with increasing
age, including the liver.1, 2 Strong evidence links increased age with impaired liver regeneration and increased risk of fibrosis, hepatocellular carcinoma and death. Age is an important adverse factor in chronic liver disorders including chronic hepatitis C virus infection,3, 4 non–alcohol-related fatty liver disease,5 primary biliary cirrhosis, alcohol-related hepatitis and hemochromatosis.1 Donor age has an enormous impact on graft survival following liver transplantation.6 The risk of death with liver disease is substantially higher in older patients.7 Impaired liver regeneration with increasing age is demonstrated clinically in acute liver failure8 and acute hepatitis A virus infection9, 10 and rodent models of partial hepatectomy, where restoration of liver mass is slower in older animals.