31 Additionally, both studies analyzed telomeres in whole liver homogenates and assumed that findings were representative of hepatocytes. This assumption is flawed, however, because only 64% of cells in liver tissue are hepatocytes,27 and in our study there selleck was no correlation between whole liver telomere length measured by real-time PCR and hepatocyte telomere length assessed by Q-FISH. This and the utilization of archived paraffin-embedded material emphasizes the advantages of Q-FISH. The ability to include only cells that meet tight definitions excludes cells with unusual morphology, and the large

numbers of cells available for analysis increases methodological robustness. Obtaining normal healthy

liver tissue for research over a broad age range is challenging. Tissue from hepatic resections for malignancy, distant to the tumor with normal macroscopic and microscopic appearances, demonstrate shortened telomeres25-27, 28-30 and is only available over a narrow age range. Our subjects were highly selected for normality and may represent unusually healthy liver. Comparison with age-matched hyperoxalosis normal liver tissue, often used in domino liver transplantation,32-38 vindicated this approach, as there was no discernible difference in telomere length between the groups. Different intrahepatic lineages in healthy liver aged at different rates. Bortezomib price Age-related telomere shortening was restricted to Kupffer cells click here and hepatic stellate cells. Maintained telomere length with increased age in cholangiocytes and hepatocytes

(in contrast to previous studies25, 26) may reflect low turnover of these populations, thus preserving regenerative capacity. The preservation of hepatocyte telomere length with age contrasts with observations of reduced regenerative capacity with increasing age and clinical experience that older individuals are more susceptible to liver injury. Two factors may explain this anomaly. First, great lengths were undertaken to identify normal liver so that excellent donor liver function at 1 year and exclusion of concomitant senescence-related disease, steatosis and graft injury were defined entry criteria and less than 8% of available donor livers were studied. The study group was healthy and normal (unlike previous studies), but not necessarily typical of the everyday. Second, liver function is not related to hepatocytes alone but to all intrahepatic cells and the finding that sinusoidal cells showed age-related telomere shortening may be an important observation in relation to age-related liver function.