Stereological analysis of hepatic fine structure in the Fischer 344 rat. Influence of sublobular location and animal age.

Abstract

Stereological analysis of hepatic fine structure in Fischer 344 male rats at 1,6,10,16,20,25, and 30 mo of age revealed differences in the amounts and distributions of hepatocellular organelles as a function of sublobular location or animal age. Between 1 and 16 mo of age, both the centrolobular and periportal hepatocytes increased in volume by 65 and 35%, respectively. Subsequently, the cell volumes declined until the hepatocytes of 30-mo-old rats approached the size of those found in the youngest animals. Regardless of animal age, the centrolobular cells were consistently larger than the corresponding periportal hepatocytes. The cytoplasmic and ground substance compartments reflected similar changes in their volumes, although there was no significant alteration in the nuclear volume.The volumes of the mitochondrial and microbody compartments increased and decreased concomitant with the changes in average hepatocyte size. Both lobular zones in the 30-mo-old rats contained significantly smaller relative volumes of mitochondria than similar parenchyma in 16-mo-old animals. The volume density of the dense bodies (lysosomes) increased markedly in both lobular zones between 1 and 30 mo of age, confirming reports of an age-dependent increase in this organelle. The surface area of the endoplasmic reticulum in the centrolobular and periportal hepatocytes reached its maximum level in the 10-mo-old rats and subsequently declined to amounts which approximated those measured in the 1-mo-old animals. This age-related loss of intracellular membrane is attributable to a significant reduction in the surface area of the smooth-surfaced endoplasmic reticulum (SER) in animals beyond 16 mo of age. The amount of rough-surfaced endoplasmic reticulum (RER) in the periportal parenchymal cells was unaffected by aging, but the centrolobular hepatocytes of 30-mo-old animals contained 90% more RER than similar cells in the youngest rats. The centrolobular parenchyma contained more SER and the portal zones more RER throughout the age span studied. These quantitative data suggest that (a) certain hepatic fine structural parameters undergo marked changes as a function of animal age, (b) there exists a gradient in hepatocellular fine structure across the entire liver lobule, and (c) J. CELL BIOLOGY 9 The Rockefeller University Press 9

Aging and the Liver: An Update

“…DePriester et al (22) suggested that an age-associated increase in the hepatocyte binuclear B315 B316 SCHMUCKER index, coupled with no change in hepatocyte volume, results in an increase in the nucleocytoplasmic ratio. In agreement with this and other studies, our own analyses demonstrated that age-associated changes in the hepatocyte nucleocytoplasmic ratio reflected concomitant shifts in cell and nuclear volumes (21,23,24; see Figure 1). Although aging appears to be accompanied by an increase in hepatocyte nuclear ploidy, changes in cell and/or nuclear volumes are less apparent owing, in part, to an age-associated increase in interindividual variability.…”

“…Several studies reported no change or an increase in the binuclear hepatocyte index during aging in rodents and humans (19,20). However, our own studies in inbred Fischer 344 rats did not demonstrate a significant age-associated change in the number of binuclear hepatocytes (21). DePriester et al (22) suggested that an age-associated increase in the hepatocyte binuclear B315 B316 SCHMUCKER index, coupled with no change in hepatocyte volume, results in an increase in the nucleocytoplasmic ratio.…”

Molecular alterations in proteasomes of rat liver during aging result in altered proteolytic activities

“…During aging, this is not necessarily the case, for example in skeletal muscle the disequilibrium between the rates of protein synthesis and degradation causes sarcopenia (Millward et al 1997). Although there is no equivalent phenomenon known in liver tissue, it has been reported that the liver volume decreases with age (Zeeh and Platt 2002;Schmucker 2005), although the volume of individual hepatocytes in rat liver rises till the age of 6 or 16 months before declining again with increasing age to the volume measured in young rats (David 1985;Schmucker et al 1978). Our investigation showed that the protein concentration was diminished by about 25 % in liver tissue of aged as compared to young rats paralleled by a 40 % decrease in the content of 20S proteasome.…”

Reconstitution of Liver Mass Via Cellular Hypertrophy in the Rat

“…In fact, hepatocytic damage is a prerequisite of extensive oval-cell proliferation. 5,6 Schmucker et al 20 reported that in normal male F344 rats, the pericentral hepatocytes are consistently larger than the periportal ones. We could not confirm this observation.…”

“…The animals were killed at the time of the last Dex injection and 24, 32, 40, 48, 56, and 64 hours later. For the electrophoretic mobility shift assay (EMSA), the rats were killed 20,22,24,26,28,30 hours after the last Dex injection.In a second series, Dex was replaced by 25 mg/kg 5-fluorouracil (FU) (Hoffman-LaRoche, Nutley, NJ) intraperitoneally daily. Rats treated by FU were killed 1 and 5 days after PH.…”