Model systems for studies on cellular basis of organ ageing

The cellular basis of the age-related decline in the functional capacity of many mammalian organs is still poorly understood. In this paper, the rat liver is presented as a promising model for studying cellular phenomena underlying organ ageing. The recent development of methods for isolation and purification of parenchymal, Kupffer and endothelial cells from the rat liver makes possible the comparison of functional and metabolic changes in the intact liver with changes in distinct liver cell classes isolated from rats of various age groups. An attempt has been made to correlate age changes in some important liver-specific functions, such as bromsulophthalein uptake and albumin synthesis, at the organ and at the cellular level. To compare cellular ageing phenomena in long-lived cells (parenchymal cells) and short lived cells (Kupffer and endothelial cells) from the same organ, the role of lysosomes in cellular ageing processes was investigated, with secial reference to the functioning of the lysosomal enzyme cathepsin D. The specific cathepsin D activity in Kupffer cells was abour 3 times higher than in endothelial cells and about 20 times higher than in parenchymal cells. The enzyme activity in the latter cell type showed a significant increase with age.