The Isolated Hepatocyte: A Cellular Model for Aging Studies

Abstract

Abstract

Based on the concept that the absence of cell division leads to senescence and that aging changes are most clearly manifest in long-lived postmitotic cells, isolated hepatocytes are proposed as a suitable model for the study of cellular aging. These cells, aged in vivo under normal physiological conditions, will be of the same age as the donor after isolation. Several possibilities and advantages of this system are discussed. Examples given of the use of isolated hepatocytes for aging studies include the investigation of the relation between age-related alterations in rat liver functions (drug clearance, albumin synthesis) and aging processes at the cellular level. The potential use of isolated hepatocytes for studies on basic cellular aspects of aging is illustrated by experiments on changes in the activities of lysosomal enzymes as well as their multiple forms. A new additional approach to the study of cell aging, particularly with regard to phenomena such as cell contacts, cell recognition, and mutual influences between cells of various types, is offered by the possibility of cocultivating hepatocytes and sinusoidal cells from young and old rat livers.