Aging Reduces the Numbers of Hepatocytes Synthesizing DNA in Response to EGF and Epinephrine

Primary cultures of hepatocytes were prepared from young (6 month) and old (24 month) Wistar rats and exposed to epinephrine or epidermal growth factor. Incorporation of [ 3H]thymidine into DNA was determined both radiochemically and autoradiographically. The numbers of responding cells and degree of response per cell were determined and the results confirmed by FACScan analysis. Such analyses clearly demonstrate a reduced number of hepatocytes capable of responding to the above stimuli in cultures obtained from old rats. Thus, changes in numbers of responding cells may be an important mechanism involved in reduced responsiveness of the aged liver to agents which stimulate DNA synthesis and cell division.