Reduced DNA synthesis in primary cultures of hepatocytes from old mice is restored by thymus grafts.

We previously observed in vivo that a neonatal thymus grafted into old mice can correct age-related changes such as occurrence of hepatocyte tetraploid nuclei and impaired isoproterenol-induced DNA synthesis in submandibular glands. The aim of the present paper was to study the influence of age and thymus on basal and beta-adrenergic-stimulated DNA synthesis using primary cultures of mouse hepatocytes. In the absence of any adrenergic agents, cells from young mice show peak DNA synthesis between 36 and 48 h; old mice show a similar time course, but the peak is significantly reduced statistically. The main result is represented by the behavior of hepatocytes from old thymus-grafted mice, which recover the levels of [3H]-thymidine incorporation toward young-like values. Grafted animals also show a correction of total DNA content that is increased in old mice. The addition of isoproterenol does not modify the DNA synthetic pattern, whereas the antagonist propranolol causes a slight but statistically significant decrease.