Proliferative potential and DNA repair in lymphocytes from short-lived and long-lived strains of mice, relation to aging.

The replicative capacity and DNA repair ability of spleen lymphocytes of young and old mice from short-lived and long-lived strains were studied. DNA repair after both UV- and gamma-induced damage was investigated. Proliferation after Con A decreased as a function of age in both mouse strains and paralleled an age-associated decline in repair of DNA damage induced by either UV or gamma-irradiation. Compared to the long-lived, the short-lived strain displayed an earlier impairment of both proliferative and repair potentials. DNA repair after gamma-induced damage only occurred if lymphocytes were stimulated to proliferate. Resting lymphocytes appeared unable to repair strand breaks. By contrast, DNA repair of UV-induced damage showed two components: one was dependent on the cell proliferative state, the other was not. Both components were stimulated or induced by mitogen. Resting lymphocytes were able to perform an appreciable amount of repair after UV irradiation. Our results suggest that resting or post-mitotic cells possess a greater possibility to regulate repair of UV-induced than gamma-induced damage. We speculate that it may be the level of this proliferation-independent, but mitogen inducible form of repair which correlates with maximum life-spans between species, thereby explaining why repair of UV- but not gamma-induced damage reveals such a correlation.