p53BP1 forms discrete foci within minutes of radiation exposure, at sites of DNA double-strand breaks, which ordinarily decay to background levels within 24 h of induction. Longer lived, persisting 53BP1 foci are thought to mark unrepaired or misrepaired damage and potentially, to be associated with genomic instability. It is known that repair of DNA damage is impaired in senescent (permanently arrested) and aged cells. We examined this further by measuring the induction and persistence of 53BP1 foci in proliferating and non-proliferating mid-passage (non-aged) and late-passage (in vitro aged) normal human bronchial epithelial cells. Our results showed background levels of 53BP1 foci to be elevated in in vitro aged cultures as expected and induction of 53BP1 foci after radiation exposure to be independent of culture age or proliferative status. In terms of 53BP1 decay, more cells with persisting foci were seen in in vitro aged cultures compared to non-aged populations; furthermore, this was observed in both non-cycling (nominally senescent) cells, as well as in actively proliferating cells. In conclusion, perturbation in radiation-induced damage processing is a function of increasing chronological cellular age per se and should be considered when extrapolating experimental data for radiation risk modeling.

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