Changes of DNA repair mechanisms during the aging of the rat.

Recent studies have shown a significant reduction in DNA repair capacity in aging rats. Therefore we were interested in investigating which repair mechanism is concerned in this reduction. We investigated: excision repair (ER); single-strand break repair (SSBR); double-strand break repair (DSBR); and gamma-endonuclease susceptibility (ES) by means of the following methods: [3H]thymidine ([3H]dThd) incorporation into DNA after damage by N-methyl-N-nitrosourea (MNU); nucleoid sedimentation after damage by methyl methanesulfonate (MMS); neutral elution techniques after damage by 4-nitroquinoline-1-oxide (NQO); and determination of ES sites by velocity sedimentation in an alkaline sucrose gradient after damage by gamma-irradiation. Studies were done with male Sprague-Dawley rats aged 9, 18 and 28 months using nine different organs. We were able to determine a distinct age dependency of excision repair, a slight reduction of single-strand break repair, an elevation of gamma-endonuclease susceptible sites and no significant change in double-strand break repair in the course of aging. Therefore we see a shift in the pattern of DNA repair: in old age strand break repair mechanisms become more important, while repair replication is reduced. From this we can conclude that genetic expression is altered during the aging process, with all the consequences for the disposition toward certain diseases.