Gender differences in age-related decline in DNA double-strand break damage and repair in lymphocytes

Abstract

DNA repair capacity has been suggested to be a genetic mechanism which influences the rate of ageing and length of life. We recently reported an age-related decline in DNA double-strand break (DSB) repair in unstimulated human lymphocytes (Mayer, Lange, Bradley, and Nichols 1989, 1990). In that work peripheral lymphocytes isolated from whole blood donated by 20 normal, healthy subjects aged 23-78 years, were X-irradiated (30 Gy) on ice and incubated at 37 degrees C for repair times of 15, 30, and 120 min, and neutral filter elution was used to assay DSB induction and completeness of DSB rejoining. Further analysis reveals that the decrease in DSB rejoining appears to be more pronounced in older women than in older men (and may begin after age 65 years). Moreover the reported age-related decline in DSB induction occurs more rapidly (by a factor of ca. 2) in women than in men. We had previously demonstrated that, independently of in vivo age, cells with lower radiosensitivity (i.e. lesser DSB induction) appear to be less repair-proficient (Mayer et al. 1990). The present analysis reveals a gender-specific pattern in this correlation between extent of DSBs induced and percentage of DSBs rejoined: at comparable levels of DSB induction, cells from men rejoin a higher percentage of DSBs than do cells from women. This preliminary study suggests the following hypothesis: age-related DSB effects (i.e. induction and rejoining) are due to changes in chromatin structure and males are less sensitive than females to the influence which age-related alterations in chromatin exert on DSB effects.