Effects of age and gender on micronucleus and chromosome nondisjunction frequencies in centenarians and younger subjects

Studies have shown a significant increase in chromosome aneuploidy with age. The aim of this study was to elucidate whether the age-related changes in the level of hypoploidy correlate with the occurrence of micronuclei (MN) and chromosome nondisjunction (ND) in men and women. We analyzed cytokinesis-blocked (binucleated) lymphocytes treated with cytochalasin B, from 127 donors varying in gender and age including 53 centenarians. Fluorescent in situ hybridization with probes specific for several autosomes (1, 4, 6, 8, 20) and for the sex chromosomes was applied to analyze the chromosomal content of MN and to analyze the frequency of reciprocal loss and gain due to ND in binucleated interphase cells. The general level of MN in Giemsa-stained preparations was higher in women and in both genders increased with age until approximately 70 years and ranged, depending on age group, from 0.5 to 1.4% in men and from 0.9 to 1.8% in women. Gender-related differences were mostly observed in the younger age groups (< or =50 years), with an almost two-fold difference between men and women (P < 0.005). Frequencies of autosome-positive MN in both genders and of sex chromosome-positive MN in men were comparable and remained unchanged in older groups. The frequency of X-positive MN in women was higher than the average frequency of autosome-positive MN and continued to increase until the oldest age. The frequency of NDs involving the analyzed chromosomes was on average two-fold higher in women than in men. In both genders, the frequency of NDs increased with age and was, on average, an order of magnitude higher than that of cells with MN, consistent with the previous reports that the efficiency of elimination of micronucleated cells is higher than of the cells presenting chromosome ND.