Protraction of anaphase B in lymphocyte mitosis with ageing: possible contribution to age-related cancer risk

Ageing is associated with a reduction in the fidelity of cell division as shown by increases in trisomic and polyploid cells; however, to date, the underlying age-specific changes in cell division have not been identified. Understanding these specific changes in cell division could give insight into the aetiology some age-related illnesses, especially cancer. Using blood collected from 72 women aged 18-53 years, this study recorded the frequencies of cells in each of the stages of mitosis in synchronised lymphocyte cultures harvested at controlled temperature without microtubule inhibitors. Factor analysis identified four components that accounted for >67.5% of the variance in the data. The component we named 'Spindle elongation efficiency', which was primarily influenced by the time taken to complete anaphase B, showed a major change with age: women aged ≥36 showed a highly statistically significant protraction of anaphase B compared with those aged ≤35 (t = -2.74, df = 70, P = 0.006) and linear regression showed a logarithmic change in this component with age (R = 0.297, P = 0.011). This phosphorylation-dependent phase of the cycle is responsible for increasing the distance between the two sets of daughter chromosomes and in older subjects the daughter nuclei at telophase were often poorly separated. Inefficient spindle elongation with ageing probably results from decreased cellular energy. Insufficient force at anaphase B might fail to resolve merotelic kinetochore attachments such that lagging at anaphase would be uncorrected and lead to trisomy and polyploidy in daughter cells.