Centromeres are epigenetically marked by the centromeric-specific histone H3 variant centromere protein A (CENP-A), and they provide the platform on which kinetochores assemble. Although ageing is known to involve epigenetic changes and can be triggered prematurely by deficiencies in kinetochore complex proteins, how ageing affects centromeres themselves is less well defined. Sikder et al. now reveal that levels of centromeric transcripts and CENP-A are downregulated in aged cells, but that these levels, and their associated mitotic defects, can be restored by concomitantly knocking down p53 and inhibiting lysine demethylase 1A (KDM1A).

Exploring the relationship between the decrease in centromeric transcripts and the changes in the protein levels of CENP-A, CENP-C and p53, the authors knocked down p53 in AgedDox cells, observing an increase in CENP-A and CENP-C protein compared with in control cells. However, the level of centromeric transcripts was not restored by p53 knockdown. Furthermore, restoring protein levels of CENP-A and CENP-C in this way did not rescue the mitotic defects that the authors had observed in AgedDox cells, suggesting that the decrease in centromeric transcription might contribute to mitotic defects in aged p53-knockdown fibroblasts.