......A plethora of data suggests that the nuclear lamina is a key player in chromatin dynamics and argue in favour of a major involvement of prelamin A in fundamental mechanisms regulating cellular senescence and organism ageing. As the best model to analyse the role of prelamin A in normal ageing, here we used cells from centenarian subjects.
We show that prelamin A is accumulated in centenarian fibroblasts due to down-regulation of its specific endoprotease ZMPSTE24, while other nuclear envelope constituents are mostly unaffected and cells do not enter senescence
. Prelamin A accumulation in centenarian nuclei elicits loss of heterochromatin, as well as recruitment of the inactive form of 53BP1, associated with rapid response to oxidative stress. These effects, including prelamin A-mediated increase of nuclear 53BP1, can be reproduced by rapamycin treatment of cells from younger individuals.....