FIGURE 1.

Mechanisms responsible for nuclear envelope dysfunction during aging. With age, prelamin A accumulates and induces NE invaginations, trapping Nup153. This results in disruption of the nuclear basket of the NPC, leading to NPC clustering and degradation that decreases NE selectivity. The mislocalization of Nup153 affects the Ran gradient by interfering with its import into the nucleus, which in turn reduce the nuclear import of large molecules, namely 53BP1. 53BP1 is a key protein for DSB repair and the decrease of its import to the nucleus compromises the DNA damage repair, leading to the accumulation of DNA damage in the cells. DSB, DNA double‐stranded break; NE, nuclear envelope; NPC, nuclear pore complex