They did not have a therapeutic effect on the Profigin-independent progeria model mice (Zmpste24–/–) but expanded the lifespan of the HGPS model mice (Lmna+/G609G), representing the in vivo relevance of blocking Progerin–Lamin A/C interaction as a new therapeutic strategy for HGPS. Here, ZMPSTE24 is linked to Hutchinson-Gilford progeria syndrome.