Thus, we examined cytoskeletal stiffness and RhoA activation in cells from HGPS patients and from a mouse model of HGPS due to a deficiency in Zmpste24 (Z24), a zinc metalloproteinase involved in the formation of mature lamin A. Z24−/− mice have premature onset of aging‐related musculoskeletal changes, similar to those observed in HGPS (Bergo et al., 2002; Fong et al., 2004; Yang et al., 2006). Here, ZMPSTE24 is linked to Hutchinson-Gilford progeria syndrome.