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Lamin A, a product of the LMNA gene, is an essential nuclear envelope component in most differentiated cells. Mutations in LMNA have been linked to premature aging disorders, including Hutchinson-Gilford progeria syndrome (HGPS). HGPS is caused by progerin, an aberrant form of lamin A that leads to premature death, typically from the complications of atherosclerotic disease. A key characteristic of HGPS is a severe loss of vascular smooth muscle cells (VSMCs) in the arteries. Various mouse models of HGPS have been created, but few of them feature VSMC depletion and none develops atherosclerosis, the death-causing symptom of the disease in humans. We recently generated a mouse model that recapitulates most features of HGPS, including VSMC loss and accelerated atherosclerosis. Furthermore, by generating cell-type-specific HGPS mouse models, we have demonstrated a central role of VSMC loss in progerin-induced atherosclerosis and premature death. M.R.H. is supported by a ‘Juan de la Cierva’ postdoctoral fellowship (FJCI-2017-33299) from the Spanish Ministerio de Ciencia, Innovación yUniversidades (MCIU). Work in V.A.’s laboratory is supported by grants from the Spanish Instituto de Salud Carlos III (AC16/00091 and AC17/00067) and MCIU (SAF2016-79490-R), with co-funding from the Fondo Europeo de Desarrollo Regional (FEDER, ‘Una manera de hacer Europa’), the Progeria Research Foundation (Established Investigator Award 2014-52), and the Fundació Marató TV3 (122/C/2015). The CNIC is supported by theMCIU and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505); Instituto de Salud Carlos III [AC16/00091 and AC17/00067]; MCIU [SAF2016-79490-R]; MCIU [FJCI2017-33299]; MCIU [SEV-2015-0505]; Progeria Research Foundation [2014-52]. Sí