Progeria syndromes, which are caused in part by methylation of prelamin A, result in a premature ageing phenotype. This study showed that a mouse model of progeria that had reduced genetic expression of isoprenylcysteine carboxylmethyltransferase (ICMT) had increased body weight, fewer bone fractures and a lower death rate. Moreover, the premature senescence of fibroblasts from these mice was abolished. Inhibition of ICMT by a short hairpin RNA delayed senescence in human progeria fibroblasts, which suggests that inhibiting ICMT might be beneficial for treating progeroid disorders.