Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare multisystem 
childhood premature aging disorder linked to mutations in the LMNA gene. The 
most common HGPS mutation is found at position G608G within exon 11 of the LMNA 
gene. This mutation results in the deletion of 50 amino acids at the 
carboxyl-terminal tail of prelamin A, and the truncated protein is called 
progerin. Progerin only undergoes a subset of the normal post-translational 
modifications and remains permanently farnesylated. Several attempts to rescue 
the normal cellular phenotype with farnesyltransferase inhibitors (FTIs) and 
other compounds have resulted in partial cellular recovery. Using proteomics, we 
report here that progerin induces changes in the composition of the HGPS nuclear 
proteome, including alterations to several components of the protein degradation 
pathways. Consequently, proteasome activity and autophagy are impaired in HGPS 
cells. To restore protein clearance in HGPS cells, we treated HGPS cultures with 
sulforaphane (SFN), an antioxidant derived from cruciferous vegetables. We 
determined that SFN stimulates proteasome activity and autophagy in normal and 
HGPS fibroblast cultures. Specifically, SFN enhances progerin clearance by 
autophagy and reverses the phenotypic changes that are the hallmarks of HGPS. 
Therefore, SFN is a promising therapeutic avenue for children with HGPS.