Accelerated aging or progeria has been a puzzling disease for many years. The 
recent findings involving the lamin A/FACE-1 (substrate/protease) system in the 
etiology of Hutchinson-Gilford progeria syndrome and related pathologies have 
shed some light on the mechanisms underlying the development of these 
devastating conditions. Thus, genetic defects in the nuclear envelope protein 
prelamin A or in the FACE-1 metalloprotease (also called Zmspte24) involved in 
prelamin A proteolytic maturation, cause the accumulation of an abnormal form of 
this protein and the subsequent disruption of nuclear envelope integrity. 
Recently, we and others have observed how this disruption leads to alterations 
in chromatin organization, genomic instability, transcriptional changes, and 
activation of a p53-linked signaling pathway. By using genetic manipulation 
approaches in mouse, we have shown that lowering prelamin A levels results in a 
total recovery of Zmpste24-deficient mice from the accelerated aging process. 
Moreover, p53 nullizygosity allows a modest but significant improvement in the 
premature aging phenotype, and contributes to delaying the onset of the 
progeroid condition. On the basis of these results, we propose different 
potential therapeutic approaches that could be tested in Zmpste24-deficient 
mice. These strategies, some of which are based on existing drugs, might 
contribute to the development of effective treatments for these dramatic 
pathologies.