Figure 1. Molecular parallels between premature aging and physiological aging. The premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by activation of a cryptic splice site in the lamin A/C gene (LMNA) leading to the production of a dominant-negative lamin A protein isoform. The protein disrupts nuclear function and leads to defects in chromatin organization and DNA repair. During normal aging, the same cryptic splice site in LMNA is used at low levels. Although the production of aberrant lamin A is tolerated in young cells, it leads to defects in aged cells similar to those in the cells of HGPS patients. CSIM, C-terminal CAAX motif (C, cysteine; A, usually an aliphatic residue; and X, any amino acid).