Long lifetime and selective accumulation of the A-type lamins accounts for the tissue specificity of Hutchinson-Gilford progeria syndrome.

Many human diseases are caused by mutations to broadly expressed proteins, yet disease mysteriously manifests only in specific tissues. An example of this is Hutchinson-Gilford progeria syndrome (HGPS), which is caused by a mutation to the Lamin A/C protein. We show that this mutation slows the turnover of Lamin A/C proteins in disease-afflicted tissues, causing the mutant "Progerin" protein to accumulate over time and interfere with the normal turnover of hundreds of other proteins. Because Progerin is a long-lived protein, effective therapies for this disease will need to attack the protein and not just the gene that encodes it.