The panoply of progerias

Premature aging syndromes in model organisms and humans provide insight into the mechanisms of natural aging. To the extent that progerias represent true acceleration of wildtype aging processes, they also draw our attention to genes that might someday be targeted by lifespan-enhancement strategies.

An excellent recent review from Navarro et al. covers a lot of ground on this subject, discussing many different human progeroid syndromes and focusing especially on the laminopathies, exemplified by Hutchinson-Gilford progeria:

Progeroid syndromes (PSs) constitute a group of disorders characterized by clinical features mimicking physiological aging at an early age. In some of these syndromes, biological hallmarks of aging are also present, whereas in others, a link with physiological aging, if any, remains to be elucidated. … [A]ll the characterized PSs enter in the field of rare monogenic disorders and several causative genes have been identified. These can be separated in subcategories corresponding to (i) genes encoding DNA repair factors, in particular, DNA helicases, and (ii) genes affecting the structure or post-translational maturation of lamin A, a major nuclear component. In addition, several animal models featuring premature aging have abnormal mitochondrial function or signal transduction between membrane receptors, nuclear regulatory proteins and mitochondria: no human pathological counterpart of these alterations has been found to date. … Recently, several studies allowed to establish a functional link between DNA repair and A-type lamins-associated syndromes, evidencing a relation between these syndromes, physiological aging and cancer. …

While I’m on the subject: There’s been some very good recent news on the Hutchinson-Gilford front. Farnesyltransferase inhibitors, a class of drugs originally developed to attack the Ras pathway in cancer, are showing great promise in reversing the nuclear abnormalities resulting from the underlying lamin A/C mutation. Often rare diseases don’t get very much attention from pharmaceutical developers, so it’s nice to know that HGPS patients and their families have some hope for a meaningful treatment.