Defects in prelamin A processing by ZMPSTE24 result in premature aging disorders including Hutchinson Gilford Progeria Syndrome (HGPS) and related progeroid diseases.
Mutations in the nuclear membrane zinc metalloprotease ZMPSTE24 lead to diseases of lamin processing (laminopathies), such as the premature aging disease progeria and metabolic disorders.
Here, we discuss the discovery of the yeast and mammalian ZMPSTE24 orthologs and review the unexpected connection between ZMPSTE24 and premature aging.
On the basis of these results, we propose that nuclear abnormalities causing premature aging in Zmpste24(-/-) mice trigger a metabolic response involving the activation of autophagy.
These data provide clues as to the cellular basis for premature aging in HGPS and support the view that cellular senescence and tissue homeostasis are important factors in the normal aging process.