Insulin-like growth factor 1 treatment extends longevity in a mouse model of human premature aging by restoring somatotroph axis function

G Mariño, AP Ugalde, ÁF Fernández… - Proceedings of the …, 2010 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2010National Acad Sciences
Zmpste24 (also called FACE-1) is a metalloproteinase involved in the maturation of lamin A,
an essential component of the nuclear envelope. Zmpste24-deficient mice exhibit multiple
defects that phenocopy human accelerated aging processes such as Hutchinson–Gilford
progeria syndrome. In this work, we report that progeroid Zmpste24-/− mice present
profound transcriptional alterations in genes that regulate the somatotroph axis, together
with extremely high circulating levels of growth hormone (GH) and a drastic reduction in …
Zmpste24 (also called FACE-1) is a metalloproteinase involved in the maturation of lamin A, an essential component of the nuclear envelope. Zmpste24-deficient mice exhibit multiple defects that phenocopy human accelerated aging processes such as Hutchinson–Gilford progeria syndrome. In this work, we report that progeroid Zmpste24-/ mice present profound transcriptional alterations in genes that regulate the somatotroph axis, together with extremely high circulating levels of growth hormone (GH) and a drastic reduction in plasma insulin-like growth factor 1 (IGF-1). We also show that recombinant IGF-1 treatment restores the proper balance between IGF-1 and GH in Zmpste24-/ mice, delays the onset of many progeroid features, and significantly extends the lifespan of these progeroid animals. Our findings highlight the importance of IGF/GH balance in longevity and may be of therapeutic interest for devastating human progeroid syndromes associated with nuclear envelope abnormalities.
National Acad Sciences