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

• DOI: 10.1073/pnas.1002696107
• Publication Date: 2010-08-31T02:49:18Z
• Authors: Guillermo Mariño; Alejandro P. Ugalde; Álvaro F. Fernández; Fernando G. Osorio; Antonio Fueyo; José M. P. Freije; Carlos López-Otín
• Keywords: Mice, Knockout; 0301 basic medicine; Base Sequence; Gene Expression Profiling; Longevity; Membrane Proteins; Metalloendopeptidases; Aging, Premature; Somatotrophs; Disease Models, Animal; Mice; MicroRNAs; 03 medical and health sciences; Gene Expression Regulation; Liver; Growth Hormone; Animals; Insulin-Like Growth Factor I

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

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− 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

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− 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.