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

Authors: Marino, G  Ugalde, AP  Fernandez, AF  Osorio, FG  Fueyo, A  Freije, JM  Lopez-Otin, C 
Citation: Marino G, etal., Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16268-73. doi: 10.1073/pnas.1002696107. Epub 2010 Aug 30.
Pubmed: (View Article at PubMed) PMID:20805469
DOI: Full-text: DOI:10.1073/pnas.1002696107

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.


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CRRD Object Information
CRRD ID: 10003141
Created: 2015-05-04
Species: All species
Last Modified: 2015-05-04
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.