title: Insulin-like growth factor 1 treatment extends longevity in a mouse model of human premature aging by restoring somatotroph axis function.
abstract: 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.
authors.affiliation: Departamento de Bioquímica y Biología Molecular and Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mariño
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Ugalde
authors.forename: Alvaro F
authors.initials: AF
authors.lastname: Fernández
authors.forename: Fernando G
authors.initials: FG
authors.lastname: Osorio
authors.forename: Antonio
authors.initials: A
authors.lastname: Fueyo
authors.forename: José M P
authors.initials: JM
authors.lastname: Freije
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Otín
mesh_terms: D019588:Aging, Premature / Q000097:blood / Q000188:drug therapy*; D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008136:Longevity / Q000187:drug effects*; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism; D008666:Metalloendopeptidases / Q000172:deficiency / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics; D052683:Somatotrophs / Q000187:drug effects*
chemical_list: D008565:Membrane Proteins; D035683:MicroRNAs; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D008666:Metalloendopeptidases; C491250:Zmpste24 protein, mouse
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