title: Rejuvenating somatotropic signaling: a therapeutical opportunity for premature aging?
abstract: We have recently reported that progeroid Zmpste24-/- mice, which exhibit multiple defects that phenocopy Hutchinson-Gilford progeria syndrome, show a profound dysregulation of somatotropic axis, mainly characterized by the occurrence of very high circulating levels of growth hormone (GH) and a drastic reduction in insulin-like growth factor-1 (IGF-1). We have also shown that restoration of the proper GH/IGF-1 balance in Zmpste24-/- mice by treatment with recombinant IGF-1 delays the onset of many progeroid features in these animals and significantly extends their lifespan. Here, we summarize these observations and discuss the importance of GH/IGF-1 balance in longevity as well as its modulation as a putative therapeutic strategy for the treatment of human progeroid syndromes.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006-Oviedo, Spain.
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Ugalde
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mariño
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Otín
mesh_terms: D019588:Aging, Premature / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005838:Genotype; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000627:therapeutic use; D008136:Longevity; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D008666:Metalloendopeptidases / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011371:Progeria / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012060:Rejuvenation; D015398:Signal Transduction
chemical_list: D008565:Membrane Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D008666:Metalloendopeptidases; C491250:Zmpste24 protein, mouse