title: Reduced brain insulin-like growth factor I function during aging.
abstract: Peripheral insulin-like growth factor I (IGF-I) function progressively deteriorates with age. However, whereas deterioration of IGF-I function in the aged brain seems probable, it has not been directly addressed yet. Because serum IGF-I can enter into the brain through the cerebrospinal fluid (CSF), we examined this route of entrance in aged mice. To distinguish endogenous murine IGF-I from exogenously applied IGF-I, we used human IGF-I. We found that after intraperitoneous injection, CSF levels of human IGF-I were significantly higher in old mice (2 year-old) as compared to young ones (4-month-old). In spite of this increase capacity to take IGF-I from the circulation, brain and plasma IGF-I levels were reduced in naive old mice. Moreover, IGF-I signaling was deteriorated in the brain of aged animals. Basal as well as IGF-I-induced activation of the brain IGF-I receptor/Akt/GSK3 pathway was markedly reduced even though old mice have higher levels of brain IGF-I receptors. These data suggest that increases in brain IGF-I receptors and in the capacity to take up serum IGF-I result ineffective because IGF-I function is reduced and aged mice are cognitively impaired, a trait dependant on preserved serum IGF-I input to the brain.
authors.affiliation: Departamento de Bioquímica, ICBS, UFRGS. Programa de Pós Graduação em Ciências Biológicas-Bioquímica. Porto Alegre, RS, Brazil.
authors.forename: Alexandre Pastoris
authors.initials: AP
authors.lastname: Muller
authors.affiliation: Cajal Institute and CIBERNED, Madrid, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Fernandez
authors.affiliation: Departamento de Bioquímica, ICBS, UFRGS. Programa de Pós Graduação em Ciências Biológicas-Bioquímica. Porto Alegre, RS, Brazil.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Haas
authors.affiliation: Departamento de Bioquímica, ICBS, UFRGS. Programa de Pós Graduação em Ciências Biológicas-Bioquímica. Porto Alegre, RS, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Zimmer
authors.affiliation: Departamento de Bioquímica, ICBS, UFRGS. Programa de Pós Graduação em Ciências Biológicas-Bioquímica. Porto Alegre, RS, Brazil.
authors.forename: Luis Valmor
authors.initials: LV
authors.lastname: Portela
authors.affiliation: Cajal Institute and CIBERNED, Madrid, Spain. Electronic address: torres@cajal.csic.es.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Torres-Aleman
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003071:Cognition / Q000502:physiology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*
chemical_list: D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3