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          Institute: MPI für Neurobiologie     Collection: Molecular Neurobiology     Display Documents

ID: 412742.0, MPI für Neurobiologie / Molecular Neurobiology
Brain IGF-1 Receptors Control Mammalian Growth and Lifespan through a Neuroendocrine Mechanism
Authors:Kappeler, L.; Filho, C. D. M.; Dupont, J.; Leneuve, P.; Cervera, P.; Perin, L.; Loudes, C.; Blaise, A.; Klein, R.; Epelbaum, J.; Le Bouc, Y.; Holzenberger, M.
Date of Publication (YYYY-MM-DD):2008-10
Title of Journal:PLoS Biology
Journal Abbrev.:PLoS. Biol.
Issue / Number:10
Start Page:2144
End Page:2153
Sequence Number of Article:e254
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Mutations that decrease insulin-like growth factor (IGF) and growth hormone signaling limit body size and prolong lifespan in mice. In vertebrates, these somatotropic hormones are controlled by the neuroendocrine brain. Hormonelike regulations discovered in nematodes and flies suggest that IGF signals in the nervous system can determine lifespan, but it is unknown whether this applies to higher organisms. Using conditional mutagenesis in the mouse, we show that brain IGF receptors (IGF-1R) efficiently regulate somatotropic development. Partial inactivation of IGF-1R in the embryonic brain selectively inhibited GH and IGF-I pathways after birth. This caused growth retardation, smaller adult size, and metabolic alterations, and led to delayed mortality and longer mean lifespan. Thus, early changes in neuroendocrine development can durably modify the life trajectory in mammals. The underlying mechanism appears to be an adaptive plasticity of somatotropic functions allowing individuals to decelerate growth and preserve resources, and thereby improve fitness in challenging environments. Our results also suggest that tonic somatotropic signaling entails the risk of shortened lifespan.
External Publication Status:published
Document Type:Article
Affiliations:MPI für Neurobiologie/Molecular Neurobiology (Klein)
External Affiliations:[Kappeler, Laurent; Filho, Carlos De Magalhaes; Leneuve, Patricia; Perin, Laurence; Blaise, Annick; Le Bouc, Yves; Holzenberger, Martin] Hop St Antoine, INSERM, U893, F-75571 Paris, France.; [Filho, Carlos De Magalhaes; Blaise, Annick; Le Bouc, Yves] Univ Paris 06, Paris, France.; [Dupont, Joelle] INRA, F-37380 Nouzilly, France.; [Cervera, Pascale] Hop St Antoine, Serv Anatomopathol, F-75571 Paris, France.; [Loudes, Catherine; Epelbaum, Jacques] Ctr Paul Broca, INSERM, U549, Paris, France.
Identifiers:ISI:000260423900010 [ID No:1]
ISSN:1544-9173 [ID No:2]
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