Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.
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. Hormone-like regulations discovered in nematodes and flies suggest that IGF sign...
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2008-10-01
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doaj-0c8d24f4a14e43c79b451ce8c5aeea142021-07-02T01:12:54ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852008-10-01610e25410.1371/journal.pbio.0060254Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.Laurent KappelerCarlos De Magalhaes FilhoJoëlle DupontPatricia LeneuvePascale CerveraLaurence PérinCatherine LoudesAnnick BlaiseRüdiger KleinJacques EpelbaumYves Le BoucMartin HolzenbergerMutations 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. Hormone-like 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.http://europepmc.org/articles/PMC2573928?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laurent Kappeler Carlos De Magalhaes Filho Joëlle Dupont Patricia Leneuve Pascale Cervera Laurence Périn Catherine Loudes Annick Blaise Rüdiger Klein Jacques Epelbaum Yves Le Bouc Martin Holzenberger |
spellingShingle |
Laurent Kappeler Carlos De Magalhaes Filho Joëlle Dupont Patricia Leneuve Pascale Cervera Laurence Périn Catherine Loudes Annick Blaise Rüdiger Klein Jacques Epelbaum Yves Le Bouc Martin Holzenberger Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism. PLoS Biology |
author_facet |
Laurent Kappeler Carlos De Magalhaes Filho Joëlle Dupont Patricia Leneuve Pascale Cervera Laurence Périn Catherine Loudes Annick Blaise Rüdiger Klein Jacques Epelbaum Yves Le Bouc Martin Holzenberger |
author_sort |
Laurent Kappeler |
title |
Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism. |
title_short |
Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism. |
title_full |
Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism. |
title_fullStr |
Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism. |
title_full_unstemmed |
Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism. |
title_sort |
brain igf-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Biology |
issn |
1544-9173 1545-7885 |
publishDate |
2008-10-01 |
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. Hormone-like 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. |
url |
http://europepmc.org/articles/PMC2573928?pdf=render |
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