The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Brain IGF-1 Receptors Control Mammalian Growth and Lifespan through a Neuroendocrine Mechanism
Open accessAbstract
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.
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Cites
IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice
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Self-citationThe plasticity of aging: insights from long-lived mutants
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Brain IRS2 Signaling Coordinates Life Span and Nutrient Homeostasis
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Regulation of C. elegans Longevity by Specific Gustatory and Olfactory Neurons
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Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739
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Fernandez, A. M., & Torres-Alemán, I. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3209 · Cited by 872
Ristow, M., & Zarse, K. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.03.014 · Cited by 789
The cerebrospinal fluid provides a proliferative niche for neural progenitor cells
Lehtinen, M. K., Zappaterra, M. W., Chen, X., Yang, Y. J., Hill, A. D., Lun, M., Maynard, T., Gonzalez, D., Kim, S., Ye, P., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.01.023 · Cited by 648
Insulin Action in Brain Regulates Systemic Metabolism and Brain Function
Kleinridders, A., Ferris, H. A., Cai, W., & Kahn, C. R. (2014) · Diabetes · doi:10.2337/db14-0568 · Cited by 625
Metadata
- Authors
- Kappeler, L., Filho, C. D. M., Dupont, J., Leneuve, P., Cervera, P., Périn, L., Loudes, C., Blaise, A., Klein, R., Epelbaum, J., Bouc, Y. L., & Holzenberger, M.
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-10-28
- Volume
- 6
- Issue
- 10
- Pages
- e254
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- OpenAlex
- W2157617952
- Cited by
- 291
- References
- 8
- FWCI
- 12.20
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: Brain IGF-1 Receptors Control Mammalian Growth and Lifespan through a Neuroendocrine Mechanism. https://app.cochat.ai/papers/10.1371/journal.pbio.0060254
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- Kappeler, L., Filho, C. D. M., Dupont, J., Leneuve, P., Cervera, P., Périn, L., Loudes, C., Blaise, A., Klein, R., Epelbaum, J., Bouc, Y. L., & Holzenberger, M. (2008). Brain IGF-1 Receptors Control Mammalian Growth and Lifespan through a Neuroendocrine Mechanism. PLoS Biology. https://doi.org/10.1371/journal.pbio.0060254
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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