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Regulation of C. elegans Life-Span by Insulinlike Signaling in the Nervous System
Abstract
An insulinlike signaling pathway controls Caenorhabditis elegans aging, metabolism, and development. Mutations in the daf-2 insulin receptor–like gene or the downstream age-1 phosphoinositide 3-kinase gene extend adult life-span by two- to threefold. To identify tissues where this pathway regulates aging and metabolism, we restored daf-2 pathway signaling to only neurons, muscle, or intestine. Insulinlike signaling in neurons alone was sufficient to specify wild-type life-span, but muscle or intestinal signaling was not. However, restoring daf-2 pathway signaling to muscle rescued metabolic defects, thus decoupling regulation of life-span and metabolism. These findings point to the nervous system as a central regulator of animal longevity.
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Citations
Cited by
The phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621
Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
Murphy, C. T., McCarroll, S. A., Bargmann, C. I., Fraser, A., Kamath, R. S., Ahringer, J., Li, H., & Kenyon, C. (2003) · Nature · doi:10.1038/nature01789 · Cited by 2,280
IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice
Holzenberger, M., Dupont, J., Ducos, B., Leneuve, P., Géloën, A., Even, P. C., Cervera, P., & Le Bouc, Y. (2003) · Nature · doi:10.1038/nature01298 · Cited by 2,109
The plasticity of aging: insights from long-lived mutants
Kenyon, C. (2005) · Cell · doi:10.1016/j.cell.2005.02.002 · Cited by 1,338
Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway
Kapahi, P., Zid, B. M., Harper, T., Koslover, D., Sapin, V., & Benzer, S. (2004) · Current Biology · doi:10.1016/j.cub.2004.03.059 · Cited by 1,293
Metadata
- Authors
- Wolkow, C. A., Kimura, K. D., Lee, M.-S., & Ruvkun, G.
- Venue
- Science
- Published
- 2000-10-06
- Volume
- 290
- Issue
- 5489
- Pages
- 147-150
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2091613063
- Cited by
- 682
- References
- 0
- FWCI
- 10.67
- Type
- journal article
- Language
- en
- Open access
- closed
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- Wolkow, C. A., Kimura, K. D., Lee, M.-S., & Ruvkun, G. (2000). Regulation of C. elegans Life-Span by Insulinlike Signaling in the Nervous System. Science. https://doi.org/10.1126/science.290.5489.147
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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