ArticleNeuron2014
Insulin/IGF1 signaling inhibits age-dependent axon regeneration.
Article in Neuron, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 163 citations in OpenAlex.
- Pooled it
- Development of aBioactive materials · 2026Article
- Three muscle-specific DAF-16/FOXO transcriptional targets activated by reduced insulin/IGF-1 signaling.G3 (Bethesda, Md.) · 2026Article
- The conserved fibroblast growth factor receptor-based signaling is required for dendrite regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Exercise-Induced Differential Transcriptional Output of AMPK Signaling Improves Axon Regeneration and Functional Recovery.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- The neuron-intrinsic membrane skeleton is required for motor neuron integrity throughout lifespan.bioRxiv : the preprint server for biology · 2025Article
- Adult single-nucleus neuronal transcriptomes of insulin signaling mutants reveal regulators of behavior and learning.Cell genomics · 2024Article
- The ketone body β-hydroxybutyrate ameliorates neurodevelopmental deficits in the GABAergic system ofeLife · 2024Article
- Lipin1 depletion coordinates neuronal signaling pathways to promote motor and sensory axon regeneration after spinal cord injury.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Age-dependent small fiber neuropathy: Mechanistic insights from animal models.Experimental neurology · 2024Review
- The neuron-specific IIS/FOXO transcriptome in aged animals reveals regulatory mechanisms of cognitive aging.eLife · 2024Article
- Article
- An intraflagellar transport dependent negative feedback regulates the MAPKKK DLK-1 to protect cilia from degeneration.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- AMPK-FOXO-IP3R signaling pathway mediates neurological and developmental defects caused by mitochondrial DNA mutations.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Molecular mechanisms of neurite regeneration and repair: insights from C. elegans and Drosophila.Cell regeneration (London, England) · 2023Review
- Femtosecond laser microdissection for isolation of regenerating C. elegans neurons for single-cell RNA sequencing.Nature methods · 2023Article
- DUSP2 deletion with CRISPR/Cas9 promotes Mauthner cell axonal regeneration at the early stage of zebrafish.Neural regeneration research · 2023Article
- Single-cell transcriptome analysis of regenerating RGCs reveals potent glaucoma neural repair genes.Neuron · 2022Article
- The FOXO family of transcription factors: key molecular players in gastric cancer.Journal of molecular medicine (Berlin, Germany) · 2022Review
32 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The ability of injured axons to regenerate declines with age, yet the mechanisms that regulate axon regeneration in response to age are not known. Here we show that axon regeneration in aging C. elegans motor neurons is inhibited by the conserved insulin/IGF1 receptor DAF-2. DAF-2's function in regeneration is mediated by intrinsic neuronal activity of the forkhead transcription factor DAF-16/FOXO. DAF-16 regulates regeneration independently of lifespan, indicating that neuronal aging is an intrinsic, neuron-specific, and genetically regulated process. In addition, we found that DAF-18/PTEN inhibits regeneration independently of age and FOXO signaling via the TOR pathway. Finally, DLK-1, a conserved regulator of regeneration, is downregulated by insulin/IGF1 signaling, bound by DAF-16 in neurons, and required for both DAF-16- and DAF-18-mediated regeneration. Together, our data establish that insulin signaling specifically inhibits regeneration in aging adult neurons and that this mechanism is independent of PTEN and TOR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.