ArticleNature aging2025
Body-to-brain insulin and Notch signaling regulates memory through neuronal CREB activity.
Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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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
7 citing papers in PubMed.
- Intestinal lipid metabolism controls molecular and behavioral immunity through NHR-68 and gut-brain signaling in Caenorhabditis elegans.PLoS biology · 2026Article
- COMPASS-mediated epigenetic regulation of transcription accelerates forgetting with age.Research square · 2026Article
- INS-17 acts as a nutrient deprivation signal to mediate adult IIS-regulated associative behaviors in C. elegans.PLoS genetics · 2026Article
- INS-17, an insulin-receptor ligand, confers specificity in adult IIS-regulated phenotypes inbioRxiv : the preprint server for biology · 2025Article
- Review
- GLP-1R agonists protect against Alzheimer's disease by rewiring energy regulation.Nature aging · 2025Article
- CRTC1 enhances PD-L1-mediated tumor immunosuppression in non-small cell lung cancer via the Notch1/Akt signaling pathway.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
While memory regulation is predominantly understood as autonomous to neurons, factors outside the brain can also affect neuronal function. In Caenorhabditis elegans, the insulin/IGF-1-like signaling (IIS) pathway regulates longevity, metabolism and memory: long-lived daf-2 insulin/IGF-1 receptor mutants more than double memory duration after a single training session, and it was assumed that memory regulation was strictly neuronal. However, here we show that degradation of DAF-2 in the hypodermis also greatly extends memory, via expression of the diffusible Notch ligand, OSM-11, which in turn activates Notch signaling in neurons. Single-nucleus RNA sequencing of neurons revealed increased expression of CREB and other memory genes. Furthermore, in aged animals, activation of the hypodermal IIS-Notch pathway as well as OSM-11 overexpression rescue both memory and learning via CREB activity. Thus, insulin signaling in the liver-like hypodermis non-autonomously regulates neuronal function, providing a systemic connection between metabolism and memory through IIS-Notch-CREB signaling from the body to the brain.
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Registered trials
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