ArticlePLoS biology2017
Reduced insulin signaling maintains electrical transmission in a neural circuit in aging flies.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Phosphatidylinositol-3-phosphate-dependent Klp98A recruitment regulates endosomal flux underlying developmental synaptic remodeling via Rab4.Journal of cell science · 2026Article
- The Drosophila escape motor circuit shows differential vulnerability to aging linked to functional decay.PLoS biology · 2025Article
- Frazzled/DCC Regulates Gap Junction Formation at aeNeuro · 2025Article
- Reduced insulin signaling in neurons induces sex-specific health benefits.Science advances · 2023Article
- Modeling aging and its impact on cellular function and organismal behavior.Experimental gerontology · 2021Review
- Tissue-specific modulation of gene expression in response to lowered insulin signalling ineLife · 2021Article
- Cell type-specific modulation of healthspan by Forkhead family transcription factors in the nervous system.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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- Shifting equilibriums in Alzheimer's disease: the complex roles of microglia in neuroinflammation, neuronal survival and neurogenesis.Neural regeneration research · 2020Review
- Transcriptomic evidence that insulin signalling pathway regulates the ageing of subterranean termite castes.Scientific reports · 2020Article
- The neuronal receptor tyrosine kinase Alk is a target for longevity.Aging cell · 2020Article
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- Overexpression of isoform B of Dgp-1 gene enhances locomotor activity in senescent Drosophila males and under heat stress.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2019Article
- Organelle aging: Lessons from model organisms.Journal of genetics and genomics = Yi chuan xue bao · 2019Review
- Impact of insulin signaling and proteasomal activity on physiological output of a neuronal circuit in aging Drosophila melanogaster.Neurobiology of aging · 2018Article
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- Review
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Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Lowered insulin/insulin-like growth factor (IGF) signaling (IIS) can extend healthy lifespan in worms, flies, and mice, but it can also have adverse effects (the "insulin paradox"). Chronic, moderately lowered IIS rescues age-related decline in neurotransmission through the Drosophila giant fiber system (GFS), a simple escape response neuronal circuit, by increasing targeting of the gap junctional protein innexin shaking-B to gap junctions (GJs). Endosomal recycling of GJs was also stimulated in cultured human cells when IIS was reduced. Furthermore, increasing the activity of the recycling small guanosine triphosphatases (GTPases) Rab4 or Rab11 was sufficient to maintain GJs upon elevated IIS in cultured human cells and in flies, and to rescue age-related loss of GJs and of GFS function. Lowered IIS thus elevates endosomal recycling of GJs in neurons and other cell types, pointing to a cellular mechanism for therapeutic intervention into aging-related neuronal disorders.
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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 OpenQuestion graph.