ArticleBMC biology2016
IMPACT is a GCN2 inhibitor that limits lifespan in Caenorhabditis elegans.
Article in BMC biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Suppression rather than activation of the integrated stress response (GCN2-ATF4) pathway extends lifespan in the fly.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Emerging Role of GCN1 in Disease and Homeostasis.International journal of molecular sciences · 2024Review
- General control nonderepressible 2 (GCN2) as a therapeutic target in age-related diseases.Frontiers in aging · 2024Review
- Expression, not sequence, distinguishes miR-238 from its miR-239ab sister miRNAs in promoting longevity in Caenorhabditis elegans.PLoS genetics · 2023Article
- Article
- Multiple Roles of the Stress Sensor GCN2 in Immune Cells.International journal of molecular sciences · 2023Review
- Perspective: Modulating the integrated stress response to slow aging and ameliorate age-related pathology.Nature aging · 2021Article
- Nutrigenomic Effects of Long-Term Grape Pomace Supplementation in Dairy Cows.Animals : an open access journal from MDPI · 2020Article
- Dietary sulfur amino acid restriction upregulates DICER to confer beneficial effects.Molecular metabolism · 2019Article
- RNA interference may result in unexpected phenotypes in Caenorhabditis elegans.Nucleic acids research · 2019Article
- Nutrient Sensing and Redox Balance: GCN2 as a New Integrator in Aging.Oxidative medicine and cellular longevity · 2019Review
- The GCN2 inhibitor IMPACT contributes to diet-induced obesity and body temperature control.PloS one · 2019Article
- Enoxacin extends lifespan of C. elegans by inhibiting miR-34-5p and promoting mitohormesis.Redox biology · 2018Article
- Maintaining a Healthy Proteome during Oxidative Stress.Molecular cell · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe General Control Nonderepressible 2 (GCN2) kinase is a conserved member of the integrated stress response (ISR) pathway that represses protein translation and helps cells to adapt to conditions of nutrient shortage. As such, GCN2 is required for longevity and stress resistance induced by dietary restriction (DR). IMPACT is an ancient protein that inhibits GCN2.
resultsHere, we tested whether IMPACT down-regulation mimics the effects of DR in C. elegans. Knockdown of the C. elegans IMPACT homolog impt-1 activated the ISR pathway and increased lifespan and stress resistance of worms in a gcn-2-dependent manner. Impt-1 knockdown exacerbated DR-induced longevity and required several DR-activated transcription factors to extend lifespan, among them SKN-1 and DAF-16, which were induced during larval development and adulthood, respectively, in response to impt-1 RNAi.
conclusionsIMPACT inhibits the ISR pathway, thus limiting the activation of stress response factors that are beneficial during aging and required under DR.
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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.