ArticleAging cell2013
The general control nonderepressible-2 kinase mediates stress response and longevity induced by target of rapamycin inactivation in Caenorhabditis elegans.
Article in Aging cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 66 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
- Novel tRNA Synthetase Inhibitors Increase Healthspan, Lifespan, and Autophagic Flux inBiomolecules · 2026Article
- Multilayered regulation of longevity in Caenorhabditis elegans.Molecules and cells · 2026Review
- The GCN-2/eIF-2α/ATF-4 signaling pathway is involved inVirulence · 2025Article
- The impacts of different dietary restriction regimens on aging and longevity: from yeast to humans.Journal of biomedical science · 2025Review
- Unraveling the functional dynamics of Caenorhabditis elegans stress-responsive omega class GST-44.The FEBS journal · 2025Article
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- Translation elongation defects activate theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Stress-Induced Eukaryotic Translational Regulatory Mechanisms.Journal of clinical and medical sciences · 2024Article
- General control nonderepressible 2 (GCN2) as a therapeutic target in age-related diseases.Frontiers in aging · 2024Review
- Neuronal mTORC1 inhibition promotes longevity without suppressing anabolic growth and reproduction in C. elegans.PLoS genetics · 2023Article
- General control nonderepressible 1 interacts with cationic amino acid transporter 1 and affects Aedes aegypti fecundity.Parasites & vectors · 2022Article
- Organismal and Cellular Stress Responses upon Disruption of Mitochondrial Lonp1 Protease.Cells · 2022Article
- ATF-4 and hydrogen sulfide signalling mediate longevity in response to inhibition of translation or mTORC1.Nature communications · 2022Article
- Molecular mechanisms of dietary restriction promoting health and longevity.Nature reviews. Molecular cell biology · 2022Review
- The Role of GCN2 Kinase in Mediating the Effects of Amino Acids on Longevity and Feeding Behaviour inFrontiers in aging · 2022Article
- Target of Rapamycin Drives Unequal Responses to Essential Amino Acid Depletion for Egg Laying inFrontiers in cell and developmental biology · 2022Article
- Vitamin BCell reports · 2021Article
- Perspective: Modulating the integrated stress response to slow aging and ameliorate age-related pathology.Nature aging · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The general control nonderepressible 2 (GCN2) kinase is a nutrient-sensing pathway that responds to amino acids deficiency and induces a genetic program to effectively maintain cellular homeostasis. Here we established the conserved role of Caenorhabditis elegans GCN-2 under amino acid limitation as a translation initiation factor 2 (eIF2) kinase. Using a combination of genetic and molecular approaches, we showed that GCN-2 kinase activity plays a central role in survival under nutrient stress and mediates lifespan extension conferred by dietary restriction (DR) or inhibition of the major nutrient-sensing pathway, the target of rapamycin (TOR). We also demonstrated that the GCN-2 and TOR signaling pathways converge on the PHA-4/FoxA transcription factor and its downstream target genes to ensure survival of the whole organism under a multitude of stress conditions, such as nutrient scarcity or environmental stresses. This is one step forward in the understanding of evolutionary conserved mechanisms that confer longevity and healthspan.
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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.