ArticleAging cell2017
Caenorhabditis elegans orthologs of human genes differentially expressed with age are enriched for determinants of longevity.
Article in Aging cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Pooled it
- Mechanisms of Anti-Aging Effect ofMolecules (Basel, Switzerland) · 2026Article
- Cellular senescence in gastric cancer: a novel prognostic stratification and immune predictor.BMC medical genomics · 2026Article
- Picolinic acid, a tryptophan metabolite, exhibits anabolic effects in muscle cells and improves lifespan and movement in C. elegans.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- From Elixirs to Geroscience: A Historical and Molecular Perspective on Anti-Aging Medicine.Molecules (Basel, Switzerland) · 2025Review
- Exercise training restores longevity-associated tryptophan metabolite 3-hydroxyanthranilic acid levels in middle-aged adults.Acta physiologica (Oxford, England) · 2025Article
- Tryptophan metabolism as a target in gut microbiota, ageing and kidney disease.International journal of biological sciences · 2025Review
- Multi-Omics Integrative Analysis to Reveal the Impacts ofInternational journal of molecular sciences · 2024Article
- 3-Hydroxyanthranilic Acid Delays Paralysis inBiomolecules · 2024Article
- The Emerging Role of 3-Hydroxyanthranilic Acid onbioRxiv : the preprint server for biology · 2024Article
- Chaperone Activators.Sub-cellular biochemistry · 2024Review
- On the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging.Nature communications · 2023Article
- Lysosome-related organelles promote stress and immune responses in C. elegans.Communications biology · 2023Article
- Extension of life span by down-regulation of enzymes catalyzing tryptophan conversion into kynurenine: Possible implications for mechanisms of aging.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Long-Term Culture of Individual Caenorhabditis elegans on Solid Media for Longitudinal Fluorescence Monitoring and Aversive Interventions.Journal of visualized experiments : JoVE · 2022Article
- Article
- Review
- Modeling Alzheimer's Disease inBiomedicines · 2022Review
- Article
- Plasma Anthranilic Acid and Leptin Levels Predict HAM-D Scores in Depressed Women.International journal of tryptophan research : IJTR · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
We report a systematic RNAi longevity screen of 82 Caenorhabditis elegans genes selected based on orthology to human genes differentially expressed with age. We find substantial enrichment in genes for which knockdown increased lifespan. This enrichment is markedly higher than published genomewide longevity screens in C. elegans and similar to screens that preselected candidates based on longevity-correlated metrics (e.g., stress resistance). Of the 50 genes that affected lifespan, 46 were previously unreported. The five genes with the greatest impact on lifespan (>20% extension) encode the enzyme kynureninase (kynu-1), a neuronal leucine-rich repeat protein (iglr-1), a tetraspanin (tsp-3), a regulator of calcineurin (rcan-1), and a voltage-gated calcium channel subunit (unc-36). Knockdown of each gene extended healthspan without impairing reproduction. kynu-1(RNAi) alone delayed pathology in C. elegans models of Alzheimer's disease and Huntington's disease. Each gene displayed a distinct pattern of interaction with known aging pathways. In the context of published work, kynu-1, tsp-3, and rcan-1 are of particular interest for immediate follow-up. kynu-1 is an understudied member of the kynurenine metabolic pathway with a mechanistically distinct impact on lifespan. Our data suggest that tsp-3 is a novel modulator of hypoxic signaling and rcan-1 is a context-specific calcineurin regulator. Our results validate C. elegans as a comparative tool for prioritizing human candidate aging genes, confirm age-associated gene expression data as valuable source of novel longevity determinants, and prioritize select genes for mechanistic follow-up.
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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.