ArticleNature2017
RNA polymerase III limits longevity downstream of TORC1.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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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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Who cites it
72 citing papers in PubMed, 112 citations in OpenAlex.
- The regulation, function and disease relevance of cytoplasmic tRNAs.Nature reviews. Molecular cell biology · 2026Review
- ß-adrenergic-like signalling engages CrebB in Drosophila gut to promote female longevity.Nature communications · 2026Article
- Multilayered regulation of longevity in Caenorhabditis elegans.Molecules and cells · 2026Review
- POLR3A mutations cause nucleolus abnormalities and aberrant telomerase RNA metabolism in induced pluripotent stem cells from Wiedemann-Rautenstrauch premature aging syndrome patient.Biogerontology · 2025Article
- Translational regulation in stress biology.Nature cell biology · 2025Review
- Loss of Pol III repressor Maf1 in neurons promotes longevity by preventing the age-related decline in 5S rRNA and translation.PLoS biology · 2025Article
- Conformation-specific synthetic intrabodies modulate mTOR signaling with subcellular spatial resolution.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Reproductive-Triggered Sterol Competition Exacerbates Age-Related Intestinal Barrier Damage in Drosophila Females.Aging cell · 2025Article
- Emerging roles for the nucleolus in development and stem cells.Development (Cambridge, England) · 2025Review
- Recent progress in regulation of aging by non-coding RNAs inAnimal cells and systems · 2025Review
- Article
- Ageing-associated long non-coding RNA extends lifespan and reduces translation in non-dividing cells.EMBO reports · 2024Article
- How does a fly die? Insights into ageing from the pathophysiology of Drosophila mortality.GeroScience · 2024Review
- Disruption of tRNA biogenesis enhances proteostatic resilience, improves later-life health, and promotes longevity.PLoS biology · 2024Article
- Pharmacology of Aging:Aging biology · 2024Article
- Increased transcriptional elongation and RNA stability of GPCR ligand binding genes unveiled via RNA polymerase II degradation.Nucleic acids research · 2024Article
- An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo.Genome medicine · 2024Article
- Timing of TORC1 inhibition dictates Pol III involvement inLife science alliance · 2024Article
- Polr3b heterozygosity in mice induces both beneficial and deleterious effects on health during ageing with no effect on lifespan.Aging cell · 2024Article
- Inhibition of S6K lowers age-related inflammation and increases lifespan through the endolysosomal system.Nature aging · 2024Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Three distinct RNA polymerases transcribe different classes of genes in the eukaryotic nucleus. RNA polymerase (Pol) III is the essential, evolutionarily conserved enzyme that generates short, non-coding RNAs, including tRNAs and 5S rRNA. The historical focus on transcription of protein-coding genes has left the roles of Pol III in organismal physiology relatively unexplored. Target of rapamycin kinase complex 1 (TORC1) regulates Pol III activity, and is also an important determinant of longevity. This raises the possibility that Pol III is involved in ageing. Here we show that Pol III limits lifespan downstream of TORC1. We find that a reduction in Pol III extends chronological lifespan in yeast and organismal lifespan in worms and flies. Inhibiting the activity of Pol III in the gut of adult worms or flies is sufficient to extend lifespan; in flies, longevity can be achieved by Pol III inhibition specifically in intestinal stem cells. The longevity phenotype is associated with amelioration of age-related gut pathology and functional decline, dampened protein synthesis and increased tolerance of proteostatic stress. Pol III acts on lifespan downstream of TORC1, and limiting Pol III activity in the adult gut achieves the full longevity benefit of systemic TORC1 inhibition. Hence, Pol III is a pivotal mediator of this key nutrient-signalling network for longevity; the growth-promoting anabolic activity of Pol III mediates the acceleration of ageing by TORC1. The evolutionary conservation of Pol III affirms its potential as a therapeutic target.
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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.