ArticleNature communications2018
DAF-16/FOXO and HLH-30/TFEB function as combinatorial transcription factors to promote stress resistance and longevity.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 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
114 citing papers in PubMed, 172 citations in OpenAlex.
- HLH-30/TFEB is necessary for chromatin reorganization and maintenance of cell quiescence during starvation in C. elegans.Nucleic acids research · 2026Article
- Fasting requires Peroxiredoxin 2 and Peroxiredoxin 6 to coordinate redox dependent mitochondrial and lipid remodelling in Caenorhabditis elegans.Redox biology · 2026Article
- FOXO/DAF-16 modulates the transcription factor ROR/NHR-23 and inhibits thebioRxiv : the preprint server for biology · 2026Article
- Cell-based screen identifies translation state modulators that extend lifespan in Drosophila melanogaster and Caenorhabditis elegans.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- Ribonuclease DIS3 delays aging and senescence by generating tRNA halves.Nature communications · 2026Article
- Natural Small Molecules Targeting Oxidative Stress and Redox Homeostasis in Aging: Mechanisms and Therapeutic Potential.Antioxidants (Basel, Switzerland) · 2026Review
- Vitamin K2 Extends Lifespan by Alleviating Mitochondrial Stress via the JNK-1/SIR-2.1/DAF-16 Signaling Axis in Caenorhabditis elegans.Aging cell · 2026Article
- Phosphatidylinositol transfer protein-1 integrates insulin/IGF-1 and TOR signaling to negatively regulate lifespan and healthspan in Caenorhabditis elegans.Journal of biomedical science · 2026Article
- Zinc excess promotes lysosome remodeling by activating HLH-30/TFEB through the action of the high zinc sensor HIZR-1.bioRxiv : the preprint server for biology · 2026Article
- Genome-wide characterization of theFrontiers in plant science · 2026Article
- RNAi-based motility screen of predicted sarcopenia-associated genes during aging inmicroPublication biology · 2026Article
- The lifespan and healthspan extending effects of ellagic acid inFrontiers in aging · 2026Article
- Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins.Nature communications · 2025Article
- Iron-deplete diet enhances Caenorhabditis elegans lifespan via oxidative stress response pathways.The EMBO journal · 2025Article
- DAF-16/FOXO and HLH-30/TFEB comprise a cooperative regulatory axis controlling tubular lysosome induction in C. elegans.Nature communications · 2025Article
- DAF-16/FOXO maintains genome integrity following genotoxic stress.bioRxiv : the preprint server for biology · 2025Article
- The loss of a ClC anion channel increases life span, health span, and stress resistance by alkalinizing a pair of glial cells inScience advances · 2025Article
- Genetic signatures of exceptional longevity: a comprehensive analysis of coding region single nucleotide polymorphisms (SNPs) in centenarians and supercentenarians.Human genomics · 2025Article
- Iron-deplete diet enhancesbioRxiv : the preprint server for biology · 2025Article
- T-CLASS: An Online Tool for the Identification and Classification of Aging and Senescence Using Transcriptome Data.Aging cell · 2025Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
The ability to perceive and respond to harmful conditions is crucial for the survival of any organism. The transcription factor DAF-16/FOXO is central to these responses, relaying distress signals into the expression of stress resistance and longevity promoting genes. However, its sufficiency in fulfilling this complex task has remained unclear. Using C. elegans, we show that DAF-16 does not function alone but as part of a transcriptional regulatory module, together with the transcription factor HLH-30/TFEB. Under harmful conditions, both transcription factors translocate into the nucleus, where they often form a complex, co-occupy target promoters, and co-regulate many target genes. Interestingly though, their synergy is stimulus-dependent: They rely on each other, functioning in the same pathway, to promote longevity or resistance to oxidative stress, but they elicit heat stress responses independently, and they even oppose each other during dauer formation. We propose that this module of DAF-16 and HLH-30 acts by combinatorial gene regulation to relay distress signals into the expression of specific target gene sets, ensuring optimal survival under each given threat.
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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.