ArticleGenetics2015
Longevity Genes Revealed by Integrative Analysis of Isoform-Specific daf-16/FoxO Mutants of Caenorhabditis elegans.
Article in Genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 79 citations in OpenAlex.
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- DAF-16/FOXO maintains genome integrity following genotoxic stress.bioRxiv : the preprint server for biology · 2025Article
- Hypoxia-reoxygenation Extends the Lifespan ofCurrent aging science · 2025Article
- Independent control of functional rewiring after axon injury byJournal of biosciences · 2025Article
- The N terminus-only (trans) function of the adhesion G protein-coupled receptor latrophilin-1 controls multiple processes in reproduction of Caenorhabditis elegans.G3 (Bethesda, Md.) · 2024Article
- Combinatorial transcriptomic and genetic dissection of insulin/IGF-1 signaling-regulated longevity in Caenorhabditis elegans.Aging cell · 2024Article
- The ACE inhibitor captopril inhibits ACN-1 to control dauer formation and aging.Development (Cambridge, England) · 2024Article
- Downregulation of transposable elements extends lifespan in Caenorhabditis elegans.Nature communications · 2023Article
- Endosomal trafficking protein TBC-2 modulates stress resistance and lifespan through DAF-16-dependent and independent mechanisms.Aging cell · 2023Article
- Further Extension of Lifespan byCells · 2022Article
- Radiation Hormesis to Improve the Quality of AdultInsects · 2022Article
- Screening Health-Promoting Compounds for Their Capacity to Induce the Activity of FOXO3.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Article
- Acrolein Promotes Aging and Oxidative Stress via the Stress Response Factor DAF-16/FOXO inFoods (Basel, Switzerland) · 2022Article
- Regulation of fatty acid desaturase- and immunity gene-expression by mbk-1/DYRK1A in Caenorhabditis elegans.BMC genomics · 2022Article
- DistinctmicroPublication biology · 2022Article
- LEA motifs promote desiccation tolerance in vivo.BMC biology · 2021Article
- daf-16/FOXO blocks adult cell fate in Caenorhabditis elegans dauer larvae via lin-41/TRIM71.PLoS genetics · 2021Article
- Context-specific regulation of lysosomal lipolysis through network-level diverting of transcription factor interactions.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling.Nature communications · 2021Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
FoxO transcription factors promote longevity across taxa. How they do so is poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms of the FoxO transcription factor DAF-16 extend life span in the context of reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed an integrative analysis of isoform-specific daf-16/FoxO mutants. In contrast to previous studies suggesting that DAF-16F plays a more prominent role in life span control than DAF-16A, isoform-specific daf-16/FoxO mutant phenotypes and whole transcriptome profiling revealed a predominant role for DAF-16A over DAF-16F in life span control, stress resistance, and target gene regulation. Integration of these datasets enabled the prioritization of a subset of 92 DAF-16/FoxO target genes for functional interrogation. Among 29 genes tested, two DAF-16A-specific target genes significantly influenced longevity. A loss-of-function mutation in the conserved gene gst-20, which is induced by DAF-16A, reduced life span extension in the context of daf-2/IGFR RNAi without influencing longevity in animals subjected to control RNAi. Therefore, gst-20 promotes DAF-16/FoxO-dependent longevity. Conversely, a loss-of-function mutation in srr-4, a gene encoding a seven-transmembrane-domain receptor family member that is repressed by DAF-16A, extended life span in control animals, indicating that DAF-16/FoxO may extend life span at least in part by reducing srr-4 expression. Our discovery of new longevity genes underscores the efficacy of our integrative strategy while providing a general framework for identifying specific downstream gene regulatory events that contribute substantially to transcription factor functions. As FoxO transcription factors have conserved functions in promoting longevity and may be dysregulated in aging-related diseases, these findings promise to illuminate fundamental principles underlying aging in animals.
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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.