ArticleNature communications2022
Intestine-specific removal of DAF-2 nearly doubles lifespan in Caenorhabditis elegans with little fitness cost.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 78 citations in OpenAlex.
- Article
- Article
- Partitioning of the truncated insulin receptor DAF-2B between homodimers and heterodimers influences insulin signaling in C. elegans.PLoS genetics · 2026Article
- Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.MedComm · 2026Review
- The neuropeptide neuromedin U receptor NMUR-1 buffers insulin receptor signaling in bacteria-dependent C. elegans survival.PLoS genetics · 2026Article
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Pharmacologic AMPK Activation Extends Lifespan inbioRxiv : the preprint server for biology · 2026Article
- Transcriptomic Evidence Reveals the IIS-FOXO-SOD2 Axis as a Core Anti-Aging Pathway in Long-Lived Queens ofInsects · 2026Article
- Strong inhibition of insulin/IGF-1 signaling in early-mid adulthood compresses morbidity, but in later life accelerates aging.bioRxiv : the preprint server for biology · 2026Article
- A conserved C. elegans zinc finger homeodomain protein, ZFH-2, is continuously required for the structural integrity and function of the alimentary tract and gonad.Development (Cambridge, England) · 2026Article
- Exercise-Induced Differential Transcriptional Output of AMPK Signaling Improves Axon Regeneration and Functional Recovery.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- A conservedbioRxiv : the preprint server for biology · 2026Article
- Effects and mechanisms of lifespan extension and healthspan promotion induced byFrontiers in nutrition · 2026Article
- The flavonoid isoliquiritigenin promotes lifespan extension of Caenorhabditis elegans through the transcription factor DAF-16 and aquaporin-2.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · 2026Article
- Multilayered regulation of longevity in Caenorhabditis elegans.Molecules and cells · 2026Review
- Engineering the auxin-inducible degron system for tunable in vivo control of organismal physiology.Nature communications · 2025Article
- Gut Microbial Genetic Variation Prolongs Host Healthy Longevity and Remodels Metabolome and Proteome in Drosophila Melanogaster.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Machine learning predicts lifespan and suggests underlying causes of death in aging C. elegans.Communications biology · 2025Article
- Multi-target synergistic anti-aging: QG extends Caenorhabditis elegans lifespan through DAF-16/FOXO pathways, mitochondrial homeostasis and metabolic reprogramming.Biogerontology · 2025Article
- Non-autonomy of age-related morphological changes in the C. elegans germline stem cell niche.Development (Cambridge, England) · 2025Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Twenty-nine years following the breakthrough discovery that a single-gene mutation of daf-2 doubles Caenorhabditis elegans lifespan, it remains unclear where this insulin/IGF-1 receptor gene is expressed and where it acts to regulate ageing. Using knock-in fluorescent reporters, we determined that daf-2 and its downstream transcription factor daf-16 are expressed ubiquitously. Using tissue-specific targeted protein degradation, we determined that intracellular DAF-2-to-DAF-16 signaling in the intestine plays a major role in lifespan regulation, while that in the hypodermis, neurons, and germline plays a minor role. Notably, intestine-specific loss of DAF-2 activates DAF-16 in and outside the intestine, causes almost no adverse effects on development and reproduction, and extends lifespan by 94% in a way that partly requires non-intestinal DAF-16. Consistent with intestine supplying nutrients to the entire body, evidence from this and other studies suggests that altered metabolism, particularly down-regulation of protein and RNA synthesis, mediates longevity by reduction of insulin/IGF-1 signaling.
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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.