ArticleAging cell2021
Mutation of daf-2 extends lifespan via tissue-specific effectors that suppress distinct life-limiting pathologies.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- The neuropeptide neuromedin U receptor NMUR-1 buffers insulin receptor signaling in bacteria-dependent C. elegans survival.PLoS genetics · 2026Article
- Early-life redox perturbation programs intergenerational redox vulnerability through DAF-16/FOXO and SKN-1/Nrf2 signaling in Caenorhabditis elegans.Redox biology · 2026Article
- Article
- Slowed Gompertzian ageing in long-lived C. elegans results from expansion of decrepitude, not decelerated ageing.Nature communications · 2026Article
- Three muscle-specific DAF-16/FOXO transcriptional targets activated by reduced insulin/IGF-1 signaling.G3 (Bethesda, Md.) · 2026Article
- The Strehler-Mildvan mortality correlation arises from changes in the variability of ageing.bioRxiv : the preprint server for biology · 2026Article
- Multilayered regulation of longevity in Caenorhabditis elegans.Molecules and cells · 2026Review
- Machine learning predicts lifespan and suggests underlying causes of death in aging C. elegans.Communications biology · 2025Article
- A hierarchy of causes of death in senescentbioRxiv : the preprint server for biology · 2025Article
- Developmental and conditional regulation of DAF-2/INSR ubiquitination in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2025Article
- Catalytic activities of wild-type C. elegans DAF-2 kinase and dauer-associated mutants.The FEBS journal · 2024Article
- Emergence of dauer larvae in Caenorhabditis elegans disrupts continuity of host-microbiome interactions.FEMS microbiology ecology · 2024Article
- Neuropeptide inactivation regulates egg-laying behavior to influence reproductive health in Caenorhabditis elegans.Current biology : CB · 2024Article
- Combinatorial transcriptomic and genetic dissection of insulin/IGF-1 signaling-regulated longevity in Caenorhabditis elegans.Aging cell · 2024Article
- Timing of TORC1 inhibition dictates Pol III involvement inLife science alliance · 2024Article
- Developmental and conditional regulation of DAF-2/INSR ubiquitination inbioRxiv : the preprint server for biology · 2024Article
- Icariin Improves Stress Resistance and Extends Lifespan inInternational journal of molecular sciences · 2023Article
- High-resolution imaging and analysis of the intestinal bacterial load ofRSC advances · 2023Article
- Intestine-specific removal of DAF-2 nearly doubles lifespan in Caenorhabditis elegans with little fitness cost.Nature communications · 2022Article
- Molecular inhibition of RAS signalling to target ageing and age-related health.Disease models & mechanisms · 2022Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
In aging Caenorhabditis elegans, as in higher organisms, there is more than one cause of death. C. elegans exhibit early death with a swollen, infected pharynx (P death), and later death with pharyngeal atrophy (p death). Interventions that alter lifespan can differentially affect frequency and timing of each type of death, generating complex survival curve shapes. Here, we use mortality deconvolution analysis to investigate how reduction of insulin/IGF-1 signaling (IIS), which increases lifespan (the Age phenotype), affects different forms of death. All daf-2 insulin/IGF-1 receptor mutants exhibit increased lifespan in the p subpopulation (p Age), while pleiotropic class 2 daf-2 mutants show an additional marked reduction in P death frequency. The latter is promoted by pharyngeal expression of the IIS-regulated DAF-16 FOXO transcription factor, and at higher temperature by reduced pharyngeal pumping rate. Pharyngeal DAF-16 also promotes p Age in class 2 daf-2 mutants, revealing a previously unknown role for the pharynx in the regulation of aging. Necropsy analysis of daf-2 interactions with the daf-12 steroid receptor implies that previously described opposing effects of daf-12 on daf-2 longevity are attributable to internal hatching of larvae, rather than complex interactions between insulin/IGF-1 and steroid signaling. These findings support the view that wild-type IIS acts through multiple distinct mechanisms which promote different life-limiting pathologies, each of which contribute to late-life mortality. This study further demonstrates the utility of mortality deconvolution analysis to better understand the genetics of lifespan.
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