ArticleNature communications2021
Insulin signaling regulates longevity through protein phosphorylation in Caenorhabditis elegans.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 82 citations in OpenAlex.
- Article
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- Effects and mechanisms of lifespan extension and healthspan promotion induced byFrontiers in nutrition · 2026Article
- Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins.Nature communications · 2025Article
- Translational regulation in stress biology.Nature cell biology · 2025Review
- Coupled dopamine and insulin signaling mediated transgenerational and multigenerational inheritance of adaptive traits inMicrobiology spectrum · 2025Article
- Topoisomerase inhibitor amonafide enhances defense responses to promote longevity in C. elegans.GeroScience · 2025Article
- Simple In-Cell Processing Enables Deep Proteome Analysis of Low-InputAnalytical chemistry · 2025Article
- MMFuncPhos: A Multi-Modal Learning Framework for Identifying Functional Phosphorylation Sites and Their Regulatory Types.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Curcumin enhances the anti-obesogenic activity of orlistat through SKN-1/NRF2-dependent regulation of nutrient metabolism in Caenorhabditis elegans.International journal of obesity (2005) · 2025Article
- Non-cell-autonomous regulation of mTORC2 by Hedgehog signaling maintains lipid homeostasis.Cell reports · 2025Article
- Baicalein fromFrontiers in pharmacology · 2025Article
- A comprehensive approach, based on the use ofCurrent research in food science · 2025Article
- Transcriptome Analysis Reveals Norathyriol Prolongs the Lifespan via Regulating Metabolism inMetabolites · 2024Article
- Catalytic activities of wild-type C. elegans DAF-2 kinase and dauer-associated mutants.The FEBS journal · 2024Article
- BubR1 and SIRT2: Insights into aneuploidy, aging, and cancer.Seminars in cancer biology · 2024Review
- On the lifespan ofAging · 2024Article
- Regulation of Caenorhabditis elegans HLH-30 subcellular localization dynamics: Evidence for a redox-dependent mechanism.Free radical biology & medicine · 2024Article
- Calorie restriction and rapamycin distinctly mitigate aging-associated protein phosphorylation changes in mouse muscles.Communications biology · 2024Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Insulin/IGF-1 Signaling (IIS) is known to constrain longevity by inhibiting the transcription factor FOXO. How phosphorylation mediated by IIS kinases regulates lifespan beyond FOXO remains unclear. Here, we profile IIS-dependent phosphorylation changes in a large-scale quantitative phosphoproteomic analysis of wild-type and three IIS mutant Caenorhabditis elegans strains. We quantify more than 15,000 phosphosites and find that 476 of these are differentially phosphorylated in the long-lived daf-2/insulin receptor mutant. We develop a machine learning-based method to prioritize 25 potential lifespan-related phosphosites. We perform validations to show that AKT-1 pT492 inhibits DAF-16/FOXO and compensates the loss of daf-2 function, that EIF-2α pS49 potently inhibits protein synthesis and daf-2 longevity, and that reduced phosphorylation of multiple germline proteins apparently transmits reduced DAF-2 signaling to the soma. In addition, an analysis of kinases with enriched substrates detects that casein kinase 2 (CK2) subunits negatively regulate lifespan. Our study reveals detailed functional insights into longevity.
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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.