ArticleDevelopmental cell2019
Age-Onset Phosphorylation of a Minor Actin Variant Promotes Intestinal Barrier Dysfunction.
Article in Developmental cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 50 citations in OpenAlex.
- Form and function of actin impacts actin health and aging.iScience · 2026Article
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- Alterations of actin in aging.Journal of cell science · 2026Review
- Tissue and cellular spatiotemporal dynamics in colon aging.Nature biotechnology · 2026Article
- Silencing lipid catabolism determines longevity in response to fasting.Nature communications · 2026Article
- Chronic intestinal immune activation reveals separable impacts of inflammation and barrier loss on hallmarks of ageing.PloS one · 2026Article
- Distinct responses to non-autonomous UPRCommunications biology · 2025Article
- Form and function of actin impacts actin health and aging.bioRxiv : the preprint server for biology · 2025Article
- Beyond genes and environment: mapping biological stochasticity in aging.GeroScience · 2025Review
- Endosomal catabolism of phosphatidylinositol 4,5-bisphosphate is fundamental in building resilience against pathogens.Protein & cell · 2025Article
- Effects ofFrontiers in physiology · 2025Article
- Accumulation of F-actin drives brain aging and limits healthspan in Drosophila.Nature communications · 2024Article
- Highly regenerative species-specific genes improve age-associated features in the adult Drosophila midgut.BMC biology · 2024Article
- Mechanical stress through growth on stiffer substrates impacts animal health and longevity inbioRxiv : the preprint server for biology · 2024Article
- Article
- ADT-OH improves intestinal barrier function and remodels the gut microbiota in DSS-induced colitis.Frontiers of medicine · 2023Article
- A framework for intestinal barrier dysfunction in aging.Nature aging · 2023Article
- Deteriorating maintenance of the intestinal wall.Nature aging · 2023Article
- Article
- Intestinal barrier dysfunction: an evolutionarily conserved hallmark of aging.Disease models & mechanisms · 2023Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Age-associated decay of intercellular interactions impairs the cells' capacity to tightly associate within tissues and form a functional barrier. This barrier dysfunction compromises organ physiology and contributes to systemic failure. The actin cytoskeleton represents a key determinant in maintaining tissue architecture. Yet, it is unclear how age disrupts the actin cytoskeleton and how this, in turn, promotes mortality. Here, we show that an uncharacterized phosphorylation of a low-abundant actin variant, ACT-5, compromises integrity of the C. elegans intestinal barrier and accelerates pathogenesis. Age-related loss of the heat-shock transcription factor, HSF-1, disrupts the JUN kinase and protein phosphatase I equilibrium which increases ACT-5 phosphorylation within its troponin binding site. Phosphorylated ACT-5 accelerates decay of the intestinal subapical terminal web and impairs its interactions with cell junctions. This compromises barrier integrity, promotes pathogenesis, and drives mortality. Thus, we provide the molecular mechanism by which age-associated loss of specialized actin networks impacts tissue integrity.
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Registered trials
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