ArticleGut2018
Age-dependent shift in macrophage polarisation causes inflammation-mediated degeneration of enteric nervous system.
Article in Gut, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
118 citing papers in PubMed, 1 synthesis or guideline pooled it, 184 citations in OpenAlex.
- Shared and niche-specific transcriptional signatures of macrophage aging revealed by a cross-tissue meta-analysis.BMC biology · 2026Pooled it
- Effects and Persistence of Bifidobacterium animalis subsp. lactis BL-99 and Fructooligosaccharides on Older Adults with Functional Constipation: A Randomized, Double-Blind, Placebo-Controlled Trial.The journal of nutrition, health & aging · 2025Trial
- A biomechanical model of inflammation-driven colon hypertrophy and dysmotility: Application to Gulf War Illness.Journal of the mechanical behavior of biomedical materials · 2026Article
- Phenotypic switching of gastrointestinal smooth muscle cells and the regulatory role of macrophages: a literature review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Isoorientin attenuates aging-induced bone deterioration by suppressing M1-mediated TLR4-MAPK-NF-κB inflammatory signaling.Biogerontology · 2026Article
- Exosomes derived from M1-macrophage promote enteric neuronal injury via MMP8-TGF-β pathway.Journal of advanced research · 2026Article
- Age-Associated Senescence of Decidual Macrophages: A Key Mediator of Adverse Pregnancy Outcomes in Advanced Maternal Age.Aging cell · 2026Article
- Immunosenescence in systemic and multi-organ aging: mechanisms, inter-organ crosstalk, and translational opportunities.npj aging · 2026Review
- Maladaptive Inflammatory Signaling in Old Mice Impairs Colonic Regeneration by Promoting a Sustained Fetal-Like Epithelial State.Aging cell · 2026Article
- Analysis of the predictive value of age and serum IL-6 level at 24-hour postoperatively for prolonged postoperative ileus after laparoscopic colorectal cancer surgery.World journal of surgical oncology · 2026Article
- Histochemical characterization of muscularis macrophage loss and disruption of a miR-93-5p-AHNAK neuro-immune axis in Hirschsprung's disease.Histochemistry and cell biology · 2026Article
- Osteolineage cells ablation promotes skin aging phenotypes via dysregulated bone marrow macrophages.iScience · 2026Article
- RNA modifications in intestinal macrophages: Implications for gut immunity and inflammation.Genes & diseases · 2026Review
- Epididymal macrophage senescence contributes to sperm motility decrease upon environmental stress.Science advances · 2026Article
- Intestinal aging-related immune dysfunction: mechanisms and interventions.Acta biochimica et biophysica Sinica · 2026Review
- Low-grade mucosal inflammation in aged senescence-accelerated mouse-prone 8 mice blunts epithelial barrier recovery after dextran sodium sulphate-induced chronic colitis.Biogerontology · 2026Article
- Mechano-immune interactions in musculoskeletal aging: Mechanisms and translational perspectives.Theranostics · 2026Review
- Development and functional adaptation of intestinal macrophages across the lifespan.Clinical & translational immunology · 2026Review
- Microbiota-targeted therapeutic strategies for elderly-onset rheumatoid arthritis: based on the gut-joint axis.Frontiers in immunology · 2026Review
- Aging rate indicators and the search for anti-aging drugs.Frontiers in science · 2026Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveThe enteric nervous system (ENS) undergoes neuronal loss and degenerative changes with age. The cause of this neurodegeneration is poorly understood. Muscularis macrophages residing in close proximity to enteric ganglia maintain neuromuscular function via direct crosstalk with enteric neurons and have been implicated in the pathogenesis of GI motility disorders like gastroparesis and postoperative ileus. The aim of this study was to assess whether ageing causes alterations in macrophage phenotype that contributes to age-related degeneration of the ENS.
designLongitudinal muscle and myenteric plexus from small intestine of young, mid-aged and old mice were dissected and prepared for whole mount immunostaining, flow cytometry, Luminex immunoassays, western blot analysis, enteric neural stem cell (ENSC) isolation or conditioned media. Bone marrow derived macrophages were prepared and polarised to classic (M1) or alternative (M2) activation states. Markers for macrophage phenotype were measured using quantitative RT-PCR.
resultsAgeing causes a shift in macrophage polarisation from anti-inflammatory 'M2' to proinflammatory 'M1' that is associated with a rise in cytokines and immune cells in the ENS. This phenotypic shift is associated with a neural response to inflammatory signals, increase in apoptosis and loss of enteric neurons and ENSCs, and delayed intestinal transit. An age-dependent decrease in expression of the transcription factor FoxO3, a known longevity gene, contributes to the loss of anti-inflammatory behaviour in macrophages of old mice, and FoxO3-deficient mice demonstrate signs of premature ageing of the ENS.
conclusionsA shift by macrophages towards a proinflammatory phenotype with ageing causes inflammation-mediated degeneration of the ENS.
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What OpenQuestion holds
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.