The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Age-dependent shift in macrophage polarisation causes inflammation-mediated degeneration of enteric nervous system
Open accessAbstract
Objective: The 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. Design: Longitudinal 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. Results: Ageing 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. Conclusions: A shift by macrophages towards a proinflammatory phenotype with ageing causes inflammation-mediated degeneration of the ENS.
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“This, together with declining immune cell function and immunosenescence, promotes a state of elevated systemic inflammation termed “inflammaging” [39, 40, 118], contributing to the functional decline in the intestine and CNS in old age [10, 13, 48].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [10]
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“Loss of intestinal barrier integrity and elevated circulating pro-inflammatory cytokine concentrations are linked with the polarization of CNS microglia toward a pro-inflammatory phenotype [11, 73, 109] and promote neurodegenerative disease [10, 13, 48].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [10]
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Cites
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189
Inflamm‐aging: An Evolutionary Perspective on Immunosenescence
FRANCESCHI, C., BONAFÈ, M., VALENSIN, S., OLIVIERI, F., DE LUCA, M., OTTAVIANI, E., & DE BENEDICTIS, G. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06651.x · Cited by 5,358
Macrophage biology in development, homeostasis and disease
Wynn, T. A., Chawla, A., & Pollard, J. W. (2013) · Nature · doi:10.1038/nature12034 · Cited by 4,684
Inflammatory Blockade Restores Adult Hippocampal Neurogenesis
Monje, M. L., Toda, H., & Palmer, T. D. (2003) · Science · doi:10.1126/science.1088417 · Cited by 2,426
Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., et al. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.016 · Cited by 2,087
Four faces of cellular senescence
Rodier, F., & Campisi, J. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201009094 · Cited by 2,070
Bain, C. C., Bravo-Blas, A., Scott, C. L., Gomez Perdiguero, E., Geissmann, F., Henri, S., Malissen, B., Osborne, L. C., Artis, D., & Mowat, A. M. (2014) · Nature Immunology · doi:10.1038/ni.2967 · Cited by 1,178
Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing
Molofsky, A. V., Slutsky, S. G., Joseph, N. M., He, S., Pardal, R., Krishnamurthy, J., Sharpless, N. E., & Morrison, S. J. (2006) · Nature · doi:10.1038/nature05091 · Cited by 972
Macrophage activation switching: an asset for the resolution of inflammation
Porcheray, F., Viaud, S., Rimaniol, A.-C., Léone, C., Samah, B., Dereuddre-Bosquet, N., Dormont, D., & Gras, G. (2005) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2005.02934.x · Cited by 840
Crosstalk between Muscularis Macrophages and Enteric Neurons Regulates Gastrointestinal Motility
Muller, P. A., Koscsó, B., Rajani, G. M., Stevanovic, K. D., Berres, M., Hashimoto, D., Mortha, A., Leboeuf, M., Li, X.-M., Mucida, D., et al. (2014) · Cell · doi:10.1016/j.cell.2014.04.050 · Cited by 727
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Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health
Parker, A., Fonseca, S., & Carding, S. R. (2019) · Gut Microbes · doi:10.1080/19490976.2019.1638722 · Cited by 745
Self-Maintaining Gut Macrophages Are Essential for Intestinal Homeostasis
Schepper, S. D., Verheijden, S., Aguilera‐Lizarraga, J., Viola, M. F., Boesmans, W., Stakenborg, N., Voytyuk, I., Schmidt, I., Boeckx, B., de Casterlé, I. D., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.048 · Cited by 602
Sharkey, K. A., & Mawe, G. M. (2022) · Physiological Reviews · doi:10.1152/physrev.00018.2022 · Cited by 447
Parker, A., Romano, S., Ansorge, R., Aboelnour, A., Le Gall, G., Savva, G. M., Pontifex, M. G., Telatin, A., Baker, D., Jones, E., et al. (2022) · Microbiome · doi:10.1186/s40168-022-01243-w · Cited by 368
Kulkarni, S., Micci, M., Leser, J. M., Shin, C., Tang, S., Fu, Y., Liu, L., Li, Q., Saha, M., Li, C., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1619406114 · Cited by 278
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Metadata
- Authors
- Becker, L., Nguyen, L., Gill, J., Kulkarni, S., Pasricha, P. J., & Habtezion, A.
- Affiliations
- Stanford Medicine (US)
- Johns Hopkins University (US)
- Corresponding author
- Becker, Laren
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2017-02-21
- Volume
- 67
- Issue
- 5
- Pages
- 827-836
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC5565713
- OpenAlex
- W2591085270
- Cited by
- 196
- References
- 44
- Citations by year
- 2026: 27 · 2025: 43 · 2024: 21 · 2023: 26 · 2022: 29 · 2021: 15 · 2020: 12 · 2019: 11 · 2018: 10 · 2017: 2
- FWCI
- 10.02
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R21AG049622, R03AG045098)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK089502, K08DK103966, R01DK080920, P30DK116074)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- enteric nervous system, macrophage polarization, aging, neurodegeneration, M1/M2 macrophages, FOXO3, apoptosis, enteric neurons, intestinal motility, inflammation, small intestine, bone marrow-derived macrophages, cytokines
- MeSH terms
- Forkhead Box Protein O3, Aging, Animals, Cells, Cultured, Flow Cytometry, Gene Expression Regulation, Inflammation, Macrophages, Male, Mice, Inbred C57BL, Phenotype, Blotting, Western, Signal Transduction, Cytokines, Apoptosis, Enteric Nervous System, Mice, Real-Time Polymerase Chain Reaction
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