ArticleDisease models & mechanisms2021
Activation of innate immunity during development induces unresolved dysbiotic inflammatory gut and shortens lifespan.
Article in Disease models & mechanisms, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- Stem cell-specific NF-κB is required for stem cell survival and epithelial regeneration upon intestinal damage.Biology open · 2025Article
- Growth phase diets diminish histone acetyltransferase Gcn5 function and shorten lifespan of Drosophila males.EMBO reports · 2025Article
- Genetic perturbation of cellular homeostasis regulates integrated stress response signaling to control Drosophila hematopoiesis.Biology open · 2025Article
- Trends in intestinal aging: From underlying mechanisms to therapeutic strategies.Acta pharmaceutica Sinica. B · 2025Review
- Article
- Pharmacology of Aging:Aging biology · 2024Article
- Antimicrobial peptides do not directly contribute to aging in Drosophila, but improve lifespan by preventing dysbiosis.Disease models & mechanisms · 2023Article
- Recognition of commensal bacterial peptidoglycans defines Drosophila gut homeostasis and lifespan.PLoS genetics · 2023Article
- Eucommia Polysaccharides Ameliorate Aging-Associated Gut Dysbiosis: A Potential Mechanism for Life Extension in Drosophila.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An early-life inflammatory response is associated with risks of age-related pathologies. How transient immune signalling activity during animal development influences life-long fitness is not well understood. Using Drosophila as a model, we find that activation of innate immune pathway Immune deficiency (Imd) signalling in the developing larvae increases adult starvation resistance, decreases food intake and shortens organismal lifespan. Interestingly, lifespan is shortened by Imd activation in the larval gut and fat body, whereas starvation resistance and food intake are altered by that in neurons. The adult flies that developed with Imd activation show sustained Imd activity in the gut, despite complete tissue renewal during metamorphosis. The larval Imd activation increases an immunostimulative bacterial species, Gluconobacter sp., in the gut microbiome, and this dysbiosis is persistent to adulthood. Removal of gut microbiota by antibiotics in the adult fly mitigates intestinal immune activation and rescues the shortened lifespan. This study demonstrates that early-life immune activation triggers long-term physiological changes, highlighted as an irreversible alteration in gut microbiota, prolonged inflammatory intestine and concomitant shortening of the organismal lifespan.
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