title: Preventing Age-Related Decline of Gut Compartmentalization Limits Microbiota Dysbiosis and Extends Lifespan.
abstract: Compartmentalization of the gastrointestinal (GI) tract of metazoans is critical for health. GI compartments contain specific microbiota, and microbiota dysbiosis is associated with intestinal dysfunction. Dysbiosis develops in aging intestines, yet how this relates to changes in GI compartmentalization remains unclear. The Drosophila GI tract is an accessible model to address this question. Here we show that the stomach-like copper cell region (CCR) in the middle midgut controls distribution and composition of the microbiota. We find that chronic activation of JAK/Stat signaling in the aging gut induces a metaplasia of the gastric epithelium, CCR decline, and subsequent commensal dysbiosis and epithelial dysplasia along the GI tract. Accordingly, inhibition of JAK/Stat signaling in the CCR specifically prevents age-related metaplasia, commensal dysbiosis and functional decline in old guts, and extends lifespan. Our results establish a mechanism by which age-related chronic inflammation causes the decline of intestinal compartmentalization and microbiota dysbiosis, limiting lifespan.
authors: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA; Department of Biology, University of Rochester, River Campus Box 270211, Rochester, NY 14627, USA.
authors: Hongjie
authors: H
authors: Li
authors: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
authors: Yanyan
authors: Y
authors: Qi
authors: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA; Department of Biology, University of Rochester, River Campus Box 270211, Rochester, NY 14627, USA. Electronic address: hjasper@buckinstitute.org.
authors: Heinrich
authors: H
authors: Jasper
mesh_terms: D000367:Age Factors; D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism / Q000382:microbiology*; D064806:Dysbiosis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000254:growth & development / Q000382:microbiology*; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D050791:STAT Transcription Factors; D053612:Janus Kinases