Aspirin Ameliorates Intestinal Barrier Function And Delays Aging Through Targeting Imd In Drosophila

Intestine is a highly regenerative tissue,which plays an important role in regulating the aging and lifespan of individuals.A large number of studies have shown that the intestinal immune barrier coordinates with the intestinal epithelial barrier to maintain the intestinal homeostasis,thus protecting the health of the body.Dysfunction or absence of gut barrier can significantly result in aging and even death.Therefore,how to maintain and promote intestinal barrier function is one of the most popular topics in the field of aging and longevity.In this study,we examined the biological functions of aspirin on the Drosophila intestinal epithelial barrier and intestinal immunity at the individual,tissue,cell and molecular levels,and elucidated the underlying molecular mechanisms.Results as follows:1.By continuously feeding fruit flies with aspirin at different concentrations(0.5 mg / L and 1 mg / L,0 mg / L was referred as the control group),we detected the intestinal barrier function,the division rate of intestinal stem cells,the population of gut microbiota on different days(10 d,30 d,60 d).The results showed that dietary supplementation of aspirin significantly improved intestinal barrier function,significantly reduced the the division rate of intestinal stem cells and the population of gut microbiota in Drosophila intestines.2.The luciferase reporter assays and qRT-PCR experiments showed that aspirin negatively regulated the Imd signaling pathway in both S2 cells and Drosophila gut tissues.3.Prevention of Drosophila intestinal Imd signal(imd,tak1,relish knock-down transgenic flies)significantly hindered the advantageous effects of aspirin in regulating gut homeostasis.4.RNA-seq and qRT-PCR analyses indicated that aspirin hardly altered the expressional levels of the major regulatory genes of the Imd signaling pathway(imd,uev1 a,bendless,effete,tak1,tab2,dredd,fadd,kenny,ird5,relish).5.In vitro and in vivo ubiquitination,protein stability,and SDD-AGE experiments showed that aspirin significantly inhibited the K63-linked ubiquitination of Imd,but not its protein stability and amyloidal aggregation.