Aspirin Positively Contributes to Drosophila Intestinal Homeostasis and Delays Aging through Targeting Imd

Abstract

The intestine, a high-turnover tissue, plays a critical role in regulating aging and health in both vertebrates and invertebrates. Maintaining the epithelial barrier function of the intestine by preserving innate immune homeostasis significantly delays aging and prevents mortality. In an effort to explore effective chemicals and materials that can improve intestinal integrity, we performed a nonbiased screen utilizing Drosophila as an animal model. We showed that long-term uptake of aspirin markedly prevented age-onset gut leakage, the over-proliferation of intestinal stem cells, and the dysbiosis of commensal microbiota in fruit flies. Mechanistically, aspirin efficiently downregulated chronic activation of intestinal immune deficiency signaling during aging. Furthermore, our in vivo and in vitro biochemical analyses indicated that aspirin is a negative modulator in control of the K63-linked ubiquitination of Imd. Our findings uncover a novel regulatory mechanism by which aspirin positively modulates intestinal homeostasis, thus delaying aging, in Drosophila .

A Feedback Regulatory Loop Involving dTrbd/dTak1 in Controlling IMD Signaling in Drosophila Melanogaster

“…Previous studies have shown that preventing the IMD signaling pathway in gut tissues positively contributes to the life longevity of Drosophila ( 15 , 41 – 43 ). We thus sought to identify whether dTrbd modulates lifespan via multiple domains.…”

“…However, the mRNA levels of these AMP genes were relatively comparable between samples from c564 ts >GFP-dTrbd DNZF , c564 ts >GFP-dTrbd DLR , and the control flies (Figures 5A, B), suggesting both the NZF domain and the LR are required for dTrbd to negatively govern IMD signaling post microbial infection. Previous studies have shown that preventing the IMD signaling pathway in gut tissues positively contributes to the life longevity of Drosophila (15,(41)(42)(43). We thus sought to identify whether dTrbd modulates lifespan via multiple domains.…”

Endoplasmic reticulum-associated protein degradation contributes to Toll innate immune defense in Drosophila melanogaster

“…Western blot assays were performed as described previously ( 51 ). In brief, fat bodies were lysed in lysis buffer (150mM NaCl, 50mM Tris-HCl, pH=7.4, 10% glycerol, 0.5% TritonX-100, and 1mM PMSF).…”

Pharmacological Approaches to Decelerate Aging: A Promising Path

“…One of the proposed antiaging mechanisms of aspirin is through its effect on the reduction of germline stem cells [ 262 ]. Another proposed mechanism is improving intestinal barrier function by restricting the K63-linked ubiquitination and preventing intestinal immune deficiency [ 264 ].…”