Open AccessAspirin Positively Contributes to Drosophila Intestinal Homeostasis and Delays Aging through Targeting Imd
Author(s) -
Yangyang Zhu,
Qingshuang Cai,
Xianrui Zheng,
Lei Liu,
Yongzhi Hua,
Bowen Du,
Guangjie Zhao,
Jinming Yu,
Zhuo Zhao,
Zhongwen Xie,
Shanming Ji
Publication year - 2021
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.808
H-Index - 54
ISSN - 2152-5250
DOI - 10.14336/ad.2020.1008
Subject(s) - aspirin , homeostasis , medicine , drosophila (subgenus) , pharmacology , bioinformatics , biology , genetics , gene
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 .