title: Rapamycin preserves gut homeostasis during Drosophila aging.
abstract: Gut homeostasis plays an important role in maintaining the overall body health during aging. Rapamycin, a specific inhibitor of mTOR, exerts prolongevity effects in evolutionarily diverse species. However, its impact on the intestinal homeostasis remains poorly understood. Here, we demonstrate that rapamycin can slow down the proliferation rate of intestinal stem cells (ISCs) in the aging guts and induce autophagy in the intestinal epithelium in Drosophila. Rapamycin can also significantly affect the FOXO associated genes in intestine and up-regulate the negative regulators of IMD/Rel pathway, consequently delaying the microbial expansion in the aging guts. Collectively, these findings reveal that rapamycin can delay the intestinal aging by inhibiting mTOR and thus keeping stem cell proliferation in check. These results will further explain the mechanism of healthspan and lifespan extension by rapamycin in Drosophila.
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Fan
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lian
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Uma
authors.initials: U
authors.lastname: Gaur
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Diyan
authors.initials: D
authors.lastname: Li
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Deying
authors.initials: D
authors.lastname: Yang
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Xueping
authors.initials: X
authors.lastname: Mao
authors.affiliation: School of Biotechnology and Chemical Engineering, Ningbo Institute of Technology, Zhejiang University, Zhejiang, P.R. China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R. China.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Yang
mesh_terms: D000367:Age Factors; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D007422:Intestines / Q000166:cytology* / Q000187:drug effects*; D011897:Random Allocation; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D029721:Drosophila Proteins; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Drosophila; Gerotarget; aging; gut homeostasis; intestinal stem cell; rapamycin