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.
Highlights
Rapamycin is the most specific TOR inhibitor known and it acts through association with the intracellular protein FKBP12, which binds to the FKBP12rapamycin-binding (FRB) domain of TOR, inhibiting TORC1 activity
We showed that rapamycin limits the proliferation rates of intestinal stem cells by moderately inhibiting mechanistic target of rapamycin (mTOR) leading to delay in the microbial expansion during gut aging
We found that the proliferation of intestinal stem cells (ISCs) in the guts of young flies (3 days old), is maintained at low level in both control and rapamycin groups (Figure 1B-1C)
Summary
Rapamycin is the most specific TOR inhibitor known and it acts through association with the intracellular protein FKBP12, which binds to the FKBP12rapamycin-binding (FRB) domain of TOR, inhibiting TORC1 activity. The effect of rapamycin on lifespan extension has been studied in many species but its effect on gut homeostasis is not fully elucidated. In order to examine whether rapamycin can preserve gut homeostasis during aging, we used Drosophila intestine as an accessible model system. We showed that rapamycin limits the proliferation rates of intestinal stem cells by moderately inhibiting mTOR leading to delay in the microbial expansion during gut aging.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
