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ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Stem Cell Research
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1576258
Dapagliflozin Ameliorates Intestinal Stem Cell Aging via Regulating the MAPK Signaling Pathway in Drosophila
Provisionally accepted- National Clinical Research Center for Geriatric Diseases, West China Hospital, Sichuan University, Chengdu, China
Intestinal stem cells (ISCs) possess the ability to self-renew and differentiate, which is essential for maintaining intestinal tissue homeostasis. However, their functionality significantly declines with age, leading to diminished tissue regeneration and an increased risk of age-associated diseases. This study investigates the effects of Dapagliflozin (DAPA), a novel insulin sensitizer and SGLT2 inhibitor, on aging ISCs using the Drosophila melanogaster model. Our findings demonstrate that DAPA can inhibit the MAPK signaling pathway, as confirmed by network pharmacology analysis and molecular docking experiments. DAPA ameliorates ISC aging, improves intestinal function (including enhanced fecal excretion ,restored intestinal barrier integrity and acid-base balance), and enhances healthspan.These results highlight the potential of DAPA as an anti-aging therapeutic agent.
Keywords: dapagliflozin, intestinal stem cell, Aging, MAPK signaling, Drosophila
Received: 13 Feb 2025; Accepted: 07 Apr 2025.
Copyright: © 2025 Jinhua, Feng, Zhang, Luo, Chen and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yan Jinhua, National Clinical Research Center for Geriatric Diseases, West China Hospital, Sichuan University, Chengdu, China
Haiou Chen, National Clinical Research Center for Geriatric Diseases, West China Hospital, Sichuan University, Chengdu, China
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