Dapagliflozin ameliorates intestinal stem cell aging by regulating the MAPK signaling pathway in Drosophila
IntroductionIntestinal 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-associa...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1576258/full |
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| author | Jinhua Yan Jinhua Yan Chenxi Feng Hanmei Zhang Ting Luo Ting Luo Haiyang Chen Haiou Chen |
| author_facet | Jinhua Yan Jinhua Yan Chenxi Feng Hanmei Zhang Ting Luo Ting Luo Haiyang Chen Haiou Chen |
| author_sort | Jinhua Yan |
| collection | DOAJ |
| description | IntroductionIntestinal 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.MethodsThis 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.ResultsDAPA 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.DiscussionThis study provides new evidence for the application of DAPA as an anti-aging treatment. |
| format | Article |
| id | doaj-art-607e1e04a6104ec9abb88b35dca283db |
| institution | DOAJ |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-607e1e04a6104ec9abb88b35dca283db2025-08-20T03:14:46ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-04-011310.3389/fcell.2025.15762581576258Dapagliflozin ameliorates intestinal stem cell aging by regulating the MAPK signaling pathway in DrosophilaJinhua Yan0Jinhua Yan1Chenxi Feng2Hanmei Zhang3Ting Luo4Ting Luo5Haiyang Chen6Haiou Chen7Center of Gerontology and Geriatrics and Laboratory of Metabolism and Aging Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, ChinaWest China School of Medicine, Sichuan University, Chengdu, Sichuan, ChinaWest China School of Medicine, Sichuan University, Chengdu, Sichuan, ChinaWest China School of Medicine, Sichuan University, Chengdu, Sichuan, ChinaCenter of Gerontology and Geriatrics and Laboratory of Metabolism and Aging Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, ChinaWest China School of Medicine, Sichuan University, Chengdu, Sichuan, ChinaCenter of Gerontology and Geriatrics and Laboratory of Metabolism and Aging Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, ChinaCenter of Gerontology and Geriatrics and Laboratory of Metabolism and Aging Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, ChinaIntroductionIntestinal 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.MethodsThis 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.ResultsDAPA 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.DiscussionThis study provides new evidence for the application of DAPA as an anti-aging treatment.https://www.frontiersin.org/articles/10.3389/fcell.2025.1576258/fulldapagliflozinintestinal stem cellagingMAPK signalingDrosophila |
| spellingShingle | Jinhua Yan Jinhua Yan Chenxi Feng Hanmei Zhang Ting Luo Ting Luo Haiyang Chen Haiou Chen Dapagliflozin ameliorates intestinal stem cell aging by regulating the MAPK signaling pathway in Drosophila Frontiers in Cell and Developmental Biology dapagliflozin intestinal stem cell aging MAPK signaling Drosophila |
| title | Dapagliflozin ameliorates intestinal stem cell aging by regulating the MAPK signaling pathway in Drosophila |
| title_full | Dapagliflozin ameliorates intestinal stem cell aging by regulating the MAPK signaling pathway in Drosophila |
| title_fullStr | Dapagliflozin ameliorates intestinal stem cell aging by regulating the MAPK signaling pathway in Drosophila |
| title_full_unstemmed | Dapagliflozin ameliorates intestinal stem cell aging by regulating the MAPK signaling pathway in Drosophila |
| title_short | Dapagliflozin ameliorates intestinal stem cell aging by regulating the MAPK signaling pathway in Drosophila |
| title_sort | dapagliflozin ameliorates intestinal stem cell aging by regulating the mapk signaling pathway in drosophila |
| topic | dapagliflozin intestinal stem cell aging MAPK signaling Drosophila |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1576258/full |
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