Yan Jinhua, Feng Chenxi, Zhang Hanmei, Luo Ting, Chen Haiyang, Chen Haiou
Center 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, China.
West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
Front Cell Dev Biol. 2025 Apr 23;13:1576258. doi: 10.3389/fcell.2025.1576258. eCollection 2025.
INTRODUCTION: 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. METHODS: This study investigates the effects of Dapagliflozin (DAPA), a novel insulin sensitizer and SGLT2 inhibitor, on aging ISCs using the model. Our findings demonstrate that DAPA can inhibit the MAPK signaling pathway, as confirmed by network pharmacology analysis and molecular docking experiments. RESULTS: 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. DISCUSSION: This study provides new evidence for the application of DAPA as an anti-aging treatment.
引言：肠道干细胞（ISC）具有自我更新和分化的能力，这对于维持肠道组织稳态至关重要。然而，它们的功能会随着年龄的增长而显著下降，导致组织再生能力减弱以及与年龄相关疾病的风险增加。 方法：本研究使用该模型研究新型胰岛素增敏剂和钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂达格列净（DAPA）对衰老肠道干细胞的影响。我们的研究结果表明，通过网络药理学分析和分子对接实验证实，达格列净可以抑制丝裂原活化蛋白激酶（MAPK）信号通路。 结果：达格列净改善肠道干细胞衰老，改善肠道功能（包括增强粪便排泄、恢复肠道屏障完整性和酸碱平衡），并延长健康寿命。这些结果凸显了达格列净作为抗衰老治疗药物的潜力。 讨论：本研究为达格列净作为抗衰老治疗的应用提供了新证据。
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