# Dapagliflozin ameliorates intestinal stem cell aging by regulating the MAPK signaling pathway in Drosophila

## TL;DR

Dapagliflozin improves aging in intestinal stem cells in fruit flies by affecting a key signaling pathway, potentially offering a new anti-aging treatment.

## Contribution

This study is the first to show that Dapagliflozin can ameliorate ISC aging by inhibiting the MAPK pathway in Drosophila.

## Key findings

- Dapagliflozin inhibits the MAPK signaling pathway in aging intestinal stem cells.
- Dapagliflozin improves intestinal function and healthspan in Drosophila.
- Dapagliflozin restores intestinal barrier integrity and acid-base balance in aged flies.

## Abstract

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.

This study provides new evidence for the application of DAPA as an anti-aging treatment.