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Ascorbic acid inhibits senescence in mesenchymal stem cells through ROS and AKT/mTOR signaling
Mengkai Yang1, Songsong Teng1, Chunhui Ma1
1Department of Orthopaedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
Abstract:
Mesenchymal stem cell (MSC) aging seriously affects its function in stem cell transplantation for treatment. Extensive studies have focused on how to inhibit senescence in MSCs. However, the mechanism of senescence in MSC was not clear. In this study, we used D-galactose to induce MSC aging. Then we found that the number of aging cells was increased compared with untreated MSCs. We discovered that ascorbic acid could inhibit the production of reactive oxygen species (ROS) and activation of AKT/mTOR signaling in MSCs caused by D-galactose. Especially, when treated together with a ROS scavenger or AKT inhibitor, the senescent cells were obviously decreased in D-galactose-induced MSCs. Taken together, we identify that ascorbic acid owns the potential to inhibit the senescence of MSCs through ROS and Akt/mTOR signaling. Together, our data supports that ascorbic acid can be used to prevent MSCs from senescence, which can enhance the efficiency of stem cell transplantation in the clinic.
Insights
Ascorbic acid prevents mesenchymal stem cell (MSC) aging by inhibiting reactive oxygen species (ROS) and AKT/mTOR signaling. This finding supports using ascorbic acid to improve stem cell transplantation efficacy.
Area of Science:
- Cell Biology
- Regenerative Medicine
- Biochemistry
Background:
- Mesenchymal stem cell (MSC) aging impairs their therapeutic function in transplantation.
- Understanding the mechanisms of MSC senescence is crucial for improving cell-based therapies.
- Current strategies focus on inhibiting MSC senescence, but underlying mechanisms require further elucidation.
Purpose of the Study:
- To investigate the mechanism of D-galactose-induced mesenchymal stem cell (MSC) aging.
- To determine the potential of ascorbic acid in preventing MSC senescence.
- To elucidate the role of reactive oxygen species (ROS) and AKT/mTOR signaling in MSC aging.
Main Methods:
- Induction of MSC aging using D-galactose.
- Assessment of senescent cell markers.
- Measurement of reactive oxygen species (ROS) production.
- Analysis of AKT/mTOR signaling pathway activation.
- Treatment with ascorbic acid, ROS scavengers, and AKT inhibitors.
Main Results:
- D-galactose treatment increased the number of senescent MSCs.
- Ascorbic acid inhibited D-galactose-induced ROS production and AKT/mTOR signaling activation.
- Co-treatment with ROS scavengers or AKT inhibitors significantly reduced senescent cells in D-galactose-treated MSCs.
- Ascorbic acid demonstrated a protective effect against MSC senescence.
Conclusions:
- Ascorbic acid inhibits MSC senescence via the ROS and AKT/mTOR signaling pathways.
- Ascorbic acid has the potential to prevent MSC aging.
- Preventing MSC senescence with ascorbic acid could enhance stem cell transplantation efficiency in clinical applications.
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