Embryonic stem cell-derived extracellular vesicles delay cellular senescence by inhibiting oxidative stress
Shun Enomoto1, Yun Ha Hur2, Tatiana Solodova3
1Department of Molecular Medicine, Cornell University, Ithaca, New York, USA.
The Journal of Biological Chemistry
|October 16, 2025
Summary
Embryonic stem cell-derived extracellular vesicles (EVs) can prevent cellular senescence. A newly identified fibronectin-initiated pathway involving AKT and Nrf2 activation explains how these EVs extend cellular lifespan and offer anti-aging potential.
Area of Science:
- Cell Biology
- Biochemistry
- Gerontology
Background:
- Cellular senescence, a state of irreversible cell cycle arrest, is a key factor in aging and age-related diseases.
- Extracellular vesicles (EVs) from embryonic stem cells (ESCs) show promise for regenerative medicine and treating aging disorders.
- The precise molecular mechanisms behind the anti-senescence effects of ESC-derived EVs are not fully understood.
Purpose of the Study:
- To elucidate the molecular signaling pathway responsible for the anti-senescence properties of ESC-derived EVs.
- To identify key molecular players mediating the protective effects of EVs against cellular senescence.
Main Methods:
- Investigated the role of fibronectin coating on ESC-derived EVs.
- Analyzed the activation of integrins, FAK, AKT, GSK3β, and Nrf2 in response to EV treatment.
- Assessed the impact of EV treatment on fibroblast and astrocyte senescence.
Main Results:
- Identified a pathway where fibronectin on EVs binds to integrins, activating FAK and AKT.
- Demonstrated that this activation inhibits GSK3β, leading to Nrf2 stabilization.
- Showed that Nrf2 activation counteracts oxidative stress, preventing cellular senescence.
Conclusions:
- Defined a novel signaling pathway by which ESC-derived EVs inhibit cellular senescence.
- This pathway involves fibronectin-mediated integrin signaling, AKT activation, GSK3β inhibition, and Nrf2 stabilization.
- Highlights the therapeutic potential of ESC-derived EVs for anti-aging strategies and age-related diseases.
Keywords:
cell signalingcellular senescenceexosomeextracellular vesiclesfibronectinglycogen synthase kinase 3 (GSK-3)microvesiclesoxidative stressreactive oxygen species (ROS)More Related Videos
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