Extracellular Vesicles of GMSCs Alleviate Aging-Related Cell Senescence

Area of Science:

• Gerontology
• Cell Biology
• Biomedical Engineering

Background:

• Cellular senescence, marked by cell cycle arrest and impaired tissue function, is central to aging.
• Aberrant activation of the mammalian target of rapamycin (mTOR) signaling pathway is implicated in senescence.
• Oxidative stress accelerates cellular senescence, contributing to age-related decline.

Purpose of the Study:

• To investigate the anti-aging potential of extracellular vesicles (EVs) from gingiva-derived mesenchymal stem cells (GMSC-EVs).
• To evaluate the effects of GMSC-EVs on oxidative stress-induced cellular senescence in human endothelial cells and skin fibroblasts.
• To assess the therapeutic efficacy of GMSC-EVs in aged mouse models.

Main Methods:

• Treatment of human umbilical vein endothelial cells (HUVECs) and skin fibroblasts with GMSC-EVs under oxidative stress conditions.
• Analysis of senescence markers (β-galactosidase, p21, p53, γH2AX) and mTOR/pS6 signaling pathway activation.
• Assessment of HUVEC proliferation and tube formation.
• Systemic administration of GMSC-EVs in aged mice and analysis of senescence markers in skin and heart tissues.

Main Results:

• GMSC-EVs significantly reduced the expression of senescence markers and inhibited mTOR/pS6 signaling in stressed cells.
• GMSC-EVs restored proliferation and tube formation capacity in HUVECs.
• In aged mice, GMSC-EVs decreased levels of p21, mTOR/pS6, IL-6, and TNF-α in skin and heart tissues.

Conclusions:

• GMSC-EVs effectively inhibit oxidative stress-induced cellular senescence in endothelial cells and skin fibroblasts.
• GMSC-EVs demonstrate anti-aging potential by attenuating age-related molecular changes in vivo.
• GMSC-EVs represent a promising cell-free therapeutic strategy for age-related skin and vascular dysfunction.