Extracellular vesicles carrying two microRNAs reduce vascular aging markers in progeria cells
Vesicles from melatonin-treated stem cells targeted SRSF1 and SP1 to lower progerin and cellular prion protein in cell models.
Pharmacological Research
In experiments using human cellular models and serum from an index patient with Hutchinson-Gilford progeria syndrome, researchers tested small extracellular vesicles from melatonin-preconditioned mesenchymal stromal cells. The patient's serum showed elevated progerin, cellular prion protein, and troponin I levels, and it impaired endothelial tube formation. Treating endothelial cells and progeria fibroblasts with these vesicles reduced endothelial dysfunction, progerin, cellular prion protein, p16, and DNA damage markers. Mechanistically, vesicle-derived miR-4651 targeted SRSF1 to lessen nuclear-lamina defects, while miR-6126 targeted SP1 to decrease cellular prion protein expression. A virtual-cohort analysis prioritized combining lonafarnib with these vesicles or microRNAs.
Why it matters
The study links cellular prion protein to progeria-associated vascular disease alongside classical progerin toxicity. It highlights dual-microRNA delivery as a potential strategy to target multiple vascular injury and cellular senescence pathways simultaneously.
Caveats
The findings are limited to cell-culture models and serum from a single index patient. Additionally, the therapeutic combinations were prioritized using a computational virtual-cohort analysis without a consistently top-ranked regimen across models.
The paper
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Jaeyoung Lee, Myung‐Shin Jeon, Myung‐Shin Jeon, Ji-Sun Park, Su-Jin Kim, Yun Seob Song, Ji-Eun Lee, Sang Hun Lee, Kwang-Sung Choi,Inha University
Pharmacological Research · 29 Sep 2026
