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 · Joo EY et al. · Paper published 29 Sep 2026
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.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
MT-Exo-derived miR-4651 and miR-6126 coordinately regulate the SRSF1-progerin and SP1-PrPᶜ axes to attenuate vascular aging in HGPS
Joo EY, Yoon U, Lee J et al.
Pharmacological research · 29 Sep 2026 · Peer-reviewed
- Relevance
- Core geroscience
- News value
- Notable
- Evidence
- Cells
- Status
- Peer-reviewed
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