Targeting <scp>SIRT1</scp> via Exosomes Derived From Oleuropein‐Treated Cells: A Novel Approach to Rejuvenation Skin Through <scp>miRNA</scp> Modulation

<i>Sirtuin1</i> (<i>SIRT1</i>) plays an important role in skin aging by regulating cellular processes such as oxidative stress response, inflammation modulation, <i>Collagen</i> and <i>Elastin</i> synthesis. This study aims to examine oleuropein's (OLE) effect on <i>SIRT1</i> gene expression and to analyze <i>SIRT1</i>-related miRNAs in exosomes produced from Mesenchymal Stem cells (MSC) and Human Fetal Foreskin Fibroblast 2 (HFFF2) cells, along with these treated exosomes' impact on <i>SIRT1</i> gene expression and the studied miRNAs in HFFF2 cells to decrease skin aging. A nontoxic concentration (400 μg/mL) of OLE was applied to the MSCs and HFFF2 cells. Then, Gradient Ultracentrifugation extracted their exosomes; cell-derived exosomes were confirmed by DLS assay and western Blot. Exosomes were applied at 50 μg/mL (exosome protein concentration) to HFFF2 cells. The expression of <i>SIRT1</i> gene and related miRNAs relative to the control group were examined using qRT-PCR. This analysis was conducted on cells OLE-treated for <i>SIRT1</i>, on exosomes treatment with OLE for miRNAs, and on HFFF2 cells treated with cell-derived exosomes for both <i>SIRT1</i> and miRNAs. <i>SIRT1</i> expression was upregulated (<i>p</i> ≤ 0.05) in both OLE and cell-derived exosomes. Also, <i>hsa-miR-29c-3p</i> and <i>hsa-miR-9-5p</i> were downregulated (<i>p</i> ≤ 0.05), whereas <i>hsa-miR-155-5p</i> was upregulated (<i>p</i> ≤ 0.05) in exosomes OLE-treated and in HFFF2 cells treated with these exosomes. This study introduces a novel approach to skin rejuvenation by using manipulated exosomes OLE-treated, which enhance <i>SIRT1</i> expression and suppress related miRNAs. This method potentially offers a more effective and less immunogenic alternative to direct OLE application due to the exosomes' ability to penetrate cells.