764 Targeting dermal fibroblast senescence with senomorphic and epigenetic properties of haritaki fruit extract: Effects on SASP and miR over-expression in senescent fibroblasts’ extracellular vesicles

Skin aging is the consequence of two biological process: intrinsic genetically programmed factors and extrinsic environmental factors. At cellular level, accumulation senescent cells (SC) also involved in skin aging. SC stop to proliferate but remain metabolically active. The secretome (Senescence Associated Secretory Phenotype: SASP), a cocktail mediators like CSF3, CXCL1, IL8, IL1b, IL6, MMP-1 -3, Extracellular vesicles (EV) have been reported act as cytokines during intercellular communication. They transport proteins, mRNAs miRNAs, over short or long distances. miRNAs are class short, single-stranded, noncoding RNA molecules. As epigenetic modulators, affect protein levels target without modifying gene sequences. Several miRs known be senescence aim our study was evaluate, effect Haritaki fruit extract (HF extract) on SASP associated contained EV. Our results showed that, 14 days after ionizing radiation (7.5 Gy), human dermal fibroblasts presented phenotype: flattened irregular shape, ß-galactosidase activity, expression (RT-PCR) miR 24a-3p, 186-5p, 30a-3p 29a-3p overexpression EV (RT-PCR). that incubation with HF strongly decreased mRNA level 34a-5p, over-expression Taken together these demonstrated strong senomorphic agent effect, suggesting it may useful for development new anti-aging dermo-cosmetic products.