• Molecules and Cells
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• v.46 no.7
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• pp.420-429
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• 2023

Age-related macular degeneration (AMD) is one of the leading causes of blindness in elderly individuals. However, the currently used intravitreal injections of anti-vascular endothelial growth factor are invasive, and repetitive injections are also accompanied by a risk of intraocular infection. The pathogenic mechanism of AMD is still not completely understood, but a multifactorial mechanism that combines genetic predisposition and environmental factors, including cellular senescence, has been suggested. Cellular senescence refers to the accumulation of cells that stop dividing due to the presence of free radicals and DNA damage. Characteristics of senescent cells include nuclear hypertrophy, increased levels of cell cycle inhibitors such as p16 and p21, and resistance to apoptosis. Senolytic drugs remove senescent cells by targeting the main characteristics of these cells. One of the senolytic drugs, ABT-263, which inhibits the antiapoptotic functions of Bcl-2 and Bcl-xL, may be a new treatment for AMD patients because it targets senescent retinal pigment epithelium (RPE) cells. We proved that it selectively kills doxorubicin (Dox)-induced senescent ARPE-19 cells by activating apoptosis. By removing senescent cells, the expression of inflammatory cytokines was reduced, and the proliferation of the remaining cells was increased. When ABT-263 was orally administered to the mouse model of senescent RPE cells induced by Dox, we confirmed that senescent RPE cells were selectively removed and retinal degeneration was alleviated. Therefore, we suggest that ABT-263, which removes senescent RPE cells through its senolytic effect, has the potential to be the first orally administered senolytic drug for the treatment of AMD.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.46 no.4
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• pp.391-401
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• 2020

Flavonoids are polyphenolic compounds derived from plants metabolites and are known to be capable of controlling various human physiological functions. Among them, fisetin (3,3', 3', 7-tetrahydroxyflavone) is found in various fruits and vegetables, and it has been recently known to restore the function of certain tissues through senolytic activity. In this study, targeting human epidermal keratinocytes, control of skin barrier genes and antioxidant efficacy of fisetin were analyzed. Fisetin increased the activity of telomerase and decreased the expression of CDKN1B. In addition, it increased the expression of KRT1, FLG, IVL, and DSP, which are main genes that make up the skin barrier. The fisetin also increased the expression of CerS3 and CerS4 genes, which are forms of ceramide synthases. These results show that the efficacy of fisetin is not limited as senolytics but is also involved in various physiological regulation of human keratinocytes. Therefore, we consider that fisetin could be used as an active ingredient in cosmetics and pharmaceuticals.