• Molecules and Cells
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• 제46권7호
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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.

• 대한화장품학회지
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• 제46권4호
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• pp.391-401
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• 2020

플라보노이드(flavonoid)는 식물 등의 대사체에서 유래한 폴리페놀 계열의 화합물이며, 다양한 인체생리작용을 조절할 수 있는 것으로 알려져 있다. 이중 3,3',3',7-tetrahydroxyflavone (fisetin)은 다양한 과일과 채소에서 발견되며, 최근 노쇠용해(senolytic) 활성을 통해 특정 조직의 기능을 회복시킨다는 것이 알려졌다. 본 연구에서는 인간 표피 각질세포를 대상으로 하여 fisetin의 피부장벽 유전자 발현 조절 및 항노화 효능을 분석하였다. Fisetin은 말단소립 역전사효소(telomerase)의 활성을 증가시켰으며, CDKN1B 유전자의 발현을 감소시켰다. 또한 피부장벽을 구성하는 주요 유전자인 KRT1, FLG, IVL, DSP의 발현을 증가시켰으며, 세라마이드 합성효소의 일종인 CerS3, CerS4 유전자의 발현을 증가시켰다. 이러한 결과는 fisetin의 효능이 노쇠용해에 국한되지 않고 인간 각질세포의 다양한 생리학적 조절에도 관여함을 보여준다. 따라서 fisetin은 화장품 및 의약품 등의 생리활성 조절물질로 활용될 수 있다고 사료된다.