Screening of Senolytics Targeting Senescent Melanocytes
- 주제(키워드) Senescent Melanocytes , Senolytics , ABT-737 , ABT-263
- 주제(DDC) 570
- 발행기관 아주대학교 일반대학원
- 지도교수 Hee Young Kang
- 발행년도 2025
- 학위수여년월 2025. 8
- 학위명 석사
- 학과 및 전공 일반대학원 의생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000035154
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
As skin ages, the accumulation of senescent melanocytes contributes to age-related pigmentation and overall skin deterioration. Senolytics, which selectively induce apoptosis in senescent cells, may offer a promising approach to mitigate these effects. In this study, investigated the effects of senolytic agents on senescent melanocytes and identified the potential of ABT-737 and ABT-263 as effective treatments. First, I established a model of UVB-induced senescent melanocytes. Then, various senolytic compounds, including FOXO4-DRI, ginkgo biloba extract, quercetin, dasatinib, resveratrol, ABT-737 and ABT-263 were tested for their ability to selectively eliminate senescent cells. ABT-737 and ABT-263 exhibited the most significant efficacy. These agents function by inhibiting Bcl-2 family of proteins, leading to increased caspase-3/7 activity and induction of apoptosis in senescent melanocytes. Furthermore, pretreatment with Z-VAD-FMK (Z-VAD), a caspase inhibitor, increased the survival of senescent cells, confirming the role of caspase activation in this process. In conclusion, ABT-737 and ABT-263 show potential as senolytic agents for targeting senescent melanocytes, offering a promising strategy for improving aging skin. Key words : Senescent melanocytes, Senolytics, ABT-737, ABT-263
more목차
Ⅰ. INTRODUCTION 1
Ⅱ. MATERIALS AND METHODS 4
1. Cell Culture 4
2. In Vitro model of UVB-induced Senescent Melanocyte (UVSM) 4
3. Materials 4
4. Senescence-Associated β-Galactosidase (SA-β-Gal) Staining 5
5. Real-Time PCR Analysis 5
6. MTT Assay 5
7. Cell Counting 6
8. Western Blot Analysis 6
9. Measurement of Caspase-3/7 Activity 6
10. PE Annexin V/7-AAD Analysis 7
11. Statistical Analysis 7
Ⅲ. RESULTS 8
1. Evaluation of senolytic drugs on senescent melanocytes 8
2. ABT-737 and ABT-263 eliminated senescent melanocytes 21
3. ABT-737 and ABT-263 induced caspase activity 24
4. Caspase inhibitors restore apoptosis in senescent melanocytes 27
Ⅳ. DISCUSSION 31
Ⅴ. REFERENCES 33
Ⅵ. 국문 요약 36
