Suda Masayoshi, Tchkonia Tamar, Kirkland James L, Minamino Tohru
Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo City, Tokyo 113-8431, Japan.
Division of Endocrinology, Diabetes, & Metabolism, Center for Advanced Gerotherapeutics, Cedars-Sinai Medical Center, 8687 Melrose Ave, Pacific Design Center, West Hollywood, CA 90069, USA.
J Biochem. 2025 Mar 4;177(3):177-187. doi: 10.1093/jb/mvae091.
Cellular senescence, which entails cellular dysfunction and inflammatory factor release-the senescence-associated secretory phenotype (SASP)-is a key contributor to multiple disorders, diseases and the geriatric syndromes. Targeting senescent cells using senolytics has emerged as a promising therapeutic strategy for these conditions. Among senolytics, the combination of dasatinib and quercetin (D + Q) was the earliest and one of the most successful so far. D + Q delays, prevents, alleviates or treats multiple senescence-associated diseases and disorders with improvements in healthspan across various pre-clinical models. While early senolytic therapies have demonstrated promise, ongoing research is crucial to refine them and address such challenges as off-target effects. Recent advances in senolytics include new drugs and therapies that target senescent cells more effectively. The identification of senescence-associated antigens-cell surface molecules on senescent cells-pointed to another promising means for developing novel therapies and identifying biomarkers of senescent cell abundance.
细胞衰老涉及细胞功能障碍和炎症因子释放（即衰老相关分泌表型，SASP），是多种疾病、失调和老年综合征的关键促成因素。使用衰老细胞溶解剂靶向衰老细胞已成为针对这些病症的一种有前景的治疗策略。在衰老细胞溶解剂中，达沙替尼和槲皮素的组合（D+Q）是最早出现且迄今为止最成功的组合之一。D+Q可延缓、预防、减轻或治疗多种与衰老相关的疾病和失调，并在各种临床前模型中改善健康寿命。虽然早期的衰老细胞溶解疗法已显示出前景，但持续的研究对于优化它们并解决脱靶效应等挑战至关重要。衰老细胞溶解剂的最新进展包括更有效地靶向衰老细胞的新药和疗法。衰老相关抗原（即衰老细胞表面分子）的鉴定为开发新疗法和识别衰老细胞丰度的生物标志物指明了另一种有前景的方法。
