Conti Anastasia, Di Micco Raffaella
San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy.
San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy; University School of Advanced Studies IUSS, Pavia 27100, Italy.
Mech Ageing Dev. 2025 Jun;225:112056. doi: 10.1016/j.mad.2025.112056. Epub 2025 Apr 6.
The selective eradication of senescent cells using senolytic compounds represents a promising strategy to treat senescence-associated diseases like aging and cancer. However, many senolytics may cause systemic toxicity. Magkouta et al., writing in Nature Aging, introduced mGL392, an advanced senolytic platform utilizing a lipofuscin-binding domain scaffold conjugated with a senolytic drug (e.g., dasatinib). mGL392 effectively eliminates senescent cells in vitro and in vivo, reducing tumor size in melanoma models while minimizing systemic toxicity. Compared to existing senolytics, it offers improved specificity, reducing off-target effects. This innovation presents a safer and more effective approach for treating senescence-related diseases.
使用衰老细胞裂解化合物选择性清除衰老细胞是治疗与衰老相关疾病（如衰老和癌症）的一种有前景的策略。然而，许多衰老细胞裂解剂可能会引起全身毒性。Magkouta等人在《自然·衰老》杂志上发表文章，介绍了mGL392，这是一种先进的衰老细胞裂解平台，利用与衰老细胞裂解药物（如达沙替尼）偶联的脂褐素结合结构域支架。mGL392在体外和体内均能有效清除衰老细胞，在黑色素瘤模型中减小肿瘤大小，同时将全身毒性降至最低。与现有的衰老细胞裂解剂相比，它具有更高的特异性，减少了脱靶效应。这一创新为治疗与衰老相关的疾病提供了一种更安全、更有效的方法。
