1. Cycloastragenol: A Novel Senolytic Agent That Induces Senescent Cell Apoptosis and Restores Physical Function in TBI-Aged Mice.
- Author
-
Zhang, Yanghuan, Gao, Dongxiao, Yuan, Yang, Zheng, Runzi, Sun, Manting, Jia, Shuting, and Liu, Jing
- Subjects
- *
PHYSICAL mobility , *BCL-2 proteins , *APOPTOSIS , *MICE , *CELL migration , *CELLULAR aging , *SKIN aging - Abstract
Accumulating evidence indicates that the increased burden of senescent cells (SCs) in aged organisms plays an important role in many age-associated diseases. The pharmacological elimination of SCs with "senolytics" has been emerging as a new therapy for age-related diseases and extending the healthy lifespan. In the present study, we identified that cycloastragenol (CAG), a secondary metabolite isolated from Astragalus membrananceus, delays age-related symptoms in mice through its senolytic activity against SCs. By screening a series of compounds, we found that CAG selectively kills SCs by inducing SCs apoptosis and that this process is associated with the inhibition of Bcl-2 antiapoptotic family proteins and the PI3K/AKT/mTOR pathway. In addition, CAG treatment also suppressed the development of the senescence-associated secretory phenotype (SASP) in SCs, thereby inhibiting cell migration mediated by the SASP. Furthermore, the administration of CAG for 2 weeks to mice with irradiation-induced aging alleviated the burden of SCs and improved the animals' age-related physical dysfunction. Overall, our studies demonstrate that CAG is a novel senolytic agent with in vivo activity that has the potential to be used in the treatment of age-related diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF