The Flavonoid 4,4 ′-dimethoxychalcone is Senolytic

In this study, we found that DMC reduced the SASP level in senescent cells. Furthermore, senescent cells enter irreversible cell cycle arrest, which involves the activation of p53/p21 and Rb/p16. In this study we found that the expression levels of p21 and p16 were decreased after DMC treatment. The downregulation of p21 may be attributed to the decrease of p53. In this study, we found that the mRNA level of p53 was reduced after DMC treatment. Ferroptosis is an iron-dependent cell death process, which is accompanied by iron accumulation. Our previous study reported an important role of FECH, an enzyme inserts ferrous ion into PPIX, in ferroptosis, and showed that the inhibition of FECH by DMC led to iron accumulation in cancer cells. In this study, we found that the expression level of FECH increased in senescent cells, which may explain the sensitivity of DMC-induced ferroptosis in senescent cells. Senescent cells are associated with impaired ferritinophagy and ferroptosis. Interestingly, in our present study, we found that DMC could induce ferritinophagy, which may underlie DMC-induced ferroptosis in senescent cells.
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs