6-Bromoindirubin-3 ′-Oxime (6BIO) Suppresses the mTOR Pathway, Promotes Autophagy, and Exerts Anti-aging Effects in Rodent Liver

In this study, we aimed to investigate the anti-aging effect, and molecular mechanism, of the novel anti-aging drug 6BIO on naturally aged mouse liver. Rapamycin, a well-known promising anti-aging drug that delays aging through mTOR-dependent autophagy (Zhou and Ye, 2018), was used as the positive control in the study. To our knowledge, this is the first study to demonstrate the effects of 6BIO treatment in models of natural aging. Our results indicated that 6BIO ameliorates the decline of liver function with age, including lipid metabolism disorder, and attenuates hepatocyte senescence in aged mice, as revealed by alterations in the cellular senescence markers. Also, we investigated the possible molecular anti-aging mechanisms of action, and respective signaling pathways, of 6BIO, some of which relate to age-associated changes, too, such as the changes in canonical p53/p21 and p16/pRB signaling pathways, oxidative stress, inflammation, autophagy, the GSK-3β signaling pathway, and the mTOR signaling pathway. Lipid and glucose metabolic disorders are common manifestations in aging models, thereby correlating closely with a decline in liver function. One characteristic of hepatic senescence is fat deposition (He et al., 2018). Our results showed an increase in fat deposition and disordered lipid metabolism during the aging process of the aged mice. In the 6BIO treatment group, the serum levels of TC and TG decreased, thereby indicating an amelioration of lipid ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research