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

Liver aging is associated with age-related histopathological and functional changes that significantly enhance the risk of numerous diseases or disorders developing in elderly populations. 6-Bromoindirubin-3′-oxime (6BIO), a potent inhibitor of glycogen synthase kinase-3 (GSK-3), has been implicated in various age-related diseases and processes, such as tumorigenesis, neurodegeneration, and diabetes. Recent studies have also revealed that 6BIO increases autophagy in yeast, mammalian cell lines, and dopaminergic neurons, which is one of the classical mechanisms strongly associated with liver aging. However, the impact or the mechanism of action of 6BIO in liver remains entirely unknown. Here, we find that 6BIO reduces oxidative stress, improves lipid metabolism, enhances autophagy, and significantly retards liver aging via modulating the GSK-3β pathway and mTOR pathway. Our findings suggest that 6BIO could be a potential agent to protect the liver in the field of anti-aging pharmacology.