Abstract
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.
Highlights
Aging is broadly defined as the time-dependent functional decline of a living organism, usually accompanied by the age-related gradual accumulation of damaged biomolecules, which eventually results in the disruption of cellular homeodynamics
Our results suggested that 6BIO treatment significantly ameliorates age-related changes, including reducing oxidative stress, improving lipid metabolism, and enhancing autophagy through the mammalian target of rapamycin (mTOR) and GSK-3β pathways
Aging is accompanied by increased levels of pro-inflammatory cytokines such as IL-6; this appears to be linked to the immunosenescence process
Summary
Aging is broadly defined as the time-dependent functional decline of a living organism, usually accompanied by the age-related gradual accumulation of damaged biomolecules, which eventually results in the disruption of cellular homeodynamics. This deterioration is the primary risk factor for major human pathologies, including neurodegenerative diseases cancer and diabetes (Lopez-Otin et al, 2013). 6-Bromoindirubin-3′-oxime (6BIO) is a selective inhibitor of glycogen synthase kinase-3α/β (GSK-3α/β) derived from Tyrian purple indirubin (Zhao et al, 2017). It is reported as a promising novel agent for therapeutic. This research implies that 6BIO diminishes phosphorylation of ribosomal protein S6 kinase B1 (RPS6KB1) and eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1), which are downstream targets of the mammalian target of rapamycin (mTOR) (Suresh et al, 2017)
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