Topic Overview:
Mammalian aging is thought to be regulated by a combination of genetic and environmental factors, but the mechanisms by which they act remain largely unknown. Liu studies the relationship between aging and the Wnt signaling pathway, an essential regulator of stem cell self-renewal, using a well established, accelerated aging mouse model. The anti-aging hormone klotho normally binds to Wnt proteins, inhibiting their endogenous signaling activity in mice. In klotho-deficient mice, however, augmented Wnt signaling causes depletion of adult stem cells and a decline in the regenerative potential of tissues and organs.

Recent genome-wide association and epidemiological studies have linked the Wnt signaling pathway to metabolic disorders in humans. Liu will discuss the pathway’s involvement in regulating systemic and cellular energy metabolism. His recent results suggest that the Wnt pathway plays an important role in hepatic metabolism; he showed that β-catenin, a downstream Wnt mediator, alters glucose concentrations and modulates hepatic insulin signaling by interacting with the Foxo1 transcription factor to regulate gluconeogenic gene expression.

Liu has also made recent progress in deciphering the role of Wnt signaling in proliferating stem and progenitor cell energy metabolism. He will describe how dysregulation of this process could contribute to aging and the pathogenesis of age-related diseases.