Study the regulation of HSC maintenance and aging by longevity pathways
2013 new Scholar Award in aging
A number of genetic studies in lower organisms have identified several pathways as key regulators of lifespan, stress response, and reproductive fitness, including the Insulin-PI3K-AKT-FoxO, target of rapamycin (TOR), and LKB1-AMPK pathways. All these longevity pathways are conserved in mammals. However, it is not clear whether or how these longevity pathways regulate aging and age-related diseases in mammals. Some aspects of mammalian aging result from an age-associated functional decline of adult stem cells, the type of cells which act as a repair system for our bodies and replenish adult tissues, particularly under stress or aging conditions. How these longevity pathways regulate adult stem cell homeostasis and aging in mammals still remains largely unknown. Utilizing sophisticated genetically engineered mouse models, we will study how these conserved longevity pathways regulate the homeostasis and aging of adult stem cells, including hematopoietic stem cells, the adult stem cells that sustain all blood lineages throughout life. We hope that our proposed studies will enable the rational targeting of the longevity pathways in the treatment of age-related diseases.