PHILADELPHIA (September 6, 2018) – Researchers at Fox Chase Cancer Center have demonstrated for the first time how two diet-dependent signaling pathways fit together to control the health and lifespan of stem cells. The paper appears in the journal Developmental Cell.
Tanu Singh, PhD, a former graduate student, and Alana O’Reilly, PhD, an associate professor in the Department of Molecular Therapeutics at Fox Chase, studied the relationship between the insulin pathway and the cholesterol-activated Hedgehog signaling pathway in stem cells from the Drosophila ovary, which are similar to stem cells in human intestines and bone marrow. Their work shows that manipulating the balance between these pathways can influence how long stem cells live and how long they can reproduce. They also identified the precise balancing of these diet-dependent signals to yield optimal lifespan and productivity of the cells.
“We know which foods are unhealthy or healthy in general, but the details of how different nutrients influence cells is not well understood,” said O’Reilly. “In this study we showed that shifting the balance between Hedgehog and Insulin signaling controls a molecular switch that activates or delays autophagy, the cellular degradation and recycling process.”
When Hedgehog signaling is high and Insulin signaling is low, as is the case in middle aged and older flies, autophagy occurs. Restoration of insulin signaling in aged flies reduces autophagy, increases stem cell lifespan, and enhances the fertile lifetime of the fly. The researchers hypothesize that a similar mechanistic balance between the two signals likely exists in other organisms.
“Understanding how this mechanism might regulate stem cells in humans will have important implications for understanding aging, fertility, and the development of diseases caused by altered stem cell function, including cancer,” O’Reilly said.
The lab’s next step will be to study the effects individual nutrients have on the balance of signaling between the two pathways.
This work was supported by R01 grant HD065800 from the Eunice Kennedy Shriver Institute for Child Health and Human Development and Cancer Center Support Grant CA06927, both from the National Institutes of Health.