Balancing Diet-Responsive Signaling Determines Stem Cell Lifespan

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.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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