Aging Stem Cells Provide Cancer Clues

Researchers have stumbled across a pathway in stem cells that gets turned off with age, and provides an interesting insight into tumour formation. 

What to do with an old stem cell

You stem cells are crucial for replenishing your entire body, but they undergo a number of changes as you age. These changes are often detrimental, leaving you with a diminishing ability to restore yourself through the years. 

It is thought some of these changes could be reversed, but we need to know exactly what’s going on as the years progress first. A team has now identified that stem cells lose sensitivity to a key signalling molecule called Notch. This is one of the major players in signalling, and is essential for embryonic development. 

A growth checkpoint

In studying Drosophila, the fruit fly, they discovered that in larval stage when development of neurons is ongoing, stem cells rapidly proliferate through this Notch signalling pathway. However, they found if the balance was upset and too much Notch was introduced, stem cells went rampant and started forming cancers. Under normal conditions this is unlikely, but when a mutation was introduced that raised Notch levels, it led to tumour formation in these flies. In humans, adult T-Cell leukemia has links to de-regulated Notch signalling. 

“Stem cells have a really tough job because they have to divide to make the millions of neurons in our brain. If they don’t divide enough, it results in microcephaly or other small brain diseases, but if they divide too much, they make tumors. They have to stay right on that boundary of dividing to make neurons but not dividing excessively and forming a tumor. It’s really walking a tightrope.”

Old stem cells fail to respond to Notch

When the researchers observed these stem cell populations aging following development, they discovered they began failing to respond to Notch levels. While this meant they had increased protection from cancer formation, as higher Notch levels failed to produce cancer in older stem cell populations, it also meant they weren’t dividing effectively. 

“If we can identify the stem cells that are relied upon during development, maybe we could find a way to use them later to recreate conditions that might be therapeutic. If you do it incorrectly, you risk over-proliferation and the development of masses—and cancer.”

A fine line

It seems likely that considering the array of damage and problems that aging brings with it, this loss of a Notch response in stem cells is an additional protective mechanism against cancer. However, it may be that modulating this factor could also re-open the door to division – and therefore better repair. If this is a ‘stop’ signal for aging stem cells, then tweaking the signal could jump start youthful activity once more. Further study could build on the findings, enabling repair of old stem cells without causing increased cancer incidence. 

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