Old age can hit animals in the gut. That’s where elderly fruit flies experience a signaling imbalance that disrupts renewal of the gut wall, new research shows. The discovery could help scientists understand why the body’s organs malfunction in old age, and why intestinal cancer is so common among older people.

Normally, “adult” stem cells in the intestinal wall churn out a steady stream of new cells to replenish the lining. A push-pull balance between two signaling pathways controls the growth and maturation of these stem cells, researchers report in the Oct. 9 Cell Stem Cell.

“In older animals, this balance seems to be breaking down so you get this abnormal cell growth in the gut, which could be considered a precursor to cancer,” says Heinrich Jasper, a geneticist who studies aging at the University of Rochester in New York. “The tissue becomes very sensitive to cancer-causing mutations.”

Even if cancer doesn’t arise, altering the renewal of the gut lining could play a role in the age-related decline of the organ, Jasper suggests. “Aging as such seems to be a process where this balance is lost.”

The imbalance appears to be triggered by stress — not psychological stress, but the chemical stresses put on cells by free radicals or by chronic inflammation, both of which get worse as an animal ages. Cells in the gut lining respond to this stress by activating a protective gene called Jun N-terminal kinase, or JNK, which is part of a signaling pathway that spurs intestinal stem cells to grow and divide. In response, another signaling pathway — called the Delta/Notch pathway — ramps up to try to keep that growth in check. But too much Delta/Notch can also derail the natural conversion of these stem cells into mature gut cells, causing an abnormal accumulation of halfway converted cells.

“I think it’s a phenomenally interesting result,” comments Norman Sharpless, a cancer and stem cell expert at the University of North Carolina at Chapel Hill. In these experiments, the malfunctioning of adult stem cells in old age “is very similar to what happens in certain human stem cell populations.”

Scientists have speculated that the decline of the body’s organs in old age is partially due to changes in those organ’s stem cells, but the idea is still relatively new.

“I think in a broader sense [this research] brings up the idea of stem cells and aging,” comments Heidi Tissenbaum, a molecular geneticist at the University of Massachusetts Medical School in Worcester, Mass. While the link to aging is more speculative, the data make a stronger case that this signaling imbalance could be involved in intestinal cancer, she says.

In humans, JNK and Delta/Notch signaling also regulate tissue-renewal by adult stem cells.

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Found in: Genes & Cells