In addition, the researchers found that the regeneration was due in part to activation of a cellular signaling pathway known as mTOR, which causes cells to produce more protein; this protein synthesis is essential for stem cells to proliferate. And they showed that mTOR activation led to production of large quantities of polyamines, small molecules that help cells grow and divide.
Another finding, though, was that if a cancer-causing gene was turned on during the refeeding stage, the mice were much more likely to develop precancerous polyps than if the gene was turned on during the fast. Cancer-linked mutations that occurred during refeeding were also much more likely to produce polyps than mutations that occurred in mice that did not undergo the cycle of fasting and refeeding. “Having more stem-cell activity is good for regeneration, but too much of a good thing over time can have less favorable consequences,” says Omer Yilmaz, an associate professor of biology and the senior author of the study.
The effects of fasting are much more complex in humans than in mice, Yilmaz says, but the work does suggest that “if you’re unlucky and you’re refeeding after a fasting, and you get exposed to a mutagen, like a charred steak or something, you might actually be increasing your chances of developing a lesion that can go on to give rise to cancer.”
Still, Yilmaz says the regenerative benefits of fasting could be significant for people who undergo radiation treatment, which can damage the intestinal lining, or for those with other types of intestinal injury. His lab is now studying whether polyamine supplements could help stimulate this kind of regeneration, without the need to fast.