Many studies have shown that strict and low-calorie diets can be the key to a healthier and longer life. But why is this so? A new study examining the effects of fasting in mice suggests that 24 hours of calorie restriction would tip a metabolic switch, which can stimulate regeneration of stem cells in the gut.
The older we get, the less our intestinal stem cells manage to regenerate. They are, however, very important to help us maintain healthy tissue and fight the disease. What if fasting for only 24 hours allowed us to reverse the trend a little? “Fasting has many effects in the gut: it can stimulate cell regeneration, but also help fight some diseases that affect the gut, such as infections or cancers,” says Omer Yilmaz, a biologist at MIT. “This study provides evidence that fasting induces a metabolic shift in intestinal stem cells from the use of carbohydrates to burning fat.”
Intestinal stem cells, which researchers describe as the “draft horses of the gut,” usually renew the intestinal lining in about five days – but it is possible to accelerate this renewal. Scientists explain that they had cultured intestinal stem cells from mice that had fasted for 24 hours, in order to grow masses of cells called organoids, a kind of “mini-intestines”. They then observed that the regeneration capacity of fasting mouse stem cells was twice that of fasting mice.
“It was obvious that fasting had a huge effect on the ability of intestinal crypts to form more organoids, which is due to stem cells,” says team member Maria Mihaylova. “We observed the same phenomenon in young mice and old mice, and we really wanted to understand the molecular mechanisms involved.”
To find out, teams sequenced fasting mouse stem cell RNA and found that fasting activated transcription factors called peroxisome proliferator activated receptors (or PPARs) that activate the genes involved in the metabolism of fatty acids. In this case, this activation has caused the cells to break down fatty acids instead of glucose, while at the same time increasing the cells’ ability to regenerate. By blocking the activation of the PPAR, the little “Regenerative boost” ended.
Researchers will need additional studies to fully understand the magnitude of this metabolic shift. It remains to be seen whether these same results could be observed in humans. However, these studies demonstrate once again that nutrition and metabolism have profound effects on cell behavior.