Low-calorie diets and intermittent fasting have been shown to have numerous health benefits: They can delay the onset of some age-related diseases and lengthen lifespan, not only in humans but many other organisms.
Many complex mechanisms underlie this phenomenon. Previous work from MIT has shown that one way fasting exerts its beneficial effects is by boosting the regenerative abilities of intestinal stem cells, which helps the intestine recover from injuries or inflammation.
In a study of mice, MIT researchers have now identified the pathway that enables this enhanced regeneration, which is activated once the mice begin "refeeding" after the fast. They also found a downside to this regeneration: When cancerous mutations occurred during the regenerative period, the mice were more likely to develop early-stage intestinal tumors.
"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 MIT associate professor of biology, a member of MIT's Koch Institute for Integrative Cancer Research, and the senior author of the new study.
Yilmaz adds that further studies are needed before forming any conclusion as to whether fasting has a similar effect in humans.
"We still have a lot to learn, but it is interesting that being in either the state of fasting or refeeding when exposure to mutagen occurs can have a profound impact on the likelihood of developing a cancer in these well-defined mouse models," he says.
MIT postdocs Shinya Imada and Saleh Khawaled are the lead authors of the paper, which appears today in Nature.
Driving regeneration
For several years, Yilmaz's lab has been investigating how fasting and low-calorie diets affect intestinal health. In a 2018 study, his team reported that during a fast, intestinal stem cells begin to use lipids as an energy source, instead of carbohydrates. They also showed that fasting led to a significant boost in stem cells'…
Anne Trafton