From my Department of I Did Not Know That, as people grow older, the stem cells in their intestines stop being able to regenerate themselves – grow new ones to replace dead ones. Since stem cells produce new gut cells, not having them slow down recovery from gastrointestinal tract infections, chemotherapy or other digestive disorders.
Intestinal stem cells maintain the lining of the intestine, which normally renews itself every five days. Stem cells are vital to mending damage caused by an injury or infection.
Biologists at MIT – the Massachusetts Institute of Technology in Cambridge – discovered that abstaining from food for a day reversed age-related stem cell dysfunction. A paper featured in the May 3, 2018, issue of Cell Stem Cell reported that tests on lab rats showed that fasting for 24 hours vastly increased stem cell regeneration in both old and young test subjects.
With no glucose (blood sugar) to process, the cells in the mice’s intestines started to break down fatty acids. This chemical transformation triggered elevated stem cell regrowth. The scientists also identified a molecule that could turn on the same metabolic switch.
Senior study author and MIT biology professor David Sabatini, a member of the Koch Institute for Integrative Cancer Research and the Whitehead Institute for Biomedical Research, talked about the importance of his team’s work:
“This study provided evidence that fasting induces a metabolic switch in the intestinal stem cells, from utilizing carbohydrates to burning fat. Interestingly, switching these cells to fatty acid oxidation enhanced their function significantly.”
Sabatini said that pharmaceutical companies could target this biological pathway to provide a therapeutic treatment to improve tissue homeostasis (stability while adjusting to conditions that are optimal for survival) in older people.
Omer Yilmaz is an Assistant Professor of biology at MIT, a member of the Koch Institute for Integrative Cancer Research, and a senior study author. He shared some of the health benefits of not eating for a day:
“Fasting has many effects in the intestine, which include boosting regeneration as well as potential uses in any type of ailment that impinges on the intestine, such as infections or cancers.”
Medical science acknowledged decades ago that a low-calorie diet is linked to longer life in humans and other organisms.
Yilmaz explained what his team wanted to determine:
“Intestinal stem cells are the workhorses of the intestine that give rise to more stem cells and to all of the various differentiated cell types of the intestine…In this line of investigation, we focused on understanding how a 24-hour fast enhances the function of young and old intestinal stem cells.”
The biologists removed intestinal stem cells from mice that had fasted for 24 hours and cultured them in a petri dish to see if the cells could produce organoids, a sort of “mini-intestine.” According to lead author and Whitehead Institute postdoctorate student Maria Mihaylova, these first findings led the researchers to explore the underlying molecular mechanism:
“It was very obvious that fasting had this really immense effect on the ability of intestinal crypts to form more organoids, which is stem-cell-driven.”
The molecular switch occurred transcription factors called PPARs were activated. PPARs trigger multiple genes involved in metabolizing fatty acids. The MIT scientists learned that turning off this biochemical pathway prevented fasting from increasing the stem cells’ regenerative rate.
The researchers then reproduced the beneficial effects of fasting by treating mice with a molecule that imitates the effects of PPARs.
Professor of biochemistry at the University of Utah School of Medicine Jared Rutter pointed out the significance of the MIT group’s experiments:
“This paper shows that fasting causes a metabolic change in the stem cells that reside in this organ and thereby changes their behavior to promote more cell division. In a beautiful set of experiments, the authors subvert the system by causing those metabolic changes without fasting and see similar effects.”
High praise indeed from one biologist to another. Rutter wasn’t finished, though:
“This work fits into a rapidly growing field that is demonstrating that nutrition and metabolism have profound effects on the behavior of cells and this can predispose for human disease.”
A molecular switching mechanism could boost intestinal stem cell regeneration in older patients without the need for fasting, something many people find difficult.