Low-Calorie Diet Enhances Intestinal Regeneration After Injury

Dramatic calorie restriction—diets reduced by 40 percent of a normal calorie total—have long been known to extend health span, the duration of disease-free aging in animal studies and even to extend lifespan in most animal species examined. Further research has shown that animals fed restricted-calorie diets are also better able to regenerate numerous tissues after injury.

A lingering question has been how these benefits are mediated. A new study led by University of Pennsylvania researchers pinpoints the cell responsible for these improved regenerative abilities in the intestines. According to the scientists’ work, when a calorie-restricted mouse is subjected to radiation, a particular type of stem cell in the intestines, known as reserve stem cells, can survive and quickly rebuild intestinal tissues. The findings align with observations by oncologists that short-term fasting prior to chemotherapy can mitigate the severity of gastrointestinal destruction.

“The moral of the story is you definitely don’t want to be eating a bunch of cheeseburgers before you get chemotherapy or radiation,” said Christopher Lengner, an associate professor in Penn’s School of Veterinary Medicine. “Our work is pointing to reserve stem cells as being the critical players in conferring the benefits of intestinal-tissue regeneration after these types of insults.”

Dr. Lengner collaborated on the work with lead author Maryam Yousefi, a graduate student in the cell and molecular biology program at Penn and a Howard Hughes Medical Institute International Student Fellow, and other colleagues from Penn and China Agricultural University. Their work appears in the journal Stem Cell Reports.

Years of research have demonstrated that existing on a calorie restricted diet, while seemingly unpleasant, can boost healthy lifespan, reducing the risk of heart attack, diabetes and other age-related conditions. Other, more recent work has shown that calorie-restricted animals regenerate tissue more effectively following injury.

In future work, the researchers hope to drill down deeper, looking beyond nutrient signaling to see what type of signaling molecules can modulate the activation of reserve stem cells.