Intestinal stem cells are crucial for tissue repair and regeneration, and their decline as we age means that it becomes harder to recover from gastrointestinal conditions and infections.
The researchers, who were led by a team from Massachusetts Institute of Technology (MIT) in Boston, discovered that fasting for 24 hours boosted regeneration of gut stem cells in younger and older mice.
They found that fasting exerted this effect by means of a metabolic switch that causes cells to break down fatty acids instead of carbohydrates such as glucose.
They also discovered a molecule that can activate the same switch â€” a finding that might lead to drugs that boost older people’s recovery from gastrointestinal infections or chemotherapy.
You can read a report on the study in a paper that is now published in the journal Cell Stem Cell.
Stem cells are immature cells that have remarkable properties. For instance, they can replicate almost indefinitely and develop into virtually any type of cell in the body, forming an essential source of new cells for growth and repair in many tissues.
In the gut, they maintain and repair tissue lining, which “renews itself” about every 5 days.
In reference to this, co-senior study author Ă–mer H. Yilmaz â€” an assistant professor of biology at MIT â€” describes intestinal stem cells as the “workhorses of the intestine.”
“[D]uring aging,” he notes, “intestinal stem [cell] function declines, which impairs the ability of the intestine to repair itself after damage.”
In their study paper, Yilmaz and his colleagues explain that diet is known to have a “profound effect” on the ability of tissue to regenerate itself.
There is also evidence that intermittent fasting can benefit health and age-related decline in tissue function.
This spurred the researchers to study how short-term fasting might impact tissue regeneration at the molecular level, particularly through its influence on stem cells.
They removed intestinal stem cells from young and aged mice that had fasted for 24 hours and cultured them in the laboratory.
They found that fasting had a very strong effect on the stem cells’ capacity for regeneration, spurring them to form “organoids,” rather like “mini-intestines.”
They saw this happen in cultured cells taken from both the young and the aged fasting mice.
Additional investigation at the molecular level revealed that fasting made the stem cells switch from metabolizing carbohydrates, such as glucose, to metabolizing fatty acids.
The switch is in a pathway that is controlled by a group of molecules that regulate gene expression, called peroxisome proliferator-activated receptors (PPARs). PPARs control several pathways that trigger cells to break down fatty acids.
When the scientists turned off the metabolic switch, they found that fasting no longer boosted intestinal stem cell regeneration.
A final experiment showed that it was possible to “mimic” the effect of fasting on the switch with a molecule that behaves like a PPAR.
This last finding suggests that it might be possible to activate intestinal tissue regeneration and repair without fasting, which many people find very difficult.
The researchers suggest that such a treatment might help individuals having chemotherapy, which, in many cases, damages the lining of the gut.
It might also help older people to recover more quickly from intestinal conditions and infections.
The researchers are also going to further explore the molecular mechanisms at work when the metabolic switch induces gut stem cells to increase their regenerative powers.
They also want to discover whether fasting has a similar effect on stem cells in other tissues.
“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.”
Ă–mer H. Yilmaz