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Aging affects the intestinal stem cells ability to regenerate, stem cells are the source for new intestinal cells, the decline can make it more difficult to recover from gastrointestinal infections or other conditions that affect the intestine.
Age-related loss of stem cell function can be reversed by a 24-hour fast, according to a new study from MIT biologists. The researchers found that fasting dramatically improves stem cells’ ability to regenerate, in aged and young mice. In fasting mice, cells begin breaking down fatty acids instead of glucose, a change that stimulates the stem cells to become more regenerative.
The researchers found that they could also boost regeneration with a molecule that activates the same metabolic switch. Such an intervention could potentially help older people recovering from GI infections or cancer patients undergoing chemotherapy.
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. Fasting induces a metabolic switch in the intestinal stem cells, from utilizing carbohydrates to burning fat.
Switching these cells to fatty acid oxidation enhanced their function significantly. Pharmacological targeting of this pathway may provide a therapeutic opportunity to improve tissue homeostasis in age-associated pathologies. Low caloric intake is linked with enhanced longevity in humans and other organisms. Intestinal stem cells are responsible for maintaining the lining of the intestine, which typically renews itself every five days.
When an injury or infection occurs, stem cells are key to repairing any damage. As people age, the regenerative abilities of these intestinal stem cells decline, so it takes longer for the intestine to recover. 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.
During aging, intestinal stem function declines, which impairs the ability of the intestine to repair itself after damage, after mice fasted for 24 hours, the researchers removed intestinal stem cells and grew them in a culture dish, allowing them to determine whether the cells can give rise to “mini-intestines”-organoids.
The researchers found that stem cells from the fasting mice doubled their regenerative capacity.
Sequencing the messenger RNA of stem cells from the mice that fasted, revealed that fasting induces cells to switch from their usual metabolism, which burns carbohydrates such as sugars, to metabolizing fatty acids. This switch occurs through the activation of transcription factors- PPARs, which turn on many genes that are involved in metabolizing fatty acids.
The researchers found that if they turned off this pathway, fasting could no longer boost regeneration. Treating mice with a molecule that mimics the effects of PPARs could produce effects of fasting, activating one metabolic pathway is sufficient to reverse certain age phenotypes.
The findings show that drug treatment could stimulate regeneration without requiring patients to fast. Cancer patients who are receiving chemotherapy, which often harms intestinal cells can benefit from this. Older people who experience intestinal infections or other gastrointestinal disorders that can damage the lining of the intestine can also benefit from this.
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