A low-calorie diet can enhance regeneration after intestinal damage.

Animal studies have long been known to limit calories, reducing calories in a normal diet by 40% to extend the healthy life of animals (without disease) and even most of the animals under study.
now a further study shows that many tissues in animals with a low-calorie diet are also more able to regenerate after injury.
an outstanding question is how these benefits are regulated.
a new study led by the University of Pennsylvania in the United States has found these cells that improve the ability of the intestines to regenerate.
studies show that when mice with limited dietary calories are exposed to radiation, a particular stem cell (reserve stem cell) in their intestines can survive and quickly rebuild intestinal tissue.
these findings are consistent with the findings of oncologists that short-term fasting prior to chemotherapy can relieve the severity of gastrointestinal damage. "This result suggests that we shouldn't eat until chemotherapy or radiotherapy," said Christopher Lengner, an assistant professor at the University of Pennsylvania's School of Veterinary Medicine at
.
reserve stem cells are crucial to the ability to regenerate the intestines after damage to intestinal tissue.
the first author of the study is Maryam Yousefi, a graduate student in the Cell and Molecular Biology Program at the University of Pennsylvania and an international student researcher at the Howard Hughes Institute of Medicine, along with other researchers from the University of Pennsylvania and the Agricultural University of China.
the study, published recently in the journal Stem Cell Reports.
years of research have shown that while limiting calories in your diet may seem unpleasant, doing so does extend a healthy life and reduce the risk of heart disease, diabetes and other geriatric diseases. other recent studies
have shown that heat-restricted animals have more ability to regenerate after their tissues are injured. "The benefits of heat restriction are indisputable at this point, and the results are clear," said
Lengner.
but there are a variety of cellular and molecular basis questions about these benefits.
" one theory is that heat restriction can slow down the degradation associated with aging and achieve more effective tissue function by affecting the integrity and activity of adult stem cells.
adult stem cells are precursor cells that are present in specific tissues and cause diversity in the cell types that make up the tissue.
In past studies, Lengner's lab has studied how specific stem cells in the gut can fight DNA damage.
researchers speculate that limiting heat may somehow act on these stem cells, enhancing their ability to resist damage.
recent research focused on the effects of calorie restriction on active intestinal stem cells.
These active intestinal stem cells, which bear the burden of daily tissue transformation and are also the underburdened of intestinal function, are also highly susceptible to DNA damage, such as radiation-induced damage, so they are less likely to enhance tissue regeneration in calorie restrictions.
Lengner's team did not focus on these active stem cells, but studied another type of intestinal stem cell, the stockpile dating stem cells.
Lengner and other research teams have found in the past that these stockpiled stem cells are often dormant and not affected by chemotherapy and radiotherapy.
these reserve stem cells "wake up" and repair tissue when active cells are killed by serious injury.
to test this hypothesis, the scientists studied the reaction of the mice's intestinal stem cell subgroups to radiation when they were limited in heat.
left: Mice are exposed to radiation after an unlimited diet, and their intestinal cells (red) have limited regenerative capacity.
right: Mice adopted a low-calorie restricted diet, and their intestinal tissue regenerative capacity was significantly increased.
image source: University of Pennsylvania researchers limited calories to normal levels of 40 percent in the diet of mice, and they observed a five-fold expansion of the reserve of intestinal stem cells.
paradoxically, the cells are dividing less frequently, and the researchers hope to continue to focus on the issue in subsequent studies.
the team selectively removed the reserve stem cells from these calorie-restricted mice, losing half of their intestinal tissue regenerative capacity, suggesting that these cells play edire in the benefits of calorie-restricted conditions. "There's very little of these stockpiled stem cells," said
Lengner.
For the average animal, the proportion of stockpiled stem cells in intestinal epithelial cells is no more than 50 percent, a slightly higher figure for animals with limited diet calories.
usually, tissues can tolerate these losses without damage because there are active stem cells in the tissue, but when animals are injured, their regenerative capacity is reduced, and when the heat-restricted animals are removed from the reserve stem cells, their tissue regenerative capacity is reduced. "To understand how these cells act, the researchers compared the open genes of normal mice with calorie-restricted mice,"
. "Obviously, these stockpiled stem cells are very important for the benefits of calorie limitation, and they inhibit multiple signaling pathways that are adjusted by the protein complex mTOR, the most famous nutritional-sensing complex," said
Lengner. researchers studying other tissues
found that activating mTOR awakens dormant cells, a necessary step in tissue regeneration.
in the study, researchers found that stockpiled stem cells had lower mTOR activity and lower activity in the event of calorie restriction. low activity
mTOR was associated with resistance to damage.
However, in order to regenerate after the damage occurs, these cells will again need mTOR. "It was strange that we found that after tissue injuries, heat-restricted mice were actually more able to activate mTOR," said
Lengner.
, although mTOR is initially inhibited, it is easier to activate after the injury occurs.
this is a mechanism that we do not fully understand.
" the team, led by Yousefi, conducted experiments using leucine (an amino acid that activates mTOR) and rapamycin (a drug that inhibits mTOR) to demonstrate that mTOR works in these stockpiled stem cells and regulates their activity.
the proliferation of reserve stem cells exposed to leucine, while the reserve stem cells that are exposed to rapamycin are inhibited.
pretreatment of mice using leucine made their stem cells more radiation-sensitive and less resilient after radiation damage, while the reserve stem cells in mice pretreated with rapamycin were more dormant.
Lengner cautions, however, that rapamycin is no substitute for heat restriction because it persists and continues to inhibit mTOR even after damage, affecting the ability to store stem cell activity and regenerate intestinal tissue. "Rapamycin does a different role than heat restriction,"
said.
calorie limit scanns mTOR, but recovers easily after damage.
, which is not the case, continues to inhibit mTOR even after damage, thereby impairing regeneration.
so far, there is no magic drug that can simulate calorie limiting.
If you want these benefits, cut back on calorie intake.
"In future studies, researchers hope to explore deeper, focusing on nutritional signals, and determining which types of signal molecules regulate the activity of stockpiled stem cells."
Source: China Biotechnology Network.