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The Regenerative Ability Of Stem Cells Is Boosted By Fasting

By Karen Foster | Prevent Disease

As people age, their intestinal stem cells begin to lose their ability to regenerate. These stem cells are the source for all new intestinal cells, so this decline can make it more difficult to recover from gastrointestinal infections or other conditions that affect the intestine. This 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.

Intermittent fasting allows the body to use fat as it’s primary source of energy instead of sugar and there are many benefits.

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, the researchers say.

“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,” says Omer Yilmaz, an MIT assistant professor of biology, a member of the Koch Institute for Integrative Cancer Research, and one of the senior authors of the study. “Understanding how fasting improves overall health, including the role of adult stem cells in intestinal regeneration, in repair, and in aging, is a fundamental interest of my laboratory.”

David Sabatini, an MIT professor of biology and member of the Whitehead Institute for Biomedical Research and the Koch Institute, is also a senior author of the paper, which appears in the May 3 issue of Cell Stem Cell.

“This study provided evidence that fasting induces a metabolic switch in the intestinal stem cells, from utilizing carbohydrates to burning fat,” Sabatini says. “Interestingly, 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.”

The paper’s lead authors are Whitehead Institute postdoc Maria Mihaylova and Koch Institute postdoc Chia-Wei Cheng.

Boosting Regeneration

For many decades, scientists have known that low caloric intake is linked with enhanced longevity in humans and other organisms. Yilmaz and his colleagues were interested in exploring how fasting exerts its effects at the molecular level, specifically in the intestine.

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. Notably, during aging, intestinal stem function declines, which impairs the ability of the intestine to repair itself after damage,” Yilmaz says. “In this line of investigation, we focused on understanding how a 24-hour fast enhances the function of young and old intestinal stem cells.”

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” known as organoids.

The researchers found that stem cells from the fasting mice doubled their regenerative capacity.

“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,” Mihaylova says. “This was something that we saw in both the young mice and the aged mice, and we really wanted to understand the molecular mechanisms driving this.”

Metabolic Switch

Further studies, including 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 called 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. They now plan to study how this metabolic switch provokes stem cells to enhance their regenerative abilities.

They also found that they could reproduce the beneficial effects of fasting by treating mice with a molecule that mimics the effects of PPARs. “That was also very surprising,” Cheng says. “Just activating one metabolic pathway is sufficient to reverse certain age phenotypes.”

Jared Rutter, a professor of biochemistry at the University of Utah School of Medicine, described the findings as “interesting and important.”

“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,” says Rutter, who was not involved in the research. “This work fits into a rapidly growing field that is demonstrating that nutrition and metabolism has profound effects on the behavior of cells and this can predispose for human disease.”

The findings suggest that drug treatment could stimulate regeneration without requiring patients to fast, which is difficult for most people. One group that could benefit from such treatment is cancer patients who are receiving chemotherapy, which often harms intestinal cells. It could also benefit older people who experience intestinal infections or other gastrointestinal disorders that can damage the lining of the intestine.

The researchers plan to explore the potential effectiveness of such treatments, and they also hope to study whether fasting affects regenerative abilities in stem cells in other types of tissue.

Read more great articles at Prevent Disease.




Study Shows One Diet Does NOT Fit All: The Best Diet for You Fits Your Genetics

By Karen Foster | Prevent Disease

Weight loss strategies are effective if they are customized to on an individual’s biomarkers to use personalized nutrition to help people achieve greater weight loss success. We can add one more thing to the list of traits affected by genetics: how our bodies respond to a particular diet.

Research with different genetics shows that one diet really doesn’t fit all, and what works for some may not be best for others, according to a Texas A&M study published in the journal Genetics.

When it comes to diet, focusing on successes rather than failures is always a recipe for progress.

Biologists have suspected for years that some kind of epigenetic inheritance occurs at the cellular level. The different kinds of cells in our bodies provide an example. Skin cells and brain cells have different forms and functions, despite having exactly the same DNA.

“Dietary advice, whether it comes from the United States government or some other organization, tends to be based on the theory that there is going to be one diet that will help everyone,” said David Threadgill, PhD, with the Texas A&M College of Medicine and College of Veterinary Medicine & Biomedical Sciences, senior author of the study. “In the face of the obesity epidemic, it seems like guidelines haven’t been effective.”

Threadgill thinks he knows why. The researchers used four different groups of animal models to look at how five diets affect health over a six-month period. The genetic differences within each group were almost non-existent, while the genetics between any two of the groups would translate to roughly the same as those of two unrelated people. The researchers chose the test diets to mirror those eaten by humans–an American-style diet (higher in fat and refined carbs, especially corn) and three that have gotten publicity as being ‘healthier’: Mediterranean (with wheat and red wine extract), Japanese (with rice and green tea extract) and ketogenic, or Atkins-like (high in fat and protein with very few carbs). The fifth diet was the control group who ate standard commercial chow.

Although some so-called healthy diets did work well for most individuals, one of the four genetic types did very poorly when eating the Japanese-like diet, for example. “The fourth strain, which performed just fine on all of the other diets, did terrible on this diet, with increased fat in the liver and markings of liver damage,” said William Barrington, lead author on the study and a recently graduated PhD student from the Threadgill lab.

A similar thing happened with the Atkins-like diet: two genetic types did well, and two did very badly. “One became very obese, with fatty livers and high cholesterol,” Barrington said. The other had a reduction in activity level and more body fat, but still remained lean. “This equates to what we call ‘skinny-fat’ in humans, in which someone looks to be a healthy weight but actually has a high percentage of body fat.”

“In humans, you see such a wide response to diets,” Barrington said. “We wanted to find out, in a controlled way, what was the effect of the genetics.” They measured physical signs, especially evidence of metabolic syndrome, which is a collection of signs of obesity-related problems, including high blood pressure and cholesterol, fatty liver and levels of blood sugar. They also studied any behavioral differences, from how much they moved around to how much they ate.

“I wanted to get the diets as close to popular human diets as possible,” Barrington said. “We matched fiber content and matched bioactive compounds thought to be important in disease.”

Perhaps as could be expected, both in earlier research and in anecdotal evidence in humans, the animal models tended not to do great on the American-style diet. A couple of the strains became very obese and had signs of metabolic syndrome. Other strains showed fewer negative effects, with one showing few changes except for having somewhat more fat in the liver. With the Mediterranean diet, there was a mix of effects. Some groups were healthy, while others experienced weight gain, although it was less severe than in the American diet. Interestingly, these effects held, even though the quantity of consumption was unlimited.

The results demonstrated that a diet that makes one individual lean and healthy might have the complete opposite effect on another. “My goal going into this study was to find the optimal diet,” Barrington said. “But really what we’re finding is that it depends very much on the genetics of the individual and there isn’t one diet that is best for everyone.”

The research team’s future work will focus on determining which genes are involved in the response to the diets. “One day, we’d love to develop a genetic test that could tell each person the best diet for their own genetic makeup,” Barrington said. “There might be a geographical difference based on what your ancestors ate, but we just don’t know enough to say for sure yet.”

Read more great articles at Prevent Disease.




1.3 Billion Tons of Food Wasted Every Year – Here’s Why and What We Can Do About It

By Karen Foster | Prevent Disease
Norbert Wilson who joined the Friedman School as a professor of food policy, has been investigating food waste, building on his past research on food choice, domestic hunger, food banking and the international trade of food products. What motivates people to spend good money on food they don’t intend to eat?

According to the United Nations’ Food and Agriculture Organization, a staggering 1.3 billion tons — is lost or wasted every year.

The impact of food waste is not just financial. Environmentally, food waste leads to an exagerrated use of chemicals such as fertilizers and pesticides; more fuel used for transportation; and more rotting food.

When Wilson turned his attention to issues related to food waste, he theorized that consumers buy food even when they’re aware they may not finish it. It’s a concept that anyone who has purchased a container of sour cream can understand–we buy it knowing we may toss the container with a hefty portion still clinging to the sides.

Wilson found a clue in 2013, when the Natural Resources Defense Council released a report showing that a substantial portion of America’s $160 billion food-waste problem could be traced to those “use by” and “sell by” dates on food containers. It turns out that many consumers, worried that food that has passed the date on its packaging is no longer worth eating, throw out plenty of perfectly good stuff. Could consumers be thinking about those labels as they buy the food?

To find out, Wilson devised an experiment that involved putting differently worded date labels on yogurt, cereal and salad greens. The labels used a variety of terms–“use by,” “best by,” “sell by” and “fresh by”–and included an expiration date. Wilson wanted to know whether certain language would result in people buying food with a greater expectation that they would waste some of it–what Wilson and his colleagues called the “willingness to waste.”

The 200 participants in the study were asked to examine food carrying the different labels and then say how much of each product they expected their household to consume. In nearly every case, the subjects’ answers indicated that they would be more willing to toss out food if it had the “use by” wording. The researchers theorized that may have been because “use by” implies that the food would no longer be safe to eat after that date.

The study found that date labels were influential even when it came to a food like boxed cereal, which is less vulnerable to spoilage. In fact, the willingness to waste was actually higher for cereal than it was for more perishable items like yogurt and bagged salad.

The cereal example also showed that the perception of a bargain can influence willingness to waste amounts. For instance, when participants in the study perceived that they were getting a better deal by buying a larger box of cereal (think Costco-size double boxes of Cheerios), they anticipated wasting more of it, even if the “use by” date was a year in the future.

“I was surprised by how strong a response they had to the cereal,” Wilson said, “and that people were willing to waste more when they saw the larger size.” The pitfall for consumers, he said, is that tossing more of the cereal may have canceled out the savings they thought they were getting.

The findings imply that the way foods are packaged can enable waste. Tweaking package sizes may keep consumers from buying more than they’ll eat. But one wide-reaching change would be to standardize date labels–currently unregulated at the federal level–so that they have a consistent meaning. “To move forward on reducing food waste,” Wilson said, “we will need collaborations between industry, consumer groups and the government to change labels.”

Lost and Tossed

“Loss” means food that doesn’t make it to market, while “waste” is the term for food that stores, restaurants and consumers toss. Loss is a greater concern in developing countries, accounting for 84 to 95 percent of the food that goes uneaten there. Waste is a bigger problem in higher-income countries, where about a third of uneaten food is simply squandered. Researchers see chances to fight both problems all along the supply chain.

FARMS
Harvests lost to poor storage and contamination. Farmers in low-income countries often can’t protect harvested crops from the elements and pests. Simple technologies, such as metal silos, could help. Some farmers cut their losses by 40 percent when they started using specialized plastic storage bags.

TRANSPORT
Food lost in packaging and handling. Without refrigeration or other ways to preserve them, foods wilt and spoil. Rough handling damages produce and hurries rot.

RETAIL
Food wasted by stores and restaurants. American stores toss about 43 billion pounds of food per year–from dented melons to discontinued cookies to ham that is nearing its “sell by” date. Restaurants cook abundant amounts and then dump what’s left at the end of the day.

CONSUMERS
Food wasted at home. What with buying too much, serving too much and not storing food properly, an average American family throws away up to $2,200 worth of food every year.

Read more great articles at Prevent Disease.