Researchers have found that AGEs, chemicals in cooked foods, can increase hunger and affect health. AGEs are caused by the Maillard reaction and can enhance the appeal of food but can also cause health problems. Research on worms shows that AGEs increase worm consumption and shorten their lifespan, underscoring the importance of healthier food choices.

Buck researchers have discovered a mechanism that explains why eating delicious but unhealthy foods leaves us craving more.

There are many reasons why people overeat and become overweight. The fact that delicious, high-calorie foods are often available anytime and anywhere doesn't help. Buck researchers have determined for the first time why certain chemicals in cooked or processed foods, called advanced glycation end products, or AGEs, increase hunger and test our willpower or ability to make healthy choices when it comes to food.

"This research in C. elegans has huge implications for humans' dietary choices and tendency to overeat certain foods," said Dr. Pankaj Kapahi, senior author of the study and a professor at Buck University. "Modern processed diets rich in AGEs are tempting, but we know very little about their long-term effects on human health." The research results were recently published in the journal eLife.

"Humans have evolved mechanisms that encourage us to eat as much as possible when food is plentiful. We store excess calories as fat to get through periods of fasting," explained Munyesh-Mutayan Shanmugam, Ph.D., a postdoctoral researcher in Kapahi's lab and first author of the study. "Natural selection favors genes that predispose us to eating palatable foods, especially foods with a higher sugar content. But what is it about the mechanisms that make it so difficult for us to say 'no' to them?"

AGEs are metabolic by-products produced when sugar combines with some proteins, lipids or nucleic acids. They are produced naturally when we metabolize sugars in our cells, but AGEs are also produced during baking, frying, and grilling, and are found in many processed foods. "The brown color produced during cooking, which makes food look and smell delicious, is the result of AGEs," Shanmugam said. Basically, we found that AGEs make food more appetizing and harder to resist. "

Maillard Reaction and Health Effects

The "browning" reaction that occurs when sugar and protein are heated is called the Maillard reaction, and it is loved by chefs. It forms hundreds of attractive AGEs.

But while the Maillard reaction's reputation is that it makes food delicious, the resulting chemicals can wreak all sorts of havoc on the human body. They cause inflammation and oxidative damage, leading to hardening of the arteries, hypertension, kidney disease, cancer and neurological diseases. Capahi, whose lab studies how nutrients influence health and disease, said the accumulation of these metabolic byproducts in multiple organs may be one of the main causes of aging in individual organs and throughout the body.

"Once advanced glycation products are formed, they cannot be detoxified," Shanmugam said. Just like toasted white bread turns brown, there is no way to reverse the process and make the bread turn white again. "Similarly, there is no way to reverse AGEs," he said, adding that the body's ability to clear AGEs declines with age, another link to age-related diseases.

Research results and dietary implications

Even the little bugs in Kapashi's lab can't escape the temptation and damage of AGEs. The researchers observed that these chemicals increased the worms' appetite, in addition to causing disease and shortened lifespan. Researchers want to understand how AGEs trigger overeating.

To uncover the biochemical signaling pathways that cause overeating in normal, healthy worms, the researchers purified some well-studied AGEs and found that two of them increased food intake. They further studied one of the compounds to find out the signaling mechanism. They found that a specific mutation (called glod-4) increased food intake mediated by a specific AGE (called MG-H1). Further analysis revealed that a tyramine-dependent pathway was the culprit.

Their study is the first to identify signaling pathways mediated by specific AGE molecules to enhance food intake and neurodegeneration. They also found that even though the mutant worms were unable to process naturally occurring AGEs, their lifespan was shortened by about 25-30%. This work is being extended to mice, where researchers will study the link between AGEs and fat metabolism.

"Understanding this signaling pathway may help us understand overeating as a result of modern AGE-rich diets," Kapahi said. "Our study highlights that the accumulation of AGEs is associated with disease, including obesity and neurodegeneration. We believe that, overall, limiting the accumulation of AGEs is associated with a global increase in obesity and other age-related diseases. Understanding this signaling pathway may help us understand overeating as a result of modern AGE-rich diets."

The message Shanmugam takes away from his work is profound. "We don't control our food intake; instead, the food tries to control us," he said. "

Because of this study and the lab's previous research, Shanmugam and Kapahi have changed their minds about their diet. They all practice intermittent fasting, which gives the body a chance to use fat instead of sugar. There are some simple things anyone can do to reduce the burden of AGEs in the body, Kapahi said, including eating whole grains (fiber helps maintain stable blood sugar levels), cooking with moist heat rather than dry heat (i.e., steaming rather than frying or roasting), and adding acid when cooking foods, which can slow the reactions that cause AGEs to form.

"We are naturally attracted to delicious foods, but we can be more mindful that we do have the ability to make healthy choices when we eat," Shanmugam said.