Researchers have made an intriguing discovery regarding the impact of chemicals known as advanced glycation end products (AGEs) found in cooked foods. While these chemicals enhance the appeal of food, they also increase hunger levels and have a negative impact on health. In a study conducted on worms, it was observed that AGEs led to increased consumption and decreased lifespan, highlighting the importance of making healthier food choices.
A team of researchers at Buck Institute for Research on Aging has uncovered a mechanism that may shed light on why we tend to crave more high-calorie, delicious yet unhealthy foods. People often overeat and become overweight for various reasons, and the widespread availability of flavorful high-calorie food only exacerbates the issue. For the first time, the researchers have identified the specific reason behind the hunger-inducing effects of AGEs, which are chemicals present in cooked or processed foods.
“This research, carried out on small nematode worms, holds significant implications for human dietary preferences and challenges in making healthy food choices,” said senior author Dr. Pankaj Kapahi, a professor at the Buck Institute. “Modern processed diets enriched with AGEs are tempting to eat, but our knowledge about the long-term consequences on health is limited.” The study was recently published in the journal eLife.
From an evolutionary perspective, humans have developed mechanisms that drive us to consume as much food as possible during times of abundance, storing excess calories as fat for survival during periods of scarcity. These mechanisms have favored our preference for flavorful foods, particularly those with higher sugar content. However, the researchers sought to understand the precise mechanism that makes it difficult to resist such foods.
AGEs are metabolic by-products that form when sugars react with proteins, lipids, or nucleic acids. While AGEs naturally occur during cellular sugar metabolism, they are also created during baking, frying, and grilling, and can be found in many processed foods. Dr. Muniesh Muthaiyan Shanmugam, lead author of the study, explains that the browning reaction that occurs during cooking, resulting from the Maillard reaction, is responsible for the formation of AGEs. These AGEs make food more appetizing and challenging to resist.
However, although the Maillard reaction contributes to the delectable taste of food, the resulting AGEs have detrimental effects on the body. They cause inflammation and oxidative damage, which contribute to the development of several health problems, including blood vessel stiffness, hypertension, kidney disease, cancer, and neurological disorders. The accumulation of these metabolic by-products in various organs is believed to be a major driver of aging. Dr. Kapahi’s lab focuses on understanding how nutrients affect health and disease.
A major concern is that once AGEs are formed, they cannot be detoxified. Just as toasted white bread cannot be turned back to its original color, AGEs cannot be reversed. Additionally, the body’s ability to clear AGEs diminishes with age, creating another connection to age-related diseases.
To investigate the mechanisms behind overeating induced by AGEs, the researchers conducted experiments using nematode worms. They found that these chemicals not only caused disease and decreased lifespan but also increased the worms’ appetite. The researchers aimed to uncover the specific biochemical signaling pathway responsible for this preferential overeating.
By purifying well-studied AGEs, the researchers identified two compounds that increased food intake in the worms. They further investigated one compound and discovered the signaling mechanism. They found that a specific mutation called glod-4 increased food intake, mediated by a specific AGE known as MG-H1. Additional analysis revealed that a tyramine-dependent pathway was responsible for the increased appetite.
This groundbreaking study is the first to identify the specific signaling pathway through which certain AGE molecules enhance feeding and neurodegeneration. The researchers also found that mutant worms unable to process naturally occurring AGEs had significantly shorter lifespans of about 25-30%. The study will be extended to mice, allowing researchers to explore the connection between AGEs and fat metabolism.
“Understanding this signaling pathway could provide insight into overeating resulting from diets rich in modern AGEs,” explained Dr. Kapahi. “Our study emphasizes that AGEs accumulation contributes to obesity and neurodegeneration. Limiting AGEs accumulation may significantly impact the global rise in obesity and age-related diseases.”
“What I take away from this research is profound – it’s not us who control our food intake, but rather the food that attempts to control us,” said Dr. Shanmugam.
As a result of this study and previous research from the lab, both Dr. Shanmugam and Dr. Kapahi have made changes to their own diets. They practice intermittent fasting, allowing their bodies to use fat as an energy source instead of relying on sugars. Dr. Kapahi suggests simple steps that individuals can take to reduce AGEs burden in their bodies, such as consuming whole grains for stable glucose levels, cooking with wet heat instead of dry heat, and adding acid to foods during cooking to slow down the formation of AGEs.
“While we are naturally drawn to delicious food, we should be mindful that we have the ability to make healthy choices,” said Dr. Shanmugam.
