What are examples of advanced glycation end products (AGEs) and how do they form?

Advanced glycation end products (AGEs) are a heterogeneous group of compounds, with studies showing that the accumulation of these molecules increases with age and is accelerated by a high-sugar, high-fat diet. To understand their health effects, it is crucial to know what are examples of advanced glycation end products and how they arise.

Quick Summary

Advanced glycation end products (AGEs) are molecules formed when sugars react non-enzymatically with proteins or lipids. Key examples include carboxymethyllysine (CML), pentosidine, and pyrraline, which accumulate through both endogenous processes and dietary intake, particularly from high-heat cooking.

Key Points

• Carboxymethyllysine (CML): A common AGE marker found in thermally processed foods and the body, resulting from glycoxidation and lipid peroxidation.

• Pentosidine: A fluorescent AGE that forms cross-links in long-lived proteins like collagen, serving as a biomarker for cumulative tissue damage, particularly in diabetes.

• Pyrraline: A non-oxidative AGE frequently detected in heat-treated food products like milk and bakery goods, which can be absorbed from the diet.

• Dietary Sources: Exogenous AGEs are abundant in foods cooked at high, dry temperatures (e.g., frying, grilling) and highly processed items rich in protein and fat.

• Endogenous Formation: AGEs form naturally during the aging process and are accelerated by high blood sugar levels (hyperglycemia) and oxidative stress.

• Health Impacts: The accumulation of AGEs contributes to inflammation, oxidative stress, and the progression of chronic diseases, including cardiovascular issues, diabetic complications, and neurodegeneration.

• Precursors and Pathways: Many AGEs, like CML and pyrraline, form in the later stages of the Maillard reaction from reactive dicarbonyl intermediates such as methylglyoxal and 3-deoxyglucosone.

What Exactly Are Advanced Glycation End Products?

Advanced glycation end products (AGEs) are complex molecules that are formed through a non-enzymatic reaction between reducing sugars and proteins, lipids, or nucleic acids, a process known as the Maillard reaction. This reaction is responsible for the browning and flavor development in cooked foods. However, the formation of AGEs is not limited to food processing; it also occurs naturally within the human body during normal metabolism and aging. The rate of AGE formation in the body is significantly accelerated by hyperglycemia, oxidative stress, and inflammation. The accumulation of AGEs can negatively impact cell structure and function and has been linked to numerous chronic and age-related diseases.

Key Examples of Advanced Glycation End Products

AGEs are a diverse class of compounds, but some have been studied extensively and serve as key markers for AGE accumulation both in the body and in food. Here are some of the most notable examples:

• Carboxymethyllysine (CML): Often considered one of the most widely used markers for AGEs, CML is a non-fluorescent AGE formed from the oxidation of Amadori products or through lipid peroxidation. It is commonly found in high concentrations in thermally processed foods, especially those high in protein and fat, such as cheese and certain canned fishes. In the body, CML levels increase with age and in conditions like diabetes, vascular disease, and cancer.
• Pentosidine: A well-characterized, fluorescent AGE that forms cross-links between arginine and lysine residues in long-lived proteins like collagen. Due to its stable nature and fluorescence, it is an excellent biomarker for cumulative AGE damage. Elevated levels of pentosidine are strongly correlated with the severity of diabetic complications, particularly in tissues like skin, and are also implicated in bone fragility.
• Pyrraline: A non-oxidative AGE derived from the reaction of lysine with 3-deoxyglucosone, an intermediate of the Maillard reaction. Pyrraline is commonly found in heat-treated foods like milk products, bakery items, and pasta. It is efficiently absorbed by the body from dietary sources and excreted in the urine, but accumulation can occur and is associated with chronic diseases.
• Acrylamide: This is a chemical contaminant formed during the high-temperature cooking of starchy foods, such as frying potatoes. While a precursor, acrylamide can form AGEs and is considered a potential carcinogen, though studies on dietary intake correlation with human cancer are ongoing. Its formation is tied to the Maillard reaction involving the amino acid asparagine.

Other notable examples of AGEs include carboxyethyllysine (CEL), imidazolone, and methylglyoxal-derived hydroimidazolones (MG-H1), all contributing to the complex picture of AGE-related health effects.

Endogenous vs. Exogenous Sources of AGEs

AGEs originate from two main sources:

Endogenous Sources:

• Internal Metabolism: Normal metabolic processes produce AGEs throughout life, but at a slow rate.
• Aging: AGEs accumulate gradually with age due to the long half-life of many proteins in the body, such as collagen and elastin.
• Hyperglycemia and Oxidative Stress: Conditions like diabetes dramatically accelerate AGE formation due to high blood sugar levels and increased oxidative stress.

Exogenous Sources:

• Dietary Intake: The Maillard reaction during high-temperature, dry-heat cooking methods like frying, grilling, and roasting produces significant amounts of AGEs in food. Processed and high-fat foods, including certain cheeses and packaged snacks, are also major sources.
• Smoking: Cigarette smoke is another source of reactive glycation products that can increase AGE accumulation in tissues.

The Health Impacts of AGE Accumulation

The buildup of AGEs has a significant impact on health by driving chronic inflammation, increasing oxidative stress, and altering the function and structure of proteins. This can contribute to:

• Vascular Damage: AGE-modified proteins can stiffen blood vessel walls, contributing to hypertension and the progression of atherosclerosis.
• Diabetic Complications: In diabetes, excessive AGEs are a major factor in the development of microvascular complications affecting the eyes, kidneys, and nerves.
• Neurodegenerative Diseases: AGEs have been implicated in the aggregation of proteins found in conditions like Alzheimer's disease and Parkinson's disease.
• Osteoporosis: In bone tissue, non-enzymatic cross-linking by AGEs can reduce bone strength and increase fracture risk, independent of bone mineral density.

Feature	Carboxymethyllysine (CML)	Pentosidine	Pyrraline
Formation	Glycoxidation & lipid peroxidation	Cross-linking of arginine and lysine residues	Non-oxidative Maillard reaction
Fluorescence	No	Yes	No
Cross-linking	No	Yes	No
Dietary Source	High-protein/fat foods, canned fish	Formed in high-heat cooked foods	Milk products, bakery goods, pasta
Biomarker Use	Widely used marker for AGEs	Specific biomarker for long-lived protein damage	Indicator of heat damage in food

Conclusion

Advanced glycation end products are a diverse group of molecules, with examples like CML, pentosidine, and pyrraline serving as significant indicators of their presence both in food and the human body. As AGE accumulation is accelerated by factors like high blood sugar, oxidative stress, and certain cooking methods, it's clear that lifestyle and dietary choices can heavily influence internal levels. By understanding what are examples of advanced glycation end products, individuals can make informed decisions to mitigate the associated health risks. Adopting a diet lower in highly processed and high-heat cooked foods, managing blood sugar levels, and reducing exposure to risk factors like smoking are all effective strategies for minimizing AGE accumulation and promoting long-term health. For further reading, an authoritative review of AGEs can be found on the National Institutes of Health website.

Review of advanced glycation end products (AGEs) and other adducts in alcohol-mediated tissue injury

Frequently Asked Questions

What is carboxymethyllysine (CML)?

Carboxymethyllysine (CML) is a non-fluorescent advanced glycation end product that is commonly used as a biomarker for AGE accumulation. It can be formed from glycoxidation or lipid peroxidation and is found in high-heat processed foods and the body.

What is pentosidine, and what does it indicate?

Pentosidine is a fluorescent, cross-linking AGE formed between lysine and arginine residues in proteins like collagen. Its presence is a biomarker for long-term tissue damage from AGE accumulation and is linked to the severity of diabetes complications.

Where does dietary pyrraline come from?

Pyrraline is a non-oxidative AGE produced during the Maillard reaction in heat-treated foods such as milk products, pasta, and bakery items. It is efficiently absorbed from the digestive tract.

Do AGEs form naturally in the human body?

Yes, AGEs form endogenously within the body as a natural part of metabolism and aging. This process is accelerated by factors like high blood sugar levels and increased oxidative stress.

How are exogenous AGEs created in food?

Exogenous AGEs are primarily formed through the Maillard reaction during cooking processes that involve high, dry heat, such as frying, grilling, and roasting. Foods high in fat and protein are particularly susceptible.

What health problems are associated with AGE accumulation?

Accumulation of AGEs is linked to chronic inflammation, oxidative stress, and numerous age-related diseases. These include diabetic complications, cardiovascular disease (e.g., atherosclerosis), kidney disease, and neurodegenerative disorders.

Is acrylamide a type of AGE?

Acrylamide is not an AGE itself but a chemical that forms AGEs, particularly during the high-heat cooking of starchy foods. It is a potential health concern and is formed via the Maillard reaction involving asparagine.

What are some lesser-known examples of AGEs?

Besides the most common examples, other AGEs include carboxyethyllysine (CEL), imidazolone, and methylglyoxal-derived hydroimidazolones (MG-H1), all contributing to the complex AGE picture.