Glycation is a non-enzymatic reaction between reducing sugars and free amino groups of proteins, lipids, or nucleic acids. Unlike glycosylation, which is enzyme-mediated and tightly regulated, glycation occurs spontaneously under physiological conditions. Over time, these reactions lead to the formation of advanced glycation end products (AGEs), which accumulate in tissues and contribute to aging, metabolic disorders, and chronic disease.

The initial step of glycation is the Maillard reaction, first described in food chemistry but now well recognized in human biology.

1. Condensation of reducing sugars with amino groups of proteins, particularly lysine and arginine residues.
2. Schiff base formation followed by rearrangement into Amadori products.

1. Progressive oxidation, dehydration, and crosslinking events lead to the accumulation of stable AGEs.

Glycation is influenced by glucose concentration, oxidative stress, and protein turnover rate. Long-lived proteins such as collagen and lens crystallins are especially susceptible.

AGEs represent the endpoint of the glycation cascade. They are chemically diverse and can be fluorescent, cross-linking, or receptor-binding molecules.

1. Carboxymethyllysine (CML) and pentosidine are common AGE biomarkers.

1. AGEs bind to the RAGE receptor (Receptor for Advanced Glycation End Products), initiating pro-inflammatory signaling pathways (NIH RAGE Signaling).
2. AGE accumulation is implicated in vascular stiffness, retinal damage, and neurodegeneration.

Glycation has profound consequences for human health, particularly in the context of diabetes and aging.

1. In diabetes, hyperglycemia accelerates AGE formation (CDC Diabetes and Hyperglycemia).

1. Hemoglobin A1c (HbA1c) is a glycated protein used clinically as a long-term marker of glucose control.
2. AGE-induced crosslinking of collagen reduces vascular elasticity, contributing to hypertension and atherosclerosis.
3. AGE accumulation in the lens causes protein aggregation and cataract formation.
4. In the kidney, glycation accelerates fibrosis and progression of chronic kidney disease.

Understanding glycation requires a combination of biochemical assays and analytical technologies :

1. Mass spectrometry for precise identification of AGE structures.
2. ELISA assays for quantification of circulating AGEs.
3. Animal models such as diabetic rodents to study tissue-specific AGE deposition.
4. Cellular systems expressing RAGE for receptor-ligand interaction studies.

Although this blog emphasizes biomedical glycation, dietary intake of AGEs from thermally processed foods also contributes to systemic AGE burden. Cooking methods such as grilling and frying generate high levels of dietary AGEs, which have been linked to inflammation and insulin resistance.

Multiple strategies are under investigation to reduce glycation and AGE accumulation :

1. Tight glycemic control in diabetes to reduce substrate availability.
2. AGE inhibitors (e.g., aminoguanidine) tested in preclinical models.
3. Crosslink breakers that disrupt AGE-protein crosslinks.
4. Dietary interventions lowering AGE intake and oxidative stress.