Glycation and AGEs
The biochemical 'caramelisation' of proteins that stiffens tissues with age
Definition
Glycation is the non-enzymatic reaction between reducing sugars (glucose, fructose) and proteins, lipids, or nucleic acids, forming Advanced Glycation End-products (AGEs). AGEs irreversibly cross-link long-lived proteins (collagen, elastin, eye lens, myelin), producing tissue stiffness, loss of function, and the visible appearance of ageing. The rate of glycation accelerates dramatically with chronic hyperglycaemia, which is why it is a central damage mechanism in diabetes.
Detailed explanation
The most-studied AGEs are CML (carboxymethyl-lysine), MGO derivatives (methylglyoxal), and pentosidine. They accumulate especially in low-turnover tissues: dermal collagen, joint cartilage, eye lens, blood vessels, bone, and nerve myelin.
Sources of AGEs: Endogenous: chronic hyperglycaemia, fructose (10× more glycating than glucose), oxidative stress (ROS accelerate intermediate steps). Exogenous: high-temperature cooking without water (roasting, frying, grilling, dry oven) — a pan-fried steak provides 20× more AGEs than the same meat steamed.
Damage mechanisms: binding to RAGE receptors (on endothelium, macrophages, neurons) → NF-κB activation → chronic inflammation → insulin resistance, atherosclerosis, neurodegeneration. AGE-cross-linked dermal collagen produces the characteristic skin stiffness of ageing (wrinkles and loss of turgor).
Measurement: glycated hemoglobin (HbA1c) reflects basic AGE of the last 90 days. Skin AGEs are measured by autofluorescence (AGE Reader), correlated with cardiovascular risk and mortality. Some studies use plasma CML.
Interventions: strict glycaemic control (CGM, low-glycaemic-load diet), steaming or boiling rather than dry-heat cooking, potentially useful supplements (carnosine, benfotiamine, alpha-lipoic acid, taurine), and reduction of free fructose.
Scientific sources
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