Glycation & Advanced Glycation End-Products (AGEs)

What it proposes

Glucose and other reducing sugars react non-enzymatically with proteins, lipids, and nucleic acids. Early adducts (Amadori products like HbA1c) slowly mature into stable advanced glycation end-products (AGEs) that:

• Cross-link long-lived structural proteins (collagen, lens crystallins), stiffening tissue.
• Engage RAGE (receptor for AGEs), driving inflammation.
• Damage lipids and DNA bases.

Evidence

• HbA1c — the prototype glycated protein — predicts diabetic complications precisely because it indexes ambient glucose exposure.
• Collagen cross-linking accumulates with age and accelerates in diabetes; explains arterial stiffening, joint changes, skin aging.
• Tissue AGE content correlates with diabetic retinopathy, nephropathy, neuropathy.

Why "theory" not just biology

The framing as a driver of aging beyond glucose-mediated tissue damage is partial. Many longevity-relevant biological changes (telomere attrition, mitochondrial decline) are not glycation-mediated. Glycation contributes to specific aspects (vascular stiffening, lens opacity, diabetic complications) more than to global aging.

Interventions

• Glycaemic control is the primary lever.
• Dietary AGE reduction: cooking methods (steaming, boiling, lower temperatures) produce less AGE than high-temperature dry-heat cooking; meaningful for diabetics; less clear for general adults.
• AGE-breaker drugs (alagebrium) reached trials for vascular stiffness; unimpressive results.

Related entries

HbA1c, Type 2 diabetes, Pulse-wave velocity.