Nutr Metab Cardiovasc Dis. 2025 Dec 30:104538. doi: 10.1016/j.numecd.2025.104538. Online ahead of print.
ABSTRACT
Advanced Glycation End Products (AGEs), formed through the non-enzymatic Maillard reaction, are pivotal molecular culprits linking metabolic dysfunction, chronic disease, and the acceleration of biological aging. While AGEs are synthesized endogenously, modern Western diets, defined by thermal food processing, introduce a substantial and increasing pool of exogenous dietary AGEs (dAGEs). This viewpoint critically assesses the evidence supporting the outdated theory that AGEs are not inert biomarkers but active, etiological factors driving pathology. The impact of AGEs is characterized by a dual mechanism: the direct impairment of structural integrity via irreversible protein cross-linking, and the systemic induction of oxidative stress and chronic inflammation ("inflammaging") through binding and activation of the Receptor for AGEs (RAGE). This persistent systemic load-heavily contributed by high-fat, high-protein foods cooked at dry, high heat-is implicated in accelerating insulin resistance, cardiovascular complications, and neurodegeneration. Nutritional strategies have focused on mitigating this exogenous burden through simple culinary modifications, such as utilizing moist heat and acidic ingredients, which significantly curb dAGE formation in the kitchen. However, a critical gap remains: while short-term mechanistic studies are compelling, definitive, long-term human intervention trials are lacking. We argue that future research must rigorously quantify the independent contribution of dAGE restriction to health span and longevity to fully legitimize its role as a primary, evidence-based nutritional intervention for preventative health.
PMID:41622099 | DOI:10.1016/j.numecd.2025.104538