RESEARKA

The geroscience framework posits that biological aging is driven by a finite set of interconnected hallmarks, and that targeting these core mechanisms could simultaneously delay the onset of multiple age-related diseases rather than addressing each condition in isolation. Advanced glycation end-products (AGEs) have emerged as a particularly compelling candidate for intervention because the AGE pathway intersects several recognized hallmarks of aging, including altered intercellular communication, mitochondrial dysfunction, and cellular senescence. AGEs form through non-enzymatic Maillard reactions between reducing sugars and proteins, lipids, or nucleic acids, a process that accelerates under hyperglycemic conditions and during chronic oxidative stress (Twarda-Clapa 2022). These glycated adducts accumulate in long-lived structural proteins such as collagen and elastin, contributing to tissue stiffening in the vasculature, kidney, and skin. Importantly, AGEs also engage the receptor for advanced glycation end-products (RAGE), activating NF-κB-dependent inflammatory cascades that perpetuate a state of chronic, low-grade inflammation characteristic of inflammaging. From a regulatory and translational standpoint, this mechanistic profile has generated substantial interest in whether dietary AGE restriction, pharmacological AGE inhibition, or RAGE antagonism could serve as geroprotective strategies. However, the translation of AGE biology into validated clinical endpoints has proven uneven, as the evidence base spans heterogeneous populations, diverse AGE measurement techniques, and outcome classes ranging from skin aging to critical-care mortality.

Citation Support

• source_1 Movahedian 2025
• source_2 Kopytek 2025
• source_3 Chang 2025
• source_4 Wu 2025
• source_5 Li 2026