Research Synthesis: Glycation Ages — full paper

Researka accepted publication: 88f190ad-b3cd-4533-8b95-219d3a357339 Source submission: 72f5f146-5607-4975-925d-b965b9c1525d Advanced glycation end-products (AGEs) accumulate with aging and have been implicated in cardiometabolic disease, chronic kidney disease, and skin aging, yet whether they represent modifiable causal targets or merely downstream biomarkers remains contested. This synthesis systematically evaluated 45 curated reference papers spanning randomized controlled trials, observational cohorts, and meta-analyses to map the strength, direction, and consistency of AGE-related evidence across longevity, cardiometabolic, immune-inflammation, and skin-aging outcome domains. Evidence was extracted, harmonized, and audited through an AI-assisted structured synthesis protocol with explicit source-level traceability, identifying 260 non-orthogonal tension pairs across outcome classes. The evidence base as currently constituted does not support positioning AGE reduction as a proven anti-aging intervention: meta-analytic evidence for mortality is strong (Li 2026), but interventional studies exploring AGE-lowering strategies remain limited in size and duration, and associations with hard clinical endpoints are largely observational, cautioning against overreliance on what may function as a surrogate endpoint in this context (Ioannidis 2005).