ntroduction (Background, research question and aims) The formation of endogenous advanced glycation end-products (AGEs) is promoted by various pathogenic processes such as inflammation, oxidation and hyperglycemia. AGEs, which accumulate during type 2 diabetes (T2D), are suspected to be involved in the complications of this disease. However, whether AGEs formation is a causal mechanism or simply a pathological consequence is still under discussion.The aim of our study was to use the Caenorhabditis elegans model to analyse the association between dietary glucose exposure, glucose metabolism, oxidation, formation of AGEs and impact on health and lifespan. Materials and methods (Study design, techniques, participants, intervention, and outcome) C. elegans worms were grown in medium containing no glucose or different concentrations of glucose. Lifespan assays were performed with live or heat-inactivated bacteria to 1- check impact of glucose and bacteria on longevity and 2-choose the type of food to give to the worms for biological analysis. After 3, 6, 10 and 13 days of incubation, expression of antioxidant and metabolic genes was measured by RTqPCR whereas protein oxidation (carbonylation) and glycation (N-carboxymethyllysine or CML and methylglyoxal-derived AGEs) were monitored by western blot. Incubating the worms with glyoxal or methylglyoxal was used to control which AGEs were formed after exposure of the endogenous proteins to these 2 compounds. Results (General results/characteristics, for the primary outcome results of each group effect size and precision) The highest concentration of glucose decreased lifespan of C. elegans. In this glucose-rich diet, worms displayed more oxidized proteins and CML-modified proteins, whereas no methylglyoxal-derived AGEs epitopes were detected on worms’proteins. Furthermore, genes coding for isozymes with sorbitol dehydrogenase (SODH) activity from the polyol pathway were modulated. CML formation, possibly induced by glyoxal, was associated with different biological alterations which were highlighted by transcriptional modulation such as cytoplasmic and mitochondrial unfolded protein response (UPR) and lysosomal functions. Discussion and conclusion (General interpretation of the results and a concise conclusion based on the research question and aims) This study has demonstrated induction of oxidation and glycation of endogenous proteins, which were possibly derived from the modulation of the polyol pathway and the formation of glyoxal. These results open perspectives on the use of the C. elegans model to better understand the health effects of endogenous glycation.This organism is certainly a valuable model for determining whether endogenous glycation is merely a consequence of certain pathologies such as TD2 or whether and how it is also involved in the development of their complications.