Advanced Glycation End Products (AGEs) may exert negative effects on the human body by altering structure/function of proteins and by activating selective receptors. We have recently contributed to demonstrate the role of diet in producing different patterns of AGEs and to elucidate the mechanisms by which AGEs mediate diet-induced metabolic changes. Nevertheless, the role of salivary AGEs as early biomarkers of transition towards diet-related disease has never been proposed.

AIMS: The main aims of SALIVAGES are: (i) the identification of the main AGEs modulated by diets, focusing on saliva as a highly accessible source of AGEs, and (ii) the validation of non-invasive methods to detect salivary AGEs as biomarkers of the risk of developing diet-related diseases.

WORK PLAN: Original models will be developed to study AGEs accumulation in oral mucosa, gut and adipose tissue and the related activation of selective molecular pathways. Advanced multidimensional analytical platforms (GC×GC-MS, HPLC-MS/MS) and highly sensitive biosensors will be used to comparatively detect AGEs in different biofluids (saliva, blood, urine). Metabolite profiling as well as targeted and untargeted fingerprinting on multidimensional analytical data will support the investigation overtaking reductionist vision limited to single biomarker discovery. Innovative glycomic analyses of biological samples will allow the study of glycosylation changes in response to AGEs and the identification of putative glycobiomarkers. Novel recognition molecules and biomimics will subsequently be developed. Analysis on salivary AGEs from healthy subjects will allow to verify whether results emerged from experimental work are relevant for humans and to identify specific AGEs as biomarkers with relevant clinical information potential. Salivary volatilome will be profiled to define correlations with AGEs distribution.

IMPACT OF THE EXPECTED RESULTS: The expected results will contribute to promote the development of innovative diagnostic approaches to classify individual patterns and/or establish the degree of health changes. These results will be achieved by multidisciplinary approaches based on the integration of preclinical and clinical studies, analytical and food chemistry, metabolomics and information technologies. Overall, SALIVAGES will contribute to reveal new horizons in the identification of strategies for monitoring key biological processes underlying the nutrition-health relationship.