ExoNutriAge

Age-related cognitive alterations participate in the progressive loss of autonomy and represents a major economic and societal challenge. The heterogeneity in the cognitive abilities found in the healthy aging population, also between men and women, indicate the involvement of complex mechanisms. Cumulative evidence indicate that nutrition is a modifiable risk factor for accelerated cognitive decline and also a potential key element to prevent it. In particular, the polyunsaturated fatty acids (PUFA) composition of the diet has been linked to detrimental effect when in low amount or beneficial effect when in high amount on cognition. There is currently no biomarker available to identify cognitive decline and more dramatically to identify subjects at risk to develop an accelerated cognitive decline. In the quest of finding a biofluid-derived biomarker, the research on EVs gained interest in the last decade. As they mimic the status of their cell of origin and can circulate from the brain to the periphery, they appear as promising source of relevant biomarker(s) for the identification of cognitive decline. Mechanistically, exosomes, a category of extracellular vesicles, have recently emerged as novel cellular communication actors and have been shown to be involved in health and disease. ExoNutriAge proposes a comprehensive analysis of the role of cerebral exosomes in the cognitive dysfunctions associated to aging and their modulation by the nutrition, taking into account the effects of sex. The project will use a translational approach combining preclinical models of cognitive aging, n-3 PUFA manipulation approaches and a clinical healthy aging human cohort with nutritional intervention. ExoNutriAge will study cerebral and circulating EV profiles, including miRNA, proteins and lipids. We will use a data-science approach to reveal the sex-specific EV signature modulated by nutritional PUFAs, specific to memory capabilities and translatable to human research. The groundbreaking nature of the project relies on its original strategy by focusing on the subcellular compartment (EVs) and the innovative approaches developed (novel EV research pipelines, data-science approach and human cohort). This will describe the mechanistic link between nutritional status, cerebral ability and aging in both sexes. Overall, ExoNutriAge aims at providing innovative knowledge on the ability of dietary PUFA to modulate cerebral exosomes and impact cognitive ability during aging. Ultimately the project aims at improving quality of life, for both men and women, thoughout aging by preventing the onset of age-associated pathologies such as neurodegenerative diseases.