** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** CURRENTLY, AMERICANS ARE CONSUMING 42% OF THEIR DAILY CALORIES FROM LOW-QUALITY CARBOHYDRATES, SUCH AS REFINED GRAINS AND SUGAR SWEETENED BEVERAGES. EXCESSIVE INTAKE OF REFINED CARBOHYDRATESIS A MAJOR DIETARY RISK FACTOR FOR THE DEVELOPMENT OF NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) WHICH IS MORE PREVALENT AND SEVERE AMONGST AGED INDIVIDUALS. WHILE CRITICAL TO RECOMMEND DECREASED CONSUMPTION OF REFINED CARBOHYDRATES, IT IS ALSO IMPORTANT TO IDENTIFY FOOD-DERIVED, BIOLOGICALLY ACTIVE COMPOUNDS, SUCH AS LYCOPENE (A RED PIGMENT) AND PHYTOENE (A PRECAUSOR OF LYCOPENE AND OTHER MAJOR CAROTENOIDS)FROM TOMATOES AND TOMATO PRODUCTS, WHICH MAY DELAY THE ONSET OF NAFLD THROUGH TARGETING THE GUT-LIVER INTERACTION. IN THE PROPOSED STUDY, WE WILL EXPLORE WHETHER AGE (YOUNG MICE AT 8 MONTHS VS. OLDER MICE AT 24 MONTHS) AND CAROTENOID BREAKDOWN ENZYMES (NORMAL MICEVS. MICE LACKING CAROTENOID BREAKDOWN ENZYMES) MAY DIFFERENTIALLY CONTRIBUTE TO HIGH REFINED CARBOHYDRATE DIET (HRCD)-INDUCED NAFLD DEVELOPMENT; AND WHETHER TOMATO POWDER (WHOLE TOMATO) AND KEY TOMATO-BASED CAROTENOIDS (LYCOPENE AND PHYTOENE) ELICIT PROTECTION AGAINST HRCD-RELATED NAFLD THROUGH MODULATING THE KEY GENES (SIRTUIN 1 SIGNALING), GUT BACTERIA PROFILE (GUT MICROBIOME) AND METABOLIC PROFILE (METABOLOMICS)IN YOUNG AND OLDER ANIMALS. WE EXPECT THAT TOMATO POWDER, LYCOPENE, AND PHYTOENE INTERVENTIONS WILL DIMINISH HRCD-, AGE-RELATED ABERRANT GENE EXPRESSION, INFLAMMATION AND OXIDATIVE STRESS, CONSEQUENTLY MINIMIZINGGUT BACTERIA AND METABOLIC ALTERATIONS AND REDUCING NAFLD PROGRESSION. THESE DATA WILL PROVIDE NEW INSIGHT INTO THE PROTECTIVE EFFECTS OF TOMATO AND TOMATO PRODUCTS AND WILL FURTHER EMBOLDEN THE PREVENTIVE ROLE OF TOMATO AGAINST HRCD-ASSOCIATED NAFLD AND METABOLIC DISORDERS IN AGED POPULATION.