METABOLOMIC AND GENOMIC MARKERS OF ATHEROSCLEROSIS AS RELATED TO OXIDATIVE STRESS INFLAMMATION AND VASCULAR FUNCTION IN TWIN ASTRONAUTSASTRONAUTS PARTICIPATING IN LONG-DURATION MISSIONS MAY BE AT AN INCREASED RISK OF OXIDATIVE STRESS AND INFLAMMATORY DAMAGE DUE TO RADIATION PSYCHOLOGICAL STRESS ALTERED PHYSICAL ACTIVITY NUTRITIONAL INSUFFICIENCY AND HYPEROXIA DURING EXTRAVEHICULAR ACTIVITY. THIS PROPOSAL EXTENDS A CURRENT NASA-FUNDED INVESTIGATION TO DETERMINE WHETHER THESE SPACEFLIGHT FACTORS CONTRIBUTE TO AN ACCELERATED PROGRESSION OF ATHEROSCLEROSIS. WE PROPOSE TO MEASURE BLOOD AND URINE BIOMARKERS OF OXIDATIVE STRESS AND INFLAMMATIONAS WELL AS ARTERIAL STRUCTURE AND FUNCTION (CAROTID INTIMA-MEDIAL THICKNESS AND BRACHIAL ARTERY FLOW-MEDIATED DILATION) IN ONE TWIN ASTRONAUT BEFORE DURING AND AFTER LONG DURATION SPACEFLIGHT AND IN HIS TWIN SERVING AS A GROUND-BASED CONTROL. FURTHERMORE WE WILL MEASURE METABOLOMIC AND GENOMIC (DNA METHYLATION MRNA GENE EXPRESSION TELOMERE LENGTH) MARKERS TO ELUCIDATE THE MOLECULAR MECHANISMS INVOLVED. WE PREDICT THAT THE SPACE-FLOWN TWIN WILL EXPERIENCE ELEVATED BIOMARKERS OF OXIDATIVE STRESS AND INFLAMMATORY DAMAGE ALTERED ARTERIAL STRUCTURE AND FUNCTION ACCELERATED TELOMERE SHORTENING DYSREGULATION OF GENES ASSOCIATED WITH OXIDATIVESTRESS AND INFLAMMATION AND A METABOLIC PROFILE SHIFT THAT IS ASSOCIATED WITH ELEVATED ATHEROSCLEROSIS RISK FACTORS. CONVERSELY THESE WILL NOT BE OBSERVED IN THE GROUND-BASED TWIN. THIS STUDY OF TWINS AFFORDS A UNIQUE OPPORTUNITY TO EXAMINE THE SPACEFLIGHT-RELATED ATHEROSCLEROSIS RISK INDEPENDENT OF THE CONFOUNDING FACTORS OF DIFFERENT GENOTYPES.