THE ULTIMATE GOAL OF THE STUDIES PROPOSED HERE IS TO ESTABLISH TEMPORAL PROFILES OF HUMAN TELOMERE LENGTH DYNAMICS AND DNA DAMAGE RESPONSES OF IMPORTANCE FOR MAINTENANCE OF HUMAN HEALTH AND PERFORMANCE DURING LONG-DURATION DEEP SPACE MISSIONS. WE HYPOTHESIZE THAT TELOMERE LENGTH DYNAMICS (CHANGES OVER TIME) REPRESENT A PARTICULARLY RELEVANT AND INFORMATIVE BIOMARKER OF HEALTH FOR THE ASTRONAUTS AS IT REFLECTS THE COMBINED EXPERIENCES AND EXPOSURES ENCOUNTERED DURING SPACEFLIGHT. THAT IS AN ASTRONAUT'S INDIVIDUAL GENETIC SUSCEPTIBILITIES UNIQUE LIFESTYLE STRESSES ENCOUNTERED (E.G. NUTRITIONAL PSYCHOLOGICAL PHYSICAL) AND PARTICULAR ENVIRONMENTAL EXPOSURES (E.G. MICROGRAVITY GALACTIC COSMIC RAYS) ARE ALL INTEGRATED AND CAPTURED AS CHANGES IN TELOMERE LENGTH. THUS THE RATE AT WHICH TELOMERES SHORTEN PROVIDES A GENERAL MEASURE OF HEALTH THAT CAN BE LINKED TO AGING AS WELL AS TO RISK OF DEVELOPING DEGENERATIVE AGE-RELATED PATHOLOGIES RANGING FROM REDUCED IMMUNE FUNCTION AND DEMENTIA TO CARDIOVASCULAR DISEASE AND CANCER. IMPORTANTLY FUNCTIONAL TELOMERES ARE ALSO ESSENTIAL FOR MAINTAINING GENOMIC INTEGRITY AND STABILITY AS THEY PROTECT CHROMOSOMAL TERMINI FROM INAPPROPRIATE DEGRADATION AND PREVENT THESE NATURAL DNA ENDS FROM BEING RECOGNIZED AS BROKEN DNA AND TRIGGERING INAPPROPRIATE DNA DAMAGE RESPONSES (DDRS). TO IDENTIFY TRENDS IN ADAPTATIONS TO HUMAN HEALTH AND PERFORMANCE DURING LONG-DURATION LOW-EARTH ORBIT WE PROPOSE TELOMERE LENGTH AND DDR/CYTOGENETIC MEASURES PIONEERED AND VALIDATED IN THE NASA TWINS STUDY/FIRST ONE YEAR MISSION ACROSS THE INTEGRATED ONE- YEAR MISSION PROJECT ONBOARD THE INTERNATIONAL SPACE STATION AND THE CONCURRENT GROUND ANALOG (PROLONGED ISOLATION) COMPONENT.