PROJECT SUMMARY/ABSTRACT Approximately 8.5 million high school and collegiate athletes engage annually in competitive sport. While competitive sport offers many benefits, it also poses underappreciated risks to long-term health. Competitive sport profoundly increases risk for injury (e.g., knee injury) and may position athletes for early onset of chronic diseases (e.g., osteoarthritis), chronic pain, poor health-related quality of life, and disability. Preliminary evidence indicates former athletes in mid-life (mean age 53) perform worse on functional tests than non-athlete peers, but did not account for prior injury status. Quantifying function in former athletes with and without a prior injury and non-athlete controls is therefore critical to informing targeted interventions and ultimately increasing healthspans and quality of life. One modifiable factor that may explain the association between sports participation and poor long-term health is physical activity (PA) patterns including prolonged sedentary behavior (SB). Even among adults who meet recommended PA guidelines, SB is strongly associated with a host of poor outcomes including chronic disease and all-cause mortality. Current male professional athletes are substantially more sedentary outside their practice times than non-athletes, but whether this harmful pattern of SB also exists in amateur (e.g., high school, collegiate) or female athletes or persists in former athletes is unknown. The long-term research goal is to improve musculoskeletal, cardiometabolic, and general health and function across the lifespan of male and female former athletes, emphasizing early behavioral interventions that prevent this underrepresented and at-risk population from developing chronic diseases by mid-life. The overarching hypothesis is that former athletes, especially those with a prior injury, will have poorer function and health in mid-life and that current and former athletes will engage in greater overall and longer bouts of SB compared to matched non-athletes. Using a cross-sectional design, Aim 1 will compare function, strength, and cardiometabolic indicators among former athletes with and without prior knee injury and non- athlete matched controls in mid-life (age 45-64). Hypothesis 1 is that former athletes with a prior injury will have the poorest (1a) function (30-second chair stand, 6-minute walk, stair climb), (1b) quadriceps and hamstring strength, and (1c) cardiometabolic indicators (body composition, cardiovascular disease risk). Aim 2 will compare SB and PA patterns in current (age 18-25) and mid-life former athletes to matched non-athlete controls. Hypothesis 2.1 is that current athletes will have greater SB, longer SB bouts, and higher levels of moderate-to-vigorous PA. Hypothesis 2.2 is that former athletes in mid-life will have greater SB, longer SB bouts, and lower PA levels. Identifying and ultimately intervening on risk factors for early chronic disease will not only benefit many millions of male and female former athletes—a group in which minorities are increasingly more represented than in the overall United States population—but also provide an efficient means to prevent or delay chronic disease development in the population at large, a recent NIH emphasis (e.g., PA-18-849).

PROJECT NARRATIVE Approximately 8.5 million Americans participate annually in competitive high school or collegiate sport, greatly elevating their risk for musculoskeletal injury and perhaps positioning them for poor long-term health and function. The proposed DP5 research will evaluate the impact of prior knee injury and sedentary behavior as two potential mechanisms of later poor health and reduced function. The findings will inform the way we rehabilitate, counsel, and educate athletes for long-term health and lead to future longitudinal and intervention studies that will ultimately decrease chronic disease in mid-life, enhancing healthspans.