Abstract Exercise training produces substantial health benefits, summarized in the Physical Activity Guidelines Advisory Committee Report and incorporated into the 2008 and 2018 Physical Activity Guidelines for Americans. Despite the well-known benefits, too few individuals adopt exercise as a health maintenance strategy. Thus, determining whether a relatively modest duration of exercise training in middle age can lead to sustained health benefits as individuals progress into older age groups (legacy effects) is of public health and clinical importance. In previously sedentary, overweight middle-aged adults with dyslipidemia, our STRRIDE I Reunion study revealed legacy effects for fitness and cardiometabolic risk factors 10 years following exercise intervention; some of these effects were specific to the amount and intensity of exercise performed. In light of the legacy benefits observed in STRRIDE I, the proposed STRRIDE-PD Reunion study seeks to determine the extent to which changes in fitness and cardiometabolic risk factors acquired in individuals aged 45-75 are maintained over a 10-year period in participants from the STRRIDE-Prediabetes (STRRIDE-PD) randomized trial. Importantly, the STRRIDE-PD Reunion will allow us to verify the observed legacy effects of aerobic exercise training in participants at greater risk for cardiometabolic disease. The STRRIDE-PD trial included a group similar to the lifestyle arm of the Diabetes Prevention Program, designed to achieve weight loss through diet and exercise. This unique design element will allow us to compare the ability of different aerobic exercise interventions – with and without weight loss – to elicit sustained cardiometabolic health benefits in adults with prediabetes. Combined with the previous STRRIDE studies, the STRRIDE-PD Reunion will solidify the scientific knowledge exploring the underlying molecular mechanisms by which exercise – differing in amount, intensity, and mode – produces sustained health benefits across the lifespan from age 45 to 85. Overall, findings from this research will demonstrate the power and value of exercise training programs of even modest duration to elicit long-term cardiometabolic health benefits.

Project Narrative In medicine, the sustained benefit of a treatment long after cessation of the intervention is termed a legacy effect. As exercise produces substantial health benefits following intervention, this proposal seeks to determine the legacy health benefits of exercise intervention in middle-aged adults and uncover novel pathways by which these exercise-induced legacy health effects occur. Findings from this project will help guide personalized exercise medicine for both short-term clinical needs and long-term health maintenance as individuals age.