Elucidating the critical role of metabolic stress in central and peripheral mechanisms of adaptation to endurance exercise training

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Objectives of proposed research program Endurance exercise training aims to improve cardiovascular function by changing how central (i.e., the heart) and peripheral (i.e., the small vessels within the muscles) mechanisms control the transport and distribution of oxygen (O2) to the muscles that need it. However, in some people, endurance training fails to achieve this goal. Although some believe that genetic factors determine whether someone will benefit from endurance training, work from my laboratory shows that every individual can improve their cardiovascular function if exercise training is of appropriate intensity. Thus, I have proposed that by using a personalized exercise program that precisely considers the stress that the exercise causes to the body will result in everyone benefiting from endurance training. The objective of my research program is to understand the mechanisms that control central and peripheral adaptations to endurance exercise training under experimental conditions where the level of stress is accurately quantified. I will explore the controversial hypotheses that: i) the so-called "non-responders" to exercise do not exist when the appropriate exercise intensity is applied; and ii) central and peripheral adaptations will contribute differently depending on the exercise intensity assigned to the intervention. Summary of scientific approach I will perform a 10-week endurance training program where participants will be assigned to 4 training groups: 1) Moderate intensity continuous exercise (MOD; minimal physical stress); 2) Heavy intensity continuous exercise 1 (HVY1; small physical stress); 3) Heavy intensity continuous exercise training 2 (HVY2; large physical stress); 4) High intensity interval training (HIIT; large physical stress). Application of this model will ensure that the stress of exercise will be different between but identical within groups. Using different measures of central and peripheral cardiovascular function during and after training, I will determine the mechanisms responsible for the adaptations in each group. My laboratory is uniquely equipped to execute this research plan using non-invasive or minimally invasive approaches. Novelty and expected significance Current approaches are inadequate to prescribe the appropriate stress of exercise to participants. This is a critical limitation that questions the validity of current methods to evaluate the mechanisms that control adaptations to endurance training. Applying a novel exercise model that precisely controls the stress of the exercise, my research program will: 1) demonstrate that cardiovascular adaptations to endurance training are determined by the stress of the intervention; 2) challenge the concept of "non-responders" to exercise. This will make a critical contribution providing scientists and practitioners with precise information to perform their work more effectively.