Importance of blood volume to sex- and age-related differences in aerobic capacity

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Research goals***The overall goal of my research program is to elucidate key mechanisms that explain the substantially different levels of exercise tolerance in humans. Specifically, I am interested in understanding the role of blood volume and cardiac output in sex- and age-related differences in aerobic capacity. ******Background***A fundamental tenet of cardiovascular physiology refers to the strict dependence of cardiac output on blood volume, which facilitates venous return, ventricular filling and stroke volume via the Frank-Starling mechanism, thereby regulating convective oxygen delivery and aerobic capacity. Blood volume is thus considered as a primary determinant of aerobic capacity. However, the vast majority of studies underpinning the current physiological understanding of aerobic capacity comprise young male individuals. Whether blood volume governs cardiac output and aerobic capacity remains uncertain in females and individuals with advanced age, both groups presenting with low blood volume and susceptibility to cardiovascular disease. ******The SPECIFIC AIMS of this project are to:***1) Characterize the relationship between blood volume, cardiac output and aerobic capacity in female and elderly individuals.***2) Determine whether sex- and age-related differences in aerobic capacity are primarily explained by blood volume.***3) Assess the mechanistic role of blood volume adaptations for training-induced improvements in aerobic capacity in female and elderly individuals. ***To accomplish these aims, hematological, cardiovascular and metabolic variables will be measured at rest and during incremental exercise in healthy young and older females and males, using between- and within-subject controlled study designs. Exercise training and moderate blood withdrawal interventions will be implemented to induce and negate, respectively, blood volume adaptations. ******Significance***This project will contribute to the establishment of the physiological basis underlying sex- and age-related variability in aerobic capacity. While most cardiovascular/exercise physiology research spanning over the last five decades has been focused on young male individuals, relatively little is known regarding female and aging populations. It is uncertain whether findings derived from youthful males can be extrapolated to other populations and specifically, it remains unclear whether low blood volume primarily restrains cardiac output and aerobic capacity in females and elderly individuals. The proposed studies will therefore address a relevant knowledge gap in our basic comprehension of human physiology. Beyond the scientific nature of this proposal, there are potential major implications for cardiovascular health: understanding the major mechanisms limiting exercise tolerance remains essential for the prevention of cardiovascular disease, the leading cause of death in female and elderly populations.**