Down syndrome (DS) is the most prevalent genetic cause of intellectual disability and occurs in approximately 1 in every 700 births in the US. Individuals with DS are at increased risk for a number of health issues. Work capacity is an important predictor of declining health or physical function, and of mortality, and is commonly measured as peak oxygen consumption. Peak oxygen consumption is very low in individuals with DS, and cannot be explained by physical inactivity, lack of motivation, or lack of understanding of the test. To date, the nature of the limitations in work capacity in DS is unknown, and the proposed research aims to address this knowledge gap. Work capacity is determined by central and peripheral regulation of blood flow (i.e. cardiac output and maintaining arterial blood pressure vs. supplying exercising muscles with oxygen and nutrients). These factors are governed by the sympathetic and parasympathetic branches of the autonomic nervous system. Central regulation of blood flow is impaired in individuals with DS due to cardiovascular autonomic dysfunction, whereby parasympathetic activity is high and sympathetic control is reduced. This results in lower heart rate, less adequate blood pressure control and attenuated catecholamine levels during exercise. It is unknown to what extent this impaired central control impacts cardiac output, and subsequently work capacity, during exercise in individuals with DS. Peripheral blood flow regulation is even less studied in individuals with DS. Peripheral regulation involves sympathetically regulated vasoconstriction in non-active muscles and tissues, and local mechanisms regulating vasodilation in working muscles, which facilitates blood flow to working muscle in order to meet metabolic demand. Individuals with DS may partly experience reduced work capacity due to this inability to shunt blood to the working tissue effectively. The aim of this research proposal is therefore to determine the impact of limitations in central and peripheral regulation of blood flow on work capacity in individuals with DS. We aim to examine the responses to exercise training to better understand the underlying mechanisms and the potential to improve health by using this knowledge in exercise interventions.