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

研究目标 * 我的研究计划的总体目标是阐明解释人类运动耐量差异的关键机制。具体来说，我感兴趣的是了解血容量和心输出量在有氧能力的性别和年龄相关差异中的作用。* 背景 * 心血管生理学的一个基本原则是指心输出量对血容量的严格依赖性，血容量通过Frank-Starling机制促进静脉回流、心室充盈和每搏输出量，从而调节对流氧输送和有氧能力。因此，血容量被认为是有氧能力的主要决定因素。然而，绝大多数支持当前对有氧能力的生理学理解的研究都是针对年轻男性的。在女性和高龄个体中，血容量是否决定心输出量和有氧能力仍然不确定，这两个群体都表现出低血容量和对心血管疾病的易感性。** 本项目的具体目标是：*1）描述女性和老年人血容量、心输出量和有氧能力之间的关系。* 2)确定有氧能力的性别和年龄相关差异是否主要由血容量解释。3)评估女性和老年人训练诱导的有氧能力改善中血容量适应的机制作用。* 为了实现这些目标，将使用受试者间和受试者内对照研究设计，在健康的年轻和老年女性和男性中测量静息和递增运动期间的血液学、心血管和代谢变量。将实施运动训练和适度抽血干预，以分别诱导和消除血容量适应。** 重要性 * 本项目将有助于建立有氧能力中与性别和年龄相关的变异性的生理基础。在过去的五十年里，大多数心血管/运动生理学研究都集中在年轻男性身上，而对女性和老龄化人群的了解相对较少。尚不确定来自年轻男性的发现是否可以外推到其他人群，具体而言，尚不清楚低血容量是否主要抑制女性和老年人的心输出量和有氧能力。因此，拟议的研究将解决我们对人类生理学基本理解的相关知识缺口。除了这项建议的科学性之外，它对心血管健康也有潜在的重大影响：了解限制运动耐量的主要机制对于预防心血管疾病仍然至关重要，心血管疾病是女性和老年人死亡的主要原因。

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.**