Understanding the impact of lifespan changes in respiratory muscle function

人类呼吸肌完成一项重要的生命维持功能：呼吸。它们高度协调的收缩产生通过肺部和呼吸道的气流(即通风)，以确保足够的氧气输送和二氧化碳的排出。在运动中，活跃的肌肉增加了对氧气的需求和二氧化碳的产生，这就需要相应地增加通气量。在运动过程中出现的换气增加通常是相当可观的，必须由呼吸肌来完成，这会带来大量的能量和神经肌肉成本。然而，我们对人类呼吸肌功能的了解是不完整的。最值得注意的是，衰老是一个基本的生物过程，几乎影响到所有的人体组织，包括骨骼肌，但它对呼吸肌的影响尚不清楚。鉴于呼吸肌在人体内的重要作用，了解呼吸肌的活动是如何协调和促进的，以及这种作用在人类一生中是如何变化的，这一点至关重要。我研究的长期目标是评估人类呼吸肌的结构和功能之间的关系，以及它们如何应对生理挑战，如运动。在接下来的五年里，我的短期目标是通过解决三个独立但相互关联的目标来确定人类呼吸肌功能在整个生命周期内如何变化，以及这可能如何影响运动的生理反应：目标1-了解衰老如何影响呼吸肌能量学，目标2-确定呼吸肌工作如何影响运动中呼吸肌的疲劳，以及目标3-确定呼吸肌功能的寿命变化是否可以通过有针对性的呼吸肌肉系统训练来改变。我的研究计划将利用一种综合的方法，考虑呼吸系统、心血管系统、神经系统和肌肉系统之间的相互作用，以便更好地了解呼吸肌的功能。实验将包括在单独的呼吸肌工作或全身运动中对呼吸肌耗氧量、机械效率和神经肌肉功能的详细测量和操作。总体而言，我的研究计划旨在提高我们对呼吸肌如何影响运动的生理反应的理解，这对研究人类生理学的生物学家来说很重要，也是相关的。此外，我的项目将为本科生和研究生提供重要的培训机会，教授他们有形的技能，并让他们参与研究过程的各个方面。

Human respiratory muscles fulfill an important life-sustaining function: breathing. Their highly coordinated contractions generate airflow through the lungs and airways (i.e., ventilation) to ensure the adequate delivery of oxygen and elimination of carbon dioxide. During exercise, active muscles increase the requirements for oxygen and the production of carbon dioxide, which necessitates a corresponding increase in ventilation. The increase in ventilation that occurs during exercise is often considerable and must be performed by the respiratory muscles, which comes at a substantial energetic and neuromuscular cost. However, our understanding of how human respiratory muscles function is incomplete. Most notably, aging is a fundamental biological process that affects almost all human tissues, including skeletal muscles, but its impact on the respiratory muscles remains unclear. Given their vital role within the human body, understanding how the action of the respiratory muscles is coordinated and fuelled, and how this changes over the course of the human lifespan is of critical importance. The long--term objective of my research is to evaluate the relationship between the structure and function of human respiratory muscles and how they respond to physiological challenges, such as exercise. Over the next five years, my short--term objective is to determine how human respiratory muscle function changes across the lifespan and how this might impact the physiological response to exercise by addressing three separate, but interrelated, aims: Aim 1 - understand how aging influences respiratory muscle energetics, Aim 2 - determine how respiratory muscle work influences the fatigue of the respiratory muscle during exercise, and Aim 3 - determine if the lifespan changes in respiratory muscle function can be altered by targeted training of the respiratory musculature. My research program will utilize an integrative approach that considers the interaction between the respiratory, cardiovascular, nervous, and muscular systems in order to better understand how the respiratory muscles function. Experiments will involve detailed measurements and manipulation of respiratory muscle oxygen consumption, mechanical efficiency, and neuromuscular function during isolated respiratory muscle work or whole-body exercise. Overall, my research program seeks to improve our understanding of how the respiratory muscles influence the physiological response to exercise, which is important and relevant to biologists studying human physiology. Furthermore, my program will provide important training opportunities for undergraduate and graduate trainees by teaching them tangible skills and involving them in every aspect of research process.