Exploring the physiological and molecular responses to environmental cross-acclimation

在常压低氧条件下间歇性缺氧训练（IHT）提出了一种潜在的解决方案，使海平面上的个体能够在不需要搬迁成本和后勤的情况下获得一些海拔的生理适应能力。虽然IHT不是最近才出现的现象，但它的使用对正常缺氧条件下的表现有模棱两可的影响，关于IHT的最佳频率、强度和持续时间证明有效还有许多问题；最近的研究表明，高强度、高频率、长时间的低氧刺激会产生有益的生理效应。此外，目前我们对急性和慢性缺氧反应的性别差异、与红细胞（RBC）功能相关的反应和适应的潜在机制以及缺氧对热交叉耐受性的影响的理解还存在空白。此外，关于间歇性缺氧暴露对具有不同功能能力的残奥会运动员的适应性和表现的影响的研究也非常有限。在这个提案中，我的目标是弥合对缺氧的急性和慢性反应的科学理解与适应解决方案之间的差距，以优化极端环境下的工作能力和表现结果。此外，我的研究项目的长期目标是了解基于性别的生理和分子机制对运动和环境压力的急性和慢性反应，以创造干预措施，优化工作能力和表现结果。研究的短期目标包括：1)通过实验研究不同海拔高度动物对急性常压缺氧暴露的性别差异和生理分子反应；2)研究短期缺氧驯化（STHA）的有效性、机制、性别差异及其对热应激反应的影响；3)研究短期热驯化和缺氧交叉耐受的性别机制和性能影响。这些目标是内在联系的，但不一定是顺序依赖的，确保了高可行性和最小的中断，如果出现意外的结果或延迟。这项创新的工作将填补现有的知识空白，并显著推进我们对运动和环境应激的急性和慢性反应的生理和分子机制的理解。这一知识将对指导缺氧和热干预的最佳实践产生广泛而重大的影响，以指导运动员（包括健全运动员和残疾人运动员）和职业工人在极端环境条件下的准备工作。

Intermittent hypoxia training (IHT) in normobaric hypoxia posits a potential solution to allow sea-level individuals the ability to acquire some of the physiological adaptations of altitude without the cost and logistics of relocation. Although IHT is not a recent phenomenon, its use demonstrates equivocal effects on performance in normoxia, with many remaining questions regarding the optimal frequency, intensity, and duration of IHT to prove effective; most recent work demonstrates that a greater hypoxic stimulus with higher intensity, more frequency, and longer durations of IHT sessions posit beneficial physiological effects. Additionally, there is a current gap in our understanding of sex-based differences in response to acute and chronic hypoxia, the underlying mechanisms of response and adaptation specifically related to red blood cell (RBC) function, and the effect hypoxia has on cross-tolerance to heat and vice versa. As well, there is very limited research investigating the effect of intermittent hypoxia exposure on adaptations and performance in Paralympic athletes with varying amounts of functional ability. In this proposal, I aim to bridge the gap between scientific understanding of acute and chronic responses to hypoxia, and acclimation solutions to optimize work capacity and performance outcomes in extreme environments. Furthermore, the long-term goal of my research program is to understand the sex-based physiological and molecular mechanisms of acute and chronic responses to exercise and environmental stress to create interventions that optimize work capacity and performance outcomes. The short-term objectives include: 1) experimentally investigate the sex-based differences and physiological and molecular responses to acute normobaric hypoxia exposure of varying ascents, 2) examine the efficacy, mechanisms, and sex-based differences of short-term hypoxia acclimation (STHA) and its impact on the response to heat stress, and 3) examine the sex-based mechanisms and performance impact of short-term heat acclimation and cross-tolerance to hypoxia. These objectives are inherently linked, but are not necessarily sequentially dependent, ensuring high feasibility and minimal disruption if unanticipated results or delays emerge. This innovative work will fill existing knowledge gaps and markedly advance our understanding of the sex-based physiological and molecular mechanisms of acute and chronic responses to exercise and environmental stress. This knowledge will have broad and significant impact on guiding best practice for use of hypoxia and heat interventions for preparation of athletes, both able-bodied and para-sport, and occupational workers for exposure to extreme environmental conditions.