Sex-specific adaptation to different resistance exercise programs in older adults

总体而言，男性和女性在以下方面经历了不同程度的年龄相关下降 身体功能障碍，女性功能受限和残疾的患病率更高。一把钥匙 这种功能能力下降的预测指标是腿部肌肉最大功率(力量的乘积)的下降 和速度)，这可以通过运动训练来提高。然而，运动的发展 以最佳方式改善老年人骨骼肌功能的干预措施一直很困难，部分原因是我们 现在知道，男性和女性对相同的运动训练刺激的反应是不同的。事实上， 习惯性运动改善老年人身体机能的基本机制仍然不是很好 明白了。拟议的研究建立在我们最近的工作基础上，旨在解决这些问题 通过检查两种不同的反应背后的分子和细胞机制来了解知识差距 运动训练模式，并确定这些反应在老年男性和女性之间有何不同。我们 假设分子、细胞和整个肌肉的收缩性能在男性中改善最大 通过传统的低速度、高负荷耐力训练，而在女子中采用高速度、低负荷的力量 训练。此外，在肌丝重塑、蛋白表达和后肌丝重建中的性别特异性结构反应。 翻译修饰将解释这些针对不同性别的表现对每种通道的适应。测试我们的 假设，数据将从50名健康、久坐的老年男性和女性(65-75岁)收集， 在为期16周的单侧运动训练计划中，一条腿接受阻力训练，并 另一种力量训练。该项目的具体目标是确定低速对性别的影响。 阻力训练与高速力量训练的对比：目的1)在分子水平上的骨骼肌功能， 细胞和整个肌肉水平，以及目标2)蛋白质表达和修饰以及 分子和细胞水平。我们在主体内部的单边干预设计提供了一个强大的模型 将主题之间的可变性的影响降至最低，我们的翻译方法将利用我们的 具有从分子到全身水平的最先进测量的独特专业知识。我们的结果将 通过确定内在骨骼肌中的性别特异性反应来挑战传统观点 适应不同的运动训练计划。我们将通过提供批判性的- 需要有关支持运动诱导的特定分子和细胞决定因素的信息 肌肉性能的改善。这一知识将对临床产生重大的积极影响 通过为改善骨骼肌的最佳运动干预提供新的见解来照顾老年人 通过为药物干预确定潜在的新的治疗靶点，为每种性别的功能提供更多的信息。 因此，该项目与NIA支持生物研究以缓解 与衰老相关的疾病，可能会限制老年人的健康和独立性。

PROJECT SUMMARY In general, men and women experience differing degrees of age-related decreases in physical function, with women having a greater prevalence of functional limitations and disability. A key predictor of this decrease in functional capacity is the reduction in leg muscle maximal power (product of force and velocity), which can be improved with exercise training. However, the development of exercise interventions to optimally improve skeletal muscle function in older adults has been difficult, in part because we now know that men and women respond differently to the same exercise training stimulus. In fact, the fundamental mechanisms by which habitual exercise improves physical function in older adults are still not well understood. The proposed studies, which build upon our recent work, are designed to address these knowledge gaps by examining the molecular and cellular mechanisms underlying the response to two distinct exercise training paradigms, and determining how these responses differ between older men and women. We hypothesize that molecular, cellular and whole muscle contractile performance will be most improved in men by traditional low-velocity, high-load resistance training, and in women by high-velocity, low-load power training. Moreover, sex-specific structural responses in myofilament remodeling, protein expression and post- translational modifications will explain these sex-specific performance adaptations to each modality. To test our hypotheses, data will be gathered from 50 healthy, sedentary older men and women (65-75 years) prior to and following a 16-week unilateral exercise training program in which one leg undergoes resistance training and the other power training. The Specific Aims of this project are to identify the sex-specific effects of low-velocity resistance training versus high-velocity power training on: Aim 1) skeletal muscle function at the molecular, cellular and whole muscle levels, and Aim 2) protein expression and modification as well as size at the molecular and cellular levels. Our within subject, unilateral intervention design provides a powerful model to minimize the effects of between-subject variability, and our translational approach will take advantage of our unique expertise with state-of-the-art measures from the molecular to whole body levels. Our results will challenge conventional wisdom by determining the sex-specific responses in intrinsic skeletal muscle adaptations to different exercise training programs. We will advance scientific knowledge by providing critically- needed information regarding the specific molecular and cellular determinants that support exercise-induced improvements in muscle performance. This knowledge will have a significant positive impact on the clinical care of older adults by providing novel insight about optimal exercise interventions to improve skeletal muscle function in each sex, and by identifying potential new therapeutic targets for pharmaceutical interventions. Thus, this project is highly relevant to the mission and vision of NIA to support biological research to mitigate conditions associated with aging that may limit health and independence in older adults.