Novel Factors for Muscle Mass and Strength in Adults

摘要/项目总结 与肥胖相关的肌肉质量和力量下降是一个重要的公共卫生问题。未来的干预措施将 这取决于识别参与这些肌肉变化的生理途径和随之而来的身体 功能我们建议调查新的危险因素，并确定影响年龄相关性的相关途径。 肌肉质量、质量、力量和步态速度下降。我们的长期目标是确定新的风险因素 以及影响与年龄相关的肌肉和身体功能下降的相关途径。目标是 确定抗氧化剂摄入、血管功能和线粒体功能在肌肉质量损失中的作用， 在成年男性和女性的质量，力量和步态速度，提供新的公共卫生见解。我们假设 抗氧化剂摄入量低，血管功能受损，线粒体DNA拷贝数（mtDNA-CN）降低， 每一个都会导致肌肉质量、质量、力量和步态速度的下降，甚至会导致 确定的风险因素。我们将通过4个目标来解决这项工作，使用来自一口井的多达1，912名参与者- 特征化队列，即Fractionary Offspring研究。目的1将研究抗氧化剂的关联 摄入量（维生素C，维生素E和总类胡萝卜素）与肌肉质量，质量，力量的措施[定义 作为apapapricular瘦肌肉质量/身高2，握力与手臂瘦肌肉质量比（手臂肌肉质量），变化 在apapapricular瘦肌肉质量/高度2，握力随时间的变化]和步态速度的变化。目的2 将检查血管功能（通过肱动脉静息特征评估， 充血性血流反应和主动脉僵硬，测量肌肉质量、质量、强度和 步态速度目的3将研究mtDNA-CN与肌肉质量、质量、力量指标的相关性。 和步态速度的变化。最后，目标4将检查评估的新风险因素的综合影响 从目标1-3沿着以及确定的风险因素（蛋白质摄入、体力活动和炎症）， 测量肌肉质量、质量、力量和步态速度的变化。我们计划验证来自 这些目标通过使用一个验证队列，心血管健康研究。 预期结果是证据表明低抗氧化剂摄入、血管受损和低mtDNA-CN是新的 与年龄相关的肌肉质量、质量、力量和步态速度下降的风险因素。的意义 建议的工作是，它将增加我们对个人贡献和综合影响的理解， 提出了与年龄相关的肌肉和身体功能下降的新风险因素。这项研究将提供一个 为未来旨在减少或预防年龄相关衰退的多模式干预研究奠定了坚实的基础 在老年人中的肌肉及其衰弱的后果。 1

ABSTRACT / PROJECT SUMMARY Age-related decline in muscle mass and strength is an important public health issue. Future interventions will depend on identifying the physiologic pathways involved in these muscle changes and consequent physical function. We propose to investigate novel risk factors and identify associated pathways that affect age-related declines in muscle mass, quality, strength and gait speed. Our long term goal is to identify novel risk factors and associated pathways that affect age-related declines in muscle and physical function. The objective is to determine the roles of antioxidant intake, vascular function and mitochondrial function in loss of muscle mass, quality, strength and gait speed in adult men and women, providing new public health insights. We hypothesize that low antioxidant intake, impaired vascular function and lower mitochondrial DNA copy number (mtDNA-CN) will each contribute towards decreased muscle mass, quality, strength and gait speed, even accounting for established risk factors. We will address this work via 4 aims using up to 1,912 participants from a well- characterized cohort, the Framingham Offspring Study. Aim 1 will examine the association of antioxidant intakes (Vitamin C, Vitamin E and total carotenoids) with measures of muscle mass, quality, strength [defined as appendicular lean muscle mass/height2, grip strength-to-arm lean mass ratio (arm muscle quality), change in appendicular lean muscle mass/height2, change in grip strength over time] and change in gait speed. Aim 2 will examine the association of vascular function (assessed by brachial artery resting characteristics, hyperemic flow response and aortic stiffness with measures of muscle mass, quality, strength and change in gait speed. Aim 3 will examine the association of mtDNA-CN with measures of muscle mass, quality, strength and change in gait speed. Finally, Aim 4 will examine the combined effect of the novel risk factors evaluated from Aims 1-3 along with established risk factors (protein intake, physical activity and inflammation), on measures of muscle mass, quality, strength and change in gait speed. We plan to validate the findings from these aims by using a validation cohort, the Cardiovascular Health Study. The expected outcome is evidence for low antioxidant intake, impaired vascular and low mtDNA-CN as novel risk factors for age-related decrease in muscle mass, quality, strength and gait speed. The significance of the proposed work is that it will increase our understanding of individual contributions and combined effect of the proposed novel risk factors on age-related declines in muscle and physical function. This study will provide a strong basis for future multi-modality intervention studies aimed at reducing or preventing age-related declines in muscle and their debilitating consequences among older adults. 1