Study of Muscle, Mobility and Aging (SOMMA)

肌肉、活动能力和衰老研究 (SOMMA)

• 批准号: 10441623
• 负责人: STEVEN RON CUMMINGS
• 金额: $ 513.29万
• 依托单位: CALIFORNIA PACIFIC MED CTR RES INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10441623
• 关键词: Address; Affect; Age; Aging; Animal Model; Autophagocytosis; Biological; Biopsy; Blood; Clinical; Communities; Complex; Contractile Proteins; Contracts; Creatine; Data; Denervation; Dependence; Dual-Energy X-Ray Absorptiometry; Elderly; Enrollment; Fresh Tissue; Gait speed; Gene Cluster; Gene Expression; Gene Expression Profile; Generations; Genetic Transcription; Glycolysis; Gold; Health Care Costs; Human; Image; Impairment; Individual; Intervention; Knowledge; Laboratories; Laboratory Study; Locomotion; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Methods; Mitochondria; Muscle; Muscle Contraction; Muscle Fibers; Muscular Atrophy; Organelles; Outcome; Oxidative Phosphorylation; Pathway interactions; Pattern; Persons; Physical activity; Play; Property; Prospective Studies; Quality Control; Quality of life; Records; Research; Research Design; Risk; Role; Science; Skeletal Muscle; Societies; Speed; Stimulus; Technology; Testing; Thinness; Tissues; Walking; Woman; age related; base; clinical phenotype; disability; disability risk; exercise regimen; fitness; forest; individual variation; innovation; macromolecule; member; men; meter; muscle aging; muscle form; new therapeutic target; novel; oxidative damage; prevent; prospective; quadriceps muscle; recruit; reduced muscle mass; sarcopenia; tissue archive; transcriptome; transcriptome sequencing; transcriptomics; walking speed

Mobility inevitably declines with age, more in some than other people, often leading to mobility disability with dependency, decreased quality of life, and enormous health care costs. The role of age-related biological changes in skeletal muscle on the decline in mobility is poorly understood. We hypothesize that muscle mass and the capacity to produce ATP are strong determinants of the mobility disability in older adults. Based on advances from laboratory studies of muscle aging, we also hypothesize that denervation, oxidative damage, and decreased autophagic flux interact and contribute to declines in fitness, endurance and an increased risk of mobility disability. We will also use transcriptomic profiling by RNAseq to discover patterns of gene expression that play important roles in the loss of mobility with aging. In the Study of Muscle Mobility and Aging (SOMMA), a prospective, longitudinal study of men and women age 70 to 90, our team of experts in clinical and laboratory sciences will use innovative and state-of- the-art technologies with rigorous quality control to test these hypotheses and discover new pathways for the loss of mobility with aging. We will measure quadriceps contractile volume by MRI and total muscle mass by d3 creatine dilution. We will use 31PMRS to assess the capacity of the quadriceps to generate ATP (ATPmax). In tissue form, muscle biopsies quantify denervation and oxidative damage to contractile proteins. SOMMA will be the first to quantify autophagic flux to assess the role of autophagy in the loss of mobility with aging. We use respirometry on fresh tissue to quantify the contribution of mitochondria to ATPmax and mobility disability. These properties interact: for example, decreased autophagic flux promotes the accumulation of oxidative damage and denervation, and understanding these relationships will guide the analysis and interpretation of our results. Furthermore, we will use unbiased RNA-sequencing (RNA-seq) to profile the entire transcriptome to discover new associations between clusters of genes and individual variation in rates of loss of fitness (peak VO2), muscle mass, and risk of mobility disability. Field centers at Wake Forest and Pittsburgh, with exceptional track records for recruiting and retaining older adults in complex studies, will enroll 875 women and men age 70–89 with a gait speed ≤ 1.0 m/s, providing sufficient power to identify important relationships between individual and combinations of properties and the risk of mobility disability. SOMMA may identify and prioritize targets for new therapeutics and tailored exercise regimens. We also will create a unique archive of tissue, blood, with longitudinal data about important clinical outcomes that the scientific community can use to efficiently test new hypotheses about muscle and loss of mobility with aging.

行动能力不可避免地会随着年龄的增长而下降，一些人的情况比另一些人更严重，这往往会导致行动不便 依赖，生活质量下降，以及巨大的医疗费用。年龄相关生物学的作用 骨骼肌的变化对运动能力下降的影响知之甚少。我们假设肌肉质量 产生三磷酸腺苷的能力是老年人行动能力障碍的重要决定因素。基于 从肌肉老化的实验室研究进展，我们还假设去神经，氧化损伤， 而自噬通量的减少相互作用，导致体能、耐力下降和风险增加 行动不便的人。我们还将使用RNAseq的转录图谱来发现基因模式 在随着年龄增长而丧失行动能力的过程中发挥重要作用的表达。 在肌肉运动和衰老研究(Somma)中，对男性和 年龄在70岁到90岁之间的女性，我们的临床和实验室科学专家团队将使用创新和最新的 具有严格质量控制的尖端技术，以检验这些假设并发现 随着年龄的增长，行动不便。我们将通过MRI测量股四头肌的收缩体积，通过 D3肌酸稀释。我们将使用31PMRS来评估股四头肌产生ATP的能力(ATPmax)。 在组织形式中，肌肉活组织检查量化了去神经和对收缩蛋白的氧化损伤。Somma将会 是第一个量化自噬通量的人，以评估自噬在随着年龄增长而丧失机动性方面的作用。我们用 对新鲜组织进行呼吸测量，以量化线粒体对ATPmax和行动障碍的贡献。 这些特性相互作用：例如，自噬通量的减少促进了氧化的积累 损伤和失神经，并了解这些关系将指导分析和解释 我们的结果。此外，我们将使用无偏rna测序(rna-seq)来描述整个转录组。 发现基因簇和个体适应度损失率变异之间的新关联(峰值 VO2)、肌肉质量和行动不便的风险。 位于维克森林和匹兹堡的外地中心，在招聘和留住方面有出色的记录 复杂研究中的老年人，将招收年龄在70-89岁的875名男女，步速≤为1米/S， 提供足够的能力来识别单个属性和属性组合之间的重要关系 以及行动不便的风险。 Somma可能会确定新疗法和量身定做的运动养生法的目标并确定其优先顺序。我们 还将创建一个独特的组织、血液档案，其中包含关于重要临床结果的纵向数据 科学界可以用来有效地测试关于肌肉和活动能力丧失的新假说 衰老。