Study of Muscle, Mobility and Aging (SOMMA)

肌肉、活动能力和衰老研究 (SOMMA)

• 批准号: 10015194
• 负责人: STEVEN RON CUMMINGS
• 金额: $ 400.15万
• 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 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10015194
• 关键词: Address; Affect; Age; Aging; Animal Model; Archives; 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; 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; 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; 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随着年龄的增长而下降，有些人比其他人更严重，往往导致行动能力残疾 依赖性，生活质量下降，以及巨大的医疗费用。与年龄相关的生物学作用 骨骼肌的变化对运动能力的下降知之甚少。我们假设肌肉质量 和产生ATP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，我们还假设去神经支配，氧化损伤， 和自噬流减少相互作用，导致健康、耐力下降， 行动不便。我们还将使用RNAseq的转录组学分析来发现基因的模式， 表达，在随着年龄的增长而丧失流动性方面发挥重要作用。 在肌肉活动性和衰老研究（SOMMA）中，一项针对男性和女性的前瞻性纵向研究 年龄在70至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先进的 最先进的技术与严格的质量控制，以测试这些假设，并发现新的途径， 随着年龄的增长而丧失流动性。我们将通过MRI测量股四头肌收缩体积，通过 d3肌酸稀释。我们将使用31 PMRS评估股四头肌产生ATP的能力（ATP最大值）。 在组织形式中，肌肉活检量化去神经和收缩蛋白的氧化损伤。SOMMA将 成为第一个量化自噬通量的人，以评估自噬在衰老导致的移动性丧失中的作用。我们使用 在新鲜组织上进行呼吸测量以量化线粒体对ATP max和移动性残疾的贡献。 这些特性相互作用：例如，自噬通量的减少促进了氧化性 损伤和去神经支配，了解这些关系将指导分析和解释 我们的成果此外，我们将使用无偏RNA测序（RNA-seq）来分析整个转录组， 为了发现基因簇与个体适应性丧失率（峰值）之间的新关联， VO 2），肌肉质量和行动能力残疾的风险。 位于维克森林和匹兹堡的现场中心，在招聘和留住人才方面有着出色的记录 复杂研究中的老年人将入组875名年龄在70-89岁之间、步态速度≤ 1.0 m/s的女性和男性， 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可以识别和优先考虑新疗法和定制运动方案的目标。我们 还将创建一个独特的组织、血液和关于重要临床结果的纵向数据档案， 科学界可以用来有效地测试新的假设，肌肉和丧失流动性， 衰老