Study of Muscle, Mobility and Aging (SOMMA)

肌肉、活动能力和衰老研究 (SOMMA)

• 批准号: 10170192
• 负责人: STEVEN RON CUMMINGS
• 金额: $ 512.25万
• 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/10170192
• 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; 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.

流动性不可避免地随着年龄的增长而下降，在某些人中，机动性通常会导致流动性残疾 依赖性，生活质量下降以及巨大的医疗保健费用。与年龄有关的生物学的作用 骨骼肌在迁移率下降时的变化知之甚少。我们假设肌肉质量 并且产生ATP的能力是老年人迁移障碍的强大决定者。基于 从肌肉衰老实验室研究的进步，我们还假设去神经，氧化损伤， 并扩大自噬的相互作用，并导致健身，耐力和风险增加的下降 流动性残疾。我们还将使用RNASEQ的转录组分析来发现基因模式 表达在失去衰老的流动性中起重要作用。 在研究肌肉流动性和衰老（Somma）的研究中，一项对男性和 70至90岁的妇女，我们的临床和实验室科学专家团队将使用创新和最新 具有严格质量控制的ART技术来检验这些假设，并发现了新的途径 衰老失去流动性。我们将通过MRI和总肌肉质量来测量股四头肌的收缩量 D3创建稀释。我们将使用31pmrs评估股四头肌生成ATP（ATPMAX）的能力。 在组织形式中，肌肉活检量化了对收缩蛋白的神经保护和氧化损害。索玛会 成为第一个量化自噬通量以评估自噬在随着衰老失去迁移率中的作用的人。我们使用 新鲜组织上的呼吸测定法，以量化线粒体对ATPMAX和迁移率障碍的贡献。 这些特性相互作用：例如，改善的自噬通量促进了氧化的积累。 损害和神学以及理解这些关系将指导的分析和解释 我们的结果。此外，我们将使用公正的RNA测序（RNA-Seq）来介绍整个转录组 发现基因簇与个体变化之间的新关联（峰值） VO2），肌肉质量和流动性残疾的风险。 Wake Forest和Pittsburgh的野外中心，并具有出色的招聘和保留记录 在复杂研究中的老年人将招募875名年龄70-89岁的男性，战斗速度≤1.0m/s， 提供足够的能力来识别个人与财产组合之间的重要关系 以及出行残疾的风险。 Somma可以确定并确定针对新的治疗剂和量身定制运动方案的目标。我们 还将创建一个独特的组织，血液的存档，并具有有关重要临床结果的纵向数据 科学界可以用来有效检验有关肌肉的新假设和通过 老化。