Study of Muscle, Mobility and Aging: SOMMA2

肌肉、活动能力和衰老研究：SOMMA2

• 批准号: 10913728
• 负责人: STEVEN RON CUMMINGS
• 金额: $ 310.9万
• 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 2024-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10913728
• 关键词: Aging; Biological; Biopsy; Blood; Cardiopulmonary; Cell Aging; Cell Nucleus; Cessation of life; Clinical; Communities; DNA Damage; DNA Sequence Alteration; Data; Dementia; Elderly; Explosion; Foundations; Gene Expression; Goals; Health; Hematopoiesis; Inflammatory; Infrastructure; Lead; Leg; Lipids; Measures; Mitochondria; Muscle; Muscle Cells; Muscle Mitochondria; Mutation; Outcome; Oxidative Stress; Participant; Pathway interactions; Phenotype; Physical Function; Property; Proteins; Research; Research Personnel; Resources; Scientist; Specimen; Talents; Testing; Time; Transcript; Translating; Walking; age related; career development; cell type; cohort; design; disability; disability risk; fitness; follow-up; healthspan; mitochondrial dysfunction; muscle aging; novel strategies; oxidative damage; pandemic disease; preservation; prevent; primary outcome; recruit; repaired; repository; senescence; sex; single nucleus RNA-sequencing; transcriptomics

The Study of Muscle Mobility and Aging (SOMMA) is a cohort uniquely designed to identify fundamental age- related pathways contributing to important clinical and gerontologic outcomes. Newly elucidated biologic pathways of aging have fueled an explosion of novel approaches hypothesized to extend health span. However, how these pathways contribute to salient health outcomes in older adults such as disability and dementia-free survival is not known. SOMMA2 extends SOMMA1, which tests the paradigm that properties of muscle, including muscle mitochondrial energetics, predict the onset of objective mobility disability i.e., the inability to walk 400m. Nevertheless, SOMMA1 established a rich repository of muscle tissue, blood, and phenotyping, to expand research to other pathways and clinical endpoints. SOMMA2 builds on this foundation. It integrates the talents of some of the nation’s leading aging researchers to understand the biological drivers of age-related changes in physical function and the onset of disability and death. SOMMA2 will add 600 new participants to increase its diversity and provide sufficient power to test whether biological pathways predict our composite outcome of ADL disability, dementia, or death, and the co-primary outcome of objective mobility disability. SOMMA2 will also gather unprecedented longitudinal data with repeat muscle biopsies to identify changes in biological pathways in muscle tissue that are associated with age-related changes in muscle power and cardiopulmonary fitness (VO2 peak). SOMMA2 will study distinct but interrelated biological pathways of aging. DNA damage and insufficient repair lead to DNA mutations and clonal hematopoiesis. Increasing oxidative stress damages lipids and proteins in muscle with aging, leading to declines in muscle power and fitness. DNA damage and mitochondrial dysfunction may trigger cellular senescence in muscle and the pro- inflammatory senescence associated secretory phenotype (SASP). SOMMA2 will also use longitudinal transcriptomics in muscle to test hypotheses related to DNA damage/repair and senescence, and to discover other pathways that influence change in power and fitness. SOMMA2 will employ repeated single nucleus snRNA seq to reveal how changes in different muscle-resident cell types with aging contribute to the loss of power and fitness. SOMMA has already become a major resource for investigators, particularly young scientists, to study diverse facets of aging and provide career development opportunities. SOMMA will continue to release data to the scientific community, provide data and specimens, and offer analytic help. SOMMA2 will serve as a translational aging research engine for decades to come.

肌肉流动性和衰老的研究（SOMMA）是一个独特的队列设计，以确定基本的年龄- 相关的途径，有助于重要的临床和老年学的结果。新阐明的生物 衰老的途径已经刺激了被假设为延长健康寿命的新方法的爆炸。 然而，这些途径如何有助于老年人的显著健康结果，如残疾和 无痴呆存活率尚不清楚。SOMMA 2扩展了SOMMA 1，它测试了 肌肉，包括肌肉线粒体能量学，预测客观移动性残疾的发作，即，的 无法行走400米。然而，SOMMA 1建立了一个丰富的肌肉组织，血液， 表型分析，将研究扩展到其他途径和临床终点。SOMMA 2就是建立在这个基础上的。 它整合了一些国家领先的老龄化研究人员的人才，以了解生物驱动因素 与年龄相关的身体功能变化以及残疾和死亡的发生。SOMMA 2将新增600个 参与者增加其多样性，并提供足够的力量来测试生物途径是否预测我们的生活。 ADL残疾、痴呆或死亡的复合结局，以及客观活动性的共同主要结局 残疾。SOMMA 2还将通过重复肌肉活检收集前所未有的纵向数据， 肌肉组织中与年龄相关的肌肉力量变化相关的生物途径变化 和心肺功能（VO 2峰值）。SOMMA 2将研究不同但相互关联的生物学途径， 衰老DNA损伤和修复不足导致DNA突变和克隆造血。增加 随着年龄的增长，氧化应激会损害肌肉中的脂质和蛋白质，导致肌肉力量下降， 健身DNA损伤和线粒体功能障碍可能引发肌肉细胞衰老， 炎性衰老相关分泌表型（SASP）。SOMMA 2还将使用纵向 肌肉转录组学用于测试与DNA损伤/修复和衰老相关的假设，并发现 其他影响力量和健康变化的途径。SOMMA 2将使用重复的单核 snRNA序列揭示了不同肌肉驻留细胞类型的变化如何随着衰老而导致 力量和健康SOMMA已经成为调查人员，特别是年轻人的主要资源 科学家，研究老龄化的各个方面，并提供职业发展机会。SOMMA将 继续向科学界发布数据，提供数据和样本，并提供分析帮助。 SOMMA 2将在未来几十年内作为一个转化衰老研究引擎。