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.

肌肉运动和衰老研究（SOMMA）是一个独特的队列设计，以确定基本年龄