Improving sarcopenia by targeting mitochondria

通过靶向线粒体改善肌肉减少症

基本信息

批准号：
10736713
负责人：
MARTHA A BELURY
金额：
$ 67.88万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-05 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10736713
关键词：
ATP Synthesis Pathway Adult Affect Age Aging Baltimore Biological Markers Blood Cardiolipins Cardiometabolic Disease Central obesity Clinical Trials Data Development Diet Dietary intake Double-Blind Method Dyslipidemias Elderly Electron Transport Essential Fatty Acids Event Exercise Extensor Extravasation FDA approved Fatigue Gait speed Health Health Care Costs Human Immobilization Impairment Inner mitochondrial membrane Insulin Resistance Intake Intramuscular Isotonic Exercise Leg Lifestyle Therapy Link Linoleic Acids Longitudinal Studies Lysophosphatidylcholines Mammals Measures Methods Mitochondria Morbidity - disease rate Mus Muscle Muscle Weakness Muscle function Muscular Atrophy Nutritional Requirements Oils Oleic Acids Omega-3 Fatty Acids Outcome Pathologic Pattern Persons Pharmaceutical Preparations Phase Phospholipids Physical Function Physical activity Placebos Plasma Postmenopause Prevention Probability Production Protons Randomized, Controlled Trials Recommendation Reporting Resistance Respiration Risk Rodent Model Role Side Skeletal Muscle Source Specific qualifier value Supplementation Testing Therapeutic Thinness Tissues Triglycerides Vegetable Oils Woman age related cardiometabolism comparison control dietary dietary approach disorder risk epidemiologic data fall risk fortification health data improved innovation linoleates long chain fatty acid mitochondrial dysfunction mortality muscle form muscle strength older men older women peer phase II trial prevent primary outcome protective effect protein intake resistance exercise sarcopenia scaffold skeletal muscle wasting targeted treatment

项目摘要

Sarcopenia, the age-related loss of skeletal muscle mass and function, predicts for morbidity, mortality and excessive healthcare costs. Other than exercise, lifestyle therapies for slowing the progression of sarcopenia in older men and women remain elusive. Mitochondrial dysfunction is a common mechanistic link between aging and many pathological factors contributing to sarcopenia. We propose to test whether supplementing the diet with an oil rich linoleic acid (LA; 18:2n6), the preferred fatty acyl constituent of cardiolipin, improves muscle strength and physical mobility. In mice, dietary LA-rich oil increases LA-rich cardiolipin (e.g., 4-LA- cardiolipin) and mitochondrial respiration. Therefore, the effect of LA-rich oil to increase 4-LA-cardiolipin and mitochondrial respiration in older people with sarcopenia will be measured evaluated. Because LA is a required nutrient for humans, e.g., an essential fatty acid that must be attained in the diet, dietary sources are the sole method to replenish LA for cardiolipin, the signature phospholipid of inner mitochondrial membranes. In a phase II double-blinded, randomized controlled trial, this study will test the effect of LA-oil supplementation to change muscle strength, physical mobility, 4-LA-cardiolipin and mitochondrial function. Identifying a mechanistic link between LA and mitochondrial capacity could aid in the development of mechanistically targeted therapies to slow or stop the progression of sarcopenia as well as other mitochondrial-related conditions that develop in older adults.

肌肉减少症，即与年龄相关的骨骼肌质量和功能丧失，可预测发病率、死亡率和过高的医疗费用。除了运动之外，生活方式疗法也可以减缓肌肉减少症的进展在老年男性和女性中仍然难以捉摸。线粒体功能障碍是线粒体之间的常见机制联系衰老和许多导致肌肉减少症的病理因素。我们建议测试是否补充富含油的亚油酸（LA；18:2n6）（心磷脂的首选脂肪酰基成分）的饮食可以改善肌肉力量和身体活动能力。在小鼠中，饮食中富含 LA 的油会增加富含 LA 的心磷脂（例如 4-LA- 心磷脂）和线粒体呼吸。因此，富含LA的油具有增加4-LA-心磷脂和将测量评估患有肌肉减少症的老年人的线粒体呼吸。因为洛杉矶是一个人类所需的营养素，例如必须从饮食中获得的必需脂肪酸，饮食来源是补充 LA 心磷脂（线粒体内膜的标志性磷脂）的唯一方法。在一项 II 期双盲、随机对照试验中，本研究将测试补充 LA 油的效果改变肌肉力量、身体活动能力、4-LA-心磷脂和线粒体功能。识别一个 LA 和线粒体能力之间的机制联系可能有助于机制的发展减缓或阻止肌肉减少症以及其他线粒体相关疾病进展的靶向治疗老年人出现的病症。