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.

肌肉减少症是与年龄相关的骨骼肌质量和功能的丧失，可预测发病率，死亡率和过多的医疗保健费用。除了运动以外，生活方式疗法减缓了肌肉减少症的发展在老年男女中，仍然难以捉摸。线粒体功能障碍是在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饮食（LA; 18：2n6）是心脂蛋白的首选脂肪酰基成分，可改善肌肉力量和身体活动能力。在小鼠中，富含饮食的油脂会增加富含LA的心脂蛋白（例如4-la- Cardiolipin）和线粒体呼吸。因此，富含LA的油增加4-LA-核脂蛋白的作用和将评估肌肉减少症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，饮食中必须获得的必需脂肪酸，饮食来源是唯一补充LA的方法是Cardiolipin，这是内部线粒体膜的特征磷脂。在II期双盲，随机对照试验中，这项研究将测试补充LA油的效果要改变肌肉力量，身体迁移，4-LA-核酸脂蛋白和线粒体功能。识别 LA和线粒体能力之间的机械联系可以有助于机械发展有针对性的疗法减慢或停止肌肉减少症以及其他与线粒体相关的疗法老年人发展的条件。