Alcohol and dysfunctional skeletal muscle mass: implications in aging

酒精和骨骼肌质量功能障碍：对衰老的影响

• 批准号: 10811081
• 负责人: Liz Simon
• 金额: $ 18.25万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10811081
• 关键词: Activities of Daily Living; Address; Age; Aging; Alcohol consumption; Alcoholic Liver Diseases; Alcohols; Area; Bioenergetics; Biological Markers; Biopsy; Caring; Chronology; Clinical Research; Cross-Sectional Studies; Data; Disease; Elderly; Electron Transport; Equilibrium; HIV; HIV Infections; Health; Health Care Costs; Heavy Drinking; High Prevalence; Homeostasis; Impairment; Individual; Infrastructure; Intervention; Life Expectancy; Life Style; Link; Liver diseases; Longevity; Maintenance; Measures; Mediating; Mitochondria; Mitochondrial DNA; Mitochondrial Proteins; Muscle; Muscle Mitochondria; Muscle function; Myoblasts; Myopathy; National Institute on Alcohol Abuse and Alcoholism; Outcome; Pathology; Patient Self-Report; Persons; Physical Performance; Physiological; Predisposition; Production; Quality of life; Reporting; Risk; Risk Factors; Risk Reduction; Role; SIV; Science; Skeletal Muscle; Strategic Planning; Syndrome; Testing; United States; alcohol consequences; alcohol effect; alcohol exposure; alcohol research; binge drinking; cohort; comorbidity; frailty; improved; indexing; insight; mitochondrial dysfunction; mortality; muscle form; muscle strength; nervous system disorder; pharmacologic; prevent; protein expression; reduced alcohol use; stressor; therapeutic target; walking speed

Abstract Alcohol and dysfunctional skeletal muscle mass: implications in aging Alcohol use decreases skeletal muscle strength and function resulting in alcohol-related myopathy; one of the earliest alcohol-associated pathologies. Alcohol use is disproportionately on the rise among older individuals, with 25% engaging in heavy drinking and 11% reporting binge drinking. The increasing average life expectancy in the United States leads us to predict that alcohol use will be an important factor exacerbating dysfunctional SKM mass in chronological aging. Functional skeletal muscle mass is a critical contributor to overall physical performance. Poor physical performance is closely linked to frailty syndrome that increases the risk of adverse health outcomes, is a significant predictor of needing specialized care, and increases the risk for all-cause mortality. Hence there is a critical need to understand the underlying mechanisms that can be targeted to reduce risk, delay onset, or better manage frailty. One of the salient skeletal muscle-mediated mechanisms contributing to physical performance and frailty is mitochondrial function. However, there is a gap in our understanding of the interactions of alcohol use on physical performance and frailty in chronological aging, and on the role of mitochondrial dyshomeostasis as a contributing factor. We propose a cross sectional study among people over the age of 60 with or without alcohol use, with no overt underlying comorbidities, to test the overall hypothesis that alcohol use decreases physical performance and increases frailty risk. We will investigate the mechanisms involved in alcohol-associated dysregulation of SKM mitochondrial homeostasis to identify modifiable targets amenable for lifestyle or pharmacological interventions. The results generated using these hypothesis-driven studies will provide data that will inform translational targeted interventions to improve muscle mitochondrial function. This application addresses one of the target areas of NIAAA's Strategic Plan to develop effective strategies to prevent consequences of alcohol use in older individuals and is highly responsive to the NOSI: “Alcohol and aging” and leverages the interdisciplinary translational team science approach within an outstanding scientific infrastructure provided by the Comprehensive Alcohol Research Center at LSUHSC-NO.

抽象酒精和功能障碍骨骼肌质量：衰老的影响 饮酒会降低骨骼肌力量和功能，从而导致与酒精有关的肌病。中的一个 最早的酒精相关病理。饮酒的年龄较大的人不成比例地增加 有25％的人参加大量饮酒，11％的报告暴饮暴食。平均预期寿命增加 在美国，我们预测酒精的使用将是加剧功能失调的重要因素 年代老化的SKM质量。功能性骨骼肌质量是整体物理的关键因素 表现。身体表现不佳与虚弱的综合症密切相关，这增加了广告的风险 健康成果，是需要专业护理的重要预测指标，并增加了全因护理的风险 死亡。因此，迫切需要了解可以降低目标的基本机制 风险，延迟发作或更好地管理脆弱。显着的骨骼肌介导的机制之一 身体表现和脆弱是线粒体功能。但是，我们对 酒精使用在时间顺序衰老中的身体性能和脆弱的相互作用，以及 线粒体dyshomeostasis是一个促成因素。我们建议在人们之间进行横断面研究 有或不使用酒精的60岁，没有明显的潜在合并症，可以检验总体假设 饮酒会降低身体表现并增加脆弱的风险。我们将研究机制 参与SKM线粒体稳态的酒精相关失调以识别可修改的靶标 适合生活方式或药理干预措施。使用这些假设驱动的结果产生的结果 研究将提供数据，这些数据将为翻译干预措施提供信息，以改善肌肉线粒体 功能。该申请涉及NIAAA战略计划的目标领域之一，以制定有效 防止老年人饮酒后果的策略，并且对NOSI有很高的反应： “酒精和老化”并利用跨学科的翻译团队科学方法 LSUHSC-NO综合性酒精研究中心提供的科学基础设施。