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.

摘要酒精和功能失调的骨骼肌质量：在衰老的影响 饮酒会降低骨骼肌强度和功能，导致与酒精相关的肌病;其中之一 早期酒精相关疾病老年人饮酒的比例不成比例地上升， 25%的人酗酒，11%的人酗酒。平均预期寿命的增长 在美国，我们预测酒精使用将是加剧功能失调的一个重要因素， 按时间顺序老化的SKM质量。功能性骨骼肌质量是整体身体健康的关键因素。 性能身体表现不佳与虚弱综合征密切相关，虚弱综合征增加了不良反应的风险。 健康结果，是需要专门护理的重要预测因素，并增加了所有原因的风险 mortality.因此，迫切需要了解可以有针对性地减少 风险，延迟发病，或更好地管理脆弱。其中一个显著的骨骼肌介导的机制， 是线粒体的功能。然而，我们对这一问题的理解存在差距。 酒精使用对身体表现和衰老中的脆弱性的相互作用，以及 线粒体平衡失调是一个促成因素。我们建议在超过10岁的人群中进行一项横断面研究， 年龄60岁，有或没有饮酒，没有明显的潜在合并症，以检验总体假设 饮酒会降低身体机能并增加虚弱的风险。我们将研究 参与酒精相关的SKM线粒体稳态失调，以确定可改变的靶点 适合生活方式或药物干预。使用这些假设驱动的结果 研究将提供数据，为翻译靶向干预提供信息，以改善肌肉线粒体 功能此应用程序解决了NIAAA的战略计划的目标领域之一，以制定有效的 预防老年人饮酒后果的策略，并对NOSI高度敏感： “酒精和衰老”，并利用跨学科的翻译团队的科学方法在一个杰出的 科学基础设施由LSUHSC-NO的综合酒精研究中心提供。