Alcohol and dysfunctional skeletal muscle mass: implications in aging

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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.