Skeletal Muscle lipid and Insulin Resistance in Aging

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Aging is associated with alterations in skeletal muscle energy metabolism, insulin resistance and a higher prevalence of type 2 diabetes mellitus (T2DM). Aging is also associated with a progressive loss of muscle mass and increased adiposity, known as sarcopenic obesity, which leads to mobility limitations and disability. However, the causes of insulin resistance and sarcopenia in humans are not known. This project will provide novel information regarding potential factors underlying both metabolic dysfunction and sarcopenia in aging muscle - namely, mitochondria and the accumulation of intramyocellular lipids. Within this conceptual framework we will help elucidate the biological underpinnings of these two significant health problems related to aging. In addition, we will provide intervention-based evidence to better understand these complex age-related disorders and whether mitochondria or intramyocellular lipids are modifiable targets for improved prevention or treatment strategies for metabolic and muscle dysfunction. Therefore, our overall objectives are to employ highly innovative methods in muscle biopsy specimens in order to determine the functional and clinically relevant consequences of these interventions as well as alterations in several novel biochemical and molecular factors potentially underlying these intervention effects on human skeletal muscle.