Skeletal muscle is a major consumer of plasma-borne free fatty acids (FFA), accounting for (50% of whole-body FFA disposal in the post-absorptive state. However, age-related changes in muscle mass and/or respiratory capacity may impair the ability of older persons to oxidize FFA released via lipolysis. Such an impairment could contribute to the increased prevalence of central obesity, dyslipidemia, and associated co-morbidities found in the elderly population. Thus, the overall goal of this project is to determine the influence of aging on muscle FFA utilization in humans. The following specific hypotheses will be tested: 1. Muscle FFA utilization is reduced in older persons, not only as a result of a decrease in muscle mass, but also as a result of a decline in FFA use per kg of muscle. The latter is hypothesized to be related to the decline in muscle respiratory capacity with age. 2. The decrease in FFA use per kg of muscle with aging is the result of a reduction in the rate of FFA transport across the inner mitochondrial membrane. 3. Endurance exercise training will ameliorate deficits in muscle FFA utilization in older individuals. These hypotheses will be tested by using tracer methodology in conjunction with arteriovenous balance measurements to quantify FFA uptake and oxidation across the legs of healthy young and older men and women. Subjects will be studied during acute exercise, as well as at rest, to magnify any age-related differences in muscle FFA metabolism, while FFA availability will be controlled via administration of acipimox, heparin, and Intralipid. Both medium-chain and long-chain fatty acid tracers (i.e., 1-14C-octanoate and 1-13C-oleate) will be used to determine whether mitochondrial membrane transport limits FFA utilization in older persons. These will be the first comprehensive studies of muscle FFA metabolism in older humans.
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