During the previous funding period several novel methodologies were developed to measure the synthesis rates of specific muscle proteins (an essential component of the remodeling process to maintain the quality of a protein) and were applied to them to determine the mechanism of age-related muscle wasting, weakness, and increased fatigability. An age-related decline in synthesis rate of mitochondrial protein (mito protein) and myosin heavy chain (MHC) was observed while the synthesis rate of the sarcoplasmic protein (sarc. protein) tends to increase. Mito protein synthesis declined maximally by middle age with no further decline with age, while the MHC synthesis rate continues to decline. Three months of resistance training enhanced MHC synthesis in the middle aged subjects and to a lesser extent in older subjects, while mito protein and sarc. protein synthesis did not change. In this renewal application we propose to measure synthesis rates of mito protein, mito oxidative enzymes, and muscle fatigability in 125 men and women from 20 to 90+ years to test a hypothesis that the ability of mitochondria to remodel decline from the fourth decade. We will determine whether the decline of muscle strength that is observed in the fifth decade is related to the decline in synthesis rates of the contractile proteins such as MHC and actin. We will measure synthesis rates of mito protein, MHC, its isoforms, actin and sarc. protein in young, middle aged, and older subjects before and after two months of aerobic training or resistance training or flexibility training (control) to determine whether the exercise stimulates synthesis rates of these proteins and whether age modulates the response to exercise. We will also determine whether previously observed changes in mito protein synthesis are prevented by chronic aerobic training and will determine whether prior aerobic training provides an advantage for stimulating synthesis rate of contractile proteins by resistance training. We will determine whether the changes in synthesis rates of these specific proteins are related to the changes in muscle functions. The studies will define age of onset of the decline in the remodeling process of these specific proteins in relation to the functional changes and the potential role of aerobic and resistance exercise in reversing the age-related changes.
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