The loss of muscle mass and strength with age (sarcopenia), as well as their gain with strength training(ST), is highly variable among men and women. A significant fraction (30-60%) of inter-individual variability in skeletal muscle phenotypes, including strength, mass, and muscle quality, is due to genetic factors. Identifying those genes that contribute to muscle phenotypes is important in order to assess risk for skeletal muscle dysfunction, especially for the elderly. A major difficulty, however, in pursuing genetic studies in humans is determining which of the 35,000+ genes to screen, given the limited information available for most genes. Consequently, we have used micro array and quantitative PCR techniques to identify 6 candidate genes important to the strength, mass and quality of skeletal muscle in the contexts of age, sex, and ST. Moreover, we have identified 4 additional genes from the literature with known polymorphisms, and have strong preliminary data for three of these genes indicating associations with muscle size and strength in a cohort of elderly men. In the present project, we propose to identify polymorphic variation in the 6 expression-based candidate genes and determine the association of specific alleles and multi-locus genotypes within all 10 candidate genes with baseline measures of muscle strength, mass and quality, as well as ST-induced gains in these phenotypes. We will achieve these aims in two existing cohorts: 1) a cross-sectional cohort of -500 men and women across the adult age span from the Baltimore Longitudinal Study of Aging (BLSA), and 2) a cohort of 100 Caucasian and 100African American men and women (>65 yr.) who have completed a controlled 16 week ST intervention(ERC cohort). The results of this investigation will determine the influence of genetic variation within these biologically plausible candidate genes on muscle phenotypes that can be important limiting factors for physical function in the elderly. The identification of such genes will provide an important foundation for understanding the genetic architecture of muscle phenotypes, with the long-term goal of identifying individuals with genetic susceptibility for sarcopenia.
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