Skeletal muscle is one of the most abundant tissues in the body because it supports fundamental processes of lifelike movement and breathing. Muscle stem cells, called satellite cells, support muscle development and life-long muscle repair through the activation of the b-catenin-mediated canonical Wnt pathway. Therefore, any changes in the number of satellite cells or in the activation of canonical Wnt signaling can impair myogenesis throughout life. In this dissertation research, we examined the role of the age-related molecule Klotho during early postnatal muscle development by testing the hypothesis that Klotho influences myogenesis through the epigenetic regulation of key genes required for satellite cell-mediated myogenesis. Regulatory pathways that influence muscle growth and repair, like Wnt/b-catenin signaling, are particularly interesting in the context of this work because activation of the Wnt/b-catenin pathway is the limiting step in myogenic differentiation. Through this work we identified a novel pathway that showed Klotho influenced myogenesis through the epigenetic regulation of canonical Wnt genes mediated by the histone 3 lysine 27 (H3K27) demethylase Jmjd3. We showed muscle cells treated with Klotho had reduced Jmjd3 expression and increased gene repressive H3K27 methylation (H3K27m2/3). Subsequent experiments revealed a reduction of canonical Wnt gene expression in muscle cells treated with Klotho and in whole muscles of mice that continuously express elevated klotho. We showed satellite cells are particularly responsive to Klotho during early postnatal development, a characteristic that did not occur in adult muscles. Our data revealed muscle cells treated with Klotho and siRNA targeting Jmjd3 did not have additive effects on Wnt gene expression indicating that Klotho and Jmjd3 operate in a similar pathway. Immunohistological analysis showed Klotho reduced the proportion of satellite cells with active b-catenin, suggesting Klotho’s effects on myogenesis may be caused by reduced Wnt/b-catenin signaling. Next, we developed a mouse model with a satellite cell-specific mutation in the Jmjd3 gene to test whether knocking down Jmjd3 in satellite cells of developing muscle would mimic the effects of Klotho on myogenesis and the canonical Wnt pathway. We were surprised to find that muscle-specific Jmjd3 is essential for neonatal survival. Although Jmjd3 mutant mice died within hours after birth, we confirmed Jmjd3 mutant mice muscles had reduced expression of the canonical Wnt genes identified in prior experiments and immunohistological work showed the proportion of satellite cells with active b-catenin was reduced in the absence of Jmjd3. Collectively, this work showed elevated Klotho and reduced Jmjd3 modulated myogenesis through a similar epigenetic regulatory pathway that influenced b-catenin-mediated canonical Wnt signaling. Of note, our work revealed expression of muscle-specific Jmjd3 is essential for survival and therefore should continue to be investigated in processes affecting myogenesis.