Changes in Myogenic Progenitor Potential with Age

• Aim 1. Identify the signaling pathways that account for the distinct function of Wnt1 Db in repressing adipogenic gene expression in myogenic progenitors compared to other Wnts that promote myogenic differentiation and hypertrophy, and determine the role of changes in Wnt signaling in altering myogenic progenitor potential with age. • Aim 2. Myofibroblasts will be characterized in vitro to determine if adipogenic potential increases with age, potentially contributing to intermyocellular lipid. Co-culture of myogenic progenitors and myofibroblasts from different aged mice will determine if age affects their interaction. • Aim 3. Myogenic progenitors will be "exercised" in vitro with a Flexcell stretcher to attempt to alter adipogenic potential, as this in vitro model has been shown to inhibit adipogenic conversion in myoblasts through enhanced expression of Wnt1 Ob. Lipid accumulation and myotube size will be quantified to determine if the effects of exercise differ with age through altered signaling pathway response. • Aim 4. Myogenic progenitors and myofibroblsts will be isolated and cultured from older compared to younger humans in collaboration with ongoing exercise intervention studies by our co-investigator Dr. Bret Goodpaster, to characterize myogenic and adipogenic differentiation potential that will be correlated with age, muscle adiposity, size, and strength. The effect of exercise on muscle properties in vivo will be assessed in relation to changes in myogenic progenitor potential in vitro. We will examine the underlying mechanisms involved, and whether response differs with age.