It is projected that the number of persons 65-years-old and over in the US will more than double by the middle of this century. A common result of aging is the age-associated atrophy of skeletal muscle, sarcopenia. Myosin heavy chain (MyHC) is an important skeletal muscle contractile protein that has different isoforms, the proportions of which are negatively impacted by age. Also, the anabolic cytokine, insulin-like growth factor (IGF-I) declines with advancing age and is associated with increased mortality. The proposed research would determine the responsiveness of the fast type II (lla, IIx, lib) MyHC promoters to exogenous IGF-I stimulation. The role of the IGF-I responsive signaling pathways calcineurin, Ca2???? protein kinase, and mitogen activated protein-kinase in type II MyHC promoter activation will be established. The proposed research will also examine which regions of the type II MyHC promoters are responsive to IGF-I stimulation and the IGF-I responsive transcription factors that bind to these promoter regions. This information will be used to study MyHC promoter transcription factor deficiency in old muscle and to restore these transcription factors and type II MyHC promoter activity in old muscle with IGF-I treatment.
| Shanely, R Andrew; Zwetsloot, Kevin A; Childs, Thomas E et al. (2009) IGF-I activates the mouse type IIb myosin heavy chain gene. Am J Physiol Cell Physiol 297:C1019-27 |
