A gradual loss of muscle mass is a common problem afflicting people as they age. Ultimately, this results in diminished strength which predisposes people to injury and may force a change to more restrictive life-styles. The long-range objectives of this project focus on mechanisms responsible for atrophy and suboptimal regeneration of muscle that accompanies aging. Specifically, this work will probe regulation of skeletal muscle satellite cells. These are muscle precursor cells that persist in a quiescent state throughout adult life and are responsible for muscle regeneration and fiber hypertrophy. In order for satellite cells to contribute to muscle repair or growth, they must first be activated from their quiescent state. The process of satellite cell activation is particularly relevant to muscle aging because there is a pronounced delay in activation of quiescent satellite cells in old muscle, and the physiological explanation for this delayed response is not clear. Based on recent research, we hypothesize that hepatocyte growth factor/scatter factor (HGF) is the primary trigger for activating quiescent satellite cells in injured adult muscle. This proposal is designed to investigate the role of HGF in satellite cell activation and the manner in which the activation process may be affected by age. In the proposed experiments, satellite cell culture and whole animal experimental systems will be employed to determine the presence and expression of HGF in rat skeletal muscle as a function of age and injury and to assess the physiological significance of HGF action on satellite cells.
The specific aims for this proposal are: (1) to evaluate the presence of HGF in skeletal muscle and to document changes in HGF expression with injury and age, and (2) to evaluate the role of HGF in satellite cell activation in vivo. A thorough understanding of these satellite cell functions will lead to possible strategies for alleviating problems associated with muscle repair and atrophy during aging.
| Sheehan, S M; Tatsumi, R; Temm-Grove, C J et al. (2000) HGF is an autocrine growth factor for skeletal muscle satellite cells in vitro. Muscle Nerve 23:239-45 |
| Temm-Grove, C J; Wert, D; Thompson, V F et al. (1999) Microinjection of calpastatin inhibits fusion in myoblasts. Exp Cell Res 247:293-303 |
| Sheehan, S M; Allen, R E (1999) Skeletal muscle satellite cell proliferation in response to members of the fibroblast growth factor family and hepatocyte growth factor. J Cell Physiol 181:499-506 |
