SATELLITE STEM CELL BIOLOGY

描述（改编自申请人的摘要）：卫星细胞是 肌肉特异性干细胞，其功能是修复受损的肌纤维， 为肌肉增大提供新的肌核。罗森布拉特指出， 敲除卫星细胞的增殖能力可以防止肥大 骨骼肌Blau和Wright发现卫星细胞过早地 年轻杜氏肌营养不良症患者的衰老， 再生循环。舒尔茨观察到， 随着大鼠年龄的增长，卫星细胞的增殖能力， 在人类身上也有报道海弗利克表明，正常的二倍体细胞有一个 有限的增殖寿命并达到细胞衰老。然而，比肖夫 指出，需要对自我维护标准进行严格评价， 将卫星细胞归类为干细胞还有待进行。这些 挑衅性的报告强调了一些概念框架， 具体目标。使用已确立并经验证的方法， 克隆形成测定以确定细胞的增殖潜力， 建议审查1.）是否一个重复循环的生理模型， 衰老骨骼肌的萎缩再生加速了卫星细胞的衰老， 它们的增殖能力在大鼠寿命之前就耗尽; 2.）的情况。确定IGF-1是否应用于骨骼肌或3.） 增加的收缩活动，或目标1和2两者导致a.） 用完或B.）补充旧卫星中的有限人口数据 细胞这些结果将揭示复制是否 衰老可由环境因素调节。因此，信息 从这些研究中收集的信息将为后续实验提供基础 这将测量细胞周期标志物，开始解释观察结果， 分子细节随着身体虚弱的人数迅速增加， 越来越多，它成为一个更紧迫的临床，社会和经济问题， 了解卫星细胞寿命是否以及如何维持/增强。这 因此，该提案将为自我维护如何提供新的见解， 卫星细胞的特性受补偿因子（IGF-1和 从而为更有效的干预措施奠定基础， 老年性萎缩和虚弱。

DESCRIPTION (Adapted from the applicant's abstract): Satellite cells are muscle-specific stem cells that function to repair damaged myofibers and provide new myonuclei for muscle enlargement. Rosenblatt has shown that knocking out the proliferative capacity of satellite cells prevents hypertrophy of skeletal muscle. Blau and Wright have found that satellite cells prematurely senesce in young patients with Duchenne's muscular dystrophy who have many cycles of regeneration. Schultz has observed a progressive loss of the proliferative capacity of satellite cells as rats age, and similar data has just been reported in humans. Hayflick showed that normal, diploid cells have a finite proliferative lifespan and reach cellular senescence. However, Bischoff indicated that a critical evaluation of the self-maintenance criteria required to categorize the satellite cell as stem cell is yet to be undertaken. These provocative reports highlight some of the conceptual framework to pose the following specific aims. Using the well-established and validated approach of clonogenecity assays to determine a cell's proliferation potential, this proposal examines 1.) whether a physiological model of repeated cycles of atrophy-regrowth in old skeletal muscle speeds satellite cells to senescence so that their proliferative capacity is depleted prior to the lifespan of rats; 2.) determine whether the application of IGF-1 to skeletal muscle or 3.) increased contractile activity, or both aims 1 and 2 results in either a.) using up or b.) replenishing the finite population doublings in old satellite cells. These results would shed much needed insight into whether replicative senescence can be modulated by environmental factors. The information thus gleaned from these studies will provide the basis for follow-up experiments that will measure cell cycle markers to begin to explain the observations in molecular detail. As the number of individuals with frailty is rapidly increasing, it becomes a more urgent clinical, social, and economic issue to find out if and how satellite cell lifespan can be maintained/enhanced. This proposal will therefore provide novel insights into how the self-maintenance properties of satellite cells is modulated by compensatory factors (IGF-1 and exercise), thereby forming the basis for more effective interventions against senile-atrophy and frailty.