AGE-RELATED CHANGES IN INTRINSIC PROPERTIES OF MUSCLE

肌肉萎缩，伴随着再生能力的丧失，是衰老的衰弱后果，目前对此仍知之甚少，不愿进行治疗干预。这项工作将对来自不同年龄的小鼠的肌肉前体/祖细胞进行表征，以了解为什么老年肌肉组织比年轻时再生得更差。我们将比较原代成肌细胞的增殖、分化和对IGF-1的反应能力。我们的初步数据显示，这些细胞的内在属性随年龄的变化而不同。肌肉谱系将在成年生物体中确定，肌肉前体细胞的相对丰度和再生能力的潜在年龄相关变化将被确定。Notch在决定成年肌肉细胞命运中的作用，以及Notch存在/活性与年龄相关的潜在变化将被研究。这项工作还将通过测试原代小鼠成肌细胞中IGF-1的生理信号是否需要CN活性，以及这一途径是否随着年龄的变化来解决老年肌肉对IGF-1反应减弱的问题。这些目的旨在揭示年轻/成人和老年肌肉在再生能力方面的关键机制差异，并提供对肌肉随年龄增长萎缩的理解。所获得的数据可能提供一个治疗机会，以恢复老年肌肉的再生能力和生长因子反应；并主动产生一个确定成人肌源性谱系的抗体小组。

Muscle atrophy, accompanied by the loss of regenerative capacity, is a debilitating consequence of aging, which remains only marginally understood and is recalcitrant to a therapeutic intervention. This work will characterize muscle precursor/progenitor cells derived from mice of different age in an approach to understand why old muscle tissue regenerates worse than young. Primary myoblasts will be compared in their ability to proliferate, differentiate, and respond to IGF-1. Our preliminary data show age-related differences in the intrinsic properties of these cells. Muscle lineage will be characterized in an adult organism, and potential age-related changes in the relative abundance of muscle precursor cells and in their regenerative capacity will be determined. Role of Notch in the cell fate determination in an adult muscle, and potential age- related changes in Notch presence/activity will be studied. This work will also address the diminished responsiveness of old muscle to IGF-1, by testing whether physiologic signaling by IGF- 1 in primary murine myoblasts requires Cn activity, and whether this pathway changes with age. These aims are designed to reveal key mechanistic differences in regenerative capacity between young/adult and old muscle, and to provide an understanding of muscle atrophy with age. Obtained data may provide a therapeutic opportunity to restore regenerative capacity and growth factor responsiveness in old muscle; and to generate an antibody panel defining adult myogenic lineage proactively.