AGE-RELATED CHANGES IN INTRINSIC PROPERTIES OF MUSCLE

肌肉萎缩，伴随着再生能力的丧失，是衰老的一个衰弱的后果，这仍然只是边缘理解，是不可行的治疗干预。 这项工作将表征来自不同年龄小鼠的肌肉前体/祖细胞，以了解为什么老年肌肉组织再生比年轻时差。 将比较原代成肌细胞增殖、分化和对IGF-1应答的能力。 我们的初步数据显示，这些细胞的内在特性与年龄有关。 肌肉谱系将在成年生物体中表征，并且将确定肌肉前体细胞的相对丰度及其再生能力的潜在年龄相关变化。 将研究Notch在成人肌肉中细胞命运决定中的作用，以及Notch存在/活性的潜在年龄相关变化。 这项工作还将通过测试原代鼠成肌细胞中IGF-1的生理信号传导是否需要Cn活性，以及该途径是否随年龄而变化，来解决老年肌肉对IGF-1的反应性降低的问题。这些目标旨在揭示年轻/成年和老年肌肉之间再生能力的关键机制差异，并提供对随年龄增长的肌肉萎缩的理解。 获得的数据可能提供一个治疗的机会，以恢复再生能力和生长因子的反应，在旧的肌肉，并产生一个抗体面板定义成人肌源性谱系积极主动。

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.