MYONUCLEAR DEGENERATION IN AGING SKELETAL MUSCLE

骨骼肌萎缩是衰老的必然结果。 与肌肉萎缩相关的肌肉萎缩与 蛋白质合成，但对细胞机制知之甚少 其合成代谢活性在老化的骨骼肌中降低。 一 可能性是，遗传物质的总量可用于 合成活性降低。 换句话说，可能会有损失。 随着年龄的增长。 肌细胞核的丢失可能会降低 转录和最终的蛋白质合成。 因此，肌肉 纤维萎缩可能随之发生。 拟议的研究将审查 肌纤维与肌细胞数量动态的关系 萎缩 据推测，肌肉萎缩和 并且在老化的骨骼肌中肌纤维增生被破坏， 肌纤维细胞核的丢失。 为了验证这一假设， 年龄对肌肉变性、增生和肌肉中群体大小的影响 显示与年龄相关的萎缩（比目鱼肌和跖肌）和肌肉， 不做（屈趾长肌（FL）和收长肌（AL）。 在 此外，运动训练对肌萎缩症人群规模的影响， 增加和损失将被检查。 据推测，如果肌肉 萎缩是由于肌肉损失和增生的不平衡， 运动训练是一种可以保持肌肉质量的干预措施， 恢复这种平衡。 成人（6个月）、中年（12岁 月龄）和老龄（24月龄）Fischer 344雄性大鼠将 被分配到一个运动训练或久坐不动的对照组。 经过十周的跑步训练，肌肉的大小 将通过形态测量来估计种群。 原位和 DNA片段化的生化测定将用于定量 肌变性的发生率。 肌层增生将是 通过标记在研究的最后一周期间形成的所有细胞核来评估 与5-溴-2-脱氧尿苷（BrdU），一种胸苷类似物。 拟议 研究是确定细胞机制的第一步， 在与年龄相关的肌肉萎缩中发挥作用。了解这些 机制对于制定预防和 抵消这个过程。

Skeletal muscle atrophy is an inevitable consequence of growing old. Age-related muscle atrophy is associated with a significant decline in protein synthesis but little is known of the cellular mechanisms by which anabolic activity is reduced in aging skeletal muscle. One possibility is that the total quantity of genetic material available for synthetic activity is reduced. In other words, there may be a loss of myonuclei with age. A loss in myonuclei could reduce overall rates of transcription and ultimately, protein synthesis. As a result, muscle fiber atrophy may ensue. The proposed research will examine the relationship between myonuclear population dynamics and myofiber atrophy. It is hypothesized that the balance between myonuclear loss and myonuclear accretion is disrupted in aging skeletal muscle resulting in a loss of myofiber nuclei. To test this hypothesis, the effect of age on myonuclear degeneration, accretion and population size in muscles that show age-related atrophy (soleus and plantaris) and muscles that do not (flexor digitorum longus (FL) and adductor longus (AL). In addition, the effect of exercise training on myonuclear population size, accretion and loss will be examined. It is reasoned that if muscle atrophy is due to an imbalance in myonuclear loss and accretion, then exercise training, an intervention shown to preserve muscle mass, should restore this balance. Adult (six months old), middle-aged (twelve months old) and old (twenty-four months old) Fischer 344 male rats will be assigned to an exercise trained or sedentary control group. Following ten weeks of run training, the size of the myonuclear population will be estimated by morphometric measurements. In situ and biochemical assays for DNA fragmentation will be used to quantitate the incidence of myonuclear degeneration. Myonuclear accretion will be assessed by labeling all nuclei formed during the last week of the study with 5-bromo-2-deoxyuridine (BrdU), a thymidine analog. The proposed research is a first step toward identifying cellular mechanisms that play a role in age-related muscle atrophy. Understanding these mechanisms is imperative for developing strategies to prevent and counteract this process.