MYONUCLEAR DEGENERATION IN AGING SKELETAL MUSCLE

衰老骨骼肌中的肌核变性

• 批准号: 2705981
• 负责人: KATHLEEN Marie MCCORMICK
• 金额: $ 7.55万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2705981
• 关键词: aging; atrophy; cell population study; exercise; image processing; in situ hybridization; laboratory rat; myofibrils; nuclear matrix; protein biosynthesis; protein degradation; statistics /biometry; striated muscles; tissue /cell preparation

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.

骨骼肌萎缩是衰老的必然结果。 与年龄相关的肌肉萎缩与 蛋白质合成，但对其细胞机制知之甚少 在衰老的骨骼肌中，哪种合成代谢活动减少。一 可能的是，可供人类使用的遗传物质总量 合成活性降低。换句话说，可能会损失 肌核随年龄增长。肌核的丢失可能会降低总的 转录，最终，蛋白质合成。因此，肌肉 纤维萎缩可能随之而来。拟议的研究将审查 肌核群体动力学与肌纤维的关系 萎缩。据推测，肌核损失之间的平衡 在衰老的骨骼肌中肌核的增殖被破坏，导致 肌纤维核的丢失。为了检验这一假设， 年龄对肌肉中肌核变性、增生和种群大小的影响 显示年龄相关性萎缩(比目鱼肌和足底肌)和肌肉 不要(指长屈肌(FL)和内收肌(AL))。在……里面 此外，运动训练对肌核群体大小的影响， 我们将检查沉积和流失情况。根据推论，如果肌肉 萎缩是由于肌核丢失和增殖不平衡所致，然后 运动训练被证明是一种保持肌肉质量的干预措施，应该 恢复这种平衡。成人(6个月大)、中年(12岁) Fischer 344只雄性大鼠将 被分配到运动训练或久坐不动的对照组。 经过10周的跑步训练，肌核的大小 种群数量将通过形态测量进行估计。原地和 DNA片段化的生化分析将被用于量化 肌核变性的发生率。肌核增生将会是 通过标记研究最后一周形成的所有原子核进行评估 5-溴-2-脱氧尿苷(BrdU)，一种胸苷类似物。建议数 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起作用。了解这些 机制对于制定预防和控制艾滋病的战略是必不可少的 抵消这一过程。