MUSCLE DAMAGE IN AGING: INFLAMMATORY MECHANISMS

衰老过程中的肌肉损伤：炎症机制

• 批准号: 3159771
• 负责人: JOSEPH G CANNON
• 金额: $ 3.3万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-03-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3159771
• 关键词: aging; animal old age; antiinflammatory agents; biopsy; blood cell count; complement deficiency; creatine kinase; cytokine; dietary supplements; exercise; growth factor; histochemistry /cytochemistry; human subject; immune complex diseases; inflammation; interleukin 1; laboratory mouse; mechanical stress; membrane permeability; muscle disorders; muscle proteins; muscle strength; myofibrils; neutrophil; nutrition related tag; superoxides; tissue /cell culture; tocopherols; tumor necrosis factor alpha; vitamin therapy

Unaccustomed physical exercise results in delayed-onset muscle soreness, release of muscle enzymes into the circulation and increased myofibrillar protein breakdown. Eccentric exercise, in which muscles are forced to lengthen as they develop tension, is a particularly potent inducer of these responses. In the initial funding period of this grant, we have characterized eccentric exercise-induced changes in host defense factors in humans, specifically activation of neutrophils and production of the cytokine interleukin-1beta. We found highly significant correlations between these defense mechanisms and the muscular responses. Moreover, these parameters were significantly influenced by age and by dietary vitamin E supplementation. In the next 3 years, we propose to determine if the host defense mechanisms do indeed mediate damage or recovery of muscle by studying the responses of young and old mice to eccentric exercise after interventions that alter in vivo levels of cytokines and neutrophils or alter their biological activity. The responses to be measured include changes in muscle membrane permeability, loss of muscle strength (measured in vitro) and the extent of muscle fiber damage (assessed histochemically). The proposal is intended to help develop an understanding of the mechanisms involved in muscle damage and recovery in response to exercise stress. In addition, these studies may lead to new therapies for injury- or age- related deficits in muscle function.

不习惯的体育锻炼会导致迟发性肌肉酸痛， 肌肉酶释放到循环中并增加肌原纤维 蛋白质分解。 离心运动，其中肌肉被迫 当它们产生紧张时会延长，是这些的特别有效的诱导剂 回应。 在这笔赠款的初始资助期内，我们有 表征了离心运动引起的宿主防御因子的变化 人类，特别是中性粒细胞的激活和 细胞因子白介素-1β。 我们发现高度显着的相关性 这些防御机制和肌肉反应之间的关系。 而且， 这些参数受到年龄和饮食的显着影响 补充维生素E。 在未来 3 年内，我们建议确定是否 宿主防御机制确实介导肌肉损伤或恢复 通过研究年轻和年老小鼠对离心运动的反应 改变体内细胞因子和中性粒细胞水平的干预措施或 改变它们的生物活性。 要测量的响应包括 肌膜通透性变化、肌力丧失（测量 体外）和肌纤维损伤的程度（组织化学评估）。 该提案旨在帮助加深对机制的理解 参与运动压力引起的肌肉损伤和恢复。 在 此外，这些研究可能会带来针对损伤或年龄的新疗法 相关的肌肉功能缺陷。